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PubMed2003

Use of probiotics in the treatment of inflammatory bowel disease.

The gut flora plays a fundamental role in maintaining normal intestinal function. A disturbance of this flora, or the host response to this flora, has been clearly demonstrated to play a role in the pathogenesis of inflammatory bowel disease (IBD). This has led to attempts to modify the bacterial flora with "live non-pathogenic organisms that confer health benefits by improving the microbial balance," otherwise known as probiotics. Recent attention has focused on this potential strategy to treat or prevent IBD. The potential therapeutic benefit is enhanced by the natural and apparently safe approach that probiotics offer. Animal models of colitis have provided the proof of principle that probiotics can prevent and treat established intestinal inflammation. Controlled clinical studies have demonstrated the efficacy of probiotics in the maintenance of remission of pouchitis, prophylaxis of pouchitis after the formation of an ileoanal reservoir, maintenance of remission of ulcerative colitis, and treatment of Crohn's disease. However, large controlled trials are needed to definitively establish the place for probiotics in the treatment of IBD and resolve issues such as the dose, duration, frequency of treatment, and use of single or multiple strains. Research is focusing on establishing the mechanism of action, so that treatments with individually tailored properties are developed and innovative approaches are explored.

Animals↗
PubMed2006

Postoperative maintenance therapy for inflammatory bowel disease.

PURPOSE OF REVIEW: This review will highlight the knowledge gained from studies published in the year 2005 on maintenance treatment after surgery for inflammatory bowel diseases. RECENT FINDINGS: In Crohn's disease the role of smoking in increasing the risk of relapse and recurrence after surgery is confirmed. Ornidazole seems effective in reducing endoscopic recurrence and clinical relapse after surgery. Probiotics do not appear to be effective in preventing endoscopic recurrence and clinical relapse: a controlled placebo trial showed that Lactobacillus johnsonii is not effective in preventing endoscopic recurrence. A retrospective study suggested that enteral nutrition after surgery may reduce the clinical relapse. Pathophysiological studies underlined the value of probiotics in pouchitis. SUMMARY: In Crohn's disease postoperative maintenance treatment is disappointing. Giving up smoking is still the only effective measure. Mesalamine remains the drug that has been widely studied with large trials and meta-analysis. Encouraging results come from small trials on antibiotics. Azathioprine and 6-mercaptopurine must be evaluated in better designed controlled trials. There is no evidence in favour of probiotics as an effective therapy to prevent recurrence. Enteral nutrition after surgery is a candidate new therapy, but further controlled trials are needed. Pathophysiological studies confirm the beneficial role of probiotics in pouchitis.

Anti-Bacterial Agents↗
PubMed2006

Review article: the intestinal lumen as a therapeutic target in inflammatory bowel disease.

Undigested carbohydrates reaching the colon can act as competitors for epithelial bacterial receptors, making it difficult for noncommensal bacteria to adhere to them. On the contrary, fermentation of these carbohydrates by anaerobic flora produces - among other substrates - butyrate that is involved in numerous important metabolic processes. These include the provision of energy to the colonocytes, the enhancement of sodium and water absorption and the synthesis of mucus and cell membranes. In addition, butyrate inhibits the nuclear translocation of the transcription factor NFkappaB, which exerts a potent anti-inflammatory activity. Clinical experience with probiotics in inflammatory bowel disease (IBD) is controversial. Whereas some probiotic preparations appear to be useful in ulcerative colitis (UC) and pouchitis, most attempts to use probiotics for treating or preventing recurrence in Crohn's disease have failed. It should be pointed out that - unlike in the small bowel - the colon and ileal pouches are well-established microbiological ecosystems with increasing amounts of a wide variety of bacterial strains. These bacterial strains have a high degree of metabolic interaction with luminal nutrients and a greater probability of developing dysbiosis. With this in mind, the rationale for using pre- and probiotics appears to be stronger for colonic IBD (UC or Crohn's colitis) and pouchitis than for IBD mostly involving the small bowel.

Enterobacteriaceae↗
PubMedDate not supplied

Persistent ileitis after ileal salvage from a failed Kock pouch.

A case of persistent ileitis following the refashioning of a Kock ileal pouch into a Brooke ileostomy for severe pouchitis is reported. Preserving the terminal ileum by a salvage procedure may not be a safe alternative to pouch excision with the formation of a new end ileostomy in the surgical management of pouchitis refractory to medical treatment.

