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A rat model of ileal pouch-rectal anastomosis.

After colectomy and ileal pouch-rectal anastomosis, pouchitis may occur. Pouchitis is a poorly defined condition with unknown etiology. The aim of this study was to develop an animal model of pouchitis. Ileal pouch-rectal anastomosis was created in Lewis and Sprague-Dawley rats. Rats were studied 4 and 8 weeks after surgery, and pouchitis was assessed by stool output, histology, and tissue myeloperoxidase (MPO) levels. Some rats were treated with allopurinol or metronidazole beginning the day of surgery. Rats with pouches demonstrated inflammation with a monocytic infiltration, luminal exudate, mucosal ulcerations, and serosal inflammation. Rats with pouches had increased anaerobic bacterial flora compared with normal ileum. After creation of pouches, Lewis rats (histology score = 8.4 +/- 1.6; MPO = 17.3 +/- 3.6, mean +/- SD) developed more severe inflammation than Sprague-Dawley rats did (histology score = 4.3 +/- 1.8; MPO = 5.5 +/- 3.6) within 4 weeks, p < 0.001 and 8 weeks after surgery, p < 0.05. Stool output was also greater in Lewis (55 +/- 7 g/kg/day) compared with Sprague-Dawley rats with pouches (43 +/- 5 g/kg/day), p < 0.05. Metronidazole treatment reduced histology score (6.0 +/- 0.5) p < 0.05 and MPO (5.9 +/- 1.6) p < 0.001 in rats with pouches compared with rats with pouches that had no treatment. Allopurinol treatment in rats with pouches reduced histology score (4.0 +/- 1.7) and MPO (3.9 +/- 1.6), p < 0.001, compared with rats with pouches that had no treatment. Ileal pouch-rectal anastomosis in rats induced inflammation within 4 weeks, demonstrated differential host genetic susceptibility, and was associated with increased number of pouch bacteria. Anaerobes, especially bacteroides sp. and free radical, may mediate inflammation. Ileal pouch-rectal anastomosis surgery in rats may be a useful animal model for the study pouchitis.

Allopurinol↗

Short- and long-term outcomes of ileal pouch-anal anastomosis for ulcerative colitis.

UNLABELLED: Ileal pouch-anal anastomosis was an important advancement in the treatment of ulcerative colitis. The aim of this study was to determine whether early complications of ileal pouch-anal anastomosis in patients with ulcerative colitis are associated with poor late functional results. PATIENTS AND METHODS: Eighty patients were operated on from 1986 to 2000, 62 patients with ileostomy and 18 without. The early and late complications were recorded. Specific emphasis has been placed on the incidence of pouchitis with prolonged follow-up. RESULTS: The ileostomy was closed an average of 9.2 months after the first operation. Fourteen patients were excluded from the long-term evaluation; 6 patients were lost to regular follow-up, 4 died, and 4 patients still have the ileostomy. Of the 4 patients that died, 1 died from surgical complications. Early complications after operation (41) occurred in 34 patients (42.5%). Late complications (29) occurred in 25 patients as follows: 16 had pouchitis, 3 associated with stenosis and 1 with sexual dysfunction; 5 had stenosis; and there was 1 case each of incisional hernia, ileoanal fistula, hepatic cancer, and endometriosis. Pouchitis occurred in 6 patients (9.8%) 1 year after ileal pouch-anal anastomosis, 9 (14.8%) after 3 years, 13 (21.3%) after 5 years, and 16 (26.2%) after more than 6 years. The mean daily stool frequency was 12 before and 5.8 after operation. One pouch was removed because of fistulas that appeared 2 years later. CONCLUSIONS: Ileal pouch-anal anastomosis is associated with a considerable number of early complications. There was no correlation between pouchitis and severe disease, operation with or without ileostomy, or early postoperative complications. The incidence of pouchitis was directly proportional to duration of time of follow-up.

Adult↗

VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases.

