Gastrointestinal aspects of Peutz-Jeghers syndrome.

There are two main problems in the clinical management of the gastrointestinal (GI) tract in patients with Peutz-Jeghers syndrome (PJS), namely long-term cancer risk and managing polyp related complications (of which the most important clinically is intussusception). Given the rarity of this condition, the evidence base upon which to make recommendations is small. Furthermore, controversies persist regarding the relationship between PJ polyps, cancer development and cancer risk. In this article we will explore some of these controversies, to put into context the recommendations for clinical management of these patients. We will provide an overview, particularly focusing on clinical data, and on the recommendations for clinical management and surveillance of the GI tract in PJS. We highlight knowledge gaps which need to be addressed by further research.

Risk of colorectal adenomas and cancer in monoallelic carriers of MUTYH pathogenic variants: a single-centre experience.

PURPOSE: The carrier frequency of MUTYH pathogenic variants in the population may be as high as one in 45. Some studies have found an increased risk of colorectal cancer (CRC) in monoallelic carriers of MUTYH pathogenic variants, but the role of early surveillance colonoscopy is not conclusive. This study aimed to assess the outcomes of colonoscopy surveillance in MUTYH carriers. METHODS: Patients, with a monoallelic pathogenic variant in MUTYH, found at cascade testing, were identified from the St Mark's Hospital Polyposis Registry database. Findings at surveillance colonoscopy were reviewed. RESULTS: Two hundred and forty-nine carriers were identified, of whom 125 had undergone at least one surveillance colonoscopy. Twenty-eight patients (22%) developed at least one adenoma; all adenomas had low-grade dysplasia (LGD). The median age at first colonoscopy was 36 years (range 16-75 years). The median age at first adenoma detection was 43 years (range 22-75 years). The cumulative incidence of adenoma development by age 30, 40, 50, 60 and 70 years was 3.2%, 8.8%, 15.2%, 18.4% and 20.8%, respectively. No CRCs were observed. CONCLUSIONS: Our cohort of monoallelic carriers of MUTYH pathogenic variants is a relatively younger group than adults entering population screening colonoscopy, but a high adenoma rate was not observed. No CRCs were detected, suggesting that current guidance that these individuals should be managed in the same way as the general population is reasonable.

Perianal fistula and the ileoanal pouch - different aetiologies require distinct evaluation.

AIM: Restorative proctocolectomy has been widely adopted as the procedure of choice for restoring gastrointestinal continuity following proctocolectomy. It is often associated with improved quality of life and high patient satisfaction; however, the development of a pouch anal fistula can cause significant morbidity. Pouch fistulas are notoriously difficult to treat and there is great heterogeneity in the management reported of these fistulas. A lack of classification, and the assumption that fistulas originating from completely different aetiologies will behave and respond similarly to a particular treatment strategy, precludes meaningful comparison of management outcomes. We aim to introduce consistency in the reporting of pouch fistulas using a novel classification system. METHODS: A consensus process involving clinicians experienced in the management of pouch fistulas from two high volume tertiary centres was performed. RESULTS: We propose that pouch anal fistulas should be classified into four distinct groups according to their aetiology: group 1, anastomotic related; group 2, inflammatory bowel disease related, with sub-classifications Crohn's (type A) and non-Crohn's (type B) in origin; group 3, cryptoglandular related; and group 4, malignancy related. CONCLUSION: Classification of pouch fistulas according to their aetiology will provide consistency in the literature and improve the quality of prospective evidence for the management of pouch fistulas.

MUTYH-associated polyposis - colorectal phenotype and management.

