Amboss Gastroenterology

Poisoning Poisoning occurs when a substance that is inhaled, ingested, or absorbed through the skin has harmful or even deadly effects on normal body function. The type of poison, the amount taken, and the size and age of the individual involved are all factors that determine if a substance is actually harmful. Substances that are commonly thought to be harmless, such as water and most vitamins, can also be harmful if taken in excess. The focus of this learning card is poisoning from organophosphates, cyanide, ethylene glycol and methanol, laundry and cleaning products, mushrooms and plants, carbon monoxide and carbon dioxide. In the United States, if poisoning is suspected, Poison Control (available 24/7 at 1-800-222-1222) should be contacted immediately to obtain information from specialists regarding management. If the poisonous substance is unknown, the patient's case history together with clinical features may help determine the causative agent, which is important for the selection of a proper antidote (if available).

AcetaminophenFormation of toxic metabolite (NAPQI) in the liver (hepatotoxicity)→ liver failure (see acetaminophen overdose)N-acetylcysteineActivated charcoal AmphetaminesEnhance sympathetic effect → serotonin syndrome (fever, ams, tone)Benzodiazepines: sedation and control of seizuresAmmonium chloride acidifies urine excretes Acetylcholinesterase inhibitors and organophosphates (e.g., parathion, E605) Cholinergic excess → cholinergic syndrome with muscarinic effects (DUMBBELLSS), nicotinic effects (flaccid paralysis, respiratory arrest), and CNS effects (seizure, coma)Atropine: reverses muscarinic effects Pralidoxime (2-PAM): treats neuromuscular dysfunction Antimuscarinic/anticholinergic agents (e.g., atropine, medications with anticholinergic effects, jimson weed, deadly nightshade) Anticholinergic excess → anticholinergic syndrome Physostigmine BarbituratesEnhance action of GABA → CNS depression (see barbiturate overdose)Sodium bicarbonate alkalinizes urine BenzodiazepinesEnhance action of GABA → CNS depression (see benzodiazepine overdose)Flumazenil Beta blockersInhibit sympathetic effect → bradycardia, hypotension, hypoglycemia (see beta blocker overdose)Glucagon: increases cardiac contractility Atropine for bradycardia Insulin and glucose to correct hypoglycemia DigitalisInhibits Na+/K+-ATPase → cardiac arrhythmias, xanthopsia (see cardiac glycoside poisoning)Digoxin-specific antibody HeparinIncreases activity of antithrombin → excessive bleedingProtamine sulfate Opioidsμ-, κ-, and δ-receptor agonism (see opioid intoxication) → miosis, altered mental status, respiratory depressionNaloxone SalicylatesSalicylate metabolites accumulate in liver → hepatic failure and metabolic acidosis (see salicylate toxicity)Sodium bicarbonateActivated charcoal Thrombolytic agents (e.g., recombinant tPA)Catalyze conversion of plasminogen to plasmin → excessive bleedingAminocaproic acid Tricyclic antidepressantsMuscarinic ACh receptor inhibition → anticholinergic syndrome(hot, dry, no pee )Sodium bicarbonate Benzodiazepines for control of seizuresActivated charcoal WarfarinVitamin K antagonism (γ-carboxylation of clotting factors) → excessive bleedingFresh frozen plasma and/or prothrombin complex concentrate (immediate antidote)Vitamin K (delayed antidote) Metals For toxicity and findings, see the specific metal poisoning. Chelating agents (bind free metal ions) Dimercaprol, succimer: arsenic, gold, lead, mercury Penicillamine: gold, copperDeferoxamine ("De-Fe-roximine"): ironEDTA: lead Carbon dioxide↑ CO2 decreases O2 concentration → headaches, cardiac arrhythmias, respiratory depression, coma Normal or high concentration oxygen depending on severity Carbon monoxideFormation of carboxyhemoglobin → tissue hypoxia → cherry-red skin tone, somnolence, agitation, headache100% hyperbaric oxygen CyanideBlocks electron transport chain → anion gap metabolic lactic acidosis, bitter almond breath, altered mental statusHydroxycobalaminMethemoglobin-formingagents (e.g.,amyl nitrite, sodium nitrite, 4-DMAP)Sodium thiosulfate Methanol, ethylene glycol (antifreeze)Formation of toxic metabolites in the liver → anion gap metabolic acidosis, seizures, dyspnea (see ethylene glycol poisoning and methanol poisoning)Fomepizole MethemoglobinCannot bind oxygen → cyanosis, coma, brown blood (see methemoglobinemia)Methylene blueVitamin C: weak reducing agent Activated charcoal effectively binds acetaminophen, aspirin, and tricyclic antidepressants. It is ineffective in the treatment of heavy metal toxicity (e.g., mercury, lead), cyanide, lithium, acids, bases, and toxic alcohols such as methanol. Organophosphates Primarily used as insecticides, herbicides, and nerve agents Example: parathion or E605 Brief description: an organophosphate insecticide and irreversible acetylcholinesterase inhibitor PathophysiologyAbsorbed through the skin, respiratory system, or gastrointestinal tractIrreversible inhibition of acetylcholinesterase → ↑ acetylcholine levels → activation of muscarinic and nicotinic acetylcholine receptorsResult: life-threatening activation of parasympathetic nervous system Clinical featuresAcute cholinergic crisis and paralysis Garlic or petrol-like odorBlue-colored saliva and mucosa Cardiovascular symptoms: bradycardia, hypotensionGastrointestinal symptoms: diarrhea, vomiting, abdominal painUncontrolled urination↑ Sweating, ↑ salivationRespiratory symptoms: bronchospasm, bronchorrheaCNS-related symptoms: lethargy, seizures, tremor, possibly comaMusculoskeletal symptoms: fasciculations, weakness, spasms, paralysis → peripheral neuromuscular respiratory failure Ocular symptoms: miosis, lacrimationChronic low-dose exposure: chronic organophosphate-induced neuropsychiatric disorder characterized by fatigue, depression, impaired memory, extrapyramidal symptoms, peripheral neuropathy, and autonomic dysfunction ManagementPatient decontamination (e.g., remove clothes, wash skin)Secure airways, ECGMeasurement of erythrocyte cholinesterase activity : ↓ acetylcholinesterase activityMedication Atropine Oximes: pralidoxime (2-PAM), obidoximeRegenerate acetylcholinesterase by dephosphorylation Function peripherally on both muscarinic and nicotinic receptors Should only be administered after atropine due to risk of transient worsening of acetylcholinesteraseinhibition Always use personal protective equipment (e.g., neoprene gloves, gown, charcoal cartridge mask) when decontaminating patients. Remove contaminated clothing and wash contaminated skin. The greatest danger in organophosphate poisoning is respiratory failure. The acronym "DUMBBELLSS" lists the clinical features of organophosphate poisoning → D = Diarrhea, U = Urination, M = Miosis, B = Bronchospasm / Bradycardia, E = Emesis, L = Lacrimation / Lethargy, S = Sweating / Salivation Cyanides Examples: CN-, HCN , KCN Brief description: chemical compound containing a cyano group (gas, liquid, or solid) ExposureFires: Cyanide is released by various substances during combustion (e.g., plastics, upholstery, rubber). Long-term or high-dose treatment with sodium nitroprusside, especially in individuals with chronic renal failure Industrial: metal industry, manufacture of nitrogen-containing materials and products (plastics and wool), electroplating Pathophysiology: Absorbed through the skin, respiratory system, and gastrointestinal tractCyanide blocks the electron transport chain by binding to cytochrome complex IV → ↓ oxidative phosphorylation→ anaerobic metabolism, ↑ lactic acid Clinical featuresOnset of symptoms 15-60 minutes after oral ingestionFew seconds after inhalationBreath smells of bitter almonds Neurologic symptoms: confusion, agitation, vertigo, headache, seizures, comaGastrointestinal: nausea, vomiting, discomfortCardiac symptoms: chest pain, cardiac arrhythmiaPulmonary symptoms: dyspnea, tachypnea, pulmonary edema, respiratory failureBright red bleeding of mucous membranesFlushing of the skinNecroses in mouth and esophagusBright red retinal veins on fundoscopic examinationPostmortem, bright red livor mortis (cherry red skin) can be seenBlood tests: high anion gap metabolic acidosis,↑ lactic acid Management Patient decontamination (e.g., remove clothes, wash skin)Administration of 100% oxygen regardless of saturation readingsSupportive careAntidote Hydroxycobalamin (precursor of vitamin B12): binds cyanide directly and forms cyanocobalamin, which is excreted in urine (first-line antidote)Sodium nitrite, amyl nitrite, or 4-dimethylaminophenol (4-DMAP) to induce methemoglobinemia: Methemoglobin binds to cyanide to form cyanomethemoglobin, which diverts cyanide from cytochrome complex IV and increases oxidative phosphorylation. Sodium thiosulfate: supplies sulfur donors to the mitochondrial enzyme rhodanese. Rhodanese detoxifies cyanide into thiocyanate, which is excreted in urine (usually coadministered with hydroxocobalamin). Induction of methemoglobinemia (e.g., with amyl nitrite or sodium nitrite) is contraindicated in patients with inhalation injuryunless concomitant carbon monoxide toxicity has been excluded because of the risk of worsening tissue hypoxia. Consider cyanide poisoning in a patient with chronic renal failure who has very recently undergone treatment for a hypertensive emergency and is now presenting with altered mental status and lactic acidosis. Ethylene glycol, methanol and isopropyl alcohol Ethylene glycol Brief descriptionSweet-tasting alcohol that is primarily used in radiators to raise the boiling point and lower the freezing point. Sources of exposureIngested as ethanol substitute by alcoholicsSelf-harm attemptsAccidental ingestion FeaturesSweet-smelling breathAltered mental status, hallucinations, seizuresTachypnea, hyperpneaCalcium oxalate deposition in the kidneys → flank pain, hematuria, oliguria, and acute kidney injurySigns of tetany due to hypocalcemia ↑ Osmolar gap Methanol Sources of exposureFuels (highly flammable)Ingested as ethanol substitute by alcoholicsImproper distillation of spirits Self-harm attemptsAccidental ingestion EffectsMetabolism of methanol in the liver → accumulation of formic acid and formaldehyde in the blood → anion gap metabolic acidosis (acidemia) → cellular toxicityMaximum effect: 48 hours after intoxicationDelayed toxicity: Coingestion of methanol with another alcohol (e.g., ethanol) will delay the metabolism of methanol and, therefore, the onset of toxicity. FeaturesNausea, abdominal crampsHeadache, altered mental statusSevere acidosisTachypnea, hyperpneaOptic neuropathy: loss of visual acuity, scotoma, blindness ↑ Osmolar gap Isopropyl alcohol Sources of exposureDisinfectantsSolventsAntifreeze Effects: isopropyl alcohol is metabolized to acetone → ↑ serum ketones FeaturesAltered mental status, comaFruity, sweet-smelling breath as in diabetic ketoacidosis Massive ingestion: features of shock Management of ethylene glycol, methanol, and isopropyl alcohol poisoning General approachSecure airways, oxygenation, monitoring, fluid resuscitation.Check serum electrolytes and osmolality (e.g., increased serum osmolar gap).Obtain serum ethylene glycol, methanol, and isopropyl alcohol (and acetone) levels.Obtain ABG: anion gap metabolic acidosis. Crystalloid infusions for enhanced renal eliminationHemodialysis for severe metabolic acidosis and renal failure For ethylene glycol and methanolAntidotes: both, ethanol and fomepizole prevent the formation of toxic metabolitesEthanol: binds alcohol dehydrogenase with higher affinity than methanol or ethylene glycol, thereby competitively inhibiting the metabolism into toxic metabolitesFomepizole: competitively inhibits alcohol dehydrogenase, thereby blocking the conversion of formaldehyde to formic acid (toxic metabolite responsible for symptoms)Sodium bicarbonate for anion gap metabolic acidosisEthylene glycol: calcium gluconate for hypocalcemiaMethanol: folic acid For isopropyl alcoholMeasure serum and urine ketonesNo use of antidotes Laundry and cleaning products Detergents Brief description: surfactants used as cleaning agents (e.g., laundry or dish detergents) Clinical featuresAbdominal pain, vomiting caused by foam formationChest pain, dyspneaDysphagia ManagementSecure airways, oxygenation, monitoring, fluid resuscitationEndoscopy to evaluate severity of injuryPerform ABG to evaluate for pHAnti-foaming agent: polydimethylsiloxane (dimethicone) Caustic agents Brief description: strong acids or alkalis used as cleaning agents (e.g., potassium hydroxide, sodium hydroxide), drain/toilet bowl cleaners, or rust removers (e.g., hydrogen fluoride, zinc chloride) Clinical features Upon ingestion Oral pain, odynophagia, heavy salivationDysphagiaAbdominal pain, nausea, vomitingChest pain, dyspneaUpon ocular exposure: also see ocular chemical burnsPain, foreign body sensationRedness, impaired vision, conjunctival injury, tearingIncreased intraocular pressureUpon skin exposure Pain, erythema, and/or blisteringPossibly permanent scarring ManagementIngestion Secure airways , oxygenation, monitoring, fluid resuscitationRemoval of contaminated clothingEndoscopy in first 12-24 hours to evaluate severity of injuryOcular exposure: eye irrigation with topical anestheticsSkin exposure Rinse affected area with copious amounts of water immediately. Necrotic tissue should be excised, blisters debrided, and the underlying tissue covered with a sterile dressing.Antibacterial cream to prevent secondary infection. [20] Complications (ingestion): gastric outlet obstruction, esophageal perforation, esophageal strictures, esophageal cancer Do not induce vomiting, as this may cause further damage to the esophagus. Do not attempt to neutralize the alkali with a weak acid, as this may lead to vomiting or local heat production. Mushrooms and plants Amanita phalloides (death cap mushroom) Brief description: toxic mushrooms containing phalloidin and α-amanitin Pathophysiologyα-amanitin: blocks RNA polymerase → inhibition of mRNA transcription and protein synthesis → apoptosis Clinical featuresAfter 6-24 hours: gastrointestinal symptoms (diarrhea, vomiting, abdominal cramps) that resolve 24-36 hoursafter ingestionAfter 2-4 days: renal and liver failureIngestion of a single cap may be lethal ManagementSupportive careGastric decontamination within first hour after ingestion if patient has not vomited yet (e.g., medically-inducedvomiting , gastric lavage and suction)AntidoteNo FDA-approved antidoteSuggested therapies: N-acetylcysteine, penicillin GLiver transplant in severe cases Atropa belladonna (belladonna, deadly nightshade) Brief description: plant with toxic berries and leaves containing atropine (tropane alkaloid) Pathophysiology: competitive inhibitor of muscarinic acetylcholine receptors (parasympathetic nervous system) Clinical featuresAnticholinergic syndrome (e.g., dry, red skin; anhidrosis, fever, mydriasis, tachycardia, delirium)Hallucinations, coma, seizuresUrinary retention, absent bowel soundsPotentially fatal cholinergic crisis (e.g., seizures, respiratory failure, asystole) ManagementSupportive care, activated charcoalInduced vomiting with ipecac is contraindicated Antidote: physostigmineFirst-line treatment in a hospital settingCNS-penetratingIndirect parasympathomimetic (reversibly inhibits acetylcholinesterase)Alkaloid poisoning must be confirmed before administration , as physostigmine may cause a potentially fatal cholinergic crisis. Features of anticholinergic syndrome can be remembered with "Blind as a bat (cycloplegia & mydriasis), mad as a hatter (delirium & hallucinations), red as a beet (cutaneous vasodilatation), hot as hell (hyperthermia), dry as a bone (anhidrosis & xerophthalmia), the bowel and bladder lose their tone (urinary retention & absent bowel sounds), and the heart runs alone (tachycardia)." Carbon monoxide and carbon dioxide Carbon monoxide (CO) Exposure: house fires, wood-burning stoves, motor vehicle exhaust, furnaces in enclosed and poorly ventilated spaces, extensive water pipe smoking. Properties: colorless, odorless, and tasteless gas PathophysiologyHemoglobin has an affinity for CO that is ∼ 240x stronger than that for oxygen → formation of COHb(carboxyhemoglobin)↑ COHb causes tissue hypoxia by the following mechanisms:Decreased oxygen-carrying capacity of hemoglobinShift in the O2 dissociation curve to the left → decreased release of O2 in tissuesBinding of CO to myoglobin → cardiac ischemia → decreased cardiac outputCO inhibits mitochondrial cytochrome c oxidase → defective oxidative phosphorylation → decreased ATPproductionCO inhibits cytochrome p450 in the brain → lipid peroxidation and leukocyte-mediated inflammatory damage Clinical featuresSymptoms depend on COHb levels COHb levels 10-30%: fatigue, headache, nauseaCOHb levels > 30%: agitation, confusion, memory loss, somnolence, dyspnea, chest painCOHb levels > 50%: shock, respiratory failure, myocardial infarction, seizures, comaCherry-red skin coloring: after excessive exposure (rare)Inhalational injury in the event of fire burnsConsider concurrent cyanide poisoning (e.g., in industrial fires) DiagnosticsConfirmatory test: ↑ COHb levels measured by CO-oximeter in arterial or venous blood The reference range of COHb in nonsmokers is < 3%, and in smokers, it is up to 15%. Serum pO2 tends to be normal [27]Other suggestive findings Acute CO poisoningABG: high anion gap metabolic acidosis ↑ Troponin ECG: arrhythmias, evidence of myocardial ischemiaCranial CT/MRI: globus pallidus is commonly affected (bilateral hypodensity) [28]Chronic CO poisoning: ↑ hemoglobin Normal-appearing SpO2 on pulse oximetry: Because standard pulse oximetry cannot distinguish between COHb and oxyhemoglobin, this test would incorrectly show high oxygen saturation levels. TreatmentPatients with inhalation injury: intubation100% oxygen via nonrebreather facemask, until asymptomatic and COHb levels normalizeHyperbaric oxygen therapy is indicated if: COHb > 25%Pregnant women with a COHb > 15%Neurological manifestations (e.g., confusion, loss of consciousness, seizures, focal neurological deficits)Acute myocardial ischemiaSevere acidosis (pH < 7.1) Since standard pulse oximetry cannot distinguish between COHb and oxyhemoglobin, it overestimates the arterial oxygenation in patients with severe CO poisoning. arbon dioxide (CO2) Properties: colorless, odorless gas Exposure: increased production during fermentation processes, e.g., in grain silos, wells, cesspools Clinical featuresIn atmospheric concentrations < 0.3%: no health risksIn atmospheric concentrations of 5-8%: headaches, vertigo, dyspnea and tachypnea, tachycardia and arrhythmias, impaired consciousnessIn atmospheric concentrations > 8%: tremors, sweating, diminished hearing, loss of consciousness, respiratory depression, respiratory arrest ManagementRemove patient from the source of carbon dioxide poisoning.Provide oxygen and supportive care Other Ingestion of cigarettes (nicotine) Exposure: accidental ingestion (usually toddlers) Clinical featuresVomiting, pallor, tachycardia, perspirationFollowing ingestion of large amounts: (↓ blood pressure, ↓ heart rate), respiratory failure) Treatment: activated charcoal up to 60 minutes after ingestion Ingestion of button batteries Exposure: accidental ingestion (usually toddlers) Pathophysiology: Button batteries lodged in the moist environment of the esophagus can result in an electrolysis reaction, leading to corrosion and tissue necrosis; serious burns may result within 2 hours of ingestion. Clinical featuresPossibly asymptomaticAirway obstruction, coughingDrooling, vomitingChest discomfort, dysphagia DiagnosticsX-ray to determine location and confirm diagnosisButton batteries can be differentiated from a coin by the battery's halo/double-rim effect on AP view (i.e., within the radiopaque density of the battery, a parallel line can be seen).On lateral view, button batteries show a "step-off" effect due to the different size of the negative (smaller) and positive pole ManagementDependent upon patient age, size of battery, and suspected location of batteryImmediate endoscopic removal indicated if:Battery is located in the esophagus.Battery is located in the stomach or lower in the digestive tract and a magnet was co-ingested. ComplicationsTracheal stenosisTracheomalaciaTracheal fistula and/or perforationMediastinitis Always consider the possibility that a button battery has been ingested if the parents think that their child has ingested a coin or another foreign object.

Nausea and vomiting Nausea refers to an unpleasant sensation that is often localized to the abdomen and typically interpreted as an urge to vomit. Vomiting is the forceful oral expulsion of gastric contents. Common causes of nausea and/or vomiting include gastrointestinal pathologies, early pregnancy, and adverse effects of medications. However, nausea and vomiting may be caused by pathology in any organ system, including the CNS, endocrine, and vestibular systems, as well as be a manifesting symptom of a functional disorder. Patients presenting with acute onset of recurrent vomiting should be evaluated for signs of dehydration and electrolyte and acid-base disorders, which should be corrected at the earliest opportunity. A thorough history and physical examination should be performed to narrow down the differential diagnoses and guide further diagnostic workup and treatment. Accompanying symptoms (e.g., fever, abdominal pain, headache) may provide clues as to the underlying disorder. Nausea and vomiting in children are not addressed here.

Approach Approach to management [1][2] ABCDE survey Establish IV access. Perform screening examination and targeted diagnostics to rule out life-threatening causes (see below). Once life-threatening causes have been ruled out: Conduct a detailed patient history and clinical examination.Consider further diagnostic testing. Identify and treat hypovolemia (see fluid resuscitation). Identify and treat electrolyte imbalance (see electrolyte repletion). Identify and treat acid-base disorders. Identify and treat the underlying cause. Minimize or discontinue any contributing medications. Administer antiemetic therapy. Consider NPO diet. Red flags for nausea and vomiting Abdominal Persistent vomitingHematemesisFeculent vomitingMelenaHematocheziaAcute and/or severe abdominal painProgressive dysphagiaUnintentional weight loss Neurologic Altered mental statusFocal neurological deficitMeningeal signs Pulmonary/cardiovascular DyspneaChest tightnessFeeling of impending doom Immediately life-threatening causes Hemorrhagic stroke CNS infection (e.g., meningitis, encephalitis) Myocardial infarction Acute pancreatitis Bowel obstruction Bowel perforation Diabetic ketoacidosis Adrenal crisis (Addison crisis) Drug overdose/withdrawal Poisoning (e.g., ingestion of toxins) Diagnostics The diagnostic workup should be guided by the pretest probability of the possible diagnoses. The following list includes some commonly used diagnostic tools that can help to diagnose or rule out possible etiologies in a patient with nausea and vomiting. Laboratory studies Routine [1] [2] CBC ESR Serum glucose BMP LFTs Beta hCG urine test In patients with severe and sustained vomiting Blood gas analysis Urine ketones HEENTN/aPure tone audiometry Perimetry visual fields Gonioscopy and tonometry Tilt table test CardiopulmonaryTroponin Digoxin level Theophylline levelECG TTEX-ray chest (upright) Abdominal/pelvicLipase, amylase Coagulation studies (e.g., INR, PT) CRP Urinalysis Stool cultureStool ova and parasitesStool leukocytesFOBTC. difficile toxin PCRStool viral PCRH. pylori antigenX-ray abdomen (upright and supine) X-ray chest (upright) Ultrasound abdomen (complete) Duplex ultrasound of the pelvis (♀)/scrotum (♂) Transvaginal ultrasound CT abdomen and pelvis with IV contrast CT abdomen and pelvis with IV and oral contrast MRI abdomen and pelvis Upper gastrointestinal endoscopy Neurologic/psychiatricToxicology screen Salicylate levelMRI brain CT head Lumbar puncture Endocrine/metabolicTSH, free T3, T4 PTH levels AM cortisol, ACTH HA1c N/a In patients with suspected gastroenteritis without signs of sepsis, it may not be necessary to do any diagnostic testing. Life-threatening causes of nausea and vomiting Acute coronary syndrome [3][4]Heavy, dull, pressure/squeezing sensationSubsternal pain with radiation to left shoulderNausea, vomitingDiaphoresis, anxietyDizziness, lightheadedness, syncopePain may improve with nitroglycerin.ECG: nonspecific changes, ST-segment elevation/depression, T-wave inversions, Q wavesIncreased or normal troponinTTE: hypokinesis, regional wall motion abnormalitiesSee the acute management checklist for STEMI and the acute management checklist for NSTEMI/UA.Acute pancreatitis [5][6][7]Severe epigastric pain that radiates to the backNausea, vomitingEpigastric tenderness, guarding, rigidityUpper abdominal painHypoactive bowel sounds History of gallstones or alcohol use↑ Lipase, amylase Abdominal ultrasound: pancreatic edema, peripancreatic fluid, gallstonesAbdominal CT with IV contrast : pancreaticedema, peripancreatic fat stranding, gallstonesSee the acute management checklist for acute pancreatitis.Mechanical bowel obstruction [8][9][10][11]Colicky abdominal pain Obstipation/bloatingProgressive nausea and vomiting (late finding)Diffuse abdominal distention, tympanic abdomen, collapsed rectum on DRETinkling bowel soundsHistory of abdominal surgeryX-ray abdomen Dilated bowel loops proximal to the obstructionRectal air shadow absentMultiple air-fluid levelsCT abdomen with IV and oral contrast Similar findings as on x-rayTransition point at site of obstructionSee the acute management checklist for mechanical bowel obstruction.DKA [12][13]Polyuria, polydipsiaNausea and vomitingSigns of volume depletionAltered mental status, comaHyperglycemia, high anion gap metabolic acidosis, ketonuria/ketonemiaSee the acute management checklist for hyperglycemic crisesMeningitis [14][15][16]Classic triad: fever, headache, and neck stiffness (nuchal rigidity)Meningism (e.g., photophobia)Dull, diffuse (holocephalic) headache that worsens over hours/daysAltered mental statusNausea, vomitingSeizures↑ WBC, ↑ procalcitonin (if bacterial)CSF analysisBacterial: WBC ≥ 1000 cells/μL (predominantly neutrophils), elevated protein, low glucose, positive gram stainViral: WBC 10-500 cells/μL (predominantly lymphocytes), normal-elevated protein, normal glucoseSee the acute management checklist for meningitis.Hyperemesis gravidarum [17][18][1][19]Severe, persistent nausea and vomiting associated with pregnancyWeight lossDehydrationKetonuriaElectrolyte and acid-base abnormalities See the acute management checklist for hyperemesis gravidarum. Other causes of nausea and vomiting Postoperative nausea and vomiting (PONV) [20][21]Nausea and/or vomiting within the first 24-48 hoursof surgeryClinical diagnosisSee the acute management checklist for PONV.Chemotherapy-induced nausea and vomiting (CINV) [22][23][24][22][25][26]Nausea and/or vomiting related to recent chemotherapyClinical diagnosisSee treatment of CINVUncomplicated first-trimester nausea and vomiting [17][18][1][19][27]Nausea and vomiting associated with early pregnancyPresumptive signs of pregnancyUrine and serum beta hCG positiveAbdominal or transvaginal ultrasound: gestational sac or embryo, fetal heartbeat See the acute management checklist for uncomplicated nausea and vomiting of pregnancyInfectious gastroenteritis [28][29][30][31][32]FeverNausea, vomitingDiarrhea, abdominal pain Blood in stool Normal abdominal examination Exposure history Clinical diagnosisStool analysis: fecal leukocytesSee the acute management checklist for infectious gastroenteritis.Migraine [33]Unilateral headache with pulsating, boring/hammering pain Nausea, vomitingHyperacusisPhotophobia, phonophobiaPreceding auraClinical diagnosis [33] Neuroimaging: typically normal findings [34][35]See the acute management checklist for migraine headache. Medications are a common cause of nausea and vomiting. Consider replacing the medication with a suitable alternative or decreasing the dose and then slowly up titrating it to minimize this adverse effect. Differential diagnosis Infectious causes of nausea and vomiting HEENTAcute otitis mediaAcute labyrinthitis Cardiopulmonary PericarditisPneumoniaEmpyema Gastrointestinal Gastroenteritis (bacterial/viral)Infectious colitisAcute cholecystitisAcute cholangitisAcute hepatitisLiver abscessAcute appendicitis Genitourinary Urinary tract infection (e.g., cystitis, pyelonephritis)PIDTubo-ovarian abscessProstatitisOrchitisEpididymitis Neurologic MeningitisEncephalitisBrain abscessCerebral toxoplasmosis Noninfectious causes of nausea and vomiting HEENTPeripheral vertigoMénière diseaseBPPVLabyrinthitisVestibular neuritisAcoustic neuromaAngle-closure glaucoma Cardiopulmonary Myocardial infarction Gastrointestinal GERDPUDAcute gastritisGastric outlet obstructionGastroparesisBowel obstructionAcute mesenteric ischemiaChronic mesenteric ischemiaIntussusceptionMalrotationIBDIBSAcute pancreatitisBiliary colicNoninfectious hepatitis Genitourinary PregnancyRenal colic (nephrolithiasis)Ovarian torsion Testicular torsion Neurologic MigraineCluster headachesBrain tumorIntracranial hemorrhage (acute/chronic) Epidural hemorrhageSubdural hemorrhageIntracerebral hemorrhageIschemic strokeHydrocephalusSeizure disorder Psychiatric BulimiaAnorexia nervosaDepressionAnxiety disorders Functional Cyclic vomiting syndrome Toxic-metabolic Diabetic ketoacidosisUremiaHyperthyroidismHypothyroidismHyperparathyroidismHypoparathyroidismAdrenal insufficiencyAdrenal crisisAlcohol withdrawal Drug-induced Antimicrobials Analgesics Cardiac drugs AnticonvulsantsAntiparkinson medicationsAntidiabetics AntidepressantsRecreational drug use Drug withdrawalChemotherapeutic agentsOCPHormone replacement therapyNicotine patchesSulfasalazine, mesalazineIron supplementsHigh-dose vitaminsCannabinoid hyperemesis syndrome

Benign liver tumors and hepatic cysts Benign liver tumors and hepatic cysts are common and may occur in all age groups. Benign liver tumors are especially frequent in young women and include hepatic hemangiomas, focal nodular hyperplasia (FNH), and hepatocellular adenoma (also known as liver cell adenoma). Use of oral contraceptives, especially such containing estrogen, and pregnancy are associated with an increased risk of hepatocellular adenoma. Hepatic cysts include solitary and hydatid (echinococcal) cysts. Benign liver tumors and cysts are mainly asymptomatic and are often incidental findings in patients undergoing abdominal imaging. However, in some cases (e.g., large lesions), symptoms like upper abdominal pain and postprandial fullness may occur. Diagnosis is usually based on imaging, but may require biopsy in unclear cases. Treatment is generally conservative; surgery is reserved for specific lesion types and the presence of symptoms or complications.

Benign liver tumors General EpidemiologyFrequency: hepatic hemangioma (most common) > focal nodular hyperplasia (FNH) > hepatocellular adenoma(rare)Sex: ♀ > ♂ (∼ 6:1)Age: can appear at any age, but mostly affects young womenMost often an incidental finding on imaging tests EtiologyMostly unknown Hepatocellular adenoma: oral contraceptives and anabolic steroidsHepatic hemangioma: possible hormonal component; estrogen therapy associated with increased growth in size Symptoms/clinical findingsUsually asymptomaticLarge tumors → upper abdominal pain, fullness, and nausea DiagnosticsBest initial test: ultrasoundFurther imaging Contrast-enhanced CTMRIBiopsy: to confirm diagnosis if imaging is inconclusive TreatmentConservative treatment is often sufficientSurgical treatment if symptomatic and/or complications ariseFor hepatic adenomaDiscontinue oral contraceptivesIf the tumor is > 5 cm → surgical resection due to increased risk of rupture, bleeding, or malignant transformation ComplicationsRupture and bleeding The typical clinical picture of a hepatic adenoma is a young woman with a history of oral contraceptive or anabolic steroid use and upper right abdominal pain. Hepatic hemangioma Usually well-demarcated, homogeneous, hyperechoic(pale) Cavernous vascular spaces of variable size, lined by flat endothelial cells Well-demarcated Early arterial phase discontinuous, nodular, or peripheral enhancement Subsequent gradual centripetal enhancement (iris diaphragm phenomenon) Delayed-phase hyperintensity due to retention of contrast Macroscopic: possibly pedunculated, cystic lesions with a dark color Focal nodular hyperplasia (FNH) Homogeneous, hypoechoic to isoechoic Round/oval, sharply defined Central, stellate scarLocalized hepatocyte nodules, with large malformed arterial branches and centralized fibrous tissue (central stellate scar) Early arterial phase enhancement Rapid washout of the contrast medium in the portal venous phase Central scar ("nest of vessels") Macroscopic: light yellow color compared with the surrounding liver tissue Microscopic: fibrous scars Hepatocellular adenoma No characteristic vascularization Mainly isoechoic Inhomogenous due to bleeding More frequent in the right lobe of the liver Enlarged hepatocytes, with small and regular nuclei, cytoplasmic glycogen and lipid deposits Arranged in sheets or 2-cell thick cords Normal hepatic lobular architecture is absent Well-demarcated Heterogenous density due to the presence of fat, glycogen, and hemorrhagic products Early arterial phase peripheral enhancement due to feeding arteries Subsequent centripetal pattern of enhancement No retention of contrast due to arteriovenous shunting on delayed-phase Hepatic cysts Simple cystsEtiology: congenitalPeak incidence: > 50 years Usually asymptomatic Diagnostics Sonography: anechoic, round lesion with dorsal acoustic enhancementCT: well-delimited lesion; shows no contrast enhancementTreatment: laparoscopic resection if symptomatic Congenital polycystic liver → see polycystic kidney disease Hydatid (echinococcal) cysts → see echinococcosis Differential diagnoses Malignant liver tumorsHepatocellular carcinoma (HCC)Intrahepatic cholangiocellular carcinoma (CCC)Liver metastases BilomaDefinition: collection of bile in the form of a cyst (biliary cyst)Etiology: common complication of hemihepatectomy or liver transplantationDiagnostics Ultrasonography: hypoechoic to anechoicCT: hypodense, possible peripheral contrast enhancementTreatment: Drainage and antibiotic treatment in patients with inflammation. Spontaneous healing is possible. Liver abscessSonography: main characteristics include irregularly shaped margins (usually hypoechoic in ultrasonography), potentially gas-filled cavity Localized non-space occupying lesions of the liver (hepatic pseudotumors) Steatohepatitis (fatty liver) with localized steatosisRegenerative nodules in liver cirrhosis Portal vein thrombosis

Cholelithiasis, choledocholithiasis, cholecystitis, and cholangitis Cholelithiasis refers to the presence of abnormal concretions (gallstones) in the gallbladder and choledocholithiasis refers to gallstones in the common bile duct. About 10-20% of American adults have gallstones. Gallstones most commonly consist of cholesterol but may be pigmented (due to hemolysis or infection) or mixed. Both cholelithiasis and choledocholithiasis can manifest with postprandial RUQ pain, nausea, and vomiting. The diagnosis is confirmed by ultrasound, although choledocholithiasis may also require ERCP. Symptomatic cholelithiasis is managed with laparoscopic cholecystectomy. Choledocholithiasis requires stone removal, usually via ERCP. Cholecystitis is inflammation of the gallbladder that most commonly occurs after cystic duct obstruction from cholelithiasis (calculous cholecystitis). Acalculous cholecystitis is less common and seen primarily in critically ill patients. In addition to the Murphy sign (inspiratory arrest during RUQ palpation due to pain), typical signs include fever and RUQguarding. The diagnosis is made clinically and confirmed via ultrasound. Cholescintigraphy (HIDA scan) is a useful adjunctive diagnostic tool if ultrasound is unrevealing. The definitive treatment for complicated cholecystitis is laparoscopic cholecystectomy, either performed within 72 hours of onset or after a course of antibiotics when inflammation subsides (usually after at least 6 weeks). Complications of cholecystitis include gallbladder gangrene and rupture, empyema, gallstone ileus, emphysematous cholecystitis, and abscess formation. Chronic gallbladder inflammation also increases the risk of gallbladder carcinoma. Cholangitis (also known as ascending cholangitis or acute cholangitis) is an infection of the biliary tract. It is caused by obstruction of the biliary tree, which may lead to bile stasis and subsequent bacterial infection. Clinically it is characterized by the Charcot triad, which consists of abdominal pain, fever, and jaundice, although jaundice is not always present. Sepsis and septic shock may develop as a complication of acute cholangitis. The diagnosis should be suspected in patients with fever, elevated inflammatory markers, and jaundice or abnormal liver enzymes. Treatment includes resuscitation, broad-spectrum antibiotics, and urgent biliary drainage.

Cholelithiasis: the presence of gallstones in the gallbladder Choledocholithiasis: the presence of gallstones in the common bile duct Cholecystitis: inflammation of the gallbladder Cholangitis: bacterial infection of the biliary tract Cholelithiasis Bile cholesterol oversaturation, bilestasis, impaired bile acid circulation → precipitation of gallstones in the gallbladder RUQ pain < 6h US: gallstones with posterior acoustic shadow Supportive care, analgesics Elective cholecystectomy for:Symptomatic cholelithiasisAsymptomatic cholelithiasis only if at increased risk of gallbladder cancer Labs normal Choledocholithiasis Cholelithiasis → migration of gallstones into the common bile duct RUQ pain > 6 h ↑ ALP ↑ AST, ALT ↑ Total bilirubin US: dilated common bile duct, intrahepatic biliary dilatation MRCP or ERCP: filling defect in the contrast-enhanced duct Supportive care, analgesics Endoscopic stone retrieval Elective cholecystectomy if concurrent cholelithiasis or cholecystitis Acute cholecystitis Cholelithiasis (most common) or biliary sludge → inflammation of gallbladder wall RUQ pain Fever Murphy sign ↑ WBC, CRP US: gallbladder wall thickening and/or edema(double wall sign) HIDA scan if diagnosis uncertain Supportive care, analgesics IV antibiotics Cholecystectomy (timing depends on severity) Acute cholangitis Choledocholithiasis → obstruction and stasis within the biliary tract → subsequent bacterial infection Charcot triad: RUQ pain, fever, jaundice Reynold pentad: Charcot cholangitis triad PLUS hypotension and mental status changes ↑ WBC and CRP ↑ ALP ↑ AST, ALT ↑ Total bilirubin US: biliary dilation and/or evidence of obstruction (e.g., cholelithiasis) MRCP if diagnosis uncertain Supportive care, analgesics IV antibiotics Urgent biliary decompression Interval cholecystectomy if gallstones are present or concurrent cholecystitis Cholelithiasis Epidemiology [1][2] Sex: ♀ > ♂ (2-3:1) Prevalence: approx. 10-20% of the adult population in the US Peak incidence: > 40 years Etiology Imbalance in bile salts, lecithin (stabilizer), cholesterol, calcium carbonate, and bilirubin Biliary stasis is a key component in gallstone formation. Impaired gallbladder emptying (e.g., due to bowel rest, prolonged total parenteral nutrition, pregnancy ) → biliary sludge → bile stasis (cholestasis) Cholesterol stones; ∼ 80% of all stones [1][2] Risk factorsObesityFemale sex Age (> 40 years of age)Multiparity or pregnancy European, Native American, or Hispanic ancestryFamily historyDrugs: fibrates (inhibition of cholesterol 7-α hydroxylase), estrogen therapy, oral contraceptivesMalabsorption (e.g., Crohn disease, ileal resection, cystic fibrosis) Pathophysiology: abnormal hepatic cholesterol metabolism → ↑ cholesterol concentration in bile and ↓ bile salts and lecithin → hypersaturated bile → precipitation of cholesterol and calcium carbonate → cholesterol stones or mixed stones During pregnancy, increased estrogen levels cause increased secretion of lithogenic bile (rich in cholesterol), resulting in the formation of cholesterol gallstones. Increased progesterone levels cause smooth muscle relaxation, decreased and impaired gallbladder contraction, and subsequent bile stasis and formation of gallstones. Rule of the 6 Fs: Fat, Female, Fertile, Forty, Fair-skinned, Family history. Black pigment stones, ∼ 10% of all stones [3][1][4] Risk factorsChronic hemolytic anemias (e.g., sickle cell disease, hereditary spherocytosis)Cirrhosis Pathophysiology: ↑ hemolysis → increase in circulating unconjugated bilirubin → increased uptake and conjugation of bilirubin → precipitation of bilirubin polymers and stone formation Mixed (brown pigment stones); ∼ 10% of all stones [3][1][4][5] Risk factors: bacterial infections and parasites (e.g., Clonorchis sinensis, Opisthorcus species) in the biliary tract Pathophysiology: infection or infestation → release of β-glucuronidase (by injured hepatocytes and bacteria) → hydrolyzes conjugated bilirubin and lecithin in the bile → increased unconjugated bilirubin and fatty acids → precipitation of calcium carbonate, cholesterol, and calcium bilirubinate (dark color) in bile Clinical features [6][7] Most gallstones are asymptomatic. Biliary colic: constant, dull RUQ pain lasting < 6 hours Especially postprandial May radiate to the epigastrium, right shoulder, and back (referred pain) Nausea, vomiting, early satiety Bloating, dyspepsia Only a minority of patients with gallstones are symptomatic! Diagnostics [6] Approach: conduct RUQ ultrasound → perform further imaging (EUS or MRCP) if concurrent common bile ductstones are suspected or if US is equivocal Laboratory findings: usually normal in uncomplicated cholelithiasis Imaging: RUQ ultrasound: best initial test (85-90% sensitivity, 99% specificity) [8]Shows gallstones with posterior acoustic shadow, possible sludge Endoscopic ultrasound (EUS) is more sensitive than transabdominal ultrasound. MRCP only if concurrent common bile duct stones are suspected X-ray is rarely diagnostic because only 10-15% of stones (i.e., pigment stones) are radiopaque. Cholesterol stones are radiolucent! Laboratory test results (e.g., WBC count, bilirubin, amylase) are usually normal in uncomplicated cholelithiasis! Treatment [9][10][11][12][13] Approach: supportive therapy and dietary modifications → elective cholecystectomy only for symptomatic patients who are surgical candidates or asymptomatic patients at risk of gallbladder cancer Supportive therapyFasting or dietary modification (decreased fat intake)Spasmolytics (e.g., dicyclomine)Analgesia: NSAIDs, opioids Surgical managementLaparoscopic cholecystectomy (curative) Indications: Symptomatic cholelithiasisAsymptomatic cholelithiasis with an increased risk of gallbladder cancer (e.g., gallbladder polyps or porcelain gallbladder present)Timing: as soon as possible for biliary colic [14] Medical management Medical litholysis (e.g., oral dissolution therapy): oral administration of bile acids (chenodeoxycholic acid, ursodeoxycholic acid) Indication: cholesterol stones without calcification (≤ 20 mm) for inoperable patients or patients who do not wish to undergo cholecystectomyTreatment duration: at least 6 monthsSuccess rate < 50% Cholecystectomy is usually not indicated in asymptomatic cholelithiasis! Meperidine (pethidine) or NSAIDs are safe to use in suspected biliary colic or biliary pancreatitis (or RUQ pain), as they do not worsen sphincter of Oddi spasm. [15] Complications [16][17] Recurrence of gallstones within the bile ducts (even after cholecystectomy) Choledocholithiasis Cholecystitis Cholangitis Mirizzi syndrome: Gallstones in the cystic duct or Hartmann pouch of the gallbladder obstruct the common hepatic duct or common bile duct.Symptoms resemble those of choledocholithiasis.Can also lead to cholecystocholedochal fistula Choledocholithiasis Epidemiology [18][5] Sex: ♀ > ♂ Prevalence: unknown. ∼ 5-20% of patients who undergo cholecystectomy have choledocholithiasis at the time of surgery. Peak incidence: similar to cholelithiasis Etiology [7][1] Primary choledocholithiasis (less common): conditions predisposing to bile stasis → intraductal stone formation Cystic fibrosisProlonged total parenteral nutrition Secondary choledocholithiasis (more common): history of cholelithiasis Cholelithiasis → passage of gallstones into the common bile duct → common bile duct obstruction → spasm of the biliary tracts Clinical features [18][7] Colicky RUQ/epigastric painMore severe and prolonged (> 6 hours) than in cholelithiasisPostprandial Nausea, vomiting Signs of extrahepatic cholestasis: jaundice, pale stool, dark urine, pruritus Diagnostics [18] Approach: conduct laboratory tests and transabdominal ultrasound to determine the risk of choledocholithiasis → further confirmatory imaging (MRCP, ERCP, EUS) if clinical suspicion remains high Laboratory findingsSigns of cholestasis: ↑ ALP, ↑ GGT, ↑ total and ↑ direct bilirubinSynthetic liver function tests: ↑ AST, ALTPossible pancreatic inflammation: ↑ lipase, ↑ amylase ImagingTransabdominal ultrasoundDilated common bile duct with possible intrahepatic biliary dilatationThe common bile duct is generally considered dilated when it is > 6 mm wide or > 10 mm in a patient who has undergone cholecystectomy, although these numbers are not definitive. Depending on the location, the occluding stone may be visualized. Further confirmatory imaging depends on the estimated risk of choledocholithiasis.[20]High risk → ERCP (see "Treatment" below) Intermediate risk→ MRCP or EUS Low risk → treatment of cholelithiasis (no further imaging) Treatment [18][20][14] Approach: supportive therapy → removal of the obstruction → prevention of recurrence with elective cholecystectomy Supportive therapySpasmolytics (e.g., dicyclomine)Analgesia: NSAIDs; consider opioids if NSAIDs are contraindicated or provide insufficient pain relief Removal of obstructionEndoscopic retrograde cholangiopancreatography (ERCP) (with papillotomy) Both diagnostic and therapeuticIndications: choledocholithiasis, acute cholangitis, gallstone pancreatitisProcedure: stone extraction using DORMIA basket and papillotomyComplication rate of up to 10%Post-ERCP pancreatitis (5% of cases): postinterventional pain over 24 hours with a simultaneous rise in pancreatic enzymes (lipase, amylase)Hemorrhaging (3% of cases)Cholangitis (3% of cases)Perforation (1% of cases)Extracorporeal shock wave lithotripsyIndications: nonimpacted stones not responsive to first-line therapy Prevention of recurrenceElective laparoscopic cholecystectomy (after ERCP)Indications: concurrent cholelithiasis, acute cholecystitisTiming: recommended within 72 hours of ERCP [14] Complications [22] Gallstone ileus: mechanical ileus due to obstructive gallstonesPathophysiology: perforation and fistula formation between the inflamed gallbladder and bowel → gallstones pass down into bowel lumenLocation: most commonly in the terminal ileum and ileocecal valve (intestinal section with the narrowest lumen)Symptoms: abdominal pain and distention, nausea, vomitingTypical signs: pneumobilia Gallstone pancreatitis Acute cholangitis Acute cholecystitis Biliary stricture Hepatic abscess (rare) Cholecystitis Acute calculous cholecystitis (90-95%) Epidemiology [23] Sex: ♀ > ♂ Prevalence: most common complication of cholelithiasis; occurs in up to 11% of patients with cholelithiasis Peak incidence: 40-50 years Etiology [23] Cause: obstructing cholelithiasis Pathophysiology: cholelithiasis → passage of gallstones into the cystic duct → cystic duct obstruction → distention and inflammation of the gallbladder Bacterial infection may also be present (E. coli, Klebsiella, Enterobacter, Enterococcus spp. most common) but is not required for the development of cholecystitis. Clinical features [23][24][25][12][7] RUQ painMore severe and prolonged (> 6 hours) than in cholelithiasisPostprandialRadiation to the right scapula Positive Murphy sign: sudden pausing during inspiration upon deep palpation of the right upper quadrant due to pain Guarding Fever, malaise, anorexia Nausea and vomiting Acute cholecystitis should always be suspected in a patient with a history of gallstones who presents with RUQ pain, fever, and leukocytosis. Diagnostics [23][24][25] Approach: laboratory tests and RUQ ultrasound to identify gallbladder wall inflammation → perform HIDA scan if USnot diagnostic but clinical suspicion remains high Laboratory findingsElevated inflammatory markers (especially leukocytes and CRP)Mild elevation in AST, ALT, amylase levels are possible.Elevation in ALP, GGT, bilirubin levels are not common in uncomplicated cholecystitis and suggest biliary obstruction. ImagingTransabdominal ultrasoundGallbladder wall thickening > 4 mm (postprandial > 5 mm) Gallbladder wall edema (double wall sign) Possible free fluid surrounding the gallbladder Sonographic Murphy signPresence of concrement or gallstones HIDA scan (cholescintigraphy) if US is not diagnosticRadioactive tracer 99mTc-hepatic iminodiacetic acid is injected intravenously → selective uptake by hepatocytes → subsequent excretion into bile → can be visualized via a gamma cameraAbnormal if gallbladder not visualized within 30-60 minutes: suggests cystic duct obstruction due to edema or obstructing stoneMRCP and abdominal CT are not routinely recommended but may be used to evaluate for complications (e.g., choledocholithiasis, perforation). Treatment [26][14][27] Approach: broad-spectrum antibiotics and supportive therapy → surgical management with cholecystectomy Supportive therapyAnalgesia (e.g., ketorolac, meperidine)Fluid and electrolyte correctionAntiemetics (e.g., oral/rectal promethazine) Intravenous antibiotics: Empiric antibiotic selection depends on individual and local factors (e.g., severity of infection, community-acquired vs. healthcare-associated infection, local resistance patterns) [28][27]For mild to moderate, community-acquired biliary infections: cefazolin, cefuroxime, OR ceftriaxoneFor severe, community-acquired biliary infections: meropenem, piperacillin-tazobactam, ciprofloxacin, or cefepimePLUS metronidazoleHealthcare-associated biliary infections: meropenem, piperacillin-tazobactam, ciprofloxacin, or cefepime PLUS metronidazole PLUS vancomycinSee empiric antibiotic therapy for acute biliary infection Surgical managementCholecystectomyLaparoscopic cholecystectomy is usually preferred. Timing In mild cases: elective cholecystectomy within 24-72 hoursIf complications are present (e.g., gangrene, perforation) or condition worsens despite conservative therapy → emergency cholecystectomyIf high risk of surgical complications and/or critically ill → emergency percutaneous biliary drainage (e.g., cholecystostomy) → follow up with interval surgery when possibleIn severe, high-risk cases: delayed elective cholecystectomy (> 2 weeks) Subtypes and variants Acalculous cholecystitis (5-10%) [31] Definition: an acute necroinflammatory disorder of the gallbladder, usually seen in critically ill patients, that is not associated with gallstones Etiology: conditions that result in biliary stasis (e.g., multiorgan failure, severe trauma, surgery, sepsis, total parenteral nutrition, prolonged fasting) and a "stressed gallbladder" with reduced perfusion Clinical features: fever, RUQ tenderness DiagnosticsSimilar to acute calculous cholecystitis; ultrasound reveals thickening of the gallbladder wall without gallstones or cystic duct obstruction TreatmentInitial treatment: antibiotics (similar to acute calculous cholecystitis)Cholecystostomy: placement of a tube into the gallbladder to drain fluidOften preferred because it is less invasive than cholecystectomy, especially considering most patients are critically ill If the patient does not improve after cholecystostomy, a cholecystectomy is required. Emphysematous cholecystitis (rare) [23][24][25] Definition: a rare form of acute cholecystitis that occurs most often in elderly diabetic men Etiology: infection of the gallbladder with gas-forming bacteria (e.g., Clostridium welchii) Clinical features: fever, RUQ pain, absent peritoneal signs with possible crepitus in the abdominal wall (rare); associated with early gangrene and gallbladder perforation Diagnostics: Ultrasound or CT demonstrates air in the gallbladder wall or lumen. Treatment: emergency cholecystectomy Complications of acute cholecystitis [26] Gallbladder empyema: collection of pus in the gallbladder Gallbladder gangrene Liver abscess Gallbladder perforation Chronic cholecystitis Complications of chronic cholecystitis Porcelain gallbladder: fibrotic and calcified gallbladder due to chronic inflammation Shrunken gallbladder: chronic inflammation can cause the gallbladder to shrink enough that it may not be identifiable on ultrasound. Gallbladder cancer Chronic gallbladder inflammation increases the risk of gallbladder carcinoma! Complications of laparoscopic cholecystectomy [17] Iatrogenic injury to bile ducts or the hepatic artery (e.g., due to incorrect clipping)Bile leakageBleeding Subhepatic abscess Postcholecystectomy syndrome: persistent abdominal pain or new symptoms following gallbladder removalFrequency: 10-15% of patientsEtiology: both biliary (e.g., biliary injury, retained cystic duct, sphincter of Oddi dysfunction) and extrabiliary (e.g., irritable bowel syndrome, pancreatitis) causes have been identified. Clinical features: abdominal pain and upper GI tract (e.g., dyspepsia) or lower GI tract (e.g., diarrhea) symptomsDiagnosis: ultrasound or CT scan followed by ERCP (preferred test if intervention is planned) or MRCPTreatment: treat the underlying cause (e.g., sphincterotomy if there is evidence of sphincter dysfunction) Cholangitis Epidemiology [32] Sex: ♀ = ♂ Incidence: up to 9% of patients with cholelithiasis Peak incidence: 50-60 years Etiology [32][29] Risk factorsCholecystitisCholelithiasis, choledocholithiasis, biliary strictures, biliary malignancyIatrogenic manipulation of the bile tract (e.g., papillotomy, stent placement, ERCP) Pathophysiology: biliary tract obstruction → bile stasis → bacterial infection → infection ascends the biliary tractand can even track into the hepatic ducts Clinical features [32][29] Charcot cholangitis triad Abdominal pain (most commonly RUQ)High feverJaundice (less common) Reynolds pentad: Charcot cholangitis triad PLUS hypotension and mental status changes Diagnostics [32] Approach: conduct laboratory tests → imaging modality depends on clinical features present If there is high suspicion for acute cholangitis (e.g., Charcot triad present) → proceed directly to diagnostic and therapeutic ERCPIn patients without Charcot triad but acute cholangitis is suspected → consider RUQ ultrasound to identify biliary obstruction → abdominal CT or MRCP if nondiagnostic Laboratory findingsLeukocytosis, ↑ CRPSigns of cholestasis (↑ bilirubin, ↑ ALP), often ↑ AST and ALTBlood cultures are positive in most cases. [29] ImagingERCP (both diagnostic and therapeutic)Ultrasound: biliary dilation, evidence of obstruction (e.g., cholelithiasis)CT scan; MRCP may also be diagnostic Treatment [29][28][32] Approach: supportive therapy, intravenous antibiotics → urgent biliary decompression → prevention of recurrence with interval cholecystectomy if there is concurrent cholelithiasis Supportive therapyAnalgesia: NSAIDs, opioidsFluid and electrolyte correction Intravenous antibiotics: See empiric antibiotic therapy for acute biliary infection. Biliary drainage and decompressionTiming: perform within 24-48 hoursERCP is the treatment of choice, possibly in combination with: Sphincterotomy (for cholangitis due to cholelithiasis or choledocholithiasis) or stent placement (acute suppurative cholangitis)Percutaneous transhepatic cholangiography (PTC) if ERCP is unsuccessful or unavailableIn this procedure, contrast material is injected into the bile ducts through the insertion of a transhepatic needle.PTC allows therapeutic interventions such as infected bile drainage and biliary tract stone extraction.Surgical decompression if no other route feasible Prevention of recurrenceInterval cholecystectomy if gallstones are presentTiming: recommended within 6 weeks Empiric antibiotic therapy for acute biliary infection Approach [34] The choice of empiric antibiotic is determined by the following parameters: Community-acquired or healthcare-associated infectionSeverity of infection (see severity grade of acute cholecystitis and severity grade of acute cholangitis)Local resistance patterns Presence of a biliary-enteric anastomosis Timing of antibiotic administration Septic shock: within 1 hour of presentationOther patients: within 6 hours of presentation Class of infectionSeverity of infectionSuggested single-agent empiric regimen Suggested combination empiric regimen Community-acquired biliary infectionGrade ICefoxitin Moxifloxacin Ertapenem Ampicillin-sulbactam (only if local resistance rate < 20%) Metronidazole or clindamycin PLUS any one of the following: Cefazolin Cefuroxime Ceftriaxone Cefotaxime Ciprofloxacin Levofloxacin Grade IIPiperacillin-tazobactam Moxifloxacin Ertapenem Metronidazole PLUS any one of the following: Ceftriaxone Cefotaxime Cefepime Ceftazidime Healthcare-associated biliary infection (any grade)/Grade III Piperacillin-tazobactam Meropenem Ertapenem Imipenem-cilastatin Metronidazole PLUS any one of the following: Cefepime Ceftazidime Aztreonam Suspected multi-drug resistant organism infection Piperacillin-tazobactam Meropenem Ertapenem Imipenem-cilastatin Metronidazole PLUS any one of the following: Cefepime Ceftazidime Aztreonam PLUS any one of the following, depending on the suspected infection: Suspected VRE Linezolid OR daptomycin Suspected MRSA : Vancomycin Many ESBL-producing gram-negative organisms are resistant to fluoroquinolones. Resistance of E. coli to ampicillin-sulbactam is becoming more common, especially in North America. Consider local resistance rates carefully before choosing an empiric antibiotic regimen. Differential diagnoses Differential diagnosis of acute abdomen Differential diagnosis of RUQ painAbdominal Acute hepatic capsule swelling (e.g., acute hepatitis, perihepatitis, congestive hepatopathy)Gastroesophageal reflux, gastritis, gastrointestinal ulcers Early appendicitisAcute pancreatitisRight-sided diverticulitis Sphincter of Oddi dysfunctionExtra-abdominalNephrolithiasisPosterior wall infarct Differential diagnoses of intraluminal gallbladder wall pathologyGallbladder polyp

Megacolon Megacolon is the dilation of the colon in the absence of a mechanical obstruction (e.g., colonic tumor/stricture). There are three etiological types of megacolon: acute, chronic, and toxic megacolon. Acute megacolon (Ogilvie's syndrome) is the acute dilation of the colon, characteristically seen in severely medically/surgically ill patients, probably secondary to an electrolyte/metabolic imbalance. Chronic megacolon is the permanent dilation of the colon caused by chronic colonicdysmotility due to an underlying neuropathic (Hirschsprung's disease, chronic Chagas disease) or myopathic (Duchenne's muscular dystrophy) disorder. Patients with acute/chronic megacolon typically present with abdominal pain, bloating, and constipation. Toxic megacolon is a life-threatening dilation of the colon associated with systemic toxicity due to infectious colitis (C. difficile pseudomembranous colitis, Salmonella enterocolitis) or inflammatory colitis (inflammatory bowel disease). Patients typically present with signs of sepsis (tachycardia, hypotension) and a history of abdominal pain and bloody diarrhea. Abdominal x-rays demonstrate a colonic dilation, with/without air-fluid levels, and without haustrae. Contrast-enhanced CT scans can identify/rule out a mechanical colonic obstruction and possible complications (colonic ischemia/perforation). Patients with acute/chronic megacolon can often be treated conservatively with bowel rest, dietary modifications, prokinetic drugs, and/or neostigmine. Colonoscopic decompression is often successful in patients with acute megacolon. Surgical intervention for acute/chronic megacolon (colectomy and ileorectal anastomosis) is indicated if conservative treatment fails. Conservative management of toxic megacolon includes bowel rest, IV antibiotics(for infectious colitis), IV steroids (for inflammatory bowel disease). There is a high risk of colonic perforation in patients with toxic megacolon. Hence, no improvement to medical therapy within 48-72 hours is an indication to perform surgery (subtotal colectomy and end ileostomy).