VSL#3 (VSL#3) is a high-concentration probiotic preparation of eight live freeze-dried bacterial species that are normal components of the human gastrointestinal microflora, including four strains of lactobacilli (Lactobacillus casei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), three strains of bifidobacteria (Bifidobacterium longum, B. breve and B. infantis) and Streptococcus salivarius subsp. thermophilus. Data from noncomparative trials suggest that VSL#3 has clinical potential in the treatment of active mild to moderate ulcerative colitis and as maintenance therapy for patients with ulcerative colitis in remission. In addition, a randomised, open-label, multicentre trial showed that VSL#3 in combination with low-dose balsalazide (a prodrug of mesalazine [mesalamine; 5-aminosalicylic acid]) was more effective than standard doses of basalazide or mesalazine monotherapy in the treatment of acute mild to moderate ulcerative colitis. Randomised, double-blind, placebo-controlled studies have shown VSL#3 is effective in preventing the onset of acute pouchitis in patients with newly formed surgical pouches, and in maintaining remission following antibacterial treatment of acute pouchitis in patients with a history of refractory or recurrent pouchitis. Treatment guidelines from the US and the UK include VSL#3 as a therapeutic option for the prevention of pouchitis relapse in patients with chronic pouchitis. In general, VSL#3 was well tolerated in clinical trials. Large, well designed, controlled confirmatory clinical trials will further determine the place of VSL#3 in the treatment of ulcerative colitis.

Colitis, Ulcerative↗

Endoscopic assessment of acute inflammation of the ileal reservoir after restorative ileo-anal anastomosis.

Forty-seven patients, undergoing ileo-anal anastomosis for ulcerative colitis (42) or familial polyposis (5), were endoscopically examined after protective ileostomy or after restorative ileo-anal anastomosis. The neorectum and the ileum above were examined in all cases and multiple biopsies were taken. No symptoms of pouch inflammation were found in 41 subjects; 80.5% of these had non-macroscopic lesions and 19.5% had focal lesions such as congestion, petechiae, mucous hypersecretion (5), or single ulcers (3). None of these developed pouchitis. Pouchitis was observed in the other six subjects, who all underwent surgery for ulcerative colitis and developed 14 clinical episodes of pouchitis during the follow-up. In these cases the entire neorectum mucosa was always affected by the lesions which, in 50%, also extended to the ileum above. The most common endoscopic features (71.4%) were congestion, potechiae, oozing areas, mucous hypersecretion, and multiple superficial ulcers. In half the remaining cases (14.3%) the neorectum showed the features, described above, while the upper ileum was affected by deep round or irregular ulcers within normal mucosa; Crohn's disease was excluded in these cases. In the remaining 14.3%, pouchitis showed a pseudomembranous feature. In our experience, the endoscopic pattern of pouchitis is polymorphic. Although an ulcerative colitis-like feature prevails, pseudomembranous and Crohn's ileitis-like features may also be present.

Adenomatous Polyposis Coli↗

Axonal necrosis of enteric autonomic nerves in continent ileal pouches. Possible implications for pathogenesis of Crohn's disease.