AIM: The aim was to determine the presentation, management and outcomes of MUTYH-associated polyposis (MAP). METHOD: A prospectively maintained database was used to identify patients with MAP. Demographic data and data on germline mutation, surgical management, histopathology of tumours and endoscopic surveillance were collected. RESULTS: In all, 134 patients with MAP were identified. The majority presented symptomatically (n = 83). Sixty-eight patients developed cancer (seven synchronous, 12 metachronous). The median age at diagnosis of first colorectal cancer was 47 years (range 33-74 years). Cancers occurred in the context of a few adenomas (< 10). The majority of patients (n = 108) had surgery as the first line management. One patient received palliative care. Twenty-five patients had endoscopic surveillance as first line management; no cancers occurred in this group. Patients who had segmental resection and postoperative surveillance still appeared to be at risk of metachronous cancer (5/30, 17%). CONCLUSIONS: MUTYH testing should be considered even in the context of cancers occurring with fewer than 10 adenomas. In cases of primary colorectal cancers, extended surgery should be considered if patients do not have access to high quality endoscopic surveillance postoperatively. For some patients, endoscopic therapy is an appropriate and safe option in expert hands.

Safety and efficacy of laparoscopic near-total colectomy and ileo-distal sigmoid anastomosis as a modification of total colectomy and ileorectal anastomosis for prophylactic surgery in patients with adenomatous polyposis syndromes: a comparative study.

AIM: Colectomy in patients with adenomatous polyposis (AP) syndromes demands good oncological and surgical outcome. Total colectomy with ileorectal anastomosis (TC-IRA) is one surgical option for these patients. Anastomotic leakage rates of 11% have been reported following TC-IRA. Ileo-distal sigmoid anastomosis (IDSA) is a recent modification of our practice. Our aim was to compare postoperative outcome in patients with AP following near-total colectomy with IDSA (NT-IDSA) and TC-IRA at a single institution. METHOD: A prospectively maintained database was reviewed to identify patients with AP who underwent laparoscopic NT-IDSA and TC-IRA. Patient demographics, early morbidity and mortality and outcome of endoscopic surveillance were evaluated. RESULTS: A total of 191 patients with AP underwent laparoscopic colectomy between 2006 and 2017, of whom 139 (72.8%) underwent TC-IRA and 52 (27.2%) NT-IDSA. The median age at surgery in the TC-IRA and NT-IDSA groups was 20 years (IQR 17-45) and 27 years (IQR 19-50), respectively. Grade II complications were comparable between the two groups. There were no anastomotic leakages in the NT-IDSA group compared with 15 (10.8%) in the TC-IRA group (P = 0.0125) and no reoperation in the NT-IDSA group compared with 17 (12.2%) in the TC-IRA group (P = 0.008). The frequency of polypectomies per flexible sigmoidoscopy was comparable between the two groups. CONCLUSION: This study demonstrates that laparoscopic NT-IDSA for polyposis is associated with a significant improvement in anastomotic leakage rates and surgical outcome. It is too soon to tell whether NT-IDSA alters the need for further intervention, either endoscopic polypectomy or further surgery.

Management of genetically determined colorectal cancer.

Surgeons are increasingly treating patients for colorectal cancer who are known to have a genetic predisposition to develop the disease; this may modify the surgical and oncological management of the patient. In this review the approach to the patient with colorectal cancer on a background of Lynch syndrome or familial adenomatous polyposis is explored.

Acceptability, effectiveness and safety of a Renew® anal insert in patients who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis.

INTRODUCTION: Restorative proctocolectomy has gained acceptance in the surgical management of medically refractive ulcerative colitis and cancer prevention in familial adenomatous polyposis. Incontinence following restorative proctocolectomy occurs in up to 25% of patients overnight. The Renew® insert is an inert single-use device which acts as an anal plug. The aim of this study was to assess the acceptability, effectiveness and safety of the Renew® insert in patients who have undergone restorative proctocolectomy. The device has yet to be assessed in patients who have undergone restorative proctocolectomy. METHOD: This was a prospective study exploring the acceptability, effectiveness and safety of the Renew® insert in improving incontinence in patients who had undergone restorative proctocolectomy. A total of 15 patients with incontinence were asked to use the Renew® insert for 14 days following their standard care. The Incontinence Questionnaire-Bowels was used pre- and posttreatment to assess response and patients were asked to report the perceived acceptability, effectiveness and safety of the device at the end of the trial. RESULTS: The device was acceptable to 8/15 (53%) of patients and was effective in 6/15 (40%). Only 2/15 (13%) of patients raised any safety concerns, and these were minor. The device was associated with a significant reduction in night seepage (P = 0.034). CONCLUSION: In a small study, the Renew® insert can be both acceptable and effective and is also associated with few safety concerns. It is also associated with significant reductions in night-time seepage.

