Ileal Pouch-anal Anastomosis Patients Research Articles

Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis patients

Background and aimPatients with ulcerative colitis (UC) are at an increased risk for low bone mineral density (BMD). It is unclear whether proctocolectomy with ileal pouch-anal anastomosis (IPAA) for UC alters the risk of bone loss. The aim of this study was to compare BMD in UC patients with and without IPAA. MethodsA total of 267 patients with UC and IPAA (study group) were compared to 119 UC patients without IPAA (control group) in this cross-sectional study. The demographic and clinical variables including dual-energy X-ray absorptiometry scan results were compared. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. Univariate and multivariate analyses were performed to assess risk factors associated with low BMD. Age, gender, race, smoking status, steroid use, alcohol use, body mass index, years of absent estrogen protection, use of calcium, vitamin D supplements and disease duration were selected as covariates. Results83 (31.1%) had low BMD in the study group vs. 18 (15.1%) in the control group (p=0.001). 2/13 (15.4%) had low BMD before surgery. The mean age of patients in the study and control groups were 44.7±14.1 vs. 52.4±17.7years, respectively (p<0.001). The hip BMD was lower in the study group (0.93±0.17g/cm2) than that in the control group (0.98±0.17g/cm2) (p=0.038). Fragility fracture was documented in 23 (8.6%) patients in the study group vs. 3 (2.5%) in the control group (p=0.038) Sixty-four (24.0%) of the study group patients were using corticosteroids after surgery in contrast to 93 (78.2%) in the control group (p<0.001). On multivariable analyses, covariate adjusted factors associated with a low BMD in UC patients were advanced age [odds ratio (OR) 1.51 per 5years; 95% confidence interval [CI], 1.34–1.71], low body mass index (OR=2.37 per 5kg/m2 decrease; 95% CI, 1.68–3.36), and the presence of IPAA (OR=6.02; 95% CI, 2.46–14.70). For the 13 IPAA patients who had information available, BMD before IPAA was low. After a median of 46 (Range 7–84) months after IPAA, BMD improved in 7/13 patients (53.8%), while it continued to be low in 6/13 (46.2%) patients. ConclusionsLow BMD is common in patients with UC. The risk appears to persist even after colectomy and IPAA surgery suggesting that these patients need to be monitored for bone loss.

Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch–anal anastomosis

We hypothesized that patients with primary sclerosing cholangitis (PSC) may have a higher risk for prepouch ileitis in the setting of ileal pouch-anal anastomosis (IPAA). The aim of this study was to compare endoscopic and histologic inflammation in the afferent limb (prepouch ileum) and pouch between IPAA patients with and without PSC. In all, 39 consecutive inflammatory bowel disease (IBD) and IPAA patients with PSC (study group) were identified and 91 IBD and IPAA patients without PSC (control group) were randomly selected with a 1:2 ratio. Demographic, clinical, endoscopic, and histologic variables were analyzed. There were no significant differences in age, gender, and nonsteroidal antiinflammatory drug use between the study and control groups. Twelve (30.8%) patients in the IPAA-PSC group had coexisting autoimmune disorders, in contrast to five (5.5%) patients in the IPAA control group (P < 0.001). More patients in the study group had endoscopic inflammation as demonstrated by the higher Pouchitis Disease Activity Index (PDAI) endoscopic scores of the afferent limb and pouch body than those in the control group (P = 0.02 and P < 0.001, respectively). In addition, more patients with PSC had higher PDAI histologic scores of the afferent limb than those without PSC (P < 0.001). Multivariate analysis showed higher PDAI endoscopy and histology subscores were associated with risk for PSC, with odds ratio 1.34 (95% confidence interval [CI]: 1.34, 3.79) and 1.61 (95% CI: 1.00, 2.58), respectively. Concurrent PSC appears to be associated with a significant prepouch ileitis on endoscopy and histology in patients with IPAA. Pouch patients with long segment of ileitis should be evaluated for PSC.

