Pouch For Ulcerative Colitis Research Articles

Mucosal Single-Cell Profiling of Crohn’s-Like Disease of the Pouch Reveals Unique Pathogenesis and Therapeutic Targets

The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses. Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently validated using immunohistochemistry. The cell populations/states in the pouch body differed from those in the prepouch ileum, likely secondary to increased microbial burden. Compared with the familial adenomatous polyposis pouch, the UC pouch was enriched in colitogenic immune cells even without inflammation. CDP was characterized by increases in T helper 17 cells, inflammatory fibroblasts, inflammatory monocytes, TREM1+ monocytes, clonal expansion of effector T cells, and overexpression of T helper 17 cells-inducing cytokine genes such as IL23, IL1B, and IL6 by mononuclear phagocytes. Ligand-receptor analysis further revealed a stromal-mononuclear phagocytes-lymphocyte circuit in CDP. Integrated analysis showed that up-regulated immune mediators in CDP were similar to those in CD and pouchitis, but not UC. Additionally, CDP pouch/ileum exhibited heightened endoplasmic reticulum stress across all major cell compartments. CDP likely represents a distinct entity of inflammatory bowel disease with heightened endoplasmic reticulum stress in both immune and nonimmune cells, which may become a novel diagnostic biomarker and therapeutic target for CDP.

MUCOSAL SINGLE-CELL PROFILING OF CROHN’S-LIKE DISEASE OF THE POUCH REVEALS COMMON PATHOGENICS AND THERAPEUTIC TARGETS

Abstract BACKGROUND & AIMS After restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), a subset of patients develop Crohn’s-like disease of the pouch (CDP), an inflammatory condition that affects both the ileoanal pouch and extra-pouch organs including pre-pouch ileum. The cellular and molecular identities of CDP are unknown, and its diagnosis and treatment remain challenging. To define the pathophysiology of CDP, we examined mucosal cells from patients with and without CDP using single cell analyses. METHODS Endoscopic samples from the pouch and pre-pouch ileum of 50 patients with an IPAA were collected for single-cell RNA sequencing (scRNA-seq) or mass cytometry (or CyTOF). We analyzed immune and non-immune cells from pouch and ileal tissues of patients with normal pouch/ileum and CDP (n = 5 or 6) using scRNA-seq. CyTOF was performed on mucosal immune cells from independent cohorts of patients with normal pouch/ileum, CDP, and pouchitis (n = 9 or 10). Mucosal samples from patients with familial adenomatous polyposis (FAP) after pouch formation were also analyzed by CyTOF. Some scRNA-seq and CyTOF findings were independently validated using immunohistochemistry (n = 6 or 8). RESULTS We revealed distinct immune and non-immune cell clusters in normal pouch and pre-pouch ileum. Colitogenic immune cells expanded in normal UC pouch compared to normal FAP pouch. Compared to normal pouch/pre-pouch ileum, CDP tissues exhibited expanded TCR clonotypes, elevated Th17 signaling, and diminished T cell exhaustion markers. Elevated frequencies of plasma cells, inflammatory fibroblasts and monocytes were noted in CDP pouch and ileum (Fig 1; only pouch data were shown). CDP also harbored elevated Th17-inducing cytokines such as IL23, IL1B, and IL6 produced by myeloid cells. ScRNA-seq and CyTOF identified increased CD14+TREM1+ pathogenic monocytes in both pouch and pre-pouch ileum of CDP. Ligand-receptor interactions further uncovered an essential role of proinflammatory myeloid cells in the pathogenesis of CDP. In addition, pouch and pre-pouch ileum of CDP showed prominent activation of the unfolded protein response (UPR) across all major cell compartments (Fig 2), which was not present in UC, CD or pouchitis based on integrated analysis of published databases. CONCLUSIONS CDP demonstrates altered immune and non-immune cell populations/states in the pouch and pre-pouch ileum. CDP represents a distinct entity of inflammatory bowel disease with extensive UPR activation, a unique feature that may serve as novel diagnostic markers and therapeutic targets using ER stress-alleviating agents including chemical chaperones. Fig 1 CDP reshapes immune and non-immune landscapes in pouch and pre-pouch ileum. (A) UMAP visualization of all cells from the pouch and ileum of CLDP and normal controls. (B) Diversity of epithelial cells, stromal cells, myeloid cells, T cells, innate lymphoid cells (ILCs), B cells and plasma cells in CLDP vs. normal controls in the pouch estimated by scRNA-seq (n = 5 or 6). *p<0.01. Fig 2 Extensive UPR activation in CDP tissues. (A) UPR gene expression in major cell compartments in CDP and normal controls, highlighted genes including CALR, XBP1, and SERP1 were upregulated in all 5 cell compartments. (B) ER stress/UPR pathways are enriched in CDP. (C) IHC of UPR proteins XBP1 and HSPA5/BiP.

