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Factors influencing the functional outcome of restorative proctocolectomy in ulcerative colitis.

BACKGROUND: Restorative proctocolectomy is considered to be the procedure of choice in the operative treatment of ulcerative colitis. The aim of this study was to evaluate the functional outcome following operation and to identify possible predictive factors. METHODS: Some 168 patients (median age 32 years, 102 men) with ulcerative colitis underwent restorative proctocolectomy. The functional outcome was evaluated by a symptom index created from a questionnaire at a median of 29 (13-123) months of follow-up. The records of these patients were reviewed, and preoperative, peroperative and postoperative variables were registered and related to outcome. RESULTS: The response rate to the questionnaire was 155 (92 per cent) of 168. The symptom index was related to patients' overall assessment of outcome. In spite of a perceived good result many patients experienced a number of symptoms. Age over 50 years (P < 0.01), presence of extraintestinal manifestations (P < 0.05) and late complications, such as anastomotic stricture (P < 0.05), pouchitis (P < 0.01) and anal pain (P < 0.05), were related to a less favourable outcome. CONCLUSION: While preoperative data may help in selecting patients suitable for restorative proctocolectomy, prevention of late complications seems most important in improving the functional outcome.

Adolescent↗

Evolution of the pelvic pouch procedure at one institution: the first 100 cases.

BACKGROUND: Total extirpation of the colon with pelvic pouch formation, and the avoidance of a permanent stoma, continues to pose a challenge for better results, both technically and functionally. The aims of this study were to investigate the first 100 pelvic ileal-pouch procedures, assessing changes in surgical technique, their relationship to morbidity and long-term outcome, and compare this to the few large international series. METHODS: Between 1984 and 1997, 100 patients had a pelvic J-shaped ileal-pouch formed, 58 two-stage and 42 three-stage procedures. Fifty had a hand-sewn pouch-anal anastomosis and 50 a double-stapled anastomosis. Seventy-three were for ulcerative colitis, five for indeterminate colitis, 20 for familial adenomatous polyposis (FAP), one for multiple primary colorectal cancers, and one for constipation. RESULTS: After a median follow-up of 68 months, 97% of patients still have a functioning pouch. There were two postoperative deaths (one after-pouch formation and one after-stoma closure). Morbidity occurred in 52 patients, including three patients with pouch leaks and three pouch-anal anastomosis leaks (6% leak rate), 27% with a small bowel obstruction (2% early, 20% late, 5% both), a 19% anal stricture rate, and a 9% pouchitis rate. Three pouches have been removed (all for Crohn's disease). Median number of bowel movements per day was six, with 85% of patients reporting a good quality of life. Patients following a double-stapled procedure have less anal seepage and improved continence over those with a hand-sewn ileal pouch-anal anastomosis. CONCLUSIONS: Despite high morbidity rates, pelvic pouch formation provides satisfactory long-term results for patients requiring total proctocolectomy, with functional results and morbidity rates comparable to larger overseas series.

Adenomatous Polyposis Coli↗

Dysplasia in the ileoanal pouch.

Formation of an ileo-anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch-anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a 'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long-term safety of the ileo-anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long-term follow-up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long-term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo-anal pouch.

Journal Article↗

A study of the complications and pelvic visceral function after restorative proctocolectomy and W pouch construction.

OBJECTIVE: Aspects of ileal pouch surgery remain controversial. The authors' single practice experience of 107 operations illustrates many of them. It was hoped that its study would contribute usefully to the debate. PATIENTS AND METHODS: Details of all 107 restorative proctocolectomies carried out since the operation was started in Gloucester in 1984 until the study period ended have been kept prospectively. All patients had proctectomy by mesorectal dissection, and 106 had W pouch restoration. Four suffered functional failure requiring reversion to ileostomy and three patients have died. The remaining 99 were sent a questionnaire concerning pelvic visceral function and evidence of pouchitis. Records of all but one of the patients have been reviewed. RESULTS: Surgical morbidity was low with neither chronic pelvic sepsis, pouch related fistula, pouch haemorrhage nor pouch ischaemia. Mucosectomised patients had similar bowel control to the stapled group. The policy change from routine to selective protective ileostomy proved satisfactory. W pouch function was found to be comparable to that reported from major J pouch series, although anti-diarrhoeal usage was reduced, and was not influenced by either gender, age or time since surgery. CONCLUSION: None of the following reasonably intuitive assumptions seem supported by our findings: that mesorectal excision necessarily poses a greater danger to pelvic visceral function than close rectal dissection, that the greater capacity of W pouches will be reflected in markedly less frequency, that mucosectomy would impair anal control, or that a defunctioning ileostomy is a mandatory precaution. Pouch frequency is less if wind can be passed separately; otherwise functional outcome seems determined by other, non-technical, factors.

