Category Archives: Gastroenterology

SCREENING

Gastric cancer has an appalling prognosis despite treatment, and earlier diagnosis has been advocated in an attempt to improve this. Unfortunately, earlier diagnosis does not necessarily mean longer survival. The patient is merely operated on at an earlier date and, although the survival may appear longer, death will still occur at the same time from the point of genesis of the cancer (called lead time bias). With length time bias a greater number of slowly growing turnours are detected when screening asymptomatic individuals. In Japan, mass screening with mobile X-ray units has increased the proportion of early gastric cancers diagnosed. Early gastric cancer is defined as a carcinoma that is confined to the mucosa or submucosa. It is associated with 5-year survival rates of approximately 90%. In a large series of patients with gastric cancer from the UK, only 0.7% were identified as having early gastric cancer and therefore screening would not be warranted.
An effective screening procedure should:
• Be cheap
• Be acceptable to all social groups so that they attend for examination
• Have a good discriminatory index from benign lesions

• Result in an improvement in prognosis
Unless all these criteria are fulfilled, screening is unwarranted except possibly in individuals with an increased risk for the disease. Nevertheless, even in this high-risk group, screening asymptomatic subjects is not justified as the overall benefit is minimal.
An alternative approach to screening asymptomatic patients is to investigate symptomatic patients as quickly as possible. At the present time the mean interval between the onset of symptoms and attendance at hospital is approximately 6-9 months. However, dyspepsia is very common in the general population without any gastric lesions and it would obviously be impractical for every dyspeptic member of the general population to consult a physician. Even if they did, most primary physicians would think it unjustified to arrange a complicated series of investigations on the first visit. Thus, the detection of early gastric cancer in symptomatic patients is not a feasible proposition at present.

lead time bias. Earlier diagnosis, at X. made by screening tests before the clinical OIa!,jncsis, at Y, suggests an increased survival time of A + B compared to B. The actual survival time (0 remains unchanged.

lead time bias. Earlier diagnosis, at X. made by screening tests before the clinical OIa!,jncsis, at Y, suggests an increased survival time of A + B compared to B. The actual survival time (0 remains unchanged.

PATHOLOGY

Most gastric cancers occur in the antrum and are almost invariably adenocarcinomas. The common type is ‘intestinal’ and the turnours are polypoid or ulcerating lesions with heaped-up, rolled edges. Intestinal metaplasia is often seen in the surrounding mucosa, along with H. pylori. The diffuse type is composed of scattered or small clusters of cells, often with extensive submucosal spread which may result in the picture of ‘linitis plastica’, where the stomach appears rigid on X-ray.

CLINICAL FEATURES

Symptoms

The commonest symptom is epigastric pain, which is indistinguishable from the pain of peptic ulcer disease, both being relieved by food and antacids. The pain can vary in intensity, but may be constant and severe. Mostpatients with carcinoma of the stomach have advanced disease at the time of presentation, and also have nausea,  anorexia and weight loss. Vomiting is frequent and can be severe if the turnour is near the pylorus. Dysphagia can occur with turnours involving the fundus. Gross haematemesis is unusual, but anaemia from occult blood loss is frequent.
Patients can present with metastases causing abdominal swelling due to ascites or jaundice due to liver involvement. Metastases also occur in bone, brain and lung, producing appropriate symptoms.

Signs

Nearly 50% of patients have a palpable epigastric mass with abdominal tenderness. Often weight loss is the only feature. A palpable lymph node is sometimes found in the supraclavicular fossa (Virchow’s node) and signs of metastases are present in up to one-third of patients. Carcinoma of the stomach is the cancer most frequently associated with dermatomyositis and acanthosis nigricans.

INVESTIGATION

ROUTINE FULL BLOOD COUNT AND LIVER BIOCHEMISTRY.

This is necessary to look for anaemia and possible liver metastases.
BARIUM MEAL. A good quality, double-contrast barium meal has a diagnostic accuracy of up to 90%. The carcinoma is usually seen as a filling defect or an irregular ulcer with rolled edges. With the infiltrating type, the Xray may show a rigid stomach.
GASTROSCOPY . Gastroscopy is usually performed as the primary procedure and has the advantage that biopsies can be performed for histological assessment and to exclude lymphoma. Positive biopsies can be obtained in almost all cases of obvious carcinoma, but a negative biopsy does not necessarily rule out the diagnosis. For this reason, eight to ten biopsies should be taken from around the ulcer margin and its base. Superficial brushings for cytology will further improve the diagnostic rate.

Carcinoma of the stomach. Endoscopic picture 'ng a large irregular ulcer.

Carcinoma of the stomach. Endoscopic picture
‘ng a large irregular ulcer.

CT, MRI AND ULTRASOUND. These are used to stage for operability, but have been disappointing in detecting nodular and peritoneal metastases. Endoscopic ultrais sound is now being used to stage the depth of the primary invasion.

TREATTMENT

The 5-year  survival rate of patients operated on for early gastic cancer (EGC) in Japan is 90%, but outside Japan EDC is rare. Surgery remains the best form of treatment if the patient is operable. Better preoperative staging hasreduced the numbers undergoing operation and has  improved the 5-year survival rates to around 30%. In curative operations, 5-year survival rates are as high as 50%.Despite these improved figures, the overall survival rate for a patient with gastric carcinoma has not dramaticed, cally advanced with a 10% 5-year survival. Treatment with chemotherapy has made little impact and is currently not justifiable apart from in clinical trials. Survival may be prolonged by a few months but the toxicity of the drugs limits their use. Cimetidine has been used with  some success in trials. Palliative care with relief of pain and counselling is essential

Primary lymphoma

Lymphome of the stomach can account for 10% of all gastic malignancies in the developed world. It is a nonlymphoma Hodgkins lymphome of the B cell type arising from mucosal-associaated lymphoid tissue. H. pylori is thought to play an aetiological role. Clinical presentation is the same as gastic  carcinoma. Treatment is surgical with postoperative radiotherapy and chemotherapy. Eradication of H. pylori is strongly recommended. Prognosisis good with a 75 % 5 year survival depending on the type of lymphoma.

