Trametinib Prevents Mesothelial-Mesenchymal Transition and Ameliorates Abdominal Adhesion Formation
Macarak et al.
Abdominal adhesions remain a leading cause of complications following gastrointestinal surgery. This study describes a mouse model of peritoneal adhesion and its complex pathogenesis, demonstrating the efficacy of trametinib in blocking adhesion formation. In vitro experiments confirmed the authors’ prior observations that trametinib (2 or 5 nM) blocks transforming growth factor-β-induced mesothelial-mesenchymal transition in rat mesothelial cells. Mice underwent cecal abrasion and were administered either 0.1, 1.0 or 3.0 mg/kg/day of trametinib for 8 days, and control mice underwent laparotomy and anesthesia only. Trametinib at highest concentration prevented adhesions with minimal effect on wound healing, while the lower doses reduced adhesion formation, evidenced by the presence of profibrotic protein isoform, FNEDA, but not alpha smooth muscle cell actin. These findings support the need for further study of the efficacy of trametinib in blocking the cascade of events leading to abdominal adhesion formation.
(see page 198)
Diabetes After Pancreaticoduodenectomy: Can We Predict it?
Singh et al.
New onset diabetes after pancreaticoduodenectomy (PD) is increasingly recognized as an important yet poorly understood long term complication in nondiabetic surgical patients. Emerging evidence suggests a relationship between percentage-pancreatic-remnant volume (%RV) and post-PD new onset diabetes. This prospective study sought to correlate %RV with new onset impaired-glucose tolerance/diabetes mellitus (IGT/DM) in nondiabetic patients after PD. A total of 50 nondiabetic participants, all with resectable periampullary carcinoma, were evaluated perioperatively and postoperative at 3-month intervals. Eleven of 50 (22%) of patients with similar demographic variables developed IGT/DM at median time of onset of 7 months over median follow-up of 36 months. %RV <48.8%, along with preoperative fasting glucose and postprandial insulin, was significantly correlated with new onset IGT/DM. These promising findings may help establish risk factors and %RV threshold for predicting post-PD diabetes.
(see page 211)
Can a Gastric Cancer Risk Survey Identify High-Risk Patients for Endoscopic Screening? A Pilot Study
In et al.
Despite its worldwide decline and low incidence in the US, gastric cancer disproportionally affects foreign-born immigrants and racial minorities in the US, and no early screening guidelines exist to address these disparities. This case control study established the feasibility of a questionnaire to discriminate between patients at high risk for gastric cancer and controls from two health care sites in a multicultural area. A total of 40 cases and 100 control subjects from primary care and community settings were included. Using focus groups, cognitive interviews and cluster analysis, the authors refined survey questions in multiple languages and narrowed 227 variables to 12. The final 8-variable logical regression model combined ethnic/cultural variables, including immigration generation, birth country, ethnic diet, and acculturation, and conventional gastric cancer risk factors. The authors aim to use this pilot data to develop a targeted gastric cancer screening program in the US.
(see page 246)
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