GASTRO-OESOPHAGEAL GASTRO-OESOPHAGEAL REFLUX DISEASEREFLUX DISEASE

Gastro-oesophageal refluxGastro-oesophageal reflux resulting in heartburn affects resulting in heartburn affects approximately 30% of the general approximately 30% of the general population. population.

AnatomyAnatomy

The oesophagus is a muscular tube The oesophagus is a muscular tube 25 cm long which extends from the 25 cm long which extends from the cricoid cartilage to the cardiac orifice cricoid cartilage to the cardiac orifice of the stomach. of the stomach.

It has an upper and a lower It has an upper and a lower sphincter. sphincter.

A peristaltic swallowing wave propels A peristaltic swallowing wave propels the food bolus into the stomach.the food bolus into the stomach.

PathophysiologyPathophysiology

Occasional episodes of gastro-Occasional episodes of gastro-oesophageal reflux are common in health. oesophageal reflux are common in health.

Reflux is followed by oesophageal Reflux is followed by oesophageal peristaltic waves which efficiently clear the peristaltic waves which efficiently clear the gullet, alkaline saliva neutralises residual gullet, alkaline saliva neutralises residual acid, and symptoms do not occur. acid, and symptoms do not occur.

Gastro-oesophageal reflux disease Gastro-oesophageal reflux disease develops when the oesophageal mucosa is develops when the oesophageal mucosa is exposed to gastric contents for prolonged exposed to gastric contents for prolonged periods of time, resulting in symptoms periods of time, resulting in symptoms and, in a proportion of cases, oesophagitis. and, in a proportion of cases, oesophagitis.

EtiologyEtiology

1. abnormal of the lower oesophageal sphincter:1. abnormal of the lower oesophageal sphincter: A. reduced tone:A. reduced tone:

dietary factors (coffee, tea), dietary factors (coffee, tea), smoking, smoking, alcohol, alcohol, pregnancy, obesity (resulting in increased intra-pregnancy, obesity (resulting in increased intra-

abdominal pressure);abdominal pressure); preparations (Papaverin, Nitrats, Teophyllin, etc.)preparations (Papaverin, Nitrats, Teophyllin, etc.)

B. inappropriate relaxation:B. inappropriate relaxation: hiatus hernia;hiatus hernia; dietary factors (fried, fatty food, macaroni; these food dietary factors (fried, fatty food, macaroni; these food

result in delayed gastric emptying, increased intra-gastric result in delayed gastric emptying, increased intra-gastric acidity)acidity)

2. defective oesophageal clearance;2. defective oesophageal clearance;

Factors associated with the Factors associated with the development of gastro-oesophageal development of gastro-oesophageal

reflux diseasereflux disease..

Abnormalities of the lower Abnormalities of the lower oesophageal sphincter:oesophageal sphincter:

In health, the lower oesophageal sphincter In health, the lower oesophageal sphincter is tonically contracted, relaxing only during is tonically contracted, relaxing only during swallowing. swallowing.

Some patients with gastro-oesophageal Some patients with gastro-oesophageal reflux disease have reduced lower reflux disease have reduced lower oesophageal sphincter tone, permitting oesophageal sphincter tone, permitting reflux when intra-abdominal pressure rises. reflux when intra-abdominal pressure rises.

In others, basal sphincter tone is normal In others, basal sphincter tone is normal but reflux occurs in response to frequent but reflux occurs in response to frequent episodes of inappropriate sphincter episodes of inappropriate sphincter relaxation. relaxation.

Hiatus hernia:Hiatus hernia: Hiatus hernia causes reflux because the Hiatus hernia causes reflux because the

pressure gradient between the abdominal and pressure gradient between the abdominal and thoracic cavities, which normally pinches the thoracic cavities, which normally pinches the hiatus, is lost. In addition, the oblique angle hiatus, is lost. In addition, the oblique angle between the cardia and oesophagus between the cardia and oesophagus disappears. disappears.

Many patients who have large hiatus hernias Many patients who have large hiatus hernias develop reflux symptoms, but the relationship develop reflux symptoms, but the relationship between the presence of a hernia and between the presence of a hernia and symptoms is poor. symptoms is poor.

Hiatus hernia is very common in individuals Hiatus hernia is very common in individuals who have no symptoms, and some who have no symptoms, and some symptomatic patients have only a very small symptomatic patients have only a very small or no hernia. or no hernia.

