The stomach receives food from the esophagus and has four functions: (1) it acts as a reservoir that permits eating reasonably large quantities of food at intervals of several hours; (2) food contained in the stomach is mixed, and delivered into the duodenum in amounts regulated by its chemical nature and texture; (3) the first stages of protein and carbohydrate digestion are carried out in the stomach; and (4) a few substances are absorbed across the gastric mucosa.
The anatomy of the stomach in Figures 23–1, 23–2, and 23–3 illustrates the structure supporting the functions.
Names of the parts of the stomach. The line drawn from the lesser to the greater curvature depicts the approximate boundary between the oxyntic gland area and the pyloric gland area. No prominent landmark exists to distinguish between antrum and body (corpus). The fundus is the portion craniad to the esophagogastric junction.
Histologic features of the mucosa in the oxyntic gland area. Each gastric pit drains three to seven tubular gastric glands. A: The neck of the gland contains many mucous cells. Oxyntic (parietal) cells are most numerous in the mid-portion of the glands; peptic (chief) cells predominate in the basal portion. B: Drawing from photomicrograph of the gastric mucosa.
Blood supply and parasympathetic innervation of the stomach and duodenum.
The cardia is located at the gastroesophageal junction. The fundus is the portion of the stomach that lies cephalad to the gastroesophageal junction. The corpus is the capacious central part; division of the corpus from the pyloric antrum is marked approximately by the angular incisure, a crease on the lesser curvature just proximal to the “crow’s-foot” terminations of the nerves of Latarjet (Figure 23–3). The pylorus is the boundary between the stomach and the duodenum.
The cardiac gland area is the small segment located at the gastroesophageal junction. Histologically, it contains principally mucus-secreting cells, though a few parietal cells are sometimes present. The oxyntic gland area is the portion containing parietal (oxyntic) cells and chief cells (Figure 23–2). The boundary between this region and the adjacent pyloric gland area is reasonably sharp, since the zone of transition spans a segment of only 1–1.5 cm. The pyloric gland area constitutes the distal 30% of the stomach and contains the G cells that manufacture gastrin. Mucous cells are common in the oxyntic and pyloric gland areas.
As in the rest of the gastrointestinal tract, the muscular wall of the stomach is composed of an outer longitudinal and an inner circular layer. An additional incomplete inner layer of obliquely situated fibers is most prominent near the lesser curvature but is of less substance than the other two layers.
The blood supply of the stomach and duodenum is illustrated in Figure 23–3. The left gastric artery supplies the lesser curvature and connects with the right gastric artery, a branch of the common hepatic artery. In 60% of persons, a posterior gastric artery arises off the middle third of the splenic artery and terminates in branches on the posterior surface of the body and the fundus. The greater curvature is supplied by the right gastroepiploic artery (a branch of the gastroduodenal artery) and the left gastroepiploic artery (a branch of the splenic artery). The mid-portion of the greater curvature corresponds to a point at which the gastric branches of this vascular arcade change direction. The fundus of the stomach along the greater curvature is supplied by the vasa brevia, branches of the splenic and left gastroepiploic arteries.
The blood supply to the duodenum is from the superior and inferior pancreaticoduodenal arteries, which are branches of the gastroduodenal artery and the superior mesenteric artery, respectively. The stomach contains a rich submucosal vascular plexus. Venous blood from the stomach drains into the coronary, gastroepiploic, and splenic veins before entering the portal vein. The lymphatic drainage of the stomach, which largely parallels the arteries, partially determines the direction of spread of gastric neoplasms.
The parasympathetic nerves to the stomach are shown in Figure 23–3. As a rule, two major vagal trunks pass through the esophageal hiatus in close approximation to the esophageal muscle. The nerves are originally located to the right and left of the esophagus and stomach during embryonic development. When the foregut rotates, the lesser curvature turns to the right and the greater curvature to the left, and corresponding shifts in location of the vagal trunks follow. Hence, the right vagus supplies the posterior and the left the anterior gastric surface. About 90% of the vagal fibers are sensory afferent; the remaining 10% are efferent.
In the region of the gastroesophageal junction, each trunk bifurcates. The anterior trunk sends to the liver a division that travels in the lesser omentum. The bifurcation of the posterior trunk gives rise to fibers that enter the celiac plexus and supply the parasympathetic innervation to the remainder of the gastrointestinal tract as far as the mid-transverse colon. Both trunks, after giving rise to their extragastric divisions, send some fibers directly onto the surface of the stomach and others along the lesser curvature (anterior and posterior nerves of Latarjet) to supply the distal part of the organ. As shown in Figure 23–3, a variable number of vagal fibers ascend with the left gastric artery after having passed through the celiac plexus.
The preganglionic motor fibers of the vagal trunks synapse with ganglion cells in the Auerbach plexus (plexus myentericus) between the longitudinal and circular muscle layers. Postganglionic cholinergic fibers are distributed to the cells of the smooth muscle layers and the mucosa.
The adrenergic innervation to the stomach consists of postganglionic fibers that pass along the arterial vessels from the celiac plexus.
Storage, mixing, trituration, and regulated emptying are accomplished by the muscular apparatus of the stomach. Peristaltic waves originate in the body and pass toward the pylorus. The thickness of the smooth muscle increases in the antrum and corresponds to the stronger contractions that can be measured in the distal stomach. The pylorus behaves as a sphincter, though it normally allows a little to-and-fro movement of chyme across the junction.
An electrical pacemaker situated in the fundal musculature near the greater curvature gives rise to regular (3/min) electrical impulses (pacesetter potential, basic electrical rhythm) that pass toward the pylorus in the outer longitudinal layer. Every impulse is not always followed by a peristaltic muscular contraction, but the impulses determine the maximal peristaltic rate. The frequency of peristalsis is governed by a variety of stimuli mentioned below. Each contraction follows sequential depolarization of the underlying circular muscle resulting from arrival of the pacesetter potential.
Peristaltic contractions are more forceful in the antrum than the body and travel faster as they progress distally. Gastric chyme is forced into the funnel-shaped antral chamber by peristalsis; the volume of contents delivered into the duodenum by each peristaltic wave depends on the strength of the advancing wave and the extent to which the pylorus closes. Most of the gastric contents that are pushed into the antral funnel are propelled backward as the pylorus closes and pressure within the antral lumen rises. Five to 15 mL enter the duodenum with each gastric peristaltic wave.
The volume of the empty gastric lumen is only 50 mL. By a process called receptive relaxation, the stomach can accommodate about 1000 mL before intraluminal pressure begins to rise. Receptive relaxation is an active process mediated by vagal reflexes and abolished by vagotomy. Peristalsis is initiated by the stimulus of distention after eating. Various other factors have positive or negative influences on the rate and strength of contractions and the rate of gastric emptying. Vagal reflexes from the stomach have a facilitating influence on peristalsis. The texture and volume of the meal both play a role in the regulation of emptying; small particles are emptied more rapidly than large ones, which the organ attempts to reduce in size (trituration). The osmolality of gastric chyme and its chemical makeup are monitored by duodenal receptors. If osmolality is greater than 200 mosm/L, a long vagal reflex (the enterogastric reflex) is activated, delaying emptying. Gastrin causes delay in emptying. Gastrin is the only circulating gastrointestinal hormone to have a physiologic effect on emptying.
The output of gastric juice in a fasting subject varies between 500 and 1500 mL/d. After each meal, about 1000 mL are secreted by the stomach.
The components of gastric juice are as follows.
Mucus is a heterogeneous mixture of glycoproteins manufactured in the mucous cells of the oxyntic and pyloric gland areas. Mucus provides a weak barrier to the diffusion of H+ and probably protects the mucosa. It also acts as a lubricant and impedes diffusion of pepsin.
Pepsinogens are synthesized in the chief cells of the oxyntic gland area (and to a lesser extent in the pyloric area) and are stored as visible granules. Cholinergic stimuli, either vagal or intramural, are the most potent pepsigogues, though gastrin and secretin are also effective. The precursor zymogen is activated when pH falls below 5.00, a process that entails severance of a polypeptide fragment from the larger molecule. Pepsin cleaves peptide bonds, especially those containing phenylalanine, tyrosine, or leucine. Its optimal pH is about 2.00. Pepsin activity is abolished at pH greater than 5.00, and the molecule is irreversibly denatured at pH greater than 8.00.
Intrinsic factor, a mucoprotein secreted by the parietal cells, binds with vitamin B12 of dietary origin and greatly enhances absorption of the vitamin. Absorption occurs by an active process in the terminal ileum.
Intrinsic factor secretion is enhanced by stimuli that evoke H+ output from parietal cells. Pernicious anemia is characterized by atrophy of the parietal cell mucosa, deficiency in intrinsic factor, and anemia. Subclinical deficiencies in vitamin B12 have been described after operations that reduce gastric acid secretion, and abnormal Schilling tests in these patients can be corrected by the administration of intrinsic factor. Total gastrectomy creates a dependence on parenteral administration of vitamin B12.
The unique characteristic of gastric secretion is its high concentration of hydrochloric acid, a product of the parietal cells. As the concentration of H+ rises during secretion, that of Na+ drops in a reciprocal fashion. K+ remains relatively constant at 5–10 mEq/L. Chloride concentration remains near 150 mEq/L, and gastric juice maintains its isotonicity at varying secretory rates.
The Parietal Cell & Acid Secretion
Many of the key events in acid secretion by gastric parietal cells are illustrated in Figure 23–4. The onset of secretion is accompanied by striking morphologic changes in the apical membranes. Resting parietal cells are characterized by an infolding of the apical membrane, called the secretory canaliculus, which is lined by short microvilli. Multiple membrane-bound tubulovesicles and mitochondria are present in the cytoplasm. With stimulation, the secretory canaliculus expands, the microvilli become long and narrow and filled with microfilaments, and the cytoplasmic tubulovesicles disappear. The proton pump mechanism for acid secretion is located in the tubulovesicles in the resting state and in the secretory canaliculus in the stimulated state.
Diagram of a parietal cell, showing the receptor systems and ion pathways in the basal lateral membrane and the apical membrane transition from a resting to a stimulated state. Ach, acetylcholine; CaM, calmodulin; G, gastrin; H, histamine; MF, microfilaments; SC, secretory canaliculus; TV, tubulovesicles. (Redrawn, with permission, from Malinowska DH, Sachs G: Cellular mechanisms of acid secretion. Clin Gastroenterol. 1984;13(2):309–326.)
The basal lateral membrane contains the receptors for secretory stimulants and transfers HCO3− out of the cell to balance the H+ output at the apical membrane. Active uptake of Cl− and K+ conduction also occur at the basal lateral membrane. Separate membrane-bound receptors exist for histamine (H2 receptor), gastrin, and acetylcholine. The intracellular second messengers are cyclic adenosine monophosphate (cAMP) for histamine and Ca2+ for gastrin and acetylcholine.
Acid secretion at the apical membrane is accomplished by a membrane-bound H+/K+-ATPase (the proton pump); H+ is secreted into the lumen in exchange for K+.
Mucosal Resistance in the Stomach & Duodenum
The healthy mucosa of the stomach and duodenum is provided with mechanisms that allow it to withstand the potentially injurious effects of high concentrations of luminal acid. Disruption of these mechanisms may contribute to acute or chronic ulceration.
The surface of the gastric mucosa is coated with mucus and secretes HCO3− in addition to H+. Protected by the blanket of mucus, the surface pH is much higher than the luminal pH. HCO3− secretion is stimulated by cAMP, prostaglandins, cholinomimetics, glucagon, cholecystokinin, and by as yet unidentified paracrine hormones. Inhibitors of HCO3− secretion include nonsteroidal anti-inflammatory agents, alpha-adrenergic agonists, bile acids, ethanol, and acetazolamide. Increases in luminal H+ result in increased HCO3− secretion, probably mediated by tissue prostaglandins.
