Faculty Bibliography

BACKGROUND: Melanoma patients who develop brain metastases (B-Met) have limited survival and are excluded from most clinical trials. In the current study, the authors attempted to identify primary tumor characteristics and clinical features predictive of B-Met development and post-B-Met survival. METHODS: A prospectively accrued cohort of 900 melanoma patients was studied to identify clinicopathologic features of primary melanoma (eg, thickness, ulceration, mitotic index, and lymphovascular invasion) that are predictive of B-Met development and survival after a diagnosis of B-Met. Associations between clinical variables present at the time of B-Met diagnosis (eg, extracranial metastases, B-Met location, and the presence of neurological symptoms) and post-B-Met survival were also assessed. Univariate associations were analyzed using Kaplan-Meier survival analysis, and the effect of independent predictors was assessed using multivariate Cox proportional hazards regression analysis. RESULTS: Of the 900 melanoma patients studied, 89 (10%) developed B-Met. Ulceration and site of the primary tumor on the head and neck were found to be independent predictors of B-Met development on multivariate analysis (P = .001 and P = .003, respectively). Clinical variables found to be predictive of post-B-Met survival on multivariate analysis included the presence of neurological symptoms (P = .008) and extracranial metastases (P = .04). Ulceration was the only primary tumor characteristic that remained a significant predictor of post-B-Met survival on multivariate analysis (P = .04). CONCLUSIONS: Primary tumor ulceration was found to be the strongest predictor of B-Met development and remained an independent predictor of decreased post-B-Met survival in a multivariate analysis inclusive of primary tumor characteristics and clinical variables. The results of the current study suggest that patients with ulcerated primary tumors should be prospectively studied to determine whether heightened surveillance for B-Met can improve clinical outcome. Cancer 2011. (c) 2010 American Cancer Society

Understanding how medical malpractice occurs and is resolved is important to improving patient safety and preserving the viability of a physician's career in academic medicine. Every physician is likely to be sued by a patient, and how the physician responds can change his or her professional life. However, the principles of medical malpractice are rarely taught or addressed during residency training. In fact, many faculty at academic medical centers know little about malpractice.In this article, the authors propose that information about the inciting causes of malpractice claims and their resolution should be incorporated into residency professionalism curricula both to improve patient safety and to decrease physician anxiety about a crucial aspect of medicine that is not well understood. The authors provide information on national trends in malpractice litigation and residents' understanding of malpractice, then share the results of their in-depth review of surgical malpractice claims filed during 2001-2008 against their academic medical center. The authors incorporated those data into an evidence-driven curriculum for residents, which they propose as a model for helping residents better understand the events that lead to malpractice litigation, as well as its process and prevention

In this study, we investigated the mechanism(s) of altered expression of protooncogene SKP2 in metastatic melanoma and its clinical relevance in patients with metastatic melanoma. The genomic status of SKP2 was assessed in cell lines by sequencing, single nucleotide polymorphism array, and genomic PCR. Copy number status was then evaluated for concordance with SKP2 mRNA and protein expression. SKP2 protein was further evaluated by immunohistochemistry in 93 human metastatic tissues. No mutations were identified in SKP2. Increased copy number at the SKP2 locus was observed in 6/14 (43%) metastatic cell lines and in 9/22 (41%) human metastatic tissues which was associated with overexpression of SKP2 protein. Overexpression of SKP2 protein in human tissues was associated with worse survival in a multivariate model controlling for the site of metastasis. Copy number gain is a major contributing mechanism of SKP2 overexpression in metastatic melanoma. Results may have implications for the development of therapeutics that target SKP2

The surgical management of primary cutaneous melanoma, from the diagnostic biopsy through the wide local excision and nodal staging, must be carefully planned, and the biology of the melanoma, microstaging and primary tumor pathologic features of the melanoma, location on the body, patient preferences, and comorbidities must be considered. The treating surgeon must balance preservation of oncologic principles, with optimization of functional and aesthetic outcome. This article reviews the rationale behind the surgical approach in the patient with a primary melanoma

Objective: Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation. Methods: 114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival. Results: High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006]. Conclusions: Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care

