Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.

BACKGROUND & AIMS: No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons). METHODS: We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells. RESULTS: Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration. CONCLUSIONS: Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103.

History, incidence, and epidemiology of diverticulosis.

Diverticulosis of the colon is a very common condition. Described as early as the 17th century, most of the information we now have is based on much of the work during the 20th century. Age, sex, race, and geography all play a specific role in the development of diverticula. It is the merging of these factors that changes the prevalence of diverticula and their manifestations. Symptomatic diverticula can lead to serious complications requiring both medical and surgical interventions to treat these complications when they occur. This review will focus on the history and epidemiology of diverticulosis in regard to age, sex, race, geography, and the epidemiology of complicated diverticular disease.

The association of Streptococcus bovis bacteremia and gastrointestinal diseases: a retrospective analysis.

There is a well-established association between Streptococcus bovis bacteremia (SBB) and colorectal cancer. However, SBB is also frequently associated with chronic liver disease and has been described with other gastrointestinal disorders. The aim of the study was to evaluate the prevalence of gastrointestinal disease in patients with SBB. Retrospective analysis of the microbiology database at Jackson Memorial Medical Center, Miami, Florida, between 1992 and 2002, was performed. Patients' clinical records were reviewed, with special focus on underlying gastrointestinal disease or other major comorbidities. Thirty-eight patients (83%) were adults and eight (17%) were pediatric patients. Nineteen patients presented with gastrointestinal disorders associated with SBB (41%). Nine adult patients (19%) had end-stage liver disease (five female). Six patients had alcohol-induced liver disease (one with concomitant chronic hepatitis C), with the remaining three cases related to autoimmune hepatitis, primary biliary cirrhosis, and nonalcoholic steatohepatitis. Colonic neoplasms (adenocarcinoma in 3 and adenomatous polyps in 3) were found in 6 of 10 adult patients in whom colonoscopic evaluation was performed. Seven adult patients had acquired immunodeficiency syndrome (AIDS) (18%). Mortality in the patients with AIDS and SBB was high (71%). No significant association with gastrointestinal diseases was found in the pediatric population. Bacteremia due to S. bovis in adults is frequently associated with hepatic dysfunction (1:4), colonic neoplasms (1:6), and AIDS (1:6). This association was valid for our adult population only. SBB is an early clue to the likely presence of these serious underlying conditions and warrants rigorous investigation when recognized.

Risk of postoperative infection in patients with bactibilia undergoing surgery for obstructive jaundice.

BACKGROUND: This study was performed to investigate the relationship between bactibilia and postoperative infection in patients undergoing surgery for obstructive jaundice. METHODS: With IRB approval, we prospectively examined 76 patients undergoing surgery for obstructive jaundice. It was the routine practice of the surgeons performing the operations to culture the common bile duct bile (CBDB). Rates of postoperative infection were analyzed with regard to the effect of positive bile cultures and biliary instrumentation preoperatively. RESULTS: Seventy-one patients had CBDB cultures, 16 of whom had bactibilia. Bactibilia was present in 15 of 47 (33%) who had preoperative ERCP versus one of 24 (4%) of those without preoperative ERCP (p = 0.0075). Postoperative infection, including pneumonia, bloodstream, central venous catheter, surgical site, intraabdominal, and urinary tract infection, occurred in six of 16 (38%) of those with bactibilia versus four of 55 (7%) of those without bactibilia (p = 0.0071). CONCLUSIONS: Preoperative ERCP was associated with an approximately eightfold increase in the likelihood of having culture-positive bile at the time of surgery for obstructive jaundice. Additionally, culture-positive bile at the time of surgery was associated with a greater than fivefold incidence of postoperative infection.

Diverticular disease of the colon.

Colonic diverticulosis refers to small outpouchings from the colonic lumen due to mucosal herniation through the colonic wall at sites of vascular perforation. Abnormal colonic motility and inadequate intake of dietary fibre have been implicated in its pathogenesis. This acquired abnormality is typically found in developed countries, and its prevalence rises with age. Most patients affected will remain entirely asymptomatic; however, 10-20% of those affected can manifest clinical syndromes, mainly diverticulitis and diverticular haemorrhage. As our elderly population grows, we can anticipate a concomitant rise in the number of patients with diverticular disease. Here, we review the incidence, pathophysiology, clinical presentation, and management of diverticular disease of the colon and its complications.

Prevalence of occult celiac disease in patients with iron-deficiency anemia: a prospective study.