DOP41 Mucosal single-cell profiling of Crohn's-like disease of the pouch reveal unique pathogenesis and therapeutic targets

Abstract Background After restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), a subset of patients develop Crohn’s-like disease of the pouch (CDP), a chronic inflammatory condition that affects both the pouch body and extra-pouch organs including the pre-pouch ileum. The cellular and molecular identities of CDP are unknown, and its diagnosis and treatment remain challenging. To define the pathophysiology of CDP, we examined mucosal cells from patients after IPAA with and without CDP using single cell analyses. Methods Endoscopic samples from the pouch body and pre-pouch ileum of 50 patients with an IPAA were collected for single-cell RNA sequencing (scRNA-seq) or mass cytometry (or CyTOF). We analyzed immune and non-immune cells from both pouch body and pre-pouch ileum of patients with normal pouch/ileum and CDP using scRNA-seq. CyTOF was performed on mucosal immune cells from independent cohorts of patients with normal pouch/ileum, CDP, and pouchitis. Mucosal samples from patients with familial adenomatous polyposis (FAP) after colectomy and pouch formation were also analyzed by CyTOF. ScRNA-seq and CyTOF findings were independently validated using immunohistochemistry. Results We revealed distinct cell clusters in normal pouch body versus normal pre-pouch ileum in UC patients. Colitogenic immune cells expanded in normal UC pouch body compared to normal FAP pouch body. Compared to normal pouch/ileum, CDP pouch/ileum exhibited expanded TCR clonotypes, elevated Th17 signaling, and diminished T cell exhaustion markers. Elevated plasma cells, inflammatory fibroblasts and monocytes were noted in CDP pouch/ileum (Figure 1). CDP also harbored elevated Th17-inducing cytokines such as IL23, IL1B, and IL6 produced by myeloid cells. ScRNA-seq and CyTOF identified increased CD14+TREM1+ pathogenic monocytes in both pouch body and pre-pouch ileum of CDP. Ligand-receptor analysis further revealed a stromal – myeloid – lymphocyte circuit in CDP. Integrated analysis showed that upregulated immune mediators in CDP tissues were similar to those in CD and pouchitis, but not UC. In addition, the pouch body and pre-pouch ileum of CDP exhibited prominent activation of the unfolded protein response (UPR) across all major immune and non-immune cell compartments (Figure 2), which was not present in UC, CD or pouchitis based on reanalysis of published databases. Conclusion CDP demonstrates altered immune and non-immune cell populations/states in the pouch body and pre-pouch ileum. CDP represents a distinct entity of inflammatory bowel disease with extensive UPR activation, a unique feature that may serve as novel diagnostic markers and therapeutic targets using ER stress-alleviating agents including chemical chaperones.

Population outcomes, trends and the future of pouch surgery for ulcerative colitis: a 19-year New South Wales data linkage study.

