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Targeted inhibition of BRAF V600E achieves tumor control in a subset of advanced thyroid tumors. Nearly all tumors develop resistance, and some have been observed to subsequently undergo dedifferentiation. The molecular alterations associated with thyroid cancer dedifferentiation in the setting of BRAF inhibition are unknown. We analyzed targeted next-generation sequencing data from 639 advanced, recurrent and/or metastatic thyroid carcinomas, including 15 tumors that were treated with BRAF inhibitor drugs and had tissue sampled during or posttreatment, 8 of which had matched pretherapy samples. Pre- and posttherapy tissues from one additional patient were profiled with whole-exome sequencing and RNA expression profiling. Mutations in genes comprising the SWI/SNF chromatin remodeling complex and the PI3K–AKT–mTOR, MAPK, and JAK–STAT pathways all increased in prevalence across more dedifferentiated thyroid cancer histologies. Of 7 thyroid cancers that dedifferentiated after BRAF inhibition, 6 had mutations in these pathways. These mutations were mostly absent from matched pretreatment samples and were rarely detected in tumors that did not dedifferentiate. Additional analyses in one of the vemurafenib-treated tumors before and after anaplastic transformation revealed the emergence of an oncogenic PIK3CA mutation, activation of ERK signaling, dedifferentiation, and development of an immunosuppressive tumor microenvironment. These findings validate earlier preclinical data implicating these genetic pathways in resistance to BRAF inhibitors, and suggest that genetic alterations mediating acquired drug resistance may also promote thyroid tumor dedifferentiation. Implications: The possibility that thyroid cancer dedifferentiation may be attributed to selective pressure applied by BRAF inhibitor–targeted therapy should be investigated further.

BACKGROUND AND OBJECTIVES 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters may help distinguish malignant from benign adrenal tumors, but few have been externally validated or determined based on definitive pathological confirmation. We determined and validated a threshold for 18 F-FDG-PET/CT maximum standard uptake value (SUVmax) in patients who underwent adrenalectomy for a nonfunctional tumor. METHODS Database review identified patients with 18 F-FDG-PET/CT images available (training cohort), or only SUVmax values (validation cohort). Discriminative accuracy was assessed by area under the curve (AUC), and the optimal cutoff value estimated by maximally selected Wilcoxon rank statistics. RESULTS Of identified patients (n = 171), 86 had adrenal metastases, 20 adrenal cortical carcinoma, and 27 adrenal cortical adenoma. In the training cohort (n = 96), SUVmax was significantly higher in malignant versus benign tumors (median 8.3 vs. 3.0, p

PURPOSE Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.

OBJECTIVE To determine if there are differences in overall survival (OS) or event-free survival (EFS) in patients with and without concomitant extra-adrenal metastases undergoing adrenal metastasectomy. BACKGROUND There is growing interest in the use of local therapies in patients with oligometastatic disease. Previously published series have indicated that long-term survival is possible with resection. Adrenalectomy has been used to treat adrenal metastases in select patients. METHODS Patients who underwent adrenal metastasectomy from 1994 to 2015 were identified from a prospectively maintained institutional database of adrenalectomy patients, excluding adrenalectomies due to tumor extension or for palliation. Sites of disease, treatment history, and survival data were extracted from chart review. RESULTS One hundred seventy-four patients were included. Tumor histology included 68 nonsmall cell lung cancer, 34 renal cancer, 18 colorectal cancer, 11 melanoma cancer, 10 hepatocellular cancer, 8 sarcoma cancer, and 25 other cancers. The median follow-up among survivors was 5.2 (1-21) years. OS at 3 and 5 years was 50% and 40%, respectively. Patients with (n = 83) and without (n = 91) extra-adrenal metastases did not differ with respect to age, adrenal tumor size, or margin status. Median OS (3.3 years for patients with concomitant extra-adrenal metastases and 3.0 years for patients with isolated adrenal metastases; P = 0.816) and EFS (9.39 vs 9.59 months; P = 0.87) were similar. Factors negatively associated with OS included adrenal tumor size (P < 0.01), renal primary versus other (P < 0.01), and adrenal margin status (P < 0.01). CONCLUSIONS In selected patients undergoing adrenal metastasectomy, there were no significant differences in OS or EFS between patients with and without concomitant extra-adrenal metastases.

BackgroundThe ThyroSeq v2 next-generation sequencing assay (ThyroSeq) estimates the probability of malignancy in indeterminate thyroid nodules (ITN). Its diagnostic accuracy in different practice settings and patient populations is not well understood.MethodsWe analyzed 273 Bethesda III/IV ITN evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n=98 and 102), a multicenter healthcare system (n=60), and an academic medical center (n=13). The positive (PPV) and negative predictive values (NPV) of ThyroSeq, and distribution of final pathology were analyzed and compared to values predicted by Bayes Theorem.ResultsAcross 4 institutions, the PPV was 35% (22-43%), and NPV was 93% (88-100%). Predictive values correlated closely with Bayes Theorem estimates (r2=.84), although PPVs were lower than expected. RAS mutations were the most frequent molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10-37%), and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12-85%, NIFTP 5-46%).ConclusionsIn a multi-institutional analysis, ThyroSeq PPVs were variable and lower than expected. This is attributable to differences in the prevalence of malignancy, and variability in pathologist interpretations of non-invasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.

BACKGROUND: Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on disease specific outcomes is not known. METHODS: We retrospectively reviewed patients from 1986 to 2017 who underwent thyroidectomy with curative intent for MTC at our institution. The association of disease specific survival (DSS) and clinicopathologic features was examined using univariate and multivariate Cox regression. RESULTS: We identified 316 patients who underwent curative resection for medullary thyroid carcinoma. Overall and disease specific survival were 76% and 86% at 10-years. To investigate the effect of prophylactic ipsilateral lateral lymph node dissection, we analyzed 89 patients without known structural disease in the neck lymph nodes at the time of resection and preoperative calcitonin > 200 pg/ml, of which 45 had an ipsilateral lateral lymph node dissection (LND) and 44 did not. There were no differences in tumor size or preoperative calcitonin levels. There was no difference at 10 years in cumulative incidence of recurrence in the neck (20.9% LND vs 30.4% no LND, p=0.46), cumulative incidence of distant recurrence (18.3% vs 18.4%, p=0.97), disease specific survival (86% vs 93%, p=0.53), or overall survival at (82% vs 90%, p=0.6). CONCLUSION: Lateral neck dissection in the absence of clinical or radiologic abnormal lymph nodes is not associated with improved survival in patients with MTC.