Classification Definition: Loss of intestinal peristalsis and subsequent dilation of the colon in the abscence of a mechanical obstruction Megacolon is classified into three etiological types Acute megacolonChronic megacolonToxic megacolon Acute megacolon (Acute colonic pseudo-obstruction or Ogilvie's syndrome) Description: Acute dilation of the colon in the absence of a mechanical obstruction, characteristically seen in severely ill or postoperative patients EtiologyOccurs in seriously ill patients or those who have undergone a major surgical procedureIdiopathic; possible factors include: Electrolyte imbalanceTrauma ; major surgery HypothyroidismDrugs (e.g., anticholinergic drugs, opioid analgesics, antipsychotics, calcium channel blockers) PathophysiologyEtiological factors → impairment/destruction of the autonomic nervous system → imbalance between sympatheticand parasympathetic control of intestinal motility → accumulation of feces, air, and intestinal secretions in the intestine → colonic dilation Clinical featuresGradual abdominal distention Abdominal pain; constipation/diarrheaTympanitic abdominal percussion; decreased frequency of bowel soundsSigns of colonic ischemia or impending perforation: Fever, tachycardia, and peritoneal signs (guarding, rigidity, rebound tenderness) DiagnosticsLaboratory values: may show signs of underlying disease; hypokalemia as a potential causeAbdominal x-ray: dilation of the cecum and right colon (occasionally up to the rectum) with/without multiple air-fluid levels; haustrae are preserved Contrast enhanced CT scan (oral and IV contrast)Confirms x-ray findingsRules out mechanical obstruction (e.g., tumor/stricture)Can diagnose complications (ischemic bowel segments or perforation peritonitis) Colonoscopy and endoscopy: indicated in hemodynamically stable patients when CECT cannot be performed; rules out a mechanical obstruction TreatmentConservative management Supportive measures Indications: patients with mild symptoms and cecal dilation < 12 cmTreat the inciting factor IV fluids and bowel rest (NPO)Bowel decompression Nasogastric tube to decompress the stomachRectal tube to decompress the rectum and distal colonPharmacologic management: Neostigmine Indications No improvement > 24-48 hours of bowel rest and decompressionCecal dilation > 12 cm and no signs of colonic ischemia/perforation or peritonitisColonoscopic bowel decompression: indicated if neostigmine is contraindicated or unsuccessful SurgeryIndications Signs of impending or actual colonic ischemia/perforation or peritonitis Failure of conservative therapyCecostomy Colectomy with/without colostomy Chronic megacolon (chronic colonic pseudo-obstruction) Description: Permanent dilation of the colon caused by congenital/acquired colonic dysmotility in the absence of a mechanical obstruction EtiologyCongenital (e.g., Hirschsprung disease)Acquired Neuropathies (e.g., diabetic neuropathy, spinal cord injury, Parkinson's disease) Myopathies (e.g., Duchenne's muscular dystrophy, myotonic muscular dystrophy)Connective tissue disorders (e.g., scleroderma, systemic lupus erythematosus, dermatomyositis)Chronic Chagas disease Idiopathic - reason unknown Pathophysiology: Etiological factors cause a neural and/or motor dysfunction of the bowel → bowel dysmotility → progressive colonic dilation Clinical featuresRecurrent episodes of: Constipation Abdominal pain and distention (bloating)Anorexia, early satiety, and nauseaExamination findings: Abdominal distention; mild abdominal tendernessSigns and symptoms of the underlying disorder DiagnosticsLaboratory values: may show signs of underlying diseaseAbdominal x-ray: dilation of the cecum and right colon (occasionally up to the rectum) with/without multiple air-fluid levels; haustrae are preserved Contrast-enhanced CT scan (CECT; oral and IV contrast) Confirms x-ray findingsRules out mechanical obstruction (e.g., tumor/stricture)Can diagnose complications (ischemic bowel segments or perforation peritonitis) Colonoscopy and endoscopy: indicated in hemodynamically stable patients when CECT cannot be performed; rules out a mechanical obstruction Colon transit studies: to assess colonic motility Colon transit scintigraphy: Investigation of choice to diagnose and determine the extent of delayed colonictransit Colon transit test using radio-opaque markers Wireless motility capsule test Manometry Colonic biopsy TreatmentConservative management Dietary modifications Osmotic laxatives and enemas to empty the colon and prevent fecal impaction Prokinetic drugs: Erythromycin, metoclopramide, neostigmine Treatment of the underlying disorderSurgery: indicated in patients who do not improve/worsen on conservative therapyTotal abdominal colectomy with ileorectal anastomosis See "Surgical treatment" of Hirschsprung's disease Toxic megacolon Description: A life-threatening, acute dilation of the colon associated with systemic toxicity EtiologyInfectious colitisBacterial: C. difficile (pseudomembranous colitis), Salmonella, Shigella, Campylobacter infectionsParasitic: Trypanosoma cruzi (Chagas disease), E. histolytica (amebic dysentery) infections Inflammatory colitis: Ulcerative colitis, Crohn's disease Pathophysiology: colitis (inflammation) → Colonic accumulation of inflammatory mediators and bacteria → Nitric oxide synthesis → Colonic dilation → Edema and inflammation of the colonic smooth muscle → Colonic dysmotility → Colonic dilation Clinical findings(Bloody) diarrhea and vomitingAbdominal distention and painSigns of sepsis (fever, tachycardia, hypotension) and dehydrationSigns of underlying disease (See Ulcerative colitis, Crohn's disease) DiagnosticsLaboratory findings: neutrophilic leukocytosis, anemia, ↑ ESR/CRP, hypokalemia Abdominal x-ray findings Dilation of the colon (transverse colon diameter > 6 cm)Loss of haustration Multiple air-fluid levelsContrast enhanced CT scan (oral and IV contrast) Confirms x-ray findingsRules out mechanical obstruction (e.g., tumor/stricture)Can diagnose complications (ischemic bowel segments or perforation peritonitis) Stool tests for C. difficile toxin: in patients with preceding diarrhea (see "Diagnostics" of clostridium difficile infection)Colonoscopy and endoscopy: contraindicated in suspected toxic megacolon due to high risk of perforating the colon Diagnostic criteriaRadiographic evidence of colonic dilatationThree of the following: fever (> 101.5°F), tachycardia (> 120 beats/min), leukocytosis (> 10,500/μL), or anemiaOne of the following: dehydration, hypotension, altered mental status, or electrolyte disturbance ComplicationsColonic ischemia → Colonic perforation→ Peritonitis Sepsis and multiorgan dysfunction TreatmentConservative treatment [22][23]Admission to intensive care unitComplete bowel rest: NPONasogastric tube insertionIV fluidsCorrection of fluid and electrolyte imbalancesBroad-spectrum IV antibiotics (e.g., ampicillin, gentamicin, and metronidazole) Oral vancomycin or fidaxomicin for C. difficile colitisRotation techniques: change position frequently to facilitate the evacuation of bowel gas (prone or knee-elbowposition)Avoid all anticholinergic or narcotic medications IV steroids (hydrocortisone, dexamethasone) for inflammatory bowel disease SurgeryIndications: no response to medical management within 24-72 hours; development of complicationsProcedure: subtotal colectomy and end ileostomy Colonoscopy should be avoided in patients with suspected toxic megacolon since it increases the risk of colonic perforation.

Volvulus and intestinal malrotation Volvulus is defined as the twisting of a loop of bowel on its mesentery and is one of the most common causes of intestinal obstruction. The sigmoid colon, and less frequently, the cecum, are the common sites of volvulus in adults. Volvulus in a neonate or infant almost always presents as a midgut volvulus secondary to intestinal malrotation. Patients typically show features of bowel obstruction (abdominal pain, distension, bilious vomiting) or of bowel ischemia and gangrene (tachycardia, hypotension, hematochezia, peritonitis) in severe cases. The whirl sign and a grossly dilated loop of bowel on an abdominal CT scan establish the diagnosis of volvulus in adults. Upper GI series is the investigation of choice in infants with suspected midgut volvulus, which is seen as a cork-screw duodenum. Sigmoid volvulus without peritonitis is initially managed with endoscopic detorsion, followed by a semi-elective surgery (sigmoid colectomy). Sigmoid volvulus with peritonitis, and all cases of cecal volvulus, require emergency surgery. Endoscopic detorsion should not be attempted in a patient with cecal volvulus because of the high risk of perforation. The Ladd procedure (laparotomyand detorsion of the volvulus) is indicated in all patients with intestinal malrotation since it is impossible to predict if volvulus of the midgut will occur in an asymptomatic patient or not.

Colon cancer and diverticulitis are the most common causes of intestinal obstruction in the United States. Volvulus is, however, the most common cause of intestinal obstruction in developing countries (e.g., Middle Eastern, African, South American, South Asian countries). Epidemiology IncidenceVolvulus: 3rd most common cause (∼ 10-15%) of intestinal obstruction in the United States Sigmoid volvulus (most common, 80%)Cecal volvulus (15%) Transverse colon volvulus (3%)Splenic flexure volvulus (2%)Intestinal malrotation: symptomatic malrotation (midgut volvulus) in 1:6000 live births in the United States Age and sexSigmoid volvulus: ∼ 70 years; ♂ > ♀Cecal volvulus: 40-60 years; ♀ >♂ Intestinal malrotation and midgut volvulus: neonates and infants Pathophysiology Torsion of bowel on its axis→ Closed-loop mechanical bowel obstruction → accumulation of gas and feces within the loop → increased intraluminal pressure → impaired capillary perfusion of bowel → bowel strangulation, ischemia, and gangrene→ Torsion of the mesenteric vascular pedicle → occlusion/thrombosis of mesenteric vessels → bowel strangulation, ischemia, and gangrene Risk factors for the development of a volvulus Long mesenteryAcquired (sigmoid volvulus): chronic constipation , high-fiber diet → chronic overloading of the sigmoid colon → lengthening of the sigmoid colon and its mesentery → increased risk of torsion Congenital (cecal volvulus): abnormally mobile cecum → predisposition of the cecum to rotate on its axis (axial torsion) or fold upwards (cecal bascule) Intestinal malrotation: abnormal rotation of the bowel with abnormal fixation of mesentery to the posteriorabdominal wall Megacolon (Hirschsprung's disease, Chaga's disease) Intestinal bands/adhesions Decreased pelvic space: pregnancy or pelvic mass Previous history of volvulus Sigmoid volvulus Clinical features Previous episodes of abdominal pain, which decreased after explosive passage of stool/gas Slowly (most common) or rapidly progressive symptoms of bowel obstruction If bowel ischemia occurs → tachycardia, hypotension, peritonitis (rebound tenderness), hematochezia or blood on DRE may be present If bowel perforation occurs → obliteration of liver dullness on percussion Differential diagnoses Acute megacolon Toxic megacolon Other causes of mechanical bowel obstruction (e.g., colon cancer, strictures, cecal volvulus) Treatment Initial resuscitation: IV fluids; acid-base and electrolyte imbalance correction; nil per oral; placement of a nasogastric tube EvaluationNo signs of peritonitis: rigid/flexible sigmoidoscopic detorsion of the volvulus → inspection of the mucosa for signs of ischemia No signs of mucosal ischemia → placement of a soft rectal tube (for bowel decompression) → semi-electivesurgery within 72 hours of detorsion Signs of mucosal ischemia → emergency surgery (see below)Signs of peritonitis/unsuccessful endoscopic detorsion → broad-spectrum IV antibiotics and emergency surgery SurgerySigmoid colectomy and primary anastomosis : indicated in hemodynamically stable patients with viable bowel Hartmann's procedure: indicated in hemodynamically unstable patients or those with ischemic/gangrenous bowel Cecal volvulus Types Axial torsion of the cecum (90% of cases): the cecum rotates on its mesenteric axis → bowel obstruction with vascular compromise Cecal bascule (10%): the cecum folds upwards onto the ascending colon → bowel obstruction often without vascular compromise Clinical features Acute presentation: features of small bowel obstruction Insidious onset: recurrent episodes of right lower abdominal pain Differential diagnoses Sigmoid volvulus Small bowel obstruction (e.g., adhesions, tumors, intussusception) Treatment Initial resuscitation (See "Treatment" of sigmoid volvulus above.) Surgery Hemodynamically stable patients: ileocecal resection or right colectomy with ileocolic anastomosis Hemodynamically unstable patients Cecostomy Detorsion with cecopexy Intestinal malrotation and midgut volvulus Definition Intestinal malrotation: arrest in the normal rotation of the gut in utero, resulting in an abnormal orientation of the bowel and mesentery within the abdominal cavity Normal intestinal rotation: the midgut starts to elongate in utero (4th week) → herniation of the midgut out of the umbilicus (6th week) → 90° counter-clockwise rotation of the midgut → re-entry of the midgut into the abdominal cavity(10th week) → 180° rotation inside the abdominal cavity (a total of 270°) → fixation of the duodenojejunal flexure and cecum to the posterior abdominal wall Nonrotation The entire colon is left-sided; the entire small bowel is right-sided The mesenteric attachment has a wider base than in incomplete rotation From the LUQ to the LLQ Cecum LLQ Incomplete rotation The cecum remains fixed in the RUQ by peritoneal bands (Ladd bands) Ladd bands cross over the duodenum and can cause extrinsic duodenal compression. The mesenteric base is narrow LUQ to RUQ Midgut volvulus: torsion of a malrotated midgut causing mechanical bowel obstruction, mostly in neonates and infants Clinical presentation Malrotation: mostly asymptomatic Midgut volvulusBilious vomiting with abdominal distension in a neonate/infant Signs of bowel ischemia: hematochezia, hematemesis, hypotension, and tachycardia Features of duodenal obstruction: bilious vomiting without abdominal distension Variable presentation in older children/adults: recurrent episodes of abdominal pain and vomiting; failure to gain weight; malabsorption Abdominal examination is unreliable Features of associated congenital anomalies Commonly associated anomalies: congenital diaphragmatic hernia (∼ 100%) ; congenital heart defects (up to 90%); omphalocele (up to 45%)Less commonly associates anomalies: gastroschisis; Meckel diverticulum; esophageal atresia; biliary atresia Differential diagnoses In neonates/infants with recurrent vomiting: duodenal atresia and stenosis , hypertrophic pyloric stenosis In neonates with features of bowel ischemia/gangrene: necrotizing enterocolitis (NEC) In older children with abdominal pain and vomiting: intussusception In older children/adults with nonspecific symptoms: GERD; chronic mesenteric ischemia; food allergy Treatment Midgut volvulus with/without peritonitisInitial resuscitation: nil per oral; nasogastric tube insertion; IV fluids; correction of electrolyte imbalance; broad-spectrum IV antibioticsEmergency surgery (Ladd procedure) Incidentally detected/asymptomatic intestinal malrotation: elective surgery (Ladd procedure) Diagnostics Volvulus Work-up follows the same protocol as that for bowel obstruction. Abdominal x-ray (erect and supine) Sigmoid volvulus: coffee bean sign (bent inner tube sign) Cecal volvulus: kidney bean sign Bowel perforation: air under diaphragm CT scan Whirl sign: pathognomonic for volvulus Specific features of sigmoid/cecal volvulus are similar to those seen in x-raysDemonstrates bowel ischemia , or perforation , if present Barium enema : bird's beak sign (tapering of the dye column at the site of the twist) In cecal bascule, the end of the barium column is rounded, rather than tapered (tear drop sign). Cecal volvulus: normal-sized colon with bird's beak sign at the cecum; dye does not enter the small bowelSigmoid volvulus: normal-sized rectum with bird's beak sign at the sigmoid; dye does not enter the sigmoid colon Intestinal malrotation and midgut volvulus Laboratory studies: complete blood count; electrolyte levels; arterial blood gas analys Intestinal malrotation Upper GI series (gold standard in hemodynamically stable patients) Displaced duodenojejunal junction Right side instead of middle Barium enema (lower GI series)Malpositioning of the cecum (left-sided cecum) Abdominal ultrasoundAbnormal position of the superior mesenteric vessels and bowel (left-sided SMV instead of right) CECT scan (oral and IV contrast) Findings similar to those seen on ultrasound Midgut volvulus Upper GI series Corkscrew duodenum Barium Enemda Lower GI series Bird's beak sign at the site of the twist Abdominal US Whirlpool sign (on color doppler) CECT Scan Findings similar to those seen on ultrasoundCan demonstrate bowel ischemia , or perforation , if present

Clostridioides difficile infection Clostridioides difficile (C. difficile; formerly known as Clostridium difficile) is a gram-positive bacillus that may cause antibiotic-associated diarrhea. Rates of C. difficile infection are particularly high among hospitalized patients and residents in long-term care facilities because C. difficile spores are easily transmitted (fecal-oral route) and difficult to eradicate. The bacterium is resistant to multiple antibiotics, so colonization with C. difficile most commonly occurs following antibiotictreatment of other diseases. The resulting damage to the intestinal flora promotes infection, which may be accompanied by high fever, abdominal pain, and foul-smelling diarrhea. The most severe form of C. difficile infection is pseudomembranous colitis, which can lead to ileus, sepsis, and toxic megacolon. In most cases, however, colonizationresults in asymptomatic carriage. Diagnosis is usually made via detection of the C. difficile toxin, C. difficile glutamate dehydrogenase antigen, and/or corresponding genes in stool samples. C. difficile infection is treated with oral vancomycinor oral fidaxomicin. Following diagnosis, strict adherence to hygiene measures and patient isolation is essential, especially in hospitals and other healthcare settings.

Complications Toxic megacolon [16] Paralytic ileus [9] Peritonitis, perforation, abscess formation, sepsis Epidemiology ∼ 220,000 cases in hospitalized patients and ∼ 13,000 deaths per year in the US [1] Individuals > 65 years old are at increased risk for hospital-acquired infections. Etiology Pathogen: Clostridioides difficile [5]Gram-positive bacillus, obligate anaerobeCan be toxigenic or non-toxigenic; must be toxigenic to cause the diseaseForms environmentally-resistant spores (capable of withstanding heat and acid)Highly contagious Route of infection: fecal-oral transmission of ubiquitous bacteria [5] Antibiotic treatment Common triggers: clindamycin, cephalosporins, fluoroquinolones and, less commonly, penicillin [3][6] Other risk factorsGastric acid suppression (e.g., with proton pump inhibitors) The C. difficile strain must be toxigenic to cause the disease. Intestinal colonization by the non-toxigenic bacteria will result in asymptomatic carriage! Pathophysiology C. difficile possesses a range of virulence factors, the most important of which are toxins A and B. [7][8] Toxin AEnterotoxin StructureActive site at N-terminal domain Central hydrophobic domain Binding site at C-terminal domain Mechanism of action: binding to brush border of enterocytes → endocytosis → change of conformation → exposure of active domain → glycosylation of target proteins (e.g., Rac, Cdc42, RhoA) → disruption of actincytoskeleton functioning → increase in epithelial permeability and apoptosis → diarrhea Toxin BCytotoxinStructureBinding site at C-terminal domain Translocation domain Cysteine protease-containing domainCatalytic domainMechanism of actionBinding to brush border of enterocytes → endocytosis → change of conformation → exposure of active domain → glycosylation of target proteins (e.g., Rac, Cdc42, RhoA) → disruption of actin cytoskeleton functioning → increase in epithelial permeability and apoptosis → diarrheaCan also result in pore formation within the endosomal membrane via insertion of the translocation domain → release of endosomal content into the cytosol → cytopathic effect Clinical features Symptoms of C. difficile-associated diarrhea (CDAD) usually develop during antibiotic treatment or 2-10 days following its initiation; however, 25-40% of cases manifest as late as 10 weeks following treatment. Watery diarrhea, characteristically foul-smellingMild disease manifests with ≥ 3 stools per day; patients with fulminant colitis may have up to 20 stools per day.May contain traces of mucus or occult bloodHematochezia and melena are both rare. Cramping abdominal pain, nausea, anorexia Fever and dehydration (especially in severe cases) Fulminant colitis: abdominal distention and severe hypovolemia Recurrent disease: symptom reoccurrence 2-8 weeks following the end of treatment (10-40% of cases) Diagnostics Patient history and clinical presentation are strong indicators for diagnosis of infection, which is then confirmed by identification of the pathogen's genes or corresponding toxins in the stool. Further diagnostics, such as blood tests or imaging, may be used to assess the severity of disease and/or the presence of complications. History [3] Treatment with antibiotics in the last three months Recent hospitalization Stool tests [11] IndicationChildren < 12 months old: if pseudomembranous colitis or toxic megacolon is suspected or if there is clinically significant diarrhea that cannot be explained by other causesChildren 1-2 years old: if all other infectious and noninfectious causes have been ruled outChildren ≥ 2 years old: if there is prolonged or worsening diarrhea in children with risk factors (e.g., inflammatory bowel disease, immunocompromising conditions) or relevant exposures (e.g., recent antibiotic treatment, contact with the healthcare system)Adults: unexplained, new-onset, loose stool ≥ 3 times in 24 hours Confirmatory tests of choicePCR for C. difficile genes alone Enzyme immunoassay (EIA) for C. difficile glutamate dehydrogenase antigen and EIA for C. difficile toxins A and B [9] Blood tests Leukocytosis Elevated serum creatinine (possible kidney injury caused by dehydration) [12][13] Lowered serum albumin [12][10] Electrolyte imbalance, particularly hypokalemia (caused by severe diarrhea) [3] Elevated lactate levels [3][10] Imaging Abdominal x-ray/CT scan: detection of toxic megacolon, abscesses, perforation, or evidence of pseudomembranous colitis Endoscopy Colonoscopy or sigmoidoscopy [9]Not indicated if C. difficile is suspected based on clinical findings, laboratory tests, and/or response to empiric treatmentPerform cautiously (increased risk of perforation).Findings Erythematous and friable mucosaPseudomembranes, often only solitary findings; widespread lesions in severe cases (pseudomembranous colitis) Disease severity [14] Nonsevere: leukocytosis < 15,000/mm3 and serum creatinine < 1.5 of baseline Severe: leukocytosis ≥ 15,000/mm3 OR serum creatinine ≥ 1.5 of baseline Fulminant: decreased blood pressure, shock, ileus or toxic megacolon Treatment General measures [3][10] Discontinue the precipitating antibiotic. Fluid replacement Avoid antidiarrheals (e.g., loperamide). Medical therapy [11] If clinical suspicion for CDAD is high, empiric antibiotic treatment may be initiated before laboratory confirmation of C. difficile. [10] Nonsevere casesFirst-line: oral vancomycin or oral fidaxomicinSecond-line: oral metronidazole Severe casesFirst-line: oral vancomycinSecond-line: fidaxomicin Fulminant casesFirst-line: oral vancomycin and intravenous metronidazoleIn patients with ileus, vancomycin per rectum (enema) may be added. C. difficile infection is one of the rare indications for oral administration of vancomycin! Medical therapy in children [11] Initial episodeNonsevere: oral vancomycin or oral metronidazoleSevere/fulminant: oral vancomycin with or without intravenous metronidazole RecurrenceFirst recurrenceNonsevere: oral vancomycin or oral metronidazoleSevere: oral vancomycinSecond or subsequent recurrence: vancomycin in a tapered and pulsed regimen or vancomycin followed by rifaximin Fecal microbiota transplantation (FMT) [11] Indication: recurrent C. difficile infections in a patient who has not responded to at least two appropriate antibioticregimens Consider FMT in children with multiple recurrences despite standard antibiotic therapy. Complications Toxic megacolon [16] Paralytic ileus [9] Peritonitis, perforation, abscess formation, sepsis Prevention Detection: C. difficile toxin stool test for at-risk patients with recent onset of diarrhea IsolationSingle-bed room with designated bathroom facilities (up to 2 days after symptoms subside)Cohort isolation is possible if control measures are implemented. Control measuresPersonal protective equipment: Wear gloves and a protective gown (change after each patient); a mask is not necessary.Hand hygiene: Wash thoroughly with soap and water. C. difficile spores are resistant to alcoholic disinfectants. Consistent disinfection of potentially contaminated surfaces with sporicidal oxidants such as peracetic acid or sodium hypochlorite Autoclaving is also sporicidal and can be used to sterilize equipment.

Biliary cancer Biliary tract cancers include cholangiocarcinoma and gallbladder carcinoma, which are both rare diseases with very poor prognoses. Cholangiocarcinoma is classified as either intrahepatic or extrahepatic according to the anatomical site of the tumor. Extrahepatic carcinoma, which is the more common form, can be further classified as perihilar (Klatskin tumor; occurs at the bifurcation of the hepatic duct) and distal extrahepatic carcinoma. Risk factors for cholangiocarcinomainclude primary sclerosing cholangitis and chronic biliary tract inflammation. The greatest risk factor for gallbladder carcinoma is cholelithiasis. Patients are often initially asymptomatic or only present with nonspecific symptoms (e.g., abdominal pain, fever, weight loss) until late stages of disease, meaning that most tumors are already advanced at the time of diagnosis. Extrahepatic cholangiocarcinoma may manifest with signs of cholestasis (e.g., jaundice, dark urine, pruritus) and a painless, enlarged gallbladder (Courvoisier sign). If liver transaminases and tumor markers are raised and/or ultrasound imaging suggests bile duct or gallbladder carcinoma, MRCP or MDCT are recommended for diagnosis. Although surgical resection of early-stage tumors is curative, approximately 90% of patients have more advanced, unresectable tumors at the time of diagnosis.

Definition Cholangiocarcinomas: originate in the bile ducts and are classified based on their anatomical site of origin [1][2]Extrahepatic cholangiocarcinoma is the most common form (90% of cases). Perihilar (Klatskin tumor): junction of the right and left hepatic ducts (50% of cases)Distal extrahepatic: common bile duct (40% of cases)Intrahepatic cholangiocarcinoma: intrahepatic bile ducts (10% of cases) Gallbladder carcinomas: originate within the mucosal lining of the gallbladder Epidemiology Cholangiocarcinoma [2][4] Incidence: ∼ 1/100,000 per year in the US Prevalence: < 1% of all cancers Peak incidence: 60-70 years of age Sex: ♂ > ♀ Gallbladder carcinoma [5] Incidence: ∼ 2/100,000 per year in the US but significantly higher in India, Chile, and Eastern Europe Sex: ♀ > ♂ Etiology Risk factors for cholangiocarcinoma [2][3][5]Primary sclerosing cholangitisLiver fluke infection (e.g., Clonorchis sinensis, Opisthorchis viverrini) Choledocholithiasis (both with and without hepatic duct involvement)Chronic viral hepatitis (e.g., hepatitis B, hepatitis C)Liver cirrhosisEnvironmental toxin exposure (e.g., asbestos, Thorotrast contrast agent)Congenital biliary tract abnormalities (e.g., choledochal cysts, congenital hepatic fibrosis) Risk factors for gallbladder carcinoma [3][4][5]Cholelithiasis with chronic inflammation (most common risk factor)Porcelain gallbladderLiver fluke infection (e.g., Clonorchis sinensis)CholedocholithiasisChronic cholecystitisChronic cholangitis (e.g., salmonellosis)Gallbladder polyps Clinical features Clinical features depend on the location and stage of the tumor. Cholangiocarcinoma [2] Extrahepatic cholangiocarcinomaSigns of cholestasis: jaundice, pale stools, dark urine, pruritusAbdominal pain and weight loss is usually a sign of late (unresectable) disease.Courvoisier sign Intrahepatic cholangiocarcinomaUsually asymptomatic in early stagesNonspecific symptoms (e.g., weight loss, nausea, fever, weakness, fatigue)Dull abdominal pain (RUQ or epigastric)Signs of cholestasis are rare. Gallbladder carcinoma [4][5] Asymptomatic in early stages Most commonly diagnosed incidentally Symptoms of biliary colic or chronic cholecystitis Advanced disease Nonspecific symptoms (e.g., weight loss, nausea, weakness, fatigue)Abdominal massAbdominal pain (RUQ or epigastric)Courvoisier sign Diagnostics The diagnostic approach varies depending on the location of the tumor and whether PSC is present. If the patient's presentation, laboratory findings (especially tumor markers), and/or transabdominal ultrasound suggest biliary cancer, then MRCP or MDCT is generally recommended for diagnosis. Biopsy is generally unnecessary. Laboratory tests [2][4]Liver function tests: possible ↑ INR, ↑ ALT, and ↑ AST (with chronic biliary obstruction and eventual hepatic dysfunction)Parameters of cholestasis (e.g., ALP, GGT, total bilirubin) may initially be normal.Tumor markers (to determine the baseline; should not be used to confirm the diagnosis) ↑ AFP↑ CA 19-9 and ↑ CEAEspecially helpful for diagnosing cholangiocarcinoma with primary sclerosing cholangitisUseful for assessing therapeutic responsiveness and detecting relapse Imaging [2][4]Transabdominal ultrasound should be the initial imaging modality for suspected biliary tract carcinomaLocalization of obstruction and evaluation for gallstonesFindings: gallbladder and/or bile duct dilatationUseful for identifying local metastases and performing ultrasound-guided biopsyMRCPRecommended for definitive diagnosisFindings: bile duct dilatation and/or mass lesionAbdominal MDCT is commonly used as an alternative to MRCPEndoscopic ultrasound (especially for distal extrahepatic lesions and staging)Chest CT for stagingPET scan: indicated if other diagnostic procedures are inconclusive and for staging Biopsy [2][5]Cholangiocarcinoma: ERCP with ductal brushings or biopsy is recommended but not always necessary for diagnosis.May be indicated if MRCP or MDCT are inconclusiveAllows for confirmation of tumor type via tissue sampling Sometimes preferred by surgeons to assess tumor resectability; allows for immediate placement of a stent if the tumor is inoperableRarely, percutaneous transhepatic cholangiography (PTC) is used for proximal lesions.Gallbladder cancer: biopsy is usually unnecessary; typically proceeds directly to surgical exploration/resection if clinical suspicion is high Surgical exploration: Exploratory laparoscopy is often performed for definitive diagnosis and/or staging prior to resection. Gallbladder carcinoma is usually diagnosed incidentally after elective cholecystectomy. Pathology Cholangiocarcinoma: usually a well-differentiated adenocarcinoma Gallbladder cancer [3]Adenocarcinoma is the most common form.< 10% are squamous cell tumors. Differential diagnoses CholangiocarcinomaHepatocellular carcinomaPancreatic cancerCholedocholithiasisChronic hepatitisChronic pancreatitisAcalculous cholecystitisCalculous cholecystitisAcute cholangitisAutoimmune cholangitis Gallbladder carcinomaCholelithiasisChronic cholecystitis Treatment The prognosis for cholangiocarcinoma and gallbladder cancer is generally poor, especially for gallbladder cancer and intrahepatic cholangiocarcinoma. Treatment is determined by tumor resectability. Resectable disease [4] < 10% of cases are resectable. Resection is the only curative therapy. Procedure: radical resection plus lymphadenectomyPreoperative biliary drainage is performed in some cases.Adjuvant chemotherapy: usually a fluoropyrimidine-based regimen Surgical approachContraindicationsIntrahepatic cholangiocarcinomaHepatic resection: usually partial resection (in rare cases, liver transplant)Distant metastasesSpread to adjacent organsLymph node involvement beyond the porta hepatisMultifocal disease within the liver Extrahepatic cholangiocarcinomaComplete resection and regional lymphadenectomy Hilar tumors: major hepatic resectionDistal tumors: Whipple procedureMid-ductal tumors: bile duct resectionDistant metastases (including the liver and peritoneum)Spread to adjacent organsLymph node involvement beyond the porta hepatisRetropancreatic node involvement Gallbladder carcinomaCholecystectomy and Resection of hepatic segments IVb and VLymphadenectomyWith or without bile duct excisionDistant metastasesSpread to adjacent organsHepatic artery or main portal vein involvementRetropancreatic/paraceliac or porta hepatis node involvementJaundice Unresectable disease [4] Unresectable carcinoma or metastatic disease accounts for > 90% of cases. Treatment is palliative Chemotherapy: fluoropyrimidine-based or gemcitabine-based regimenBiliary stent placement: in patients with jaundice and extrahepatic cholangiocarcinoma or gallbladder carcinoma Transarterial chemoembolization (TACE): local application of chemotherapy and occlusive substance → induces fibrosis and shrinkage of intrahepatic cholangiocarcinoma

Celiac disease Celiac disease, also referred to as celiac sprue or non-tropical sprue, is a common condition characterized by a maladaptive immune response to gluten, a protein found in many grains (e.g., wheat). The disease often occurs in patients with other autoimmune illnesses, as both are associated with HLA variants (human leukocyte antigens, which encode immunoregulatory proteins) that cause pathologically increased immune responses. The underlying pathophysiology is believed to be a combination of gluten intolerance, which triggers an autoimmune reaction, and production of autoantibodies that target tissue transglutaminase, specifically within the proximal small intestine. Typical findings include changes in bowel habits and symptoms associated with malabsorption (e.g., fatigue, weight loss, vitamin deficiencies). Diagnostic tests include the detection of various antibodies. To confirm the diagnosis, an endoscopic biopsy from the small intestine is needed. Histopathological findings often include villous atrophy and crypt hyperplasia. A firm diagnosis is necessary, as therapy involves a lifelong commitment to a gluten-free diet. If patients comply with this diet, the prognosis is generally very good and the increased risk of celiac-associated malignancies (e.g., intestinal lymphoma) is mitigated.

Definition Definition: autoimmune disorder characterized by an intestinal hypersensitivity to gluten, a grain protein [1] Synonyms: celiac sprue; gluten-sensitive enteropathy Epidemiology Sex: ♀ > ♂ Age of onset: The disease can occur at any age.Peak incidence is bimodal: At 8-12 months (or 2-3 months following the first exposure to gluten through diet containing wheat)Third to fourth decade of life Prevalence: in the US ∼ 1:3000 More common in individuals of northern European descent Etiology Genetic predisposition with association to HLA antigensCommon: HLA-DQ2 (90-95%)Alternatively: HLA-DQ8 (5-10%) Consuming gliadin from grains such as wheat, rye, and barley leads to an autoimmune reaction within the small intestinal wall. Commonly associated with autoimmune diseases (see "Clinical features" below) Pathophysiology Symptoms manifest when a genetically predisposed individual develops an immunological response to gliadin, an alcohol-soluble fraction of gluten. Consumption of food containing gluten → tissue transglutaminase is released → modifies gliadin from glutenproteins → pathogenic T cells react to and are activated by modified gliadin → mediate chronic intestinal inflammation→ epithelial damage resulting in villous atrophy, crypt hyperplasia, and loss of brush border → impaired resorption of nutrients in the small intestine (especially in the distal duodenum and proximal jejunum) → malabsorption symptoms Clinical features Gastrointestinal symptoms Chronic or recurring diarrhea: steatorrhea Flatulence, abdominal bloating, and pain Nausea/vomiting Lack of appetite Constipation (rarely) Extraintestinal symptoms and associations Malabsorption symptoms: fatigue, weight loss, vitamin deficiency, iron deficiency anemia, osteoporosis, hypocalcemia In children: failure to thrive, growth failure, delayed puberty Dermatologic associations: dermatitis herpetiformis Neuropsychiatric symptoms: peripheral neuropathies (numbness, burning and tingling of the hands and feet) , headache, ataxia, depression, irritability Gynecological associations: reduced fertility or infertility Endocrine associations: autoimmune thyroid disease, type 1 diabetes mellitus Associated chromosomal syndromes: Turner syndrome, Down syndrome Other associated conditions: autoimmune hepatitis, inflammatory bowel disease, rheumatoid arthritis, sarcoidosis, selective IgA deficiency [5][8] In both children and adults, mild or asymptomatic cases are more common than the classic presentation of the disease. Diagnostics If celiac disease is suspected (based on the medical history and clinical features), serum antibodies may be tested. Ultimately, the diagnosis should be confirmed via biopsy. Laboratory tests Gold standard: IgA (anti‑)tissue transglutaminase antibody (tTG)The single recommended test to diagnose celiac disease. In addition to the initial diagnosis, also useful for follow-up. Quantitative IgA test: In the case of an IgA deficiency, patients are tested for IgG-based antibodies. IgG deamidated gliadin peptide (DGP) indications: IgA deficiencyAlso the test of choice in children under the age of two Anti-endomysial antibody (EMA) D-xylose absorption test: low urine d-xylose levels (the passive absorption of d-xylose in the proximal small intestineis impaired by the mucosal defect and bacterial overgrowth) Fat malabsorption can be detected by quantitative stool fat assays or qualitatively by fat stains (e.g., Sudan III stain). Endoscopy with small intestine biopsy Confirmatory test At least five duodenal biopsies should be taken and histologically examined. Characteristic histological findings:Villous atrophyCrypt hyperplasia Intraepithelial lymphocytic infiltration Differential diagnoses Tropical sprue Definition: A disease characterized by chronic diarrhea with subsequent malabsorption in association with a stay in the tropics or subtropics. Epidemiology: occurs in residents of the tropics and subtropics or in travelers returning from these areas (after trips lasting several weeks) Etiology: exact cause not known; most likely due to bacterial infection that leads to structural damage of the intestinal mucosa Clinical findingsChronic diarrhea with steatorrheaAbdominal crampsProgressive weight lossFatigueSee clinical features of malabsorption DiagnosticsBlood tests: megaloblastic anemia (due to deficiency of folate and vitamin B12), hypoalbuminemia, hypocalcemia, vitamin D deficiencySerology for antibodies to rule out celiac disease (see "Diagnostics" above)Stool analysisFecal fat 10-40 g/d Rule out infection with pathogens (e.g., Giardia lamblia, Entamoeba histolytica)Endoscopy of the small bowel and biopsyVillous atrophy, elongated crypts, presence of inflammatory cells (plasma cells, lymphocytes, eosinophils)Mainly affects duodenum and jejunum but may progress to ileum Treatment: tetracycline in combination with folic acid for 3-6 months Celiac disease and tropical sprue have similar features (e.g., steatorrhea, abdominal pain, weight loss), but only tropical sprueresponds to antibiotics. Whipple disease Definition:an infectious disease caused by Tropheryma whipplei, an intracellular gram-positive bacteria EpidemiologyVery rareMost commonly occurs in males older than 40 years [14] Clinical featuresIntestinal manifestationsAbdominal painMalabsorption syndrome (including diarrhea and/or steatorrhea): commonly occurs later in the disease progressionExtraintestinal manifestationsEnteropathic arthritis (60% of cases) Arthralgias and arthritis, especially sacroiliitis (40% of cases)FeverPolyserositisLymphadenopathyCardiac symptoms (e.g., valve insufficiencies)Neurological symptoms (e.g., myoclonia, ataxia, impairment of oculomotor function) DiagnosticsSmall intestine biopsies: detection of PAS-positive foamy macrophages in the lamina propria If gastrointestinal symptoms are absent, biopsies may also be taken from other sites with disease activity PCR testing and immunohistochemistry staining Imaging may show enlarged mesenteric nodes.If neurological complaints occur: Perform a lumbar puncture and CSF analysis and neuroimaging (MRI). TreatmentIV ceftriaxone for 2 weeksMaintenance treatment with oral trimethoprim-sulfamethoxazole for 1 year Anyone who CANT appreciate the foamy, PAStoral rivers of England gets Whipped: the most important features of Whipple disease are Cardiac symptoms, Arthralgias, Neurologic symptoms, Trots (diarrhea), and foamy, PAS-positive macrophages on biopsy. Whipple disease is lethal if left untreated! Treatment Lifelong gluten-free diet Abstain from products containing: wheat, rye, barley, speltRecommended foods: rice, maize, potatoes, soy beans, millet, potentially oats In ∼ 70% of cases, clinical improvement occurs within two weeks after initiating the diet. Histological improvement occurs within weeks to months after beginning the diet. In case of secondary lactase deficiency: avoid milk products Iron and vitamin substitution Supplementation of calcium and vitamin D to prevent bone loss Managing celiac disease mainly consists of maintaining a lifelong gluten-free diet! Complications See clinical features of malabsorption Secondary lactase deficiency Moderately increased risk of malignanciesEnteropathy-associated T-cell lymphoma (EATL): Origin: intraepithelial T cellsLocalization: often proximal jejunumClinical presentation: initially often asymptomatic, but B symptoms and gastrointestinal symptoms may be present Adenocarcinoma of the small bowel Prevention There is no proven measure to prevent celiac disease. With infants, introducing small amounts of wheat (into the supplementary diet) between 4-6 months of age does not increase the risk of developing celiac disease

Diarrhea Diarrheal diseases are very common and, in most cases, self-limiting. Diarrhea is defined either as the presence of more than three bowel movements per day, water content exceeding 75%, or a stool quantity of at least 200-250 g per day. Acute diarrhea lasts for no longer than 14 days and is typically caused by viral or bacterial infection or food poisoning. Chronic diarrhea is often caused by underlying gastrointestinal or endocrinological conditions, such as inflammatory bowel disease or hyperthyroidism. Further symptoms may include fever, bloody stools, abdominal pain, and nausea and vomiting in cases of gastroenteritis. Diagnostic tests for acute diarrhea are usually unnecessary, but they may include CBC, stool samples, or colonoscopy for severe or chronic cases. Most cases of diarrhea only require symptomatic treatment, such as oral rehydration, while severe cases may necessitate administration of antibiotics and hospitalization for IV fluid replacement.

Definition Diarrhea is present if one of the following criteria is fulfilled: Frequent defecation: ≥ three times per dayAltered stool consistency: water content > 75%Increase in stool quantity: more than 200-250 g per day Acute diarrhea: lasting ≤ 14 days Persistent diarrhea: lasting > 14 days Chronic diarrhea: lasting > 30 days ViralNorovirus infectionRotavirus infectionCytomegalovirus infection BacterialCampylobacter enteritisShigellosisSalmonellosisCholeraDiarrheagenic E. coli infectionYersiniosisAntibiotic-associated diarrhea (Clostridium difficile infection)Typhoid fever Mycobacterium avium-intracellulare ParasiticProtozoanGiardiasisAmebiasisCryptosporidiosis Helminth infectionsToxocariasisEnterobiasisAscariasisTrichinosisTaenia infections (taeniasis)Hookworm infectionDiphyllobothriasis Foodborne toxinsS. aureus intoxicationBotulismBacillus cereus infection Food poisoningAflatoxinHistamine toxicityChemical contaminants (e.g., lead, cadmium, insecticides) GastrointestinalMalabsorptionCeliac diseaseLactose intolerancePancreatic insufficiencyDiabetic autonomic neuropathyInflammatory bowel disease: Crohn's disease, ulcerative colitisMicroscopic colitisIrritable bowel syndromeTumor/stenotic processes → paradoxical diarrhea EndocrinologicalCarcinoidHyperthyroidismAddison's diseaseGastrinomaMedicationQuinidine, cytotoxic agents Risk factors and disease transmission Transmission by direct contact and droplets Day care attendance, nursing home residency, hospitalization Contaminated food and water (see traveler's diarrhea) Animal exposure Exudative-inflammatory diarrheaDamage to the intestinal mucosa may cause cytokine-induced water hypersecretion, impair absorption of osmotically active substances or fat, or disrupt water and electrolyte absorption.Mucus, blood, and leukocytes present in stoolShigellosis, salmonellosis, enteroinvasive E. coli, enterohemorrhagic E. coli, campylobacteriosis, amebiasisUlcerative colitis, Crohn disease Secretory diarrheaActive secretion of water into the intestinal lumen via inhibition/activation of enzymes (e.g., ↑ cAMP activity)(Foodborne) infections (cholera, enterotoxigenic E. coli)Endocrine tumors (e.g., carcinoid tumors, gastrinoma)Impaired absorption of bile acids/saltsMalabsorption disorders or history of ilealresection Drugs (e.g., colchicine) Osmotic diarrheaWater is drawn into the intestinal lumen by poorly absorbed substances (e.g., salt, sugar, laxatives).Laxatives, citrate of magnesia Malabsorption, lactose intolerance Motor diarrheaRapid intestinal passage due to increased bowel movements HyperthyroidismCarcinoid syndromeDrugs (e.g., erythromycin) The loss of bicarbonate-rich fluid in severe diarrhea may cause non-anion gap metabolic acidosis! Clinical features Acute or chronic diarrhea (see "Definition" above) Further possible symptoms FeverAbdominal pain and crampingBlood in stoolNausea and vomiting in cases of gastroenteritisSigns of dehydration in severe cases Chronic cases: malnutrition and, in children, failure to thrive Disease courses can range from mild to severe with need of hospitalization. Traveler's diarrhea Infections which typically occur in patients with a history of recent travel Very common while traveling in Asian ("Delhi belly"), African, and Latin American countries ("Montezuma's Revenge") A major cause of diarrhea among children in developing countries May be exudative-inflammatory diarrhea or secretory diarrhea Most commonly caused by enterotoxigenic Escherichia coli (ETEC) Other pathogens: Campylobacter jejuni, Shigella spp., Salmonella spp., other E. coli strains (e.g., EAEC), protozoa (e.g., Giardia), viral diarrhea (norovirus, rotavirus, astrovirus) Factitious diarrhea Definition: self-induced diarrhea, usually by laxative abuse; often occurs in individuals with factitious disorders EpidemiologyMost prevalent in womenPatients are usually employed in the health field. History of multiple hospital admissions Clinical findings: chronic watery diarrhea without identifiable cause DiagnosisLaboratory tests: metabolic alkalosis, hypokalemia, hypermagnesemia Colonoscopy: may show melanosis coli in cases of anthraquinone abuse TreatmentCorrection of electrolyte disturbances and dehydrationReferral to psychotherapy Laxative abuse SubstancesBulking agent: flaxseedOsmotic laxatives: lactulose, macrogols (polyethylene glycol), magnesium sulfate, sodium sulfateDiphenolic laxatives: bisacodyl, sodium picosulfateAnthraquinones: senna, aloe vera, rhubarb Clinical featuresOsmotic diarrhea, meteorismDehydrationHypokalemia Melanosis coli: benign hyperpigmentation of the colonic mucosa caused by anthraquinone abuse Colonoscopy: dark brown pigmentation of the colon, interspersed with pale patches reflecting lymph folliclesBiopsy: lipofuscin-laden macrophages on PAS staining Diagnostics The workup for diarrhea includes a detailed patient history (e.g., recent travel), physical examination, and laboratory tests to assess severe cases. Laboratory tests Laboratory tests are usually not required in acute cases and are instead reserved for diagnosis of severe or chronic disease. IndicationsDiarrhea lasting > 4 daysHigh feverBlood in stoolsSuspicion of IBDImmunosuppression TestsCBC: may show anemia or leukocytosisStool samples: leukocytes; ova and parasitesStool culture Indications: suspected invasive bacterial enteritis, severe illness, or fever (> 38.5 degrees), required hospitalization, or stool tests positive for leukocytes/occult blood/lactoferrinC. difficile toxin assay Imaging Colonoscopy: in patients with chronic diarrhea without identifiable cause CT: if diverticulitis or IBD is suspected Treatment Since most cases of acute diarrhea are self-limited, treatment is mostly symptomatic, focusing on oral rehydration, and rarely requires medication. Rehydration (especially in children)Mild to moderate dehydration: oral rehydration therapy with electrolyte-containing fluids, e.g., apple juice or oral rehydration solution Severe cases: consider hospitalization; hydration with IV sodium chloride at 0.9% Antidiarrheal agents (e.g., loperamide): may be given in mild to moderate cases; should be avoided if there is fever or blood in stools (indicative of systemic disease) Antibiotics: are generally not indicated Treatment of the underlying condition in cases of chronic diarrhea

Diverticular disease Diverticular disease is an umbrella term for a spectrum of intestinal pathologies characterized by abnormal outpouching of the colonic mucosa (diverticula). Diverticulosis refers to the presence of asymptomatic diverticula, while diverticulitisrefers to symptomatic diverticular inflammation. The condition is considered a lifestyle disease, seen especially in industrialized nations with low fiber diets and slow fecal transit (e.g., from lack of exercise). Incidence increases with age and more than 50% of individuals are affected by the 7th decade of life. Diverticula are caused by increased intraluminal pressure in the distal colon, resulting in herniation of the inner colonic wall through areas of weakness in the outer muscular layer. This may occur in any part of the colon but is especially common in the sigmoid colon. Most patients are asymptomatic but may present with lower left abdominal pain, change in bowel habits, and fever in the event of diverticulitis. Diagnosis is based on the clinical features and elevation of inflammatory markers in blood tests. Abdominal CT scan is the imaging method of choice and indicated to assess the extent of the disease as well as potential complications. Colonoscopy is contraindicated during acute inflammation but is essential in ruling out malignancy in follow-ups. Uncomplicated diverticulitis may be managed conservatively with antibiotics and bowel rest, while complicated cases may require surgery with colonic resection. Further intervention may be indicated if complications such as diverticular bleeding, perforation, or abscesses arise. Elective surgery is recommended for patients with recurrent diverticulitis or associated conditions such as strictures and fistulae.

Definition Diverticula: pouches protruding from the colon wallTrue diverticula: affect all layers of the intestinal wall; rarely occur and are often congenital; manifest mainly in the cecumPseudodiverticula: not all layers of the intestinal wall protrude; the diverticulum is only covered by a layer of mucosa and submucosa, not by a muscular layer Diverticulosis: merely describes the presence of asymptomatic diverticula Diverticulitis: describes the inflammation of diverticula resulting in clinical symptomsUncomplicated diverticulitis: acute localized inflammation of a colonic diverticulum with no evidence of complicationsComplicated diverticulitis: inflammation of a colonic diverticulum associated with complications, such as, perforation, abscess, fecal peritonitis, bowel obstruction, or fistula formation. Epidemiology Common in Western countries and industrialized societies (∼ 50% of people > 60 years affected) Low prevalence in developing countries (estimated as low as < 0.5%) In Western societies left-sided diverticulosis, in Asia right-sided more common Etiology Caused mainly by lifestyle and environmental factors Increasing ageGenetic factorsDiet (low-fiber, rich in fat and red meat)Obesity, low physical activitySmoking Pathophysiology DiverticulosisChronic constipation and increasing weakness of connective tissue due to age → protrusion of herniated intestinal mucosa and submucosa through gaps in the muscular layer of the intestinal wallLocalized particularly in the sigmoid colon (75% of cases) Diverticulitis: stool gets lodged in diverticula → obstruction of intestinal lumen → increased intraluminal pressure and erosion of diverticula wall → inflammation Clinical features Diverticulosis Mostly asymptomatic Most common cause of lower GI bleeding in adults Can present with abdominal pain in patients with chronic constipation Diverticulitis Low-grade fever Sigmoid colon most commonly affected → left lower quadrant pain Possibly tender, palpable mass (pericolonic inflammation) Change in bowel habits (∼ 50% constipation, 25-35% diarrhea) Nausea and vomiting; caused by bowel obstruction or ileus ↑ Urinary urgency and frequency (∼ 15%) Acute abdomen → indicates possible perforation and peritonitis In elderly or immunocompromised patients clinical symptoms may only be mild! Diagnostics Laboratory tests Blood testsLeukocytosis↓ Hemoglobin (in diverticular bleeding)↑ CRP (> 5mg/100ml) Stool test: rule out pathogens in patients with diarrhea Imaging studies 1st-line: abdominal CT with oral and IV contrast Diverticula, bowel wall thickening (> 4mm), inflammation of the pericolonic fat with fat stranding (visible traces of fluid in the fat)Assessment of complications Abscess: fluid collections, surrounding inflammatory changesObstruction: dilated intestinal loops, visualization of air-fluid levelsPerforation: free air in the abdominal cavity in the event of perforationFistula: air in organs other than the bowel Abdominal ultrasound Performed if CT is not availableShows diverticula, hypoechoic peridiverticular inflammation, abscess formations (detecable fluid), bowel wall thickening Colonoscopy Not indicated during an acute episode → ↑ risk of perforation and exacerbating diverticulitis Performed once inflammation has subsided (after 6 weeks) to assess extent of diverticulitis and rule out malignancy Asymptomatic diverticulosis is often an incidental finding during routine endoscopy Performing a colonoscopy during the acute phase of diverticulitis should be avoided due to risk of perforation! Differential diagnoses Differential diagnostic considerations: Crohn disease and ulcerative colitis Intestinal ischemia (ischemic colitis) Colorectal cancer Acute appendicitis Ileus , colonic obstruction Treatment Diverticulosis No treatment can reverse the growth of existing diverticula Prevention of progressionRegulation of bowel movementsIncrease physical activityHigh-fiber diet Plenty of fluids Treatment of diverticulitis DiseaseConservative management Surgical management(Acute) uncomplicated diverticulitisOutpatient treatmentRestricted, clear liquid diet and bowel rest until pain improvesBroad-spectrum oral antibiotics for 7-10 daysCiprofloxacin plus metronidazoleTrimethoprim/sulfamethoxazole plus metronidazoleAmoxicillin-clavulanatePain management, if necessary (e.g., acetaminophen, ibuprofen)[7] Not necessary unless conservative methods fail or there is high risk of recurring episodes (Acute) complicated diverticulitis Inpatient treatment IV fluids and bowel rest Broad-spectrum IV antibiotics Piperacillin/tazobactamAmpicillin/sulbactamImipenem, meropenem Pain management(e.g., acetaminophen, ketoprofen, morphine); often severe due to localized peritonitis CT-guided percutaneous abscess drainage Indications: stable patient with abscess > 3 cm Emergency surgeryIndication: in case of peritonitis, sepsis or intestinal obstructionResection of the affected segment; primary anastomosis or temporary, protective ileostomyAlternatively Hartmann procedure Elective surgeryIndication: recurrent disease unresponsive to antibiotics; complicated diverticulitis in young patientsResection of the affected segment once the acute inflammation has passedManagement of complications in recurring diverticulitis (e.g., intestinal strictures, fistulas) Complications Diverticular bleedingFrequency: occurs in around 5% of cases of patients with diverticulosisCaused by erosions around the edge of diverticula Clinical findings Painless hematocheziaSevere or ongoing bleeding: significant drop in hemoglobin, hemodynamic instability (hypotension, tachycardia, dizziness, reduced level of consciousness)In 70-80% of cases bleeding ceases spontaneously Differential diagnosis: other causes of lower gastrointestinal bleeding (e.g., hemorrhoidal bleeding)Therapy Endoscopic hemostasis during colonoscopy (epinephrine injection, thermal coagulation, ligation)Angiography with vessel embolization AbscessPeridiverticular localization; causes similar symptoms to acute diverticulitisSuspect an abscess in patients with persistent fever and abdominal pain despite antibiotic treatment Perforation: symptoms of acute abdomen caused byRupture of an inflamed diverticulum → free communication with the peritoneum, generalized fecal peritonitisRupture of a diverticular abscess → generalized purulent peritonitis FistulasColovesical (most common) Symptoms: pneumaturia and fecaluria; may cause recurring urinary tract infections, including urosepsisDiagnosis: CT with oral contrastLocalized thickening of colon and bladderAir or contrast material in the bladderTreatment Primary anastomosisAntibiotics if surgery is not possibleOther forms: colovaginal, coloenteric, colocutaneous Intestinal obstructionCauses: inflammatory swelling, compression through abscesses, ileus caused by localized irritationSymptoms: abdominal pain and distension, constipation, nausea, vomiting, acute abdomen

Achalasia Achalasia is a failure of the lower esophageal sphincter (LES) to relax that is caused by the degeneration of inhibitory neurons within the esophageal wall. It is classified as either primary (idiopathic) or secondary (in the context of another disease). In patients with achalasia, the chief complaint is dysphagia to both solids and liquids, although regurgitation, retrosternal pain, and weight loss may also occur. Upper endoscopy, esophageal barium swallow, and esophageal manometry play complementary roles in the diagnosis of achalasia. While upper endoscopy and/or esophageal barium swallow are often obtained initially, manometry usually confirms the diagnosis, and upper endoscopy is indicated to rule out a malignant underlying cause. In good surgical candidates, achalasia is usually treated with pneumatic dilation or myotomy. In most other cases, an injection of botulinum toxin is attempted. If these measures fail to provide relief, medical therapy (e.g., nifedipine) is indicated.

Definition Esophageal mobility disorder characterized by inadequate relaxation of the lower esophageal sphincter (LES) and nonperistaltic contractions in the distal two-thirds of the esophagus due to the degeneration of inhibitory neurons Etymology: A (absent) -chalasia (relaxation) Epidemiology Rare disorder (∼ 1.6/100,000 individuals) Most commonly occurs in middle-aged individuals Etiology Primary achalasia (most common): cause is unknown Secondary achalasia (pseudoachalasia): the presentation and manometric findings of a mechanical cause of obstruction (e.g., a malignancy) that mimics achalasiaEsophageal cancerStomach cancer and other extraesophageal cancers (symptoms may be due to mass effect or paraneoplasia)Chagas diseaseAmyloidosisNeurofibromatosis type ISarcoidosis CHAgas disease may lead to secondary aCHAlasia. Pathophysiology Swallowing is controlled through excitatory (acetylcholine, substance P) and inhibitory (NO, VIP) neurohumoral substances. Atrophy of inhibitory neurons in the Auerbach plexus → lack of inhibitory neurotransmitters (e.g., NO, VIP) → inabilityto relax and increased resting pressure of the LES, as well as dysfunctional peristalsis → esophageal dilation proximalto LES Clinical features Dysphagia to solids and liquids; can be progressive or paradoxical Regurgitation Retrosternal pain and cramps Weight loss Achalasia typically manifests with progressive dysphagia to solids and liquids while esophageal obstruction manifests with dysphagia to solids only. Diagnostics ApproachIn general, all patients with suspected achalasia should initially undergo upper endoscopy and/or esophageal barium swallow; findings may support the diagnosis.Esophageal manometry is indicated to establish the diagnosis (confirmatory test of choice), irrespective of the initial imaging findings.If manometry is inconclusive and an esophageal barium swallow was not obtained initially, esophagram can also play a confirmatory role.Endoscopy should be performed to rule out pseudoachalasia because the presentation and manometric findings of a mechanical cause of obstruction (e.g., a malignancy) may mimic achalasia. Esophageal barium swallow: supportive and/or confirmatory testBird-beak sign: dilation of the proximal esophagus with stenosis of the gastroesophageal junction Delayed barium emptying or barium retention Upper endoscopy: to rule out pseudoachalasiaUsually normalMay show retained food in esophagus or increased resistance of LES during passage with endoscope If malignancy is suspected, biopsy and endoscopic ultrasound are indicated Esophageal manometry: confirmatory test of choicePeristalsis is absent or uncoordinated in the lower two-thirds of the esophagus. Incomplete or absent LES relaxationHigh LES resting pressure No evidence of mechanical obstruction Chest x-rayWidened mediastinumAir-fluid level on lateral view Possible absence of gastric air bubble Differential diagnoses Differential diagnoses of achalasia Esophageal cancer Schatzki ring Esophageal stricture Chagas disease Extrinsic compression (e.g., mediastinal lymphadenopathy) Scleroderma Differential diagnosis of esophageal motility disorders Esophageal motility disorders range from hypomotile dysfunction (achalasia) to hypermotile dysfunction (diffuse esophageal spasm, nutcracker esophagus) of the esophagus. They have similar symptoms with dysphagia, chest pain, and regurgitation of food, but are differentiated based on findings in esophagograms and esophageal manometry. AchalasiaProgressive dysphagia or paradoxical dysphagia Regurgitation of undigested food/saliva Weight loss LES pressure: high (failure to relax) LES relaxation: incomplete/absent Simultaneous, nonprogressive contractionDilated esophagus that tapers distally (bird-beak sign/rat tail appearance) LES spasm and delayed barium emptying High LES resting pressure High esophageal body pressure Low peristaltic contraction pressure Esophageal manometry Normal (40-100 mm Hg) Distal esophageal spasm (Corkscrew esophagus/rosary bead esophagus) Dysphagia Retrosternal squeezingchest pain similar to angina; occurs with eating Regurgitation Corkscrew esophagus(pseudodiverticulosis) Simultaneous multi-peak contractions High pressure contractions Intermittent normal peristalsis MedicalAvoid trigger foods Calcium channel blockersNitratesTricyclic antidepressants EndoscopicBougie dilation (severe dysphagia)Botox injections Surgery: long esophagomyotomy for severe symptoms Hypertensive peristalsis (Supersqueeze esophagus/nutcracker esophagus) Retrosternal chest pain Dysphagia Normal progressive contractions, but high amplitude (supersqueeze, nutcracker) Hypertensive contractions(> 400 mm Hg) MedicalAvoid trigger foodsCalcium channel blockersAntispasmodicsNitrates Treatment If a low surgical risk The preferred treatment often depends on the surgeon and the patient's situation. However, attempting pneumatic dilation before myotomy is gaining popularity because it is less invasive and the time of recovery is faster. This approach is already more popular in Europe. Pneumatic dilationEndoscope-guided graded dilation of the LES that tears the surrounding muscle fibers with the help of a balloon The success rate at one month is ∼ 85%; perforation risk is ∼ 2%. LES myotomy (Heller myotomy) If a high surgical risk Botulinum toxin injection in the LESA good choice for patients who are poor surgical candidates More than 50% of patients require treatment again within 6-12 months. If other measures are unsuccessful: nitrates or calcium channel blockers Complications Pulmonary complications (e.g., pneumonia, abscess, asthma) caused by aspiration Megaesophagus Increased risk of esophageal cancer.

Intestinal ischemia Intestinal ischemia occurs when blood flow to the bowels is reduced. The condition can be acute or chronic and may affect the large and/or the small intestine. Possible causes for decreased blood flow include thromboembolism, atherosclerosis, and severe hypotension. Mild forms of intestinal ischemia lead to abdominal discomfort (e.g., postprandial pain) and a change in bowel habits (e.g., bloody diarrhea). In severe cases, infarction of intestinal tissue leads to perforation of the bowel, sepsis, and death. Early diagnosis and therapy are, therefore, essential and sometimes emergency surgery is vital. Imaging techniques (e.g., CT angiography, ultrasound, colonoscopy) are used to detect stenoses, occlusions, and/or mucosal changes. Chronic and mild acute forms are associated with a better prognosis and patients benefit from revascularization procedures (e.g., stents, bypass surgery) and symptomatic therapy. Complications such as peritonitis and sepsis result in a poor prognosis.