MENETRIER’S DISEASE

Menetrier’s disease is a rare condition in which there is  thickening and enlargement of the gastric mucosal folds. Histologically there is hyperplasia of the mucin-producing cells with glandular proliferation and loss of the parietal and chief cells.
The patient may complain of epigastric pain and occasionally peripheral oedema may occur due to hypoalbuminaemia resulting from protein loss through the gastric mucosa. Symptomatic treatment is all that is required for this condition. It is possibly premalignant.

GASTRIC TUMOURS

Benign

The commonest benign tumour is a leiomyoma. This tumour is usually discovered by chance but it can occasionally ulcerate and produce haematemesis. Treatment is surgical removal.
Gastric polyps are uncommon and are again found usually by chance. They produce no symptoms. The commonest are regenerative or hyperplastic polyps, which are often multiple and require no treatment. Rarely, adenomatous polyps are found and endoscopic removal is recommended because of possible malignant potential. Most gastric cancers appear not to arise from pre-existing adenomas (in contrast to colonic carcinomas).

Malignant

Carcinoma of the stomach is one of the commonest malignant turnours of the gastrointestinal tract and is the sixth most common fatal cancer in the UK. The frequency varies throughout the world, being high in Japan and Chile and relatively low in the USA. In the UK, 15 per 100000 males are affected per year. The worldwide incidence of gastric carcinoma appears to be falling, even in Japan, for no obvious reason. The incidence increases with age and more men than women are affected.

EPIDEMIOLOGY

There is a strong link between H. pylori infection and gastric cancer. It is suggested that H. pylori infection results in chronic active gastritis which eventually leads to gastritis with atrophy and intestinal metaplasia-a premalignant pathological change. Much of the previous epidemiological data, i.e. the increase of cancer in lower socio-economic groups, can be explained by the intrafamilial spread of H. pylori. Dietary factors may still be important as both initiators and promoters may have separate roles in carcinogenesis. These include alcohol, spiced, salted or pickled foods and nitrate ingestion. Nitrates can be converted into nitrosamines by bacteria at neutral pH and nitrosamines are known to be carcinogenic in animals. Nitrosamines are also present in the stomach of patients with achlorhydria who have an increased cancer risk. Smoking is also associated with an increased incidence of stomach cancer.

Flow diagram showing the development of gastric cancer associated with H. pylori infection.

Flow diagram showing the development of gastric cancer associated with H. pylori infection.

Genes underlying the inherited susceptibility to gastric cancer have not yet been identified, but certain patterns are emerging as seen in colonic cancer. There is a higher incidence of gastric cancer in blood group A patients. Possible precancerous conditions Benign gastric ulcers do not develop into gastric cancer. It can, however, be difficult to differentiate a benign ulcer from a malignant ulcer, as even malignant ulcers can partially heal on medical treatment. For these reasons it was originally thought that gastric ulcers could become malignant. Pernicious anaemia carries a small increased risk of developing gastric carcinoma. Gastritis with atrophy present in the body and fundus of the stomach of these patients may be a precancerous lesion.
Gastritis with atrophy and also areas of intestinal metaplasia are areas where many gastric cancers develop. Intestinal metaplasia and chronic gastritis are also found in the resected stomach and there is an increased incidence of gastric cancer after partial gastrectomy (especially with a gastrojejunostomy). This increased incidence is the same whether the gastric resection was for a gastric or duodenal ulcer and may all be a reflection of H. pylori infection.

COMPLICATIONS OF PEPTIC ULCER

In all patients with any complications of peptic ulcer disease H. pylori eradication is imperative. If the patient has been given eradication therapy previously a further course  of eradication therapy is necessary.

Haemorrhage

This is dealt with below.

Perforation 

The frequency of perforation of peptic ulcer is decreasing;
this is partly attributable to the introduction of Hy-receptor antagonists. Duodenal ulcers perforate more commonly than gastric ulcers, usually into the peritoneal cavity. Perforation into the lesser sac may occur.
MANAGEMENT OF PERFORATION. Detailed management is described on p. 233. Surgery is performed to close the perforation and drain the abdomen. Conservative management using nasogastric suction, intravenous fluids and antibiotics is occasionally used in elderly and very sick patients.

Pyloric stenosis or obstruction

This is more accurately called gastric outflow obstruction, as the obstruction may be prepyloric or in the duodenum. The obstruction occurs either because of an active ulcer with surrounding oedema or because the healing of an ulcer has been followed by scarring. The obstruction can also be due to a gastric malignancy or external compression from a pancreatic carcinoma. The main sym ptom of this condition is vomiting, usually without pain as the characteristic ulcer pain has abated owing to healing.

Vomiting is projectile and huge in volume, and the vomitus contains particles of the previous day’s food. On examination of the abdomen the patient may have a succussion splash. Severe or persistent vomiting causes loss of acid from the stomach and a metabolic alkalosis occurs .

The diagnosis is made by barium meal examination (less commonly by endoscopy) but can be suspected when large quantities of fluid are removed by gastric intubation in the fasting state. Fluid and electrolyte replacement is necessary, together with the regular removal of gastric contents via a nasogastric tube. In some patients with oedema rather than scarring, the symptoms will settle with this conservative management. However, most patients require surgery. Postoperative gastric stasis canbe a problem, particularly if a vagotomy has been performed, even when accompanied by drainage.

Perforation of peptic ulcer.

Perforation of peptic ulcer.

PEPTIC ULCER DISEASE

This is an ulcer of the mucosa in, or adjacent to, an acidbearing area. Most ulcers occur in the stomach or proximal duodenum but they can occur in the oesophagus (with oesophageal reflux), in the jejunum in the Zollinger- Ellison syndrome or after a gastroenterostomy, and finally in a Meckel’s diverticulum, which contains ectopic gastric mucosa.

EPIDEMIOLOGY

Duodenal ulceration is common; 15% of the population will suffer from a duodenal ulcer at some time. They are two to three times commoner than gastric ulcers. Duodenal ulcers are commoner in men than women (4:1) and both gastric and duodenal ulcers are more common in elderly people, i.e. an age-related incidence. There is considerable geographical variation. Duodenal ulcer is commoner in northern England and Scotland than in other parts of the UK. Much of the previous epidemiological data can be explained on the prevalence of H. pylori infection.