Gastric mucus is a gel composed of high-molecular-weight glycoproteins and 95% water. Since it forms an unstirred layer, it helps the underlying mucosa to maintain a higher pH than that of gastric juice, and it also acts as a barrier to the diffusion of pepsin. At the surface of the layer of mucus, peptic digestion continuously degrades mucus, while below it is continuously being replenished by mucous cells. Gastric acid is thought to enter the lumen through thin spots in the mucus overlying the gastric glands. Secretion of mucus is stimulated by luminal acid and perhaps by cholinergic stimuli. The layer of mucus is damaged by exposure to nonsteroidal anti-inflammatory agents and is enhanced by topical prostaglandin E2.
Mucosal defects produced by mechanical or chemical trauma are rapidly repaired by adjacent normal cells that spread to cover the defect, a process that can be enhanced experimentally by adding HCO3− to the nutrient side of the mucosa.
The duodenal mucosa possesses defenses similar to those in the stomach: the ability to secrete HCO3− and mucus and rapid repair of mucosal injuries.
Regulation of Acid Secretion
The regulation of acid secretion can best be described by considering separately those factors that enhance gastric acid production and those that depress it. The interaction of these forces is what determines the levels of secretion observed during fasting and after meals.
A. Stimulation of Acid Secretion
Acid production is usually described as the result of three phases that are excited simultaneously after a meal. The separation into phases is of value principally for descriptive purposes.
Stimuli that act upon the brain lead to increased vagal efferent activity and acid secretion. The sight, smell, taste, or even thought of appetizing food may elicit this response. The effect is vagally mediated and is abolished by vagotomy. The vagal stimuli have a direct effect on the parietal cells to increase acid output.
Food in the stomach (principally protein hydrolysates and hydrophobic amino acids) stimulates gastrin release from the antrum. Gastric distention has a similar but less intense effect.
The presence of food in the stomach excites long vagal reflexes, impulses that pass to the central nervous system via vagal afferents and return to stimulate the parietal cells.
A third aspect of the gastric phase involves the sensitizing effect of distention of the parietal cell area to gastrin that is probably mediated through local intramural cholinergic reflexes.
The role of the intestinal phase in the stimulation of gastric secretion has been incompletely investigated. Various experiments have shown that the presence of food in the small bowel releases a humoral factor, named entero-oxyntin, that evokes acid secretion from the stomach.
B. Inhibition of Acid Secretion
Without systems to limit secretion, unchecked acid production could become a serious clinical problem. Examples can be found (Billroth II gastrectomy with retained antrum) where acid production rose after surgical procedures that interfered with these inhibitory mechanisms.
pH below 2.50 in the antrum inhibits the release of gastrin regardless of the stimulus. When the pH reaches 1.20, gastrin release is almost completely blocked. If the normal relationship of parietal cell mucosa to antral mucosa is changed so that acid does not flow past the site of gastrin production, serum gastrin may increase to high levels, with marked acid stimulation. Somatostatin in gastric antral cells serves a physiologic role as an inhibitor of gastrin release (a paracrine function).
The intestine participates in controlling acid secretion by liberating hormones that inhibit both the release of gastrin and its effects on the parietal cells. Secretin blocks acid secretion under experimental conditions but not as a physiologic action. Fat in the intestine is the most potent method of inhibition, affecting gastrin release and acid secretion.
Integration of Gastric Physiologic Function
Ingested food is mixed with salivary amylase before it reaches the stomach. The mechanisms stimulating gastric secretion are activated. Serum gastrin levels increase from a mean fasting concentration of about 50 pg/mL to 200 pg/mL, the peak occurring about 30 minutes after the meal. Food in the lumen of the stomach is exposed to high concentrations of acid and pepsin at the mucosal surface. Food settles in layers determined by sequence of arrival, but fat tends to float to the top. The greatest mixing occurs in the antrum. Antral contents therefore become more uniformly acidic than those in the body of the organ, where the central portion of the meal tends to remain alkaline for a considerable time, allowing continued activity of the amylase.
Peptic digestion of protein in the stomach is only about 5%–10% complete. Carbohydrate digestion may reach 30%–40%. A lipase originating from the tongue initiates the first stages of lipolysis in the stomach.
The gastric contents are delivered to the duodenum at a rate determined by the volume and texture of the meal, its osmolality and acidity, and its content of fat. A meal of lean meat, potatoes, and vegetables leaves the stomach within 3 hours. A meal with a very high fat content may remain in the stomach for 6–12 hours.
Peptic ulcers result from the corrosive action of acid gastric juice on a vulnerable epithelium. Depending on circumstances, they may occur in the esophagus, the duodenum, the stomach itself, the jejunum after surgical construction of a gastrojejunostomy, or the ileum in relation to ectopic gastric mucosa in Meckel diverticulum. When the term peptic ulcer was first used, it was thought that the most important factor was the peptic activity in gastric juice. Since then, evidence has implicated acid as the chief injurious agent; in fact, it is axiomatic that if gastric juice contains no acid, a (benign) peptic ulcer cannot be present. Appreciation of the role of acid has led to the emphasis on therapy with antacids and H2 blocking agents for the medical therapy of ulcers and to operations that reduce acid secretion as the major surgical approach. In the case of duodenal and gastric ulcers, Helicobacter pylori must colonize and weaken the mucosa before acid is able to do the damage, and therapy directed against this organism has a more definitive effect on the disease.
It has been estimated that about 2% of the adult population in the United States suffers from active peptic ulcer disease, and about 10% of the population will have the disease during their lifetime. Men are affected three times as often as women. Duodenal ulcers are ten times more common than gastric ulcers in young patients, but in the older age groups the frequency is about equal. Probably as a result of a declining prevalence of H pylori infection, the incidence has declined to less than half what it was 30 years ago.
In general terms, the ulcerative process can lead to four types of disability: (1) Pain is the most common. (2) Bleeding may occur as a result of erosion of submucosal or extraintestinal vessels as the ulcer becomes deeper. (3) Penetration of the ulcer through all layers of the affected gut results in perforation if other viscera do not seal the ulcer. (4) Obstruction may result from inflammatory swelling and scarring and is most likely to occur with ulcers located at the pylorus or gastroesophageal junction, where the lumen is narrowest.
The clinical features and prognosis of duodenal ulcer and gastric ulcer are sufficiently different to be dealt with separately here.
ESSENTIALS OF DIAGNOSIS
Epigastric pain often relieved by food or antacids
Normal or increased gastric acid secretion
Signs of ulcer disease on upper gastrointestinal x-rays or endoscopy
Evidence of H pylori infection
Duodenal ulcers may occur in any age group but are most common in the young and middle-aged (20–45 years). They appear in men more often than women. About 95% of duodenal ulcers are situated within 2 cm of the pylorus, in the duodenal bulb.
Considerable evidence implicates H pylori as the principal cause of duodenal ulcer disease. This microaerophilic gram-negative curved bacillus can be found colonizing patches of gastric metaplasia within the duodenum in 90% of patients with this disease. The bacilli remain on the surface of the mucosa rather than invading it. They are thought to render the duodenum more vulnerable to the injurious effects of acid and pepsin by releasing urease or other toxins.
The epidemiology of peptic ulcer disease reflects the prevalence of H pylori infection in different populations. In areas of the world where peptic ulcer is uncommon (eg, rural Africa), human infection is rare. Duodenal ulcer disease has emerged as a major clinical entity in Western society only since the latter part of the 19th century. The incidence reached a peak about 35 years ago and then declined to reach a lower plateau a few years ago. These changes are thought to be explained by variations in H pylori infection resulting from public health factors. Within countries like the United States, the distribution of H pylori is explainable by a fecal-oral theory of transmission. The prevalence of infection is higher among lower socioeconomic groups. Interestingly, only a minority of infected persons develop ulcers. H pylori also has an important role in the etiology of gastric ulcer, gastric cancer, and gastritis. The 10% of duodenal ulcers that are not associated with helicobacter infection are caused by nonsteroidal anti-inflammatory drugs and other agents.
Gastric acid secretion is characteristically higher than normal in patients with duodenal ulcer compared with normal subjects, but only one-sixth of the duodenal ulcer population have secretory levels that exceed the normal range (ie, acid secretion in normal subjects and those with duodenal ulcer overlap considerably), so the disease cannot be explained simply as a manifestation of increased acid production. Whether acid secretion increases in response to helicobacter infection is doubted. One possibility is that the patches of metaplastic gastric epithelium in the duodenum on which helicobacter take up residence result from the action of acid. Then the colonized patches undergo ulceration.
Chronic liver disease, chronic lung disease, and chronic pancreatitis have all been implicated as increasing the possibility of duodenal ulceration.
Pain, the presenting symptom in most patients, is usually located in the epigastrium and is variably described as aching, burning, or gnawing. Radiologic survey studies indicate, however, that some patients with active duodenal ulcer have no gastrointestinal complaints.
The daily cycle of the pain is often characteristic. The patient usually has no pain in the morning until an hour or more after breakfast. The pain is relieved by the noon meal, only to recur in the later afternoon. Pain may appear again in the evening, and in about half of cases, it arouses the patient during the night. Food, milk, or antacid preparations give temporary relief.
When the ulcer penetrates the head of the pancreas posteriorly, back pain is noted; concomitantly, the cyclic pattern of pain may change to a more steady discomfort, with less relief from food and antacids.
Varying degrees of nausea and vomiting are common. Vomiting may be a major feature even in the absence of obstruction.
The abdominal examination may reveal localized epigastric tenderness to the right of the midline, but in many instances no tenderness can be elicited.
Gastroduodenoscopy is useful in evaluating patients with an uncertain diagnosis, those with bleeding from the upper intestine, and those who have obstruction of the gastroduodenal segment and for assessing response to therapy.
A gastric analysis may be indicated in certain cases. The standard gastric analysis consists of the following: (a) Measurement of acid production by the unstimulated stomach under basal fasting conditions; the result is expressed as H+ secretion in mEq/h and is termed the basal acid output (BAO). (b) Measurement of acid production during stimulation by histamine or pentagastrin given in a dose maximal for this effect. The result is expressed as H+ secretion in mEq/h and is termed the maximal acid output (MAO).
Interpretation of the results is outlined in Table 23–1.
Table 23–1.Mean values for acid output during gastric analysis for normals and patients with duodenal ulcer. The upper limits of normal are basal, 5 meq/h; maximal, 30 meq/h. ||Download (.pdf) Table 23–1. Mean values for acid output during gastric analysis for normals and patients with duodenal ulcer. The upper limits of normal are basal, 5 meq/h; maximal, 30 meq/h.
| || ||Mean Acid Output (meq/h) |
| ||Sex ||Normal ||Duodenal Ulcer |
|Basal ||Male ||2.5 ||5.5 |
| ||Female ||1.5 ||3 |
|Maximal (pentagastrin) ||Male ||30 ||40 |
| ||Female ||20 ||30 |
Depending on the laboratory, normal basal gastrin levels average 50–100 pg/mL, and levels over 200 pg/mL can almost always be considered high.
Gastrin concentrations may rise in hyposecretory and hypersecretory states. In the former conditions (eg, atrophic gastritis, pernicious anemia, acid-suppressant medications), the cause is higher antral pH with loss of antral inhibition for gastrin release. More important clinically is elevated gastrin levels with concomitant hypersecretion, where the high gastrin level is responsible for the increased acid and resulting peptic ulceration. The best-defined clinical condition in this category is Zollinger–Ellison syndrome (gastrinoma). Antrum attached to the duodenum, but out of continuity with the gastric alimentary flow after gastrectomy (retained antrum), is another cause of elevated gastrin driving excess gastric acid secretion.
A fasting serum gastrin determination should be obtained in patients with peptic ulcer disease that is unusually severe or refractory to therapy.
On an upper gastrointestinal series or CT scan with gastrointestinal contrast, the changes induced by duodenal ulcer consist of duodenal deformities and an ulcer niche. Inflammatory swelling and scarring may lead to distortion of the duodenal bulb, eccentricity of the pyloric channel, or pseudodiverticulum formation. The ulcer itself may be seen either in profile or, more commonly, en face.
