The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Prevalence of 'pouch failure' of the ileoanal pouch in ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The ileoanal pouch (IPAA) provides patients with ulcerative colitis (UC) that have not responded to medical therapy an option to retain bowel continuity and defecate without the need for a long-term stoma. Despite good functional outcomes, some pouches fail, requiring permanent diversion, pouchectomy, or a redo pouch. The incidence of pouch failure ranges between 2 and 15% in the literature. We conducted a systematic review and meta-analysis aiming to define the prevalence of pouch failure in patients with UC who have undergone IPAA using population-based studies. METHODS: We searched Embase, Embase classic and PubMed from 1978 to 31st of May 2021 to identify cross-sectional studies that reported the prevalence of pouch failure in adults (≥ 18 years of age) who underwent IPAA for UC. RESULTS: Twenty-six studies comprising 23,389 patients were analysed. With < 5 years of follow-up, the prevalence of pouch failure was 5% (95%CI 3-10%). With ≥ 5 but < 10 years of follow-up, the prevalence was 5% (95%CI 4-7%). This increased to 9% (95%CI 7-16%) with ≥ 10 years of follow-up. The overall prevalence of pouch failure was 6% (95%CI 5-8%). CONCLUSIONS: The overall prevalence of pouch failure in patients over the age of 18 who have undergone restorative proctocolectomy in UC is 6%. These data are important for counselling patients considering this operation. Importantly, for those patients with UC being considered for a pouch, their disease course has often resulted in both physical and psychological morbidity and hence providing accurate expectations for these patients is vital.

The impact of the ileoanal pouch on female fertility in ulcerative colitis: A systematic review and meta-analysis.

AIM: Ileal pouch-anal anastomosis is a restorative option for patients with ulcerative colitis (UC) requiring surgery. The primary outcome of this study was the relative risk of infertility in women with UC undergoing restorative proctocolectomy (RPC) compared to the same patients before undergoing RPC. Infertility was defined as the inability to conceive after 1 year of regular sexual intercourse without contraception. METHODS: A systematic review and meta-analysis were performed to include all relevant articles from 1946 from MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Studies included reported on the fertility rate of a cohort with UC and also reported the rate after RPC in those within the cohort who underwent surgery. This study was registered on PROSPERO (CRD42021259745). RESULTS: Thirteen studies met the inclusion criteria and accounted for 793 patients pre-pouch and 802 post-pouch. The mean and median age of the patients at analysis was 36.8 and 32.7 years respectively; and the median duration of follow-up following ileal pouch-anal anastomosis was 110.4 (68-139) months. Our results highlight that following RPC the relative risk of infertility is 4.17 (95% CI 1.99, 8.74) compared with patients before RPC who had UC. CONCLUSIONS: The findings of this meta-analysis provide an update on a previous meta-analysis published over a decade ago and results remain congruent. This suggests that despite advancements in surgical techniques the risk to fertility remains similar to a decade ago. However, further high quality studies are needed to try and decipher independent risk factors associated with a decrease in infertility.

Prevalence of pouchitis in both ulcerative colitis and familial adenomatous polyposis: A systematic review and meta-analysis.

AIM: Pouchitis is a clinically significant complication of ileal pouch-anal anastomosis with its prevalence varying in the literature. Pouchitis is thought to occur more commonly in patients with ulcerative colitis (UC) than in patients with familial adenomatous polyposis (FAP). We conducted a systematic review with meta-analysis of all published literature to report the prevalence of pouchitis in all pouch patients as well as specifically in UC and FAP. We also investigated the prevalence of acute and chronic pouchitis in UC and FAP. METHODS: A meta-analysis was conducted by searching the Embase, Embase Classic and PubMed databases between 1978 and 2021 exploring the prevalence of pouchitis in UC and FAP. We then performed a random effects model in order to find the pooled prevalence of pouchitis and used odds ratios to report differences in the prevalence of pouchitis in UC and FAP. RESULTS: Fifty-nine full papers and conference abstracts were included in the meta-analysis comprising 18 117 patients with UC and 860 with FAP. The prevalence of pouchitis in UC was 0.32 (95% CI 0.27-0.37) and in FAP was found to be 0.06 (95% CI 0.03-0.15). The odds ratio of pouchitis in UC patients compared with FAP patients was 4.95 (95% CI 3.17-7.72, P < 0.0001). CONCLUSIONS: Our findings support the consensus that the prevalence of pouchitis is higher in UC than in FAP. More significantly our findings suggest that the true prevalence of pouchitis is higher than commonly reported in the literature. This literature may help counsel patients prior to undergoing restorative proctocolectomy.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

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.

Biofeedback in patients with ileoanal pouch dysfunction: a specialist centre experience.

