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Peptic ulcer disease

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Peptic ulcer remains a common outpatient diagnosis, but the number of physician visits, hospital admissions, and elective operations for peptic ulcer disease have decreased steadily and dramatically over the past three decades. These trends all predated the advent of fiberoptic endoscopy, highly selective vagotomy, and H2 blockers. The incidence of emergency operation and the death rate for peptic ulcer are fairly stable however. These epidemiologic trends probably represent the net effect of several factors including decreased prevalence of Helicobacter infection, better medical therapy, increase in outpatient management, and NSAID/aspirin use (with and without ulcer prophylaxis).


A variety of factors may contribute to the development of peptic ulcer. Although it is now recognized that the large majority of duodenal and gastric ulcers are “caused by” Helicobacter infestation and/or nonsteroidal anti-inflammatory drug use, the final common pathway to ulcer formation is acid-peptic injury of the gastroduodenal mucosal barrier. Thus the adage, “no acid, no ulcer,” is as true today as it ever was. Acid suppression either with medication or surgery remains a mainstay in healing both duodenal and gastric ulcers and in preventing recurrence. It is generally thought that Helicobacter predisposes to ulceration both by acid hypersecretion and by compromise of mucosal defense mechanisms. NSAIDs are thought to lead to peptic ulcer predominantly by compromise of mucosal defenses. Duodenal ulcer has typically been thought of as a disease of increased acid peptic aggression on the duodenal mucosa, whereas gastric ulcer has been viewed as a disease of weakened mucosal defenses in the face of relatively normal acid peptic aggression. However increased understanding of the pathophysiology of peptic ulcer has blurred this distinction. Clearly weakened mucosal defenses play a role in many duodenal and most gastric ulcers (e.g., duodenal ulcer in Helicobacter negative patient on NSAIDs; or typical type I gastric ulcer with acid hyposecretion); whereas acid peptic aggression may result in a duodenal or gastric ulcer in the setting of normal mucosal defenses (e.g., duodenal ulcer in patient with Zollinger-Ellison syndrome; gastric ulcer in patient with gastric outlet obstruction, antral stasis, and acid hypersecretion). Elimination of H. pylori infection or NSAID use is important for optimal ulcer healing and perhaps even more important in preventing recurrence and/or complications. A variety of other diseases are known to cause peptic ulcer, including Zollinger-Ellison Syndrome (gastrinoma), antral G-cell hyperfunction and/or hyperplasia, systemic mastocytosis, trauma, burns, and major physiological stress. Other “causative agents” are drugs (all NSAIDs, aspirin, cocaine), smoking, alcohol and psychological stress. Probably in the United States, over 90 percent of serious peptic ulcer complications can be attributed to Helicobacter infection, NSAID use, and cigarette smoking. The H. pylori bacteria are uniquely equipped for survival in the hostile environment of the stomach. It possesses the urease enzyme which converts urea into ammonia and bicarbonate creating an environment around the bacteria which buffers the acid secreted by the stomach. H. pylori infection is associated with decreased levels of gastric mucosal somatostatin production, hypergastrinemia and acid hypersecretion. The acid hypersecretion and the antral gastritis are thought to lead to antral epithelial metaplasia in the postpyloric duodenum. This duodenal metaplasia allows H. pylori to colonize the duodenal mucosa and in these patients the risk of developing a duodenal ulcer increases 50-fold. When H. pylori colonizes the duodenum, there is a significant decrease in acid-stimulated duodenal bicarbonate release. Likewise, Helicobacter predisposes to gastric ulcer at least in part by weakening mucosal defenses. It is clear from multiple randomized prospective studies that curing H. pylori infection dramatically decreases the risk of recurrent ulcer. As a rule duodenal ulcer patients secrete more acid than patients with gastric ulcer. It has long been recognized that duodenal ulcer patients as a group have a higher mean basal acid output (BAO) and also a higher mean maximal acid output (MAO) than normal controls. However many duodenal ulcer patients have basal and peak acid outputs in the normal range and there is no correlation between acid secretion and the severity of the ulcer disease. Some patients with duodenal ulcer also have increased rates of gastric emptying which delivers an increased acid load per unit of time to the duodenum. Finally the buffering capacity of the duodenum in many patients with duodenal ulcer is compromised because of decreased duodenal bicarbonate secretion. In patients with gastric ulcer, acid secretion is variable. Generally, four types of gastric ulcer are described. The most common Johnson type I gastric ulcer is typically located near the angularis incisura on the lesser curvature, close to the border between the antrum and the body of the stomach. Usually these patients have normal or decreased acid secretion. Type II gastric ulcer is associated with active or quiescent duodenal ulcer disease, and type III gastric ulcer is prepyloric. Both type II and type III gastric ulcers are associated with normal or increased gastric acid secretion. Type IV gastric ulcer occurs near the gastroesophageal junction and acid secretion is normal or below normal. Patients with Type I or IV gastric ulcer may have weak mucosal defenses which permit an abnormal amount of injurious acid back-diffusion into the mucosa. Duodenogastric reflux may play a role in weakening the gastric mucosal defenses in patients with gastric ulcer.Avariety of components in duodenal juice, including bile, lysolecithin, and pancreatic juice, has been shown to cause injury and inflammation in the gastric mucosa. NSAIDs and aspirin have similar effects. NSAIDs (including aspirin) are inextricably linked to peptic ulcer disease. Patients with rheumatoid arthritis and osteoarthritis who take NSAIDs have a 15–20 percent annual incidence of peptic ulcer, and the prevalence of peptic ulcer in chronic NSAID users is about 25 percent (15 percent gastric and 10 percent duodenal). Complications of peptic ulcer disease (specifically hemorrhage and perforation) are much more common in patients taking NSAIDs. More than half of patients who present with peptic ulcer hemorrhage or perforation report the recent use of nonsteroidal antiinflammatory drugs, including aspirin. Many of these patients remain asymptomatic up until the time they develop these life threatening complications. This problem is put into prospective when one realizes that approximately 20 million patients in the United States take NSAIDs on a regular basis; perhaps as many regularly take aspirin. Factors which clearly put patients at increased risk for NSAID-induced GI complications include age older than 60, prior GI event, high NSAID dose, concurrent steroid intake, and concurrent anticoagulant intake. Any patient taking NSAIDs or aspirin who has one or more of these risk factors should receive concomitant acid suppressive medication or misoprostol at a therapeutic dose or should be considered for alternative treatment with cyclooxygenas-2 (COX-2) inhibitors. Epidemiologic studies suggest that smokers are about twice as likely to develop peptic ulcer disease as nonsmokers. Smoking increases gastric acid secretion and duodenogastric reflux. Smoking decreases both gastroduodenal prostaglandin production and pancreaticoduodenal bicarbonate production. These observations may be related, and any or all could explain the observed association between smoking and peptic ulcer disease. Although difficult to measure, both physiological and psychological stress undoubtedly play a role in the development of peptic ulcer in some patients. In 1842, Curling described duodenal ulcer and/or duodenitis in burn patients. Decades later, Cushing described the appearance of acute peptic ulceration in patients with head trauma (Cushing ulcer). Recently, the use of crack cocaine has been linked to juxtapyloric peptic ulcers with a propensity to perforate. Alcohol is commonly mentioned as a risk factor for peptic ulcer disease, but confirmatory data are lacking.