Medullary thyroid carcinoma (MTC) is a rare nonfollicular cell-derived tumor. A robust grading system may help better stratify patients at risk for recurrence and death from disease. In total, 144 MTC between 1988 and 2018 were subjected to a detailed histopathologic evaluation. Clinical and pathologic data were correlated with disease specific survival (DSS), local recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Median age was 53 years (range: 3–88). Median tumor size was 1.8 cm (range: 0.2–11). Lymph node metastases were present in 84 (58%) cases while distant metastases at presentation were found in 9 (6%) patients. Seven (5%) had ≥5 mitoses/10 HPFs. Tumor necrosis was present in 30 cases (20%) while lymphovascular invasion occurred in 41 (28%) of tumors. Extra-thyroidal extension was found in 44 (31%) and positive margins were seen in 19 (14%). There was a strong correlation between increasing tumor size and tumor necrosis (p

Emerging data suggest that not all grade 3 (G3) pancreatic neuroendocrine neoplasms (panNENs) behave the same; tumor differentiation may predict outcome.Patients with G3 panNENs treated at our institution between 1999 and 2014 were identified. Demographics, response to therapy, and overall survival were determined.Forty-five patients were identified, 16 with G3 well differentiated pancreatic neuroendocrine tumors (WD-panNETs) and 29 with poorly differentiated neuroendocrine carcinomas (PDNEC). Median overall survival in G3 WD-panNET patients was 52.2 months (95% confidence interval, 19.3-86.9 months) compared with 10.1 months (95% confidence interval, 6.9-12.4 months) in PDNEC patients (P = 0.0009). Response rate to platinum agents was 10% in G3 WD-panNETs and 37% in PDNEC. Response rate to alkylating agents was 50% in G3 WD-panNETs and 50% in PDNEC.Both G3 WD-panNETs and PDNEC responded to platinum and alkylating agents. Overall survival was significantly greater in G3 WD-panNETs compared with PDNEC. These findings challenge current classification and suggest that G3 panNENs should be classified by morphology.

PURPOSE Adrenocortical carcinomas (ACC) are rare and aggressive malignancies with limited treatment options. This study was undertaken to evaluate the immunogenicity of ACC. PATIENTS AND METHODS Patients with advanced ACC were enrolled in a phase II study to evaluate the clinical activity of pembrolizumab 200 mg every 3 weeks, without restriction on prior therapy. The primary end point was objective response rate. Efficacy was correlated with tumor programmed death-ligand 1 expression, microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D) status, and somatic and germline genomic correlates. RESULTS We enrolled 39 patients with advanced ACC and herein report after a median follow-up of 17.8 months (range, 5.4 months to 34.7 months). The objective response rate to pembrolizumab was 23% (nine patients; 95% CI, 11% to 39%), and the disease control rate was 52% (16 patients; 95% CI, 33% to 69%). The median duration of response was not reached (lower 95% CI, 4.1 months). Two of six patients with MSI-H/MMR-D tumors responded. The other seven patients with objective responses had microsatellite stable tumors. The median progression-free survival was 2.1 months (95% CI, 2.0 months to 10.7 months), and the median overall survival was 24.9 months (95% CI, 4.2 months to not reached). Thirteen percent of patients (n = 5) had treatment-related grade 3 or 4 adverse events. Tumor programmed death-ligand 1 expression and MSI-H/MMR-D status were not associated with objective response. CONCLUSION MSI-H/MMR-D tumors, for which pembrolizumab is a standard therapy, are more common in ACC than has been recognized. In advanced ACC that is microsatellite stable, pembrolizumab provided clinically meaningful and durable antitumor activity with a manageable safety profile.

Long-term outcomes after curative resection in patients with germline RET mutations and medullary thyroid cancer (MTC) are highly variable and mutation-specific oncologic outcomes are not well-described. Sixty-six patients identified from 1986 to 2017 from a single-institution cancer database were assessed for recurrence and survival using Kaplan–Meier estimates, and correlated with clinicopathologic features using log-rank or Cox proportional hazards. Median follow-up was 9.3 years (range 0.3–31.5), median tumor diameter was 1.5 cm (range 0.1–7.5), and preoperative calcitonin was known in 41 patients [median 636 (range 0–9600)]. Overall survival (OS) of the cohort was 94% at 10 years, the cumulative incidence of locoregional recurrence was 38% at 10 years, and 19/24 (79%) patients underwent repeat neck operation. The cumulative incidence of distant recurrence was 27% at 10 years. Predictors of distant recurrence were tumor size, positive lymph nodes, and pre- and postoperative carcinoembryonic antigen, but not calcitonin. M918T mutation-bearing patients had 10-year distant recurrence-free survival of 0%, compared with 83% in all other patients (p

Surgery remains the most important treatment modality for most types of thyroid cancer. Thyroid cancers have a remarkable spectrum of clinical behavior; well-differentiated subtypes have excellent 10-year survival rates after surgery in contrast to anaplastic thyroid cancer, which is highly lethal even with aggressive treatment. The extent of thyroidectomy and lymph node dissection should be guided by cancer subtype, preoperative workup including imaging, and disease extent. Thyroidectomy should be carried out in a stepwise fashion with the goal of removing the gland and the cancer while limiting the risk of injury to the recurrent laryngeal nerve (RLN) and parathyroid glands. The surgeon should be vigilant in identifying RLN anatomy variability, and using intraoperative nerve monitor (IONM) can be a helpful adjunct to the surgeon, particularly in complex dissections. Critical to postoperative management is the recognition and treatment of complications from thyroidectomy and lymph node dissection. Surgery for recurrent thyroid cancer can be challenging, but good surgical and oncologic outcomes can be achieved with optimal surgical planning.

