Ileal Pouch-anal Anastomosis For Ulcerative Colitis Research Articles

Extensive Colitis and Smoking Are Associated With Postoperative Complications Within 30 Days of Ileal Pouch-Anal Anastomosis.

Our understanding of outcomes after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is largely based on analyses of selected populations. We created a state-level registry to evaluate the epidemiology of IPAA surgery and pouch-related outcomes across the major healthcare systems performing these surgeries in our state. We created a retrospective cohort of all patients undergoing restorative proctocolectomy with IPAA for UC at 1 of 4 centers between January 1, 2018, and December 31, 2020. The primary outcomes of this study were the rate of complications and all-cause readmissions within the first 30 days of the final stage of IPAA surgery. During the study period, 177 patients underwent IPAA surgery with 66 (37%) experiencing a complication within 30 days. After adjusting for the number of stages in IPAA surgery, patients with extensive UC (odds ratio, 3.61; 95% confidence interval, 1.39-9.33) and current or former smokers (odds ratio, 2.98; 95% confidence interval, 1.38-6.45) were more likely to experience a complication. Among all patients, 57 (32%) required readmission within 30 days. The most common reasons for readmission were ileus/small bowel obstruction (22%), peripouch abscess (19%), and dehydration (16%). In this first state-level examination of the epidemiology of IPAA for UC, we demonstrated that the complication rate after IPAA for UC was 37%, with one-third of patients being readmitted within 30 days. Extensive disease at the time of colectomy appears to be an indicator of more severe disease and may portend a worse prognosis after IPAA.

The Natural History After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Population-Based Cohort Study From the United States.

There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1, 3, 5, and 10 years: the incidence of pouchitis, Crohn's-like disease of the pouch, use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records. We performed a retrospective cohort study in TriNetX, a research network of electronic health records. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching, expressed as adjusted hazard ratios (aHRs). Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After propensity score matching, nicotine dependence (aHR 1.61, 95% confidence interval [CI] 1.19-2.18), antitumor necrosis factor therapy (aHR 1.33, 95% CI 1.13-1.56), and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06-1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of Crohn's-like disease of the pouch increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA. The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.

Antibiotic Use in the 12 Months Prior to Ileal Pouch-Anal Anastomosis Increases the Risk for Pouchitis

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC); however, clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis. We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC from 1996-2020. We used Cox proportional hazard modeling to assess the impact of antibiotic, nonsteroidal anti-inflammatory drug (NSAID) exposure, and appendectomy on diagnosis of acute pouchitis in the first 2 years after IPAA surgery. Among 1616 eligible patients, 46% developed pouchitis in the first 2 years after IPAA. Antibiotic exposure in the 12 months before IPAA was associated with an increased risk of pouchitis (adjusted hazard ratio [aHR], 1.41; 95% confidence interval [CI], 1.22-1.64) after adjusting for anti-tumor necrosis factor alpha use and sex. Compared with persons without any antibiotic prescriptions in the 12 months before IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR, 1.30; 95% CI, 1.11-1.52) and 3 or more courses (aHR, 1.77; 95% CI, 1.41-2.21). NSAID exposure in the 12 months before IPAA and appendectomy were not associated with risk of acute pouchitis (P= .201 and P= .865, respectively). In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months before IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.

Is extended venous thromboprophylaxis required in patients undergoing ileal pouch procedure for ulcerative colitis?

Venous thromboembolic events (VTEs) are relatively common adverse surgical complications. Extended VTE prophylaxis for 4 weeks is recommended after colorectal cancer surgery, but its use in inflammatory bowel disease surgery lacks high-quality evidence. This retrospective study aimed to assess and characterize VTEs within the first 30 days after ileal pouch-anal anastomosis (IPAA) procedures and subtotal colectomies (STCs) for ulcerative colitis (UC). All patients who underwent IPAA for UC between 1 January 2017 and 31 December 2021 were included. VTE rates after IPAA, in-hospital or at-home occurrences, utilization of in-hospital thromboprophylaxis, and prescribed anticoagulant treatment were evaluated. Retrospectively, the same variables were analysed if patients of the cohort underwent STC before the IPAA construction. In all, 204 patients underwent IPAA (61.8% men, 73% laparoscopic), with an average hospital stay of 6.8 days. Among them, 116 patients underwent STC prior to IPAA. Thirteen patients (6.3%) experienced VTEs after IPAA, with 76.9% (10/13) of cases occurring during hospitalization and under adequate thromboprophylaxis. The VTE rate after STC was 10.3% (12/116), with 58.2% (7/12) occurring in hospital and under appropriate thromboprophylaxis. No reoperations or mortality were attributed to thrombotic events. The type and duration of anticoagulant treatment varied considerably. The VTE rate after IPAA for UC was 6.3%, with the majority of events occurring in hospital and under adequate thromboprophylaxis. These findings suggest that routine use of extended VTE prophylaxis in our cohort may not be supported. Further research is needed to clarify the optimal VTE prophylaxis strategy for inflammatory bowel disease surgery.