Technical Aspects of Ileoanal Pouch Surgery in Patients with Ulcerative Colitis

Restorative proctocolectomy with ileal pouch-anal anastomosis is the procedure of choice for patients with ulcerative colitis requiring surgery. A J-pouch with a stapled anastomosis has been the preferred technique because it is quicker, safer, and associated with good functional outcomes. A diverting loop ileostomy is usually created at the time of ileal pouch-anal anastomosis. In patients with severe fulminant colitis or toxic megacolon, restorative proctocolectomy with ileal pouch-anal anastomosis is performed in multistages. The technical aspects of ileal pouch-anal anastomosis in patients with ulcerative colitis are reviewed in this article.

Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis and impact of anti-tumor necrosis factor on postoperative outcomes

The anti-tumor necrosis factor alpha (infliximab) has become an effective drug in the medical treatment of moderate or severe ulcerative colitis [1]. Infliximab can delay the incidence of complications and disease progression. However, the definitive treatment of ulcerative colitis is a surgical approach. Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) remains the standard of care for most patients with ulcerative colitis [2]. The short-term postoperative outcomes can substantially be improved by laparoscopic surgery for gastrointestinal diseases, including colorectal cancer and gastric cancer [3–9]. This advance in laparoscopic surgery has been translated into laparoscopic restorative proctocolectomy (LRPC) with IPAA for the treatment of ulcerative colitis [10]. However, the impact of medical treatment with infliximab on a subsequent surgical treatment is unclear and because the data are still scarce, there is debate whether infliximab increases postoperative complications. Given this uncertainty, Coquet-Reinier and colleagues [11] evaluated the effect of infliximab on postoperative morbidity after LRPC with IPAA in patients who were previously treated with this anti-tumor necrosis factor. In this report published in the August issue of Surgical Endoscopy, the authors compared the results regarding operating time, complications, and hospital stay between patients with LRPC and IPAA with or without preoperative treatment with infliximab. There was no significant difference between patients treated with and those treated without infliximab regarding mean operative time (353 vs. 355 min), complication rate (23 vs. 38%), and mean hospital stay (22 vs. 25 days). Coquet-Reinier and colleagues concluded that there was no adverse impact of infliximab previous therapy on postoperative morbidity of patients with ulcerative colitis treated with laparoscopic restorative proctocolectomy with IPAA. Laparoscopic restorative proctocolectomy with IPAA is a highly demanding procedure. It can be safe and effective only when it is performed in specialized institution by high-volume surgeons. The difficulties in both disease management and laparoscopic surgery are reflected by the long hospital stay, more than 3 weeks, and a mean operating time of approximately 6 hours in this study. Although it is hard to draw conclusions from a small retrospective analysis, this study provides useful information that infliximab does not likely increase postoperative complications after laparoscopic RPC and IPAA. Certainly further evaluation is needed. Given the aggressiveness of surgery with adverse effects in quality of life, current research is focused on how to design and develop novel biologic agents that would be effective in reversing the progression of disease or even associated with cure-sparing large surgical procedures and adverse effects. However, ulcerative colitis and morbus Crohn are complex multifactorial disorders, such as cancer, and there are still major challenges for the development of novel biomarkers and biologic drugs that may successfully treat complicated disorders. The advent of next-generation sequencing technology for partial or complete sequencing of human genomes advances in genome-wide association studies, genetics, and personal genomics along with E. Hanisch Klinik fur Allgemein-Viszeral-und Endokrine Chirurgie, Asklepios Klinik Langen, Akademisches Lehrkrankenhaus der JWG, Universitat Frankfurt, Rontgenstr 20, 63225 Langen, Germany

Diagnosis and Management of Pouchitis and Ileoanal Pouch Dysfunction

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to inflammatory and noninflammatory sequelae, such as pouchitis, Crohn's disease of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiology into idiopathic and secondary types, and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the mainstay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. Although management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.

