Randomized controlled trials: a systematic review of laparoscopic surgery and simulation-based training.

INTRODUCTION: This systematic review was conducted to analyze the impact and describe simulation-based training and the acquisition of laparoscopic surgery skills during medical school and residency programs. METHODS: This systematic review focused on the published literature that used randomized controlled trials to examine the effectiveness of simulation-based training to develop laparoscopic surgery skills. Searching PubMed from the inception of the databases to May 1, 2014 and specific hand journal searches identified the studies. This current review of the literature addresses the question of whether laparoscopic simulation translates the acquisition of surgical skills to the operating room (OR). RESULTS: This systematic review of simulation-based training and laparoscopic surgery found that specific skills could be translatable to the OR. Twenty-one studies reported learning outcomes measured in five behavioral categories: economy of movement (8 studies); suturing (3 studies); performance time (13 studies); error rates (7 studies), and global rating (7 studies). CONCLUSION: Simulation-based training can lead to demonstrable benefits of surgical skills in the OR environment. This review suggests that simulation-based training is an effective way to teach laparoscopic surgery skills, increase translation of laparoscopic surgery skills to the OR, and increase patient safety; however, more research should be conducted to determine if and how simulation can become apart of surgical curriculum.

International women physicians' perspectives on choosing an academic medicine career.

UNLABELLED: Concerns about recruiting physicians into academic careers is an international issue. A qualitative study with United States (US) women physicians revealed insights into how, when, and why physicians choose an academic career in medicine. The current study explored international women physicians' perspectives on their career choice of academic medicine and determined if different themes emerged. We expanded the 2012 study of US women physicians by interviewing women physicians in Canada, Pakistan, Mexico, and Sweden to gain an international perspective on choosing an academic career. Interviews were thematically analyzed against themes identified in the previous study. Based on themes identified in the study of US physicians, qualitative analysis of 7 international women physicians revealed parallel themes for the following areas: Why academic medicine? Fit; People; Aspects of academic health centre environment. How the decision to enter academic medicine was made? Decision-making style; Emotionality When the decision to enter academic medicine was made? Practising physician; Fellowship; Medical student. Work-life balance, choosing academic medicine by default, serendipity, intellectual stimulation, mentors, research and teaching were among the areas specifically highlighted. CONCLUSION: Parallel themes exist regarding how, why, and when US and international women physicians choose academic medicine as a career path.

Patient factors affecting operative times for single-incision trans-axillary robotic-assisted (STAR) thyroid lobectomy: does size matter?

BACKGROUND: Single-incision, transaxillary, robotic-assisted (STAR) thyroid lobectomy using a robotic surgical system is a novel surgical approach that is extensively described in Korean patients. Some have suggested that this experience will not translate into the American population because of differing body habitus and because the mean size of the thyroid nodules removed in Korea are <1 cm. We reviewed our experience with STAR thyroid lobectomy. METHODS: We retrospectively reviewed our prospectively collected data on consecutive cases of STAR thyroid lobectomy performed by a single surgeon. Operative times and patient outcomes were evaluated. RESULTS: Seventeen operations were performed on 15 patients. Mean total operative time was 219.3 (range, 183-256) minutes. All patients were discharged on postoperative day 1. Postoperative complications were seromas (n = 2) and cellulitis (n = 2). Operative time did not vary with the size or volume of the nodule or gland. The mean nodule diameter was 1.9 (range, 0.5-3.1) cm. The mean nodule volume and thyroid volume were 5.0 (range, 0.1-16.7) cm(3) and 20.7 (range, 11.8-45.8) cm(3), respectively. When stratified by body mass index (range, 19.6-37.8), normal versus overweight or obese, total operative time increased from 204 to 225 min, and console time from 114 to 125 min. CONCLUSIONS: STAR thyroid surgery is a feasible technique. Factors, such as mass size, specimen volume, and patient body mass index, had little effect on operative times. These differences should not hinder the adoption of this procedure in North America, because new retractor systems help to overcome them. Further evaluation of this procedure is reasonable and safe.

Women physicians: choosing a career in academic medicine.

PURPOSE: Despite recent efforts to understand the complex process of physician career development, the medical education community has a poor understanding of why, how, and when women physicians embark on careers in academic medicine. METHOD: In 2010, the authors phone-interviewed women physicians in academic medicine regarding why, how, and when they chose academic medicine careers. Project investigators first individually and then collectively analyzed transcripts to identify themes in the data. RESULTS: Through analyzing the transcripts of the 53 interviews, the investigators identified five themes related to why women choose careers in academic medicine: fit, aspects of the academic health center environment, people, exposure, and clinical medicine. They identified five themes related to how women make the decision to enter academic medicine: change in specialty, dissatisfaction with former career, emotionality, parental influence, and decision-making styles. The authors also identified four themes regarding when women decide to enter academic medicine: as a practicing physician, fellow, resident, or medical student. CONCLUSIONS: Choosing a career in academic medicine is greatly influenced by the environment in which one trains and by people-be they faculty, mentors, role models, or family. An interest in teaching is a primary reason women choose a career in academic medicine. Many women physicians entering academic medicine chose to do so after or during fellowship, which is when they became more aware of academic medicine as a possible career. For many women, choosing academic medicine was not necessarily an active, planned decision; rather, it was serendipitous or circumstantial.