P214 Effects of rectal stump proctitis on short-term postoperative complications after proctectomy and ileal pouch-anal anastomosis for Ulcerative Colitis

Abstract Background Inflammation of the rectal stump (proctitis) after subtotal colectomy with ileostomy for ulcerative colitis (UC) is common. Proctitis may affect the postoperative outcomes of ileal pouch-anal anastomosis (IPAA). This study aims to explore associations between rectal stump proctitis and short-term postoperative complications (POCs) after proctectomy and IPAA for UC. Methods This retrospective single-centre study included patients who underwent proctectomy, IPAA and protective ileostomy for UC from 2000-2023. Data were retrieved from our prospectively-maintained database. Exclusion criteria were dysplasia or cancer (103 pts), missing pathology results (50 pts), undetermined colitis or Crohn’s Disease features at proctectomy (18 pts). All patients underwent three-staged IPAA and were divided into four groups according to the rectal stump proctitis status at pathology: remission, mild, moderate, and severe proctitis. A stepwise binary logistic regression analysis was performed for each short-term outcome. Models included variables with a different distribution according to the outcome (p-value ≤0.1). Results We included 785 patients who underwent proctectomy and IPAA. At pathology, remission was achieved by 162 (20.6%) patients, while proctitis of the rectal stump was mild in 211 (26.9%), moderate in 246 (31.3%), and severe in 166 (21.1%) patients, respectively. Table 1 details population characteristics and outcomes according to the proctitis status. Patients with moderate and severe proctitis received more preoperative biologics and ongoing systemic steroids at surgery. While they underwent previous abdominal surgery less frequently, the laparoscopy rate was lower with a longer postoperative length of stay. At multivariate (Table 2), Medical POCs were independently associated with ongoing antibiotics (OR 2.29 [1.01-5.20] p=0.047) and ASA score≥3 (OR 1.93 [1.11-3.35] p=0.019). Surgical POCs were independently associated with ongoing systemic steroids (OR 2.09 [1.19-3.68] p=0.011, while ongoing antibiotics (OR 0.2 [0.04-0.86] p=0.031) and laparoscopy (OR 0.53 [0.28-1.00] p=0.049) were protective. Intra-abdominal septic complications (IASCs) and abdominal/pelvic abscesses were independently associated with the proctitis status (OR 1.1 [1.06-2] p=0.018 and OR 1.56 [1.08-2.25] p=0.017, respectively). Conclusion Rectal stump proctitis was independently associated with postoperative abdominal and pelvic abscesses and IASCs after proctectomy and IPAA for UC. The association between proctitis and IPAA’s long-term outcomes and pouch failure need to be further explored.

P1142 Antibiotic use in the twelve months prior to ileal pouch-anal anastomosis increases the risk for pouchitis: A population-based Danish cohort study

