Reflux Esophagitis + Gastric adenocarcinoma

What are common causes of reflux oesophagitis? (condensed)

- exposure in the oesophagus to acid repetitively/excessively - increase the rate of spontaneous transient lower esophageal sphincter relaxations - impair reflexes that normally follow transient lower esophageal sphincter relaxations with a secondary wave of esophageal peristalsis - Conditions that increase gastric volume or pressure - alkaline injury - Hiatal hernia

What are the clinical manifestations of reflux oesophagitis? (condensed)

- heartburn (worse lying down) - strictures - dysphagia (food 1st liquids later) - haemorrhage, perforation - hoarseness, coughing, wheezing, pneumonia --> gastric contents getting into lungs - Barret's esophagus --> increased risk of adenocarcinoma

What imaging studies can we use with gastric cancer?

1) Esophagogastroduodenoscopy (EGD): To evaluate gastric wall and lymph node involvement 2) Double-contrast upper GI series and barium swallows: May be helpful in delineating the extent of disease when obstructive symptoms are present or when bulky proximal tumors prevent passage of the endoscope to examine the stomach distal to an obstruction 3) Chest radiography: To evaluate for metastatic lesions 4) CT scanning or MRI of the chest, abdomen, and pelvis: To assess the local disease process and evaluate potential areas of spread 5) Endoscopic ultrasonography (EUS): Staging tool for more precise preoperative assessment of the tumor stage

What are some lifestyle modifications you can do for reflux oesophagitis?

1) Quit Smoking. The chemicals from cigarettes relax the circular band of muscle (sphincter) at the bottom of the gullet (oesophagus) and make acid leaking up (refluxing) more likely. 2) Some foods and drinks may make reflux worse in some people and these should be avoided. Also, avoiding large-volume meals may help. 3) Some medicines may make symptoms worse. They may irritate the oesophagus or relax the sphincter muscle and make acid reflux more likely. The most common culprits are anti-inflammatory painkillers (such as ibuprofen or aspirin). Others include diazepam, theophylline, calcium-channel blockers (such as nifedipine) and nitrates. 4) Lose Weight. If you are overweight it puts extra pressure on the stomach and encourages acid reflux. Losing some weight may ease the symptoms. 5) Posture. Lying down or bending forward a lot during the day encourages reflux. Sitting hunched or wearing tight belts may put extra pressure on the stomach, which may make any reflux worse. 6) Bedtime. If symptoms recur most nights, the following may help: Go to bed with an empty, dry stomach. To do this, don't eat in the last three hours before bedtime and don't drink in the last two hours before bedtime. If you are able, try raising the head of the bed by 10-20 cm (for example, with books or bricks under the bed's legs). This helps gravity to keep acid from refluxing into the oesophagus. If you do this, do not use additional pillows, because this may increase tummy (abdominal) pressure.

How can we manage gastric cancers? (surgery)

1) Total gastrectomy, if required for negative margins 2) Esophagogastrectomy for tumors of the cardia and gastroesophageal junction 3) Subtotal gastrectomy for tumors of the distal stomach 4) Lymph node dissection: Controversy exists regarding extent of dissection; the National Comprehensive Cancer Network (NCCN) recommends D2 dissections over D1 dissections; a pancreas- and spleen-preserving D2 lymphadenectomy provides greater staging information and may provide a survival benefit while avoiding its excess morbidity when possible

Why does Reflux Oesophagitis sometimes present with cough/resp problems?

A persistent cough, particularly at night, sometimes occurs. This is due to the refluxed acid irritating the windpipe (trachea). Asthma symptoms of cough and wheeze can sometimes be due to acid leaking up (reflux). Other mouth and throat symptoms sometimes occur, such as gum problems, bad breath, sore throat, hoarseness and a feeling of a lump in the throat. Severe chest pain develops in some cases (and may be mistaken for a heart attack).

