Topic 5: DISORDERS OF DEGLUTITION, DYSPHAGIA, and GASTROESOPHAEGEAL REFLUX DISEASE

Clinical presentation of reflux esophagitis

- burning chest pain (heartburn) resulting from recurrent mucosal injury -often worse at night, when lying supine, or after consumption of foods or drugs that diminish lower esophageal sphincter tone.

CMV infection in a newborn

-90% of newborns who are congenitally infected with CMV are asymptomatic at birth. -Manifestations of congenital CMV infection in symptomatic neonates include: -Petechiae -"Blueberry muffin" rash (due to extramedullary hematopoiesis) -Jaundice -Hepatosplenomegaly -Sensorineural hearing loss -Chorioretinitis (most common ocular abnormality) -Seizures

Pathogenesis of Esophageal SCC

-A majority of esophageal SCC in Europe and the US are at least partially related to the use of alcohol and tobacco, the effects of which synergize to increase risk. -However, esophageal SCC also is common in some regions where alcohol and tobacco use are uncommon due to religious or societal norms. -In these areas, nutritional deficiencies, as well as exposure to polycyclic hydrocarbons, nitrosamines, and other mutagenic compounds, such as those found in fungus-contaminated foods, are suspected to be the risk factors. -HPV infection also has been implicated in esophageal SCC in high-risk but not in low-risk regions. -The molecular pathogenesis of esophageal SCC remains incompletely defined.

sliding or type I hernia

-A sliding or type I hernia, in which the gastroesophageal junction is displaced above the diaphragmatic hiatus, is the most common type. -Type I hiatal hernias typically are not associated with symptoms or are associated with heartburn or acid regurgitation. -Treatment is the same as for GERD.

Achalasia

-Achalasia is characterized by the triad of incomplete lower esophageal sphincter (LES) relaxation, increased LES tone, and esophageal aperistalsis. -Achalasia (literally, failure to relax) is a condition in which food accumulates in the esophagus and the organ can become massively dilated. -due to increased resting LES tone and incomplete relaxation on swallowing. -achalasia can be thought of as a disorder caused by defective inhibitory pathways of the esophageal enteric nervous system. -The myenteric plexus of the esophagus is deficient at the LES in this condition and the release of NO and VIP is defective. -Achalasia can be treated by pneumatic dilation of the sphincter or incision of the esophageal muscle (myotomy). -Inhibition of ACh release by injection of botulinum toxin into the LES is also effective and produces relief that lasts for several months.

Achalasia-like disease

-Achalasia-like disease may be caused by diabetic autonomic neuropathy; infiltrative disorders such as malignancy, amyloidosis, or sarcoidosis; lesions of dorsal motor nuclei, particularly polio or surgical ablation; in association with Down syndrome; or as part of Allgrove (triple A) syndrome, an autosomal recessive disorder characterized by achalasia, alacrima, and adrenocorticotrophic hormone-resistant adrenal insufficiency. -The association of some achalasia cases with remote herpes simplex virus 1 (HSV1) infection, linkage of immunoregulatory gene polymorphisms to achalasia, and occasional coexistence of Sjögren syndrome or autoimmune thyroid disease suggest that achalasia may also be driven by immune-mediated destruction of inhibitory esophageal neurons.

Barrett Esophagus

-Barrett esophagus is a complication of chronic GERD that is characterized by intestinal metaplasia within the esophageal squamous mucosa. -The incidence of Barrett esophagus is rising; it is estimated to occur in as many as 10% of individuals with symptomatic GERD. ○ White males are affected most often and typically present between 40-60 y/o -Barrett esophagus confers an increased risk for development of esophageal adenocarcinoma. -Molecular studies suggest that Barrett epithelium may be more similar genetically to adenocarcinoma than to normal esophageal epithelium, consistent with the view that Barrett esophagus is a direct precursor of cancer. -epithelial dysplasia, considered to be a preinvasive lesion, develops in 0.2% to 1% of individuals with Barrett esophagus each year; its incidence increases with duration of symptoms and increasing patient age. -Although the vast majority of esophageal adenocarcinomas are associated with Barrett esophagus, it should be noted that most individuals with Barrett esophagus do not develop esophageal cancer.