Indications and outcomes of home parenteral nutrition in patients with an ileoanal pouch.

INTRODUCTION: Restorative proctocolectomy is a surgical treatment for patients with medically refractory ulcerative colitis and some cases of familial adenomatous polyposis. Intestinal failure, defined as an inability to maintain adequate hydration and micronutrient balances when on a conventionally accepted normal diet, is a rare complication of restorative proctocolectomy. We describe our experience of patients with restorative proctocolectomy who have developed intestinal failure requiring parenteral support. MATERIAL AND METHODS: This was a retrospective analysis using a database of patients referred to our intestinal failure unit from January 1998 to January 2016. We analysed the records of all those patients who had restorative proctocolectomy who developed intestinal failure. RESULTS: 807 patient records analysed, 35 patients were found to have had a restorative proctocolectomy (13 male and 22 female). Ninety-one percent (n = 32) of patients developed IF as a consequence of unpredictable complications which occurred after RPC formation. Potentially predictable complications were noted in 9% (n = 3) of patients. DISCUSSION AND CONCLUSIONS: Most cases of intestinal failure in restorative proctocolectomy were unpredictable. In a small number of patients, accurate assessment and measurement of the small intestine may have better predicted the adverse outcome of intestinal failure allowing improved pre-operative counseling of patients.

Risk of desmoid formation after laparoscopic versus open colectomy and ileorectal anastomosis for familial adenomatous polyposis.

BACKGROUND: Laparoscopy is used increasingly in prophylactic surgery for patients with familial adenomatous polyposis (FAP) undergoing colectomy with ileorectal anastomosis (IRA). Little is known about the impact of laparoscopy on subsequent desmoid risk. This study documented the risk of desmoid in patients undergoing laparoscopic and open IRA. METHODS: This was an observational study of patients with FAP and known germline APC mutation, undergoing IRA at a tertiary referral centre between 1996 and 2016. Patients were retrieved from a prospectively maintained polyposis registry. Data included genotype, family history of desmoid, sex, surgical approach at IRA and postoperative complications. The main outcome was development of either a clinically or radiologically significant desmoid. RESULTS: Some 112 patients (61 female) underwent colectomy and IRA. A laparoscopic approach was used in 69 patients (61·6 per cent). Baseline characteristics did not differ between patients having an open or laparoscopic approach. Median follow-up was 5·8 (i.q.r. 2·4-11·2) years. Patients who underwent laparoscopic IRA had a reduced risk of desmoid formation (3 of 69 (4 per cent) versus 7 of 43 (16 per cent) in the open group; P = 0·043). DISCUSSION: Laparoscopic IRA may reduce risk of subsequent desmoid formation in patients with FAP.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Clinical value of pouchogram prior to ileostomy closure after ileal pouch anal anastomosis.

