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Clinical use of Infliximab in Crohn's disease: the Edinburgh experience.

UNLABELLED: Infliximab is an established treatment for steroid-resistant and fistulating Crohn's disease. Although efficacy has been shown in clinical trials, financial implications often limit its use and limited data exist regarding clinical practice. AIMS: To audit the clinical effectiveness of Infliximab. METHODS: We prospectively audited 50 consecutive patients [28 females; median age, 34 years (17-70 years)]. Disease activity and response rates were assessed by the Harvey-Bradshaw index. Clinical and disease data were collected and blood was taken for inflammatory markers, complement and double-stranded DNA antibodies. Patients received Infliximab at 5 mg/kg and were followed for 12 weeks. RESULTS: Indications for Infliximab were refractory Crohn's disease in 39 patients, fistulating Crohn's disease in six, pyoderma gangrenosum in one, pouchitis in two and coeliac disease in two. Thirty-one (79%) of the refractory Crohn's disease patients and four (66%) of the fistulating patients responded at 4 weeks. Twenty-one (54%) of the refractory Crohn's disease patients had a continued response at 12 weeks. Perianal disease was more prevalent in non-responders (7/8 vs. 12/31, P < 0.02). CONCLUSIONS: Response rates to Infliximab in our group are comparable to those of clinical trials. Despite the expense, it remains a useful adjunct to treatment in this otherwise difficult group of patients. Patients with perianal disease responded less well in our cohort.

Adolescent↗

J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients.

AIM: The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch-anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design. METHODS: Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis. RESULTS: Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981-1985 to 3 per cent in 1991-1994 (P = 0.02). After mean follow-up of 6.5 (range 2-15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and nighttime incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of 'clinical' pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively. CONCLUSION: These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.

Adolescent↗

Manipulation of the bacterial flora in inflammatory bowel disease.

In this chapter we summarize the clinical and experimental data which indicate that bacteria, especially from the endogenous microflora, play a role in the pathogenesis of Crohn's disease, ulcerative colitis and pouchitis. We review the clinical trials, focusing on randomized controlled trials which used antibiotics or probiotics to treat situations of IBD or prevent recurrence, and we discuss the future of this approach.

Anti-Bacterial Agents↗

Tissue-engineered colon exhibits function in vivo.

BACKGROUND: Postcolectomy morbidities include important changes in enterohepatic circulation, stool microbiology, and absorption. The surgical substitution of an ileal pouch for the absent colon also has a number of serious complications. We report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an ileal pouch. METHODS: End-ileostomies were created in 22 male Lewis rats. In 11 animals, side-to-side ileum-TEC anastomosis was performed 1 cm from the stoma. This group was compared with end-ileostomy alone. Serial weights were measured, and animals were harvested sequentially for assessment of histologic signs of pouchitis. Transit times, stool dry and wet weights, and serum and stool colon function markers were collected. RESULTS: Animals survived 41 days. Weight loss was more than 1.5 times greater in the end-ileostomy alone group compared with the ileum-TEC group. Transit times were significantly longer in the ileum-TEC group than the end-ileostomy alone group, with lower stool moisture content and higher total serum bile acids. Animals without TEC had statistically significant hyponatremia, elevated serum urea nitrogen, and lower stool short chain fatty acids (13.5 micromol/kg vs 84.2) with an abnormal distribution. CONCLUSIONS: TEC successfully recapitulates some major physiologic functions of native large intestine in vivo.

Anastomosis, Surgical↗

Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis.

