Pouchitis Disease Activity Index Score Research Articles

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. This was a retrospective and multicentre study. We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

P910 Emerging role of IL-33/ST2 and Gut Microbiota axis in the inflammatory process of ulcerative colitis patients with ileal pouch-anal anastomosis

Abstract Background IL-33/ST2 axis and gut microbiota are important factors in the pathogenesis of IBD with a potential reciprocal influence. IL-33/ST2 axis controls the mucosal healing process during intestinal inflammation. Pouchitis, after restorative proctocolectomy with ileal pouch-anal anastomosis, is the most common complication. We aimed to explore the potential correlation between mucosal cytokines and gut microbiota in the inflammatory process of pouchitis. Methods 23 patients with ileal pouch-anal anastomosis were enrolled. 13 showed pouchitis and 10 a normal pouch. Mucosal samples were collected from the afferent ileal loop and from the pouch. Multiplex analysis for cytokines was performed. ELISA, western blot and IHC were run to assess IL-33/ST2 axis. Microbiota was analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. Pouchitis Disease Activity Index and Pouchitis Histological Score were calculated. Multivariate analyses were run to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches. Results IL-1Ra, IL-6, IL-8, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b were increased in the inflamed pouch vs. normal pouch. No differences were registered in samples from the afferent ileal loop. In pouchitis, IL-7 resulted reduced in the inflamed pouch vs. the ileal loop. In normal pouch, no differences were recorded. In pouchitis, IL-33 and ST2 protein levels were significantly reduced in the pouch vs. the ileal loop and resulted decreased vs. normal pouch. Full-length, bioactive IL33, ST2L and sST2 were expressed in all experimental groups; the cleaved, less active form of IL33 was increased only in pouchitis. IL-33 and ST2 stainings were less intense within the inflamed and ulcerated mucosa of pouchitis compared to the normal pouch and in close proximity to areas of re-epithelialization. Microbiota analysis showed a decreased biodiversity in pouchitis vs. normal pouch (both at pouch and ileal loop level). Lower levels of Verrucomicrobia and increased abundance of Actinobacteria were recorded in inflamed pouch vs normal pouch. In pouchitis, the ileal loop and the pouch showed decreased levels of Akkermansia muciniphila and augmented abundance of Collinsella vs. samples from the normal pouch. In pouchitis, multivariate analyses evidenced a significant inverse correlation between Collinsella e Collinsella aereofaciens abundance and ST2 levels. Conclusion Pouchitis and normal pouch are characterized by divergent inflammatory molecular pathways and microbial populations with a specific pattern between the pouch and afferent ileal loop. Our results suggest a potential role for IL-33/ST2 and gut microbiota axis in driving the gut mucosal wound healing in patients with ileal pouch-anal anastomosis.

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

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

Safety and Efficacy of Fecal Microbiota Transplant in Chronic 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. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of fecal microbiota transplant (FMT) in chronic antibiotic dependent and refractory pouchitis. Multiple databases were searched through April 2022 for studies that reported the efficacy and safety of FMT in patients with chronic pouchitis. Meta-analysis using random effects model was performed to calculate pooled rates. Eight studies with a total of 89 patients were included in our review, with 74 patients having received FMT and 15 patients having received placebo. The mean age ranged from 32.6 to 51.5 years. In patients that received FMT, the pooled rates of overall remission was (Pouchitis Disease Activity Index score < 7) 22% (95% CI, 9%-43%; I2, 29%), clinical remission was 20% (95% CI, 6%-49%; I2, 25%), clinical response rate was 42% (95% CI, 30%-54%; I2, 7%), and the relapse rate 60% (95% CI, 40%-77%, I2 16%) over the mean follow up of 4.67 months (range 1-12 months). The pooled proportion of patients with adverse events was 54% (95% CI, 21%-84%; I2, 73%). There were no serious adverse events or deaths. In patients with chronic pouchitis, FMT is safe though there are mixed results in terms of its long-term efficacy. Future Randomized Controlled Trials with larger sample sizes and greater standardization in terms of preparation, delivery, and length of treatment of FMT are needed to determine efficacy.