^ Clinical Manifestations and Diagnosis

Over 90 percent of patients with peptic ulcer complain of abdominal pain. The pain is typically nonradiating, burning in quality and located in the epigastrium. Other signs and symptoms include nausea, bloating, weight loss, positive stool for occult blood, and anemia. In the young patient with dyspepsia and/or epigastric pain, it may be appropriate to initiate empiric therapy for peptic ulcer disease without confirmatory testing. All patients with the above symptoms over 45 should have an upper endoscopy, and all patients regardless of age should have this study if any alarm symptoms (see Table) are present. A good double contrast upper GI radiograph study may be useful. All gastric ulcers should be adequately biopsied, and any sites of gastritis should be biopsied to rule out Helicobacter, and for histologic evaluation. Additional testing for Helicobacter may be indicated. Although somewhat controversial, it is not unreasonable to test all peptic ulcer patients for Helicobacter. A baseline serum gastrin is appropriate to rule out gastrinoma. The three complications of peptic ulcer disease, in decreasing order of frequency, are bleeding, perforation, and obstruction now account for the large majority of operations performed for peptic ulcer disease, and essentially all of the deaths (most of which are because of bleeding). Medical Treatment of Peptic Ulcer Patients with peptic ulcer should stop smoking, and avoid alcohol and NSAIDs (including aspirin). If Helicobacter infection is documented, it should be treated with one of numerous acceptable regimens (Table 25-6). If initial Helicobacter testing is negative, the ulcer patient may be treated withH2 receptor blockers or proton pump inhibitors. Sucralfate or misoprostol may also be effective. If ulcer symptoms persist, an empiric trial of anti-Helicobacter therapy is reasonable