OBJECTIVE: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed microecology in the pouch has been suggested as one possible explanation. In a previous double-blind, randomized, controlled study we demonstrated clinical improvement of symptoms in patients with ulcerative colitis (UC) operated on with IPAA, during intervention with live probiotic microbes Lactobacilli and Bifidobacteriae. The aim of the present study was to confirm our previous results in a much larger material, including clinical symptoms, faecal flora and endoscopic evaluation, and to compare the results in UC/IPAA patients with those of patients with familial adenomatous polyposis (FAP) with IPAA and UC patients with ileorectal anastomosis (IRA). MATERIAL AND METHODS: Five hundred millilitres of a fermented milk product (Cultura) containing live lactobacilli (La-5) and bifidobacteriae (Bb-12) was given daily for 4 weeks to 51 UC patients and 10 patients with FAP, operated on with IPAA, and six UC patients operated on for IRA. Stool samples were cultured for examination of lactobacilli, bifidobacteriae, fungi and pH before, during and after intervention. Before, during and after intervention, endoscopic evaluation was performed. Categorized symptomatology was examined prospectively using diary cards in addition to an interview, before and on the last day of intervention. RESULTS: The number of lactobacilli and bifidobacteriae increased significantly during intervention in the UC patients operated on with IPAA and remained significantly increased one week after intervention. Involuntary defecation, leakage, abdominal cramps and the need for napkins (category I), faecal number and consistency (category II) and mucus and urge to evacuate stools (category III) were significantly decreased during intervention in the UC/IPAA group. In the FAP group there was a significant decrease in faecal leakage, abdominal cramps and use of napkins (category I) during intervention. The median endoscopic score of inflammation was significantly decreased during intervention in the UC/IPAA patients. Blood tests, faecal fungi and faecal pH did not change significantly during intervention. CONCLUSIONS: Results of this extended study, showing an effect of probiotics on symptoms and endoscopic inflammation in UC patients operated on with IPAA confirm our previously reported effect of probiotics on clinical symptoms and endoscopic score in a smaller, double-blind, randomized, controlled study. The significantly higher response to probiotics in families with increased risk of IBD will have to be repeated in future studies.

Adult↗

Metabolic consequences of total colectomy.

Colectomy is performed for inflammatory bowel disease, familial polyposis syndrome and colorectal carcinoma. Surgical procedures are ileostomy with or without pouch, ileorectal anastomosis or ileal pouch-anal anastomosis. One of the major functions of the intact large intestine is to absorb water and electrolytes. After colectomy, as much as 400-1000 ml of nearly isotonic ileostomy fluid may be excreted, resulting in a chronic salt and water depletion. This is compensated for by an activation of the renin-angiotensin-aldosterone system. Reduced urine volumes may cause kidney stones. Both dehydration and renal sodium retention are probably less frequent in patients with ileal pouch-anal anastomosis. Absorption of nutrients in general is not impaired by colectomy. The large intestine salvages energy from malabsorbed organic matter through absorption of the short-chain fatty acids produced in bacterial fermentation. In ileostomy patients, fermentation is negligible, which leads to a significant loss of energy in the ileostomy fluid. Pouches are colonized by a bacterial flora similar to colonic bacteria. In these patients conservation of energy from malabsorbed substrate may be similar to healthy subjects. Resection of ileum and bacterial colonization may lead to malabsorption of vitamin B12 and bile acids. The latter may cause increased incidence of biliary cholesterol stones. Pouchitis is a frequent problem which may be caused by a deficiency of short-chain fatty acids and glutamine in the pouch contents. It is concluded that although the colon is not essential as a digestive organ in man, colectomy results in a number of metabolic changes. The ileal pouch-anal anastomosis may in part substitute for the functions of the large intestine.

Bile Acids and Salts↗

Effects of short-chain fatty acids on the inflamed colonic mucosa.

Selected inflammatory conditions of the distal alimentary tract may respond to topical SCFA treatment. The rationale for using SCFA enemas is based on Roediger's (1980) observation that butyrate is the preferred fuel of colonocytes and that SCFA deficiency could lead, in the short term, to mucosal hypoplasia and, in the long term, to colitis. The absence of luminal nutrients is especially evident in the excluded rectum after complete diversion of the faecal stream. Harig et al. (1989) were the first to treat successfully diversion colitis with SCFA irrigation (acetate 60 mM, propionate 30 mM, n-butyrate 40 mM). However, subsequent studies could not reproduce the initial positive data. In distal ulcerative colitis an impaired mucosal oxidation of SCFAs has been described despite their luminal abundance. Pilot studies using either the SCFA mixture or butyrate monotherapy have yielded promising results. However, extended confirmatory studies with a larger sample size have not yet been performed. Preliminary data are also available for the use of SCFA in pouchitis and radiation proctitis. In summary, SCFA topical therapy seems to be a promising option in distinct forms of inflammatory bowel disease; however, the routine use of SCFAs cannot be recommended until their efficacy has been confirmed in larger trials.