Associations between Pouchitis and Fecal Calprotectin after Restorative Proctocolectomy in Patients with Ulcerative Colitis

Introduction: Recently, fecal calprotectin has been identified and used as an assessment tool for the confirmation of disease activity in ulcerative colitis. Although a meta-analysis suggested the usefulness of fecal calprotectin for the assessment of pouchitis, the number of participants was still insufficient. Therefore, we prospectively measured fecal calprotectin levels during pouchoscopy and analyzed their associations with pouchitis. Methods: Patients who underwent pouchoscopy after total proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis were included. Fecal samples were collected for the measurement of calprotectin during pouchoscopy. Patients either with or without suspicious pouchitis were included. Pouchitis was defined as a modified pouchitis disease activity index (m-PDAI) score of ≥5. The associations between the development of pouchitis and the m-PDAI score and fecal calprotectin and serum markers, including C-related protein, albumin, and white blood cells, were assessed. Results: A total of 170 patients were included. Seventy-two patients were diagnosed with pouchitis with an m-PDAI score of 7.3 ± 1.5. The values of fecal calprotectin were 1,500 ± 1,544 μg/g in patients with pouchitis and 259 ± 402 μg/g in patients without pouchitis (p < 0.01). The correlation coefficient between calprotectin and the m-PDAI score was significant (r² = 0.279, p < 0.001). The cutoff value of fecal calprotectin in receiver operating characteristic analysis was 246 μg/g (area under curve 0.85, sensitivity 83.9%, specificity 71.0%). Fecal samples were able to be collected from 6 patients. The levels of fecal calprotectin significantly decreased from 2,101.3 ± 880.3 μg/g to 284.2 ± 96.9 μg/g in response to the treatment. Conclusions: Elevated fecal calprotectin appeared to be significantly correlated with pouchitis. We should consider the alteration of this marker during treatments in further studies.

P412 Drug persistence and endoscopic, histologic and biochemical remission rates among patients following ileal pouch-anal anastomosis treated with biologic therapy: Results from a prospective patient cohort

Abstract Background Patients with ulcerative colitis (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) may develop chronic pouchitis or Crohn’s like disease of the pouch (CLDP). These patients may need treatment with biologic therapies. Data regarding treatment persistence as well as clinical, biochemical, endoscopic, and histologic remission rates are lacking Methods Patients after IPAA were followed prospectively at a dedicated pouch clinic. Patients with CP or CLDP who were antibiotic/steroid-refractory or dependent, had antibiotics/steroids side effects or had extraintestinal manifestations were treated with biologics. Clinical, endoscopic, histologic, and laboratory data were extracted from medical records at the last follow-up. Patient’s quality of life (QoL) was assessed by visual analog scale (VAS), with scores of, 0–100 (higher=better QoL). Time to biologic therapy discontinuation was measured for all patients; patients were censored if still on biologic therapy at the time of the last follow-up. Biochemical remission was defined as C-reactive protein (CRP)&amp;lt;, 0.5 mg/dl and a fecal calprotectin (FC)&amp;lt;, 150 ug/dl with a normal albumin level. Endoscopic and histologic remission was defined by the pouchitis disease activity index (PDAI) as an endoscopic subscore ≤2 and a histologic subscore, 0 or, 1, respectively. Results The prospective cohort constituted, 130 patients. Females:, 73 (56%). Before IPAA, most (70%) patients had pancolitis, 95% received steroids and mesalamine, and, 37% - biologic therapies. Median follow-up after ileostomy closure:, 16 years. Biologic therapy was started in, 28 patients (22%) due to CP or CLDP. The first line biologic for all, 28 patients was anti-TNF’s and, 9 patients received more than one line of biologics. Median time to commencing biologics:, 130 months. Median first-line biologic drug persistence:, 222 weeks. Among patients treated with biologic therapy, at the last clinic visit, median CRP was, 0.58 mg/dl, median FC:, 255ug/g, median HB:, 12.46 mg/dl, and median albumin was, 4.5 mg/dl.Median PDAI endoscopic and histologic scores were, 2; median VAS rating was, 80. Biologic remission criteria were fulfilled by, 43% of patients (N-12). An additional, 43% (N-12) were also in endoscopic remission with an endoscopic PDAI subscore of, 2 or below, and an additional, 29% of patients (N-8) were in histologic remission with a histologic PDAI score of, 0 or 1. Conclusion Biologics reintroduction after IPAA was relatively common, albeit after a very long interval. Biologic therapy was effective, with a sizable proportion of patients in biochemical, endoscopic, and histologic remission. Likewise, drug persistence was long. We suggest that early initiation of biologic therapy in certain patients may be prudent.

