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Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA.A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18).Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] μg/g vs 550 [IQR, 250-1051] μg/g; P.0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of460 μg/g had80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of125 μg/g had over 80% specificity in predicting endoscopic remission.FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.

Post operative ventral hernias are common following Hartmann's procedure. There is a debate whether hernia repair is safe when performed concomitantly with colostomy closure. In this study we aimed to evaluate the outcomes of synchronous Hartmann reversal (HR) with a hernia repair, compared to a staged procedure. A retrospective multi-center study was conducted, including all patients who underwent Hartmann’s procedure from January 2004 to July 2017 in 5 medical centers. Patient data included demographics, surgical data and post-operative outcome. Two hundred and seventy-four patients underwent colostomy reversal following Hartmann's procedure. In 107 patients (39%) a concomitant ventral hernia was reported during the Hartmann's reversal. Out of this cohort, 62 patients (58%) underwent hernia repair during follow-up. Thirty two patients (52%) underwent a synchronous hernia repair and 30 patients (48%) underwent hernia repair as a separate procedure. Post operative complication rate was significantly higher in the colostomy reversal with synchronous hernia repair group when compared to HR alone group (53% vs. 20%; p

Summary Aim Hartmann's procedure is the surgical treatment of choice for perforated acute diverticulitis. Hartmann's reversal (HR) that is performed at a later stage may be challenging. The optimal timing for HR is still a subject for controversy. The aim of this study is to assess whether the timing of HR affects surgical outcome. Patients and methods A retrospective-cohort multi-center study was conducted, including all patients who underwent HR for acute diverticulitis from January 2004 to June 2015 in 5 medical centers. Patient data included demographics, surgical data and post-operative outcome. Results One hundred and twenty-two patients were included in the database. Median time from Hartmann's procedure to reversal was 182.7 days, with the majority of patients (76 patients, 62.2%) operated 60 to 180 days from the Hartmann's procedure. Fifty-seven patients (46.7%) had post-operative complications, most commonly wound infections (27 patients, 22.1%). Receiver operating characteristic (ROC) curve and a propensity score match analysis (P = 0.43) correlating between days to HR from the index procedure showed no specific cut-off point regarding post-operative complications (P = 0.16), Major (Clavien–Dindo score of 3 or more) complications (P = 0.19), Minor (Clavien Dindo 1-2) and no complications (P = 0.14). Median length of stay was 10.9 days (range 3-90) and Pearson correlation failed to demonstrate a correlation between timing of surgical intervention and length of stay (P = 0.4). Conclusion Hartmann's Reversal is a complex surgical procedure associated with high rates of complications. In our series, timing of surgery did not affect surgical complications rate or severity or the length of hospital stay.

Background Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. Methods Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. Results We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). Conclusions Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

Hartmann’s procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann’s procedure and evaluated factors affecting decision-making. Data on patient demographics, comorbidities, causes for Hartmann’s procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann’s procedure in five medical centers. Six hundred forty patients underwent Hartmann’s procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann’s reversal patients vs 73.5 years in non-reversal patients; P

Mediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery. Consecutive patients after pouch surgery due to ulcerative colitis (UC) were recruited at a comprehensive pouch clinic. Adherence to MED was calculated according to MED score, ranging from 0 (low adherence) to 9 (high adherence), based on food-frequency questionnaires. Pouch behavior was defined as normal pouch (NP) or pouchitis based on Pouchitis Disease Activity Index (PDAI) and disease activity was defined as active or inactive. C-reactive protein (CRP) and fecal calprotectin were assessed. Overall 153 patients were enrolled (male gender 47%; mean age 46 ± 14 years; mean pouch age 9.5 ± 7 years). MED scores were higher in patients with normal vs. elevated CRP and calprotectin levels (4.6 ± 1.8 vs. 4.4 ± 1.6, p = 0.28; 4.8 ± 1.8 vs. 4.07 ± 1.7, p

BackgroundPatients with ulcerative colitis [UC] who undergo proctocolectomy with an ileal pouch–anal anastomosis commonly develop pouch inflammation [pouchitis]. Pouchitis develops in a previously normal small intestine and may involve environmental factors. We explored whether diet and microbiota alterations contributed to the pathogenesis of pouchitis.MethodsPatients were recruited and prospectively followed at a comprehensive pouch clinic. Pouch behaviour was clinically defined as a normal pouch [NP] or pouchitis. Patients completed Food Frequency Questionnaires [FFQs]. Faecal samples were analysed for microbial composition [16S rRNA gene pyrosequencing].ResultsNutritional evaluation was performed in 172 patients [59% females], and of these, faecal microbial analysis was performed in 75 patients (microbiota cohort: NP [n = 22], pouchitis [n = 53]). Of the entire cohort, a subgroup of 39 [22.6%] patients had NP at recruitment [NP cohort]. Of these, 5 [12.8%] developed pouchitis within a year. Patients at the lowest tertile of fruit consumption [ConclusionsFruit consumption is associated with modification of microbial composition, and lower consumption was correlated with the development of pouchitis. Thus, fruit consumption may protect against intestinal inflammation via alteration of microbial composition.

The aim of the present study was to document long-term clinical recurrence and re-resection rates of segmental and extended colectomy in patients with Crohn’s colitis and to identify risk factors causing recurrence. Records of patients with isolated colonic Crohn’s disease who underwent colectomy between 1995 and 2013 and were followed at our medical center were identified. Data on age at diagnosis, gender, smoking, disease location at diagnosis, perianal and rectal disease, indication for surgery, preoperative disease duration, type of operation, primary anastomosis at first operation, length of resected specimen, recurrence of symptoms, postoperative medication, reoperation, and total follow-up time were retrieved. Thirty-five suitable patients (18 segmental colectomy, 17 extensive colectomy; 17 males; mean age at operation 36.6 years) were identified. Mean age at primary operation was 36 years. The mean preoperative disease duration was 121 months. Postoperative medical treatment was needed in 10 (56 %) patients undergoing segmental colectomy and in 16 (94 %) of those undergoing extensive colectomy (p = 0.01). There was longer reoperation-free survival in the segmental colectomy patient group (p = 0.02) and also a trend toward longer symptom-free survival compared to the extensive colectomy patient group (p = 0.105). There was no correlation between the length of resected bowel and recurrence. Patients operated on at a younger age did not have a higher rate of recurrence of symptoms. Shorter disease duration, smoking, and male gender were risk factors for clinical recurrence. Segmental resection with primary anastomosis can be safely performed in patients with limited Crohn’s colitis with reasonable clinical recurrence rates.