OBJECTIVE: Axonal necrosis was first described in samples of small intestine from patients with Crohn's disease (A.M. Dvorak et al. Hum Pathol 1980; 11:620-634). Clinically evident inflammation of continent ileal reservoirs (pouches) has clinical features that resemble Crohn's disease. Possible similarities in the pathogenesis of Crohn's disease and pouchitis were sought using ultrastructural and microbiologic tools to identify damaged enteric nerves and tissue bacteria. METHODS: An encoded ultrastructural and microbiologic study of replicate biopsies from 114 samples of human intestine was done. Biopsies from ileum, colon, conventional ileostomy or continent pouch were obtained from patients with ulcerative colitis, Crohn's disease, or familial polyposis and grouped into three clinical study groups (control, normal pouch, pouchitis), based on clinical and endoscopic criteria. Biopsies were prepared for electron microscopy with standard methods; replicate biopsy samples were washed extensively before preparing cultures designed to identify aerobic as well as facultative and obligate anaerobic bacteria (Onderdonk et al. J Clin Microbiol 1992; 30:312-317). The ultrastructural diagnosis of damaged enteric nerves was based on previously published criteria for axonal necrosis (A.M. Dvorak and W. Silen. Ann Surg 1985; 201:53-63). Intergroup comparisons were tested for significance using Chi-square analysis. RESULTS: The highest incidence of axonal necrosis was present in Crohn's disease control biopsies (53%), regardless of whether bacteria were present (or not) in cultures of replicate biopsies. Axonal necrosis also occurred in more ulcerative colitis and familial polyposis biopsies (regardless of biopsy site) that had positive bacterial cultures than in those that did not (p < 0.001). In addition, axonal necrosis was documented in 42% of the pouch biopsies from ulcerative colitis and familial polyposis patients, particularly in those pouches that were found to be inflamed by clinical criteria and that also had positive bacterial cultures of the biopsied tissues. Control biopsies from patients with ulcerative colitis and familial polyposis had significantly less nerve damage than pouch biopsies in the presence of positive cultures (p < 0.01). Among the clinically inflamed pouches biopsied in ulcerative colitis or familial polyposis patients, we found that none had damaged enteric nerves when bacterial cultures were negative (p < 0.005). If the presence of axonal necrosis alone was compared with the presence of undamaged enteric nerves in all biopsies from patients with ulcerative colitis, a highly significant number of ulcerative colitis biopsies with axonal necrosis occurred in pouches (72%) compared with controls (p < 0.001). CONCLUSIONS: The ultrastructural finding of axonal necrosis in Crohn's disease confirms previous studies. The presence of damaged enteric nerves in patients with pouchitis provides ultrastructural support to the clinical impression of similarities between pouchitis and Crohn's disease. The association of damaged nerves and invasive bacteria in pouchitis suggests mechanistic similarities for the pathogenesis of Crohn's disease that requires further investigation.

Adenomatous Polyposis Coli↗

Carriage of adhesive Escherichia coli after restorative proctocolectomy and pouch anal anastomosis: relation with functional outcome and inflammation.

Restorative proctocolectomy with pelvic ileal reservoir is a well accepted option for the surgical treatment of ulcerative colitis. Acute pouchitis is a common complication and resembles acute ulcerative colitis. Patients with ulcerative colitis carry Escherichia coli that adhere to epithelial cells and thus this study examined whether acute pouchitis is associated with the carriage of adhesive E coli. E coli isolated from stool samples from 24 patients (median age 34 years, range 16-64; 13 men, 11 women) who had had restorative proctocolectomy with pelvic ileal reservoir were examined by means of the buccal epithelial cell adhesion assay. Patients were studied at a median of 12 months (range 7-21) after operation. Eight of 24 patients had acute pouchitis at the time of study. Adhesive E coli were detected in nine of 24 patients with a pelvic ileal reservoir compared with none of 12 controls (p < 0.05). The buccal epithelial cell adhesion index was inversely related to the degree of acute pouchitis (rs = 0.46, p = 0.024) and to the functional outcome (rs = -0.49, p = 0.022). Carriage of adhesive E coli was not related to the design of the reservoir. By contrast with ulcerative colitis, acute pouchitis is not associated with the carriage of adhesive E coli.

Adolescent↗

Clinical and physiological aspects of ileal pouch-anal anastomosis.

Proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for severe chronic ulcerative colitis and familial polyposis coli because the entire colonic mucosa is removed while anal function can be preserved and the necessity for permanent ileostomy is eliminated. Long-term functional results are generally gratifying, as defecation frequency and degree of incontinence are acceptable in most patients. Pouchitis, however, a non-specific inflammation of the ileal reservoir, is a major long-term complication occurring in a considerable number of patients. The etiology of pouchitis is unknown. Since pouchitis occurs more frequently or even exclusively in ulcerative colitis patients it is assumed that pouchitis is a novel manifestation of inflammatory bowel disease. However, bacterial overgrowth in the ileal pouch may also play a pathogenetic role. Chronic inflammation and villous atrophy of varying severity is found in virtually all pouches. Acute inflammatory changes and ulceration are associated with pouchitis.

Adenomatous Polyposis Coli↗

Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease.

BACKGROUND: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. METHODS: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered t an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5-10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). RESULTS: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35-203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. CONCLUSION-: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted.