BACKGROUND: In patients who undergo restorative proctocoletomy (RPC) a pouchogram is often used to assess the integrity of the ileal pouch-anal anastomosis (IPAA) before closing the covering ileostomy. There are no good data to support this practice. The aim of the study was to investigate whether contrast pouchography was clinically useful after RPC. METHODS: We conducted a retrospective study of patients who had undergone RPC with a covering ileostomy between September 2013 and September 2015. RESULTS: 61 patients were included. 7 (11%) presented with anastomotic leak and 2 (3%) with pelvic collection, detected on cross-sectional imaging for early postoperative symptoms. In the remaining 52 patients, without immediate postoperative complications, pouchography was performed at a median of 14 weeks (range 7-71 weeks) after RPC. Each patient also underwent examination under anaesthesia (EUA) to assess the integrity of the IPAA on the day of the ileostomy closure. One asymptomatic patient (2%) had an anastomotic leak demonstrated on pouchogram which was subsequently confirmed at EUA. Two patients (3%) with a normal pouchogram, 1 symptomatic and 1 asymptomatic, subsequently had an anastomotic leak demonstrated at EUA. CONCLUSIONS: Pouchogram has a low sensitivity in identifying anastomotic leak before ileostomy reversal in patients after RPC and only rarely changes management. In our series it identified the diagnosis of anastomotic leak in only 1 patient and gave false reassurance in two others. Complications are more frequently detected by clinical history and formal EUA before ileostomy closure.

Management of early pouch-related septic complications in ulcerative colitis: a systematic review.

AIM: It is well established that ileo-anal pouch-related septic complications (PRSC) increase the risk of pouch failure. There are a number of publications that describe the management of early PRSC in ulcerative colitis (UC) in small series. This article aims to systematically review and summarize the relevant current data on this subject and provide an algorithm for the management of early PRSC. METHOD: A systematic review was undertaken in accordance with PRISMA guidelines. Studies published between 2000 and 2017 describing the clinical management of PRSC in patients with UC within 30 days of primary ileo-anal pouch surgery were included. A qualitative analysis was undertaken due to the heterogeneity and quality of studies included. RESULTS: A total of 1157 abstracts and 266 full text articles were screened. Twelve studies were included for analysis involving a total of 207 patients. The studies described a range of techniques including image-guided, endoscopic, surgical and endocavitational vacuum methods. Based on the evidence from these studies, an algorithm was created to guide the management of early PRSC. CONCLUSION: The results of this review suggest that although successful salvage of early PRSC is improving there is little information available relating to methods of salvage and outcomes. Novel techniques may offer an increased chance of salvage but comparative studies with longer follow-up are required.

Urological sequelae of desmoids associated with familial adenomatous polyposis.

The aim of this retrospective cohort study was to review urological complication rates arising from familial adenomatous polyposis associated desmoid tumours and their management. All patients over a 35-year period were identified from a prospectively maintained polyposis registry database and had an intra-abdominal desmoid tumour. Those without ureteric complications (n = 118, group A) were compared to those that developed ureteric obstruction (n = 40, group B) for demographics, treatment interventions and survival outcomes. 158 (56% female) patients were identified. Median age at diagnosis was 31 years and desmoids typically occurred 3.6 years after colectomy for familial adenomatous polyposis. Ureteric obstruction secondary to tumour growth occurred in 25% of cases. There was no significant difference in gender distribution or overall age at desmoid diagnosis between the two groups. In group B, the median age at desmoid diagnosis was significantly younger in women compared to men (25 and 43 years, respectively) (p = 0.01). Thirty-eight percent of patients already had ureteric obstruction at desmoid diagnosis, the remainder occurred after 48.6 months, but 20 years in two cases. Seventy-three percent (29/40) had ureteric stenting, a long-term requirement for most. Permanent renal injury occurred in six cases but survival between the two groups was not significantly different. Ureteric obstruction occurs frequently in patients with familial adenomatous polyposis and an intra-abdominal desmoid tumour. Those most at risk are the young following colectomy. Clinicians should actively survey the renal tract at regular intervals after a diagnosis of an intra-abdominal desmoid tumour as complications can arise insidiously, at any stage.

Systematic review: ileoanal pouch microbiota in health and disease.

