PEPTIC ULCER DISEASE OF THE STOMACH AND DUODENUM



For convenience peptic ulcer of the stomach and duodenum will be discussed together, al­though there are a number of differences that will warrant comment.

Incidence. Peptic ulcers are very common causes of morbidity but rare causes of death. As many as one fourth of men and one sixth of women develop a peptic ulcer sometime during life, as judged by typical scars at autopsy, but far fewer (5 to 10 per cent) develop symptomatic ul­cers during life. Furthermore, the incidence seems to be declining in the United States. Duodenal ul­cers are more frequent than gastric ulcers; men have a higher incidence of duodenal ulcers but the same incidence of gastric ulcers when com­pared to women.

Pathogenesis. Peptic ulcers are presumed to represent some breakdown in the balance of acid-pepsin secretion and the relevant mucosal de­fense mechanisms (Fig. 39-2). The mechanisms involved may be multifactorial for a given indi­vidual and certainly are so in different patients with peptic ulcers. Patients with duodenal ulcer tend as a group to have increased basal and max­imal acid output rates of HC1 secretion, but there is a large overlap with normal controls, and pa­tients with gastric ulcers usually have normal or even reduced rates of acid secretion. Basal levels of serum gastrin are normal with duodenal ulcers, but the level tends to rise excessively following a protein meal. The acid response to graded doses of gastrin or pentagastrin also tends to be en­hanced, thought possibly to represent a greater number of gastric parietal cells. Overall the evi­dence of hyperacidity as the cause of duodenal ulcer is marginal, and for gastric ulcer it is non­existent.

Genetic factors seem to be important in some patients with peptic ulcer. There is an increased incidence in first-degree relatives of patients with duodenal ulcers and a positive association with high levels of serum pepsinogen I, which appears to be inherited as a dominant trait and may reflect total chief cell mass. There are weaker associa­tions with blood group O and with HLA-B5. Fam­ilial gastrinomas will be discussed later.

There is a strong association of peptic ulcer with cigarette smoking, possibly due to dimin­ished bicarbonate secretion by the pancreas for duodenal ulcers and to diminished pyloric sphincter tone with reflux for gastric ulcers. Fur­thermore, peptic ulcer has been reported to be in­creased in uremia, chronic obstructive pulmonary disease, alcoholic cirrhosis, hyperparathyroidism (hypercalcemia), mastocytosis (histamine), clus­ter headaches (Horton’s cephalgia), and polycy­themia vera. The use of nonsteroidal anti-inflam­matory agents definitely increases the incidence of superficial gastric mucosal erosions, but the possible role of these agents, and of .glucocorti­coids, in the pathogenesis of chronic peptic ulcers is more controversial. Reflux of bile and pan­creatic juice from the duodenum through an in­competent pyloric sphincter has been postulated to play a role in some cases of gastric ulcer. The possible role of psychological factors is unclear, but emotional distress may increase gastric secre­tion.
Clinical Manifestations. The cardinal manifes­tation of peptic ulcer is epigastric pain that is re­lieved by the ingestion of food or antacids. The pain, frequently described as burning or gnawing, most typically occurs one to three hours after eat­ing. This is related to gastric emptying, when the continuing secretion of gastric acid is unbuffered and presumably produces pain by direct irritation of nerve endings in the ulcer or, as some think, by inducing spasm. The pain tends- to occur in clusters, perhaps over several weeks, with subsequent periods of remission of varying duration. The pain of peptic ulcer may be atypical in lo­cation, in character, and in its relationship to meals. It may also be absent despite the presence of an active peptic ulcer demonstrated radio-graphically or endoscopically.

In addition to pain, patients with peptic ulcer tend to have a variety of symptoms that can be best summarized as “dyspepsia”—bloating, nau­sea, anorexia, excessive eructations, and epigas­tric discomfort. Not infrequently patients present with one of the complications of peptic ulcer.

In the absence of complications, the physical examination is rarely of help in the diagnosis of peptic ulcer disease. Most frequently there is a moderate amount of epigastric tenderness. The physical examination may give evidence of one of the diseases associated with ulcer diathesis as noted above.

