Faculty Bibliography

Background: Surgical resection is required for curative treatment of patients with extra-hepatic cholangiocarcinoma (EH-CCA). The objective of this study was to determine if the distance of surgical margin was associated with outcome.
Method(s): Patients who underwent curative-intent resection for EH-CCA between 2000 and 2015 at 10 hepatobiliary centers across the U.S. were evaluated using prospectively collected data. Cox proportional hazard model was utilized to evaluate the influence of the extent of the margin on outcome.
Result(s): 538 patients with EH-CCA who underwent curative-intent resection were included: 383 (71%) undergoing R0 resection, 153 (28%) undergoing R1 resection, and 2 with R2 resection. A negative surgical margin (R0) was associated with improved recurrence-free (RFS) and overall survival (OS) (RFS: 10.5% vs. 3.6% (R1) and OS: 25.8% vs. 9.3% (R1). Subsequently, further analysis on 161 patients with complete data on distance of resection margin, all undergoing R0 resection, was performed to assess the impact of extent of margin on outcome. On multi-variable analysis, the resection margin distance, analyzed as a continuous variable, was not associated with either improved RFS (RR 1.00, 95% CI 0.96-1.05; p 0.71) or OS (RR 0.99, 95% CI 0.96-1.01; p 0.49). Increasing age, increased tumor size, and LN metastasis were identified as independent predictors of OS; while RFS were mainly dependent on tumor size and LN metastasis (Table).
Conclusion(s): Achieving R0 resection is acceptable for EH-CCA tumors, and obtaining additional margin does not confer a benefit on overall survival. Increasing age, tumor size, and LN metastasis are independent predictors of RFS and OS, but increased margin width is not associated with improvement in either. Multivariable analysis of factors affecting OS of patients with extra-hepatic CCA who underwent surgical resection, with significant factors noted in bold

Vascular neoplasms of the head and neck present with a wide spectrum of signs and symptoms. Diagnosis requires a high index of suspicion and is usually made after tumors are large enough to be visually apparent or cause symptoms. This article discusses the most common acquired benign and malignant vascular tumors, with an emphasis on their evaluation and treatment.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

Purpose: Obesity is an established risk factor for many types of cancer. While obesity has been linked to worse long-term outcomes among patients with breast and colorectal cancer, the relationship of body mass index (BMI) and adrenocortical carcinoma (ACC) remains ill-defined. Since ACC can express adipokine and estrogen receptors, the impact of BMI on outcomes in this patient population is important. We sought to define the association of BMI on ACC clinical and biologic factors, as well as long-term survival. Methods: Data was obtained on 187 patients who underwent surgery for ACC at 13 institutions for whom BMI data were available. Patients were stratified according to the WHO classification of BMI: BMI<25, 25-29.9, 30-34.9, 35-39.9 and >=40. Demographics, tumor biology, management strategies and clinical outcomes were assessed relative to BMI category. Categorical data were analyzed by Fisher's exact test, while continuous variables were analyzed by ANOVA model; disease-free and overall survival were analyzed by Kaplan-Meier survival curves. Results: Mean BMI was 29.5, with a range of 19 to 69. Patient age was comparable among all BMI groups (p=0.9917). Patient sex (p=0.0079) and race (p=0.0373) varied by BMI category. Mean tumor size was 12.1 cm and mean tumor weight was 875 grams, which was similar in all BMI groups. AJCC stage (Stage I: n=12; Stage II: n=62; Stage III: n=47; and Stage IV: n=48) and ENSAT stage (Stage I: n=12; Stage II: n=62; Stage III: n=72; and Stage IV: n=23) did not vary by BMI. BMI tended to be associated with mean mitotic rate (BMI<25: 12.4; 25-29.9: 14.2; 30-34.9: 21.0; 35-39.9: 33.8 and >=40: 8.7; p=0.0773) and percent lymphatic invasion (BMI<25: 37%; 25-29.9: 68%; 30-34.9: 60%; 35-39.9: 67% and>=40: 44%; p=0.0818). In addition, R0 resection rate differed by BMI group (BMI<25: 68%; 25-29.9: 76%; 30-34.9: 50%; 35-39.9: 27% and >=40: 71%; p=0.0029). BMI was not associated with disease-free interval or overall survival. Conclusion: Increased BMI was associated with ACC tumor characteristics but did not affect disease-free or overall survival in our cohort. Further studies are needed to evaluate whether the endocrine effect of lipocytes influences ACC pathology