AETIOLOGY

Peptic ulceration is caused by an imbalance between:
• Acid and pepsin, and
• Mucosal defences: mucus, bicarbonate and prostaglandins.
H. pylori plays a central role in both gastric and duodenal ulceration, although the mechanisms are unclear. Genetic susceptibiity may also playa role, particularly in patients who do not secrete blood group 0 antigen into gastric secretions.
Possible pathogenetic factors of H. pylori infection are:
• An increase in fasting and meal-stimulated gastrin release
• A decrease in somatostatin (D cells) in the antrum
• An increase in parietal cell mass
• An increase in pepsinogen I
• An alteration in the mucus protective layer
• Cytotoxin release
All of these affect acid secretion or the mucosal barrier. The only other important cause of gastric ulceration is SAIDs. Peptic ulceration is also seen in hyperparathyroidism (since calcium stimulates acid secretion) and in the Zollinger-Ellison syndrome.

PATHOLOGY

Gastric ulcer can occur in any part of the stomach, but is most commonly found on the lesser curve. Most duodenal ulcers are found in the duodenal cap with the surrounding mucosa appearing inflamed, haemorrhagic and friable (duodenitis).
Histologically there is a break in the superficial epithelium penetrating down to the muscularis mucosa with a fibrous base and an increase in inflammatory cells. The ulcer may heal with fibrosis.

CLINICAL FEATURES

Symptoms

Indigestion is a frequent symptom, but epigastric pain is the characteristic feature of ulcer disease. If the patient points directly to the epigastrium as the site of the pain, this has a high discriminatory value for diagnosis. The pain of a duodenal ulcer classically occurs at night as well as during the day. In both types of ulcer, pain is helped by antacids. The relationship of the pain to food is variable and on the whole is not helpful in diagnosis. However, patients with a duodenal ulcer may complain of pains when they are hungry. Nausea may accompany the pain, but vomiting is not frequent and when it occurs it may relieve the pain.
Another symptom is heartburn, which is due to acid regurgitation. Anorexia and weight loss may occur, particularly with gastric ulcers.
The symptoms of a duodenal ulcer are periodic with spontaneous relapses and remissions. Eighty per cent of patients will have a recurrence of symptoms within 1 year of the first episode. The natural history appears to be for the disease to remit over many years with the onset of gastritis with atrophy and decrease in acid secretion. Fifty per cent of patients with a gastric ulcer will have a recurrence within 2 years. If the patient complains of persistent and severe pain, complications such as penetration into other organs should be considered. Back pain may suggest a penetrating posterior duodenal ulcer. Patients can present for the first time with either a haematemesis or melaena or with a perforation. Signs The only signs are those of epigastric tenderness but this is a poor discriminating sign. Tenderness does not necessarily imply disease and is frequently found in nonulcer dyspepsia.

INVESTIGATION

Many patients, particularly the young presenting with indigestion, can be treated symptomatically for 4-5 weeks without investigation.
ENDOSCOPY is often the first investigation, with biopsy of all gastric ulcers, or BARIUM MEAL (double-contrast technique). A gastric ulcer is shown in Fig. 4.11 and a duodenal ulcer is ACID SECRETION STATUS. This is not useful to measure in most cases of peptic ulcer disease. The main use of this test is in the Zollinger-Ellison syndrome, but a serum gastrin is more useful. Secretions from the stomach are collected via a nasogastric tube before (basal secretion) and following stimulation by an injection of pentagastrin. This is a synthetic peptide containing the terminal five peptides of gastrin.
BLOOD TESTS are unhelpful in uncomplicated cases.

TREATMENT

Duodenal ulcer

There are two main approaches.
1 Eradication of H. pylori. This therapy is now thought to ‘cure’ duodenal ulcers providing the organism is successfully eradicated. Eradication therapy is being given increasingly more frequently and may become the first-line therapy in all patients.

Barium meal showing a gastric ulcer (arrow).

Barium meal showing a gastric ulcer (arrow).

Barium meal showing a large chronic duodenal ulcer (arrow).

Barium meal showing a large chronic duodenal ulcer (arrow).

2 Acid suppression
(a) Omeprazole, a protein pump inhibitor, 20 mg daily produces an 80-90% inhibition of 24 hour intragastric acidity and healing rates of 90% after

4 weeks’ treatment. It is being increasingly used for treatment of ulcers as it produces good symptom relief.

(b) H2 receptor antagonists  have been the first choice of therapy. They have molecular structures that fit the H2 receptors on the parietal cells. A single therapeutic dose in the evening produces, at least, an 80% reduction of nocturnal acid production until the following morning. Over 80% of duodenal ulcers will heal with a 2-month course of this group of drugs and symptoms are relieved quickly. There is little difference between the different H2 antagonists, but cimetidine is not usually given to young males because of the incidence of impotence which is low.
3 Other drugs. A number of other drugs have been shown to be effective, but are rarely used compared with the above.
(a) Misoprostol. A synthetic analogue of prostaglandin E, inhibits gastric acid secretion and does promote gastric and duodenal ulcer healing. It is mainly used as a cytoprotective agent against NSAIDassociated gastric ulcers. Prophylaxis is 200 ILg, two to four times per day. Treatment is 800 ILg daily in divided doses, the main side-effect being diarrhoea.
(b) Sucralfate possibly acts by protecting the mucosa from acid pepsin attack. It is a complex of aluminium hydroxide and sulphated sucrose, but it has minimal antacid properties. It is also used in the treatment of benign gastric ulceration and sometimes as a cytoprotective agent at a dose of 2 g daily in divided doses.
4 Miscellaneous. Stopping smoking should be strongly encouraged as smoking slows healing. Special diets, together with avoidance of coffee, alcohol or acid substances, are not required.
The effectiveness of treatment should be assessed symptomatically.
There is no need for follow-up endoscopy. If the patient fails to respond, the diagnosis should be reviewed. Duodenal ulcers are common and care must be taken not to falsely attribute abdominal symptoms to the finding of an ulcer.

