Gastrointestinal effects of nonsteroidal anti-inflammatory therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of many conditions including rheumatoid arthritis, osteoarthritis, gouty arthritis, the joint and muscle discomfort associated with systemic lupus erythematosus, and other musculoskeletal disorders. Yet, their benefits, which are believed to be a result of their ability to inhibit cyclooxygenase-2 (COX-2), are accompanied by considerable toxicity. NSAIDs' untoward effects are attributed to their inhibition of the constitutively expressed enzyme cyclooxygenase-1 (COX-1), with attendant suppression of the synthesis of prostanoids, substances that mediate key homeostatic functions. Side effects include suppression of hemostasis through inhibition of platelet aggregation, adverse effects in patients with heart failure and cirrhosis, and those with certain renal diseases, as well as complicating antihypertensive therapies involving diuretics or beta-adrenoceptor blockade. Perhaps most importantly, NSAIDs disrupt the gastrointestinal mucosal-protective and acid-limiting properties of prostaglandins, frequently leading to upper gastrointestinal erosions and ulceration, with possible subsequent hemorrhage and perforation. These complications can be reduced through identification of patients at risk, with circumspect use of NSAIDs, careful functional monitoring, and, in the case of gastrointestinal toxicity, co-administration of such agents as misoprostol or omeprazole. However, these strategies introduce complexity into the treatment paradigm. Moreover, side effects and adverse events may be significantly reduced through the use of COX-2-specific inhibitors, new agents that alleviate pain and inflammation without the liability for adverse events caused by COX-1 inhibition.

'Domino' liver transplantation combined with multivisceral transplantation.

Transplantation of the liver contemporaneously with another organ from the same donor is thought to confer an immunologic advantage. The latter is particularly desirable in intestinal transplantation because of the propensity of the intestinal graft to early and late rejections and because in some cases it may facilitate the operation. In clinical practice, shortage of liver grafts constrains liver transplantation to cases in which there is coexisting end stage liver disease.

Recent developments in gastrointestinal endoscopy.

Endoscopic findings can be extremely valuable in directing or altering specific treatment. Endoscopy also has therapeutic applications, such as removal of polyps (gastric or colonic), coagulation of bleeding sites in cases of upper gastrointestinal bleeding, and the removal of foreign objects from the gastrointestinal tract. Laparoscopy is an easily performed procedure with minimal risk. On of its greatest values is in investigating diseases of the liver. Coloscopy has many uses, including evaluation of equivocal x-ray findings and histologic confirmation of cancer. Endoscopic retrograde cholangiopancreatography (ERCP) is a new, highly sophisticated procedure that offers a major advantage in investigating pancreatic disease and evaluating jaundice.

Juvenile polyposis coli concurrent with neurofibromatosis.

Juvenile polyposis coli associated with neurofibromatosis in a 24-year-old white man is reported. Juvenile polyposis coli is now recognized as a distinct clinical entity. Differentiating it from the other hereditable gastrointestinal polyposis syndromes is important because of the lack of reported malignancies. Radical surgery is unnecessary unless warranted by the clinical features of bleeding or diarrhea. The known gastrointestinal and extra gastrointestinal associations with juvenile polyposis coli are reviewed along with the gastrointestinal manifestations of neurofibromatosis. This is the first reported association of neurofibromatosis with this unusual syndrome.

Diverticular disease of the colon.

Diverticular disease of the colon is quite common in developed countries, and its prevalence increases with age. Although present in perhaps two thirds of the elderly population, the large majority of patients will remain entirely asymptomatic. Nonetheless, an estimated 20% of those affected may manifest clinical illness, mainly diverticulitis, with its potential complications of abscesses, fistulas, and obstruction, as well as lower intestinal hemorrhage. The purpose of this report is to review our understanding of the epidemiology, pathophysiology, clinical presentation, and treatment options for this disorder.

Esophageal biopsy findings in the acquired immunodeficiency syndrome (AIDS): clinicopathologic correlation in 20 patients.