BACKGROUND: The resident gut microbiota is essential for physiological processes; the disturbance of its balance is linked to intestinal inflammation. The ileoanal pouch is a model for the study of intestinal inflammation, as inflammation of the pouch is common and mostly develops within 12 months following ileostomy closure. This allows the longitudinal study of the microbiota, giving insight into the microbiota changes during transition from a normal to an inflamed pouch. AIM: To explore the literature on the microbiota of the ileoanal pouch in health and disease. METHODS: A systematic computer search of the on-line bibliographic databases MEDLINE and EMBASE was performed between 1966 and February 2017. Randomised controlled trials, cohort studies and observational studies were included. Studies were included if they reported microbiota analysis on faecal samples or tissue from the ileoanal pouch. RESULTS: Twenty-six papers were eligible. Following ileostomy closure, anaerobic bacteria are the abundant species in the ileoanal pouch with presence of a diverse microbiota key to maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an increase in Clostridia species, while chronic pouchitis is associated with an increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in Clostridia species appears to be associated with treatment response. CONCLUSION: The microbiota plays an important role in both the inflamed and the healthy ileoanal pouch. A direct causal relationship between individual microbiota changes and inflammation has not yet been established, but manipulation of the ileoanal pouch microbiota may be a novel therapeutic avenue to explore.

British Society of Gastroenterology position statement on serrated polyps in the colon and rectum

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

Risk of metachronous colorectal cancer following colectomy in Lynch syndrome: a systematic review and meta-analysis.

AIM: Lynch syndrome (LS) accounts for 2-4% of all colorectal cancer (CRC) cases, and is associated with an increased risk of developing metachronous colorectal cancer (mCRC). The role of extended colectomy in LS CRC is controversial. There are limited studies comparing the risk of mCRC following segmental colectomy and extended colectomy. The objective of this systematic review is to evaluate the risk of developing mCRC following segmental and extended colectomy for LS CRC and endoscopic compliance. METHOD: A systematic review of major databases was performed using predefined terms. All original articles published in English comparing the risk of mCRC in LS patients after segmental and extended colectomy from 1950 to January 2016 were included. RESULTS: The search retrieved 324 studies. Six studies involving 871 patients met the inclusion criteria. Of these, 705 (80.9%) underwent segmental colectomy and 166 (19.1%) extended colectomy. Average follow-up was 91.2 months. The mCRC rate was 22.8% and 6% in the segmental and extended colectomy groups, respectively. The segmental group were over four times more likely to develop mCRC (OR 4.02, 95% CI: 2.01-8.04, P < 0.0001). mCRC occurred in patients after segmental colectomy despite 1-2-yearly postoperative endoscopic surveillance. CONCLUSION: This result suggests that extended colectomy reduces the risk of mCRC by over four-fold compared with segmental colectomy. mCRC occurred in the segmental group despite postoperative endoscopic surveillance. This needs to be borne in mind when deciding on the appropriate surgical management of LS patients with CRC. We recommend that extended colectomy should be considered for patients with confirmed LS CRC.

Systematic review with meta-analysis: the management of chronic refractory pouchitis with an evidence-based treatment algorithm.

BACKGROUND: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis. AIM: To determine the efficacy of medical therapies for the treatment of chronic refractory pouchitis in patients undergoing IPAA for UC. METHODS: A systematic computer-assisted search of the on-line bibliographic database MEDLINE and EMBASE was performed between 1966 and February 2016. All original studies reporting remission rates following medical treatment for chronic pouchitis were included. All study designs were considered. Remission was defined according to the individual study. Remission endpoints ranged from 15 days to 10 weeks. Chronic pouchitis was defined by each study. RESULTS: Twenty-one papers were considered eligible. Results from all studies combined suggested that overall remission was obtained in 59% of patients (95% CI: 44-73%). Antibiotics significantly induced remission in patients with chronic pouchitis with 74% remission rate (95% CI:56-93%), (P < 0.001). Biologics significantly induced remission in patients with chronic pouchitis with 53% remission rate (95% CI:30-76%), (P < 0.001). Steroids, bismuth, elemental diet and tacrolimus all can induce remission but failed to achieve significance. Faecal microbiota transplantation in a single study was not found to achieve remission. CONCLUSIONS: Treatment of chronic refractory pouchitis remains difficult and is largely empirical. Larger randomised controlled trials will help aid the management of chronic pouchitis.