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PubMed2006

Infliximab and ulcerative colitis.

Tumour necrosis factor (TNF)-alpha is an inflammatory cytokine that plays a main role in the inflammatory process underlying inflammatory bowel disease (IBD). Despite the fact that the cytokine profiles associated with ulcerative colitis (UC) and Crohn's disease (CD) are classically considered different (a Th2 pattern in UC and a Th1 pattern in CD), there are several evidences in vitro and in vivo that TNF-alpha has an important role in UC. For this reason, infliximab, the chimeric monoclonal antibody to TNF-alpha, has been evaluated in the therapy of UC. The drug has been evaluated in different clinical settings both in adults and in children: in moderate-severe steroid-dependent UC, in severe refractory UC as rescue therapy, in active non-steroid-refractory UC, in resistant pouchitis and in maintenance of moderate-severe UC responsive to infliximab. On the basis of the randomised controlled trials (RCTs), it is possible to draw the following conclusions for adults: infliximab seems active in severe steroid-refractory UC, allowing colectomy to be spared even if further controlled trials are needed with a larger sample of patients adopting strict and well-defined inclusion criteria. The drug seems active in inducing remission after 8 weeks in steroid-refractory patients, in patients taking steroids (even if it is not clear at which dosage of steroid dependence the drug is more active) and also in patients failing aminosalicylates therapy. The long-term response of infliximab in comparison to placebo in these subgroups of patients is not clinically impressive even if it is statistically significant. Further trials are warranted in order to establish the role of infliximab in steroid-dependent UC (defined with clear criteria), in maintaining remission after severe UC, in non-steroid-dependent moderate-severe UC and in refractory pouchitis. For children it is not possible to draw the same conclusions, due to a lack of RCTs, despite the encouraging data coming from open studies, mainly in steroid-refractory UC.

Antibodies, Monoclonal↗
PubMed1990

Ileoanal pouches: comparison of CT, scintigraphy, and contrast enemas for diagnosing postsurgical complications.

The value of CT of the pelvis, 111In-labeled leukocyte scintigraphy, and contrast enema (pouchography) for detecting postsurgical complications was assessed in 44 patients with total colectomy, rectal mucosectomy, and ileoanal pouches. Ileoanal pouches were created as reservoirs from an ileal loop that was anastomosed to the dentate line of the anus and stayed connected to the remainder of the ileum. This pouch preserves the normal defecatory pathway and eliminates disease-producing mucosa. A total of 57 sets of examinations revealed 22 cases of normal postoperative findings, 22 of pouchitis, 13 of abscess, and three of fistula. Overall sensitivity for detecting complications with pouchography was 60% (18 of 30 findings); with CT, 78% (28 of 36 findings); and with scintigraphy, 79% (23 of 29 findings). Pouchitis was best diagnosed by scintigraphy (sensitivity, 80%), followed by CT (sensitivity, 71%) and pouchography (sensitivity, 53%). Only CT correctly diagnosed all cases of abscess. Fistulas were frequently missed by all three methods. If tests were combined, the overall sensitivity rose to 93% for the combination CT/scintigraphy and to 86% for CT/pouchography, but did not improve for pouchography/scintigraphy (78%). For evaluation of complications in patients with ileoanal pouches, CT should be the initial test. If an abscess is found, no further tests are needed. If CT findings are negative, a scintigram should be obtained. Our data did not establish a clear role for pouchography.

Abscess↗
PubMed1993

The influence of ileal pouch-anal anastomosis for ulcerative colitis on ileal glycoprotein synthesis.

Restorative proctocolectomy and ileal pouch-anal anastomosis are frequently associated with the onset of low-grade inflammation, colonic metaplasia, and pouchitis. The influence of intestinal adaptation and inflammatory activity on ileal glycoprotein synthesis (GS) has been assessed. Ileal GS activity in controls (n = 13, 28.9 +/- 3.6) was similar to that of patients with ulcerative colitis (n = 18, 26.4 +/- 3.6) irrespective of the presence of backwash ileitis (n = 6, 22.0 +/- 4.0). Ileoanal pouch construction was not associated with a significant change in ileal GS activity regardless of the presence of low-grade inflammation (n = 19, 25.9 +/- 2.2), frank pouchitis (n = 5, 24.4 +/- 4.6), or transformation to a colonic type of mucosa (n = 6, 25.4 +/- 5.2). The transformation of ileal mucosa from an absorptive to a storage function is associated with characteristic morphologic and inflammatory changes but does not produce a protective response mediated by increased GS.