Gastric ulcer

Treatment is given to ensure ulcer healing which must be checked with follow-up endoscopy and biopsies at 6 weeks. Failure to heal raises the question of malignancy and further treatment and follow-up endoscopy is required.
There are a number of approaches to treatment.
1 H2-receptor antagonists have been the most common agents used for treatment, but omeprazole is being increasingly used as the initial therapy as symptom relief is rapid; follow-up with endoscopy and biopsies at 6 weeks.
2 Eradication of H. pylori. Eradication treatment should be given to all patients with a gastric ulcer; usually the presence of H. pylori has been documented at endoscopy. If the patient is taking an NSAID when the ulcer is discovered, eradication therapy should still be given if H. pylori is demonstrated.

3 Smoking should be strongly discouraged. Dietary changes are unnecessary.
4 Attempts should be made to stop NSAIDs in patients with peptic ulceration. This may be difficult in those with severe arthritis and if it is essential to continue NSAIDs either misoprostol or ranitidine should be prescribed concurrently.

The chemical formula of the first available H2• receptor antagonist showing the similarity to histamine. Other -irreceptor antagonists include ranitidine, famotidine and idine.

The chemical formula of the first available H2•
receptor antagonist showing the similarity to histamine. Other -irreceptor antagonists include ranitidine, famotidine and idine.

SURGICAL MANAGEMENT

Since the introduction of Hy-receptor antagonists, surgery for peptic ulceration is rarely performed. In the past, two type of operation were performed:

1 Partial gastrectomy. The principle in both types of gastrectomy performed for peptic ulcer disease is to remove the antral area that secretes gastrin, since this in turn stimulates acid production.
(a) Billroth I partial gastrectomy. The lower part of the stomach is removed and the stomach remnant is connected to the duodenum.
(b) Billroth II (Polya gastrectomy). The stomach remnant is connected to the first loop of jejunum (a gastroenterostomy) and the duodenum is closed.

2 Vagotomy.
(a) Truncal vagotomy plus gastroenterostomy/ pyloroplasty
(b) Selective vagotomy (preserving coeliac branch of the gastroenterostomy/pyloroplasty.
(c) Highly selective vagotomy or proximal gastric vagotomy, in which only the nerves supplying the parietal cells are transected, and therefore no drainage is required. With this type of operation there is little diarrhoea but the recurrence rate is still 5-10%.

Diagrammatic representation of the mechanisms involved in acid secretion.

Diagrammatic representation of the mechanisms involved in acid secretion.

Currently, surgery is reserved for complications:
• Recurrent uncontrolled haemorrhage when the bleeding vessel is ligated
• Perforation which is oversown (For both of these conditions no other procedure such as a gastrectomy or vagotomy is required.)
• Outflow obstruction which requires gastric resection

LONG-TERM COMPLICATIONS OF SURGERY are still occasionally seen. A recurrent ulcer, which can appear in the stomach, duodenum or jejunum, often occurs at the stoma. The symptoms are similar to those seen in the unoperated stomach, with pain invariably being present, although patients may present with haemorrhage.
Because of the deformity of the stomach, investigation by endoscopy is preferred to X-ray examination. Treatment is now usually medical, using acid suppression and eradication of H. pylori. Consideration should be given to the possibility of the Zollinger-Ellison syndrome. Dumping. This is the term used to describe a number of upper abdominal symptoms, e.g. nausea and distension associated with sweating, faintness and palpitations, that occur in patients following gastrectomy or gastroenterostomy. It is due to ‘dumping’ of food into the jejunum, which is followed by rapid fluid dilution of the high osmotic load. A number of patients have mild symptoms of dumping but learn to cope with them. It is rare for it to be a clinical problem and, if it is, the symptoms will have a functional element. Treatment should be with reassurance and symptomatic therapy. Further operations are rarely needed.

Diarrhoea

This is chiefly seen after vagotomy. Urgency or recurrent severe episodes occur in 1% and can be a major problem. Treatment consists of antidiarrhoeals such as codeine phosphate but is not entirely satisfactory. Cholestyramine, a resin that binds bile salts, helps in some cases. Very occasionally the diarrhoea or steatorrhoea can be due to bacterial overgrowth in the blind loop of a Polya gastrectomy. Vomiting (afferent loop syndrome/bilious vomiting). The incidence of vomiting has decreased with the introduction of the more conservative operations. Vomiting occurs because food gets trapped owing to the altered anatomy. Treatment is symptomatic, except on the rare occasions when reconstructive surgery is required. Nutritional complications. Anaemia is most commonly due to iron deficiency caused by poor absorption. Treatment is with oral iron, which may be needed long-term.
Megaloblastic anaemia is uncommon, but can be due to either folate deficiency (due to poor intake) or vitamin BI2 deficiency (due to long-term gastritis with atrophy resulting in intrinsic factor deficiency). Osteomalacia is an uncommon late complication. Patients often fail to gain weight owing to anorexia after gastric surgery and a few suffer from severe protein-energy malnutrition as a result.

Chronic gastritis

Chronic active gastritis consists of an infiltration of the lamina propria with lymphocytes and plasma cells. This can lead to the development of atrophic changes in the mucosa including loss of parietal and chief cells, and subsequent intestinal metaplasia. Helicobacter pylori is the chief cause of chronic active gastritis affecting the antrum and body of the stomach. Other causes include:
AUTOIMMUNE GASTRITIS; affecting the fundus and body of the stomach (pangastritis) resulting in pernicious anaemia. Autoantibodies to gastric parietal cells and intrinsic factors are found in the serum (perniciousanaemia ).
CHRONIC INGESTION OF SAIDs, aspirin  and possibly biliary reflux produces gastritis.

CLINICAL FEATURES

A consistent relationship between upper gut symptoms and histological chronic gastritis has not been established. There may be a subset of patients in whom the gastritis may account for the symptoms. Most chronic gastritis is asymptomatic and requires no treatment. Helicobacter pylori and the upper gastrointestinal tract. This spiral-shaped urease-producing bacterium  is found in the stomach and in areas of gastric metaplasia in the duodenum. H. pylori is found in greatest numbers under the mucus layers in gastric pits in close apposition to gastric epithelial cells. Intrafamilial clustering suggests person-to-person spread, but the exact mode of transmission is unclear. Childhood acquisition of H. pylori is very prevalent in developing countries. There is a clear relationship between the age of acquisition and lower socio-economic status worldwide. A relationship between H. pylori infection and crowded domestic living conditions in childhood has been established.

