A 45-year-old man presents with a 2-month history of epigastric abdominal pain. He describes the pain as burning and says that it occurs at night or early in the morning. The patient has found that eating food generally improves these symptoms. The patient admits to having had similar symptoms intermittently during the past several years, and over-the-counter H2 antagonists have always resolved his symptoms. He denies any weight loss, vomiting, or melena. He has no family history of significant medical problems. The patient’s physical examination reveals a normal head and neck, and cardiopulmonary examinations show no abnormalities. The abdomen is nondistended, minimally tender in the epigastrium, and without masses. A rectal examination reveals Hemoccult-negative stool. Laboratory studies reveal normal values for the white blood cell (WBC) count, hemoglobin and hematocrit levels, platelet count, electrolyte levels, serum amylase level, and liver function tests.
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ANSWERS TO CASE 39: Peptic Ulcer Disease
Summary: A 45-year-old man has signs and symptoms consistent with peptic ulcer disease (PUD). The patient has self-medicated with H2-receptor antagonists in the past with success, but the symptoms are currently unrelieved with medication.
• Next step: Perform diagnostic esophagogastroduodenoscopy (EGD).
• Most likely diagnosis: PUD.
• Treatment options: Testing for Helicobacter pylori should be performed, and, if positive results are obtained, treatment should be administered. If the H pylori status is negative, conventional treatment for PUD should be administered (described next).
1. Be familiar with the five types of gastric ulcers and their implications in pathogenesis and treatment.
2. Be able to discuss the relationship between H pylori and PUD.
3. Become familiar with the mechanisms of action and the efficacy of medications used for the treatment of PUD.
4. Become familiar with the indications for surgery in the treatment of ulcer disease.
The case involves a 45-year-old man with “burning” epigastric pain that improves with eating. This scenario suggests a diagnosis of PUD that is refractory to medical management. However, whenever such a patient is encountered, the initial step should be to evaluate for other disease processes (ie, pancreatitis, gastric malignancy, biliary colic). In this case, upper gastrointestinal (GI) endoscopy is indicated to assess the ulcer disease, as well as the esophagus, stomach, and duodenum. When indicated, ultrasonography and computed tomography (CT) imaging of the abdomen may be useful to help identify pathology in the upper abdomen. When it is confirmed that the patient is indeed suffering from PUD, it is important to question the patient to see if he has been compliant with the medical therapy. Failure of optimal medical therapy may be influenced by the presence of H pylori, high gastrin levels, or noxious stimuli such as nonsteroidal anti-inflammatory drugs (NSAIDs).
APPROACH TO: Ulcer Disease
Despite advances in medical therapy for the inhibition of acid secretion and the eradication of H pylori, surgery remains important in treating patients suffering from PUD. Moreover, the introduction of more effective antiulcer medications has not decreased the mortality from PUD-related complications, which has remained stable or risen slightly. Furthermore, with the high recurrence rate of ulcers following the discontinuation of medical therapy, a renewed interest in operative therapy has emerged. There has been a change in the type of surgery performed on patients with PUD in the H pylori era. Specifically, gastric resections are now less frequently performed, and vagotomy procedures with or without drainage seem to be preferred. Operative approach to patients with PUD requires a balanced approach to address the PUD while minimizing postoperative symptoms, gastrointestinal dysfunction, and complications.
Pathophysiology of Peptic Ulcer Disease
Benign Gastric Ulcer
The number of hospitalizations and operations for patients with benign gastric ulcers may be increasing slightly because of the greater use and abuse of NSAIDs, particularly among women. As shown in Table 39–1, there are five types of gastric ulcers. The most common, accounting for 60% to 70% of these ulcers, are type I ulcers located on the lesser curvature at or proximal to the incisura. Hypersecretion of acid is generally not a causative factor, but acid likely plays a permissive role in ulcer development and accentuates its progression once it occurs. Evidence also suggests that H pylori has a role in ulcer pathogenesis, although the etiologic role is not as strong as in the case of duodenal ulcers. In general, hemorrhage is infrequent in this setting, although penetration with or without perforation is not uncommon. Type II ulcers account for approximately 20% and are in the same location as type I lesions but are also associated with duodenal ulcer disease and excessive acid secretion. Hemorrhage, obstruction, and perforation are frequently seen with this type of gastric ulcer. Type III gastric ulcers are located within 2 cm of the pylorus (ie, prepyloric) and are also associated with excess acid secretion. Again, hemorrhage and perforation are frequent with this type of gastric ulcer. Type IV gastric ulcers are rarely encountered but are situated within 2 cm of the gastroesophageal junction, are associated with hypochlorhydria, and carry a significant operative mortality risk, as most patients with type IV ulcers are elderly. Hemorrhage is uncommon in this type of ulcer, although penetration is frequent. Type V gastric ulcer can occur anywhere in the stomach and is a direct result of chronic ingestion of aspirin or NSAIDs.