Administration, Oral↗

Role of stasis and oxidative stress in ileal pouch inflammation.

BACKGROUND: Although ileal pouch-anal anastomosis has become the operation of choice for patients with chronic ulcerative colitis and familial adenomatous polyposis coli, ileal pouch inflammation or pouchitis remains a significant postoperative complication. Numerous factors such as fecal stasis have been implicated in the etiology of pouchitis; however, pouchitis remains poorly understood due to the lack of a small animal model. One of the primary goals of this study was to surgically create a reservoir or U-pouch in the ileum of a rat in which stasis would occur in a manner that was unimpeded by other complicating factors such as a colectomy. This model would allow investigation of the hypothesis that intestinal stasis leads to biochemical changes that predispose the ileal pouch to inflammation and oxidative stress. MATERIALS AND METHODS: A U-pouch was surgically created in the terminal ileum of Lewis rats just proximal to the ileocecal valve without a colectomy. Stasis was assessed by serial barium radiographs over 48 h. Thirty days after surgery, mucosa was obtained from the ileal U-pouches and nonoperated ileum to assess inflammation and neutrophil infiltration histologically and by measuring myeloperoxidase activity. Oxidative stress was assessed by measuring 8-isoprostane levels in urine. Once the model was validated and it was established that stasis and inflammation occurred in the pouch, either vitamin E or allopurinol was administered for 30 days after which myeloperoxidase and 8-isoprostane levels were again measured. RESULTS: In our experimental model, ileal stasis resulted in increases in both mucosal myeloperoxidase activity and urinary 8-isoprostane levels, suggesting that oxidative stress was associated with stasis. Thirty-day treatment with vitamin E or allopurinol reduced ileal myeloperoxidase activity and urinary 8-isoprostane levels. CONCLUSION: These studies demonstrated that stasis in the ileum occurred and was associated with neutrophil infiltration and oxidative stress. Antioxidant treatment reduced the inflammatory response suggesting a role for antioxidant therapy in the treatment of pouchitis.

Animals↗

CXC and CC chemokine expression in inflamed and noninflamed pelvic ileal pouch tissue.

BACKGROUND AND AIMS: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis (IPAA) in patients operated on for ulcerative colitis. The cause is unknown, but both the history of ulcerative colitis and increased bacterial concentration are important factors. Chemokines are mediators for the recruitment of inflammatory cells to the site of inflammation. This study examined the tissue expression of a panel of specific chemokines and the corresponding recruitment of inflammatory cells in IPAA tissue with and without inflammation and after antibiotic treatment. PATIENTS AND METHODS: Biopsy specimens postoperatively from ulcerative colitis patients with IPAA were obtained by endoscopy. Biopsies were taken from 8 patients with noninflamed IPAA and from 14 patients with an episode of acute pouchitis, before and after antibiotic treatment. Biopsies were stained for CD68, CD3, elastase, eotaxin, IP-10, MCP-1, MCP-3, and IL-8 and analyzed by NIH Image analyzer. RESULTS: Expression of IL-8, MCP-1, MCP-3, and IP-10 was significantly higher in pouchitis than normal pouch. The expression of MCP-1, MCP-3 and IP-10 were significantly lower after antibiotic treatment. CONCLUSION: These data support the importance of chemokines for the leukocyte recruitment in pouch tissue during acute pouchitis.

Adult↗

Anatomic and functional characteristics of the rat ileal pouch.

BACKGROUND: The definitive operation for chronic ulcerative colitis (UC) and familial adenomatous polyposis is total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Mild inflammation (pouchitis) is omnipresent in pouches and becomes severe in 50% of UC patients with IPAA. The etiology of pouchitis is likely due to combined genetic, microbial, and immunologic factors. Epithelial cell exposure to surgical trauma and/or to changes in intestinal bacterial composition may account for the inflammatory infiltrate. Progress in understanding pouchitis is restricted by the lack of suitable animal models. METHODS: An ileal pouch-rectal anastomosis [IPRA] in rats was developed to reproduce a model of human IPAA and clinical, gross and histologic criteria were determined. RESULTS: Many shared features with human ileal pouch were observed. CONCLUSION: IPRA is an important in vivo model to study mechanisms of repair, defense and immunity that may contribute to pouchitis.