Management of pouch related symptoms in patients who underwent ileal pouch anal anastomosis surgery for adenomatous polyposis.

BACKGROUNDAdenomatous polyposis syndromes (APS) patients with ileal pouch anal anastomosis (IPAA) suffer frequent symptoms with scarce signs of inflammation, distinct from ulcerative colitis patients. While the management of pouchitis in ulcerative colitis patients is well established, data regarding response to treatment modalities targeting pouch-related disorders in APS patient population is scarce.AIMTo assess clinical, endoscopic and histologic response to various treatment modalities employed in the therapy of pouch related disorders. METHODSAPS patients who underwent IPAA between 1987-2019 were followed every 6-12 mo and pouch-related symptoms were recorded at every visit. Lower endoscopy was performed annually, recording features of the pouch, cuff and terminal ileum. A dedicated gastrointestinal pathologist reviewed biopsies for signs and severity of inflammation. At current study, files were retrospectively reviewed for initiation and response to various treatment modalities between 2015-2019. Therapies included dietary modifications, probiotics, loperamide, antibiotics, bismuth subsalicylate, mebeverine hydrochloride, 5-aminosalicylic acid compounds and topical rectal steroids. Symptoms and endoscopic and histologic signs of inflammation before and after treatment were assessed. Pouchitis disease activity index (PDAI) and its subscores was calculated. Change of variables before and after therapy was assessed using Wilcoxon signed rank test for continuous variables and using McNemar's test for categorical variables.RESULTSThirty-three APS patients after IPAA were identified. Before treatment, 16 patients (48.4%) suffered from abdominal pain and 3 (9.1%) from bloody stools. Mean number of daily bowel movement was 10.3. Only 4 patients (12.1%) had a PDAI ≥ 7. Mean baseline PDAI was 2.5 ± 2.3. Overall, intervention was associated with symptomatic relief, mainly decreasing abdominal pain (from 48.4% to 27.2% of patients, P = 0.016). Daily bowel movements decreased from a mean of 10.3 to 9.3 (P = 0.003). Mean overall and clinical PDAI scores decreased from 2.58 to 1.94 (P = 0.016) and from 1.3 to 0.87 (P = 0.004), respectively. Analyzing each treatment modality separately, we observed that dietary modifications decreased abdominal pain (from 41.9% of patients to 19.35%, P = 0.016), daily bowel movements (from 10.5 to 9.3, P = 0.003), overall PDAI (from 2.46 to 2.03, P = 0.04) and clinical PDAI (1.33 to 0.86, P = 0.004). Probiotics effectively decreased daily bowel movements (from 10.2 to 8.8, P = 0.007), overall and clinical PDAI (from 2.9 to 2.1 and from 1.38 to 0.8, P = 0.032 and 0.01, respectively). While other therapies had minimal or no effects. No significant changes in endoscopic or histologic scores were seen with any therapy.CONCLUSIONAPS patients benefit from dietary modifications and probiotics that improve their pouch-related symptoms but respond minimally to anti-inflammatory and antibiotic treatments. These results suggest a functional rather than inflammatory disorder.

Appendiceal inflammation in colectomy is independently correlated with early pouchitis following ileal pouch anal anastomosis in ulcerative colitis and indeterminate colitis