Quality of Life Ten and More Years After Restorative Proctocolectomy for Patients With Familial Adenomatous Polyposis Coli

Few studies on long-term quality of life after restorative proctocolectomy and ileal pouch-anal anastomosis have been published. Most of them survey a mixed patient population of familial adenomatous polyposis and ulcerative colitis. The present study analyzes long-term results more than 10 years after ileal pouch-anal anastomosis for patients with familial adenomatous polyposis, exclusively. One hundred thirty-five patients who underwent ileal pouch-anal anastomosis more than 10 years ago were identified from the prospective familial adenomatous polyposis registry at Heidelberg University hospital. They received the German version of the health-specific Short Form 36 Health Survey and the disease-specific Gastrointestinal Quality of Life Index by mail. To assess the impact of disease-specific factors, 10 questions asking for ability to work, current medication, pouchitis, and extracolonic manifestations of familial adenomatous polyposis were added to the Gastrointestinal Quality of Life Index questionnaire. Among 84 patients who answered the questionnaires the median follow-up was 13.4 years (range, 10.3-23.8 y).The results of the Short Form 36 Health Survey were comparable to a German normative population in all dimensions, whereas the overall score for the Gastrointestinal Quality of Life Index was significantly reduced compared with healthy individuals (111.8 vs 120.8, P = .0014). Carcinoma at the time of ileal pouch-anal anastomosis, desmoid tumors, or duodenal adenomas had no significant influence on quality of life. More than 7 bowel movements during the daytime were found to reduce quality of life significantly (103.5 vs 115, P = .0127). More than 2 defecations per night diminished the score further (101 vs 125, P < .0001). Patients younger than 40 years at the time of ileal pouch-anal anastomosis had significantly better results than older patients (120 vs 109.5, P = .0076). Ileal pouch-anal anastomosis is a safe surgical procedure with a high quality of life comparable to that of a normative population after long-term follow-up of patients with familial adenomatous polyposis.

Timing and Indications for Colectomy in Chronic Ulcerative Colitis: Surgical Consideration

Total proctocolectomy (TPC) cures a patient of the intestinal manifestation of chronic ulcerative colitis. The timing of surgery during the illness will influence the choice of operation, the frequency of post-operative complications, and the long-term functional outcomes. Surgery is divided into emergency, urgent, and elective procedures. Emergency cases are performed for complications of fulminant colitis: hemorrhage, perforation, toxic megacolon or sepsis. A subtotal colectomy (STC) with a Brooke ileostomy (BI) is the procedure of choice. STC removes the bulk of the disease, allows the patient’s health to be restored, medication to be withdrawn, and permits a future restorative operation. Urgent operations occur in hospitalized patients with continued symptoms after seven days of maximal medical therapy. Once again the preferred operation is a STC-BI. Indications for elective colectomy include: persistent symptoms despite maximal medical therapy, medication side-effects, persistent chronic disease state, dysplasia/malignancy. Elective surgical options include TPC-BI, TPC with ileal-pouch anal anastomosis (IPAA), or STC-BI. The choice of operation is based upon patient preference and preoperative physiologic and functional status. Factors associated with increased post-operative complications are weight loss >10%, multiple preoperative blood transfusions, albumin <3.0 gm/dl, and degree of immuno-suppression. In high-risk patients, STC-BI should be performed. IPAA can be performed later after the patient’s health is restored. In conclusion, numerous factors affect the timing and choice of operation in patients with CUC. Avoiding complications in IPAA patients is essential as they negatively impact the long-term function and durability of the IPAA.