Background and Objectives Patients with metastatic RCC can undergo metastasectomy to improve survival time. Our goal was to provide and compare characteristics and oncological outcomes of RCC patients who underwent complete metastasectomy at a single organ site. Methods A total of 138 RCC patients were identified as undergoing complete metastasectomy at a single organ site including adrenal, lung, liver, pancreas, or thyroid. Competing risk regression analysis was used to assess RFS and CSS adjusting for several covariates. Results In this highly selected cohort, RFS and CSS was 27% and 84% at 5 years following metastasectomy, respectively. Univariate analysis revealed that removal of multiple tumors, younger age, and a shorter interval between nephrectomy and metastasis was associated with worse RFS. Larger tumors and sarcomatoid histology at nephrectomy was associated with worse CSS. We found no evidence that metastases at the time of RCC diagnosis influenced recurrence or survival. Tumor size, number of metastases resected, and time from nephrectomy to first recurrence was significantly different, but recurrence rates were not found to be significantly different, when compared across all organ sites. Conclusions These findings inform clinical and surgical management of select RCC patients with isolated metastasis to one of several organ sites. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

To analyze the natural history of small asymptomatic pancreatic neuroendocrine tumors (PanNET) and to present a matched comparison between groups who underwent either initial observation or resection. Management approach for small PanNET is uncertain. Incidentally discovered, sporadic, small (

Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined.To describe the kinetics of PTC tumor growth during active surveillance.Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States.Active surveillance.The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics.Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99).The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.

Of the three RAS oncoproteins, only HRAS is delocalized and inactivated by farnesyltransferase inhibitors (FTI), an approach yet to be exploited clinically. In this study, we treat mice bearing Hras-driven poorly differentiated and anaplastic thyroid cancers (Tpo-Cre/HrasG12V/p53flox/flox) with the FTI tipifarnib. Treatment caused sustained tumor regression and increased survival; however, early and late resistance was observed. Adaptive reactivation of RAS–MAPK signaling was abrogated in vitro by selective RTK (i.e., EGFR, FGFR) inhibitors, but responses were ineffective in vivo, whereas combination of tipifarnib with the MEK inhibitor AZD6244 improved outcomes. A subset of tumor-bearing mice treated with tipifarnib developed acquired resistance. Whole-exome sequencing of resistant tumors identified a Nf1 nonsense mutation and an activating mutation in Gnas at high allelic frequency, supporting the on-target effects of the drug. Cell lines modified with these genetic lesions recapitulated tipifarnib resistance in vivo. This study demonstrates the feasibility of targeting Ras membrane association in cancers in vivo and predicts combination therapies that confer additional benefit. Significance: Tipifarnib effectively inhibits oncogenic HRAS-driven tumorigenesis and abrogating adaptive signaling improves responses. NF1 and GNAS mutations drive acquired resistance to Hras inhibition, supporting the on-target effects of the drug. Cancer Res; 78(16); 4642–57. ©2018 AACR.

4112 Background: Adrenocortical carcinomas (ACC) are rare and aggressive. Treatment options are limited and marked by poor efficacy and substantial toxicity. In this phase II single-center study, the efficacy and safety of pembrolizumab was assessed in patients (pts) with advanced ACC. Methods: Enrolled pts were aged ≥18 y with advanced ACC, ECOG ≤ 1, available tumor samples for biomarker analysis. Pts received pembrolizumab 200 mg Q3W for 2 y or until disease progression, intolerable toxicity, physician/patient decision to stop treatment. Imaging was performed every 9 wks. Tumor PD-L1 positivity (modified proportion score ≥ 1% or presence of stromal interface) was evaluated. Primary endpoint was ORR (by RECIST v1.1). Secondary endpoints included DOR, PFS, OS, safety. Somatic and germline next-generation sequencing was performed. Results: 39 pts were treated. Median age 62 (range, 19-87), 28% ECOG 0, 72% received ≥ 1 therapy. In available samples to date, 7/31 (23%) PD-L1+. At time of analysis, median follow-up among survivors was 17.8 mo (range, 5.4-34.7). ORR was 23.1% (95% CI, 11.1-39.3); 0 CR, 9PR. Seven pts (17.9%) had SD as best response. Among the 9 PRs, median time to PR was 4.1 mo (range, 1.7-10.5) and median DOR was not reached (95% CI, 4.1-not reached). Three pts achieving PR have completed 2 y of treatment with ongoing response noted. Tumor PD-L1 status is currently available in 6 pts with PR, 2/6 (33%) PD-L1+. Median PFS was 2.1 mo (95% CI, 2.0-10.7). Median OS was 24.9 mo (95% CI, 4.2-not reached); 2-year OS rate was 50% (95% CI, 36-69%). In the 34 tested tumors, germline testing identified 2 PR pts with Lynch syndrome; the remaining 7 PRs were MSS. Median tumor mutation burden for all PRs was 4.1 mutations/megabase (range, 0-31.5). There was no significant relationship between somatic alterations and response to treatment. Grade 3/4 treatment-related AEs occurred in 7/39 (17.9%) pts. Two pts discontinued therapy due to AEs; both pts achieved PRs and continue to respond. All pts with PRs had LFT elevation ≥ grade 2. Conclusions: Pembrolizumab demonstrated antitumor activity and was well tolerated in advanced ACC. Durable responses were noted. Complete evaluation of tumor PD-L1 and microsatellite status will be reported at the meeting. Clinical trial information: NCT02673333.

Bilateral (or four gland) exploration remains an important component of parathyroid surgery.

Purpose Based largely on reports that predate modern reporting standards, mitotane has been considered a systemic treatment option for both hormone control and antitumor control of metastatic adrenocortical cancer (ACC), although the therapeutic window is narrow. Methods We searched electronic medical records to identify patients with metastatic ACC treated and prescribed single-agent mitotane at Memorial Sloan Kettering Cancer Center from March 15, 1989–September 18, 2015. Reference radiologists reviewed all imaging and determined efficacy according to Response Evaluation Criteria in Solid Tumors 1.1. Patient demographics, toxicities, and treatment outcomes were reviewed. Next-generation sequencing was performed in selected cases. Results Thirty-six patients were identified. The mean age was 54 and 50% had functional tumors. Grade 3 or greater toxicities were documented in 16 out of 36 patients (44%) and 17% had documented long term adrenal insufficiency. Progression of the disease as the best response occurred in 30 out of 36 patients (83%) and one patient (3%) experienced clinical progression. Three patients achieved a complete response (CR) (8%), one patient achieved a partial response (3%), and one patient (3%) had stable disease after slow disease progression prior to initiation of therapy (durable for 6 months). All responders had nonfunctional tumors. Next-generation sequencing in two of the three CR patients was performed and failed to identify any novel alterations. Conclusion In this retrospective series, mitotane had a low response rate and low tumor control rate; however, a disproportionately high complete response rate suggested it should be used in selected individuals. Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities. Biomarkers are desperately needed to further define this disease.