The most common diseases simulating peptic ulcer are (1) chronic cholecystitis, in which cholecystograms show either nonfunctioning of the gallbladder or stones in a functioning gallbladder; (2) acute pancreatitis, in which the serum amylase is elevated; (3) chronic pancreatitis, in which endoscopic retrograde cholangiopancreatography (ERCP) shows an abnormal pancreatic duct; (4) functional indigestion, in which x-rays are normal; and (5) reflux esophagitis.
The common complications of duodenal ulcer are hemorrhage, perforation, and duodenal obstruction. Each of these is discussed in a separate section. Less common complications are pancreatitis and biliary obstruction.
Prevention of ulcer disease entails avoidance of H pylori infection.
Acute duodenal ulcer can be controlled by suppressing acid secretion in most patients, but the long-term course of the disease (ie, frequency of relapses and of complications) is unaffected unless H pylori infection is eradicated. Surgical therapy is recommended principally for the treatment of complications: bleeding, perforation, or obstruction.
The goals of medical therapy are: (1) to heal the ulcer and (2) to cure the disease. Treatment in the first category is aimed at decreasing acid secretion or neutralizing acid. The principal drugs consist of H2 receptor antagonists (eg, cimetidine, ranitidine) and proton pump blockers (eg, omeprazole, pantoprazole).
After the ulcer has healed, discontinuation of therapy results in an 80% recurrence rate within 1 year, which may be avoided by chronic nighttime administration of a single dose of acid suppressive agent. A better approach is to treat the H pylori infection along with the ulcer, since eradication of H pylori diminishes recurrent ulceration unless the infection recurs–an uncommon event. The following combination is an effective regimen: lansoprazole, 30 mg twice daily for 14 days; amoxicillin, 1 g twice daily for 14 days; and clarithromycin, 500 mg twice daily for 14 days.
If medical treatment has been optimal, a persistent ulcer may be judged intractable, and surgical treatment is indicated. This is now uncommon.
The surgical procedures that can cure peptic ulcer are aimed at reduction of gastric acid secretion. Excision of the ulcer itself is not sufficient for either duodenal or gastric ulcer; recurrence is nearly inevitable with such procedures.
The surgical methods of treating duodenal ulcer are vagotomy (several varieties) and antrectomy plus vagotomy. All of these procedures can be performed laparoscopically. With rare exceptions, one of the vagotomy operations is sufficient (Figure 23–5).
Various types of operations currently popular for treating duodenal ulcer disease. Total gastrectomy is reserved for Zollinger-Ellison syndrome. The choice among the other procedures should be individualized according to principles discussed in the text.
Truncal vagotomy consists of resection of a 1- or 2-cm segment of each vagal trunk as it enters the abdomen on the distal esophagus. The resulting vagal denervation of the gastric musculature produces delayed emptying of the stomach in many patients unless a drainage procedure is performed. The method of drainage most often selected is pyloroplasty (Heineke–Mikulicz procedure, Figure 23–6); gastrojejunostomy is used less often. Neither procedure gives a superior functional result, and pyloroplasty is less time consuming.
Vagal denervation of just the parietal cell area of the stomach is called parietal cell vagotomy or proximal gastric vagotomy. The technique spares the main nerves of Latarjet (Figures 23–3 and 23–5) but divides all vagal branches that terminate on the proximal two-thirds of the stomach. Since antral innervation is preserved, gastric emptying is relatively normal, and a drainage procedure is unnecessary. Nevertheless, parietal cell vagotomy plus pyloroplasty gives better results (ie, fewer recurrent ulcers) than parietal cell vagotomy alone. Parietal cell vagotomy appears to have about the same effectiveness as truncal or selective vagotomy for curing the ulcer disease, but dumping and diarrhea are much less frequent.
The vagotomy procedures have the advantages of technical simplicity and preservation of the entire gastric reservoir capacity. The principal disadvantage is recurrent ulceration in about 10% of patients. The recurrence rate after parietal cell vagotomy is about twice as high in patients with prepyloric ulcer, and most surgeons use a different operation for an ulcer in this location.
2. Antrectomy and vagotomy
This operation entails a distal gastrectomy of 50% of the stomach, with the line of gastric transection carried high on the lesser curvature to conform with the boundary of the gastrin-producing mucosa.
The terms antrectomy and hemigastrectomy are loosely synonymous. The proximal remnant may be reanastomosed to the duodenum (Billroth I resection) or to the side of the proximal jejunum (Billroth II resection). The Billroth I technique is most popular, but there is no conclusive evidence that the results are superior. When creating a Billroth II (gastrojejunostomy) reconstruction, the surgeon may bring the jejunal loop up to the gastric remnant either anterior to the transverse colon or posteriorly through a hole in the transverse mesocolon. Since either method is satisfactory, an antecolic anastomosis is elected in most cases because it is simpler. Truncal vagotomy is performed as described in the preceding section; antrectomy by itself will not prevent a high recurrence rate. In most instances, the surgeon will be able to remove the ulcerated portion of duodenum in the course of resection.
Vagotomy and antrectomy is associated with a low incidence of marginal ulceration (2%) and a generally good overall outcome, but the risk of complications is higher than after vagotomy without resection.
This operation consists of resection of two-thirds to three-fourths of the distal stomach. After subtotal gastrectomy for duodenal ulcer, a Billroth II reconstruction is preferable. Subtotal gastrectomy is largely of historical interest.
Heineke-Mikulicz pyloroplasty. A longitudinal incision has been made across the pylorus, revealing an active ulcer in the duodenal bulb. The insert shows the transverse closure of the incision that widens the gastric outlet. The accompanying vagotomy is not shown.
Complications of Surgery for Peptic Ulcer
Duodenal stump leakage, gastric retention (poor gastric emptying), and hemorrhage may develop in the immediate postoperative period.
4. Recurrent ulcer (marginal ulcer, stomal ulcer, anastomotic ulcer)
Recurrent ulcers formed in about 10% of duodenal ulcer patients treated by vagotomy and pyloroplasty or parietal cell vagotomy; and in 2%–3% after vagotomy and antrectomy or subtotal gastrectomy without chronic acid suppression. Recurrent ulcers nearly always develop immediately adjacent to the anastomosis on the intestinal side.
The usual complaint is upper abdominal pain, which is often aggravated by eating and improved by antacids. In some patients, the pain is felt more to the left in the epigastrium, and left axillary or shoulder pain is occasionally reported. About a third of patients with stomal ulcer have major gastrointestinal hemorrhage. Free perforation is less common (5%).
Diagnosis and treatment are essentially the same as for the original ulcer.
5. Gastrojejunocolic and gastrocolic fistula
A deeply eroding ulcer may occasionally produce a fistula between the stomach and colon. Most examples have resulted from recurrent peptic ulcer after an operation that included a gastrojejunal anastomosis.
Severe diarrhea and weight loss are the presenting symptoms in over 90% of cases. Abdominal pain typical of recurrent peptic ulcer often precedes the onset of the diarrhea. Bowel movements number 8–12 or more a day; they are watery and often contain particles of undigested food.
The degree of malnutrition ranges from mild to very severe. Laboratory studies reveal low serum proteins and manifestations of fluid and electrolyte depletion. Appropriate tests may reflect deficiencies in both water-soluble and fat-soluble vitamins.
An upper gastrointestinal series reveals the marginal ulcer in only 50% of patients and the fistula in only 15%. Barium enema unfailingly demonstrates the fistulous tract.
Initial treatment should replenish fluid and electrolyte deficits. The involved colon and ulcerated gastrojejunal segment should be excised and colonic continuity reestablished. Vagotomy, partial gastrectomy, or both are required to treat the ulcer diathesis and prevent another recurrent ulcer. Results are excellent in benign disease. In general, the outlook for patients with a malignant fistula is poor.
Symptoms of the dumping syndrome are noted to some extent by most patients who have an operation that impairs the ability of the stomach to regulate its rate of emptying. Within several months, however, dumping is a clinical problem in only 1%–2% of patients. Symptoms fall into two categories: cardiovascular and gastrointestinal. Shortly after eating, the patient may experience palpitations, sweating, weakness, dyspnea, flushing, nausea, abdominal cramps, belching, vomiting, diarrhea, and, rarely, syncope. The degree of severity varies widely, and not all symptoms are reported by all patients. In severe cases, the patient must lie down for 30–40 minutes until the discomfort passes.
Diet therapy to reduce jejunal osmolality is successful in all but a few cases. The diet should be low in carbohydrate and high in fat and protein content. Sugars and carbohydrates are least well tolerated; some patients are especially sensitive to milk. Meals should be taken dry, with fluids restricted to between meals. This dietary regimen ordinarily suffices, but anticholinergic drugs may be of help in some patients; others have reported improvement with supplemental pectin in the diet, or the use of somatostatin analogs.
Reflux of duodenal juices into the stomach is an invariable and usually innocuous situation after operations that interfere with pyloric function, but in some patients, it may cause marked gastritis. The principal symptom is postprandial pain, and the diagnosis rests on endoscopic and biopsy demonstration of an edematous inflamed gastric mucosa. Since a minor degree of gastritis is found in most patients after Billroth II gastrectomy, the endoscopic findings are to some degree nonspecific. Persistent severe pain is an indication for surgical reconstruction. Roux-en-Y gastrojejunostomy with a 40-cm efferent jejunal limb is the treatment of choice.
Iron deficiency anemia develops in about 30% of patients within 5 years after partial gastrectomy. It is caused by failure to absorb ingested iron bound in an organic molecule. Before this diagnosis is accepted, the patient should be checked for blood loss, marginal ulcer, or an unsuspected tumor. Inorganic iron—ferrous sulfate or ferrous gluconate—is indicated for treatment and is absorbed normally after gastrectomy.
Vitamin B12 deficiency and megaloblastic anemia appear in a few cases after gastrectomy.
About 5%–10% of patients who have had truncal vagotomy require treatment with antidiarrheal agents at some time, and perhaps 1% are seriously troubled by this complication. The diarrhea may be episodic, in which case the onset is unpredictable after symptom-free intervals of weeks to months. An attack may consist of only one or two watery movements or, in severe cases, may last for a few days. Other patients may continually produce 3–5 loose stools per day.
Most cases of postvagotomy diarrhea can be treated satisfactorily with constipating agents.
10. Chronic gastroparesis
Chronic delayed gastric emptying is seen occasionally after gastric surgery. Prokinetic agents (eg, metoclopramide) are often helpful, but some cases are refractory to any therapy except a completion gastrectomy and Roux-en-Y esophagojejunostomy (ie, total gastrectomy).
MM. Management of Helicobacter pylori infection. Expert Rev Anti Infect Ther 2010 Aug;8(8):887–892.
DA. Control of gastric acid secretion in health and disease. Gastroenterology 2008;134:1842.
ZOLLINGER-ELLISON SYNDROME (GASTRINOMA)
ESSENTIALS OF DIAGNOSIS
Peptic ulcer disease (often severe) in 95%
Elevated serum gastrin
Non-B islet cell tumor of the pancreas or duodenum
Zollinger-Ellison syndrome is manifested by gastric acid hypersecretion caused by a gastrin-producing tumor (gastrinoma). The normal pancreas does not contain appreciable amounts of gastrin. Most gastrinomas occur in the submucosa of the duodenum; others are found in the pancreas and rarely as primary tumors of the liver or ovary. About one-third of patients have the multiple endocrine neoplasia type I syndrome (MEN 1), which is characterized by a family history of endocrinopathy and the presence of tumors in other glands, especially the parathyroid glands and pituitary. Patients with MEN 1 usually have multiple gastrinomas. Those without MEN 1 usually have solitary gastrinomas that are often malignant. The tumors may be as small as 2–3 mm and are often difficult to find.
The diagnosis of cancer can be made only with findings of metastases or blood vessel invasion, because the histologic pattern is similar for benign and malignant tumors.
Symptoms associated with gastrinoma are principally a result of acid hypersecretion—usually from peptic ulcer disease. Some patients with gastrinoma have severe diarrhea from the large amounts of acid entering the duodenum, which can destroy pancreatic lipase and produce steatorrhea, damage the small bowel mucosa, and overload the intestine with gastric and pancreatic secretions. About 5% of patients present with diarrhea only.