Adaptation, Physiological↗
PubMed1999

[Surgical treatment of ulcerative colitis].

Continence-preserving coloproctectomy for ulcerative colitis is technically demanding and is relatively often afflicted with complications. We have retrospectively reviewed the files of all patients being operated for ulcerative colitis at Ullevål Hospital from 1992 to 1997 (n = 53). Most of the patients (n = 50) were examined clinically; 12 patients had anal manometry before and after operation. 44 patients were operated with continence-preserving coloproctectomy with J-pouch and handsewn anastomosis; of these, 42 were followed more than six months. Eight had pouchitis, four perianal abscess/fistula, three septicaemia and three were operated for ileus. Two had anastomotic leakage and pelvic abscess that required transanal drainage. One had the pouch removed six years after operation due to chronic pouchitis and pouch-vaginal fistula. There was no deterioration of anal maximal resting and squeezing pressures on pre- and post-operative anal manometry. Mean number of stools from the reservoir per 24 hours were 6.2 (range 3-11); 11 patients had leakage of air and loose stool, three at day-time and eight at night. Two patients (4%) died from colorectal cancer and three (7%) had Crohn's disease. Nine patients were unfit for pouch surgery and underwent coloproctectomy (n = 7) or subtotal colectomy (n = 2). Our results indicate that pouch surgery for ulcerative colitis is a good option for most patients.

Adolescent↗
PubMed2004

Probiotics, prebiotics and antibiotics in inflammatory bowel disease.

Probiotics and prebiotics are the sort of therapy that most patients with inflammatory bowel disease (IBD) wish for. They are without significant side effects, except possibly an increase in gas with prebiotics, and so far, appear to be entirely safe. However, are they effective? More than a dozen studies using probiotics in IBD have now been reported, and there is dear benefit in pouchitis and possibly also in Crohn's, although there are so many clinical types of this condition that a clear indication has yet to emerge. For ulcerative colitis (UC) more studies are needed. The use of prebiotics in IBD is only just starting, although significant effects on both the luminal and mucosa-associated flora have been demonstrated in healthy subjects. Antibiotics offer more certain hope in IBD treatment, although with a much greater risk of unwanted effects. Their efficacy in clinical studies varies, with Crohn's disease and pouchitis reporting more benefit than ulcerative colitis. However, the ideal combination of antibiotics, and rationale for their use has not been determined.

Anti-Infective Agents↗
PubMed1990

[Ileal pouch in the treatment of ulcerative rectocolitis and familial polyposis. Analysis of morbidity in a series of 30 cases].

Between 1984 and 1989, 30 patients underwent total coloproctectomy with J ileal pouch and ileo-anal anastomosis. They corresponded to 29 cases of ulcerative colitis and one case of familial polyposis. The authors report their own experience and the related morbidity and functional results. There were 23% fistulae, 6.6% pouchitis, 10% stenoses, 8.7% pelvic abscesses, 10% bowel obstructions, 6.6% fistulae after ileostomy closure. Only one pouch had to be removed for severe pouchitis. Functional results were partly related to post-operative complications: 50% of patients had normal continence, 57% at least 6 stools per day, 81% had one stool per night, 15% had soiling. Morbidity is discussed for the various types of complications.

Adenomatous Polyposis Coli↗
PubMed1994

[A clinical and instrumental study of the functionality of ileoanal "reservoirs"].

Twenty-five patients with ileo-anal "reservoir" have been evaluated by clinical examination, manometry, proctography, endoscopy and biopsy, at least six months from the closure of ileostomy. 80% of them presented with a satisfactory condition, although only one third reached a normal function; 20% suffered for one or more dysfunctions which lead to a variable degree of social handicap. The most frequent dysfunctions were incontinence (13 patients), urgency (10), frequency (9), pouchitis (6), incapacity to evacuate (2). The mean values at manometry showed a halved anal tone, a slightly impaired external sphincter, a halved compliance of the pouch in comparison to normal rectum. Radiology demonstrated that half the patients with dysfunctions had a reduced motility of the pouch and anomalies in sphincter coordination. Endoscopy and biopsies demonstrated inflammation in 12 patients and 6 of them developed an acute pouchitis. From a general point of view, apart from particular conditions, it has been impossible to correlate clinical dysfunctions with a specific abnormality at the instrumental evaluation. Therefore, while good results are assumed to be due to a normally restored anatomical and motility condition, we must recognize that most clinical dysfunctions are not univocally correlated to abnormalities of the pouch or of the sphincteric apparatus.