Important features of Important features of hiatus herniahiatus hernia

Occurs in 30% of the population over Occurs in 30% of the population over the age of 50 years;the age of 50 years;

Often asymptomatic;Often asymptomatic; Heartburn and regurgitation can Heartburn and regurgitation can

occur;occur; Gastric volvulus may complicate Gastric volvulus may complicate

large para-oesophageal hernias. large para-oesophageal hernias.

Types of hiatus herniaTypes of hiatus hernia. .

Delayed oesophageal Delayed oesophageal clearance:clearance:

Defective oesophageal peristaltic Defective oesophageal peristaltic activity is commonly found in patients activity is commonly found in patients who have oesophagitis. who have oesophagitis.

It is a primary abnormality, since it It is a primary abnormality, since it persists after oesophagitis has been persists after oesophagitis has been healed by acid-suppressing drug healed by acid-suppressing drug therapy. therapy.

Poor oesophageal clearance leads to Poor oesophageal clearance leads to increased acid exposure time. increased acid exposure time.

Gastric contents:Gastric contents: Gastric acid Gastric acid is the most important is the most important oesophageal irritant and there is oesophageal irritant and there is a close relationship between acid a close relationship between acid exposure time and symptoms. exposure time and symptoms.

Defective gastric emptying:Defective gastric emptying: Gastric emptying is delayed in Gastric emptying is delayed in patients with gastro-oesophageal patients with gastro-oesophageal reflux disease. reflux disease.

Increased intra-abdominal Increased intra-abdominal pressure:pressure: Pregnancy and obesity Pregnancy and obesity are established predisposing causes. are established predisposing causes. Weight loss may improve symptoms. Weight loss may improve symptoms.

Dietary and environmental Dietary and environmental factors:factors: Dietary fat, chocolate, Dietary fat, chocolate, alcohol and coffee relax the lower alcohol and coffee relax the lower oesophageal sphincter and may oesophageal sphincter and may provoke symptoms. There is little provoke symptoms. There is little evidence to incriminate smoking or evidence to incriminate smoking or NSAIDs as causes of gastro-NSAIDs as causes of gastro-oesophageal reflux disease. oesophageal reflux disease.

Clinical featuresClinical features The major symptoms are The major symptoms are heartburnheartburn and and regurgitationregurgitation, often provoked by bending, , often provoked by bending, straining or lying down. straining or lying down.

'Waterbrash', which is salivation due to 'Waterbrash', which is salivation due to reflex salivary gland stimulation as acid reflex salivary gland stimulation as acid enters the gullet, is often present. enters the gullet, is often present.

A history of weight gain is common. A history of weight gain is common. Some patients are woken at night by Some patients are woken at night by

choking as refluxed fluid irritates the choking as refluxed fluid irritates the larynx. larynx.

Others develop dysphagia. Others develop dysphagia. A few present with atypical chest pain A few present with atypical chest pain

which may be severe, can mimic angina which may be severe, can mimic angina and is probably due to reflux-induced and is probably due to reflux-induced oesophageal spasm. oesophageal spasm.

Complications Complications 1. Oesophagitis1. Oesophagitis

A range of endoscopic findings, from A range of endoscopic findings, from mild redness to severe, bleeding mild redness to severe, bleeding ulceration with stricture formation, is ulceration with stricture formation, is recognised.recognised.

There is a poor correlation between There is a poor correlation between symptoms and histological and symptoms and histological and endoscopic findings. endoscopic findings.

A normal endoscopy and normal A normal endoscopy and normal oesophageal histology are perfectly oesophageal histology are perfectly compatible with significant gastro-compatible with significant gastro-oesophageal reflux disease. oesophageal reflux disease.

Reflux oesophagitisReflux oesophagitis. The gullet is inflamed and . The gullet is inflamed and ulcerated (small arrows) and there is early ulcerated (small arrows) and there is early

stricturing (large arrow).stricturing (large arrow).

2. Barrett's oesophagus2. Barrett's oesophagus

Barrett's oesophagus ('columnar lined Barrett's oesophagus ('columnar lined oesophagus'-CLO) is a pre-malignant oesophagus'-CLO) is a pre-malignant glandular metaplasia of the lower glandular metaplasia of the lower oesophagus, in which the normal squamous oesophagus, in which the normal squamous lining is replaced by columnar mucosa lining is replaced by columnar mucosa composed of a cellular mosaic containing composed of a cellular mosaic containing areas of intestinal metaplasia. areas of intestinal metaplasia.