Oesophageal Adenocarcinoma

Accumulation of genetic p53 and epigenetic changes Risk Factors: - documented dysplasia - tobacco use - obesity - prior radiation therapy - lack of fresh fruits and vegetables in diet Macroscopically • Usually in the distal 1/3 of oesophagus; may invade gastric cardia • Initially - flat / raised patches in otherwise intact mucosa • Eventually - diffuse infiltration / ulcers Microscopically • Barrett metaplasia / dysplasia is frequently adjacent to the tumour • Formation of mucin-secreting glands, often with intestinal-type morphology Clinical presentation: Typically arises on a background of Barrett oesophagus and long-standing GORD - Mostly in Causasians; mostly men (7x) - pain, dysphagia, weight loss, haematemesis, chest pain, vomiting Prognosis- overall 5-year survival: <25%

What is Motilin?

An amino acid polypeptide hormone. Motilin is secreted by endocrine M cells that are numerous in crypts of the small intestine, especially in the duodenum and jejunum. It is released into the general circulation during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions; and it also stimulates endogenous release of the endocrine pancreas The main function of motilin is to increase the migrating myoelectric complex component of gastrointestinal motility and stimulate the production of pepsin. Motilin is also called "housekeeper of the gut" because it improves peristalsis in the small intestine and clears out the gut to prepare for the next meal. A high level of motilin secreted between meals into the blood stimulates the contraction of the fundus and antrum and accelerates gastric emptying. It then contracts the gallbladder and increases the squeeze pressure of the lower esophageal sphincter. Other functions of motilin include increasing the release of pancreatic polypeptide and somatostatin

What are some treatments for acid reflux and oesophagitis?

Antacids - alkaline liquids or tablets that reduce the amount of acid. A dose usually gives quick relief. Acid-suppressing medicines - PPI, H2 blockers (histamine receptor blockers)

What is Barrett's oesophagus?

Barrett's oesophagus is a pre-malignant condition, in which the normal squamous lining of the lower oesophagus is replaced by columnar mucosa (columnar lined oesophagus; CLO) that may contain areas of intestinal metaplasia. It is an adaptive response to chronic gastro-oesophageal reflux. The condition is often asymptomatic until discovered when the patient presents with oesophageal cancer. The prevalence is increasing, and it is more common in men (especially white), the obese and those over 50 years of age. It is weakly associated with smoking but not alcohol intake. The risk of cancer seems to relate to the severity and duration of reflux rather than the presence of CLO per se and it has been suggested that duodenogastro-oesophageal reflux of bile, pancreatic enzymes and pepsin, as well as gastric acid, may be important in pathogenesis. The molecular events underlying progression of CLO to dysplasia and cancer are incompletely understood but inactivation of the tumour suppression protein p16 by loss of heterozygosity or promoter hypermethylation is a key event, followed by somatic inactivation of p53, which promotes aneuploidy and tumour progression.

Biopsy of gastric cancer

Biopsy of any ulcerated lesion should include at least six specimens taken from around the lesion because of variable malignant transformation. In selected cases, endoscopic ultrasonography may be helpful in assessing depth of penetration of the tumor or involvement of adjacent structures. Histologically, the frequency of different gastric malignancies is as follows : Adenocarcinoma - 90-95% Lymphomas - 1-5% Gastrointestinal stromal tumors (formerly classified as either leiomyomas or leiomyosarcomas) - 2% Carcinoids - 1% Adenoacanthomas - 1% Squamous cell carcinomas - 1%

What chemotherapy may be used?