Morphology of Barrets Esophagus

-Barrett esophagus is recognized endoscopically as tongues or patches of red, velvety mucosa extending upward from the gastroesophageal junction -This metaplastic mucosa alternates with residual smooth, pale squamous (esophageal) mucosa proximally and interfaces with light-brown columnar (gastric) mucosa distally -High-resolution endoscopes have increased the sensitivity of Barrett esophagus detection. -Most experts require both endoscopic evidence of abnormal mucosa above the gastroesophageal junction and histologically documented gastric or intestinal metaplasia for diagnosis of Barrett esophagus. -The defining feature of intestinal metaplasia, and a feature of Barrett esophagus, is the presence of goblet cells, which have distinct mucous vacuoles that stain pale blue by H&E and impart the shape of a wine goblet to the remaining cytoplasm -Dysplasia is classified as low-grade or high-grade on the basis of morphologic criteria. -Intramucosal carcinoma is characterized by invasion of neoplastic epithelial cells into the lamina propria

Esophageal Varices

-Because the submucosal veins of the inferior esophagus drain to both the portal and systemic venous systems, they constitute a portosystemic anastomosis. -In portal hypertension (an abnormally increased blood pressure in the portal venous system), blood is unable to pass through the liver via the hepatic portal vein, causing a reversal of flow in the esophageal tributary. -The large volume of blood causes the submucosal veins to enlarge markedly, forming esophageal varices -These distended collateral channels may rupture and cause severe hemorrhage that is life-threatening and difficult to control surgically. -Esophageal varices commonly develop in persons who have developed alcoholic cirrhosis (fibrous scarring) of the liver

Benign esophageal stenosis

-Benign esophageal stenosis , or narrowing of the lumen, is generally caused by fibrous thickening of the submucosa and is associated with atrophy of the muscularis propria as well as secondary epithelial damage. -Although occasionally congenital, stenosis is most often due to inflammation and scarring that may be caused by chronic GERD, irradiation, or caustic injury. -In general, patients with functional obstruction or benign strictures maintain their appetite and weight, while, malignant strictures are often associated with weight loss.

Transmission of CMV

-Bodily fluids -organ transplantation -Transplacentally -CMV establishes a active infection in epithelial cells and macrophages and a latent infection in lymphocytes. -MHC-I viral peptide complex is unstable in CMV-infected cells, allowing CMV to effectively thwart cytotoxic T-cell mediated killing by blocking MHC I expression of viral antigens on the surface of CMV-infected white blood cells.

Cytomegalovirus

-CMV is an icosahedral, enveloped, double-stranded linear DNA herpesvirus. -CMV is the number one cause of: Congenital infection in the developed world, Viral-associated intellectual disability in the US, Sensorineural hearing loss -Immunocompetent individuals can clinically present with heterophile-negative mononucleosis that can be described as having a "typhoidal" presentation and can include: fever, fatigue and atypical lymphocutes on a peripheral smear -Reactivation of a latent CMV infection within leukocytes can occur when hosts becomes immunocompromised -Transmission occurs through bodily fluids, organ transplantation, and transplacentally

Clinical Features esophageal SCC

-Clinical manifestations of SCC of the esophagus begin insidiously and include dysphagia, odynophagia (pain on swallowing), and obstruction. -As with other forms of esophageal obstruction, patients may unwittingly adjust to the progressively increasing obstruction by altering their diet from solid to liquid foods. -Extreme weight loss and debilitation may occur as consequences of both impaired nutrition and tumor-associated cachexia. -As with adenocarcinoma, hemorrhage and sepsis may accompany tumor ulceration. -Occasionally, SCC of the upper and mid esophagus present with symptoms caused by aspiration of food via a tracheoesophageal fistula. -Increased use of endoscopic screening has led to earlier diagnosis of esophageal SCC -Early detection is critical, because 5-year survival rates are 75% for patients with superficial esophageal carcinoma but much lower for patients with more advanced tumors. -The overall 5-year survival rate remains a dismal 9%.