Hartmann’s reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann’s reversal. A retrospective study of all patients who underwent Hartmann’s reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes. 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann’s procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann’s procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien–Dindo score for distinguishing between minor (0–2 score, p = 1) and major complications (3–5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien–Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups. In this series, a laparoscopic approach to Hartmann’s reversal did not offer any short-term advantage when compared to an open surgical approach.

Background & Aims Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. Methods We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Results Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae . Conclusions Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.

Background Patients with familial adenomatous polyposis (FAP) may carry various adenomatous polyposis coli (APC) mutations. However, genotype-phenotype correlation for APC mutations is still debated and is yet to be evaluated with regard to pouch polyp formation. Objective To evaluate the association between APC mutation type and exon location and the outcome of pouch adenoma. Design setting and patients Forty-five FAP patients with defined pathogenic APC mutations, who underwent total proctocolectomy and ileal pouch anal anastomosis were classified by mutation type and location. Analysis was conducted for clinical and endoscopic parameters. Results Twenty patients had either indel/deletion mutations and 25 had nonsense/missense mutations. The indel/deletion group was associated with higher prevalence of preoperative hundreds of colonic adenomas (66.7% vs. 30%; P=0.030), lower rates of stapled versus sewn anastomosis (46.7% vs. 76%; P=0.060), of single stage surgery (13.3% vs. 44%; P=0.045) and with higher pouch adenoma formation rate (50% vs. 8%; P=0.002). Twenty-seven were carriers of exons 1 to 14 mutations and 18 were carriers of exon 15 mutations. Carriers of exon 15 mutations had higher prevalence of preoperative hundreds of colonic adenomas (55.6% vs. 22.2%; P=0.003) and a higher tendency for pouch and cuff adenoma formation rate. Adjusted odds ratio for pouch adenoma formation was 8.32 (1.42-48.80; P=0.019) for the indel/deletion group versus nonsense/missense, but no significant independent association was noted with mutation location. The mean number of pouch and cuff adenoma formation (per endoscopy) was higher among carriers of exon 15 mutations, but no significant independent association was noted the with mutation type. Conclusions Type and location of APC mutation are associated with colonic polyp burden, surgical outcome and likelihood of developing pouch adenomas. These findings may contribute to surgical and endoscopic surveillance decisions for FAP patients.

Background and aims: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). Methods: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. Results: Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8±15.4 years and duration of follow-up was 7.93±6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC–IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3±1.4 years and mean transplant-free survival was 23.5±1.6 years. Cox proportional-hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 ( p = 0.004) and 2.58 ( p = 0.046), respectively]. Conclusions: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD. * Abbreviations: : PSC : primary sclerosing cholangitis; IBD : inflammatory bowel disease; CCA : cholangiocarcinoma; LT : liver transplantation; UC : ulcerative colitis; ERCP : endoscopic retrograde cholangiopancreatography; UDCA, ursodeoxycholic acid; MRCP : magnetic resonance cholangiopancreatography; CD : Crohn’s disease.

To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR).Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists.The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8 %). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9 ± 11.9 vs. 68.7 ± 10.8 years, respectively, p = 0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS).Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.

BACKGROUND: Rates of postoperative complications are particularly high among patients with Crohn’s disease. OBJECTIVE: The aim of this study was to assess whether positive inflammatory histological margins, among other factors, pose a risk for intra-abdominal septic complications in patients with Crohn’s disease undergoing ileocolic resection. DESIGN: A retrospective study of patient records, during 2000–2010, was conducted. SETTINGS: This investigation was performed at a single medical center. PATIENTS: Included were 166 individuals with Crohn’s disease (85 males, mean age 35.6). INTERVENTION: Ileocolic resection with primary anastomosis was performed. MAIN OUTCOME MEASURE: The primary outcomes measured were postoperative intra-abdominal septic complications. RESULTS: Twenty-five patients (15%) developed intra-abdominal septic complications, including anastomotic leak, intra-abdominal abscesses and collections, and enterocutaneous fistulas. There were no postoperative deaths. Univariate analysis revealed that a long course of disease before surgery, an emergency surgery, steroid treatment of more than 3 months before surgery, additional sigmoidectomy, and positive surgical margins detected on histopathological examination were associated with intra-abdominal septic complications. In a multivariate analysis, only disease duration longer than 10 years (OR 4.575 (CI 1.592–13.142), p = 0.005), additional sigmoidectomy (OR 5.768 (CI 1.088–30.568), p = 0.04), and positive histological resection margins (OR 2.996 (CI 1.085–8.277), p = 0.03) were found to be independent risk factors. LIMITATIONS: This study was limited by the incomplete data regarding preoperative albumin levels. CONCLUSIONS: Positive histological margins, disease duration of more than 10 years, and added sigmoidectomy are independent risk factors that are associated with postoperative intra-abdominal septic complications in patients undergoing ileocolic resection for Crohn’s disease. These risk factors should be considered when the need for a diverting stoma is questionable. A frozen section of the margins may assist in the decision as to a temporary ileostomy construction.

Background Instillation of fibrin glue, a simple and safe procedure, has been shown to have a moderate short-term success rate in the treatment of cryptogenic perianal fistulas. Objective This study aimed to assess the long-term outcome of this procedure. Design This study included a retrospective chart review and telephone interviews. Settings This study was conducted at 4 university-affiliated medical centers. Patients Patients were included who underwent fibrin glue instillation for complex cryptogenic fistula between 2002 and 2003 within a prospective trial and had successful healing. Interventions Fibrin glue was instilled for complex cryptogenic fistula. Main outcome measures The main outcome measure was long-term fistula healing. Results Sixty patients participated in the initial trial; the fistulas in 32 of these patients were healed at 6 months. We have located and interviewed 23 (72%) of those patients. Seventeen (74%) patients remained disease free at a mean follow-up of 6.5 years. Six (26%) patients had variable degrees of recurrence; 4 needed further surgical intervention and 2 were treated with antibiotics only. Recurrent disease occurred at an average of 4.1 years (range, 11 mo to 6 y) from surgery, and on several occasions was at a different location in the perianal region. None of the patients experienced incontinence following the procedure. Limitations The retrospective nature of this long-term follow-up was a limitation. Twenty-eight percent of the potentially eligible patients were lost to long-term follow-up. Conclusions Short-term success of fibrin glue in the treatment of cryptogenic perianal fistula is predictive of long-term healing, but a quarter of those healed in the short term may develop recurrent symptoms in the long run. Injection of fibrin glue remains a safe and simple procedure and may preclude extensive surgery.

