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IntroductionPouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment.MethodsIn a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed.ResultsThe cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures—more commonly in the ultra-long-term antibiotic users.ConclusionsPatients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

The primary aim of this study was to determine whether the microscopic presence of Crohn’s disease (CD) in the resected specimen margins in patients undergoing ileocecectomy predicts disease recurrence. The secondary aim was to identify other risk factors which can predict recurrence. All CD patients who underwent ileocecectomy in a single colorectal unit between 2000 and 2015 were retrospectively evaluated. The diagnosis of CD and margin involvement status were retrieved from pathology reports. Recurrence was determined according to medical records or via a telephone questionnaire. Demographic, clinical, and surgical parameters were compared between patients with and without histopathologic evidence of CD in the resected margins. A total of 202 CD patients were included, 49 with and 153 without evidence of microscopic involvement in the resected margins. The main demographic characteristics, surgical approach and procedure, and postoperative course, including medical treatment, clinical or endoscopic recurrence, and reoperation rates, were similar for both groups. Patients who were operated laparoscopically (n=58, p 0.016), conversion from laparoscopic to open (n=25, p 0.016), stapled anastomosis (n=150, p 0.004), when stricturoplasty was required (n=12, p 0.046), and those with perianal disease (n=32, p 0.045) had shorter time to recurrence. Male gender had increased hazard ratio (n=106, HR 1.38) for reoperation, but not significantly (p=0.058). The presence of microscopic CD at the resected specimen margins was not associated with the risk of disease recurrence. Other demographic, clinical, and technical features that did correlate with early recurrence were identified. These results support a conservative approach to the extent of resection in CD patients undergoing ileocecectomy. Not relevant

Introduction: Rectal cancer is a common and lethal disease, with approximately 44,180 new cases of diagnosed annually in the United States and a five-year survival of 67% [1, 2]. The interval from diagnosis to chemoradiation treatment, or waiting time (WT), is considered to be an important quality indicator for cancer care and has been demonstrated to be associated with oncologic outcomes in various cancers [3, 4]. The current recommendation for pre-treatment staging evaluation includes rigid proctoscopy, PET CT, transrectal ultrasound (TRUS) and often rectal MRI. These diagnostic procedures may significantly postpone the start of treatment. We aim to examine the effect of WT on overall survival (OS) and disease free survival (DFS) of rectal cancer patients. Methods: Retrospective analysis was performed in a detailed database of patients with resectable primary rectal cancer who underwent chemoradiation between January 2000 and January 2019. Univariate and multivariate cox proportional hazard regressions were conducted in order to evaluate the effect of WT on oncological outcomes. Results: 387 patients were enrolled in our database; of them 297 patients were eligible by the inclusion criteria. Median WT was 6.3 weeks (IQR 4.3-8.7). Multivariate analysis showed adjusted Hazard Ratio (HR) for OS increases by 1.07 for each additional week of therapeutic delay in all age groups (p=0.025). Furthermore, focusing on the majority of patients in the age group 45 - 70 years, adjusted HR for OS increases by 1.12 for each additional week of therapeutic delay (p=0.011). Adjusted HR for DFS increases by 1.06 for each additional week of therapeutic delay in all age groups (p=0.045) and an increment by 1.09 for each additional week of therapeutic delay in age group 45-70 years (p=0.02). Conclusion: Prolonged WT leads to significant poorer overall survival in patients with primary rectal cancer who underwent chemoradiation and curative surgical treatment. This marks the importance of efficient diagnostic evaluation and clinical multidisciplinary decision making in a timeframe of 6 weeks in order to not jeopardize oncological outcomes.