Table 39–1 • TYPES OF GASTRIC ULCERS
The number of hospitalizations and elective operations for duodenal ulcer disease has decreased dramatically over the past three decades. However, the number of urgent operations appears to be increasing; also, because patients requiring surgery tend to be older than previously, there is increased perioperative morbidity and mortality. Duodenal ulcer disease has multiple etiologies. The most common contributing mechanisms to PUD are acid and pepsin secretion in conjunction with an H pylori infection or the ingestion of NSAIDs. Gastric acid secretory rates are usually increased in patients with duodenal ulcer disease. There is strong evidence for an association between gastric antral infestation with H pylori and duodenal ulcer disease, particularly in ulcers that are resistant to or recur after standard antisecretory therapy. Moreover, in patients infected with H pylori, complete eradication of the organism results in extraordinarily high healing rates and low recurrence rates of approximately 2%.
Treatment of Uncomplicated Peptic Ulcer Disease
Following a review of the patient’s history, a physical examination, and routine laboratory studies, endoscopy is generally performed (Figure 39–1). Testing for H pylori should be performed because H pyloriis present in most gastric ulcer patients (60%-90%), and those who are not infected tend to be NSAID users. H pylori is found in more than 90% of patients with duodenal ulcer disease. Nearly all of the currently available tests for detecting H pylorihave good sensitivity and specificity. Noninvasive testing includes a serologic study and a urea breath test. Useful invasive tests include the rapid urease assay or a histologic study and cultures in conjunction with endoscopy. For an initial diagnosis without endoscopy, a serologic study is the test of choice. With endoscopy, the rapid urease assay and a histologic examination are both excellent options, although the rapid urease test is less expensive. If patients test positive for H pylori, treatment should be instituted. Failure to eradicate H pylori leads to an annual relapse of roughly 58%, as opposed to roughly 2% when H pylori has been eradicated. In general, triple therapy regimens are more successful than dual therapy or monotherapy for eradicating H pylori. Three promising triple regimens are currently available: OAC, OMC, and OAM (O, omeprazole or other proton pump inhibitor [PPI]; A, amoxicillin; C, clarithromycin; and M, metronidazole). These medications are used for 1 to 2 weeks, do not contain bismuth, and are taken twice daily. For patients who are negative for H pylori, conventional treatment with an antisecretory agent (PPI or H2 antagonist) should be administered.
Figure 39–1. Algorithm for the management of peptic ulcer disease. CBC, complete blood count; NSAIDs, nonsteroidal anti-inflammatory drugs; UGI, upper gastrointestinal.
Table 39–2 shows the agents available for the medical treatment of gastric ulcers along with their mechanism of action. In general, drugs can heal ulcers by neutralizing acid secretion or by restoring mucosal defenses. Although both H2-receptor antagonists and PPIs inhibit acid secretion, PPIs block all types of acid secretion because of their direct inhibition of the proton pump. As a result, they also produce more effective and prolonged inhibition of acid secretion than H2 blockers.
Table 39–2 • MEDICAL THERAPY FOR PEPTIC ULCER DISEASE
A gastric ulcer should be treated for 8 to 12 weeks and then evaluated for healing. If it has not healed, a biopsy should be repeated to rule out malignancy. If it has healed, maintenance therapy should be considered provided the patient is not taking NSAIDs and does not have documented H pylori infection.