We reviewed 20 esophageal biopsy specimens from 180 adult patients with the acquired immunodeficiency syndrome (AIDS). Ten (50%) showed superficial Candida infection, and four revealed esophagitis due to cytomegalovirus. Candida was never invasive, even though it was associated with significant ulceration. Esophageal candidiasis did not necessarily imply the presence of oral candidiasis, and conversely, oral candidiasis did not imply esophageal candidiasis. Odynophagia was associated with significant histologic ulcerations in eight of ten patients. In the patients who had odynophagia, biopsy was almost equally likely to show Candida or viral cytopathic effect. We discuss the clinicopathologic implications of these findings.

Pancreatic ascites: successful treatment with pancreatic radiation.

A 51-year-old man with clinical and laboratory findings consistent with the diagnosis of pancreatic ascites is reported. Response to usual medical measures was inadequate. Single-dose irradiation to the pancreatic area (550 rads) resulted in marked improvement in his ascites. Operative pancreatogram months later revealed no evidence of ductal leakage. Low-dose pancreatic irradiation may be a unseful therapeutic adjunct in the older, high-risk patient with pancreatic ascites in whom surgery is not considered feasible.

The uncleared fundal pool in acute upper gastrointestinal bleeding: implications and outcomes.

BACKGROUND: The implications and outcomes of patients with an uncleared fundal pool of blood found at emergent upper endoscopy are not well described. METHODS: We reviewed the records of 484 consecutive patients who presented over a 12-month period to our medical center with acute upper gastrointestinal hemorrhage. All patients underwent upper endoscopy within 24 hours of their initial presentation. Patients with an uncleared fundal pool of blood at initial endoscopy were included in this study, and their findings and outcomes were compared with a randomly selected subgroup of these same patients who did not have residual gastric blood. RESULTS: Sixty-one patients (13%) had uncleared fundal pools despite gastric lavage and patient positioning. Findings on initial endoscopy included esophageal varices in 29 (47%), gastric ulcer in 12 (20%), portal hypertensive gastropathy in 5 (8%), Mallory-Weiss tear in 5 (8%), duodenal ulcer in 5 (8%), gastric varices in 4 (7%), Dieulafoy's lesion in 2 (3%), and other in 7 (11%). Twelve of these 61 patients had multiple findings and 4 (7%) had no lesion identified. Thirty-two of the 61 patients (52%) had at least one follow-up endoscopy, with new fundal lesions identified in 13 (41%): portal hypertensive gastropathy in 8, gastric ulcer in 2, gastric varices in 2, and leiomyoma in 1. Of these 13 new findings, 5 (38%) were judged significant either by the presence of active bleeding or stigmata of recent hemorrhage. Of the 4 patients with no identifiable lesion on initial endoscopy, 3 had a follow-up endoscopy and 2 were found to have a significant new finding in the fundus. The control group had a statistically significant lower percentage of endoscopic findings related to portal hypertension. Recurrent bleeding during the index hospitalization occurred in 54% of the patients with uncleared fundal pools versus 11% of the control group (0 < 0.01). Length of stay, number of units of blood transfused, need for emergent surgery for bleeding, as well as overall and bleeding-related mortality were all significantly greater in the patients with the uncleared fundal pool than in the control patients. CONCLUSIONS: The inability to clear a fundal pool of blood at emergent upper endoscopy is associated with significant morbidity and mortality. Further, new fundal lesions can be identified in 41% of patients on follow-up examination, with many being clinically significant. These data support the importance of clearing a fundal pool in patients undergoing endoscopy for upper gastrointestinal bleeding.

Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.

