Faculty Bibliography

Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little is known about the mechanisms that drive innate therapeutic resistance in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) is overexpressed in pancreatic cancer and promotes tumor growth and metastasis. Our study reveals that increased ATDC levels protect cancer cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related factor 2 (NRF2). Mechanistically, ATDC binds to Kelch-like ECH-associated protein 1 (KEAP1), the principal regulator of NRF2 degradation, and thereby prevents degradation of NRF2 resulting in activation of a NRF2-dependent transcriptional program, reduced intracellular ROS and enhanced chemoresistance. Our findings define a novel role of ATDC in regulating redox balance and chemotherapeutic resistance by modulating NRF2 activity.

BACKGROUND:Although consensus guidelines generally discourage any surgical management (ASM; i.e., resection and/or transplantation) in patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT), recent series from Asia have challenged this paradigm. METHODS:Patients from the US Safety Net Collaborative database (2012-2014) with localized HCC and radiographically confirmed PVT were propensity-score matched based on demographic and clinicopathologic factors associated with receipt of ASM and overall survival (OS). OS was compared between patients undergoing ASM and those not selected for surgery. RESULTS:Of 1910 HCC patients, 207 (14.5%) had localized disease and PVT. The majority received either liver-directed therapies (LDTs; 34%) and/or targeted systemic therapies (36%). Twenty-one patients (10.1%) underwent ASM (resection [n = 11], transplantation [n = 10]); a third experienced any complication with no 30-day mortalities. Independent predictors of undergoing ASM were younger age, recent hepatology consultation, and lower model of end-stage liver disease (MELD) score. After matching for age, comorbidities, MELD, tumor size, receipt of LDT, or systemic therapy, OS was significantly longer for patients selected for ASM versus non-ASM patients (median not reached vs. 5.8 months, p < .001). CONCLUSION/CONCLUSIONS:In a large North American multi-institutional cohort, a minority of HCC patients with PVT were selected for ASM. Resection or transplantation was associated with improved survival and may have a role in the multimodality management in selected patients.

Management of patients with lung cancer continues to be challenging during the COVID-19 pandemic, due to the increased risk of complications in this subset of patients. During the COVID-19 surge in New York City, New York University Langone Health adopted triage strategies to help with care for lung cancer patients, with good surgical outcomes and no transmission of COVID-19 to patients or healthcare workers. Here, we will review current recommendations regarding screening and management of lung cancer patients during both a non-surge phase and surge phase of COVID-19.

BACKGROUND:Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC. METHODS:All patients with primary HCC in the US Safety-Net Collaborative database (2012-2014) were included. Patients were categorized into "safety-net" or "tertiary referral center" based on where they received treatment. Socioeconomic factors were determined at the zip-code level and included median income and percent of adults who graduated from high-school. Primary outcomes were receipt of treatment and OS. RESULTS:On MV Cox regression, neither race/ethnicity, median income, nor care provided at a SNH were associated with decreased OS (all p > 0.05). Independent predictors of decreased OS included lack of insurance (HR 1.34), less educational attainment (HR 1.59) higher MELD score (HR 1.07), higher stage at diagnosis (II:HR 1.34, III:HR 2.87, IV:HR 3.23), and not receiving treatment (HR 3.94) (all p < 0.05). Factors associated with not receiving treatment included history of alcohol abuse (OR 0.682), increasing MELD (OR 0.874), higher stage at diagnosis (III: OR 0.234, IV: OR 0.210) and care at a safety net facility (OR 0.424) There were no racial/ethnic or socioeconomic disparities in receipt of treatment. CONCLUSIONS:There is no intrinsic or direct association of race/ethnicity, socioeconomic status, or being treated at select safety-net hospitals with worse outcomes. Poor liver function, no insurance, and advanced stage of presentation are the main determinants of not receiving treatment and decreased survival.

BACKGROUND:Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC. METHODS:All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into "safety net" and "academic" based on where they received their care. The primary outcome was the OS. RESULTS:< .001), which persisted in a subset analysis of both academic and safety net populations. CONCLUSION/CONCLUSIONS:Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes.

BACKGROUND: Intraoperative instrument recounts are performed to avoid retained foreign surgical items. These additional counts, however, beget risks of their own, including prolonged operative times, exposure to radiation, and increased cost. Our study aimed to identify factors that increase the likelihood of instrument recounts during plastic surgery procedures, and use our findings to guide potential solutions for preventing unnecessary recounts across all surgical fields. STUDY DESIGN: This is a retrospective review of all plastic surgical cases in the main operating setting at New York University Langone Medical Center (NYULMC) between March 2014 and February 2015. RESULTS: Of 1285 plastic surgery cases, 35 (2.7%) reported a missing instrument necessitating a recount. Of all subspecialties within plastic surgery, only microsurgery conferred an increased risk of a recount event. We identified multiple factors that increased the odds of a recount event, including increased operative time, number of surgical sites, and intraoperative instrument handoffs. CONCLUSION: Instrument recounts, although designed to prevent inadvertently retained surgical items, present inherent risks of their own. In a large retrospective review of plastic surgery cases at our medical center, we identified many factors that increased the likelihood of an instrument recount. On the basis of our findings and prior literature, we recommend limiting the number of staff handling instrument, the number of handoffs, and a heightened awareness by surgeons and perioperative staff of specific procedures and factors that increase the risk of a miscount event.

PURPOSE: The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC) and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. METHODS: Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. RESULTS: Out of a total of 1964 patients, 190 (10%) patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p = 0.0003) compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p < 0.0001, p = 0.0007). A prior history of breast cancer was significantly associated with TNBC (p = 0.0003). There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. CONCLUSIONS: We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

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.