Chemotherapy 1) Platinum-based combination chemotherapy: First-line regimens include epirubicin/cisplatin/5-FU or docetaxel/cisplatin/5-FU; other regimens include irinotecan and cisplatin; other combinations include oxaliplatin and irinotecan 2) Trastuzumab in combination with cisplatin and capecitabine or 5-FU: For patients who have not received previous treatment for metastatic disease 3) Ramucirumab for the treatment of advanced stomach cancer or gastroesophageal (GE) junction adenocarcinoma in patients with unresectable or metastatic disease following therapy with a fluoropyrimidine- or platinum-containing regimen

What are common causes of reflux oesophagitis? (Detailed)

Common causes of reflux esophagitis are those conditions that result in persistent or repetitive acid exposure to the esophageal mucosa. These include disorders that increase the rate of spontaneous transient lower esophageal sphincter relaxations (Table 13-5) or impair reflexes that normally follow transient lower esophageal sphincter relaxations with a secondary wave of esophageal peristalsis. Conditions that increase gastric volume or pressure (eg, partial or complete gastric outlet obstruction and conditions that increase acid production) also contribute. Occasionally, reflux esophagitis can be caused by alkaline injury (eg, pancreatic juice refluxing through both an incompetent pyloric sphincter and a relaxed lower esophageal sphincter). Hiatal hernia, a disorder in which 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.

Factors explained: Delayed oesophageal clearance

Defective oesophageal peristaltic activity is commonly found in patients who have oesophagitis. It is a primary abnormality, since it persists after oesophagitis has been healed by acid-suppressing drug therapy. Poor oesophageal clearance leads to increased acid exposure time.

Describe the two types of dysphagia causes and presenting symptoms

Dysphagia can occur due to problems in the oropharynx or oesophagus. Oropharyngeal disorders affect the initiation of swallowing at the pharynx and upper oesophageal sphincter. The patient has difficulty initiating swallowing and complains of choking, nasal regurgitation or tracheal aspiration. Drooling, dysarthria, hoarseness and cranial nerve or other neurological signs may be present. Oesophageal disorders cause dysphagia by obstructing the lumen or by affecting motility. Patients with oesophageal disease complain of food 'sticking' after swallowing, although the level at which this is felt correlates poorly with the true site of obstruction. Swallowing of liquids is normal until strictures become extreme.

What is Dysphagia?

Dysphagia is defined as difficulty in swallowing. It may coexist with heartburn or vomiting but should be distinguished from both globus sensation (in which anxious people feel a lump in the throat without organic cause) and odynophagia (pain during swallowing, usually from gastro-oesophageal reflux or candidiasis).

What are investigations for dysphagia?

Dysphagia should always be investigated urgently. Endoscopy is the investigation of choice because it allows biopsy and dilatation of strictures. If no abnormality is found, then barium swallow with videofluoroscopic swallowing assessment is indicated to detect major motility disorders. In some cases, oesophageal manometry is required. High-resolution manometry allows accurate classification of abnormalities.

What are the signs and symptoms of Gastric cancer?

Early gastric cancer has no associated symptoms; however, some patients with incidental complaints are diagnosed with early gastric cancer. Most symptoms of gastric cancer reflect advanced disease. All physical signs in gastric cancer are late events. By the time they develop, the disease is almost invariably too far advanced for curative procedures. - Indigestion - Nausea or vomiting - Dysphagia - Postprandial fullness - Loss of appetite - Melena or pallor from anemia - Hematemesis - Weight loss - Palpable enlarged stomach with succussion splash - Enlarged lymph nodes such as Virchow nodes (ie, left supraclavicular) and Irish node (anterior axillary)

Benign oesophageal stricture

Fibrous strictures can develop as a consequence of long-standing oesophagitis, especially in the elderly and those with poor oesophageal peristaltic activity. The typical presentation is with dysphagia that is worse for solids than for liquids. Bolus obstruction following ingestion of meat causes absolute dysphagia. A history of heartburn is common but not invariable; many elderly patients presenting with strictures have no preceding heartburn. Diagnosis is by endoscopy, when biopsies of the stricture can be taken to exclude malignancy. Endoscopic balloon dilatation or bouginage is helpful. Subsequently, long-term therapy with a PPI drug at full dose should be started to reduce the risk of recurrent oesophagitis and stricture formation. The patient should be advised to chew food thoroughly, and it is important to ensure adequate dentition.