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

Aim: Surgery is indicated in selected patients with inflammatory bowel disease (IBD). However, due to a negative perception, surgery may be delayed, leading to possible unfavourable outcomes. The aim of this work was to investigate patients’ perceptions of surgery and the impact on reported outcomes. Method: An international multilingual online survey was used to query IBD patients’ experiences of surgery, information sources, expectations and concerns, quality of life (QoL) and feelings. Results: The survey was completed by 425 of 510 participants. Crohn's disease was more frequent (61%) than ulcerative colitis (36%). Most patients primarily learned about surgery from their gastroenterologist and were informed of the risks and benefits by the surgeon. In almost one-third of patients indication for surgery was not a shared decision between gastroenterologist and surgeon. Seventy per cent of patients naïve to surgery were not aware of any surgical options. The majority of patients (80%) perceived surgery as the last option after many medical treatments rather than an alternative therapeutic option (20%). Sixteen per cent of patients obtained their primary information from the Internet, while 82.4% used the Internet to obtain additional information. Fear of surgical complications was cited by 73% of patients, while relief from symptoms was indicated by 31%. Most patients coped with their stoma better than expected or as they expected. Negative feelings decreased after surgery, while a lasting improvement in positive feelings and QoL was reported. Conclusion: Despite the negative perception of surgery and the delayed involvement of surgeons as a source of information and in the decision-making process, the majority of respondents experienced positive outcomes from surgery, including improvement QoL and acceptance of the stoma.

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.

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1–8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn’s and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

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.

Background An accurate and non-invasive surrogate marker of inflammation is needed for managing patients after Ileal pouch-anal anastomosis (IPAA). In this study, we evaluate the performance of fecal calprotectin (FC) in patients with ulcerative colitis (UC) who underwent IPAA and were assessed with clinical, endoscopic, and histologic examination of the pouch. Methods Medical records of patients who underwent IPAA with J-pouch formation registered in a prospectively collected database at the Tel Aviv Sourasky Medical Center, Israel, were evaluated. Clinical, endoscopic, histologic, and laboratory data were extracted. Each pouch evaluation was regarded separately. Pouchitis was defined as a Pouchitis Disease Activity Score (PDAI) of ≥7 (maximum score: 18). Results One hundred and fifty-six patients underwent 296 unique pouch evaluations. Fifty-two percent of patients were male, the median age at the time of evaluation was 43 years (IQR 35–58), and the median pouch age from the closure of the ileostomy was 10 years (IQR 2.5–15). The median [IQR] FC values were significantly lower in patients without pouchitis than in patients with pouchitis (208 [96–478] vs. 550 [250–1051] ug/g, p Conclusion FC levels increase among patients with pouchitis and increase with increasing endoscopic and histologic inflammation. A FC of over 400 ug/g had good discriminative ability as a predictor of significant endoscopic disease. We suggest that in patients with symptoms of pouchitis and an FC level above 400 ug/g, antibiotic treatment can be initiated without awaiting pouchoscopy. Further research is needed to define FC concentrations more precisely among various outcome measures of interest in these patients.

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

SummaryBackground Pouch surgery, a common intervention for ulcerative colitis (UC) complications, is often associated with the development of pouchitis. Aim To identify predictors of pouch outcome in a cohort of patients with UC. Methods We conducted a retrospective unmatched case-cohort study in a tertiary IBD referral centre. Adult patients with UC were classified into the worst phenotype throughout follow-up: normal pouch, a form of chronic pouchitis (either chronic pouchitis or Crohn's like disease of pouch [CLDP]), or episodic recurrent acute pouchitis (RAP). Risk factors for pouchitis (chronic forms) were detected using statistical models. Results Two hundred and fifty-three pouch patients were followed up for 13.1±7.3 years. Only 71 patients (28.1%) maintained a favourable outcome of a sustained normal pouch. These patients were older at UC diagnosis (27.8±12.5 vs 23.0±11.4 years), had longer UC duration until surgery (13.4±9.5 vs 8.2±7.9 years), and had higher rates of referral to surgery due to nonrefractory (dysplasia/neoplasia) complications (42.3% vs 16.2%) compared with pouchitis patients. Median survival for sustained normal pouch was 10.8 years (95% CI 8.9-12.7 years), and it was longer in the nonrefractory group (20.3 vs 9.4 years for the refractory group, HR=2.37, 95% CI 1.25-3.52, P=.004). Conclusions Most patients with UC undergoing pouch surgery will develop pouchitis. Patients operated for nonrefractory indications have a more favourable outcome. These results may contribute to pre- and post-surgical decision-making. The findings imply that the processes determining UC severity may be similar to that causing pouchitis.