Ulcer symptoms are often refractory to large doses of antacids or standard doses of H2 blocking agents. Hemorrhage, perforation, and obstruction are common complications. Marginal ulcers appear after surgical procedures that would cure the ordinary ulcer diathesis.
Hypergastrinemia in the presence of acid hypersecretion is necessary for the diagnosis of gastrinoma. Gastrin levels are normally inversely proportionate to gastric acid output; therefore, diseases that result in increased gastric pH may cause a rise in serum gastrin concentration (eg, pernicious anemia, atrophic gastritis, gastric ulcer, postvagotomy state, and acid-suppressing medications). Serum gastrin levels should be measured in any patient with suspected gastrinoma or ulcer disease severe enough to warrant consideration of surgical treatment. H2 receptor blocking agents, omeprazole, or antacids frequently increase serum gastrin concentrations and should be avoided for several days before gastrin measurements are made. It is often helpful to measure gastric acid secretion to rule out H+ hyposecretion as a cause of hypergastrinemia.
The normal gastrin value is less than 200 pg/mL. Patients with gastrinoma usually have levels exceeding 500 pg/mL and sometimes 10,000 pg/mL or higher. Patients with borderline gastrin values (eg, 200–500 pg/mL) and acid secretion in the range associated with ordinary duodenal ulcer disease should have a secretin provocative test. Following intravenous administration of secretin (two units/kg as a bolus), a rise in the gastrin level of > 150 pg/mL within 15 minutes is diagnostic.
Marked basal acid hypersecretion (> 15 mEq H+ per hour) occurs in most Zollinger-Ellison patients who have an intact stomach. In a patient who has previously undergone an acid-reducing operation, a basal acid output of 5 mEq/h or more is suggestive. Since the parietal cells are already under near maximal stimulation from hypergastrinemia, there is little increase in acid secretion following an injection of pentagastrin, and the ratio of basal to maximal acid output (BAO/MAO) characteristically exceeds 0.6.
Hypergastrinemia and gastric acid hypersecretion may occur in patients with gastric outlet obstruction, retained antrum after a Billroth II gastrojejunostomy, and antral gastrin cell hyperactivity (hyperplasia). These conditions are differentiated from gastrinoma by use of the secretin test. Because associated hyperparathyroidism is so common, serum calcium concentrations should be measured in all patients with gastrinoma.
Serum levels of neuron-specific enolase, β-hCG, and chromogranin-A are often elevated in patients with functioning neuroendocrine tumors. Although they are probably of no physiologic importance, the high levels of these peptides may be useful in following the results of therapy.
A CT or MR scan often demonstrates the pancreatic tumors. Somatostatin-receptor scintigraphy is extremely sensitive for detection of gastrinoma primary and metastatic sites. Transhepatic portal vein blood sampling to find gradients of gastrin production has been supplanted by the intra-arterial secretin test. Infusion of secretin into the artery supplying a functional gastrinoma causes an increase in hepatic vein gastrin levels. This invasive test is usually reserved for difficult situations.
Although used less frequently now with the availability of endoscopy, an upper gastrointestinal series can show ulceration in the duodenal bulb, though ulcers sometimes appear in the distal duodenum or proximal jejunum. The presence of ulcers in these distal (“ectopic”) locations is nearly diagnostic of gastrinoma. The stomach contains prominent rugal folds, and secretions are present in the lumen despite overnight fasting. The duodenum may be dilated and exhibit hyperactive peristalsis. Edema may be detected in the small bowel mucosa. The barium flocculates in the intestine, and transit time is accelerated.
Initial treatment should consist of proton pump inhibitor (eg, omeprazole 20–40 mg, once or twice daily) or H2 blocking agents (eg, cimetidine, 300–600 mg, four times daily; ranitidine, 300–450 mg, four times daily). The dose should be adjusted to keep gastric H+ output below 5 mEq in the hour preceding the next dose.
Resection is the ideal treatment for gastrinoma and is appropriate in all patients with apparently localized disease and no other significant limitations to their survival. Surgical cure may be possible when there are resectable metastases in peripancreatic lymph nodes or the liver. Overall, about 70% of patients have immediate biochemical cure, and about 30% of patients remain disease-free after 5 years.
Every patient with sporadic Zollinger-Ellison syndrome should be considered a candidate for tumor resection. The preoperative workup should include a CT or MR scan of the pancreas and somatostatin-receptor scintigraphy. Regardless of other findings, exploratory laparotomy is then recommended in the absence of evidence of unresectable metastatic disease. If the tumor is found in the pancreas, it is enucleated if possible. Operative ultrasound may help in the examination of the pancreas. Most lesions will be found either in the head of the pancreas or in the duodenum. All patients should have longitudinal duodenotomy and palpation of the duodenal mucosa to identify the frequent primary tumors in this site.
Since H2 blocking agents become less effective with time, omeprazole is eventually required in medically treated patients. Because it is usually multifocal, the disease can rarely be cured surgically in patients with MEN 1. Malignant gastrinomas can cause death from growth of metastases.
RT. Zollinger-Ellison syndrome: recent advances and controversies. Curr Opin Gastroenterol 2013 Nov;29(6):650–661.
RT. Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison syndrome. Ann Surg 2012 Sep;256(3):509–517.
The peak incidence of gastric ulcer is in patients aged 40–60 years, or about 10 years older than the average for those with duodenal ulcer. Ninety-five percent of gastric ulcers are located on the lesser curvature, and 60% of these are within 6 cm of the pylorus. The symptoms and complications of gastric ulcer closely resemble those of duodenal ulcer.
Gastric ulcers may be separated into three types with different causes and different treatments. Type I ulcers, the most common variety, are found in patients who on the average are 10 years older than patients with duodenal ulcers and who have no clinical or radiographic evidence of previous duodenal ulcer disease; gastric acid output is normal or low. The ulcers are usually located within 2 cm of the boundary between parietal cell and pyloric mucosa, but always in the latter. As noted above, 95% are on the lesser curvature, usually near the incisura angularis.
Antral gastritis is universally present, being most severe near the pylorus and gradually diminishing. This is associated in most cases with the presence of H pylori beneath the mucus layer, on the luminal surface of epithelial cells, and gastric ulcer disease is probably the result of infection with this organism.
Type II ulcers are located close to the pylorus (prepyloric ulcers) and occur in association with (most often following) duodenal ulcers. The risk of cancer is very low in these gastric ulcers. Acid secretion measured by gastric analysis is in the range associated with duodenal ulcer.
Type III ulcers occur in the antrum as a result of chronic use of nonsteroidal anti-inflammatory agents.
Ulcer identified on x-ray or by endoscopy could be an ulcerated malignant tumor rather than a simple benign ulcer. Efforts must be expended during the initial stage of the workup to establish this distinction. Despite the generally discouraging results of surgery for gastric adenocarcinoma, those whose tumors are difficult to distinguish from benign ulcer have a 50%–75% chance of cure after gastrectomy.
The principal symptom is epigastric pain relieved by food or antacids, as in duodenal ulcer. Epigastric tenderness is a variable finding. Compared with duodenal ulcer, the pain in gastric ulcer tends to appear earlier after eating, often within 30 minutes. Vomiting, anorexia, and aggravation of pain by eating are also more common with gastric ulcer.
Achlorhydria is defined as no acid (pH > 6.00) after pentagastrin stimulation. Achlorhydria is incompatible with the diagnosis of benign peptic ulcer and suggests a malignant gastric ulcer. About 5% of malignant gastric ulcers will be associated with this finding.
B. Upper Endoscopy and Biopsy
Upper endoscopy should be performed as part of the initial workup to attempt to find malignant lesions. The rolled-up margins of the ulcer that produce the meniscus sign on x-ray can often be distinguished from the flat edges characteristic of a benign ulcer. Multiple (preferably six) biopsy specimens and brush biopsy should be obtained from the edge of the lesion. False positives are rare; false negatives occur in 5%–10% of malignant ulcers.
Upper gastrointestinal x-rays can show an ulcer, usually on the lesser curvature in the pyloric area. In the absence of a tumor mass, the following suggest that the ulcer is malignant: (1) the deepest penetration of the ulcer is not beyond the expected border of the gastric wall; (2) the meniscus sign is present (ie, a prominent rim of radiolucency surrounding the ulcer), caused by heaped-up edges of tumor; and (3) cancer is more common (10%) in ulcers greater than 2 cm in diameter. Coexistence of duodenal deformity or ulcer favors a diagnosis of benign ulcer in the stomach.
The characteristic symptoms of gastric ulcer are often clouded by nonspecific complaints. Uncomplicated hiatal hernia, atrophic gastritis, chronic cholecystitis, irritable colon syndrome, and undifferentiated functional problems are distinguishable from peptic ulcer only after appropriate radiologic studies and sometimes not even then.
Gastroscopy and biopsy of the ulcer should be performed to rule out malignant gastric ulcer.
Bleeding, obstruction, and perforation are the principal complications of gastric ulcer. They are discussed separately elsewhere in this chapter.
Medical management of gastric ulcer is the same as for duodenal ulcer. The patient should be questioned regarding the use of ulcerogenic agents, which should be eliminated as far as possible.
Repeat endoscopy should be obtained to document the rate of healing. After 4–16 weeks (depending on the initial size of the lesion and other factors), healing usually has reached a plateau. In order to cure the disease and avoid recurrent ulcers, H pylori must be eradicated. The success of therapy in this regard can be checked by serologic testing for H pylori antibodies.
Before the significance of H pylori in the etiology of gastric ulcer was appreciated, the most effective surgical treatment was distal hemigastrectomy (including the ulcer); somewhat less effective but still useful in high-risk patients was vagotomy and pyloroplasty. Parietal cell vagotomy for prepyloric ulcers was followed by a high (eg, 30%) recurrence rate, but parietal cell vagotomy plus pyloroplasty worked well.
Intractability to medical therapy has now become a rare indication for surgery in gastric ulcer disease, since H2 receptor antagonists or omeprazole can bring the condition under control, and treatment of H pylori infection can almost eliminate the problem of recurrence. Consequently, surgery is needed principally for complications of the disease: bleeding, perforation, or obstruction.
Jr. Emergency ulcer surgery. Surg Clin North Am 2011 Oct;91(5):1001–1013.
UPPER GASTROINTESTINAL HEMORRHAGE
Upper gastrointestinal hemorrhage may be mild or severe but should always be considered an ominous manifestation that deserves thorough evaluation. Bleeding is the most common serious complication of peptic ulcer, portal hypertension, and gastritis, and these conditions taken together account for most episodes of upper gastrointestinal bleeding in the average hospital population.
The major factors that determine the diagnostic and therapeutic approach are the amount and rate of bleeding. Estimates of both should be made promptly and monitored and revised continuously until the episode has been resolved. It is important to know at the outset that bleeding stops spontaneously in 75% of cases; the remainder includes those who will require surgery, experience complications, or die.
Hematemesis or melena is present except when the rate of blood loss is minimal. Hematemesis of either bright-red or dark blood indicates that the source is proximal to the ligament of Treitz. It is more common from bleeding that originates in the stomach or esophagus. In general, hematemesis denotes a more rapidly bleeding lesion, and a high percentage of patients who vomit blood require surgery. Coffee-ground vomitus is due to vomiting of blood that has been in the stomach long enough for gastric acid to convert hemoglobin to methemoglobin.
Most patients with melena (passage of black or tarry stools) are bleeding from the upper gastrointestinal tract, but melena can be produced by blood entering the bowel at any point from mouth to cecum. The conversion of red blood to dark depends more on the time it resides in the intestine than on the site of origin. The black color of melenic stools is probably caused by hematin, the product of oxidation of heme by intestinal and bacterial enzymes. Melena can be produced by as little as 50–100 mL of blood in the stomach. When 1 L of blood was instilled into the upper intestine of experimental subjects, melena persisted for 3–5 days, which shows that the rate of change in character of the stool is a poor guide to the time bleeding stops after an episode of hemorrhage.