A Prospective Analysis of Clinical Variables, Serologic Factors, and Outcome of Ileal Pouch-Anal Anastomosis in Patients With Backwash Ileitis

The outcome of ileal pouch-anal anastomosis in patients with backwash ileitis is controversial. We prospectively compared the outcomes of ileal pouch-anal anastomosis in colitis patients with backwash ileitis and colitis patients without backwash ileitis. Consecutive colitis patients undergoing ileal pouch-anal anastomosis were reviewed. All patients were classified after surgery as being either backwash ileitis-positive or backwash ileitis-negative. Serum drawn preoperatively was assayed, using enzyme-linked immunosorbent assay, for anti-Saccharomyces cerevisiae, anti-outer membrane of porin C, anti-CBir1, anti-I2, and perinuclear anti-neutrophil cytoplasmic antibody. Outcomes included acute pouchitis (antibiotic responsive), chronic pouchitis (antibiotic dependent or refractory), or de novo Crohn's disease (small inflammation above the pouch inlet or pouch fistula). Out of 334 patients, 39 (12%) were backwash ileitis-positive. Compared with backwash ileitis-negative patients, backwash ileitis-positive patients had a higher incidence of pancolitis (100% vs 74%; P = .0001), primary sclerosing cholangitis (15% vs 2%; P = .001) and high-level (>100 enzyme-linked immunosorbent assay units/ml) perinuclear anti-neutrophil cytoplasmic antibody expression (29% vs 9%; P = .001). After a median follow-up of 26 months, 53 patients (16%) developed acute pouchitis, 37 (11%) developed chronic pouchitis, and 40 (12%) developed de novo Crohn's disease. There was no significant difference between the backwash ileitis-positive and backwash ileitis-negative patient groups in the incidence of acute pouchitis, chronic pouchitis, or de novo Crohn's disease. There was a significantly higher incidence of pancolitis, primary sclerosing cholangitis, and high-level perinuclear anti-neutrophil cytoplasmic antibody expression in backwash ileitis-positive patients than in backwash ileitis-negative patients. The incidence of acute pouchitis, chronic pouchitis, and de novo Crohn's disease after ileal pouch-anal anastomosis does not differ significantly between backwash ileitis-positive and backwash ileitis-negative patients.

T1293 Risk for Dysplasia and Adenocarcinoma of Ileal Pouch-Anal Anastomosis in Patients With Underlying Inflammatory Bowel Disease

T1293 Risk for Dysplasia and Adenocarcinoma of Ileal Pouch-Anal Anastomosis in Patients With Underlying Inflammatory Bowel Disease

Preoperative Wireless Capsule Endoscopy Does Not Predict Outcome After Ileal Pouch-Anal Anastomosis

The extent of preoperative small-bowel mucosal inflammation may be an important predictor of pouchitis after ileal pouch-anal anastomosis. This study examined the value of preoperative wireless capsule endoscopy in predicting outcome of ileal pouch-anal anastomosis in patients with ulcerative colitis or indeterminate colitis. Patients undergoing complete wireless capsule endoscopy before ileal pouch-anal anastomosis were identified. Findings on wireless capsule endoscopy were classified as positive (erosions, ulcers or erythema) or negative. Outcome was assessed prospectively and included no pouchitis, acute pouchitis, chronic pouchitis, or de novo Crohn disease. Patients with acute pouchitis, chronic pouchitis, or de novo Crohn disease were considered to have pouch inflammation. The 68 study patients (48 ulcerative colitis; 20 indeterminate colitis) had a median age of 38 years and included 34 males. Median follow-up time after ileostomy closure was 12 months (range, 3-63 months). Wireless capsule endoscopy was positive in 15 patients (22%) and negative in 53 patients (78%). Pouch inflammation was observed in 23 patients (34%), and included 8 patients with acute pouchitis, 3 patients with chronic pouchitis, and 12 patients with de novo Crohn disease. The incidence of acute pouchitis, chronic pouchitis, de novo Crohn disease, and pouch inflammation in the wireless capsule endoscopy-positive patient group was 7%, 7%, 20%, and 33% compared with 13%, 4%, 17%, and 34% in the wireless capsule endoscopy-negative patient group (all P = NS). There was no statistical association between the results of preoperative wireless capsule endoscopy and outcome after ileal pouch-anal anastomosis in patients with ulcerative colitis or indeterminate colitis. There seems to be little value of wireless capsule endoscopy in the preoperative evaluation of these patients.

