Cannabinoids: A Guide for Use in the World of Gastrointestinal Disease.

Cannabinoids have been known as the primary component of cannabis for decades, but the characterization of the endocannabinoid system (ECS) in the 1990s opened the doors for cannabis' use in modern medicine. The 2 main receptors of this system, cannabinoid receptors 1 and 2, are found on cells of various tissues, with significant expression in the gastrointestinal (GI) tract. The characterization of the ECS also heralded the understanding of endocannabinoids, naturally occurring compounds synthesized in the human body. Via secondary signaling pathways acting on vagal nerves, nociceptors, and immune cells, cannabinoids have been shown to have both palliative and detrimental effects on the pathophysiology of GI disorders. Although research on the effects of both endogenous and exogenous cannabinoids has been slow due to the complicated legal history of cannabis, discoveries of cannabinoids' treatment potential have been found in various fields of medicine, including the GI world. Medical cannabis has since been offered as a treatment for a myriad of conditions and malignancies, including cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis, chronic pain, nausea, posttraumatic stress disorder, amyotrophic lateral sclerosis, cachexia, glaucoma, and epilepsy. This article hopes to create an overview of current research on cannabinoids and the ECS, detail the potential advantages and pitfalls of their use in GI diseases, and explore possible future developments in this field.

Pre-clinical Implants of the Levitronix PediVAS® Pediatric Ventricular Assist Device - Strategy for Regulatory Approval.

The PediVAS blood pump is a magnetically levitated centrifugal pump designed for pediatric bridge-to-decision or bridge-to-recovery in pediatric patients from 3-20kg in weight. In preparation for submission of an investigational device exemption (IDE) application, we completed a final six-animal series of pre-clinical studies. The studies were conducted under controlled conditions as prescribed by the recently released FDA guidance document for animal studies for cardiovascular devices. Three 30-day chronic left ventricular support studies were completed in a juvenile lamb model to demonstrate the safety and hemocompatibility of the PediVAS pump. Three additional 8-hour acute biventricular support studies were performed to demonstrate the feasibility of this approach from a hemodynamic and systems standpoint. It is estimated that 50% of pediatric patients who require left ventricular support also require right ventricular support. All studies were successfully completed without complications, device malfunctions, or adverse events. End-organ function was normal for the chronic studies. We noted small surface lesions on one kidney from each chronic study as well as the presence of ring thrombus on connectors, as expected for these types of studies in animal models. The strategy and challenges imposed by performing a controlled cardiovascular device study in a juvenile lamb model are discussed. We believe that these successful implants demonstrate safety and performance for the PediVAS device for support of an IDE application to initiate human clinical trials and provide a roadmap for other researchers.

Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization.

BACKGROUND: Complete tumor regression may develop after neoadjuvant chemoradiation therapy for distal rectal cancer. Studies have suggested that selected patients with complete clinical response may avoid radical surgery and close surveillance may provide good outcomes with no oncologic compromise. However, definition of complete clinical response is often imprecise and may vary between different studies. The aim of this study is to provide a clear definition for a complete clinical response after neoadjuvant chemoradiation therapy in patients with distal rectal cancer in addition to actual endoscopic videos from patients managed nonoperatively. METHODS: Patients with nonmetastatic distal rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response at least 8 weeks after chemoradiation therapy completion. Complete and incomplete clinical responses were defined based on clinical and endoscopic findings. Patients with complete clinical response were not immediately operated on and were closely followed. Early and late endoscopic findings were recorded. RESULTS: Definition of a complete clinical response should be based on very strict clinical and endoscopic criteria. The finding of any residual superficial ulceration, irregularity, or nodule should prompt surgical attention, including transanal full-thickness excision or even a radical resection with total mesorectal excision. Standard or incisional biopsies should be avoided in this setting. Complete clinical responders should harbor no more than whitening of the mucosa, teleangiectasia with mucosal integrity to be considered for a nonoperative approach. In the presence of these findings, regularly scheduled reassessments may provide a safe alternative to these patients with early detection of recurrent disease. CONCLUSION: Strict definition of the clinical and endoscopic findings of patients experiencing complete clinical response after neoadjuvant chemoradiation therapy may provide a useful tool for the understanding of outcomes of patients managed with no immediate surgery allowing standardization of classifications and comparison between the experiences of different institutions.