CLINICAL SIGNIFICANCE

Initially, H. pylori infection produces acute gastritis which rapidly becomes chronic active gastritis and in some peptic ulcer disease may develop. Long-standing chronic active gastritis leads to atrophy, intestinal metaplasia and increases the risk of gastric carcinoma.
Thus the earlier the H. pylori is acquired, the greater the risk of atrophy and metaplasia.H. pylori is present in a greater proportion of patients with non-ulcer dyspepsia than in asymptomatic controls, but the relationship with symptoms is poor.

DIAGNOSIS

1 Invasive endoscopy
(a) Rapid urease test: biopsies are added to a urea solution containing phenol red. If H. pylori is present, the urease enzyme splits the urea to release ammonia which raises the pH of the solution and causes a rapid colour change.
(b) H. pylori can be Gram stained or cultured on special medium and sensitivities to antibodies can be ascertained.
(c) H. pylori can also be detected histologically with routine stained sections.

2 Non-invasive
(a) Urea breath test with 13Cor 14C , but using urea as the substrate). This is a quick and easy way of detecting the presence of H. pylori and is used as a screening test and also to demonstraten eradication of the organism following treatment.
(b) Serum antibodies. Reasonably sensitive and specific serological tests are available and are used mainly for epidemiological studies.

TREATMENT AND ERADICATION

In patients with peptic ulcer disease, it is necessary to eradicate the organism as this leads to a ‘cure’ with very low recurrence of ulceration unless reinfection occurs; this is, however, uncommon. The best regimen for eradication is not yet clear, but all regimens must take into account the following factors:
• A good compliance with treatment regimens is required
• The high incidence of antibiotic resistance to metronidazole (25%+)
• That oral metronidazole, when given, increases the side-effects of treatment
• That bismuth chelate is unpleasant to take even as tablets.
Two regimens are currently used, but these will undoubtedly change over the years:
1 Triple therapy-bismuth chelate, 2 tablets four times daily for 4 weeks, 30 min before a meal, metronidazole 400 mg three times daily for the first week, tetracycline, 500 mg three times daily for the first week.

2 An alternative therapy is omeprazole 40 mg daily, together with amoxycillin, or possibly clarithromycin, 500 mg three times per day for 1-2 weeks. All these treatments give eradication figures of approximately 80%.
Patients with gastritis without peptic ulceration should not be treated, but this is an area which is increasingly changing as more is discovered about the organism and better eradication therapy is found.

The stomach and duodenum

STRUCTURE

The stomach, which varies considerably in size, is divided into the upper portion (the fundus), the mid-region or body, and the antrum, which extends into the pyloric region.
There are two sphincters, the gastro-oesophageal sphincter and the pyloric sphincter; the latter is largely made up of a thickening of the circular muscle layer. The muscle wall of the stomach has three layers-an outer longitudinal, an inner circular, and an innermost oblique layer of smooth muscle.
The duodenum has outer longitudinal and inner smooth muscle layers. It is C-shaped and the pancreas sits in the concavity. It terminates in the jejunum at the duodenojejunal flexure. The mucosal lining of the stomach, particularly in the greater curvature, is thrown into thick folds or rugae. The upper two-thirds of the stomach contains parietal cells, which secrete hydrochloric acid, and chief cells, which secrete pepsinogen. The junction between the body and the antrum of the stomach can often be seen macroscopically, but can be confirmed by measuring surface pH. The antrum contains only mucus-secreting and G cells, which secrete gastrin. There are two major forms of gastrin, G17 and G34, depending on the number of amino-acid residues. G17 is the major form found in the antrum.
The duodenal mucosa contains Brunner’s glands, which secrete alkaline mucus. This, along with the pancreatic and biliary secretions, helps to neutralize the acid secretion from the stomach when it reaches the duodenum.

FUNCTION

Acid secretion

The factors controlling acid secretion. Secretion is under neural and hormonal control. Both stimulate acid secretion through the release of histamine, which acts on the parietal cells either directly or via immunocytes. Other major gastric functions
• Reservoir for food

• Emulsification of fat and mixing of gastric contents

• Secretion of intrinsic factor
• Absorption (of only minimal importance) Gastric emptying epends on many factors. There are osmoreceptors in the duodenal mucosa that control gastric emptying by local reflexes and the release of gut hormones. In particular, intraduodenal fat delays gastric emptying by negative feedback through duodenal receptors.

Control of acid secretion.

Control of acid secretion.

GASTRITIS

There is no universally accepted classification of this condition partly because there is a poor correlation between clinical, pathological and endoscopic findings. Acute gastritis, acute ulceration and erosions.
In acute gastritis there is an acute inflammatory infiltrate in the superficial gastric mucosa predominantly with neutrophils, This is sometimes accompanied by mucosal erosions. Multiple small erosions, often with an oedematous mucosa, are described as acute erosive gastritis.Acute gastric ulceration occurs in the same setting as  erosions, but are larger and less superficial. Gastritis can be commonly produced by drugs such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) (Information box 4.2), and occasionally by infections, e.g. cytomegalovirus and herpes simplex, particularly in the imrnunocornprornised. Aspirin and other NSAIDs deplete mucosal prostaglandins which leads to mucosal damage. Alcohol in high concentrations damages the gastric mucosal barrier and is associated with acute gastric mucosal lesions and upper gastrointestinal bleeding.Acute ulcers are also seen after severe stress (stress ulcer) and secondary to burns (Curling’s ulcer), trauma, shock, renal or liver disease. The underlying mechanism for these ulcers is unknown but may be related to analteration in mucosal flow.

NSAIDs and the upper gastrointestinal tract.

NSAIDs and the upper gastrointestinal tract.

CLINICAL FEATURES

The correlation between the pathological changes and symptoms is poor, but some patients with acute gastritis may suffer from indigestion and vomiting, usually shortlived. Gastrointestinal haemorrhage can occur.

