Dietary Interventions and Supplementation in Patients With an Ileal Pouch-Anal Anastomosis: A Systematic Review.

The restorative proctocolectomy with ileal pouch­anal anastomosis is the preferred surgery for patients with medically refractory ulcerative colitis. Although the ileal pouch­anal anastomosis provides gastrointestinal continuity and is an excellent alternative to a permanent end ileostomy, it is not without its complications including acute pouchitis, which occurs in up to 80% of patients. Diet may have a significant impact on pouch function and the development of pouchitis by virtue of its impact on motility and the microbiome. Multiple studies have evaluated the ability of different diets and supplements to improve pouch function and manage pouchitis, yet results are conflicting; thus, evidence-based dietary recommendations are lacking. Patients with an ileoanal pouch routinely ask about dietary interventions to maintain pouch health, and it is crucial that concrete evidence-based recommendations are identified to provide guidance. The goal of this systematic review is to summarize the available data on dietary patterns in patients with an ileoanal pouch, dietary interventions in this cohort, and the impact of supplements on pouch function and pouchitis.

Extensive Disease and Exposure to Multiple Biologics Precolectomy Is Associated with Endoscopic Cuffitis Post-Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

INTRODUCTION: To better inform the risk of cuffitis in patients with ulcerative colitis (UC), we aimed to identify its occurrence and associated precolectomy factors in a large multicenter cohort of patients who underwent restorative proctocolectomy (RPC) with stapled ileal pouch-anal anastomosis (IPAA). METHODS: This study was a retrospective cohort analysis of individuals diagnosed with UC or indeterminate colitis who underwent RPC with IPAA for refractory disease or dysplasia at Mount Sinai Hospital or the University of Chicago followed by at least 1 pouchoscopy with report of the pouch-anal anastomosis. The primary outcome was cuffitis defined as ulceration of the cuff as reported in each pouchoscopy report. RESULTS: The pouch-anal anastomosis was mentioned in the pouchoscopy reports of 674 patients, of whom 525 (77.9%) had a stapled anastomosis. Among these, cuffitis occurred in 313 (59.6%) patients a median of 1.51 (interquartile range 0.59-4.17) years after final surgical stage. On multivariable analysis, older age (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02), extensive disease (HR, 1.34; 95% CI, 1.01-1.78), exposure to biologics before colectomy (HR, 2.51; 95% CI, 1.93-3.27), and exposure to at least 2 or more biologics before colectomy (HR, 2.18; 95% CI, 1.40-3.39) were significantly associated with subsequent cuffitis. CONCLUSIONS: In this multicenter study of patients who underwent RPC with stapled IPAA and at least 1 follow-up pouchoscopy, cuffitis occurred in approximately 60% and was significantly associated with extensive disease and exposure to multiple biologics precolectomy.

In this multicenter study of patients who underwent restorative proctocolectomy with stapled ileal pouch­anal anastomosis and at least 1 subsequent pouchoscopy, endoscopic cuffitis occurred in 60% and was significantly associated with extensive disease and exposure to multiple biologics.

The Ileal Pouch-Anal Anastomosis: Identifying Structural Disorders.

Chronic disorders of a pelvic pouch may result from structural complications secondary to postoperative surgical complications which manifest as a variety of symptoms. Knowing the crucial pitfalls of pouch construction can guide treatment options in patients suffering from signs of pouch failure.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Iron Deficiency Is Common after Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis in Patients with Ulcerative Colitis.

Background: Micronutrient deficiencies may occur after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC), largely due to malabsorption and/or pouch inflammation. Objectives: The objective of this study was to report the frequency of iron deficiency in patients with UC who underwent RPC with IPAA and identify associated risk factors. Methods: We conducted a retrospective chart review of patients with UC or IBD-unclassified who underwent RPC with IPAA at Mount Sinai Hospital between 2008 and 2017. Patients younger than 18 years of age at the time of colectomy were excluded. Descriptive statistics were used to analyze baseline characteristics. Medians with interquartile range (IQR) were reported for continuous variables, and proportions were reported for categorical variables. Iron deficiency was defined by ferritin <30 ng/mL. Logistic regression was used to analyze unadjusted relationships between hypothesized risk factors and the outcome of iron deficiency. Results: A total of 143 patients had iron studies a median of 3.0 (IQR 1.7-5.6) years after final surgical stage, of whom 73 (51.0%) were men. The median age was 33.5 (IQR 22.7-44.3) years. Iron deficiency was diagnosed in 80 (55.9%) patients with a median hemoglobin of 12.4 g/dL (IQR 10.9-13.3), ferritin of 14 ng/mL (IQR 9.0-23.3), and iron value of 44 µg/dL (IQR 26.0-68.8). Of these, 29 (36.3%) had a pouchoscopy performed within 3 months of iron deficiency diagnosis. Pouchitis and cuffitis were separately noted in 4 (13.8%) and 13 (44.8%) patients, respectively, and concomitant pouchitis-cuffitis was noted in 9 (31.0%) patients. Age, sex, anastomosis type, pouch duration, and history of pouchitis and/or cuffitis were not associated with iron deficiency. Conclusion: Iron deficiency is common after RPC with IPAA in patients with UC. Cuffitis is seen in the majority of patients with iron deficiency; however, iron deficiency may occur even in the absence of inflammation.

