Ileal Pouch-anal Anastomosis Patients Research Articles

Trends and Distribution of Ileal Pouch Anal Anastomosis (IPAA) in the United States; Becoming Harder to Find in Colon and Rectal Surgery Residency Training?

BACKGROUND: There has been concern among colon and rectal surgery residency training programs in the United States that ileal pouch anal anastomosis procedures have been decreasing, however evidence is limited. OBJECTIVE: To evaluate the number of ileal pouch anal anastomosis performed by colon and rectal surgery residents in the United States and examine the distribution of these cases on a national level. DESIGN: Retrospective. SETTINGS: The Accreditation Council for Graduate Medical Education Case Log National Data Reports were used to examine the number of ileal pouch anal anastomosis performed by residents from 2005 to 2021. The Nationwide Inpatient Sample database was used to identify all patients undergoing these procedures from 2005 to 2019. PATIENTS: All ileal pouch anal anastomosis procedures regardless of indication. MAIN OUTCOME MEASURE: Primary outcome is the number of ileal pouch anal anastomosis performed by residents yearly. Secondary outcome is the national distribution of these procedures. RESULTS: Among colon and rectal surgery residents, case log data revealed an increase in mean and total number of ileal pouch anal anastomosis from 2005 to 2013, followed by a decline in both metrics after 2013. Despite the decrease, the mean number of cases per resident remained >6 between 2011 and 2021. A weighted national estimate of 48,532 ileal pouch anal anastomosis patients were identified in the Nationwide Inpatient Sample database. A significant decrease was noted in the number of ileal pouch anal anastomosis after 2015 that persisted through 2019. There was a significant decrease in rural and urban non-teaching hospitals (from 2.1% to 1.6% and 25.6% to 4.3% respectively, p < 0.001) and an increase in urban teaching hospitals (from 72.4% to 94.1%, p < 0.001). LIMITATIONS: Nonrandomized retrospective study. CONCLUSION: Despite the recent increase in the percentage of ileal pouch anal anastomosis performed at urban academic centers, there has been a decrease in cases performed by colon and rectal surgery residents. This can have significant implications for residents who graduate without adequate experience in performing this complex procedure independently, as well as training programs that may face challenges with maintaining accreditation. See Video Abstract.

MEDICAL, ENDOSCOPIC, AND SURGICAL THERAPIES FOR THE TREATMENT OF RECTAL CUFFITIS IN ULCERATIVE COLITIS PATIENTS WITH AN ILEAL POUCH-ANAL ANASTOMOSIS: A SYSTEMATIC REVIEW

Abstract BACKGROUND Patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy are left with a rectal cuff, which can develop inflammation known as cuffitis. Treatment of cuffitis typically includes mesalamine suppositories or corticosteroids, but individuals with refractory cuffitis may require advanced therapies, endoscopic intervention, or surgical intervention. The aim of this review is to summarize the existing literature regarding treatments options for cuffitis. METHODS A broad search strategy was created by a medical librarian to capture rectal cuffitis in IPAA patients. The following databases were searched: Ovid Medline® ALL, Ovid Embase, Cochrane Central Register of Controlled Trials (Wiley), and 3 indexes in Web of Science from Clarivate: Science Citation Index-Expanded, Conference Proceedings Citation Index, and BIOSIS Citation Index. A total of 1,652 citations were identified, and 836 studies remained after removal of 816 duplicates. Two reviewers screened all 836 abstracts and 241 full-text articles to determine if they were eligible for inclusion in this review. RESULTS A total of 21 studies (10 cohort studies, 9 case-series, 2 open-label clinical trials) met the inclusion criteria. Medical interventions were investigated in 15 studies (Table 1) with mesalamine being the most common (4 studies) followed by corticosteroids (3 studies), ustekinumab (3 studies), vedolizumab (2 studies), tofacitinib (1 study), and infliximab (1 study). Studies investigating mesalamine and corticosteroid use generally had larger sample sizes (ranging 4-120 patients) and showed symptomatic improvement in 51.7-100% of patients and decreases of 1.14-1.8 points in endoscopic disease activity indices. In contrast, studies investigating advanced therapies had small sample sizes (ranging 1-21 patients) and showed variable responses ranging from no clinical (tofacitinib) or endoscopic (ustekinumab, vedolizumab) improvements to clinical (ustekinumab) or endoscopic (vedolizumab) responses in 75% of patients. Endoscopic and surgical approaches were explored in 6 studies (Table 2) and included secondary mucosectomy (2 studies), endoscopic cuff resection, transanal minimally invasive surgery, endoscopic needle-knife therapy, and balloon dilation for cuffitis patients with concomitant outlet strictures (1 study each). These techniques generally resulted in resolution of symptoms but were limited by small sample sizes (ranging 3-16 patients). CONCLUSIONS Most studies evaluating therapies used to treat rectal cuffitis suggest beneficial effects of conventional mesalamine or corticosteroid-based therapies, whereas data regarding the efficacy of advanced therapies and interventional procedures are inconsistent given small sample sizes. Further research is needed to effectively characterize additional management options for this condition. Table 1. Medical therapies used for treatment of cuffitis. Abbreviations – BM: bowel movements, CRP: C-reactive protein, UST: ustekinumab, HBOT: hyperbaric oxygen therapy, mPDAI: modified Pouch Disease Activity Index, 5-ASA: 5-aminosalicylate, ESR: erythrocyte sedimentation rate, PDAI: Pouch Disease Activity Index, CGQOL: Cleveland Global Quality of Life score, IPS: Irritable Pouch Syndrome, CAI: Cuffitis Activity Index. Table 2. Endoscopic and surgical therapies used for treatment of cuffitis. Abbreviations – FISI: Fecal Incontinence Severity Index, CGQOL: Cleveland Global Quality of Life score, PDAI: Pouch Disease Activity Index, BM: bowel movements.

