A career exploration didactic and simulation-based session increases student knowledge in and exposure to urology.

INTRODUCTION: Though urology attracts well-qualified applicants, students are not typically provided exposure to this smaller specialty until later in their medical education. While simulation-based training continues to supplement medical education, there is a lack of programming to teach specialty-specific procedural skills to medical students and those outside the specialty. We report a half-day simulation and didactic-based approach to increase exposure to urology to interested second-year medical students. METHODS: A half-day didactic- and simulation-based session was offered to second-year medical students (N=57). After a didactic-based overview of the specialty performed by urology providers and a surgical educator, the students participated in small-group simulations, including hands-on simulations. The students completed a post-curriculum survey measuring knowledge gains and soliciting feedback on the session. RESULTS: Students were 57.1% Caucasian, 66.7% female, with a mean age of 24.2 years; 80% stated they were potentially interested in pursuing a surgical specialty such as urology prior to the start of the session. Students reported pre- to post-curriculum gains in knowledge (mean=37%) about a career in urology and basic urologic procedures (p<0.001). Participants were also likely to recommend the curriculum to their peers (p<0.001). CONCLUSIONS: Given that exposure to urology in medical school is usually limited and offered later in training, a half-day didactic- and simulation-based experience for second-year students provides an early introduction and experience within the specialty and its common bedside procedures.

Temozolomide renders murine cancer cells susceptible to oncolytic adenovirus replication and oncolysis.

The preclinical evaluation of oncolytic adenoviruses (OAds) has been limited to cancer xenograft mouse models because OAds replicate poorly in murine cancer cells. The alkylating agent temozolomide (TMZ) has been shown to enhance oncolytic virotherapy in human cancer cells; therefore, we investigated whether TMZ could increase OAd replication and oncolysis in murine cancer cells. To test our hypothesis, three murine cancer cells were infected with OAd (E1b-deleted) alone or in combination with TMZ. TMZ increased OAd-mediated oncolysis in all three murine cancer cells tested. This increased oncolysis was, at least in part, due to productive virus replication, apoptosis, and autophagy induction. Most importantly, murine lung non-cancerous cells were not affected by OAd+TMZ. Moreover, TMZ increased Ad transduction efficiency. However, TMZ did not increase coxsackievirus and adenovirus receptor; therefore, other mechanism could be implicated on the transduction efficiency. These results showed, for the first time, that TMZ could render murine tumor cells more susceptible to oncolytic virotherapy. The proposed combination of OAds with TMZ presents an attractive approach towards the evaluation of OAd potency and safety in syngeneic mouse models using these murine cancer cell-lines in vivo.

Large-bowel disease presenting as small-bowel obstruction is associated with a poor prognosis.

INTRODUCTION: Small-bowel obstruction (SBO) is a common cause of admission to the surgical service. On rare occasions, a diagnosed SBO is actually due to large-bowel pathology combined with an incompetent ileocecal valve. The purpose of this study was to investigate this phenomenon. METHODS: We performed a retrospective medical record review of patients that were admitted with a diagnosis of SBO at University of Louisville hospital and the Veterans Affairs hospitals in Louisville, KY, from 2006 until 2014. RESULTS: A total of 498 patients were admitted with SBO during this time period. Forty-one patients were found to have an underlying large-bowel disease. The most common large-bowel pathologies included malignancy (51%), inflammation (15%), and infection (15%). Fifteen (43%) of these patients died during admission; 93% of these were due to either their bowel obstruction or the underlying disease state. This was significantly higher than the general population (9.4% mortality, 6% due to underlying disease). CONCLUSIONS: Patients that present with SBO due to a large-bowel source have a much higher mortality rate than those that present with other causes. Rapid identification of these patients will allow for more timely and appropriate treatment.

Combined therapy of oncolytic adenovirus and temozolomide enhances lung cancer virotherapy in vitro and in vivo.

Oncolytic adenoviruses (OAds) are very promising for the treatment of lung cancer. However, OAd-based monotherapeutics have not been effective during clinical trials. Therefore, the effectiveness of virotherapy must be enhanced by combining OAds with other therapies. In this study, the therapeutic potential of OAd in combination with temozolomide (TMZ) was evaluated in lung cancer cells in vitro and in vivo. The combination of OAd and TMZ therapy synergistically enhanced cancer cell death; this enhanced cancer cell death may be explained via three related mechanisms: apoptosis, virus replication, and autophagy. Autophagy inhibition partially protected cancer cells from this combined therapy. This combination significantly suppressed the growth of subcutaneous H441 lung cancer xenograft tumors in athymic nude mice. In this study, we have provided an experimental rationale to test OAds in combination with TMZ in a lung cancer clinical trial.