Anal Canal↗
PubMed1994

[Results of ileoanal anastomosis with mucosectomy and "J" pouch in hemorrhagic rectocolitis].

The aim of this study was to assess the results of ileal "J" pouch-anal anastomosis in ulcerative colitis. One hundred and fifty six patients operated on between 1983 and 1991 for ulcerative colitis were followed-up prospectively since the surgical procedure with a mean of 29 +/- 16 months (range: 6 to 92 months). There was no postoperative death. Forty-four patients (28%) presented 48 post-operative complications and 14 (9%) were reoperated. Twenty-five patients (16%) were reoperated because of a late complication. Three pouches had to be removed for untreatable fistulas which appeared to be related to a Crohn's disease in 2 cases; the reestablishment of a diverting loop ileostomy was mandatory in 2 further patients for anoperineal sepsis. The mean stool frequency at 1 year was 4.5 +/- 1.9; 40% of patients did not have nocturnal stooling. Daytime and nighttime continence were normal in 90.7% and 77.5% of cases respectively, 87% of patients considered their social life improved by the surgical cure of the disease. The results observed 5 years after the surgical procedure in 37 patients were similar to those observed at 1 year. Twenty-five patients (16%) presented one or several episodes of pouchitis, including 5 cases of chronic pouchitis. It is concluded that the treatment of ulcrerative colitis, ileal "J" pouch-anal anastomosis, is a safe and effective procedure which provides good functional results.

Adolescent↗
PubMed1999

Ileoanal pouch procedures: clinical outcomes and quality-of-life assessment.

Ileoanal pouch (IAP) anastomosis following total colectomy for ulcerative colitis or familial adenomatous polyposis is performed with the goal of avoiding a permanent ileostomy and its effects on life satisfaction. During a retrospective 10-year study period, 55 patients underwent IAP construction for ulcerative colitis (36) and familial adenomatous polyposis (19). We assessed complications by chart review and surveyed patients regarding quality of life via a standardized questionnaire. There was no operative mortality, and there were three late deaths (6%). Twenty-nine patients (54%) sustained 68 early and late complications. Pouchitis was the most common complication (24%), and two patients required pouch excision (4%), one for pouchitis and one for rectovaginal fistula. Thirty-one patients (65%) have completed questionnaires. Forty-seven patients (87%) responded that their overall quality of life is "always" better since creation of the IAP, and only one patient in the IAP group has greater than ten bowel movements a day. Twenty-one patients (68%) never have interference with intimate relationships and 20 (65%) never have interference with physical activities. However, 20 patients (65%) sometimes have sleep interference, and 19 patients (61%) sometimes have fecal soilage. None of the patients continue to take steroids. We conclude that the complication rate following IAP construction is high, but pouch loss is infrequent. Despite a high complication rate, the majority of patients experience an improvement in quality of life.

Adenomatous Polyposis Coli↗
PubMed1996

Disconnection, pouch revision and reconnection of the ileal pouch-anal anastomosis.

The aim of this retrospective study was to determine the outcome of patients with a dysfunctional pelvic ileal reservoir in whom disconnection of an ileal pouch-anal anastomosis (IPAA), pouch revision and reanastomosis had been carried out. There were 23 patients (15 women). At the revision operation functional problems were found to be due to a long efferent spout (nine patients), sepsis and/or fistula (four), a redundant blind limb (three), a twisted pouch (three), anastomotic problems (three) or no reservoir (one). The pouch was salvaged in 16 patients and a new pouch was constructed in seven. The pouch-anal anastomosis was resutured in 22 patients and stapled in one. Postoperative complications (all minor) occurred in six patients. Two patients underwent two revision of IPAA. At a median follow-up of 5 (range 1-10) years, 11 patients reported good to excellent function, five reported fair function and one reported recurrent pouchitis. Revision surgery was unsuccessful in six of 23 patients (three had gross incontinence, two excessive bowel movements and one Crohn's disease), and they subsequently underwent pouch excision. It is concluded that revision of an ileal reservoir and IPAA can be undertaken safely with good results in carefully selected patients.

Adenomatous Polyposis Coli↗
PubMed2001

Long-term results of ileal pouch-anal anastomosis for colorectal Crohn's disease.