Administration, Topical↗

Probiotics in gastroenterology: indications and future perspectives.

Nowadays. there is a growing interest in probiotics as a safe way of changing the intestinal bacterial flora. Probiotics may have potential in several gastroenterological conditions, especially when the intestinal flora has been disturbed. Most scientific evidence is available for diarrhoea patients treated with Lactobacillus GG, Lactobacillus reuteri or Saccharomyces boulardii. Meta-analyses have shown an overall reduction in the risk of antibiotic-associated diarrhoea during treatment with probiotics, and benefits have also been demonstrated for patients with rota-virus-associated diarrhoea. Patients with inflammatory bowel disease, an inflammatory disorder characterized by a change in the intestinal flora, are another important target group for which probiotics may be beneficial. It has been claimed that in ulcerative colitis and Crohn disease patients, lactobacilli, S. boulardii and Escherichia coli reduce relapses. but most studies were not placebo-controlled. A reduction in relapses has also been demonstrated in pouchitis patients treated with a multispecies probiotic. Irritable bowel syndrome might be another clinical indication for probiotic therapy, but results of clinical trials performed in these patients are inconsistent. Additionally, probiotics may improve lactose absorption. Helicobacter pylori eradication and constipation. Finally, in animal models of colorectal cancer, treatment with probiotics reduces the prevalence of this disease, and in humans the amount of genotoxic substances in faeces has been reduced. In conclusion, the results of studies on the effects of probiotics in gastrointestinal conditions are encouraging. but well-designed placebo-controlled studies are warranted before recommendations for therapeutic or preventive use can be given. Many issues still have to be resolved, including optimal dose and duration of treatment, selection of and differences between the several available probiotic strains, and, importantly, their mechanisms of actions have to be elucidated.

Colorectal Neoplasms↗

Probiotics in the treatment of inflammatory bowel disease.

The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens; (2) immunomodulation and/or stimulation of an immune response; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier activity; and (5) induction of T cell apoptosis. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. While level 1 evidence now supports the therapeutic use of some probiotics in the maintenance treatment of pouchitis, only level 2 and 3 evidence are currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged over the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials, to investigate the unresolved issues related to efficacy, dose, duration of use, single or multistrain formulation, and the concomitant use of prebiotics, synbiotics or antibiotics, are vital.

Colitis, Ulcerative↗

Incidence of dysplasia in pelvic pouches in pediatric patients after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: The purpose of this study was to evaluate the incidence of dysplasia and the mucosal adaptation patterns of pelvic pouches in children and adolescents who had undergone ileal pouch-anal anastomosis for ulcerative colitis. METHODS: Between 1982 and 1996, 176 pediatric patients with ulcerative colitis underwent ilial pouch-anal anastomosis. Seventy-six patients were followed up after surgery at the Cleveland Clinic. Pouch biopsy specimens were reviewed for dysplasia and to determine mucosal adaptation patterns. Fifty-eight of the 76 patients had an average of three mucosal biopsies during a mean follow-up of 5 years. Demographic and surgical data were abstracted from archives of medical records. All previously obtained pouch biopsy specimens were re-evaluated by a single pathologist to ensure standardized interpretation. RESULTS: No dysplasia was identified in screening specimens of 76 children and adolescents including 5 patients who showed dysplasia in resected colon specimens. The pattern of mucosal adaptation was categorized using previously reported criteria. Type A was defined as normal mucosa or mild villous atrophy with no or mild inflammation. Type B mucosa showed transient atrophy with temporary moderate inflammation followed by normalization of architecture. Type C mucosa was defined as a pattern of persistent atrophy with severe inflammation. In the study cohort, the patterns of mucosal adaptation, type A (56.9%; n = 33), type B (32.8%; n = 19), and type C (10.3%; n = 6), were comparable with those reported in adults. The rate of pouch failure and diagnosis of Crohn's disease were similar in each group and were not related to the specific adaptation pattern. Most of the patients with type C mucosa had clinical symptoms of pouchitis requiring periodic antibiotic therapy. No dysplasia was identified in any biopsy specimen reviewed. CONCLUSIONS: Similar morphologic changes can be seen in ileal pouches in pediatric and adult patients. There seemed to be no increased risk of dysplasia in children and young adults who had undergone ilial pouch-anal anastomosis surgery for ulcerative colitis during a 5 year follow-up. Because the long-term risk of development of dysplasia is unknown, an initial screening should be performed 5 years after the creation of a pelvic pouch in children or when the total disease duration exceeds 7 years. Once identified, patients with Type C mucosa should have annual screening for dysplasia until further data become available.