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

Background and Aims The pathogenesis of pouch inflammation may involve epithelial barrier disruption. We investigated whether faecal proteolytic activity is increased during pouchitis and results in epithelial barrier dysfunction through protease activating receptor [PAR] activation, and assessed whether the intestinal microbiome may be the source of the proteases. Methods Faecal samples were measured for protease activity using a fluorescein isothiocyanate [FITC]-casein florescence assay. Caco-2 cell monolayers were exposed to faecal supernatants to assess permeability to FITC-dextran. Tight junction protein integrity and PAR activation were assessed by immunoblot and immunofluorescence. A truncated PAR2 protein in Caco-2 cells was achieved by stable transfection using CRISPR/Cas9 plasmid. PAR2 activation in pouch biopsies was examined using antibodies directed to the N-terminus of the protein. Microbial composition was analysed based on 16S rRNA gene sequence analysis. Results Ten pouchitis patients, six normal pouch [NP] patients and nine healthy controls [HC] were recruited. The pouchitis patients exhibited a 5.19- and 5.35-fold higher faecal protease [FP] activity [p ≤ 0.05] compared to the NP and HC participants, respectively. The genus Haemophilus was positively associated with FP activity [R = 0.718, false discovery rate < 0.1]. Faecal supernatants from pouchitis patients activated PAR2 on Caco-2 monolayers, disrupted tight junction proteins and increased epithelial permeability. PAR2 truncation in Caco-2 abrogated faecal protease-mediated permeability. Pouch biopsies obtained from pouchitis patients, but not from NP patients, displayed PAR2 activation. Conclusions Protease-producing bacteria may increase faecal proteolytic activity that results in pouch inflammation through disruption of tight junction proteins and increased epithelial permeability in a PAR2-dependent manner. This mechanism may initiate or propagate pouch inflammation.

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.

Objective: To examine whether patients with a mature normal pouch [> 1 year post ileostomy closure] have microbial stool characteristics that can predict pouch inflammation. Design: Patients undergoing pouch surgery were recruited prospectively. Microbiota analysis of faecal samples was by 16S rRNA gene pyrosequencing. All patients had a normal pouch at baseline [T1]. Those without pouchitis during the first year of follow-up [T2] comprised the ‘Normal Pouch-sustained’ group and those who had experienced an episode of pouchitis comprised the ‘Pre-Pouchitis’ group. Results: Twenty patients were recruited (age 53.6±13.1 years, pouch age [time from ileostomy closure] 8.1±5.1 years). Seven patients developed pouchitis during follow-up [within 265±93.6 days] and they were assigned to the Pre-Pouchitis group at T1: they had a decreased microbial diversity at T1 compared with the Normal Pouch-sustained patients [n = 13]. The Shannon diversity index for the Pre-Pouchitis patients was 3.4 vs 4.23 for the Normal Pouch-sustained patients [p = 0.011]. There were no substantial group differences in high taxonomic levels [order or above]. The genus Ruminococcus was significantly decreased in the Pre-Pouchitis patients’ samples compared with those of the Normal Pouch-sustained patients (0.19% vs 0.78%, respectively, false discovery rate [FDR] = 0.05). The linear discriminant analysis with effect size estimation algorithm revealed that Lachnospira and Coprococcus genera were also decreased among Pre-Pouchitis patients compared with Normal Pouch-sustained patients [0.6% vs 1.95% and 2.1% vs 4%, respectively]. Conclusions: Patients with a normal mature pouch may be predisposed to acute pouchitis when faecal microbial diversity and certain microbial groups are decreased. These findings may aid in risk stratification of those patients.

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.