Definition Intestinal ischemia is classified into three main types: Ischemic colitis (colonic ischemia): hypoperfusion of the large bowel, which is mostly transient and self-limiting(non-gangrenous form), but can also lead to severe acute ischemia with bowel infarction (gangrenous form) Acute mesenteric ischemia: acute inadequate blood flow to the small intestine (arterial or venous) that can result in bowel infarction Chronic mesenteric ischemia: constant or episodic hypoperfusion of the small intestine, usually due to atherosclerosis Ischemic colitis Epidemiology Most common form of intestinal ischemia Mainly occurs in adults > 60 years In ∼ 80-85% mild, non-gangrenous form Etiology Usually caused by transient hypoperfusion Thromboembolism Hypotension, hypovolemia (e.g., sepsis, dehydration, hemorrhage) Cardiovascular surgery (especially aortic repairs or cardiac bypass) Vasoconstrictive drugs Thrombophilias (e.g., anticardiolipin syndrome) Colonic obstruction from tumors, adhesions, etc. Pathophysiology Intestinal blood flow of the superior mesenteric artery (SMA) and/or inferior mesenteric artery (IMA) is suddenly compromised (see "Etiology" for causes) → intestinal hypoxia → intestinal wall damage → mucosal inflammation + possibly bleeding → may progress to infarction and necrosis (gangrenous type) → disruption of mucosal barrier and perforation → release of bacteria, toxins, vasoactive substances → life-threatening sepsis Depending on the degree of ischemia, there may be two types: Non-gangrenous (80-85%) Gangrenous (15-20%) Sites of compromise Superior mesenteric artery (SMA): supplies the distal duodenum, jejunum, ileum, and the right colon from the cecum to the splenic flexureInferior mesenteric artery (IMA): supplies the left colon from the splenic flexure to the rectumThe splenic flexure and the rectosigmoid junction are at high risk for colonic ischemia because they are "watershed areas". The intestines can tolerate a state of ischemia for approx. 6 hours! Clinical features Typically presents with 3 clinical stages: Hyperactive phase Sudden onset of crampy abdominal pain (usually left lower quadrant)Bloody, loose stools> 80% of patients recover and do not progress beyond this phase Paralytic phase Pain more diffuseBowel sounds become absent. BloatingBloody stools cease Shock phase Acute abdomen with abdominal guarding and rebound tenderness Signs of septic shock A classic case of ischemic colitis is a patient who presents with bloody diarrhea and severe abdominal pain after an abdominal aortic aneurysm repair! Diagnostics No specific laboratory findings in mild ischemic colitis In severe ischemic colitis: ↑ Lactate, ↑ LDH, ↑ creatine kinaseLeukocytosisMetabolic acidosis Colonoscopy Procedure of choice in mild to moderate cases of ischemic colitisFindings include edema, cyanosis, and/or ulceration of mucosa Plain abdominal radiograph: insensitive, unspecific (air-filled, distended bowel), but helps exclude other disorders CT scan: wall thickening, pneumatosis intestinalis (suggests transmural ischemia or infarction) Exploratory laparotomy in severe cases Differential diagnoses See also acute abdomen Therapy Mild to medium-severe forms:Supportive care (IV fluids, bowel rest, nasogastric tube in case of an ileus)Antiplatelet drugsReduce risk of atherosclerosis Severe forms (signs of peritonitis, sepsis): surgical intervention (laparotomy and bowel resection) Complications Non-gangrenous form: strictures or chronic ischemic colitis Gangrenous form: peritonitis → sepsis → multi-organ failure Prognosis Non-gangrenous ischemic colitis:mortality rate of approx. 6% Gangrenous ischemic colitis: mortality rate of ∼ 50-75% Acute mesenteric ischemia Epidemiology Mainly occurs in adults > 60 years Young people with A-fib, vasculitis (e.g., polyarteritis nodosa), or hypercoagulable states can also be affected Acute mesenteric ischemia: 0.1% of all hospital admissions Etiology Acute arterial embolism (∼ 50% of cases): generally resulting from atrial fibrillation, myocardial infarction, valvular heart disease, or endocarditis Arterial thrombosis (∼ 25% of cases): due to preexisting visceral atherosclerosis, arteritis, aortic aneurysm, or dissection Nonocclusive mesenteric ischemia (NOMI; ∼ 20% of cases) Typically seen in critically ill people with low cardiac outputHypotension, vasopressive drugs, digitalis, ergotamines, cocaine Mesenteric venous thrombosis (< 10% of cases): Predisposing factors include infection, malignancies, estrogentherapy, and hypercoagulability disorders. Pathophysiology Sudden interruption of blood flow to small bowel (see "Etiology" above for cause) → intestinal hypoxia → hemorrhagic infarction and necrosis → disruption of mucosal barrier and perforation → release of bacteria, toxins, vasoactive substances → life-threatening sepsis Sites of interruption SMA (∼ 90% of cases): supplies the distal duodenum, jejunum, ileum, and colon to the splenic flexureSuperior mesenteric vein (∼ 10% of cases): drains blood from the small intestineIMA and the celiac artery are less commonly affected. Clinical features Periumbilical pain that is disproportionate to physical findings Nausea and vomiting Diarrhea (bloody in later stages) Gangrenous bowel: rectal bleeding and signs of sepsis (e.g., tachycardia, hypotension) Clinical courses Acute arterial embolism: most abrupt and painful onset of all types ("abdominal apoplexy")Acute arterial thrombosis: presentation less severe because patients have better collateral supplyNonocclusive ischemia: symptoms develop over several daysVenous thrombosis: symptoms less dramatic, worsen gradually (e.g., abdominal discomfort evolves over a week) A patient with acute arterial embolism typically presents with severe abdominal pain, fever, bloody diarrhea, leukocytosis and atrial fibrillation!A patient with acute arterial thrombosis typically has a known cardiovascular or peripheral vascular disease and/or symptoms of chronic mesenteric ischemia in addition to acute symptoms! Diagnostics Laboratory findings ↑ Lactate, ↑ LDH, ↑ creatine kinaseLeukocytosisMetabolic acidosis CT angiography (confirmatory test)Detects disrupted flow and vascular stenosisDistended intestinal loops and air-fluid levels, wall thickening, pneumatosis intestinalis (suggests transmural ischemia or infarction)Alternative: MR angiographyAdvantage: no radiationDisadvantage: less accurate evaluation of the IMA Ultrasound Detection of distended intestinal loops and free fluid in the abdominal cavity in case of perforationColor Doppler ultrasound to detect stenosis in arterial branches Evaluation of underlying disease (e.g., ECG for atrial fibrillation or myocardial infarction) If an acute mesenteric ischemia is suspected, quickly initiating imaging studies (CT angiography, color Doppler sonography) is essential. In cases with peritonitis or risk of shock, however, emergency surgery without prior imaging is indicated! Differential diagnoses See acute abdomen Treatment If signs of advanced ischemia (e.g., peritonitis, sepsis) or hemodynamically unstable patient → emergency laparotomy Open surgical embolectomy or mesenteric artery bypass depending on the cause of occlusionResection of necrotic bowel segments Hemodynamically stable patients without signs of advanced ischemia → endovascular approachBalloon angioplasty and stentingCatheter-based pharmacologic (thrombolytics) and/or mechanical thrombectomy Supportive: IV fluids, nasogastric tube , analgesics and broad-spectrum antibiotics Infusion of a vasodilator (e.g., papaverine) during arteriography to relieve occlusion and vasospasm Heparin anticoagulation in cases of venous thrombosis Long-term measures Reduce risk of further atherosclerosis (antiplatelet and statin therapy)Treat underlying cardiac disease (e.g., anticoagulation therapy in patients with A-fib) Complications Peritonitis Sepsis Multi-organ failure Prognosis Acute mesenteric arterial ischemia: mortality rate of 60-80% In cases of bowel infarction, mortality rate is 90-100% Chronic mesenteric ischemia Epidemiology A clinically manifested chronic mesenteric ischemia is rare Generally occurs in adults > 60 years Etiology See risk factors for atherosclerosis (e.g., high blood pressure, smoking, diabetes mellitus, high cholesterol levels) Pathophysiology Slowly progressing stenosis of two or more main arteries (SMA, IMA, or celiac artery) → postprandial mismatch between splanchnic blood flow and intestinal metabolic demand → postprandial pain If only one main artery is affected, collateral connections between the arteries can form and compensate for the reduced flow → patient may be asymptomatic Thrombus formation in addition to progressive stenosis can lead to acute-on-chronic mesenteric ischemia → acute mesenteric ischemia Clinical features Some patients may be asymptomatic (see "Pathophysiology") So-called 'abdominal/intestinal angina'Recurrent, dull, postprandial epigastric pain usually within the first hour after eatingCan lead to a fear of eating → weight loss and malabsorption Bloating, nausea, occasional diarrhea Abdominal bruit caused by stenosis of mesenteric vessels A patient typically presents with postprandial abdominal pain (abdominal angina), food aversion, and weight loss! Diagnostics No specific laboratory findings in chronic mesenteric ischemia Clinical suspicion → CT scan of the abdomen (identifies atherosclerotic vascular disease and rules out other abdominal disorders) CT angiography or MR angiography: High-grade stenoses of at least two major vessels must be established for diagnosis Duplex sonography of the mesenteric vessels: best screening modality in an office setting Differential diagnoses Malignancy Chronic cholecystitis Chronic pancreatitis Peptic ulcer disease Therapy Nutritional support (frequent, small meals; low-fat diet) [14] Long-term anticoagulation for patients not healthy enough for vascular repair Revascularization procedures to prevent bowel infarction in patients with abdominal pain and weight loss: Angioplasty and stentingMesenteric artery bypass surgery Prognosis In chronic mesenteric ischemia, surgical revascularization and reduction of risk factors can lead to significant painreduction.

Lactose intolerance Lactose intolerance is caused by the malabsorption of lactose. It may be genetically determined or due to a functional deficiency of the lactase enzyme in the epithelium of the small intestine. After consuming food or beverages containing lactose, affected individuals develop abdominal symptoms such as pain, diarrhea, and bloating. Lactose intolerance is diagnosed with a hydrogen breath test or lactose intolerance test. The condition may be managed well with lactasesupplements or by avoiding lactose altogether.

Definition Lactose intolerance is the inability to absorb lactose, caused by lactase deficiency. Epidemiology Approximately 70% of the world's population is lactose intolerant. Lactose intolerance is more common in certain regions, particularly Asia, parts of Africa, and South America, where up to 90% of the population is affected. The prevalence increases with age Etiology Primary (lactase non‑persistence): most common type of lactose intolerance; a decrease in lactase activity is primarily observed during childhood or adolescence Secondary (acquired): due to underlying disorders of the small intestine that result in mucosal damage (e.g., gluten‑sensitive enteropathy following gastroenteritis) Developmental: occurs in children born prematurely, as lactase activity develops late during pregnancy Congenital: autosomal recessive gene defect (extremely rare) Pathophysiology Lactase is a brush‑border enzyme that cleaves lactose, a disaccharide, into absorbable monosaccharides (galactose and glucose). In the case of lactase deficiency, an almost complete absence of lactose digestion is observed, resulting in decreased absorption in the small intestine (particularly the jejunum).The transfer of osmotically active amounts of lactose into the large intestine leads to the osmotic binding of water→ diarrheaIncreased peristalsis due to increased intestinal filling → stomach painMetabolism of lactose via the physiological bacterial flora of the colonFormation of short‑chain fatty acids that exacerbate diarrheaIncreased gas formation and flatulence Lactase deficiency is a malabsorption disorder! Clinical features Symptoms occur about an hour to several hours following consumption of milk products. The intensity of symptoms correlates with the amount of lactose consumed. Diarrhea (often watery, bulky, and frothy) Cramping abdominal pain (often periumbilical or in the lower abdomen) Abdominal bloating Flatulence Nausea Symptoms vary widely as most patients have residual amounts of lactase! Diagnostics Stool analysis: ↑ stool osmotic gap , stool pH < 6 Hydrogen breath testThe amount of hydrogen in the expired air increases after administering lactose in the fasting state. Measurement at baseline and at 30‑minute intervals over 3 hours following the ingestion of 50 g of lactose(children: 2 g/kg lactose (max. amount 25 g)) Lactose tolerance test: Following the administration of lactose, the normal rise in blood glucose levels is pathologically reduced and symptoms appear → rarely used, as the test has low sensitivity and specificity. Trial lactose‑free diet: to see if symptoms resolve Biopsy of the small intestine: qualitative and quantitative assessment of lactase via an endoscopic tissue biopsy(conclusive, although rarely used). Histologic analysis shows normal intestinal architecture. Differential diagnoses Food protein intolerance Common antigens: cow milk proteins (lactalbumin or casein, among others); soy protein; egg proteinReactions are either IgE‑mediated (e.g., cow's milk allergy) or non‑IgE‑mediatedClinical findingsAbdominal pain, nausea, vomiting, and diarrheaFood protein-induced proctocolitis (e.g., caused by milk or soy protein)Affects primarily young infants; typically manifests at 2-8 weeks of ageStools tinged with blood and mucus in otherwise healthy childrenA clinical diagnosisManagement: continue breastfeeding and advise the mother to avoid dairy and soy productsResolution of symptoms once causative antigen is removed Irritable bowel syndrome Inflammatory bowel disease Gastrointestinal infections (e.g., giardiasis, bacterial, viral) Small bowel bacterial overgrowth Cystic fibrosis Bowel malignancy Treatment Avoid or reduce intake of milk products: lactose‑free or lactose‑reduced products have become more readily available Many patients tolerate small amounts of milk (∼ 240 mL per day).Use of alternative foods, such as soy‑based productsAwareness of lactose in processed foods or foods other than dairy products (e.g., bread, salad dressings) Oral lactase supplementsRecommended when traveling or before consuming food or milk products containing lactoseA wide variety of non‑standardized over‑the‑counter lactase supplements are available

Portal hypertension Portal hypertension refers to a pathological elevation of portal venous pressure resulting from obstructions in portal blood flow, which may be either prehepatic (e.g., portal vein thrombosis), hepatic (e.g., liver cirrhosis), or posthepatic (e.g., right-sided heart failure). The subsequent backflow of blood may lead to portosystemic anastomoses, splenomegaly, and/or ascites. While portal hypertension may be diagnosed purely based on the presence of clinical signs and potential risk factors, medical imaging and laboratory tests are used to support the diagnosis in suspected cases. Management requires treating the underlying condition and reducing portal pressure with nonselective beta-blockers and portosystemic shunts. A potentially life-threatening complication is acute hemorrhage of the esophageal varices caused by increased blood flow via portosystemic anastomoses. Patients present with sudden hematemesis and melena, as well as hypovolemic shock in some cases. In addition to stabilizing the patient, acute management of variceal bleeding includes reducing splanchnicblood flow with octreotide and endoscopic variceal band ligation. Prevention of (recurring) bleeding involves nonselective beta-blockers, endoscopic variceal ligation, or placement of transjugular intrahepatic portosystemic shunts (TIPS).

Definition Portal hypertension is defined as a portal venous pressure of ≥ 6 mm Hg. Portal venous pressure > 10 mm Hg is clinically significant and > 12 mm Hg is associated with complications. Etiology PrehepaticPortal vein thrombosisSplenic vein thrombosis Hepatosplenic schistosomiasis IntrahepaticCirrhosis including fibrous proliferation (most common cause of portal hypertension in the US)Massive hepatic metastases PosthepaticBudd-Chiari syndromeRight-sided heart failureConstrictive pericarditis Clinical features Depending on the cause, portal hypertension may be either acute or chronic. Acute portal hypertension arises from acute portal vein thrombosis, while chronic portal hypertension may be due to chronic thrombosis, cirrhosis, or schistosomiasis. Signs and symptoms of the underlying disease (e.g., cirrhosis, right-sided heart failure) ↑ Blood flow via portosystemic anastomoses Via paraumbilical veins and epigastric veins → caput medusae Via rectal veins → hemorrhoidal or anorectal varices Via veins of the gastric fundus and distal 1/3 of the esophagus, leading to:Esophageal varices: risk of life-threatening esophageal variceal bleeding (hematemesis)Gastric varices: melenaConsequences: impaired liver function (see cirrhosis) Congestive splenomegaly, followed by signs of hypersplenism (e.g., thrombocytopenia) Upper gastrointestinal bleeding from portal hypertensive gastropathy, gastrointestinal ulcers, or diffuse lower gastrointestinal bleeding Transudative ascites SAAG >1.1 Diagnostics Clinical manifestations of portal hypertension (e.g., ascites) in a patient with a known risk factor (e.g., cirrhosis) may already suffice for diagnosis. In addition to investigating underlying conditions, diagnostic steps may include: UltrasoundSpecific findings: on duplex ultrasonography, visualization of a cavernous transformation of the portal veinindicates (chronic) portal vein thrombosis Unspecific finding: portal vein dilated to > 13 mm Indirect indicationsVisualization of ↑ blood flow via portosystemic anastomoses using duplex ultrasonography SplenomegalyAscites Abdominal CT: portal vein thrombosis is visible Esophagogastroduodenoscopy (EGD): assessment of and, if necessary, treatment of esophageal varices Treatment Medical therapy First-line medication: nonselective beta-blocker (i.e., propranolol or nadolol)Effect: inhibits beta-2-adrenergic receptors in the gastrointestinal tract → splanchnic vasoconstriction → ↓ portaland collateral blood flow → ↓ portal hypertensionAlso used to prevent variceal bleeding Beta-blocker treatment in patients suffering from advanced liver cirrhosis (Child class C) may lead to circulatory dysregulation. If negative effects outweigh the benefits, beta-blocker treatment should be reconsidered! Portosystemic shunts Transjugular intrahepatic portosystemic shunt (TIPS or TIPSS)IndicationsPersistent, recurring, or treatment-resistant upper gastrointestinal bleeding resulting from portal hypertension, e.g., from esophageal varices Refractory ascitesAcute thrombosis of portal vein Patients with hepatorenal syndrome who are not eligible for or are awaiting liver transplantation .ProcedureA needle catheter inserted via the internal jugular vein → passed along to hepatic vein → pierced through liverparenchyma to intrahepatic branch of the portal vein → expandable metal stent is placed → side-to-sideportocaval shuntAssures blood drainage from the portal to the systemic system bypassing the liver, thus lowering portal pressureContraindicationsPre-existing hepatic encephalopathy or cirrhosis (Child's class C): Shunt implementation results in reduced hepatic elimination of ammonia and worsening of encephalopathy.Heart failureSevere pulmonary hypertension > 45 mm HgUncontrolled systemic infection or sepsisHepatic cysts or tumorsCavernous transformation of the portal vein following thrombosis Total portosystemic shunts: The portal vein is completely shunted to the vena cava, thereby reducing portal pressure. Selective portosystemic shunts: The portal vein is partially shunted to the vena cava, thereby reducing portal pressure. This partial shunt prevents varices while continuing to allow portal perfusion Complications Esophageal variceal hemorrhage Definition Esophageal variceal hemorrhage refers to the bleeding of dilated sub-mucosal veins (varices) of the distal esophagus and is a dangerous consequence of portal hypertension. It is the most common form of upper gastrointestinal (GI) bleeding in patients presenting with cirrhosis. Clinical features Symptoms of upper GI bleeding (see clinical features of gastrointestinal bleeding): signs of circulatory insufficiency, hematemesis, melena, and/or hematochezia Clinical diagnosis Sudden onset of severe upper GI bleeding in a patient with signs of portal hypertension, typically in combination with liver failure If bleeding occurs following retching or vomiting, consider a Mallory-Weiss tear as a differential diagnosis. Treatment Acute management of variceal hemorrhage Resuscitation and stabilizationPlace (at least) two peripheral venous cathetersSubstitute crystalloids to maintain plasma volumeIntubate patient (with decreased consciousness) to prevent the possibility of aspiration or airway obstructionTransfuse blood or blood products to stabilize coagulation, if indicated Medical therapyOctreotide for 3-5 days → inhibits secretion of vasodilative hormones, e.g., glucagon → indirect splanchnicvasoconstriction → reduces splanchnic blood flowVitamin K is indicated for patients with coagulation disordersAntibiotic prophylaxis for 7 days: prevention of infections (SBP, urinary tract infection, pneumonia) and of septiccomplications due to bacteremia, as well as colon decontamination to reduce ammonia production of gut floraFirst-line: IV ceftriaxoneAlternative: oral ciprofloxacin Endoscopic managementErythromycin (a strong prokinetic agent) may be administered before gastroscopy. ProceduresEndoscopic band ligation (procedure of choice)HemostasisUsed for primary prophylaxis and prevention of recurring hemorrhageAlternative: injection sclerotherapy, absolute alcohol, and fibrin glue, as well as cyanoacrylate, to stop acute variceal bleeding Balloon tamponade using a Sengstaken-Blakemore tube or Minnesota tubeIndication: alternative treatment in case of extreme hemorrhage, unsuccessful endoscopic treatment, or ineffective hemostatic medication; consider in hemodynamically unstable patients until they can be stabilizedComplication: risk of decubitus gangrene → prevention: deflation of balloon every 5 hours for 5 minutes Interventional radiologic treatment: See "TIPS" above. Bleeding prevention Primary prophylaxis Medication to lower portal pressure, irrespective of variceal grading: nonselective beta-blockers (e.g., propranolol, nadolol)Endoscopic esophageal variceal ligation: only indicated for patients with a high risk of bleeding (cirrhosis Child B-C, coagulopathy or varices Paquet grade II) Secondary prophylaxis Combine endoscopic variceal ligation and medication (e.g., propranolol) to reduce portal pressure for residual varices If bleeding occurs despite secondary prophylaxis → placement of TIPS Other complications Portal hypertensive gastropathy: Condition caused by cirrhosis (leading to portal hypertension) or portal vein thrombosis, which can cause gastrointestinal ulcers or diffuse lower gastrointestinal bleeding. Ascites Spontaneous bacterial peritonitis Hepatorenal syndrome Pulmonary complications of portal hypertension Cardiac cirrhosis

Hiatal hernia A hiatal (or hiatus) hernia is the abnormal protrusion of any abdominal structure/organ, most often a portion of the stomach, into the thoracic cavity through a lax diaphragmatic esophageal hiatus. It may be congenital or secondary to ageing, obesity, and/or smoking. There are four types of hiatal hernia: sliding, paraesophageal, mixed, and complex. Sliding hiatal hernias, where the gastroesophageal junction (GEJ) and the gastric cardia migrate into the thorax, account for 95% of hiatal hernias. In paraesophageal hernias (PEH), only the gastric fundus herniates into the thorax, whereas in mixed hiatal hernias, the GEJ as well as the gastric fundus herniate. Complex hiatal hernias are rare and characterized by protrusion of any abdominal organ other than the stomach. Nearly half of all patients with hiatal hernia are asymptomatic and require no medical or surgical intervention. Symptomatic patients with sliding hiatal hernia present with features of gastroesophageal reflux disease (GERD), which are usually managed with lifestyle modification and proton pump inhibitors. Patients with PEH or mixed hiatal hernias typically present with intermittent dysphagia, substernal discomfort, or abdominal pain, and in rare cases present acutely with gastric volvulus and strangulation. All symptomatic PEH, mixed, and complex hiatal hernias require operative intervention to avoid life-threatening complications. Also see our learning card "Congenital diaphragmatic hernias".

Definition Protrusion of any abdominal structure/organ into the thorax through a lax diaphragmatic esophageal hiatus. (In 95% of cases, a portion of the stomach is herniated.) Epidemiology Incidence increases with: Age: affects ∼ 70% of people > 70 years↑ BMI PrevalenceMore prevalent in females and Western populations Most commonly occur on the left side, as the liver protects the right diaphragm. Etiology The etiology is multifactorial. Lax diaphragmatic esophageal hiatusAdvanced age Smoking ObesityGenetic predisposition (rare) Prolonged periods of increased intra-abdominal pressurePregnancyAscitesChronic coughChronic constipationDefects of the pleuroperitoneal membrane (see congenital diaphragmatic hernias) Classification Types of hiatal hernias Type I: sliding hiatal hernia Most common type (95% of cases) The GEJ and the gastric cardia slide up into the posterior mediastinum. The gastric fundus remains below the diaphragm (hourglass stomach) Type II: paraesophageal hiatal hernia Part of the gastric fundus herniates into the thorax. The GEJ remains in its anatomical position below the diaphragm. Upside-down stomach (extreme type): a rare type of paraesophageal hernia in which the entire stomach herniates into the thoracic cavity and rotates on its organoaxial axis. It is associated with a high mortality and morbidity rate due to strangulation of the stomach. Type III: mixed hiatal hernia Mix of types I and II The GEJ and a portion of the gastric fundus prolapse through the hiatus. Type IV: complex hiatal hernia Herniation of any abdominal structure other than the stomach (e.g., spleen, omentum, or colon) Rarest type Pathophysiology Anatomy Esophageal hiatus: central opening of the diaphragm, which allows the esophagus to pass through into the peritoneal cavity; forms the upper part of the esophageal sphincter and the reflux barrier Formed by: Left and right paravertebral tendinous cruraMedian arcuate ligament Gastroesophageal junction (GEJ)Normally lies at the level of the esophageal hiatusPhrenoesophageal ligament (PEL) attaches to the esophagus at the GEJPeritoneal fold that encircles the distal portion of the esophagus and gastroesophageal junction and connects them to the peritoneal surface of the diaphragmCloses the esophageal hiatus and helps maintain the intra-abdominal position of the GEJ Changes in the presence of a hiatal hernia Predisposing factors lead to laxity of the esophageal hiatus, e.g.: Advanced age → phrenoesophageal ligament weakensSmoking → loss of elastin fibres in the diaphragmatic cruraObesity → deposition of fat in and around the crura → widened hiatus Relative negative intrathoracic pressure + the lax hiatus → herniation of the abdominal contents into the thorax → loss of reflux barrier + compromised fluid emptying of distal esophagus → gastroesophageal reflux disease (GERD) Clinical features Most patients are asymptomatic Type I: symptoms of GERD Type II, III, and IV: Epigastric/substernal painEarly satiety RetchingSymptoms of GERD can occur. Saint triad: a combination of cholelithiasis, diverticulosis, and hiatal hernia may occur in ∼ 1.5% of patients. Diagnostics Barium swallow: most sensitive test Assesses type and size of a hernia (including location of the stomach and the GEJ) (see "Classification" above) Endoscopy: used to diagnose hiatal hernia and evaluate for possible complications (see "Complications" below) Z-line: squamocolumnar junction, which represents the transition from the squamous epithelium-lined esophageal mucosa to the columnar epithelium-lined gastric mucosa; corresponds to the GEJTypes I and III: Z-line lies above the diaphragmatic hiatusTypes II and IV: Z-line remains undisplaced (below the diaphragmatic hiatus) Other tests that can detect hiatal hernias include:Chest x-ray Usually incidental finding Types I, II, III: retrocardiac soft tissue opacity with/without an air-fluid levelType IV: retrocardiac visceral gas (small bowel/colon) or soft tissue shadows (spleen/omentum)CT Thorax: recommended for urgent preoperative evaluation of complicated type II, III, and IV herniasEsophageal manometry: helps calculate the size of a sliding hiatal hernia by accurately identifying the level of the diaphragmatic hiatus Esophageal pH monitoring: not a diagnostic test; useful for determining the extent of gastroesophageal reflux Treatment Management of patients with sliding hiatal hernia Conservative managementLifestyle modifications Proton pump inhibitors (PPIs) or histamine H2-receptor antagonists if symptoms of GERD occur Surgery: laparoscopic/open fundoplication + hiatoplasty . Indications Persistence of symptoms despite conservative managementRefusal or inability to take long-term PPIsSevere symptoms/complications of gastroesophageal reflux disease: bleeding, strictures, ulcerations Management of patients with types II, III, IV hiatal hernias Conservative management: older patients or those with other comorbidities Surgery: laparoscopic/open herniotomy + fundoplication, hiatoplasty, and gastropexy/fundopexy Indications Asymptomatic, small hernias in patients < 50 years of age Symptomatic type II, III, IV hernias Complications Complications of type I Arise from long-standing gastroesophageal reflux (see "Complications" in gastroesophageal reflux disease) Complications of type II, III, IV Occur mainly due to vascular compromise of the herniated portion of the stomach, which leads to mucosal ischemia They include: Upper gastrointestinal bleeding (occult/massive) Gastric ulcersGastric perforationGastric volvulus Total gastric obstruction

Mallory-Weiss syndrome Mallory-Weiss syndrome refers to acute upper gastrointestinal bleeding caused by mucous membrane lacerations at the gastroesophageal junction, although it may extend above or below. Forceful vomiting in the presence of a damaged gastric mucous membrane, often related to alcoholism, is a common cause of Mallory-Weiss syndrome. Patients typically present with a history of epigastric pain and hematemesis. Esophagogastroduodenoscopy is important in both the diagnosis of the condition and its treatment, which involves simultaneous hemostasis.

Definition Upper gastrointestinal bleeding caused by tears to the longitudinal mucous membrane at the gastroesophageal junction Tears may extend above or below the gastroesophageal junction. Epidemiology Sex: ♂ > ♀ (3:1) Mallory-Weiss lesions account for approx. 5% of cases of gastrointestinal bleeding Etiology Mechanism: A sudden and severe rise in the esophageal intraluminal pressure results in tearing of the esophageal mucous membrane, as well as the submucosal arteries and veins Precipitating factorsSevere vomitingBlunt abdominal traumaStrained defecation Predisposing conditionsAlcoholismBulimia nervosaHiatal hernia (higher pressure gradient)Gastroesophageal reflux disease (GERD) Clinical features May be asymptomatic Epigastric or back pain Hematemesis Possible shock with massive hemorrhage Diagnostics EsophagogastroduodenoscopyOften a single longitudinal tear (multiple tears are possible) in the mucosa at the gastroesophageal junction; limited to mucosa and submucosaA clot or active bleeding may be evident. Differential diagnoses Boerhaave syndrome Esophagitis Esophageal ulcers Treatment General measures If bleedings stops spontaneously conservative treatment is usually sufficient Control of precipitating factors (e.g., omeprazole for GERD) Inpatient monitoring Treat hemodynamic instability if present Surgical treatment Indication: actively bleeding lesion Gold standard: esophagogastroduodenoscopyTherapeutic injection of an adrenaline solution or a fibrin sealantElectrocoagulationEndoscopic band ligation Second-line treatment : angiography (embolization, vasopressin infusion)

Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive metabolic disorder in which impaired copperexcretion causes copper to accumulate in the body. In its initial stages, Wilson disease leads to copper deposits in the liver. As the disease progresses, copper also accumulates in other organs, most importantly in the brain and cornea. The disease often goes undiagnosed until the typical combination of hepatitis (or even cirrhosis), dementia, and parkinsonismraises clinical suspicion. Kayser-Fleischer rings, brownish copper deposits visible around the iris, are a further indication of Wilson disease. Low serum ceruloplasmin (copper transport protein) concentrations and increased urinary copperexcretion confirm the diagnosis. Genetic testing or liver biopsies with quantitative copper assays can provide further information if the diagnosis is indeterminate. Primary management consists of maintaining a low-copper diet and the administering a chelating agent such as penicillamine. The prognosis is good if the condition is diagnosed and treated early.

Epidemiology Age of onset: 5-35 years (mean age 12-23 years) Prevalence: ∼ 1/30,000 Pathophysiology Autosomal recessive mutations in the ATP7B gene (Wilson gene) on chromosome 13, which encodes for a membrane-bound, copper-transporting ATPase → defective ATP7B proteinInadequate incorporation of copper into apoceruloplasmin → ↓ serum ceruloplasminReduced biliary copper excretion Results in ↑ free serum copper → accumulation in the liver, cornea, CNS (basal ganglia, brain stem, cerebellum), and enterocytes Clinical features Liver: different degrees of liver disease possible, including acute liver failure, acute or chronic hepatitis, and cirrhosisHepatosplenomegalyPortal hypertensionAbdominal painJaundiceAscitesHepatic encephalopathy Kayser-Fleischer rings: Copper accumulation in Descemet membrane of the cornea results in 1-2 mm wide, green-brown rings in the periphery of the iris. While the rings are characteristic for Wilson disease and occur in ∼ 98%of patients who also have neurological symptoms, their absence does not rule out the condition. Neurological symptoms: extrapyramidal motor disturbances, but no sensory changesDysarthriaParkinsonismDroolingTremor (usually asymmetric, affecting the hands), which may be any combination of: Resting tremorIntention tremorWing-beating tremor Behavioral changes (e.g., depression, irritability, psychosis) Cognitive impairment Diagnostics Slit lamp examination: Kayser-Fleischer rings (best initial test) Blood tests↑ TransaminasesCBC: Coombs-negative hemolytic anemia, thrombocytopenia ↓ Serum ceruloplasmin (normal value > 20 mg/dL)↑ Free serum copper, but ↓ total serum copper ↑ Urine copper excretion (over 24 hours) Liver biopsy: if other tests are inconclusiveHepatic copper concentration (> 250 μg/g dry weight) Histology: copper staining Screen family members for mutation if diagnosis is confirmed. Differential diagnoses Hepatic: autoimmune and viral hepatitis, cirrhosis, hemochromatosis Neuropsychologic: Parkinson disease, Huntington disease, multiple sclerosis, schizophrenia, personality disorders reatment General management Low-copper diet: avoid foods such as organs, shellfish, nuts, and chocolate Regular check-ups: liver biochemical tests every 6 months if disease is stable Liver transplantation in cases of fulminant liver failure Medical therapy Initial therapy: chelating agents Penicillamine: side effects in ∼ 30% of cases (e.g., sensitivity reactions)Alternatives: trientine or zinc salts Maintenance therapy: zinc salts or low dose chelating agents Treatment with a chelating agent should be administered gradually over the course of 3 to 6 months, as mobilizing the copperstored in tissues too rapidly may exacerbate neurological symptoms!

MALT lymphoma Mucosa-Associated Lymphoid Tissue (MALT) lymphoma (also called MALToma or extranodal marginal zone lymphoma) is a B-cell non-Hodgkin lymphoma (NHL) that typically affects elderly patients in the 7th and 8th decades. MALTomas can be categorized according to their location as either gastric or nongastric. Gastric MALTomas are frequently associated with Helicobacter pylori (H. pylori) infection, whereas nongastric MALTomas are rather associated with autoimmune conditions (e.g., Sjögren syndrome, Hashimoto's thyroiditis). MALTomas typically present with nonspecific symptoms (e.g., fatigue, weight loss) and an unremarkable physical exam. Diagnosis is based on histopathology and immunohistochemistry. In the case of gastric MALTomas, a biopsy should be performed by upper gastrointestinal (UGI) endoscopy. Imaging techniques such as computed tomography (CT) are used for staging purposes. Treatment depends on the type of MALToma: Gastric MALTomas, for example, are treated in most cases with the eradication of the underlying H. pylori infection, whereas nongastric MALTomas are treated with radiation, chemotherapy, and surgery.

Epidemiology Approx. 5% of NHLs are due to MALTomas Peak incidence: 7th and 8th decades Etiology Gastric MALTomas: multiple studies show an association with H. pylori infection. Nongastric MALTomas: frequent association with autoimmune conditions Salivary gland MALTomas → see Sjögren syndromeThyroid MALTomas → see Hashimoto thyroiditis linical features Symptoms depend on the affected organ Physical exam is often unremarkableLymphadenopathy is rarely present Gastric MALTomas Present similarly to peptic ulcer disease and gastritisAbdominal painMelena, hematemesis, potentially anemiaFatigue, weight loss Non-gastric MALTomas: Salivary MALToma: parotid enlargement Diagnostics General approach Blood analysis: anemia Histopathology and immunohistochemistryThick infiltrates of small to medium-sized lymphoid cellsGranulation tissue, ulcerations Immunologic phenotyping: markers of B-cell lymphoma (e.g., CD20) Imaging: CT, MRI for tumor staging Gastric MALToma Additionally, upper gastrointestinal (UGI) endoscopy Determination of tumor spreadBiopsies possibly revealing type B gastritis and H. pylori Treatment Gastric MALTomas First-line: H. pylori eradication therapy omeprazole + clarithromycin + amoxicillin Should be performed even if patient tests negative Eradication of H. pylori is curative in up to 90% of low-malignant gastric MALTomas If H. pylori eradication therapy fails → radiotherapy or chemotherapy Surgery: gastric resection only necessary if complications (e.g., perforation, bleeding, obstruction) occur. Nongastric MALToma Depends on the exact type and staging Treatment options include : radiation, chemotherapy, surgery for local diseases

Esophageal perforation Perforation of the esophagus is most commonly caused by upper endoscopy (iatrogenic), foreign body ingestion, or trauma. It can be located at any point along the esophagus, in the cervical, thoracic, or abdominal region. Boerhaave syndrome is a spontaneous subtype of esophageal perforation characterized by transmural rupture of the esophagusfollowing an episode of forceful vomiting/retching or increased intrathoracic pressure. The condition is associated with recent consumption of large amounts of alcohol or food, repeated episodes of vomiting, and other causes of elevated intrathoracic pressure (e.g., childbirth, seizure, prolonged coughing). The classic symptom is severe retrosternal pain, which is due to the development of mediastinal emphysema after massive emesis. Diagnosis of esophageal perforation is confirmed via neck or chest x-ray, esophagram, and/or CT of the neck and chest. Surgical repair of the esophageal rupture is often necessary, although conservative treatment alone may be considered in select cases (e.g., if the perforation is very small and the patient is stable).

Epidemiology Boerhaave syndrome: ♂ > ♀ (3:1) Etiology Esophageal perforation (general) [1][2] Iatrogenic: most common cause of esophageal perforationMost often injury during upper endoscopyInjury related to surgery Ingestion of a foreign body or caustic material Bone, dentures Alkali or acidic agents (e.g., batteries) Trauma (blunt or penetrating) Malignancy Infection Candida spp.Herpes simplexTuberculosisSyphilis Boerhaave syndrome Risk factors Intake of large amounts of alcohol or food in the recent pastRepeated episodes of vomitingChildbirthSeizuresProlonged coughingWeightlifting Pathophysiology Severe vomiting/increased intrathoracic pressure → rupture of all layers of the esophageal wallIn > 90% of cases, the rupture occurs in the distal third of the esophagus on the left dorsolateral wall surface. Clinical features Neck, retrosternal chest, and/or epigastric pain with radiation to the back Mackler triad, esp. in Boerhaave syndromeVomiting and/or retchingSevere retrosternal pain that often radiates to the backSubcutaneous or mediastinal emphysema: crepitus in the suprasternal notch or crunching or crackling sound on chest auscultation (Hamman sign) Dyspnea, tachypnea, tachycardia Dysphagia Signs of sepsis History of recent endoscopy: Symptoms usually occur within 24 hours of endoscopy. Delayed presentations: critically ill with sepsis and multiorgan dysfunction Diagnostics Approach: If esophageal perforation or Boerhaave syndrome is suspected, a neck or a chest x-ray is first conducted. If inconclusive, an esophagram and/or CT scan is conducted to confirm the diagnosis [1][2] Initial diagnostic studyNeck x-ray lateral : Subcutaneous emphysemaChest x-ray posteroanterior and lateral, upright AXR Widened mediastinumPneumomediastinum, pneumothorax, pneumoperitoneum, subcutaneous emphysema Pleural effusionMediastinal air-fluid levels Confirmatory test that reveals location and size of ruptureContrast esophagography (gold standard): Contrast leak [3] If the patient is unstable/uncooperative, pneumoperitoneum is detected on x-ray, or x-rays and contrast esophagography are inconclusiveCT scan (with oral contrast)Widened mediastinumEsophageal wall thickening, hematomaExtraluminal air: pneumomediastinum, pneumothorax, pneumoperitoneum, subcutaneous emphysemaPleural effusion If CT scan is inconclusiveConsider flexible endoscopy: should be reserved for patients with a poorly localized esophageal perforation and those with a therapeutic indication for endoscopy. Differential diagnoses Mallory-Weiss syndrome See differential diagnosis of chest pain. Treatment Initial approach [1][2][4] ABCDE survey Establish airway and/or provide supplemental oxygen as needed. IV fluid resuscitation Nothing by mouth (NPO) and supply nutritional support Broad-spectrum IV antibiotics (see empiric antibiotic treatment for intra-abdominal infection) IV proton pump inhibitor (e.g., pantoprazole ) Parenteral analgesics (see acute pain management) Nonsurgical treatment [1][2][4] IndicationsSmall, contained perforation, demonstrated by: Either a contained leak with the neck, within the mediastinum, or between the mediastinum and visceral lungpleuraContrast can flow back into the esophagus from the cavity surrounding the perforation.The perforation site is benign, outside of the abdomen, and distal to an obstruction.The patient is stable with no evidence of sepsis.Contrast studies are available at any time for follow-up evaluation.A skilled thoracic surgeon is continuously available. Consider endoscopic interventionEsophageal stent placementEndoclipFibrin glue application Surgical treatment [1][2][4] IndicationsHemodynamic instabilityPatients who do not fulfill the criteria for conservative management Clinical deterioration during conservative management Surgical repairClosure of the ruptured esophageal segment Last resort: esophagectomy Complications Mediastinitis Clinical featuresRetrosternal and/or back painSubcutaneous emphysema in the neck and faceFever, tachycardia, tachypneaBacteremia leading to sepsis and signs of shockSuperior vena cava syndromeObstruction of the upper airwaysPleuritis and pericarditis Diagnosis: Chest x-ray (posteroanterior and lateral views) shows a widened mediastinum and mediastinal emphysema. Management: resuscitation, IV antibiotic therapy, and surgical debridement Others Peritonitis in intra-abdominal perforations Empyema Severe sepsis or shock Multiorgan dysfunction Prognosis Mortality: 10-50%

Acute appendicitis Acute appendicitis refers to acute inflammation of the appendix, typically due to an obstruction of the appendiceal lumen. In both children and adults, it is the most common cause of acute abdomen requiring emergency surgical intervention. The characteristic features of acute appendicitis are periumbilical abdominal pain that migrates to the right lower quadrant (RLQ), anorexia, nausea, fever, and RLQ tenderness. In association with neutrophilic leukocytosis, these features are sufficient to make a clinical diagnosis of acute appendicitis. Imaging (e.g., abdominal CT with IV contrast, abdominal ultrasonography) may be considered if the clinical features are inconclusive. The current standard of management of acute appendicitis is emergency appendectomy (open or laparoscopic) and broad-spectrum antibiotics. Conservative management, which includes bowel rest, antibiotics, and analgesics, is indicated in patients with an inflammatory appendiceal mass (phlegmon) or an appendiceal abscess because surgical intervention is associated with a higher risk of complications in these patient groups. Interval appendectomy 6-12 weeks after resolution of the acute episode can be performed in these patients to prevent a recurrence.

Epidemiology Common cause of acute abdomen [1] Lifetime risk: ∼ 8% Peak incidence: 10-19 years of age [2] Sex: ♂ > ♀ Etiology Caused by obstruction of the appendiceal lumen due to: [3] Lymphoid tissue hyperplasia (60% of cases): most common cause in children and young adults Fecalith and fecal stasis (35% of cases): most common cause in adult Neoplasm (uncommon): more likely in patients > 50 years of age [4] Parasitic infestation (uncommon): e.g., Enterobius vermicularis, Ascaris lumbricoides, and species of the Taenia and Schistosoma genera Pathophysiology Obstructed proximal appendiceal lumen (closed-loop obstruction), resulting in: [7]Stasis of mucosal secretions → bacterial multiplication and local inflammation → transmural spread of infection → clinical features of appendicitisIncreased intraluminal pressure → obstruction of veins → edema of the appendiceal walls → obstruction of capillaries → ischemia → gangrenous appendicitis with/without perforation Inflammation can spread to serosa, leading to peritonitis Clinical features Migrating abdominal pain: most common and specific symptom Typically constant and rapidly worsensMost patients present within 48 hours of symptom onset.Initial diffuse periumbilical pain: caused by the irritation of the visceral peritoneum (pain is referred to T8-T10dermatomes) [9]Localizes to the RLQ within ∼ 12-24 hours: caused by the irritation of the parietal peritoneum Associated nonspecific symptomsNauseaAnorexia: up to 80% of cases Hamburger sign: If there is no loss of appetite, appendicitis is unlikely. [6]Vomiting Low-grade feverDiarrhea Constipation Clinical signs of appendicitis [7][2]McBurney point tenderness (RLQ tenderness) Tenderness at the junction of the lateral third and medial two-thirds of a line drawn from the right anteriorsuperior iliac spine to the umbilicusThis point corresponds to the location of the base of the appendix.RLQ guarding and/or rigidityRebound tenderness (Blumberg sign), especially in the RLQ Rovsing sign: RLQ pain elicited on deep palpation of the LLQ [7]Psoas sign Can be elicited on flexing the right hip against resistanceRLQ pain may be elicited on passive extension of the right hipObturator sign: RLQ pain on passive internal rotation of the right hip with the hip and knee flexed Hyperesthesia within Sherren triangle: formed by the anterior superior iliac spine, umbilicus, and symphysis pubisLanz point tenderness: at the junction of the right third and left two-thirds of a line connecting both the anteriorsuperior iliac spinesPain in the Pouch of Douglas: pain elicited by palpating the rectouterine pouch on rectal examination Baldwin sign: pain in the flank when flexing the right hip (suggests an inflamed retrocecal appendix) The location of the pain may be variable as the appendix's location varies, especially in pregnant women. [10] Diagnostics Acute appendicitis is often a clinical diagnosis. Laboratory testsInflammatory markers: ↑ CRP, mild leukocytosis (11,000-15,000 cells/μL) with left shift Urine analysis: mild pyuria may be present[6] Imaging Abdominal ultrasound : non-compressible and enlarged appendix (> 6-8 mm) Target sign Loss or absence of appendix in advanced or phlegmonous appendicitis Wall thickeningEdema surrounding the appendixAppendix not compressibleIn perforation → intra-abdominal free fluidAbdominal CT scan (∼ 98% sensitivity): periappendiceal streaking and enlarged appendix Abnormal urine analysis does not necessarily rule out appendicitis! Appendicitis is a clinical diagnosis. Further examination, such as blood tests and imaging, is not essential to diagnosis but may be considered if the diagnosis is uncertain! Pathology The appendix is composed of the same four histological layers of the alimentary canal. See "Microscopic anatomy" in large intestine for the histological features of a healthy appendix. Transmural neutrophilic infiltration is the characteristic histological feature of acute appendicitis. Blood vessel thrombosis, mucosal ulceration, and/or gangrene of the appendiceal wall may also be present. Differential diagnoses See differential diagnoses of acute abdomen. Ectopic pregnancy Pseudoappendicitis [11] Meckel's diverticulum Diverticulitis (especially in elderly individuals) Inflammatory bowel disease Bacterial gastroenteritis Colon cancer Urolithiasis and renal colic Urinary tract infections Psoas abscess (in patients with a positive psoas sign) Gynecological diseases (e.g. pelvic inflammatory disease, ovarian cyst) Right-sided carcinoma of the colon may manifest as acute appendicitis! [12] Treatment General approach Conservative therapy is considered in exceptional cases or if findings are unclear ("soft" signs). Bowel rest (keep patient NPO), IV fluid therapy, and observation Analgesia Antibiotics with anaerobic and gram negative cover (e.g., cefazolin and metronidazole) Appendectomy Appendectomy Suspected appendicitis warrants surgical intervention! Surgical approach may be laparoscopic or open and is decided on a case-by-case basis Complications Inflammatory appendiceal mass (appendiceal phlegmon) Description: an ill-defined mass of inflammatory periappendiceal tissue Clinical features: manifests as a tender mass in the RLQ in a patient who is not acutely ill Management: conservative (bowel rest, IV fluids, IV antibiotics, with/without interval appendectomy) Gangrenous appendicitis Description: irreversible necrosis of the appendiceal wall Clinical featuresManifests with high-grade fever, tachycardia, severe RLQ pain and tendernessTypically diagnosed intraoperatively: appendix appears mottled purple Management: immediate appendectomy and IV antibiotics Perforated appendix Description: rupture of the appendix Clinical features: manifests similarly to gangrenous appendicitis, with signs of localized/generalized peritonitis and ↓ bowel sounds Generalized peritonitis indicates a free rupture of the appendix into the peritoneal cavity.Localized peritonitis suggests a concealed perforation. Management: immediate appendectomy and IV antibiotics Appendiceal abscess Description: localized collection of pus and necrotic tissue that forms around an inflamed appendix, which typically follows an untreated perforated appendix Clinical features: manifests as a tender mass in the RLQ in an acutely ill patient (i.e., high-grade fever, with/without paralytic ileus, leukocytosis, signs of sepsis) Management: IV antibiotics, CT-guided drainage of the abscess if > 4 cm, and interval appendectomy Pylephlebitis Description: septic thrombosis of the portal vein or its branches Etiology: complication of intraabdominal sepsis (e.g., due to perforated appendicitis, diverticulitis, or necrotizing pancreatitis) Clinical features: fever, abdominal pain DiagnosticsCT: filling defect in portal vein or its branchesBacteremia Management: broad-spectrum antibiotics Prognosis: Thrombosis of the portal circulation can result in bowel infarction and death. Prognosis Uncomplicated appendicitis with adequate management (surgical intervention) has an excellent prognosis. [8] Perforation and peritonitis: ∼ 1% mortality rate [8] Up to 20% of patients are found to have a normal appendix following surgery. [7] The mortality rate is higher (∼ 5%) in elderly patients with complicated appendicitis. [8] Special patient groups Appendicitis in children [10][18] The reliability of signs and symptoms in children is lower. The most reliable symptoms: emesis and duration of painThe most reliable signs: abdominal tenderness and pain with walking, jumping or coughing. Ultrasound is the diagnostic procedure of choice. Appendicitis in pregnancy [19][10] Atypical (higher) pain localization Perforated appendix is associated with a higher risk of fetal loss Ultrasound is the diagnostic procedure of choice Appendicitis in older patients [20] Clinical presentation Chronic and atypical historyLow-grade fever (not always present)ConfusionSubtle abdominal guarding Consider they usually have multiple comorbidities. CT scan or MRI imaging is preferred because of atypical presentation and higher malignancy rates Children, pregnant women, and the elderly are at a higher risk of perforation!

Hepatocellular carcinoma Hepatocellular carcinoma (HCC) is a malignant, most often solitary tumor of the liver, which occurs primarily in patients with preexisting liver cirrhosis or chronic hepatitis. Typically, it is an incidental diagnosis in these high-risk patients that is made either via ultrasound or an increase in the hepatic tumor marker alpha-fetoprotein. Most patients typically present with symptoms caused by underlying disease (e.g., ascites, jaundice) rather than the tumor itself. Potentially curative treatment options include tumor resection, liver transplantation, and ablative therapies. Unfortunately, it is usually not possible to remove all tumor tissue, which explains the poor prognosis of HCC. In western countries, the five-yearsurvival is less than 50%.

Epidemiology Fifth most common malignancy worldwide Most common primary liver malignancy in adults Highest incidence in Southeast Asia and Africa Peak incidence in the US: 70-75 years ♂ > ♀ Etiology Liver cirrhosis: 80% of cases (see "Etiology" in cirrhosis) Risk factors independent of cirrhosisChronic hepatitis B or C virus infection Alcoholic liver diseaseNonalcoholic steatohepatitis (NASH) HemochromatosisWilson's diseaseAlpha-1 antitrypsin deficiencyHepatic autoimmune diseases (e.g., autoimmune hepatitis)SchistosomiasisGlycogen storage diseaseChronic ingestion of food contaminated with aflatoxin (carcinogen produced by Aspergillus flavus) Results in G:C → T:A transversion in codon 249 of TP53 gene leading to an inactivating mutation Clinical features Usually asymptomatic apart from symptoms of the underlying disease (mostly cirrhosis or hepatitis) Possible symptoms in advanced diseaseWeight loss, anorexiaHepatomegaly and right upper quadrant tenderness JaundiceAscites Diagnostics Laboratory tests ↑ Serum alpha-fetoprotein (AFP) Laboratory studies consistent with hepatitis and cirrhosis (e.g., ↑ transaminases, positive hepatitis serologies, ↓ coagulation factors) Paraneoplastic syndromes: erythrocytosis , hypoglycemia, hypercalcemia (EPO/PTHrP) Imaging Ultrasound: best initial test Irregular mass bordersEchogenicity ranging from homogeneous to inhomogeneous and from hypoechoic to hyperechoicVascular invasion of the tumor may be visible (e.g., portal vein thrombosis)Underlying cirrhosis may be seen Abdominal CT or MRI (with contrast): confirmatory test Hypodense lesions (single or multifocal)Irregular mass bordersPossible local invasion Liver biopsy Can provide a definitive diagnosis but carries the risk of bleeding and tumor spread Recommended when both lab and imaging studies are inconclusive Differential diagnoses Malignant liver tumors Metastatic liver diseaseEpidemiologyMost common malignant lesion of the liverTypical primary tumor site: gastrointestinal tract (colon, stomach, pancreas), lungs, and breastsDiagnostics Abnormal liver function testsUltrasound CT scan: typically multiple hypodense lesions (solitary metastases are very rare) Alternative: MRI Intrahepatic cholangiocellular carcinoma (CCC): second most common primary hepatic malignancy after HCC Hepatic angiosarcomaEpidemiology: third most common primary hepatic malignancyEtiology: associated with exposure to vinyl chloride, arsenic, and thorium dioxideHistology (biopsy): endothelial cells positive for PECAM-1 (CD31)Treatment: surgical resection +/- adjuvant therapy Prognosis: high rate of recurrence, poor overall prognosis Primary hepatic lymphoma Benign liver tumors Hepatic cyst Liver hemangioma Focal nodular hyperplasia (FNH) Hepatocellular adenoma with/without dysplasia Arteriovenous malformation Hepatic lipoma Regenerative liver nodules in cases of cirrhosis Treatment Curative therapeutic options: potentially for patients with retained liver function Surgical resection Liver transplantation Ablative therapies (mostly palliative, but can also be curative) result in shrinking and scarring of the tumor Follow-up: Vaccination against HBV in high-risk individualsSurveillance with ultrasound in patients with cirrhosis or chronic hepatitis B Palliative care: primarily for decompensated disease, unresectable, multinodular disease, or metastatic disease Complications May cause Budd-Chiari syndrome Metastasis (hematogenous): rare, usually only occurs in advanced stages

Typhoid and paratyphoid fever Typhoid and paratyphoid fever are infectious diseases caused by the bacteria Salmonella typhi and Salmonella paratyphi. Transmission occurs via the fecal-oral route. The incubation period is typically 7-21 days, although it may be as long as 30 days. Typhoid and paratyphoid fever classically have three clinical stages. In the first week of symptoms, body temperature rises gradually and relative bradycardia as well as diarrhea or constipation may occur. The second week of illness is characterized by persistent fever, rose-colored spots on the abdomen, nonspecific abdominal pain, and profuse diarrhea. During the third week, complications such as hepatosplenomegaly, intestinal bleeding, and/or perforation with secondary bacteremia and peritonitis may occur. Symptoms begin to subside in the fourth week. Pathogen detection in blood and stool cultures confirms the diagnosis. The treatment of choice includes fluoroquinolone antibiotics such as ciprofloxacin. Up to 6% of patients become chronic carriers after symptoms have resolved.

Epidemiology Globally, there are an estimated ∼ 22 million cases occur per year. Mainly in underdeveloped areas with poor sanitation In the United States, approx. 300 culture-confirmed cases of typhoid fever and 100 cases of paratyphoid fever are reported annually, mostly in individuals who have traveled to endemic regions. Etiology PathogenSalmonella: gram-negative rods; facultative anaerobes with peritrichous flagellaProduces hydrogen sulfide (H2S) on TSI agar; oxidase-negative; cannot ferment lactoseTyphoid fever: Salmonella typhi Paratyphoid fever: Salmonella paratyphi Transmission: fecal-oralDirect: person-to-person contact; asymptomatic carriers are frequently involved Indirect: contaminated food and water Humans are the main reservoir for Salmonella typhi! Salmonella have flagella, which allow them to swim like a salmon. Pathophysiology Lifecycle Oral uptake of pathogen Distal ileum: migration into the Peyer patches Infection of macrophages → nonspecific symptoms Spread from macrophages to the bloodstream: septicemia → systemic disease Migrates back to intestine → excretion in feces Clinical features General Incubation period: 5-30 days (most commonly 7-14 days) If left untreated, three different disease stages, each lasting a week, classically occur. After 3 weeks of disease: slow regression of symptoms; patients may become chronic Salmonella carriers (see "complications" below) Typhoid fever is a systemic disease; it is not limited to the gastrointestinal system! Typhoid fever must always be considered in the case of persistent fever of unknown origin and a history of travel to an endemicregion! Progression of illness Week 1 Body temperature rises gradually Relative bradycardia Constipation or diarrhea Headache Week 2 Persistent fever , but no chills; mostly unresponsive to antipyretics Nonspecific abdominal pain and headaches Rose-colored spots: In 30% of patients, a small, speckled, and rose-colored exanthem appears on the lower chest and abdomen (most commonly around the navel). Typhoid tongue: greyish/yellowish-coated tongue with red edges Yellow-green diarrhea, comparable to pea soup (caused by purulent, bloody necrosis of the Peyer patches), or obstipation and bowel obstruction (as a result of swollen Peyer patches in the ileum) Neurological symptoms (delirium, coma) Week 3 Clinical features of week 2 Additional possible complications include: Intestinal bleeding and perforation HepatosplenomegalyRarely causes sepsis, meningitis, myocarditis, and renal failure Diagnostics Laboratory testsAnemiaLeukopenia or leukocytosis [3]Abnormal liver function tests Pathogen detectionBlood cultures: Bacteremia is detectable starting in week 1 of the disease. Stool cultures Serology (Widal test) Blood culture is the most important diagnostic tool at disease onset, as stool cultures are often negative despite active infection! Treatment First-line treatment: fluoroquinolone antibiotics (e.g., ciprofloxacin) Azithromycin, if resistance to fluoroquinolone antibiotics is suspected (e.g., in patients with infection acquired from certain regions, such as South Asia) Third-generation cephalosporins (e.g., ceftriaxone) are preferred for severe infection. Complications Chronic Salmonella carrier Definition: positive stool cultures 12 months after overcoming the disease Incidence: up to 6% of the patients become chronic carriers Presentation: typically asymptomatic Increased risk for gallbladder cancer Treatment: fluoroquinolones (e.g., ciprofloxacin) administered for at least 1 monthChronic carriers are not allowed to work in the food industry. Prevention Food and water Vaccination is not entirely effective. Measure must therefore be implemented to avoid exposure (see food and water safety). Vaccination Indication: The WHO recommends typhoid fever vaccination to those traveling to high-risk areas (East and Southeast Asia, South and Central America, Africa). Administration: A parenteral, inactivated vaccine and an oral, live vaccine are available for active immunization, and both provide similar levels of protection. Inactivated vaccine: one intramuscular injection containing Vi polysaccharide, ideally administered at least 10 daysbefore traveling Live-attenuated vaccine: oral ingestion of capsules containing live attenuated S. typhi; ideally administered at least 10 days before traveling Overcoming an infection with Salmonella typhi/paratyphi does not confer lifelong immunity!Vaccination is not entirely protective! Reporting requirements Legislation varies from state to state. However, in general, physicians must report cases of typhoid/paratyphoid fever to their state's department of health.

Hepatitis A Hepatitis A infection is caused by the hepatotropic hepatitis A virus (HAV) and is usually transmitted via the fecal-oralroute. About half of all cases of HAV infection that occur in the US are acquired during visits to countries that are endemic for HAV (e.g., tropical or subtropical regions). HAV infection results in acute hepatitis with a clinical course characterized by prodromal symptoms of fever and malaise, followed by jaundice. As in any other case of acute viral hepatitis, high levels of serum transaminase and mixed hyperbilirubinemia are observed. Serological detection of anti-HAV IgM, which is elevated during an acute infection, confirms the diagnosis. While prodromal symptoms resolve within a few weeks, jaundice usually resolves within 1-3 months. No chronic sequelae occur and acute hepatic failureoccurs only in very rare cases. Therefore, supportive care is usually the only treatment required. As of 2006, routine immunization against hepatitis A is recommended for all children older than 12 months. Certain high-risk groups, such as tourists to areas where HAV is endemic, should also be immunized against HAV if they have not been vaccinated in the past. An important differential diagnosis is another feco-orally transmitted viral infection: hepatitis E (HEV). The clinical presentation of HEV is almost identical to that of HAV, with the exception that pregnant women are at a high risk of developing acute liver failure. Serological tests help to distinguish HEV from HAV.

Epidemiology Hepatitis A infection is the second most common cause of acute hepatitis in the US. Hepatitis A is very common in tropical and subtropical regions. Incidence (in the US): 2,000 cases per year (50% acquired during travels abroad) Etiology Pathogen: hepatitis A virus Belongs to the family of Picornaviridae and the genus Hepatoviridae. It is a small (27 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA Route of transmission: fecal-oralContaminated food, e.g., raw shellfish Risk groups: children, employees of day care centers, convicts, men who have sex with men Infectious period: 2 weeks before to 1 week after the onset of the illness When it comes to viral hepatitis, vowels (A and E) are bowels (i.e., transmitted feco-orally)! Pathophysiology HAV is not cytopathic in itself; research suggests that liver damage is caused by cellular immunity (especially CD8+ Tcells). Clinical features Incubation period: 2-6 weeks HAV infection in children is typically asymptomatic. The risk of symptomatic infection increases with age and coinfection (e.g., with hepatitis B). Acute viral hepatitis: three phases Prodromal phase: ∼ 1-2 weeksFever, malaiseAnorexia, nausea, vomitingRight upper quadrant pain and tender hepatomegalyIcteric phase: ∼ 2 weeks JaundiceDark urine and pale stools PruritusResolution of symptoms The mortality rate is 0.1-0.3% because few patients progress to acute liver failure. Patients do not become carriers nor develop chronic hepatitis (unlike in hepatitis B and C). Diagnostics Laboratory findings ↑↑ Serum transaminase (AST, ALT) Mixed hyperbilirubinemiaPossibly ↑ ALP, ↑ γ-GT Urine analysis: ↑ urine bilirubin, ↑ urobilinogen Confirmatory test↑ Anti-HAV IgM: active infection (Anti-HAV IgM antibody levels begin to rise 1 week after the onset of the illness and peak at around 3 weeks, after which point they decline. Anti-HAV IgM can be found in serum 3-6 monthsafter the infection.)↑ Anti-HAV IgG: past infection or vaccinationHAV RNA can be detected by PCR in stool and serum samples. Liver biopsy (not normally necessary): Periportal inflammation, ballooning degeneration, bridging necrosis, and Councilman bodies (apoptotic hepatocytes) Differential diagnoses For an overview comparing the different types of viral hepatitis: see differential diagnosis of viral hepatitis. Hepatitis E Pathogen: hepatitis E virus (HEV)The hepatitis E virus, which belongs to the family of Hepeviridae and the genus Orthohepeviridae, is a small (34 nmin diameter), non-enveloped virus with single-stranded, positive-sense RNA. Epidemiology: HEV is not common in the US. Route of transmission: fecal-oral Pathophysiology: the degree of hepatic injury is usually mild and the patient may present with clinical features of acute hepatitis Clinical features: Incubation period: 2-8 weeksClinical features are similar to those of hepatitis A (see "Symptoms/clinical findings" above).In the majority of cases, the disease is self-limiting with complete recovery. Fulminant hepatitis among pregnant womenPatients do not become carriers nor develop chronic hepatitis (unlike in hepatitis B and C). DiagnosticsLaboratory findings are the same as in hepatitis A.Confirmatory test Anti-HEV IgM: active infectionAnti-HEV IgG: past infectionHEV RNA can be detected by PCR in stool and serum samples. Treatment: supportive care Prevention: no vaccine available Fulminant hepatitis due to HEV is relatively common among pregnant women (occurring in up to 20% of cases) and is life-threatening for both the mother and fetus! Treatment Disease is self-limiting → supportive care. Prevention Hepatitis A pre-exposure prophylaxis Travelers should be advised to follow primary preventive measures such as hand-washing and following proper food and water safety Routine active immunization is now recommended for all children over 12 months consisting of a first IM dose of hepatitis A vaccine followed by a booster dose after 6 months (see also "Immunization schedule") Active immunization is also recommended for certain high-risk groups who have not been immunized in the past: Travelers to foreign countries where HAV is endemic.Men who have sex with menPatients with chronic liver disease Hepatitis A post-exposure prophylaxis Post-exposure prophylaxis is indicated for all previously unvaccinated individuals who have been exposed to a serologically confirmed case of HAV infection. In order to be effective, post-exposure prophylaxis should be administered within two weeks of exposure. Healthy individuals aged 1-40 years: active immunization with hepatitis A vaccine Infants, individuals older than 40 years, patients with chronic liver disease and/or immunosuppression: passive immunization with anti-HAV immunoglobulins Hepatitis A is a notifiable disease.