Praise for the previous edition: "At once a textbook, a surgical atlas, and a source of current practice guidelines...This is a high-quality, thorough and insightful resource that provides accessible and essential information...recommend[ed]." -- Doody's Review Thyroid and Parathyroid Diseases, Second Edition, has been revised and updated to reflect recent advances in the medical and surgical management of thyroid and parathyroid diseases. This new edition serves as both a comprehensive guide to patient evaluation as well as an atlas of advanced surgical techniques for managing patients needing operative intervention. Separate chapters are devoted to minimally invasive techniques and remote access/robotic thyroidectomy techniques, both of which have enjoyed increased application throughout the world. New in the second edition: * A section on state-of-the-art, evidence-based management of challenging parathyroid conditions such as multiple endocrine neoplasia and renal hyperparathyroidism * A more detailed discussion of thyroid cancer evaluation and staging * A new chapter dedicated to parathyroid cancer * Nearly 200 additional full-color illustrations This new edition is a valuable resource for all surgeons, endocrinologists, and residents seeking to expand their knowledge of thyroid and parathyroid diseases, as well as seasoned clinicians who want to improve patient care and incorporate the latest surgical advancements into their practice.

This chapter will focus on anaplastic thyroid carcinoma (ATC), thyroid lymphoma, and metastases to the thyroid gland from non-thyroid cancers. Although these entities represent three uncommon clinical scenarios, thyroid physicians should be knowledgeable on how to manage each. ATC is a highly lethal disease with survival usually measured in months. Management should be focused on diagnosis, appropriate counseling, and supportive care, and when possible, clinical trial enrollment. Thyroid lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), is not typically treated with thyroidectomy, but patients often present to the surgeon for initial management and biopsy. Lastly, metastatic disease that has spread to the thyroid gland has a number of important considerations, most notably that patients undergoing thyroid metastasectomy should be highly selected and offered resection only after multidisciplinary evaluation.

Background: Somatostatin receptor ligands are used for the detection and treatment of neuroendocrine tumors. Mutations of MEN1 are frequently observed in human pancreatic neuroendocrine tumors (PanNETs). We utilized a previously described murine model of PanNET that harbors a floxed Men1 allele to study the feasibility of somatostatin receptor type 2 (SSTR2) imaging and therapy in mice. Methods: Mice with pancreatic-specific expression of Cre recombinase and floxed Men1 (Pdx1-cre, Men1f/f) were aged to 9-12 months to allow for the development of PanNETs. Mice were injected with either the SSTR2 agonist 68Ga-DOTA-TATE or antagonist 177Lu-DOTA-JR11 via tail vein. Imaging with 68Ga-DOTA-TATE was performed using PET/CT. Percent uptake of injected activity was calculated for visualized tumors. 177Lu-DOTA-JR11 binding was visualized with autoradiography. Immunofluorescence (IF) detected SSTR2 expression and a marker of DNA damage (γ-H2AX). Results: IF staining for SSTR2 showed membranous localization of the receptor limited to areas of neoplasia with high and low levels of SSTR2 expression variable by individual animal and tumor. Tumors were successfully detected in mice injected with 68Ga-DOTA-TATE using PET/CT. The mean maximum percent uptake of injected activity for visualized tumors was 2.8% +/- 0.34. Injection of 177Lu-DOTA-JR11 and subsequent autoradiography confirmed localization of radionuclide to areas of histology-confirmed neoplasia. Treatment effect (DNA damage) was observed with co-localization of γ-H2AX and SSTR2 staining in neoplastic areas as compared to hyperplastic islets and normal pancreatic parenchyma that were both SSTR2 and γ-H2AX negative. Conclusion: PanNETs from Pdx1-cre, Men1f/f mice can be successfully imaged and treated using somatostatin-based radionuclides. This genetically accurate model can be employed to study peptide receptor radionuclide therapy efficacy and toxicity either alone or in combination with other treatment strategies. Citation Format: Janet W. Li, Hanwen Zhang, Sean D. Carlin, Nitya Raj, David S. Klimstra, Steven K. Libutti, Wolfgang A. Weber, Diane Reidy-Lagunes, Brian R. Untch. Somatostatin receptor-based imaging and treatment of murine pancreatic neuroendocrine tumors induced by MEN1-loss [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3735.

275 Background: To assess the utility of molecular profiling to predict tumor biology, we performed next-generation sequencing (NGS) of metastatic well differentiated (WD) pancreatic neuroendocrine tumors (panNETs) in the routine practice setting. Our institutional NGS platform allows for evaluation of genetic alterations that contribute to tumorigenesis (sequence variants, copy number alterations, insertions/deletions, select rearrangements) as well as somatic loss of heterozygosity (LOH). Methods: NGS was performed using MSK-IMPACT, a matched tumor-normal sequencing platform that interrogates 468 cancer-related genes. LOH for all cases was determined by analysis of total, allele-specific, and integer DNA copy number genome-wide using the FACETS algorithm. Results: Since 2014, NGS has been performed in 96 tumor samples from 80 patients. The most commonly altered genes were MEN1 (56%), DAXX (40%), ATRX (25%), and TSC2 (25%). LOH was highly prevalent, identified in 51/96 samples (53%). A significant association (q-value < 0.05) was noted between LOH and the presence of altered MEN1, DAXX, PTEN, or TSC2. LOH was recurrently observed in chromosomes 1, 2, 3, 6, 8, 10, 11, 15, 16, 21, and 22. Since MEN1 alterations predict improved outcome, comparison was made between patients with LOH present/MEN1 wild type (WT) tumors (n = 16) and LOH absent/MEN1 altered tumors (n = 21); inferior overall survival (OS) was noted with LOH present/MEN1 WT status (p < 0.01). High grade pathology was observed in 6/16 (38%) LOH present/MEN1 WT tumors and in 1/21 (5%) LOH absent/MEN1 altered tumors (p < 0.0001). The mean Ki-67 index of LOH present/MEN1 WT tumors was 22% and that of LOH absent/MEN1 altered tumors was 9%. Conclusions: This is the first study to report widespread somatic LOH in metastatic WD panNETs. PanNETs appear to exhibit more LOH overall than virtually any tumor type studied. In this cohort, LOH was a prognostic marker of inferior OS and was associated with more aggressive pathologic features. LOH warrants further investigation as it may help better characterize these clinically heterogeneous tumors.