Adenomatous Polyposis Coli↗

Probiotic bacteria enhance murine and human intestinal epithelial barrier function.

BACKGROUND & AIMS: The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T(84) monolayers. METHODS: IL-10 gene-deficient and control mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T(84) monolayers. RESULTS: Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor alpha and interferon gamma and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. CONCLUSIONS: Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.

Animals↗

Medical therapy for ulcerative colitis 2004.

There continue to be evolutionary changes in the management of ulcerative colitis despite the fact that, aside from a variety of aminosalicylate formulations, no new therapies have been approved over the past few decades. Nevertheless, debates continue regarding the optimization of treatment with aminosalicylates and the short- and long-term benefits of immunomodulation in ulcerative colitis. This article focuses on the most recent clinical studies pertaining to the management of ulcerative colitis and explores both the advances and controversies pertaining to aminosalicylate therapy, corticosteroids, cyclosporine, and the purine antimetabolites. Novel therapeutic approaches--including preliminary experience with biological therapies directed at tumor necrosis factor and other cytokines, adhesion molecules, growth factors, and probiotics--will be reviewed. Recent data regarding potential chemoprevention in long-standing ulcerative colitis and management of postoperative complications and pouchitis will also be discussed.

Adjuvants, Immunologic↗

Ileoanal pouch procedures in children.

PURPOSE: The aim of this study was to review the long-term experience with colectomy and the ileoanal pouch procedure (IAPP) in children from one hospital. METHODS: Between 1977 and 2001, 168 children under 18 years of age underwent colectomy and IAPP. One hundred thirty-one had ulcerative colitis (UC). Twenty-six had familial colonic polyposis (FP), 9 had Hirschsprung's disease (HD), and 2 had colonic inertia. Ninety-seven had a J-pouch, 62 had a lateral pouch, and 9 had a straight pull-through (SP). The mean age was 13.9 years. RESULTS: Complications within 2 years included pouchitis (16%), ileoanal strictures (14%), and adhesions (7%). There were no deaths. Fifty-six patients (33%) required reoperation, including 20 revisions of large pouches and 8 conversions of SP to pouches because of stool frequency. Six children (3.6%) had later pouch removal (3 had Crohn's disease). Stool frequency at 6 months was 3.8 (mean). At 6 months 5% had occasional soiling. Eighty-four percent can delay defecation over 1(1/2) hours; 82% can urinate without a bowel movement. With a mean follow-up of 11.2 years, 94.6% are functioning well. CONCLUSIONS: Colectomy with IAPP is the preferred operation for children with UC, FP, and selected HD. The J-pouch is the preferred technique because of simplicity of construction and sparsity of complications.

Adenomatous Polyposis Coli↗

Total colectomy and straight ileo-anal soave endorectal pull-through: personal experience with 42 cases.

During the period from 1974 to June 2000 we used the straight ileo-anal Soave pull-through to treat 42 patients (24 affected by total colonic aganglionosis [TCA], 10 with ulcerative colitis and 8 with familial polyposis). The aim of this paper is to show that this operation, associated with total colectomy, is highly recommended, causing a lower number of complications when compared to the various "reservoir" techniques. The mean age of the 24 patients with TCA at the time of the pull-through was 2.8 years; in the ulcerative colitis group, it was 14.3 years and in the familial polyposis group 27.2 years. We always used an ileo-anal deferred anastomosis and never performed temporary loop-diverting ileostomy at the time of the pull-through. In the TCA patients we had no immediate or long-term serious post-operative complications: ileal adaptation, after a frequency of 10 - 12 liquid stools a day, showed a gradual, constant and in some cases amazing improvement in all children. Two years after surgery, the mean stool frequency was 3.6 per 24 hours with no significant differences between the 3 main groups; only 4 children still presented with occasional soiling. After pull-through, all children showed normal growth curves in the long term. There was no malabsorption, no serious electrolyte imbalance, no perianal excoriation, no strictures or intestinal obstruction; their quality of life was considered more than satisfactory by the children's families. We have no direct experience with the various ileal "reservoir" techniques for ulcerative colitis and ileal polyposis nor with colon-sparing operations for TCA; as reported in the literature, all these surgical procedures seem to have a higher number of complications such as pelvic sepsis, pouchitis, enterocolitis, etc. compared with our series; we therefore confirm that total colectomy with the straight ileo-anal Soave pull-through is our treatment of choice, as it is simpler to perform and has fewer short- and long-term complications.