Background & Aims Pouchitis that develops in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis is usually treated with antibiotics. Some patients have recurrence of flares, or become antibiotic-dependent, and require repeated courses or prolonged periods of antibiotic therapy. We investigated microbial factors associated with response to antibiotic treatment and development of antibiotic dependence in patients with pouchitis. Methods We performed a prospective study of 49 patients who had undergone pouch surgery at a tertiary center. Disease activity was determined based on clinical, endoscopic, and histologic criteria. Pouch phenotype was defined as recurrent-acute pouchitis (n = 6), chronic pouchitis and Crohn's-like disease of the pouch (n = 27), normal pouch from patient with ulcerative colitis (n = 10), and normal pouch from patient with familial adenomatous polyposis (n = 6). Fecal samples (n = 234) were collected over time during or in the absence of antibiotic treatment (ciprofloxacin and/or metronidazole). Thirty-three patients were treated with antibiotics, for a median of 425 days of cumulative antibiotic therapy, during follow-up. Calprotectin was measured and fecal DNA was sequenced using shotgun metagenomics and analyzed with specifically designed bioinformatic pipelines. Bacterial strains were isolated from fecal samples. We assessed their ciprofloxacin resistance and ability to induce secretion of inflammatory cytokines by HT-29 intestinal epithelial cells. Results Most antibiotic-treated patients (79%) had a clinical response to each course of antibiotics; however, 89% of those who completed a 4-week course relapsed within 3 months. Median calprotectin levels decreased by 40% in response to antibiotics. Antibiotic treatment reduced disease-associated bacteria such as Clostridium perfringens, Ruminococcus gnavus, and Klebsiella pneumoniae, but also beneficial species, such as Faecalibacterium prausnitzii. The microbiomes of antibiotic-responsive patients were dominated by facultative anaerobic genera (Escherichia, Enterococcus, and Streptococcus), with multiple ciprofloxacin-resistance mutations in drug target genes and confirmed drug resistance. However, these strains had lower potential for virulence and did not induce secretion of inflammatory cytokines by epithelial cells. After antibiotic cessation, patients had an abrupt shift in microbiome composition, with blooms of oral and disease-associated bacteria. In addition, antibiotic treatment enriched for strains that acquired multidrug resistance loci, encoding enzymes that confer resistance to nonrelated antibiotics, including extended-spectrum beta-lactamases. Conclusions The efficacy of antibiotic treatment of pouchitis might be attributed to the establishment of an antibiotic-resistant microbiome with low inflammatory potential. This microbiome might provide resistance against colonization by bacteria that promote inflammation. To avoid progression to antibiotic-dependent disease and its consequences, strategies such as short-term alternating antibiotics and nutrition- and microbiome-based interventions should be considered.

Background Past research has identified different factors which are associated with post-operative recurrence of Crohn’s disease (CD). However, controversy remained whether the microscopic presence of CD in the margins of the resected specimen increases the risk of recurrence. The main aim of our study was to determine whether microscopic presence of CD in the resected specimen margin in patients who underwent ileocecal resection predicts disease recurrence. The secondary aim was to identify other risk factors for recurrence. Methods We retrospectively evaluated all CD patients who underwent ileocecal resection in our unit between 2000 and 2015. The diagnoses of CD and information regarding the margins’ involvement were retrieved from pathology reports. Recurrence was indicated according to medical records or according to specific phone questionnaire. Demographic and clinical parameters where compared between patients with and without histopathological evidence of CD in the resected margins. Results 202 CD patients were included: 49 patients with histopathological evidence of CD in the resected margins and 153 patients without involvement. The main demographic characteristics were similar. Patients who received preoperative medical treatment had statistically significant higher rate of uninvolved margins (90.8 vs. 77.6%, p = 0.03). Technical aspects including surgical approach, conversion rates to open surgery, and anastomotic methods were similar. Likewise, the post-operative course regarding medical treatment, endoscopic and clinical recurrence, and reoperation rates was also similar. We found a statistically significant shorter time for disease recurrence in laparoscopic surgery (HR 1.6, CI 1.1–2., p = 0.02(, stapled anastomosis (HR 1.7, CI 1.2–2.6, p = 0.01), if stricturoplasty was done in addition to the ileocecal resection (HR 1.7, CI 1.1–2.6, p = 0.02(, and in patients with perianal disease (HR 1.7, CI 1.1–2.6, p = 0.02(. Male gender and conversion from laparoscopic to open surgical technique had increased HR but did not reach statistical significance. Conclusion The presence of microscopic CD at the resection margins was not associated with disease recurrence. We found that male gender, perianal disease, laparoscopic approach, conversion to laparotomy and stapled anastomosis were associated with early disease recurrence. Our results support a conservative approach in the determination of the extent of resection in CD patients having ileocecal resection.