BackgroundAppendiceal inflammation in colectomy is one of the histologic predictors of pouchitis in ulcerative colitis (UC) following ileal pouch anal anastomosis (IPAA). Fecal calprotectin level has been shown to increase 2 months prior to the onset of pouchitis. We evaluated whether inflammation and calprotectin expression in appendiceal specimens correlate with early-onset pouchitis in UC and indeterminate colitis (IC). Materials and methodsIPAA (2000-2018) cases with appendix blocks available in colectomy specimens were identified (n = 93, 90 UC, 3 IC). Histologic features thought to predict pouchitis were evaluated. The degree of appendiceal inflammation was scored. Calprotectin immunostain was performed on the appendix blocks and the extent of mucosal staining was quantified. Electronic medical records were reviewed for demographics, smoking history, clinical pouchitis, time of onset of pouchitis, and clinical and endoscopic components of the Pouchitis Disease Activity Index (PDAI) score. Follow-up pouch biopsies were reviewed and scored to generate histologic PDAI score, when available. ResultsAmong the patients with clinical pouchitis (n = 73), moderate to severe appendiceal inflammation independently correlated with earlier pouchitis compared to no/mild inflammation (median time to pouchitis 12.0 vs. 23.8, log rank p = 0.016). Calprotectin staining correlated with inflammatory scores of the appendix (Spearman's rho, r = 0.630, p < 0.001) but not with early pouchitis (p > 0.05). ConclusionsThe presence of moderate to severe appendiceal inflammation at the time of colectomy was associated with a shorter time to pouchitis following IPAA. Calprotectin immunostain may be used to demonstrate the presence of inflammation in the appendix but its role in predicting early pouchitis remains limited.

Clinical Discrimination of Chronic Pouchitis After Ileal Pouch-Anal Anastomosis in Patients with Ulcerative Colitis

PurposeWe aimed to identify predictive factors for the development of chronic pouchitis after ileal pouch-anal anastomosis in patients with ulcerative colitis. MethodsThree hundred eighty-seven patients who underwent ileal pouch-anal anastomosis for diagnosis of ulcerative colitis from January 2002 to March 2019 were included in this retrospective analysis. ResultsOf 115 patients with pouchitis, 40 patients exhibited acute pouchitis, and 75 patients exhibited chronic pouchitis. Of 75 patients with chronic pouchitis, 11 patients were diagnosed with chronic antibiotic-refractory pouchitis. Multivariate analysis revealed that early pouchitis onset and modified Pouchitis Disease Activity Index score ≥ 7 were independent predictive factors for chronic pouchitis (p = 0.0004 and p = 0.029, respectively). Mean onset of pouchitis after intestinal continuity was significantly earlier in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 3.72±2.98 years vs. 1.85±2.40 years, p < 0.0001). Total modified Pouchitis Disease Activity Index score was significantly higher in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 5.9±1.2 vs. 6.9 ± 1.6, p = 0.0020). ConclusionPatients with ulcerative colitis were more likely to develop chronic pouchitis if they exhibited early onset or severe disease activity at onset. Evaluation of both factors can aid in early treatment decisions to alleviate chronic pouchitis.

Non-invasive Monitoring of Pouchitis After Total Proctocolectomy Using Fecal Calprotectin Levels.

Fecal calprotectin (FC) is the most widely used marker for evaluating the disease activity of ulcerative colitis (UC). However, studies on FC in pouchitis after total proctocolectomy are scarce. We aimed to examine the correlations between the FC level and clinical findings and Pouchitis Disease Activity Index (PDAI) in UC patients who underwent total proctocolectomy (TP) with ileal pouch-anal canal anastomosis (IPAA) or ileal pouch-anal canal anastomosis (IACA). Between April 2008 and March 2018, 15 patients, consisting of 8 males and 7 females, with an average age at operation of 46.5 years, participated in this study. The average observation period was 68.3 months. The subjects underwent FC level measurements and endoscopic examinations. The mean FC level was 418.69 μg/g (range: 10-1650 μg/g). Pouchitis was found in one (6.6%) patient, as detected by endoscopy. Among the 15 cases, FC levels were positively correlated with white blood cell count as well as albumin and C-reactive protein levels. There was a significant positive correlation between the PDAI score and FC levels (p<0.05). The median FC level was 111 mg/g in those with pouchitis, which was significantly higher than the 16 mg/g in those without pouchitis (p<0.05). Moreover, a significant positive correlation was found between the endoscopic findings of inflammation and FC levels (p<0.00005). FC levels were correlated with the PDAI score, blood testing data, and endoscopic findings, suggesting that the FC level could be a useful index of postoperative pouchitis and ileal pouch condition in patients undergoing TP with IPAA as UC treatment.

Hyperbaric Oxygen Therapy in Chronic Inflammatory Conditions of the Pouch.