The Rational Use of Advanced Therapies for Inflammatory Conditions of the Pouch.

We have seen an emergence of new literature supporting the use of advanced therapies in the treatment of chronic inflammatory conditions of the pouch. In this discussion, we review the use of advanced therapies for chronic pouchitis and Crohn's-like disease of the pouch and suggest future directions for research and clinical care.

Systematic review: Scores used to predict outcomes in acute severe ulcerative colitis.

Predictive scores for ASUC outcomes according to time of application.

Pouch Body Anastomotic Ulcerations Are Not Associated With an Increased Risk of Pouchitis.

Patients with isolated pouch body anastomotic ulcers may present with clinically significant symptoms such as increased stool frequency and hematochezia. Isolated pouch body anastomotic ulcers do not increase the risk of future pouchitis.

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions of the Pouch in a Prospective Cohort.

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited. Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. Results: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. Conclusions: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis.

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4+OTOP2+ absorptive and BEST2+WFDC2+ secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC+KLRD1+HOPX+ γδ+ T cells with RORA+CCL20+S100A4+ TH17 cells and the influx of inflammatory myeloid cells. The EC transcriptome (exemplified by S100A8, HIF1A, TREM1, CXCR1) correlated with clinical, endoscopic, and histological severity of UC in an independent validation cohort (n=649). Furthermore, therapeutic relevance of the observed cellular and transcriptomic changes was investigated in 3 additional published UC cohorts (n=23, 48 and 204 respectively) to reveal that non-response to anti-Tumor Necrosis Factor (anti-TNF) therapy was associated with EC related myeloid cell perturbations. Altogether, these data provide high resolution mapping of the EC to facilitate therapeutic decision-making and personalization of therapy in patients with UC.

Barriers to optimizing inflammatory bowel disease care in the United States.

Significant progress in the management and modification of inflammatory bowel disease (IBD) has been made; however, significant barriers to the optimization of IBD care in the United States still exist. The majority of these barriers are constructed by insurance carriers and the integration of market pressures into healthcare decision-making. In this review, we highlight the barriers to IBD care optimization within the context of the US insurance system and review current and proposed solutions.

Systematic review and meta-analysis of randomised controlled trials: Medical therapies for the treatment and prevention of pouchitis.

BACKGROUND AND AIMS: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. METHODS: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis. RESULTS: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence). PROPHYLAXIS: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence). CONCLUSIONS: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

AIM: Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. METHODS: A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. RESULTS: Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. CONCLUSIONS: Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making.

Intestinal ultrasound (IUS) is a non-invasive, real-time, cross-sectional imaging tool that can be used at the point-of-care to assess disease activity in patients with Crohn's disease or ulcerative colitis. IUS promotes quick and impactful treatment decisions that can modify disease progression and enhance patient compliance. This review will summarize the technical aspects of IUS, the evidence to support the use of IUS in disease activity monitoring, the comparison of IUS to current standard of care monitoring modalities such as colonoscopy and calprotectin, and the optimal positioning of IUS in a tight-control monitoring strategy.

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

PURPOSE: The 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. METHODS: This 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). RESULTS: A 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). CONCLUSION: Three-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.

Acute Severe Ulcerative Colitis Is Associated With an Increased Risk of Acute Pouchitis.

BACKGROUND: Pouchitis occurs in up to 80% of patients after total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) and has been associated with microbial and host-related immunological factors. We hypothesized that a more robust immune response at the time of colectomy, manifested by acute severe ulcerative colitis (ASUC), may be associated with subsequent acute pouchitis. METHODS: This was a retrospective cohort analysis of all patients with UC or indeterminate colitis complicated by medically refractory disease or dysplasia who underwent TPC with IPAA at Mount Sinai Hospital between 2008 and 2017 and at least 1 subsequent pouchoscopy. Acute pouchitis was defined according to the Pouchitis Disease Activity Index. Cox regression was used to assess unadjusted relationships between hypothesized risk factors and acute pouchitis. RESULTS: A total of 416 patients met inclusion criteria. Of the 165 (39.7%) patients who underwent urgent colectomy, 77 (46.7%) were admitted with ASUC. Acute pouchitis occurred in 228 (54.8%) patients a median of 1.3 (interquartile range, 0.6-3.1) years after the final surgical stage. On multivariable analysis, ASUC (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.04-2.17) and a greater number of biologics precolectomy (HR, 1.57; 95% CI, 1.06-2.31) were associated with an increased probability of acute pouchitis, while older age at colectomy (HR, 0.98; 95% CI, 0.97-0.99) was associated with a decreased probability. Time to pouchitis was significantly less in patients admitted with ASUC compared with those not (P = .002). CONCLUSION: A severe UC disease phenotype at the time of colectomy was associated with an increased probability of acute pouchitis.

In a retrospective cohort analysis of 416 patients, acute severe ulcerative colitis at the time of colectomy was significantly associated with subsequent acute pouchitis. The risk of pouchitis may be driven by immune activation and disease severity precolectomy.