Primary adenocarcinoma in the ileostomy of a woman with familial adenomatous polyposis: a case report and literature review.

INTRODUCTION: Ileal adenomas associated with familial adenomatous polyposis are a common finding. Many recent studies following panproctocolectomy for familial adenomatous polyposis have confirmed the presence of multiple ileal adenomas and an increase in ileal mucosal proliferation. In this study, we present a case of invasive adenocarcinoma arising in a severely dysplastic tubulovillous adenoma in the ileostomy of a patient with familial adenomatous polyposis; also, we present a literature review. To the best of our knowledge, only very few cases have been reported in the literature. CASE PRESENTATION: A 59-year-old Caucasian woman developed a primary adenocarcinoma in her ileostomy, complicating the stoma 31 years after its formation. CONCLUSIONS: Primary adenocarcinoma following panproctocolectomy for familial adenomatous polyposis is a very rare clinical entity. The risk of developing adenocarcinoma in those patients increases with time. Patient education and medical examination of the stoma are of paramount importance and should be implemented early with the need of designing a surveillance protocol for early detection and management of ileal adenomas, especially in longstanding stomas.

Nitrous oxide for colonoscopy.

BACKGROUND: Colonoscopy is the gold standard investigation for large bowel disease. With the increase in demand, pressure is on clinics to shorten lengths of time per procedure in addition to maintaining high levels of patient safety. Analgesia has always been the mainstay of adequate pain relief, but it leads to prolonged recovery and lengths of hospital stay, in addition to increased risk of cardio-respiratory side effects. N2O/O2 mixtures have been used for its effective analgesic effect and short half life and provides an alternative method of sedation for colonoscopy procedures. OBJECTIVES: The primary objective was to compare the overall effectiveness of nitrous oxide mixtures to other types of pain relief used during colonoscopy procedures to provide adequate pain/discomfort relief.The secondary objective was to compare between nitrous oxide and other types of pain relief with respect to hospitalisation/recovery time, side effects, patients and endoscopists satisfaction, and colonoscopy completion rates. SEARCH STRATEGY: The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (1966- present), EMBASE (1980 - present), and the Internet (Google Scholar). SELECTION CRITERIA: Randomised controlled trials which compared nitrous oxide to placebo or active comparators for patients undergoing elective colonoscopic procedures. Patients with known underlying causes of pain/discomfort were excluded.  DATA COLLECTION AND ANALYSIS: Seven randomised trials were included. Each trial compared a nitrous oxide/oxygen mixture to a placebo or sedation +- other analgesic drugs on patients undergoing elective colonoscopic procedures. The results of these studies were analysed and discussed. MAIN RESULTS: There were a total of 547 patients included.There were 257 patients randomised to receive the N2O/O2 mixture (7 studies), while 225 patients received some form of sedation with or without other analgesia (6 studies), and 65 patients received a placebo (3 studies).Four studies showed that N2O/O2 is as good in controlling pain/discomfort as conventional methods, while one showed sedation was better and another study showed N2O/O2 was better.Six of the studies showed that N2O/O2 groups had quicker recovery times and shorter lengths of hospital stays while one study showed that there was no difference between the two groups.Two studies showed that N2O/O2 was safer while one reported that sedation was safer. AUTHORS' CONCLUSIONS: Nitrous oxide is as efficient and safer than various pain relief methods used during colonoscopy procedures, but further trials are necessary.

The APC Variant p.Glu1317Gln predisposes to colorectal adenomas by a novel mechanism of relaxing the target for tumorigenic somatic APC mutations.

Multiple rare nonsynonymous variants in APC predispose to colorectal adenomas. The mechanisms through which such variants act have been unclear, but it has been proposed that a specific ("just-right") level of beta-catenin signaling is required for colorectal tumorigenesis. This appears to be mediated by selection for APC genotypes that retain one, or rarely two, 20 amino acid beta-catenin downregulating repeats (20AARs). We investigated the mechanism through which the variant p.Glu1317Gln (c.3949G>C) contributes to colorectal tumorigenesis. We compared the patterns of somatic APC mutations in tumors from patients with attenuated familial adenomatous polyposis (AFAP) who did, or did not, coinherit p.Glu1317Gln with their AFAP-causing APC mutations. Only 8.2% (4/49) of tumors carrying p.Glu1317Gln had somatic mutations predicted to result in mutant polypeptides retaining a single 20AAR, compared to 62.1% (36/58) of those which did not carry this variant (P=5.64 x 10(-9)). Furthermore, tumors with p.Glu1317Gln often carried somatic mutations that were unusually early or late (downstream of the second 20AAR) in the APC open reading frame. These data support a novel mechanism in which p.Glu1317Gln in combination with other weak mutant APC alleles (generating polypepetides with zero, two, or three 20AARs) can provide the necessary growth advantage for colorectal tumorigenesis.