Shape-memory compression bowel anastomosis using a nickel and titanium alloy may reduce leak rates and eliminate foreign anastomotic material. Its safety and efficacy had been demonstrated by animal studies. We conducted the first prospective multi-center clinical evaluation of the safety and effectiveness of BioDynamix anastomosis with ColonRing™ for large-bowel end-to-end or side-to-end anastomosis.The ColonRing™ was compared to the standard double-stapled colorectal/colocolonic anastomosis. Intraoperative and immediate postoperative and 1- and 3-month postoperative follow-up data were recorded.Ten study patients (four males, median age 62 years, range 35-75) were compared to 13 demographically matched controls (six males, median age 62 years, range 47-82). Colorectal neoplasia was the most frequent indication for surgery (21/23 patients, 91%). The median anastomotic distance from the anal verge for both groups was 10 cm (6-20 cm). The first postoperative bowel movement was on day 5 ±2.2 (study group) and on day 4 ±1.8 (controls), and the median hospital stay was 8 days (6-14 days) and 7 days (6-13 days), respectively. There were no anastomotic leaks. There were three minor complications in each group, unrelated to the device in the study group. Two patients required transanal digital extraction of the ring which was detached but not expelled (one had a soft anastomotic stricture).Our preliminary results in this first study on humans indicate that the safety and efficacy of BioDynamix anastomosis with ColonRing™ in colorectal anastomosis in human is comparable to standard staples technology and warrant larger studies for further validation.

Urinary bladder drainage for several days after pelvic surgery is a common surgical practice, despite insufficient evidence supporting its routine use. The aim of this study was to prospectively evaluate the utility of urinary bladder drainage after pelvic colorectal surgery.Patients undergoing pelvic surgery were prospectively randomly assigned to 3 groups. In group A, the Foley catheter was removed on postoperative day 1, and in groups B and C it was removed on postoperative days 3 and 5, respectively. Male patients with severe prostatic symptoms were excluded from the study. The main outcome criterion was acute urinary retention requiring reinsertion of the Foley catheter.A total of 118 patients (68 males) at a mean age of 55 years were included in this study (group A, 41 patients; group B, 38; and group C, 39). Overall, urinary retention after removal of the Foley catheter occurred in 12 (10%) of the patients: 6 (14.6%) in group A, 2 (5.3%) in group B, and 4 (10.5%) in group C (P = .39). Symptomatic urinary tract infection was diagnosed in 5 patients in group A, 3 in group B, and 9 in group C, but this difference did not reach statistical significance. Likewise, there were no significant differences in anastomotic leak and intra-abdominal abscess rates among the 3 groups.Routine prolonged urinary bladder catheterization after pelvic surgery may not be required, and the Foley catheter may be safely removed on postoperative day 1. Larger studies are needed to confirm the findings of this study.

Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

Galectin-3, an endogenous pleiotropic beta-galactoside-binding protein, which is expressed by various malignant and normal cells, regulates many biological and pathological processes, including inflammation. In the present study, we tested a possible correlation between the severity of pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA) and the presence of galectin-3(+) macrophages in pouch mucosa. Paraffin-embedded pouch biopsies from patients with normal pouch function or chronic and recurrent acute pouchitis were immunohistostained with galectin-3, CD68, and smooth muscle actin (SMA) antibodies. Microscopic examination was performed in a blinded fashion. There was a significant decrease in the staining index of galectin-3 in the subepithelial macrophages in patients with chronic pouchitis (0.53, P=0.001; n=12) or recurrent acute pouchitis (0.43, P=0.008; n=10) when compared to patients with no clinical manifestations of pouchitis (0.63, n=12). No significant differences were noted in the lamina propria of small intestine biopsies from the same patients (from 0.63 to 0.68, P=0.24). Galectin-3 staining was restricted to CD68(+) macrophages and not present in myofibroblasts. Clinical manifestation of pouchitis is inversely correlated with galectin-3 expression in the pouches' subepithelial lamina propria macrophages.

Local excision for early rectal cancer has low morbidity and good functional results. Its use is limited by the inability to assess regional lymph nodes and by the uncertainty of oncologic outcome. We conducted a retrospective chart review of all patients who underwent local excision of early rectal cancer in two colorectal units between 1995 and 2007. The retrieved and analyzed data were patient age and gender, tumor size, tumor distance from the anal verge, tumor differentiation, and additional treatment. There were 42 patients with T1 rectal cancer: 24 underwent transanal endoscopic microsurgery and 18 had a transanal excision. The surgical margins were free of tumor in 39 patients (93%), they were involved by tumor in one (2%) and margin status was unclear in two (5%). Seven patients (16%) had postoperative complications. There was no postoperative mortality. The mean hospital stay was 67 h. Thirty-nine patients (93%) were followed up for 57 months (mean). Two patients had local recurrence, at 7 and 41 months post-surgery. They had a tumor that invaded into the lower third of the submucosa, sm3. Both received chemoradiotherapy, and underwent an abdominoperineal resection and a low anterior resection. One of them died of metastatic disease 13 months later and the other is alive with no evidence of disease. Another two patients had salvage low anterior resection, one for suspected local recurrence and one for lymphovascular invasion: the specimens were tumor free. Six patients died of unrelated causes. Local excision of early rectal cancer is a feasible and acceptable alternative to radical resection. It has low complication and recurrence rates and a short postoperative hospital stay.

The purpose of this study was to investigate the oncological and clinical outcome of ulcerative colitis (UC) patients with coexisting colorectal cancer/dysplasia following stapled ileal pouch-anal anastomosis (IPAA).One hundred eighty-five UC patients who underwent stapled IPAA were followed prospectively in a comprehensive pouch clinic. They were divided into three groups: colorectal cancer, dysplasia, and no cancer/dysplasia. Demographic parameters, clinical data, and oncological and functional outcome of the three groups were compared.Sixteen patients had cancer and 14 had dysplasia. Two of the three cancer patients who developed metastatic disease died. One patient who had rectal cancer was found to have cancer cells in the rectal cuff 10 years after IPAA. All other cancer/dysplasia patients were disease-free at 62 months (median). The 5-year survival rate was 87.5% for the cancer group and 100% for the others (p0.0001). Chemotherapy (nine patients) did not affect pouch function. Two rectal cancer patients who received radiotherapy did not maintain a functioning pouch. Overall pouch failure rates were 19%, 7%, and 6% for cancer, dysplasia, and no-cancer/dysplasia patients, respectively (p = 0.13). The mean frequency of bowel movements in 24 h was similar between the groups.Stapled IPAA is a reasonable option for UC patients with cancer/dysplasia. Chemotherapy is safe, but the effect of radiation on pouch outcome is worrisome. Close long-term follow-up for UC patients with cancer/dysplasia is recommended for early detection of possible recurrence.