EPITHELIAL MITOCHONDRIAL DYSFUNCTION IN CHRONIC POUCHITIS

Abstract BACKGROUND Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC). However, patients with IPAA are at risk of pouch-related disorders like “pouchitis” with an incidence rate range from 20-50%. The underlying etiopathogenesis of pouchitis has been unclear, which makes management and treatment of active pouchitis difficult. Mitochondrial (Mito) dysfunction is commonly associated with pathogenesis of inflammatory bowel diseases (IBD). We posit the reduced Mito function contributes to chronic pouchitis in IPAA patients. In this study we performed comparative analysis of Mito complex levels in pouchitis patients compared to normal controls. METHODS Biopsies collected from ileal pouches +/- inflammation (n=6), and normal (n=3) and inflamed ileum (CD Ileitis; n=3 mean SES=5.2) were preserved in Allprotect® or formalin. Total RNA was extracted, cDNA synthesized and analyzed by RT-qPCR for genes specific for Mito biogenesis and complexes, cytokines and cellular antioxidant machinery. Formalin-fixed tissues were processed for IHC staining of Mito complex-I (NDUFB6) and complex-IV (MTCO1). RESULTS Transcriptomic analysis of active pouchitis tissue showed significant (**p<0.01) reduction of Mito biogenesis genes (PGC1α: 69.5±13.9%, TFAM: 48.7±14.5%, NRF1:48.9±17.7%) compared to normal pouch. Similar mRNA analysis in CD-ileitis showed 90.6±15.2% reduction in PGC1α gene (**p<0.01) and more than 62% reduction in TFAM and NRF1 genes compared normal ileum. We also observed 21.6±9.8% reduction in Mito complex I (Ndufa1, Ndufa4, Ndufb2, Ndufb6), 33.6±8.7% reduction in complex-IV (Cox5a Cox6a1, Cox5e) and 38.8±11.8% reduction in complex-V (ATP5a, ATP5b, ATP5e) in chronic pouchitis compared to normal controls. In contrast, CD-ileitis showed 59.5±10.2% reduction in Mito complexes at mRNA level compared to normal ileum. Altogether, CD-ileitis showed 26.3% and 23.8% reduction in Mito complexes and biogenesis genes, respectively, compared to pouchitis. At protein level, tissues from chronic pouchitis showed significantly reduced expression of NDUFB6 and MTCO1 compared to normal controls. However, the decreased expression of NDUFB6 and MTCO1 was more pronounced in active CD-ileitis patients. Concertedly, suppression of Mito biogenesis and complex genes correlated with upregulation of pro-inflammatory cytokines (IL1β and IL-6) and concomitant reduction of anti-oxidant genes (Sod1, Sod2, Gpx, Prdx-2,3,4,6). CONCLUSION These data indicate decreased levels of Mito complexes in pouchitis, although reductions are less prominent in active CD. We postulate that Mito dysfunction plays a role in the pathogenesis of chronic pouchitis after IPAA surgery in IBD patients. Furthermore, we posit mitochondria-targeted therapy may deliver therapeutic benefits in refractory pouchitis.