Adolescent↗

Extraintestinal manifestations of ulcerative colitis following restorative proctocolectomy.

BACKGROUND: Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. OBJECTIVE: To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. METHODS: One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. RESULTS: Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. CONCLUSIONS: A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.

Adult↗

Probiotics and the management of inflammatory bowel disease.

The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple barrier and antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium; (2) immunomodulation and/or stimulation of an immune response of gut-associated lymphoid and epithelial cells; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier function; and (5) induction of T cell apoptosis in the mucosal immune compartment. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. Though level 1 evidence now supports the therapeutic use of probiotics in the treatment of postoperative pouchitis, only levels 2 and 3 evidence is currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged during the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials are vital to investigate the unresolved issues related to efficacy, dose, duration of use, single or multi-strain formulation, and the concomitant use of probiotics, synbiotics, or antibiotics.

Acute Disease↗

Place of probiotics.

PURPOSE OF REVIEW: This review reports on the recent progress understanding mechanisms of action and clinical applications of probiotics. RECENT FINDINGS: New insights on regulating mechanisms of intestinal commensal bacteria to prevent and treat different gastrointestinal diseases have been reported. Some probiotics, though not all, exert beneficial effects by modulating the mucosal barrier function and immune activity. It seems that a combination of different probiotics is more effective than a single strain. It was demonstrated that not only viable bacteria administered to the intestinal tract but also isolated probiotic DNA is active, even if injected subcutaneously. There is reasonable evidence to recommend probiotics in infectious diarrhoea for prevention and treatment (mainly in children) and to prevent antibiotic-induced gastrointestinal side effects. Furthermore, probiotics are effective in maintaining remission in ulcerative colitis and preventing and treating pouchitis. Promising positive effects were published in major surgery patients (gastric resection, pancreatic resection, liver transplantation) and in severe necrotising acute pancreatitis. SUMMARY: Increasing knowledge on probiotics is exciting, but in the near future it must be defined which probiotics (single strains or a combination) are most effective in specific diseases. Well-designed, randomized clinical trials are still required to further define the role of probiotics as preventive and therapeutic agents.

Colitis, Ulcerative↗

The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis.

OBJECTIVE: To evaluate in what manner ageing affects functional outcome and quality of life (QoL) in patients with chronic ulcerative colitis (CUC) after ileal pouch-anal anastomosis (IPAA). SUMMARY BACKGROUND DATA: Short-term function and QoL after IPAA is good. However, patients are usually young, and little is known about the influence of time and ageing on long-term outcomes after IPAA. METHODS: Using a standardized questionnaire, functional outcome, QoL, and complications were assessed prospectively in a cohort of 409 patients followed annually for 15 years after IPAA. RESULTS: Follow-up was complete in the single cohort of 409 patients and functional and QoL outcomes summarized at 5, 10, and 15 years. Daytime stool frequency changed little (mean 6), while nighttime frequency increased from 1 stool to 2 stools. Incontinence for gas and stool increased from 1% to 10% during the day and from 2% to 24% at night over 15 years. The cumulative probability of pouchitis increased from 28% at 5 years to 38% at 10 years and to 47% at 15 years. Bowel obstruction and stricture were other principal long-term complications. At 15 years, 91% of patients had kept the same job. Work was not affected by the surgery in 83%, while social activities, sports, traveling, and sexual life all improved after surgery and did not deteriorate over time. CONCLUSIONS: These long-term results in a single cohort of 409 IPAA patients are unique and are likely a more accurate reflection of long-term outcome than has been previously reported. These data support the conclusion that IPAA is a durable operation for patients requiring proctocolectomy for CUC; functional and QoL outcomes are good, predictable, and stable for 15 years after operation.