Background Successful parathyroidectomy for sporadic primary hyperparathyroidism (pHPT) is predicted by a 50% drop in PTH intra-operatively. Vitamin D is a known inhibitor of PTH secretion and is associated with secondary HPT following adenoma resection. This study examined the impact of 25-hydroxyvitamin D (25OHD) deficiency on perioperative PTH kinetics and outcomes following parathyroidectomy. Methods Patients undergoing adenoma resection for pHPT (n=93) had PTH levels recorded at six perioperative time points. Preoperative 25OHD levels were examined retrospectively. Patients were considered 25OHD deficient if the level was

The fate of the circulatory system in response to vascular injury is governed by a series of complex biochemical reactions involving cellular elements and plasma proteins. Alteration of this hemostatic balance can result in excessive bleeding or procoagulant complications. In the field of vascular surgery, modulation of this process can have severe implications with respect to the maintenance of vascular conduit patency by avoiding thromboembolic events and the prevention of excess bleeding in the operative setting. The nature of the hemostatic response in the setting of surgical-induced injury and stress is increasingly complex and not fully understood. When faced with the management of bleeding in the operative setting, the vascular surgeon must first understand the theories of hemostatic regulation before adapting these concepts to the surgical milieu. This review addresses the management of blood loss in the setting of vascular surgery. In so doing, insight will be shed on the interdependence and manipulation of hemostatic events as they relate to surgery. Topics related to preoperative evaluation, surgical technique, monitoring, and pharmacologic manipulation will be discussed.

Anaplastic thyroid carcinoma, thyroid lymphoma, and secondary metastasis to the thyroid gland are uncommon thyroid malignancies. They represent significant challenges for the surgeon owing to difficulties in diagnosis, aggressive biology, and the infrequency of their presentation. An awareness and appreciation of multimodality treatment strategies is essential for their management.

Isolated pancreatic metastases may occur in patients with many types of cancer. Several retrospective case series have been published demonstrating the feasibility of resection in selected patients. Here we report our experience with pancreatic metastasectomy in 70 patients and review the published literature. Our findings suggest that long-term survival is associated with resection in selected patients but these outcomes must be weighed against the significant morbidity that is associated with pancreatic resection.

INTRODUCTION AND OBJECTIVES: Carefully selected renal cell carcinoma (RCC) patients with isolated metastases undergoing metastasectomy can have prolonged survival. The goal of this study was to evaluate the oncologic outcomes in patients undergoing metastasectomy from 5 organ sites. METHODS: RCC patients were identified from 5 individual organ-based databases from a single institution and analyzed. Synchronous patients (distant metastases at nephrectomy or within 6 months (mos) of nephrectomy) were compared to metachronous patients (recurrence greater than 6 mos from nephrectomy). Patients with diffuse metastases at the time of nephrectomy or residual disease after metastasectomy were excluded. RESULTS: There were 138 patients undergoing metastasectomy for RCC in this study with a median follow-up of 2.4 years (range: 0-14.2 years) after metastasectomy. The lung was the most commonsite ofmetastasectomy (n1⁄478, 57%) followedby adrenal (n1⁄427, 20%), liver (n1⁄412, 9%), pancreas (n1⁄415, 11%), and thyroid (n1⁄46, 4%). The 5-year overall survival (OS) after nephrectomy was 88% and the 5 year OS after metastasectomy was 73%. Patients undergoing resection of synchronous metastases (n1⁄432) did not differ from those with metachronous metastases (n1⁄4106) with respect to age, gender, KPS, histology, primary tumors size, metatasectomy site or number of metastases. Median recurrence-free survival was similar after metastasectomy between synchronous and metachronous patients (Hazard ratio for metachronous: 0.76, 95% CI: 0.4-1.2). However, univariate analysis for OS identified initial metachronous presentation (p1⁄40.02), time from initial recurrence diagnosis to metastasectomy >12 mos (p1⁄40.02), and disease free interval (DFI) >6 mos after metastasectomy (p

Ecarin clotting time (ECT) is currently developed for the specific monitoring of antithrombin drugs, such as hirudin, argatroban, and hirulog. Aqueous reagent and dry chemistry technology have become available for ECT monitoring of antithrombin agents. Currently, many heparinoids and heparinomimetic drugs are being developed. These agents activate heparin cofactor 11 (HCII) and primarily mediate their effects by inhibiting thrombin. Atthough the test is specific for antithrombin agents, heparin cofactor II-mediated thrombin inhibitors are capable of prolonging the ECT. In order to study the relative effects of some of these agents, ECT was measured in human plasma supplemented with PI-88 (a sutfated pentomanose ; Progen Industries Limited. Sydney, Australia), aprosulate, pentosan polysulfate, dermatan Sulfate, unfractionated heparin (UFH), and recombinant hirudin (r-hirtadin). All agents were supplemented to the citrited-pooled plasma prepared from 10 healthy volunteers at a graded dosage of 0 to 100 These techniques gave comparable results for all of the agents used (PI-88. r2 = 0.99; r-hirudin, r2= 0.98, UFH. r2 =0.98; dermatan sutfate, r2 = 0.95; aprosulate, r2 = 0.95; pentosan polysulfate, r2 = 0.94). The relative anticoagulant effects of various agents used on ECT varied widely, exhibiting their potency in the following order: r-hirudin = pentosan polysulfate > dermatan sulfate > PI-88 > aprosulate > UFH. The sensitivity of ECT was adjusted by varying the concentration of the ecarin reagent. The results suggest that HCIImediated inhibition of thrombin can be detected by using ECT reagents.