P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case series

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting. Methods A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation. Results In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10). Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table). Conclusion In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.

Total Proctocolectomy vs Subtotal/total Colectomy for Neoplasia in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients. We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR. Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum. In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.

Efficacy of transanal drainage tube placement in preventing anastomotic leakage after ileal pouch-anal anastomosis in patients with ulcerative colitis.

Transanal drainage tube (TDT) is used to prevent anastomotic leakage after surgery for rectal cancer. However, it remains unclear whether intraoperative TDT placement is also useful in preventing anastomotic leakage after ileal pouch-anal or ileal pouch-anal canal anastomosis (IPAA) in patients with ulcerative colitis (UC). This study aimed to evaluate the efficacy of intraoperative TDT placement in preventing anastomotic leakage after IPAA in patients with UC. Patients with UC who underwent proctectomy with IPAA in the study institution between January 2000 and December 2021 were enrolled in this retrospective cohort study. The relationship between TDT placement and anastomotic leakage was evaluated by logistic regression analysis. The study population included 168 patients. TDT was placed intraoperatively in 103 of the 168 patients (61.3%). The rate of anastomotic leakage was significantly lower in the TDT group than in the non-TDT group (7.8% vs 18.5%, p = 0.037). Reoperation was not needed in any patient in the TDT group whereas two reoperations were necessary in the non-TDT group (3.1%). By logistic regression analysis, intraoperative TDT placement was an independent protective factor for anastomotic leakage. TDT placement was significantly associated with anastomotic leakage of IPAA in patients with UC undergoing surgery. Although two-stage surgery with ileostomy is usually preferred in UC surgery, our findings suggest that TDT placement might contribute to the improvement of postoperative outcomes after UC surgery.

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.

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.

Emergent Subtotal Colectomies Have Higher Leak Rates in Subsequent J-Pouch Stages

PurposeThe most common surgery for ulcerative colitis (UC) is the staged restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). On occasion, an emergent first-stage subtotal colectomy must be performed. The purpose of this study was to compare rates of postoperative complications in three-stage IPAA patients who underwent emergent vs non-emergent first-stage subtotal colectomies in the subsequent staged procedures. MethodsThis was a retrospective chart review conducted at a single tertiary care inflammatory bowel disease (IBD) center. All UC or IBD-Unspecified patients who underwent a three-stage IPAA between 2008 and 2017 were identified. Emergent surgery was defined as that performed on an inpatient who had perforation, toxic megacolon, uncontrolled hemorrhage, or septic shock. The primary outcomes were the presence of anastomotic leak, obstruction, bleeding, and the need for reoperation for each within a 6-month postoperative period of the second (RPC with IPAA and DLI) and third surgical stages (ileostomy reversal). ResultsA total of 342 patients underwent a three-stage IPAA, of which 30 (9.4%) had emergent first-stage operations. Patients who underwent an emergent STC were more likely to have a post-operative anastomotic leak and need an additional procedure following the subsequent second and third-staged operations on both univariate and multivariate analysis (p < 0.05). No difference was found for obstruction, wound infection, intra-abdominal abscess, or bleeding (p > 0.05). ConclusionThree-stage IPAA patients with emergent first-stage subtotal colectomies were more likely to have a post-operative anastomotic leak and need an additional procedure for a leak following the subsequent second- and third-stage operations.

Histologic Predictors of Clinical Outcomes and Healthcare Utilization in Patients With Ileal Pouch-Anal Anastomosis.