Adolescent↗

[Probiotics as therapeutic agents in irritable bowel syndrome].

Probiotics are defined as living micro-organisms which, when administered in large amounts, confer a health benefit on the host. The use of probiotics in the therapy of infectious bowel diseases as well as maintaining remission of ulcerative colitis and in pouchitis is evidence-based. Also, in several studies proof could be supplied that specific probiotics relieve the symptoms and the course of irritable bowel syndrome. Some trials showed a significant improvement of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in reducing pain and abdominal bloating. However, in most of the studies rather small numbers of patients were examined. Furthermore, these studies do not always closely follow scientific standards (randomised, double-blind, placebo-controlled). Therefore, confirmatory studies are necessary to examine the effect of probiotics in irritable bowel syndrome.

Follow-Up Studies↗

Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer.

The prevalence of inflammatory bowel disease (IBD) in patients with PSC differs in various part of the world. Ulcerative colitis (UC) is most common, but 1 to 14% of all primary sclerosing cholangitis (PSC) patients have Crohn disease with colonic involvement. Many PSC patients without clinical symptoms of IBD have colonoscopic and histological findings compatible with IBD, and the subclinical phase may last several years before onset of symptoms of active colitis. The characteristics of UC in patients with PSC are different from those in UC patients without PSC. The colitis is usually substantial, the clinical course of the colitis is quiescent, and rectal sparing is common. Moreover, PSC patients with UC have a higher risk of developing colorectal dysplasia/carcinoma than UC patients without PSC. In patients having an ileal pelvic pouch with ileal anal anastomosis, PSC is a risk factor for development of pouchitis. It is important that all PSC patients with UC are included in colonoscopic surveillance programs.

Cholangitis, Sclerosing↗

Reduced Paneth cell alpha-defensins in ileal Crohn's disease.

The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of alpha-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.

Analysis of Variance↗

Intestinal flora and mucosal immune responses.

The normal intestinal flora and the mucosal immune system exist in close spatial proximity. A normal structure and function of both very complex systems is required for health and develops in a constant and interactive process. An abnormal host response to the normal intestinal flora leads to chronic intestinal inflammation. Probiotic bacteria may modulate the intestinal flora and the mucosal immune response and are an effective therapy for remission maintenance of ulcerative colitis and pouchitis.

Animals↗

Probiotics as modulators of the gut flora.

Probiotic ingestion can be recommended as a preventative approach to maintaining the balance of the intestinal microflora and thereby enhance 'well-being'. Research into the use of probiotic intervention in specific illnesses and disorders has identified certain patient populations that may benefit from the approach. Undoubtedly, probiotics will vary in their efficacy and it may not be the case that the same results occur with all species. Those that prove most efficient will likely be strains that are robust enough to survive the harsh physico-chemical conditions present in the gastrointestinal tract. This includes gastric acid, bile secretions and competition with the resident microflora. A survey of the literature indicates positive results in over fifty human trials, with prevention/treatment of infections the most frequently reported output. In theory, increased levels of probiotics may induce a 'barrier' influence against common pathogens. Mechanisms of effect are likely to include the excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation and the formation of specific antimicrobial agents. As such, persons susceptible to diarrhoeal infections may benefit greatly from probiotic intake. On a more chronic basis, it has been suggested that some probiotics can help maintain remission in the inflammatory conditions, ulcerative colitis and pouchitis. They have also been suggested to repress enzymes responsible for genotoxin formation. Moreover, studies have suggested that probiotics are as effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome. The approach of modulating the gut flora for improved health has much relevance for the management of those with acute and chronic gut disorders. Other target groups could include those susceptible to nosocomial infections, as well as the elderly, who have an altered microflora, with a decreased number of beneficial microbial species. For the future, it is imperative that mechanistic interactions involved in probiotic supplementation be identified. Moreover, the survival issues associated with their establishment in the competitive gut ecosystem should be addressed. Here, the use of prebiotics in association with useful probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate selectively metabolised by probiotics. Combinations of probiotics and prebiotics are known as synbiotics.

Animals↗

Inulin and oligofructose: impact on intestinal diseases and disorders.

A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimised by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favour the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.

Animals↗

Long-term follow-up of patients with jejunal pouch reconstruction after total gastrectomy. A randomized prospective study.