Hematochezia is defined as the passage of bright-red blood from the rectum. Bright-red rectal blood can be produced by bleeding from the colon, rectum, or anus. However, if intestinal transit is rapid during brisk bleeding in the upper intestine, bright-red blood may be passed unchanged in the stool.
Normal subjects lose about 2.5 mL of blood per day in their stools, presumably from minor mechanical abrasions of the intestinal epithelium. Between 50 and 100 mL of blood per day will produce melena. Tests for occult blood in the stool should be able to detect amounts between 10 and 50 mL/d. False-positive results may be due to dietary hemoglobin, myoglobin, or peroxidases of plant origin. Iron ingestion does not give positive reactions. The sensitivity of the guaiac slide test (Hemoccult) is in the desired range, and this is the best test available at present.
In an apparently healthy patient, melena of a week or more suggests that the bleeding is slow. In this type of patient, admission to the hospital should be followed by a deliberate but nonemergency workup. However, patients who present with hematemesis or melena of less than 12 hours’ duration should be handled as if exsanguination were imminent. The approach entails a simultaneous series of diagnostic and therapeutic steps with the following initial goals: (1) assess the status of the circulatory system and replace blood loss as necessary; (2) determine the amount and rate of bleeding; (3) slow or stop the bleeding by ice-water lavage; and (4) discover the lesion responsible for the episode. The last step may lead to more specific treatment appropriate to the underlying condition.
The patient should be admitted to the hospital and a history and physical examination performed. Experienced clinicians are able to make a correct diagnosis of the cause of bleeding from clinical findings in only 60% of patients. Peptic ulcer, acute gastritis, esophageal varices, esophagitis, and Mallory-Weiss tear account for over 90% of cases (Table 23–2). Questions concerning the symptoms and predisposing factors should be asked. The patient should be questioned about salicylate intake and any history of a bleeding tendency.
Table 23–2.Causes of massive upper gastrointestinal hemorrhage. Note that cancer is rarely the cause. ||Download (.pdf) Table 23–2. Causes of massive upper gastrointestinal hemorrhage. Note that cancer is rarely the cause.
| ||Relative Incidence (%) |
|Common Causes || || |
| Peptic ulcer || ||45 |
| Duodenal ulcer ||25 || |
| Gastric ulcer ||20 || |
| Esophageal varices || ||20 |
| Gastritis || ||20 |
| Mallory-Weiss syndrome || ||10 |
|Uncommon Causes || ||5 |
| Gastric carcinoma || || |
| Esophagitis || || |
| Pancreatitis || || |
| Hemobilia || || |
| Duodenal diverticulum || || |
Of the diseases commonly responsible for acute upper gastrointestinal bleeding, only portal hypertension is associated with diagnostic clues on physical examination. However, gastrointestinal bleeding should not be automatically attributed to esophageal varices in a patient with jaundice, ascites, splenomegaly, spider angiomas, or hepatomegaly; over half of cirrhotic patients who present with acute hemorrhage are bleeding from gastritis or peptic ulcer.
Blood should be drawn for cross-matching, hematocrit, hemoglobin, creatinine, and tests of liver function. An intravenous infusion should be started and, in the presence of massive bleeding, a large-bore nasogastric tube inserted. In cases of melena, the gastric aspirate should be examined to verify the gastroduodenal source of the hemorrhage, but about 25% of patients with bleeding duodenal ulcers have gastric aspirates that test negatively for blood. The tube must be larger than the standard nasogastric tube (16F) so the stomach can be lavaged free of liquid blood and clots. After its contents have been removed, the stomach should be irrigated with copious amounts of ice water or saline solution until blood no longer returns. If the patient was bleeding at the time the nasogastric tube was inserted, iced saline irrigation usually stops it. The large tube can then be exchanged for a standard nasogastric tube attached to continuous suction so further blood loss can be measured.
It is common to give H2 receptor antagonists or omeprazole, though controlled trials have shown no benefit. If bleeding continues or if tachycardia or hypotension is present, the patient should be monitored and treated as for hemorrhagic shock.
In acute rapid hemorrhage, the hematocrit may be normal or only slightly low. A very low hematocrit without obvious signs of shock indicates more gradual blood loss.
All of the above tests and procedures can be performed within 1 or 2 hours after admission. By this time, in most instances, bleeding is under control, blood volume has been restored to normal, and the patient is being adequately monitored so that recurrent bleeding can be detected promptly. When this stage is reached, additional diagnostic tests should be performed.
Diagnosis of Cause of Bleeding
Once the patient is stabilized, endoscopy should be the first study. In general, endoscopy should be performed within 24 hours after admission, and under these circumstances the source of bleeding can be demonstrated in about 80% of cases. Longer delays have a lower diagnostic yield. Two lesions are seen in about 15% of patients. An upper gastrointestinal series should be performed if endoscopy is equivocal or unavailable. Although the diagnostic information provided by endoscopy does not appear to have resulted in decreased blood loss or improved outcome, endoscopic therapy, in the form of sclerosis of varices or injection of a bleeding ulcer, may do so. Having the diagnosis will also help in planning subsequent treatment, including the surgical approach if operation becomes necessary.
Rarely, selective angiography will have diagnostic or therapeutic usefulness. For diagnosis, it is most helpful when other studies fail to demonstrate the cause of bleeding. Infusion through the angiographic catheter of vasoconstrictors (eg, vasopressin) and embolization of the bleeding vessel with Gelfoam may be able to halt the bleeding in special cases.
Although a precise diagnosis of the cause of the bleeding may be valuable in later management, the patient must not be allowed to slip out of clinical control during the search for definitive diagnostic information. The decision for emergency surgery depends more on the rate and duration of bleeding than on its specific cause.
The need for transfusion should be determined on a continuing basis, and blood volume must be maintained. Blood pressure, pulse, central venous pressure, hematocrit, hourly urinary volume, and amount of blood obtained from the gastric tube or from the rectum all enter into this assessment. Many studies have shown the tendency to underestimate blood loss and inadequately transfuse massively bleeding patients who truly need aggressive therapy. Continued slow bleeding is best monitored by serial determinations of the hematocrit.
Several factors are associated with a worse prognosis with continued medical management of the bleeding episode. These are not absolute indications for laparotomy, but they should alert the clinician that emergency surgery may be required.
High rates of bleeding or amounts of blood loss predict high failure rates with medical treatment. Hematemesis is usually associated with more rapid bleeding and a greater blood volume deficit than melena. The presence of hypotension on admission to the hospital or the need for more than four units of blood to achieve circulatory stability implies a worse prognosis; if bleeding continues and subsequent transfusion requirements exceed one unit every 8 hours, continued medical management is usually unwise.
Total transfusion requirements also correlate with death rates. Death is uncommon when fewer than seven units of blood have been used, and the death rate rises progressively thereafter.
In general, bleeding from a gastric ulcer is more dangerous than bleeding from gastritis or duodenal ulcer, and patients with gastric ulcer should always be considered for early surgery. Regardless of the cause, if bleeding recurs after it has once stopped, the chances of success without operation are lower. Most patients who rebleed in the hospital should have consideration of surgery.
Patients over age 60 years tolerate continued blood loss less well than younger patients, and their bleeding should be stopped before secondary cardiovascular, pulmonary, or renal complications arise.
In 85% of patients, bleeding stops within a few hours of admission. About 25% of patients rebleed once bleeding has stopped. Rebleeding episodes are concentrated within the first 2 days of hospitalization, and if the patient has had no further bleeding for a period of 5 days, the chance of rebleeding is low. Rebleeding is most common in patients with varices, peptic ulcer, anemia, or shock. About 10% of patients require surgery to control bleeding, and most of these patients have bleeding ulcers or, less commonly, esophageal varices. The death rate is 30% among patients who rebleed and 3% among those who do not. The mortality rate is also high in the elderly and in patients who are already hospitalized at the onset of bleeding.
JY. Management of massive peptic ulcer bleeding. Gastroenterol Clin North Am 2009 Jun;38(2):231–243.
A: The pharmacological therapy of non-variceal upper gastrointestinal bleeding. Gastroenterol Clin North Am 2010 Sep;39(3):419–432.
HEMORRHAGE FROM PEPTIC ULCER
Approximately 20% of patients with peptic ulcer experience a bleeding episode, and this complication is responsible for about 40% of the deaths from peptic ulcer. Peptic ulcer is the most common cause of massive upper gastrointestinal hemorrhage, accounting for over half of all cases. Chronic gastric and duodenal ulcers have about the same tendency to bleed, but the former produce more severe episodes.
Bleeding ulcers in the duodenum are usually located on the posterior surface of the duodenal bulb. As the ulcer penetrates, the gastroduodenal artery is exposed and may become eroded. Since no major blood vessels lie on the anterior surface of the duodenal bulb, ulcerations at this point are not as prone to bleed. Patients with concomitant bleeding and perforation usually have two ulcers, a bleeding posterior ulcer and a perforated anterior one. Postbulbar ulcers (those in the second portion of the duodenum) bleed frequently, though ulcers are much less common in this site than near the pylorus.
In some patients, the bleeding is sudden and massive, manifested by hematemesis and shock. In others, chronic anemia and weakness due to slow blood loss are the only findings. The diagnosis is unreliable when based on clinical findings, so endoscopy should be performed early (ie, within 24 hours) in most cases.
In the preceding section, the management of acute upper gastrointestinal hemorrhage, the selection of diagnostic tests, and the factors suggesting the need for operation were discussed. Most patients (75%) with bleeding peptic ulcer can be successfully managed by medical means alone. Initial therapeutic efforts usually halt the bleeding. H2 blockers and proton pump inhibitors decrease the risk of bleeding but have no effect on active bleeding.
After 12–24 hours have passed and the bleeding has clearly stopped, a patient who feels hungry should be fed. Twice-daily hematocrit readings should be ordered as a check on slow continued blood loss. Stools should be tested daily for the presence of blood; they will usually remain guaiac-positive for several days after bleeding stops.
Rebleeding in the hospital has been attended by a death rate of about 30%. Considering early surgery for those who rebleed could improve this figure. Patients who are over age 60 years, present with hematemesis, are actively bleeding at the time of endoscopy, or whose admission hemoglobin is below 8 g/dL have a higher risk of rebleeding. About three times as many patients with gastric ulcer (30%) rebleed compared with those with duodenal ulcer. Most instances of rebleeding occur within 2 days from the time the first episode has stopped. In one study, only 3% of patients who stopped bleeding for this long bled again.
Treatments administered through the endoscope may stop active bleeding or prevent rebleeding. Effective methods include injection into the ulcer of epinephrine, epinephrine plus 1% polidocanol (a sclerosing agent), or ethanol; application of clips to bleeding areas; or cautery using the heater probe, monopolar electrocautery, or the Nd:YAG laser. At least two modalities should be available to the endoscopist in the event one is unsuitable for a specific case or fails to work. Except for the laser, all are inexpensive. The indications for treatment are: (1) active bleeding at the time of endoscopy and (2) the presence of a visible vessel in the base of the ulcer. When treatment fails the first time, it may often be repeated with a good chance of success. It is important, however, not to allow the patient to deteriorate during nonoperative attempts at halting the bleeding.
Less than 10% of patients bleeding from a peptic ulcer require emergency surgery. Selection of those most likely to survive with surgical compared with medical treatment rests on the rate of blood loss and the other factors associated with a poor prognosis.
The overall death rate is significantly less after vagotomy and pyloroplasty than after gastrectomy for bleeding ulcer, and rebleeding occurs with about equal frequency after either procedure.
During laparotomy, the first step is to make a pyloroplasty incision if the endoscopic diagnosis is a bleeding duodenal ulcer. If a duodenal ulcer is found, the bleeding vessel should be suture-ligated and the duodenum and antrum inspected for additional ulcers. The pyloroplasty incision should then be closed and a truncal vagotomy performed. If the posterior wall of the duodenal bulb has been destroyed by a giant duodenal ulcer, a gastrectomy and Billroth II gastrojejunostomy may be preferable, since this somewhat uncommon ulcer is especially prone to bleed again if left in continuity with the stomach. Gastric ulcers can be handled by either gastrectomy or vagotomy and pyloroplasty. A thorough search should always be made for second ulcers or other causes of bleeding.