The prognostic significance of histology in ileal pouch-anal anastomosis (IPAA) remains unclear. The aim of this study was to evaluate if histologic variables are predictive of IPAA clinical outcomes and healthcare utilization. This was a retrospective cohort study of patients with IPAA undergoing surveillance pouchoscopy at a tertiary care institution. Pouch body biopsies were reviewed by gastrointestinal pathologists, who were blinded to clinical outcomes, for histologic features of acute or chronic inflammation. Charts were reviewed for clinical outcomes including development of acute pouchitis, chronic pouchitis, biologic or small molecule initiation, hospitalizations, and surgery. Predictors of outcomes were analyzed using univariable and multivariable logistic and Cox regression. A total of 167 patients undergoing surveillance pouchoscopy were included. Polymorphonuclear leukocytes (odds ratio [OR], 1.67), ulceration and erosion (OR, 2.44), chronic inflammation (OR, 1.97), and crypt distortion (OR, 1.89) were associated with future biologic or small molecule initiation for chronic pouchitis. Loss of goblet cells was associated with development of chronic pouchitis (OR, 4.65). Pyloric gland metaplasia was associated with hospitalizations (OR, 5.24). No histologic variables were predictive of development of acute pouchitis or surgery. In an exploratory subgroup analysis of new IPAA (<1 year), loss of goblet cells was associated with acute pouchitis (OR, 14.86) and chronic pouchitis (OR, 12.56). Pyloric gland metaplasia was again associated with hospitalizations (OR, 13.99). Histologic findings may be predictive of IPAA outcomes. Pathologists should incorporate key histologic variables into pouchoscopy pathology reports. Clinicians may need to more closely monitor IPAA patients with significant histologic findings.

Laparoscopic ileal pouch-anal anastomosis reduces the risk of surgical site infections: An ACS-NSQIP study

Previous literature related to postoperative outcomes after laparoscopic vs. open ileal pouch-anal anastomosis (IPAA) is primarily based on small numbers of patients from single institutions. The aim of this study is to evaluate these outcomes in a large number of patients using propensity score matching (PSM). The ACS-NSQIP Program data files (2016-2019) were reviewed to identify patients who underwent an IPAA creation. The impact of surgical approach on operative and postoperative outcomes were evaluated. 1:1 propensity score matching (PSM) on all patient characteristics was used to obtain matched groups. Fisher's Exact/Chi-Squared tests were used to compare outcomes between groups. A Bonferroni correction was applied to the outcomes, with a p-value of 0.0031 representing statistical significance. 1802 patients were identified, with 1001 patients in the laparoscopic group and 801 patients in the open group. PSM yielded 702 patients in each matched group. Median operative time was longer for laparoscopic IPAA (278vs218.5 minutes, p<0.001). Laparoscopic IPAA patients were less likely to develop superficial and deep SSIs (3.0% vs 6.6% p=0.003). There were no differences in in-hospital mortality (0.4% vs 0.0%, p=0.3), anastomotic leak (4.0% vs 3.3%, p=1.0), organ-space SSI (6.7% vs 6.0, p=1.0), or reoperation (5.7% vs 4.0%, p=0.2) between groups. Length of stay was lower after laparoscopic IPAA (5.0 vs 6.0 days, p=0.004). There were no differences between groups in other postoperative complications. These data suggest that when matched for other confounding variables, laparoscopic IPAA is associated with reduced length of stay and superficial/deep SSIs when compared to open IPAA. Other surgical complications, including in-hospital mortality and anastomotic leak, are similar. Given the recovery benefit of the laparoscopic approach and the reduced SSI, laparoscopy should be the method of choice for the majority of patients undergoing IPAA.

Prevalence of Clostridioides difficile Infection After Ileal Pouch-anal Anastomosis in Patients With Chronic Antibiotic-dependent Pouchitis and Crohn's-like Disease of the Pouch.

Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn's-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn's-like disease of the pouch. We conducted a retrospective cohort study of patients with CADP or Crohn's-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes. Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%). Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA.

A systematic review and meta-analysis of the outcome of ileal pouch-anal anastomosis in patients with ulcerative colitis versus patients with familial adenomatous polyposis.

Ileal pouch-anal anastomosis (IPAA) is commonly used to restore gastrointestinal continuity after surgical treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). The aim of the present systematic review was to compare the outcomes of patients with MUC and patients with FAP who underwent IPAA. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review was performed. PubMed, Scopus, and Web of Science were searched through December 2021. Cohort and randomized studies were eligible for inclusion if they directly compared patients with MUC and FAP who underwent IPAA. The main outcome measures were pouch failure, complications, and need for pouch excision or revision. ROBINS-I tool was used to assess the risk of bias across the studies. A random-effect meta-analysis was conducted. Twenty-three studies (9200 patients) were included in this meta-analysis. Seven thousand nine hundred fifty (86.4%) had MUC and 1250 (13.6%) hadFAP. The median age of patients was 33.1years. The male to female ratio was 1.4:1. MUC had higher odds of pouchitis (OR 3.9, 95% CI 2.8-5.4, p < 0.001), stricture (OR 1.82, 95% CI 1.25-2.65, p = 0.002), fistula (OR 1.74, 95% CI 1.18-2.54, p = 0.004), and total complications (OR 1.89, 95% CI 1.3-2.77, p < 0.001) as compared to FAP. Both groups had similar odds of pelvic sepsis, leakage, pouch failure, excision, revision, and fecal incontinence. Although patients with MUC undergoing IPAA may be at a higher risk of developing complications, particularly pouchitis, stricture, and fistula; the ultimate and functional outcome of the pouch is similar to patients with FAP. Pouch failure, excision and revision were similar in the two groups.