Clinical utility of C-reactive protein in patients with ileal pouch anal anastomosis†

Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy for ulcerative colitis (UC). The clinical utility of C-reactive protein (CRP) in ileal pouch disorders has not been investigated. All IPAA patients with underlying UC who had serum CRP tested within 2 weeks of pouch endoscopy were included. The correlation between the level of serum CRP and the Pouch Disease Activity Index (PDAI) scores were evaluated. Diagnostic accuracy of CRP in assessing disease activity by PDAI endoscopy subscores was evaluated. There were 83 patients (with a total 88 CRP tests), including normal pouches (n = 7), active pouchitis (n = 6), chronic pouchitis (n = 18), Crohn's disease of the pouch (n = 23), cuffitis (n = 13), irritable pouch syndrome (n = 10), and surgery-associated complications (n = 11). Levels of CRP did not differ significantly among healthy and diseased pouch groups. CRP levels significantly correlated with the PDAI endoscopy subscores in the pouch body (P = 0.006) and afferent limb (P = 0.03). A CRP level of greater than 0.7 mg/dL for CRP using the receiver operating characteristics curve obtained the best sensitivity of 69.7% and specificity of 63.6% to detect active pouch inflammation. Serum CRP levels correlated with endoscopic inflammation in the pouch and afferent limb. Elevated CRP levels might be useful to monitor the degree of inflammatory activity in pouch noninvasively. However, the CRP level as a snapshot had a limited role in distinction between healthy and diseased pouch conditions diagnosed based on longitudinal clinical and endoscopic evaluation.

A Prospective Evaluation of the Long-Term Outcome of Ileal Pouch-Anal Anastomosis in Patients with Inflammatory Bowel Disease-Unclassified and Indeterminate Colitis

A Prospective Evaluation of the Long-Term Outcome of Ileal Pouch-Anal Anastomosis in Patients with Inflammatory Bowel Disease-Unclassified and Indeterminate Colitis

Secondary Pouchitis: Those With Identifiable Etiopathogenetic or Triggering Factors

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for the majority of patients with medically refractory ulcerative colitis (UC) or UC with dysplasia, or familial adenomatous polyposis. Various forms of pouchitis frequently occur after surgery. In fact, pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. The etiology and pathogenesis of pouchitis are not entirely clear. It is generally believed that the initiation and development of the disease process of pouchitis is associated with dysbiosis of pouch reservoir, as evidenced by a favorable response to antibiotic therapy. However, the majority of the patients do not show identifiable etiopathogenetic or triggering factors, therefore being labeled to have idiopathic pouchitis. In contrast, a subgroup of patients, particularly those with antibiotic-refractory pouchitis, may have obvious triggering factors for disease flare-up and progression and may be considered to have secondary pouchitis. Therefore, pouchitis can be classified on the basis of etiology into idiopathic and secondary causes. Approximately 20-30% of patients who present with chronic pouchitis have secondary identifiable and triggering factors, including cytomegalovirus or Clostridium difficile infection, ischemia, concurrent immune-mediated disorders, radiation, collagen deposition, and use of nonsteroidal anti-inflammatory drugs. Careful evaluation of these secondary causes of pouchitis that may contribute to resistance to antibiotics should be performed before the introduction of next-line medical therapy.