^ Surgical Treatment of Peptic Ulcer

Fundamentally, the vast majority of peptic ulcers requiring operation are adequately treated by a variant of one of three basic procedures: highly selective vagotomy; vagotomy and drainage; vagotomy and distal gastrectomy. Highly selective vagotomy (HSV), also called parietal cell vagotomy or proximal gastric vagotomy, is safe (mortality risk <0.5 percent) and causes minimal side effects. The operation severs the vagal supply to the proximal two thirds of the stomach, in which essentially all the parietal cells are located. It preserves the vagal innervation to the antrum and pylorus, and the remaining abdominal viscera. HSV decreases total gastric acid secretion by about 65–75 percent, which is quite comparable to truncal vagotomy or acid suppressive medication. Gastric emptying of solids is typically normal in patients

^ Clinical Results of Surgery for Duodenal Ulcer

Parietal Truncal Truncal cell vagotomy and vagotomy and vagotomy pyloroplasty antrectomy

Operative mortality 0 <1 1 rate (%) Ulcer recurrence 5–15 5–15 < 2 rate (%)

Dumping (%) Mild < 5 10 10–15 Severe 0 1 1–2

Diarrhea (%) Mild <5 25 20 Severe 0 2 1–2

Source: Modified with permission from Mulholland MW, Debas HT: Chronic

duodenal and gastric ulcer. Surg Clin North Am 67:489, 1987.

after parietal cell vagotomy; liquid emptying may be normal or increased because of decreased compliance associated with loss of receptive relaxation and accommodation. When applied to uncomplicated duodenal ulcer, the recurrent ulcer rate is higher with HSV than with vagotomy and antrectomy. However our increased understanding of the pathophysiologic role of Helicobacter and NSAIDs in the development of recurrent ulcer may mitigate this concern. HSV has not performed particularly well as a treatment for type II (gastric and duodenal) and III (prepyloric) gastric ulcer, perhaps because of hypergastrinemia caused by gastric outlet obstruction and persistent antral stasis. Truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy are the paradigmatic vagotomy and drainage procedures (TV and D), although total gastric vagotomy (selective vagotomy [SV]) and drainage, and HSV and gastrojejunostomy have also been shown to be effective ulcer operations in selected patients. The advantage of TV and D is that it can be performed safely and quickly by the experienced surgeon. The main disadvantage is the side effect profile (10 percent with significant dumping and/or diarrhea), and a 10 percent recurrent ulcer rate. Whether the incidence of these postoperative problems (heretofore determined in studies predominantly involving patients with intractable uncomplicated duodenal ulcer) will be different in the current era of complicated ulcer, Helicobacter, and NSAIDs is unknown. Truncal vagotomy denervates the antropyloric mechanism and therefore some sort of procedure is necessary to ablate or bypass the pylorus, otherwise gastric stasis often results. Gastrojejunostomy or pyloroplasty are the classic drainage procedures. The advantage of vagotomy and antrectomy (V and A) is the extremely low ulcer recurrence rate and the applicability of the operation to many patients with complicated peptic ulcer (e.g., bleeding duodenal and gastric ulcer; obstructing peptic ulcer; nonhealing gastric ulcer; recurrent ulcer). When applied to gastric ulcer, the resection is usually extended far enough proximally to include the ulcer. The disadvantage of V and A is the somewhat higher operative mortality rate when compared with HSV, or V and D. Following antrectomy, gastrointestinal continuity may be re-established either as a Billroth I gastroduodenostomy or a Billroth II loop gastrojejunostomy. Because antrectomy routinely leaves a 60–70 percent gastric remnant, reconstruction as a Roux gastrojejunostomy should be avoided. The Roux operation is an excellent procedure for keeping duodenal contents out of the stomach and esophagus.