Colonic polyps Colonic polyps are abnormal colonic mucosal overgrowths. They are a common finding in people over the age of 50. In rare cases, they may be seen in younger individuals as part of hereditary polyposis syndromes (e.g., familial adenomatous polyposis, Peutz‑Jeghers syndrome, etc.). On macroscopic examination, colonic polyps are either pedunculated (with a stalk) or sessile (without a stalk). Histologically, colonic polyps are most commonly adenomas (∼ 70%), followed by hyperplastic polyps, and, rarely, serrated polyps and hamartomatous polyps. Colonic polyps may be benign or have malignant potential. Adenomas have the highest malignant potential (5%) and most colonic carcinomas arise from them (adenoma‑carcinoma sequence). Most patients are asymptomatic, but they may present with altered bowel habits, blood/mucus in stool, and iron deficiency anemia. Colonoscopy is the diagnostic modality of choice, since it allows for direct visualization of the polyps, biopsy, and therapeutic snare polypectomy (of pedunculated polyps) or endoscopic submucosal resection (of sessile polyps). Large polyps (> 2 cm) or malignant polyps require surgical resection.

Epidemiology Incidence increases with age: ∼ 30% of individuals > 50 years . Frequency∼ 70% are adenomatous polyps∼ 20% are hyperplastic polyps< 10% are other kinds of polyps (traditional serrated adenomas, sessile serrated adenomas, and mixed mucosal polyps). Sex: ♂ > ♀ Etiology The exact etiology is unknown. Risk factorsLifestyle Diet: high in red meat and fat; low in fiber and folic acid Obesity and lack of exerciseCigarette smokingAlcohol consumptionGenetic predisposition Black populations Hereditary polyposis syndromes Low malignant potential Hamartomatous polypsJuvenile polyposis syndromePeutz-Jeghers syndromeCowden syndromeCronkhite-Canada syndromeIncreased risk of colonic and extra-colonic malignancies Polyps throughout the GIT Autosomal dominant inheritance Inflammatory polyps(pseudopolyps)Seen in ulcerative colitis Multiple, benign polyps Mucosal polypsBenign Typically small < 5 mm Submucosal polypsBenign Submucosal lipoma (most common) Moderate malignant potentialSerrated polypsHyperplastic polyps Hyperplasia of normal cellular components and sawtooth/serrated pattern of crypt epitheliumMinimal risk of malignancy Small (< 5 mm)Common in distal colon (rectosigmoid) Sessile serrated polyps Morphology similar to hyperplastic polyps Risk of malignancy: ∼ 5%Sessile lesions > 5 mm in sizeCommon in proximal colon (ascending colon) Traditional serrated adenoma Serrated architecture with dysplasiaRisk of malignancy: ∼ 5%Common in rectosigmoid High malignant potential Adenomatous polyps Tubular adenoma Histology: proliferating cells form tubules Risk of malignancy: < 5%Frequency: ∼ 80%Location: anywhere in the colon Tubulovillous adenoma Histology: Mixture of tubular and villous histological pictureRisk of malignancy: ∼ 20%Frequency: 5-15% Villous adenoma Histology: finger-like projections lined by dysplasticepitheliumRisk of malignancy: ∼ 50% Frequency: 5-15%Location: common in the rectumLarger than other adenomas(cauliflower-like), and often sessile. The majority of colon carcinomas develop from adenomas (adenoma‑carcinoma sequence). However, only ∼ 5% of adenomasdevelop into colon cancers! Although villous adenoma is rarer than tubular adenoma, it has the highest malignant potential! Clinical features Mostly asymptomatic If symptomatic Blood in stool (hematochezia) is the most common symptom.Change in bowel habits (constipation/diarrhea)Mucus in stool Physical examination Pallor Digital rectal examination: for rectal polyps Hereditary polyposis syndrome Adenomatous polyposis syndromes Hamartomatous polyposis syndromes Adenomatous polyposis syndromes Familial adenomatous polyposis (FAP) InheritanceMutation of the tumor suppressor gene APC (adenomatous polyposis coli)Autosomal dominant (positive family history)Up to 25% of cases have a negative family history. EpidemiologyOccurs in one in 10,000-30,000 live births< 1% of colorectal cancers in the U.S. are due to FAPBoth sexes equally affectedPolyposis typically develops within the third decade of life Clinical featuresMost are initially asymptomatic until progressing to colon cancerAltered bowel habits (constipation/diarrhea), blood in stool, and abdominal painCongenital hypertrophy of the retinal pigment epithelium (CHRPE): multiple lesions in both eyes appearing in infancy DiagnosisFlexible sigmoidoscopy/colonoscopy: > 100 polyps are typically detected in the classic FAP [8]Genetic testing: detection of germline mutations in the APC gene establishes the diagnosis [9]Histology: tubular, tubulovillous, and villous adenomasDesmoid tumors (aggressive fibromatosis): extremely rare musculoaponeurotic fibromatoses. TreatmentScreening beginning at 10 years of age Prophylactic proctocolectomy + ileoanal anastomosis at time of diagnosis Screening upper endoscopy beginning at 25 years of age Medical adjuncts: Celecoxib (a COX-2 inhibitor) and sulindac (an NSAID) can cause regression of polyps. Prognosis: The lifetime risk of colorectal cancer is 100% by 45 years of age. Variants of FAPAttenuated FAPLesser polyps (> 10 but < 100), mainly in the right colonMore advanced age at presentation Lower risk (80%) of developing colorectal cancer than with classic FAPGardner syndromeFAP + extracolonic bony and/or soft tissue tumors (e.g., osteomas, desmoid tumors, sebaceous cysts, lipomas, fibromas)APC gene mutation with autosomal dominant inheritanceThe lifetime risk of developing colorectal cancer is 100%. Turcot SyndromeAdenomatous colonic polyps + brain tumorsAssociated with FAP and Lynch syndromeMedulloblastomas are associated with FAP and gliomas with Lynch syndrome. Primarily hamartomatous Peutz-Jeghers syndrome InheritanceAutosomal dominantNew mutations: 20% of cases Clinical features: 95% of patients have mucocutaneous hyperpigmentation that typically affects the lips (perioral lentigines), buccal mucosa, palms, and soles Enteroscopy: multiple hamartomatous polyps throughout the gastrointestinal tract PrognosisThe lifetime risk of colorectal cancer is ∼40%. Increased risk of ovarian, breast, and pancreatic cancer Juvenile polyposis syndrome (JPS) Etiology: autosomal dominant with incomplete penetrance Clinical features: Onset is within the first decade of life, often with gastrointestinal bleeding and anemia Colonoscopy: > 10 polyps throughout the gastrointestinal tract Cowden syndrome Etiology: autosomal dominant Clinical featuresMultiple GI polyps + skin manifestations such as papules and hyperkeratosis of the skin and mucous membranes Changes in the thyroid and mammary glands: > 50% of patients have thyroid disorders (e.g., multinodular goiter, adenomas, etc.) and benign breast disorders (e.g., fibroadenomas, intraductal papillomas, etc.). Cronkhite-Canada syndrome Etiology: probably immune-mediated (rare, nonfamilial disorder) Clinical features: GI polyposis with alopecia and cutaneous hyperpigmentation Treatment: immune suppression with glucocorticoids and azathioprine Diagnostics Laboratory testsFecal occult blood testHemoglobin levels: AnemiaGenetic studies: in patients with a strong family history of polyposis syndromes Imaging Virtual colonoscopy: Air contrast barium enema: can detect left-sided colonic polyps Flexible sigmoidoscopy Advantage: does not require extensive bowel preparation before the procedure. Disadvantage: The rest of the colon is not visualized. Colonoscopy (confirmatory test)Preferred screening tool for diagnosed cases of hereditary polyposes/colonic cancer Advantages: Enables biopsy, histological confirmation, and therapeutic polypectomy (see "Classification" above) Disadvantages: Requires bowel preparation with laxatives; Risk of bowel perforation. Treatment Treatment depends on the etiology and nature of the polyp or polyps. Snare polypectomy: of pedunculated polyps (< 2 cm in size) Endoscopic mucosal resection: large sessile polyps Surgical resectionFor large polyps (> 2 cm)For suspected malignancy: see colorectal cancerHereditary polyposis syndromes For follow‑up, see colorectal cancer prevention.

Carcinoid tumor Carcinoids are small, slow-growing neuroendocrine tumors. They are most commonly located in the gastrointestinal tractand can synthesize a variety of hormones (especially serotonin). Most carcinoids are asymptomatic because most of the hormones they produce are metabolized by the first-pass effect in the liver. Carcinoid syndrome - characterized by diarrhea, flushing, dyspnea, and wheezing - may occur if a serotonin-producing tumor has metastasized to the liver, bypassing first-pass metabolism. Elevated 5-HIAA in the urine helps to establish the diagnosis. Imaging techniques such as CT, MRI, and somatostatin receptor scintigraphy are used to detect the primary tumor as well as its metastases. Surgical resection is the first-line treatment. In inoperable cases, somatostatin analogs can be given.

Epidemiology Incidence: 1.5/100,000 per year Bimodal distribution: 15-25 years and 65-75 years (but can occur at any age) Pathophysiology Carcinoid tumors are neuroendocrine tumors. Tumor locationTumors appear most frequently in the gastrointestinal (GI) tract, especially in the intestines (55% of cases) Bronchopulmonary organ system (30% of cases)Carcinoid lung tumor Carcinoid tumors can synthesize different hormones (most commonly serotonin). Serotonin can reach systemic circulation under the following conditions: Intestinal carcinoid tumors with liver metastases Extraintestinal carcinoid tumors ↑ serotonin in systemic circulation leads toCarcinoid syndromeCarcinoid heart disease: endocardial fibrosis that especially affects the right heart (tricuspid and/or pulmonary valve). May cause pellagra (niacin deficiency) due to increased serotonin metabolism The rule of thirds for carcinoid tumors: ⅓ are multiple, ⅓ have a second malignancy, ⅓ metastasize. Clinical features Asymptomatic Abdominal pain Carcinoid syndromeDiarrhea and abdominal crampsCutaneous flushing Possible triggers: alcohol consumption, food intake, stressIn severe cases, may be accompanied by tachycardia and fluctuating blood pressureDyspnea, wheezing (asthma-like attacks)Possible weight loss despite normal appetitePalpitations Carcinoid heart disease Tricuspid insufficiency and/or pulmonary stenosisSymptoms of right-sided heart failure Possible pellagra (niacin deficiency)Presents as a triad of dermatitis, diarrhea, and dementia. In a patient presenting with secretory diarrhea, episodic flushing, wheezing, and cardiac valvular abnormalities, consider a carcinoid tumor! Subtypes and variants Carcinoid lung tumorClinical features May be asymptomaticCough, dyspnea, hemoptysis, recurrent pneumonia Carcinoid syndromeExcellent prognosisMetastasis is rare.Association with smoking is not as strong as with lung adenocarcinomaCan be centrally or peripherally located Diagnostics Biochemistry tests should be performed first if a carcinoid tumor is suspected. Imaging tests are then used to localize and stage the tumor. Biochemistry tests↑ 5-hydroxyindoleacetic acid (5-HIAA) in 24-hour urine↑ Serotonin serum levels ImagingCT scans of the abdomen and pelvisSomatostatin-receptor scintigraphy MRITransabdominal ultrasound: although not part of the workup, sometimes detects a mass if routinely conducted Biopsy (with histology and immunohistochemistry) Numerous small monomorphic cells with salt and pepper chromatinNeuroendocrine origin confirmed on immunostaining with synaptophysin, chromogranin A, and neuron-specificenolase (NSE) Differential diagnoses Angioedema Anaphylaxis Irritable bowel syndrome, celiac disease VIPomaDefinition: neuroendocrine tumor that secretes excess VIP (vasoactive intestinal polypeptide)PathophysiologyExcess VIP → increases relaxation of gastric and intestinal smooth muscles and adenylate cyclase (cAMP) activity (similar to cholera toxin) → secretory diarrhea and inhibition of gastric acid productionVIP also stimulates vasodilation, bone resorption, and glycogenolysisAssociated with MEN1 syndrome (5% of cases)Tumor location: The primary tumor is most frequently found in the pancreas. Clinical featuresWDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria)Tea-colored watery diarrhea (> 700 mL/day) → dehydrationWeight lossAbdominal pain, nausea, vomitingAchlorhydria → ↓ iron and B12 absorption → anemiaDiagnosis↑ Serum VIP concentration (> 75 pg/mL)Hypokalemia, hypercalcemia, hyperglycemiaGastric achlorhydria or hypochlorhydria CT scan to localize the primary tumorTreatment: tumor resection or octreotide Treatment Operable diseaseSurgical resection is the treatment of choice. The exact procedure depends on the location of the tumor: In the small intestine → resection of the affected segment and mesenteryIn the appendix → appendectomy Inoperable disease Somatostatin analogs (e.g., octreotide) relieve symptomsTryptophan hydroxylase inhibitor (e.g., telotristat) as adjunctive therapy if diarrhea is not controlled with somatostatin analogsRadiotherapy with radioactively-marked somatostatin analogs: indicated for neuroendocrine tumors expressing somatostatin receptors

Irritable bowel syndrome Irritable bowel syndrome (IBS) is a common chronic condition affecting 20-50% of patients with gastrointestinal complaints. The exact pathophysiology is unknown, but may involve changes in gastrointestinal motility, visceralhypersensitivity, and altered gastrointestinal permeability. The condition presents with recurrent, non‑specific changes in bowel movements (e.g., diarrhea and/or constipation) and abdominal symptoms (e.g., diffuse pain, pressure). The Rome IV diagnostic criteria, which are based on alterations in bowel habits, are used to diagnose IBS. Laboratory studies and imaging reveal no abnormalities. Treatment consists of dietary modifications and administration of symptom‑based medication (antidiarrheals, laxatives, antispasmodics).

Epidemiology Prevalence: 10-20% in North America and Europe (accounts for 20-50% of referrals to gastroenterologists) Sex: In Western countries, women are 1.5-2 times more likely to be affected than men. Age: highest prevalence in individuals aged 20-39 Pathophysiology IBS is a functional gastrointestinal disorder without a specific organic cause. The pathophysiological processes leading to IBS are multifaceted and not yet fully understood. The most common findings associated with IBS are: Altered gastrointestinal motility Visceral hypersensitivity/hyperalgesia Altered permeability of the gastrointestinal mucosa Psychosocial aspects Clinical features IBS is characterized by chronic abdominal pain and changes in bowel habits - both of which are typical, but not specific, symptoms of the condition. Abdominal painFrequency, intensity, and localization generally vary widely from patient to patientTypically alleviated by defecation Altered bowel habits: diarrhea and/or constipation Other gastrointestinal symptomsNausea, reflux, early satietyPassing of mucus, abdominal bloating Extraintestinal symptomsGeneralized somatic symptoms (e.g., pain or fatigue, as in fibromyalgia)Disturbed sexual functionDysmenorrheaIncreased urinary frequency and urgency Physical examination: normal Red flag symptoms: nighttime diarrhea and abdominal pain, fever, bloody stools, weight loss and acute onset of symptoms! Subtypes and variants Four different patterns are seen in the presentation of irritable bowel syndrome: IBS‑D (diarrhea is the predominant symptom) IBS‑C (constipation is the predominant symptom) IBS‑M (mixed diarrhea and constipation) IBS‑A (alternating diarrhea and constipation) Diagnostics IBS is a clinical diagnosis based on the patient's history (Rome IV criteria) and symptoms. However, any suspected differential diagnoses should be ruled out before making a definitive diagnosis. Patient history Rome IV criteria for irritable bowel syndrome: diagnosis can be made if the following criteria are present Recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with 2 or more of the following: Pain related to defecationChange in stool frequencyChange in stool form or appearance Other symptoms consistent with IBS (see "Symptoms/clinical findings") A family history of inflammatory bowel disease, celiac disease, or colorectal cancer is unusual in patients with IBS. Ruling out organic disease If no other differential diagnosis is suspected, laboratory tests and imaging are generally not recommended for individuals under the age of 50 if they show typical signs of IBS and lack any alarming signs, such as iron-deficiency anemia, weight loss, or a family history of organic gastrointestinal diseases. Differential diagnoses Irritable bowel syndromeHealthy; no weight lossAlleviated by defecation; diffuse; no nighttime painDiarrhea or constipation, possibly alternating; no blood; no nighttime diarrhea Crohn's diseaseWeight loss; malnourishmentUsually constant; occurs particularly in the right lower abdomen; may appear at nightNon‑bloody, watery diarrhea; increased frequency; possible nighttime diarrhea Ulcerative colitisWeight loss only in severe casesMostly left lower abdomen; may occur at nightBloody diarrhea with mucus Colorectal carcinomaWeight lossOften no painRight-sided carcinomas: melena, diarrheaLeft-sided carcinomas: constipation Other differential diagnoses to consider Bacterial or viral gastroenteritis Hypothyroidism/hyperthyroidism Celiac disease Lactose intolerance Bacterial overgrowth syndrome Treatment General measures Regular consultations and reassurance that the disease, although chronic, is benign Lifestyle changes Dietary adjustments Plenty of fluidHigh‑fiber foods Avoidance of: Gas‑producing foods (e.g., beans, onions, prunes)Fermentable, short‑chain carbohydrates (e.g., foods with high fructose content: honey, apples, corn syrup) Lactose Gluten Physical activityStress management (identification of stress factors, avoidance techniques, relaxation therapy) Psychological therapy (patients with psychological conditions): e.g., cognitive-behavioral therapy Medical therapy Medical therapy of IBS is symptom‑directed: DiarrheaAntidiarrheals (loperamide) ConstipationSoluble fibers/bulk‑forming laxatives (psyllium)Osmotic laxatives (polyethylene glycol)Lubiprostone (chloride channel activator) Cramping/painAntispasmodics (dicyclomine, hyoscyamine) Tricyclic antidepressants (e.g., amitriptyline, nortriptyline)

Pyogenic liver abscess A pyogenic liver abscess is a rare disease characterized by solitary/multiple collections of pus within the liver. The infection is caused by bacteria and is usually polymicrobial, with E. coli and K. pneumoniae being the common causative organisms. The majority of cases are caused by ascending infection from a biliary tract pathology (e.g., cholangitis due to choledocholithiasis, i.e. biliary strictures). Due to the liver's dual blood supply from the portal vein and the hepatic artery, an infectious focus in the gastrointestinal tract or bacteremia exposes the liver to high bacterial loads. Patients, typically middle-aged/elderly males, present with non-specific symptoms, such as fever, malaise, and weight loss. Right upper quadrant pain and tender hepatomegaly are specific features of a liver abscess but are often absent. Diagnosis is confirmed on abdominal imaging (ultrasound or CT), which demonstrates intrahepatic fluid-filled lesions with surrounding edema. Broad-spectrum IV antibiotics (ampicillin + sulbactam) and percutaneous/surgical drainage of the abscess cavity is the mainstay of treatment. Complications include sepsis, pneumonia, and abscess rupture into the peritoneum/thorax. Advancements in diagnostics and treatment have reduced the complications and mortality rates of pyogenic liverabscesses.

Epidemiology Incidence: 2-3 cases per 100,000 people in the United States Peak incidence: 50-60 years Sex: slight male predominance Etiology Risk factors Diabetes mellitus Hepatobiliary disease (e.g., cholelithiasis, transplant recipients, hepatic tumors) Pancreatitis Gastrointestinal malignancy (esp. colorectal carcinoma) Crohn's disease Biliary tract (∼ 60%): Most common cause Choledocholithiasis Biliary strictures Cholangitis Portal vein (∼ 20%) Acute appendicitis Diverticulitis Crohn's disease Gastrointestinal malignancies Peritonitis (bowel perforation) Hepatic artery (∼ 15%) Sepsis Bacteremia (infectious endocarditis, IV drug use) Contiguous area (< 5%) Subphrenic abscess Perinephric abscess Pancreatic abscess Trauma (Rare) Penetrating trauma (e.g. gunshot or surgery) Blunt trauma Others Cryptogenic (∼ 20%) Secondary infection of hepatic tumors Secondary bacterial infection of amebic liver abscess Secondary infection of hydatid cyst of the liver Hepatic chemoembolization Microbiology Pyogenic liver abscess (80% of liver abscesses)Polymicrobial infection (most common)E. coli is the most common causative organism.K. pneumoniae is the second most common. Other causative bacteria: Enterococci, Streptococci, Staphylococcus aureus, Proteus vulgaris, anaerobes Non-pyogenic liver abscessFungal infection (< 10% of cases): Candida species (most common) Amebic liver abscess (< 10% of cases): Entamoeba histolytica Clinical features Classic triad of pyogenic liver abscess Fever (with/without chills and rigors) MalaiseRight upper quadrant pain Other symptomsAnorexia and weight lossNausea and vomitingSymptoms of diaphragmatic irritation Physical examinationJaundiceTender hepatomegalyIntercostal tenderness Epigastric tenderness Decreased breath sounds in right lower lobe of the lung Features of sepsis The symptoms of pyogenic liver abscess are often non-specific (e.g., fever, weight loss, etc.). Diagnostics Laboratory tests Complete blood count: neutrophilic leukocytosis, normocytic normochromic anemia Liver function tests: ↑ alkaline phosphatase (90%), ↑ AST and ALT, hypoalbuminemia, hyperbilirubinemia Inflammatory markers: ↑ ESR and CRP Blood culture: positive in ∼ 50% of cases Imaging Abdominal imaging is a confirmatory test for pyogenic liver abscess Abdominal ultrasound (US): seen as solitary/multiple, poorly demarcated, fluid-filled, round hypoechoic lesion(s) within the hepatic parenchyma with surrounding edema and hyperemia . Abdominal CT scan: Findings are similar to those on abdominal ultrasound; a peripheral rim enhancement is seen on IV contrast administration. Percutaneous aspiration and culture of the aspirate Both diagnostic and therapeutic (see "Treatment" section below) Performed under US or CT guidance Aspirated material is cultured to determine the organism and its antibiotic-susceptibility profile. Differential diagnoses Pyogenic liver abscesses need to be differentiated from other space-occupying lesions of the liver. Amebic liver abscess Hepatic echinococcosis (hydatid cyst of the liver) Hepatic cysts Benign liver tumors Hepatocellular carcinoma Liver metastases Treatment Pyogenic liver abscesses are generally treated with both IV antibiotics and percutaneous drainage of the abscess. Some patients may require surgical drainage. Antibiotics Indicated in all cases Broad-spectrum IV antibiotics: ampicillin + sulbactam; piperacillin + tazobactam; 3rd generation cephalosporin+ metronidazole (until antibiotic susceptibility is available) Drainage of the abscess cavity Indicated in nearly all cases of pyogenic liver abscess Indication for percutaneous drainage/needle aspiration: solitary abscess Small (< 5 cm) abscess: percutaneous needle aspirationLarge (> 5 cm) abscess: percutaneous drainage and intracavitary catheter placement If percutaneous drainage/aspiration fails, a second attempt at percutaneous drainage/aspiration can be made before abscess will require surgical drainage. Indications for surgical drainage (open/laparoscopic)Multiple or loculated abscessesDeep-seated abscess not amenable to percutaneous drainageRuptured abscessThick viscous pus which cannot be drained percutaneouslyUnderlying disease which requires surgical intervention (e.g., choledocholithiasis, appendicitis, etc.) Contraindications: coagulopathy (e.g., international normalized ratio (INR) > 1.5; thrombocytopenia due to sepsis) The underlying etiology (e.g, choledocholithiasis, biliary stricture, etc.) should also be treated to prevent recurrent pyogenic liverabscesses. Complications Rupture Into the abdomen → peritonitisInto the chest → empyemaInto the retroperitoneum → retroperitoneal abscess Sepsis Pneumonia Pleural effusion Prognosis Mortality ratesUntreated pyogenic liver abscess: 100%With treatment: ∼12 % Poor prognostic factorsPyogenic abscess with sepsisAdvanced age (> 70 years)Multiple abscessesPolymicrobial infection; anaerobic infectionImmunosuppression (e.g., malignancy, diabetes)Need for surgical drainage

Peptic ulcer disease Peptic ulcer disease (PUD) refers to the presence of one or more ulcerative lesions in the stomach or lining of the duodenum. Possible etiologies include infection with the bacterium Helicobacter pylori (most common), prolonged use of nonsteroidal anti-inflammatory medicines (possibly in combination with glucocorticoids), conditions associated with an overproduction of stomach acid (hypersecretory states), and stress. Epigastric pain is a typical symptom of PUD, however, some patients may remain asymptomatic. Diagnosis occurs via direct visualization of the ulcer on esophagogastroduodenoscopy (EGD) and H. pylori detection (via biopsy or non-invasive testing). The first-line treatment for most peptic ulcers involves H. pylori eradication via triple therapy (a course of two different antibiotics in combination with a proton-pump inhibitor) and the withdrawal of offending agents. Antisecretory drugs (e.g., proton-pump inhibitors, or PPIs), which reduce stomach acid production, are continued for 4-8 weeks after eradication therapy and may be considered for maintenance therapy if symptoms recur. Surgical intervention may be necessary in rare cases, especially if complications such as perforation or massive bleeding occur. Stomach cancer is an important differential diagnosis and must be ruled out if risk factors are present.

Epidemiology Incidence: > 6 million cases annually in the US Duodenal ulcers are 3 times more common than gastric ulcers. Duodenal ulcers occur on average 10-20 years earlier than gastric ulcers.Sex: ♂ = ♀ Etiology Risk factorsChronic gastritis caused by H. pylori, a curved, flagellated gram-negative rodDuodenal ulcers: up to 90% are due to H. pylori infectionGastric ulcers: up to 80% are due to H. pylori infectionChronic gastritis of other etiology Long-term use of NSAIDs (e.g., patients with rheumatoid arthritis, SLE, etc.): Risk for gastroduodenal ulcers increases 5-fold.NSAID use seems to have a stronger association with gastric ulcers than with duodenal ulcers.Long-term use of NSAIDs plus glucocorticoids: Risk increases 10 to 15-fold! SSRIsSmokingChronic alcohol consumptionPatients with blood type O have a higher risk for duodenal ulcers. Age > 65 yearsStress (see "Subtypes and variants" below)Rare risk factors: Zollinger-Ellison syndrome (can result in duodenal ulcer)Hyperparathyroidism Classification Gastric ulcer: an ulcerative lesion in the stomach lining; typically manifests along the lesser curvature and the gastric antrum Duodenal ulcer: an ulcerative lesion located in the duodenum, typically in the first part (i.e., the duodenal bulb) Erosive gastritis: acute mucosal inflammation of the stomach that does not extend beyond the muscularis mucosae An atypical location is suspicious for carcinoma! Pathophysiology Gastric secretions Parietal cellsSecrete hydrochloric acid (HCl) and intrinsic factorStimulated by acetylcholine, histamine, and gastrinInhibited by prostaglandins and somatostatin Mucosal cellsSecrete protective mucusStimulated by acetylcholine, prostaglandins, and secretin Chief cellsSecrete pepsinogenStimulated by acetylcholine, gastrin, secretin, and vasoactive intestinal polypeptide (VIP) Disturbances Helicobacter pylori gastritis: increased acid secretion, decreased protective factors/mucus production NSAIDs inhibit COX-1 and COX-2 → decrease in PGE2 (normally decreased gastric acid secretion and increased HCO3- and mucus secretion) → gastric mucosa erosions Findings common to both Dyspepsia: postprandial heaviness, early satiety, and gnawing, aching or burning epigastric pain Pain relief with antacids Potential signs of internal bleeding (anemia, hematemesis, melena) ∼ 70% of patients with PUD are asymptomatic Stool sample positive for occult blood (see gastrointestinal bleeding) Gastric ulcer Pain increases shortly after eating → weight loss Nocturnal pain30-40% of patients Duodenal ulcer Pain increases 2-5 hours after eating Pain on an empty stomach (hunger pain) that is relieved with food intake →weight gain Noturnal Pain 50-80% of patients Gastric ulcer is associated with pain after light (weight loss) Gorging. Duodenal ulcer is associated with relief after massive(weight gain) Desserts. Taking NSAIDs can often mask PUD symptoms until complications such as hemorrhage and perforation occur! Subtypes and variants Dieulafoy's lesionDescription: In this rare disease, minor mucosal trauma can lead to major bleeding. It is caused by an abnormal submucosal artery.Location: proximal stomachClinical presentation: signs of acute upper GI bleedingTreatment: endoscopic hemostasis (injection therapy, hemoclips, etc.), excision of the susceptible mucosa Stress ulcer Causes: polytrauma, major surgery, SIRS, kidney failure, etc.Types Curling ulcer: severe burns → decreased plasma volume → decreased gastric blood flow → hypoxic tissue injury of stomach surface epithelium → weakening of the normal mucosal barrierCushing ulcer: In patients with brain injury, increased vagal stimulation leads to increased production of stomach acid via acetylcholine release.Management: stress ulcer prophylaxis Nonulcer dyspepsia: Symptoms including bloating, nausea, and belching persisting ≥ 3 months without organic cause (synonym: functional dyspepsia). Diagnostics Diagnostic approach ≤ 60 years of age without alarm features: Urea breath test for H. pylori > 60 years of age or presence of ≥ 1 alarm features: EGD with biopsies and rapid urease testing for H. pylori Negative for H. pylori infection and NSAID intake; trial therapy unsuccessful Measure serum gastrin level at baseline and after secretin stimulation test: high levels in gastrinoma (Zollinger-Ellison syndrome)Measure serum calcium and parathyroid hormone: high levels in primary hyperparathyroidism Testing for Helicobacter pylori See "Helicobacter pylori diagnostics" Esophagogastroduodenoscopy (EGD) Most accurate test Patients > 60 years of age or presence of ≥ 1 alarm features, which include: Certain symptoms: progressive dysphagia, painful swallowing (odynophagia), and/or persistent vomitingSigns of active GI bleeding (e.g., melena, unexplained iron-deficiency anemia)Signs of malignancy (e.g., unintended weight loss, lymphadenopathy, palpable mass)Family history of upper GI malignancy in a first-degree relativeJaundice Biopsy samples from: Edge and base of the ulcer (essential to rule out malignancy) .Stomach lining distant from the ulcer (Helicobacter pylori testing for detection of underlying type B gastritis) If active bleeding, EGD can be performed for diagnosis and subsequent hemostasis treatment (electrocautery) in the same session. Alarm features of PUD include progressive dysphagia, odynophagia, persistent vomiting, jaundice, signs of GI bleeding, signs of malignancy, and a family history of upper GI malignancy! To rule out gastric cancer, patients with stomach ulcers should undergo follow-up EGD and histology until the ulcer has healed completely! Treatment General management of dyspepsia H. pylori positive → eradication therapy (with antibiotics and a PPI) and supportive treatment → continue PPIs for 4-8 weeks → follow-up H. pylori negative → medical acid suppression (with a PPI) and supportive treatment for 4-8 weeks → follow-up Medical treatment Helicobacter pylori eradication therapy (with antibiotics) Acid suppression: PPIs (most effective), H2 blockers, antacids (mainly used for symptom relief) Mucosal protection: misoprostol , sucralfate (both substances are rarely used in PUD) Supportive treatment Discontinue NSAIDs Restrict alcohol use/smoking/emotional stress Avoid eating before bedtime Surgical treatment With the advent of potent acid suppression in the form of PPIs, surgical intervention is rarely needed. IndicationsRefractory syndromes despite appropriate medical treatmentIf cancer is suspectedComplications that cannot be treated endoscopically (see "Complications" below) Partial gastrectomy (Billroth)Billroth I: distal gastrectomy with end-to-end or side-to-end gastroduodenostomy Billroth II: resection of the distal ⅔ of the stomach with a blind-ending duodenal stump and end-to-sidegastro-jejunostomy. The Billroth I and II methods without a Brown's anastomosis often lead to bile reflux into the stomach. This may result in type C gastritis in the region of the anastomosis. The chronic inflammation causes atrophic changes and increases the risk of cancer (anastomosis carcinoma). Vagotomy Complications Bleeding (see gastrointestinal bleeding)Most common complication of PUDLocated posterior more commonly than anteriorPerforated gastric ulcers of the lesser curvature may cause hemorrhage of the left gastric artery.Duodenal ulcers of the posterior wall are more likely to cause massive bleeding because of their proximity to the gastroduodenal artery. Gastric/duodenal perforation (see also secondary peritonitis and gastrointestinal perforation) Second most common complication of PUDLocated anterior more commonly than posterior Duodenal ulcers of the anterior wall are more likely to perforate into the abdominal cavity, causing pneumoperitoneum (free air below the diaphragm) and irritation of phrenic nerve (e.g., shoulder pain). Subhepatic abscessEtiology: may result from a perforated duodenal or gastric ulcerClinical presentation: fever and vomiting (see also "Gastric/duodenal perforation" above)Diagnosis: subhepatic gas on abdominal x-rayManagementTreat underlying causeIV antibiotics, percutaneous drainageSee also "Therapy" in pyogenic liver abscess. Gastric outlet obstruction (GOO) Definition: mechanical obstruction of the pyloric channel or duodenumEtiologyMalignancy (most common) PUD Acute PUD → inflammation and edemaChronic PUD → scarring and fibrosisGastric volvulusLess common causes that cause strictures in the pyloric channel: Crohn disease, history of ingestion of a caustic substance, chronic pancreatitisClinical presentationPostprandial, nonbilious vomitingSuccussion splash Early satietyProgressive gastric dilationWeight lossDiagnosis Barium swallow Upper endoscopy (confirmatory test): identification of the gastric pathologyLaboratory tests: hypokalemic hypochloremic metabolic alkalosisSaline load test ManagementSymptomatic: nasogastric suction, electrolyte and fluid replacement, and parental nutritionDefinitive: surgery or endoscopic dilation Fistula formation Clinical presentationIncreased severity of pain, which is no longer relieved by eating; radiation of pain to the backWeight loss, diarrhea Malignant transformationGastric ulcers: high malignant potential (progression to cancer in 5-10% of cases) → malignancy should be ruled out with biopsy [21]Duodenal ulcers: usually benign → routine biopsy is not required Postgastrectomy syndromes Posterior ulcers are more likely to bleed and anterior ulcers are more likely to perforate: Postal workers wear Blue collars and should not have an Antisocial Personality. Prevention Recurrence prophylaxis Smoking cessation and avoidance of other offending agents such as alcohol Reduce coffee consumption Avoid medications that are associated with the development of ulcersNSAIDs GlucocorticoidsSSRIs Rule out: Zollinger-Ellison syndrome, hyperparathyroidism Successful H. pylori eradication therapy Stress ulcer prophylaxis PPIs or H2 blockers Indicated in severe organic disease/stress → shock, acidosis, brain trauma, severe burns, major surgery Disadvantage of prolonged PPI intake: potentially higher risk of pneumonia and gastroenteritis!

Colorectal cancer Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both women and men in the United States. Risk factors include a positive family history, hereditary syndromes, diet, and a number of conditions, such as inflammatory bowel disease. Most colorectal cancers are adenocarcinomas (95%). Clinical signs are often nonspecific and may include a change in bowel habits, rectal bleeding, and weight loss. Iron deficiency anemia in men > 50 years and postmenopausalwomen should be considered a warning sign for CRC. Since the introduction of screening with colonoscopy or sigmoidoscopy and fecal occult blood testing, early stage carcinomas have become easier to diagnose in asymptomatic patients. Complete colonoscopy with histopathologic analysis confirms the diagnosis. Staging of the cancer is necessary to evaluate the extent of the disease and determine the appropriate treatment. Curative surgical resection of colorectal cancers and metastases is the preferred method of treatment. Colon cancers are resected via hemicolectomy, while rectal cancers are preferably resected via low anterior resection with total mesorectal excision. Resection is complemented by adjuvant chemotherapy for colon cancer, and neoadjuvant and adjuvant chemoradiation for rectal cancer. Regular follow-ups are recommended after surgical resection.

Epidemiology Incidence: ∼ 130,000 new cases per year Third most common cancer in women and men Age: continuous increase in incidence after the age of 50 Mortality: third leading cause of cancer-related deaths in the US overall Etiology Predisposing factors Colorectal adenomas (see colonic polyps) Family history Hereditary syndromes Familial adenomatous polyposis: 100% risk by age 40 Hereditary nonpolyposis colorectal cancer (HNPCC): 80% progress to CRC. Conditions associated with an increased risk of colorectal cancerInflammatory bowel disease (IBD): ulcerative colitis and Crohn's diseaseChronic inflammation → hyperplasia → non-polypoid dysplasia→ neoplasiaEndocarditis and bacteremia due to Streptococcus gallolyticus is associated with CRC. Diet and lifestyle SmokingAlcohol consumptionObesityProcessed meat; high-fat, low-fiber diets Older age Protective factors Physical activity Diet rich in fiber and vegetables and lower in meat Long-term use of aspirin and other NSAIDs Clinical features Often asymptomatic, particularly during the early stages of disease Nonspecific symptoms: constitutional symptoms (weight loss, fever, night sweats), fatigue, abdominal discomfort In general, right-sided tumors chronically bleed, and left sided tumors cause obstruction Symptoms according to locationRectosigmoid > ascending colon > descending colonRight-sided carcinomas (10%): cecum and ascending colonIron deficiency anemiaMelenaDiarrheaLeft-sided carcinomas (10%): transverse and descending colonChanges in bowel habits (size, consistency, frequency) Blood-streaked stools Colicky abdominal pain due to obstruction Rectum (50%) and sigmoid (30%) Hematochezia↓ Stool caliber (pencil-shaped stool)Rectal painTenesmusFlatulence with involuntary stool loss Symptoms according to stage of diseaseAdvanced disease Palpable abdominal massIntestinal obstruction or perforationMetastatic disease: 20% of patients already have distant metastasis on initial diagnosis. Liver metastases : abdominal distention, hepatomegaly, ascitesLung metastases : dyspnea, cough, hemoptysis, pleural effusionLymphatic spread to mesenteric, para-aortic, and pelvic lymph nodes Colorectal cancer must be ruled out in a patient presenting with rectal bleeding, even if the patient has a history of hemorrhoids! Iron deficiency anemia in men > 50 years and postmenopausal women should be considered a sign of colorectal cancer until proven otherwise! The stages of colorectal cancer are based on the TNM staging system by the American Joint Committee for Cancer (AJCC). AJCC staging(simplified)TNM stageCorresponding Dukes classification stageDescriptionIUp to T2, N0, M0AInvasion of submucosaIIUp to T4, N0, M0BInvasion of muscularis propria but no lymph node involvement IIIAny T, N1/N2, M0CInvasion of subserosa or beyond (e.g., pericolic and perirectal fat) with no involvement of other organs but with lymph node involvementIVAny T, any N, M1DInvasion of visceral peritoneum or adjacent organs (distant metastasis) Diagnostics Work-up of colorectal cancer is indicated in symptomatic patients and asymptomatic patients with abnormalities detected during routine screening. Initial work-up Digital rectal examination: Up to 10% of cancers are palpable! Complete colonoscopy: gold standard Complete surveillance of the colon is mandatory!If colonoscopy is incomplete → perform double-contrast barium enemaApple-core lesion In up to 5% of cases, multiple adenocarcinomas are present. A complete colonoscopy is necessary to rule out additional tumors! Staging and further tests Determine the extent of local and distant disease Endorectal ultrasound: determine depth of tumor infiltration CT of abdomen, pelvis, and chestCXR Tumor marker: carcinoembryonic antigen (CEA) serum levels prior to initiating treatment Pathology Adenocarcinoma (most common): 95% arise from adenomatous polyps Chromosomal instability pathway in colon cancer: The adenoma-carcinoma sequence is the progressive accumulation of mutations in oncogenes (e.g., KRAS) and tumor suppressor genes (e.g., APC, TP53) that results in the slow transformation of adenomas into carcinomas. APC gene mutation (loss of cellular adhesion and increased cellular proliferation) → KRAS gene mutation (unregulated cellular signaling and cellular proliferation) → TP53 and DCC gene mutation (malignant transformation of adenoma to carcinoma) Microsatellite instability pathway in colon cancer: due to methylation or mutations in mismatch repair genes MLH-1 and MSH-2 COX-2 overexpression: associated with colorectal cancer. Thus, the possible protective effect of long-term use of aspirin and other NSAIDs 95% of all colorectal cancers are adenocarcinomas! Differential diagnoses Small bowel neoplasms EpidemiologyLess than 5% of all gastrointestinal cancersMainly benign lesions (> 95%)Malignant small bowel cancers (1-3%) 40% adenocarcinoma30% neuroendocrine tumors20% lymphoma10% gastrointestinal stromal tumors (GIST), leiomyosarcoma, liposarcoma, metastatic disease ComplicationsBleedingIleusMetastatic spreadCarcinoid syndrome in the case of neuroendocrine cancers of the small bowel Diagnostics: ultrasound, hydro-MRI, capsule endoscopy Treatment: resection of the small bowel; R1 resection requires adjuvant chemotherapy Prognosis (if malignant)5-year survival rate: ∼ 20% Treatment Treatment primarily depends on the location of the tumor and the TNM stage. Colon cancer Curative approach: any primary tumor with or without regional spread; resectable metastases in the liver and/or lungTreatment involves surgical resection and adjuvant chemotherapy. Palliative approach: distant metastases beyond the liver and/or lung or if the patient is not a surgical candidate due to poor general health Treatment involves palliative chemotherapy. Surgical management Colectomy: The extent of the resection depends on the location of the tumor. Open approach or laparoscopic approach Right hemicolectomy Arterial blood supply: ileocolic, right colic, and right branch of the middle colic artery arising from the superior mesenteric arteryExtended right hemicolectomy: if the tumor is in the proximal or middle transverse colon Left hemicolectomy Arterial blood supply: left colic artery arising from the inferior mesenteric artery Sigmoid colectomy Total abdominal colectomy: indicated for hereditary and multifocal carcinomas Regional lymph node dissection (for pathologic staging) Resection of resectable metastases in liver and/or lung Systemic therapy ChemotherapyAdjuvant chemotherapy if lymph nodes are positive (Stage III) Palliative chemotherapy for metastatic disease (Stage IV) Regimens FOLFOX: FOLinic acid (leucovorin) + 5-Fluorouracil (5-FU) + OXaliplatin FOLFIRI: FOLinic acid (leucovorin) + 5-Fluorouracil (5-FU) + IRInotecan XELOX: capecitabine (XELoda ®) + OXaliplatin Biologicals: Anti-VEGF antibodies (e.g., bevacizumab) or EGFR antibody (e.g., cetuximab) may be added to the chemotherapy regimen for metastatic disease. Radiation therapy: not a standard modality for treatment of colon cancer Radiation therapy is not a standard modality in the treatment of colon cancers! Rectal cancer Surgical management Transanal excisionProcedure: minimally invasive excision of small superficial tumorsIndications: early, localized disease (stage I) Low anterior resection (LAR)Procedure: sphincter-preserving resection of the rectum and sigmoid Total mesorectal excision (TME): en bloc excision of the mesorectum , regional lymph nodes, and vasculature Resection 5 cm beyond the proximal margin of the tumorResection > 2 cm beyond the distal margin of well-differentiated tumors or > 5 cm beyond the distal margin of poorly differentiated tumorsReconstruction (e.g., side-to-side anastomosis) and optional diverting ostomyIndications: locally advanced disease (Stage III-IV) The completeness of the TME has a strong impact on the prognosis! Abdominoperineal resection (APR)Procedure: resection of the rectum, sigmoid, and anus with TME and permanent colostomyIndications: last resort if the distal margin to the rectum cancer is < 2-5 cm to the anus Palliative procedures include transanal excision or diverting colostomy to facilitate defecation. Systemic therapy Neoadjuvant radiochemotherapy: locally advanced disease (stages II-III) typically followed by surgery and postoperative chemotherapy Adjuvant chemotherapy after surgical resection depending on the pathologic work-up Palliative chemotherapy: inoperable, metastatic disease (stage IV) Follow-up Monitor patients for 5 years following the completion of treatment Patient history, physical examination, CEA level: every 3-6 months for 3 years, then every 6 months for 2 yearsElevated CEA warrants further evaluation to determine site of recurrence or metastasis with CT of the chest and abdomen, PET, and/or colonoscopy.Colonoscopy: after surgical resection, then 1 year after surgery, then every 3-5 years 85% of recurrences occur within the first three years following treatment! Prognosis Overall 5-year survival rate: 65% Survival rate according to disease stage Stage I: 95%Stage II: ∼ 80% [31]Stage III: 60%Stage IV: 5-10% Prevention Screening for colorectal cancer Screening for colorectal cancer and adenomatous polyps is performed in asymptomatic men and women ≥ 50 years of age. Low-risk individuals: several options Complete colonoscopy (gold standard): Repeat every 10 years if no polyps or carcinomas are detected. Annual fecal occult blood test (FOBT): screening for occult bleeding, which may indicate colorectal cancer Sigmoidoscopy every 5 years and FOBT every 3 yearsAnnual fecal immunochemical testing (FIT) CT colonography every 5 years High-risk individuals Complete colonoscopy 10 years earlier than the index patient's age at diagnosis or no later than 40 years of ageIn case of genetic predisposition: individual screening (see FAP and HNPCC for details) Histology of removed polypRecommended interval until next control colonoscopyHyperplastic polyp < 10 mm in size in the rectum or sigmoid10 yearsLow risk adenoma: 1-2 tubular polyps < 10 mm in size and without intraepithelial neoplasia (IEN)5-10 yearsHigh risk adenoma3-10 tubular polyps1 polyp ≥ 10 mm1 villous or tubulovillous polyp1 tubular polyp with high-grade dysplasia3 yearsMore than 10 adenomas < 3 years; depends on the case (i.e., family history)

Anal cancer Anal cancer is a rare tumor. Risk factors include infection with human papillomavirus (HPV), immunodeficiency, and receptive anal intercourse. The most common clinical features are rectal bleeding (up to 45% of cases), pruritus ani, and tenderness or pain in the anal area. Anal cancer presents mainly as squamous cell carcinoma and in rare cases as adenocarcinoma or other non-epidermoid cancers. Depending on the exact localization and stage, it requires excision and/or radiochemotherapy. If the condition is treated in its early stages, the prognosis is favorable.

Epidemiology Incidence: ∼ 8000 cases diagnosed per year in the U.S. More common in HIV-positive individuals and men who have sex with men Etiology Risk factorsImmunodeficiency (e.g., HIV)Receptive anal intercourseSmokingHPV infection Clinical features Rectal bleeding (most important initial symptom) A lump or tumor around the anus Pruritus ani Tenderness, pain in the anal area Fecal incontinence History of anorectal condyloma Diagnostics Physical examinationInspection Digital rectal exam Invasive proceduresAnoscopyBiopsy for histology (small tumors are fully excised) Staging: endosonography, abdominal ultrasound, abdominal CT, pelvic MRI, chest x-ray/CT Pathology Histology: primarily squamous cell carcinoma; rarely adenocarcinoma or other non-epidermoid cancers Location Above the anal verge → Anal canal tumorsBelow the anal verge → Anal margin tumors Treatment Anal canal cancerTreatment of choice: radiochemotherapy Recurrent cancers are treated surgically. Anal margin cancerIf possible, local excision with safety marginAdvanced tumor(Neoadjuvant) radiochemotherapySubsequent resection depending on the size of the tumorIn some cases, remission may be achieved with radiochemotherapy alone. Complications MetastasisLocal invasion of adjacent organsLymphatic spread (30% of patients): perirectal, paravertebral, inguinal, femoral Hematogenous spread (< 10% of patients): liver, bone, lung

Amebiasis Amebiasis is an infectious disease caused by the anaerobic protozoan Entamoeba histolytica. Transmission usually occurs via the fecal-oral route (e.g., via contaminated drinking water) when traveling in an endemic region. Depending on its manifestation, amebiasis is termed either intestinal or extraintestinal. After an incubation period of one to four weeks, symptoms such as loose stools with mucus and fresh blood in combination with painful defecation develop. In extraintestinal amebiasis, amebic abscesses (mostly a single liver abscess in the right lobe of the liver) may form, resulting in pain as well as a feeling of pressure in the right upper quadrant (RUQ). Important diagnostic steps include stool analysis and liver ultrasound to assess extraintestinal amebiasis. Treatment consists of paromomycin to destroy intestinal amebae and metronidazole for invasive disease. Image-guided needle aspiration may be indicated in cases involving complicated liver abscesses.

Epidemiology Occurence: E. histolytica is very common in tropical and subtropical regions (e.g., Mexico, Southeast Asia, India) and affects more than 50 million people worldwide. Amebic infection is relatively rare in the US. Men and especially immunocompromised individuals have a higher risk of developing liver abscesses. Etiology Pathogen: Entamoeba histolytica, a protozoan TransmissionFecal-oralAmebic cysts are excreted in stool → contaminate drinking water or foodTransmission may also occur through sexual contact.Infection typically occurs following travel to endemic regions such as the tropics and subtropics. Pathophysiology StagesCyst stage: Cysts are very resilient (even against gastric acid) and are able to survive outside the host for months.Vegetative stage: trophozoite formation Trophozoites can produce proteolytic enzymes that allow them to invade the intestinal submucosa. They can then enter the bloodstream where they consume erythrocytes and disseminate to target tissues like the livervia the portal system. Clinical features Incubation period Intestinal amebiasis: 1-4 weeks Extraintestinal amebiasis: a few weeks to several years Clinical courses Intestinal amebiasis (dysentery)Loose stools with mucus and bright red bloodPainful defecation, tenesmus, abdominal pain, cramps, weight loss, and anorexiaFever in 10-30% of cases and possible systemic symptoms (e.g., fatigue)High risk of recurrence, e.g., through self-inoculation (hand to mouth)A chronic form is also possible, which is clinically similar to inflammatory bowel disease. Extraintestinal amebiasisMostly acute onset of symptoms; subacute courses are rareIn 95% of cases: amebic liver abscess, usually a solitary abscess in the right lobeFever in 85-90% of cases (compared to amebic dysentery) RUQ pain or pressure sensationChest pain, pleuralgiaDiarrhea precedes only a third of all cases of amebic liver abscesses. In 5% of cases: abscesses in other organs (e.g., especially the lungs; in rare cases, the brain), with accompanying organ-specific symptoms Diarrhea precedes only a third of all cases of amebic liver abscess! Always consider amebiasis when a patient presents with persistent diarrhea after traveling to a tropical or subtropical destination! Diagnostics Travel history Intestinal amebiasisStool analysisMicroscopic identification of cysts or trophozoites in fresh stool Trophozoites often contain ingested erythrocytesThe following tests confirm the microscopic findings (important since E. histolytica and Entamoeba dispar are morphologically identical ): EIA or copro-antigen ELISA (antigens found in feces)Molecular methods: e.g., PCRStool microscopy is not sensitive, especially in later phases, so at least three stool samples should be examined before reporting a negative result. Extraintestinal amebiasisSerological antibody detectionLiver function testsALP, AST, ALT, bilirubin slightly elevatedImaging: shows a solitary lesion, typically in the right lobeUltrasound: hypoechoicCT/MRI Treatment Medical therapy Asymptomatic intestinal amebiasisNo treatment in endemic areasIn nonendemic areas: a luminal agent such as paromomycin or diloxanide to eradicate the infection Symptomatic intestinal amebiasis and invasive extraintestinal amebiasisInitial treatment with a nitroimidazole derivative such as metronidazole or tinidazole to eradicate invasive trophozoitesFollowed by a luminal agent (e.g., paromomycin or diloxanide) to eradicate intestinal cysts and prevent relapse Invasive procedures Aspiration: ultrasound or CT-guided puncture of complicated abscesses at risk for perforationIndications: Localized in the left lobe Pyogenic abscessMultiple abscessesFailure to respond to pharmacotherapy Surgical drainage: should generally be avoided, but may be indicated for inaccessible abscesses or ruptured abscessesin combination with peritonitis To ensure successful treatment, the patient's stool must be analyzed regularly! Complications Intestinal amebiasis Fulminant or necrotizing colitis Toxic megacolon → colon rupture Ameboma Fistula formation (e.g., rectovaginal) Extraintestinal amebiasis Secondary infection → pyogenic abscess Abscess rupture → peritonitis Dissemination, possibly resulting in a brain abscess Direct extension to the pericardium or pleura Prevention Food and water hygiene Unpeeled fruits or vegetables should not be consumed if there is a potential risk of contamination by Entamoeba histolytica cysts (e.g., endemic region with low hygiene standards). Even chlorinated water can contain high concentrations of amebae; therefore, water should be boiled before use. "Boil it, cook it, peel it, or forget it."

Norovirus infection Noroviruses are a frequent cause of viral gastroenteritis in individuals of all ages worldwide. Transmission commonly occurs from person to person, as well as through contact with contaminated surfaces, food, and water. Given their virulence and short incubation period, illnesses caused by noroviruses may quickly lead to outbreaks, which must be reported. The elderly, immunocompromised patients, and those who reside in long-term care facilities are at an increased risk of contracting the illness. The clinical presentation of norovirus infection includes acute-onset vomiting and watery diarrhea. Diagnosis can be confirmed with reverse transcription polymerase chain reaction (RT-PCR). Treatment is supportive and mainly involves fluid replacement therapy.

Epidemiology Peak incidence: November-March (winter months) Community outbreaks (in nursing homes, hospitals, preschools, cruise ships, etc.) are common Elderly and immunocompromised patients are commonly affected. Most common cause of Adult gastroenteritis Severe acute gastroenteritis in children younger than 5 years of ageFoodborne illness Etiology Pathogen: Norovirus is a non‑enveloped RNA calicivirus. TransmissionFecal‑oral route through contaminated food or water, person‑to‑person contact, via airborne droplets, and contact with contaminated surfacesThe virus is highly virulent. Individuals are highly infectious during the acute phase and 24-72 hours following onset of symptoms Viral pathogens in gastroenteritis (Rotavirus is a Reovirus, Norovirus is a Calicivirus): Rotate Reo, the calico cat off to Norway! Clinical features Incubation period: 12-48 hours Nausea and acute-onset vomiting Watery, non-bloody diarrhea Abdominal cramps Symptoms resolve after 48-72 hours. Diagnostics Norovirus should be suspected in potentially exposed individuals if vomiting and/or diarrhea consisting ≥ 2 loosestools occur within a 24‑hour period. Clinical suspicion of norovirus infection should be confirmed with reverse transcription PCR (RT-PCR). Enzyme immunoassays: not a standard procedure due to low sensitivity (∼ 50%) Differential diagnoses Rotavirus infection Bacterial gastroenteritis Food poisoning Treatment Supportive therapyRehydration, if necessary with IV fluids (especially in the elderly and children)If myalgia and/or headache are present: NSAIDs or acetaminophen Prevention Obligation to report Health care providers are required to report all outbreaks. Many cases go underreported, as symptoms are usually mild in healthy individuals → higher chance of further transmission

Atrophic gastritis Atrophic gastritis is a condition characterized by chronic inflammation of the gastric mucosa with atrophy, gland loss, and metaplastic changes. It is classified into autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis (EMAG). Chronic infection with Helicobacter pylori (H. pylori) is the most common cause. Patients suffering from atrophic gastritis often do not display any symptoms or may only experience nonspecific discomfort in the epigastric region. Important diagnostic steps include gastroscopy with biopsy and laboratory studies (e.g., gastrin). Therapeutic emphasis depends on the underlying etiology: substitution of vitamin B12 (AMAG) or H. pylorieradication therapy (helicobacter-associated atrophic gastritis). If left untreated, atrophic gastritis may lead to peptic ulcer disease or result in the development of various cancers.

Epidemiology Prevalence in the general population: Autoimmune metaplastic atrophic gastritis (AMAG): ∼ 2-5% Environmental metaplastic atrophic gastritis (EMAG): strongly correlates with level of endemic H. pylori infection → increases with advancing age and affects the majority of elderly patients Etiology AMAGAssociated with major histocompatibility haplotypes HLA-B8 and HLA-DR3Associated with other autoimmune diseases (e.g., autoimmune thyroiditis) EMAGHelicobacter pylori infection (most important risk factor of atrophic gastritis overall) Dietary factors (e.g., N-nitroso compounds , alcohol intake, high salt intake) Pathophysiology AMAG Autoimmune destruction of the parietal cells → Achlorhydria → increased release of gastrin (due to loss of negative feedback) → G cell hyperplasia → hypergastrinemiaHypergastrinemia may lead to hyperplasia of enterochromaffin-like cells and, consequently, to an increased risk of carcinoid tumors. Autoantibodies against intrinsic factor → vitamin B12 deficiency → pernicious anemia EMAG Helicobacter-associated: colonization by H. pylori → decreased production of mucins → increased production of gastric acids → inflammation primarily of the antrum→ ascending propagation → shift of the corpus-antrum border → in cases of chronification: atrophy of the gastric glands → hypochlorhydria (not achlorhydria) and epithelialmetaplasia → increased risk of gastric cancers Diet: bacteria in the stomach metabolize nitrates present in food → formation of N-nitroso compounds (carcinogenic) → epithelial metaplasia → increased risk of gastric cancers Clinical features Intensity of symptoms may be inconsistent and vary widely Hematemesis (coffee-ground appearance or bright red in color), possibly melenaEpigastric pain is possible Nausea, vomitingAbdominal paresthesia and dyspepsia Additionally in AMAGAnemia: iron deficiency (early) and pernicious anemia (late)Achlorhydria impairs the intestinal absorption of inorganic iron → iron deficiency anemiaLack of intrinsic factor → vitamin B12 deficiency → pernicious anemiaFeatures of Vitamin B12 deficiency: triad of hematologic, neurologic, and gastrointestinal disorders (see vitamin B12 deficiency) Evidence of other autoimmune diseases (e.g., Hashimoto's thyroiditis) Additionally in EMAGAsymptomatic progression is commonSymptoms often a consequence of gastric or duodenal ulcer bleeding Diagnostics Esophagogastroduodenoscopy and biopsy Diagnostic test of choice To evaluate the gastric mucosa and collect biopsy samples from the gastric antrum and corpus, possibly also from the fundus Helicobacter pylori diagnostics Collection of biopsiesFor histology: 2 biopsy samples from the antrum (peripyloric and angular incisure) and corpus (lesser curvature and greater curvature) eachFor the urease test: 1 biopsy sample from antrum and corpus each Applied methods: As a rule, there should always be a combination of two methods. Histology (gold standard) including staining and direct microscopic identificationCurved, flagellated gram-negative rodRapid urease test: detection of ammonia production by the urease of H. pylori Culture and resistogram Non-invasive methodsH. pylori stool antigen test: detects the presence of H. pylori antigens in a stool sample. Can be used for diagnosis of H. pylori infection and proof of eradication post-treatmentPositive Urea breath test: detection of a labeled carbon isotope in breath samples Serum IgG antibodies against H. pylori: H. pylori antibodies may be detected even after eradication → test indicates (past) exposure, not necessarily current infection (lower specificity) Additional tests HematologyIn case of chronic bleeding (any type): possibly microcytic anemiaIn AMAG: possibly macrocytic anemia Serum pepsinogen isoforms Vitamin B12 levels: decreased in AMAG Serum gastrin levels: increased in AMAG Serology : anti-intrinsic factor and anti-parietal cell antibodies Differential diagnoses Chemical gastritisEtiology: various substances cause reactive gastritisDrugs, particularly NSAIDs (additional intake of glucocorticoids and/or SSRIs further increases the risk)Alcohol (especially high-proof and if consumed regularly)NicotineClinical featuresGeneral symptoms of chronic gastritis (epigastric pain , nausea, vomiting, hematemesis, melena, dyspepsia)Complaints of varying intensity are commonTherapyAvoid harmful substances (e.g., discontinue NSAIDs, abstaining from smoking and alcohol)Proton pump inhibitor (PPI) therapyIf H. pylori is detected → Helicobacter pylori eradication therapyComplications: gastric ulcers → bleeding, perforation Noninfectious granulomatous gastritisCrohn diseaseLocalization: most commonly in the duodenum, thereafter in descending frequency in the gastric antrum and gastric corpusDiagnosisEndoscopy: normal findings are frequentBiopsyOther: e.g., sarcoidosis, vasculitis Ménétrier's disease Definition: gastritis featuring massive enlargement of the mucosal foldsClinical features: dyspeptic symptoms (i.e., abdominal pain, nausea, vomiting, diarrhea, weight loss)DiagnosticsEndoscopy: prominent rugae in the gastric fundusBiopsy: foveolar hyperplasia and parietal cell atrophyComplications: Loss of protein → edemaMalignant degenerationTherapy: if H. pylori is detected → eradication, otherwise symptomatic treatment and regular gastroscopic check-ups Treatment General Avoid intake of substances that may exacerbate ongoing inflammation (e.g., alcohol, NSAIDs) Symptomatic treatment with proton pump inhibitors (PPIs), antacids, sucralfate, or H2-receptor blockers AMAG Vitamin B12 replacement therapy (parenteral) If H. pylori is detected: attempt to eradicate → may lead to healing Risk of malignant degeneration requires regular endoscopic check-ups Helicobacter-associated atrophic gastritis Helicobacter pylori eradication therapy with proton pump inhibitors (PPIs) at twice the standard dose + 2 antibiotics (+ possibly bismuth) for a minimum of 7 (possibly 10) days , thereafter continue one PPI at standard dose Indications ; Test-and-treat strategy : for patients that are < 55 years old, suffer from uninvestigated dyspepsia, and have no record of "alarm features" (e.g., bleeding)Active peptic ulcer diseaseHistory of peptic ulcer diseaseMALT lymphoma: disease may be cured by sole H. pylori eradication in stage I (success rate of 80%), in stage II eradication therapy as part of a therapeutic framework) First-line therapies Triple therapy: PPI + clarithromycin + amoxicillin or metronidazoleBismuth containing quadruple therapy: PPI or an H2-receptor antagonist + bismuth + tetracycline + metronidazole PPI: omeprazole, esomeprazole, lansoprazole, rabeprazole, and pantoprazole. Complications AMAG Vitamin B12 deficiency (→ pernicious anemia, funicular myelosis) Gastric adenocarcinoma Gastric neuroendocrine tumors: particularly carcinoid tumors (commonly featuring polypoid precursors) Esophageal squamous cell carcinoma EMAG Ulcerations in the stomach/duodenum (peptic ulcer disease) → upper gastrointestinal bleeding or perforation Gastric adenocarcinoma Gastric MALT lymphoma Extraintestinal manifestations (chronic urticaria, Parkinson's disease, migraine, immune thrombocytopenic purpura, iron deficiency anemia, rosacea) Helicobacter-associated atrophic gastritis frequently presents with ulcerations. Atrophic gastritis of autoimmune origin does not!