At our institution, thyroid lobectomy is employed as a definitive operation for unifocal intrathyroidal low risk cancers and thus completion thyroidectomy is rarely performed. The purpose of this study was to identify the indications for selective completion thyroidectomy and to report oncologic outcomes. A retrospective review was performed to identify patients who underwent planned completion thyroidectomy for well-differentiated thyroid carcinoma (WDTC) from 2001 to 2010 based on initial lobectomy pathology. Assessment for risk of recurrence was based on the American Thyroid Association Initial Risk Stratification. During the 10-year study period, 79 patients underwent completion thyroidectomy for WDTC. Forty-four (56 %) patients were low risk and 35 (44 %) were intermediate risk. Completion thyroidectomy was recommended for 64 patients, whereas 15 patients were given an option of surveillance but ultimately decided to have surgery. Patients in the “recommended group” had more T3 tumors and fewer T1a tumors (p = 0.005 and 0.006, respectively). These patients also were more likely to be intermediate risk (p = 0.008) and to present with aggressive histology (p = 0.002). The rate of contralateral tumors (n = 27) was similar between both groups (35 and 33 %, respectively). Contralateral cancers were micropapillary in 24 of 27 (89 %) patients, 10 (40 %) of whom had multifocal disease. There were two pulmonary recurrences and no local-regional recurrences (median follow-up of 42.3 months). Completion thyroidectomy is infrequent and performed for a select group of intermediate and low risk WDTCs at our institution with low recurrence rates. Incidental multifocal and unifocal contralateral cancers are common after completion thyroidectomy.

Duodenal neuroendocrine tumors are rare and few studies exist to guide surgical management. This study identifies factors associated with recurrence after resection. A retrospective, single institution review was performed between 1983 and 2011 on patients with a pathologic diagnosis of duodenal neuroendocrine tumor. Tumor grade was assigned based on WHO 2010 criteria (Ki-67 and mitotic rate). Seventy-five patients were identified that underwent curative resection. This included 12 patients with endoscopic mucosal resection, 34 that had local resection, and 29 that underwent pancreaticoduodenectomy. Two-year and 5-year recurrence-free survival was 84 and 81 %, respectively. There were 11 tumor recurrences (either local or distant), and four patients died of their disease (3/4 had high-grade lesions) with an overall median follow-up of 27 months. On univariate analysis, tumor size and tumor grade were identified as being associated with recurrence, but not intervention type, lymph node metastases, ampullary location, or margin status. Tumor grade and size are associated with recurrence-free survival in duodenal neuroendocrine tumors. When feasible, a less aggressive surgical approach to treat low-grade and low-stage duodenal NETs should be considered.

An area of ongoing controversy in the management of patients with differentiated thyroid cancer is the role of prophylactic central neck dissection (pCND). This review describes the natural history of differentiated thyroid cancer and provides the limited data regarding the role of routine pCND. An evidence-based analysis was performed of the rationale for routine pCND was performed, including reduced rates of central neck recurrence, reduced morbidity with secondary central neck lymphadenectomy, improved rates of postoperative athyroglobulinemia, and improved stratification of radioactive iodine (RAI) dosage. A critical appraisal of the available literature demonstrates insufficient evidence to indicate that this extra procedure performed routinely leads to improvement in clinically meaningful end points.

Recurrent laryngeal nerve (RLN) injury is a rare complication for patients undergoing neck exploration for primary hyperparathyroidism (pHPT). Distances between RLNs and parathyroid adenomas have not been previously published. In this study we used a RLN monitor to identify the RLN and to measure the proximity to parathyroid tumors. Patients with pHPT (n = 136) underwent neck exploration and had the clinical data recorded prospectively. Adenomas were recorded in 1 of 4 locations (right upper, right lower, left upper, left lower). Measurement of RLN to adenoma distances were recorded intraoperatively with the gland in situ. The RLN location was confirmed with a RLN monitor. The average RLN to adenoma distance was 0.52 ± 0.52 cm. Adenomas in the right upper position were significantly closer to the nerve (0.25 ± 0.39 cm) compared with adenomas in the left upper (0.48 ± 0.61 cm, p = .03), left lower (0.70 ± 0.53 cm, p

Surgeon-performed cervical ultrasound (SUS) and 99Tc-sestamibi scanning (MIBI) are both useful in patients with primary hyperparathyroidism (PHPT). We sought to determine the relative contributions of SUS and MIBI to accurately predict adenoma location.We performed a database review of 516 patients undergoing surgery for PHPT between 2001 and 2010. SUS was performed by 1 of 3 endocrine surgeons. MIBI used 2-hour delayed anterior planar and single-photon emission computerized tomography images. Directed parathyroidectomy was performed with extent of surgery governed by intraoperative parathyroid hormone decline of 50%.SUS accurately localized adenomas in 87% of patients (342/392), and MIBI correctly identified their locations in 76%, 383/503 (p0.001). In patients who underwent SUS first, MIBI provided no additional information in 92% (144/156). In patients who underwent MIBI first, 82% of the time (176/214) SUS was unnecessary (p = 0.015). In 32 patients SUS was falsely negative. The reason for these included gland location in either the deep tracheoesophageal groove (n = 9) or the thyrothymic ligament below the clavicle (n = 5), concurrent thyroid goiter (n = 4), or thyroid cancer (n = 1). In 13 cases, the adenoma was located in a normal ultrasound-accessible location but was missed by the preoperative exam. In the 32 ultrasound false-negative cases, MIBI scans were positive in 21 (66%). Of the 516 patients, 7.6% had multigland disease. Persistent disease occurred in 4 patients (1%) and recurrent disease occurred in 6 (1.2%).When performed by experienced surgeons, SUS is more accurate than MIBI for predicting the location of abnormal parathyroids in PHPT patients. For patients facing first-time surgery for PHPT, we now reserve MIBI for patients with unclear or negative SUS.

A relationship between primary hyperparathyroidism (PHPT) and obesity has been observed but is incompletely understood. Furthermore, obesity has been associated with vitamin D deficiency, suggesting that the three conditions may be linked.We hypothesized that PHPT in morbidly obese patients is more severe and that the difference may be explained by vitamin D deficiency. DESIGN AND SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Records of 196 patients with surgically treated PHPT and known body mass index (BMI) were examined. Patients were stratified into three BMI groups: group I (nonobese), BMI25 kg/m(2) (n = 54); group II (non-severely obese), BMI 25-34 kg/m(2) (n = 102); and group III (severely obese), BMI 35 kg/m(2) or greater (n = 40).Preoperative PTH levels were higher in group ΙΙΙ compared with group Ι (181 ± 153 vs. 140 ± 80 pg/ml, p = 0.04). Group III patients had larger tumors on average compared with group I (1.8 ± 1.5 vs. 1.04 ± 1.5 g, P = 0.0002). In group III, BMI positively correlated with parathyroid tumor weight (r = 0.5, P = 0.002). Postoperative PTH was higher in group III compared with group Ι (61 ± 41 vs. 44 ± 28 pg/ml, P = 0.02). There was higher frequency of depression, musculoskeletal symptoms, weakness, and gastroesophageal reflux disease in group III patients.BMI positively correlated with parathyroid tumor weight independent of vitamin D. Severely obese patients have larger parathyroid tumor weight, higher pre- and postoperative PTH, and greater symptoms.