Etiology of reflux esophagitis

-Common causes of reflux esophagitis are conditions that result in persistent or repetitive acid exposure to the esophageal mucosa. -include disorders that increase the rate of spontaneous transient LES relaxations or impair reflexes that normally follow transient LES relaxations with a secondary wave of esophageal peristalsis. -Conditions that increase gastric volume or pressure (partial or complete gastric outlet obstruction and conditions that increase acid production) -Occasionally, reflux esophagitis can be caused by alkaline injury (pancreatic juice refluxing through both an incompetent pyloric sphincter and a relaxed LES). -Hiatal hernia (a portion of the proximal stomach slides into the chest cavity with upward displacement of the lower esophageal sphincter, can contribute to the development of reflux)

Conditions that decrease LES tone (contributing to GERD)

-Conditions that decrease LES tone or increase abdominal pressure contribute to GERD and include: - alcohol and tobacco use -obesity -CNS depressants -pregnancy -hiatal hernia -delayed gastric emptying -increased gastric volume. -In many cases, no definitive cause is identified.

secondary achalasia.

-Degenerative changes in neural innervation, either intrinsic to the esophagus or within the extraesophageal vagus nerve or the dorsal motor nucleus of the vagus, may lead to secondary achalasia. -Secondary achalasia may arise in Chagas disease, in which T. cruzi infection causes destruction of the myenteric plexus, failure of peristalsis, and esophageal dilatation. -Duodenal, colonic, and ureteric myenteric plexuses can also be affected in Chagas disease. -Treatment modalities for both primary and secondary achalasia aim to overcome the mechanical obstruction, and include laparoscopic myotomy and pneumatic balloon dilatation. -Botulinum neurotoxin (Botox) injection, to inhibit LES cholinergic neurons, can also be effective.

Clinical features of Barrets Esophagus

-Diagnosis of Barrett esophagus is usually prompted by GERD symptoms and requires endoscopy and biopsy. -The best course of management is a matter of debate, but most clinicians recommend periodic surveillance endoscopy with biopsy to screen for dysplasia. -Dysplasia is often treated and more advanced lesions, including high-grade dysplasia and intramucosal carcinoma, always require therapeutic intervention. -Available modalities include surgical resection (esophagectomy); newer approaches include photodynamic therapy, radiofrequency ablation, and endoscopic mucosectomy.

Diffuse esophageal spasm

-Diffuse esophageal spasm is characterized by repetitive, simultaneous contractions of the distal esophageal smooth muscle.

Eosinophilic Esophagitis

-Eosinophilic esophagitis is a chronic immunologically mediated disorder that is being increasingly recognized. -Symptoms include food impaction and dysphagia in adults and feeding intolerance or GERD-like symptoms in children. -The cardinal histologic feature is epithelial infiltration by large numbers of eosinophils, particularly superficially and at sites far from the gastroesophageal junction. -Their abundance can help to differentiate eosinophilic esophagitis from GERD, Crohn disease, and other causes of esophagitis. -Endoscopically evident rings in the upper and mid portions of the esophagus, may also help to distinguish eosinophilic esophagitis from GERD. -Patients with eosinophilic esophagitis are typically refractory to high-dose PPI treatment. -Most patients are atopic, and many have atopic dermatitis, allergic rhinitis, asthma, or modest peripheral eosinophilia. -Treatments include dietary restrictions to prevent exposure to food allergens, such as cow milk and soy products, and topical or systemic corticosteroids.