It occurs as an adaptive response to chronic It occurs as an adaptive response to chronic gastro-oesophageal reflux and is found in gastro-oesophageal reflux and is found in 10% of patients undergoing gastroscopy for 10% of patients undergoing gastroscopy for reflux symptoms. reflux symptoms.

CLO principally occurs in Western Caucasian CLO principally occurs in Western Caucasian males and is rare in other racial groups. males and is rare in other racial groups.

It is the major risk factor for oesophageal It is the major risk factor for oesophageal adenocarcinoma, with a lifetime cancer risk adenocarcinoma, with a lifetime cancer risk of around 10%. of around 10%.

The prevalence is increasing, and it is more The prevalence is increasing, and it is more common in men (especially white) and those common in men (especially white) and those over 50 years of age. over 50 years of age.

It is weakly associated with smoking but not It is weakly associated with smoking but not alcohol. alcohol.

Recent studies suggest that cancer risk is Recent studies suggest that cancer risk is related to the severity and duration of reflux related to the severity and duration of reflux rather than the presence of CLO per se but rather than the presence of CLO per se but this remains to be proven.this remains to be proven.

DiagnosisDiagnosis requires multiple systematic requires multiple systematic biopsies to maximise the chance of biopsies to maximise the chance of detecting intestinal metaplasia and/or detecting intestinal metaplasia and/or dysplasia.dysplasia.

ManagementManagement Neither potent acid suppression nor Neither potent acid suppression nor

antireflux surgery will stop progression or antireflux surgery will stop progression or induce regression of CLO, and treatment is induce regression of CLO, and treatment is only indicated for symptoms of reflux or only indicated for symptoms of reflux or complications such as stricture. complications such as stricture.

Endoscopic ablation therapy or Endoscopic ablation therapy or photodynamic therapy can induce regression photodynamic therapy can induce regression but 'buried islands' of glandular mucosa may but 'buried islands' of glandular mucosa may persist underneath the squamous epithelium persist underneath the squamous epithelium and cancer risk is not eliminated. and cancer risk is not eliminated.

At present these therapies remain At present these therapies remain experimental but show promise; they are experimental but show promise; they are used in patients with high-grade dysplasia used in patients with high-grade dysplasia (HGD) or early malignancy that is not (HGD) or early malignancy that is not suitable for surgery. suitable for surgery.

Barrett's oesophagusBarrett's oesophagus. Pink columnar mucosa . Pink columnar mucosa extends up the gullet. Small islands of squamous extends up the gullet. Small islands of squamous

mucosa remain (arrow).mucosa remain (arrow).

AnaemiaAnaemia

Iron deficiency anaemia occurs as a Iron deficiency anaemia occurs as a consequence of chronic, insidious blood consequence of chronic, insidious blood loss from long-standing oesophagitis.loss from long-standing oesophagitis.

Almost all such patients have a large Almost all such patients have a large hiatus hernia. hiatus hernia.

Nevertheless, hiatus hernia is very Nevertheless, hiatus hernia is very common and other causes of blood loss, common and other causes of blood loss, particularly colorectal cancer, must be particularly colorectal cancer, must be considered in anaemic patients, even considered in anaemic patients, even when endoscopy reveals oesophagitis and when endoscopy reveals oesophagitis and a hiatus hernia. a hiatus hernia.

Benign oesophageal Benign oesophageal stricturestricture

Fibrous strictures develop as a consequence Fibrous strictures develop as a consequence of long-standing oesophagitis. of long-standing oesophagitis.

Most patients are elderly and have poor Most patients are elderly and have poor oesophageal peristaltic activity. oesophageal peristaltic activity.

They present with dysphagia which is worse They present with dysphagia which is worse for solids than for liquids. for solids than for liquids.

Bolus obstruction following ingestion of meat Bolus obstruction following ingestion of meat can lead to absolute dysphagia. can lead to absolute dysphagia.

A history of heartburn is common but not A history of heartburn is common but not invariable; many elderly patients presenting invariable; many elderly patients presenting with strictures have no preceding heartburn. with strictures have no preceding heartburn.