Adult↗
PubMed2007

Ileal pouch-anal anastomosis: the Australasian experience.

OBJECTIVE: The aim of this project was to establish and maintain an internet-based database of all ileal pouch procedures performed in major centres in Australasia. METHOD: The initial three colorectal units contributing data are Auckland, northern Brisbane and Central Sydney Area Health Service. A web-based database was designed. The data collection method was tested on a subgroup of 20 patients to ensure functionality. Data were collected in five main categories: patient demographics, preoperative data, operative details, postoperative complications and functional results. RESULTS: Initial data are presented for 516 patients [363 J, (70%), 133 W (26%), 16 S pouches (3%)]. There were two deaths within 30 days (0.4%). The anastomotic leak rate overall, in handsewn (HSA) and stapled anastomoses (SA) respectively was 5.0%, 8.5% and 3.3% (P=0.02 for difference HSA vs SA). Incidence of pouchitis was 20% (ulcerative colitis 23%, Crohn's disease 20%, indeterminate colitis 22%, familial adenomatous polyposis 9%). Incidence of anal stricture requiring intervention (11% overall) was significantly greater in HSAs than in SAs (16%vs 9%, P=0.02). Incidence of small bowel obstruction at any time postoperatively was 16%. Functional data were available for 234 patients. The median frequency of bowel actions during waking hours was significantly less in W pouches than in J pouches (four vs five, P=0.0005). CONCLUSION: A national web-based database has been developed for access by all Australasian colorectal units. Initial Australasian data compare favourably with other international studies. Pouchitis continues to be a long-term problem. The leak rate and rate of late anal stricture requiring a procedure are higher if the anastomosis is handsewn rather than stapled. Functional results are better with the W pouch than with the J pouch.

Anal Canal↗
PubMed1998

Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506).

OBJECTIVE: Steroid treatment failure in acute Crohn's disease and ulcerative colitis frequently necessitates surgical intervention. Several alternative therapeutic strategies have been raised. The most promising so far has been intravenous cyclosporine, but the results in the long term have been discouraging. We assessed the efficacy and safety of the new macrolide immunomodulator tacrolimus as an alternative to cyclosporine A. METHODS: Eleven patients with steroid-refractory disease (six ulcerative colitis, two indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity according to the Truelove and Witts criteria or Crohn's disease activity index > 150, respectively, were eligible for the study. All patients were treated with intravenous tacrolimus for 7-10 days followed by oral treatment over a median period of 7 months (range 0.25-16). Azathioprine and mesalamine were given concomitantly. Steroids were tapered according to clinical activity. RESULTS: Seven of 11 patients achieved remission rapidly, whereas a modest improvement was noted in two. Only two patients required an early and one a delayed colectomy. Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an improvement of pouchitis was observed. A tapering to low dose steroids was possible during oral tacrolimus therapy in all nine responders and remission was maintained in five of them (mean follow-up 9.2 months). The drug was well tolerated and side effects were managed conservatively. CONCLUSION: Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.

Adolescent↗
PubMed2004

Treatment of rectal cuff inflammation (cuffitis) in patients with ulcerative colitis following restorative proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice in the majority of patients with ulcerative colitis (UC) who require surgery. To ease the construction of the IPAA and improve functional outcome by minimizing sphincter related stretch injury, a stapling technique is being commonly used in the pouch-anal anastomosis. Despite its advantages, the procedure normally leaves a 1-2 cm of anal transitional zone or rectal cuff, which is susceptible to recurrence of residual UC or cuffitis. Cuffitis can cause symptoms mimicking pouchitis. AIM: To conduct an open-labeled trial of topical mesalamine in patients with cuffitis. METHODS: We treated 14 consecutive patients with cuffitis by giving mesalamine suppositories 500 mg b.i.d. (mean 3.2 months, range 1-9 months). The Cuffitis Activity Index (adapted from the Pouchitis Disease Activity Index) scores and improvement in symptoms of bloody bowel movements and arthralgias were measured as primary and secondary outcomes. RESULTS: All patients had surgery for medically refractory UC. There were significant reductions in the total Cuffitis Activity Index scores after the therapy (11.93 +/- 3.17 vs 6.21 +/- 3.19, p < 0.001). Symptom (3.24 +/- 1.28 vs 1.79 +/- 1.31), endoscopy (3.14 +/- 1.29 vs 1.00 +/- 1.52), and histology (4.93 +/- 1.77 vs 3.57 +/- 1.39) scores each were significantly reduced (p < 0.05). Ninety-two percent of patients with bloody bowel movements and 70% of patients with arthralgias improved after the therapy. No systemic or topical adverse effects were reported. CONCLUSION: Topical mesalamine appears well tolerated and effective in treating patients with cuffitis, with improvement in symptom as well as endoscopic and histologic inflammation.