Pouchitis can be a chronic complication of ileal pouch-anal anastomosis. We aimed to determine the efficacy and safety of hyperbaric oxygen therapy (HBOT) for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. This was a retrospective case series of adults with inflammatory bowel disease (IBD) who underwent ileal pouch-anal anastomosis and then developed CARP and received HBOT between January 2015 and October 2019. A modified Pouchitis Disease Activity Index (mPDAI) score was used to quantify subjective symptoms (0-6) and endoscopic findings (0-6) before and after HBOT. A total of 46 patients were included, with 23 (50.0%) being males with a mean age of 43.6 ± 12.9 years. The median number of HBOT sessions was 30 (range 10-60). There was a significant reduction in the mean mPDAI symptom subscore from 3.19 to 1.91 after HBOT (P < 0.05). The pre- and post-HBOT mean mPDAI endoscopy subscores for the afferent limb were 2.31 ± 1.84 and 0.85 ± 1.28 (P = 0.006); for the pouch body, 2.34 ± 1.37 and 1.29 ± 1.38 (P < 0.001); and for the cuff, 1.93 ± 1.11 and 0.63 ± 1.12 (P < 0.001), respectively. Transient side effects included ear barotrauma in 5 patients (10.9%) and hyperbaric myopic vision changes in 5 patients (10.9%). Despite minor adverse events, HBOT was well tolerated in patients with CARP and significantly improved symptoms and endoscopic parameters.

Endoscopic activity in asymptomatic patients with an ileal pouch is associated with an increased risk of pouchitis.

The significance of endoscopic activity in asymptomatic ulcerative colitis (UC) patients with an ileal pouch is unknown. To investigate the association of endoscopic pouch activity in asymptomatic patients with the subsequent development of pouchitis. We analyzed a retrospective cohort of patients with UC or IBD-unspecified who underwent a total proctocolectomy with ileal pouch anal anastomosis (IPAA). Asymptomatic patients with a Pouchitis Disease Activity Index (PDAI) symptom sub-score of zero who underwent an index surveillance pouchoscopy were included. Endoscopic pouch body activity was graded as 0: normal, 1: mucosal inflammation, or 2: mucosal breaks (ulcers and/or erosions). The primary outcome was primary acute idiopathic pouchitis defined as PDAI score≥7 with symptoms lasting less than four weeks and responsive to standard antibiotics, not otherwise meeting criteria for secondary pouchitis. The secondary outcome was chronic idiopathic pouchitis defined as PDAI score≥7 with symptoms lasting greater than four weeks despite standard antibiotics. Predictors of pouchitis were analyzed using Kaplan-Meier and Cox regression methods with hazard ratios (HR) and 95% confidence intervals (CI) reported. 143 asymptomatic pouch patients were included. Index endoscopic pouch body activity was 0 in 86 (60.1%) patients, 1 in 26 (18.2%) and 2 in 31 (21.7%). The median length of follow-up after index surveillance pouchoscopy was 3.03 [IQR 1.24-4.60] years. Primary acute idiopathic pouchitis occurred in 44 (31%) patients and chronic idiopathic pouchitis in 12 (8.4%). Grade 2 endoscopic pouch activity was associated with the development of acute pouchitis (HR 2.39, 95% CI 1.23-4.67), although not chronic pouchitis (HR 1.76, 95% CI 0.53-5.87). Histologic inflammation in endoscopically normal pouch mucosa was not associated with acute or chronic pouchitis. Mucosal breaks are present in nearly a quarter of asymptomatic patients with IPAA and are associated with an increased risk of acute pouchitis.

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis. A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing. Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance. A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

