Faculty Bibliography

Tumor infiltrating lymphocytes (TILs) in primary melanomas are thought to represent the host anti-tumor immune response, but controversy exists over whether TILs offer independent prognostication of survival. We studied a cohort of 1241 primary melanoma patients to assess the association of absent, non-brisk, and brisk TIL grade with survival outcomes. We tested whether quantitative TIL counts using immunohistochemical lymphocyte markers CD3, CD45, and FOXP3 add prognostic value to TIL grading compared to histology alone in 15% of the cohort. To assess for inter-group immunologic heterogeneity among TIL grades, we investigated differential expression of 594 immunoregulatory genes in 67 primary melanomas. On histologic evaluation of 1241 primary melanomas, TILs were graded as absent (n=388, 31%), non-brisk (n=330, 27%), and brisk (n=523, 42%). Patients with brisk TILs had improved recurrence-free survival (RFS) (P=.025) and overall survival (OS) (P=.006) compared to patients with non-brisk and absent TILs, for which there were no differences in RFS (P=.40) or OS (P=.41). TIL quantitation by immunohistochemistry did not improve prognostication compared to TIL grading on hematoxylin and eosin stained sections. Melanomas with non-brisk and absent TILs share similar immunoregulatory gene expression profiles. In contrast, melanomas with brisk TILs demonstrate upregulation of T-cell activation pathways and inhibition of upstream immune checkpoint regulators. The presence of TILs in primary melanomas represents a heterogeneous group and caution in prognostic interpretation is warranted. Melanomas with brisk TILs are defined by an immunostimulatory gene expression profile and improved prognosis compared to melanomas with non-brisk or absent TILs.

OBJECTIVES: Professionalism education is a vital component of surgical training. This research attempts to determine whether an annual, year-long professionalism curriculum in a large surgical residency can effectively change professionalism attitudes. SUMMARY OF BACKGROUND DATA: The ACGME mandated 6 competencies in 2003. The competencies of Professionalism and Interpersonal/Professional Communication Skills had never been formally addressed in surgical resident education in the past. METHODS: A professionalism curriculum was developed focusing on specific resident professionalism challenges: admitting mistakes, effective communication with colleagues at all levels, delivering the news of an unexpected death, interdisciplinary challenges of working as a team, the cultural challenge of obtaining informed consent through an interpreter, and the stress of surgical practice on you and your family. These professionalism skills were then evaluated with a 6-station Objective Structured Clinical Examination (OSCE). Identical OSCE scenarios were administered to 2 cohorts of surgical residents: in 2007 (before instituting the professionalism curriculum in 2008) and again in 2014. Surgical residents were rated by trained Standardized Patients according to a behaviorally anchored professionalism criteria checklist. RESULTS: An analysis of variance was conducted of overall OSCE professionalism scores (% well done) as the dependent variable for the 2 resident cohorts (2007 vs 2014). The 2007 residents received a mean score of 38% of professionalism items "well done" (SD 9%) and the 2014 residents received a mean 59% "well done" (SD 8%). This difference is significant (F = 49.01, P < .001). CONCLUSIONS: Professionalism education has improved surgical resident understanding, awareness, and practice of professionalism in a statistically significant manner from 2007 to 2014. This documented improvement in OSCE performance reflects the value of a professionalism curriculum in the care of the patients we seek to serve.

PURPOSE: The identification of personalized germline markers with biological relevance for the prediction of cutaneous melanoma (CM) prognosis is highly demanded but to date it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating CM outcomes. EXPERIMENTAL DESIGN: Using whole genome eQTL data from a healthy population, we identified 385 variants -significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 CM patients for their association with overall (OS) and recurrence-free survival using Cox regression models. RESULTS: We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR 0.56, 95% CI 0.41-0.77; P= 0.0002) and rs6695772, controlling the expression of BATF3 (HR 1.64, 95% CI 1.19-2.24; P= 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR 1.92, 95% CI 1.43-2.60; P= 2.38e-5). CONCLUSIONS: Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of CM prognosis that are independent of current histopathological markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers.