Free radical activity and lipid soluble antioxidant vitamin status in patients with long‐term ileal pouch‐anal anastomosis

OBJECTIVE: Ileal pouch-anal anastomosis (IPAA) is the operation of choice for patients with ulcerative colitis. Free radical activity and the status of lipid soluble antioxidant vitamins have not been previously assessed in patients with IPAA. The aim of the present study was to measure the plasma concentrations of lipophyllic antioxidants and free radical activity in IPAA patients and compare them with normal subjects. METHOD: Forty-eight IPAA patients and 50 healthy controls were studied. A dietary assessment of vitamin E (alpha-tocopherol) and carotene was undertaken and plasma antioxidant status was assessed. Plasma malondialdehyde (MDA) was measured to assess the extent of free radical damage. In IPAA patients, association between the degree of inflammation in the pouch mucosa and the plasma concentration of lipophyllic antioxidants and extent of free radical activity was investigated. RESULTS: The dietary intake of carotene was similar in both groups. Intake of vitamin E was significantly lower in patients than controls (P = 0.01). In the IPAA group plasma concentrations of alpha-carotene, beta-carotene and lycopene were significantly lower (P < 0.001) and alpha-tocopherol:cholesterol ratio significantly higher (P < 0.001). Free radical damage was significantly greater in patients than controls (P < 0.01). There were no significant correlations between the degree of inflammation in the pouch and plasma concentrations of MDA, carotenoids, alpha-tocopherol:cholesterol ratio or intake of vitamins. CONCLUSION: Compared with normal subjects, patients with IPAA have significantly lower plasma concentrations of lipophyllic antioxidants alpha-carotene, beta-carotene and lycopene and higher free radical activity suggesting increased oxidative stress. These differences do not appear to be related to diet and do not correlate with histological severity of pouch inflammation.

Efficacy of infliximab in refractory pouchitis and Crohnʼs disease-related complications of the pouch: A Belgian case series

Up to 25% of inflammatory bowel disease (IBD) patients undergoing surgery with an ileal pouch-anal anastomosis (IPAA) will develop chronic pouchitis not responding to antibiotics. In case reports, thiopurine analogs and infliximab (IFX) have been proposed as effective therapy in this setting. We analyzed the long-term efficacy of IFX in Belgian patients with refractory pouch complications. We identified 28 IPAA patients who received IFX for refractory luminal inflammation (pouchitis and/or pre-pouch ileitis, n = 25) and/or pouch fistula (n = 7). Patients with elements of Crohn's disease after review of the colectomy specimen were excluded. Clinical response was defined as complete in case of cessation of diarrhea, blood loss, and abdominal pain, and as partial in case of marked clinical improvement. Fistula response was defined as complete in case of cessation and as partial in case of reduction of fistula drainage. Eighty-two percent of patients were concomitantly treated with immunomodulatory agents. At week 10 following start of IFX, 88% of patients with refractory luminal inflammation showed clinical response (14 partial, 8 complete), while 6 patients (86%) showed fistula response (3 partial, 3 complete). The mPDAI dropped significantly from 9.0 (interquartile range [IQR] 8.0-10.0) to 4.5 (3.0-7.0) points (P < 0.001). After a median follow-up of 20 (7-36) months, 56% showed sustained clinical response while 3 out of 7 fistula patients showed sustained fistula response. Five patients needed permanent ileostomy. In this series, IFX was effective long-term in IPAA patients with refractory luminal inflammation and pouch fistula. These results warrant a prospective multicenter randomized controlled trial.

Risk Factors for Abnormal Liver Function Tests in Patients With Ileal Pouch–Anal Anastomosis for Underlying Inflammatory Bowel Disease