Feasibility and reproducibility of microarray biomarkers in clinical settings are doubted because of reliance on fresh frozen tissue. We sought to develop and validate a paradigm of frozen tissue collection from early breast tumors to enable use of microarray in oncology practice. Frozen core needle biopsies (CNBx) were collected from 150 clinical stage I patients during image-guided diagnostic biopsy and/or surgery. Histology and tumor content from frozen cores were compared to diagnostic specimens. Twenty-eight patients had microarray analysis to examine accuracy and reproducibility of predictive gene signatures developed for estrogen receptor (ER) and HER2. One hundred twenty-seven (85%) of 150 patients had at least one frozen core containing cancer suitable for microarray analysis. Larger tumor size, ex vivo biopsy, and use of a new specimen device increased the likelihood of obtaining adequate specimens. Sufficient quality RNA was obtained from 90% of tumor cores. Microarray signatures predicting ER and HER2 expression were developed in training sets of up to 363 surgical samples and were applied to microarray data obtained from core samples collected in clinical settings. In these samples, prediction of ER and HER2 expression achieved a sensitivity/specificity of 94%/100%, and 82%/72%, respectively. Predictions were reproducible in 83-100% of paired samples. Frozen CNBx can be readily obtained from most breast cancers without interfering with pathologic evaluation in routine clinical settings. Collection of tumor tissue at diagnostic biopsy and/or at surgery from lumpectomy specimens using image guidance resulted in sufficient samples for array analysis from over 90% of patients. Sampling of breast cancer for microarray data is reproducible and feasible in clinical practice and can yield signatures predictive of multiple breast cancer phenotypes.

To characterize hemostatic differences imposed by 2 common cardiac surgeries, the authors studied patients undergoing coronary artery revascularization by off-pump (n = 13) or cardiopulmonary bypass on-pump (n = 26) technique. Blood samples collected to 4 days post-surgery were evaluated by flow cytometry and enzyme-linked immunosorbent assay. A significant inflammatory response occurred in both the groups after surgery shown by increased interleukin cytokines and C-reactive protein; however, levels peaked lower and hours later in the off-pump group. Platelets (P-selectin; platelet-leukocyte complexes) and leukocytes (CD11b) were activated only in on-pump patients. Thrombin generation was enhanced in both groups after surgery. Only in the on-pump patients, the thrombin-antithrombin complex, pro-thrombin fragment 1.2, and thrombomodulin (vascular integrity) decreased intraoperatively. Tissue plasminogen activator and plasminogen activator inhibitor-1 were greater in the on-pump patients. Off-pump surgery may place patients at higher risk of postoperative hypercoagulability because of normal platelet function, intraoperative thrombin generation, less fibrinolytic activity, and lack of vascular protection.

Minimally invasive parathyroidectomy can reduce operative morbidity and operative time. Radio-guided parathyroidectomy utilizing Tc-99m Sestamibi is one approach to minimally invasive parathyroidectomy. Here, we report a multimedia case study of minimally invasive radio-guided parathyroidectomy.A 60-year-old African American female was found to have total calcium of 11.1 mg/dl, intact parathyroid hormone (iPTH) of 175 pg/ml, and a 24-h urine calcium of 620 mg/24 h. A Tc-99 Sestamibi scan (23.5 mCi of Tc-99 Sestamibi injected i.v.) and ultrasound localized a candidate adenoma to the right upper position. The patient was injected with 5.3 mCi Tc-99m Sestamibi 3 h before incision.A gamma probe (C-Trak Automatic System, Care Wise Medical Products) recorded in vivo counts of the right upper parathyroid (3,465) that were 160% of the background. Background counts were recorded from the resected tumor bed (2,224). A 1.4-g adenoma was identified in this location; ex vivo counts (3,226) were 150% of the background. Intra-operative iPTH baseline values were 176 pg/ml and 148 pg/ml, and 5- and 10-min post-resection levels were 17 pg/ml (90% drop) and 18 pg/ml (90% drop), respectively. The patient's recovery was uncomplicated. At 1 week postoperatively, total calcium was 8.9 mg/dl and iPTH was 16 pg/ml. At 1 year, the calcium and iPTH levels were 8.7 mg/dl and 53 pg/ml, respectively.Radio-guided minimally invasive parathyroidectomy using Tc-99 Sestamibi localization is an effective approach to hyperparathyroidism. For patients without localization, exposure of all four parathyroid glands is preferable. Surgeons should be familiar with both techniques.

4105 Background: ACC is a rare but devastating disease, with short life expectancy in the setting of metastatic, unresectable disease. Mitotane, an oral adrenocorticolytic agent, is often used as a systemic treatment though its therapeutic window is narrow. We retrospectively assessed outcomes of patients (pts) with metastatic ACC who received single-agent mitotane therapy to determine treatment toxicities and effectiveness. Methods: In this retrospective IRB-approved study, we identified 35 pts with metastatic ACC treated with single-agent mitotane at MSKCC from 3/15/1989-9/18/2014. All pts had follow-up at MSKCC and all imaging was reviewed according to RECIST 1.1 by reference radiologists. We reviewed pt demographics, clinical symptoms, toxicity (based on CTCAE Version 4), and treatment outcomes. Results: 35 pts were identified with mean age of 53 years (range, 23-87), 60% female. 18/35 tumors (51%) were functional: estradiol (n = 1), cortisol (n = 12), testosterone (n = 3), or both testosterone and co...