BACKGROUND: The significant global variations in surgical oncology training paradigms can have a detrimental effect on tackling the rising global cancer burden. While some variations in training are essential to account for the differences in types of cancer and biology, the fundamental principles of providing care to a cancer patient remain the same. The development of a global curriculum in surgical oncology with incorporated essential standards could be very useful in building an adequately trained surgical oncology workforce, which in turn could help in tackling the rising global cancer burden. MATERIALS AND METHODS: The leaders of the Society of Surgical Oncology and European Society of Surgical Oncology convened a global curriculum committee to develop a global curriculum in surgical oncology. RESULTS: A global curriculum in surgical oncology was developed to incorporate the required domains considered to be essential in training a surgical oncologist. The curriculum was constructed in a modular fashion to permit flexibility to suit the needs of the different regions of the world. Similarly, recognizing the various sociocultural, financial and cultural influences across the world, the proposed curriculum is aspirational and not mandatory in intent. CONCLUSIONS: A global curriculum was developed which may be considered as a foundational scaffolding for training surgical oncologists worldwide. It is envisioned that this initial global curriculum will provide a flexible and modular scaffolding that can be tailored by individual countries or regions to train surgical oncologists in a way that is appropriate for practice in their local environment.

BACKGROUND: The significant global variations in surgical oncology training paradigms can have a detrimental effect on tackling the rising global cancer burden. While some variations in training are essential to account for the differences in types of cancer and biology, the fundamental principles of providing care to a cancer patient remain the same. The development of a global curriculum in surgical oncology with incorporated essential standards could be very useful in building an adequately trained surgical oncology workforce, which in turn could help in tackling the rising global cancer burden. MATERIALS AND METHODS: The leaders of the Society of Surgical Oncology and European Society of Surgical Oncology convened a global curriculum committee to develop a global curriculum in surgical oncology. RESULTS: A global curriculum in surgical oncology was developed to incorporate the required domains considered to be essential in training a surgical oncologist. The curriculum was constructed in a modular fashion to permit flexibility to suit the needs of the different regions of the world. Similarly, recognizing the various sociocultural, financial and cultural influences across the world, the proposed curriculum is aspirational and not mandatory in intent. CONCLUSIONS: A global curriculum was developed which may be considered as a foundational scaffolding for training surgical oncologists worldwide. It is envisioned that this initial global curriculum will provide a flexible and modular scaffolding that can be tailored by individual countries or regions to train surgical oncologists in a way that is appropriate for practice in their local environment. (c) 2016 Society of Surgical Oncology and the European Society of Surgical Oncology. Published by SpringerNature. All rights reserved.

BACKGROUND: The global cancer burden is predicted to rise significantly over the next few decades. While there are several barriers to providing optimal cancer care on the global stage, some are related to the absence of an adequately trained workforce. This could be attributed in part to the significant global variations in the training of surgical oncology professionals. There are currently no published data mapping the training pathways for surgical oncologists for all countries in the world. The aims of this descriptive article are to report on the training paradigms in surgical oncology for all countries in the world, and to correlate the influence of economic standing on these training paradigms. MATERIALS AND METHODS: The training paradigms for all countries in the world were analyzed and categorized on the basis of the six World Health Organization geographic regions and economic standing stratified by the Human Development Index. RESULTS: Data on the training paradigms were obtained for 174 countries from a total of 211 (82 %). We noted extremely significant and concerning variations in the length, availability and structure of training paradigms depending on the geographic region and economic standing. CONCLUSIONS: The results of our study demonstrated significant global variations in the training paradigms of surgical oncologists. These variations call for a global curriculum which has been developed by the Society of Surgical Oncology and the European Society of Surgical Oncology. It is hoped that this curriculum will serve a role in streamlining education to tackle the rising global cancer burden. (c) 2016 Society of Surgical Oncology and the European Society of Surgical Oncology. Published by SpringerNature. All rights reserved.

BACKGROUND: The global cancer burden is predicted to rise significantly over the next few decades. While there are several barriers to providing optimal cancer care on the global stage, some are related to the absence of an adequately trained workforce. This could be attributed in part to the significant global variations in the training of surgical oncology professionals. There are currently no published data mapping the training pathways for surgical oncologists for all countries in the world. The aims of this descriptive article are to report on the training paradigms in surgical oncology for all countries in the world, and to correlate the influence of economic standing on these training paradigms. MATERIALS AND METHODS: The training paradigms for all countries in the world were analyzed and categorized on the basis of the six World Health Organization geographic regions and economic standing stratified by the Human Development Index. RESULTS: Data on the training paradigms were obtained for 174 countries from a total of 211 (82%). We noted extremely significant and concerning variations in the length, availability and structure of training paradigms depending on the geographic region and economic standing. CONCLUSIONS: The results of our study demonstrated significant global variations in the training paradigms of surgical oncologists. These variations call for a global curriculum which has been developed by the Society of Surgical Oncology and the European Society of Surgical Oncology. It is hoped that this curriculum will serve a role in streamlining education to tackle the rising global cancer burden.

BACKGROUND: Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma. STUDY DESIGN: Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival. RESULTS: There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001). CONCLUSIONS: Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.