Ileal pouch-anal anastomosis (IPAA) is considered the gold standard reconstructive option in ulcerative colitis (UC). Recent efforts to improve pouch outcomes have seen a push towards centralisation of surgery. This study aimed to document outcomes following pouch surgery at a population level within New South Wales (NSW), and identify factors associated with, and temporal trends of these outcomes. A retrospective data linkage study of the NSW population over a 19-year period was performed. The primary outcome was pouch failure in patients with UC who underwent IPAA. The influence of hospital level factors (including annual volume) and patient demographic variables on this outcome were assessed using Cox proportional hazards modelling. Temporal trends in annual volume and evidence for centralisation over the studied period were assessed using Poisson regression analysis. The annual volume of UC pouches reduced over the study period. The pouch failure rates were 8.6% (95% CI 6.3-10.8%) and 10.6% (95% CI 8.0-13.1%) at 5- and 10-years, respectively. Increasing age and non-elective admission were associated with higher failure rates. One-third of UC pouches (31.6%) were performed in a single institution, which averaged 6.5 pouches/year throughout the study period. Three-quarters (19/25) of NSW public hospitals who performed pouches performed less than one UC pouch annually. The outcomes following UC pouch surgery in NSW are comparable with global standards. Concentrating IBD pouch surgery with the aim of producing specialist surgical teams may be a reasonable way forward in NSW and would ensure equity of access and facilitate research and training collaboration.

Surgical Options for Appropriate Length of J-Pouch Construction for Better Outcomes and Long-term Quality of Life in Patients with Ulcerative Colitis after Ileal Pouch-Anal Anastomosis.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.

DOP70 Crohn’s Disease Like Inflammation of The Pouch is a Distinct Type of Pouchitis

Abstract Background Pouchitis occurs in up to 80% of patients with ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA). The pathogenesis of pouchitis is unclear, but is thought to involve a complex interaction between the microbiome and mucosal immune system. To examine the underlying pathophysiological mechanisms of pouchitis, the present study aims to simultaneously define immuno-histological and microbial parameters associated with different pouch phenotypes. Methods Endoscopic biopsies from the pre-pouch ileum (PI) and the pouch body (PB) were obtained from 51 subjects age>18 who underwent TPC with IPAA, n=48 for UC and n=3 for familial adenomatous polyposis (FAP). Mucosal mononuclear cells (MMC) were isolated from the intra-epithelial compartment (IEC) and lamina propria (LP) and examined for lymphoid, myeloid and innate immune subsets by multiparameter flow-cytometry (FC). Histological sections were examined by two pathologists, blinded to clinical identifiers and scored for inflammatory parameters that included neutrophilic activity, lymphoplasmacytic infiltration, eosinophilia, villous atrophy and submucosal fibrosis. Metagenomic sequencing of stool was performed and analyzed for microbial beta and alpha diversity. Results IPAA subjects were classified into the following phenotypes: normal pouch (NP) n=15 (29.4%), acute pouchitis (AP) n=9 (17.6%), chronic antibiotic dependent pouchitis (CADP) n=9 (17.6%), Crohn’s disease like pouch inflammation (CDLPI) n=15 (29.4%), and FAP NP n=3 (5.9%). Among subjects with NP, the PB had a higher frequency of naïve-CD4+ and CD8+ T cells, central memory- CD4+ T cells, and naïve B cells and a lower frequency of homeostatic IELs relative to the PI (Fig. 1A). Immune remodeling of the PB was further confirmed on histology that demonstrated increased lymphoid aggregates and decreased IELs. Subjects with CDLPI had significantly higher levels of inflammation, chronicity, and lymphoid aggregates but decreased IELs in the PI than NP or AP patients (Fig. 1B and 1C). In contrast to immune parameters, the composition of the microbiota in non-inflamed UC pouches was more similar to inflamed UC pouches than to FAP pouches. Alpha diversity and genus relative abundance differences between UC and FAP pouch stool samples were not statistically significant (Fig. 1D). Conclusion CDLPI represents a distinct entity of pouchitis that is associated with heightened levels of chronic inflammation relative to AP despite similarities in microbiota.

