It has been proposed that multiple rare variants in numerous genes collectively account for a substantial proportion of multifactorial inherited predisposition to a variety of diseases, including colorectal adenomas (CRA). We have studied this hypothesis by sequencing the adenomatous polyposis coli (APC) gene in 691 unrelated North American patients with CRAs and 969 matched healthy controls. Rare inherited nonsynonymous variants of APC were significantly overrepresented in patients who did not carry conventional pathogenic mutations in the APC or MutY homologue genes [non-familial adenomatous polyposis (FAP) non-MUTYH-associated polyposis (MAP) patients; 81 of 480, 16.9%] compared with patients with FAP or MAP (20 of 211, 9.5%, P = 0.0113), and this overrepresentation was highest in those non-FAP non-MAP patients with 11 to 99 CRAs (30 of 161, 18.6%, P = 0.0103). Furthermore, significantly more non-FAP non-MAP patients carried rare nonsynonymous variants in the functionally important B-catenin down-regulating domain compared with healthy controls (32 of 480 versus 37 of 969, P = 0.0166). In silico analyses predicted that f46% of the 61 different variants identified were likely to affect function, and upon testing, 7 of 16 nonsynonymous variants were shown to alter B-catenin-regulated transcription in vitro. These data suggest that multiple rare nonsynonymous variants in APC play a significant role in predisposing to CRAs. [Cancer Res 2008;68(2):358-63]

Background Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site. Methods In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964.

Component separation is established for complex hernia repairs. This case presents early component separation and release of the anterior and posterior sheath to facilitate closure of the abdominal wall following emergency laparotomy, reinforcing the repair with a biological mesh. On Day 11 following an emergency laparotomy for penetrating trauma, this patient underwent component separation and release of the anterior and posterior sheath. An intra-abdominal biological mesh was secured, and the fascia and skin closed successfully. Primary abdominal closure can be achieved in patients with penetrating abdominal trauma with the use of component separation and insertion of intra-abdominal biological mesh, where standard closure is not possible.

<div>Abstract<p>It has been proposed that multiple rare variants in numerous genes collectively account for a substantial proportion of multifactorial inherited predisposition to a variety of diseases, including colorectal adenomas (CRA). We have studied this hypothesis by sequencing the <i>adenomatous polyposis coli</i> (<i>APC</i>) gene in 691 unrelated North American patients with CRAs and 969 matched healthy controls. Rare inherited nonsynonymous variants of <i>APC</i> were significantly overrepresented in patients who did not carry conventional pathogenic mutations in the <i>APC</i> or <i>MutY homologue</i> genes [non–familial adenomatous polyposis (FAP) non–<i>MUTYH</i>-associated polyposis (MAP) patients; 81 of 480, 16.9%] compared with patients with FAP or MAP (20 of 211, 9.5%, <i>P</i> = 0.0113), and this overrepresentation was highest in those non-FAP non-MAP patients with 11 to 99 CRAs (30 of 161, 18.6%, <i>P</i> = 0.0103). Furthermore, significantly more non-FAP non-MAP patients carried rare nonsynonymous variants in the functionally important β-catenin down-regulating domain compared with healthy controls (32 of 480 versus 37 of 969, <i>P</i> = 0.0166). <i>In silico</i> analyses predicted that ∼46% of the 61 different variants identified were likely to affect function, and upon testing, 7 of 16 nonsynonymous variants were shown to alter β-catenin–regulated transcription <i>in vitro</i>. These data suggest that multiple rare nonsynonymous variants in <i>APC</i> play a significant role in predisposing to CRAs. [Cancer Res 2008;68(2):358–63]</p></div>

Supplementary Tables S1 & S2 from Multiple Rare Nonsynonymous Variants in the <i>Adenomatous Polyposis Coli</i> Gene Predispose to Colorectal Adenomas