Patients Undergoing Pouch Surgery Research Articles

Management of Dysplasia in Ulcerative Colitis.

Surveillance colonoscopies for patients with ulcerative colitis (UC) are necessary to monitor for the development of cancer and its precursor, dysplasia. The management of dysplasia in the setting of UC has been evolving over the past two decades. This is in large part due to higher resolution colonoscopes and development of advanced endoscopic techniques, such as chromoendoscopy, endoscopic mucosal resection, and endoscopic submucosal dissection. Mucosal evaluation, as well as identification and removal of dysplastic tissue, has improved markedly, such that the majority of dysplasia is now considered visible. Whereas previously random biopsies were deemed necessary for surveillance, currently their value is uncertain. Surveillance with high-definition colonoscopes is recommended and consideration of chromoendoscopy is suggested. During colonoscopy, if visible dysplasia is identified and removed completely, continued surveillance is appropriate. If dysplasia is unresectable or there are other high-risk factors such as primary sclerosing cholangitis or multifocality, patients should undergo colectomy. If random biopsies are taken and high-grade dysplasia is identified, that is, invisible dysplasia, patients should similarly consider colectomy. Surgical options include total proctocolectomy with end ileostomy versus ileal pouch-anal anastomosis. Patients undergoing pouch surgery must continue surveillance for dysplasia of the rectal cuff and the pouch. Although surgical management remains an important option for dysplasia in the setting of UC, endoscopic surveillance and resection have improved tremendously, leading to a shift in the overall management strategies for these patients.

Review of current practice and outcomes following ileoanal pouch surgery: lessons learned from the Ileoanal Pouch Registry and the 2017 Ileoanal Pouch Report.

The second Association of Coloproctology of Great Britain and Ireland (ACPGBI) Ileoanal Pouch Registry (IPR) report was released in July 2017 following a first report in 2012. This article provides a summary of data derived from the most recent IPR report (2017 Ileoanal Pouch Report. https://www.acpgbi.org.uk/content/uploads/2016/07/Ileoanal-Pouch-Report-2017-FINAL.compressed.pdf). The IPR is an electronic database of voluntarily submitted data including patient demographics, disease, intra-operative and postoperative factors submitted by consultant surgeons or delegates. Data up to 31 March 2017 have been analysed for this report. A total of 5352 pouch operations were carried out at 76 UK and four European centres by 154 surgeons over four decades. Recorded procedures have increased over time but data submission is voluntary and underestimates actual volume. Significant variation exists in institutional volume; 73 centres entered data on patients undergoing pouch surgery during the past 5 years. Of these, 44 centres have submitted ≤ 10 cases, with 10 centres submitting one patient and nine centres two cases. Since 2013, minimal access surgery has been employed in 54% of cases. Rectal dissection was undertaken in the total mesorectal excision plane in 69%. J-pouch configuration was used in 99% of cases and 90% of pouch-anal anastomoses were performed using a stapled technique. Including all years, the IPR rate of pelvic sepsis was 9.4% and the rate of pouch failure was 4.7%. The IPR holds the largest voluntary repository of data on ileoanal pouch surgery. The second report from the IPR records marked refinements in surgical technique over time but also highlights wide variation in institutional caseload and outcome across the UK.

Faecal transplantation for IBD management-pitfalls and promises.

Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis. This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published. Early signals of short to medium-term efficacy of FMT for UC are promising. Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial. Many trials of FMT in adults and children are currently recruiting. Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.

The outcome of ulcerative colitis patients undergoing pouch surgery is determined by pre-surgical factors.

Pouch surgery, a common intervention for ulcerative colitis (UC) complications, is often associated with the development of pouchitis. To identify predictors of pouch outcome in a cohort of patients with UC. 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. 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). 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.

Alterations of Enteric Microbiota in Patients with a Normal Ileal Pouch Are Predictive of Pouchitis.

To examine whether patients with a mature normal pouch [> 1 year post ileostomy closure] have microbial stool characteristics that can predict pouch inflammation. 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. 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]. 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.

Defunctioning Ileostomy is not Associated with Reduced Leakage in Proctocolectomy and Ileal Pouch Anastomosis Surgeries for IBD.