Abstract Background Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), however clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis. Methods We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC between January 1, 1996 and May 31, 2020. We used Cox Proportional Hazard modeling and logistic regression to assess the impact of antibiotic and non-steroidal anti-inflammatory drug (NSAID) exposure and appendectomy on the primary outcome of diagnosis of acute pouchitis in the first 2 years after IPAA surgery. A 2-year time window was utilized given the clinical relevance of early pouchitis and to mirror prior studies in both administrative claims and the Danish health registers. Results Among 1,616 eligible patients, 738 (46%) developed pouchitis in the first 2 years after IPAA. Among all patients undergoing IPAA surgery for UC, 51% were prescribed antibiotics in the 12 months prior to the index date and 17% were prescribed NSAIDs in the 12 months prior to the index date. In Kaplan-Meier analyses, those persons who were prescribed antibiotics in the 12 months prior to the final stage of IPAA surgery were significantly more likely to develop pouchitis in the 2 years after the index date when compared to patients who were not prescribed antibiotics (p<0.001, Figure 1B). Additionally, male patients demonstrated a decreased risk for pouchitis in the first 2 years after the index date when compared to female patients (p=0.014, Figure 1A). Antibiotic exposure in the 12 months prior to IPAA was associated with an increased risk of pouchitis (adjusted Hazard Ratio [aHR] 1.40, 95% CI 1.21-1.62) after adjusting for year of surgery and sex (Table 1). In a secondary analysis, compared to persons without any antibiotic prescriptions in the 12 months prior to IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR 1.29, 95% CI 1.10-1.51) and 3 or more courses (aHR 1.79, 95% CI 1.43-2.23, Figure 1C). NSAID exposure in the 12 months prior to IPAA and appendectomy were not associated with risk of acute pouchitis (p=0.201 and p=0.865 respectively). Conclusion In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months prior to IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.

P854 Tofacitinib demonstrates preliminary efficacy in induction of remission in chronic pouchitis

Abstract Background Pouchitis is common following total proctocolectomy for ulcerative colitis (UC) and ileal pouch-anal anastomosis (IPAA) and generally responds to antibiotics. However, up to 20% of patients develop either antibiotic-dependent or antibiotic-refractory pouchitis, collectively referred to as chronic pouchitis. Methods We report our preliminary induction results from a multi-center open label induction with randomized withdrawal trial to assess the efficacy of tofacitinib in chronic pouchitis. All eligible participants received 10mg tofacitinib twice daily for 8 weeks, with an additional 8 weeks of therapy given to patients with an inadequate initial clinical response. The primary endpoint was clinical response (a reduction of clinical PDAI≥2) at week 8. Secondary endpoints included endoscopic response (a reduction of endoscopic PDAI≥2), mPDAI remission (modified pouchitis disease activity index (mPDAI)≤ 4 and a reduction of mPDAI≥2), mPDAI response (a reduction of mPDAI≥2) and improvement in health-related quality of life (HRQoL) using the short inflammatory bowel disease questionnaire (SIBDQ). Serum cytokine levels was analyzed using LEGENDplex human inflammation panel 1. Univariate analysis was performed to identify clinical and biochemical predictors of response to tofacitinib. Results A total of 33 patients with chronic pouchitis (Table 1) were included in the preliminary analysis. The clinical and endoscopic response rates at week 8 were 55% and 58% respectively, with a median improvement of 1 (p<0.05) and 3 (p<0.05) respectively (Figure 1). The mPDAI remission rate was 49% at week 8 with an mPDAI response rate of 73%. Endoscopic responders exhibited significant improvements in endoscopic oedema, granularity, friability, and mucous exudate (p<0.05). There was significant improvement in HRQoL, with the median SIBDQ score increasing from 35 at baseline to 54 at week 8 (p<0.05). Eleven patients received a further 8 weeks of therapy with a clinical response rate of 36%, yielding an overall response rate including extended induction of 67%. Univariate analysis did not reveal significant differences in baseline characteristics, clinical, or biochemical markers between responders and non-responders. However, a history of corticosteroid use (p=0.08) and high baseline levels of faecal calprotectin (p=0.15) demonstrated a non-significant association with treatment response. Elevated baseline serum levels of IL-1b, IFN-a and IL-33 were associated with a treatment response at week 8 (p<0.05). Conclusion Tofacitinib demonstrated preliminary efficacy in inducing both clinical and endoscopic response in patients with chronic pouchitis who have undergone IPAA for UC.

Extraintestinal Manifestations and Family History of Inflammatory Bowel Disease Increase the Risk of Pouchitis in a State-Level Epidemiology Study.