Anastomosis, Surgical↗

Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora.

BACKGROUND: Preliminary trials of probiotics in preventing recurrent chronic pouchitis have been encouraging. AIM: To investigate the efficacy of Lactobacillus GG supplementation as primary therapy for ileal pouch inflammation, and its effect on the microbial flora. METHODS: Twenty patients, with a previous history of pouchitis and endoscopic inflammation, were recruited for a prospective, randomized, double-blind, placebo-controlled trial of Lactobacillus GG supplementation (10 LGG, 10 placebo) in two gelatine capsules [(0.5-1) x 10(10) colony-forming units/capsule] b.d. for 3 months. Quantitative bacterial culture of fresh faecal samples and biopsies taken from the pouch and afferent limb was performed before and after supplementation. RESULTS: Lactobacillus GG supplementation changed the pouch intestinal flora by increasing the ratio of total faecal lactobacilli to total faecal anaerobes (P = 0.03) and enhancing the frequency of lactobacilli-positive cultures in the pouch and afferent limb mucosal biopsy samples. However, only 40% of patients were colonized with Lactobacillus GG. No differences were observed between the groups with regard to the mean pouchitis disease activity index or the total anaerobes or aerobes of faecal or tissue biopsy samples. CONCLUSIONS: A single-strain probiotic bacterium supplement of Lactobacillus GG changed the pouch intestinal bacterial flora, but was ineffective as primary therapy for a clinical or endoscopic response. More clinical trials are needed to evaluate the right placement and dosage of probiotics within a treatment regimen for pouchitis.

Adult↗

Increased bacterial permeation in long-lasting ileoanal pouches.

BACKGROUND AND AIMS: Bacterial overgrowth appears to play an important role in the pathogenesis of ileoanal pouches. Therefore, the capability of bacterial permeation and its determinants is of great interest. The aim of this study was to examine bacterial permeation in the ileoanal pouch and to correlate the results with the degree of inflammation, the epithelial resistance, the mucosal transport function, and the age of the ileoanal pouches. MATERIALS AND METHODS: Biopsies were taken from 54 patients before colectomy (n = 13; preileal pouch-anal anastomosis [IPAA]), and closure of ileostomy (n = 7; deviation), <1 year after closure of ileostomy (n = 8; intact pouch I), >1 year after closure of ileostomy (n = 16; intact pouch II), in the case of pouchitis (n = 11), and in 11 controls. Tissues were mounted in a miniaturized Ussing chamber. Escherichia coli was added to the mucosal side of the Ussing chamber, and the permeation was proven by serosal presence of E. coli. Epithelial and subepithelial resistance was determined by transmural impedance analysis. Active Na-glucose cotransport and active Cl secretion were measured. Specimens were analyzed by fluorescent in situ hybridization with oligonucleotide probes targeting the bacterial 16s ribosomal RNA. The bacteria in and on the tissue were enumerated. RESULTS: Bacterial permeation occurred in 2 of 13 pre-IPAA, 2 of 7 deviations, 0 of 8 intact pouch I, 9 of 16 intact pouch II, 5 of 11 pouchitis specimens, and 0 of 11 ileum controls. The frequency of bacterial permeation in the intact pouch II group is higher than in the intact pouch I group (P < 0.001). Epithelial resistance, mannitol fluxes, electrogenic chloride secretion, sodium-glucose cotransport of the bacterially permeated specimens versus nonpermeated of the intact pouch II group, and the pouchitis group and subepithelial resistance remained unchanged. Intramural bacteria could be detected by fluorescence in situ hybridization mainly in long-lasting pouches, but there was no correlation with bacterial permeation. CONCLUSIONS: The long-lasting ileoanal pouch is associated with increased bacterial permeability. This is not correlated with a disturbed function of the pouch mucosa but could be a precursor of pouchitis.

3-O-Methylglucose↗

Prognostic significance of superficial fissuring ulceration in patients with severe "indeterminate" colitis.