DiagnosisDiagnosis ofofbenign oesophageal benign oesophageal

stricturestricture Endoscopy and biopsies of the Endoscopy and biopsies of the

stricture are taken to exclude stricture are taken to exclude malignancy.malignancy.

Endoscopic balloon dilatation or Endoscopic balloon dilatation or bouginage is undertaken. bouginage is undertaken.

ManagementManagement ofofbenign oesophageal benign oesophageal

stricturestricture Subsequently, long-term therapy Subsequently, long-term therapy

with a proton pump inhibitor drug at with a proton pump inhibitor drug at full dose should be started to reduce full dose should be started to reduce the risk of recurrent oesophagitis and the risk of recurrent oesophagitis and stricture formation. stricture formation.

The patient should be advised to The patient should be advised to chew food thoroughly, and it is chew food thoroughly, and it is important to ensure adequate important to ensure adequate dentition. dentition.

InvestigationsInvestigations Investigation is advisable if patients present in Investigation is advisable if patients present in

middle or late age, if symptoms are atypical or if middle or late age, if symptoms are atypical or if a complication is suspected. a complication is suspected.

Endoscopy is the investigation of choiceEndoscopy is the investigation of choice. . This is performed to exclude other upper This is performed to exclude other upper gastrointestinal diseases which can mimic gastro-gastrointestinal diseases which can mimic gastro-oesophageal reflux, and to identify complications. oesophageal reflux, and to identify complications. A normal endoscopy in a patient with compatible A normal endoscopy in a patient with compatible symptoms should not preclude treatment for symptoms should not preclude treatment for gastro-oesophageal reflux disease. gastro-oesophageal reflux disease.

When, despite endoscopy, the diagnosis is When, despite endoscopy, the diagnosis is unclear or if surgical intervention is under unclear or if surgical intervention is under consideration, consideration, 24-hour pH monitoring24-hour pH monitoring is is indicated. A pH of less than 4 for more than 6-7% indicated. A pH of less than 4 for more than 6-7% of the study time is diagnostic of reflux disease. of the study time is diagnostic of reflux disease.

ManagementManagement

Lifestyle advice, including:Lifestyle advice, including: weight loss, weight loss, avoidance of dietary items which the avoidance of dietary items which the

patient finds worsen symptoms, patient finds worsen symptoms, elevation of the bed head in those elevation of the bed head in those

who experience nocturnal symptoms,who experience nocturnal symptoms, avoidance of late meals, avoidance of late meals, giving up smoking.giving up smoking.

AntacidsAntacids

Antacids widely available for self-Antacids widely available for self-medication and are used for relief of medication and are used for relief of minor dyspeptic symptoms.minor dyspeptic symptoms.

Magnesium Trisilicate Mixture 10 – Magnesium Trisilicate Mixture 10 – 20 ml 3 – 4 times daily before meals;20 ml 3 – 4 times daily before meals;

Aluminium Hydroxide 300 mg\5 ml Aluminium Hydroxide 300 mg\5 ml Liquid 300 – 600 mg as needed Liquid 300 – 600 mg as needed between meals and at bedtime or as between meals and at bedtime or as directed by physician.directed by physician.

The majority are based on The majority are based on combinations of calcium, aluminium combinations of calcium, aluminium and magnesium salts, all of which have and magnesium salts, all of which have individual side-effects. individual side-effects.

Calcium compounds cause constipation, Calcium compounds cause constipation, Magnesium-containing agents cause Magnesium-containing agents cause

diarrhoea, diarrhoea, Aluminium compounds block absorption Aluminium compounds block absorption

of digoxin, tetracycline and dietary of digoxin, tetracycline and dietary phosphates. phosphates.

Most have a high sodium content and Most have a high sodium content and can exacerbate congestive heart can exacerbate congestive heart failure. failure.

Histamine H2-receptor Histamine H2-receptor antagonist drugsantagonist drugs. .

Cimetidine 800 mg at bedtime; treatment should Cimetidine 800 mg at bedtime; treatment should be continued for at least 4 – 8 weeks; be continued for at least 4 – 8 weeks; maintenance: 400mg at bedtime;maintenance: 400mg at bedtime;

Ranitidine (Zantac) 150 mg twice a day or 300 Ranitidine (Zantac) 150 mg twice a day or 300 mg at night for 4 – 8 weeks; maintenance: 150 – mg at night for 4 – 8 weeks; maintenance: 150 – 300 mg at night;300 mg at night;

Dyspeptic symptoms remit promptly, usually Dyspeptic symptoms remit promptly, usually within days of starting treatment. within days of starting treatment.