Our understanding of the epidemiology of inflammatory conditions of the pouch and effectiveness of treatment is largely based on selected populations. We created a state-level registry to evaluate the incidence of pouchitis and the effectiveness of treatments used in an initial episode of pouchitis. In a state-level retrospective cohort of all patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis between January 1, 2018, and December 31, 2020, we evaluated the incidence of pouchitis and compared the proportion of patients developing recurrent pouchitis and chronic antibiotic-dependent pouchitis according to initial antibiotic therapy. A total of 177 patients underwent surgery with 49 (28%) developing pouchitis within the 12 months after the final stage of IPAA. Patients with extraintestinal manifestations of inflammatory bowel disease (IBD) were significantly more likely to develop pouchitis within the first 12 months after IPAA (adjusted odds ratio 2.45, 95% confidence interval 1.03-5.81) after adjusting for family history of IBD (adjusted odds ratio 3.50, 95% 1.50-8.18). When comparing the proportion of patients who developed recurrent pouchitis or chronic antibiotic-dependent pouchitis with those who experienced an isolated episode of pouchitis, there were no significant differences among the initial antibiotic regimens used. In a state-level examination of outcomes after IPAA for ulcerative colitis, patients with extraintestinal manifestations of IBD were more likely to develop pouchitis; however, the initial antibiotic regimen chosen did not seem to affect long-term outcomes.

Ethnic Variation Trends in the Use of Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

Approximately 15%-20% of patients with ulcerative colitis (UC) will require surgery during their lifetime. Ileal pouch-anal anastomosis (IPAA) is the preferred surgical option, which typically requires access to a specialist experienced in surgery for inflammatory bowel diseases (IBD). The aims of this study are the assessment of the comparative use of IPAA for UC among different racial/ethnic groups and observe trends over the past decade in the United States as well as the comparative assessment of their respective postoperative outcomes. This was an observational retrospective study using the National Inpatient Sample (NIS) 2009-2018 dataset. All patients with ICD-9/10CM codes for UC were included. The primary outcome was comparative trends in IPAA construction across races/ethnicities in the past decade, which was compared to White patients as reference. Multivariate regression analyses were used to adjust for age, gender, Charlson comorbidity index, income in patient zip code, insurance status, hospital region, location, size, and teaching status. The number of patients discharged from US hospitals with an associated diagnosis of UC increased between 2009 and 2018, but the number of patients undergoing an IPAA decreased during that time period. Of 1 153 363 admissions related to UC, 60 688 required surgery for UC, of whom 16 601 underwent IPAA in the study period. Of all the patients undergoing surgery for UC, 2862 (4.7%) were Black, while 44 351 were White. This analysis indicated that Black patients were less likely to undergo IPAA both in 2009 and in 2018 compared to Whites. Hispanic patients were significantly less likely to receive IPAA in 2009 but were no longer less likely to receive IPAA in 2018 when compared to Whites. The use of IPAA among Black patients requiring surgery for UC remains less common than amongst their White counterparts. Further research is needed to determine if racial disparity is a factor in decreased access to specialized care.

Very Early Pouchitis Is Associated with an Increased Likelihood of Chronic Inflammatory Conditions of the Pouch.

Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We aimed to investigate the relationship between acute pouchitis within 180days of the final stage of IPAA surgery (very early pouchitis) and the future development of chronic antibiotic dependent pouchitis (CADP) and Crohn's-like disease of the pouch (CLDP). We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between very early pouchitis and the development of CADP and CLDP. Among 626 patients undergoing IPAA for UC, 137 (22%) developed very early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed CLDP in a median follow-up of 5.18years (interquartile range 0.94-10.8years). Very early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR3.65, 95% CI 2.19-6.10) as was primary sclerosing cholangitis (aOR 3.97, 95% CI 1.44-11.0). Very early pouchitis was associated with increased odds for developing CLDP (aOR 2.77, 95% CI 1.54-4.98) along with a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96). In this cohort, very early pouchitis was associated with an increased risk of developing CADP and CLDP. These findings highlight very early pouchitis as a unique risk factor for chronic inflammatory conditions of the pouch and the need for future studies evaluating potential strategies for secondary prophylaxis strategies in this population.

The Safety of Dilation of Ileoanal Strictures With Mechanical or Balloon Dilation Is Similar Among Patients After Ileal Pouch-Anal Anastomosis.