Adult↗
PubMed1991

Mucosal characteristics of pelvic ileal pouches.

This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur.

Adenomatous Polyposis Coli↗
PubMed1991

Effects of the faecal stream and stasis on the ileal pouch mucosa.

This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diamine-alcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year.

Adult↗
PubMed1993

Distribution of mucosal pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir.

The mucosa of the pelvic ileal reservoir undergoes adaptive changes--inflammatory, architectural, and metaplastic--on exposure to the faecal stream. Twenty three quadruple loop ileal pouches constructed for ulcerative colitis (20 patients) and familial adenomatous polyposis (FAP) (three patients) were studied. No patient fulfilled clinical, endoscopic, or histopathological criteria for pouchitis. Standard duplicate biopsy specimens were taken from the proximal limb, the anterior wall, the posterior wall, and the body of the reservoir. An established scoring system was used and showed a highly significant increase in inflammatory scores in posterior wall biopsy specimens compared with those from the anterior wall. These results suggest that the adaptive changes are the direct result of contact with static faecal contents. One patient only showed significant inflammation in the proximal limb. There was no evidence of mucosal prolapse in any anterior wall biopsy specimen. Patients with colitis showed substantially more inflammatory and architectural changes than those with FAP. Ninety six per cent of pouches showed some colonic phenotypic expression as defined by mucin histochemical and PR 3A5 immunohistochemical studies. Our results suggest, however, that there may not be complete colonic metaplasia and that the mucin changes and other phenotypic alterations may represent a non-specific response to pouch inflammation and not a prerequisite for the development of pouchitis. The focal nature of the inflammatory and architectural changes, which may be the result of direct contact with static faecal residue, are clearly shown. A single random biopsy specimen of pouch mucosa is of limited value in assessing pathological changes and screening for potential neoplastic change within the reservoir.

Adenomatous Polyposis Coli↗
PubMed1996

Outcome of restorative proctocolectomy with ileal reservoir for ulcerative colitis: comparison of distal colitis with more proximal disease.

BACKGROUND: An increasing number of patients with severe or refractory ulcerative colitis involving only the rectum and sigmoid colon are being offered restorative proctocolectomy with ileal reservoir but very few data are available concerning the outcome for these patients. AIM: This study was designed to compare the outcome of ileal pouch procedures for distal ulcerative colitis with procedures performed for more extensive disease. PATIENTS: A consecutive series of 177 patients undergoing restorative proctocolectomy for ulcerative colitis between January 1984 and December 1994. METHODS: Data were collected prospectively in a dedicated ileal pouch database and included demographic details, indication for surgery, surgical procedures performed, early (< 30 days) and late morbidity, functional outcome, and histopathology. RESULTS: There was no mortality in the series. The incidence and range of early morbidity (< 30 days) and the functional outcome (daytime stool frequency, nocturnal frequency, and the incidence of incontinence) were similar for all groups. Log rank analysis of Kaplan-Meier estimates showed no significant difference between groups in the likelihood of developing pouchitis (p > 0.2). CONCLUSIONS: Patients undergoing restorative proctocolectomy for distal colitis experience a similar outcome to patients with more extensive disease. These data refute the hypothesis that pouchitis is more common in patients with total colitis.

Adolescent↗
PubMed1997

Contribution of gastrointestinal transit and pouch characteristics in determining pouch function.