In the setting of NSAID use, it is best to discontinue these drugs if possible while the ulcer is being treated. Ulcer therapy is still initiated with an antacid secretory agent, preferably a PPI. H pylori infection should also be treated if present. For NSAID-dependent patients, cotherapy with misoprostol, a prostaglandin analogue, should be considered, or switching to a safer NSAID that selectively inhibits the inducible isoform of cyclo-oxygenase (ie, COX-2 inhibitor).
In both gastric and duodenal ulcer disease, surgery is indicated for the complications of PUD. Gastrointestinal hemorrhage, perforation, intractable pain, and obstruction are indications for surgical intervention. Ulcer disease is considered intractable if it persists for more than 3 months despite active and appropriate drug therapy, the ulcer recurs within 1 year after initial healing despite maintenance therapy, or if the ulcer disease is characterized by cycles of prolonged activity with brief remissions. Gastric ulcers should undergo biopsy early in the evaluation process because of the risk for carcinoma. Thus, for intractable gastric ulcers, excision of the ulcer should be performed in conjunction with proximal gastric vagotomy or some type of gastrectomy. For a type 1 gastric ulcer in the setting of intractability, elective distal gastrectomy with gastroduodenal (Billroth I) anastomosis is usually performed. The ulcer should be included in the antrectomy specimen. For type 2 gastric ulcers, antrectomy that includes the gastric ulcer is generally performed in conjunction with a truncal vagotomy to further reduce acid secretion and remove the gastric mucosa at risk for ulcer as well as the ulcer itself. The type of reconstruction, gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II), depends on how badly the duodenum is inflamed. An alternative is truncal vagotomy and gastrojejunostomy. A third option is vagotomy and pyloroplasty. For type 3 gastric ulcers, a vagotomy and antrectomy that include the ulcer is usually performed. As previously mentioned, type 4 gastric ulcers are difficult to treat, and the choice of operation depends on a number of factors. These include the size of the ulcer and the degree of surrounding inflammation, as well as the distance of the ulcer from the gastroesophageal junction. Type 5 gastric ulcers rarely require surgery, and, if this type of ulcer does not heal rapidly with the standard medical therapy mentioned earlier, malignant disease must be excluded.
For treatment of perforated duodenal ulcers, when there is no prior history of ulcer disease or if the patients are positive for H pylori, an omental patch closure may be performed followed by treatment for H pylori. If the patient has an underlying history of ulcer disease or is known to be negative for H pylori and is hemodynamically stable at the time of operation, a highly selective vagotomy is another option in addition to closure of the perforation. For the treatment of perforated gastric ulcers, the possibility of malignancy still must be addressed as well as the possibility of H pylori infection. Thus, depending on the type of gastric ulcer, the area requires biopsy with closure of the perforation. Alternatively, the ulcer can also be excised and/or resected with primary repair or a Billroth I or II reconstruction. For an obstruction, the patient can be treated with antrectomy and gastroduodenostomy, although if scarring is so severe as to preclude a safe anastomosis, gastrojejunostomy in conjunction with a truncal vagotomy should be performed.
39.1 A 42-year-old woman has progressive epigastric pain, which has improved somewhat with PPI. She underwent upper endoscopy and a gastric ulcer is diagnosed. Which of the following best describes a characteristic of gastric ulcers?
A. Type 1 gastric ulcers are usually not associated with excess acid secretion.
B. Type 1 gastric ulcers are usually located in the prepyloric region of the stomach.
C. Type 2 gastric ulcers are usually associated with esophageal disease.
D. Type 5 is a gastric ulcer associated with chronic steroid use.
E. Type 3 gastric ulcer is not associated with excess acid production.
39.2 A 35-year-old stock broker has midabdominal pain throughout the day, which is relieved somewhat by meals and antacids. A gallbladder ultrasound is negative. He undergoes an upper GI endoscopy which revealed a duodenal ulcer. Which of the following best describes characteristics of duodenal ulcer disease?
A. It is rarely associated with hypersecretion of acid.
B. It is a disease of multiple etiologies.
C. Complete eradication of H pylori is difficult and associated with frequent recurrences.
D. H pylori infestation usually occurs in the gastric cardia.
E. Duodenal ulcer predisposes the patient to subsequent malignancy.
39.3 Which of the following is correct regarding medical therapy of PUD?
A. PPIs and H2 antagonists have approximately equal efficacy in controlling ulcer disease.
B. Prostaglandin compounds such as misoprostol promote resolution of gastric ulcers by inhibiting the proton pump, thereby decreasing acid production.