Anastomotic strictures occur in up to 38% of patients after ileal pouch-anal anastomosis (IPAA). We sought to compare the safety, effectiveness, and durability of mechanical dilation using a Hegar dilator to endoscopic through-the-scope balloon dilation (EBD) among IPAA patients with a rectal or ileoanal anastomotic stricture. We identified adult patients with an IPAA for ulcerative colitis (UC) who underwent a pouchoscopy between January 1, 2015, and December 31, 2019, at a single institution. We compared the effectiveness (median maximum diameter of dilation [MMD]), safety, and durability of mechanical and balloon dilation using standard statistical comparisons. A total 74 patients had a stricture at the ileoanal anastomosis and underwent at least 1 mechanical or balloon dilation. The MMD with mechanical dilation was 19 (interquartile range [IQR], 18-20) mm for the first dilation and 20 (IQR, 18-20) mm for the second and third dilations. With balloon dilation, the MMD was 12 (IQR, 12-18) mm for the first dilation, 15 (IQR, 12-16.5) mm for the second dilation, and 18 (IQR, 15-18.5) mm for the third dilation. Patients undergoing mechanical dilation experienced a longer duration to second dilation (median 191 days vs 53 days: P < .001), with no difference in complications such as bleeding or perforation noted. Among patients with ileoanal and rectal strictures, mechanical and balloon approaches to dilation demonstrated similar safety profiles and effectiveness. Mechanical dilation with Hegar dilators appears to be an effective and safe approach to the treatment of distal strictures after IPAA.

Risk factors and outcomes of restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Retrospective study of 75 single center cases.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical gold standard in patients with ulcerative colitis (UC). Results are generally satisfactory but there is a significant rate of patients who experience postoperative complications. The aims of our study were to identify the pre- and intraoperative risk factors and their correlation with the reported outcomes. A retrospective study was conducted on the medical records of all consecutive patients undergoing restorative proctocolectomy with IPAA for UC in our center from 2010 to 2021. Pre- and intraoperative factors were examined and correlated with pouchitis, endoscopic pouchitis, pouch failure, anastomotic leak, postoperative complications classified according to Clavien-Dindo score and stoma outlet obstruction. A univariate and multivariate statistical analysis was performed. Out of 75 patients undergoing 3- or 2-stage IPAA surgery, the coexistence of extraintestinal clinical manifestations and preoperative topical rectal stump therapy for active proctitis were significantly associated with the occurrence of pouchitis (OR=4.4, p=0.03 and OR=7.6, p=0.01). Endoscopic pouchitis was found to be related to preoperative topical rectal therapy (OR=10.2, p=0.007), but not to extraintestinal manifestations of disease. Anastomotic leak was found to be significantly related to pouch failure (OR=22.7, p=0.007). Surgical indication for malignancy increased the risk for early complications (Clavien-Dindo >2) (OR=16.0, p=0.04). Young age was associated with the occurrence of outlet stoma obstruction in patients with recent IPAA surgery (OR=0.97, p=0.05). Based on observed results, an appropriate preoperative patient assessment aimed at detecting specific risk factors is crucial to identify early or prevent worse outcomes in patients undergoing IPAA surgery.

P449 Minimally invasive IPAA in UC: Preliminary results from a referral center

Abstract Background Minimally invasive approaches in performing restaurative total proctocolectomy in Ulcerative Colitis(UC) have been increasingly adopted. In particular, the robotic approach could be used with more benefits in proctectomy with ileal pouch anal anastomosis (IPAA). In fact, the robotic device seems to potentially overcome all the limitations found in laparoscopic and conventional open surgery. The aim of our study was to compare and evaluate early and late functional postoperative outcomes and complications after IPAA, performed with open, laparoscopic and robotic techniques in UC patients. Methods At our institution, 397 UC patients who underwent restorative proctocolectomy with IPAA during the period 1986-2022, consecutively treated either with open surgery, laparoscopic or robotic techniques were enrolled. The incidence of early (&amp;lt;30 days) and late (&amp;gt;30 days) postoperative complications (intestinal occlusion, haematoma/wound infection, anastomotic dehiscence), hospital stay and an assessment about continence, autonomic nerve damage, incidence of pouchitis and cuffitis was evaluated. Results About the 397 patients, 344 underwent conventional open IPAA, 31 laparoscopically and 22 robotically. Comparable early and late postoperative surgical complications were recorded among the different techniques [early and late complications respectively 24/53 (45,2%) and 146/344(42,4%)] in minimally invasive and open groups. Minimally invasive surgery showed a better outcome regarding wound infections [0/53 (0%)], anastomotic dehiscence and reduced length of stay but open surgery demonstrated a better result on early and late intestinal occlusion [8/53 (15%)vs 22/344 (6,39%)] and anastomotic stenosis [5/53 (9,43%) vs 15/344 (4,36%)]. Lastly, the rate of cuffitis was higher in open surgery than in the minimally invasive group [(3/53 (5,66%) vs 46/344(13,37%)] and within these, robotic approach seems to show better results compared to laparoscopy. Conclusion UC patients undergoing IPAA could benefit from a minimally invasive surgical approach. Our experience confirms that robotics seems to be related to hopeful outcomes both in the short and long term period, even if more studies are needed to refine the promising results.