Background: We designed and evaluated a novel concept in enhancing postoperative care of patients following restorative proctocolectomy (RPC) for ulcerative colitis (UC) and determined the risk factors, incidence, and nature of RPC-associated complications in this population. Methods: The study cohort consisted of consecutive UC patients post-RPC attending a comprehensive pouch clinic run by a gastroenterologist and a colorectal surgeon in a tertiary care medical center (from January 2003 to December 2005). Data were collected on their medical history, physical examination, laboratory tests, pouch endoscopy and biopsies, and anonymous in-house patient satisfaction questionnaires mailed to the first 90 patients. Assessment was also done on data regarding risk factors, incidence, and nature of RPC-associated complications. Results: A total of 120 UC patients with a functioning pouch visited the clinic: mean age 37 years, range 13–75; 57 males; mean disease duration 11 years; mean follow-up 65 months. Of the 55 patients who responded to the questionnaire, 48 (87%) felt that the comprehensive clinic significantly improved the quality of their care. The major complications were pouchitis (52%), extraintestinal manifestations, pouch-related fistula, and mechanical dysfunction. The risk factors for the development of pouchitis were time since surgery, >1-stage surgery, and reason for surgery (acute exacerbation/intractable disease more than dysplasia/cancer); the latter was the only independent risk factor. Conclusions: The pouch clinic concept significantly enhanced patient satisfaction. The most common RPC-associated complication was pouchitis. Risk factors for developing pouchitis were duration since operation, >1-stage operation, and indication for surgery. (Inflamm Bowel Dis 2008)

We assessed whether the time interval between neoadjuvant therapy and surgery affects the operative and postoperative morbidity and mortality, the pathologic complete response (pCR) rate, and disease recurrence in locally advanced rectal cancer. One–hundred and thirty-two patients with locally advanced low– and mid–rectal cancer underwent neoadjuvant chemoradiation followed by radical resection (October 2000 to December 2006). Data on the neoadjuvant regime, neoadjuvant–surgery interval, final pathology, type of operation, operative time, intraoperative blood transfusions, postoperative complications, length of hospital stay, disease recurrence, and mortality were reviewed. The patients were divided into two groups according to the neoadjuvant–surgery interval: ≤7 weeks (group A, n = 48), and >7 weeks (group B, n = 84). The groups were demographically comparable except for the group A patients being younger at operation. The median interval between chemoradiation and surgery was 56 days (range 13–173 days). Thirty-seven patients (28%) had a pCR and near pCR. Fifty three patients (40%) had complications. There was no in-hospital mortality. Surgery type, operative time, number of intraoperative blood transfusions, postoperative complications, and length of hospitalization were not influenced by the interval length. The pCR and near pCR rates were higher with longer interval: 17% in group A, 35% in group B (P = 0.03). Patients operated at an interval >7 weeks had significantly better disease–free survival (P = 0.05). A neoadjuvant–surgery interval >7 weeks was associated with higher rates of pCR and near pCR, decreased recurrence and improved disease–free survival.

Background Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation. Methods We performed a large-scale analysis of ileal mucosal miRNA. Biopsies were retrieved from patients with ileal Crohn’s disease (CD), unoperated ulcerative colitis (UC) patients, UC patients after pouch surgery, and normal controls (NC). Pouch UC patients were classified as having a normal pouch (NP), chronic pouchitis (CP), and Crohn’s-like disease of the pouch (CLDP). miRNA expression was analyzed by parallel massive (next-generation) sequencing (NGS). Bioinformatics tools were applied for clustering and the detection of potential targets. Results Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes. Conclusions Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs.

BACKGROUND The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. METHODS Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. RESULTS A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. CONCLUSIONS The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

Aim This study aimed to assess the progression-free and overall survival of patients with residual microscopic disease following neoadjuvant chemoradiation and rectal resection for locally advanced rectal cancer. Methods Two-hundred and thirty-four consecutive rectal cancer patients who had neoadjuvant chemoradiotherapy followed by radical resection (5/2000-4/2012) were divided according to pathologic tumor response: residual microscopic disease (MIC), complete response (pCR), and partial/no response (nonCR). Data on the neoadjuvant regime, treatment-to–surgery interval, final pathology, type of operation, operative time, postoperative complications, length of hospital stay, disease recurrence, and mortality were compared between the groups. Results There were 13 (5.5%) MIC patients, 48 (20.5%) with pCR, and 173 (73.9%) in the nonCR group. The groups were demographically comparable. MIC patients had more retrieved lymph nodes compared to the nonCR and pCR patients (median 13 compared to 8 and 10, respectively, p = 0.0086). The 5-year overall survival rates were 93.4% for the pCR and MIC patients versus 82.1% for the nonCR patients (p = 0.0324). The 5-year progression-free survival was 85.2% for the pCR and MIC patients versus 73.8% for the non-CR patients (p = 0.086). Conclusions We identified and assessed a new pathologic subgroup of rectal cancer patients who had residual microscopic disease post-neoadjuvant therapy. The survival analysis aligned them closely with pCR patients. This article is protected by copyright. All rights reserved.

Aim: This study aims at identifying the risk factors for the development of pre-cancerous pouch and/or cuff adenomas post ileal pouch anal anastomosis (IPAA) in familial adenomatous polyposis patients. Method: We retrospectively studied 59 patients operated at a single medical center during a 26-year period. Data on the timing and location of adenoma recurrence were recorded and possible correlations with patients' gender, age, presence of desmoid tumor, duodenal adenomas, type of anastomosis and number of operation stages were analyzed. Results: Thirty-five (59%) patients had at least one adenoma in either the cuff or the pouch, including 20 with isolated cuff adenomas, 4 with isolated pouch adenomas and 11 patients with adenomas in both the pouch and cuff. There was no significant correlation between gender, age at surgery, type of anastomosis, number of operative stages and the development of pouch or cuff adenomas. Desmoid tumor and pouch adenomas were significantly correlated with cuff adenomas formation. Duodenal adenomas were associated with pouch adenomas. There was some relationship between the development of cuff adenomas and the burden of colonic polyps, as well as the presence of duodenal adenomas. Conclusion: Adenomas in both the pouch and cuff commonly occur following IPAA, mandating lifelong annual endoscopic surveillance.