Defining normal pouch function in patients with ileal pouch-anal anastomosis: a pilot study.

Most patients experience good functional outcomes following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. We aimed to determine if asymptomatic patients with an IPAA had findings consistent with normal defecation on standard objective anorectal tests. Patients 18-65years old with IPAA and self-reported healthy pouch function were recruited. Patients with chronic pouchitis, Crohn's disease, anastomotic stricture, or indication for IPAA other than ulcerative or indeterminate colitis were excluded. Patients underwent an interview with an abbreviated Rome Questionnaire followed by high-resolution ano-pouch manometry, balloon expulsion test, pouch barostat, and magnetic resonance (MR) defecography. Twenty patients completed all testing. Six patients were excluded from the final analysis due to symptoms suggestive of pouch evacuation disorder on the abbreviated Rome Questionnaire (n=2), structural abnormality on MR imaging (n=3), or both (n=1). Of the remaining 14 patients, mean anal resting pressure during high-resolution manometry was 72±16mmHg, mean anal squeeze pressure was 247±69mmHg, and mean pouch-anal gradient during the simulated evacuation was -27±37mmHg. The meantime to balloon expulsion was 54seconds. During dynamic MR defecography, the mean descent of ano-pouch junction was 2.6cm, and mean pouch evacuation was 44.5% and 74.2% pre- and posttoilet phase, respectively. A substantial proportion of patients with IPAA and self-reported healthy pouch function have anatomic and/or functional abnormalities of the pouch. In asymptomatic IPAA patients with an anatomically normal pouch, we have proposed normal parameters for high-resolution ano-pouch manometry, time to balloon expulsion, pouch barostat, and MR defecography.

Magnitude of Preoperative C-Reactive Protein Elevation Is Associated With De Novo Crohn's Disease After Ileal Pouch-Anal Anastomosis in Patients With Severe Colitis.