The death rate for an acute massive hemorrhage is about 15%. Careful study of the causes of death suggests that this figure could be improved by: (1) more precise blood replacement, since undertransfusion is the cause of some complications and deaths; and (2) earlier surgery in selected patients who fall into serious-risk categories, since the tendency has been to perform surgery on too few patients too late in the illness. Patients who stop bleeding should be treated as outlined in the section on duodenal ulcer.
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JY: Management of massive peptic ulcer bleeding. Gastroenterol Clin North Am 2009 Jun;38(2):231–243.
Mallory-Weiss syndrome is responsible for about 10% of cases of acute upper gastrointestinal hemorrhage. The lesion consists of a 1- to 4-cm longitudinal tear in the gastric mucosa near the esophagogastric junction; it usually follows a bout of forceful retching. The disruption extends through the mucosa and submucosa but not usually into the muscularis mucosae. About 75% of these lesions are confined to the stomach, 20% straddle the esophagogastric junction, and 5% are entirely within the distal esophagus. Two-thirds of patients have a hiatal hernia.
The majority of patients are alcoholics, but the tear may appear after severe retching for any reason. Several cases have been reported following closed-chest cardiac compression.
Typically, the patient first vomits food and gastric contents. This is followed by forceful retching and then bloody vomitus. Rapid increases in gastric pressure, sometimes aggravated by hiatal hernia, cause the tear. Actual rupture of the distal esophagus can also be produced by vomiting (Boerhaave syndrome), but the difference seems to depend on vomiting of food in rupture and nonproductive retching in gastric mucosal tear.
Esophagogastroscopy is the most practical means of making the diagnosis.
Initially, the patient is handled according to the general measures prescribed for upper gastrointestinal hemorrhage. In about 90% of patients, the bleeding stops spontaneously after ice-water lavage of the stomach. Patients who are still bleeding vigorously by the time endoscopy is performed are likely to require surgery. The bleeding can sometimes be controlled by endoscopic therapy (eg, electrocautery). If bleeding persists, surgical repair of the tear will be required.
If the diagnosis has been made before laparotomy, the surgeon should make a long, high gastrotomy after the abdomen is opened. The tear may be difficult to expose adequately. The search must be thorough, since in about 25% of patients there are two tears. A running absorbable acid suture should be used to oversew the lesion. Postoperative recurrence is rare.
PYLORIC OBSTRUCTION DUE TO PEPTIC ULCER
The cycles of inflammation and repair in peptic ulcer disease may cause obstruction of the gastroduodenal junction as a result of edema, muscular spasm, and scarring. To the extent that the first two factors are involved, the obstruction may be reversible with medical treatment. Obstruction is usually due to duodenal ulcer and is less common than either bleeding or perforation. The few gastric ulcers that obstruct are close to the pylorus. Obstruction due to peptic ulcer must be differentiated from that caused by a malignant tumor of the antrum or of the pancreas. Malignancy is becoming the more common cause, and it may be difficult to identify.
Most patients with obstruction have a long history of symptomatic peptic ulcer, and as many as 30% have been treated for perforation or obstruction in the past. The patient often notes gradually increasing ulcer pains over weeks or months, with the eventual development of anorexia, vomiting, and failure to gain relief from antacids. The vomitus often contains food ingested several hours previously, and absence of bile staining reflects the site of blockage. Weight loss may be marked if the patient has delayed seeking medical care.
Dehydration and malnutrition may be obvious on physical examination but are not always present. A succussion splash can often be elicited from the retained gastric contents. Peristalsis of the distended stomach may be visible on gross inspection of the abdomen, but this sign is relatively rare. Most patients have upper abdominal tenderness. Tetany may appear with advanced alkalosis.
Anemia is present in about 25% of patients. Prolonged vomiting leads to metabolic alkalosis with dehydration. Measurement of serum electrolytes shows hypochloremia, hypokalemia, hyponatremia, and increased bicarbonate. Vomiting depletes the patient of Na+, K+, and Cl−; the latter is lost in excess of Na+ and K+ as HCl. Gastric HCl loss causes extracellular HCO3− to rise, and renal excretion of HCO3− increases in an attempt to maintain pH. Large amounts of Na+ are excreted in the urine with the HCO3−. Increasing Na+ deficit evokes aldosterone secretion, which in turn brings about renal Na+ conservation at the expense of more renal loss of K+ and H+. Glomerular filtration rate may drop and produce a prerenal azotemia. The eventual result of the process is a marked deficit of Na+, Cl−, K+, and H2O. Treatment involves replacement of water and NaCl until a satisfactory urine flow has been established. KCl replacement should then be started.
This is a simple means of assessing the degree of pyloric obstruction and is useful in following the patient’s progress during the first few days of nasogastric suction.
Through the nasogastric tube, 700 mL of normal saline (at room temperature) is infused over 3–5 minutes, and the tube is clamped. Thirty minutes later, the stomach is aspirated and the residual volume of saline recorded. Recovery of more than 350 mL indicates obstruction. It must be recognized that the results of a saline load test do not predict how well the stomach will handle solid food. Solid emptying can be measured with technetium-99 m-labeled chicken liver.
Plain abdominal x-rays may show a large gastric fluid level. An upper gastrointestinal series should not be performed until the stomach has been emptied, because dilution of the barium in the retained secretions makes a worthwhile study impossible.
Upper endoscopy is usually indicated to rule out the presence of an obstructing neoplasm.
A large (32F) tube should be passed and the stomach emptied of its contents and lavaged until clean. After the stomach has been completely decompressed, a smaller tube should be inserted and placed on suction for several days to allow pyloric edema and spasm to subside and to permit the gastric musculature to regain its tone. A saline load test may be performed at this point to provide a baseline for later comparison. If chronic obstruction has produced severe malnutrition, total parenteral nutrition should be instituted.
After decompression of the stomach for 48–72 hours, the saline load test should be repeated. If this indicates sufficient improvement, the tube should be withdrawn and a liquid diet may be started. Gradual resumption of solid foods is permitted as tolerated.
If 5–7 days of gastric aspiration do not result in relief of the obstruction, the patient should be treated surgically. Persistence of nonoperative effort beyond this point in the absence of progress rarely achieves the result hoped for. Failure of the obstruction to resolve completely (eg, if the patient can take only liquids) and recurrent obstruction of any degree are indications for surgery.
Surgical treatment may consist of a truncal or parietal cell vagotomy and drainage procedure (Figure 23–5). Truncal vagotomy and gastrojejunostomy is the easiest to perform laparoscopically.
About two-thirds of patients with acute obstruction fail to improve sufficiently on medical therapy and require operation to relieve the blockage. Patients who respond to medical treatment should be treated as outlined in the section on duodenal ulcer.
Perforation complicates peptic ulcer about half as often as hemorrhage. Most perforated ulcers are located anteriorly, though occasionally gastric ulcers perforate into the lesser sac. The 15% death rate correlates with increased age, female gender, and gastric perforations. The diagnosis is overlooked in about 5% of patients, most of whom do not survive.
Anterior ulcers tend to perforate instead of bleed because of the absence of protective viscera and major blood vessels on this surface. In less than 10% of cases, acute bleeding from a posterior “kissing” ulcer complicates the anterior perforation, an association that carries a high death rate. Immediately after perforation, the peritoneal cavity is flooded with gastroduodenal secretions that elicit a chemical peritonitis. Early cultures show either no growth or a light growth of streptococci or enteric bacilli. Gradually, over 12–24 hours, the process evolves into bacterial peritonitis. Severity of illness and occurrence of death are directly related to the interval between perforation and surgical closure.
In an unknown percentage of cases, the perforation becomes sealed by adherence to the undersurface of the liver. In such patients, the process may be self-limited, but an intraperitoneal abscess develops in many.
Perforation usually elicits a sudden, severe upper abdominal pain whose onset can be recalled precisely. The patient may or may not have had preceding chronic symptoms of peptic ulcer disease. Perforation rarely is heralded by nausea or vomiting, and it typically occurs several hours after the last meal. Shoulder pain, if present, reflects diaphragmatic irritation. Back pain is uncommon.
The initial reaction consists of a chemical peritonitis caused by gastric acid or bile and pancreatic enzymes. The peritoneal reaction dilutes these irritants with a thin exudate, and as a result the patient’s symptoms may temporarily improve before bacterial peritonitis occurs. The physician who sees the patient for the first time during this symptomatic lull must not be misled into interpreting it as representing bona fide improvement.
The patient appears severely distressed, lying quietly with the knees drawn up and breathing shallowly to minimize abdominal motion. Fever is absent at the start. The abdominal muscles are rigid owing to severe involuntary spasm. Epigastric tenderness may not be as marked as expected because the board-like rigidity protects the abdominal viscera from the palpating hand. Escaped air from the stomach may enter the space between the liver and abdominal wall, and upon percussion the normal dullness over the liver will be tympanitic. Peristaltic sounds are reduced or absent. If delay in treatment allows continued escape of air into the peritoneal cavity, abdominal distention and diffuse tympany may result.
The above description applies to the typical case of perforation with classic findings. In as many as one-third of patients, the presentation is not as dramatic, diagnosis is less obvious, and serious delays in treatment may result from failure to consider this condition and to obtain the appropriate abdominal x-rays. Many of these atypical perforations occur in patients already hospitalized for some unrelated illness, and the significance of the new symptom of abdominal pain is not appreciated.
Lesser degrees of shock with minimal abdominal findings occur if the leak is small or rapidly sealed. A small duodenal perforation may slowly leak fluid that runs down the lateral peritoneal gutter, producing pain and muscular rigidity in the right lower quadrant, and thus raising a problem of confusion with acute appendicitis.
Perforations may be sealed by omentum or by the liver, with the later development of a subhepatic or subdiaphragmatic abscess.
A mild leukocytosis in the range of 12,000/μL is common in the early stages. After 12–24 hours, this may rise to 20,000/μL or more if treatment has been inadequate. The mild rise in the serum amylase value that occurs in many patients is probably caused by absorption of the enzyme from duodenal secretions within the peritoneal cavity. Direct measurement of fluid obtained by paracentesis may show very high levels of amylase.
Plain x-ray or CT scan of the abdomen reveals free subdiaphragmatic air in 85% of patients.
If no free air is demonstrated and the clinical picture suggests perforated ulcer, an emergency CT scan with gastrointestinal contrast, or upper gastrointestinal series should be performed. If the perforation has not sealed, the diagnosis is established by noting escape of the contrast material from the lumen.
The differential diagnosis includes acute pancreatitis and acute cholecystitis. The former does not have as explosive an onset as perforated ulcer and is usually accompanied by high serum levels of lipase and amylase. Acute cholecystitis with perforated gallbladder could mimic perforated ulcer closely but free air would not be present with ruptured gallbladder. Intestinal obstruction has a more gradual onset and is characterized by less severe pain that is crampy and accompanied by vomiting.
The simultaneous onset of pain and free air in the abdomen in the absence of trauma usually means perforated peptic ulcer. Free perforation of colonic diverticulitis and acute appendicitis are other rare causes.
The diagnosis is often suspected before the patient is sent for confirmatory imaging. Whenever a perforated ulcer is considered, the first step should be to pass a nasogastric tube and empty the stomach to limit further contamination of the peritoneal cavity. Blood should be drawn for laboratory studies, and intravenous antibiotics (eg, cefazolin, cefoxitin) should be started. If the patient’s overall condition is precarious owing to delay in treatment, fluid resuscitation should precede diagnostic measures. Imaging should be obtained as soon as the clinical status will permit.
The simplest surgical treatment, laparoscopy (or laparotomy) and suture closure of the perforation solves the immediate problem. The closure most often consists of securely plugging the hole with omentum (Graham-Steele closure) sutured into place rather than bringing together the two edges with sutures. All fluid should be aspirated from the peritoneal cavity, but drainage is not indicated. Reperforation is rare in the immediate postoperative period.
