Biological therapy for the treatment of prepouch ileitis: a retrospective observational study from three centers.

AIM: Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity has been poorly studied, but it is generally treated concurrently with pouchitis. This to our knowledge is the largest study to explore the efficacy of biologics for the specific treatment of PPI. METHODS: This was a retrospective observational study reporting outcomes following biological treatment in patients with PPI across three centers. Data were collected between January 2004 and February 2018 from two centers in the UK and one center in Italy. Outcomes included the continued presence of PPI following biologic therapy, pouch failure defined by the need for an ileostomy, and remission of PPI defined by the absence of any prepouch inflammation on endoscopic assessment within a year of biologic therapy. RESULTS: There were 29 patients in our cohort. On last endoscopic follow-up, 20/29 still had endoscopic evidence of PPI, seven had achieved endoscopic remission and avoided an ileostomy, and two had no endoscopic follow-up. In our cohort 11 patients had an ileostomy after a median time from starting a biologic of 25 months (range 14-91). CONCLUSION: Biologics fail to induce endoscopic remission of PPI in the majority of patients. Just under one-third patients with PPI coexistent with pouchitis can achieve endoscopic remission with biologics. In a large proportion of patients with PPI, surgery may be required despite biologic use.

Long term outcomes of initial infliximab therapy for inflammatory pouch pathology: a multi-Centre retrospective study.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases, pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn's-like inflammation is based on studies that include relatively small numbers of patients. METHODS: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab (IFX) for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of IFX failure defined by early failure to IFX or secondary loss of response to IFX. RESULTS: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 3/34 (8%) had early failure and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of 366 days (1-130 months). CONCLUSIONS: Initial IFX therapy for pouch inflammatory conditions is associated with IFX failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three-quarters of patients at four years by using other medical therapies.

Incidence and Long-term Implications of Prepouch Ileitis: An Observational Study.

BACKGROUND: Restorative proctocolectomy is the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Prepouch ileitis is characterized by mucosal inflammation immediately proximal to the pouch. Prepouch ileitis is uncommon, and long-term follow-up data are lacking. OBJECTIVE: The aim of this study is to report the long-term outcomes of prepouch ileitis. DESIGN: We followed up a cohort of patients with prepouch ileitis that was originally described in 2009. Patients were followed up until the last recorded clinic attendance or at the point of pouch failure. Follow-up data collected included stool frequency, endoscopic findings, treatment, and overall pouch function. SETTING: We accessed a prospectively maintained database at our institution between January 2009 and January 2017. PATIENTS: Three of the 34 patients originally described in 2009 were lost to follow-up; we reanalyzed data on the remaining 31. MAIN OUTCOME MEASURE: The rate of pouch failure was defined as the need for ileostomy or pouch revision. RESULTS: All 31 patients had coexisting pouchitis at index diagnosis of prepouch ileitis. The median length of follow-up from the index pouchoscopy was 98 (range, 27-143) months. Seven (23%) patients who had an index pouchoscopy with prepouch ileitis went on to pouch failure, which is significantly higher than expected (p = 0.03). Five (71%) of these patients had chronic pouchitis, and 2 (29%) had small-bowel obstruction due to prepouch stricture. Two patients had evidence that would support possible Crohn's disease at long-term follow-up. LIMITATIONS: This was a retrospective analysis. Because of the nature of the study, there was some missing information that may have influenced the results. Our study is further limited by small patient numbers. CONCLUSIONS: Prepouch ileitis is associated with a significantly increased risk of pouch failure compared with the overall reported literature for restorative proctocolectomy. Prepouch ileitis does not appear to be strongly predictive of Crohn's disease at long-term follow-up. See Video Abstract at http://links.lww.com/DCR/A480.

Celiac disease: management of persistent symptoms in patients on a gluten-free diet.

AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.

The bacteriology of pouchitis: a molecular phylogenetic analysis using 16S rRNA gene cloning and sequencing.

OBJECTIVE: To identify, compare, and contrast the microbiota in patients with and without pouchitis after restorative proctocolectomy (RPC) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). SUMMARY BACKGROUND DATA: Pouchitis is the most common complication following RPC. An abnormal host-microbial interaction has been implicated. We investigated the pouch microbiota in patients with and without pouchitis undergoing restorative proctocolectomy for UC and FAP. METHODS: Mucosal pouch biopsies, taken from 16 UC (pouchitis 8) and 8 FAP (pouchitis 3) patients were analyzed to the species (or phylotype) level by cloning and sequencing of 3184 full-length bacterial 16S rRNA genes. RESULTS: There was a significant increase in Proteobacteria (P = 0.019) and a significant decrease in Bacteroidetes (P = 0.001) and Faecalibacterium prausnitzii (P = 0.029) in the total UC compared with the total FAP cohort, but only limited differences were found between the UC nonpouchitis and pouchitis groups and the FAP pouchitis and nonpouchitis groups. Bacterial diversity in the FAP nonpouchitis group was significantly greater than in UC nonpouchitis (P = 0.019) and significantly greater in UC nonpouchitis compared with UC pouchitis (P = 0.009). No individual species or phylotype specifically associated with either UC or FAP pouchitis was found. CONCLUSIONS: UC pouch patients have a different, less diverse, gut microbiota than FAP patients. A further reduction in bacterial diversity but no significant dysbiosis occurs in those with pouchitis. The study suggests that a dysbiosis occurs in the ileal pouch of UC RPC patients which predisposes to, but may not directly cause, pouchitis.