Total proctocolectomy with ileal pouch-anal anastomosis has become the standard procedure for patients with medically refractory ulcerative colitis, although a subset will develop de novo Crohn's disease. In this study, we investigated the association of preoperative C-reactive protein levels with the development of de novo Crohn's disease after ileal pouch-anal anastomosis. A prospectively maintained database of patients undergoing ileal pouch-anal anastomosis was reviewed. Preoperative C-reactive protein levels were compared between patients who developed de novo Crohn's disease and those who did not. De novo Crohn's disease was defined as small-bowel inflammation proximal to the ileal pouch or perianal disease identified more than 3 months after ileostomy closure. To minimize the heterogeneity of the timing of preoperative C-reactive protein measurement and the severity of ulcerative colitis, only hospitalized patients who had proctocolectomy for severe ulcerative colitis were included in the study. Development of de novo Crohn's disease was analyzed. Of 105 patients, 23 (22%) developed de novo Crohn's disease. Having C-reactive protein in the third tertile significantly increased the risk of developing de novo Crohn's disease (HR 3.44, 95% CI 1.10- 10.70, p = 0.03) compared to in the first tertile. In a multivariable model, a C-reactive protein in the third or second tertile vs the first tertile and younger age was associated with the development of de novo Crohn's disease. Limited to only hospitalized patients with severe ulcerative colitis. In hospitalized patients undergoing ileal pouch-anal anastomosis for medically refractory ulcerative colitis, higher preoperative C-reactive protein levels appear to increase the risk of developing de novo Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B750.LA MAGNITUD DE LA ELEVACIÓN PREOPERATORIA DE LA PROTEÍNA C REACTIVA SE ASOCIA CON APARICIÓN DE UNA ENFERMEDAD DE CROHN DE NOVO DESPUÉS DE UNA ANASTOMOSIS DE BOLSA ILEAL AL ANO EN PACIENTES CON COLITIS SEVERAANTECEDENTES:La proctocolectomía total con anastomosis bolsa ileal-anal se ha convertido en el procedimiento estándar para los pacientes con colitis ulcerativa refractaria al tratamiento médico, aunque un subgrupo desarrollará una enfermedad de Crohn de novo.OBJETIVO:En este estudio investigamos la asociación de los niveles de proteína C reactiva preoperatoria con el desarrollo de la enfermedad de Crohn de novo, después de la anastomosis bolsa ileal-anal.DISEÑO:Se revisó una base de datos recolectada en forma prospectiva, de pacientes sometidos a anastomosis bolsa ileal-anal.PACIENTES:Se compararon los niveles de proteína C reactiva preoperatoria entre los pacientes que desarrollaron la enfermedad de Crohn de novo y los que no la desarrollaron. La enfermedad de Crohn de novo se definió como una inflamación del intestino delgado proximal a la bolsa ileal o una enfermedad perianal identificada más de 3 meses después del cierre de la ileostomía. Para minimizar la heterogeneidad del momento de la medición de la proteína C reactiva preoperatoria y la gravedad de la colitis ulcerativa, solo se incluyeron en el estudio los pacientes hospitalizados que se sometieron a una proctocolectomía por colitis ulcerativa grave.PRINCIPALES MEDIDAS DE RESULTADO:se analizó el desarrollo de la enfermedad de Crohn de novo.RESULTADOS:De 105 pacientes, 23 (22%) desarrollaron enfermedad de Crohn de novo. Tener una proteína C reactiva en el tercer tercil aumentó significativamente el riesgo de desarrollar la enfermedad de Crohn de novo (HR 3,44, IC del 95%: 1,10-10,70, p = 0,03) en comparación con el primer tercil. En un modelo multivariable, una proteína C reactiva en el tercer o segundo tercil frente al primer tercil y una edad más joven se asoció con el desarrollo de la enfermedad de Crohn de novo.LIMITACIONES:Limitado solo a pacientes hospitalizados con colitis ulcerativa grave.CONCLUSIONES:En pacientes hospitalizados sometidos a anastomosis bolsa ileal-anal por colitis ulcerativa refractaria al tratamiento médico, niveles más elevados de proteína C reactiva preoperatoria parecen aumentar el riesgo de desarrollar enfermedad de Crohn de novo. Consulte Video Resumen en http://links.lww.com/DCR/B750. (Traducción-Eduardo Londoño-Schimmer).

Ileal Pouch Anal Anastomosis (IPAA) for colitis; development of Crohn's and Pouchitis

BackgroundChronic pouchitis and Crohn's disease after Ileal pouch anal anastomosis (IPAA) for ulcerative colitis could be a larger issue than previously reported. MethodsAll patients receiving care for their IPAA over a 10-year period at a community hospital were included. Primary outcomes were incidence of Crohn's disease and pouchitis. ResultsThe study included 380 IPAA patients. Indication for pouch creation was either UC (n = 362) or indeterminate colitis (n = 18). Cumulative incidence of Crohn's was 19.5%. Five-, 10- and 20-year incidence of Crohn's was 3.4%, 8.4% and 16.9%. Chronic pouchitis occurred in 28.7%. Mean time to pouchitis and Crohn's diagnosis was 8.4 (SD ± 8.0) and 11.6 (SD ± 7.5) years. Pouch failure occurred in 12.4%. Patients who developed Crohn's were more likely to suffer pouchitis and pouch failure (OR 3.5, 95%CI 2.0–6.0 and 5.3, 95%CI 2.8–10.1). ConclusionDuring long term follow up, almost 20% are diagnosed with Crohn's contributing significantly to pouch failure.

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.

P024 Anorectal Manometry in Patients with Fecal Incontinence After Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease: A Cohort Study.