About three-fourths of patients whose perforation is the culmination of a history of chronic symptoms continue to have clinically severe ulcer disease after simple closure. This had led to a more aggressive treatment policy involving a definitive ulcer operation for most patients with acute perforation (eg, parietal cell vagotomy plus closure of the perforation or truncal vagotomy and pyloroplasty). Now that ulcer disease can be cured by eradicating H pylori, the value of anything more than simple closure is limited.
Concomitant hemorrhage and perforation are most often due to two ulcers, an anterior perforated one and a posterior one that is bleeding. Perforated ulcers that also obstruct cannot be treated by suture closure of the perforation alone. Vagotomy plus gastroenterostomy or pyloroplasty should be performed. Perforated anastomotic ulcers require a vagotomy or gastrectomy, since in the long run, closure alone is nearly always inadequate.
Nonoperative treatment of perforated ulcer consists of continuous gastric suction and the administration of antibiotics in high doses. Although this has been shown to be effective therapy, with a low death rate, it is occasionally accompanied by a peritoneal and subphrenic abscess, and side effects are greater than with laparoscopic closure.
About 15% of patients with perforated ulcer die, and about a third of these are undiagnosed before surgery. The death rate of perforated ulcer seen early is low. Delay in treatment, advanced age, and associated systemic diseases account for most deaths.
STRESS GASTRODUODENITIS, STRESS ULCER, & ACUTE HEMORRHAGIC GASTRITIS
The term stress ulcer has been used to refer to a heterogeneous group of acute gastric or duodenal ulcers that develop following physiologically stressful illnesses. There are four major etiologic factors associated with such lesions: (1) shock, (2) sepsis, (3) burns, and (4) central nervous system tumors or trauma.
Acute ulcers following major surgery, mechanical ventilation, shock, sepsis, and burns (Curling ulcers) have enough common features to suggest they evolve by a similar pathogenetic mechanism.
Hemorrhage is the major clinical problem, though perforation occurs in about 10% of cases. Despite the predilection of stress ulcers to develop in the parietal cell mucosa, in about 30% of patients the duodenum is affected, and sometimes both stomach and duodenum are involved. Morphologically, the ulcers are shallow, discrete lesions with congestion and edema but little inflammatory reaction at their margins. Gastroduodenal endoscopy performed early in traumatized or burned patients has shown acute gastric erosions in the majority of patients within 72 hours after the injury. Such studies illustrate how frequently the disease process remains subclinical; clinically apparent ulcers develop in about 20% of susceptible patients. Clinically evident bleeding is usually seen 3–5 days after the injury, and massive bleeding generally does not appear until 4–5 days later.
Decreased mucosal resistance is the first step, which may involve the effects of ischemia (with production of toxic superoxide and hydroxyl radicals) and circulating toxins, followed by decreased mucosal renewal, decreased production of endogenous prostanoids, and thinning of the surface mucus layer. Decreased gastric mucosal blood flow also plays a role by decreasing the supply of blood buffers available to neutralize hydrogen ions that are diffusing into the weakened mucosa. Experimental evidence has implicated platelet-activating factor, released by endotoxin, as a possible mediator of gut ulceration in sepsis. The mucosa is thus rendered more vulnerable to acid-pepsin ulceration and lysosomal enzymes. Acid hypersecretion may be involved to some extent, since burn patients who manifest serious bleeding have higher gastric acid output than patients with a more benign course. Disruption of the gastric mucosal barrier to back diffusion of acid has been found in less than half of patients and is now thought to be a manifestation of the disease rather than a cause.
Acute ulcers associated with central nervous system tumors or injuries differ from stress ulcers because they are associated with elevated levels of serum gastrin and increased gastric acid secretion. Morphologically, they are similar to ordinary gastroduodenal peptic ulcers. Cushing ulcers are more prone to perforate than other kinds of stress ulcers.
C. Acute Hemorrhagic Gastritis
This disorder may share some causative factors with the above conditions, but the natural history is different and the response to treatment considerably better. Most of these patients can be controlled medically. When surgery is required for alcoholic gastritis, a high proportion of patients are cured by pyloroplasty and vagotomy.
Hemorrhage is nearly always the first manifestation. Pain rarely occurs. Physical examination is not contributory except to reveal gross or occult fecal blood or signs of shock.
Acid suppressing medications given prophylactically to critically ill patients decrease the incidence of stress erosions and overt bleeding. Sucralfate is also effective. Patients receiving total parenteral nutrition appear to be protected by this therapy and experience no increased benefit from H2 antagonists.
Initial management should consist of gastric lavage with chilled solutions and measures to combat sepsis if present. H2 receptor blockers are of no value in the actively bleeding patient, but they probably decrease the rate of rebleeding once bleeding has stopped.
Perform laparotomy if the nonoperative regimen fails to halt the bleeding. Surgical treatment should consist of vagotomy and pyloroplasty, with suture of the bleeding points, or vagotomy and subtotal gastrectomy. There is a trend toward the first of these options, particularly in the sickest patients. When it occurs, rebleeding is nearly always from an ulcer left behind at the initial procedure. Rarely, total gastrectomy has had to be used because of the extent of ulceration and severity of bleeding or because of rebleeding after a lesser operation.
RF. Stress-induced ulcer bleeding in critically ill patients. Gastroenterol Clin North Am 2009 Jun;38(2):245–265.
There are about 21,000 new cases of carcinoma of the stomach in the United States annually. The incidence has dropped to one-third of what it was 40 years ago. This may reflect changes in the prevalence of H pylori infection, which has a role in the etiology of this disease. H pylori is known to be a cause of chronic atrophic gastritis, which in turn is a recognized precursor of gastric adenocarcinoma. Epidemiologic studies have linked gastric H pylori infection with a 3.6-fold to 18-fold (all patients vs. women) increase in the risk of developing carcinoma of the body or antrum (not the cardia), and the risk is proportionate to serum levels of H pylori antibodies.
The present incidence in American men is 10 new cases per 100,000 population per year. The highest rate, 63 per 100,000 men, is observed in Costa Rica; in eastern and central European countries, it is about 35 per 100,000 per year. Epidemiologic studies suggest that the incidence of gastric carcinoma is related to low dietary intake of vegetables and fruits and high intake of starches. Carcinoma of the stomach is rare under age 40 years, from which point the risk gradually climbs. The mean age at discovery is 63. It is about twice as common in men as in women.
Gastric epithelial cancers are nearly always adenocarcinomas. Squamous cell tumors of the proximal stomach involve the stomach secondarily from the esophagus. Five morphologic subdivisions correlate loosely with the natural history and outcome.
1. Ulcerating carcinoma (25%)
This consists of a deep, penetrating ulcer-tumor that extends through all layers of the stomach. It may involve adjacent organs in the process. The edges are shallow by contrast with overhanging edges noted in benign ulcers.
2. Polypoid carcinomas (25%)
These are large, bulky intraluminal growths that tend to metastasize late.
3. Superficial spreading carcinoma (15%)
Also known as early gastric cancer, superficial spreading carcinoma is confined to the mucosa and submucosa. Metastases are present in only 30% of cases. Even when metastases are present, the prognosis after gastrectomy is much better than for the more deeply invading lesions of advanced gastric cancer. In Japan, screening programs have been so successful that early gastric cancer now constitutes 30% of surgical cases, and survival rates have improved accordingly.
4. Linitis plastica (10%)
This variety of spreading tumor involves all layers with a marked desmoplastic reaction in which it may be difficult to identify the malignant cells. The stomach loses its pliability. Cure is rare because of early spread.
5. Advanced carcinoma (35%)
This largest category contains the big tumors that are found partly within and partly outside the stomach. They may originally have qualified for inclusion in the preceding groups but have outgrown that early stage.
Gastric adenocarcinomas can also be classified by degree of differentiation of their cells. In general, rate and extent of spread correlate with lack of differentiation. Some tumors are found histologically to excite an inflammatory cell reaction at their borders, and this feature indicates a relatively good prognosis. Tumors whose cells form glandular structures (intestinal type) have a somewhat better prognosis than tumors whose cells do not (diffuse type); the diffuse type is often associated with a substantial stromal component. The intestinal type of tumor accounts for a much larger proportion of cases in countries such as Japan and Finland where gastric cancer is especially common. The gradual decline in incidence in these areas is due principally to decreased occurrence of the intestinal type of tumor. Signet ring carcinomas, which contain more than 50% signet ring cells, have become increasingly more common and now constitute one-third of all cases. They behave as the diffuse type of cancer and occur more frequently in women, in younger patients, and in the distal part of the stomach. Previous H pylori—infection is not associated with the development of any specific histologic type of gastric cancer.
Extension occurs by intramural spread, direct extraluminal growth, and lymphatic metastases. Pathologic staging, which correlates closely with survival, is illustrated in Figure 23–7. Three-fourths of patients have metastases when diagnosed. Within the stomach, proximal spread exceeds distal spread. The pylorus acts as a partial barrier, but tumor is found in 25% of cases in the first few centimeters of the bulb.
Staging system for gastric carcinoma. The darkly shadowed areas represent cancers with different depths of mucosal penetration.
Early gastric cancer, defined as a primary lesion confined to the mucosa and submucosa with or without lymph node metastases, is associated with an excellent prognosis (5-year survival rate of 90%) after resection. In Japan, mass screening programs detect about 30% of patients with this lesion, whereas in the United States, only 10% of patients have early gastric cancer.
Forty percent of tumors are in the antrum, predominantly on the lesser curvature; 30% arise in the body and fundus, 25% at the cardia, and 5% involve the entire organ. Frequency of location has gradually changed, so that proximal lesions are more common now than 10–20 years ago. Benign ulcers develop at the greater curvature and cardia less commonly than malignant ones. Ulcers at these points are particularly suspect for neoplasm.
The earliest symptom is usually vague postprandial abdominal heaviness that the patient does not identify as a pain. Sometimes the discomfort is no different from other vague dyspeptic symptoms that have been intermittently present for years, but the frequency and persistence are new.
Anorexia develops early and may be most pronounced for meat. Weight loss, the most common symptom, averages about 6 kg. True postprandial pain suggesting a benign gastric ulcer is relatively uncommon, but if it is present, one may be misled if subsequent x-rays show an ulcer. Vomiting may be present and becomes a major feature if pyloric obstruction occurs. It may have a coffee-ground appearance owing to bleeding by the tumor. Dysphagia may be the presenting symptom of lesions at the cardia.
An epigastric mass can be felt on examination in about one-fourth of cases. Hepatomegaly is present in 10% of cases. The stool will be positive for occult blood in half of patients, and melena is seen in a few. Otherwise, abnormal physical findings are confined to signs of distant spread of the tumor. Metastases to the neck along the thoracic duct may produce a Virchow node. Rectal examination may reveal a Blumer shelf, a solid peritoneal deposit anterior to the rectum. Enlarged ovaries (Krukenberg tumors) may be caused by intraperitoneal metastases. Further dissemination may involve the liver, lungs, brain, or bone.
Anemia is present in 40% of patients. Carcinoembryonic antigen levels are elevated in 65%, usually indicating extensive spread of the tumor.
An upper gastrointestinal series is diagnostic for many tumors, but the overall false-negative rate is about 20%. Major diagnostic problems are posed by ulcerating tumors, a few of which may not be distinguishable radiologically from benign peptic ulcers. The differential features are listed in the section on gastric ulcer, but x-rays alone will not establish a diagnosis of benign ulcer. All patients with a newly discovered gastric ulcer should undergo upper endoscopy and gastric biopsy.
D. Gastroscopy and Biopsy
Large gastric carcinomas can usually be identified as such by their gross appearance at endoscopy. All gastric lesions, whether polypoid or ulcerating, should be examined by taking multiple biopsy and brush cytology specimens during endoscopy. False negative results are seen occasionally as a result of sampling error, and a minimum of six biopsies is necessary for greatest accuracy.