TABLE Surgical Options in the Treatment of Duodenal and Gastric Ulcer Disease

Indication Duodenal Gastric


1. Oversew

2. Oversew, V + D

3. V + A

1. Oversew and biopsya

2. Oversew, biopsy, V + D

3. Distal gastrectomyb


1. Patch

2. Patch, HSVb

3. Patch, V + D

1. Biopsy and patch

2. Wedge excision, V + D

3. Distal gastrectomyb


1. HSV + GJ

2. V + A

1. Biopsy; HSV + GJ

2. Distal gastrectomyb



1. HSVb

2. V + D

3. V + A

1. HSV and wedge excision

2. Distal gastrectomy

A. Unless the patient is in shock or moribund, a definitive procedure should be considered.

B.Operation of choice in low-risk patient.

GJ=gastrojejunostomy; HSV=highly-selective vagotomy; V+A=vagotomy and antrectomy; V + D = vagotomy and drainage.

in the presence of a large gastric remnant, this reconstruction will predispose to marginal ulceration and/or gastric stasis. Distal gastrectomy without vagotomy (usually approximately 50 percent gastrectomy to include the ulcer) has traditionally been the procedure of choice for type I gastric ulcer. Reconstruction may be done as a Billroth I (preferable) or II. Truncal vagotomy is added for Type 2 and 3 gastric ulcers, or if the patient is believed to be at increased risk for recurrent ulcer, and should be considered if Billroth II reconstruction is contemplated. Although not routinely used nowadays in the surgical treatment of peptic ulcer, subtotal gastrectomy (75 percent distal gastrectomy) without vagotomy may be an appealing operation for an occasional ulcer patient. The choice of operation for the individual patient with peptic ulcer disease depends on a variety of factors including (inter alia) the type of ulcer (duodenal, gastric, recurrent or marginal), the indication for operation, and the condition of the patient. Other important considerations are intraabdominal factors (duodenal scarring/inflammation; adhesions; difficult exposure), the virulence of the ulcer diathesis, the surgeon’s experience and personal preference, the Helicobacter status, the need for continued NSAID therapy, previous treatment, and the likelihood of future compliance with treatment. Table 25-8 shows the surgical options for managing various aspects of peptic ulcer disease. In general, resective procedures have a lower ulcer recurrence rate, but a higher operative morbidity and mortality (see Table 25-7) when compared to nonresective ulcer operations.We now know that ulcer recurrence is often related to Helicobacter and/or NSAIDs, and usually is managed adequately without reoperation. Thus gastric resection to minimize recurrence in duodenal ulcer disease is often not justified today; resection for gastric ulcer remains the standard because of the risk of cancer.


Patients coming to operation for bleeding peptic ulcer today are more selected toward a poor surgical result then ever before. The surgical options for treating bleeding peptic ulcer are three: suture ligation of the bleeder (and biopsy for gastric ulcer); suture ligation and definitive nonresective ulcer operation (HSV or V and D); and gastric resection (usually including vagotomy and ulcer excision). Indications for operation in bleeding ulcer are: (1) massive hemorrhage unresponsive to endoscopic control, (2) transfusion requirement of greater than 4 to 6 units of blood despite attempts at endoscopic control. Unavailability of therapeutic endoscopist, recurrent hemorrhage after one or more attempts at endoscopic control, unavailability of blood for transfusion, repeat hospitalization for bleeding duodenal ulcer and concurrent indication for surgery such as perforation or obstruction are also indications for operation. Early operation should be considered in patients over 60, those presenting in shock, those requiring more than four units of blood in 24 h or eight units of blood in 48 h, those with rebleeding, and those with ulcers greater than 2 cm in diameter or strategically located as described above. The two operations most commonly used for bleeding duodenal ulcer are: vagotomy and drainage combined with oversewing of the ulcer, or vagotomy and antrectomy. The trade-off appears to be an increased risk of rebleeding with the vagotomy and drainage procedure versus the increased operative mortality of vagotomy and antrectomy. When the mortality for reoperation for rebleeding is considered, the overall mortality is probably comparable for the two approaches. Patients who are in shock or medically unstable should not have gastric resection. Bleeding gastric ulcer tends to occur in older and/or medically complicated patients that tend to increase the operative risk. Although this has been used by some as an excuse not to operate early on these patients, experience shows that planned operation in a resuscitated patient results in a better operative mortality than emergent operation in a patient who has rebled and is in shock. Those patients with gastric ulcer bleeding likely to require operation have bled more than six units and have presented in shock. Endoscopically their ulcers tend to be on the lesser curvature with the usual stigmata of recent hemorrhage. Distal gastric resection to include the bleeding ulcer is the operation of choice for bleeding gastric ulcer. Second best is vagotomy and drainage, with oversewing and biopsy of the ulcer. Oversewing of the bleeder followed by long-term acid suppression is a reasonable alternative in extremely high risk patients. The specter of cancer is ever present in the patient with gastric ulcer whether it is bleeding or not.