Liver involvement is common in patients with inflammatory bowel disease (IBD). However, the frequency and the significance of liver function test (LFT) abnormalities in patients with ileal pouch-anal anastomosis (IPAA) for underlying IBD have not been studied. The aim of this study was to evaluate the prevalence and to identify risk factors for abnormal LFTs in patients with IPAA and underlying IBD. All patients were identified from our prospectively maintained Pouchitis Database between 2002 and 2008. Abnormal LFTs were classified as the following: (i) any abnormal elevation of transaminases, and/or alkaline phosphatase (ALP), and/or bilirubin; (ii) hepatitis, if there was more than twice the elevation of transaminases; and (iii) cholestatic, if there was more than 1.5 times elevation of ALP. Clinical, endoscopic, and histological variables were assessed using Cox proportional hazard models for evaluating risk for abnormal LFTs. A total of 545 IPAA patients with underlying IBD were identified from the database, of which 373 patients who had LFTs done after their pouch surgery were included. This included 346 patients with ulcerative colitis, 25 with indeterminate colitis, and 2 with Crohn's colitis before surgery. Their mean age was 45.9+/-13.8 years. A total of 65 patients (17.4%) (40 men, 25 women, median age: 47 years) had abnormal LFTs. Of the patients, 52 (13.9%) had abnormal transaminases, whereas 15 (4%) were classified as having hepatitis. Thirty-five (9.4%) patients had an abnormal ALP level, with 18 (4.8%) classified as cholestatic. The most common cause of an abnormal LFT was transient elevation in 32 (49.2%) patients, followed by fatty liver (fatty change on imaging with body mass index (BMI) > or =25 kg/m(2) in the absence of other causes, including alcohol abuse and drug-induced hepatitis) in 10 (15.4%), drug-induced abnormal LFTs in 7 (10.7%), and chronic hepatitis B or C in 6 (9.2%). Primary sclerosing cholangitis (PSC) was responsible for abnormal LFTs in 10 patients (15.4%). Cox proportional hazard model analysis showed that BMI (hazard ratio (HR)=1.07, 95% confidence interval (95% CI): 1.02, 1.12; P=0.003), the presence of PSC (HR=4.49, 95% CI: 1.45, 13.89; P=0.009), autoimmune disorder (HR=2.54, 95% CI: 1.09, 5.93; P=0.031), a family history of IBD (HR=2.32, 95% CI: 1.29, 4.17; P=0.005), and extensive colitis before colectomy (HR=4.59, 95% CI: 2.04, 10.33; P<0.001) predicted any abnormal LFTs. Abnormal LFTs were common in patients with IPAA in this cohort. The presence of co-existing autoimmune disorder, a family history of IBD, extensive colitis before colectomy, the presence of PSC, and a high BMI appear to be a significant risk factors for abnormal LFTs. Whether abnormal LFTs affect health-related quality of life, pouch survival, and selection of pouch-related medical therapy requires further investigation.

Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease

The etiology of pouchitis after coloproctomucosectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis is still unknown. Beside changes in luminal antigens, the immunological predisposition is assumed to be responsible. In previous electrophysiological studies, we showed that mucosal barrier and transport function in pouchitis is markedly reduced. Thus, the aim of the present study was to analyze barrier function on the molecular level. Pouch biopsies of 36 ulcerative colitis patients were analyzed. Time points were (1) intraoperative immediately prior to ileal pouch-anal anastomosis (n = 13), (2) >1 year after ileostomy closure (pouch, n = 12), and (3) during pouchitis (n = 11). Control terminal ileum biopsies were obtained from eight patients undergoing hemicolectomy due to carcinoma. Expression of tight junction proteins was analyzed by Western blotting and confocal laser-scanning microscopy. To elucidate effects on epithelial barrier properties, impedance spectroscopy was performed in miniaturized Ussing chambers. In pouchitis, epithelial resistance was markedly reduced compared to non-inflamed pouch and control ileum. Expression of tight junction proteins claudin-1, 3, 4, 5, and 7 and occludin revealed differential expression regulation with the tightening tight junction protein claudin-1 being decreased and an increase of the pore-forming claudin-2, whereas other claudins remained constant. Morphometry indicated the mucosal surface to be unchanged. Pouchitis is characterized by a selective change of tight junction proteins in favor of opening the epithelial tight junction and, thus, the paracellular pathway, which contributes to the inflammatory process. This resembles changes in inflammatory bowel disease (IBD) and indicates IBD recurrence in pouchitis.

