Presentation, management and outcomes of ileoanal pouch cancer: a single-centre experience.

AIM: This study aimed to determine the clinical presentation, management and outcomes for patients with ileoanal pouch cancer. METHOD: Patients who were diagnosed with ileoanal pouch cancer were identified from our polyposis registry (1978-2019) and operative and referral records (2006-2019). Details of presentation, endoscopic surveillance, cancer staging and management were retrieved from hospital records. RESULTS: Eighteen patients were identified (12 with ulcerative colitis, one with Crohn's disease, three with familial adenomatous polyposis [FAP], two with dual diagnosis of FAP and inflammatory bowel disease). The median time from pouch formation to cancer diagnosis was 16.5 years (range 5-34 years) and the median age of the patient at pouch cancer diagnosis was 54 years (range 35-71 years). Eleven of the 18 patients were undergoing surveillance. Four of five FAP patients developed pouch cancer whilst on surveillance. Eight patients were asymptomatic at the time of pouch cancer diagnosis. Two patients had complete clinical response following chemoradiotherapy. Fourteen patients underwent pouch excision surgery (eight with exenteration). Median survival was 54 months; however, only eight patients had outcomes available beyond 24 months follow-up. CONCLUSIONS: Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.

Clonality assessment and clonal ordering of individual neoplastic crypts shows polyclonality of colorectal adenomas.

BACKGROUND & AIMS: According to the somatic mutation theory, monoclonal colorectal lesions arise from sequential mutations in the progeny of a single stem cell. However, studies in a sex chromosome mixoploid mosaic (XO/XY) patient indicated that colorectal adenomas were polyclonal. We assessed adenoma clonality on an individual crypt basis and completed a genetic dependency analysis in carcinomas-in-adenomas to assess mutation order and timing. METHODS: Polyp samples were analyzed from the XO/XY individual, patients with familial adenomatous polyposis and attenuated familial adenomatous polyposis, patients with small sporadic adenomas, and patients with sporadic carcinoma-in-adenomas. Clonality was analyzed using X/Y chromosome fluorescence in situ hybridization, analysis of 5q loss of heterozygosity in XO/XY tissue, and sequencing of adenomatous polyposis coli. Individual crypts and different phenotypic areas of carcinoma-in-adenoma lesions were analyzed for mutations in adenomatous polyposis coli, p53, and K-RAS; loss of heterozygosity at 5q, 17p, and 18q; and aneuploidy. Phylogenetic trees were constructed. RESULTS: All familial adenomatous polyposis-associated adenomas and some sporadic lesions had polyclonal genetic defects. Some independent clones appeared to be maintained in advanced adenomas. No clear obligate order of genetic events was established. Top-down growth of dysplastic tissue into neighboring crypts was a possible mechanism of clonal competition. CONCLUSIONS: Human colorectal microadenomas are polyclonal and may arise from a combination of host genetic features, mucosal exposures, and active crypt interactions. Analyses of tumor phylogenies show that most lesions undergo intermittent genetic homogenization, but heterotypic mutation patterns indicate that independent clonal evolution can occur throughout adenoma development. Based on observations of clonal ordering the requirement and timing of genetic events during neoplastic progression may be more variable than previously thought.

Pancreaticoduodenectomy for advanced duodenal and ampullary adenomatosis in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) develop duodenal and ampullary polyps that may progress to malignancy via the adenoma-carcinoma sequence. OBJECTIVE: The aim of this study was to review a large series of FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary polyposis. METHODS: A retrospective case notes review of all FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary adenomatosis was performed. RESULTS: Between October 1993 and January 2010, 38 FAP patients underwent pancreaticoduodenectomy for advanced duodenal and ampullary polyps. Complications occurred in 29 patients and perioperative mortality in two. Postoperative histology revealed five patients to have preoperatively undetected cancer (R = 0.518, P < 0.001). CONCLUSIONS: Pancreaticoduodenectomy in FAP is associated with significant morbidity, but low mortality. All patients under consideration for operative intervention require careful preoperative counselling and optimization.

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Nonelective excisional colorectal surgery in English National Health Service Trusts: a study of outcomes from Hospital Episode Statistics Data between 1996 and 2007.

BACKGROUND: Nonelective colorectal surgery is associated with substantial patient morbidity and mortality. This study sought to describe the practice of emergency colorectal surgery in the United Kingdom during an 11-year period using the Hospital Episode Statistics (HES) database. STUDY DESIGN: All nonelective admissions in patients undergoing 1 of 8 colorectal resectional procedures between 1996 and 2007 were included. Time trends, univariate, and multivariate mortality and length of stay outcomes were analyzed. RESULTS: A total of 102,236 major urgent/emergency procedures were performed in English National Health Service Trusts between April 1996 and March 2007. Thirty-day in-hospital postoperative mortality rates in patients with colorectal cancer and diverticular disease were 13.3% and 15.4%, respectively. The corresponding 1-year postoperative mortality was 34.7% and 22.6%. On multivariate analysis, benign diagnosis, advanced age, high comorbidity score, social deprivation, and specific procedure types were independent predictors of early and 1-year postoperative mortality (p < 0.001). Independent risk factors for extended hospital stay were advanced age, social deprivation, distal (compared with proximal) bowel resection, and a diagnosis of ulcerative colitis (p < 0.001). CONCLUSIONS: HES data suggest that in everyday practice, postoperative mortality among patients undergoing nonelective admission followed by colorectal resection is high. Additional investigation is required to assess the reliability of HES data for monitoring institutional variation in this context.

Jejunal perforation in gallstone ileus - a case series.

INTRODUCTION: Gallstone ileus is an uncommon complication of cholelithiasis but an established cause of mechanical bowel obstruction in the elderly. Perforation of the small intestine proximal to the obstructing gallstone is rare, and only a handful of cases have been reported. We present two cases of perforation of the jejunum in gallstone ileus, and remarkably in one case, the gallstone ileus caused perforation of a jejunal diverticulum and is to the best of our knowledge the first such case to be described. CASE PRESENTATIONS: Case 1A 69 year old man presented with two days of vomiting and central abdominal pain. He underwent laparotomy for small bowel obstruction and was found to have a gallstone obstructing the mid-ileum. There was a 2 mm perforation in the anti-mesenteric border of the dilated proximal jejunum. The gallstone was removed and the perforated segment of jejunum was resected.Case 2A 68 year old man presented with a four day history of vomiting and central abdominal pain. Chest and abdominal radiography were unremarkable however a subsequent CT scan of the abdomen showed aerobilia. At laparotomy his distal ileum was found to be obstructed by an impacted gallstone and there was a perforated diverticulum on the mesenteric surface of the mid-jejunum. An enterolithotomy and resection of the perforated small bowel was performed. CONCLUSION: Gallstone ileus remains a diagnostic challenge despite advances in imaging techniques, and pre-operative diagnosis is often delayed. Partly due to the elderly population it affects, gallstone ileus continues to have both high morbidity and mortality rates. On reviewing the literature, the most appropriate surgical intervention remains unclear.Jejunal perforation in gallstone ileus is extremely rare. The cases described illustrate two quite different causes of perforation complicating gallstone ileus. In the first case, perforation was probably due to pressure necrosis caused by the gallstone. The second case was complicated by the presence of a perforated jejunal diverticulum, which was likely to have been secondary to the increased intra-luminal pressure proximal to the obstructing gallstone.These cases should raise awareness of the complications associated with both gallstone ileus, and small bowel diverticula.