OBJECTIVE: To compare ranitidine to misoprostol with respect to the prevention of gastric and duodenal ulcers in patients on chronic NSAID therapy. METHODS: A multi-center, 8-wk, randomized, double-blind study. Eligible patients were on chronic NSAID therapy and were experiencing NSAID-related upper gastrointestinal (UGI) pain without UGI endoscopic evidence of gastric or duodenal ulcers. Patients enrolled in the study were randomized to either misoprostol 200 micrograms q.i.d. or ranitidine 150 mg b.i.d.. Follow-up UGI endoscopy was performed after 4 and 8 wk of treatment. Therapeutic failure was considered the development of a gastric or duodenal ulcer > or = 0.3 cm in diameter with perceptible depth. RESULTS: Gastric ulcers were found in only 1/180 (0.56%) patient on misoprostol and in 11/194 (5.67%) patients on ranitidine, a difference that was statistically significant (p < 0.01). Duodenal ulcer rates were similar for the ranitidine (2/185 or 1.08%) and misoprostol (2/181 or 1.10%) groups. CONCLUSION: Misoprostol is significantly more effective than ranitidine in the prevention of NSAID-induced gastric ulcers. Ranitidine was as effective as misoprostol for the prevention of NSAID-induced duodenal ulcers. Misoprostol should be used for prophylaxis against both gastric and duodenal ulceration in patients on chronic NSAID therapy.

Colonoscopic evaluation of rectal bleeding: a study of 304 patients.

We studied 258 patients with rectal bleeding and 46 patients with anemia and occult blood in the stool. All 304 patients had negative proctosigmoidoscopies, single-contrast barium studies that were negative or showed diverticula only, and colonoscopic evaluation. In the 258 patients, the overall incidence of finding significant lesions by colonoscopy was 41.5%. Twenty-nine patients (11.2%) had carcinoma and 17 patients (6.6%) had cecal telangiectasia. In the 46 patients, the overall incidence of finding significant lesions was 19.6%. Three patients with carcinoma were found in this group. A significant number of both benign and malignant lesions were detected by colonoscopy proximal to the splenic flexure. Colonoscopy should be done in patients with rectal bleeding or anemia and occult blood in the stool who have had negative proctosigmoidoscopies and single-contrast barium studies interpreted as normal or showing diverticula.

The unusual presentation of "large" gallstones. The diagnostic role of endoscopy.

Large gallstones are usually seen in old people, but are distinctly uncommon. They may cause complicated gallbladder disease requiring extensive surgery. Unusual presentations of such stones include Mirizzi's syndrome, biliary fistulas, and gastric outlet obstruction (Bouveret's syndrome). Preoperative endoscopy can accurately define these complications to facilitate their surgical management.

Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens.

OBJECTIVE: To compare the effectiveness and tolerability of three misoprostol dosing regimens for the prevention of gastric and duodenal ulcers associated with long-term nonsteroidal anti-inflammatory drug (NSAID) therapy. DESIGN: A multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel, four-limb study. PATIENTS: Eligibility criteria included upper gastrointestinal symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession and regimen-compliance criteria and completed the trial. These 1197 patients composed the evaluable group. INTERVENTIONS: Patients were randomly assigned to one of four regimens: placebo four times daily; 200 micrograms of misoprostol twice daily and placebo twice daily; 200 micrograms of misoprostol three times daily and placebo once daily; and 200 micrograms of misoprostol four times daily. MEASUREMENTS: Upper gastrointestinal endoscopic examinations for ulcers were done after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were assessed by adverse-event monitoring. RESULTS: In the placebo group, the incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was 7.5%. The incidence of gastric ulcers was significantly lower in the groups receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to 12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to 16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to 16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was significantly higher in patients receiving misoprostol twice daily compared with those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to 7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was significantly lower in the groups receiving misoprostol twice daily (2.6%; difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%; difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%; difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No significant difference was detected between patients receiving misoprostol twice daily and those receiving misoprostol three times daily, and no dose-response effect was noted with duodenal ulcers. The incidence of withdrawals for adverse events was significantly lower in the groups receiving misoprostol twice daily (12%) and three times daily (12%) than in the group receiving it four times daily (20%). The incidence of gastrointestinal adverse events was significantly higher in the group receiving misoprostol four times daily (74%) than in the placebo group (62%). CONCLUSION: Misoprostol, 200 micrograms twice or three times daily, offers substantial protection against gastric and duodenal ulcers in patients receiving long-term NSAID therapy. These dosages were better tolerated than the currently approved regimen of 200 micrograms four times daily.

Cimetidine, antacid, and hospitalization in the treatment of benign gastric ulcer: a multicenter double blind study.

Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.