Mesalamine Suppository Treatment in Crohnʼs Disease of the Pouch

Introduction: Mesalamine suppository is used to treat mild or moderate active left-sided colitis, pancolitis, or extensive colitis. However, there are no published data on its efficacy and safety in Crohn's disease (CD) of the pouch. Aim of this study was to evaluate the efficacy and safety of mesalamine suppository in patients with CD of the pouch. Methods: This case series included all patients with CD of the pouch from our prospectively maintained, IRB-approved Pouchitis Registry from 2007 to 2017. All patients were either actively taking mesalamine suppository or had used it in the past. Disease activity in pouch patients can be monitored using the modified Pouchitis Disease Activity Index (mPDAI) scores, consisting of symptom and endoscopy subscores. Pre- and post- treatment (minimum 6 months) pouchoscopy and clinical visits were used to calculate mPDAI symptom (range 0 - 6) and endoscopy (range 0 - 6) subscores. Analysis was performed using the paired nonparametric test, SPSS 22.0. Results: A total of 8 patients were included in this study, who underwent restorative proctocolectomy with ileal pouch anal anastomosis due to medical refractory ulcerative colitis (UC). The mean age at the time of pre-colectomy diagnosis of UC was 25.0±11.5 years. The mean current age was 46.1 ±15.3 years, with 4 (50.0%) being females, 1(12.5%) having smoked and 6 (75.0%) having used anti-tumor necrosis factor agents prior to mesalamine suppository use. The mean duration of mesalamine suppository use was 7.9±3.7 months. Patients on mesalamine suppository noted to have statistically significant lower mPDAI symptom subscores post treatment using univariate analysis (6.38±1.40 and 2.60±0.70, P = 0.011). Numerical improvement in endoscopy subscores was also noted with mesalamine suppository use. The pre- and post- treatment mean endoscopy subscores were 0.77±1.72 and 0.50±1.07 in the afferent limb (P =0.180); 1.56±1.94 and 1.13±1.80 (P =0.279) in the pouch body; and 2.00±1.87 and 1.75±1.98 (P =0.157) in the cuff, respectively. None of the patients experienced side effects throughout the therapy. Demographic and clinical data are depicted in Table 1. Treatment outcomes are demonstrated in Figure 1. Pouchoscopy images before (A) and after (B) mesalamine suppository therapy are shown in Figure 2.2815_A Figure 1. mPDAI symptom sub scores for 8 patients before & after Mesalamine suppository.2815_B Figure 2. Pouchoscopy before (A) and after (B) mesalamine suppository therapyConclusion: Our study suggests that Mesalamine suppository appears to be effective and safe in treating CD of the pouch.2815_C Figure 3. Demographic and Clinical Characteristics in patients with Crohn's Disease (CD) of the Pouch.

MRI defecography of the ileal pouch-anal anastomosis-contributes little to the understanding of functional outcome.

Variability in functional outcome after ileal pouch-anal anastomosis (IPAA) is to a large extent unexplained. The aim of this study was to use MRI to evaluate the morphology, emptying pattern and other pathology that may explain differences in functional outcome between well-functioning and poorly functioning pouch patients. A secondary aim was to establish a reference of normal MRI findings in pelvic pouch patients. From a previous study, the best and worst functioning patients undergoing IPAA surgery between 2000 and 2013 had been identified and examined with manovolumetric tests (N = 47). The patients were invited to do a pelvic MRI investigating pouch morphology and emptying patterns, followed by a pouch endoscopy. Forty-three patients underwent MRI examination. We found no significant morphological or dynamic differences between the well-functioning and poorly functioning pouch patients. There was no correlation between urge volume and the volume of the bony pelvis, and no correlation between emptying difficulties or leakage and dynamic MRI findings. Morphological MRI signs of inflammation were present in the majority of patients and were not correlated to histological signs of inflammation. Of the radiological signs of inflammation, only pouch wall thickness correlated to endoscopic pouchitis disease activity index scores. It seems MRI does not increase the understanding of factors contributing to functional outcome after ileal pouch-anal anastomosis. Unless there is a clinical suspicion of perianal/peripouch disease or pelvic sepsis, MRI does not add value as a diagnostic tool for pelvic pouch patients. Endoscopy remains the golden standard for diagnosing pouch inflammation.

The Use of Oral Herbal Medicine (Hange-Shashin-To) in Patients with Pouchitis: A Pilot Study.