Activities of Daily Living↗

Review article: antibiotics and probiotics in inflammatory bowel disease.

Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

Anti-Bacterial Agents↗

The risk of dysplasia and cancer in the ileal pouch mucosa after restorative proctocolectomy for ulcerative proctocolitis is low: a long-term term follow-up study.

AIM: Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis. PATIENTS AND METHODS: Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns. RESULTS: The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed. CONCLUSION: Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.

Adult↗

Risk of dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis.

OBJECTIVE: Restorative proctocolectomy (RPC) with or without mucosectomy is the treatment of choice for most patients with ulcerative colitis (UC) requiring surgery. The ileal mucosa in the reservoir and the anorectal columnar epithelium below the ileo-anal anastomosis are at risk of neoplastic transformation. METHOD: The literature has been reviewed to identify patients developing this complication and an attempt has been made to develop a rational follow-up policy based on the data available. RESULTS: Dysplasia in the ileal reservoir is rare. It is associated with histological type C changes, sclerosing cholangitis and unremitting pouchitis in the ileal mucosa and to the presence of sclerosing cholangitis. Nine patients who have developed adenocarcinoma in the residual anorectal mucosa and seven in the reservoir have been reported in the literature. A further hitherto unreported patient treated by the authors brings the total to 17 patients. Twelve of these had histopathological data on either dysplasia or carcinoma in the original operative specimen. The time intervals from the onset of UC and from the RPC to the development of cancer were 120-528 (median 246) and 16-216 (median 60) months respectively. Cancer appeared to be related to the duration of disease rather than to the interval from RPC. In all the reported patients the interval from the onset of UC was 10 years. CONCLUSION: Based on these data a surveillance programme should begin at 10 years from the onset of disease. Patients with dysplasia or carcinoma in the original specimen, those with type C ileal mucosal changes and patients with sclerosing cholangitis should be selected for surveillance. This will involve multiple biopsies of the ileal reservoir and the anorectal mucosa below the ileo-anal anastomosis.

Adenocarcinoma↗

Safety of selective cyclooxygenase-2 inhibitors in inflammatory bowel disease.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in patients with inflammatory bowel disease (IBD) for fear of disease aggravation. Cyclooxygenase-2 inhibitors have fewer GI side effects than traditional NSAIDs in unselected patients. We report the safety of these agents in patients with IBD. METHODS: Patients with Crohn's disease, ulcerative colitis, or pouchitis who used celecoxib or rofecoxib were identified from computerized prescription records. A retrospective chart review was conducted. Concomitant medications, past NSAID use, indication for cyclooxygenase-2 inhibitor, dose, and duration were obtained. IBD disease activity before cyclooxygenase-2 inhibitor use was graded using a modified disease activity index. Change in disease activity was graded as improved, no change, or worsened. Patients were contacted to provide data not found in the charts. The proportion of patients receiving cyclooxygenase-2 inhibitors who experienced exacerbation of IBD was determined. RESULTS: Eleven patients were treated with celecoxib (median dose = 200 mg/day), and 16 patients were treated with rofecoxib (median dose = 25 mg/day). Median duration of therapy was 9 months (range = 1 wk-22 months). The drug was beneficial in 14 patients, of partial benefit in eight, and of no benefit in five. Two patients (7.4%) (95% CI = 2-23%) had aggravations of IBD. Three patients (11%) had other adverse events (renal insufficiency, rash, and asymptomatic colonic ulceration). All adverse events were reversible. CONCLUSIONS: Our preliminary results suggest that cyclooxygenase-2 inhibitors may be safe and beneficial in most patients with IBD. A placebo-controlled trial to confirm these preliminary observations is needed.

Adult↗