Some colectomy specimens from patients with severe colitis contain superficial fissuring-type ulcers but do not have any other features of Crohn's disease (CD). This finding may cause difficulty with regard to distinguishing ulcerative colitis (UC) from CD and, thus, lead to a diagnosis of "indeterminate" colitis. The aim of this study was to evaluate the clinical and pathologic features, and outcome, of a cohort of patients with colitis and superficial fissuring ulcers, but without any other features that may suggest a diagnosis of CD. We retrospectively identified 21 patients (male-to-female ratio, 10/11; mean age, 38 years) with severe chronic active colitis, all of whom had at least one (range, 1-3) superficial fissuring ulcer in their colectomy specimens (but without any other features of CD), as well as a control group of 18 patients (male-to-female ratio, 10/8; mean age, 41 years) with equally severe disease, but without fissuring ulcers. Both groups were evaluated for a variety of clinical and pathologic features, such as clinical presentation, degree, extent, and duration of colitis, and follow-up information, such as the development of pouchitis, pouch fistulae, and any other features of CD. Overall, 81% of the study patients presented clinically with fulminant colitis and underwent an emergent or urgent colectomy, compared with only 41% of the control patients (P = 0.02). Nine (43%) study patients had active serositis in their colectomy specimens, whereas only 1 (6%) control patient had this finding (P = 0.002). However, no significant differences were noted in either the extent or severity of disease or the presence of active ("backwash") ileitis, between the study and control groups. Upon follow-up (mean, 42 months; range, 4-121 months), the study patients with superficial fissuring ulcers developed pouchitis significantly more often (68% vs. 20%, P = 0.007) than the control group following an ileal pouch-anal anastomosis (IPAA) procedure. One patient from each group developed an anal fissure and another from each group developed an anastomotic stricture. In addition, 1 study patient developed a pouch-cutaneous fistula, and 1 control patient developed an enterocutaneous fistula to a loop ileostomy. Finally, 1 control patient ultimately had her pouch excised because of recurrent intractable pouchitis. However, none of the other study or control patients developed any clinical or pathologic manifestations of CD. We conclude that superficial fissuring ulcers may occur in patients with severe chronic active UC, particularly those who present with fulminant disease. Affected individuals should not be considered to have CD or "indeterminate" colitis and should not be denied an IPAA procedure. Nevertheless, the presence of superficial fissuring-type ulcers in patients with severe chronic active UC denotes a subgroup with a higher risk of pouchitis following surgical resection.

Adult↗

Pre-pouch ileitis: a disease of the ileum in ulcerative colitis after restorative proctocolectomy.

OBJECTIVE: Ileal inflammation in ulcerative colitis can occur as backwash ileitis or prestomal ileitis. After restorative proctocolectomy (RPC), ileal inflammation may be present in the pouch (pouchitis) but inflammation proximal to the pouch in the neo-terminal ileum, so called pre-pouch ileitis (PI), has also been observed. As pouchitis is increasingly common and PI can mimic it, our aim was to characterize this condition. SUBJECTS AND METHODS: A review of prospectively collected data on 571 inflammatory bowel disease patients undergoing follow-up after RPC in a single centre over 22 years was performed. The histology of biopsy material was reviewed and staining for colonic mucosal phenotypic changes was undertaken. It was not routine practice to prospectively assess all patients for pre-pouch ileitis when the database was constructed. RESULTS: Of 19 patients with inflammation of the pre-pouch neo-terminal ileum (NTI) identified three had Crohn's disease and one a NSAID stricture. The remaining 15 had a characteristic diffuse inflammation extending from the NTI-pouch junction proximally: pre-pouch ileitis. The inflammation extended proximally for up to 50 cm. Fistula formation was seen in only one. Seven (47%) of 15 had pouchitis but only two had suffered backwash ileitis pre-operatively. Seven responded to medical therapy and four to surgery. The histological appearances including staining for colonic phenotypic change were similar in PI and pouchitis. CONCLUSION: Pre-pouch ileitis is uncommon. As the patients' previous diagnosis of UC was confirmed and there was no radiological or histological evidence of Crohn's disease, PI appears to have a distinct pathogenesis from Crohn's disease.