Objectives: Hange-Shashin-To (HST), which is a combination of seven herbs, has previously been used in the treatment of inflammatory or ulcerative gut disease. The aim of this study was to evaluate the safety and efficacy of HST for the treatment of chronic pouchitis. Methods: Nineteen patients with chronic pouchitis, defined as either frequent episodes (≥ three episodes per six months) of pouchitis or persistent symptoms that required continuous antibiotic therapies, were selected and treated with ciprofloxacin (CPFX) 600 mg/day for 2 weeks (week 0~2) and HST 3,750 mg/day for 32 weeks (week 0~32). The Pouchitis Disease Activity Index (PDAI) score was measured at week 0 and 6 for short-term evaluation. For long-term evaluation, total CPFX dose in the 26-week period prior to study entry (from 30 weeks before study entry to 5 weeks before study entry) was compared with the total CPFX dose during the 26-week study period (week 7~32). Although no concomitant administration of CPFX was permitted from week 2-6, patients whose condition deteriorated were prescribed CPFX from week 7 to week 32. Results: Fourteen patients completed this 32-week study. The PDAI scores of eight patients decreased below seven. The mean total PDAI scores decreased significantly from 11 ± 2.5 to 6.5 ± 2.5 (P < 0.001). The mean value of total CPFX dose decreased significantly from 491.6 ± 182.4 mg/kg to 392.5 ± 184.0 mg/kg (P < 0.05). No severe adverse events were noted. Conclusions: Our data suggest that HST has a positive effect on chronic pouchitis with no adverse effects.

Efficacy of granulocyte and monocyte apheresis for antibiotic-refractory pouchitis after proctocolectomy for ulcerative colitis: an open-label, prospective, multicentre study.

Background:Granulocyte and monocyte apheresis (GMA) has shown therapeutic efficacy in active ulcerative colitis (UC). We thought that in patients with pouchitis after proctocolectomy for UC, GMA might produce immunological effects in the intestinal mucosa, and improve clinical symptoms. This prospective study was to evaluate the efficacy of GMA for antibiotic-refractory pouchitis after proctocolectomy for UC.Methods:A total of 13 patients with pouchitis disease activity index (PDAI) > 7 unresponsive to 2 weeks of antibiotic therapy were included. All patients received 10 GMA sessions at 2 sessions/week over 5 consecutive weeks. The primary endpoints were response (a decrease of ⩾3 points in the PDAI) and remission (PDAI < 4). Secondary endpoints included reduction of white blood cells (WBCs), C-reactive protein (CRP), faecal markers (calprotectin and lactoferrin), reduction of the PDAI endoscopic subscore, and GMA safety.Results:The median PDAI score was significantly decreased from 11 (range, 9–15) at entry to 9 (range, 6–13) after the GMA therapy (p = 0.02). A total of six patients (46%) responded to the treatment, but none achieved remission. The median endoscopic subscore (maximum: 6) was 5 (range, 4–6) at entry and 5 (range, 1–6) after the treatment (p = 0.10). None of the laboratory markers (WBCs, CRP, faecal calprotectin and lactoferrin) significantly changed during the treatment. Transient adverse events (AEs) were observed in two patients (15%), dyspnoea in one and headache in one. The AEs were not serious, and all patients completed the 10 GMA sessions.Conclusions:GMA has a good safety profile, but its efficacy appears to be limited in the management of chronic refractory pouchitis. However, a large controlled study should be conducted to evaluate the efficacy of GMA therapy in patients with pouchitis at an earlier clinical stage, before the disease has become refractory to conventional medical therapy.

Consecutive Monitoring of Fecal Calprotectin and Lactoferrin for the Early Diagnosis and Prediction of Pouchitis after Restorative Proctocolectomy for Ulcerative Colitis.

This prospective study was conducted to evaluate the significance of consecutive monitoring of fecal calprotectin and lactoferrin for the early diagnosis and prediction of pouchitis after restorative proctocolectomy for ulcerative colitis (UC). Sixty patients who had ileostomy closure following total proctocolectomy and ileal pouch-anal anastomosis for UC were included. Stool samples were collected for the measurement of calprotectin and lactoferrin every 2 months up to 12 months after the ileostomy closure. When patients had symptoms suggestive of pouchitis, endoscopic examination was immediately undertaken. All asymptomatic patients underwent endoscopy at 12 months. Pouchitis was defined as a pouchitis disease activity index score of ≥7. During the 12 months, 10 patients (17%) developed pouchitis. In patients with pouchitis, fecal calprotectin and lactoferrin levels were elevated already 2 months before the diagnosis of pouchitis. In contrast, these fecal biomarkers remained at low levels, and they did not change significantly in patients without pouchitis. A cutoff value of 56 μg/g for calprotectin had a sensitivity of 100% and a specificity of 84% to predict pouchitis, whereas a cutoff value of 50 μg/g for lactoferrin had a sensitivity of 90% and a specificity of 86%. At the time of endoscopy, the median calprotectin and lactoferrin levels were significantly higher in patients with pouchitis than those without pouchitis. Elevated fecal calprotectin and lactoferrin levels appeared to be significant predictors of pouchitis after restorative proctocolectomy for UC. Consecutive monitoring of these fecal biomarkers is useful for the early diagnosis of pouchitis.

