Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of adenomatous polyps in the colon and rectum, with inevitable development of colorectal cancer if left untreated. FAP is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Somatic mutations in the APC gene are an early event in colorectal tumorigenesis, and can be detected in the majority of colorectal tumours. The APC gene encodes a large protein with multiple cellular functions and interactions, including roles in signal transduction in the wnt-signalling pathway, mediation of intercellular adhesion, stabilization of the cytoskeleton and possibly regulation of the cell cycle and apoptosis. The fact that APC is an integral part of so many different pathways makes it an ideal target for mutation in carcinogenesis. This review deals with our understanding to date of how mutations in the APC gene translate into changes at the protein level, which in turn contribute to the role of APC in tumorigenesis.

Objective: The aim of this meta-analysis was to summarize the current available evidence on nonoperative management (NOM) with antibiotics for uncomplicated appendicitis, both in adults and children. Summary Background Data: Although earlier meta-analyses demonstrated that NOM with antibiotics may be an acceptable treatment strategy for patients with uncomplicated appendicitis, evidence is limited by conflicting results. Methods: Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized and nonrandomized studies comparing antibiotic therapy (AT) and surgical therapy-appendectomy (ST) for uncomplicated appendicitis. Literature search was completed in August 2018. Results: Twenty studies comparing AT and ST qualified for inclusion in the quantitative synthesis. In total, 3618 patients were allocated to AT (n = 1743) or ST (n = 1875). Higher complication-free treatment success rate (82.3% vs 67.2%; P < 0.00001) and treatment efficacy based on 1-year follow-up rate (93.1% vs 72.6%; P < 0.00001) were reported for ST. Index admission antibiotic treatment failure and rate of recurrence at 1-year follow-up were reported in 8.5% and 19.2% of patients treated with antibiotics, respectively. Rates of complicated appendicitis with peritonitis identified at the time of surgical operation (AT: 21.7% vs ST: 12.8%; P = 0.07) and surgical complications (AT: 12.8% vs ST: 13.6%; P = 0.66) were equivalent. Conclusions: Antibiotic therapy could represent a feasible treatment option for image-proven uncomplicated appendicitis, although complication-free treatment success rates are higher with ST. There is also evidence that NOM for uncomplicated appendicitis does not statistically increase the perforation rate in adult and pediatric patients receiving antibiotic treatment. NOM with antibiotics may fail during the primary hospitalization in about 8% of cases, and an additional 20% of patients might need a second hospitalization for recurrent appendicitis.

Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers. Another 20% of all colorectal cancers are thought to occur in individuals with a significant inherited multifactorial susceptibility to colorectal cancer that is not obviously familial. Incompletely penetrant, comparatively rare missense variants in the adenomatous polyposis coli gene, which is responsible for familial adenomatous polyposis, have been described in patients with multiple colorectal adenomas. These variants represent a category of variation that has been suggested, quite generally, to account for a substantial fraction of such multifactorial inherited susceptibility. The aim of this study was to explore this rare variant hypothesis for multifactorial inheritance by using multiple colorectal adenomas as the model. Patients with multiple adenomas were screened for germ-line variants in a panel of candidate genes. Germ-line DNA was obtained from 124 patients with between 3 and 100 histologically proven synchronous or metachronous adenomatous polyps. All patients were tested for the adenomatous polyposis coli variants I1307K and E1317Q, and variants were also sought in AXIN1 (axin), CTNNB1 (␤-catenin), and the mismatch repair genes hMLH1 and hMSH2. The control group consisted of 483 random controls. Thirty of 124 (24.9%) patients carried potentially pathogenic germ-line variants as compared with 55 (Ϸ12%) of the controls. This overall difference is highly significant, suggesting that many rare variants collectively contribute to the inherited susceptibility to colorectal adenomas. polyposis ͉ cancer ͉ subpolymorphic ͉ mismatch repair ͉ founder