Complications. Complications are not infre­quent in peptic ulcer disease. It has been esti­mated that as many as one third of patients in whom the diagnosis is made in life will have one or sometimes more than one of these complica­tions during the course of illness. These compli­cations are also the main indications for surgery for peptic ulcer disease, to be discussed subse­quently.

Bleeding from peptic ulcer disease, the most common cause of upper gastrointestinal bleeding, occurs in about 10 to 15 per cent of patients. It may be the first manifestation of the disease, and carries an overall mortality rate of about 7 per cent. Death from peptic ulcer bleeding is more likely to occur in older patients (above age 60), in those with other illnesses, with gastric ulcers, or with severe and recurrent bleeding (> 3 units of blood required per day), and when there is an ex­posed bleeding vessel in the ulcer visualized en­doscopically. The approach to the patient with upper gastrointestinal bleeding is described in Chapter 36B. In approximately 85 per cent of pa­tients, bleeding from peptic ulcer disease will stop under medical therapy; about 15 per cent of patients require emergency surgery. This usually consists of ligation of a bleeding vessel for duo­denal ulcer together with a truncal vagotomy and a gastric antrectomy or pyloroplasty. Distal gas­trectomy is usually indicated for emergency sur­gery for gastric ulcer in the distal stomach and biopsy, ligation of bleeding vessels, and distal gas­trectomy for more proximal ulcers. Patients who have bled once from a peptic ulcer have an in­creased chance of bleeding again (30 to 50 per cent chance).

Perforation occurs when a peptic ulcer has eroded through the entire wall of the duodenum or stomach. Sometimes this leads to penetration of an adjacent organ such as the pancreas, with resulting pancreatitis and intractable pain. More frequently, especially with anterior duodenal ul­cers and lesser curvature gastric ulcers, there is free perforation into the peritoneal cavity. This complication occurs in 5 to 10 percent of patients with duodenal ulcers and 2 to 5 per cent with gastric ulcers of sufficient severity to be diagnosed during life. Not infrequently there is associated hemorrhage. Rarely perforation is the first symp­tom of a peptic ulcer; more frequently the patient has a long history of more typical symptoms. The presentation is typically that of an acute abdomen with the sudden onset of severe abdominal pain, peritoneal signs [abdominal muscle rigidity, re­bound tenderness), and hypotension with tachy­cardia. Free air in the abdominal cavity can usu­ally be demonstrated by an upright radiograph. In most patients with free perforation, emergency surgery is indicated to repair the site and to wash out the peritoneal cavity. Depending upon the state of the patient, more definitive surgery (trun­cal or selective vagotomy and antrectomy, for ex­ample) may be carried out at the same operation. In some poor-risk patients the perforation is al­lowed to seal spontaneously while the patient is maintained on nasogastric suction, fluids, and an­tibiotics.

Obstruction of the gastric outlet may be caused by the inflammation, spasm, and fibrosis induced by an ulcer. This complication is most frequent in ulcers involving the pyloric channel. The symptoms are usually those of early satiety, nau­sea, vomiting after eating, epigastric pain, and fullness. On physical examination the patient may present with a succussion splash and signs of dehydration. Laboratory studies may show met­abolic alkalosis and hypokalemia. Most patients with this complication, which occurs in about 5 per cent of patients diagnosed as having peptic ulcer, have had long-standing clinical illness. It is very unusual for this complication to be the initial presentation. Obstruction can be readily demonstrated by a positive saline load test (> 400 ml of gastric juice recovered 30 minutes after in­stilling 750 ml of saline by nasogastric tube into an empty stomach). This test may not be necessary if there is 200 ml of gastric juice in the stomach after an overnight fast. The obstruction can be di­rectly demonstrated by endoscopy or indirectly by an upper GI series. An attempt should be made to treat all patients with gastric outlet obstruction initially by medical means—nasogastric tube drainage, repair of fluid and electrolyte deficits, cimetidine or ranitidine (to reduce HC1 loss by the drainage), and parenteral nutrition. At least half of patients so treated, presumably those in whom spasm and edema are of particular importance, will respond to this therapy over several days and can be spared surgical therapy.
Intractable pain as a complication of a peptic ulcer is fortunately rare if the patient is compliant with a treatment regimen. When present it may represent penetration posteriorly or into an ad­jacent viscus.