BACKGROUND: Occult celiac disease has been reported in 0 to 6% of adults presenting with iron-deficiency anemia. Most prior studies have been retrospective or screened only a selected population of patients with small bowel biopsies. To more accurately define the true prevalence of this disorder in patients presenting with iron-deficiency anemia (with or without stool hemoccult positivity), we initiated this prospective study. METHODS: Esophagogastroduodenoscopy with small bowel biopsies and colonoscopy were performed in all iron-deficiency anemia patients (including those with hemoccult-positive stools) referred to the gastroenterology service during a 2-year period (1998-2000). Inclusion criteria included iron-deficiency anemia as defined by a serum ferritin < 25 ng/ml and anemia with hemoglobin < 12 g/dl. Patients were excluded for documented prior erosive, ulcerative, or malignant disease of the gastrointestinal tract, previous gastrointestinal surgery, overt gastrointestinal bleeding within the past 3 months, or inability to access the duodenum for biopsy. All patients underwent upper endoscopy with more than two biopsies of the distal duodenum and colonoscopy. A serum immunoglobulin A antiendomysial antibody test was to be performed in those patients with a positive small bowel biopsy to confirm the diagnosis of celiac disease. RESULTS: One hundred five of 139 consecutive patients with iron-deficiency anemia met the inclusion criteria and were enrolled in the study. Fifty-seven men (mean age, 51.6 yr) and 48 women (mean age, 54.1 yr) constituted the study population. The demographics of this study population included 36 blacks, 38 Hispanics, and 22 whites. Nine patients were of mixed or unknown ethnic background. Forty-three and eight-tenths percent of the men and 37.5% of women had hemoccult-positive stools, accounting for a total of 40.9% of the study patients. Upper endoscopic findings included gastritis in 22.8%, gastric ulcers in 9.5%, duodenitis in 8.5%, esophagitis in 7.6%, Barrett's ulcer in 2.8%, duodenal ulcer in 2.8%, gastric polyp in 2.8%, and celiac disease in 2.8%. Colonoscopic findings included colon polyps in 21.9%, diverticula in 10.4%, and hemorrhoids in 16.1%. Multiple findings were found in 32.3% of patients, and there were no findings in 28.5% of patients. CONCLUSION: The prevalence of occult celiac disease in this prospective study of patients presenting with iron-deficiency anemia was 2.8%. A significant number of other gastrointestinal lesions amenable to therapy were also found on upper and lower endoscopy in these patients. Given the treatable nature of celiac disease, it should be screened for in patients with unexplained iron-deficiency anemia with or without hemoccult-positive stools.

Acquired hyperplastic gastric polyps in solid organ transplant patients.

OBJECTIVE: We report a series of patients who developed hyperplastic gastric polyps after solid organ transplantation. METHODS: A retrospective review of patients with solid organ transplantation from January 1997 to December 1999 was performed. Patients with gastric polyps found during endoscopy were included. Demographic data, polyp characteristics (endoscopic and histological), time of endoscopy, and treatment regimens were analyzed. RESULTS: A total of 10 (seven men, three women) transplanted patients (six cardiac, three liver, and one kidney) with gastric polyps were identified. The median age was 61 yr (27-71 yr), and median time of endoscopy after transplantation was 11 months (3-28 months). Eight patients had endoscopy before or soon after transplantation, with no evidence of polyps. Nine patients had multiple polyps (three or more), and one had a single pedunculated polyp. Polyps were confined to the antrum in eight patients, antrum and body in one patient, and fundus in one patient. All polyps biopsied were found to be hyperplastic and without adenomatous or malignant changes. Cytomegalovirus serology was negative in nine patients. Each patient received standard immunosuppression that included a calcineurin inhibitor and steroids. Steroids were tapered and stopped by 3 months. Azathioprine was added in five patients and mycophenolate mofetil in one patient. CONCLUSIONS: The development of gastric polyps after organ transplantation has not been previously reported. The development of these gastric polyps (hyperplastic and multiple) is concerning as a malignant potential has been recognized in patients harboring multiple hyperplastic gastric polyps. The exact cause of these polyps is unknown. The association with immunosuppressive therapy as well as the natural history of these acquired hyperplastic gastric polyps needs further investigation.

Small Bowel Ulcers.

Treatment of small intestinal ulcers depends on the cause of the ulcers. Ulcerations of the small intestine (apart from duodenal ulcers) are uncommon. Two diverse syndromes of idiopathic small bowel ulcerations include the isolated nonspecific ulcer and idiopathic chronic ulcerative enteritis (ICUE). Treatment of isolated nonspecific ulcers include discontinuation of medications known to cause nonspecific ulcerations, balloon dilation of strictures, and segmental resection of involved segments. Treatment of ICUE includes a diet trial of gluten restriction and consideration of early surgery because of the potential for associated malignancies. Steroid therapy has not been shown to be effective in the treatment of ICUE.