They are moderately effective for the They are moderately effective for the management of reflux disease. management of reflux disease.

H2-receptor antagonist drugs help symptoms H2-receptor antagonist drugs help symptoms without healing oesophagitis. without healing oesophagitis.

They are well tolerated, and the timing of They are well tolerated, and the timing of medication and dosage should be tailored to medication and dosage should be tailored to individual need. individual need.

H+/K+ ATPase ('proton H+/K+ ATPase ('proton pump') inhibitorspump') inhibitors. .

Omeprazole (Losec) 20 – 80 mg once daily or twice Omeprazole (Losec) 20 – 80 mg once daily or twice daily up to 8 – 12 weeks;daily up to 8 – 12 weeks;

Lansoprazole (Prevacid) 30 mg once daily or twice Lansoprazole (Prevacid) 30 mg once daily or twice daily for 4 – 8 weeks;daily for 4 – 8 weeks;

They are the most powerful inhibitors of gastric They are the most powerful inhibitors of gastric secretion yet discovered, with maximal inhibition secretion yet discovered, with maximal inhibition occurring 3-6 hours after an oral dose. They have an occurring 3-6 hours after an oral dose. They have an excellent safety profile. excellent safety profile.

Proton pump inhibitors (omeprazole and Proton pump inhibitors (omeprazole and lansoprazole) are also much more effective than H2-lansoprazole) are also much more effective than H2-antagonists for healing and maintenance of reflux antagonists for healing and maintenance of reflux oesophagitis. oesophagitis.

Proton pump inhibitors are the treatment of choice Proton pump inhibitors are the treatment of choice for severe symptoms and for complicated reflux for severe symptoms and for complicated reflux disease. disease.

Recurrence of symptoms is common when therapy is Recurrence of symptoms is common when therapy is stopped and some patients require life-long stopped and some patients require life-long treatment at the lowest acceptable dose.treatment at the lowest acceptable dose.

Treatment of gastro-oesophageal Treatment of gastro-oesophageal reflux disease: a 'step-down' reflux disease: a 'step-down'

approachapproach..

Anti-reflux surgeryAnti-reflux surgery Patients who fail to respond to medical therapy,Patients who fail to respond to medical therapy, those who are unwilling to take long-term proton those who are unwilling to take long-term proton

pump inhibitors, pump inhibitors, those whose major symptom is severe those whose major symptom is severe

regurgitation should be considered for regurgitation should be considered for anti-anti-reflux surgery.reflux surgery.

This can be undertaken by an open operation but This can be undertaken by an open operation but is increasingly being carried out laparoscopically. is increasingly being carried out laparoscopically.

Although heartburn and regurgitation are Although heartburn and regurgitation are alleviated in most patients, a proportion develop alleviated in most patients, a proportion develop complications such as inability to vomit and complications such as inability to vomit and abdominal bloating ('gas-bloat syndrome'). abdominal bloating ('gas-bloat syndrome').

Issues in older people Issues in older people gastro-oesophageal reflux gastro-oesophageal reflux

diseasedisease The prevalence of gastro-oesophageal The prevalence of gastro-oesophageal reflux disease is higher in older people and reflux disease is higher in older people and complications are more common.complications are more common.

The severity of symptoms does not The severity of symptoms does not correlate with the degree of mucosal correlate with the degree of mucosal inflammation in old age.inflammation in old age.

Late complications such as peptic Late complications such as peptic strictures or bleeding from oesophagitis strictures or bleeding from oesophagitis are more common in older people.are more common in older people.

Aspiration from occult gastro-oesophageal Aspiration from occult gastro-oesophageal reflux disease should be considered in reflux disease should be considered in older patients with recurrent pneumonia. older patients with recurrent pneumonia.

GASTRITISGASTRITIS

Gastritis is a histological diagnosis, Gastritis is a histological diagnosis, although it can sometimes be although it can sometimes be recognised at endoscopy. recognised at endoscopy.