One Sentence SummaryThe majority of the gut microbiome develops antibiotic resistance via point-mutations in addition to collateral resistance whereas its density is only moderately decreased following long-term antibiotic treatment.ABSTRACTAntibiotic resistance in bacterial pathogens represents a growing threat to modern medicine. Limitation of lengthy and broad-spectrum antibacterial treatment regimens is generally recommended. Nevertheless, some conditions may require prolonged antibiotic treatment. The effects of such treatments on bacterial communities, specifically their resistome, is yet unknown. Here, we followed a unique cohort of patients with ulcerative colitis who underwent total large bowel resection and the formation of an ileal pouch from their normal small bowel. The majority of these patients tend to develop inflammation of this previously normal small bowel, known as “pouchitis”. Pouchitis is commonly treated with repeated or prolonged courses of broad-spectrum antibiotics. By using metagenomics of faecal samples obtained longitudinally from patients treated with antibiotics for prolonged periods, we hereby show that the majority of their gut commensal bacteria develop antibiotic resistance by point-mutations. In addition, some bacterial species had acquired multidrug resistance loci with genes that confer resistance to the drug used in the treatment (ciprofloxacin) but co-localized with genes encoding extended-spectrum β-lactamases and other resistance-conferring enzymes. We further show that bacterial density in faecal samples is only modestly reduced despite the long-term antibiotic treatment, thereby questioning the current rationale that antibiotic efficacy in treating pouch inflammation is due to the reduction of bacterial load. This study reveals the impact and dynamics of prolonged antibiotic treatment on human gut microbiomes and provides insights that may guide the development of future IBD therapies. It also provides novel insights into bacterial community recovery after cessation of such prolonged treatment, and highlights the increased risk of spreading mobile antibiotic resistance.

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.

Patients with unresectable metastatic colorectal cancer can either receive systemic chemotherapy as first treatment or have a palliative resection of the primary tumor or endoscopic placement of a self-expanding metallic stent if they present with colonic obstruction. The ongoing dilemma is whether resection of the primary tumor in asymptomatic patients is beneficial. The effectiveness of current systemic treatment regimens on the primary tumor as well as the survival benefit of primary tumor resection in the era of new chemotherapy agents, biologics, and targeted therapy is underreported. No prospective randomized studies have yet been published; nevertheless, based on the available literature, it seems that primary tumor (PTR) can possibly improve short- and long-term outcome in highly selected patients with favorable characteristics, specifically low tumor burden and good performance status.

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 and Objective 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. Methods 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). Results 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. Conclusions 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. J. Surg. Oncol. 2014 109:266–269. © 2013 Wiley Periodicals, Inc.

The impact of IPAA on long-term outcomes in adults is favorable. Studies on functional outcome and quality of life in children are sparse.The aim of this study was to evaluate the functional and quality-of-life outcomes after IPAA in children and to investigate the possible correlations between the two.Standardized validated questionnaires of bowel/psychosocial functioning and quality of life were used to assess outcome.This study was conducted at a tertiary medical center.All children who had surgery at18 years of age and were followed up at our institute were included. Global Assessment of Function Scale questionnaires were used to evaluate functional outcome. Quality of life in patients18 years at the time of follow-up was scored by using the Short Form 36 questionnaire completed by the patients. Quality of life in the younger patients at the time of follow-up was scored using the Child Health Questionarie-28 filled by the parents.Data were obtained in 26 patients (25 with a preoperative diagnosis of ulcerative colitis) at a median follow-up of 6 years. The median age at surgery was 15 years. Quality of life was comparable to the general population for children18 at the time of follow-up in 7 of 8 items, but was lower than in the general population in 7 of 12 items for those who were younger at the time of follow-up. The mean functional score was found to be negatively correlated to all 8 Short Form 36 parameters (r0.5; p0.005), but only to one of the Child Health Questionarie-28 parameters.This study was limited by its small sample size.The functional outcomes among pediatric patients undergoing IPAA are good. Parents' perception of their child's quality of life is poorer in comparison with the perception by patients themselves when older and with no correlation to the functional results.

Rectal cancer treatment is a multidisciplinary process highly dependent on accurate clinical staging at diagnosis. Defining the height, local invasion, and nodal invasion of the primary tumor determines the extent and order of the treatment scheme, which combines both surgery and chemo–radiotherapy. This review discusses the means by which the clinical stage is determined and the advantages and disadvantages of the different modalities.