A Prospective Evaluation of the Long-Term Outcome of Ileal Pouch-Anal Anastomosis in Patients with Inflammatory Bowel Disease-Unclassified and Indeterminate Colitis

The long-term outcome of ileal pouch-anal anastomosis in patients with indeterminate colitis is controversial. The aim of this study was to prospectively evaluate the long-term outcome of ileal pouch-anal anastomosis in a closely monitored cohort of patients with ulcerative colitis or indeterminate colitis. Prospectively generated clinical profiles on consecutive patients with ulcerative colitis or indeterminate colitis undergoing ileal pouch-anal anastomosis with close postoperative follow-up by one surgeon were reviewed. All patients were classified before surgery as either ulcerative colitis or inflammatory bowel disease-unclassified, and after surgery as either ulcerative colitis or indeterminate colitis. Long-term outcomes included acute pouchitis (antibiotic responsive), chronic pouchitis (antibiotic dependent or refractory), or de novo Crohn's disease (small inflammation above the pouch inlet or pouch fistula). The study cohort of 334 patients were classified before surgery as ulcerative colitis in 237 (71 percent) and inflammatory bowel disease-unclassified in 97 (29 percent). After surgery, patients were classified as ulcerative colitis in 236 (71 percent) and indeterminate colitis in 98 (29 percent). After a median follow-up after stoma closure of 26 months, 53 patients (16 percent) developed acute pouchitis, 37 patients (11 percent) developed chronic pouchitis, and 40 patients (12 percent) developed de novo Crohn's disease. There was no significant difference in the incidence of acute pouchitis, chronic pouchitis, or de novo Crohn's disease between the ulcerative colitis, inflammatory bowel disease-unclassified, and indeterminate colitis patient groups. The incidence of acute pouchitis, chronic pouchitis, and de novo Crohn's disease after ileal pouch-anal anastomosis do not differ significantly between patients with ulcerative colitis, inflammatory bowel disease-unclassified, or indeterminate colitis. Patients with inflammatory bowel disease-unclassified and indeterminate colitis can undergo ileal pouch-anal anastomosis and expect a long-term outcome equivalent to patients with ulcerative colitis.

1104 A Prospective Analysis of Clinical Variables, Serologic Factors and Outcome of Ileal Pouch-Anal Anastomosis in Patients with Backwash Ileitis

1104 A Prospective Analysis of Clinical Variables, Serologic Factors and Outcome of Ileal Pouch-Anal Anastomosis in Patients with Backwash Ileitis

Anastomotic Sinuses After Ileoanal Pouch Construction

This study was designed to analyze the incidence, management, and outcome of pouch sinuses after ileal pouch-anal anastomosis at one institution. We identified 282 ileal pouch-anal anastomosis patients between 1992 and 2002 who had a pouchogram before planned ileostomy closure. The management and outcome of patients with pouchograms revealing pouch sinuses were reviewed. Twenty-two patients (7.8 percent) had a pouch sinus at pouchogram. Nineteen patients were observed and underwent repeat pouchogram. Of these, ten had sinus resolution (mean, 3.6 months) and underwent successful ileostomy closure. Eight patients underwent examination under anesthesia +/- sinus debridement. Six of these patients had subsequent pouchograms with five showing sinus resolution. The patient without resolution was not reversed. Of the eight patients who underwent examination under anesthesia +/- debridement, seven underwent ileostomy closure (mean, 4.9 months), with healing in six and pelvic sepsis in one. Four patients underwent successful ileostomy takedown despite persistent sinus. Overall, 21 of the 22 pouch sinus patients underwent ileostomy closure and only 1 had postoperative pelvic sepsis. Pouch sinuses after ileal pouch-anal anastomosis with ileostomy are uncommon. Most heal within six months. The majority of patients with sinuses eventually undergo successful ileostomy closure. Pelvic septic complications are rare but can occur despite sinus healing on pouchogram.