Esophageal injuries

-Esophageal injuries are the rarest kinds of penetrating neck trauma; however, they cause most complications after a surgical procedure or other treatment. -Most esophageal injuries occur in conjunction with airway injuries because the airway lies anterior to the esophagus and provides some protection to it. -Esophageal injuries are often occult (hidden), which makes the injury difficult to detect, especially if it is isolated. -Unrecognized esophageal perforation is fatal in nearly all non-operative cases and in approximately 50% of surgical occurances

Esophageal mucosal webs

-Esophageal mucosal webs are idiopathic ledge-like protrusions of mucosa that may cause obstruction. -These uncommon lesions typically occur in women older than age 40 and can be associated with GERD, chronic graft-versus-host disease, or blistering skin diseases. -In the upper esophagus, webs may be accompanied by iron-deficiency anemia, glossitis, and cheilosis as part of the Paterson-Brown-Kelly or Plummer-Vinson syndrome -In general, esophageal webs are semi-circumferential lesions that protrude less than 5 mm, have a thickness of 2 to 4 mm, and are composed of a fibrovascular connective tissue and overlying epithelium. -The main symptom of webs is nonprogressive dysphagia associated with incompletely chewed food.

Esophageal rings, or Schatzki rings

-Esophageal rings, or Schatzki rings, are similar to webs, but are circumferential, thicker, and include mucosa, submucosa, and, occasionally, hypertrophic muscularis propria. -When present in the distal esophagus, above the gastroesophageal junction, they are termed A rings and are covered by squamous mucosa -those located at the squamocolumnar junction of the lower esophagus are designated B rings and may have gastric cardia-type mucosa on their undersurface.

CMV Treatment

-Ganciclovir, a guanosine analog that inhibits viral DNA polymerase -Valganciclovir, which has better oral bioavailability -Foscarnet for ganciclovir-resistant CMV infections, which functions to inhibit viral DNA/RNA polymerase -Cidofovir, which functions to inhibit viral DNA polymerase -Acyclovir is ineffective against CMV, because, unlike HSV and VZV, CMV does not have thymidine kinase. -Foscarnet is used for ganciclovir-resistant CMV with a mutation in the UL97 kinase gene.

Clinical manifestations of reflux esophagitis

-Heartburn is the usual symptom of reflux esophagitis, typically worse lying prone. -With recurrent reflux, a range of complications may develop. -The most common is the development of stricture in the distal esophagus. -Progressive obstruction, presents as dysphagia. -Other complications of recurrent reflux include hemorrhage or perforation; hoarseness, coughing, or wheezing; and pneumonia as a result of aspiration of gastric contents into the lungs, particularly during sleep. -Chronic recurrent reflux can also result in a change in the esophageal epithelium from squamous to columnar histology (Barrett esophagus) the disorder is more common in men and in smokers, and it leads to a greatly increased risk of adenocarcinoma. -Adenocarcinomas in the distal esophagus and proximal (cardiac) stomach related to Barrett esophagus are among the most rapidly increasing types of cancer in young male patients in the United States.

Hiatal hernia

-Hiatal hernia is characterized by separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap. -Congenital hiatal hernias are recognized in infants and children, but many are acquired in later life. -Hiatal hernia is symptomatic in fewer than 10% of adults; symptoms when present resemble GERD since hiatal hernia can cause LES incompetence. -

type II or true paraesophageal hernia

-In a type II or true paraesophageal hernia, which is uncommon, the gastroesophageal junction is in its normal location, but the fundus and parts of the greater curvature of the stomach herniate into the mediastinum alongside the esophagus. -Both types of paraesophageal hernias present with symptoms of postprandial distress, such as epigastric pain, chest pain, substernal fullness, shortness of breath, nausea, or vomiting. -Iron deficiency anemia may be seen with large hiatal hernias in which at least one third of the stomach is in the chest; linear gastric erosions at the top of gastric folds at the level of the diaphragm have been implicated as a cause of chronic blood loss. -Asymptomatic paraesophageal hernias do not require surgery. -Symptomatic paraesophageal hernias warrant surgical therapy because of the risk for strangulation, bleeding, perforation, or obstruction.

Mechanical Esophageal Obstruction

-In contrast to functional obstruction, mechanical obstruction, which can be caused by strictures or cancer, presents as progressive dysphagia that begins with inability to swallow solids. -With progression ingestion of liquids is also affected. -Because obstruction develops slowly, patients may subconsciously modify their diet to favor soft foods and liquids and be unaware of their condition until the obstruction is nearly complete.