Meckel diverticulum A Meckel diverticulum is the most common congenital anomaly of the gastrointestinal tract and is caused by an incomplete obliteration of the omphalomesenteric duct. It is generally about 2 inches long and located 2 feet proximal to the ileocecal valve. It is seen in 2% of the general population and is more common in males. The mucosal lining of the diverticulum may be either native ileal mucosa or heterotopic mucosa (most commonly gastric). It is often asymptomatic and detected incidentally on imaging or abdominal surgery. The characteristic presentation of symptomatic Meckel diverticulum is painless lower gastrointestinal bleeding (hematochezia) in children < 2 years. Patients may also present with acute intestinal obstruction (intussusception or volvulus), diverticulitis, and, rarely, peritonitis due to perforation of a Meckel diverticulum. A Meckel diverticulum should be suspected when the work-up of a patient with lower gastrointestinal bleed or acute abdomen reveals no abnormalities. Sensitive and specific diagnostic tests for Meckel diverticulum include Meckel scan (99m technetium scintigraphy), CT angiography, and diagnostic laparoscopy. All symptomatic/complicated cases of Meckel diverticulum must be surgically resected. An asymptomatic Meckel diverticulum detected incidentally during abdominal surgery in a child should be resected. In adults < 50 years, only an incidentally detected Meckel diverticulum with risk factors for complications (e.g., a long, broad-based diverticulum) should be resected. An asymptomatic Meckel diverticulum incidentally detected on imaging does not require treatment.

Epidemiology Prevalence: most common congenital gastrointestinal tract anomaly (∼ 2% of the population) Sex: ♂ > ♀ (2:1) Age: < 2 years of age Pathophysiology The omphalomesenteric (vitelline or vitellointestinal) duct is a patent tubular structure connecting the yolk sac to the alimentary tract in the embryo. The duct is normally obliterated by the 6th week of intrauterine life. Incomplete obliteration of the omphalomesenteric duct → persistence of the proximal (intestinal) segment of the duct → Meckel diverticulum Anatomy Meckel diverticulum is a true diverticulum. Located ∼ 2 feet proximal to the ileocecal valve Usually ≤ 2 inches in size There may be 2 types of mucosal lining: Native ileal mucosaHeterotopic mucosa Blood supply: vitelline artery The rule of two's: Meckel diverticulum occurs in 2% of the population, 2% are symptomatic, mostly in children < 2 years, affects males twice as often as females, is located 2 feet proximal to the ileocecal valve, is ≤ 2 inches long, and can have 2 types of mucosal lining. The vitelline artery is a branch of the superior mesenteric artery that crosses over the ileum to supply the diverticulum. It is normally obliterated by the 9th week of intrauterine life. Its presence (on CT angiography) indicates a Meckel diverticulum. Clinical features Asymptomatic (∼ 96%) Symptomatic (2-4%) Painless lower gastrointestinal bleeding (most common presentation) Hematochezia Tarry stools Currant jelly stools See "Complications" below Diagnostics The initial work-up follows the same protocol as that for lower gastrointestinal bleeding and/or acute abdomen. Only the imaging tests specific to Meckel diverticulum are mentioned here. Imaging Meckel scintigraphy scan (Meckel scan): a noninvasive nuclear medicine imaging technique using radiolabelled technetium (99mTc), which is preferentially absorbed by the gastric mucosa and can identify ectopic gastric mucosa CT angiography: may demonstrate the vitelline artery or even contrast extravasation from a bleeding Meckel diverticulum Recent advances in imaging Double balloon enteroscopy: A long endoscope is advanced, either through the mouth or the rectum, into the small intestine. The sequential inflation and deflation of the two balloons helps advance the scope into the intestine by pleating the bowel onto the scope.Capsule endoscopy: The patient is asked to swallow a small, encapsulated camera, which takes multiple images of the bowel as it passes through the gastrointestinal tract. Diagnostic laparoscopy Treatment Asymptomatic Meckel diverticulum Incidentally detected on imaging studies: no treatment necessary Incidentally detected on laparotomy/laparoscopy Children or young adults: surgical resection of all incidentally detected Meckel diverticuliAdults < 50 years: surgical resection only for Meckel diverticuli that have a high risk of developing complications Adults > 50 years: no treatment necessary Symptomatic or complicated Meckel diverticulum Initial stabilization of the patient Surgical resection of all symptomatic/complicated Meckel diverticuli Surgical procedures Segmental resection : Indicated for a Meckel diverticulum that is bleeding, has a broad base, or a palpable abnormality Diverticulectomy: Meckel diverticulum is resected at the base. Complications Hemorrhage (most common) Bowel obstruction due to: IntussusceptionVolvulus Littre's hernia Bowel perforation → peritonitis or intra-abdominal abscess Infection (Meckel diverticulitis)

Constipation Constipation is the infrequent passage of stool. It is generally defined as ≤ 3 bowel movements per week, which may be associated with straining to defecate, the passage of hard stools, tenesmus, or the need for self-digitation to evacuate stool. It may be primary or secondary. Types of primary constipation (i.e., no identifiable organic cause) include normal transit constipation (e.g., due to inadequate calorie, fiber, or water intake), slow transit constipation, and pelvic floor dyssynergia. Secondary constipation may be drug-induced (e.g., opioid-induced constipation) or due to metabolic disorders (e.g., hypothyroidism), neurological disorders (e.g., spinal cord lesion), or mechanical obstruction of the bowel (e.g., colon cancer). Any identifiable underlying cause should be managed accordingly. In the absence of organic disease, constipation may resolve with regular exercise, hydration, and fiber supplementation. Osmotic or secretory laxatives may be considered in patients with persisting constipation. Long-term use of laxatives may result in dependency and paradoxical constipation.

Epidemiology Prevalence: ∼ 14% of the general population experiences chronic constipation. [1] Sex: ♀ > ♂ (3:1) [2] Accounts for 3-5% of pediatric outpatient visits [3] Classification By course: acute or chronic By etiologyPrimary constipation (functional constipation): constipation in the absence of an identifiable medical disorderSecondary constipation: constipation due to a medical disorder or medication Etiology Primary constipation (functional constipation)Most commonly due to poor diet and insufficient exerciseIn children: typically occurs during weaning, the toilet training phase, or once attending school (because of avoidance of school toilets) [3] Secondary constipation: See differential diagnoses below. Pathophysiology Both primary and secondary constipation can cause changes in stool consistency and defecation habits. Mechanism of altered stool consistencyExternal factors such as lack of exercise or inadequate fluid and fiber intake (primary constipation)/internal factors such as changes within the colon or rectum (secondary constipation) → slow passage of stool → prolonged absorption of water by the bowel → dry, hard stool → painful defecation → sensation of incomplete and irregular bowel emptying → constipation Mechanism of altered bowel motilityEffective peristalsis of the bowel is controlled by intrinsic (e.g., myenteric plexus) and extrinsic (e.g., sympatheticand parasympathetic) innervation. Any alteration in bowel innervation may lead to ineffective peristalsis. Drugs (e.g., calcium channel blockers, opiates, antispasmodics, antidepressants) [5] → altered autonomic outflow and bowel muscle contraction [6]Endocrine pathology (e.g., hypothyroidism) → downregulated bowel motilityNeurological pathology (e.g., spinal injury, enteric neuropathy) → disease or trauma of bowel innervationIneffective peristalsis → difficult passage of stool regardless of stool consistency → sensation of incomplete and irregular bowel emptying Diagnostics Constipation is a clinical diagnosis and laboratory tests and imaging are not routinely indicated. Indications for diagnostics include the presence of any red flags (see above) or a suspected secondary cause of constipation, such as hypothyroidism. Patient history Ask about dietary habits, medication use, mobility, stool character and frequency, problems with defecation, and anorectal pain. Additionally in children: delayed passage of meconium (e.g., Hirschsprung disease), voluntary withholding of stool (e.g., squatting, crying, crossing ankles, hiding), fecal (overflow) incontinence Rome IV diagnostic criteria for functional constipation in adults At least two of the following must have occurred in ≥ 1/4 of defecations during the past 12 weeks with onset of symptoms ≥ 6 months ago: Passage of stool < 3 times/week Passage of hard or lumpy stool Sensation of anorectal obstruction/blockage Manual aid to evacuate stool Straining during attempts to defecate Sensation of incomplete evacuation Physical examination Inspect the anorectal area. Possible fissuresHemorrhoidsCheck the anal wink reflex : An absent anal wink reflex suggests a pathology (e.g., sacral nerve injury). [4][8] Digital examination of the rectumCheck for rectal carcinoma.Test the sphincter tone to evaluate for pelvic floor dysfunction. Additional investigations Laboratory investigations: exclude hypokalemia, hypothyroidism, diabetes mellitus Imaging: abdominal x-ray [2] Colonoscopy: to exclude mechanical obstruction (e.g., tumor, stenosis), especially in the presence of red flags (see table below) [5][4][2] In patients with no red flag features, laboratory tests and imaging are not routinely recommended. Red flags in patients with constipation Children Delayed passage of meconium > 48 hours Constipation when < 1 month old Family history of disorders that may cause constipation (e.g., Hirschsprung disease) Bilious vomiting Severe abdominal distention Blood in stool Fever Failure to thrive Possible congenital abnormalities detected on examination (e.g., tuft of hair on spine, sacral dimple, abnormal position of anus) AdultsFamily history (e.g., colorectal carcinoma, inflammatory bowel disease) Iron deficiency anemia Blood in stool Palpable abdominal mass Reduced stool caliber Rectal prolapse Significant unexplained weight loss Sudden onset of new change in bowel habit Persistent constipation, despite treatment > 50 years of age and no previous screening for colorectal cancer A change in stool caliber (i.e., pencil-thin stool) and/or rectal bleeding in any patient > 50 years of age must be further investigated, as these features may be signs of colorectal cancer! Acute-onset constipation should raise suspicion for bowel obstruction! In patients with constipation, do not forget to examine the inguinal and pelvic region for an obstructed inguinal or femoral hernia! Primary constipation/functional constipation Normal transit constipation Slow transit constipation Pelvic floor dysfunction (e.g., pelvic floor dyssynergia ) Secondary constipationGastrointestinal causesColorectal carcinomaDiverticulosisAnal cancerColonic or rectal stricturesThrombosed hemorrhoidsIncomplete bowel obstructionComplete bowel obstructionVolvulusIleusObstructed herniaDiverticulitis Irritable bowel syndrome Neurological causesAutonomic neuropathy (e.g., diabetic neuropathy)StrokeHirschsprung diseaseParkinson diseaseChagas disease (megacolon)BotulismMultiple sclerosisPeripheral neuropathy (e.g., vitamin B12 deficiency, diabetes mellitus)Spinal cord injuryPelvic dyssynergiaEndocrine causesHypothyroidismDiabetes mellitusElectrolyte imbalance (especially hypokalemia, hypercalcemia)HyperparathyroidismConnective tissue disordersSclerodermaSystemic lupus erythematosusDermatomyositisAmyloidosisDrug-induced(constipation-inducing medication)Opioid analgesicsIron supplements Antacids Anticholinergics Antidepressants (e.g., tricyclic antidepressants) Calcium channel blockers Bile acid resins NSAIDs Beta blockers Calcium supplements Antipsychotics Antiparkinson medicationAnticonvulsants5-HT3 receptor antagonists Treatment Identify and treat any underlying conditions (see differential diagnoses). Approach in adults [12]Begin with lifestyle changes: high-fiber diet, increased fluid intake, and exerciseIf constipation persists, start an osmotic laxative (e.g., polyethylene glycol ).If osmotic laxatives are unsuccessful, add a stimulant laxative (e.g., senna or bisacodyl ). Approach in children [9][3]Infants 2 weeks to 6 months of age, without alarming features May only require reassurance Passage of stool is particularly variable in breastfed infants.Parents who formula feed their children should be properly instructed on correct formula preparation.Reassess in 2-4 weeks. [9]If constipation persists, consider drug therapy (best initial: polyethylene glycol).Children ≥ 6 months of age without suspected organic disease Prompt laxative therapy (best initial: polyethylene glycol) In combination with age-appropriate fiber, fluid, and physical activity requirementsToilet training, if applicable [13]Maintenance therapy: laxative therapy (polyethylene glycol or lactulose) until constipation is resolved for at least 1 month (treatment should then be tapered gradually) [9]Further investigation to exclude an underlying disorder is warranted if there is a poor response to the treatments mentioned above or if constipation affects a child < 2 weeks of age. Osmotic laxativesPolyethylene glycol (PEG): very effective and well-tolerated (best initial treatment) Glycerin Magnesium hydroxide Magnesium citrate Lactulose Sorbitol Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motilityLactulose is degraded by intestinal microbiota into lactic acid and acetic acid: Induces nitrogen (NH4+) excretionUsed in the treatment of hepatic encephalopathyDiarrheaDehydrationMagnesium salts: hypernatremia, hypermagnesemia Lactulose and sorbitol: severe flatulence Osmotic laxative misuse is frequently seen in patients with bulimia nervosa Stimulant laxatives/secretory laxativesSenna Bisacodyl Stimulation of nitric oxide-mediated epithelial cell secretion of electrolytes into the colonic lumenMyenteric neuronal depolarization → coloncontractionsFor short-term use onlyDiarrhea: Stimulant laxatives may result in severe water and potassium loss.Senna may result in melanosis coli. Emollient stool softenerDocusate Emulsification (i.e., integration of water and fat) of stool → softening of stool → easier passage through the intestinal tractDiarrheaBloating, cramping Bulk-forming laxativesMethylcellulose: chemical compound derived from cellulose Psyllium husks Polycarbophil Bulk-forming laxatives are indigestible, not systemically absorbedSoluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall →stimulation of peristalsisBloatingWorsening constipation or ileus if the patient doesn't take enough water with doses Chronic laxative use may lead to dependency and/or hypokalemia, which can further reduce bowel motility! Patients taking osmotic laxatives should be instructed to increase their water consumption. Complications Fecal incontinence Fecal impaction Anal fissures Hemorrhoids Megacolon Urinary retention Pelvic floor damage in women Fecal impaction Clinical features Inability to defecate for days or weeks Normal bowel sounds Distended, tympanitic abdomen DRE: hard, impacted stools distending the rectum Tenesmus Diagnostics Clinical diagnosis Abdominal x-ray (to rule out bowel perforation) Findings: Dilated bowel loopsFecal shadows in the colon and rectumAir-fluid levels may be visible. Treatment [17][18] Rule out bowel perforation. Manual disimpaction Administer osmotic enema (e.g., warm water enema or mineral oil enema). Consider the addition of stimulatory suppositories Bisacodyl suppository Glycerine suppository Prevention of recurrence Start maintenance bowel regimen with osmotic laxative (e.g., polyethylene glycol or lactulose ).Stop contributing medications.Lifestyle modificationsSee treatment of constipation and laxatives. For severe cases, consult surgery. Opioid-induced constipation Clinical features Recent initiation of an opioid or dose adjustment New or worsening constipation Fecal impaction may be present Physical examination typically normal Diagnostics [19] Clinical diagnosis Rome IV diagnostic criteria for OICRecent initiation of opioid treatment or a dose increaseAND ≥ 2 of the characteristic clinical features of functional constipation: Passage of spontaneous bowel movement < 3 times/weekPassage of hard or lumpy stool (more than 25% of defecations)Sensation of anorectal obstruction/blockage (more than 25% of defecations)Manual aid to evacuate stool necessary (more than 25% of defecations)Straining during attempts to defecate (more than 25% of defecations)Sensation of incomplete evacuation (more than 25% of defecations)Loose stools are rarely present without the use of laxatives Consider x-ray of the abdomen to rule out fecal impaction Treatment [20][19] Similar to the treatment of primary constipation (see "Treatment" and "Laxatives" above) Identify and treat any underlying organic cause. Lifestyle and dietary modification Evaluate the need for opiate therapy and discontinue/reduce dose if appropriate. Medical therapy Laxative therapyOsmotic laxative (e.g., polyethylene glycol or lactulose )and/or stimulant laxative (e.g., senna )Options for laxative-refractory OIC: Peripherally acting μ-opioid receptor antagonistsMethylnaltrexone Naldemedine Naloxegol Lubiprostone Discontinue any additional laxatives when initiating a peripherally acting μ-opioid receptor antagonist.

Ulcerative colitis Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic mucosal inflammation of the colonand cecum. Common symptoms include bloody diarrhea, abdominal pain, and fever. Laboratory findings typically show elevated inflammatory markers and the presence of autoantibodies (pANCA). Definitive diagnosis requires biopsiesshowing abnormal colonic mucosa and characteristic histopathology. Aminosalicylic acid derivatives are the mainstay of treatment, although severe episodes typically require corticosteroids and immunosuppressants to achieve remission. In the case of distal colitis, some drugs may be administered topically (e.g., via enema), whereas more proximal inflammationrequires systemic treatment. Proctocolectomy is curative and indicated for complicated UC or dysplasia. Individuals with UC are predisposed to colorectal cancer and should thus undergo regular surveillance colonoscopy.

Epidemiology PrevalenceApprox. 600,000 adults in the U.S. are affected by UC [1]Ethnicity Higher in the white than in the black, Hispanic, or Asian populationsHighest among individuals of Ashkenazi Jewish descent.Slightly higher in men than women [2] Peak incidence15-35 years [3] Another smaller peak may be observed in individuals > 55 years [4] Truelove and Witts' severity index CriteriaMildModerateSevereBowel movements/day< 44-6> 6 Blood in stoolsIntermittentFrequentContinuous Temperature< 37.5°C (99.5°F)≤ 37.8°C (99.68°F)> 37.8°C (100.4°F) Heart rate< 90/min≤ 90/min> 90/min Hemoglobin> 11.5 g/dL≥ 10.5 g/dL< 10.5 g/dLESR< 20 mm/h≤ 30 mm/h> 30 mm/h Pathophysiology Pathogenesis The exact mechanism is unknown but studies suggest that ulcerative colitis is the result of abnormal interactions between host immune cells and commensal bacteria. [8][2] Dysregulation of intestinal epithelium: increased permeability for luminal bacteria → activation of macrophages and dendritic cells → antigen presentation to macrophages and naive CD4+ cells leads to Secretion of pro-inflammatory cytokines (IL-6, IL-12, TNF-α) and chemokines (CXCL1, CXCL3, and CXCL8) → recruitment of other immune cells (e.g., neutrophils) to the siteDifferentiation of naive CD4+ cells to Th2 effector cellsRecruitment of NK cells Dysregulation of the immune system: upregulation of lymphatic cell activity in bowel walls (T cells, B cells, plasma cells) → enhanced immune reaction and cytotoxic effect on colonic epithelium → inflammation with local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosaAutoantibodies (pANCA) against cells of the intestinal epitheliumTh2 cell-mediated response Pattern of involvementAscending inflammation beginning in the rectum and spreading continuously proximally throughout the colon Mucosal and submucosal inflammation The rectum is always involved in UC! Risk factors [8][2][4] Genetic predisposition (e.g., HLA-B27 association) Ethnicity (white populations, individuals of Ashkenazi Jewish descent) Family history of inflammatory bowel disease Episodes of previous intestinal infection Increased fat intake (esp. saturated fat and animal fat) Oral contraceptive intake NSAIDs may exacerbate UC Protective factors [8][2] Appendectomy Smoking has a protective effect Clinical features Intestinal symptoms Bloody diarrhea with mucus Fecal urgency Abdominal pain and cramps Tenesmus Extraintestinal symptoms Skeletal (most common extraintestinal manifestation of ulcerative colitis): osteoarthritis, ankylosing spondylitis, sacroiliitis [9][10] Ocular: uveitis, episcleritis, iritis Biliary: primary sclerosing cholangitis (PSC) Rare for patients with UC to develop PSC, but up to 90% of all patients affected by PSC will also be affected by UC. Cutaneous: erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, General: fatigue, fever In children/adolescents: growth retardation and delayed puberty Primary sclerosing cholangitis (PSC) is often associated with inflammatory bowel disease, especially UC. However, only around 4% of people with inflammatory bowel disease develop PSC! To remember the characteristics of ulcerative colitis, think "ULCCCERS" for Ulcers, Large intestine, Continuous/Colon cancer/Crypt abscesses, Extends proximally, Red diarrhea, Sclerosing cholangitis Diagnostics Laboratory tests Blood↑ ESR, ↑ CRP, leukocytosisAnemiaThrombocytosis in some cases↑ Perinuclear ANCA (pANCA)Medium sensitivity but high specificity [14][15]No correlation between titer and disease activitySerologic testing is not recommended for definitive diagnosis or exclusion of UC but can support the diagnosis. [3]In case of concurrent PSC: elevated gamma-glutamyl transferase Stool analysisTest for bacteria to rule out infectious causes. [3]Calprotectin and lactoferrin are indicators of mucosal inflammation. Endoscopy Endoscopy (e.g., colonoscopy) with histological examination is considered the best test to definitively diagnose UC. Typical findings: see "Gross pathology" below Pattern of disease involvement [3]Proctosigmoiditis: limited to the rectum, with possible sigmoid involvement Left-sided colitis: extends distally to the splenic flexure Extensive colitis: extends beyond the splenic flexure Recommendations [3]Evaluate the ileum to rule out Crohn diseaseStepwise biopsy (for findings, see "Pathology" below)Colonoscopy is contraindicated in patients with acute flare because of the high risk of perforation but should be performed once symptoms improve. Sigmoidoscopy may be considered as an alternative. Observe caution in taking biopsies from patients with severe disease, as the risk of perforation is high. Imaging [16][3] Imaging studies may serve as useful adjunct diagnostic procedures for UC, particularly when it comes to detecting complications. RadiographyPlain radiographyTypically normal in mild to moderate diseaseFindings Loss of colonic haustra (lead pipe appearance) may be seen in severe cases Massive distention in cases of toxic megacolonPneumoperitoneum in cases of perforationBarium enema radiographyAble to detect very early changesFindings Granular appearance of the mucosaDeep ulcerationsLoss of haustraPseudopolyps that appear as filling defects CT: Detection of bowel wall thickening is possible in severe disease. MRI: can be helpful in assessing disease severity and extent of bowel wall involvement Ultrasound: can detect bowel wall thickening (manifests with absent hyperechoic reflection from the lumen) Pathology Gross pathology Early stagesInflamed, erythematous, edematous mucosa Friable mucosa with bleeding on contact with endoscope Fibrin-covered ulcers Small mucosal ulcerationsLoss of superficial vascular pattern Chronic diseaseLoss of mucosal foldsLoss of haustra StricturesPseudopolyps Raised areas of normal mucosal tissue that result from repeated cycles of ulceration and healingUlceration → formation of granulation tissue → deposition of granulation tissue → epithelizationMorphologically resemble polyps but do not undergo neoplastic transformationFound in advanced disease In ulcerative colitis, the extent of intestinal inflammation is limited to the mucosa and submucosa. In contrast, Crohn diseaseshows a transmural pattern of intestinal involvement. Histological findings Early stagesGranulocyte (neutrophil) infiltration: limited to mucosa and submucosaCrypt abscesses: an infiltration of neutrophils into the lumen of intestinal crypts due to a breakdown of the crypt epithelium Chronic diseaseLymphocyte infiltrationMucosal atrophyAltered crypt architectureBranching of cryptsIrregularities in size and shape Epithelial dysplasia Noncaseating granulomas are seen in Crohn disease but are not a feature of ulcerative colitis! Differential diagnoses Crohn disease (see Differential diagnostic considerations: Crohn disease and ulcerative colitis) Exudative-inflammatory diarrhea Diverticular disease Appendicitis Ischemic colitis Infectious colitisC. difficile colitisShigella dysenteriaeSalmonella enterocolitisEscherichia coli colitisCampylobacter enterocolitisYersiniosisTuberculosisCMV colitis Radiation colitis Celiac disease Inflammatory diarrhea Microscopic colitis: An idiopathic form of colitis that is characterized by a normal macroscopic appearance of bowel on colonoscopy and collagenous or lymphocytic infiltrates on microscopy. Patients present with chronic, non-bloody diarrhea, weight loss, and abdominal pain Treatment Initially, UC is treated conservatively with drugs to induce and maintain disease remission. Curative proctocolectomy is generally indicated if medical therapy fails or complications arise. General management Rehydration Supplementation of nutritional deficiencies (e.g., iron) Supplementation of nutrition: severe cases may warrant consideration of a feeding tube or parenteral nutrition. Medical therapy [3] Supportive care Antidiarrheal agents (e.g., loperamide) Anticholinergic medication (e.g., propantheline, dicyclomine): relieves abdominal cramping NSAIDs, opioids, and anticholinergics should be avoided in severe disease. Recommended medical therapy by the severity of disease [3] Mild disease 5-aminosalicylic acid derivatives (5-ASAs)Anti-inflammatory and immunosuppressive effects on the bowelCan be administered orally, as suppositories, or as enemas Examples: mesalamine, sulfasalazine , olsalazine If no improvement or 5-ASA agents are not toleratedTopical corticosteroids (e.g., budesonide)Oral systemic corticosteroids Moderate disease Oral and topical 5-ASAs Topical corticosteroids (e.g., budesonide) → systemic corticosteroids only if no response Anti-TNF therapy (adalimumab, golimumab, or infliximab) Severe or refractory disease High‑dose oral and topical 5-ASAs Systemic corticosteroids Anti-TNF therapy (e.g., adalimumab, golimumab, or infliximab) Calcineurin antagonists (e.g., cyclosporine, tacrolimus) Thiopurines (e.g., azathioprine) may be considered but are no longer recommended as monotherapy due to lack of efficacy [3] Referral for surgical proctocolectomy (see below) Systemic corticosteroids should only be used for the treatment of an active flare and are not recommended as a maintenance medication for ulcerative colitis! Surgical intervention GoalCurative approach with full recoveryReduce risk of colorectal cancer IndicationsEmergent: Acute complications despite adequate conservative management (e.g., toxic megacolon, perforation, sepsis, uncontrolled bleeding, etc.) Elective: epithelial dysplasia, severe relapses, long-term dependence on steroids, impairment of the patient's general condition Procedure: proctocolectomy with an ileal pouch-anal anastomosis (IPAA or J pouch) Resection of the entire colon and rectal mucosa while sparing the anal sphincters.Loops of small intestine (serving as the pouch) are used to create an artificial rectum (reservoir for feces) and thus a continence-conserving connection between the ileum and anus. In contrast to Crohn disease, ulcerative colitis can be cured surgically (proctocolectomy)! Complications Gastrointestinal bleeding (both acute and chronic) Toxic megacolon Perforation → peritonitis Fulminant colitis: A condition of severe bowel inflammation that typically causes > 10 stools per day, lower gastrointestinal bleeding, abdominal pain, and abdominal distension. ↑ Risk of cancer (see colorectal carcinoma)Risk increases with increased duration and/or extent of disease Risk is not significantly increased in patients with mild UCPrevention: Screening colonoscopy with biopsies every 1-3 years starting 8 years after the initial diagnosis to screen for colorectal cancer [3] Colonic stenosis Amyloidosis Prognosis On average, the life expectancy of patients with UC is normal.

Lynch syndrome Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is a familial cancer syndrome caused by an autosomal dominant mutation in DNA mismatch repair (MMR) genes. Affected individuals develop a small number of adenomas that can rapidly progress to colorectal cancer (CRC), resulting in a considerably earlier symptom onset compared to sporadic colorectal cancer. Individuals with Lynch syndrome are also at increased risk of developing other forms of cancer, especially endometrial, gastric, and ovarian cancer. Individuals are asymptomatic until they present with symptoms of advanced cancer. To identify those at high risk for Lynch syndrome, individuals are assessed according to the Amsterdam II criteria. Subsequent genetic analysis with detection of MMR mutations confirms the diagnosis. Treatment of CRC consists of surgical colectomy and immunotherapy. Preventative screening for colorectal cancer and associated tumors is recommended in individuals with family members known to have a Lynch syndrome gene mutation; it should occur every 1-2 years, starting at 20-25 years of age, or 2-5 years before the earliest recorded case of a tumor in the family.

Epidemiology PrevalenceMost common cause of inherited CRCAccounts for approx. 3-8% of all new cases of CRCIndividuals with Lynch syndrome have a 70-80% lifetime risk of developing CRC Sex: ♂ = ♀ Average age of onset: 44 years Increased lifetime risk of associated cancers (by age 70) Endometrial cancer: up to 40%Gastric cancer: ∼ 10%Ovarian tumors: ∼ 10%Urothelial cancer: up to 10%Skin: ∼ 4%Small bowel cancer: ∼ 2%Brain tumor: ∼ 2%Biliary tract cancer: ∼ 2% Etiology Hereditary disease: autosomal dominant with varying penetrance Mutations in various DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) cause microsatellite instability.Increased occurrence of adenomas with significantly increased progression to carcinomas Clinical features Patients are usually asymptomatic until CRC develops (see colorectal cancer). Signs of right CRC are more likely than signs of left CRC. Possibly extracolonic symptoms of associated cancers (see "Epidemiology" section above) Subtypes and variants Muir-Torre syndromeA variant of Lynch syndrome caused by mutations also occurring in MLH1, MSH2, or MSH6Characterized by sebaceous gland tumors and keratoacanthomas in addition to Lynch syndrome-associatedcancers Turcot syndrome: increased association between Lynch syndrome-related CRC and gliomas Amsterdam II criteriaPresence of at least three relatives with a Lynch syndrome-associated cancer; all the following criteria should be present:One should be a first-degree relative of the other twoAt least two consecutive generations affectedAt least one relative with a diagnosis before 50 years of ageExclude cases of familial adenomatous polyposis.Verify tumors with pathological examination. 3-2-1 rule: (3 affected family members, 2 generations, 1 relative under 50 years of age). Genetic testing First test: tumor microsatellite instability (MSI) and/or immunohistochemical staining (IHC)Low MSI/stable microsatellite and normal IHC: rules out Lynch syndromeHigh MSI and/or abnormal IHC: requires further evaluation Confirmatory test: germline testing via DNA sequencing Detection of mutations in DNA repair genes (MLH1, MSH2, MSH6, and PMS2) Colorectal cancer For diagnosis of CRC, see colorectal cancer. Lynch syndrome typically manifests with colorectal cancer of the proximal colon, with only a few adenomatous polyps, in contrast to familial adenomatous polyposis, in which hundreds of adenomatous polyps are present Treatment SurgerySubtotal colectomy with ileorectal anastomosisTotal colectomy with ileostomyTotal colectomy with ileorectal anastomosis Immunotherapy with an immune checkpoint inhibitor (pembrolizumab or nivolumab) may be used for high MSI or mismatch repair deficient (dMMR) metastatic colorectal cancer. [5][6] For more specific guidelines regarding management, see colorectal cancer. For women with Lynch syndrome, prophylactic hysterectomy and bilateral salpingo-oophorectomy should be offered when they are no longer of child-bearing age. Prevention Genetic counselingGenetic testing is generally not recommended for at-risk individuals < 18 years of age.Genetic screening should be initiated 10 years before the earliest manifestation of the condition in the family. Cancer screening: for Lynch syndrome patients with a confirmed mutation or who meet Amsterdam criteria Colonoscopy: every 1-2 years, starting at 20-25 years of age, or 2-5 years before the earliest recorded case of a tumor in the family (only if it occurred before 25 years of age), whichever comes first [8]Annual pelvic examination with transvaginal sonography and endometrial biopsy starting at 30-35 years of age or 3-5 years before the earliest reported case of a tumor in the familyAnnual upper endoscopy with biopsy of the gastric antrum starting at 30-35 years of ageAnnual physical exam and urinalysis Total colectomy: not generally recommended in patients with normal endoscopy

Esophageal diverticula Esophageal diverticula are abnormal pouches that arise from the wall of the esophagus. They tend to occur in middle-aged and older patients and are classified based on localization, pathophysiology, and histological findings. The most common type of esophageal diverticulum is referred to as a "Zenker's diverticulum," which extends posteriorily in the hypopharynx directly proximal to the upper esophageal sphincter. Esophageal diverticula occur either when an underlying motility disorder exerts high intraluminal pressures on a weak esophageal wall or as a result of forces pulling on the outside of the esophagus. The clinical presentation varies with pouch size and localization, with the most common symptoms being dysphagia, regurgitation, retrosternal pain, and pulmonary symptoms secondary to aspiration. A barium swallow confirms the diagnosis, assesses the size of the diverticulum, and rules out the possibility of cancer. Surgical treatment is rarely required and only recommended in symptomatic patients - primarily those with Zenker's diverticula.

Epidemiology Rare diverticula compared to other gastrointestinal sites Peak incidence: middle-aged and older patients Zenker's diverticulum is the most common type Classification Esophageal diverticula are classified according to their localization, histology, and pathophysiology. LocalizationUpper esophageal diverticulumPharyngoesophageal diverticulumMost common type: Zenker's diverticulum at Killian's triangle (A triangular weak point in the muscular wall between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor muscle.) Middle esophageal diverticulum: diverticulum at the tracheal bifurcation Lower esophageal diverticulum: epiphrenic diverticulum Although a Zenker's diverticulum is considered to be an esophageal diverticulum, it actually arises from the hypopharynx! HistologyTrue diverticula: All layers of the esophageal wall protrude.False diverticula: Increased intraluminal pressure causes only the mucosa and submucosa to bulge through weak points in the muscularis propria. Pathophysiology (see "Pathophysiology" below) Pulsion DiverticulaTraction Diverticula Pathophysiology Inadequate relaxation of the esophageal sphincter (e.g., caused by achalasia or spastic motility) and increased intraluminal pressure results in outpouching of the esophageal wall → pulsion diverticulumUsually a false diverticulumCommon sites Upper esophageal sphincter (UES) → pharyngoesophageal pulsion diverticulum (e.g., Zenker's diverticulum)Lower esophageal sphincter (LES) → epiphrenic pulsion diverticulum Inflammation of the mediastinum with scarring and retraction (e.g., secondary to tuberculosis or fungal infection) → traction diverticulumUsually true diverticulumCommon site: the middle esophagus Clinical features Clinical presentation depends on diverticulum size and localization Dysphagia (most common) Regurgitation of undigested food Aspiration Coughing after food intake Retrosternal pressure sensation and pain Halitosis Weight loss Neck mass Diagnostics Barium swallow (best confirmatory test) with dynamic continuous fluoroscopy Visualization of diverticula via barium swallow or gastrografin (soluble in water) Best detected using lateral projectionShows a contrast-filled pouch protruding dorsally from the hypopharynx at the level of C5/C6.Allows detection of underlying motor abnormalities, possible malignancy, and diverticulum size A traction diverticulum presents as a pointed, triangular bulge arising from the esophageal wall; the base of the triangle is oriented towards the wall. Endoscopy Indication: to rule out malignancy in the pouch and exclude other causes of the patient's symptoms (e.g., tumorand reflux esophagitis) Less sensitive, since diverticula with small openings may be missed Risk of diverticulum perforation, since the course of the esophagus is often irregular Treatment There is no medical treatment for any kind of esophageal diverticula. Surgical treatmentIndicationsSymptomatic Zenker's diverticulaIn rare cases, epiphrenic diverticula that become symptomatic Endoscopy (rigid or flexible, with the former requiring general anaesthesia) with diverticulostomy and myotomyOpen surgery Zenker's diverticulum: cricopharyngeal myotomy Epiphrenic diverticula: esophagomyotomy Diverticula of the middle and distal esophagus (traction diverticula and epiphrenic diverticula) usually do not require treatment! Complications Aspiration pneumonia is a common complication of large Zenker's diverticula. In rare cases, perforation with mediastinitis and fistula formation occurs.

Alcoholic liver disease Alcoholic liver disease (ALD) refers to a range of progressive liver conditions caused by chronic and excessive alcohol consumption. One-third of the US population consumes alcohol above the recommended levels, increasing their risk of ALD. There are three stages of ALD, which may or may not occur sequentially. The first stage is typically asymptomatic and involves the development of (potentially) reversible alcoholic fatty liver. Continued alcohol consumption may lead to alcoholic hepatitis, the second stage, which often becomes chronic. Clinical findings in this stage include jaundice, fatigue, and fever. In the third and final stage, the patient develops alcoholic cirrhosis. Patient history, transaminase levels, and imaging studies are crucial for diagnosis and show different patterns of hepatic injury. Nonalcoholic steatohepatitis is a differential diagnosis and is currently regarded as an important cause of cirrhosis. Treatment of ALD requires complete cessation of alcohol use.

Epidemiology Second most common cause of liver cirrhosis in the United States 28% of the US population exceeds the recommended limits of alcohol consumption. Lifetime prevalence of alcohol abuse: 18% ∼ 10-20% of heavy drinkers develop cirrhosis. Etiology Alcoholism is a very important cause of chronic liver diseases. Significant alcohol consumption Men: > 210 g pure alcohol per weekWomen: > 140 g pure alcohol per week Pathophysiology Hepatic degradation of ethanol to acetyl-CoA by alcohol dehydrogenase results in NADH excess (see breakdown of ethanol for more details) → ↑ NADH drives the formation of glycerol 3-phosphate (G3P) from dihydroxyacetone phosphate (DHAP) → ↑ in both G3P and fatty acids causes increased triglyceride synthesis in the liver →steatohepatitis Clinical features The stages of ALD may overlap and do not necessarily occur in sequence. Alcoholic fatty liver (reversible) Mostly asymptomatic Some patients report feeling a sensation of pressure in the upper abdominal area. Hepatomegaly: soft in consistency Regresses after cessation of alcohol consumption Alcoholic hepatitis (reversible in mild cases) Develops as a result of persistent, long-term alcohol use Nonspecific symptoms: nausea, loss of appetite, weight loss, low-grade fever with tachycardia Hepatomegaly with hepatic tenderness Jaundice Symptoms of withdrawal in alcohol-dependent individuals Splenomegaly and ascites may be present. Alcohol-related cirrhosis (irreversible) Final stage of ALD See "Clinical features" in cirrhosis. Diagnostics A history of alcohol abuse that correlates with typical laboratory and imaging findings is diagnostic of alcoholic liverdisease. Alcoholic fatty liver Laboratory testsAST (aspartate aminotransferase) > ALT (alanine aminotransferase) (both ↑ ALT and ↑ AST)↑ GGT ↑ Serum ferritinMacrocytic anemia ↑ CDT(carbohydrate-deficient transferrin) Most specific biomarker of heavy alcohol use regardless of the presence of liver diseaseLevels elevated up to 6 weeks after abuse ImagingUltrasoundMild hepatomegalyBlood vessels cannot be visualized ↑ Liver echogenicity because of steatosis: may be focal or diffuse CT: ↓ liver attenuation Imaging and laboratory studies in the case of alcoholic fatty liver will show a reversal of changes within a month if the patient abstains from alcohol! Alcoholic hepatitis Laboratory testsAST/ALT ratio > 2 ↑ AST: usually ≤ 500 U/LALT: normal or only mildly elevated↑ Alkaline phosphatase (ALP) ↑ GGTImpaired liver function↑ Bilirubin ↓ Serum albumin↑ Prothrombin time Macrocytic anemia, thrombocytosis , and absolute neutrophilic leukocytosis may be present. ImagingUltrasoundResembles alcoholic fatty liver; however, disease is typically diffuseIn addition to those findings: hepatomegaly and periportal edemaCT: ↓ liver attenuation Alcohol-related cirrhosis See cirrhosis. Diagnosis confirmed by biopsy Pathology Alcoholic fatty liverAccumulation of lipid droplets in the hepatocytes with gradual single cell necrosis within the lobules Alcoholic hepatitisFatty liver with hydropic swelling and ballooning degeneration of hepatocytes within the lobulesDamaged hepatocytes typically contain Mallory bodies (hyaline inclusion bodies that contain keratin filaments and appear eosinophilic on H&E stain)Immunoreaction: Neutrophilic granulocytes infiltrate hepatic tissue.Fibrosis: pronounced excess formation of fibrous collagenous connective tissue in perivenous zones Alcohol-related cirrhosisInfiltration of lymphocytesMassive accumulation of fat in hepatocytesFormation of fibrous septa and regenerative nodulesPerivascular sclerosis of central veins (especially in the early stage) Alcoholic fatty liver and mild alcoholic hepatitis may be reversible after cessation of alcohol intake. However, severe alcoholic hepatitis and cirrhosis are not reversible! Differential diagnoses Non-alcoholic steatohepatitis (NASH) Definition: non-alcohol related accumulation of fat in the liver cells with risk of inflammation and cirrhosis EpidemiologyVery widespread EtiologyObesity and/or type 2 diabetes (metabolic syndrome) Medication (amiodarone, glucocorticoids, estrogen, antiretroviral drugs)Parenteral nutrition, after resection of the small intestine and other gastrointestinal interventions PathologyHepatocellular lipid accumulation, mostly macrovesicularBallooning degeneration and necrosis Inflammatory infiltrates, with scattered lymphocytes, neutrophils, and Kupffer cells Pathophysiology↑ Insulin resistance ↑ Peripheral lipolysis↑ Triglyceride synthesis↑ Hepatic uptake of fatty acids Clinical presentation Often asymptomaticHepatomegalyMay progress to cirrhosis Diagnostics↑ Transaminases (AST/ALT ratio < 1) The reversal of the AST/ALT ratio to values > 1 may indicate progression to cirrhosis.Rule out other causes of chronic hepatitis (e.g., heavy alcohol use, hepatitis B, hepatitis C, Wilson disease, autoimmune hepatitis, hemochromatosis, α1-antitrypsin deficiency) TherapyWeight loss, optimization of diabetic treatmentDiscontinue responsible medication Complications: cirrhosis, hepatocellular carcinoma NASH is a diagnosis of exclusion! Other causes of chronic liver disease must be ruled out by laboratory studies and/or biopsy. A distinction between alcoholic and non-alcoholic fatty liver disease can only be drawn based on patient history! There is more ALT than AST (AST/ALT < 1) if the Liver is infiltrated with Lipids. Treatment Immediate cessation of alcohol use In some cases, glucocorticoids (e.g., prednisolone in severe disease) Complications Decompensated cirrhosis Mainly characterized by a constellation of clinical features resulting from decreased hepatic function: Portal hypertension Ascites Hepatic encephalopathy Coagulopathy Hepatorenal syndrome Hyperestrogenism End-stage liver disease Other organ damage following chronic alcohol use Gastritis Malabsorption Chronic pancreatitis Wernicke-Korsakoff syndrome See alcohol use disorder. Zieve syndrome Acute hemolytic anemia after excessive alcohol use over the course of several years, characterized by the following triad: Alcoholic hepatitisJaundiceHyperlipidemia

Cystic fibrosis Cystic fibrosis (CF) is an autosomal recessive disorder caused by a mutation in the CFTR gene, which encodes for the cystic fibrosis transmembrane conductance regulator protein. The mutation leads to the production of defective chloridechannels in cell membranes of the exocrine glands, and symptoms are caused by these glands producing abnormally hyperviscous secretions. Failure to pass meconium (meconium ileus) is often the first clinical sign of cystic fibrosis. Later, the lungs, digestive system, and sweat glands are commonly affected. Bronchial accumulation of hyperviscous mucus and impaired ciliary clearance predispose patients to chronic respiratory infection, pulmonary colonization with multiresistant bacteria, and long-term complications such as emphysema. Impaired secretion of pancreatic and biliary juices leads to digestive problems and chronic organ damage. The sweat test (pilocarpine iontophoresis) is considered the gold standard for detecting elevated levels of chloride in sweat, which is a characteristic sign of cystic fibrosis. The mainstay of treatment is symptomatic management. The median life expectancy is 39 years. Complications of chronic lung disease are the leading cause of death.

Epidemiology Second most common hereditary metabolic disorder in white populations Most common lethal genetic disorder in white populations IncidenceNon-Hispanic whites: ∼1/3300 Heterozygote frequency among non-Hispanic whites: 1/25 Children of heterozygous parents have a 25% chance of developing cystic fibrosis! Etiology Hereditary autosomal recessive disorderDefective CFTR (cystic fibrosis transmembrane conductance regulator) protein due to mutation in CFTR geneThe most common mutation is delta F508 on chromosome 7.Delta F508 (ΔF508 mutation) denotes the absence of the amino acid phenylalanine (F) in position 508 of the protein (present in 70% of non-Hispanic white patients with CF). Pathophysiology The CFTR gene, which is located on the long arm of chromosome 7, encodes the CFTR protein, which is an important component of the ATP-gated chloride channel in cell membranes. Mutated CFTR gene (ΔF508 mutation) → misfolded protein → defective protein is retained in the rough endoplasmic reticulum (rER) for degradation → ATP-gated chloride channel is absent on the cell surface of epithelial cells throughout the body (e.g., intestinal and respiratory epithelia, sweat glands, exocrine pancreas, exocrine glands of reproductive organs)In sweat glands: The chloride channel is responsible for transporting Cl- from the lumen into the cell(reabsorption).Defective ATP-gated chloride channel → inability to reabsorb Cl- from the lumen of the sweat glands → reduced reabsorption of Na+ and H2O → excessive loss of salt and elevated levels of NaCl in sweatIn all other exocrine glands: The chloride channel is responsible for transporting Cl- from the cell into the lumen (secretion).Defective ATP-gated chloride channel → inability to transport intracellular Cl- across the cell membrane → reduced secretion of Cl- → accumulation of intracellular Cl- → ↑ Na+ reabsorption (via ENaC) → ↑ H2O reabsorption → formation of hyperviscous mucus → accumulation of secretions and blockage of small passages of affected organs → chronic inflammation and remodeling → organ damage (see "Clinical features" below for details)↑ Na+ reabsorption → transepithelial potential difference between interstitial fluid and the epithelial surface increases (i.e., becomes more negative: e.g., from normal -13 mv to abnormal -25 mv) In all exocrine glands, the Cl- channel is responsible for transporting intracellular Cl- across the cell membrane. However, in sweat glands, the Cl- channel is responsible for transporting Cl- from the lumen into the cell. The sweat test relies on the inability of the sweat glands to reabsorb salt, which results in elevated NaCl levels in sweat (see "Diagnostics" below). Clinical features Gastrointestinal Meconium ileus in newborns Failure to thrive due to malabsorption Gastrointestinal symptoms are common in infancy. Pancreatic diseasePancreatitisExocrine pancreatic insufficiencyFoul-smelling steatorrhea (fatty stools) may occur.MalabsorptionAbdominal distention DiarrheaDeficiency of fat-soluble vitamins (e.g., night blindness due to vitamin A deficiency, rickets due to vitamin D deficiency)CF-related diabetes mellitus (CFRD) Liver and bile duct abnormalitiesCholecystolithiasis, cholestasisFatty metamorphosis of the liver, eventually progressing to liver cirrhosis Biliary cirrhosis with portal hypertension Intestinal obstruction: abdominal distention, pain, and a palpable mass Rectal prolapse (rare) Respiratory Respiratory symptoms are common in adulthood. Obstructive lung disease with bronchiectasis Chronic sinusitis; nasal polyps may eventually develop Recurrent or chronic productive cough and pulmonary infections with characteristic microorganismsS. aureus is the most common cause of recurrent pulmonary infection in infancy and childhood.P. aeruginosa is the most common cause of recurrent pulmonary infections in adulthood. Dangerous bacteria (especially Pseudomonas aeruginosa) are easily transmitted to patients with CF → rapid decline in pulmonary function and increased risk of death (multiple antibiotic courses in their lifetime → high resistance to commonly used antibiotics!)Expiratory wheezing (obstruction), barrel chest , moist rales (indicate pneumonia), hyperresonance to percussionSigns of chronic respiratory insufficiency: digital clubbing associated with chronic hypoxia Airway hyperreactivity (e.g., wheezing) Sweat glands Especially salty-tasting sweat → electrolyte wasting Hyperhidrosis does not occur. Musculoskeletal Frequent fractures because of osteopenia Kyphoscoliosis Urogenital UrinaryNephrolithiasis, nephrocalcinosisFrequent urinary tract infections GenitalThe following factors may compromise the fertility of patients or cause them to be completely infertile: MenObstructive azoospermia is common. The vas deferens may also be absent. Undescended testicleWomenViscous cervical mucus can obstruct fertilization.Menstrual abnormalities (e.g., amenorrhea) Delayed secondary sexual development in both sexes Diagnostics General In most cases, CF is suspected based on clinical features, a positive newborn screen, or a sibling with CF. Best initial test is the sweat chloride test.If results are abnormal or borderline, DNA testing for the two CFTR mutations is indicated to confirm the diagnosis.If only one or no CFTR mutations are identified, an expanded DNA analysis or second sweat test should be performed; a positive result on either one of these confirms the diagnosis. Diagnostic criteria Typical clinical manifestations of CF: chronic sinopulmonary disease, gastrointestinal and nutritional irregularities, syndromes of salt loss, obstructive azoospermia AND evidence of CFTR dysfunction Sweat chloride ≥ 60 mmol/L on two occasionsOR CFTR gene mutationOR abnormal nasal potential difference test Neonatal screening ↑ Immunoreactive trypsinogen (IRT)Usually the first screening assay performed on neonatesDetects elevated levels of IRT in heel-prick blood DNA assayEither primary screening test or confirmation of CF after abnormal IRT resultIdentification of common CFTR mutations All neonates are screened for CF in the US! Laboratory tests Quantitative pilocarpine iontophoresis (sweat test) is the best initial test.Chloride levels > 60 mmol/L on two or more occasions are consistent with CF.The test should be conducted in patients > 2 weeks of age and > 2 kg in weight (more accurate). DNA analysisPrenatalIndication: if both parents are carriers of a CFTR mutationSpecimen collected via chorionic villus sampling or amniocentesisPostnatal/adult analysis: may be required if the sweat test is negative in a patient with suspected CF Nasal potential difference testIndication: unclear findings in sweat chloride and DNA tests despite CF-like disease in an organ systemVoltage measurements before and after the nose is perfused with different solutions show abnormal epithelialsecretion of chloride (e.g., more negative baseline potential difference and no difference in nasal potential difference after a chloride-free solution is administered). Supportive tests Other blood tests Contraction alkalosis and hypokalemia may occur (due to excessive loss of H2O and NaCl via the sweat glands and renal H+/K+ wasting) Stool: ↓ chymotrypsin and pancreatic elastase Chest x-ray/CT: hyperinflation Pulmonary function tests: ↓ FEV1:FVC ratio and ↑ residual volume (RV) and total lung capacity (TLC) ratio Findings are consistent with an obstructive ventilatory disorder; see spirometry. Ultrasound: increased liver echogenicity (fatty liver) Treatment Symptomatic management Ideally, management should be supervised by specialists in cystic fibrosis centers. RespiratoryHypertonic saline nebulization or aerosolized dornase alpha (recombinant DNAse that is a specific mucolytic agent that breaks down extracellular DNA in sputum) Bronchodilator therapy (e.g., albuterol)Chest physiotherapyIn chronic rhinosinusitis: intranasal glucocorticoids (see sinusitis)Mucolytics (e.g., N-acetylcysteine)High-dose ibuprofen has been shown to reduce respiratory disease progression. In chronic respiratory insufficiency Long-term oxygen inhalation therapyTreatment of last resort: lung transplantation Diet Additional sodium chloride intake High-energy diet to compensate for increased demand Pancreatic enzyme supplementsOral supplementation of lipophilic vitamins A, D, K, and E CFTR modulators [12] Indication: patients with CF who are homozygous for the delta F508 mutation in the CFTR gene Mechanism of action: These drugs modulate the expression of the defective CFTR protein by improving the production, intracellular processing, and function of the defective protein. Combination therapy: The drugs work synergistically to increase both the quantity and function of the CFTR protein on the cell surface, resulting in enhanced chloride transport. DrugsIvacaftor: improves Cl- transport by increasing the likelihood that the Cl- channel is open at the cell surface.Combination therapy with either tezacaftor or lumacaftorLumacaftor: improves the conformational stability of the defective CFTR protein, which leads to increased intracellular processing and trafficking of functional CFTR protein to the cell surfaceTezacaftor: increases the amount of mature CFTR protein on the cell surface by improving intracellular processing and trafficking of the CFTR protein Because CFTR modulators are only effective in patients with certain CFTR mutations, it is essential to perform CFTRgenotyping prior to initiating treatment. InfantsStaphylococcus aureusHaemophilus influenzaeIV vancomycin AdultsPseudomonas aeruginosaBurkholderia cepaciaFirst line: inhaled tobramycinAlternative: ciprofloxacin PO + inhaled colistinTreatment-resistant cases or if inhalation is not possible IV antibiotics: tobramycin, ceftazidime, or meropenemAspergillusItraconazole or voriconazole POStenotrophomonas maltophilia Trimethoprim/sulfamethoxazole (TMP/SMX) Preventive measures Annual influenza vaccine for all CF patients > 6 months with inactivated influenza vaccine (IIV) Pneumococcal vaccine (see the immunization schedule) Palivizumab: antibody against respiratory syncytial virus (RSV) for infants < 24 months Long-term treatment with azithromycin may be used to prevent recurrent pulmonary infections. Complications Gastrointestinal Meconium ileusDefinition: failure to pass the first stool in neonates (meconium usually passes in the first 24-48 hours after birth)Etiology: Cystic fibrosis is the leading cause in (> 90%) of cases.Clinical findings: signs of a distal small bowel obstructionBilious vomitingAbdominal distentionNo passing of meconium or stoolDiagnostics: abdominal x-ray (with contrast agent) Dilated small bowel loops, microcolon, Neuhauser sign ("soap bubbles" effect) Air-fluid levels are uncommon because of the viscous consistency of meconium.Differential diagnosis: See differential diagnosis of intestinal obstruction in neonates.TreatmentEnema with a contrast agent Surgery is required in complicated cases: intestinal perforation or volvulus Small bowel obstruction can also occur in older children and adults. Respiratory Hemoptysis Allergic bronchopulmonary aspergillosis (ABPA): ∼ 10% of patients develop this condition. Pulmonary emphysemaPneumothorax Cor pulmonale Prognosis Median life expectancy: ∼ 39 years The main determinant of life expectancy is the severity of pulmonary disease: chronic respiratory infections and mucus plugging → bronchiectasis (irreversible) → progressive respiratory failure → death Progress in the medical and psychological management of patients with CF has lead to: Significant improvement in survival in recent yearsSuccessful pregnancies

Insulinoma Insulinomas are predominantly benign, pancreatic islet beta-cell tumors associated with increased insulin production. While most insulinomas are sporadic, some are associated with multiple endocrine neoplasias (e.g., parathyroid tumors, pituitary adenomas, gastrinomas). Insulinomas present clinically with recurrent attacks of hypoglycemic symptoms that subside after glucose intake. The diagnosis is established by demonstrating inappropriately elevated serum insulinfollowing a fasting test. Insulinomas are differentiated from other causes of hyperinsulinemia (e.g., exogenous insulinadministration) by the presence of elevated levels of proinsulin and C-peptide. The treatment of choice is surgical enucleation of the insulinoma. In inoperable cases and patients with persistent hypoglycemic attacks, diazoxide can be used to decrease insulin secretion.

Epidemiology Sex: ♀ > ♂ Age range: ∼30-60 years Incidence: ∼ 5 cases/1,000,000 persons per year Pathophysiology Insulinomas are neuroendocrine tumors that arise from beta cells of the pancreas ∼ 90% of insulinomas occur as solitary tumors Most insulinomas occur sporadically Over 90% of insulinomas are benign ∼5% of insulinomas are associated with multiple endocrine neoplasia type 1 (MEN 1). Clinical features Clinical features of hypoglycemia Relief of symptoms after administering glucose (See also Whipple's triad.) Weight gain Symptoms characteristic of other endocrine neoplasias may occur. (See MEN.) Diagnostics Hypoglycemia with inappropriately high insulin levels (hyperinsulinism) Fasting test: Positive if serum glucose levels remain low (< 40 mg/dL) and insulin levels remain high even after fastingfor 72 hours. ↑ C-peptide and ↑ proinsulin levels Elevated C-peptide levels are not seen with the use of exogenous insulin (e.g., factitious hypoglycemia) Imaging (endoscopic ultrasonography, CT, MRI, selective angiography): for surgical planning Elevated C-peptide and proinsulin levels may also be the result of sulfonylurea use! This can be ruled out by screening serum samples for sulfonylureas. Treatment SurgeryTreatment of choice if tumor is operableSurgical enucleation of the pancreatic adenoma (by either open surgery or laparoscopy) MedicationTreatment of inoperable tumors or recurrent hypoglycemic attacks despite surgeryInhibitors of insulin release Diazoxide [7]Octreotide

Primary biliary cholangitis Primary biliary cholangitis (PBC; also known as primary biliary cirrhosis) is a chronic progressive liver disease of autoimmune origin that is characterized by destruction of the intralobular bile ducts. The pathogenesis of PBC is unclear; however, it primarily affects middle-aged women and is frequently associated with other autoimmune conditions. In the early stages, PBC is typically asymptomatic. Fatigue is the most common initial complaint. In advanced disease, increased fibrotic changes lead to typical signs of cholestasis (e.g., jaundice) and portal hypertension (e.g., ascites, gastrointestinal bleeding). Elevated cholestasis parameters (ALP, γ-GT, bilirubin) as well as antimitochondrial antibodies (AMAs) help establish the diagnosis. Management consists of slowing disease progression with ursodeoxycholic acid and relieving symptoms. Liver transplantation is the only definitive treatment.