Risk Factors and Quality of Life in Patients with Diffuse Pouchitis After Ileal Pouch Anal Anastomosis According to the Chicago Classification for J Pouch: a Retrospective Multicenter Cohort Study in China

BackgroundPouchitis is a common late complication in patients with ulcerative colitis (UC) who undergo ileal pouch–anal anastomosis (IPAA). The heterogeneous nature of the clinical and endoscopic presentations could affect the evaluation of therapeutic interventions for pouchitis. Thus, identifying the risk factors and clinical outcomes of pouch inflammation at different sites and severity is becoming increasingly important for colorectal surgeons. MethodsData on patients who underwent IPAA January from 2008 to June 2022 in our three pouch centers affiliated with the China UC Pouch Center Union were retrospectively collected. Pouchitis was categorized as a different phenotype according to the Chicago Classification. J pouches were classified into short (14 ± 2 cm) and long pouches (22 ± 2 cm) according to the distribution of ileal pouch length in our institute. ResultsAltogether, 143 patients with a median follow-up time of 5.0 years (interquartile range: 2.0–8.0) were enrolled. Among them, 41 patients (28.7%) developed pouchitis and 32 patients (78%) had diffuse inflammation of the pouch. Patients with diffuse pouchitis had a higher pouchitis disease activity index and more seriously impaired improvement of long-term quality of life than those with pouch phenotypes. A short J pouch, recurrent UC, and preoperative high white blood cell count were independent risk factors for diffuse pouchitis. Furthermore, a short J pouch could effectively predict the occurrence of diffuse pouchitis with an area under the receiver-operating characteristic curve of 0.614, a sensitivity of 62.5%, and a specificity of 60.4% (p = 0.049) and significantly decreased the overall diffuse pouchitis-free survival compared to a long J pouch (p = 0.0002). ConclusionDiffuse pouchitis is a common phenotype of pouchitis that seriously impairs long-term prognosis. For colorectal surgeons, decision-making regarding pouch construction with an appropriate length should be considered to prevent the development of diffuse pouchitis. Graphical Abstract [Display omitted]

Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.

Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

Outcome of restorative proctocolectomy with an ileo-anal pouch for ulcerative colitis: effect of changes in clinical practice.

Surgery for ileal pouch-anal anastomosis (IPAA) has evolved over time, especially since the introduction of laparoscopy. The aim of this retrospective study was to report the impact of surgical evolution on outcome over a period of 25years. All patients who had IPAA surgery for ulcerative colitis from 1990 to 2015 at the University Hospitals of Leuven were included. Patients were divided into three period arms (period A 1990-1999; period B 2000-2009; period C 2010-2015). The main outcome measure was anastomotic leakage. A total of 335 patients (58.8% male) with a median age of 39years (interquartile range 32-49years) at surgery were included. Median follow-up was 5years (interquartile range 2-10years). Overall anastomotic leakage (grades A-C) was 14.9%. A significant decrease in leakage rate was observed over time (from 21.4% in period A to 12.1% in period B to 10.0% in period C; P=0.04). The defunctioning ileostomy rate at the time of pouch construction decreased from 91.7% (period A) to 40.3% (period B) to 11.1% (period C) (P<0.001). We observed an increase in the use of laparoscopy (23.9% in period A vs 72.6% in period B, vs 84.4% in period C; P=0.001) and a shift to a modified two-stage procedure (4.1% in period A, vs 66.7% in period C; P<0.0001). In a monocentric study with some of the data retrieved retrospectively it was not possible to account for the impact of preoperative nutritional status (weight loss, serum albumin level) or disease burden. Other outcome factors were not measured, for example sexual function and fecundity. A higher rate of laparoscopic IPAA surgery, together with a shift towards modified two-stage procedures, was associated with a lower leakage rate despite a reduction in the use of defunctioning ileostomy.

Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis.

Ulcerative colitis (UC) only involves the colonic mucosa. Yet, nearly 50% of patients with UC who undergo total proctocolectomy with ileal pouch anal anastomosis develop UC-like inflammation of the ileal pouch (pouchitis). By contrast, patients with familial adenomatous polyposis (FAP) with ileal pouch anal anastomosis develop pouchitis far less frequently. We hypothesized that pathogenic events associated with the development of UC are recapitulated by colonic-metaplastic transcriptomic reprogramming of the UC pouch. We prospectively sampled pouch and prepouch ileum mucosal biopsies in patients with UC with ileal pouch anal anastomosis 4, 8, and 12 months after their pouch was in continuity. Mucosal samples were also obtained from patients with FAP. Transcriptional profiles of the UC and FAP pouch and prepouch ileum were investigated via RNA sequencing and compared with data from a previously published microarray study. Unlike patients with FAP, subjects with UC exhibited a large set of differentially expressed genes between the pouch and prepouch ileum as early as 4 months after pouch functionalization. Functional pathway analysis of differentially expressed genes in the UC pouch revealed an enhanced state of immune/inflammatory response and extracellular matrix remodeling. Moreover, >70% of differentially expressed genes mapped to published inflammatory bowel diseases microarray data sets displayed directional changes consistent with active UC but not with Crohn's disease. The UC pouch, well before histologic inflammation, already displays a systems-level gain of colon-associated genes and loss of ileum-associated genes. Patients with UC exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease and may in part explain their susceptibility to the development of pouchitis.