P-036 YI Clinical and Serological Factors Associated With Response to Infliximab in Chronic Refractory Pouchitis and Pouch Complications

Pouchitis refractory to first-line therapies and pouch complications remains problematic following colectomy and ileal-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). Evidence for infliximab (IFX) use in this setting and factors predicting its success remain limited. Here, we investigated IFX use in refractory pouchitis and clinical and serological variables associated with treatment response. Patients were identified from the Mount Sinai Hospital IBD and Pelvic Pouch Databases, Toronto, Canada. Clinical, endoscopic and serological data were reviewed from 579 individuals who underwent colectomy and IPAA from 2000 to 2014. Patients with chronic refractory pouchitis and Crohn’s Disease- like outcome treated with IFX were included. Pretreatment parameters were measured within 4 weeks of induction and IFX response at a median of 9 (initial) and 48 weeks (sustained) respectively. Complete response was defined as symptomatic and endoscopic resolution with modified Pouchitis Disease Activity Index (mPDAI) score <5. Partial response was defined as improvement in symptoms with reduction in mPDAI >2. Endoscopic mucosal healing, pouch excision, pouch complications and CRP were recorded. Serum was analyzed for antibodies against Saccharomyces cerevisiae (ASCA), OmpC, CBir1 and perinuclear neutrophil cytoplasm (pANCA). Fisher’s exact testing and Kruskal-Wallis detected differences in clinical and serological variables between subgroups. Logistic regression models were applied to estimate odds ratio (OR) and 95% confidence interval (CI) of clinical and serological factors with initial and sustained clinical response as dependent variables. Results were deemed significant if P-value was ≤0.05. Thirty-one patients were included (33% male; age 32.6 ± 2.6 [mean ± SE]). 26% were on combined therapy with immune-modulator. Seventy-four present achieved post-induction response at median 9 weeks (IQR [6.5–13]) (48% complete, with concomitant mucosal healing). At median 48 weeks (IQR [25–71.5]), 62.6% retained response (29.6% complete). There were significant reductions in mPDAI in the entire cohort from a pre-induction score of 8.5 ± 0.3 to 2 ± 3.4 at final follow-up (mean, SE; P < 0.002) and in CRP from 29.48 ± 6.2 mg/L to 5.76 ± 1.6 mg/L (P < 0.001). Age, gender, smoking, pre-pouch disease extent and CRP did not affect response to IFX. Pretreatment mPDAI score did not significantly affect sustained IFX response but higher pretreatment mPDAI scores were negatively associated with early mucosal healing (P = 0.056; OR = 0.5, 95% CI, [0.2–1.010]). Patients with pretreatment mPDAI >10 were less likely to have initial mucosal healing (P = 0.03). Initial mucosal healing was associated with sustained complete response (P < 0.05; [OR] = 13.2; 95% confidence interval [CI], 1.0–165). Presence of ASCA was associated with higher initial mPDAI (P = 0.016), but no difference in treatment response. IFX responders had a lower number of positive antibody titers (2 positive titers versus 3, mean; P < 0.05). Having >2 positive titers was associated with longer term non-response to IFX though not significantly. IFX was effective in the short- and longer term in patients with chronic refractory pouchitis and pouch complications. Mucosal healing after induction is the strongest clinical association with a complete sustained response to IFX in this group and pretreatment mPDAI may help predict this.

Oral beclomethasone dipropionate in chronic refractory pouchitis

BackgroundPouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AimTo evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. MethodsTen consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10mg⁄day for 8weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). ResultsEight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8–14) and 3 (range 2–9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77–175) to 175 (range 85–220) (p<0.001). ConclusionEight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.