Pyrosis

-Pyrosis or "heartburn," is the most common type of esophageal discomfort or substernal pain. -This burning sensation in the abdominal part of the esophagus is usually the result of regurgitation of small amounts of food or gastric fluid into the lower esophagus (GERD). -Pyrosis may also be associated with hiatal hernia -As indicated by its common name, heartburn, pyrosis is commonly perceived as a "chest" (vs. abdominal) sensation.

Infectious esophagitis

-Infectious esophagitis may occur in otherwise healthy individuals but is most frequent in those who are debilitated or immunosuppressed. -In these pts, esophageal infection by HSV, CMV, or fungal organisms is common. -Among fungi, Candida is the most common pathogen, although mucormycosis and aspergillosis may also occur. -The esophagus may also be involved in desquamative skin diseases such as bullous pemphigoid and epidermolysis bullosa and, rarely, Crohn disease. -Infection by fungi or bacteria can be primary or complicate a preexisting ulcer. -Nonpathogenic oral bacteria frequently are found in ulcer beds, while pathogenic organisms, which account for about 10% of infectious esophagitis cases, may invade the lamina propria and cause necrosis of overlying mucosa. -Candidiasis in its most advanced form is characterized by adherent, gray-white pseudomembranes composed of densely matted fungal hyphae and inflammatory cells covering the esophageal mucosa. -Herpesviruses typically cause punched-out ulcers, and histopathologic analysis demonstrates nuclear viral inclusions within a rim of degenerating epithelial cells at the ulcer edge. -By contrast, CMV causes shallower ulcerations. -Biopsy of these lesions show the characteristic nuclear and cytoplasmic inclusions within capillary endothelium and stromal cells -Immunohistochemical staining for viral antigens can be a useful ancillary diagnostic tool

Lower Esophageal Sphincter (LES)

-LES is tonically active but relaxes during swallowing -prevents reflux of gastric contents into the esophagus -3 components: (1) Esophageal sm. muscle (more prominent at the jxn w/the stomach (intrinsic sphincter)) (2) Fibers of the crural portion of the diaphragm (Sk. muscle) surround esophagus and exert a pinch-cock action (extrinsic sphincter) (3) the oblique or sling fibers of the stomach wall create a flap valve that helps close off the esophagogastic jxn and prevent regurgitation -LES tone is under neural control -ACh release from vagal endings causes the intrinsic sphincter to contract -Release of NO and VIP from interneurons cause relaxation of the intrinsic sphincter -the crural part of the diaphragm is innervated by the phrenic n. and is coordinated with respiration and contraction of chest and abdominal muscles

Pathology & Pathogenesis

-LES normally provides an effective barrier to reflux of acid from the stomach back into the esophagus -This is reinforced by secondary esophageal peristaltic waves in response to transient LES relaxation. -Effectiveness of that barrier can be altered by loss of LES tone (ie, the opposite of achalasia), increased frequency of transient relaxations, loss of secondary peristalsis after a transient relaxation, increased stomach volume or pressure, or increased production of acid, all of which can make more likely reflux of acidic stomach contents sufficient to cause pain or erosion. -Recurrent reflux can damage the mucosa, resulting in inflammation, hence the term "reflux esophagitis." -Recurrent reflux itself predisposes to further reflux because the scarring that occurs with healing of the inflamed epithelium renders the LES progressively less competent as a barrier. -Pepsin and bile can also be refluxed in addition to acid to cause esophagitis. -In most cases of esophageal reflux disease, a common pathophysiologic thread can be identified -Recurrent mucosal damage results in infiltration of granulocytes and eosinophils, hyperplasia of basal cells, and eventually the development of friable, bleeding ulcers and exudates over the mucosal surface. -These pathologic changes set the stage for scar formation and sphincter incompetence, predisposing to recurrent cycles of inflammation. -Increased frequency of transient LES relaxations may be partly in response to increased gastric distention -normally transient LES relaxations are accompanied by increased esophageal peristalsis -people with defects in excitatory pathways that promote peristalsis may be at increased risk for development of reflux -types of prostaglandins produced by the esophagus have been noted in reflux esophagitis (possibly due to impairment of healing and predisposing to recurrences)

Lower esophageal sphincter dysfunction

-Lower esophageal sphincter dysfunction, such as high resting pressure or incomplete relaxation, are present in many patients with nutcracker esophagus or diffuse esophageal spasm.