Epidemiology Sex: ♀ > ♂ (∼ 9:1) Age range: 30-65 years Most common cause of vanishing bile duct syndrome Etiology Idiopathic: however, generally accepted as an autoimmune disease Associated with other autoimmune conditions (see "Clinical features" below) Positive family history is a predisposing factor. Pathophysiology Inflammation and progressive destruction (likely due to an autoimmune reaction) of the small and medium-sizedintrahepatic bile ducts (progressive ductopenia) → defective bile duct regeneration → chronic cholestasis → secondary hepatocyte damage due to increased concentration of toxins that typically get excreted via bile → gradual portal and periportal fibrotic changes → liver failure → liver cirrhosis and portal hypertension (in advanced stage) Clinical features Patients are initially often asymptomatic (25% of cases are diagnosed incidentally). Signs and symptoms are mainly due to the resulting cholestasis, liver cirrhosis, and portal hypertension. Fatigue (usually the first symptom) Marked generalized pruritus Hyperpigmentation Hepatomegaly, dull lower margin, RUQ discomfort Splenomegaly Jaundice Maldigestion (may involve manifestations of deficiency of fat-soluble vitamins, e.g., osteoporosis) Xanthomas and xanthelasma Common associations include: sicca syndrome, autoimmune thyroid disease, CREST syndrome, rheumatoid arthritis Diagnostics Laboratory tests↑ Cholestasis parameters (ALP, γ-GT, conjugated bilirubin)Transaminases (AST/ALT) are within normal limits or slightly elevated↑ Antimitochondrial antibodies (AMA) (> 95%)↑ ANA (up to 70%)↑ IgM Liver biopsyCan confirm the diagnosis (although not required)Necessary for staging Pathology Histopathological stages Stage I: lymphocytic infiltration of portal areas and periductal granulomas Stage II: bile duct ductopenia, progressive fibrosis Stage III: bridging fibrosis Stage IV: liver cirrhosis Differential diagnoses Autoimmune hepatitis Primary sclerosing cholangitis (see differential diagnoses of primary cholangitis) Biliary obstruction Drug-induced liver damage Sarcoidosis Treatment There is no cure for PBC. Treatment consists of slowing disease progression and alleviating symptoms. Liver transplantation is the only definitive treatment. First-line medical therapy: ursodeoxycholic acid (aka ursodiol, or UDCA) Slows progression of the disease and improves clinical symptomsDelays the need for transplantationActive ingredient is a hydrophilic bile acidHepatoprotective; antiapoptotic Immunomodulatory: UDCA suppresses immune reactions that promote disease progression Also used in primary sclerosing cholangitis, cholestasis of pregnancy, and small cholesterol stones Treatment of cholestatic pruritus Liver transplantation necessary if liver cirrhosis is advanced Complications Malabsorption Liver cirrhosis and portal hypertension Osteoporosis

Pancreatic cancer Pancreatic cancer is the fourth leading cause of cancer deaths in the US and typically affects older individuals in the sixth to eighth decades of life. Underlying risk factors include smoking, obesity, heavy alcohol consumption, and chronic pancreatitis. Pancreatic carcinomas are mostly ductal adenocarcinomas and frequently located in the pancreatic head. The disease is commonly diagnosed at an advanced stage because of the late onset of clinical features (e.g., epigastric pain, painless jaundice, and weight loss). In many cases, the tumor has already spread to other organs (mainly the liver) when it is diagnosed. Treatment is often palliative as surgical resection is only possible in approx. 15% of cases. The most commonly used surgical technique is the pancreaticoduodenectomy ("Whipple procedure"). Five-year survival rates range from 1-20% depending on the extent, spread, and resectability of the tumor.

Epidemiology Sex: ♂ > ♀ Age of onset: 60-80 years More common in African Americans Accounts for ∼ 3% of all cancers in the US and ∼ 7% of cancer deaths The average lifetime risk: ∼ 1.5% Etiology Risk factorsSmoking Chronic pancreatitisHigh alcohol consumption Type 2 diabetesObesityOccupational exposure to chemicals used in the dry cleaning and metal working industriesCirrhosis of the liverH. pylori infection; excess stomach acidInherited genetic syndromes (10% of pancreatic cancers) Familial pancreatic carcinomaHereditary pancreatitis (mutations in the PRSS1 gene)Peutz-Jeghers syndromeFamilial atypical multiple mole melanoma (FAMMM) syndromeHereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutations)HNPCCVon-Hippel-Lindau syndromeNeurofibromatosis type 1Multiple endocrine neoplasia type 1 Clinical features Often no early signs present! Belt-shaped epigastric pain which may radiate to the back JaundiceCourvoisier sign: enlarged gallbladder and painless jaundice Pale stools, dark urine, and pruritus Weight loss, nausea, weakness, poor appetite Diarrhea (possibly steatorrhea secondary to exocrine pancreatic insufficiency) Superficial thrombophlebitis (in 10% of cases, also called Trousseau syndrome or thrombophlebitis migrans)Recurring thrombophlebitis in various locationsClassically associated with pancreatic cancer Thrombosis (e.g., phlebothrombosis, splenic vein thrombosis) Impaired glucose tolerance (rarely) Diagnostics Blood No screening tests available Tumor markers: CA 19-9 and CEAUsed to monitor the progression of cancer and treatment efficacy Possibly ↑ lipase Imaging First test: usually either contrast-enhanced abdominal CT or ultrasound → if ultrasound reveals a pancreatic mass → subsequent CT Poorly defined, hypodense/hypoechoic and hypovascular mass Double-duct sign : With increasing size, tumors of the pancreatic head may block bile drainage in both the common bile duct and the pancreatic duct, leading to dilatation of both structures. Endoscopic or magnetic retrograde cholangiopancreatography (ERCP/MRCP): to rule out choledocholithiasis and/or if biliary decompression is indicated, e.g., in case of palliative treatment to alleviate jaundice Endoscopic ultrasound (EUS) Used when other diagnostic tests are inconclusive or to perform fine needle aspiration Findings similar to transcutaneous ultrasound Fine needle aspirationNot routinely performed Can help differentiate pancreatic cancer from pancreatitis (e.g., chronic or autoimmune)Can be done via EUS (preferred) or percutaneously (US or CT-guided) Pathology LocationPancreatic head: 75% of casesPancreatic body: 15-20% of casesPancreatic tail: 5-10% of cases Pancreatic exocrine tumors (95%)Mostly ductal adenocarcinoma Less common: acinar adenocarcinoma (acinar cells produce digestive enzymes) and others Pancreatic endocrine tumors (neuroendocrine tumors/NET, < 5% of tumors) Insulinomas (result in hypoglycemia)GastrinomasVasoactive intestinal peptide-producing tumors (VIPomas), pancreatic polypeptide-secreting endocrine tumors of the pancreas, glucagonomas, somatostatinomas Differential diagnoses Pancreatitis Metastasis (e.g., breast carcinoma, bronchial carcinoma) Pancreatic pseudocyst Pancreatic cyst: Epithelium-lined cyst, filled with serous or mucous liquid, often associated with the rare von-Hippel-Lindau syndrome; can be benign, precancerous or cancerous. Clinical features: abdominal pain, back pain, jaundice, and in case of infection, fever and sepsisCT scan: cyst appears as a well-circumscribed hyperdense mass in comparison to the surrounding tissue. Pancreatic cancer, on the other hand, is hypodense.ERCP: cyst shows contrast-enhancement Treatment Asymptomatic cyst: no surgical treatmentSymptomatic cyst: CT-guided, endoscopic, or surgical drainage Treatment As the only curative treatment option for pancreatic cancer is surgical resection, patients with operable tumors (∼ 20%) are always recommended for surgery. If surgical tumor resection is not possible or distant metastasis is present, a palliative approach is chosen. Curative approach Surgery Pancreatic head carcinoma: pancreaticoduodenectomy ("Whipple procedure"; method of choice)Resection of pancreatic head, distal stomach, duodenum, gallbladder, and common bile ductLymphadenectomy Reconstruction by enteroenterostomy or Roux-en-Y anastomosisPylorus-preserving pancreaticoduodenectomy (Traverso-Longmire procedure): a modification of the Whipple procedure that preserves the gastric antrum, the pylorus and a small part of the duodenum (anastomosed to the jejunum) to provide a more physiologic stomach emptying Pancreatic body and tail carcinomaResection of the left side of the pancreas with splenectomyIn some cases, duodenopancreatectomy with splenectomyIndicated in a curative treatment approach if partial removal of the pancreas is insufficient Neoadjuvant or adjuvant chemoradiotherapy To reduce tumor size, improve symptoms, and prolong life Chemotherapy or radiation therapy without surgery cannot cure the patient. Palliative approach Palliative chemotherapy: indicated in patients with advanced or metastatic pancreatic cancer Analgesia according to the WHO step-by-step planEarly consultation with a pain therapist for optimizing the need of coanalgesics and adjuvants may be indicated. Cholestasis : ERCP with stent implantation Percutaneous transhepatic bile duct drainage (PTCD) Indication: if endoscopic access path is complicated (e.g., in duodenal stenosis, duodenal resection, and inaccessibility of the biliodigestive anastomosis) Gastroenterostomy: best supportive care in patients with gastric outlet stenosis. The stomach is anastomosed with the small intestine bypassing the duodenum. Percutaneous endoscopic gastrostomy (PEG) tube as a relief tube: indicated for severe palliative patients with chronic ileus and subileus that are inoperable Complications Lymphogenic and hematogenous metastasisEarly stage: nearby lymph nodes and liverAdvanced stage: surrounding visceral organs (duodenum, stomach, colon) and lungs StenosisGastric outlet stenosisStenosis of the common bile duct (cholestasis) Other complicationsSecondary diabetes mellitusDisseminated intravascular coagulation (DIC) Necrolytic migratory erythema Prognosis The overall 5-year survival rate is 7%, but mainly depends on the stage of disease. Median survival for patients who undergo successful resection: ∼ 12-19 months, with a 5-year survival rate of 15-20% A metastatic pancreatic cancer has a 5-year survival rate of ∼ 2%.

Gastric cancer Gastric cancer refers to neoplasms in the stomach, including cancers of the esophagogastric junction. The incidence is declining in the United States and Europe, while it is rising in Japan and South Korea. Gastric cancer is associated with several risk factors (e.g., consumption of foods high in nitrates, increased nicotine intake, Helicobacter pylori infection). In its early stages, the disease is often asymptomatic or accompanied by nonspecific symptoms (e.g., epigastric discomfort, postprandial fullness, or nausea). Late-stage disease may present with gastric outlet obstruction (mechanical obstruction of the pyloric canal), leading to weight loss and vomiting. Biopsy during endoscopy confirms the diagnosis. Adenocarcinomas are the most common form of gastric cancer. Treatment includes endoscopic or surgical resection. Depending on staging, chemotherapy may be indicated before or after surgery (neoadjuvant or adjuvant chemotherapy), or as a palliative therapy.

Epidemiology Sex: ♂ > ♀ Peak incidence: 70 years Geographical distribution: strong regional differences High incidence in South Korea and JapanDeclining incidence in the United States and Europe Etiology Exogenous risk factorsDiet rich in nitrates and/or salts (e.g., dried, preserved food) Nicotine useLow socioeconomic status Endogenous risk factorsDiseases associated with a higher risk of gastric cancer Atrophic gastritisH. pylori infection: associated with a higher risk of intestinal gastric cancer but not with diffuse gastric cancerGastric ulcersPartial gastrectomyGastroesophageal reflux disease (GERD; for cancers of the gastroesophageal junction) Adenomatous gastric polypsHereditary factors (positive family history, hereditary non‑polyposis colorectal cancer)Higher incidence in individuals with blood type A. Clinical features Gastric cancer is often asymptomatic. Early signs are nonspecific and often go unnoticed. At later stages the following symptoms may occur: General signsWeight lossChronic iron deficiency anemia (paleness, fatigue, headaches) Gastrointestinal signsAbdominal painEarly satietyNausea or vomitingDysphagiaAcute gastric bleeding (hematemesis or melena) Late stage gastric cancerPalpable tumor in epigastric regionGastric outlet obstructionHepatomegaly, ascitesVirchow's node: left supraclavicular adenopathy, located where the thoracic duct joins the subclavian vein at the venous angle.Sister Mary Joseph's node: umbilical node indicating metastasis from a gastrointestinal or abdominopelvic malignancyMalignant acanthosis nigricans (in particular associated with gastric adenocarcinoma) Subtypes and variants Metastatic Disease Lymphangitic spreadAll local lymph nodes (lesser and greater curvature)Celiac, paraaortic, and mesenteric lymph nodesCarcinoma of the cardia may spread to mediastinal lymph nodes. Hematogenous spread: liver, lung, skeleton, brain Local invasion of adjacent structuresPeritoneal carcinomatosisEsophagus, transverse colon, pancreas, etc. Direct seedingTo the ovaries (Krukenberg tumor): an ovarian malignancy comprised of signet ring cells that has metastasizedfrom a primary site, most commonly the stomachTo the pouch of Douglas Diagnostics Diagnostic procedures Upper endoscopy with biopsy (best initial test) : Biopsy confirms the diagnosis Barium upper GI series may be considered and would show loss of intestinal folds and stenosis Laboratory test Iron deficiency anemia Serologic markers : TNF-α as possible future tumor marker Staging Abdominal ultrasound EndosonographyAssessment of tumor depth and local lymph nodes Abdominal and pelvic CT-scan using intravenous and oral contrast; Thoracic CT-scan Diagnostic laparoscopy Staging of gastric cancer is essential to determine the correct treatment options. When first diagnosed with gastric cancer, ∼ 70% of patients already show metastatic spread to the lymph nodes! Pathology Adenocarcinoma (90% of cases)Typically localized, exophytic lesion +/- ulcerationArise from glandular cells in the stomach; usually located on the lesser curvature of the stomach Signet ring cell carcinomaDiffuse growthMultiple signet ring cells = round cells filled with mucin, with a flat nucleus in the cell periphery Less common Adenosquamous carcinomaSquamous cell carcinoma Lauren classification of gastric adenocarcinoma Intestinal type (∼ 50% of cases): polypoid, glandular formation; expanding (not infiltrative) growth pattern; clear border Diffuse type (∼ 40% of cases): infiltrative growth and diffuse spread in the gastric wall, no clear border Mixed type (∼ 10% of cases) Differential diagnoses Gastric ulcer Gastroesophageal reflux disease (GERD) Ménétrier's disease Non-ulcer dyspepsia Other types of cancer MALT lymphomaSarcomaGastrointestinal stromal tumor (GIST) Treatment Exact therapy, which may be either curative or palliative, depends on staging and the type of tumor. Endoscopic resection SurgeryPerioperative chemotherapy, sometimes radiotherapyTrastuzumab is indicated for HER2+ gastric adenocarcinomas Surgery Radical gastrectomy and lymphadenectomy (operative standard) Resection of the lesser and greater omentum and radical lymphadenectomy Roux-en-Y gastric bypassThe surgeon separates the proximal jejunum from the duodenum and creates an end-to-end anastomosis of the jejunum with the remaining part of the stomach (gastrojejunostomy), or in the case of a total gastrectomy, with the esophagus (esophagojejunostomy). Duodenal stump is connected distally with the jejunum using an end-to-side anastomosis. Alternative: subtotal gastrectomy Complications Malignant acanthosis nigricans A paraneoplastic syndrome seen in adenocarcinomas of GI origin, especially in gastric adenocarcinoma Pathophysiology: caused by exogenous transforming growth factor TGF-α and epidermal growth factor (GF) Clinical findingsBrown to black, intertriginous and/or nuchal hyperpigmentation that can turn into itching, papillomatous, poorly-defined efflorescenceRapid growth and verrucous or papulous surface helps to differentiate it from benign acanthosis nigricansLocalization: axilla, groin, neck Malignant acanthosis nigricans always requires further diagnostic measures to look for malignancy! Postgastrectomy syndromes Related to resorption MaldigestionConsequences and management Iron deficiency → supplement ironPernicious anemia due to lack of intrinsic factor, usually produced by gastric parietal cells → supplement vitamin B12 Related to anastomosis Small intestinal bacterial overgrowth (SIBO)Definition: bacterial overgrowth within the small intestineCausesAnatomic abnormalities: (e.g., surgery causing blind intestinal loops - blind loop syndrome ), strictures)Motility disorders Pathophysiology: bacterial overgrowth → bacteria deconjugate bile acids, increase vitamin B12 turnover, and produce increased amounts of vitamin K and folic acidClinical features: diarrhea, steatorrhea, weight loss, malabsorption (e.g., deficiency of vitamin B12, A, E, D, zinc, and iron)DiagnosticsJejunal aspirate cultures collected during endoscopy Positive lactulose breath test Treatment: antibiotics and parenteral supplementation of vitamins and proteins, possibly surgical treatment Related to motility Dumping syndrome: rapid gastric emptying due to either defective gastric reservoir function or pyloric emptying mechanism, or anomalous postsurgery gastric motor function.Early dumpingCause: rapid emptying of undiluted chyme into the small intestine caused by a dysfunctional or bypassed pyloric sphincter Clinical featuresAppears within 15-30 minutes after ingestion of a mealSymptoms may include nausea, vomiting, diarrhea, and cramps, as well as vasomotor symptoms such as sweating, flushing, and palpitations. ManagementDietary modifications: Small meals that include a combination of complex carbohydrates and foods rich in protein and fat to cover protein and energy requirements are preferable.30-60 min of rest in the supine position after meals Often spontaneous improvement after a couple of months Late dumping Cause: postprandial hypoglycemia; dysfunctional pyloric sphincter → chyme containing glucose immediately reaches the small intestine → glucose is quickly resorbed → hyperglycemia → excessive release of insulin → hypoglycemia and release of catecholaminesTreatmentDietary modificationsOctreotide and surgery are second and third-line therapies Suspect late dumping syndrome in a patient with previous gastric surgery and hypoglycemia! Remnant carcinoma is a complication associated with the remnant stomach. Follow-up is important! Prognosis Since there are no early signs, gastric cancer is often diagnosed very late. At diagnosis, 60% of cancers have already reached an advanced stage that does not allow for curative treatment. Early gastric cancer has the best prognosis .Distant metastases or peritoneal carcinomatosis dramatically worsen the prognosis and are lethal most of the time.

Gastrinoma A gastrinoma (Zollinger-Ellison syndrome) is a gastrin-secreting neuroendocrine tumor that is most often localized to the duodenum and pancreas. Most gastrinomas occur sporadically, but some are associated with other endocrine neoplasias (e.g., pituitary adenomas, parathyroid adenomas, insulinomas). Although some gastrinomas are benign, more than half of all gastrinomas are malignant. Gastrinomas release high levels of gastrin, which then increases the production of gastric acid. Patients typically present with recurrent, therapy-resistant peptic ulcer disease and diarrhea. Patients with gastrinomas have low gastric pH and elevated serum gastrin. Furthermore, serum gastrin levels increase with the administration of secretin (positive secretin stimulation test). Surgical resection of the tumor is indicated in patients with localized disease. Proton pump inhibitors (PPIs) and octreotide may be used to control acid secretion.

Epidemiology Sex: ♂ > ♀ (2:1) Age of onset: 30-50 years Etiology Gastrinomas are assumed to arise from endocrine cells of the gut (mostly the duodenum) or the pancreas. Most gastrinomas occur sporadically . Some gastrinomas occur in association with multiple endocrine neoplasia type 1 (MEN 1) . Pathophysiology Gastrinomas are neuroendocrine tumors of the GI tract that secrete gastrin. Hypergastrinemia → stimulation of parietal cells → gastric acid hypersecretion, which leads to:Peptic ulcer diseaseInactivation of pancreatic enzymes → diarrhea, steatorrhea → malabsorption Tumor locationDuodenum (∼ 70% of cases) Pancreas (∼ 25% of cases): typically the head Ectopic locations (5-15% of cases): e.g., liver, peripancreatic lymph nodes, ovaries ∼ 60% of gastrinomas are malignant (but slow-growing) Clinical features Most patients manifest with recurrent, therapy-resistant peptic ulcer disease. Abdominal pain Diarrhea and steatorrhea Dyspeptic symptoms (e.g., heartburn) Upper gastrointestinal bleeding Weight loss Possible symptoms of other endocrine neoplasias (See MEN 1.) Diagnostics Best initial test: esophagogastroduodenoscopyImportant to rule out H. pylori infection and malignant ulcersTypically reveals multiple ulcers and thick gastric folds ↓ Gastric pH Confirmatory tests↑ Serum gastrin (in a fasting serum sample) A gastrin level > 1000 pg/mL (or 10-fold increase in gastrin levels) is conclusive evidence of a gastrinoma. If serum gastrin levels increase (> 100 pg/mL) but are not more than 1000 pg/mL, a secretin stimulation testshould be performed. Proton pump inhibitors (PPIs) and histamine 2 (H2) blockers generally elevate serum gastrin levels. Before testing, treatment with PPIs should therefore be paused for 6 days, and treatment with H2 blockers should be paused for one day. Secretin stimulation test (if fasting serum gastrin test is inconclusive) A two-fold increase in gastrin above the basal level is indicative of a gastrinoma. No increase or only a very slight increase is observed in cases of secondary hypergastrinemia. Imaging: only after diagnosis is confirmed to localize the tumorCT/MRI scan, somatostatin receptor scintigraphy (octreotide scan) and/or endoscopic ultrasonography The presence of multiple, large (> 2 cm) ulcers in atypical locations (e.g., the jejunum) should raise suspicion of gastrinoma! Low gastric pH along with gastrin levels > 1000 pg/mL is virtually sufficient to diagnose gastrinoma. If gastrin levels are less than 1000 pg/mL, a secretin stimulation test must be performed! Treatment Reduce acid productionPPIs (e.g., omeprazole), H2 antagonists (e.g., ranitidine) Octreotide (a somatostatin analog) may be used in refractory cases. Nonmetastatic disease: surgical resection of the gastrinoma Metastatic disease: chemotherapy In approximately 50% of cases, the tumor has already metastasized at the time of diagnosis!

Primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a progressive chronic inflammation of both the intrahepatic and extrahepatic bileducts. While the exact etiology is unknown, there is a strong association with autoimmune diseases, particularly ulcerative colitis (UC). In the early stages, PSC is usually asymptomatic. Later in the course of the disease, patients present with symptoms of cholestasis (e.g., pruritus, jaundice). Laboratory abnormalities include elevated liver function tests and autoantibodies (pANCA in up to 80% of cases). Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) is performed to confirm the diagnosis. Management is primarily symptomatic, with liver transplantation reserved for end-stage liver disease.

Epidemiology Sex: ♂ > ♀ (2:1) Age: The median age at diagnosis is ∼ 40. Etiology AssociationsChronic inflammatory bowel diseases (IBD)∼ 90% of PSC patients have IBD (from these patients, 87% have ulcerative colitis (UC) and 13% have Crohn's diseaseHowever, only ∼ 5% of patients with UC and < 5% of patients with Crohn's disease develop PSC.HLA-B8 and HLA-DR3Other autoimmune conditions (e.g., hypergammaglobulinemia IgM) The majority of PSC patients also have ulcerative colitis! Clinical features Often initially asymptomatic Signs of cholestasisJaundice/scleral icterusPruritusFatigueAcute cholangitis (fever, chills, right upper quadrant pain) Later stages: signs of cirrhosisHepatomegalyPortal hypertensionLiver failure Symptoms of chronic inflammatory bowel disease, which is frequently associated with PSC, or other associated comorbidities Diagnostics Laboratory findings Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are present in up to 80% of cases ↑ ALP, GGT, conjugated bilirubin Potentially, ↑ transaminases (however, they are usually < 300 U/L) Imaging CholangiographyMethod of choice: magnetic resonance cholangiopancreatography (MRCP)Alternatives Endoscopic retrograde cholangiopancreatography (ERCP) More invasive but also more accurate than MRCPGood alternative for patients who cannot undergo MRI testing (e.g., patients with pacemaker)Percutaneous transhepatic cholangiography (PTC) Most invasive testFor patients who cannot undergo ERCPFindings: multifocal strictures alternating with dilation and beading of bile ducts UltrasoundIrregular diameter of the bile ductDiffuse thickening of the wall of the common hepatic and bile ducts Following diagnosis → colonoscopy (to assess for UC) Liver biopsy Not an essential part of the workup; usually done if small duct PSC is suspected, which is not always detectable via cholangiography Typical finding: "onion skin" scarring and fibrosis of bile ducts If a patient with pre-existing chronic inflammatory bowel disease displays increased ALP, GGT, and conjugated bilirubin, always consider PSC! Primary sclerosing cholangitis More common among middle-aged men Progressive chronic inflammation of both intrahepatic and extrahepatic bile ducts Pruritus Fatigue Jaundice Hepatomegaly pANCA ↑ ALP, GGT, and conjugated bilirubin Ulcerative colitis and cholangiocarcinoma Primary biliary cholangitis More common among middle-aged women Progressive destruction of only intrahepatic small and medium-sized bile ducts Similar to PSC Potentially xanthomas and xanthelasma Anti-mitochondrial antibodies (AMA) ↑ ALP, GGT, and conjugated bilirubin Autoimmune conditions Treatment SymptomaticUrsodeoxycholic acid and immunosuppressives (e.g., tacrolimus): may decrease transaminases, ALP, and serum bilirubin, but do not prevent disease progressionTreatment of pruritus (e.g., cholestyramine, rifampicin, naltrexone)Supplementation of fat-soluble vitamins (see "Complications" below)In the case of bile duct stenosis: ERCP with duct dilation; potentially, stent placement Surgical: Liver transplantation is the only curative option and is performed in the case of advanced liver cirrhosis. Complications Steatorrhea and deficiency of fat-soluble vitamins Liver cirrhosis Cholangiocarcinoma (∼ 10-15% of cases) Increased risk of hepatocellular, colorectal, pancreatic, and gallbladder cancer

Esophageal cancer Esophageal cancer typically assumes the form of adenocarcinoma or squamous cell carcinoma, although there are some rarer tumors. Adenocarcinomas are considered the fastest-growing neoplasia in Western countries, while squamous cell carcinoma is still most common in the developing world. Adenocarcinoma, which usually affects the lower third of the esophagus, may be preceded by Barrett's esophagus, a complication of gastroesophageal reflux disease (GERD). In addition to GERD, other risk factors include obesity and smoking. Squamous cell carcinomas mostly occur in the upper two-thirds of the esophagus. Known risk factors for squamous cell carcinoma include carcinogen exposure from alcohol and tobacco consumption, and dietary factors (e.g., diet low in fruits and vegetables). Esophageal cancers are often asymptomatic in early stages of the disease. Locally advanced disease is common at presentation, progressive dysphagiabeing the primary symptom. Hoarseness, weight loss, and hematemesis may also be present. Endoscopy is the primary diagnostic test, enabling direct visualization and biopsy of the lesion for histopathological confirmation. Curative surgical resection may be considered for locally invasive cancers. Esophageal cancer is unresectable at presentation in about 60% of patients. Chemotherapy, radiation, and palliative stenting play a role in the management of unresectable disease.

Epidemiology Sex: ♂ > ♀ (3:1) Peak incidence: 60-70 years of age Adenocarcinoma: most common type of esophageal cancer in the US [1] Squamous cell carcinoma (SCC): most common type of esophageal cancer worldwide [2] Etiology Adenocarcinoma Risk factorsGastroesophageal reflux: Barrett's esophagusObesitySmokingAchalasia Localization: mostly in the lower third of the esophagus Squamous cell carcinoma (SCC) Risk factors [4]Alcohol consumptionSmokingDiet low in fruits and vegetablesDrinking hot beveragesAchalasiaNitrosamines exposure (e.g., cured meat, fish, bacon) [5]Plummer-Vinson syndromeCaustic stricturesDiverticula (e.g., Zenker's diverticulum) RadiotherapyEsophageal candidiasisBetel or areca nut chewing Localization: mostly in the upper two-thirds of the esophagus The primary risk factors for squamous cell esophageal cancer are alcohol consumption, smoking, and dietary factors (e.g., diet low in fruits and vegetables)! Clinical features Early stages: Often asymptomatic but may present with swallowing difficulties or retrosternal discomfort Late stagesCommon Progressive dysphagia (from solids to liquids) with possible odynophagiaWeight loss Retrosternal chest or back painAnemia Less common Hematemesis, melenaHoarseness Esophageal cancer is a "silent" disease and typically becomes symptomatic at advanced stages! Diagnostics Esophagogastroduodenoscopy (best initial and confirmatory test) [8]Direct visualization of the tumor With biopsy of any suspicious lesions Barium swallow: asymmetrical and irregular borders of the esophagus with characteristic stenosis and proximaldilatation (apple core lesion) Sensitive, but does not allow confirmation or staging of a malignancy. Inferior to endoscopy, but indicated in the case of: Severe stricture that inhibits endoscopic evaluation Suspected tracheoesophageal fistula due to esophageal cancer Staging [8]Transesophageal endoscopic ultrasound Chest and abdominal CT and/or PET Bronchoscopy or laparoscopy Pathology Adenocarcinoma Histological characteristics: often present with adjacent Barrett mucosa (columnar epithelium with goblet cells) and high-grade dysplasia Squamous cell carcinoma Histological characteristics Breakdown of uniform tissue structureSquamous cell carcinoma clusters with circular keratinizationLymphocytic infiltration between the carcinoma clusters Treatment Curative IndicationLocally invasive disease that has not invaded surrounding structuresHigh-grade metaplasia in Barrett syndrome MethodsNeoadjuvant chemoradiationFor downstaging → potentially allows for later resection As definitive treatment in patients with proven complete response (e.g., during endoscopy) Surgical resectionEndoscopic submucosal resection for removal of superficial, epithelial lesions Subtotal or total esophagectomy with gastric pull-through procedure or colonic interposition Palliative Indication: patients with advanced disease (majority of patients) Methods: Chemoradiation Stent placement Other endoscopic treatments (e.g., laser therapy) Complications Esophageal stenosis Tracheoesophageal fistula: passage of food and fluid into the respiratory tract Postoperative Anastomotic leak or strictureRecurrent laryngeal nerve injury Prognosis Generally poor prognosis due to an aggressive course (due to an absent serosa in the esophageal wall) and typically late diagnosis [1][8] The more distal the tumor, the better the prognosis Esophageal cancer has an aggressive course and metastasizes early because of the absence of serosa in parts of the esophagus!

Hemochromatosis Hemochromatosis is a condition that leads to abnormal iron deposition in specific organs. There are two main types: primary (hereditary) and secondary (e.g., transfusion-related). The most common form is hereditary autosomal recessivehemochromatosis type 1, which is caused by an underlying genetic defect that results in partially uninhibited absorption of iron in the small intestine. Hemochromatosis is mostly asymptomatic but can become symptomatic, usually between the third and fifth decade of life, when poisonous levels of iron have had time to accumulate in the body. Symptoms include fatigue,hyperpigmentation, diabetes mellitus ("bronze diabetes"), and arthralgia. The deposits may lead to various organ diseases, the most typical being the development of liver cirrhosis, which is accompanied by an increased risk of hepatocellular carcinoma (HCC). Serum ferritin and transferrin saturation levels are typically elevated. Molecular genetic testing or a liver biopsy may be used to confirm the diagnosis. Treatment primarily consists of repeated phlebotomy to reduce iron levels. In addition, dietary changes and drug therapy (chelating agents such as deferoxamine) may be used to influence the amount of iron in the body.

Epidemiology The most frequent genetic disease in the white population 1:200 Etiology Primary (hereditary) hemochromatosis Classical and most frequent form: adult hemochromatosis type 1 Homozygous or heterozygous for the HFE gene defectLocated on chromosome 6Most commonly affects C282Y and H63DAssociated with HLA-A3 genotypeInheritance: autosomal recessive with incomplete penetrance Further forms: Hemochromatosis types II-IV are also hereditary, but significantly less frequent. HLA A3 as in HA3mochromatosis! Secondary hemochromatosis Caused by iron overloadTransfusion-related (e.g., for correcting chronic anemia)ThalassemiaSickle-cell anemiaSideroblastic anemiaPathogenesis: ineffective erythropoiesis with disturbances in the uptake of iron in heme or iron metabolismdisorder → iron overloadExamples: hereditary sideroblastic anemia; anemia of chronic diseaseExcessive alcohol consumption Pathophysiology Hemochromatosis type I: HFE gene defect (homozygous) → defective binding of transferrin to its receptor → liver stops producing the acute phase reactant hepcidin → unregulated ferroportin causes ↑ iron reabsorption in duodenalenterocytes → iron accumulation throughout the body → damage to the affected organs In hereditary hemochromatosis, decreased hepcidin leads to iron overload. In secondary hemochromatosis, iron overload leads to increased hepcidin! Clinical features Asymptomatic in 75% of cases The onset of symptoms: typically between the 3rd and 5th decade of life Abdominal pain, hepatomegaly → liver cirrhosis (+ hepatocellular carcinoma) Fatigue, lethargy Hyperpigmented, bronze skin Signs of diabetes mellitus (polydipsia, polyuria) Arthralgia , chondrocalcinosis Erectile dysfunction, testicular atrophy, loss of libido, amenorrhea Features of cardiac hemochromatosis [9]Cardiomyopathy (restrictive or dilated) Cardiac arrhythmias: paroxysmal atrial fibrillation (most common), sinus node dysfunction, complete AV block, atrial and ventricular tachyarrythmias, and sudden cardiac death Congestive heart failure Diagnostics As a result of its subtle and primarily asymptomatic course, hemochromatosis is often an incidental diagnosis first detected during routine checks or diagnosed only once signs of advanced organ involvement become apparent. Laboratory tests ↑ Serum iron ↑ Ferritin in serum > 200 μg/L ↑ Transferrin saturation (> 45%) ↑ Liver enzymes (AST, ALT) Genetic tests IndicationsFirst-degree relative with hemochromatosisConfirmed iron overload Findings: homozygote C282Y mutation of the HFE gene confirms the diagnosis. Liver biopsy Indications: elevated liver enzymes caused by hereditary hemochromatosis; increased serum ferritin levels (> 1000 μg/L) Histology Color stain: Prussian bluePronounced siderosis in iron staining with iron deposits primarily observed in hepatocytesMacrophages containing cytoplasmic granules which stain golden-yellow → hemosiderin from chronic hemolysis Treatment Primary hemochromatosis Dietary changesDiet low in iron Restriction of alcohol and vitamin C supplementsConsumption of tea Therapeutic phlebotomy (first-line treatment)Initially 1-2 phlebotomy sessions per week → After reaching target ferritin and hemoglobin levels, phlebotomyshould be performed every 2-4 months.Target levels: serum ferritin 20-50 μg/L; hemoglobin > 12 g/dL (or 120 g/L) Prognosis: initiation of therapy in the pre-cirrhotic phase → normal life expectancy and no organ damage Drug-induced iron chelationAgent: deferoxamine Indication: particularly when phlebotomy is contraindicated, e.g., in cases of anemia, severe heart disease, or difficult venipuncture Secondary hemochromatosis Depends on the underlying cause Consider iron chelation therapy Phlebotomy is often not advisable

Asplenia The spleen is primarily responsible for the elimination of damaged erythrocytes and plays a central role in the opsonization and removal of encapsulated organisms from the bloodstream. Asplenia is the absence of normal spleenfunction (functional asplenia) or of the spleen itself (anatomic asplenia). Anatomic asplenia is most commonly due to elective or emergency splenectomy, while functional asplenia is due to conditions that result in the loss of splenic function (e.g., multiple infarctions in sickle cell disease). Asplenic patients typically have Howell-Jolly bodies on peripheral blood smears as well as neutrophilia and thrombocytosis. Patients with asplenia have a lifelong risk of fulminant, life-threatening infections. Asplenic sepsis and overwhelming postsplenectomy sepsis have a very poor prognosis. Therefore, preventive measures including immunization against encapsulated bacteria and early empiric antibiotic treatment for fever are vital.

Etiology Acquired aspleniaAnatomic asplenia: due to splenectomy, which may be indicated inThrombocytopenia (e.g., refractory idiopathic thrombocytopenic purpura)Severe hemolytic anemias (e.g., spherocytosis)Splenic rupture (e.g., from blunt abdominal trauma)Hypersplenism with splenomegaly (See "Pathophysiology" in splenomegaly) Functional asplenia Autosplenectomy: sickle cell anemia Splenic infarction (splenic artery thrombosis) Congenital asplenia (very rare) Hematologic changes in asplenic patients Peripheral blood smearHowell-Jolly bodies Target cells Lymphocytosis Neutrophilia Decreased production of immunoglobulins (IgG, IgM): leads to decreased complement activation and C3b opsonization Reactive thrombocytosis: usually for the first weeks to months after splenectomy The lack of Howell-Jolly bodies in asplenic patients is suggestive of the presence of an accessory spleen! Infection in asplenic patients General: Increased risk of fulminant and life-threatening infections and sepsis for up to 30 years or longer after splenectomy Overwhelming postsplenectomy infection (OPSI) and asplenic sepsis Definition: a bacterial infection that rapidly progresses to fulminant, overwhelming sepsis in the setting of anatomic or functional aspleniaEtiology: encapsulated bacteria e.g., Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Clinical features: initially flu-like symptoms, followed by rapid deterioration within hours with fever, severe malaise, signs of sepsis, and meningitisTherapy: immediate IV antibiotic therapy with vancomycin plus ceftriaxone or cefotaxime PrognosisMortality approx. 10-40% with early treatmentMortality 70% without treatment An asplenic patient with fever requires immediate empiric antibiotic treatment. Asplenic infection and sepsis are a medical emergency! Preventing the infection is vital (see "Management of asplenic patients" below) Management of asplenic patients General measuresPatient identification card or Medic Alert® bracelet/necklace Prevent infectionsImmunization against Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type B (see immunization schedule) If elective surgery: vaccination should be performed 14 days prior Prevention steps if emergency splenectomy S. pneumoniae vaccines2 weeks after surgery → administer 13-valent pneumococcal conjugate vaccine (PCV13)8 weeks after PCV13 → administer 23-valent pneumococcal polysaccharide vaccine (PPSV23)5 years later and at age 65 → revaccinate with PPSV23Meningococcal quadrivalent vaccine → once after 2 weeks and then every 5 yearsHib vaccine → once after 2 weeksAnnual inactivated influenza vaccination Daily antibiotic prophylaxis: oral penicillin or amoxicillin administration in asplenic children up to at least age 5 years and at least one year after splenectomy Early empiric antibiotic therapy: if signs of infection appear (fever, chills), patients should immediately begin treatment Oral amoxicillin-clavulanate or cefuroxime or fluoroquinolones (e.g., levofloxacin) Prevent thrombosisIndication: Severe reactive thrombocytosis after splenectomy and risk factors for thrombosis (e.g., malignancy)Treatment Low-dose heparin for at least 4 weeksOptionally acetylsalicylic acid (100 mg daily) for one year

Chronic pancreatitis Chronic pancreatitis is caused by progressive inflammation and irreversible damage to the structure and function (exocrine and endocrine) of the pancreas. Alcohol abuse is the most common known etiological factor, followed by pancreatic ductal obstruction. Idiopathic pancreatitis accounts for up to 30% of cases. Patients may be asymptomatic or present with abdominal pain and features of pancreatic enzyme insufficiency (e.g., steatorrhea, weight loss, impaired glucose tolerance). Diagnosis is confirmed on imaging, which demonstrates pancreatic calcifications, ductal strictures, and ductal dilations. Pancreatic function tests (e.g., fecal elastase-1 measurement, 72-hour fecal fat estimation) assess the degree of enzyme deficiency. Symptomatic patients are successfully managed with oral pancreatic enzyme replacements and analgesics. Patients with chronic pain require additional interventions (e.g., celiac ganglion block, partial/complete pancreatic resection).

Etiology Alcohol abuse (60-70% of cases, esp. men) , Pancreatic ductal obstruction (< 10%): strictures (e.g., due to trauma, stones) Tobacco use Idiopathic pancreatitis (20-30%) Hereditary pancreatitis (∼1%): autosomal dominant inheritance (PRSS1 gene mutation), age of onset < 20 years Autoimmune pancreatitis Systemic disease Severe hypertriglyceridemia (levels > 1000mg/dl) Primary hyperparathyroidism (hypercalcemia) Cystic fibrosis: ∼ 2% of cystic fibrosis patients develop chronic pancreatitis Tropical pancreatitis: most common cause in the Tropics (esp. Southern India); young age at onset Pathophysiology Autodigestion and inflammation: damage to pancreatic acinar cells (e.g., alcohol), outflow obstruction of pancreatic enzymes or premature activation of trypsinogen to trypsin → intrapancreatic activation of digestive enzymes (e.g., amylase and lipase) → autodigestion of pancreatic tissue → inflammatory reaction Fibrosis: exposure to toxins and/or inflammatory mediators (e.g., alcohol, cytokines) → activation of pancreaticstellate cells (which play a key role in the formation of pancreatic fibrosis) Pancreatic insufficiency (due to tissue atrophy and fibrosis) Exocrine insufficiency → deficiency of lipase, amylase, and protease → maldigestion, steatorrhea, malabsorptionEndocrine insufficiency → destruction of β-cells → pancreatic diabetes Clinical features Epigastric abdominal pain (main symptom) Pain radiates to the back, is relieved on bending forward, and is exacerbated after eating.Pain is initially episodic and becomes persistent as the disease progresses.Often associated with nausea and vomiting Features of pancreatic insufficiency Late manifestation (after 90% of the pancreatic parenchyma is destroyed) Steatorrhea (exocrine enzyme deficiency)Cramping abdominal pain, bloating, diarrhea, weight lossMay cause fat-soluble vitamin deficiencies (A, D, E, and K)Malabsorption and weight loss Pancreatic diabetes (endocrine hormone deficiency) In the later stages of chronic pancreatitis, patients may not experience any pain! Diagnostics Imaging Abdominal CT (plain and contrast-enhanced): best initial imaging modality to screen for CPFindings: pancreatic atrophy, pancreatic ductal dilations; pancreatic ductal calcifications on plain CT (more sensitive than x-ray); "chain of lakes" appearance Can simultaneously rule out a pancreatic carcinoma or a gastrointestinal malignancy as a possible cause of epigastric pain and weight loss MRCP: indicated when CT findings are equivocal but clinical suspicion of CP is high Findings: ductal strictures and dilations, pancreatic calcifications Abdominal x-ray: visible pancreatic calcifications (highly specific, but only seen in ∼ 30% of cases) UltrasoundAbdominal ultrasound: indistinct margins and enlargement; pancreatic calcifications; ductal strictures, dilation or stones Endoscopic ultrasound: parenchymal lobularity and hyperechoic foci; ductal dilation and calcification ERCP: detection of early pathologies and simultaneous treatment possible (e.g., duct dilation, stent insertion) Ductal stones, seen as filling defects"Chain of lakes" or "string of pearls" appearance (characteristic feature)Irregularity, dilation of the main pancreatic duct Laboratory tests Serum pancreatic enzyme levels: lipase (specific) and amylase (non-specific) Pancreatic function testsIndirect tests: Fecal elastase-1 (FE-1) activity: confirms that steatorrhea is due to pancreatic lipase insufficiency. Elastase-1 level < 200 μg/g → pancreatic exocrine insufficiencyElastase-1 level < 100 μg/g → severe pancreatic exocrine insufficiency72-hour quantitative fecal fat estimation: Fecal fat > 7 g per day is diagnostic of steatorrhea. Direct tests (e.g., cholecystokinin test, secretin test, cholecystokinin-secretin pancreatic function test) Genetic testing Indication: family history of chronic pancreatitis; young patients with idiopathic pancreatitis PRSS-1 mutations: diagnostic of hereditary pancreatitis CFTR gene: 40% of patients with idiopathic chronic pancreatitis have a CFTR gene mutation. Treatment General measures Abstinence from alcohol and nicotine Small, regular meals (rich in carbohydrates, low in fat), supplementation with medium-chain triglycerides (MCT) Pancreatic enzyme replacement (with meals) Parenteral administration of fat-soluble vitamins (A, D, E, K) if necessary Endocrine insufficiency: Insulin administration For management of acute attacks see "Treatment" in acute pancreatitis. Pain management Analgesics: NSAIDs, opioids for severe pain (e.g., long-acting fentanyl/morphine), low dose tricyclic antidepressants(e.g., amitriptyline) Intractable painCeliac ganglion block (offers temporary relief) Endoscopic papillotomy + ductal dilation and stent placement + removal of stones, if present Extracorporeal shock wave lithotripsy (ESWL): for intraductal stones Surgery Indication: if pancreatic cancer is suspected or in those with intractable pain ProceduresPancreaticojejunostomy: if the main pancreatic duct is dilated (> 5 mm)Resection of the affected part of the pancreas (distal pancreatectomy, Whipple's procedure)Thoracoscopic bilateral splanchnicectomy Complications Pancreatic pseudocysts Definition: encapsulated collection of pancreatic fluid which develops 4 weeks after an acute attack of pancreatitis; can occur in both acute and chronic pancreatitis Pathophysiology: pancreatic secretions leak from damaged ducts → inflammatory reaction of surrounding tissue → encapsulation of secretions by granulation tissue Clinical featuresOften asymptomaticPainless abdominal massPressure effectsGastric outlet obstruction (early satiety, non-bilious vomiting, abdominal pain)Obstruction of the distal duodenum (bilious vomiting)Results in steatorrheaBile duct obstruction with jaundice Diagnostics: abdominal ultrasound/CT/MRI → extrapancreatic fluid collection within well-defined wall/capsule, no solid cyst components detectable Treatment : Surgical/endoscopic cystogastrostomy/cystoduodenostomy/cystojejunostomy ; ultrasound/CT-guided percutaneous drainage ComplicationsInfection → fever, abdominal pain, sepsisRupture → pancreatic ascites/pancreaticopleural fistula Erosion into an abdominal vessel with hemorrhage into the cyst → sudden abdominal pain, signs of hemorrhagic shock Splenic vein thrombosis Can occur in 10% of patients with chronic pancreatitis Pathophysiology: inflammation of the splenic vein → thrombus formation → left-sided portal hypertension → gastric varices Clinical features: can present with upper GI bleeding, ascites, and splenomegaly Diagnosis: ultrasound with doppler, CT/MR angiography TreatmentAcute: anticoagulation and/or thrombectomyChronic and symptomatic: splenectomy Pancreatic ascites Pathophysiology: Ductal disruption (due to an acute attack of pancreatitis; pancreatic surgery/trauma) or a pseudocyst leak/rupture → pancreatic ascites Clinical featuresAbdominal distension; variable abdominal pain; dyspnea ; peripheral edema Free fluid in the peritoneal cavity DiagnosisAscitic fluid analysis: Exudate with high amylase levels (> 1000 IU/L)ERCP: Demonstrates the site(s) of leak CECT and MRCP can also demonstrate ascites and the site of leak; ERCP is preferred since treatment can be performed in the same sitting TreatmentConservative manangement: Indicated in all patients; ∼ 30% will require no further treatment Nil per oral, IV fluids, parenteral nutritionSomatostatin analogues (octreotide) Repeated ascitic tapsStenting of the pancreatic duct: If ERCP demonstrates ductal disruption Surgery: Indicated in patients with no improvement on conservative management for 4 weeks (See Pancreatic and hepatic surgery) Pancreatic resection Surgery for pancreatic pseudocyst Lateral pancreaticojejunostomy Further complications Pancreatic abscess Portal vein thrombosis Pancreatic diabetes Pancreatic cancer (especially in patients with hereditary pancreatitis)

Splenic rupture Injury to the spleen is most often the result of blunt abdominal trauma. In rare cases, it may also be caused by spontaneous rupture from an infection or a hematological condition. A ruptured spleen may result in massive intra-abdominal bleeding and should therefore be treated as a medical emergency. Rupture of the spleen may be acute or delayed: acute rupture, in which the patient immediately presents in severe pain and shock, is differentiated from a delayed rupture, which presents with sudden onset of pain and shock following a symptom-free interval lasting days to weeks. Depending on the severity of the injury, conservative therapy with observation in a high dependency unit may be considered, but most patients require surgical intervention. A splenic salvage maneuver (i.e., suturing, coagulation) is performed when possible; however, a splenectomy is commonly indicated in extensive injury involving the splenic hilumand may be a life-saving procedure.

Etiology Blunt abdominal traumaMost frequently caused by motor vehicle accidents leading to liver and spleen injuryAlso caused by falls from high heights, domestic violence, and sport-related trauma Other causesLeft-sided thoracic trauma with fractures of the lower ribs Penetrating abdominal trauma (e.g., stab wounds, gunshot wounds)Injury related to explosions: combination of blunt and penetrating traumaSpontaneous rupture (e.g., in cases of splenomegaly caused by malaria, mononucleosis, hematological illness)Iatrogenic (post-surgery or post-endoscopy) Pathophysiology AnatomyThe spleen lies within the intraperitoneal cavity and is protected by the rib cage.Close proximity to: stomach (intraperitoneal), colon (transverse: intraperitoneal, descending: retroperitoneal), left kidney, pancreas (both retroperitoneal)Highly vascularized organ Lymphatic organ with filtering function Mechanisms of splenic ruptureAcute rupture: injury of the splenic capsule and possibly the splenic parenchymal tissue → acute intra-abdominalbleedingDelayed rupture: injury of the splenic parenchymal tissue in an initially intact splenic capsule → central or subcapsular hematoma → asymptomatic interval (days to weeks) as hematoma distends inside the capsule → subsequent capsular rupture with intra-abdominal bleeding Clinical features Diffuse abdominal pain, especially in the left upper quadrant (LUQ), possible abdominal guardingKehr's sign: referred pain in the left shoulder Ballance's sign: dullness on percussion in the LUQ Hemorrhagic shock (often delayed): tachycardia and hypotension In delayed splenic rupture, symptoms may not present until days to weeks after trauma It is important to identify signs of any other major life-threatening injury in a polytrauma patient! (see blunt abdominal traumafor details) Diagnostics Laboratory tests: low Hb, leukocytosis, and thrombocytosis ; crossmatch for blood transfusion if needed In hemodynamically unstable patientsFirst ultrasound: focused assessment with sonography (FAST):Screening for central or subcapsular hematomaFree intra-abdominal fluid - preferred sites of collection: Koller pouch: splenorenal recessMorrison's pouch: hepatorenal recessPouch of Douglas: between the rectum and, the bladder (in males) or uterus (in the females)If free intraabdominal fluid → diagnostic laparoscopy/laparotomy In hemodynamically stable patients (or in unstable patients in which temporary stabilization with IV fluid resuscitationis successful) Method of choice: abdominal CT scan (with contrast)Alternative: MRI , angiographySometimes: chest x-ray, abdominal x-ray Always consider other organs that could be injured (see "Differential diagnosis" below) Differential diagnoses Other injuries related to blunt abdominal traumaLiver injury (e.g., hematoma, rupture)Pancreatic injury (e.g., laceration, rupture)Duodenal damage and hematoma, especially in children Treatment If low-grade injury in hemodynamically stable patientsConservative management (e.g. hospital observation with frequent ultrasound examination)Angiographic embolization of the injured blood vessel is becoming more widely-used in stable patients If high-grade splenic injuries and/or hemodynamically unstable patientsLaparotomyIf only peripheral rupture: trial of splenic salvage - suturing, coagulation, or ligation of the injured blood vessel Alternative: partial splenic resectionIf hilar rupture: splenectomyIf necessary, reimplantation of splenic tissue Alternative: consider angiographic embolization if patients are stable Splenectomy is a life-saving procedure in cases of high-grade spleen rupture or continuous bleeding! Complications Life-threatening hypovolemic and hemorrhagic shock Post-splenectomy: higher incidence of infection, overwhelming post-splenectomy infection (OPSI; see asplenism) Pancreatic injury (tail)

Acute pancreatitis Acute pancreatitis is an inflammatory condition of the pancreas most commonly caused by biliary tract disease or alcohol abuse. Damage to the pancreas causes local release of digestive proteolytic enzymes that autodigest pancreatic tissue. Acute pancreatitis usually presents with epigastric pain radiating to the back, nausea and vomiting, and epigastric tenderness on palpation. The diagnosis is made based on the clinical presentation, elevated serum pancreatic enzymes, and findings on imaging (CT, MRI, ultrasound) that suggest acute pancreatitis. Treatment is mostly supportive and includes bowel rest, fluid resuscitation, and pain medication. Enteral feeding is usually quickly resumed once the pain and inflammatory markers begin to subside. Interventional procedures may be indicated for the treatment of underlying conditions, such as ERCP or cholecystectomy in gallstone pancreatitis. Localized complications of pancreatitis include necrosis, pancreatic pseudocysts, and abscesses. Systemic complications involve sepsis, ARDS, organ failure, and shockand are associated with a considerable rise in mortality.

Etiology Most common causesBiliary pancreatitis (e.g., gallstones, constriction of the ampulla of Vater) ∼ 40% of cases Alcohol-induced (∼ 30% of cases)Idiopathic (∼ 15%-25% of cases) Other causesHypertriglyceridemia, hypercalcemiaPost-ERCP Toxic drugs (e.g., steroids, azathioprine, sulfonamides, furosemide, estrogen, protease inhibitors, NRTIs)Scorpion stingsViral infections (e.g., coxsackievirus B, mumps)Trauma Autoimmune and rheumatological disorders (e.g., Sjögren's syndrome)Pancreas divisum Hereditary (e.g., mutation of the trypsinogen gene, cystic fibrosis) Pathophysiology Sequence of events leading to pancreatitis: Intrapancreatic activation of pancreatic enzymes: secondary to pancreatic ductal outflow obstruction (e.g., gallstones, cystic fibrosis) or direct injury to pancreatic acinar cells (e.g., alcohol, drugs) Enzymatic autodigestion of pancreatic parenchyma Attraction of inflammatory cells (neutrophils, macrophages) → release of inflammatory cytokines → pancreaticinflammation (pancreatitis) Sequelae of pancreatitis (depending on the severity of pancreatitis) Capillary leakage: Release of inflammatory cytokines and vascular injury by pancreatic enzymes → vasodilation and increased vascular permeability → shift of fluid from the intravascular space into the interstitial space (third space loss) → hypotension, tachycardia → distributive shock Pancreatic necrosis: Uncorrected hypotension and third space loss → decreased organ perfusion → multiorgan dysfunction (mainly renal) and pancreatic necrosis Hypocalcemia: Lipase breaks down peripancreatic and mesenteric fat → release of free fatty acids that bind calcium → hypocalcemia Disease progression Mild acute pancreatitis: interstitial edema, no necrosis; no local and systemic complications, no organ failure Moderate acute pancreatitis: associated with local (e.g., necrosis, abscesses, pseudocysts) or systemic complications, such as temporary organ failure (e.g., kidney failure), which improves within 48 hours Severe pancreatitis: associated with persistent pancreatic failure (> 48 hours), as well as single or multiple organ failure Clinical features Constant, severe epigastric painClassically radiating towards the backWorse after meals and when supineImproves on leaning forwards Nausea, vomiting General physical examination Signs of shock: tachycardia, hypotension, oliguria/anuria Possibly jaundice in patients with biliary pancreatitis Abdominal examinationAbdominal tenderness, distention, guarding Ileus with reduced bowel sounds and tympany on percussionAscitesSkin changes (rare) Cullen's sign: periumbilical ecchymosis and discoloration (bluish-red) Grey Turner's sign: flank ecchymosis with discoloration Fox's sign: ecchymosis over the inguinal ligament Diagnostics Acute pancreatitis is diagnosed based on a typical clinical presentation, with abdominal pain radiating to the back, and either detection of highly elevated pancreatic enzymes or characteristic findings on imaging. Serum hematocrit is an easy test that should be conducted to help quickly predict disease severity. Laboratory tests Tests to confirm clinical diagnosis↑ Serum pancreatic enzymes Lipase: if ≥ 3 x the upper reference range → highly indicative of acute pancreatitisAmylase (nonspecific) The enzyme levels are not directly proportional to severity or prognosis! Tests to assess severityHematocrit (Hct)Should be conducted at presentation as well as 12 and 24 hours after admissions ↑ Hct (due to hemoconcentration) indicates third space fluid loss and inadequate fluid resuscitation↓ Hct indicates the rarer acute hemorrhagic pancreatitisWBC count Blood urea nitrogen ↑ CRP and procalcitonin levels ↑ ALT Tests to determine etiologyAlkaline phosphatase, bilirubin levels (evidence of gallstone pancreatitis) Serum calcium levelsSerum triglyceride levels (fasting) Determining calcium values is very important: Hypercalcemia may cause pancreatitis, which may then, in turn, cause hypocalcemia! Imaging Ultrasound (most useful initial test): indicated in all patients with acute pancreatitis Main purpose: detection of gallstones and/or dilatation of the biliary tract (indicating biliary origin)Signs of pancreatitisIndistinct pancreatic margins (edematous swelling)Peripancreatic build-up of fluid ; evidence of ascites in some casesEvidence of necrosis, abscesses, pancreatic pseudocysts CT scan: not routinely indicated IndicationsAt admission: only when the diagnosis is in doubt (e.g., not very highly elevated pancreatic enzymes, non-specific symptoms)> 72 hours of symptom onset: if complications such as necrotizing pancreatitis or pancreatic abscess (e.g., persistent fever and leukocytosis, no clinical improvement or evidence of organ failure > 72 hours of therapy) are suspected Findings Enlargement of the pancreatic parenchyma with edema; indistinct pancreatic margins with surrounding fat stranding Necrotizing pancreatitis: lack of parenchymal enhancement or presence of air in the pancreatic tissuePancreatic abscess: circumscribed fluid collection MRCP and ERCPIndications: suspected biliary or pancreatic duct obstructionsMRCP is noninvasive but less sensitive than ERCP ERCP can be combined with sphincterotomy and stone extraction; but may worsen pancreatitis. Conventional x-raySentinel loop sign: dilatation of a loop of small intestine in the upper abdomen (duodenum/jejunum) Colon cut off sign: gaseous distention of the ascending and transverse colon that abruptly terminates at the splenic flexure Evidence of possible complications: pleural effusions, pancreatic calcium stones; helps rule out intestinal perforation with free air Treatment General measures Admission to hospital and assessment of disease severity (consider ICU admission) Fluid resuscitation: aggressive hydration with crystalloids (e.g., lactated Ringer's solution , normal saline) Analgesia: IV opioids (e.g., fentanyl) Bowel rest (NPO)and IV fluids are recommended until the pain subsides Nasogastric tube insertion: not routinely recommended; indicated in patients with vomiting and/or significant abdominal distention Nutrition Begin enteral feeding (oral/nasogastric/nasojejunal) as soon as the pain subsides Total parenteral nutrition: only in patients who cannot tolerate enteral feeds (e.g., those with persistent ileus and abdominal pain) Drug therapy Analgesics: fentanyl or hydromorphone; consider pump administration (patient controlled analgesia = PCA) AntibioticsProphylactic antibiotic therapy is not recommended.Antibiotics should only be used in patients with evidence of infected necrosis. Fenofibrates: in hyperlipidemia-induced acute pancreatitis Procedures/surgery Biliary pancreatitisUrgent ERCP and sphincterotomy (within 24 hours): in patients with evidence of choledocholithiasis and/or cholangitis; followed by cholecystectomyCholecystectomy (preferably during same admission once the patient is stabilized; or within 6 weeks): in all patients with biliary pancreatitis The most important therapeutic measure is adequate fluid replacement (minimum of 3-4 liters of crystalloids per day)! "PANCREAS" - Perfusion (fluid replacement), Analgesia, Nutrition, Clinical (observation), Radiology (imaging), ERC (endoscopic stone extraction), Antibiotics, Surgery (surgical intervention, if necessary). Patients may have samples from CT-guided fine needle aspiration sent for culture and Gram stainingto identify the appropriate antibiotic or be started on empiric antibiotic courses. Complications Localized Bacterial superinfection of necrotic tissue → feverDiagnosis: CT-guided percutaneous drainage + culture of the aspirateTreatment: surgical debridement, antibioticsHigh mortality rate; multiple organ failure in ∼ 50% of cases Pancreatic pseudocysts Pancreatic abscessWalled-off infected necrotic tissue or pancreatic pseudocyst; typically develops > 4 weeks after an attack of acute pancreatitisAbdominal CT: visible contrast-enhanced abscess capsule with evidence of fluid (pus)Ultrasound: complex cystic, fluid collection with irregular walls and septationsTreatment: cannulation and drainage; necrosectomy if other measures are not effective Pleural effusion Abdominal compartment syndrome Blood vessel erosion with bleeding Systemic SIRS, sepsis, DIC Pneumonia, respiratory failure, ARDS Shock Prerenal failure due to volume depletion Hypocalcemia Pleural effusion, pancreatic ascites Paralytic ileus Prognosis MortalityIn patients without organ failure: < 1%In patients with organ failure: ∼ 30% Higher mortality in patients with biliary pancreatitis than in patients with alcoholic pancreatitis Important predictors of severityAge > 55Gastrointestinal bleedingAbnormal hematocrit within 48 hoursAcute hemorrhagic pancreatitis: ↓ HctThird space fluid loss: ↑ HctHypocalcemia and/or hyperglycemiaInflammatory markers: ↑↑ CRP, ↑ IL-6, ↑ IL-8Evidence of shock and/or organ failure ↑ AST, ↑ ALT↑ BUN, creatinine↑ LDHABG: pO2 < 60 mmHg, metabolic acidosis with a base deficit > 4 mmol/LCT findings: pancreatic edema, peripancreatic fluid collection, and/or necrosis of > 33% of the pancreas Amylase and lipase, which are used for the diagnosis of pancreatitis, cannot be used to predict the prognosis! Numerous scoring systems exist (e.g, Ranson criteria) for assessing the severity and predicting the prognosis of acute pancreatitis A scoring system used to predict patient prognosis in acute pancreatitis. Includes age, leukocytosis, hyperglycemia, LDH levels, AST levels, hematocrit, BUN, calcium, blood oxygenation, fluid status, and base deficit.