Common cause of Common cause of gastritisgastritis

Acute gastritisAcute gastritis Acute gastritis is often erosive and haemorrhagic.Acute gastritis is often erosive and haemorrhagic. Neutrophils are the predominant inflammatory cell Neutrophils are the predominant inflammatory cell

in the superficial epithelium. in the superficial epithelium. Acute gastritis often produces no symptoms but Acute gastritis often produces no symptoms but

may cause dyspepsia, anorexia, nausea or may cause dyspepsia, anorexia, nausea or vomiting, haematemesis or melaena. vomiting, haematemesis or melaena.

Many cases resolve quickly and do not merit Many cases resolve quickly and do not merit investigation; in others, endoscopy and biopsy may investigation; in others, endoscopy and biopsy may be necessary to exclude peptic ulcer or cancer. be necessary to exclude peptic ulcer or cancer.

Treatment should be directed to the underlying Treatment should be directed to the underlying cause.cause.

Short-term symptomatic therapy with antacids, Short-term symptomatic therapy with antacids, acid suppression (e.g. H2-receptor antagonists) or acid suppression (e.g. H2-receptor antagonists) or antiemetics (e.g. metoclopramide 10 mg 3 times a antiemetics (e.g. metoclopramide 10 mg 3 times a day) may be necessary.day) may be necessary.

Chronic gastritis due to Chronic gastritis due to Helicobacter pylory Helicobacter pylory

infectioninfection The predominant inflammatory cells are The predominant inflammatory cells are

lymphocytes and plasma cells. lymphocytes and plasma cells. Correlation between symptoms and Correlation between symptoms and

endoscopic or pathological findings is endoscopic or pathological findings is poor. poor.

Most patients are asymptomatic and do Most patients are asymptomatic and do not require any treatment. not require any treatment.

Patients with dyspepsia and H. pylori-Patients with dyspepsia and H. pylori-associated gastritis may benefit from H. associated gastritis may benefit from H. pylori eradication. pylori eradication.

Autoimmune chronic Autoimmune chronic gastritisgastritis

This involves the body of the stomach, spares the This involves the body of the stomach, spares the antrum and results from autoimmune activity antrum and results from autoimmune activity against parietal cells. against parietal cells.

The histological features are diffuse chronic The histological features are diffuse chronic inflammation, atrophy and loss of fundic glands, inflammation, atrophy and loss of fundic glands, intestinal metaplasia and sometimes hyperplasia of intestinal metaplasia and sometimes hyperplasia of enterochromaffin-like (ECL) cells. enterochromaffin-like (ECL) cells.

Circulating antibodies to parietal cell and intrinsic Circulating antibodies to parietal cell and intrinsic factor may be present. factor may be present.

In some patients the degree of gastric atrophy is In some patients the degree of gastric atrophy is severe, and loss of intrinsic factor secretion leads to severe, and loss of intrinsic factor secretion leads to pernicious anaemia. pernicious anaemia.

The gastritis itself is usually asymptomatic but The gastritis itself is usually asymptomatic but some patients have evidence of other organ-some patients have evidence of other organ-specific autoimmunity, particularly thyroid disease. specific autoimmunity, particularly thyroid disease.

There is a fourfold increase in the risk of gastric There is a fourfold increase in the risk of gastric cancer development. cancer development.

Menetrie`s diseaseMenetrie`s disease In this rare condition the gastric pits are elongated In this rare condition the gastric pits are elongated

and tortuous, with replacement of the parietal and and tortuous, with replacement of the parietal and chief cells by mucus-secreting cells. As a result, the chief cells by mucus-secreting cells. As a result, the mucosal folds of the body and fundus are greatly mucosal folds of the body and fundus are greatly enlarged. enlarged.

Most patients are hypochlorhydric. Most patients are hypochlorhydric. Whilst some patients have upper gastro-intestinal Whilst some patients have upper gastro-intestinal

symptoms, the majority present in middle or old symptoms, the majority present in middle or old age with protein-losing enteropathy due to age with protein-losing enteropathy due to exudation from the gastric mucosa. exudation from the gastric mucosa.

Barium meal shows enlarged, nodular and coarse Barium meal shows enlarged, nodular and coarse folds which are also seen at endoscopy. folds which are also seen at endoscopy.

Treatment with anti-secretory drugs may reduce Treatment with anti-secretory drugs may reduce protein loss but unresponsive patients require protein loss but unresponsive patients require partial gastrectomy. partial gastrectomy.