Anastomotic leakage is a serious complication after restorative proctocolectomy with ileal pouch-anal anastomosis. Previous studies have shown significantly decreased leak rates in diverted patients with less severe clinical consequences. The aim of this study was to evaluate short- and long-term outcome of selective ileostomy formation in a multicentre cohort of patients undergoing pouch surgery. In a retrospective study, 621 patients undergoing pouch surgery for inflammatory bowel disease [IBD] were identified from three large centres. Anastomotic leakage was defined as any leak confirmed by either contrast extravasation on imaging or during surgical re-intervention. In 305 patients [49.1%], primary defunctioning ileostomy was created during pouch surgery and 41 [6.6%] patients received a secondary ileostomy because of a leaking non-diverted pouch. Primary ileostomy formation was associated with male sex, weight loss, American Society of Anesthesiologists score [ASA] > 2, steroid use, one-stage surgery, hand-sewn anastomosis, and blood transfusion. Leak rates were comparable between diverted and non-diverted patients [16.7% vs 17.1%, p = 0.92], which remained unchanged in subgroups with immunosuppressive medication. Having had an ileostomy was demonstrated to be an independent predictor of small bowel obstruction (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.45 - 4.67) and pouch fistulas [OR 3.05, 95%CI 1.06 - 8.73]. The 10-year pouch survival was comparable for patients with and without ileostomy [89% versus 88%, p = 0.718]. Leakage rates of diverted and non-diverted pouches in IBD patients were similar and relatively high. Defunctioning was independently associated with long-term complications. A staged approach without defunctioning might be the best strategy.

Sa1178 Concomitant Use of Enteral Nutrition Therapy Increases Sustained Response to Infliximab in Patients With Crohn's Disease

Methods: Adult UC patients, after pouch surgery, followed at a tertiary pouch clinic were recruited. Characteristics of patients with NP outcome, including demographic, inflammatory, serologic, and genetic markers (NOD2 InsC mutation; R702W/rs2066844) were analyzed and compared to those of patients who developed CP and CLDP (together defined as pouchitis). Patients with dual indication for surgery were excluded. Stepwise logistic regression was used to assess possible predictors. Results: Overall, 128 eligible pouch patients were identified: mean age 47.2±15.6 years, females 45.3%, Ashkenazi Jewish 45.3%, non smokers 71%, PSC 3.9%. Fifty-three patients (41.1%) had a favorable outcome a NP phenotype. Disease extent before pouch surgery was pancolitis in 58% and proctitis in 4.3%. Mean follow-up period was 136.1±79.1 months. Family history of IBD was more prevalent in the pouchitis group compared with NP (41.9% vs. 21.2% respectively, p=0.021). BMI was decreased in pouchitis compared with NP (23.5±4.6 vs. 25.5±5.7 p<0.001, respectively). Patients who developed pouchitis were younger at the time of UC diagnosis, as well as at the time of operation, compared with patients who had a NP phenotype (mean age: 22.3±11.1 vs. 27.9±12.0 years, p=0.001, and 32.6±14.6 vs. 41.3±15.5 years, p= 0.007, respectively). Only 28 patients (18%) were operated for non-refractory disease. Almost 70% of the non-refractory group attained a NP phenotype, in contrast to 35.5% NP phenotype in the refractory disease group (p=0.004). Inflammatory markers and serology were similarly distributed. NOD2 insC mutation was detected in 4 patients, all were operated for refractory disease, and following surgery developed pouchitis (P=NS). Stepwise logistic regression revealed two significant predictors for a favorable outcome: surgery due to non-refractory disease, OR=3.73 (95%CI=1.339-10.393), and increased BMI OR=1.151 (95%CI=1.063-1.247). Conclusions: UC patients undergoing pouch surgery due to non-refractory disease have better outcome compared with those operated due to refractory disease. This suggests different immunopathology and may affect therapeutic decisions.