Fecal calprotectin as an indicator in risk stratification of pouchitis following ileal pouch–anal anastomosis for ulcerative colitis

Background Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis. Patients and methods This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups. Results Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (n = 40) and pouchitis group (n = 26). The correlation coefficient between the FC concentration and the PDAI score was 0.651 (p < 0.001). Receiver operating characteristic analysis showed that the FC cut-off value for predicting pouchitis was 579.60 μg/g (area under the curve, 0.938). The patients were then divided into three subgroups according to their PDAI score (0–2, 3–6, and ≥7), and significant differences in the FC concentration were found among the three subgroups. The best FC cut-off value for predicting a high risk of pouchitis (PDAI score of 3–6) was 143.25 μg/g (area under the curve, 0.876). Conclusions FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25–579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients. KEY MESSAGES Fecal calprotectin can be used to quantify pouch inflammation. Fecal calprotectin can be used to predict a high risk of pouchitis.

Crohn's of the Pouch: Now What?

Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the gold standard surgical treatment for the majority (∼90%) of ulcerative colitis (UC) patients. In cases of carefully selected Crohn's colitis patients without small bowel or perianal involvement an "intentional IPAA" may be a viable option for disease resection and restoration of intestinal continuity. More commonly, Crohn's is incidentally found either in the resection specimen or, more commonly, when inflammatory complications subsequently arise after pouch construction for UC or indeterminate colitis. These incidental Crohn's pouches may be diagnosed early or late period post-IPAA. Crohn's may manifest within the pouch, in the proximal small bowel, and/or distally in the rectal cuff or anus. Like intestinal Crohn's, Crohn's disease of the pouch may be of an inflammatory, fibrostenosing, or fistulizing phenotype. Treatment depends on the phenotype and includes medical treatment, most commonly in the form of tumor necrosis factor inhibitor medications; however, the newer small molecules offer a potential treatment for these patients. Surgery first entails treating the sequelae of Crohn's and is typically staged. In up to 60% of Crohn's pouches, particularly in fistulizing disease and/or recalcitrant perianal disease, the pouch fails and must be defunctioned or excised. In patients with Crohn's pouches in situ long term, outcomes including quality of life are comparable to patients who underwent IPAA for UC.

Systematic C-reactive protein monitoring reduces hospital stay after laparoscopic ileal pouch-anal anastomosis. A comparative study of 158 consecutive patients with ulcerative colitis.

C-reactive protein (CRP) is a common biomarker of inflammation which has largely been used to predict the risk of postoperative septic complications after colorectal surgery. However, no data exist concerning its potential benefit after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The aim of this study was to evaluate a CRP-driven monitoring discharge strategy after laparoscopic IPAA for UC. Since 2012, 158 patients undergoing a laparoscopic IPAA for UC have been included: 66 patients (CRP group) operated since 2016 had a CRP-driven monitoring discharge on postoperative day 5 (POD 5) and were discharged on POD 6 if CRP < 100 mg/L; these patients were matched (according to age, gender, body mass index, IPAA in two or three steps) to 92 patients operated between 2012 and 2016 without any CRP monitoring (control group). Median length of hospital stay was shorter in the CRP than the control group (7 vs. 9 days; P < 0.001) and discharge on POD 6 occurred more frequently in the CRP group (47% vs. 7%, P < 0.001). No difference was observed between the two groups concerning overall morbidity (P=0.980), surgical site infection (P=0.554), Clavien-Dindo ≥ IIIa morbidity (P=0.523), unplanned rehospitalization (P=0.734) and 30-day reoperation (P=0.240). CRP-driven monitoring discharge strategy after laparoscopic IPAA for UC is associated with a significant reduction in length of hospital stay, without increasing morbidity, reoperation or rehospitalization rates.

Relationship Between Stages of Ileal Pouch-Anal Anastomosis, Timing of Restoration of Fecal Continuity, and Pouchitis.