BACKGROUND: Fifty-one patients were operated on during 1988-1992 and randomized after total gastrectomy to one of two reconstruction types. Twenty patients with jejunal pouch reconstruction and 14 patients with Roux-en-Y reconstruction (67% of all) survived at least 3 years after total gastrectomy. We studied symptoms, eating capacity, and nutrition in these patients during the clinical follow-up; 21 patients were assessed by mail questionnaire 8 years after total gastrectomy. METHODS: Postoperative symptoms, number of meals, and eating capacity were assessed by standard questionnaire during 3 years' follow-up. Weight loss and nutritional laboratory variables were measured, and upper intestinal endoscopy with biopsy was performed during the follow-up. Eight years after the operation symptoms, ability to eat, and number of meals consumed were studied by means of a mail questionnaire. RESULTS: Three years postoperatively dumping (64% compared with 10%, P < 0.05) and early satiety (86% compared with 5%, P < 0.05) were commoner in the Roux-en-Y group. In the pouch group eating capacity was better (96% of normal compared with 67%, P < 0.05), and the patients ate fewer meals per day (mean, 2.7 versus 5.3, P < 0.05) at 3 years. Mean weight loss at 3 years was 9.9 kg in the Roux-en-Y group compared with 1.5 kg in the pouch group (P < 0.05). 25 (OH) vitamin D concentration tended to be higher in the pouch group (47.3 nmol/l compared with 33.9 nmol/l). In the Roux-en-Y group serum alkaline phosphatase activity increased significantly during the 3 postoperative years (from mean 163 U/l to 248 U/l, P < 0.01) and tended to be higher (248 U/l compared with 216 U/l in the pouch group). None of the patients developed oesophagitis or pouchitis during the follow-up. One patient developed a bezoar in the pouch 5 years after gastrectomy. CONCLUSIONS: Pouch reconstruction after total gastrectomy is associated with diminished postoperative symptoms, better eating capacity, and decreased weight loss compared with Roux-en-Y reconstruction. Jejunal pouch reconstruction is thus the recommended surgical method after total gastrectomy.

Adult↗

Risk of osteopenia after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: The aim of our study was to evaluate the influence of pouchitis and villous atrophy on bone mineral density and metabolism at least 5 years after ileal pouch-anal anastomosis for ulcerative colitis (UC). METHODS: Eighty-eight subjects with a J-pouch operated on between 1985 and 1994, and 20 ulcerative colitis subjects with a conventional ileostomy were enrolled. Endoscopy was performed and spine and femoral neck bone mineral densities measured. Bone metabolism was assessed by measurement of serum levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D3, calcium, alkaline phosphatase and urinary N-telopeptide cross-linked of type I collagen (NTX). RESULTS: In the lumbar spine, 37% of the J-pouch subjects with subtotal to total villous atrophy had osteopenia (Z score <-1), whereas none of the subjects with normal villous structure had reduced bone densities in the spine or femoral neck. The highest prevalence of osteopenia (66.7%) and the lowest spine (mean -0.89+/-0.36; P = 0.006) and femoral neck (mean -0.63+/-0.29; P = 0.07) Z scores were found among the patients (n = 12) with inflammation in the proximal limb of the pouch. No biochemical parameters were found to predict osteopenia and in stepwise regression analysis, the only independent risk factors for osteopenia were low body mass index and villous atrophy. CONCLUSIONS: Patients with a J-pouch showing high inflammatory activity and villous atrophy in the pouch need long-term follow-up and should be ensured adequate intake of calcium and vitamin D.

Bone Density↗

Recognition of bactericidal/permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance.

BACKGROUND: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis.

Adolescent↗

Understanding inflammatory bowel disease--the clinician's perspective.

The treatment of patients with ulcerative colitis and Crohn's disease is a huge challenge to the clinician mainly because the etiology of IBD is still completely unknown. Pathogenetic mechanisms, in constrast, have partly been elucidated thanks to immunohistochemical investigation of the tissue in IBD and the study of experimental animal models of gut inflammation. There is extensive evidence that at least in Crohn's disease tolerance for commensal bacteria is lost which leads to uncontrolled inflammation mediated by a T-helper 1 response and to tissue destruction of the gut epithelium with inadequate repair. Genetic factors are probably responsible for increased susceptibility and may define disease phenotypes. These insights have led to a dramatic improvement of our therapeutic means with the development of the chimeric monoclonal antibody to TNF. The pathogenetic mechanisms are less clear in UC. The hypothesis is that UC is a T-helper 2 mediated disease. We have a very attractive way to study the early onset of Crohn's disease in the postoperative Crohn's situation. Newer therapeutic approaches should aim at preventing recurrence of Crohn's lesions in the normal postoperative bowel. Such model is also available for UC since there is increasing evidence that pouchitis is recurrent ulcerative colitis in the small bowel. Cooperation between clinicians and basic scientists is the best way to achieve fast progress in understanding IBD.

Humans↗