Diagnosis. The diagnosis of a peptic ulcer can be established only by the demonstration of the ulcer by direct inspection endoscopically (the most sensitive and specific method) or indirectly by radiographic studies (an upper GI series). An upper GI series is usually the first screening study because it is usually much less expensive than endoscopy and less difficult for the patient. If no ulcer is found radiographically, however, and the suspicion of peptic ulcer is still high, endoscopic examination may still be indicated, since as many as one fifth of such ulcers may be missed by an upper GI series. If a gastric ulcer is found radi­ographically, it is imperative to demonstrate that it is benign rather than malignant. A number of findings make a malignant ulcer more or less likely (age of the patient, location and size of the ulcer, the topography of the mucosal folds around the ulcer, the presence or absence of achlorhy-dria), but this can be established with acceptable clinical accuracy only by inspection and biopsy of the lesion endoscopically. Some physicians supplement this approach by cytological exami­nations.

When the presence of a typical peptic ulcer has been established radiographically or endoscopi­cally, other studies are rarely indicated, since the pathogenesis of these lesions is still obscure in most cases. In only a few clinical situations is the measurement of serum gastrin or of the basal and peak acid outputs of the stomach indicated (Table 39-1), primarily for the suspicion of a gastrinoma (to be discussed subsequently).

In addition to the occasional need to rule out a gastrinoma, after the presence of a peptic ulcer has been demonstrated, the nonspecific symptoms of peptic ulcer must be differentiated from those of functional dyspepsia, gastric cancer, biliary tract disease, pancreatitis, and a wide variety of other abdominal disorders.

Treatment Most patients with peptic ulcer can be treated successfully by medical methods. Sur­gery is usually required only for the compli­cations of the disease noted above: bleeding, perforation, gastric outlet obstruction, and intract­able pain. In addition to the specific measures to be described, all patients with peptic ulcer disease should be advised to reduce markedly or discon­tinue cigarette smoking, to drink alcohol only in moderation, and to limit the use of nonsteroidal anti-inflammatory agents. Although diet was once considered to be of great importance in the treatment of peptic ulcer, there is no good evidence that changes in diet influence the rate of healing. Patients are best advised simply to avoid foods that in their personal experience lead to dyspeptic symptoms and to limit eating between meals and at bedtime, since eating during that time may fur­ther enhance gastric secretion.
MedicaJ management of peptic ulcer is in gen­eral directed either toward reducing the concen­tration of gastric acid or toward reducing mucosal damage from acid-pepsin exposure.

Reduction or Gastric Acid. A number of agents can reduce substantially the rate of secretion of acid by acting at various sites in the normal or hyperstimulated parietal cell (Fig. 39-3). Of these agents only the H2-receptor antagonists are being currently used as primary therapy in the United States. Cimetidine (in a usual dose of 300 mg four times daily) or ranitidine (150 mg twice daily) is highly effective in blocking the secretion of HC1. Cimetidine in its usual doses may cause confusion in some older patients, especially in the presence of renal insufficiency, and sometimes has an an-tiandrogenic effect characterized by gynecomastia and impotence. It may also inhibit the metabolism of certain other drugs by the liver as an important example of drug interaction. Ranitidine is thought to be less likely to cause mental symptoms in sus­ceptible patients, is not antiandrogenic, and in­hibits the metabolism of other drugs less mark­edly. The substituted benzimidazoles show considerable promise but have not as yet come into general use.

The concentration of gastric acid can be re­duced not only by inhibiting its secretion but also by neutralizing it intraluminally with antacids. The antacids more frequently used contain mag­nesium and/or aluminum hydroxide as their main ingredient. Calcium-containing antacids are no longer in favor because of the effect of ionized calcium in stimulating the secretion of gastrin, and sodium-containing antacids are generally too brief in their effectiveness and often add too much sodium to the diet with the danger of edema, hy­pertension, or metabolic alkalosis. The alumi­num- and magnesium-containing antacids have comparatively few side effects (constipation for Al, diarrhea for Mg, the potential for phosphate depletion due to its enteric trapping), but they are often inconvenient to the patient. In general 15 to 30 ml of the liquid antacid should be taken one and three hours after meals and also at bedtime.