P459 Obesity in patients with an ileoanal pouch due to ulcerative colitis is not associated with an increased risk for pouchitis

Background: Obesity is characterized by low grade inflammation in the visceral fat tissue (VFT) which may be a major causative factor in the development of insulin resistance (IR). A surrogate marker for IR is the ratio between triglycerides (TG) and high density lipoprotein (HDL). VFT wrapping the small bowel characterizes Crohn's disease (CD) and has been shown to produce proinflammatory cytokines. Patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) commonly develop pouchitis-de novo inflammation in a previously normal small bowel. We hypothesize that pouchitis may represent the small intestinal inflammation characterizing CD. We aimed to assess whether obesity affected intestinal inflammation in obese UC-pouch patients. Methods: Retrospective case control series in UC pouch patients recruited at a tertiary referral center. Clinical and biochemical indices were compared between obese (BMI≥30 kg/m2) and normal BMI (nBMI, 18.5–24.9 kg/m2) pouch patients, matched for age and gender. Nutritional trends were obtained from food frequency questionnaires (FFQs). Results: Thirty one patients (8.6% of pouch patients in our cohort, 20 females) were obese with a mean BMI of 33.9±4.5 kg/m2, pouch patients with nBMI - 22.9±2.6 kg/m2. Groups were comparable for smoking, disease duration, indication for surgery and pouch age. However, significantly lower rates of pouchitis were detected in the obese compared to nBMI group, 41% vs 79% (p=0.028) respectively. Obese patients had significant metabolic abnormalities: Glucose 103.5±39.9 vs. 83.8±10.7 mg/dl (p=0.028); HDL 47.9±14.2 vs 63.9±17.08 mg/dl (p=0.003); TG 190.33±124.8 vs 118.7±58.76 mg/dl (p=0.015), respectively. TG/HDL ratio was higher in the obese group 4.4±3.4 vs 2.1±1.4 (p=0.006 vs. nBMI). Sugared beverages consumption was significantly higher in the obese group (p<0.01 vs. nBMI). Conclusions: Pouchitis rates were surprisingly lower in obese UC-pouch compared to nBMI UC pouch patients. This may be due to dietary intake restriction in patients with pouchitis, potentially contributing to lower weight so obesity may prevail mainly in patients with a normal pouch, eating freely. An alternative explanation may be that in pouchitis metabolic expenditure is increased contributing to lower BMI. Obese UC-pouch patients are prone to metabolic abnormalities and IR. A high consumption of simple carbohydrates may impact TG levels and weight gain in these patients. Dietary treatment for IBD patients should target all nutritional aspects including metabolic abnormalities to improve health status and quality of life.

P210 The associations of optimism, social support, and coping strategies with health-related quality of life in a cohort of patients after proctocolectomy with ileal Pouch-anal anastomosis