Pathogenesis of Esophageal adenocarcinoma

-Molecular studies suggest that the progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes. -This model is supported by the observation that epithelial clones identified in nondysplastic Barrett metaplasia persist and accumulate mutations during progression to dysplasia and invasive carcinoma. -Chromosomal abnormalities and TP53 mutation are often present in the early stages of esophageal adenocarcinoma. -Additional genetic changes and inflammation are thought to contribute to tumor progression.

Nutcracker esophagus

-Nutcracker esophagus describes patients with high-amplitude contractions of the distal esophagus that are, in part, due to loss of the normal coordination of inner circular layer and outer longitudinal layer smooth muscle contractions.

Clinical Features of esophageal adenocarcinoma

-Patients most commonly present with pain or difficulty in swallowing, progressive weight loss, chest pain, or vomiting. -By the time S/S appear, the tumor usually has invaded submucosal lymphatic vessels. -As a result of the advanced stage at diagnosis, the overall 5-year survival rate is less than 25%. -By contrast, 5-year survival approximates 80% in the few patients with adenocarcinoma limited to the mucosa or submucosa

Primary achalasia

-Primary achalasia is caused by failure of distal esophageal inhibitory neurons and is, by definition, idiopathic. -Primary achalasia is the result of distal esophageal inhibitory neuronal, that is, ganglion cell, degeneration. -This leads to increased tone, an inability to relax of the LES, and esophageal aperistalsis. -Degenerative changes in the extraesophageal vagus nerve or the dorsal motor nucleus of the vagus may also occur. -The cause is unknown; rare familial cases have been described.

Reactivation of latent CMV

-Reactivation of a latent CMV infection within leukocytes can occur when hosts becomes immunocompromised, such as immunosuppressed organ transplant patients and AIDS patients with CD4 counts less than 100/mm3. -Immunocompromised patients have a more severe clinical course, and can present with: -Retinitis that can lead to full-thickness retinal necrosis and edema, leading to the formation of scar tissue. -Colitis -Pneumonia (atypical/interstitial) -Esophagitis with linear ulcerations, in contrast to the "punched-out" ulcerations characteristic of HSV-1 esophagitis. -CMV is the most common cause of progressive lumbosacral polyradiculopathy in individuals with HIV and severe immunosuppression (CD4 <50/ul). CMV-related polyradiculopathy presents as a cauda equina syndrome

Morphology of Reflux Esophagitis

-Simple hyperemia, evident to the endoscopist as redness, may be the only alteration. - In mild GERD the mucosal histology is often unremarkable. -With more significant disease, eosinophils are recruited into the squamous mucosa, followed by neutrophils, which usually are associated with more severe injury -Basal zone hyperplasia exceeding 20% of the total epithelial thickness and elongation of lamina propria papillae, such that they extend into the upper third of the epithelium, also may be present

Esophageal Obstruction

-The esophagus is, essentially, a tube that delivers ingested solid food and fluids to the stomach. -This can be impeded by structural, i.e. (mechanical) obstruction or functional obstruction. -The latter results from disruption of the coordinated waves of peristaltic contractions that follow swallowing -mechanical obstruction, which can be caused by strictures or cancer, presents as progressive dysphagia that begins with inability to swallow solids.