Improvement or Mucosal Defense. Mucosal de­fense is a general concept that covers many as­pects of susceptibility that cannot be readily measured, as can the secretion and concentration of HC1. Only one drug is widely used currently in the United States for this purpose, sucralfate. This agent, an aluminum hydroxide salt of sucrose that has been modified by sulfation, is unabsorbed fol­lowing its usual dose of 1 gram four times daily. Its mechanism of action is unclear, but it is thought to adhere to and protect the surface of the ulcer as an artificial mucin and may also locally stimulate prostaglandin synthesis. Exogenous prostaglandins may also be useful in this mech­anism of treatment in the future.

The four main first-line agents—cimetidine, ranitidine, antacids, and sucralfate—have been roughly equally effective in bringing about the healing of peptic ulcer, and all tend to be more effective with duodenal than with gastric ulcer. It has been shown that ranitidine given as a single 300-mg dose at bedtime is as effective as the other less convenient regimens. Treatment for four to six weeks will be associated with healing in ap­proximately 90 per cent of patients. Treatment is then discontinued unless symptoms recur.

If this initial approach to treatment of a duo­denal ulcer is not successful, care should be taken to assure that the patient is compliant and that an unhealed ulcer is actually present endoscopi-cally. Other doses or combinations of the above agents can then be tried. True intractability, or the development of a complication, may then indicate the need for surgery.
A gastric ulcer requires special consideration because of the danger of carcinoma and should be carefully followed until healing. If healing does not occur on one of the above regimens by eight weeks, it is usually advisable to carry out endos­copy again with further biopsies and cytological studies. If they prove negative, a trial of another eight weeks on a different regimen may be indi­cated prior to the consideration of elective sur­gery.

The indications for long-term maintenance therapy are not certain. In many patients with pri­mary healing and without complications, treat­ment can be discontinued. In those who are con­sidered at high risk for recurrence or who have had complications of peptic ulcer disease, long-term therapy is probably indicated (Fig. 39-4).
Surgical Management. Surgery for peptic ulcer is indicated usually for complications of the disease and when medical management has failed. The surgical procedures most frequently employed are shown in Figure 39-5. In various combinations they are devised to decrease acid secretion by reducing the cephalic phase of gastric secretion (va­gotomy) or the gastric phase of gastric secretion (antrectomy to remove a major source of gastrin). Various drainage procedures are then employed to maintain gastric emptying in the postvagotomy state. Increasingly proximal (”superselectrve”) vagotomy rather than truncal vagotomy is being employed to reduce acid secretion more selec­tively without the adverse effects on gastric mo­tility and emptying. In patients with intractable benign gastric ulcers, vagotomy may not be re­quired, since acid production is usually normal or low. Antrectomy or subtotal gastrectomy may be the treatment of choice.

Complications of Treatment. Although surgi­cal treatment of peptic ulcer is usually successful in relieving symptoms and preventing recurrence and carries a low mortality rate, there are not in­frequently late complications that are distressing to the patient:
The Dumping Syndrome. With disruption of the normal storage function of the stomach, for which the pylorus is the gatekeeper, ingested food may be prematurely dumped in excessive amounts into the small intestine, leading to nausea, vom­iting, abdominal pain, and diarrhea. These symp­toms occur soon after eating. More rarely there are late symptoms (one to three hours after eating), which probably result from reactive hypoglyce­mia from excessive rapidity of carbohydrate ab­sorption followed by an overshoot of insulin re­lease.

Weight Loss. Many patients lose weight after partial gastric resection procedures. In part this is due to early satiety, but sometimes there is an as­sociated malabsorption syndrome of complex pathogenesis (see Chapter 36C).
Postvagotomy Diarrhea. Many patients have diarrhea after truncal vagotomy for reasons that are unclear. In a very few these symptoms may persist and be incapacitating.

Afferent Loop Syndrome. When the afferent loop formed in a Billroth II procedure (Fig. 39-5) be­comes partially occluded, pancreatic and biliary secretions accumulate and cause distention and pain. This is typically followed by opening up of the obstruction to release these secretions back into the gastric remnant where they commonly cause vomiting. This complication may require reconstructive surgery.

Anemia. Anemia is common after reconstructive surgery for peptic ulcer and is often complex in pathogenesis—iron deficiency, vitamin B12 defi­ciency, and/or folate deficiency.