Gastric contents Defective gastric emptying Increased intra-abdominal pressure Dietary and environmental factors: Patient factors

Gastric contents: Gastric acid is the most important oesophageal irritant and there is a close relationship between acid exposure time and symptoms. Pepsin and bile also contribute to mucosal injury. Defective gastric emptying: Gastric emptying is delayed in patients with gastro-oesophageal reflux disease. The reason is unknown. Increased intra-abdominal pressure: Pregnancy and obesity are established predisposing causes. Weight loss may improve symptoms. Dietary and environmental factors: Dietary fat, chocolate, alcohol and coffee relax the lower oesophageal sphincter and may provoke symptoms. The foods that trigger symptoms vary widely between affected individuals. Patient factors: Visceral sensitivity and patient vigilance play a role in determining symptom severity and consulting behaviour in individual patients.

What is Gastrin?

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

What is heartburn/regurgitation?

Heartburn describes retrosternal, burning discomfort, often rising up into the chest and sometimes accompanied by regurgitation of acidic or bitter fluid into the throat. These symptoms often occur after meals, on lying down or with bending, straining or heavy lifting. They are classical of gastro-oesophageal reflux but up to 50% of patients present with other symptoms, such as chest pain, belching, halitosis, chronic cough or sore throats. In young patients with typical symptoms and a good response to dietary changes, antacids or acid suppression, investigation is not required, but in patients over 55 years of age, those with alarm symptoms or atypical features, urgent endoscopy is necessary.

What are the clinical manifestations of reflux esophagitis?

Heartburn is the usual symptom of reflux esophagitis, typically worsening on lying prone. With recurrent reflux, a range of complications may develop. The most common complication is the development of stricture in the distal esophagus. Progressive obstruction, initially to solid food and later to liquid, 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 (resembling that of the stomach and/or intestine). Termed 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.

Factors explained: Hiatus hernia

Hiatus hernia causes reflux because the pressure gradient between the abdominal and thoracic cavities, which normally pinches the hiatus, is lost. In addition, the oblique angle between the cardia and oesophagus disappears. Many patients who have large hiatus hernias develop reflux symptoms, but the relationship between the presence of a hernia and symptoms is poor. Hiatus hernia is very common in individuals who have no symptoms, and some symptomatic patients have only a very small or no hernia. Nevertheless, almost all patients who develop oesophagitis, Barrett's oesophagus or peptic strictures have a hiatus hernia.

Anaemia with oesophagitis

Iron deficiency anaemia can occur as a consequence of occult blood loss from long-standing oesophagitis. Most patients have a large hiatus hernia and bleeding can stem from subtle erosions in the neck of the sac ('Cameron lesions'). Nevertheless, hiatus hernia is very common and other causes of blood loss, particularly colorectal cancer, must be considered in anaemic patients, even when endoscopy reveals oesophagitis.

What are late complications of gastric cancer?

Late complications of gastric cancer may include the following features: - Pathologic peritoneal and pleural effusions - Obstruction of the gastric outlet, gastroesophageal junction, or small bowel - Bleeding in the stomach from esophageal varices or at the anastomosis after surgery - Intrahepatic jaundice caused by hepatomegaly - Extrahepatic jaundice - Inanition from starvation or cachexia of tumor origin

Management of GORD/Oesophagitis

Lifestyle advice, including weight loss, avoidance of dietary items that the patient finds worsen symptoms, elevation of the bed head in those who experience nocturnal symptoms, avoidance of late meals and giving up smoking, should be recommended. Patients who fail to respond to these measures should be offered PPIs, which are usually effective in resolving symptoms and healing oesophagitis. Recurrence of symptoms is common when therapy is stopped and some patients require life-long treatment at the lowest acceptable dose. When dysmotility features are prominent, domperidone can be helpful. There is no evidence that H. pylori eradication has any therapeutic value. Proprietary antacids and alginates can also provide symptomatic benefit. H 2 -receptor antagonist drugs also help symptoms without healing oesophagitis.