AIM: To determine the contributions of gastrointestinal transit and pouch characteristics to bowel frequency in patients with an ileoanal reservoir and no pouchitis. METHODS: Twenty one patients who had undergone restorative proctocolectomy, with ileostomy closure at least eight months previously, and who had no history of pouchitis were recruited. They were prospectively classified on the basis of their bowel frequency: 11 patients had good pouch function (bowel frequency less than six per day) and 10 had poor function (bowel frequency more than six per day). Gastrointestinal transit was studied using a dual isotope technique and anal and pouch physiological examination was performed on all patients. RESULTS: Lag phase, 25% and 50% gastric emptying, small bowel transit time, and 10% and 50% pouch filling times, all for solids and liquids, were not significantly different between patients with good and poor function. Anal manometry and pouch and anal electrical sensitivity were also similar in the two groups. The volume of air and water required to elicit an initial sensation and the urge to defaecate were similar in both groups, but the maximum tolerated volume to both air (525 v 245 ml, good v poor function, median values) and water (625 v 370 ml) infusion was significantly (both p < 0.02) lower in patients with poor function. CONCLUSION: Maximum tolerated volume in the pouch, which may reflect pouch size, sensitivity, compliance, or a combination of these is the major determinant of pouch function. Gastrointestinal transit does not seem to be an important determinant of function.

Adult↗
PubMed1994

Expression of colonic antigens by goblet and columnar epithelial cells in ileal pouch mucosa: their association with inflammatory change and faecal stasis.

AIMS: To investigate colonic metaplasia of goblet and columnar epithelial cells in ileal pouch mucosa; to correlate this with the degree of morphological and inflammatory change; and to assess whether such changes are related to the presence of faecal stasis. METHODS: Biopsy specimens of ileal pouch mucosa were taken from 31 patients (30 with ulcerative colitis, one with familial adenomatous polyposis) either before (eight patients) or after (23 patients) ileostomy closure. A simple morphological technique was used to assess changes in villous height. Inflammatory change was estimated using an established scoring system for pouchitis, and acquisition of colonic antigens was determined by immunohistochemistry using three monoclonal antibodies which recognise components of the two major epithelial cell types in the colorectum. The degree of staining with the monoclonal antibodies was graded and the grades correlated with an index of villous atrophy and with the inflammatory scores. RESULTS: Five of eight (63%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens showed increased staining with an antibody against components of columnar epithelial cells. One of eight (12%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens stained with an antibody for colonic mucin. Although both types of staining showed a positive correlation with the pouchitis score, they also occurred in the absence of inflammation. CONCLUSIONS: Both goblet and columnar cells acquire colonic characteristics which are incomplete, but may represent a true adaptive response as they can develop in the absence of inflammation. As the change in goblet cells occurs after ileostomy closure, faecal stasis is likely to be a major contributory factor. Changes in columnar cells may occur before ileostomy closure in the absence of faecal stasis.

Autoantigens↗
PubMed2003

Carcinoma of pelvic pouch following restorative proctocolectomy: report of a case and review of the literature.

One of the possible long-term complications following an ileoanal pouch procedure is the development of malignancy in the mucosa of the rectal stump. Only 10 such cases have been reported so far. We report the case of a 23-year-old male who had ulcerative colitis with high-grade dysplasia and underwent an ileoanal pouch procedure. He was found to have a malignancy in the rectal stump 5 years after surgery. The malignancy presented with symptoms of refractory pouchitis. Pouch excision was performed. The risk of developing malignancy in the rectal mucosa after an ileoanal pouch procedure mandates regular follow-up in these patients, with a high index of suspicion especially in patients with delayed onset pouchitis.

Adenocarcinoma↗
PubMed2004

Ileo-neorectal anastomosis: medium- and long-term follow-up of 37 patients.

BACKGROUND: Ileo-neorectal anastomosis (INRA), an alternative restorative procedure, was developed to reduce the pouch-related complication rate with an (at least) equal functional result. METHODS: For this surgical outcome, data of all INRA patients, including bowel function and complications, were prospectively recorded. The reservoir capacity was determined repeatedly by physiologic tests. The anal sphincter complex was assessed by manometry and ultrasound examination. Evaluation of the neorectal mucosa was performed by endoscopy. RESULTS: An INRA procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6 familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch anal anastomosis or proctectomy only, because of impossibility to completely remove the rectal mucosa or short of length of the rectal stump. The median operation time for INRA was 323 min (range 240-518), with 1,400 ml blood loss (400-4,500). The reservoirs were permanently defunctioned in 2 patients--one because of reclassification into Crohn's disease, and one with pouchitis refractory to medical treatment. In 18 out of 37 cases, web-like stenoses occurred at the mucosa-anal level, which were treated by single (9) or repeated (5) dilatation or surgical stenoplasty (2). No pouch-related complications like pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had episodes of 'pouchitis', successfully treated with antibiotics, and 7 other cases, with functioning reservoirs, also had proximal 'non-specific' (i.e. no histological criteria of Crohn's disease found) small bowel inflammation. The median bowel frequency decreased from 15x/24 h initially to 7x/24 h at 2 years. Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37 patients. The neorectal compliance volume recovered from 12.5 ml kPa after subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance of 24 ml/kPa at 2 years' follow-up (p < 0.002; Wilcoxon signed rank test). CONCLUSION: The INRA procedure shows a low complication rate and reasonable functional results, there was however a considerable conversion rate in these first 53 cases and a high incidence of reclassification to CD.