Background: Inflammatory bowel diseases (IBD) are associated with reduced health-related quality of life (HRQoL). We aimed to identify factors that influence patients HRQoL by exploring the role of optimism, social support and coping strategies in contributing to patients' HRQoL. We focused on patients with ulcerative colitis (UC) after pouch surgery representing a distinct population which is followed up in a dedicated referral clinic. Methods: Patients were recruited at the Comprehensive Pouch Clinic and completed six questionnaires: demographics, HRQoL (IBDQ), dispositional optimism (revised Life Orientation Test, LOT-R), social support inventory (ENRICHD), Coping strategies (brief COPE), and illness acceptance (DDAQ). Pouch behavior was determined clinically and defined as normal pouch (NP) or pouchitis. Results: A total of 151 pouch patients were recruited: 75 (50%) females, average age 47.91±15.51 years, average age of UC diagnosis 27.11±13.53 years, mean time since pouch surgery 10.03±8.09 years. At the time of recruitment 48 (32%) had NP. Women had lower HRQoL than man (p=0.04), education level was correlated with HRQoL (r=0.27, p=0.001), age at diagnosis was negatively correlated to HRQoL (r=−0.19, p=0.02). Optimism was associated with higher HRQoL (R=0.40. p<0.001). Pessimism was associated to older age at diagnosis (r=0.23, p=0.01) and to lower education level (r=−0.20, p=0.02). Optimists and pessimists differed in the manner they cope with disease – optimists used more positive reframing and tended to find alternative meaningful activities, while pessimists tended to use self-blame, behavioral and mental disengagement. Furthermore, optimists reported better social support (r=0.29, p=0.00). Social support was also associated with higher HRQoL (R=0.40. p<0.001). Patients with pouchitis had lower HRQoL and social support (all p<0.01 compared to NP) but did not differ in the level of optimism. Predictors of HRQoL in the multivariate Hierarchical Regression analysis were gender (β=−0.12; p<0.05), educational level (β=0.22; p<0.001), social support (β=0.12; p<0.05) and coping strategies: behavioral disengagement (β=−0.19; p=0.05), mental disengagement (β=−0.22; p<0.001), activities engagement (β=0.29; p<0.001), and symptom tolerance (β=0.19; p=0.05). Conclusions: Factors affecting HRQoL levels in UC pouch patients are Gender, education level, age at disease diagnosis and pouch behavior. Dispositional optimism, social support and coping strategies play significant role in patients HRQoL.

Systematic Review of Cuff and Pouch Cancer in Patients with Ileal Pelvic Pouch for Ulcerative Colitis

Ileal pouch-anal anastomosis (IPAA) is the procedure of choice for refractory or complicated ulcerative colitis (UC). Since 1990, pouch-related adenocarcinomas have been described. The aim of this study was to review the literature to evaluate the burden of this complication, seeking for risk factors, prevention, and ideal management. We performed a systematic review of the literature to identify all described pouch-related adenocarcinoma in patients operated on with IPAA for UC. Studies were thoroughly evaluated to select authentic de novo pouch carcinomas. Some authors were contacted for additional information. Data of patients were pooled. Meta-analyses of suitable studies were attempted to identify risk factors. Thirty-four articles reported on 49 patients (2:1, male:female) who developed unequivocal pouch-related adenocarcinoma, 14 (28.6%) and 33 (67.3%) arising from the pouch and anorectal mucosa, respectively. Origin was not reported in 2 (4%). Pooled cumulative incidence of pouch-related adenocarcinoma was 0.33% (95% confidence interval [CI], 0.31-0.34) 50 years after the diagnosis and 0.35% (95% CI, 0.34-0.36) 20 years after IPAA. Primary pouch cancer incidence was below 0.02% 20 years after IPAA. Neoplasia on colectomy specimen was the strongest risk factor (odds ratio, 8.8; 95% CI, 4.61-16.80). Mucosectomy did not abolish the risk of subsequent cancer but avoiding it increased 8 times the risk of cancer arising from the residual anorectal mucosa (odds ratio, 8; 95% CI, 1.3-48.7; P = 0.02). Surveillance is currently performed yearly starting 10 years since diagnosis, but cancers escaping this pathway are reported. In patients receiving mucosectomy, a 5-year delay for surveillance could be proposed. Pouch-related adenocarcinomas are rare. Diagnosis of Crohn's disease in the long term may further decrease the rates in UC. Presumed evolution from dysplasia might offer a time window for cancer prevention. Abdominoperineal excision should be recommended for pouch-related adenocarcinomas.