Osteoporosis in patients over 50 years of age following restorative proctocolectomy for ulcerative colitis: is DXA screening warranted?

BACKGROUND: Ulcerative colitis (UC) and increasing age are associated with an increased risk of osteoporosis. Screening of postmenopausal women and men older than 50 years with ulcerative colitis for osteoporosis is recommended. The prevalence of osteoporosis in restorative proctocolectomy (RPC) patients more than 50 years old is not known. METHODS: Fifty-three consecutive patients older than age 50 who had undergone RPC for UC underwent a bone density scan (DXA). Sex, smoking status, age at diagnosis of UC, duration of UC, age at RPC, years since RPC, age at DXA, and pouch histological inflammatory score were recorded. The Kruskal-Wallis test and Spearman's correlation coefficient were used to analyze the data. RESULTS: Fifty-three patients were studied; their median age was 58 years, and the median age at RPC was 45. The prevalence of osteopenia and osteoporosis was 43.4% and 13.2%, respectively. Age at RPC was negatively correlated with bone density (P = 0.041, r = 0.281), and there was a negative correlation approaching significance with age at the time of DXA (P = 0.071, r = -0.250). No other factor studied correlated with bone density. CONCLUSIONS: The prevalence of osteoporosis and osteopenia found in this study is similar to that reported for UC patients who have not undergone RPC. Patients having RPC should be screened in line with current UC guidelines, targeting those older than 50 years.

Incidence and short-term implications of prepouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis.

PURPOSE: Pouchitis following restorative proctocolectomy is common. Inflammation proximal to the pouch, prepouch ileitis (PPI) has recently been described. Its incidence and implications are unknown. The aim of this study was to identify the incidence of PPI at pouchoscopy and correlate this with symptoms, diagnosis, and outcome. METHODS: The authors searched the endoscopy database at our institution for the terms "pouchitis" and "ileitis" and reviewed hospital records. RESULTS: A total of 1448 pouchoscopies were performed on 742 patients. PPI was diagnosed in 34 (5.7 percent) patients with ulcerative colitis/indeterminate colitis and 1 (0.6 percent) with polyposis. All of the patients had concurrent pouch inflammation, and in this group the incidence was 13 percent. The median length of the PPI was 10 cm. Asymptomatic patients totaled 26 percent. At follow-up (median, 12 months) no patient was reclassified to Crohn's disease, and no patients required an ileostomy for poor function. CONCLUSIONS: The incidence of PPI in patients with ulcerative colitis/indeterminate colitis is 5.7 percent, and it occurs in 13 percent of patients with pouch inflammation. All of the patients had associated pouch inflammation; however, not all of the patients were symptomatic. Our results demonstrate that PPI is common in patients with pouchitis; it does not imply missed Crohn's disease or predict an increased rate of pouch failure, at least in the short term.

Guide to endoscopy of the ileo-anal pouch following restorative proctocolectomy with ileal pouch-anal anastomosis; indications, technique, and management of common findings.

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the surgical procedure of choice for patients with ulcerative colitis (UC). It is also performed in selected patients with familial adenomatous polyposis (FAP). A significant proportion of patients will develop pouch dysfunction. Flexible pouchoscopy is the most important initial investigation in patients with dysfunction. It is also important in UC and FAP surveillance. The aim is to provide gastroenterologists with a clear understanding of the technique, indications, and diagnostic pitfalls when investigating RPC patients with flexible pouchoscopy. Flexible pouchoscopy for the investigation of RPC patients with pouch dysfunction has a high diagnostic yield, with most causes of pouch dysfunction identifiable during this procedure. The risk of developing dysplasia following RPC is low. Surveillance pouchoscopy is only recommended in those with FAP, those with a previous history of dysplasia or carcinoma, primary sclerosing cholangitis, those with a retained rectal cuff, and those with Type C histological changes. Flexible pouchoscopy is a useful first-line investigation in patients with pouch dysfunction. It can be performed without sedation and has a high diagnostic yield; it is also important as part of surveillance in FAP and selected UC patients.

Ileoanal pouch dysfunction and the use of a Medena catheter following hospital discharge.

With the advent of new surgical techniques to manage colorectal disease, the number of ileoanal pouch operations has amplified and therefore increased numbers of pouch patients are being discharged into the community setting. Community nurses will now encounter the ileoanal pouch patient and may be required to manage related complications. Restorative proctocolectomy with ileoanal pouch anastomosis (RPC) has become established as the gold standard operation for patients with ulcerative colitis (UC) and selected patients with familial adenomatous polyposis (FAP). Using a reservoir constructed from small bowel as a substitute rectum is a medical triumph which in the majority of cases improves the quality of life for patients, not only by eradicating disease and preserving anal sphincter function but also by avoiding a permanent ileostomy. Recent investigation into the use of Medena catheterization for pouch dysfunction has found that it is tolerated in the long-term and is associated with satisfactory quality of life in pouch patients with outflow obstruction.