INTRODUCTION: The aim of this study is to report ten-year results of ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease for whom coloproctectomy and definitive end ileostomy was the only alternative. METHODS: 41 patients (22 females/19 males) with a mean age of 36 +/- 13 (range, 16-72) years underwent ileal pouch-anal anastomosis for colorectal Crohn's disease between 1985 to 1998. None had past or present history of anal manifestations or evidence of small-bowel involvement. Diagnosis of Crohn's disease was established preoperatively in 26 patients, on the resected specimen after ileal pouch-anal anastomosis, or after occurrence of Crohn's disease-related complication in 15 patients. RESULTS: Follow-up was 113 +/- 37 months, (18-174) 20 patients having been followed for more than 10 years. There was no postoperative death. Eleven (27 percent) patients experienced Crohn's disease-related complications, 47 +/- 34 months (8-101) after ileal pouch-anal anastomosis: 2 had persistent anal ulcerations with pouchitis and granulomas on pouch biopsy and were treated medically; 2 experienced extrasphincteric abscesses and 7 presented pouch-perineal fistulas which were treated surgically. Among them, 3 patients with persistent perineal fistula despite surgery required definitive end-ileostomy. Of the 20 patients followed for more than 10 years, 7 (35 percent) experienced Crohn's disease-related complications which required pouch excision in 2 (10 percent). CONCLUSIONS: Ten years after ileal pouch-anal anastomosis for colorectal Crohn's disease, rates of Crohn's disease-related complications and pouch excision were 35 and 10 percent, respectively. These good long-term results justify for us to propose ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease (i.e., no past or present history of anal manifestations and no evidence of small-bowel involvement) for whom the only alternative is definitive end ileostomy.

Adolescent↗
PubMed1998

Development of an ulcer in the side-to-side anastomosis of a jejunal pouch after proximal gastrectomy reconstructed by jejunal interposition: report of a case.

We present herein the first reported case of a deep ulceration developing in the pouch of a jejunal side-to-side anastomosis following the interposition of a jejunal U-shaped pouch (jejunal pouch), performed as reconstruction. A 47-year-old woman underwent a proximal gastrectomy and interposition of a jejunal pouch for early gastric cancer, 4 months after which she began to develop a fever. Esophagogastroscopy revealed a deep ulceration in the side-to-side anastomosis of the jejunal pouch. Her serum gastrin level was much higher than the normal range, and 24-h monitoring of the intraremnant stomach pH revealed that it was below 7.0 at night. A peptic ulcer was thought to be one of the causes of the pouchitis. Due to the drug-resistant ulceration and fever, a reoperation was performed, in which the jejunal pouch and remnant stomach were removed and Roux-en-Y reconstruction was done. There were no postoperative complications, and the fever resolved after surgery. Reconstruction of the jejunal pouch after proximal gastrectomy is recommended from the standpoint of quality of life (QOL); however, further studies on the size of the remnant stomach and the length of the interposed jejunal pouch are necessary.

Duodenal Ulcer↗
PubMed2002

[Colonic J-pouch reconstruction in cases of insufficiency and severe complications after ileocecal pouch in rectal cancer].

In order to reduce the high frequency of bowel movement after resection of the rectum in cases of rectal cancer, the creation of a colonic J-pouch was developed. Meanwhile this operation is well established. As a variation to the standard technique, von Flüe introduced in 1994 the interposition of an ileocecal segment, intended to improve the reservoir function via its own distensibility. Despite the conserved neural and vascular integrity of the ileocecal segment, major complications arise such as pouchitis with necrosis. In these cases, resection of the pouch and permanent discontinuity of stool passage is routine therapy. Patients with permanent stoma face many difficulties both physical and psychological, and often the quality of life diminishes. In the literature there is no detailed case of colonic J-pouch reconstruction following resection of an insufficient ileocecal pouch. This operation is technically highly demanding but feasible.

Anal Canal↗
PubMed1998

Patterns of distribution of endoscopic and histological changes in the ileal reservoir after restorative proctocolectomy for ulcerative colitis. A long-term follow-up study.