Surgical resection is the only curative treatment. About 85% of patients are operable, and in 50% the lesions are amenable to resection; of the resectable lesions, half are potentially curable (ie, no signs of spread beyond the limits of resection). Preoperative chemotherapy with a multidrug regimen is recommended for most patients.
The surgical objective should be to remove the tumor, an adjacent uninvolved margin of stomach and duodenum, the regional lymph nodes, and, if necessary, portions of involved adjacent organs. The proximal margin should be a minimum of 6 cm from the gross tumor. If the tumor is located in the antrum, a curative resection would entail distal gastrectomy with en bloc removal of the omentum, a 3- to 4-cm cuff of duodenum and the subpyloric lymph nodes, and, in some instances, excision of the left gastric artery and nearby lymph nodes. Reconstruction after gastrectomy may be by either a Billroth I or II procedure, but the latter is preferable because postoperative growth of residual tumor near the pylorus may obstruct a gastroduodenal anastomosis early.
Total gastrectomy with splenectomy is required for tumors of the proximal half of the stomach and for extensive tumors (eg, linitis plastica). Whether or not the spleen should be removed in such cases is a subject of debate. Alimentary continuity is most often reestablished by a Roux-en-Y esophagojejunostomy. Construction of an intestinal pouch as a substitute food reservoir (eg, Hunt–Lawrence pouch) is of no nutritional value, and it increases the risks of immediate complications.
Esophagogastrectomy plus splenectomy with intrathoracic esophagogastrostomy is the operation usually performed for tumors of the cardia. The procedure is usually done through two separate incisions: first, a laparotomy for the gastric part, and then a right posterolateral thoracotomy for the anastomosis.
The propensity for proximal submucosal spread must be appreciated at surgery. It is often advisable to perform a frozen section at the proximal margin before constructing the anastomosis. If tumor is found, the gastrectomy should be extended.
Palliative resection is usually indicated if the stomach is still movable and life expectancy is estimated to be more than 1–2 months. Palliative gastrectomy is usually performed to remove an antral lesion and prevent obstruction, but in selected cases, total gastrectomy is appropriate palliative treatment if the operation can be done safely and the amount of extragastric tumor is minimal. Whenever technically feasible, palliative gastrectomy is preferable to palliative gastrojejunostomy.
Adjuvant chemotherapy after curative surgery is recommended, particularly for patients who have undergone preoperative chemotherapy and responded.
In the United States, the overall 5-year survival rate is about 12%. The 5-year survival rate for patients with early gastric cancer is about 90%. The 5-year survival rates in relation to the extent of spread are stage I, 70%; stage II, 30%; stage III, 10%; and stage IV, 0%.
Death from tumor may follow dissemination to other organs or may be the result of progressive gastric obstruction and malnutrition.
et al.: Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw May 1 , 2013;11(5):531–546.
Gastric polyps are single or multiple benign tumors that occur predominantly in the elderly. Those located in the distal stomach are more apt to cause symptoms. Whenever gastric polyps are discovered, gastric cancer must be ruled out.
Gastric polyps can be classified histologically as hyperplastic, adenomatous, or inflammatory. Other polypoid lesions, such as leiomyomas and carcinoid tumors, are discussed elsewhere. Hyperplastic polyps, which constitute 80% of cases, consist of an overgrowth of normal epithelium; they are not true neoplasms and have no relationship to gastric cancer. About 30% of adenomatous polyps contain a focus of adenocarcinoma, and adenocarcinoma can be found elsewhere in the stomach in 20% of patients with a benign adenomatous polyp. The incidence of cancer in an adenomatous polyp rises with increasing size. Lesions with a stalk and those less than 2 cm in diameter are usually not malignant. About 10% of benign adenomatous polyps undergo malignant change during prolonged follow-up.
Anemia may develop from chronic blood loss or deficient iron absorption. Over 90% of patients are achlorhydric after maximal stimulation. Vitamin B12 absorption is deficient in 25%, although megaloblastic anemia is present in only a few.
Excision with a snare through the endoscope can be performed safely for most polyps. Otherwise, surgical excision is indicated for polyps greater than 1 cm in diameter or when cancer is suspected. Single polyps may be excised through a gastrotomy and a frozen section performed. If the polyp is found to be carcinoma, an appropriate type of gastrectomy is indicated. Partial gastrectomy should be performed for multiple polyps in the distal stomach. If 10–20 polyps are distributed throughout the stomach, the antrum should be removed and the fundic polyps excised. Total gastrectomy may be required for symptomatic diffuse multiple polyposis.
These patients should be followed because they have an increased risk of late development of pernicious anemia or gastric cancer. Recurrent polyps are uncommon.
GASTRIC LYMPHOMA & PSEUDOLYMPHOMA
Lymphoma is the second-most common primary cancer of the stomach but constitutes only 2% of the total number, 95% being adenocarcinomas. Almost all are non-Hodgkin lymphomas and are generally classified as B cell mucosa-associated lymphoid tissue (MALT) lymphomas. They are further subclassified as low-grade or high-grade based on nuclear pattern. About 20% of patients manifest a second primary cancer in another organ.
The principal symptoms are epigastric pain and weight loss, similar to those of carcinoma. Characteristically, the tumor has attained bulky proportions by the time it is discovered; by comparison with adenocarcinoma of the stomach, the symptoms from a gastric lymphoma are usually mild in relation to the size of the lesion. A palpable epigastric mass is present in 50% of patients. Imaging studies will demonstrate the lesion, although it usually is mistaken for adenocarcinoma or benign gastric ulcer. Gastroscopy with biopsy and brush cytology provides the correct diagnosis preoperatively in about 75% of cases. If a pathologic diagnosis has not been made, the surgeon may incorrectly judge the lesion to be inoperable carcinoma because of its large size. Preoperative staging should include a CT scan and bone marrow biopsy.
Treatment of limited extent, low-grade gastric lymphoma consists of antibiotic treatment for H pylori, if present. More extensive disease may require therapy with external beam radiation or rituximab.
Gastric pseudolymphoma consists of a mass of lymphoid tissue in the gastric wall, often associated with an overlying mucosal ulcer. It is thought to represent a response to chronic inflammation. The lesion is not malignant, though the presentation, which includes pain, weight loss, and a mass on imaging, cannot be distinguished from a malignant lesion.
Treatment of gastric pseudolymphoma consists of resection. The distinction from lymphoma is made on histologic examination of the specimen, which shows mature germinal centers in pseudolymphoma. No additional therapy is indicated postoperatively.
et al.. for the National Comprehensive Cancer Network. Non-Hodgkin’s lymphomas, version 1.2013. J Natl Compr Canc Netw 2013 Mar 1 ;11(3):257–272.
GASTRIC LEIOMYOMAS & GASTROINTESTINAL STROMAL TUMOR
Leiomyomas are common submucosal growths that are usually asymptomatic but may cause intestinal bleeding. GIST (previously called leiomyosarcomas) may grow to a large size and most often present with bleeding. Radiologically, the tumor usually contains a central ulceration caused by necrosis from outgrowth of its blood supply. In most cases the tumor arises from the proximal stomach. It may grow into the gastric lumen, remain entirely on the serosal surface, or even become pedunculated within the abdominal cavity. Spread is by direct invasion or blood-borne metastases. CT scans provide useful information on the amount of extragastric extension. Leiomyomas should be removed by enucleation or wedge resection. After the more radical resections required for leiomyosarcomas, the 5-year survival rate is 20%. If technically possible, complete resection of metastases (eg, peritoneal, hepatic) in addition to the primary tumor may improve the outcome. The results are affected by tumor size, DNA ploidy pattern, and tumor grade. Lesions that exhibit 10 or more mitoses in a high-powered field rarely can be cured. Imatinib mesylate is an effective systemic agent used for disseminated disease and as an adjuvant therapy after complete resection.
Ménétrier disease, a form of hypertrophic gastritis, consists of giant hypertrophy of the gastric rugae; high, normal, or low acid secretion; and excessive loss of protein from the thickened mucosa into the gut, with resulting hypoproteinemia. Clinical manifestations include edema, diarrhea, anorexia, weight loss, and skin rash. Chronic blood loss may also be a problem. Indigestion may respond to antacids, but this treatment does not improve the gastric pathologic process or secondary hypoproteinemia. The hypertrophic rugae present as enormous filling defects on upper gastrointestinal imaging and are frequently misinterpreted as carcinoma. The protein leak from the gastric mucosa may respond to atropine (and other anticholinergic drugs), hexamethonium bromide, eradication of H pylori, or H2 blocking agents or omeprazole. Rarely, total gastrectomy is indicated for severe intractable hypoproteinemia, anemia, or inability to exclude cancer. Medical management is best for most patients, though the gastric abnormalities and hypoproteinemia may persist. Some cases gradually evolve into atrophic gastritis. In children the disease characteristically is self-limited and benign. There is an increased risk of adenocarcinoma of the stomach in adults with Ménétrier disease.
PROLAPSE OF THE GASTRIC MUCOSA
This uncommon lesion occasionally accompanies small prepyloric gastric ulcers. Episodes of vomiting and abdominal pain simulate peptic ulcer disease. X-ray shows prolapse of antral folds into the duodenum. One must be alert to the presence of gastric or duodenal ulcer as the underlying cause.
Antrectomy with a Billroth I anastomosis is occasionally required. Generally, conservative treatment suffices.
The stomach may rotate about its longitudinal axis (organoaxial volvulus) or a line drawn from the mid-lesser to the mid-greater curvature (mesenteroaxial volvulus). The former is more common and is often associated with a paraesophageal hiatal hernia. In other patients, eventration of the left diaphragm allows the colon to rise and twist the stomach by pulling on the gastrocolic ligament.
Acute gastric volvulus produces severe abdominal pain accompanied by a diagnostic triad (Borchardt triad): (1) vomiting followed by retching and then inability to vomit, (2) epigastric distention, and (3) inability to pass a nasogastric tube. The situation calls for immediate laparotomy to prevent death from acute gastric necrosis and shock. Emergency imaging shows blockage at the point of the volvulus. The death rate is high.
Chronic volvulus is more common than acute. It may be asymptomatic or may cause crampy intermittent pain. Cases associated with paraesophageal hiatal hernia should be treated by repair of the hernia and anterior gastropexy. When cases are due to eventration of the diaphragm, the gastrocolic ligament should be divided the entire length of the greater curvature. The colon rises to fill the space caused by the eventration, and the stomach will resume its normal position, to be fastened by a gastropexy.
Gastric diverticula are uncommon and usually asymptomatic. Most are pulsion diverticula consisting of mucosa and submucosa only, located on the lesser curvature within a few centimeters of the esophagogastric junction. Those in the prepyloric region generally possess all layers and are more likely to be symptomatic. A few patients have symptoms from hemorrhage of inflammation within a gastric diverticulum, but for the most part these lesions are incidental findings on imaging or endoscopy. Radiologically, they can be confused with a gastric ulcer.
Bezoars are concretions formed in the stomach. Trichobezoars are composed of hair and are usually found in young girls who pick at their hair and swallow it. Phytobezoars consist of agglomerated vegetable fibers. Pressure by the mass can create a gastric ulcer that is prone to bleed or perforate.
The postgastrectomy state predisposes to bezoar formation because pepsin and acid secretion are reduced and the triturating function of the antrum is gone. Orange segments or other fruits that contain a large amount of cellulose have been implicated in most cases. Improper mastication of food is a contributing factor that can sometimes be obviated by providing the patient with properly fitted dentures. The fruit may remain in the stomach or pass into the small intestine and cause obstruction.
Large semisolid bezoars of Candida albicans have also been found in postgastrectomy patients. Some can be fragmented with the gastroscope. The patient should also be treated with oral nystatin.
Patients with symptomatic gastric bezoars may complain of abdominal pain. Ulceration and bleeding are associated with a death rate of 20%.
Nearly all gastric bezoars can be broken up and dispersed by endoscopy. Neglected lesions with complications (ie, bleeding or perforation) require gastrectomy.