DIAGNOSIS

In many patients symptoms settle without diagnosis, but endoscopy is necessary in patients with a gastrointestinal haemorrhage to confirm the presence of acute ulcers or erosions.

TREATMENT

No specific therapy is required apart from removal of the offending cause, if possible.

Oesophageal Tumours

Benign

Leiomyomas are the commonest benign tumours. They are usually discovered accidentally and they do not often produce symptoms. Malignant These occur in the middle of the oesophagus and are squamous carcinomas. Adenocarcinomas occur in the lower third of the oesophagus and at the cardia. Kaposi’s sarcoma is frequently found in the mouth and hypopharynx in patients with AIDS . These tumours rarely lead to symptoms and consequently do not require treatment.

EPIDEMIOLOGY AND AETIOLOGICAL FACTORS

SQUAMOUS CARCINOMA. The incidence of carcinoma varies throughout the world, being high in China, parts of Africa and in the Caspian regions of Iran (where the incidence is the highest observed for any type of cancer anywhere in the world). In the UK it is 5-10 per 100000 and represents 2.5% of all malignant disease. The variation in incidence throughout the world is greater than for any other carcinoma and is unusual in that sharp differences occur in regions very close to one another. Dietary and other environmental causes have been looked for and it is probable that different causative agents are involved in different parts of the world. Carcinoma of the oesophagus is commoner in men and there is an increased incidence in heavy drinkers of alcohol as well as heavy smokers. Predisposing factors include Plummer- Vinson syndrome, achalasia, coeliac disease and the familialcondition of tylosis (hyperkeratosis of palms and  soles).
ADENOCARCINOMA. These arise in the columnar lined epithelium of the lower oesophagus (Barrett’s oesophagus). This columnization results from long-standing reflux, although one-third of patients will have no preceding symptoms. This premalignant lesion increases the chances of adenocarcinoma 30-40 times. Extension of adenocarcinoma of the gastric cardia can cause oesophageal obstruction.

CLINICAL FEATURES

Carcinoma of the oesophagus occurs mainly in those aged 60-70 years. Dysphagia is the commonest single symptom and is progressive and unrelenting. Initially there is difficulty in swallowing solids, but eventually dysphagia for liquids also occurs. Benign strictures, on the other hand, initially produce intermittent dysphagia. Impaction of food causes pain, but more persistent pain implies infiltration. The lesion is usually ulcerative, extending around the wall of the oesophagus to produce a stricture. Direct invasion of the surrounding structures rather than widespread metastases occurs, and at presentation 50% have regional lymph node involvement. Weight loss, due to the dysphagia as well as to anorexia, frequently occurs. The oesophageal obstruction eventually causes difficulty in swallowing saliva, and coughing and aspiration into the lungs is common. Signs are often absent. Weight loss, anorexia and lymphadenopathy are occasionally found.

INVESTIGATION

BARIUM SWALLOWis often the initial investigation. although many gastroenterologists like to go directly to oesophagoscopy which provides histological or cytological proof of the carcinoma; 90% of oesophageal carcinomas can be confirmed with this technique.
CT SCAN will show the volume of the tumour and also possible spread outside the oesophagus. It has been used to attempt to stage tumours prior to surgery, but results are disappointing.
ENDOSCOPIC ULTRASOUND has an accuracy rate of nearly 90% for assessing depth of tumour infiltration and 80% for staging lymph node involvement and is being increasingly used.

TREATMENT

The overall results are poor (2% 5-year survival) and only symptomatic and palliative treatment is a realistic possibility in most cases. Dilatation of the stricture and the placing of a tube to keep the oesophagus open is the usual therapy and can be performed via an endoscope. Tumours can be photo coagulated using a laser beam directed through an endoscope or sloughed using alcohol injections. Both are useful to improve dysphagia.
Surgery carries a high morbidity and mortality, but in some series in which preoperative staging shows no spread outside the wall a 5-year survival rate of 25% has been achieved. Radiotherapy and chemotherapy can be used for squamous carcinoma with limited success. Good palliative care with support for the patient and family is vital in this distressing disease.

Barium swallow showing carcinoma of the oesophagus. There is an irregular narrowed area (arrow) at the lower end of the oesophagus.

Barium swallow showing carcinoma of the oesophagus. There is an irregular narrowed area (arrow) at the lower end of the oesophagus.

Oesophageal rupture

This can occur with violent vomiting producing severe chest pain and collapse. It may follow alcohol ingestion and a chest X-ray shows a hydropneumothorax.

HIATUS HERNIA

In a sliding hiatus hernia, the gastro-oesophageal junction ‘slides’ through the hiatus so that it lies above the diaphragm. This type of hernia occurs in approximately 30% of people of 50 years of age and by itself is of no diagnostic significance. It does not produce symptoms on its own; symptoms occur because of the presence of associated reflux.
A para-oesophageal or rolling hernia is when a small part of the stomach rolls up through the hernia alongside the oesophagus. The sphincter stays below the diaphragm and remains competent. Occasionally a rolling para-oesophageal hernia will produce pain and require surgical treatment.

GASTRO-OESOPHAGEAL REFLUX

DISEASE (GORD)

Gastro-oesophageal reflux occurs as a normal event, and the clinical features of GORD only occur when the antireflux mechanisms fail sufficiently to allow gastric contents to make prolonged contact with the lower oesophageal mucosa.
ANTI REFLUX MECHANISMS. The most important is the LOS which is formed by the distal 4 em of oesophageal smooth muscle. It rapidly regains its normal tone after relaxation to allow a bolus to enter the stomach and thereby prevent reflux. It is capable of increasing tone in response to rises in intra-abdominal and intra gastric pressure.

The main antireflux mechanisms.

The main antireflux mechanisms.

Other antireflux measures involve the intra-abdominal segment of the oesophagus which acts as a flap valve and the mucosal rosette formed by folds of the gastric mucosa also help to occlude the gastro-oesophageal junctional lumen.

Factors associated with increased gastrooesophageal reflux.

Factors associated with increased gastrooesophageal reflux.

The oesophagus is normally rapidly cleared of any reflux contents by secondary peristalsis.