Primary Diffuse Large B Cell Lymphoma Developing at the Ileocolonic Anastomosis Site after Right Hemicolectomy for Adenocarcinoma: A Case Report

Lymphoma is rarely associated with pouch surgery. To date, only five reports in the literature described lymphoma in an ileal pouch for ulcerative colitis (1-5) and only two papers reported about lymphoma in the anastomosis site for colonic adenocarcinoma which were anaplastic large cell lymphoma and T-cell lymphoma (6, 7). We report a very rare case of primary diffuse large B-cell lymphoma (DLBL) arising in an ileocolonic anastomosis site which was found five years after a right hemicolectomy for adenocarcinoma in the ascending colon.

Gene Expression Profiles of Ileal Inflammatory Bowel Disease Correlate with Disease Phenotype and Advance Understanding of Its Immunopathogenesis

Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD). Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools. Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis. Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.

Quality of life in patients with ileal pouch for ulcerative colitis

Introductionproctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical procedure for the treatment of ulcerative colitis (UC) and is associated with the prospect of cure. Experience gained over the years has demonstrated the occurrence of a high number of complications as well as bowel disorders that can compromise quality of life (QoL). Objectiveevaluate QoL in patients with IPAA for ulcerative colitis. Patients and methodsthe Inflammatory Bowel Disease Questionnaire (IBDQ) was used to assess QoL in patients with IPAA after its validation in Portuguese. Resultsthirty-one patients submitted to IPAA by the same group of professionals were evaluated. QoL was classified as regular in all domains evaluated (intestinal and systemic symptoms and emotional and social aspects). There were no differences in relation to gender, type of pouch or postoperative time. However, elderly patients showed a tendency toward lower scores. Having a professional activity was associated with higher scores in systemic symptoms and social aspects (p < 0.05). Patients with ileostomy showed lower values in the domains of systemic symptoms, emotional and social aspects (p <0.05). Conclusionin all domains assessed, patients with IPAA for UC had QoL classified as regular. Ileostomy and lack of professional activity negatively influenced QoL.

Carcinoid tumour complicating a restorative ileo‐anal pouch for ulcerative colitis

Carcinoid tumour complicating a restorative ileo‐anal pouch for ulcerative colitis

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC). In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs. Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression. The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.

Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation

Dimeric M2-pyruvate kinase (dM2-PK) is overexpressed in tumour cells with rapid cell turnover. Its concentrations correlate well with the staging and metastatic capability of the tumour cells. We investigated the use of faecal dM2-PK as a noninvasive marker of pouch inflammation (pouchitis) in patients having undergone restorative proctocolectomy. Stool samples were obtained from 46 patients with ulcerative colitis (UC) and eight with familial adenomatous polyposis. Pouchitis was defined using the objective pouchitis score (OPS) and the pouch disease activity index. Faecal dM2-PK was measured using a quantitative sandwich-type enzyme immunoassay (ScheBo Biotech UK) and the results compared with reciprocal faecal calprotectin concentrations. Using the OPS, 6 of the 46 patients with UC had pouchitis and prepouch ileitis, 13 had UC pouchitis alone, and 27 had a non-inflamed UC pouch. One patient with familial adenomatous polyposis had pouchitis and prepouch ileitis and 7 had an non inflamed pouch. Respective median dM2-PK values (U/ml) for these five groups were 49.5 (4.5-110), 12 (1-192.3), 2.2 (0.1-95.2), 19.5 and 1 (0.1-3). Statistically significant differences were noted between inflamed and non inflamed pouches (P<0.0001). dM2-PK correlated significantly with the OPS, pouch disease activity index, endoscopic appearances, acute histological and neutrophil scores (<0.0001). The receiver operating characteristic analysis demonstrated a sensitivity and specificity of 80 and 70.6%, respectively. dM2-PK and faecal calprotectin concentrations correlated closely (r=0.87, P<0.0001). This study demonstrates that faecal dM2-PK is a sensitive marker of pouch inflammation and that its concentration directly correlates with the objective markers of pouchitis severity.

Adenocarcinoma arising in a background of chronic atrophic pouchitis in an ileoanal pouch for ulcerative colitis

Adenocarcinoma arising in a background of chronic atrophic pouchitis in an ileoanal pouch for ulcerative colitis