What is Esophageal Cancer?

Malignancy that typically presents with progressive dysphagia (first solids, then liquids) and weight loss; poor prognosis

Oesophageal Squamous Cell Carcinoma

Mostly loss of tumour suppressor genes (p53, p16/INK4a) Risk factors: • Alcohol & tobacco • Poverty • Caustic oesophageal injury • Achalasia • Frequent very hot beverages Macroscopically • Mostly middle 1/3 of oesophagus • Initially - in situ lesion (squamous dysplasia) - small, grey-white, plaque-like thickenings • Months /years - polypoid/exophytic (extending outward) tumour that obstructs the lumen • Ulceration may occur Microscopically • Moderate- to well-differentiated Clinical: Adults >45 years; mostly male (4x) Insidious onset; dysphagia, obstruction Subconscious alteration of diet to liquid foods to adjust to progressive obstruction - Haemorrhage & sepsis - due to ulceration

What is the Pathophysiology of Osophageal reflux disease?

Normally, the tonically contracted lower esophageal sphincter 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 lower esophageal sphincter relaxation. Effectiveness of that barrier can be altered by loss of lower esophageal sphincter 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 lower esophageal sphincter 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 (Figure 13-17). 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 lower esophageal sphincter relaxations may be partly in response to increased gastric distension. Normally, transient lower esophageal sphincter relaxations are accompanied by increased esophageal peristalsis. Individuals with defects in excitatory pathways that promote peristalsis may, therefore, be at increased risk for the development of esophageal reflux. Changes in the types of prostaglandins produced by the esophagus have been noted in reflux esophagitis, perhaps contributing to impairment of healing and predisposing to recurrences. In contrast to other forms of acid-mediated injury, H pylori infection does not appear to contribute to the development of reflux or esophagitis.

Complications of GERD?

Oesophagitis Barrett's oesophagus

What is Gastro-oesophageal reflux disease?

Reflux is normally followed by oesophageal peristaltic waves which efficiently clear the gullet, alkaline saliva neutralises residual acid, and symptoms do not occur. Gastro-oesophageal reflux disease develops when the oesophageal mucosa is exposed to gastroduodenal contents for prolonged periods of time, resulting in symptoms and, in a proportion of cases, oesophagitis.

What is cholecystokinin?

Source: I cells (duodenum, jejunum) Action: - increase pancreatic secretion - increase gallbladder contraction - decrease gastric emptying - increase sphincter of Oddi relaxation Regulation: increased by fatty acids, amino acids Acts on neural muscarinic pathways to cause pancreatic secretion

What is secretin?

Source: S cells (duodenum) Action: - increase pancreatic HCO3- secretion - decrease gastric acid secretion - increase bile secretion It increases HCO3- which neutralizes gastric acid in duodenum, allowing pancreatic enzymes to function - regulated --> increased release by fatty acids in lumen of duodenum and acid

Condensed explanation of Barrett's Esophagus

Specialized intestinal metaplasia - replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells in distal esophagus. Due to chronic reflux oesophagitis (GORD). Associated with increase risk of oesophageal adenocarcinoma.

How do we diagnose gastric cancer? (Just in terms of testing)

Testing: 1) CBC: May be helpful to identify anemia, which may be caused by bleeding, liver dysfunction, or poor nutrition; approximately 30% of patients have anemia 2) Electrolyte panels 3) Liver function tests 4) Tumor markers such as CEA and CA 19-9: Elevated CEA in 45-50% of cases; elevated CA 19-9 in about 20% of cases

How do we diagnose Reflux Oesophagitis?

The diagnosis of reflux is usually made by a combination of the typical clinical presentation in conjunction with investigations such as a barium swallow x-ray or gastroscopy.