PATHOGENESIS OF GORD

The following mechanisms have been implicated:
• The resting LOS tone is low and LOS tone fails to increase, as occurs in normal patients, when lying flat.

• LOS tone fails to increase when intra-abdominal pressure increases.
• Oesophageal mucosal resistance to acid is reduced.
• There is relatively poor oesophageal peristalsis which leads to poor clearance of gastric contents.
• Delayed gastric emptying occurs and this may increase the chance of reflux.
• Prolonged episodes of gastro-oesophageal reflux occur at night and postprandially. Factors associated with increased gastro-oesophageal.
Allor some of these features playa role in the individual patient and can occur whether or not a hiatus hernia is present. GORD can undoubtedly occur without a hiatus hernia.

24-Hour intraluminal pH monitoring. Five reflux episodes (pH < 4) occurred, but only three gave symptoms (arrows).

24-Hour intraluminal pH monitoring. Five reflux episodes (pH < 4) occurred, but only three gave symptoms (arrows).

Symptoms of gastro-oesophageal reflux and myocardial ischaemia.

Symptoms of gastro-oesophageal reflux and myocardial ischaemia.

CLINICAL FEATURES

Heartburn is the major feature of GORD. Pain is mainly due to direct stimulation of the hypersensitive oesophageal mucosa, but is also partly due to spasm of the distal oesophageal muscle. The burning is aggravated by bending, stooping or lying down and may be relieved by antacids. The patient may complain of pain on drinking hot liquids or alcohol. The correlation between heartburn and minor degrees of oesophagi tis is poor. Some patients have mild oesophagi tis, but severe heartburn; others have severe oesophagi tis without symptoms and present with a haematemesis or an iron deficiency anaemia from chronic blood loss. Regurgitation of food and acid into the mouth can occur, particularly when the patient is bending or lying flat. Aspiration into the lungs, producing pneumonia, is unusual without an accompanying stricture, but cough and nocturnal asthma from regurgitation and aspiration can occur. The differential diagnosis from angina can be difficult; 20% of cases admitted to a coronary care unit have GORD (Information box 4.1).

INVESTIGATION

BARIUM SWALLOWis still the most widely used investigation. A hiatus hernia by itself is of no diagnostic significance and free reflux of barium must be demonstrated. Reflux can also be demonstrated with radio labelled technetium.

24 HOUR INTRALUMINAL pH MONITORING .

The number of reflux episodes (below pH 4) occurring over 24 hours is noted (Fig. 4.7). This is now considered the most accurate test available, there being a reasonable correlation between frequency of reflux and symptoms.
OESOPHAGOSCOPY is used to show the presence of oesophagi tis with a red friable mucosa and, in more severe cases, linear ulceration. The mucosa can be normal in GORD.
BERNSTEIN TEST may be helpful in investigating retrosternal chest pain to differentiate oesophageal pain from angina.

TREATMENT

Many patients (approximately 50%) can be treated successfully with simple antacids, loss of weight, and raising the head of the bed at night. Precipitating factors should be avoided with a reduction in alcohol consumption and cessation of smoking. These measures are simple to say, difficult to carry out, but are useful in mild cases. The chief antacids are magnesium trisilicate and aluminium hydroxide; the former often causes diarrhoea whilst the latter causes constipation. Many antacids contain sodium which may exacerbate fluid retention; aluminiumhydroxide has less sodium than magnesium trisilicate.
ALGINATE-CONTAINING ANTACIDS (10 ml three times daily) are the most frequently prescribed agents for GORD. They form a gel or ‘foam raft’ with gastric contents and thereby prevent reflux.
H2-RECEPTOR ANTAGONISTS are frequently used , to be taken at 6 p.m., doubling the normal dosages if necessary.
PROTON PUMP INHIBITORS, such as omeprazole, a substituted benzimidazole which inhibits the H+, K+ proton pump. This produces almost complete reduction of gastric acidity, is extremely effective, and is the drug of choice for all but mild cases. Patients with severe symptoms need prolonged treatment, often for years.
METOCLOPRAMIDE, a dopamine antagonist, is occasionally helpful as it enhances peristalsis and speeds gastric emptying.
CISAPRIDE, a prokinetic agent devoid of dopaminergic activity, increases oesophageal peristalsis, increases LOS pressure and is of value, particularly for maintenance therapy.
Surgery should never be performed for a hiatus hernia alone. The properly selected case with severe reflux and oesophagi tis responds well to surgery. Repair of the hernia and some sort of additional antireflux surgery, e.g. Nissen fundoplication, is required. Surgery can now be performed laparoscopically.

COMPLICATIONS

The major complication of reflux is peptic stricture, which usually occurs in patients over the age of 60. The symptoms are those of intermittent dysphagia over a long period. Treatment is by dilatation of the stricture and management of the reflux usually medical, with orneprarole, but very occasionally surgery is required. There is no increased incidence of carcinoma in hiatus hernia per se. However, long-standing acid reflux causes colurnnization of the oesophageal mucosa (Barrett’s oesophagus) vhich is premalignant, but can be reversed with antireflux therapy.

Systemic sclerosis

In 90% or more of patients with this disease there is oesophageal involvement, with diminished peristalsis detected manometrically or by barium swallow. This is due to replacement of the smooth muscle layers by fibrous tissue. The LOS pressure is also decreased, allowing reflux; mucosal damage may occur as a consequence. Strictures may develop. Initially there are no symptoms, but dysphagia and heartburn occur as the oesophagus becomes severely involved. Similar motility abnormalities may be found in other connective-tissue disorders, particularly if Raynaud’s phenomenon is present. Treatment is as for reflux and stricture formation

Diffuse oesophageal spasm

This is a severe form of abnormal oesophageal motility that can sometimes produce retrosternal chest pain and dysphagia. Swallowing is accompanied by bizarre and marked contractions of the oesophagus without progression of the waves. On barium swallow the appearance may be of a ‘corkscrew’. However, asymptomatic changes in oesophageal motility are not infrequent, particularly in patients over the age of 60 years (presbyoesophagus). Care must therefore be taken that the symptoms, the manometry and X-ray findings of oesophageal spasm are not falsely attributed. A variant of diffuse oesophageal spasm is the nutcracker oesophagus, which is characterized by finding very highamplitude peristalsis (pressures >200 mmHg) within the oesophagus. Chest pain and dysphagia occur.