Background: Beyond the most common adenocarcinoma type, several gallbladder cancer (GBC) histologies have been described as being associated with more favorable (papillary) or less favorable outcome (adenosquamous, mucinous, signet ring). We sought to examine the added value of histologic type and grade on the existing AJCC staging system for resected GBC. Methods: Patients who underwent resection of GBC from 1988-2013 were identified using the Surveillance Epidemiology End Results (SEER) registry. A prognostic score was created by assigning points for T stage, N stage, grade and histology based on the regression coefficient in multivariate analysis. The score was externally validated using the US Extrahepatic Biliary Malignancy Consortium (USEBMC) database (2000- 2015) and compared with the AJCC staging system. Results: Of 7,915 patients identified in SEER, 83% had adenocarcinoma, 7% papillary, 4% adenosquamous, 4% mucinous, and 2% signet ring. In the USEBMC database, the frequencies of the respective histologies were 86, 9, 2, 1 and 2%. Median survival per histologic type, for SEER and USEBMC respectively, were 45 and 110 mos for papillary, 16 and 24 mos for adenocarcinoma, 14 and 12mos for mucinous, 8 and 4mos for adenosquamous, and 9 and 15mos for signet ring (P between histologies < 0.001 for both cohorts). On multivariate analysis, T stage, N stage, grade and histology were independent predictors of survival. The developed prognostic score, based on points for each of these 4 variables, showed excellent discriminatory ability both in the SEER and USEBMC cohorts. The AUC for the prognostic score was significantly improved compared with the AJCC system (0.69 vs. 0.64, both P < 0.001 using SEER, and 0.76 vs. 0.66, both P < 0.001 using USEBMC). Conclusions: The incorporation of histology and grade into the TNM system allows for a simple and accurate tool to determine prognosis following resection of GBC. (Table Presented)

Background: Although several studies have reported on actuarial survival outcomes following resection of hilar cholangiocarcinoma, the characteristics of patients who actually reached the 5-year milestone have not been adequately described. Methods: Patients who underwent resection for hilar cholangiocarcinoma from 2000-2015 in 10 US academic institutions participating in the Extrahepatic Biliary Malignancy Consortium were analyzed. Patients alive at last encounter with less than 5 years of follow-up were excluded. The clinicopathologic characteristics, perioperative, and long-term outcomes of actual 5-yr survivors and of patients who died within 5 years were compared. Results: Of 328 patients explored, 257 (78%) underwent curative resection and had an actuarial 5-year survival of 17%. After excluding 63 survivors with < 5 years follow-up, 194 patients were further classified as 5-year survivors (n = 23, 12%) and non-5-yr survivors. None of the 5-yr survivors had preoperative systemic biliary sepsis, portal vein embolization, T3 tumors with unilateral portal vein or hepatic artery invasion, or T4 tumors necessitating main portal vein or hepatic artery resection. However, actual 5-year survival was still achieved in the setting of bile duct resection only, R1 margins, poor differentiation, lymphovascular or perineural invasion, nodal metastasis, intraoperative blood transfusion, and serious postoperative complications. Fiveyear survival did not equal cure, as five 5-year survivors experienced disease recurrence, 2 before and 3 after the 5-year mark. There were ten actual 7-year survivors and four actual 10-year survivors. Conclusions: Although nodal metastasis, poor differentiation, and R1 margins are established predictors of poor outcome for hilar cholangiocarcinoma, the mere presence of these factors does not preclude patients from achieving a 5-year survival. In contrast, preoperative biliary sepsis, T3 or T4 stage, and the necessity for vascular resection and reconstruction appear to be prohibitive in reaching the 5-year milestone. This information can be utilized in the perioperative counseling of patients with this challenging malignancy