Fecal incontinence (FI) affects up to 1 in 4 patients with inflammatory bowel disease (IBD) and is associated with inflammation, surgeries, and altered rectal sensitivity. Ileal pouch-anal anastomosis (IPAA) is a surgical intervention for select IBD patients to avoid a permanent stoma. High-resolution anorectal manometry (HRAM) studies in IBD patients with FI demonstrate lower resting pressures and rectal sensory dysfunction. However, HRAM data in IBD patients with FI post-IPAA remains limited. We hypothesized patients with FI would have lower resting and squeeze pressures and rectal hypersensitivity compared to healthy controls and that these changes would be similar after IPAA. Retrospective review of prospectively collected data was conducted on patients undergoing HRAM from 2017-2021 at a single urban academic medical center. Patient characteristics (age, gender, BMI, stool frequency, diabetes, pregnancy history) and surgical history (prior perianal surgery, index vs. re-do IPAA) were obtained. HRAM variables included rectoanal inhibitory reflex (RAIR), sphincter length, resting, squeeze, cough, and push pressures, sensation thresholds (first sensation, constant sensation, desire to defecate, urgency to defecate, max tolerable volume), and balloon expulsion test (BET). HRAM outcomes in IPAA patients with FI (IPAA-FI) were compared to non-IBD patients with FI (non-IBD-FI). HRAM data for both patient cohorts were also compared to existing normative data of healthy controls. Non-IBD patients with constipation and FI were excluded from analysis. An independent samples t-test was performed (p < 0.05) for continuous variables, and chi-square test was used for categorical variables. Fifty-six patients (66% female) were in the non-IBD-FI group. Eighteen patients (67% female) were in the IPAA-FI group. Average age in the IPAA-FI cohort was 44.8 ± 13.6 vs. 66.3 ± 14.4 in the non-IBD-FI group (p< 0.01). Sphincter length in the IPAA-FI group was 2.7 ± 1.1cm vs. 3.2 ± 0.6cm in the non-IBD-FI group (p=0.03). There was no significant difference in sensation thresholds or resting, squeeze, cough, and push pressures between the two groups. Urinary incontinence was observed in 5.6% of IPAA-FI patients vs. 44.6% of non-IBD-FI patients (p < 0.01). RAIR was present in 38.5% of IPAA-FI patients vs. 100% of non-IBD-FI patients (p < 0.01). Both patient cohorts had significantly shorter sphincter length, lower squeeze and push pressures, and lower sensation thresholds compared to normative data. Resting pressures for the IPAA-FI group was not significantly different compared to healthy controls. Overall, anorectal pressures and sensation are similar between IPAA-FI and non-IBD-FI patients. However, the underlying FI mechanism seems to differ. Higher rates of urinary incontinence in the non-IBD-FI cohort suggests global pelvic floor dysfunction compared to IPAA-FI patients who are younger and have post-operative neuromuscular dysfunction, as evidenced by shorter sphincter length and absent RAIR. Though rectal hypersensitivity and lower squeeze/push pressures are observed in both patient groups compared to healthy controls, normal resting pressure in IPAA-FI suggests that potentially different normative ranges are needed for this cohort to accurately assess post-surgical changes and guide pre-operative counseling.

Risk factors for failure of ileal pouch-anal anastomosis in patients with refractory ulcerative colitis

BackgroundProctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. MethodsIn total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. ResultsThe rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P < .001), and had extraintestinal manifestations more frequently (65.4% vs 26.3%, P < .001). Further risk factors for failed ileal pouch-anal anastomosis were hypertension and Cushing’s syndrome. ConclusionTechnical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

Safety and Efficacy of Biological Therapy in Chronic Antibiotic Refractory Pouchitis: A Systematic Review With Meta-analysis.

Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis in patients with ulcerative colitis. Those with ≥3 episodes of pouchitis/year and symptoms despite antibiotics are considered to have chronic antibiotic refractory pouchitis (CARP). While several agents including probiotics, steroids and immunomodulators have been used, treatment of CARP remains challenging. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of various biological agents in treatment of CARP. Multiple databases were searched through June 2020 for studies that reported the efficacy and safety of biological therapy including antitumor necrosis factor-alpha agents [infliximab (IFX) and adalimumab (ADA)], vedolizumab (VDZ), and ustekinumab in CARP. We excluded studies on Crohn's like and/or other inflammatory complications of the pouch. Meta-analysis was performed to calculate pooled rates of clinical as well as endoscopic improvement and remission. We included 15 studies with 311 patients in our final analysis. Ninety-two patients were treated with IFX, 42 with ADA, 144 with VDZ and 33 with ustekinumab. Pooled rate of clinical improvement was 71.4%, 58.2%, 47.9% and clinical remission was 65.7%, 31%, 47.4% with IFX, ADA, and VDZ, respectively. Pooled rate of endoscopic improvement was achieved in 61.2% patients treated with VDZ while endoscopic remission was achieved in 70.3% patients treated with IFX. Adverse events were reported in 3.9% patients. Biologic therapy is safe and effective in the treatment of CARP.