TREATMENT

True oesophageal spasm producing severe symptoms is rare and treatment is often unhelpful. Antispasmodics, nitrates, or calcium channel blockers such as sublingual nifedipine 10 mg three times daily may be tried.Occasionally, balloon dilatation or even myotomy is  necessary.
Miscellaneous motility disorders

Abnormalities of motility that are mostly asymptomatic but occasionally produce dysphagia are found in the elderly in diabetes mellitus, myotonica dystrophica and myasthenia gravis, as well as in any neurological disorder involving the brain stem.

OTHER OESOPHAGEAL DISORDERS

Oesophageal diverticulum

This is a pouch lined with epithelium that can produce dysphagia and regurgitation. It is usually asymptomatic and often detected accidentally on a barium swallow performed for other reasons. Diverticula can occur:

• Immediately above the upper oesophageal sphincter (pharyngeal pouch). If large, it may cause dysphagia as well as spillage of contents into the trachea.
• Near the middle of the oesophagus (traction diverticulum produced by extrinsic inflammation).
• Just above the LOS (epiphrenic diverticulum). Only when symptoms are severe should surgery be undertaken. Rings and webs.
A number of rings and webs have been described throughout the oesophagus. Lower oesophageal or Schatzki ring This is a narrowing of the lower end of the oesophagus due to a ridge of mucosa or a fibrous membrane. The ring may be asymptomatic, but it can very occasionally produce dysphagia after swallowing a large bolus of bread or meat. The narrowing or ring is seen on a barium swallow, with the oesophagus well distended with barium. The treatment is reassurance and dietary advice.

Upper oesophageal web

This is a constriction near the upper oesophageal sphincter in the postcricoid region and appears radiologically as a web. The web may be asymptomatic or may produce dysphagia. In the Plummer-Vinson syndrome (Paterson- Brown-Kelly syndrome) this web is associated with ironeficiency anaemia, glossitis and angular stomatitis. This rare syndrome affects mainly women and its aetiology is not understood. At oesophagoscopy the web may be difficult to see. Dilatation of the web is rarely necessary. Iron is given for the iron deficiency.

Benign oesophageal stricture

Peptic stricture secondary to reflux is the commonest cause of benign strictures. They also occur after the ingestion of corrosives, after radiotherapy, after sclerosis of varices  and following prolonged nasogastric intubation. All strictures give rise to dysphagia. They are usually treated by dilatation, but occasionally surgery is necessary.

Oesophageal infections

Infection is becoming increasingly recognized as a cause is painful  swallowing, particularly in immunosuppressed debilitated patients and patients with AIDS. Infection can can with:
• Canadida
• Hiper simplex
• Cytomegalovirus
It is occasionally difficult to distinguish between these either on barium swallow or oesophagoscopy, as only widespread ulceration is seen. In candidiasis the characteristic white plaques on top of friable mucosa are frequently found, but oral candidiasis is not always present.
The dianosis is of Candida can be confirmed by examining a direct smear taken at endoscopy, but often infections are mixed and cultures and biopsies must be performed.

TREATMENT

Most patients on large doses of immunosuppressive agents are treated prophylactically with nystatin or amphotericin. Other antifungal or antiviral treatment is given appropriately

MOTILITY DISORDERS

Achalasia

Achalasia is a disease of unknown aetiology which is characterized by aperistalsis in the body of the oesophagus and failure of relaxation of the LOS on initiation of swallowing.

PATHOLOGY

Degenerative lesions are found in the vagus as well as a decrease in ganglionic cells in the nerve plexus of the oesophageal wall.

CLINICAL FEATURES

The disease can present at any age but is rare in childhood. The incidence is about 1 : 100000 per year. Patients usually have a long history of intermittent dysphagia for both liquids and solids. Regurgitation of food from the dilated oesophagus may be induced by the patient or may occur spontaneously, particularly at night, and aspiration pneumonia may result. Occasionally food gets stuck but patients often learn to overcome this by drinking large quantities, thereby increasing the head of pressure in the oesophagus and forcing the food through. Severe retrosternal chest pain occurs particularly in younger patients with vigorous non-peristaltic contraction of the oesophagus. The dysphagia in these patients can be mild and the pain misdiagnosed as cardiac in origin. Weight loss is usually not marked.

INVESTIGATION

A CHEST X-RAY may show a dilated oesophagus, with an occasional fluid level, behind the heart. The fundal gas shadow is not present.
A BARIUM SWALLOW will show dilatation of the oesophagus, lack of peristalsis and often synchronous contractions. The lower end gradually narrows (beak deformity); this appearance is due to failure of the sphincter to relax.

OESOPHAGOSCOPY is necessary to exclude a carcinoma at the lower end of the oesophagus, as this can produce a similar X-ray appearance. When there is marked dilatation, extensive cleansing is necessary to remove food debris in.order to obtain a clear view. In achalasia the oesophagoscope easily flops through the apparent narrowing without resistance.

Barium swallow showing achalasia with atonic body of the oesophagus and a narrowed distal end. Note food residue in dilated oesophagus.

Barium swallow showing achalasia with atonic body
of the oesophagus and a narrowed distal end. Note food
residue in dilated oesophagus.

MANOMETRY is used to measure oesophageal motility. It shows aperistalsis of the oesophagus as well as the failure of relaxation of the LOS . Chagas’ disease (American trypanosomiasis, damages the neural plexus of the gut and produces a similar clinical picture.

TREATMENT

The LOS is dilated forcibly using a pneumatic bag (passed under X-ray control) so as to weaken the sphincter. This is successful in 80% of cases. Surgical division of the muscle at the lower end of the oesophagus (cardiomyotomy or Heller’s operation) is now being performed laparoscopically. Reflux oesophagi tis complicates both procedures and the aperistalsis of the oesophagus remains. In older patients, nifedipine (20 mg sublingually) can be tried initially.

COMPLICATIONS

There is an increased incidence of 5-10% of carcinoma of the oesophagus in both treated and untreated cases.