Factors explained: Abnormalities of the lower oesophageal sphincter

The lower oesophageal sphincter is tonically contracted under normal circumstances, relaxing only during swallowing. Some patients with gastro-oesophageal reflux disease have reduced lower oesophageal sphincter tone, permitting reflux when intra-abdominal pressure rises. In others, basal sphincter tone is normal but reflux occurs in response to frequent episodes of inappropriate sphincter relaxation.

Symptoms of Reflux Eophagitis (online)?

The major symptoms are heartburn (burning feeling rising up the back of the breastbone), regurgitation of acid and food into the mouth with a sour taste (waterbrash), and burning pain on swallowing food (oesophageal sensitivity). Other symptoms include difficulty swallowing (dysphagia), irritation of the throat and chronic cough. Lung problems such as asthma and even lung infections can occur.

What are the clinical features of GERD?

The major symptoms are heartburn and regurgitation, often provoked by bending, straining or lying down. 'Waterbrash', which is salivation due to reflex salivary gland stimulation as acid enters the gullet, is often present. The patient is often overweight. Some patients are woken at night by choking as refluxed fluid irritates the larynx. Others develop odynophagia or dysphagia. A variety of other features have been described, such as atypical chest pain which may be severe and can mimic angina, and may be due to reflux-induced oesophageal spasm. Others include hoarseness ('acid laryngitis'), recurrent chest infections, chronic cough and asthma. The true relationship of these features to gastro-oesophageal reflux disease remains unclear.

What are the clinical presentations of Reflux Esophagitis?

The predominant presenting symptom of reflux is 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.

What is Reflux Oesophagitis?

The reflux of stomach contents into the oesophagus (tube leading to the stomach) is known as gastro-oesophageal reflux (GOR). The consequence is a chemical insult to the oesophagus from acid, enzymes, and sometimes bile. Reflux occurs commonly, but infrequently, in most people, and probably causes little harm because the natural movement (peristalsis) of the oesophagus clears the acid and food back into the stomach. When acid reflux from the stomach is frequent and persistent, the result is damage to the lining of the oesophagus. This is known as reflux oesophagitis or peptic oesophagitis.

Complications of Oesophagitis are?

Ulceration Haematemesis Melena Stricture Barret's oesophagus

Background on the Oesophagus

When we eat, food passes down the gullet (oesophagus) into the stomach. Cells in the lining of the stomach make acid and other chemicals which help to digest food. Stomach cells also make mucus which protects them from damage from the acid. The cells lining the oesophagus are different and have little protection from acid. There is a circular band of muscle (a sphincter) at the junction between the oesophagus and stomach. This relaxes to allow food down but then normally tightens up and stops food and acid leaking up (refluxing) into the oesophagus. In effect, the sphincter acts like a valve.

Investigations for GORD

Young patients who present with typical symptoms of gastro-oesophageal reflux, without worrying features such as dysphagia, weight loss or anaemia, can be treated empirically without investigation. Investigation is advisable if patients present over the age of 50-55 years, if symptoms are atypical or if a complication is suspected. Endoscopy is the investigation of choice. This is performed to exclude other upper gastrointestinal diseases that can mimic gastro-oesophageal reflux and to identify complications. A normal endoscopy in a patient with compatible symptoms should not preclude treatment for gastro-oesophageal reflux disease. Twenty-four-hour pH monitoring is indicated if the diagnosis is unclear or surgical intervention is under consideration. This involves tethering a slim catheter with a terminal radiotelemetry pH-sensitive probe above the gastro-oesophageal junction. The intraluminal pH is recorded whilst the patient undergoes normal activities, and episodes of symptoms are noted and related to pH. A pH of less than 4 for more than 6-7% of the study time is diagnostic of reflux disease. In a few patients with difficult reflux, impedance testing can detect weakly acidic or alkaline reflux that is not revealed by standard pH testing.