OBJECTIVES: To report outcomes following biofeedback for functional problems associated with an ileoanal pouch. Incontinence and evacuatory disorders associated with the ileoanal pouch can be particularly problematic and difficult to treat using conventional therapies. Biofeedback therapy is a behavioural treatment that offers a non-surgical approach as an alternative or adjunct for patients. MATERIALS AND METHODS: This was a retrospective single centre study. We reviewed the notes of all patients attending for biofeedback at our institution between January 2012 and October 2017 and identified all those that did so for ileoanal pouch related problems. We recorded patient reported subjective improvements following biofeedback. The validated International Consultation on Incontinence Questionnaire was used to assess improvement in incontinent symptoms and the evacuatory disorder questionnaire was used to assess improvement in evacuatory disorders. RESULTS: Twenty-six patients with ileoanal pouch related problems underwent biofeedback. Based on patients' feedback at next clinical encounter following biofeedback, nine reported much improvement, 11 reported some improvement and six reported no improvement. In the group treated for incontinence, quality of life improved significantly from a median pre-treatment score of 80 to a post-treatment score of 41 (p = .01). Biofeedback reduced pain, bloating straining and laxative use in patients with evacuatory disorders. CONCLUSIONS: Biofeedback may be associated with significant improvement in quality of life as well as possible improvements in symptoms related to both incontinence and evacuatory disorders. It is probably an underused service. Further larger prospective studies are required to properly assess the efficacy of biofeedback in ileoanal pouch related dysfunction.

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.

Hepatic sarcoid resembling lymphoma.

Sarcoidosis is an inflammatory disease characterised by non-caseating granulomas that can affect any organ, although lung involvement is the most common. It is rare to find sarcoidosis isolated to extrapulmonary organs. We describe a case of extrapulmonary sarcoidosis with involvement of the liver in a man in his late 40s. His initial clinical history and investigations were more consistent with a diagnosis of lymphoma until a liver biopsy was performed revealing non-caseating granulomas more suggestive of a diagnosis of sarcoidosis. This patient had a history of young-onset ischaemic heart disease (IHD). We discuss the possible links between sarcoidosis, an inflammatory condition, and IHD, as well as the challenges to treating such patients with concurrent metabolic syndrome. This case also highlights the heterogeneous nature of sarcoidosis, with the diagnosis being important as prompt treatment can prevent complications of end-stage liver disease, including portal hypertension and cirrhosis.

British Society of Gastroenterology guidelines on the management of functional dyspepsia.

In 2022, the British Society of Gastroenterology released guidelines on the management of functional dyspepsia (FD), providing a long-anticipated evidence-based approach to the diagnosis, classification and management of patients with FD. This review summarises the key recommendations of the recent guidelines on the management of FD.

Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases.

BACKGROUND: Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking. AIM: Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission. METHODS: We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675). RESULTS: Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08). CONCLUSIONS: Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

Prevalence of Extraintestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and haematological systems. The extraintestinal manifestations of IBD are frequent, common in both ulcerative colitis (UC) and Crohn's disease (CD), and impact the morbidity and mortality of patients. METHODS: The Embase, Embase classic, and PubMed databases were searched between January 1979 and December 2021. A random effects model was performed to find the pooled prevalence of joint, ocular, and skin extraintestinal manifestations of UC and CD. RESULTS: Fifty-two studies were included that reported on 352 454 patients. The prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in all IBD, UC, and CD was 24%, 27%, and 35% respectively. The prevalence between UC and CD were similar for pyoderma gangrenosum and axial joint manifestations. Ocular manifestations were found to be more common in CD than in UC. Peripheral joint manifestations and erythema nodosum were found to be more common in CD than UC. DISCUSSION: To our knowledge, this is the first meta-analysis that reports on the prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in IBD. Our results are largely consistent with figures and statements quoted in the literature. However, our findings are based on significantly larger cohort sizes. Thus, our results have the potential to better power studies and more accurately counsel patients.

The prevalence of joint, ocular, or skin extraintestinal manifestations in IBD, UC, and CD was 24%, 27%, and 35% respectively. Ocular manifestations were more common in CD. Peripheral joint manifestations and erythema nodosum were more common in CD.

The aetiology of pouchitis in patients with inflammatory bowel disease.

Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis.

The prevalence of pouch fistulas in ulcerative colitis following restorative proctocolectomy: a systematic review and meta-analysis.

Background/Aims: One complication of restorative proctocolectomy with ileo-anal pouch anastomosis is fistula formation in the pouch. Fistulas can be associated with significant morbidity and pouch failure. We conducted a systematic review with meta- analysis to try and understand the prevalence of pouch fistulas in patients with ulcerative colitis following restorative proctocolectomy. Methods: The Embase, Embase Classic, and PubMed databases were searched between January 1979 and April 2022. Studies were included if there were cross-sectional, case-controlled, population-based or cohort studies reporting on prevalence of pouch fistulas in ulcerative colitis. Studies had to report the number of patients with pouch fistulas using either clinical, endoscopic, or radiological diagnosis in an adult population. Results: Thirty-three studies screened met the inclusion criteria. The pooled prevalence of developing at least 1 fistula was 0.05 (95% confidence interval [CI], 0.04-0.07). The pooled prevalence of pouch failure in patients with pouch fistula was found to be 0.24 (95% CI, 0.19-0.30). The pooled prevalence of developing a pouch fistula at 3 years, 5 years and more than 5 years was 0.04 (95% CI, 0.02-0.07), 0.05 (95% CI, 0.02-0.07), and 0.05 (95% CI, 0.02-0.10), respectively. Conclusions: This is the first systematic review and meta-analysis to report the prevalence of pouch fistula. It also provides a pooled prevalence of pouch failure in these patients. These results can help to shape future guidelines, power future studies, and help counsel patients.