Echinococcosis Human echinococcosis, also known as hydatidosis or hydatid disease, is a parasitic disease caused by small tapeworms of the genus Echinococcus. The two most common forms of hydatidosis are cystic echinococcosis (CE), caused by E. granulosus, and alveolar echinococcosis (AE), caused by E. multilocularis. Infection occurs by ingesting Echinococcus eggs, most commonly via hand-to-mouth transmission or through food, water, or soil contaminated with feces. Following a long incubation period, infection with E. granulosus typically results in the formation of a single liver cyst (hydatid cyst), which may be asymptomatic or cause upper abdominal pain and other GI complaints. In contrast, infection with E. multilocularis resembles a hepatic malignancy that invades and destroys the surrounding tissue, which can lead to complications such as portal hypertension, cholangitis, jaundice, and even cirrhosis. Other extrahepatic manifestations may also occur as a result of metastasis to distant sites. Because of its malignant nature, AE is more difficult to treat and has a much higher mortality rate than CE. Treatment for both diseases consists of antihelminthic agents (e.g., albendazoleor mebendazole), often in combination with surgical intervention. NOTES

Etiology Pathogens: Echinococcus tapewormsEchinococcus granulosus causes CEEchinococcus multilocularis causes AE TransmissionHand-to-mouthFrom the fur of definitive hosts (e.g., petting a dog or cat) Contaminated dirt (e.g., dog feces)Fecal-contaminated food or water (e.g., wild berries, mushrooms) Pathophysiology Life cycle Definitive hosts: foxes, dogs, and cats Intermediate hosts: hoofed animals (e.g., sheep, goats, camels, horses, cattle, and pigs) Humans are accidental hosts (e.g., sheep farmers) The definitive host consumes hydatid cysts from an intermediate host → adult tapeworms develop and inhabit the small intestine → tapeworms produce eggs that are shed through stool, contaminating the ground → eggs are ingested by intermediate hosts → eggs hatch within the intestine and penetrate the intestinal wall → travel through the bloodstream and lymphatic system → liver or other organs → hydatid cysts Cystic echinococcosis Single hepatic cyst (hydatid cyst) Hepatomegaly → RUQ pain Malaise, nausea, vomiting Lung involvement in 25% of cases → chest pain, cough, dyspnea, hemoptysis Involvement of other organs is rare Alveolar echinococcosis 5-10 years Hepatic cystHepatomegaly → RUQ painMalaise, weight loss, nausea, vomiting Cyst that invades and destroys the liver and surrounding tissue Portal hypertension, cholestatic jaundice, cholangitisBudd-Chiari syndromeLiver cirrhosisMay resemble hepatocellular carcinoma Primary involvement of other organs is very rare (< 1% of cases) Metastasis to other organs (especially lungs, brain, spleen) in ∼ 13% of cases Cyst rupture may lead to a severe allergic reaction and even death! Echinococcus granulosus (cystic echinococcus): singular hydatid cyst; Echinococcus multilocularis (alveolar echinococcosis): infiltrative growth! Diagnostics Suspected echinococcosis is generally confirmed via ELISA and ultrasonography. Laboratory tests (nonspecific; low diagnostic value): mild eosinophilia, leukopenia or thrombocytopenia, liver function abnormalities Serology: positive ELISAFalse negatives are common. ImagingUltrasonographyCystic echinococcosis: unilocular, anechoic, smooth, well-defined hepatic cyst with or without daughter cystsPossibly daughter cysts and hyperdense internal septa Eggshell calcifications within the cyst wall may be visible Alveolar echinococcosis: lesions with irregular, poorly defined margins, central necrosis, and irregular calcifications within the cyst and cyst wall CT scan: indicated for further evaluation of cysts Alveolar echinococcosis usually not well-defined, but shows infiltration of the liver and surrounding tissueBest test for evaluating extrahepatic cysts Treatment Cystic echinococcosis Observation: inactive cyst with heterogeneous hypoechoic/hyperechoic contents, or solid, calcified wall Medical therapy: may be considered as the sole treatment for cysts < 5 cmDrug of choice: albendazole Alternative drugs: mebendazole, praziquantel Ultrasonography/CT-guided percutaneous drainageShould only be done in combination with medical therapy (albendazole) SurgeryGoal: resect the whole cyst to prevent spillage of its content Indications: > 10 cm, complicated cysts Follow-up: Because relapse is common, patients should be closely monitored via imaging for up to five years. Alveolar echinococcosis Curative resection followed by at least 2 years of treatment with albendazole to prevent a potential relapse Palliative care if surgery is not possible or unsuccessful: see "Medical therapy" above Follow-up for at least 10 years Prognosis Cystic echinococcosis: the long-term outcome depends on organ manifestation Alveolar echinococcosis: 90% of patients die within 10 years if left untreated. However, patients who receive treatment have a life expectancy only 2-3 years lower than the general population.

PeritonitisPeritonitis is an inflammation of the peritoneum that is often caused by a bacterial infection. Based on the etiology, peritonitis may be classified as primary or secondary. Primary peritonitis usually occurs in patients with underlying ascites, whereas secondary peritonitis affects those with a preexisting acute abdominal disease. Patients typically present with severe abdominal pain and guarding, as well as nausea and vomiting. In most cases, peritonitis constitutes a surgical emergency. Diagnosis is established based on the clinical presentation, laboratory tests, imaging, and peritoneal fluid analysis. Treatment includes administration of antibiotics as well as surgical interventions. Peritonitis may be further complicated by ileus, sepsis, or abdominal compartment syndrome.

Etiology Primary peritonitis (spontaneous bacterial peritonitis, or SBP) Absent acute abdominal disease Route of infection: hematogenous, lymphogenic, migration of bacteria through the intestinal wall and colonization of mesenteric lymph nodes (bacterial translocation) Predisposing conditions AscitesCirrhosisPeritoneal dialysis Usually monomicrobial infection (∼ 90% of cases) Gram-negative: Escherichia coli, Klebsiella pneumoniae, BacteroidesGram-positive: Streptococcus pneumoniae (less common) Secondary peritonitis (secondary bacterial peritonitis); more common Pre‑existing acute abdominal conditionHollow organ perforation: peptic ulcer, diverticulum, volvulus, cholecystitisInflammation of intra-abdominal organs: appendicitis, diverticulitis, necrotizing pancreatitisPostoperative complications: anastomosis insufficiency, unsterile puncture site, or surgical procedureTraumatic (external perforation)Peritoneal dialysisIntra-abdominal abscess Mixed infection: aerobic (E. coli, Klebsiella, Enterobacter, Streptococci, Enterococci) and anaerobic (Bacteroides species, Eubacteria, Clostridia) Further causes Peritonitis in immunosuppressed (mainly HIV-positive) patients Chemical peritonitis: nonbacterial, caused by irritants such as blood, bile, urine, or barium contrast in the peritoneal cavity Clinical features Individuals with SBP are often asymptomatic In cases of unexplained liver decompensation, SBPshould also be considered.. General symptomsDiffuse abdominal pain with abdominal guarding and/or rebound tendernessNausea, and vomitingFever and chillsPossibly shoulder pain Ascites in SBPSparse peristaltic sounds (none in cases of ileus) Peritonitis is considered a surgical emergency, as it may cause sepsis with shock and organ failure! Diagnostics The diagnosis of peritonitis is based primarily on physical manifestations. Peritoneal fluid analysis confirms the diagnosis, while imaging tests may help to identify the underlying disease and exclude differential diagnoses. Laboratory testsCBC significant for leukocytosis Peritoneal fluid analysisDiagnostic paracentesis should be performed before administration of antibiotics. Primary peritonitis (SBP)Neutrophil count of > 250 cells/μL indicates SBPSerum-ascites albumin gradient (SAAG) > 1.1 Indicates portal hypertension-related ascites, and potentially SBP. Bacterial culture and/or gram stain: Results are often negative. Secondary peritonitisGlucose < 50 mg/dLPeritoneal fluid LDH > serum LDH,pH < 7.0Positive bacterial culture and/or gram stain ImagingUltrasound may detect Underlying disease: e.g., pancreatitis, appendicitis, cholangitisPeritoneal fluidAbdominal x-ray may detect: Air-fluid levels (e.g., in ileus)Free air secondary to organ perforationCT scan of the abdomen and pelvisShould not cause delay for surgical intervention if the diagnosis is clinically madeTest of choice for suspected visceral abscessIndicated if diagnosis is unclear based on clinical or other imaging findings Differential diagnoses In certain conditions, patients show symptoms of peritonitis, although actual inflammation of the peritoneum is absent. See differential diagnoses of acute abdomen. Metabolic: diabetic ketoacidosis; acute intermittent porphyria Further: hemolytic crisis; lead poisoning Treatment Primary peritonitis [2] Indications: fever > 37.8°C (100°F), neutrophil count in ascitic fluid > 250 cells/μL; altered mental status Empiric antibiotic therapy: 3rd generation cephalosporins IV (e.g., cefotaxime, ceftriaxone) Follow-up after 48 h via repeated paracentesisIf granulocytes decrease to < 250 /μL, treatment can be terminated after five additional daysIf granulocytes do not decrease by ≥ 25%: modify treatment according to resistogram Secondary peritonitis Approach: remove the source of infection and treat the underlying cause via interventional procedures, eliminate bacteria via antibiotics, and maintain organ function via fluid resuscitation and supportive care Interventional procedures [1]SurgeryExtensive laparoscopic irrigation (lavage), debridement, drainageUltrasound or CT-guided percutaneous drainage of abscessesScheduled revision surgery (second-look surgery) frequently necessary for extensive disease General Hospital monitoring (possibly intensive care)Fluid replacement MedicalBroad-spectrum antibiotics (several treatment options are possible) [3]Piperacillin + tazobactamAmpicillin + sulbactam, possibly in combination with gentamicinCiprofloxacin +/- metronidazoleIn severe peritonitis: carbapenems, e.g., imipenem or meropenemAnalgesics, thrombosis prophylaxis Complications Paralytic ileus Sepsis Adhesions Enterocutaneous fistulae Abdominal compartment syndrome SBP: high recurrence and mortality rate Aggravation of pre-existing hepatic encephalopathy

Ascites Ascites is the abnormal accumulation of fluid in the peritoneal cavity and a common complication of diseases presenting with portal hypertension (e.g., liver cirrhosis, acute liver failure) and/or hypoalbuminemia (e.g., nephrotic syndrome). Other conditions resulting in ascites include chronic heart failure, visceral inflammation (e.g., pancreatitis), and malignant tumors. Clinical features include progressive abdominal distension, shifting dullness, and a positive fluid wave test. Ascites may be associated with abdominal pain in rare cases. An adequate clinical assessment should be followed by imaging (e.g., ultrasound), which helps to identify even very small quantities of ascitic fluid in the peritoneal cavity. If the onset of ascites is spontaneous or the origin is unclear, an abdominal paracentesis and ascitic fluid assessment may be performed (i.e., to determine the appearance, composition). Management involves treating the underlying condition in addition to sodium restriction and diuretic therapy. Severe or refractory ascites may require therapeutic abdominal paracentesis. A severe complication is spontaneous bacterial peritonitis.

Etiology The etiology can be determined using the serum-ascites albumin gradient (SAAG) based on Starling's law. Calculation: SAAG = (albumin levels in serum) - (albumin levels in ascitic fluid) High SAAG ascites ≥ 1.1 g/dL(obsolete term: transudate) Portal hypertensionPresinusoidal Splenic or portal vein thrombosisSchistosomiasisSinusoidal Hepatic (common) CirrhosisAlcohol-relatedliver diseaseLiver metastasesPostsinusoidal CardiacRight heart failureConstrictive pericarditisBudd-Chiari syndrome Arterial vasodilation hypothesis in cirrhosis : Portal hypertension → vasodilation → reduced systemic vascular resistance and reduced meanarterial blood pressureActivation of endogenous vasoconstrictors, renal sodium and water retention, and renal vasoconstriction → hyperdynamic circulation Right-sided heart failure: backflow of blood obstructing the venous outflow of the liver Budd-Chiari syndrome: congestion of the portal/hepatic collateral veins and hypertrophy of the caudate lobe of the liver → compression of the sinusoids and intrahepatic inferior vena cava All result in ↑ pressure in portal vein → ↑ hydrostatic pressure in the hepatic vessels→ pushing of fluid out from the intravascularspace to the peritoneal cavity Low SAAGascites < 1.1 g/dL(obsolete term: exudate) HypoalbuminemiaNephrotic syndromeSevere malnutritionProtein-losing enteropathy Nephrotic syndrome → primary renal sodium retention Malignancy Typical in ovarian or bladder cancer and peritoneal mesothelioma. Various mechanisms of malignant-related ascitesexist: Peritoneal carcinomatosis → blockage of lymphatic channels and increased vascular permeability → accumulation of peritoneal fluid Lymph obstruction (by a lymphoma) → chylous ascitesIf an underlying liver condition exists (typically hepatocellular carcinoma) → loss of synthetic liverfunction or portal vein thrombosis Infections (e.g., tuberculosis) Production of protein-rich fluid from tubercles Pancreatitis Accumulation of pancreatic fluid in the peritoneal cavity All result in ↓ intravascular osmotic gradient→ secondary influx of water from the intravascular space to the peritoneal cavity Clinical features Progressive abdominal distension Fluid wave test: a wave produced by tapping one side of the abdomen in a patient in supine position; this wave will be transmitted to the other side via ascitic fluid. Shifting dullness: change of resonance from dull to tympanic resonance when patient changes from supine to lateraldecubitus position. Abdominal pain may be present Abdominal wall hernias (e.g., umbilical, inguinal, or incisional hernias) Peripheral or generalized edema Symptoms associated with increased abdominal distensionEarly satietyWeight gainDyspnea Features of malnutrition; diarrhea Signs of underlying diseaseEnlarged liver, jaundice, spider angioma, palmar erythema: chronic liver diseaseElevated jugular venous pressure: heart failureVirchow's node and weight loss: upper abdominal malignancy Subtypes and variants Chylous ascitesDefinition: collection of lymph in the abdominal cavity, which is characteristically triglyceride-rich and has a milky appearanceEtiology: malignancy (e.g., lymphoma), hepatic cirrhosis, or other lymph disorders (e.g., lymphatic hyperplasia) which result in increased lymph production Bloody ascitesDefinition: ascitic fluid with RBC > 50,000 mm3Etiology: may be spontaneous (e.g, malignant mass eroding into vessels) or iatrogenic (e.g., following paracentesisor biopsy in patients with cirrhosis) Diagnostics Clinical chemistryDilutional hyponatremia as a result of overhydration despite normal or increased sodium concentration (see electrolyte imbalance of sodium) Hypoalbuminemia ImagingUltrasound (best initial test): Reliable detection even of smaller quantities of ascitic fluid: lower limit of detection approx. 30 mLCT scanIsodense areas of fluid in the lower region of the abdomenFluid can also be found around the liver , spleen, and flanks (e.g., perihepatic, posterior subhepatic, rectouterine pouch) Ultrasound-guided diagnostic paracentesisIndications: first diagnosed ascites, worsening ascites or suspected complication. Ascitic fluid analysisAppearance and color Cell count and differentiation Lymphocytosis signals tuberculosis or lymphoma. Peritoneal carcinomatosis will always increase the cell count. Albumin and total protein Albumin is used to determine SAAG, in order to identify whether portal hypertension is present (i.e. SAAG ≥ 1.1 g/dL). LDH An increase in LDH indicates a bacterial infection of the ascitic fluid or that the ascites is malignant in origin. Gram stain and microbial culture Acid-fast bacilli smear, mycobacterial culture, NAAT, and adenosine deaminase level if tuberculosis is suspected Cytopathology Analysis of the ascitic fluid is used for qualitative differentiation between the cells. Detection of malignant cells is a sign of peritoneal carcinomatosis. Criteria for analyzing ascitic fluidAscites due to portal hypertension (SAAG ≥ 1.1 g/dL) (Previously referred to as transudate) Ascites due to other causes (SAAG < 1.1 g/dL)(Previously referred to as exudate) Color Clear, sometimes opalescent (SAAG ≥ 1.1 g/dL) Cloudy (infx) Bloody (malig) Milky (lymph) Dark brown (bile) (SAAG < 1.1 g/dL) Cell count and differentiation ↓ Cell count (SAAG ≥ 1.1 g/dL) ↑ Cell count Neutrophil count > 250/μL (SAAG < 1.1 g/dL) Protein concentration (SAAG ≥ 1.1 g/dL) ↑ Protein levels (> 2.5 g/dL)Right heart failure ↓ Protein levels (< 2.5 g/dL)Hepatic cirrhosis Protein concentration (SAAG < 1.1 g/dL) ↑ Protein levels (> 2.5 g/dL) Hepatic malignancy Peritoneal carcinomatosis Pancreatitis Chylous ascites Tuberculosis ↓ Protein levels (< 2.5 g/dL)Nephrotic syndrome Treatment General measures Treatment of the underlying disease (e.g., using anticoagulation in case of a thrombosis or tuberculostatics in case of a tubercular peritonitis) Sodium restriction Regular weight control Water restriction or avoiding overhydration Diuretic therapy IndicationsPortal hypertensive ascites: usually responsive; may be treated in the same way as ascites caused by liver cirrhosis(see treatment of cirrhosis).Non-portal hypertensive ascites (exudate): usually not effective; therefore it is essential to focus on treating the underlying disease! ApproachSpironolactoneAdditionally, or in the case of massive ascites: loop diuretics Regular control of potassium and creatinine during diuretic therapy Diuretics should be used with precaution in cases of severe hyponatremia, hepatic encephalopathy, or deterioration of renal function! Treatment of refractory ascites Indication: inadequate response to diuretics, frequent recurrence, or when diuretic therapy is contraindicated ProceduresTherapeutic large-volume paracentesis Transjugular intrahepatic portosystemic shunt (TIPS) Complications Spontaneous bacterial peritonitis (ascitic fluid infection): abdominal tenderness, fever, altered mental status (see peritonitis for more information)

Gastrointestinal bleeding Gastrointestinal bleeding is categorized as either upper or lower bleeding, with the ligament of Treitz serving as an anatomical landmark to differentiate between the two. In approx. 70-80% of cases, the source of bleeding is localized in the esophagus, stomach, or duodenum (upper gastrointestinal bleeding, or UGIB). Lower gastrointestinal bleeding (LGIB) may occur in the colon, jejunum, and, in rare cases, the ileum. Although gastric and duodenal ulcers are frequently the cause, angiodysplasia, inflammatory diseases, and carcinomas may also contribute to gastrointestinal bleeding. Depending on the source of the bleeding and how long the blood remains in the digestive tract, clinical symptoms may include vomiting blood (hematemesis), black, tarry stool (melena), and fresh blood in stools (hematochezia). Hospitalization is essential to monitor for signs of hemodynamic instability and shock caused by anemia and blood loss, which require swift intervention. The source of bleeding can often be located and treated simultaneously during endoscopy with injection therapy (e.g., epinephrine, sclerosants, fibrin glue) or ligation.

Etiology of upper and lower gastrointestinal bleeding Upper gastrointestinal bleeding (UGIB): approx. 70-80% of gastrointestinal hemorrhagesThe source is located proximal to the ligament of Treitz. Lower gastrointestinal bleeding (LGIB): approx. 20-30% of all gastrointestinal hemorrhagesThe source is located distal to the ligament of Treitz (usually in the colon) LGIB/UGIB: Angiodysplasia: Most commonly located in the right-sided colon (∼ 75%)Episodic bleeding that ceases spontaneously in > 90% of casesColonoscopy challenging given episodic nature → diagnosis usually requires angiographyAssociated with advanced age (>60 years), end-stage renal disease, von Willebrand disease, and aortic stenosis Upper gastrointestinal bleeding Erosive or inflammatory:Gastric or duodenal ulcers (∼ 30% of cases)Erosive gastritis or duodenitisEsophagitis Risk factorsGERDMedications (NSAIDs, corticosteroids, anticoagulants, chemotherapeutics, antibiotics)Infections (e.g., Helicobacter pylori, candida esophagitis) Vascular:Esophageal variceal hemorrhage Dieulafoy lesion Tumors:Esophageal or gastric carcinoma Traumatic or iatrogenic: Mallory-Weiss syndrome, Following endoscopic intervention/polypectomy FurtherPortal hypertensive gastropathy Lower gastrointestinal bleeding Diverticulosis (∼ 30% of cases) Inflammatory bowel disease (IBD), ulcerative colitis, Crohn disease Infectious diarrhea Hemorrhoids Ischemia (e.g., ischemic colitis, mesenteric ischemia) Rectal varices Colorectal and anal cancer Colon polyps Following interventions such as polypectomy or biopsy Post-surgery anastomotic bleeding Hemorrhoids and anal fissures Clinical features of gastrointestinal bleeding Anemia due to chronic blood loss Acute hemorrhage: signs of circulatory insufficiency or hypovolemic shockTachycardiaHypotension (dizziness, collapse, shock) Reduced vigilance UGIB Melena (black, tarry stool) Hematemesis Hematochezia: indicates brisk bleeding; may cause severe blood loss with hemodynamic instability LGIB Hematochezia Melena Colonic bleeding (maroon, jelly-like traces of blood in stools) Rectal bleeding (streaks of fresh blood on stool Diagnostics Lower gastrointestinal bleeding Occult bleeding or hemodynamically stable hematochezia → colonoscopy→ if negative, perform esophagogastroduodenoscopy (EGD) Melena (more common with a UGI source of bleeding) → EGD → if negative, perform colonoscopy Hemodynamically unstable hematocheziaConsider nasogastric tube aspiration to differentiate upper from lower GI bleedingIn the case of massive, life-threatening bleeding: angiography If EGD and colonoscopy fail to locate the bleeding → evaluate small bowel bleeding or consider angiography for vascular etiologies (e.g., angiodysplasia) Upper gastrointestinal bleeding Hematemesis or melena → EGD → if negative, perform colonoscopy Nasogastric tube aspirationCan be considered if suspicion of UGIB is only low to moderateBright red blood or coffee-ground material is indicative of UGI source If EGD and colonoscopy fail to locate the bleeding → evaluate small bowel bleeding Small bowel bleeding There is no one test that can be recommended, as it depends entirely on the circumstances. Push enteroscopy Video capsule endoscopy Radionuclide scan (RBCs labeled with technetium 99) Treatment Conservative treatment General support: nasal cannula oxygen supplementation, IV substitution of fluids (no oral intake of food or fluids) Consider elective intubation in patients with altered mental or respiratory state and severe, ongoing hematemesis IV proton pump inhibitors Prepare for blood transfusion (typing and cross-matching) Interventional treatment Emergency EGD : in the event of significant bleedingInjection therapy (epinephrine), sclerotherapy, ligation, or thermal coagulation may be used to treat an identified source of bleeding. Bleeding polyp (e.g., in the colon) → polypectomyIf present, see treatment of esophageal variceal hemorrhage. Angiography: vasoconstriction via vasopressin Surgery (laparotomy): if bleeding cannot be contained through endoscopic intervention (rarely the case) If there is any suspicion of gastrointestinal bleeding, two large caliber peripheral venous catheters should be inserted and preparations made for a possible blood transfusion! Complications Hypovolemic shock Anemia In patients with liver cirrhosis, there is a risk of hepatic encephalopathy. Aspiration pneumonia

Gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) is a chronic condition in which retrograde flow of stomach contents into the esophagus causes irritation to the epithelial lining. Reflux episodes are primarily caused by inappropriate, transient relaxation of the lower esophageal sphincter (LES). Risk factors include smoking, alcohol consumption, stress, obesity, and anatomical abnormalities of the esophagogastric junction (e.g., hiatal hernia). The chief complaint is retrosternal burning pain (heartburn), but a variety of other symptoms, such as dysphagia and a feeling of increased pressure, are also common. Suspected GERD should already receive empirical treatment, but further diagnostic steps, such as an upper endoscopy and/or 24-hour pH test, may be indicated to confirm the diagnosis. Management involves lifestyle modifications, medications, and possibly surgery. Proton pump inhibitors (PPIs) are the treatment of choice, although other agents - such as histamine H2-receptor antagonists (H2RAs) - may also be helpful. In addition to relieving symptoms, treating esophagitis is especially important, as chronic mucosal damage can lead to a premalignant condition known as Barrett's esophagus, further progressing to adenocarcinoma of the esophagus.

Gastroesophageal reflux: regurgitation of stomach contents into the esophagus (can also occur in healthy individuals, e.g., after consuming greasy foods or wine) Gastroesophageal reflux disease (GERD): A condition in which reflux causes troublesome symptoms (typically including heartburn or regurgitation) and/or esophageal injury/complications. The most common endoscopic finding associated with esophageal mucosal injury is reflux esophagitis. [1]NERD (non-erosive reflux disease): characteristic symptoms of gastroesophageal reflux disease in the absence of esophageal injury, such as reflux esophagitis, on endoscopy (50-70% of GERD patients) [2]ERD (erosive reflux disease): gastroesophageal reflux with evidence of esophageal injury, such as reflux esophagitis, on endoscopy (30-50% of GERD patients) [2][3][4] Epidemiology Prevalence: ∼ 15-30% in the US (increases with age) [3] Sex: ♀ = ♂ [3] Etiology Main mechanism: transient lower esophageal sphincter relaxations (tLESRs) [5]The dysfunctional LES loosens independent of swallowing and has a decreased ability to constrict, which allows stomach contents to uncontrollably flow back into the esophagus (otherwise known as sphincter insufficiency). Causes ∼⅔ of reflux episodes Risk factors/associationsLifestyle habits such as smoking, caffeine and alcohol consumption [5][6]Stress [2]Obesity [7]Pregnancy [5][3]Diaphragm dysfunction [3]Angle of His enlargement (> 60°) [8][9]Iatrogenic (e.g., after gastrectomy) Inadequate esophageal protective factors (i.e., saliva, peristalsis) [5]Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric cardiac carcinomaScleroderma [5]Sliding hiatal hernia: ≥ 90% of patients with severe GERD , [5][10] Clinical features Chief complaint: retrosternal burning pain (heartburn) that worsens while lying down (e.g., at night) and after eating [3] Pressure sensation in the chest Belching, regurgitation [4] Dysphagia [4] Chronic non-productive cough and nocturnal cough [11] Nausea and vomiting [4] Halitosis Triggers: Bending down, supine positionHabits: smoking and/or alcohol consumptionPsychological factors: especially stress Diagnostics Empirical therapy: If GERD is clinically suspected and there are no indications for endoscopy, empiric therapy - ranging from lifestyle modifications to a short trial with PPIs - should be initiated. A GERD diagnosis is assumed in patients who respond to this therapeutic regimen. Upper endoscopy (esophagogastroduodenoscopy (EGD)) Used to classify reflux esophagitis and conduct biopsies [4]Indications for endoscopy Signs of complicated disease (e.g., dysphagia, painful swallowing, weight loss, iron deficiency anemia, and aspiration pneumonia) [12]Extended course of symptoms [12][7]Noncardiac chest pain [7]No response to PPI treatment [13] Esophageal pH monitoringMeasured over 24 hours via nasogastric tube with a pH probe [4]Sudden drops to a pH ≤ 4 are consistent with episodes of acid reflux into the esophagus [4]Indications To confirm suspected NERD [4]Before endoscopic or surgical treatment options are initiated in patients with NERD [7]GERD is diagnosed when drops in esophageal pH correlate with symptoms of acid reflux and precipitating activities noted in the patient's event diary. Esophageal manometry [4]A pressure-sensitive nasogastric tube measures the muscle contractions in several sections of the esophagus while the patient swallows [14]Indications: Ensure correct placement of pH probes [15]Evaluate peristaltic function prior to anti-reflux surgery [7][4]Exclude motor disorders that may mimic the symptoms of GERD [4] Pathology The histopathological findings vary depending on the severity of mucosal damage: [4] Superficial coagulative necrosis in the non-keratinized squamous epithelium Thickening of the basal cell layer Elongation of the papillae in the lamina propria and dilation of the vascular channels at the tip of the papillae (→ hyperemia) Inflammatory cells (granulocytes, lymphocytes, macrophages) Transformation of squamous into columnar epithelium → Barrett's metaplasia [3] Differential diagnoses Other forms of esophagitis Infectious esophagitis: generally in immunocompromised patients Esophageal candidiasis: Endoscopy shows white or yellowish adherent plaques.Herpes esophagitis: Endoscopy shows superficial ulcers in the upper or mid esophagus in the absence of plaques.CMV esophagitis: Endoscopy shows distal mucosal erosions and ulcers; viral inclusion bodies in cell nuclei on biopsy. Drug-induced esophagitis: Some medications may cause esophageal mucosal irritation, leading to erosions and ulcers.[17] Causes: Antibiotics (e.g., tetracycline, doxycycline, and clindamycin)Anti-inflammatory drugs (e.g., Aspirin)Bisphosphonates (e.g., Alendronate)Others (e.g., potassium chloride, quinidine, and iron compounds)Endoscopic findings: punched-out ulcers with mild inflammatory changes of the surrounding mucosa Eosinophilic esophagitisAssociated with allergic disease (allergic asthma, allergic rhinitis) in 50% of cases Endoscopic findings Circumferential mucosal lesions (rings/corrugations)Mucosal fragilityHistological finding: increased number of eosinophils Conditions not involving esophagitis Cardiac: See differential diagnosis of chest pain (especially angina pectoris). GastrointestinalDiffuse esophageal spasmAchalasia Osteochondrosis Da Costa's syndrome (or neurocirculatory asthenia) Treatment Lifestyle modifications DietarySmall portions; avoid eating (< 3 hours) before bedtime [3][7]Avoid foods with high fat content [13] PhysicalNormalize body weight [7]Elevate the head of the bed for patients with nighttime symptoms [7] Avoid toxins: nicotine, alcohol, coffee [13][7] , and certain drugs (e.g., calcium channel blockers, diazepam) [6] Medical therapy Treatment of choice: Standard-dose of PPI for at least 8 weeks (once-daily therapy) No response: further diagnostic evaluationPartial response: increase the dose (to twice daily therapy) or switch to a different PPIGood response: discontinue PPI after 8 weeks Maintenance therapy: if symptoms recur after discontinuation of PPIs and in the case of complications (see "Complications" below) After 8 weeks of initial treatment, reduce PPI to lowest effective dose or switch to H2RAs (only in patients without complications!) Surgical therapy IndicationsEqually effective alternative to medical therapy in certain patients with chronic GERD [7]Complications (e.g., Barrett esophagus, strictures, recurrent aspiration) [18][19] FundoplicationSymptoms resolve in 85% of cases, but recurrence is possible [19][20]Technique: The gastric fundus is wrapped around the lower esophagus and secured with stitches to form a cuff, leading to a narrowing of the distal esophagus and the gastroesophageal junction (GEJ)and prevents reflux. [21]Nissen fundoplication (= complete fundoplication) [18][19]Complications [20]Intraoperative damage to the stomach and/or surrounding organs, especially the esophagus, spleen, lungs/pleura (→ pneumothorax) Gas bloat syndrome: inability to belch, leading to bloating and an increase in flatulence Dysphagia (especially to solids) Telescope phenomenon ("slipped Nissen"): the esophagus slides out of the wrapped stomach portion Gastric denervation: Vagal nerve injury leads to bloating and cardiac complaints, resembling Roemheld syndrome If hiatal hernia is present [19]Hiatoplasty: margins of the widened hiatus are sutured together Fundopexy or gastropexy: the protruding part of the stomach is tethered to the diaphragm → keeps it in place and relieves the tension placed on the cuff Complications Reflux esophagitis: most common complication of GERD [23] Iron deficiency anemia: mucosal erosions and ulcerations → chronic bleeding → anemia Esophageal stricture: most common sequela of reflux esophagitis [23]Clinical features: cause solid food dysphagiaDiagnosticsBarium esophagram (best initial test): narrowing of the esophagus at the gastroesophageal junctionEndoscopy with biopsies: to rule out malignancy and eosinophilic esophagitisTreatmentFirst-line treatment: dilation with bougie dilator/balloon dilator + proton pump inhibitors in patients with reflux In refractory cases (multiple recurrences): steroid injection prior to dilation, endoscopic electrosurgical incisionRecurrence occurs in the majority of patients; often multiple treatment attempts necessary Esophageal ring: [24]Schatzki rings at the squamocolumnar junction are the most common typeClinical features and management similar to that of an esopahgeal stricture Aspiration of gastric contents leads to:Aspiration pneumoniaChronic bronchitisAsthma (exacerbation) Laryngitis and hoarseness Barrett esophagusPathophysiologyReflux esophagitis → stomach acid damages squamous epithelium → squamous epithelium becomes replaced by columnar epithelium and goblet cells (intestinal metaplasia, Barrett's metaplasia) [3]The physiological transformation zone ("Z-line") between squamous and columnar epithelium is shifted upwards PathologyShort-segment Barrett's esophagus (< 3 cm of columnar epithelium between Z-line and GEJ)Long-segment Barrett's esophagus (> 3 cm of columnar epithelium between Z-line and GEJ) → higher cancer risk!Complications: precancerous condition for adenocarcinoma (see esophageal cancer) Management and surveillance [25]Medical treatment with PPIsEndoscopy with four-quadrant biopsies at every 2 cm of the suspicious area (salmon colored mucosa) If no dysplasia: repeat endoscopy every 3-5 yearsIf indefinite for dysplasia: repeat endoscopy with biopsies after 3-6 months of optimized PPI therapyIf low-grade dysplasiaEndoscopic therapy of mucosal irregularities Alternatively: surveillance every 12 months with biopsies every 1 cmIf high-grade dysplasia: endoscopic therapy of mucosal irregularities

Malabsorption Despite the distinct underlying pathological mechanisms of malabsorption and maldigestion, the term malabsorption is used to refer to both disorders in clinical practice. Malabsorption (e.g., celiac disease, lactose intolerance) describes a malfunction of the intestinal wall, resulting in the insufficient absorption of breakdown products. Maldigestion (e.g., exocrine pancreas insufficiency or cholestasis) is caused by an intraluminal disorder (insufficient secretion of pancreatic enzymes or bile), which prevents the adequate breakdown of food in the intestinal lumen. Both disorders can lead to malnourishment, which, in children, may manifest with delayed and inadequate physical development. Adults mainly present with chronic diarrhea, weight loss, and signs of malnutrition (e.g., iron deficiency anemia). Diagnostic tests assess the digestion of individual food components. Management focuses on the underlying disease; e.g., patients with celiac disease should adhere to a gluten-free diet.

Global malabsorption: in diseases causing diffuse mucosal damage or a reduction of the absorptive surface (e.g., celiac disease) Partial malabsorption: caused by a localized absorption impairment, resulting in deficiencies of specific nutrients (e.g., vitamin B12 deficiency in patients with diseases affecting the terminal ileum) Maldigestion Impaired breakdown of food in the intestinal lumen Exocrine pancreatic insufficiency → lack of enzymes → reduced hydrolysis of carbohydrates, proteins, and lipidsCystic fibrosisShwachman-Diamond syndrome: rare autosomal recessive condition and second most common cause of exocrine pancreatic insufficiency in children (after cystic fibrosis) Following gastric resection → lack of gastric acid → impaired breakdown of nutrients Bile acid deficiency (e.g., cholestasis, bile acid malabsorption) → incomplete emulsification of fats Medications: Orlistat (reversibly inhibits gastric and pancreatic lipase) Malabsorption Impaired absorption of digested food caused by alterations of the intestinal mucosa Inflammatory bowel disease (e.g., Crohn's disease) Celiac disease (gluten-sensitive enteropathy) Infections (e.g.,tropical sprue, giardiasis, traveler's diarrhea, Whipple's disease) Lactose intolerance Small intestine resection (short bowel syndrome)Definition: a condition in which the small intestine is unable to adequately absorb nutrients, water, and electrolytesEtiologies: surgical resection (e.g., for Crohn disease or trauma), congenital abnormalitiesComplications: intestinal failure that requires intravenous supplementation Small intestinal bacterial overgrowth (SIBO; blind loop syndrome) HIV enteropathy General symptoms Global malabsorption Diarrhea (most common), steatorrhea, abdominal distension, flatulenceWeight loss, fatigueAdditional symptoms of specific deficiencies Partial (isolated) malabsorption: only symptoms specific to individual nutrient deficiencies (e.g., impaired cobalaminabsorption with megaloblastic anemia) Deficiencies Deficiency of fat-soluble vitamins (e.g., night blindness and xeroderma due to vitamin A deficiency; osteomalacia and rickets due to vitamin D deficiency) Deficiency of water-soluble vitamins (vitamin B complex, vitamin C) Zinc deficiencyEtiology Inadequate dietary intake Acrodermatitis enteropathica (congenital deficiency)Crohn disease, liver and renal diseaseClinical findings: immune dysfunction, impaired wound healing, hypogonadism, diarrhea, dermatitis, alopecia, abnormal taste and smellDiagnosis: measurement of plasma zinc levels Treatment: oral zinc supplementation Other deficienciesProtein: edema, cachexiaIron deficiency anemia or microcytic anemiaElectrolytes: hypokalemia or hypocalcemia Diagnostics Blood tests: macrocytic and/or microcytic anemia; ↓ electrolytes, ↓ total protein, vitamin deficiencies Stool testsAnalysis of fecal fat over 72 hoursDetection of pathogens D-xylose absorption test: assesses the absorptive function of the upper small intestine Overnight fast → collection of urine for 5 hours following oral administration of 25 g xylose → if urine xylose levels < 4 g/5 h, diagnostic for malabsorptive disorders with damage to the intestinal mucosa (e.g., celiac disease, Whipple's disease)Collection of a venous blood sample after one hour → levels < 20 mg/dL of serum D-xylose are pathological Hydrogen breath test: assess the intestinal absorption of individual carbohydrates Lactulose breath test: determination of orocecal transit time (small intestine transit time) Glucose hydrogen breath test: if abnormal bacterial colonization of the small intestine is suspected Further testing for underlying diseases: e.g., celiac disease or lactose intolerance Differential diagnoses Protein-losing enteropathy EtiologyMassive loss of protein caused by various gastrointestinal disordersErosive or ulcerative (e.g., Crohn's disease, clostridium difficile infection)Increased intestinal permeability to proteins (e.g., celiac disease, bacterial overgrowth)Impaired lymphatic circulation (e.g., intestinal lymphangiectasia, Whipple's disease) Clinical features: hypoalbuminemia with peripheral edemaIn cases of systemic diseases, symptoms may be those of the underlying condition.Further gastrointestinal symptoms may occur depending on the underlying disorder. TreatmentTreatment of the underlying disease Treatment Symptomatic treatment Oral supplementation of fluid, nutrients, and vitaminsCalorie and protein-enriched dietIV nutrition in severe cases (e.g., following extensive intestinal resection) Causal treatment of the underlying disease

Esophageal barium swallow Esophageal barium swallow, also known as esophagogram, is a contrast-enhanced X-ray modality for visualizing the esophagus. It allows for the anatomy and function of the esophagus to be examined and is used in the evaluation of dysphagia, odynophagia, and regurgitation of undigested food particles. Along with esophageal manometry, it is the diagnostic modality of choice for evaluation of esophageal motility disorders.

Indications Barium swallow is indicated in the evaluation of the following symptoms and related conditions: Symptoms: dysphagia (inability to swallow or difficulty swallowing), odynophagia (painful swallowing), regurgitation of undigested food, noncardiac retrosternal chest pain (see "Differential diagnoses of acute chest pain" in the learning card on Boerhaave syndrome) ConditionsEsophageal motility disorders Esophageal diverticulumTracheoesophageal fistulaEsophageal stenoses, constrictionEsophagogastric anastomosis insufficiency or rupture Esophageal cancerHiatal hernia, reflux disorders Endoscopy should always be considered when evaluating symptoms involving the esophageal region (particularly to rule out carcinoma)! Contraindications Suspected esophageal perforation (see "Complications" below) Severe dysphagia (risk of aspiration) Pregnancy Procedure/application Esophagram via barium or gastrografin swallow Performed after an overnight fast Patient swallows solution containing barium sulfate (radiopaque heavy metal) , followed by single static image Barium solution coats the inner lining of the esophagus, showing the size and shape of the esophagus, as well as contractions and peristaltic waves. Barium appears white on x-ray; soft tissues appear gray. If a perforation is suspected, gastrografin, a water-soluble contrast agent should be used in place of barium to avoid complications such as mediastinitis, peritonitis, or pneumonia Videofluoroscopy (modified barium swallow) Real-time contrast-enhanced imaging Patient swallows barium solution while a continuous x-ray beam is focused on the esophagus. Ideal for continuous evaluation of swallowing mechanism Test of choice for suspected oropharyngeal dysphagia A barium-based contrast medium is contraindicated in suspected perforation, as leakage increases the risk of severe mediastinitis, peritonitis, or pneumonia! Complications Generally rare Abdominal pain and constipation most common; easily managed with laxatives Allergic reactions to barium Aspiration of barium → hypersensitivity pneumonitis Esophageal perforation with barium leakage → mediastinitis, peritonitis

Specialized nutrition support Specialized nutrition support (SNS) is required when oral intake is either limited or not possible for a prolonged period of time. Common indications for SNS include patients in critical care, those with dysphagia, unconscious patients who cannot be fed, severely malnourished patients, and those with intestinal malabsorption. The two forms of SNS are enteral nutrition and parenteral nutrition. Enteral feeding is always preferred whenever possible, but parenteral feeding may be instituted if the patient has a nonfunctional GI tract (e.g., gastroschisis, short bowel syndromes), and/or if enteral feedingis contraindicated. Patients who are on SNS may develop several complications related to feeding tubes or intravenous catheters, as well as additional metabolic complications such as electrolyte imbalances, hyperglycemia, refeeding syndrome, gallstone disease, and nonalcoholic fatty liver disease.

Indications Dysphagia (e.g., post-stroke state, multiple sclerosis, esophageal carcinoma) Patients with a low GCS who cannot be fed Difficulty with oral intake in the early postoperative state Severe anorexia (e.g., terminally ill cancer patients, anorexia nervosa) Severe malnutrition Critically-ill patients Intestinal malabsorption Types First-line: enteral feedingAdvantages Easier to performMetabolic complications occur less oftenIntestinal motility is stimulated, preventing mucosal atrophyLower risk of blood stream infection Second-line: parenteral feeding The following principle applies in most situations: oral before enteral, enteral before parenteral! Enteral feeding Definition: administration of nutrients directly into the stomach, duodenum, or jejunum with the help of feeding tubes ContraindicationsMechanical ileus, bowel obstructionAcute abdomen (e.g., severe pancreatitis, peritonitis)Upper GI bleedingMucositisSevere substrate malabsorptionCongenital GI anomaliesHigh-output fistulasNonfunctional GI tract (e.g., gastroschisis, short bowel syndromes) RoutesShort-term: nasogastric tube Long-term (> 2-3 weeks): Gastrostomy tube: gastric feeding tube inserted endoscopically through a small incision through the abdomen into the stomach orJejunostomy tube: feeding tube inserted through a small incision through the abdomen into the jejunum to bypass the distal small bowel and/or colon ComplicationsFeeding-tube-related: Blockage of the feeding tubeNasogastric tube: Accidental placement of the tube inside the trachea Injury to, or perforation of the stomach wallGastrostomy or jejunostomy: Peristomal infectionHigh-output fistulasDiarrhea Gastroesophageal refluxMetabolic complications of specialized nutrition support Parenteral nutrition Definition: intravenous administration of nutrients that bypasses the gastrointestinal tractTotal parenteral nutrition: provision of all nutritional requirements intravenously without using the gastrointestinal tract ContraindicationsEnteral nutrition is feasibleSerum hyperosmolalitySevere hyperglycemiaSevere electrolyte abnormalitiesVolume overload RoutesParenteral nutrition is required for < 2 weeks: peripheral venous line, or peripherally inserted central catheterParenteral nutrition is required for > 2 weeks: tunneled central venous catheter or a port ComplicationsVenous catheter-related:Catheter displacementThrombosis and/or embolismCatheter-related blood stream infectionFluid overloadMetabolic complications of specialized nutrition support Metabolic complications Severe electrolyte imbalances (e.g., hypocalcemia, hypomagnesemia, hypophosphatemia) Hyperglycemia Refeeding syndrome Hyperlipidemia Acalculous cholecystitis Gallstone disease Non-alcoholic fatty liver disease Renal damage Bone demineralization Metabolic complications are more common with parenteral nutrition than enteral nutrition!

Jaundice and cholestasis Jaundice, or icterus, refers to the yellowish discoloration of tissue caused by accumulated deposits of bilirubin. Bilirubindeposition most commonly occurs in the skin and the sclerae. It results from elevated bilirubin, starting at levels > 2 mg/dL. Hyperbilirubinemia may be of prehepatic, intrahepatic, or posthepatic origin. Prehepatic causes include an accumulation of unconjugated bilirubin; intrahepatic and posthepatic jaundice may be due to cholestasis (i.e., the reduced formation or secretion of bile or extrahepatic biliary obstruction). In addition to jaundice, clinical features can include pruritus, pale stool in cases of intrahepatic or posthepatic cholestasis, and darkening of urine. Diagnosis relies on the analysis of laboratory values for cholestasis, liver function, and hemolysis, as well as ultrasound of the biliary tract. Management of jaundice involves treatment of the underlying condition. In cases of moderate to severe pruritus, medication such as cholestyramine, rifampin, opioid antagonists, or ursodeoxycholic acid may be administered.

Jaundice: yellowish discoloration of the skin, sclerae, and mucous membranes due to the deposition of bilirubinScleral icterus: discoloration of the whites of the eyes, starting at serum bilirubin levels > 2-3 mg/dL Jaundice: discoloration of the skin and mucous membranes, starting at serum bilirubin levels > 4-5 mg/dL Cholestasis: any condition affecting bile formation or secretion (nonobstructive intrahepatic cholestasis), or leading to biliary obstruction within the liver (obstructive intrahepatic cholestasis) or in the biliary ducts between the liver and the duodenum (obstructive extrahepatic or posthepatic cholestasis) Etiology Unconjugated hyperbilirubinemiaIncreased hemoglobin breakdownHemolysis (e.g., glucose-6-phosphate dehydrogenase deficiency, sickle cell anemia, spherocytosis, hemolytic disease of the fetus and newborn, and blood transfusions )Dyserythropoiesis (e.g., thalassemia, pernicious anemia, erythropoietic porphyria, and sideroblastic anemia) Resolving hematoma or internal hemorrhage (e.g., in trauma patients or postoperatively) Impaired hepatic uptake of bilirubinDrugs (e.g., rifampin, probenecid, sulfonamides)Portosystemic shuntDefective conjugation of bilirubinInherited hyperbilirubinemia: Gilbert syndrome and Crigler-Najjar syndromeNeonatal jaundice Liver disease: hepatitis (e.g., viral, autoimmune, toxic/alcoholic), cirrhosis, Wilson diseaseHyperthyroidism Conjugated hyperbilirubinemiaDecreased excretion/reuptake of bilirubinInherited disorders: Dubin-Johnson syndrome, Rotor syndrome, and progressive familial intrahepatic cholestasis )Intrahepatic cholestasisLiver disease (e.g., hepatitis or cirrhosis)Primary biliary cholangitis Drugs (e.g., estrogens, arsenic) Postoperative cholestasis: precipitated by hypotension/massive blood loss with subsequent hepatic ischemiarequiring transfusionsSepsisPregnancyInfiltrative process (e.g., tuberculosis, sarcoidosis, and amyloidosis)Extrahepatic cholestasis (biliary obstruction)CholedocholithiasisTumors (pancreatic cancer, cholangiocellular carcinoma, gallbladder cancer)Inflammatory processes (e.g., primary sclerosing cholangitis, acute and chronic pancreatitis, and abscesses)Malformations of the bile ducts (e.g., postoperative/inflammatory strictures, and biliary cysts)Parasitic infection (e.g., liver flukes)Postoperative bile leaks or biliary duct strictures Jaundice is not always a sure sign of cholestasis; it may also indicate prehepatic causes. Conversely, cholestasis may be present in the absence of jaundice, particularly during the early stages of cholestasis! Common causes of hyperbilirubinemia can be remembered with HOT Liver: Hemolysis, Obstruction, Tumor, and Liver disease! Hepatitis and cirrhosis can cause conjugated or unconjugated hyperbilirubinemia! Pathophysiology Jaundice is due to an elevated level of serum bilirubin, which may be caused by prehepatic, intrahepatic, or posthepaticdefects. Serum bilirubin concentration depends on the rate of formation and hepatobiliary elimination of bilirubin. Causes of ↑ unconjugated (indirect) serum bilirubinIncreased hemoglobin breakdownDefective hepatic uptake/conjugation of unconjugated bilirubin Causes of ↑ conjugated (direct) serum bilirubinReduced drainage via biliary tractIncreased reuptake Clinical features In addition to jaundice, the following signs may also indicate cholestasis: Pale, clay-colored (acholic) stool Darkening of urine Pruritus Fat malabsorption (steatorrhea, weight loss) Diagnostics Liver function tests (LFTs) Parameters of cholestasis↑ Alkaline phosphatase (ALP)↑ Gamma glutamyltransferase (γ-GT)↑ Bilirubin Elevated liver enzymes: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) See AST/ALT ratio. Albumin and PT/INR Other liver tests: e.g., hepatitis serology, markers of hemolysis (LDH, haptoglobin, indirect bilirubin), autoantibodies Inflammatory markers Imaging Ultrasound → high specificity and sensitivity for differentiating between different forms of cholestasisObstructive cholestasisDilated bile ducts Extrahepatic: dilated common bile duct ; may show the double-duct signIntrahepatic: double barrel shotgun sign Cause of biliary obstruction, if present (e.g., stones, tumors, cysts, cholangitis)Nonobstructive cholestasisNo signs of the dilation observed in obstructive cholestasisUltrasound may provide evidence of underlying disease (e.g., liver cirrhosis). Further imaging, if necessary (e.g., ERCP, MRCP, or CT) CauseColor of stoolIndirect bilirubinDirect bilirubinBilirubin in urineUrinary urobilinogen Other significant findingsPrehepatic jaundiceDark↑↑ NormalNormal↑↑ (no darkening of urine , but dark urinemay occur in the case of hemoglobinuria)Hemolytic markersAnemia Intrahepatic jaundicePale, clay-colored(rarely dark)↑ ↑↑ (dark urine)Normal or ↑ ↑ Transaminases↑ Cholestatic enzymesExtrahepatic jaundicePale, clay-coloredNormal ↑↑ ↑↑ (very dark urine) Low Dilated bile ducts↑ Cholestatic enzymes Differential diagnoses PseudojaundiceDeposition of carotene in the skin (carotenoderma) can also cause yellowing and usually occurs following excessive consumption multivitamin supplements or fruits and vegetables rich in carotenes, such as carrots, sweet potatoes, kale, and oranges.In contrast to jaundice, it does not lead to scleral icterus. Treatment Management of the underlying conditionCirrhosisHepatitis B, hepatitis CAlcoholic liver diseasePrimary biliary cholangitis, primary sclerosing cholangitisInherited hyperbilirubinemiaPancreatic cancer, cholangiocarcinomaCholelithiasis and cholecystitisSurgical excision of biliary cysts is the preferred treatment. Cholecystectomy is not necessary unless the gallbladder contains stones. Complications Hepatomegaly: Chronic biliary obstruction leading to backflow of bile may result in inflammation. Risk of kernicterus in newborns with neonatal jaundice

Bowel obstruction Bowel obstruction is the interruption of the normal passage of bowel contents either due to a functional decrease in peristalsis or mechanical obstruction. Functional bowel obstruction, or paralytic ileus, is a temporary disturbance of peristalsis in the absence of mechanical obstruction. Postoperative ileus is the most common cause of paralytic ileus, which can also be caused by metabolic disturbances (e.g., hypokalemia), endocrinopathies (e.g., hypothyroidism), and certain drugs (e.g., anticholinergics). Mechanical bowel obstruction is classified according to the location as either small bowel obstruction (SBO) or large bowel obstruction (LBO) and, depending on the severity of obstruction, as either partial or complete. The most common cause of SBO is postoperative bowel adhesions, while the most common cause of LBO is malignant tumors. Regardless of the cause, bowel obstruction typically manifests with nausea, vomiting, abdominal pain, abdominal distention, and constipation or obstipation. In paralytic ileus, bowel sounds are usually absent on auscultation, whereas a high-pitched tinkling sound would be heard in the early phase of a mechanical bowel obstruction. Bowel distention leads to third-space volume loss, resulting in dehydration and electrolyte abnormalities. Symptoms are less severe in partial bowel obstruction. Diagnosis is confirmed on imaging with contrast-enhanced CT scan and abdominal x-rays. Typical findings in mechanical bowel obstruction include dilated bowel loops proximal to the obstruction, collapse of bowel loops distal to the obstruction, and, on contrast-enhanced imaging, a cut-off or transition point at the site of obstruction. In paralytic ileus, findings include generalized dilatation of bowel loops with no transition point and air that is visible in the rectum. Additional laboratory tests include CBC and BGA for the assessment of infection, electrolyte imbalances (e.g., hypokalemia), and metabolic imbalances (e.g., alkalosis). Surgical intervention (i.e., exploratory laparotomy) is recommended for suspected closed-loop bowel obstruction, if there are signs of perforation or peritonitis, or if there is no improvement following conservative management. In all other cases, conservative treatment is usually successful and involves bowel rest, gastric decompression (nasogastric suction), fluid resuscitation, and correction of electrolyte abnormalities.

Mechanical bowel obstruction SBO/LBO EtiologyInterruption in the normal passage due to a structural barrier Colicky abdominal pain Vomiting Bilious vomiting is an early symptom of SBO.Feculent vomiting is a late symptom of LBO. Obstipation or constipation Abdominal distention High-pitched, tinkling bowel sounds (early) Absent bowel sounds (late) Dilated bowel loops proximal to obstruction Collapsed bowel loops distal to obstruction No air within rectum Multiple air-fluid levels Cause of obstruction (e.g., tumor) Small bowel obstruction (SBO) Bowel adhesions (e.g., prior abdominal surgery, abdominal tuberculosis) Incarcerated hernias: second most common cause of SBO Large bowel obstruction(LBO) Malignant tumors (e.g., colorectal carcinoma) Volvulus Paralytic ileus Temporary impairment of peristalsis in the absence of a mechanical obstruction Recent abdominal surgery Atherosclerotic disease Abdominal infections or inflammatory conditions Certain medications (opioids, anticholinergics, antiparkinsonian agents) Diffuse, continuous abdominal pain Vomiting Obstipation or constipation Marked abdominal distention Tympany on percussion Absent bowel sounds Diffusely dilated small and large bowel loops Air within rectum No evidence of mechanical obstruction Definition Bowel obstruction An interruption in the normal passage of bowel contents. Etiology Mechanical bowel obstruction: an interruption in the normal passage of intestinal contents due to a structural barrier (e.g., bowel cancer, adhesions) Paralytic ileus: a temporary impairment of peristalsis in the absence of a mechanical obstruction Degree of obstruction Partial bowel obstruction: bowel obstruction in which passage of some intestinal content through the blocked segment is possible Complete bowel obstruction: total interruption of the passage of intestinal contents Closed loop obstruction: a type of complete mechanical bowel obstruction in which a segment of bowel is occluded at two contiguous points (e.g., volvulus) Site of obstruction Small bowel obstruction (SBO): obstruction occurring in the duodenum, jejunum, or ileum Large bowel obstruction (LBO): obstruction occurring in the cecum, colon, or rectum Progression Simple bowel obstruction: obstruction without evidence of bowel ischemia Strangulated bowel obstruction: obstruction with compromised intestinal blood flow, resulting in bowel ischemia Small bowel obstruction Most common causesAdhesions (e.g., prior abdominal surgery, abdominal tuberculosis): most common cause of SBOIncarcerated hernias: second most common cause of SBO Other causesMeckel diverticulumStrictures (e.g., Crohn disease)Malignant tumors or metastasesGall stone ileusSuperior mesenteric artery syndrome (bowel obstruction due to compression of the third portion of the duodenum in between the aorta and the superior mesenteric artery) Foreign body impactionTumorInternal hernia Specific to infants and childrenCongenital intestinal atresia (e.g., duodenal atresia, jejunal atresia)Intussusception (e.g., secondary to Meckel diverticulum)Congenital strictures and bands (e.g., Ladd bands in intestinal malrotation) Large bowel obstruction Malignant tumors (e.g., colorectal carcinoma): most common cause of LBO Volvulus: second most common cause of LBO Diverticulitis Adhesions (e.g., postoperative, prior abdominal surgery) Strictures (e.g., inflammatory bowel disease, congenital strictures) Fecal impaction Foreign body impactionHirschsprung disease Congenital strictures and bands (e.g., Ladd bands in intestinal malrotation) Meconium ileus Rectal atresia Pathophysiology [7] Bowel obstruction → stasis of luminal contents and gas proximal to the obstruction → ↑ intraluminal pressure, which leads to the following: Gaseous abdominal distention → sequestration of fluids within the distended bowel loops (third spacing) → dehydration and hypovolemiaVomiting → loss of fluid and Na+, K+, H+, and Cl- → hypokalemia, metabolic alkalosis, and hypovolemiaCompression of intestinal veins and lymphatics → bowel wall edema → compression of intestinal arterioles and capillaries → bowel ischemia→ ↑ Bowel wall permeability → translocation of intestinal microbes to the peritoneal cavity → sepsis→ Necrosis and perforation of the bowel wall → peritonitis→ Anaerobic metabolism and lysis of ischemic cells → accumulation of lactic acid and release of intracellular K+→ metabolic acidosis and hyperkalemia SBO Abdominal painColicky, periumbilical Vomiting/nauseaEarly-onsetLarge volumeBiliousConstipation or obstipation Late-onset in proximal SBO Abdominal distentionTypically less significant than in LBO LBO Colicky or constant Vomitting is Late-onset Initially bilious Progresses to fecal vomiting (presence of feces in vomitus) Constipaiton Early-onset in distal LBO Early and significant abdominal distention Dehydration and possible hypovolemia (hypotension, dry mucous membranes) Diffuse abdominal tenderness Tympanic percussion Increased high-pitched, tinkling bowel sounds (early) or absent bowel sounds (late) Collapsed, empty rectum on digital rectal examination Partial bowel obstruction causes gradually progressive symptoms that are milder than those of complete obstruction. Obstipation is absent in partial bowel obstruction. Diagnostics In the workup of suspected mechanical bowel obstruction, imaging allows for quick confirmation of the diagnosis as well as detection of conditions requiring immediate surgery (e.g., perforation). Laboratory tests may further help to assess the severity of the condition (e.g., electrolyte imbalance due to vomiting). Laboratory tests If recurrent vomiting Hypochloremic hypokalemic metabolic alkalosisHyponatremia If bowel strangulation Metabolic acidosis Hyperkalemia Neutrophilic leukocytosis (left shift) If dehydration: ↑ Hct If sepsis: abnormal coagulation profile Potentially prerenal azotemia Imaging [10][11][12][13] Abdominal series Consists of erect and supine abdominal x-rays and an erect chest x-ray. Indication: Best initial test in hemodynamically unstable patients or in resource-poor health centers FindingsDilatation of bowel loops proximal to the obstruction3-6-9 rule to define bowel dilatation on imaging Small bowel dilatation if > 3 cmLarge bowel dilatation if > 6 cmCecal dilatation if > 9 cmIn SBO: The dilated loops are predominantly central.In LBO (esp. distal LBO): The dilated loops are predominantly peripheral.Minimal/no air within the bowel loops distal to the obstructionStepladder sign (x-ray) Multiple air-fluid levels and a stacked appearance of dilated small bowel loops Best seen on an erect abdominal x-ray CT abdomen and pelvis More sensitive than x-ray IndicationsWith IV and oral contrast: Best initial test in hemodynamically stable patients with suspected partial bowel obstruction [14][15] [16] With IV contrast: Indicated in patients with suspected complete bowel obstruction.Non-contrast: Indicated in patients with contrast-allergy and suspected complete bowel obstruction. FindingsTransition point: sudden narrowing of bowel lumen at the site of obstructionDilatation of proximal loops Signs of bowel ischemiaUnenhanced bowel loopsPneumatosis intestinalisMesenteric fat strandingPneumoperitoneum indicates bowel perforation MRI abdomen and pelvis (with and/or without IV contrast)[17] [16] Indication: patients who have a contraindication for radiation exposure Findings: similar to CT Abdominal ultrasound Indication: critically ill patients (easy bedside test) or patients with a suspected SBO and a contraindication for CT(e.g., contrast allergy) or radiation exposure (e.g., pregnancy) Findings Stepladder sign (ultrasound): prominent plicae circulares of dilated small bowel loops Pendular peristalsis: dysfunctional "to-and-fro" peristalsisKeyboard sign: prominent plicae circulares within the dilated bowel loops Thickening of the bowel wall Barium or water-soluble contrast enema Indication: in suspected distal LBO FindingsTapering of bowel lumen at the site of obstruction Complete bowel obstruction: contrast would not be visible beyond obstructionPartial bowel obstruction: a trickle of contrast would be visible beyond obstructionBird beak sign seen in volvulusApple core sign seen in colonic malignancy When imaging with contrast (CT, enema) and perforation is expected, use water-soluble oral contrast. Treatment Conservative management IndicationsPartial bowel obstruction casesComplete bowel obstruction with no signs of ischemia/necrosis or signs of clinical deterioration MeasuresFluid resuscitation, correction of electrolyte imbalanceIntestinal decompression: nasogastric tube insertion Bowel rest (NPO)Administration of IV analgesics and antiemeticsGradual increase of oral intake, starting with clear fluids, can be initiated once the abdominal pain and distention subside and bowel sounds return to normal. Etiology-specific treatmentsFecal impaction: stool evacuation (manual disimpaction, distal softening/washout with enemas or suppositories, proximal softening/washout with oral solutions such as polyethylene glycol or sodium phosphate)Sigmoid volvulus with no signs of strangulation: rigid/flexible sigmoidoscopic detorsion Peristalsis-inducing medication (e.g., metoclopramide) is contraindicated in complete mechanical bowel obstruction. Surgery IndicationsSuspected bowel obstruction and hemodynamic instability or features of sepsis Complete bowel obstruction with signs of ischemia/necrosis or clinical deteriorationPersistent partial obstruction (> 3-5 days)Closed-loop obstruction Procedure: exploratory laparotomyRestoration of intestinal transit: depends on intraoperative findings If bowel resection is required, the intervention may be carried out in a single procedure with anastomosis or permanent ostomy creation, or in a multistaged procedure with a temporary diverting ostomy. Bowel obstruction requires a swift workup to establish whether emergent surgery is necessary! Prognosis 100% mortality in cases of untreated intestinal strangulation Mortality rate for those undergoing surgery: 8-25% High risk of recurrence, particularly with chronic or recurring etiologies (Crohn disease, adhesions, radiation enteritis, volvulus, etc.) Paralytic ileus Definition Paralytic ileus: temporarily impaired peristalsis of the gastrointestinal tract in the absence of mechanical obstruction Etiology Intra-abdominal surgery (postoperative ileus) Abdominal trauma (e.g., due to retroperitoneal hemorrhage) Endocrine abnormalities (e.g., hypothyroidism, porphyria, uremia) Electrolyte disturbances (e.g., hypokalemia) Neuropathy (e.g., diabetes mellitus, spinal injury) Neurosurgical procedures (e.g., spinal surgery) Vascular diseases (e.g., mesenteric ischemia) Peritonitis Inflammation of intra-abdominal organs (e.g., appendicitis, cholecystitis, pancreatitis, severe gastroenteritis) Medications (e.g., anticholinergics, opioids, antidepressants) The common causes of paralytic ileus can be memorized using "5 Ps": Peritonitis, Postoperative, low Potassium, Pelvic and spinal fractures, and Parturition.[22] References:[23][21] Pathophysiology Stressful stimuli to the bowel (e.g., surgery, peritonitis) → sympathetic nervous system activation → decreased/arrested peristalsis Inflammation or intraoperative manipulation → local release of nitric oxide → relaxation of intestinal smooth muscles→ decreased/arrested peristalsis Decreased/arrested peristalsis → bowel wall distention → progresses as detailed above in mechanical bowel obstruction Clinical features Continuous (noncolicky) abdominal pain or discomfort Nausea, vomiting Abdominal distention Percussion: tympany Palpation: no tenderness unless peritonitis is present Auscultation: bowel sounds are absent (silent abdomen) or decreased (early paralytic ileus) Diagnostics Laboratory[24] Leukocytosis with left shift suggests intestinal infection or ischemia. Anemia may be a sign of intra-abdominal hemorrhage (e.g., in postoperative or trauma patients). Hypokalemia, hypomagnesemia Imaging[25][26] Abdominal x-ray: best initial testGeneralized small and large bowel gaseous distention Visible gas shadows in the rectumNo transition or cut-off point on contrast x-rays, such as enteroclysis or barium/water-soluble contrast enemaIf caused by retroperitoneal hemorrhage: obliteration of the psoas muscle outline Abdominal CT: to rule out suspected mechanical bowel obstruction or if abdominal x-ray is inconclusive Has the highest sensitivity and specificity for differentiating ileus from mechanical obstructionIdentifies uniformly distended loops with no transition point and no structural/mechanical cause Treatment Conservative treatment: in patients with no signs of localized or diffuse sepsis (e.g., appendicitis, secondary peritonitis) Bowel restNasogastric tube insertionIV fluids and electrolyte repletionStop or decrease causative medications (e.g., opioids).Gradual increase in enteral feeding as tolerated by the patientEarly postoperative ambulation (although still recommended to prevent DVT) and use of prokinetics have not been proven to improve peristalsis. Surgical intervention: in patients with signs of peritonitis (e.g., appendectomy, exploratory laparotomy) Differential diagnoses Differential diagnosis of bowel obstructionBowel perforation (secondary peritonitis)Mesenteric ischemiaInflammatory bowel diseaseOvarian torsion Differential diagnosis of SBOAcute appendicitisAcute pancreatitisPelvic inflammatory disease Differential diagnosis of LBODiverticulitisToxic megacolonChronic megacolon See differential diagnoses of acute abdomen. Complications Bowel ischemia Bowel perforation Peritonitis A change in the character of pain (colicky pain becoming continuous), rebound tenderness on examination, and/or signs of sepsis in a patient with bowel obstruction indicate the onset of complications and necessitate emergency surgical intervention!