Perforation is the second most common complication of peptic ulcer. As with bleeding peptic ulcer, NSAIDS also have been inextricably linked with perforated peptic ulcer disease especially in the older adult population. Well over 20 percent of patients older than the age of 60 presenting with a perforated ulcer are taking NSAIDS at the time of perforation. Operation is almost always indicated although occasionally nonoperative treatment can be used in the stable patient without peritonitis and in whom radiologic studies document a sealed perforation. The options for surgical treatment of perforated duodenal ulcer are simple patch closure, patch closure and HSV, or patch closure and TV/D. Simple patch closure alone should be done in patients with hemodynamic instability and/or exudative peritonitis signifying a perforation over 24 h old. In all other patients the addition of a definitive ulcer operation (HSV or V and D) should be considered. Numerous studies have reported a negligible mortality with this approach. Early data now suggest that simple closure of perforated duodenal ulcer may achieve satisfactory long term results when H. pylori infection (present in 50–75 percent with perforated duodenal ulcer) is eliminated. On the other hand it is sometimes difficult to determine the H. pylori status of the patient having emergent operation for perforated ulcer. Furthermore it is doubtful whether many of these patients will comply with the medication regimen required to eradicate Helicobacter. Thus using possible H. pylori infection as an excuse not to do a definitive ulcer operation in any patients with perforated duodenal ulcer is irrational. Perforated gastric ulcer carriers a higher mortality rate than perforated duodenal ulcer (10–40 percent). This is generally through to represent the gastric ulcer patients’ higher age, increased medical comorbidities, delay in seeking medical attention and large size of gastric ulcers. Perforated gastric ulcers are associated with NSAIDS and tobacco use, and often present without prior symptoms. All perforated gastric ulcers are best treated by gastric resection (to include the ulcer) with or without truncal vagotomy depending on ulcer type. Vagotomy is usually performed for type II and III gastric ulcers. Patch closure with biopsy; or local excision and closure; or biopsy, closure, truncal vagotomy and drainage are alternative operations. All perforated gastric ulcers even those in the pre pyloric position should be biopsied if they are not removed at surgery.


Gastric outlet obstruction is the least common ulcer complication requiring operative treatment. Endoscopic balloon dilation can often transiently improve obstructive symptoms, but many of these patients ultimately fail and come to operation. The most common operations for obstructing peptic ulcer disease are vagotomy and antrectomy, and vagotomy and drainage. HSV and gastrojejunostomy is an appealing operation for obstruction, both because it can be done as a laparoscopic assisted procedure, and because it does not complicate future resection should this be needed. All gastric ulcers associated with obstruction should be adequately biopsied if not resected.