Adolescent↗

Long term metabolic consequences of ileal pouch-anal anastomosis for ulcerative colitis.

OBJECTIVES: Chronic inflammation in the ileal pouch is the most significant late complication after ileal pouch-anal anastomosis (IPAA). It leads to changes in mucosal morphology, with consequent decreased vitamin B12, bile acid and cholesterol absorption documented. The aims of this study were to evaluate long term metabolic consequences at least 5 yr after IPAA and the influence of pouchitis on pouch histology and on bile acid, lipid, and vitamin B12, A, E, and D metabolism. METHODS: A total of 104 patients with a J-pouch who were operated on between 1985 and 1994, as well as 21 ulcerative colitis patients with a conventional ileostomy were enrolled for the study. Routine blood tests, vitamin status, vitamin B12 levels, and bile acid absorption were determined, as well as endoscopy with biopsies. The pouchitis disease activity index (PDAI) was calculated. On the basis of histology, IPAA patients were divided into three subgroups: 1) those with no villous atrophy, 2) those with partial villous atrophy, and 3) those with subtotal or total villous atrophy. RESULTS: Incidence of pouchitis was 42.3%, and was strongly associated with villous atrophy. In IPAA patients with subtotal or total villous atrophy (32.7%), serum levels of albumin, calcium, total cholesterol, triglycerides, and vitamin E were significantly reduced (p < 0.05). The lowest bile acid and vitamin B12 absorption rates were seen in patients with inflammation in the proximal limb. Vitamin D deficiency was seen in 10.6%, and vitamin A and B12 deficiency in approximately 5% of IPAA patients. CONCLUSIONS: Metabolic consequences after IPAA are associated with pouchitis, grade of villous atrophy, and extent of inflammation in the remaining ileum. Patients with active chronic inflammation need long term follow-up.

Adult↗

Ileal pouch-anal anastomosis. Patterns of failure.

During the period from 1980 through 1990, our institution constructed 253 ileoanal reservoirs in 253 patients, of whom 25 (9.9%) experienced pouch failure. A poor functional result was the most common cause of pouch failure (seven [28%] of 25 patients). Unsuspected Crohn's disease became manifest in 13 (5%) of the 253 patients, resulting in pouch loss due to perianal sepsis or pouch fistulas in six patients (24% of 25 failures), and resulted in a significantly increased risk of pouch failure compared with that of the non-Crohn's population. Pouchitis occurred in 78 patients (31%) and accounted for four (16%) of 25 failures, but patients with pouchitis were not at higher risk for pouch failure than were patients who did not have pouchitis (failure rates of 6.4% vs 10.4%, respectively; not significant). Significant pelvic sepsis in the absence of Crohn's disease developed in 13 patients, five (38%) of whom lost their pouches. Poor functional results, pelvic sepsis, and unsuspected Crohn's disease were the major causes of pouch failure, while pouchitis was not.

Age Factors↗

Anti-neutrophil cytoplasmic auto-antibodies (ANCA) in ulcerative colitis (UC): no relationship with disease activity.

The relationship between anti-neutrophil cytoplasmic auto-antibodies (ANCA) and disease activity in inflammatory bowel diseases remains controversial. The aim of this study was to highlight the relationship between ANCA presence or titers and disease activity in ulcerative colitis (UC). Three groups of patients with UC were studied: 1) group A included 39 patients who had not undergone colectomy, 2) group B, 43 patients with subtotal colectomy and ileo-rectal anastomosis, 3) group C, 98 patients with proctocolectomy and ileo-anal anastomosis, including 88% with pouchitis and 12% without pouchitis at the time of the study. Determination of ANCA was performed using the standardized indirect immunofluorescence assay. ANCA were positive in 59%, 65%, and 54% of patients from groups A, B, and C, respectively (NS). No relationship between ANCA presence or titers and UC activity could be detected within groups A and B. In group C, 45 of 86 patients (52%) without pouchitis and 8 of 12 patients (67%) with pouchitis, were ANCA positive (NS). These results do not support a relationship between ANCA and UC activity in this cohort of 180 patients.

Adult↗