The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. We aimed to investigate whether a shorter period between pouch creation and restoration of fecal flow through an IPAA was associated with an increased risk of development of pouchitis within the first 2years after IPAA. We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. We used Kaplan-Meier testing and Cox Proportional Hazards Modeling to evaluate the relationship between the time between restoration of fecal continuity and time to subsequent development of pouchitis, adjusting for other clinical and demographic factors. We identified 624 patients who underwent proctocolectomy with IPAA for UC, of whom 246 (39%) developed pouchitis within the first 2years after IPAA. There was no difference when comparing the median time to restoration of continuity among those patients who developed pouchitis and those who did not (49days vs. 49days, p = 0.85) or in multivariable analysis. Primary sclerosing cholangitis (Hazard Ratio [HR] 2.14, 95% CI 1.12-4.08), family history of inflammatory bowel disease (HR 1.49, 95% CI 1.08-2.06), and delayed pouch creation (HR 0.75, 95% CI 0.57-1.00) were significantly associated with time to development of pouchitis. Although a staged approach to IPAA may have benefits in the surgical management of UC, the timing interval between pouch creation and restoration of continuity did not impact the subsequent development of early pouchitis in this cohort.

MASS CYTOMETRY ANALYSIS OF CROHN’S DISEASE-LIKE PHENOTYPE OF THE ILEOANAL POUCH FOLLOWING ILEAL POUCH-ANAL ANASTOMOSIS FOR ULCERATIVE COLITIS

Abstract BACKGROUNDS For patients with medically refractory ulcerative colitis (UC), total proctocolectomy and ileal pouch-anal anastomosis (IPAA) has been the definitive surgery of choice. Approximately 10% of patients who were initially diagnosed with UC and underwent an IPAA, subsequently develop a condition referred to as Crohn’s disease-like phenotype of ileoanal pouch (CDP). CDP is typified by ulcers in the pre-pouch ileum, stricture involving the pouch or pre-pouch ileum, and/or fistulas. The etiology of CDP remains unknown and remains difficult to diagnose and treat. To define the mucosal immunology of CDP, we analyzed ileal samples from patients with CDP and patients with a normal pouch and pre-pouch ileum using mass cytometry (CyTOF). METHODS Ileal mucosal biopsies from patients with a history of CDP with long-segmental pre-pouch ileitis (n=10) and those with a normal pouch and pre-pouch ileum after IPAA for UC (n=9) were collected during routine pouchoscopy, frozen in medium, and processed, barcoded and analyzed in one CyTOF experiment. Data were analyzed by using viSNE for dimensionality reduction and CITRUS for clustering in Cytobank. RESULTS Compared with patients with a normal pouch/ileum, we observed the following in ileal samples from CDP based on viSNE analysis (Figure 1): 1) A decreased abundance of CD8+CD103+ tissue-resident T cells (TRM). This result is similar to data from colonic mucosal samples in patients with UC (our internal data not shown here and others), but unlike data from prior studies derived from inflamed ileal mucosal specimens in patients with CD (native bowel anatomy without IPAA) which had increased CD8+ TRM. 2) An increase in CD4+CD103-CD161+ Th17 cells previously linked to an activated Th17 phenotype in Crohn’s disease specimens. 3) Increased CD4+CD103-CD45RA+ T cells associated with reduced IL-10/IL-4 and increased TNF-a in IBD. 4) A higher abundance of CD4+CD103-TIGIT+ T cells that were previously shown to predict severity of pediatric IBD. 5) A decrease in CD8+CD103+CD127+ TRM in CDP, although its role in IBD is unclear. The findings from viSNE were confirmed by CITRUS (Figure 2). Further analyses of pouch samples as well as ileal samples from UC and CD with native GI anatomy (for comparison) using CyTOF and scRNAseq are currently underway. CONCLUSIONS We used mass cytometry to identify immune cells specific to ileal mucosa from patients with CDP. Interestingly, immune cells from the inflamed pre-pouch ileum share some features of those from either UC or CD with native bowel anatomy. We also identified an altered immune cell population which appears to be specific to CDP. These data reveal a unique immune landscape of CDP which may serve as a foundation for identifying therapeutic approaches that target specific cell populations for medical management of CDP.