Background: Although the current median survival time of stage-IV melanoma patients is less than 12 months, there is a subset of patients who experience long-term survival. Due to poor response rates to standard cytotoxic agents in metastatic melanoma, patients are encouraged to participate in clinical trials, the overall impact of which has not been studied, however. The aim of our study was to identify the factors associated with long-term survival and to determine the impact of clinical trial enrollment on patient outcome. Methods: We studied stage-IV melanoma patients prospectively enrolled at New York University Medical Center from 2002-2008. Associations between clinicopathologic variables and overall post-stage-IV survival were examined. Kaplan-Meier survival analysis was used to identify univariate predictors of post-stage-IV survival and the independent effect of these variables was assessed in a multivariate Cox proportional hazards regression model. The associations between clinicopathologic variables and long-term survival status (>/=2 vs. <2 years) were examined by chi(2) analysis and the independent effect of these variables on the latter was assessed in a multivariate logistic regression model. Results: Site of metastasis, treatment (systemic vs. localized) and pretreatment lactate dehydrogenase (LDH) level independently correlated with post-stage-IV survival. Participation in clinical trials and normal LDH levels were associated with a long-term survival of >/=2 years. Conclusion: Our data suggest that enrollment in clinical trials independently correlates with prolonged survival after a diagnosis of stage IV melanoma.

Introduction: Surgery offers the only chance for cure in patients with pancreatic cancer. Currently, pancreaticoduodenectomy can be performed with a mortality of under 5% and a morbidity of 40-50%. Little, however, is known about outcomes of pancreaticoduodenectomy (PD) in octogenarians. This manuscript details outcomes after PD for adenocarcinoma in patients 80 years and older. Methods: From our comprehensive pancreatic adenocarcinoma database of 248 patients, we identified 200 patients who underwent PD (1990-2009). We categorized patients into two groups, according to age at time of surgery: Group I (>= 80 year-old) and Group II (< 80 year-old). The study end-points were length of post-operative stay (LOS), overall morbidity, 30-day mortality, overall survival (OS). Differences between groups were evaluated using t-test or chi-squared test. Survival was compared using Kaplan-Meier analysis and log-rank test. Results: There were 25 patients in group I (mean age 83.1) and 175 patients in Group II (mean age 64.4). Octogenarians had worse ECOG performance status (PS >= 1 in 90% vs. 50.8%, p < 0.01) and ASA score (ASA 3- 4 in 70.8% vs. 47.4%, p < 0.01). The two groups were similar in regard to underlying co-morbidities (including coronary artery disease, COPD, diabetes, chronic renal failure), operative time, rates of portal vein resection, intraoperative complications, blood loss, pathologic AJCC stage, status of resection margins. Octogenarians had longer LOS (20 vs. 13.7 days, p=0.01) and higher overall morbidity (68% vs. 44%, p=0.03). There was a single death in each group (p=0.23). At median follow-up of 13 months older patients had a median OS of 17.3 months compared to 13.1 months in younger patients (p=0.06). Conclusions: Surgical morbidity and LOS are significantly increased in octogenarians. However 30-day mortality was not significantly increased and OS was superior (but not statistically significant) when compared to younger patients. The decision for PD should be individualized and offered to carefully selected octogenarians

Background: The AJCC staging for pancreatic cancer is relatively non-discriminatory for prediction of survival after resection. At the Moffitt Cancer Center a prognostic score for patients with localized pancreatic cancer (AJCC <= IIb) has been developed. In the Moffitt Prognostic Index (MPI) patients are grouped in 5 risk categories on the basis of extra-pancreatic tumor extension, degree of differentiation and lymphatic invasion. The aim of this study is to assess the MPI's predictive value in an independent cohort of patients who underwent pancreaticoduodenectomy (PD) at the New York University. Methods From our retrospective pancreatic adenocarcinoma database of 248 patients, we identified and grouped by MPI category patients with AJCC stage <= IIb who underwent PD (1990-2009). Differences between groups were evaluated using ANOVA and chi-squared test. Overall survival (OS) for each group was estimated using the Kaplan-Meier method and compared using the log-rank statistic. Results Among 131 patients with stage Ia-IIb cancer, MPI could be calculated for 126 (96%). Only few patients fell in MPI lower-risk groups 1- 4 (respectively 1, 4, 3, 22), while the majority (96, 76.1%) fell in MPI group 5 (poor prognosis). The 5 groups were similar in demographics, underlying comorbidities, laboratory data, ASA score and ECOG performance status. There were no differences in operative time, blood loss, intra- and post-operative complications, length of stay, 30-day mortality. Pathology revealed more advanced stage in groups 3 to 5 (p=0.001). At mean follow-up of 18 months, there was no difference in median OS across MPI groups (respectively 19, 6, 16, 17, 12 months, p=0.91). Of note, AJCC staging did correlate with median OS (respectively 43, 12, 16, 11 months in stages Ia to IIb, p = 0.004). Conclusions In our experience the MPI performed worse than AJCC staging as a prognostic tool. The clustering of patients in the worst-prognosis group defied the very purpose of prognosis discrimination. Furthermore, in our experience MPI did not correlate with overall survival in patients undergoing DP for earlystage (<= IIb) pancreatic cancer