C. NSAID-induced ulcers are sometimes associated with H pylori and require antibiotic therapy.
D. H1 receptors are associated with gastric acid secretion.
E. Patients with NSAID-induced ulcers generally do not respond to medical treatment.
39.4 A 35-year-old man is diagnosed with a duodenal ulcer. He asks about the indications for surgical therapy versus medical treatment. Which one of the following conditions would necessitate surgical therapy?
A. Development of diabetes mellitus
B. Persistent H pylori infection
C. Gastric outlet obstruction
D. Need for taking NSAID
E. Occult gastrointestinal hemorrhage
39.5 Which one of the following patients is most likely to require surgical intervention for the management of PUD?
A. A 44-year-old man with a 1-cm duodenal ulcer that is causing epigastric pain for 3 weeks. His H pylori serology is positive.
B. A 68-year-old woman who has been consuming NSAIDs for osteoarthritis and develops melena. She has remained hemodynamically stable and on endoscopy is found to have superficial ulcerations throughout the body of the stomach.
C. A 40-year-old man with epigastric and coffee-ground emesis. His endoscopy revealed a small ulcer in the gastric antrum and a second ulcer in the duodenal bulb. His H pylori serology is positive.
D. A 90-year-old man with decompensated congestive heart failure (CHF) with active GI bleeding from a duodenal ulcer visualized by endoscopy.
E. A 57-year-old man with a history of gastric ulcer that was biopsied 4 months ago and found to be benign. He has received treatment for H pylori and has been maintained on PPI and continues to have pain. Repeat endoscopy demonstrates a persistent gastric ulcer involving the lesser curve of the stomach near the antrum.
39.1 A. Type 1 gastric ulcers are usually not associated with excess acid secretion and are usually located on the lesser curvature of the stomach. Type 3 gastric ulcers are prepyloric ulcers and are associated with hyperacidity. Type 5 gastric ulcers are associated with chronic NSAID or aspirin use.
39.2 B. Duodenal ulcer disease has multiple etiologies and is commonly associated with acid hypersecretion. Acid-reduction therapy results in a high rate of ulcer resolution, but the eradication of H pylorihelps maintain a long-term ulcer cure. PUD does not predispose the patient for the development of malignancy.
39.3 C. Patients with NSAID-induced ulcers not uncommonly also have H pylori involvement, and when H pylori is documented, those affected require antibiotic therapy to promote complete healing. In general, PPIs have superior efficacy over H2 blockers. Ulcers produced by NSAIDs generally will heal with cessation of the NSAIDs and the administration of prostaglandin analogue.
39.4 C. Gastric outlet obstruction caused by a chronic duodenal ulcer is an indication for surgical therapy, as is the inability to exclude malignancy, intractable symptoms, active overt hemorrhage, and perforation.
39.5 E. This man has continued pain and nonhealing of his type I gastric ulcer, despite having received a course of therapy for H pylori, and is maintained on PPI. The patients described in choices A and C have duodenal ulcer and type 2 gastric ulcer, respectively. Because both patients are H pylori positive, they should respond to medical management that includes H pylori eradication. The patient described in choice B has gastric ulcers related to NSAID use. This should respond to the cessation of NSAID and treatment with misoprostol. The patient described in choice D has active bleeding from a duodenal ulcer. He also has decompensated CHF. His condition is probably best managed with nonoperative approaches such as endoscopic treatment and embolization.
Appreciation of the types of gastric ulcers helps in identifying the problem and directing the most appropriate therapy.
Prevention of ulcer recurrence requires H pylori eradication rather than treatment alone in selected cases.
In general, gastric ulcers should be biopsied to exclude malignancy.
Type 5 gastric ulcers related to NSAIDs or aspirin use rarely require surgery.
The indications for surgery for PUD are obstruction, hemorrhage, perforation, and intractable symptoms.
Dempsey DT. Stomach. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:889-948.
Gaughan CB, Dempsey DT. Management of duodenal ulcer. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Mosby Elsevier; 2011:68-73.
Newman NA, Mufeed S, Makary MA. Benign gastric ulcer. In: Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Mosby Elsevier; 2011:63-68.