Tracheo-esophageal fistula

-The most common birth defect of the esophagus is tracheo-esophageal fistula (TEF). -Usually, it is combined with some form of esophageal atresia. -In the most common type of TEF (approximately 90% of cases), the superior part of the esophagus ends in a blind pouch and the inferior part communicates with the trachea -In these cases, the pouch fills with mucus, which the infant aspirates. -In some cases, the superior esophagus communicates with the trachea and the inferior esophagus joins the stomach, but sometimes it does not, producing TEF with esophageal atresia -TEFs result from failures in partitioning of the esophagus and trachea

Esophageal Lacerations, Mucosal Injury, and Infections

-The most common esophageal lacerations are Mallory- Weiss tears, which are often induced by severe retching or vomiting. -Normally, a reflex relaxation of the gastroesophageal musculature precedes the anti-peristaltic contractile wave associated with vomiting. -This relaxation may fail during prolonged vomiting, with the result that refluxing gastric contents cause the esophageal wall to stretch and tear. -Pts usually present with hematemesis. -The roughly linear lacerations of Mallory-Weiss syndrome are longitudinally oriented and usually cross the gastroesophageal junction -These superficial tears generally heal quickly without surgical intervention. -By contrast, severe, transmural esophageal tears (Boerhaave syndrome) result in mediastinitis, are catastrophic, and require prompt surgical intervention.

Esophageal cancer

-The most common presenting complaint of esophageal cancer is dysphagia (difficulty in swallowing), which is not usually recognized until the lumen is reduced by 30-50%. -Esophagoscopy is a common diagnostic tool for observing these cancers. -Painful swallowing in some patients suggests extension of the tumor to peri-esophageal tissues. -Enlargement of the inferior deep cervical lymph nodes also suggests esophageal cancer. -Compression of the recurrent laryngeal nerves by an esophageal tumor produces hoarseness.

LES incompetence

-The opposite condition is LES incompetence, which permits reflux of acid gastric contents into the esophagus (GERD) -common condition -most frequent digestive disorder causing patients to seek care -causes heartburn and esophagitis and can lead to ulceration and stricture of the esophagus due to scarring. -In severe cases, the intrinsic sphincter, the extrinsic sphincter, and sometimes both are weak -less severe cases are caused by intermittent periods of poorly understood decreases in the neural drive to both sphincters. -GERD is treated with H2 receptor blockers or PPIs -surgical treatment is available as well

Chemical and Infectious Esophagitis

-The stratified squamous mucosa of the esophagus may be damaged by a variety of irritants including alcohol, corrosive acids or alkalis, excessively hot fluids, and heavy smoking. -Medicinal pills, most commonly doxycycline and bisphosphonates, may adhere to the esophageal lining and dissolve in the esophagus rather than passing immediately into the stomach, resulting in pill-induced esophagitis. -Esophagitis due to chemical injury generally causes only self-limited pain, particularly odynophagia (pain with swallowing). -Hemorrhage, stricture, or perforation may occur in severe cases. -Iatrogenic esophageal injury may be caused by cytotoxic chemotherapy, radiation therapy, or graft-versus-host disease. -The morphologic changes are nonspecific, consisting of ulceration and acute inflammation. -Irradiation causes blood vessel damage adding an element of ischemic injury.

Squamous Cell Carcinoma of the Esophagus

-US, esophageal SCC typically occurs in adults older than 45 years of age and affects males 4x more frequently than females. -Risk factors include alcohol and tobacco use, poverty, caustic esophageal injury, achalasia, Plummer-Vinson syndrome, frequent consumption of very hot beverages, and previous radiation therapy to the mediastinum. -It is nearly 6x more common in African Americans than in whites -The incidence of esophageal SCC can vary by more than 100-fold between and within countries, being more common in rural and underdeveloped areas. -The countries with highest incidences are Iran, central China, Hong Kong, Argentina, Brazil, and South Africa.