Recapitulation of pancreatic neuroendocrine tumors in human multiple endocrine neoplasia type I syndrome via Pdx1-directed inactivation of Men1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal syndrome caused by mutations in the MEN1 tumor suppressor gene. Whereas the protein product of MEN1, menin, is ubiquitously expressed, somatic loss of the remaining wild-type MEN1 allele results in tumors primarily in parathyroid, pituitary, and endocrine pancreas. To understand the endocrine specificity of the MEN1 syndrome, we evaluated biallelic loss of Men1 by inactivating Men1 in pancreatic progenitor cells using the Cre-lox system. Men1 deletion in progenitor cells that differentiate into exocrine and endocrine pancreas did not affect normal pancreas morphogenesis and development. However, mice having homozygous inactivation of the Men1 in pancreas developed endocrine tumors with no exocrine tumor manifestation, recapitulating phenotypes seen in the MEN1 patients. In the absence of menin, the endocrine pancreas showed increase in cell proliferation, vascularity, and abnormal vascular structures; such changes were lacking in exocrine pancreas. Further analysis revealed that these endocrine manifestations were associated with up-regulation in vascular endothelial growth factor expression in both human and mouse MEN1 pancreatic endocrine tumors. Together, these data suggest the presence of cell-specific factors for menin and a permissive endocrine environment for MEN1 tumorigenesis in endocrine pancreas. Based on our analysis, we propose that menin's ability to maintain cellular and microenvironment integrity might explain the endocrine- restrictive nature of the MEN1 syndrome.

Tumor-associated endothelial cells display GSTP1 and RARbeta2 promoter methylation in human prostate cancer.

BACKGROUND: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. METHODS: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARbeta2 promoters via the QMS-PCR method. RESULTS: Comparing GSTP1 and RARbeta2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. CONCLUSION: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.

A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas.

BACKGROUND: Preoperative imaging studies localize insulinomas in less than 50% of patients. Arteriography with calcium stimulation and venous sampling (ASVS) regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with the other localization procedures in patients with a sporadic insulinoma. METHODS: Between March 2001 and October 2004, 14 patients (7 women and 7 men; mean age, 53) with an insulinoma were enrolled in an IRB-approved protocol. Computed tomography, magnetic resonance imaging, ultrasound scan, and arteriography with calcium stimulation and venous sampling were performed preoperatively. A surgeon, blinded to the results of the localizing studies, performed a laparoscopic exploration with intraoperative ultrasound (IOUS). At the completion of the exploration, the success of laparoscopy for localization was scored, and the tumor was resected. RESULTS: Twelve of 14 tumors were localized successfully before laparoscopy (noninvasive, 7 of 14; invasive, 11 of 14). Laparoscopic IOUS localized successfully 12 of 14 tumors. All lesions were resected, and all patients were cured (median follow-up, 36 months). CONCLUSION: Laparoscopic IOUS identified 86% of tumors. The authors consider laparoscopic IOUS to be equivalent to ASVS in localizing insulinomas. Further study is therefore warranted to determine the role of laparoscopy with IOUS in the localization and treatment algorithm for patients with sporadic insulinoma.

Simultaneous targeting of CD3 on T cells and CD40 on B or dendritic cells augments the antitumor reactivity of tumor-primed lymph node cells.

To date, molecular targets chosen for Ab activation to generate antitumor effector cells have been confined on T cells, such as TCR/CD3, CD28, CD137 (4-1BB), CD134 (OX40), and inducible costimulator. In this report we investigated the immune function of murine tumor-draining lymph node (TDLN) cells after simultaneous Ab targeting of CD3 on T cells and CD40 on APCs. Anti-CD3 plus anti-CD40-activated TDLN cells secreted significantly higher amounts of IFN-gamma, but less IL-10, compared with anti-CD3-activated cells. In adoptive immunotherapy, ligation of CD3 and CD40 resulted in the generation of more potent effector cells in mediating tumor regression. Freshly harvested TDLN cells were composed of approximately 60% CD3+ T cells, 30-35% CD19+ B cells, 5% CD11c+ dendritic cells (DC), and few CD14+ or NK cells (each <3%). CD40 was distributed predominantly on B cells and DCs. Cell depletion indicated that simultaneous targeting was toward CD3 on T cells and CD40 on APCs, respectively. Elimination of APCs completely abrogated the augmented antitumor responses induced by anti-CD40. Either B cell or DC removal partially, but significantly, reduced the therapeutic efficacy conferred by CD40 engagement. Furthermore, the immunomodulation function of anti-CD40 was associated with its capability to increase IL-12 secretion while inhibiting IL-4 production. Our study establishes a role for CD40 expressed on B cells or DCs in the costimulation of TDLN cells. Eliciting antitumor activity via simultaneous targeting of CD3 on T cells and CD40 on APCs is relevant for the design of effective T cell-based cancer immunotherapy.

Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model.

BACKGROUND: Sentinel lymph node (SLN) biopsy allows surgeons to identify patients with subclinical nodal involvement who may benefit from lymphadenectomy and, possibly, adjuvant therapy. Several factors have been variably, and sometimes discordantly, reported to have predictive value for SLN metastasis to best select which patients require SLN biopsy. METHODS: We reviewed 419 patients who underwent SLN biopsy for melanoma from a prospectively collected melanoma database. To derive a probabilistic model for the occurrence of a positive SLN, a multivariate logistic model was fit by using a stepwise variable selection method. The accuracy of each model was evaluated by using receiver operator characteristic curves. RESULTS: On univariate analysis, the number of mitoses per square millimeter, increasing Breslow depth, decreasing age, ulceration, and melanoma on the trunk showed a significant relationship to a positive SLN. Multivariate analysis revealed that once age, mitotic rate, and Breslow thickness were included, no other factor, including ulceration, was significantly associated with a positive SLN. The data suggest that younger patients with tumors <1 mm may still have a substantial risk for a positive SLN, especially if the mitotic rate is high. CONCLUSIONS: In addition to Breslow depth, mitoses per square millimeter and younger age were factors identified as independent predictors of a positive SLN. This model may identify patients with thin melanoma at sufficient risk for metastases to justify SLN biopsy.

Isolated hepatic perfusion for the treatment of patients with advanced liver metastases from pancreatic and gastrointestinal neuroendocrine neoplasms.

BACKGROUND: We report results of using isolated hepatic perfusion (IHP) in patients with advanced progressive liver metastases (LM) from pancreatic and gastrointestinal neuroendocrine neoplasms (NENs). METHODS: Thirteen patients with LM from NENs (mean percent hepatic replacement, 30; range, 10-60) were treated with a 1-hour hyperthermic IHP via a laparotomy with the use of 1.5 or 2.0 mg/kg melphalan and/or 1 mg tumor necrosis factor. An oxygenated extracorporeal circuit with inflow through the gastroduodenal artery and common hepatic artery, and outflow to a segment of the inferior vena cava was used. Portal flow and inferior vena cava flow were shunted to the axillary vein. Radiographic response, recurrence pattern, and survival were assessed. RESULTS: Mean operative time was 9 hours (8-11 hours), and a median hospital stay was 10 days (6-64 days). Fifty percent of evaluable patients had a radiographic partial response in the liver (mean duration, 15 months; range, 6-26 months; 2 ongoing). Four had a marginal response (25%-49% reduction in the neoplasm). The median, hepatic, progression-free survival was 7 months (range, 3-27 months). The median actuarial survival was 48 months including 1 treatment mortality (median follow-up, 23 months). CONCLUSIONS: For patients with advanced LM from NENs, IHP provides a reasonable response rate and duration with acceptable morbidity; continued clinical evaluation is important.

Therapeutic effects of tumor reactive CD4+ cells generated from tumor-primed lymph nodes using anti-CD3/anti-CD28 monoclonal antibodies.

T-cell activation involves multiple signaling pathways. In this report, we conducted in vitro and in vivo immune function analysis of tumor-draining lymph node (TDLN) cells after anti-CD3/anti-CD28 activation versus anti-CD3 activation alone in a murine tumor model. In cytokine release assays, the doubly activated TDLN cells secreted significantly greater amounts of IFN-gamma and GM-CSF in response to specific tumor antigen compared with anti-CD3 activated cells. In adoptive immunotherapy, the doubly activated TDLN cells were more effective in mediating regression of 3-day pulmonary metastases compared with anti-CD3 activated cells. Although there was predominant proliferation of CD8+ cells after either activation procedure, the mean-fold expansion of CD4+ cells was significantly greater after anti-CD3/anti-CD28 activation than anti-CD3 activation alone. Using magnetic bead-enriched T-cell subsets, we found that either CD4+ or CD8+ doubly activated TDLN cells could independently mediate tumor regression. Furthermore, the doubly activated CD4+ cells were more effective than CD8+ cells in adoptive immunotherapy on a per-cell basis. The antitumor activity mediated by CD4+ or CD8+ cells could be significantly enhanced with the exogenous administration of IL-2. CD28 co-stimulation of tumor-primed lymphoid cells promotes the generation of potent tumor reactive effector cells, particularly CD4+ T cells, with antitumor activity in adoptive immunotherapy.