BACKGROUND Patients with ulcerative colitis undergoing total proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. Alpha-1-antitrypsin (AAT) is an acute phase reactant produced mainly by hepatocytes, but also locally in the gut. Data on noninvasive biomarkers of pouchitis are scarce. METHODS To identify biomarkers that correlate with pouch inflammation, ulcerative colitis pouch patients were prospectively recruited and underwent clinical, endoscopic, and histologic evaluations. The Pouchitis Disease Activity Index (PDAI) was calculated, and pouchitis was defined by a score ≥7. Serum and fecal AAT, C-reactive protein (CRP), fecal calprotectin, ferritin and albumin levels were measured. RESULTS Seventy-one ulcerative colitis pouch patients (mean age 43.8 ± 8.3 yr, 50.7% males) were included. The main indication for ileal pouch-anal anastomosis was intractable colitis (83.1%). Median serum AAT level (183.0 mg/dL, 155.1-232.0) was significantly higher in patients with a PDAI ≥7 compared with those with a PDAI

Background: Patients with rectal cancer who have complete rectal wall tumor regression after neoadjuvant chemoradiation probably have eradication of tumor cells in the mesorectum as well, thus raising the possibility of transanal excision. Methods: All pathology reports of all patients with locally advanced low and mid rectal cancer who underwent preoperative chemoradiation followed by radical resection from May 2000 to June 2004 were reviewed to evaluate the correlation between complete tumor response (ypT0) and nodal response. Results: One hundred one consecutive patients had neoadjuvant chemoradiation followed by definitive operation. Four were excluded, leaving 64 men and 33 women (median age, 62 years). Fifty-three patients (55%) had mid rectal cancer, and 44 (45%) had low rectal cancer. Fifty-eight patients (60%) underwent low anterior resection, and 36 (37%) underwent abdominoperineal resection. In 17 patients (18%), no residual tumor cells were present within the rectal wall. One patient (6%) with ypT0 disease had positive lymph nodes. Conclusions: No residual tumor in the rectal wall correlates with the absence of viable cancer cells in the mesorectal tissue (94%). Approximately 10% of T1 tumors have involved lymph nodes, and local excision is an accepted option. Transanal excision could probably be considered in a highly selected group of patients with a mural pathologic complete response to neoadjuvant therapy. This approach should be prospectively investigated, and strict selection guidelines should be used.

This study was designed to assess the efficacy of gracilis muscle transposition in repairing rectovaginal and rectourethral fistula. All patients had fecal diversion as a preliminary or concurrent step to fistula repair. Success was defined as healed fistula after stoma closure. Results: Six females and four males underwent gracilis muscle transposition from 1999 to 2006. Gracilis muscle transposition is a viable option for repairing fistulas between the urethra, vagina and the rectum, especially after failed perineal or trans-anal repair. It is associated with low morbidity and good success rate. Underlying Crohn?s disease and previous radiation are associated with poor prognosis.

Objective Perianal Paget's disease (PPD) is a rare entity. The standard treatment for either in situ or invasive extra mammary Paget's disease (EMPD) is surgical excision. Local recurrence and morbidity from surgery, especially in the elderly, can, however, be high. The aim of this article is to review our experience with PPD and question the currently preferred treatment approaches in light of its histopathology and therapeutic outcome. Patients and methods A chart review of our patients with PPD from 1996 to 2002 was carried out to determine their outcome after treatment. Data from review of the literature are presented. Results Five patients with in situ disease (four females, median age 68 years) were diagnosed as having PPD. A complete surgical excision was attempted in 4 patients and the fifth was treated by photodynamic therapy. At present, all patients are alive, two are free of disease, one has persistent disease and two have local recurrence. Conclusion Considering the significant rate of recurrence even after wide local excision, the extent of surgery needed and the good prognosis with long-term survival, we question whether nonsurgical modalities should be considered in place of surgery as primary treatment for noninvasive PPD, with radical surgery being reserved for failures or invasive disease.

Objectives To evaluate molecular profiles in the small bowel (SB) mucosa proximal to the pouch in ulcerative colitis (UC) patients after pouch surgery. Design Patients were prospectively recruited and stratified according to disease behaviour: normal pouch (NP), chronic pouchitis (CP), and Crohn9s-like disease of the pouch (CLDP). Biopsies obtained from the pouch and the normal-appearing proximal SB (40 cm proximal to the anal verge) were compared to ileal biopsies from normal controls (NC). A histopathological score based on the degree of polymorphonuclear and mononuclear infiltrates was used to assess inflammation in the pouch and the proximal SB. Gene expression analysis was performed using microarrays, and validated by real-time PCR. Gene ontology and clustering were evaluated by bioinformatics. Results Thirty-six subjects were recruited (age 18–71 years, 16 males). Histopathology scores demonstrated minimal differences in the normal-appearing proximal SB of all groups. Nonetheless, significant (fold change ≥2, corrected p [FDR] ≤ 0.05) molecular alterations in the proximal SB were detected in all groups (NP n=9; CP n=80; and CLDP n=230) compared with NC. The magnitude of DUOX2 alteration in the proximal SB was highest. An increase of 6.0, 9.8 and 21.7 folds in DUOX2 expression in NP, CP, CLDP, respectively was observed. This was followed by alterations in MMP1, SLC6A14 and PGC. Gene alterations in the proximal SB overlapped with alterations within the pouch (76% and 97% overlap in CP and CLDP, respectively). Gene ontology analysis in the proximal SB and pouch were comparable. Conclusions Significant gene expression alterations exist in an apparently unaffected proximal SB. Alterations in the pouch and the proximal SB were comparable, suggesting that inflammation may not be limited to the pouch, but that it extends to the proximal SB.

BACKGROUND Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD). METHODS Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools. RESULTS Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis. CONCLUSIONS Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.