CMV diagnosis

-Urinalysis reveals renal tubule cells with intranuclear inclusions. -Culture buffy coat (WBCs) with cells that reveal large cells ("cyto" "megalo") with prominent basophilic intranuclear inclusions surrounded by a clear/white halo ("owl's eyes"). -PCR assay for CMV DNA or RNA in bodily fluids. -Serology will have a negative monospot test as compared to EBV mononucleosis, but is not specific for CMV mononucleosis.

type III or mixed paraesophageal hernia

-With type III or mixed paraesophageal hernia, the gastroesophageal junction and a large part of the stomach herniate into the mediastinum. -Both types of paraesophageal hernias present with symptoms of postprandial distress, such as epigastric pain, chest pain, substernal fullness, shortness of breath, nausea, or vomiting. -Asymptomatic paraesophageal hernias do not require surgery. -Symptomatic paraesophageal hernias warrant surgical therapy because of the risk for strangulation, bleeding, perforation, or obstruction.

epiphrenic diverticulum

-due to increased wall stress, esophageal dysmotility may result in development of small diverticulae, primarily the epiphrenic diverticulum located immediately above the lower esophageal sphincter

Morphology of Esophageal SCC

-half of SCC occur in the middle third of the esophagus -SCC begins as an in situ lesion in the form of squamous dysplasia. -Early lesions appear as small, gray-white plaquelike thickenings. -Over months to years, they grow into tumor masses that may be polypoid and protrude into and obstruct the lumen. -Other tumors are either ulcerated or diffusely infiltrative lesions that spread within the esophageal wall, where they can cause thickening, rigidity, and luminal narrowing. -These cancers may invade surrounding structures including the respiratory tree, causing pneumonia; the aorta, causing catastrophic exsanguination; or the mediastinum and pericardium. -Most SCCs are moderately to well-differentiated -Regardless of the histology symptomatic tumors have often invaded the esophageal wall at time of diagnosis. -The rich submucosal lymphatic network promotes circumferential and longitudinal spread, and intramural tumor nodules may be present several centimeters away from the main mass. -The sites of lymph node metastases vary with tumor location: Cancers in the upper third of the esophagus favor cervical lymph nodes; those in the middle third favor mediastinal, paratracheal, and tracheobronchial nodes; and those in the lower third spread to gastric and celiac nodes.

Zenker diverticulum

-impaired relaxation and spasm of the cricopharyngeus muscle after swallowing can result in increased pressure w/in the distal pharynx and development of a Zenker diverticulum (pharyngoesophageal diverticulum), which is located immediately above the UES -Zenker diverticulae are uncommon, but typically develop after age 50 and may reach several centimeters in size. -When small they may be asymptomatic, but larger Zenker diverticulae may accumulate significant amounts of food, producing a mass and symptoms that include regurgitation and halitosis.

Esophageal Adenocarcinoma

-typically arises in a background of Barrett esophagus and long-standing GERD -Risk factors: documented dysplasia, those who use tobacco, are obese, or who have had previous radiation therapy. -In US esophageal adenocarcinoma occurs most frequently in whites and is 7x more common in men than in women. - incidence varies by a factor of 60-fold worldwide, with rates being highest in Western countries, including the US, the UK, Canada, Australia, and the Netherlands, and lowest in Korea, Thailand, Japan, and Ecuador. -In countries where esophageal adenocarcinoma is more common, the incidence has increased markedly since 1970, more rapidly than for almost any other cancer. -As a result, esophageal adenocarcinoma, which represented less than 5% of esophageal cancers before 1970, now accounts for half of all esophageal cancers in some Western countries, including the United States.

Morphology of esophageal adenocarcinoma

-usually occurs in the distal third of the esophagus and may invade the adjacent gastric cardia -While early lesions may appear as flat or raised patches in otherwise intact mucosa, later tumors may form large exophytic masses, infiltrate diffusely, or ulcerate and invade deeply. -On microscopic examination, Barrett esophagus frequently is present adjacent to the tumor. -Tumors typically produce mucin and form glands

Esophageal manometry

Esophageal manometry allows separation of esophageal dysmotility into three principal forms, termed nutcracker esophagus, diffuse esophageal spasm, and hypertensive lower esophageal sphincter -In the absence altered patterns of esophageal contraction, these sphincter abnormalities are termed hypertensive lower esophageal sphincter