Proton pump inhibitorsProton pump inhibitors (PPIs) are a group of drugs used primarily to inhibit gastric acid secretion. They have largely replaced H2 blockers such as ranitidine in the management of conditions caused by excessive gastroesophageal acidity (e.g., dyspepsia, GERD, Barrett's esophagus, peptic ulcers). PPIs act by completely and irreversibly inhibiting the H+/K+ ATPase enzyme system (gastric proton pump) in the parietal cells of the stomach, resulting in decreased acid production and an increase in gastric pH. PPIs are available in oral and intravenous forms, of which the oral form is more commonly administered. Intravenous PPIs are reserved for management of severe disease, since they can cause irreversible visual disturbances in rare cases. Other side effects are predominantly gastrointestinal, including symptoms such as nausea and abdominal pain, and usually decrease during the course of treatment. Significant drug interactions occur especially with anticoagulants (warfarin, clopidogrel) and should be considered before prescribing PPIs.

Overview Commonly used PPIs Omeprazole EsomeprazolePantoprazole Lansoprazole, dexlansoprazole Rabeprazole Administration 1 Tablet/day taken in the morning on an empty stomach (see "Effects" below) Duration: 1-12 weeks depending on the underlying condition; long-term administration for complicated disease, but should generally be avoided (see "Side effects" below) The individual PPIs differ in their pKa, bioavailability, peak plasma levels, and route of excretion. However, because these differences have not yet proven to be clinically relevant, PPIs are often used interchangeably! Effects Irreversible inhibition of H+/K+ ATPase in parietal cells → increases stomach pH Complete suppression of gastric acid secretion Side effects Gastrointestinal (up to 10% of cases) Nausea, diarrhea, abdominal pain, flatulence↑ Risk of C. difficile infection Reactive hypergastrinemia ↓ Absorption of iron and vitamin B12↓ Absorption of calcium and magnesium → ↑ risk of osteoporosis in long-term use→ ↑ risk of fractures in elderly individuals NeurologicalLightheadedness, headachesPossibly increased risk of developing cognitive impairment/dementia OthersExanthemaVisual disturbances (rare) ↑ Risk of pneumonia In rare cases, acute interstitial nephritis Indications Peptic ulcer disease (gastric and duodenal ulcers) Prevention of stress ulcers Gastroesophageal reflux disease Gastritis Combination treatment in Helicobacter pylori eradication therapy Zollinger-Ellison syndrome (gastrinoma) Gastropathy caused by NSAIDs Special indication: MALT lymphoma (stages I and II) Interactions Although several drug interactions are suspected, those with omeprazole and esomeprazole have proven to be of clinical significance, mainly in CYP2C19-mediated interactions: Clopidogrel: ↓ activation, ↓ amount Warfarin, phenprocoumon: ↑ Amount ↓ clearance Phenytoin, carbamazepine: ↑ Amount ↓ clearance Nifedipine: ↑ absorption, ↑ Amount , ↓ clearance Diazepam: ↑ Amount ,↓ clearance

Chest pain Nontraumatic chest pain is one of the most common causes of emergency department visits and is common in both inpatients and outpatients. The differential diagnosis is broad and includes cardiac (e.g., acute coronary syndrome, pericarditis), gastrointestinal (e.g., GERD, gastritis, PUD), musculoskeletal (e.g., costochondritis), and psychiatric (e.g., generalized anxiety disorder, panic attack) etiologies. Any life-threatening causes of chest pain, such as acute coronary syndrome and pulmonary embolism, should be immediately evaluated and assessed. Once life-threatening causes have been ruled out (either by patient history, examination, or rapid diagnostics), a more thorough history and examination should be performed to narrow the differential diagnosis and guide further diagnostic workup and therapy. Traumatic causes of chest pain are not addressed here.

STEMI [4]Heavy, dull, pressure/squeezing sensationSubsternal pain with radiation to left shoulderNausea, vomitingDiaphoresis, anxietyDizziness, lightheadedness, syncopePain may improve with nitroglycerin.ECG: ST-segment elevation/depression, T-waveinversions, Q waves ↑ Troponin TTE: hypokinesis, regional wall motion abnormalitiesSee the acute management checklist for STEMI.NSTEMI/UA [5]ECG: nonspecific changes, including T-wave inversions, ST-segment depressions Increased or normal troponinTTE: Regional wall motion abnormalities may be present.See the acute management checklist for NSTEMI/UA.Aortic dissection [6][7][8]Sudden onset of severe, sharp tearing chest or abdominal pain that radiates to the back Hypotension, syncope, neurological symptoms Asymmetrical blood pressure, pulse deficit New diastolic murmur Symptoms of myocardial ischemia Elevated D-dimer ECG: nonspecific ST-segment changesCXR: widening of the aorta CT angiography of chest/abdomen/pelvis: intimal flap with false lumen TEE: proximal aortic dissection, tamponade, aortic regurgitation See the acute management checklist for aortic dissection.Cardiac tamponade [9]Tachypnea, dyspneaTachycardiaPulsus paradoxusCardiogenic shockBeck triad: hypotension, elevated JVD, muffled heart soundsECG: low voltage, electrical alternans CXR: enlarged cardiac silhouette TTE: circumferential fluid layer, collapsible chambers , high EF, dilated IVC Inspiration: Both ventricular and atrial septa move sharply to the left.Expiration: Both ventricular and atrial septa move sharply to the right.See the acute management checklist for cardiac tamponade.Pericarditis [10][11]Sharp, pleuritic, retrosternal chest painExacerbated by lying down; improved by leaning forwardNot relieved with nitratesHigh-pitched pericardial friction rub ↑ ESR, ↑ CRP, leukocytosis↑ Troponin [10]ECG: diffuse, ST-segment elevations without reciprocal ST-segment depression, PR-segment depression, or T-wave inversionsCXR: normalTTE: Pericardial effusion may be present.See the acute management checklist for acute pericarditis. Heart failureexacerbation[12][13][14][15]Chest pressureCough, dyspneaHypoxemiaCrackles, JVD, peripheral edemaClinical diagnosisLabs: ↑ BNP, ↑ troponin, hyponatremiaCXR: diffuse opacities, Kerley B linesTTE: global or focal wall abnormalities, systolic and/or diastolic dysfunction, decreased LVEFSee the acute management checklist for heart failure exacerbation. Esophageal perforation [17][18] Retrosternal chest pain, neck pain, epigastric pain with radiation to the back Dyspnea, tachypnea, tachycardia Dysphagia Signs of sepsis Mackler triad (chest pain, vomiting, subcutaneous emphysema) Mediastinal crepitus History of recent endoscopy or severe emesis (Boerhaave syndrome) CXR, upright AXR: mediastinal air and/or subdiaphragmatic air, pleural effusion, pneumothorax Lateral neck x-ray: subcutaneous emphysema Contrast esophagography (gold standard): contrast leak [19] CT chest (with oral contrast) : extraluminal air, esophageal thickening See the acute management checklist for esophageal perforation. GERD and erosive esophagitis [20][21] Postprandial substernal chest pain, pressure, burning, reflux symptoms Aggravated by lying in the supine position and certain foods (e.g., coffee, spices) Epigastric tenderness Clinical diagnosis Definitive diagnosis requires EGD and/or 24-hour esophageal pH monitoring See the acute management checklist for GERD. Peptic ulcer disease [22][23][24] Epigastric pain Duodenal ulcer: pain relieved with food; weight gain Gastric ulcer: pain exacerbated by food; weight loss Signs of GI bleed History of NSAID intake Anemia, positive FOBT (in cases of bleeding ulcer) Urea breath test for H. pylori: positive in most cases of PUD EGD: mucosal erosions and/or ulcers See the acute management checklist for PUD. Acute pancreatitis[25][26][27] Severe epigastric pain that radiates to the back Nausea, vomiting Epigastric tenderness, guarding, rigidity Upper abdominal pain Hypoactive bowel sounds History of gallstones or alcohol use ↑ Lipase, amylase Abdominal ultrasound: pancreatic edema, peripancreatic fluid, gallstones Abdominal CT with IV contrast : pancreaticedema, peripancreatic fat stranding, gallstones See the acute management checklist for acute pancreatitis. Mallory-Weiss syndrome [28][29] Epigastric pain that radiates to the back Repeated episodes of severe vomiting Hematemesis Melena, dizziness, syncope CBC: anemia EGD: longitudinal mucosal tears, typically at the gastroesophageal junction See the acute management checklist for Mallory-Weiss syndrome. Pulmonary embolism [30] Pleuritic chest painAcute onset dyspnea, hypoxemiaCough, hemoptysisUnilateral leg swelling or history of DVTHypotension, shock (if massive PE)Elevated D-dimer ↑ Troponin, BNP ECG: normal sinus rhythm (most common), sinus tachycardia, signs of right ventricular strain CTA chest: pulmonary artery filling defect V/Q scan: perfusion-ventilation mismatch TTE: right ventricle hypokinesis with normal apical movement Wells criteria for pulmonary embolismSee the acute management checklist for pulmonary embolism.Tension pneumothorax [31][32]Severe, sharp chest painDyspnea, hypoxemiaHistory of traumaHyperresonance, decreased breath sounds, tracheal deviationTachycardia, hypotensionClinical diagnosisCXR: absent lung markings, tracheal deviation, pneumomediastinumSee the acute management checklist for tension pneumothorax.Pneumonia [33]Fever, chillsCough, dyspneaHypoxemiaCrackles, egophonyLabs: leukocytosis, ↑ ESR/CRP, ↑ procalcitoninPositive sputum cultureCXR: consolidation, pleural effusionCT chest with IV contrast: hyperdense consolidation See the acute management checklist for pneumonia. Spontaneous pneumothorax [34][31][35]Sudden, sharp unilateral chest pain Acute dyspneaHypoxemiaHyperresonance, decreased breath sounds on affected sideCrepitusHistory of lung disease or trauma CXR (in inspiration): increased lucency, displaced lung markings, subcutaneous emphysemaUltrasound: absent lung slidingSee the acute management checklist for spontaneous pneumothorax. Asthmaexacerbation [36]Dyspnea, coughTachycardiaTachypnea, hypoxemiaDiffuse wheezing, decreased or absent breath soundsIncreased work of breathingABG: ↓ pH, ↑ PaCO2, ↓ PaO2 (respiratory acidosis) Peak expiratory flow: decreased from predicted or personal bestSee the acute management checklist for asthma exacerbation. Pleural effusion[37][38]Unilateral, pleuritic chest painDyspneaDry, nonproductive coughDullness to percussion, decreased breath sounds, decreased tactile fremitusPleural friction rubCXR: homogeneous opacity with blunting of the costophrenic angle Ultrasound: hypoechoic space between the parietal and visceral pleuraSee the acute management checklist for pleural effusion. Differential diagnoses CardiacAcute coronary syndromeCardiac tamponadePericarditisMyocarditisEndocarditisTakotsubo cardiomyopathyAortic dissectionValvular disease (e.g., aortic stenosis, mitral regurgitation, aortic regurgitation)Stable anginaVasospastic anginaHypertensive crisisHeart failure exacerbationPostcardiac injury syndromePostmyocardial infarction syndromePostpericardiotomy syndrome PulmonaryPulmonary embolismTension pneumothoraxPneumothoraxPneumoniaBronchitisAsthma exacerbationCOPD exacerbationHemothoraxPulmonary edemaPleural effusionPleuritisFibrinous pleuritisRheumatoid pleuritisLupus pleuritisPulmonary sarcoidosisLung contusionPulmonary infarctLung abscessLung cancer MusculoskeletalCostochondritisChest traumaChest wall painRib fractureRib contusionOsteoarthritis of the sternoclavicular or manubriosternal jointOsteoarthritis of the shoulder jointsFibromyalgiaSlipping rib syndromeTietze syndromeOveruse myalgiaThoracic outlet syndrome GastrointestinalEsophageal perforationBoerhaave syndromeMallory Weiss syndromeGastroesophageal reflux diseaseAcute erosive gastritisAcute erosive esophagitisEosinophilic esophagitisDyspepsiaPeptic ulcer diseaseEsophageal motility disorder AchalasiaDistal esophageal spasmHypercontractile esophagusEsophageal hypersensitivitySliding hiatal herniaBiliary colicCholelithiasisCholedocholithiasisCholecystitisAcute pancreatitisAcute hepatitisLiver abscessFitz-Hugh-Curtis syndrome RenalRenal infarctRenal capsular hematoma DermatologicalAcute Herpes zosterPostherpetic neuralgia Hematologic/OncologicAcute pain crisisAcute chest syndromeMalignancyMalignant pleural effusionSplenic infarct RheumatologicRheumatoid arthritisSLEFibromyalgia Functional chest pain PsychiatricGeneralized anxiety disorderPanic disorderMajor depressive disorderSomatic symptom disorderSubstance use disorders (e.g., cocaine, methamphetamines, alcohol)Illness anxiety disorder

Bacterial gastroenteritis Bacterial gastroenteritis is caused by a variety of organisms, including Campylobacter, Salmonella, Shigella, Yersinia, Vibrio cholerae, Staphylococcus aureus, diarrheagenic Escherichia coli, Clostridium difficile, Clostridium perfringens, and noncholeraVibrio species. Infection may be foodborne, fecal-oral, or involve direct or indirect animal transmission. Clinical features can be mild, manifesting as abdominal pain and diarrhea, or severe, including vomiting and watery or inflammatory diarrhea, fever, and hypotension. Stool analysis may reveal leukocytes or blood in certain cases. Stool cultures may be considered in severe gastroenteritis. Bacterial gastroenteritis is usually self-limiting and only requires supportive therapy. However, antibiotics are indicated when supportive therapy does not suffice or in immunosuppressed patients. Adequate food and water hygiene is crucial for preventing disease.

Secretory diarrheaBacillus cereusEnterotoxin or bacterial invasion shifts water and electrolyte excretion/absorption in proximalsmall intestine → watery diarrheaRice, vomitingWBC negativeNo bloodETECRecent travel (e.g., Asia, Africa, the Middle East, Mexico, Central, and South America) Clostridium perfringensUndercooked meat and raw legumesStaphylococcus aureusInadequately refrigerated foodVibrio choleraeProfuse secretory diarrhea Invasive diarrheaYersiniaPathogens penetrate the mucosa and invade the reticuloendothelial system of the distal small intestine → enteric feverMilk/porkMay manifest as pseudoappendicitisWBC positive (fecal mononuclear leukocytes)Blood may be presentSalmonella typhi or paratyphiRecent travel (e.g., Asia, Africa, Central, and South America)Typically manifests in three stages: fever with relative bradycardia; rose-colored exanthem on the lower chest and abdomen; and hepatosplenomegaly Inflammatory diarrheaCampylobacterBacteria or cytotoxins damage the colonicmucosa → blood in stool and feverMost common bacterial organism pathogen responsible for foodborne gastroenteritis in the USWBC positive (fecal polymorphonuclear leukocytes)Blood presentEHECUndercooked meat; most common association with hemolytic-uremic syndrome (HUS)Clostridium difficileRecent antibiotic useShigellaSecond most common association with hemolytic-uremicsyndrome (HUS)NoncholeraVibrio speciesShellfishSalmonella(non-typhoidal)Poultry/eggs

Food poisoning Food poisoning, or foodborne illness, occurs following the ingestion of food or water contaminated with bacteria, bacterial toxins, viruses, parasites, or chemical substances. According to the Centers for Disease Control and Prevention (CDC), an estimated 1 in every 6 people in the US is annually affected with a foodborne illness. Risk factors include the cross-contamination of food, as well as improper handling and storage. In addition, immunocompromised individuals are at an increased risk of infection. Common pathogens attributed to food poisoning include Norovirus, Salmonella, Clostridium perfringens, Campylobacter jejuni, Staphylococcus aureus, and Escherichia coli. Incubation periods depend on the cause, and range from a few hours to days. The clinical presentation associated with food poisoning varies, but typical symptoms include diarrhea, nausea, vomiting, and abdominal cramping. Various laboratory tests (e.g., stool analysis, blood tests) help confirm the suspected diagnosis. Young children and the elderly are at greater risk for developing complications related to food poisoning and must be closely monitored. For most patients, supportive care, including fluid replenishment, is sufficient.

Staphylococcal food poisoning Pathogen: Staphylococcus aureusGram-positive bacteriumSome strains produce heat-stable enterotoxins that cause staphylococcal food poisoning. [1] Transmission: ingestion of preformed toxins in contaminated food [1] CharacteristicsTypically involves a short latency period; resolution of symptoms after 24-48 hours Bacteria proliferate in inadequately refrigerated food (canned meats, mayonnaise/potato salad, custards).[2] Incubation period: 1-4 hours Clinical findings: nausea, vomiting, abdominal discomfort, diarrhea Treatment: supportive[2]Antibiotics are unnecessary Bacillus cereus infection Pathogen: Bacillus cereus, a heat-stable, spore-forming bacterium that produces two different enterotoxins Transmission: The bacterium grows in heated food that cools down too slowly or is improperly refrigerated. Reheated rice is a common source of infection.[1] Incubation period and clinical findingsEnterotoxin I (emetic form): 30 min to 6 h after ingestion → nausea and vomitingEnterotoxin II (diarrheal form): 6-15 h after ingestion → watery diarrhea for 24-48 h Treatment: Supportive[3] "Food poisoning from reheated rice? Be serious!" (B. cereus). Histamine fish poisoning (Scombroid) Transmission: ingestion of contaminated, inadequately refrigerated fish (e.g., fish cakes) Clinical findingsAfter 5 min to 1 h: fever, vomiting, diarrhea, erythema/flushing, urticaria, and oral burning sensation Treatment: Symptoms usually resolve within 48 hours. Antihistamines may be administered in severe cases. Predominantly vomiting Commonly due to delayed gastric emptying caused by changes to gastric motility. Staphylococcus aureus (Enterotoxins cause the symptoms) Canned meats, mayonnaise/potato salad, custards 1-3 h Supportive Bacillus cereusReheated rice, food kept warm but not hotVomiting: 30 min to 6 hDiarrhea: 6-15 hSupportiveNoroviruses (e.g., Norwalk)(Vomiting more common in children)Fecal-oral12-48 hSupportive Predominantly diarrhea Watery diarrhea Typical pathomechanism of watery diarrhea: pathogen or toxin enters gastrointestinal tract → binds epithelial cells, sometimes damaging microvilli → ↑ secretion or ↓ absorption of hydrophilic molecules or electrolytes (e.g., NaCl) → ↑ intestinal water due to osmosis → diarrhea. Enterotoxin or bacterial invasion shifts water and electrolyte excretion/absorption in proximal small intestine → watery diarrhea Clinical featuresMild-moderate: abdominal pain, diarrheaSevere: tachycardia, hypotension, fever, bloody or profuse watery diarrhea, and metabolic acidosis WBC negative No blood Staphylococcus aureusInadequately refrigerated foodClostridium perfringensEnterotoxinscause the symptomsReheated meat dishesUndercooked meat and raw legumes6-24 hSupportiveAntibiotics are not recommended Enterotoxic Escherichia coli(ETEC) Heat-labile toxin induces diarrheaMost common cause of traveler's diarrheaRecent travel (e.g., Asia, Africa, the Middle East, Mexico, Central, and South America) Undercooked meat, endogenousFecal-oral9 h to 3 daysSupportiveFluoroquinolonesListeria monocytogenesCheese, deli meats, coleslaw, hot dogs, unpasteurized milk1-2 daysImmunocompetent patients: ampicillinImmunocompromised patients: ampicillin + gentamicinVibrio choleraeProfuse secretory diarrheaEnteric viruses(adenovirus, norovirus, rotavirus)Norovirus: diarrhea more common in adultsFecal-oralAdenovirus: 4-5 daysNorovirus: 12-48 hRotavirus: 1-3 daysSupportiveVaccine (rotavirus)Cryptosporidium Fecal-oral5-7 daysImmunocompetent patients: self-limiting; nitazoxanide may be shorten the durationImmunocompromised patients: Antiretroviral therapy to elevate the CD4 cell count/restore the immune system is essential prior to eradication with antiparasitic drugs. Cyclospora(Cryptosporidiumcyclospora cayetanensis)Fecal-oral5-7 daysSupportiveTrimethoprim-sulfamethoxazole (TMP-SMX) Intestinal tapewormsLarvae in undercooked pork/beef, raw freshwater fish6-8 weeksAsymptomatic for yearsPraziquantel, niclosamide Invasive diarrhea Pathogens penetrate the mucosa and invade the reticuloendothelial system of the distal small intestine → enteric fever WBC positive (fecal mononoculear leukocytes) Blood may be present YersiniaMilk/porkMay present as pseudoappendicitisSalmonella typhi or paratyphiPoultry/eggs Inflammatory diarrhea Typical pathomechanism of inflammatory diarrhea: pathogen enters gastrointestinal tract → inflammation → mucosal damage → barrier defect → diarrhea. Bacteria or cytotoxins damage the colonic mucosa → blood in stool and fever WBC positive (fecal polymorphonuclear leukocytes) Blood presentSalmonella (100s of strains, including S. enteritidis and S. typhimurium)Poultry/eggsChicken products: eggs, raw chicken6-48 hSalmonella gastroenteritis: supportiveAntibiotics are not recommended! Campylobacter jejuni Most common bacterial organism pathogen responsible for foodborne gastroenteritis in the USPoultryFecal-oralDays Supportive treatment with fluids and electrolytesErythromycin or azithromycin in severe casesResistance to penicillin, ciprofloxacin, fluoroquinolonesShigella dysenteriaeSecond most common association with hemolytic-uremic syndrome (HUS)Fecal-oralDays Fluoroquinolones, azithromycin, TMP-SMXDo not use ampicillin as some Shigella strains may be resistant!Yersinia enterocoliticaContaminated milk, porkDays SupportiveFluoroquinolones,TMP-SMX, 3rd generation cephalosporins in severe casesVibrio (usually parahaemolyticus) ShellfishUndercooked seafood16-72 hoursSupportiveDoxycycline, fluoroquinolones in severe cases Enterohemorrhagic Escherichia coli (EHEC) O157:H7: most common pathogenic strain; associated with HUSUndercooked meat; most common association with hemolytic-uremic syndrome (HUS)Non-disinfected water; contaminated food, such as unpasteurized dairy products (milk, soft cheese) or apple ciderFecal-oral3-4 days(range: 24 h to 10 days)SupportiveAntibiotics are contraindicated because they increase the risk of HUSClostridium difficileRecent antibiotic use Additional non-gastrointestinal symptoms Clostridium botulinumDescending paralysisAdult botulism: inadequately canned foodsWound botulism: contaminated woundsInfant botulism: contaminated soil, honeyAdult botulism: 12-36 hoursWound botulism: 10 days (range 4-14 days)Infant botulism: 2-4weeksAdults: respiratory support, antitoxinInfants: respiratory support, hyperimmune human serumDo not use antibiotics! .Histamine fish poisoningFlushing, urticariaInadequately refrigerated fish 5 min to 1 hSupportiveAntihistaminesBrucellosis(Brucella spp.)Cyclical fever, arthralgiasUnpasteurized dairy productsContact with animals (e.g., hunter) 2-4 weeks (range: 5 days to 5 months) Doxycycline, rifampin, TMP-SMXHepatitis A(Hepatitis A virus)Jaundice, commonly following initial GI symptoms Fecal-oral28 days (range 14-50 days) Supportive (generally self-limiting)Immune serum globulin VaccineVibrio vulnificusSepsis (especially in immunocompromisedindividuals)Cellulitis (from wound infections)Self-limiting gastroenteritisOysters, undercooked seafood1-7 daysDoxycycline + 3rd generation cephalosporinsSalmonella typhiand paratyphiTyphoid fever (endemic in developing countries)Fecal-oralHours Fluoroquinolones , 3rd generation cephalosporins, azithromycinVaccine available but not effective

Crohn disease Crohn disease (CD) is an inflammatory bowel disease, the pathogenesis of which is not fully understood. The clinical presentation of CD may be similar to ulcerative colitis (UC), the other most common inflammatory bowel disease. CD mostly affects young adults and adolescents between the ages of 15 and 35. It is typically located in the terminal ileum, but can discontinuously affect the entire gastrointestinal tract and commonly leads to complications such as fistulas, abscesses, and stenosis. Clinical features include diarrhea, weight loss, and abdominal pain in the right lower quadrant(RLQ), as well as extraintestinal manifestations in the eyes, joints, or skin. It is often difficult to diagnose because there is no confirmatory test. Diagnosis is therefore based on the patient's medical history, physical examination, lab tests, imaging (e.g., MRI), endoscopy, and serological testing. Acute episodes are treated with corticosteroids, and in severe cases, immunosuppressants may be indicated. Antibiotics and surgical intervention may be needed to help treat complications. Because the entire gastrointestinal tract may be affected, Crohn disease cannot be cured (in contrast to ulcerative colitis). The goal of treatment is thus to avoid the progression and recurrence of inflammatory episodes.

Surgical intervention GoalResect affected and non-functional intestinal loop(s) while preserving intestinal length and functionMinimally-invasive surgery if possible IndicationsFailed medical therapySevere complications (e.g., abscesses, perforation, toxic megacolon, obstruction, stricture, hemorrhage etc.) MethodsResection of affected bowel (e.g., ileostomy, ileocolostomy, colectomy, proctocolectomy)Intestinal stenosis: balloon dilatation or tissue-sparing end-to-end anastomosisFistulas, abscesses: percutaneous drainage (prevents retention of secretions and abscessation); if unsuccessful, surgical drainageObstruction, stricture: conservative resectionAfter multiple resections: strictureplasty (bowel-sparing technique) Crohn disease is mainly treated with medication, but surgical interventions may be required to treat complications or if medical therapy fails. Surgical intervention alone cannot cure Crohn disease and should therefore be considered as a last resort to avoid complications in which significant amounts of bowel are lost (e.g., short bowel syndrome)! Epidemiology Prevalence: up to 200 cases per 100,000 adults Incidence: 3-15 cases/100,000 persons per year Sex: ♂ = ♀ Average age at diagnosis: 15-35 yearsA second peak is observed around the age of 60, when 10% of cases occur. More common in white populations and people of Jewish descent (especially Ashkenazi Jews, middle European Jews) Etiology Cause: Unknown factors lead to an imbalance between proinflammatory and anti-inflammatory mediators. Risk factorsNicotine abuseFamilial predisposition (e.g., mutation of the NOD2 gene, HLA-B27 association ) Nicotine consumption is the only (known) controllable risk factor for Crohn disease. Therefore, quitting smoking is especially important for patients with CD! Pathophysiology Unknown mechanisms lead to the activation of lymphatic cells (Th1) in the intestinal walls → inflammation is triggered → local tissue damage (edema, erosions/ulcers, necrosis) → obstruction, fibrotic scarring, stricture, and strangulation of the bowelMutations in nucleotide oligomerization binding domain 2 (NOD2) protein implicated in the development of Crohn disease but mechanism currently not fully understood Loss of function mutations in NOD2 → likely allow bacteria to enter the intestinal mucosa and cause an unregulated inflammationDysfunctional NOD2 can cause overactivity of the NF-κB signaling pathway → ↑ production of pro-inflammatory cytokines and antimicrobial peptides → chronic autoinflammation Abscess and fistula formation: intestinal aphthous ulcers → transmural fissures and inflammation of the intestinal walls → adherence to other organs or the skin → penetration of these structures → microperforation and abscessformation → macroperforation into these structures → fistula formation Main locations: terminal ileum and colon but it can be located anywhere between the mouth and the anus (the rectum is spared) Clinical features Typically, CD occurs episodically and there is a 30% risk of recurring inflammation over the span of one year. If symptoms persist for six months, the disease is considered chronic. Intestinal symptoms Typically non-bloody, chronic diarrhea Abdominal pain, typically in the RLQ Signs of malabsorptionWeight lossFailure to thrive and growth failure in childrenAnemiaIntestinal blood loss can cause iron deficiency anemiaAnemia of chronic diseaseVitamin B12 malabsorption due to a chronically inflamed ileum Complications of disturbed reabsorption of bile acidsBile acid diarrhea Bile acid malabsorption SteatorrheaDeficiencies in fat-soluble vitaminsGallstones Kidney stones Abdominal mass : the solid mass is often palpable in the RLQ Enterocutaneous fistula formation, typically seen in the perianal region Clinical features of abscesses (∼ 50% of cases) and fistulas (∼ 30% of cases)Typically involve the terminal ileum and/or perianal regionRecurrences are commonSee intestinal fistulas and abscesses and anal abscess and fistula If intestinal stenosis/strictures: possible signs of bowel obstruction/(sub‑)ileus (vomiting, obstipation) If perforation → signs of peritonitis Perianal fistulas and abscesses are often the first signs of Crohn disease! Extraintestinal symptoms Joints: enteropathic arthritis (e.g., sacroiliitis) Eye: iritis, episcleritis, uveitis Liver/bile ducts: primary sclerosing cholangitis (PSC; less common than in UC) Dermatologic diseaseErythema nodosumAcrodermatitis enteropathica Pyoderma gangrenosum Associated with various conditions, including Crohn disease, UC, rheumatoid arthritis, and traumaMost common site: extensor side of the lower limbsClinical features: very painful, rapidly-progressive, red spots that can change into purulent pustules or deep ulcerated lesions with central necrosisTherapy: immunosuppressants (corticosteroids, cyclosporine A)Pyostomatitis vegetans (oral aphthae) Diagnostics Approach[6] Initially: if a patient has clinical features indicating CD, conduct blood and stool tests Confirm with endoscopy and/or radiographic imaging and/or biopsy Perform contrast radiological studies and/or ultrasonography to assess extent, severity and complications (i.e., abscesses, fistulas or stenoses) Laboratory tests Blood↑ Inflammatory markers (↑ CRP, ↑ ESR, ↑ thrombocytes, and ↑ leukocytes)Anemia↑ ASCA Anti-Saccharomyces cerevisiae antibodies FecesStool analysis to rule out gastroenteritis caused by bacteria (e.g., Clostridium difficile) Possible detection of fecal calprotectin and/or lactoferrin Inflammation in the intestines should be suspected if fecal calprotectin is > 50 μg/g (sometimes first at levels > 100 μg/g) or if lactoferrin is > 7 μg/g Imaging Plain abdominal x-rays: bowel distention, pneumoperitoneum Plain radiography with barium swallow (enteroclysis) Indication: to detect fistulas or stenosesFindings String sign Creeping fat Ultrasound findingsGastrointestinal wall thickening caused by inflammation and edemaPossible detection of abscesses/fistulas MR enterography with contrast medium (MRI enteroclysis, Hydro-MRI) Indication: identification of the extent and pattern of intestinal inflammation, detection of perianal and pelvic disease, and prediction of activity: Findings: edematous thickening of intestinal loops and enlarged lymph nodes Endoscopy Endoscopy confirms the diagnosis, assesses the extent of the disease, differentiates CD from other diseases (e.g., ulcerative colitis, peptic ulcers, etc.), and may also be used as a therapeutic tool (e.g., dilatation of ducts, intestinal loops). IleocolonoscopyTypical findings Pattern of involvement: segmental/discontinuousMacroscopic findings Linear ulcers (snail trails)Other aphthous hemorrhagic mucosa defects (pinpoint lesions)Cobblestone sign: characteristic appearance of the mucosa Fissures, fistulasErythema and transmural inflammation EsophagogastroduodenoscopyIndication: to evaluate the possible involvement of the esophagus, stomach, and duodenumFindings include aphthae on mucosa Pathology Skip lesions (discontinuous inflammation) Hypertrophic lymph nodes Transmural inflammationNon-caseating granulomas Giant cellsDistinct lymphoid aggregates of the lamina propria Crohn diseaseFrequency/type of defecationIncreased (constipation may also result from obstruction)Typically non-bloody, watery diarrhea; may be bloody in some cases Nutritional statusPoor or malnourished PainMostly constantMainly RLQ FistulasVery common Pattern of involvementDiscontinuous inflammation of the entire gastrointestinal tractPreferred location: terminal ileum and colon HistologyTransmural inflammationNon-caseating granulomasGiant cellsNeutrophilic inflammation of the crypts Ulcerative colitis Greatly increased Bloody diarrhea with mucus Mostly normal, but weight loss may occur in the case of severe disease Mostly before or during defecation Mainly left lower quadrant Fistulas Very rare Continuous inflammation, starting in the rectum Localized inflammation of the colon Only mucosal and submucosal inflammation No granulomas Neutrophilic inflammation of the crypts Other differential diagnoses Acute appendicitis Infectious gastroenteritis Non-infectious colitis (ischemic, after radiation therapy, after ingestion of drugs, etc.) Diverticulitis Irritable bowel syndrome Gastrointestinal tuberculosis Malignant intestinal transformations Treatment General Nicotine abstinence Secondary lactose intolerance (approx. 30% of cases): lactose-free diet Malabsorption syndrome: appropriate substitution of vitamins, calories, protein, zinc, calcium Bile acid diarrhea: administration of ion-exchange resins to bind bile acids (e.g., cholestyramine) During acute episodes: avoid dietary fiber and consider parenteral nutrition Pharmacotherapy Treatment of Crohn disease can be approached in two different ways: step‑up therapy and top‑down therapy. Step-up therapy involves treatment with weak medication; if the drug regimen is ineffective, treatment with stronger medication is indicated. Top-down therapy works the other way around, beginning with stronger medications. Therapy goalDrugCharacteristicsSymptomaticAntidiarrheal agentsLoperamideBile acid bindersCrohn disease generally responds well to antidiarrheal agents.Topical corticosteroids: triamcinoloneFor pain relief in oral lesionsTopical 5‑Aminosalicylic acid derivatives (5-ASA derivatives, 5-ASAs) (e.g., suppository, foam, enema)In the case of inflammation of the distal colon Acute episodeFor mild to moderate disease Topical corticosteroids: oral budesonideLiver cirrhosis impairs the metabolism of corticosteroids. They should therefore be administered with caution! 5-ASAs Mesalamine (rectal, systemic)Sulfasalazine Consider as initial treatment for patients with no systemic symptoms. May be given in combination with corticosteroids Indication: contraindications to corticosteroids, patients without systemic symptoms AntibioticsMetronidazoleCiprofloxacin Goal: reduction of intestinal bacteria, immune response, and risk of infection Indications: fistulas, perianal abscesses, colonic disease, postoperative recurrence, and/or pouchitis Moderate to severe disease First-line treatment: systemic corticosteroidsPrednisone Alternative: budesonide Start with 30-60 mg prednisone per day, then reduce dose gradually for weeks until a maintenance dose of 10 mg every other day is reached. Afterwards, continue the maintenance dose for 3-6 months. Tapering is important! Effective in gastroduodenal Crohn disease Steroid-refractorydisease, escalation therapy ImmunosuppressantsFirst‑line treatment: TNF-αantibodies (e.g., infliximab, adalimumab, certolizumab)If necessary in combination with azathioprine (or 6-mercaptopurine)Alternatives MethotrexateAlpha 4 integrin inhibitors(e.g., natalizumab, vedolizumab) Azathoprine and 6-mercaptopurine: Results may be seen after 3-6 months of treatment ; regular tests to measure toxicity are required. Indications for treatment with alpha 4 integrin inhibitors: ineffective treatment with corticosteroids, TNF-α antibodies, and/or immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) Maintenance therapyFirst-line treatment: 5-ASAsAlternatives Azathioprine, 6-mercaptopurineMethotrexateTNF-α antibodiesIf ineffective, a combination of the previously mentioned drugs may be considered.Methotrexate may be used in children, but not in pregnant women! Surgical intervention GoalResect affected and non-functional intestinal loop(s) while preserving intestinal length and functionMinimally-invasive surgery if possible IndicationsFailed medical therapySevere complications (e.g., abscesses, perforation, toxic megacolon, obstruction, stricture, hemorrhage etc.) MethodsResection of affected bowel (e.g., ileostomy, ileocolostomy, colectomy, proctocolectomy)Intestinal stenosis: balloon dilatation or tissue-sparing end-to-end anastomosisFistulas, abscesses: percutaneous drainage (prevents retention of secretions and abscessation); if unsuccessful, surgical drainageObstruction, stricture: conservative resectionAfter multiple resections: strictureplasty (bowel-sparing technique) Crohn disease is mainly treated with medication, but surgical interventions may be required to treat complications or if medical therapy fails. Surgical intervention alone cannot cure Crohn disease and should therefore be considered as a last resort to avoid complications in which significant amounts of bowel are lost (e.g., short bowel syndrome)! Prevention Check-ups: Because of the increased risk of colorectal carcinoma and/or recurrence of the disease, regular check-upsthat include intestinal endoscopy should be conducted. The patient should stop smoking! Medical prophylaxis (mesalamine, antibiotics, azathioprine, 6-mercaptopurine, TNF-α antibodies) Complications General Intestinal complications (see "Clinical findings" above) Increased risk of carcinomaGrowth retardation in children Short bowel syndrome and associated issues after surgeries Amyloidosis Osteoporosis Intestinal fistulas and abscesses EtiologyAbdominal surgery Intra-abdominal inflammation, infection (e.g., IBD, diverticular disease, appendicitis, ulcers)Percutaneous drainageRadiationMalignoma (e.g., gynecologic cancers, pancreatic cancer)TraumaAneurysms Clinical featuresEnterocutaneous fistulas: drainage of intestinal content through the skinGastrocolic fistula: abdominal pain, weight loss, foul‑smelling burps (feculent belching)Enterovesical/colovesical fistula: passing urine together with air (pneumaturia), excrements in urine (fecaluria), recurrent urinary tract infections (UTI)Rectovaginal/anovaginal fistula: passage of stool/gas through the vagina, pain during sex (dyspareunia), perineal painAortoenteric fistula: rectal bleeding Prognosis Currently not curable Relapses and complications are very common without treatment. 70% of all patients require surgery within 15 years of the onset of complications. Life expectancy is normal with ideal, evidence-based treatment.

Cirrhosis Cirrhosis is a condition caused by chronic damage to the liver, most commonly due to excessive alcohol consumption or hepatitis C infection. Other causes may include inflammatory or metabolic diseases, such as primary biliary cirrhosis or hemochromatosis. Cirrhosis is characterized by hepatic parenchymal necrosis and an inflammatory response to the underlying cause. Subsequent hepatic repair mechanisms lead to fibrosis and abnormal tissue architecture, which impair liver function. Patients may present with a range of symptoms, including jaundice, ascites, hepatosplenomegaly, and typical skin manifestations such as spider angioma or palmar erythema. Men may further display signs of feminization (e.g., gynecomastia, hypogonadism). In severe cases, accumulation of toxic metabolites or involvement of further organs can lead to complications such as hepatic encephalopathy or hepatorenal syndrome. Laboratory tests show signs of hepatocyte destruction (e.g., elevated liver enzymes, hyperbilirubinemia) or impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal ultrasonography typically shows a shrunken, heterogeneous liverparenchyma with a nodular surface. Biopsy is the method of choice for confirming the diagnosis. However, it is usually only performed if previous testing was inconclusive. Management consists of treatment of the underlying disease (e.g., avoiding toxic substances, antiviral drugs), adequate calorie intake, and medication for treating complications (e.g., spironolactone for ascites). In cases of decompensated cirrhosis, interventional procedures (e.g., paracentesis to drain ascites) may be used to alleviate symptoms or bridge the time until liver transplantation is possible.

idemiology Prevalence: approx. 0.27% in U.S. adults Sex: ♂ > ♀ (2:1) Responsible for approx. 1-2% of all deaths in the United States; most deaths occurring in the fifth to sixth decade of life Etiology HepatotoxicityLong-standing alcohol abuse (one of the two most common causes of chronic liver disease in the USA)Medications (e.g., acetaminophen, amiodarone or chemotherapy drugs such as methotrexate)Ingesting aflatoxin created by Aspergillus Inflammation(Chronic) viral hepatitis B, C, and D (see, e.g., "Hepatitis C") → Chronic hepatitis C is now the most common cause of cirrhosis in the USPrimary biliary cirrhosis Primary sclerosing cholangitisAutoimmune hepatitisParasitic infections (e.g., schistosomiasis, leishmaniasis, malaria) Metabolic disordersNon-alcoholic steatohepatitis (NASH) HemochromatosisWilson's diseaseAlpha‑1 antitrypsin deficiencyHepatic vein congestion or vascular anomaliesBudd-Chiari syndrome Cardiac cirrhosis (congestive hepatopathy)Osler‑Weber‑Rendu syndrome (Vascular dysplasia that leads to an increase of fibrous septa in the liver. Since portal architecture remains unchanged, this type of cirrhosis is considered atypical.) Cryptogenic cirrhosisCirrhosis of uncertain etiology despite adequate diagnostical efforts Child-Pugh score Points123Serum albumin g/dL> 3.52.8-3.5< 2.8Serum bilirubin mg/dL< 2.02.0-3.0> 3.0INR< 1.71.7-2.3> 2.3 AscitesNoneMildModerateHepatic encephalopathyNoneMinimalAdvancedChild-Pugh class A: 5-6 points; Child-Pugh class B: 7-9 points; Child-Pugh class C: 10-15 points Pathophysiology Although many factors contribute to the development of cirrhosis, cytokine‑mediated activation of stellate cells has been identified as a central element, as these cells promote fibrosis, which ultimately leads to cirrhosis. Hepatic inflammation → hepatocyte destruction which triggers repair mechanisms → excess formation of connective tissue (fibrosis) → loss of normal liver function (exocrine and metabolic) Inflammatory cytokines → hepatocyte destruction and stellate cell activation → excess collagen production → loss of normal liver function (exocrine and metabolic) Further pathophysiological mechanisms: Intrahepatic shunting between the portal vein and tributaries of the vena cava Portal hypertension (→ esophageal varices)Impaired liver functionDecreased synthesis ofCoagulation factors → bleeding diathesisUrea → ↑ ammonia → hepatic encephalopathy Albumin → ascites Bile acids → ↓ intestinal absorption of fat‑soluble vitaminsTransport proteins for hormones Further possible consequences Poor metabolism of medications → accumulation with increased risk of toxicityIncreased insulin resistance (diabetes mellitus secondary to liver disease)Impaired hepatic metabolism of estrogen and androstenedione (which is then converted to estrogen by aromatase in adipose cells) → hyperestrogenismLimited enzymatic activation of vitamin D → secondary hyperparathyroidism Clinical features Nonspecific symptoms (patients are often initially asymptomatic) Fatigue, malaise, weight lossJaundice PruritusAsterixis Fetor hepaticus Dupuytren's contracture Abdominal symptomsHepatomegaly (possibly causing RUQ pain) Splenomegaly Ascites Skin changesGenerally dry and atrophicTelangiectasia: most commonly spider angiomata Caput medusae: periumbilical dilation of subcutaneous veins Palmar erythema (plantar erythema also possible)White nails with ground glass opacity Clubbed nails Hormone disordersHyperestrogenismChanges in the hepatic metabolization of sex hormones causes an imbalance in the estrogen‑androgen ratio, resulting in a marked increase of systemic estrogen levels. In men, increased estrogen causes feminization. As liver insufficiency worsens, plasma testosterone concentrations decrease. GynecomastiaHypogonadism (testicular atrophy)Decreased body hair (e.g., loss of chest hair, female pattern of pubic hair distribution)Reduced libido; erectile dysfunction; infertilityPalmar erythema; spider angiomataAmenorrhea Gynecomastia can also be caused by treatment with spironolactone! Diagnostics Laboratory tests Signs of hepatocyte destruction↑ Liver enzymes (AST, ALT) ↑ Bilirubin ↑ Gamma‑glutamyl transpeptidase (GGT) ↑ Alkaline phosphatase ↑ GLDH ↑ Ammonia Signs of impaired hepatic synthesis↑ Prothrombin time (↑ INR) ↓ Total protein (↓ albumin)↓ Cholinesterase See liver function tests Macrocytic anemia due to vitamin deficiency (B12, folic acid) Microcytic anemia due to chronic blood loss Thrombocytopenia in hypersplenism Serum protein electrophoresis↓ Albumin band↑ Gamma band Alpha‑1, alpha‑2, and beta globulin fractions are unchanged Imaging studies Abdominal ultrasound should be performed first. Possible findings include: Liver form and structureNodular liver surfaceAtrophy of the right lobeLoss of structural homogeneity (hyperechoic or variable increase in echogenicity) with fibrous septa. Liver size: initially enlarged, atrophies and shrinks with disease progressionHypertrophy of the caudate lobe Other possible findings Loss of intrahepatic portal and liver veins Complications of cirrhosis such as portal hypertension. CT scan Typical findings Relative hypertrophy of the left and caudate lobeRegenerative nodulesIrregular liver surfaceIndirect findings: ascites, splenomegaly, portocaval collaterals Biopsy Indication: Although biopsy is the gold standard for diagnosis, it is unnecessary in the light of clinical, laboratory, and ultrasound evidence. However, it can aid in identifying the etiology of the cirrhosis if prior testing was inconclusive. Screening procedures and monitoring the disease course HCC screening: abdominal ultrasound for patients with cirrhosis every 6 months and periodic monitoring of alpha-fetoprotein (AFP) Early diagnosis of hepatocellular carcinoma is possible. Before taking a biopsy, check the patient's coagulation status as the risk of bleeding may be increased! Pathology FindingsFibrosisReplacement of normal liver tissue with collagenous regenerative nodules (histological staging is based on the size of the regenerative nodules) See alsoAlcoholic liver diseaseHepatitis BHepatitis C Treatment General approachTreatment of the primary condition Avoidance of hepatotoxic substances (e.g., alcohol, medication) Routine vaccinations (influenza, pneumococcal disease, hepatitis A/B, tetanus ) Balanced diet with adequate calorie intake, no protein restriction Supplemental B vitamins Vitamin B complex with thiamine (B1) and pyridoxine (B6)Vitamin B12 substitution Medication (for treatment of complications see respective section) Non‑selective beta blockers (e.g., propranolol) to lower portal pressure and prevent variceal bleeding (see treatment of portal hypertension). Spironolactone and furosemide to manage ascites and edema in patients with hypoalbuminemiaIn cases of coagulation factor deficiency (possibly combined with thrombocytopenia): leads to coagulation disturbances and bleeding diathesis Treatment with vitamin K substitution Cryoprecipitate transfusion Interventional proceduresIndicationsRefractory ascitesRecurring esophageal varicesBridging time until possible liver transplantMethodsParacentesis of ascites to decompress abdomen TIPS (transjugular intrahepatic portosystemic shunt) to lower portal pressure Surgery: A liver transplant is the only curative option in advanced liver disease. Complications The following complications are covered in separate sections below or in other separate cards: Portal hypertension Hepatic encephalopathy Hepatorenal syndrome Portal vein thrombosis Pulmonary complications of portal hypertensionHepatopulmonary syndromePortopulmonary hypertension Tumors (late complication) Hepatocellular carcinoma (HCC) Decompensated cirrhosis Definition: worsening of liver function in cirrhosis characterized by the presence of jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy Clinical manifestationsHematologic manifestations Coagulopathy : Prolonged prothrombin time (PT)Prolonged international normalized ratio (INR)Prolonged activated partial thromboplastin time (aPTT)This condition does not respond to Vitamin K because the liver cannot utilize it for the synthesis of coagulation factorsComplications caused by portal hypertensionEsophageal variceal hemorrhageAscites and subsequent spontaneous bacterial peritonitisMetabolic complications or associated organ impairmentJaundiceHepatic encephalopathyHepatorenal syndromeHepatopulmonary syndrome The associated ascites and edema as well as the high risk of bleeding considerably increase the risk for hypovolemic shock! Hepatic encephalopathy Definition: Hepatic encephalopathy (HE) is defined as fluctuations in mental status and cognitive function in the presence of severe liver disease. Hepatic dysfunction results in inadequate elimination of metabolic products with subsequent accumulation of neurotoxic metabolites (like ammonia). TriggersDeterioration of liver functionInfections (e.g., spontaneous bacterial peritonitis)Gastrointestinal bleeding ConstipationPortal vein thrombosisHypovolemia/exsiccosis and electrolyte disturbances (hypokalemia, hyponatremia)Renal failureExcessive protein consumption Clinical manifestations Disturbances of consciousness, ranging from mild confusion to comaMultiple neurological and psychiatric disturbances like:Asterixis Fatigue, lethargy, apathyMemory lossImpaired sleeping patternsIrritabilityDisoriented, socially aberrant behavior (for e.g., defecating/urinating in public, shouting at strangers, etc.)Slurred speechMuscle rigidity DiagnosticsElevated blood ammonia levels Assessment of mental status Number connection test: completed slower than the age-normalized standard or cannot completePsychometry‑based diagnostic method (e.g., Mini‑Mental State Examination, MMSE) TreatmentGeneral measures Avoidance of trigger substances (e.g., hepatotoxic medication, alcohol)Treatment of further complications which might aggravate HE (see "Triggers" above)Lactulose: synthetic disaccharide laxativeFirst-line treatment for HE Improves HE by decreasing absorption of ammonia in the bowel: lactulose is converted to lactic acid by intestinal flora → acidification in the gut leads to conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentrationRifaximin [21]Non‑absorbable antibioticMay be added to lactulose to prevent recurrent episodes of HE after the second episode Hepatorenal syndrome (HRS) Definition: deterioration of kidney function in patients with advanced liver disease. The condition is caused by renal vasoconstriction resulting in hypoperfusion of the kidneys. Triggers: loss of volumeDrainage of ascitesGastrointestinal bleedingForced diuresisExcess use of laxatives (lactulose) SymptomsOliguria up to anuria with progressive kidney failureClinically associated with decompensated cirrhosisRenal water retention leads to edema and hydrops (ascites, pleural, or pericardial effusion) Diagnosis Serum creatinine > 1.5 mg/dLElevated BUN:creatinine ratio (> 20:1)Protein excretion < 500 mg/dHyponatremia with relative sodium deficiency Low sodium excretion in urine (< 10 mmol/L) See also fractional excretion of sodium TherapyGeneral measures: improvement of liver function if possible (e.g., cessation of alcohol use) Pharmacotherapy: combination of midodrine, octreotide, and albumin Surgical/interventionalPlacement of a transjugular intrahepatic portosystemic shunt (TIPS) A liver transplant is the only curative option in advanced liver disease Portal vein thrombosis Definition: complete or partial closure of the portal vein EtiologyComplication of cirrhosis or chronic liver disease Myeloproliferative syndromeThrombophilia (e.g., antiphospholipid syndrome) or general risk factors of phlebothrombosis.Chronic mesenteric venous thrombosisLocal complications of intra-abdominal malignancy (e.g., pancreatic carcinoma) or inflammation (e.g., liver abscess) Symptoms: The condition can take many different courses, depending on the extent of thrombosis and the speed of manifestation. Long standing cases of portal vein thrombosis are often asymptomatic (incidental finding) Esophageal variceal hemorrhageAbdominal pain (right upper quadrant, or generalized )Hepatic encephalopathy Jaundice and pruritus due to portal cholangiopathy Hypersplenism DiagnosticsColor duplex sonographyEchogenic or isoechoic thrombus in the portal veinWidening of the portal veinDecreased flow velocity or complete halt of flow Dilated, coiled periportal veinsVariable portion of mostly echogenic thrombus material in the portal veinCT or MRI of the abdomen with contrast agent TherapyTreatment with anticoagulants for 3-6 months results in fibrinolysis and recanalization (complete recanalization occurs in about 50% of cases). Treatment of complications (such as stopping acute bleeding from esophageal varices)Transhepatic thrombolysis with tissue plasminogen activator. Recommended in acute portal vein thrombosis TIPS Pulmonary complications of portal hypertension Hepatopulmonary syndromeDefinition: A condition characterized by hypoxemia, intrapulmonary vasodilatation, and portal hypertension in the presence of cirrhosis. Clinical findingsDyspneaPatients may also manifest with platypnea or orthodeoxia TherapyThe only definitive treatment is a liver transplant. Long‑term treatment with oxygen (as in patients with COPD) is recommended. Prognosis is very poor. Portopulmonary hypertensionDefinition: portopulmonary hypertension is a form of pulmonary arterial hypertension (PAH), which is associated with portal hypertension. It is a well recognized complication of chronic liver disease.Clinical findings: same symptoms as pulmonary hypertension Diagnostic: echocardiography; right heart catheter for specific diagnosticsTherapy: supportive measures, no causal therapy Further pulmonary complications in cirrhosisPneumonia: especially due to immunosuppression, possibly increased risk of aspiration in hepatic encephalopathy.Interstitial lung edema with decreased oxygenation Atelectasis: Diaphragm is elevated because of massive ascites (also promotes pneumonia). Prognosis Survival is poor in patients with decompensated cirrhosis unless they receive liver transplantation. One‑year survival rate based on Child‑Pugh score: Child‑Pugh class A: almost normalChild‑Pugh class B: 80%Child‑Pugh class C: 45%

Inherited hyperbilirubinemia Hyperbilirubinemia describes serum bilirubin levels ≥ 1.1 mg/dL. In contrast to acute or chronic cholestatic liverdisorders, which may also lead to increased serum bilirubin levels, syndromes associated with hyperbilirubinemia lead to isolated hyperbilirubinemia and hence do not affect liver enzymes. These syndromes cause a rise in either unconjugated or conjugated bilirubin. The clinical manifestation of hyperbilirubinemia is relatively mild, with the main symptom being transient jaundice. Aside from Crigler-Najjar syndrome type I, there is no need for management of inherited hyperbilirubinemia syndromes. Therefore, patients with hyperbilirubinemia generally have a good prognosis.

↑ Unconjugated (indirect) bilirubinExcess releaseHemolytic anemiaDefective conjugationGilbert syndromeCrigler-Najjar syndrome ↑ Conjugated (direct) bilirubinDefective excretionDubin-Johnson syndromeRotor syndrome Gilbert syndrome (Gilbert-Meulengracht syndrome; Meulengracht disease) EpidemiologyMost common inherited hyperbilirubinemia: The prevalence is 3-7% in the US. ♂ > ♀Age of onset: adolescence EtiologyMutation in the promoter region of UGT1A1 gene → ↓ activity of UDP-glucuronosyltransferase→ decreased conjugation of bilirubin → ↑ indirect bilirubinAutosomal recessive inheritance Clinical featuresAsymptomatic or unspecific symptoms such as fatigue and loss of appetiteTransient jaundice (varying from mild scleral jaundice to general jaundice) [3] Trigger factors of transient jaundicePhysical stress (trauma, disease, exhaustion)Fasting periodsAlcohol consumption Diagnosis↑ Indirect bilirubin but < 3 mg/dL (higher levels are possible during episodes of increased bilirubin breakdown) Normal liver functionNo evidence of hemolysisDetection of mutation using PCR Treatment: no management required Crigler-Najjar syndrome Crigler-Najjar syndrome type I Etiology: UDP-glucuronosyltransferase is (almost) absent. Inheritance: autosomal recessive Clinical featuresExcessive, persistent neonatal jaundiceNeurological symptoms caused by kernicterus Diagnosis↑↑ Indirect bilirubin (20-50 mg/dL)Normal liver function testsNo evidence of hemolysis ManagementPhototherapy Plasmapheresis during acute rises in serum bilirubin levels Tin protoporphyrin Calcium carbonate Liver transplantation is the only curative treatment. PrognosisWithout treatment, Crigler-Najjar syndrome type I is incompatible with life because it causes kernicterusIf treated, patients may survive past puberty, but most will eventually develop kernicterus. Crigler-Najjar syndrome type II (Arias syndrome) Etiology: reduced levels of UDP-glucuronosyltransferase Inheritance: autosomal recessive Clinical featuresOften asymptomaticNo neonatal jaundice, although jaundice may occur during the patient's first year of life No neurological symptoms Diagnosis↑ Indirect bilirubin (< 20 mg/dL)Normal liver function testsNo evidence of hemolysisResponds to phenobarbital → ↓ serum bilirubin levels Treatment: Patients are less likely to develop kernicterus. Specific treatment may therefore not be required. The following treatment options are, however, available if patients become icteric. Phototherapy (as in type I)Phenobarbital Avoid hormonal contraception and hepatic enzyme inhibitors Prognosis: usually favorable; management of jaundice allows for normal quality of life Dubin-Johnson syndrome Etiology: defective multidrug resistance-associated protein 2 (MRP2) → impaired movement of conjugated (direct) bilirubin from the hepatocyte to the bile canaliculi Inheritance: autosomal recessive Clinical featuresMild to moderate jaundiceOnset often occurs during adolescenceMay worsen because of medication (particularly contraceptives) or pregnancySplenomegaly may occur in rare cases. DiagnosisDirect hyperbilirubinemia (direct bilirubin/total bilirubin up to 50%)Liver biopsy: darker granular pigmentation Treatment: not required Special considerationsBe careful when administering medication that is toxic to the liver → may worsen jaundice!Contraindication for oral contraception Rotor syndrome Etiology: Defective organic anion transport proteins (OATP) 1B1 and 1B3 in hepatocytes → impaired transport and reduced storage capacity of conjugated (direct) bilirubin Inheritance: autosomal recessive Clinical features: usually asymptomatic DiagnosisModerate, direct hyperbilirubinemia and mild, indirect hyperbilirubinemiaNormal liver function test↑ Urinary coproporphyrins I and III (fraction of isomer I < 70% of total)Liver biopsy: normal, no pigmentation Treatment: not required Special considerationsBe careful when administering medication that is toxic to the liver → may worsen jaundice!Contraindication for oral contraception