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.

Aim The study assessed the clinicopathological features and survival rates of inflammatory bowel disease (IBD) patients with colorectal carcinoma (CRC), which accounts for ∼15% of all IBD associated death. Method The medical records of patients operated on for CRC in three institutions between 1992 and 2009 were reviewed, and those with Crohn’s colitis (CC) and ulcerative colitis (UC) were identified. Data on age, gender, disease duration, colitis severity, surgical procedure, tumour stage and survival were retrieved. Results Fifty-three patients (40 UC and 13 CC, 27 men, mean age at operation 54 years) were found. All parameters were comparable between the groups. Mean disease duration before CRC was 22.7 years for UC and 16.6 years for CC patients (P = 0.04). CRC was diagnosed preoperatively in 43 (81%) patients. Twenty-eight patients had colon cancer, 23 had rectal cancer and two patients had more than one cancer. All malignancies were located in segments with colitis. Over one-half were diagnosed at an advanced stage (36% stage III; 17% stage IV). At a mean follow up of 56 ± 65 months, 60% were alive (54% disease free) and 40% were dead from cancer-related causes. The 5-year survival rate was 61% for the UC and 37% for the CC patients (P = NS). Conclusion CRC in IBD patients is frequently diagnosed at an advanced stage, a factor that contributes to poor prognosis. The risk of CRC in CC patients is comparable to those with UC. Long-term surveillance is recommended for patients with long-standing CC and UC.

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.

Aim The study aimed to characterize the pathological and clinical response of rectal gastrointestinal stromal tumours (GISTs) to neoadjuvant Imatinib. Method The medical records of patients with rectal GISTs who were diagnosed and treated in five medical centres in Israel between January 2002 and January 2009 were retrospectively examined. Twelve patients who fulfilled the inclusion criteria of nonmetastatic rectal GIST for which preoperative neoadjuvant treatment with Imatinib was considered were suitable for enrollment. Results Of the 12 patients, nine received neoadjuvant treatment with Imatinib. The three patients who had immediate surgery were excluded. There were five men and four women with a median age of 63 years and a median follow up of 32 months. All tumours were located in the lower two-thirds of the rectum. One patient had a complete clinical response, six had a partial response and two had stable disease. Seven patients subsequently underwent surgery; six had an R0 resection and one had an R1 resection. Three patients had recurrence. There was no disease-related mortality. The reduction in both tumour size and mitotic activity during preoperative Imatinib therapy was significant. Conclusion Preoperative Imatinib therapy can shrink large rectal GISTs, improving the chances of successful radical surgery and decreasing the risk of considerable morbidity.

IBDs are characterized by increased influx of immune cells to the mucosa of genetically susceptible persons. Cellular migration to injury sites is mediated by chemokines. CXCL12 is a ubiquitous, constitutive chemokine that participates in stem cell proliferation and migration and mediates T lymphocyte migration to inflamed tissues. We have recently reported that CXCL12 and its receptor, CXCR4, are expressed in normal and more prominently, inflamed human intestinal mucosa. However, the interactions and roles of CXCL12 and its receptors, CXCR4 and the recently discovered CXCR7, in intestinal inflammation have not been defined. In the present study, we further dissected the effects of CXCL12 on lymphocytes in intestinal homeostasis and inflammation and delineated the interplay between CXCL12 and its receptors CXCR4 and CXCR7. To that end, fresh mononuclear cells were isolated from mucosa and PB of healthy or IBD patients. Phenotypical and functional assays were conducted using flow cytometry, Transwell migration chambers, and ELISA. The data show that CXCL12-mediated migration of T cells is CXCR4- but not CXCR7-dependent. T cell activation reciprocally regulates CXCR7 and CXCR4 expression and migratory capacity. IBD PBTs expressed more CXCR7 than normal PBTs. Finally, T cells attracted by CXCL12 are mostly of a memory phenotype. In conclusion, the present study suggests that the interplay between CXCL12 and its receptors affects homeostasis and inflammation in the intestinal mucosa.

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.

Background: Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Methods: Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. Results: IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. Conclusions: CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;)

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.