Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and temporizing the development of extracolonic disease. An ideal chemoprevention agent should have a biologically plausible mechanism of action, be safe and easily tolerated over a prolonged treatment period, and produce a durable and clinically meaningful effect. To date, no chemoprevention agent tested has fulfilled these criteria. New agents targeting novel pathways in FAP are needed. Substantial preclinical literature exists linking the molecular target of rapamycin (mTOR) pathway to FAP. A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Here, we review the prior literature on chemoprevention in FAP, discuss the rationale for rapamycin in FAP, and outline a proposed clinical trial testing rapamycin as a chemoprevention agent in patients with FAP.

Surgical resection and liver transplant remain the only curative therapies for most patients with hepatocellular carcinoma (HCC). Systemic therapy options have typically been ineffective, but recent advances, such as the combination of immune checkpoint inhibitors and targeted therapies, have shown great promise. Neoadjuvant systemic therapy in resectable or locally advanced HCC is under active investigation with encouraging results in small, early-phase trials. Many of these completed and ongoing trials include combinations of systemic therapy (e.g. immune checkpoint inhibitors, tyrosine kinase inhibitors), transarterial therapies, and radiation. Despite early successes, larger trials with evaluation of long-term oncologic outcomes are needed to determine the role of neoadjuvant systemic therapy in patients with HCC who may be eligible for curative intent surgery or transplant.

BACKGROUND: Secondary overtriage is a problematic phenomenon because it creates unnecessary expense and potentially results in the mismanagement of healthcare resources. The rates of secondary overtriage among patients with complicated mild traumatic brain injury (cmTBI) are unknown. OBJECTIVE: To determine the rate of secondary overtriage among patients with cmTBI using the institutional trauma registry. METHODS: An observational study using retrospective analysis of 1447 hospitalizations including all consecutive patients with cmTBI between 2004 and 2013. Data on age, sex, race/ethnicity, insurance status, GCS, Injury Severity Score (ISS), Trauma Injury Severity Score, transfer mode, overall length of stay (LOS), LOS within intensive care unit, and total charges were collected and analyzed. RESULTS: Overall, the rate of secondary overtriage among patients with cmTBI was 17.2%. These patients tended to be younger (median: 41 vs 60.5 yr; P < .001), have a lower ISS (9 vs 16; P < .001), and were more likely to be discharged home or leave against medical advice. CONCLUSION: Our findings provide evidence to the growing body of literature suggesting that not all patients with cmTBI need to be transferred to a tertiary care center. In our study, these transfers ultimately incurred a total cost of $13 294 ($1337 transfer cost) per patient.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results. There is considerable interest in using immunotherapy approaches in the neoadjuvant setting in order to prime the immune system to detect and prevent micrometastatic disease and recurrence. A scoping review was conducted to identify published and ongoing trials utilizing preoperative immunotherapy. In total, 9 published trials and 27 ongoing trials were identified. The published trials included neoadjuvant immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents that target mechanisms distinct from that of immune checkpoint inhibition. Most of these are early phase trials which suggest improvements in disease-free and overall survival when combined with standard neoadjuvant therapy. Ongoing trials are exploring various combinations of these agents with each other and with chemotherapy and/or radiation. Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further clinical trials are needed, particularly those which utilize an adaptive trial design.