This should indeed be a rare indication for operation nowadays. Arguably, the patient referred for surgical evaluation because of intractable peptic ulcer disease should raise red flags with the surgeon. Acid secretion can be totally blocked and Helicobacter eradicated with modern medication, so why does the patient have a persistent ulcer diathesis? The surgeon should review the differential diagnosis of nonhealing ulcer (Table 25-9) prior to any consideration of operative treatment. Surgical treatment should be considered in patients with nonhealing or intractable peptic ulcer who have multiple recurrences, large ulcers (>2 cm), complications (obstruction, perforation or hemorrhage), or suspected gastric cancer. Operation should be considered most cautiously in the thin or marginally nourished individual. If operation is necessary for intractability, less is often better. Our preferred operations for this group of patients is HSV. In patients with nonhealing gastric ulcer, wedge resection either with HSV or TV and D should be considered in thin or frail patients, and it patients with inconveniently situated ulcers (biopsy alone is sometimes appropriate). Otherwise distal gastrectomy (to include the ulcer) is recommended. It is unnecessary to add a vagotomy to distal gastrectomy in all patients with Type I gastric ulcer.

TABLE Differential Diagnosis of Intractability or Nonhealing Peptic Ulcer Disease





Persistent H. pylori infection

Tests may be false-negative

Consider empiric treatment

Noncompliant patient

Failure to take prescribed medication

Surreptitious use of nonsteroidal anti-inflammatory drugs

Motility disorder

Zollinger-Ellison syndrome

Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is caused by the uncontrolled secretion of abnormal amounts of gastrin by a pancreatic or duodenal neuroendocrine tumor, i.e., gastrinoma. The inherited or familial form of gastrinoma (20 percent of cases) is associated with multiple endocrine neoplasia type I (MEN I) which consists of parathyroid, pituitary, and pancreatic (or duodenal) tumors. Patients with MEN I usually have multiple gastrinoma tumors and surgical cure is unusual. Sporadic gastrinomas are more often solitary and amenable to surgical cure. Nowadays about 50 percent of gastrinomas are malignant, with lymph node, liver, or other distant metastases at presentation. Five-year survival in patients presenting with metastatic disease is around 40 percent. The most common symptoms of ZES are epigastric pain, GERD, and diarrhea. The average age of presentation is 50 years, and over 90 percent of patients with gastrinoma have peptic ulcer. Most ulcers are in the typical location (proximal duodenum), but atypical ulcer location (distal duodenum, jejunum, multiple ulcers) should prompt an evaluation for gastrinoma.

Gastrinoma should also be considered in the differential diagnosis of recurrent or refractory peptic ulcer, secretory diarrhea, gastric rugal hypertrophy, esophagitis with stricture, bleeding or perforated ulcer, familial ulcer, and ulcer in the setting of hypercalcemia. Causes of hypergastrinemia can be divided into those associated with hyperacidity and those associated with hypoacidity. The diagnosis of ZES is confirmed by the secretin stimulation test.

TABLE Differential Diagnosis of Hypergastrinemia with excessive gastric acid formation (ulcerogenic)

Zollinger-Ellison syndrome

Gastric outlet obstruction

Retained gastric antrum (after Billroth II reconstruction)

G-cell hyperplasia

Without excessive gastric acid formation (nonulcerogenic)

Pernicious anemia

Atrophic gastritis

Renal failure


Short gut syndrome (after significant intestinal resection)

Eighty percent of primary tumors are found in the gastrinoma triangle and many tumors are small (<1 cm) making preoperative localization difficult. Transabdominal ultrasound is quite specific, but not very sensitive. CT scan will detect most lesions over 2 cm and MRI is comparable. Endoscopic ultrasound is more sensitive than these other noninvasive imaging tests, but it still misses many of the smaller lesions, and may confuse normal lymph nodes for gastrinoma. Currently, the imaging study of choice for gastrinoma is somatostatin receptor scintigraphy (SRS, the octreotide scan). Arteriography with selective visceral arterial infusion of secretin, and simultaneous hepatic venous gastrin sampling, may help localize the tumor as inside or outside the gastrinoma triangle. All patients with sporadic (nonfamilial) gastrinoma should be considered for surgical resection and possible cure. Thorough exploration by an experienced surgeon is important. The lesion should be found in 90 percent of patients and 60 percent are cured. Acid hypersecretion in patients with gastrinoma can always be managed with high dose proton pump inhibitors. Highly selective vagotomy may make management easier in some patients and should be considered in patients with surgically untreatable or unresectable gastrinoma.


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