Sa1177 Ulcerative Colitis Patients Undergoing Pouch Surgery Due to Non-Refractory Disease Have a Better Outcome Compared to Those Operated Due to Refractory Inflammation

Sa1177 Ulcerative Colitis Patients Undergoing Pouch Surgery Due to Non-Refractory Disease Have a Better Outcome Compared to Those Operated Due to Refractory Inflammation

P271. Ulcerative colitis patients undergoing pouch surgery due to non-refractory disease have a better outcome compared to those operated due to refractory inflammation

P271. Ulcerative colitis patients undergoing pouch surgery due to non-refractory disease have a better outcome compared to those operated due to refractory inflammation

P363 Growing up with ileal pouch: Adult-patient controlled and coetaneous population-based long-term evaluation of patients undergoing pouch surgery in the developmental age

disease (CD). We updated our first experience with unselected stem cell autotransplantation in refractory CD. Methods: Ten patients (4 male, age 22 46 years) with active moderate-severe CD (median CDAI 340, range 236 395; four with perianal disease), refractory or intolerant to multiple drugs including anti-TNF-alpha agents and immunosuppressors, were enrolled. Unselected PBSCs were collected after mobilisation with CTX 1.5 g/m2 and G-CSF 10mcg/kg. The conditioning regimen included CTX 50mg/kg on days 5 to 2 and rabbit ATG 2.5mg/kg on days 4 to 2. Toxicity, clinical remission (CDAI <150), endoscopic remission (SES-CD) and extramucosal response (ultrasound sonography [US]) were assessed after mobilisation and at 3, 12 months and then every year after stem cells reinfusion. Results: No improvement was confirmed after mobilisation (median CDAI 364, range 201 404). Eight patients were in clinical remission at the first month (median CDAI 141, range 90 198). At the third month, all patients were in clinical remission (median CDAI 91, range 56 132) despite discontinuation of all medications. After a median follow-up of 56 (range 23 68) months, clinical remission was maintained in 80%, 50%, 40%, 30% and 30% at the 1st, 2nd, 3rd, 4th and 5th year after HSCT, respectively. Complete mucosal healing was observed in 50% and 60% after 3 and 12 months, respectively, but maintained in only 30% at their last visit. Perianal fistulas closure was observed in 3/4 patients. No deaths or life-threatening infections occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another, BK virusrelated macrohaematuria in one case, and acute pielonephritis in another patient, all rapidly resolved with conservative treatment. Conclusions: Unselected CD34+ cells transplantation can induce and maintain both clinical and endoscopic remission in refractory CD patients.

Serological Antibodies in Inflammatory Bowel Disease: A Systematic Review

The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD.

Pouch-related dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis

Restorative proctocolectomy (RPC) is the criterion standard surgical treatment for ulcerative colitis (UC). Restorative proctocolectomy is indicated for UC that is refractory to medical treatment, for emergency conditions, and in case of neoplastic transformation. The procedure substantially reduces the risk of UC-associated dysplasia/neoplasia. However, after RPC surgery, even with mucosectomy, cancers of the pouch and/or the anal-transitional zone (ATZ) have been reported with increasing frequency since the first report in 1984. This review highlights pouch-related dysplastic and neoplastic transformation, prevalence and adverse events, risk factors and surveillance following surgery for UC. Reports in the literature about patients undergoing pouch surgery from different institutions reported through May 2010 were reviewed to identify patients who developed these complications, and an attempt was made to develop a rational follow-up policy based on the data available. To date, there are 43 reported cancers of the pouch or inlet after RPC for UC: 16 from retrospective series, 1 from a prospective study, and 26 in case reports. Thirty patients underwent mucosectomy and 13 had stapled anastomoses. To date, the number of 28 patients has been diagnosed with dysplasia after RPC for UC. Mucosectomy was performed in 27 of them and in 1 a stapled anastomosis was constructed without mucosectomy. In all cases reviewed, the time interval from the onset of UC to dysplasia/neoplasia was over 10years. Neoplastic lesions occurring in UC patients after RPC have been shown to be absolutely inevitable. Even mucosectomy does not completely eliminate the risk. There is little evidence to support routine biopsy of the ileal mucosa or the anal-transition zone except in patients with histological type C changes, sclerosing cholangitis, and unremitting pouchitis in the ileal mucosa. Such patients should be selected for endoscopic surveillance to detect dysplasia preceding pouch adenocarcinoma.