The influence of ileostomy closure timing on surgical and oncologic outcome was investigated in patients with locally advanced rectal cancer receiving adjuvant chemotherapy after low anterior resection.Consecutive patients diagnosed with T3-4/N+ rectal cancer, treated by neoadjuvant chemoradiation and low anterior resection during 2000-2012 were retrospectively evaluated. Patients undergoing closure during adjuvant chemotherapy (Group A) were compared to patients undergoing closure after completing chemotherapy (Group B).A total of the 165 patients met inclusion criteria, of whom 104 received adjuvant chemotherapy (25 in Group A and 79 in Group B). The pathologic stage was higher in Group B (P = 0.015). The rates of postoperative complications were similar (16% for Group A and 15% for Group B, P = 0.88), as was hospital stay (mean 5.78 days for Group A and 6.25 days for Group B, P = 0.7). There was no significant difference in recurrence rate and overall survival between the groups.Referral to ileostomy closure in relation to adjuvant chemotherapy is influenced by pathologic stage. Early referral appears to be reserved to a small number of patients with lower pathologic stage. Timing of ileostomy closure does not change short- or long-term results.

Background and Aims: Restorative proctocolectomy in elderly inflammatory bowel disease [IBD] patients is controversial and limited data are available on the outcomes of surgery. The aim of this study was to evaluate the safety, efficacy, and long-term results of ileal-pouch-anal anastomosis in elderly patients, in a multicentre survey from European referral centres. Methods: The International Pouch Database [IPD] combined 101 variables. Patients aged >= 65 years were matched on the basis of open versus laparoscopic surgery with a control group of consecutive younger unselected patients with a ratio of 1:2. Statistical analysis was performed using two-tailed t test, chi square and Fisher's exact tests, Kaplan-Meier function, and log-rank tests where appropriate. Results: In the IPD, 77 patients aged >= 65 years [Group A] and 154 control patients [Group B] were identified. Elderly patients had more comorbidities [p = 0.0001], longer disease duration [p = 0.001], less extensive disease [p = 0.006], more previous abdominal operations [p = 0.0006], surgery for cancer or dysplasia more frequently [p = 0.0001], fewer single-stage procedures [p = 0.03], more diversions after ileal pouch-anal anastomosis [IPAA] [p = 0.05], and a higher laparoscopic conversion rate [p = 0.04]. Postoperative complications and pouch failure were similar between the groups, but Group A had more Clavien-Dindo IV-V complications [p = 0.04], and longer length of stay [p = 0.007]. Laparoscopy was associated with a shorter duration of surgery [p = 0.0001], and length of stay [p = 0.0001], and the same complication rate as open surgery. Conclusions: Restorative proctocolectomy can be performed in selected elderly patients, but there is a higher risk of postoperative complications and longer length of stay in this group. Laparoscopy is associated with shorter operating time and length of stay

Background and aims: The Crohn's disease (CD)-specific pancreatic auto-antibodies (PAB), have been recently identified to target glycoprotein 2 (GP2). Pouchitis is an inflammation of the small bowel developing in up to 60% of ulcerative colitis patients undergoing proctocolectomy and ileal pouch anal anastomosis. Occurrence of CD-specific antibodies was reported to be a predictor of pouchitis. We aimed to assess the prevalence of anti-GP2 antibodies (anti-GP2) in the serum and feces of pouch patients and to correlate them with clinical parameters. Furthermore, we examined mucosal expression of the GP2 protein in the pouch. Methods: Pouch patients were prospectively recruited and checked for clinical, endoscopic, and laboratory markers of inflammation. IgG and IgA anti-GP2 levels in serum and fecal samples were determined using ELISA. GP2 protein was assessed by immunohistochemistry. Results: Anti-GP2 was elevated in both serum and fecal samples of patients with inflamed compared to those with non-inflamed pouches and patients with familial-adenomatous polyposis after surgery (p < 0.05, respectively). Moreover, patients with CD-like complications exhibited significantly higher anti-GP2 titers than those without CD-like complications (p ≤ 0.01). High levels of anti-GP2 correlated with more frequent bowel movements per day and with the presence of at least one anti-glycan antibody (p ≤ 0.05). GP2 itself was more abundant in the mucosa of patients with chronic pouchitis. Conclusions: Anti-GP2 exists in the serum and feces of pouch patients and correlates with pouch inflammation, and presence of other serological markers. Thus, anti-GP2 may contribute to better stratification of pouchitis, more-so when the inflammation exhibits CD-like complications. * Abbreviations : ACCA : anti-chitobioside carbohydrate antibodies ALCA : anti-laminaribioside carbohydrate antibodies AMCA : anti-mannobioside carbohydrate antibodies ASCA : anti- Saccharomyces cerevisiae antibodies CD : Crohn's disease CRP : C-reactive protein FAP : familial adenomatous polyposis GP2 : glycoprotein 2 IBD : inflammatory bowel diseases IPAA : ileal pouch anal anastomosis PAB : pancreatic (auto)-antibody PDAI : pouchitis disease activity index UC : ulcerative colitis

Aim The effect of restorative proctocolectomy (RPC) on fertility and pregnancy in women with ulcerative colitis (UC) was evaluated. Method Post-RPC female patients with UC who were attempting to become pregnant filled out questionnaires on fertility and pregnancy. Demographic and pouch data of pregnancies ending with delivery were collected from a prospective database. Results Forty-one women, 44 ± 10 years of age, completed the questionnaires. The median follow-up period post-RPC was 167 (range, 20–352) months. Before RPC, 26 women had 70 pregnancies and 62 deliveries. After RPC, 17 women had 32 pregnancies and 26 deliveries (P = 0.0035). Post-RPC, 10 (37%) of 27 patients failed to conceive compared with 26/26 successful attempts before RPC (P = 0.0006). The number of offspring per patient was 2.38 ± 1.27 before, and 0.68 ± 0.93 after, RPC (P

Ileal pouch-anal anastomosis is considered the surgical treatment of choice for patients with ulcerative colitis. It is safe and effective but associated with long-term complications, making functional outcome and quality of life important factors in determining patient outcome. Longitudinal studies on long-term functional outcome and quality of life are sparse. The purpose of this study was to longitudinally evaluate the long-term functional outcome and quality of life of ulcerative colitis patients who underwent proctocolectomy with ileal pouch-anal anastomosis.The study group was composed of ulcerative colitis patients who underwent pouch operation in our institution between 1990 and 2001 who had filled in quality of life and functional outcome questionnaires 60 months (mean) after ileostomy closure and responded to the same questionnaires at 133 months (mean) after ileostomy closure. They served as their own controls. Quality of life was scored using the Medical Outcomes Study Short Form 36. Global Assessment of Functioning Scale was used to evaluate functional outcome.Data were obtained for 63 of the 77 patients (82%) who had answered the first questionnaire. The mean interval between responding to the 2 questionnaires was 73 +/- 3 months. Functional outcome did not deteriorate over time. Some quality of life scores (bodily pain, general health perception, and the physical component summary) worsened over time, whereas the other scales of the Short Form 36 scores did not change.The functional outcome of ulcerative colitis patients after a pouch operation did not change significantly over time. The overall quality of life was generally stable, however, some aspects did deteriorate over time. These findings merit further investigation.