Clinical Competence↗
PubMed2006

Antimicrobials in the management of inflammatory bowel disease.

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics may therefore represent a potentially effective therapeutic option. However, the available studies do not support the use of antimicrobials in ulcerative colitis and larger studies are required. These drugs are however effective in treating septic complications of Crohn's disease (CD). The use of antibacterial agents as primary therapy for CD is more controversial, although this approach is frequently and successfully adopted in clinical practice. Despite the fact that properly controlled trials have been not carried out, antimicrobials are the mainstay of the treatment of pouchitis. Rifaximin is a poorly absorbed, broad-spectrum antibiotic that, thanks to its efficacy and long-term safety, could represent the preferred tool of manipulating enteric flora in patients with IBD. Preliminary data suggest that rifaximin may be beneficial in the treatment of active ulcerative colitis (and pouchitis), mild to moderate CD as well as prevention of post-operative recurrence of CD.

Animals↗
PubMed2006

Probiotics: do they help to control intestinal inflammation?

There is currently a growing appreciation for the role of the enteric flora in health and disease. In the past years overwhelming evidence has accumulated for the role of commensal gut bacteria in the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Both entities are mainly located in areas with high bacterial concentrations. Reduction of the enteric bacterial concentration by antibiotics, lavage, or surgical bypass results in a mitigation of symptoms, while experimental colitis models depend on the presence of the bacterial flora and the NOD2/CARD15-mutation results in inefficient clearance of invasive bacteria. Those findings helped to bring the concept of probiotic therapy to the forefront, a therapy that had been known for millennia, but had been disregarded by the scientific world. Probiotics are meanwhile established in the maintenance therapy of ulcerative colitis and chronic recurrent or refractory pouchitis. Promising data exist for the primary prevention of pouchitis. Probiotic research at the intersection of gastroenterology, immunology and microbiology is highly dynamic in both the basic and the clinical field. Further understanding of the complex molecular mechanisms leading to the effectiveness of probiotics will also spur the development of more successful probiotic formulations.

Animals↗
PubMed2000

Fecal pancreatic elastase 1 in the work up of patients with chronic diarrhea.

BACKGROUND: Quantitative determination of pancreatic elastase-1 (E1) in stools has been proposed as a novel, noninvasive test of pancreatic function. The aim of the study was to verify its role in the differential diagnosis of chronic diarrhea. METHODS: E1 was measured in spot stool samples of 50 patients with pancreatic disease (PD), 62 with inflammatory bowel disease (IBD), 45 with chronic diarrhea (CD), 34 with other gastroduodenal and liver disease (gastrointestinal; GI), and in 18 normal controls, by a commercial kit (Schebo-Tech., Wettemburg, Germany). RESULTS: In PD, patients with severe damage and diarrhea displayed E1 levels below 100 microg/g; normal values were found in mild-moderate disease. Abnormal values were detected in 4 CD and in 14 IBD patients, either in the presence of severe protein malnutrition or in patients with previous ileo-anal pouch anastomosis and pouchitis. In nine cases, values reverted to normal after adequate treatment. Diagnostic accuracy of E1 in discriminating diarrhea of pancreatic and nonpancreatic origin was: SS, 97%; SP, 84%; VP+, 66%; VP-, 100%. CONCLUSION: 1) The finding of a normal E1 value rules out a malabsorption of pancreatic origin. 2) in CD and IBD, decreased E1 might be owing to bacterial elastase degradation (pouchitis) or transient defective pancreatic enzyme secretion.

Adolescent↗