OBJECTIVE: This study was undertaken to assess the long-term macroscopic appearance of the ileal reservoir after restorative proctocolectomy for ulcerative colitis, to determine whether there is any correlation between macroscopic and histological changes and whether the distribution of these is homogeneous, focal or patchy. BACKGROUND: No study has examined the macroscopic appearance of the ileal reservoir over a long period and it is still unknown to what degree histological changes are diffuse or patchy. Moreover, the relationship between macroscopic and histological changes is poorly understood. METHOD: Fifty-nine patients were examined by one clinician (PSC) 5.3-14.5 years (median 8.2 years) postoperatively. A rigid sigmoidoscopy of the reservoir was performed. Four zones in the posterior midline at 5-cm intervals from the ileoanal anastomosis were inspected. At each level a macroscopic score of severity of inflammation was given and a biopsy taken. The degree of acute and chronic inflammation was assessed using a histopathological scoring system. RESULTS: All reservoirs showed macroscopic abnormalities, which were more marked distally in 14 (24%). There was no case in which severity of inflammation was greater in proximal than in distal zones. Endoscopy overall correlated with both acute and chronic histological changes. On histological examination the patients could be divided into three groups as follows: (1) all four biopsies were normal (group 1, n = 8, 14%), (2) the score of acute and chronic inflammation decreased from distal to proximal zones (group 2, n = 25, 42%) and (3) all four biopsies were abnormal with the same score (group 3, n = 26, 44%). The latter group significantly correlated with a present or past history of pouchitis. CONCLUSION: The study has shown that when there is a gradation of inflammation within the ileal reservoir this is more severe in distal than in proximal zones.

Adolescent↗
PubMed2006

Restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis revisited.

Since restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA) removes the entire diseased mucosa, it has become firmly established as the standard operative procedure of choice for familial adenomatous polyposis (FAP). Many technical controversies still persist, such as mesenteric lengthening techniques, close rectal wall proctectomy, endoanal mucosectomy vs. double stapled anastomosis, loop ileostomy omission and a laparoscopic approach. Despite the complexity of the operation, IPAA is safe (mortality: 0.5-1%), it carries an acceptable risk of non-life-threatening complications (10-25%), and it achieves good long-term functional outcome with excellent patient satisfaction (over 95%). In contrast to the high incidence in patients operated for ulcerative colitis (UC) (15-20%), the occurrence of pouchitis after IPAA seems to be rare in FAP patients (0-11%). Even after IPAA, FAP patients are still at risk of developing adenomas (and occasional adenocarcinomas), either in the anal canal (10-31%) or in the ileal pouch itself (8-62%), thus requiring lifelong endoscopic monitoring. IPAA operation does not jeopardise pregnancy and childbirth, but it does impair female fecundity and has a low risk of impairment of erection and ejaculation in young males. The latter can almost completely be avoided by a careful "close rectal wall" proctectomy technique. Some argue that low risk patients (e.g. <5 rectal polyps) can be identified where ileorectal anastomosis (IRA) might be reasonable. We feel that the risk of rectal cancer after IRA means that IPAA should be recommended for the vast majority of FAP patients. We accept that in some very selected cases, based on clinical and genetics data (and perhaps influenced by patient choice regarding female fecundity), a stepwise surgical strategy with a primary IPA followed at a later age by a secondary proctectomy with IPAA could be proposed.

Adenomatous Polyposis Coli↗
PubMed2003

Probiotics in inflammatory bowel disease: a critical review.

Intestinal bacteria play a key role in inflammatory bowel disease. Probiotics attempt to modify disease by favourably altering bacterial composition, immune status, and inflammation. Until recently, probiotic therapy was considered 'folk' medicine, but there now is emerging interest on the part of the general public and scientific communities in the use of probiotics in human disease. This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans. There are very few such published randomized clinical trials, but some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis. Obstacles to providing probiotic therapy include selection of appropriate strains, poorly regulated probiotic quality standardization, processing and human biologic factors which impair probiotic viability, difficulty in maintaining new bacterial populations in the gut, and local product unavailability. Studies have focused on specific inflammatory bowel disease subgroups, limiting general applicability for the practitioner. Basic research highlights the importance of bacteria in these conditions, and the possibility that probiotics will modify physiological parameters. Well-designed, randomized clinical studies are still required to define the role of probiotics as therapeutic agents in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed2002

Probiotics--role in inflammatory bowel disease.

The aetiology of inflammatory bowel disease is still unclean. Whilst a specific pathogen agent associated with these diseases has not been found, the rationale for probiotic therapy in inflammatory bowel disease is based on convincing evidence involving intestinal bacteria in their pathogenesis. Encouraging results have been obtained with probiotic therapy in several animal models of experimental colitis. The administration of highly concentrated probiotic preparations represents a valid approach both for the prevention of pouchitis onset and relapses. The encouraging results obtained in ulcerative colitis and Crohn's disease need to be further assessed in large double-blind trials.

Animals↗
PubMed1998

Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.

Acute Disease↗