Objective Complex anal fistulas traverse a significant portion of the external sphincter muscle, making their treatment a surgical challenge. Several surgical options are used with conflicting results. The aim of this study was to analyse the results of permanent loose seton in the management of high anal fistulas in Crohn’s disease (CD) patients and two-stage seton fistulotomy in patients without CD. Method We retrospectively reviewed the clinical records of 77 patients with complex anal fistula treated by loose seton over a 4-year period, in two medical centres. Recorded parameters included demographics, medical history, type of fistula, disease duration, previous surgery, morbidity, recurrence and mortality. Results Sixty patients without CD underwent 107 fistula-related surgical procedures, and 17 CD patients underwent 29 procedures. Early postoperative complications were recorded in eight (10%) patients. Perioperative complications, mainly local sepsis or bleeding, were recorded in eight (10%) patients. Long-term complications were observed in nine non-CD and four CD patients. During a median follow-up period of 24 months, the recurrence rate was 40% in CD patients and 47% in patients without CD. Five patients (four non-CD patients and one CD patient) developed some degree of faecal incontinence. Conclusion The fistula recurrence rate following two-stage seton fistulotomy in non-CD patients was high. In CD patients the use of permanent loose seton is effective in controlling local sepsis in about half of patients and has low rates of subsequent incontinence.

To review the experience of a major medical teaching center with diagnostic and therapeutic colonoscopies and to assess the incidence and management of related colonic perforations.All colonoscopies performed between January 1994 and December 2001 were studied. Data on patients, colonoscopic reports and procedure-related complications were collected from the departmental computerized database. The medical records of the patients with post procedural colonic perforation were reviewed.A total of 120067 colonoscopies were performed during the 8 years of the study. Seven colonoscopic perforations (4 females, 3 males) were diagnosed (0.058%). Five occurred during diagnostic and two during therapeutic colonoscopy. Six were suspected during or immediately after colonoscopy. All except one had signs of diffuse tenderness and underwent immediate operation with primary repair done in 4 patients. No deaths were reported.Perforation rate during colonoscopy is low. Nevertheless, it is a serious complication and its early recognition and treatment are essential to optimize outcome. In patients with diffuse peritonitis early operative intervention makes primary repair a safe option.

We report a case of a 23-year-old Turcot female patient who was first diagnosed as having a pinealoblastoma. Thyroid papillary carcinoma was diagnosed a few months later, and multiple colonic polyps were detected three years after that. A genetic workup revealed an APC gene mutation in her family. Long-term survival (i.e., >5 years) of pinealoblastoma is considered to be 20 percent. A review of 25 documented Turcot cases determined that the average age at death is 20.3 years, raising the difficult question of whether she should undergo restorative proctocolectomy. Restorative proctocolectomy may itself cause major morbidity but is currently the only way to prevent colon cancer.

PURPOSE: The surgical management of complex perianal fistulas is challenging and may be associated with the risk of sphincter injury. Instillation of fibrin glue to the fistula tract is a simple procedure that does not involve any muscle division, and potentially results in healing of the fistula. This study was designed to assess the use of highly concentrated fibrin glue with intra-adhesive antibiotics in the treatment of complex cryptogenic perianal fistulas. METHODS: Patients with complex perianal fistulas of cryptogenic origin were prospectively included in this multicenter study. Injection of the fibrin glue mixed with antibiotics was performed in a uniform fashion. After the procedure, patients were actively examined at fixed time intervals; in cases of recurrent fistula, reinjection of fibrin glue was offered. RESULTS: Sixty patients were enrolled; complete healing of the fistula was achieved in 32 patients (53 percent). Eight of 28 patients (29 percent) who were not completely healed had significant symptomatic improvement. All patients resumed normal daily activity the day after surgery and none had any deterioration in continence related to the procedure. The majority of the 26 (43 percent) adverse events were considered mild and spontaneously resolved; 2 patients (3 percent) with perianal septic complications were successfully treated by drainage. CONCLUSIONS: Injection of fibrin glue for the treatment of perianal fistulas is safe, simple, and associated with early return to normal activity. Although moderately successful, it may preclude extensive surgery in more than one-half of these patients.

Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra-intestinal manifestations are inherent to the procedure.To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP patients operated in our department.The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow-up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.Median age at surgery was 33 years (range 13-61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock's pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required reoperation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow-up was 74 months (range 3-288 months). Four patients were lost to follow-up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow-up, 37 IPAA patients have (median) six bowel movements/24 hours and good fecal control.Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

Closure of ileostomy is considered a contaminated operation. The infection rate of the stoma wound isor = 30%. Several ileostomy-closure techniques intended to reduce the high rate of infection have been described in the literature. Among them, delayed primary closure of the stoma wound is a commonly used method that was reported to reduce the infection rate according to several retrospective studies. We therefore conducted the first prospective randomized trial comparing primary with delayed primary closure of a stoma wound.During 2003, 40 patients were admitted to our ward for closure of ileostomy. The ileostomies were taken down by the same team using the same surgical technique except for the technique of wound closure. We randomly divided the patients into two groups. In Group 1 (n = 20), the wound was left open for delayed primary closure and not closed until postoperative day 4. In Group 2, the wound was primarily closed at the end of the procedure.The total wound infection rate was relatively low (15%). Infection occurred more frequently (4 cases, 20%) in Group 1 than in Group 2 (2 cases, 10%). The length of hospital stay was similar for both groups.In this first prospective comparison of two techniques during ileostomy take down, primary closure unexpectedly produced less wound infection than delayed primary closure.