OP04 Vedolizumab intravenous is effective across multiple treatment targets in chronic pouchitis: Results of the randomised, double-blind, placebo-controlled EARNEST trial

Abstract Background Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) after proctocolectomy in ulcerative colitis (UC). There are currently no approved therapies for chronic pouchitis. Here, we report a multicentre trial of intravenous (IV) vedolizumab (VDZ) for chronic pouchitis after IPAA in patients with UC. Methods EARNEST was a randomised, double-blind, placebo (PBO)-controlled, phase 4 study of VDZ in patients aged 18–80 years with chronic pouchitis after proctocolectomy with IPAA for UC (NCT02790138). Male and female patients with a history of IPAA for UC and chronic pouchitis were eligible. Patients were randomised (1:1) to receive VDZ IV (300 mg) or PBO on Day 1 and at Weeks (W) 2, 6, 14, 22 and 30, as well as ciprofloxacin for the first 4 weeks. The primary endpoint was modified Pouchitis Disease Activity Index (mPDAI) remission at W14; efficacy was also assessed through other mPDAI/PDAI secondary endpoints and endoscopic exploratory endpoints (assessed by a central reviewer) at W14 and W34. Safety (adverse events [AEs]) was monitored throughout the study. Results In total, 102 patients were treated (51 per group). Patients had a mean age of 40.8 years (VDZ) and 42.9 years (PBO). mPDAI remission rates (comprising clinical symptoms and endoscopy domains) were 31.4% (n=16/51) for VDZ vs 9.8% (n=5/51) for PBO at W14 (p=0.013; Figure 1). Significant differences in favour of VDZ over PBO were also seen in mPDAI remission at W34, mPDAI response at W14 and W34, and PDAI remission (comprising clinical symptoms, endoscopy and histology domains) at W14 and W34 (Figure 1). The rate of sustained remission (defined as remission at both W14 and W34) was higher for VDZ vs PBO on both the mPDAI (VDZ 27.5% [n=14/51] vs PBO 5.9% [n=3/51]; difference 21.6 percentage points [95% confidence interval (CI), 6.5–37.0]) and the PDAI (VDZ 31.4% [n=16/51] vs PBO 7.8% [4/51]; difference 23.5 percentage points [95% CI, 8.0–38.8]). Endoscopic ulceration analysis showed greater reductions in number of ulcers from baseline for VDZ over PBO at W14 and W34 (Figure 2). A higher proportion of patients in the VDZ vs PBO group had an improved SES-CD score and achieved SES-CD remission of pouchitis (Figure 2). AE rates were similar between groups and no new safety signals were identified (Table). Conclusion This is the first and largest randomised, double-blind PBO-controlled trial of biologic therapy to show significant benefits across multiple treatment outcomes in patients with chronic pouchitis after IPAA for UC. VDZ showed consistent treatment benefits over PBO across clinical, endoscopic and histologic endpoints, together with safety consistent with its established profile.

DOP35 Increasing incidence of pouchitis among patients undergoing ileal pouch-anal anastomosis between 1996 and 2018: A population-based Danish cohort study

Abstract Background Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis (UC) in the first 2 years after ileal pouch-anal anastomosis (IPAA) and analyze time trends of the incidence of pouchitis. Methods We used national registries to establish a population-based cohort of all Danish patients undergoing proctocolectomy with IPAA UC between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after IPAA, evaluated by time period of IPAA. The period of IPAA was categorized as follows: 1996–2000 (pre-biologic-1), 2001–2005 (pre-biologic-2), 2006–2010 (early-anti-TNF), 2011–2014 (expanding anti-TNF), 2015–2018 (current biologic). Pouchitis was defined using a previously developed case-finding definition for use in administrative claims data. Kaplan Meier and Cox Proportional Hazard modeling were utilized in the evaluation of time to development of pouchitis. Results We identified 1,664 patients that underwent an IPAA for UC. The cumulative incidence of pouchitis in the 2 years after IPAA increased throughout the study period, from 40% in 1996–2000, (95% CI:35%-46%) to 55% in 2015–2018, (95% CI:48%-63%, Table 1). Patients undergoing surgery between 2015–2018 also demonstrated an increased risk of pouchitis compared to the earliest study period (1996–2000) after adjusting for sex, age, and socioeconomic status (Hazard Ratio [HR] 1.57, 95% CI:1.20–2.05, Table 2, Figure 1). In a separate model adjusting for the same clinical and demographic factors, there was no significant relationship between the preoperative use of anti-tumor necrosis factor alpha therapy use and the risk of pouchitis when evaluated in the entire population (HR 1.14, 95% CI:0.93–1.40) and when evaluated by time period of surgery. Conclusion This first population-based study demonstrated a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis demonstrated in the most recent era (2015–2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.