OBJECTIVE To establish the incidence and causes of late failure in patients undergoing restorative proctocolectomy for a preoperative diagnosis of ulcerative colitis was the objective of this investigation. SUMMARY BACKGROUND DATA Restorative proctocolectomy is the elective surgical procedure of choice for ulcerative colitis. Most patients have a satisfactory outcome but failures occur. The reasons and rates of early failure are well documented, but there is little information on long-term failure. METHODS A series of 634 patients (298 females, 336 males) underwent restorative proctocolectomy for inflammatory bowel disease between 1976-1997, with a mean follow-up of 85 +/- 58 months. Failure was defined as removal of the pouch or the need for an indefinite ileostomy. It was divided into early and late, occurring within 1 year or more than 1 year postoperatively. RESULTS There were 3 (0.5%) postoperative deaths, leaving 631 patients for analysis. Of these, 23 subsequently died (disseminated large bowel cancer, 12; unrelated causes, 9; related causes, 2). There were 61 (9.7%) failures (15 early [25%], 46 late [75%]) due to pelvic sepsis (32 [52%]: 7 early, 25 late), poor function (18 [30%]: 2 early, 16 late), pouchitis (7 [11%]: 2 early, 5 late) and miscellaneous (4, all early). A final diagnosis of Crohn's disease, type of reservoir (J,S), female gender, postoperative pelvic sepsis and a one-stage procedure were significantly associated with failure. Failure rate rose with time of follow-up from 9% at 5 years to 13% at 10 years. CONCLUSIONS Pelvic sepsis and poor function were the main reasons for later failure. Failure rates should be reported based on the duration of follow-up.

To investigate the diet of pouch patients compared to healthy controls, and to correlate pouch patients' diet with disease behavior.Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center. Pouch behavior was determined based on clinical, endoscopic and histological criteria. Healthy age- and sex-matched volunteers were selected from the "MABAT" Israeli Nutrition and Public Health Governmental Study and served as the control group. All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid. Data on Dietary behavior, food avoidance, the use of nutritional supplements, physical activity, smoking habits, and body-mass index (BMI) were also obtained. Pouch patients who had familial adenomatous polyposis (n = 3), irritable pouch syndrome (n = 4), or patients whose pouch surgery took place less than one year previously (n = 5) were excluded from analysis.The pouch patients (n = 80) consumed significantly more from the bakery products food group (1.2 ± 1.4 servings/d vs 0.6 ± 1.1 servings/d, P0.05) and as twice as many servings from the oils and fats (4.8 ± 3.4 servings/d vs 2.4 ± 2 servings/d, P0.05), and the nuts and seeds food group (0.3 ± 0.6 servings/d vs 0.1 ± 0.4 servings/d, P0.05) compared to the controls (n = 80). The pouch patients consumed significantly more total fat (97.6 ± 40.5 g/d vs 84.4 ± 39 g/d, P0.05) and fat components [monounsaturated fatty acids (38.4 ± 16.4 g/d vs 30 ± 14 g/d, P0.001), and saturated fatty acids (30 ± 15.5 g/d vs 28 ± 14.1 g/d, P0.00)] than the controls. In contrast, the pouch patients consumed significantly fewer carbohydrates (305.5 ± 141.4 g/d vs 369 ± 215.2 g/d, P = 0.03), sugars (124 ± 76.2 g/d vs 157.5 ± 90.4 g/d, P = 0.01), theobromine (77.8 ± 100 mg/d vs 236.6 ± 244.5 mg/d, P0.00), retinol (474.4 ± 337.1 μg/d vs 832.4 ± 609.6 μg/d, P0.001) and dietary fibers (26.2 ± 15.4 g/d vs 30.7 ± 14 g/d, P = 0.05) than the controls. Comparisons of the food consumption of the patients without (n = 23) and with pouchitis (n = 45) showed that the former consumed twice as many fruit servings as the latter (3.6 ± 4.1 servings/d vs 1.8 ± 1.7 servings/d, respectively, P0.05). In addition, the pouchitis patients consumed significantly fewer liposoluble antioxidants, such as cryptoxanthin (399 ± 485 μg/d vs 890.1 ± 1296.8 μg/d, P0.05) and lycopene (6533.1 ± 6065.7 μg/d vs 10725.7 ± 10065.9 μg/d, P0.05), and less vitamin A (893.3 ± 516 μg/d vs 1237.5 ± 728 μg/d, P0.05) and vitamin C (153.3 ± 130 mg/d vs 285.3 ± 326.3 mg/d, P0.05) than the patients without pouchitis. The mean BMI of the pouchitis patients was significantly lower than the BMI of the patients with a normal pouch: 22.6 ± 3.2 vs 27 ± 4.9 (P0.001).Decreased consumption of antioxidants by patients with pouchitis may expose them to the effects of inflammatory and oxidative stress and contribute to the development of pouchitis.

Hypothesis Extracolonic manifestations have a major effect on the morbidity and mortality of patients with familial adenomatous polyposis following proctocolectomy. Design Case review study. Setting Colorectal unit, university-affiliated hospital. Patients Fifty patients (25 males and 25 females) with familial adenomatous polyposis WHO underwent proctocolectomy between January 1988 and October 2003. Interventions Ileal pouch–anal anastomosis (n = 41), Kock pouch (n = 1), end ileostomy (n = 6). Two patients underwent total colectomy with an ileorectal anastomosis. Main Outcome Measures Clinical follow-up and telephone interview; contact with clinicians following up patients elsewhere. Results The patients’ median age at surgery was 33 years. The mean length of follow-up was 74 months. Four patients were lost to follow-up. Extracolonic manifestations were diagnosed in 38 patients (76%). Twelve patients had 14 desmoid tumors: 7 were treated surgically and 7 medically (these patients received celecoxib and tamoxifen citrate therapy). Of the 41 patients who underwent upper gastrointestinal tract endoscopy, 11 developed duodenal and/or ampullary adenomas. Three patients had endoscopic polypectomy and 1 underwent a Whipple operation. Among the 29 patients who underwent pouchoscopy, 5 had pouch adenomas and 3 had adenomas that were found in the rectal stump. Two patients died—one of a huge mesenteric desmoid tumor and the other of an aggressive mesenteric malignant fibrous histiocytoma. Conclusions Long-term morbidity and mortality were strongly related to the development of mesenteric tumors and ampullary-duodenal polyps. Early detection of desmoid tumors, duodenal, pouch, and rectal cuff adenomas by periodic computed tomography, gastroduodenoscopy, and pouchoscopy, respectively, may allow control by medical therapy, endoscopy, or limited surgical procedures. In most patients control of desmoid tumors was achieved using a combination of celecoxib and tamoxifen citrate therapy.