Heparin-induced thrombocytopenia (HIT) syndrome is a catastrophic complication of heparin therapy that may result in arterial/venous thromboembolic events. The pathophysiology of HIT is mediated by the generation of a functionally and molecularly heterogeneous group of anti-heparin-platelet factor 4 (AHPF4) antibodies that cause platelet/endothelial cell activation/destruction. These AHPF4 antibodies may be of various subtypes and cause differential pathogenic responses during HIT. This study evaluated the differential prevalence and functionality of AHPF4 Ig subtypes (IgA, IgG, and IgM) in plasma samples obtained from clinically suspected HIT patients (n = 111) and two clinical trials. In these trials, a low-molecular-weight heparin, clivarin and unfractionated heparin (UFH) were used to treat deep-vein thrombosis (CORTES) and for prophylaxis of the orthopedic surgery (ECHOS). In the CORTES study, three randomized groups of patients (n = 312-328) received prophylactic treatment with either UFH or clivarin (o.d. or b.i.d.). In the ECHOS study, there were approximately 600 patients per group. Citrated plasma samples were analyzed for cumulative IgA/IgG/IgM and individual Ig subtypes of AHPF4 utilizing ELISA. Functionality of the ELISA-positive samples was ascertained by 14C-serotonin release assay. In clinically confirmed HIT patients (and UFH-treated CORTES and ECHOS samples), the Ig subtyping revealed a predominance of IgG AHPF4 antibodies in contrast to the asymptomatic high AHPF4 antibody titers, which were found to be mostly IgM and/or IgA subtypes. In the clivarin-treated patients in both trials, the prevalence of AHPF4 antibodies was found to be lower (2-3 fold, p0.01) in comparison to UFH group. In addition, the clivarin-treated patients with positive AHPF4 antibodies were found to be predominantly of the non-functional type and were found in the order of IgMIgAIgG Together, these observations demonstrate that ELISA-detectable IgG subtype in UFH-treated patients may be more likely to cause functional/pathologic responses during HIT syndrome. Thus, determination of IgG subtype of AHPF4 antibodies during HIT syndrome may be crucial in the diagnosis; however, the relevance of the pathologically non-functional (IgA and/or IgM) antibodies and the overall mechanism(s) of these HIT-associatied antibodies need further investigation.

Objective We report a case of an adrenal collision tumor composed of a small cell lung carcinoma metastasis and a benign adrenal adenoma identified preoperatively on FDG-PET, CT and MRI and confirmed pathologically. Methods The patient’s history, preoperative imaging characteristics, postoperative course, and histopathology are described. A review of the literature addressing adrenal collision tumors is provided. Results A 47-year-old female was found to have a left upper lobe lung mass and an adrenal lesion on imaging. FDG-PET, CT and MRI of the adrenal suggested a metastatic lesion adjacent to an adrenal adenoma. CT-guided biopsy of the adrenal gland was consistent with a small cell lung cancer metastasis. The patient underwent systemic chemotherapy and had complete resolution of the left upper lobe mass. Post-treatment FDG-PET demonstrated a persistently enlarged adrenal gland with decreased but persistent FDG uptake. The patient underwent adrenalectomy and pathologic examination demonstrated a small cell lung cancer/adenoma collision tumor. Conclusions This case and a review of the literature demonstrate that FDG, CT and MR imaging can all characterize the separate components of collision tumors within the adrenal gland.

e14724 Background: Outcomes are poor in patients with gastric cancer, and recurrence is common. Perioperative chemotherapy and adjuvant chemoradiation therapy (CRT) improve survival in patients with resectable disease. Experience with neoadjuvant CRT for potentially resectable disease is limited, and its role remains undefined. We report our experience using neoadjuvant CRT for potentially resectable gastric cancer. Methods: An IRB-approved, retrospective review from 1994 to 2007 identified 23 patients with biopsy-proven, potentially resectable gastric cancer. Patients had T2/T3 and/or N1 disease and no evidence of metastatic disease by endoscopic ultrasound and cross-sectional imaging. All underwent neoadjuvant external beam radiation with concurrent 5-FU or platinum-based chemotherapy followed by restaging and surgery if appropriate. Results: Of the 23 patients, 20 completed neoadjuvant CRT and surgical exploration. Two patients (n=2) had radiographic disease progression during neoadjuvant CRT and did not undergo resection. One patient (n=1) developed a perforated gastric ulcer during CRT and underwent emergent resection. The median time from diagnosis to surgery and completion of neoadjuvant CRT to surgery was 104 days and 37.5 days, respectively. Gastrectomy was performed in 17 (85%) patients who completed neoadjuvant CRT. Metastatic disease was identified in the remaining 3 (15%) patients. Following gastrectomy, a complete pathologic response was observed in 4 (23.5%) patients, a partial response in 11 (64.7%) patients, and no response was identified in 2 (11.8%) patients. One (6%) patient had microscopic positive margins, and 9 (53%) had positive lymph nodes. There was no perioperative mortality. Two (11.8%) patients had anastomotic leaks, which were managed non-operatively. The median length of stay was 10 days. The median disease-free survival was 10.5 months, and median overall survival was 19.6 months. Conclusions: Gastric cancer carries a poor prognosis. Surgical resection after neoadjuvant CRT has low treatment-associated morbidity and mortality. Survival and complete response rates are comparable to published series. Further evaluation of this treatment strategy is warranted to assess its efficacy.

Background: It is our hypothesis that the extent of thyroid resection for benign nodular thyroid disease (NTD) should be based on the extent of disease. Methods: Patients operated on for benign NTD from 1990-2007 were divided into three groups, those who underwent lobectomy for unilateral NTD (Group 1), near-total or total thyroidectomy for bilateral NTD (Group 2), and reoperation for NTD initially treated at other institutions (Group 3). The incidence of recurrence was determined for Groups 1 and 2 and the timing of diagnosis was compared to Group 3. Potential risk factors for recurrent disease were examined. Results: 511 patients were operated on for benign NTD. Contralateral disease was excluded in Group 1 patients using ultrasound (45%) and/or intraoperative palpation. Five (2%) of 246 patients in Group 1 and one (0.4%) of 230 patients in Group 2 developed recurrent NTD after 8 / 5 and 4 yrs compared to a mean 19 / 11 yrs for the 35 patients in Group 3 following one to three previous thyroidectomies. Recurrent disease was diagnosed by physical exam in 22 (54%) and imaging in 19 (46%) patients. Thyroid hormone was required for post-surgical hypothyroidism in 70 (28%) patients in Group 1. Patients with recurrent disease were younger (38 / 18 yrs vs. 50 / 15 yrs, p 0.05), had a higher body mass index (BMI) (33.3 / 7.3 kg/m vs. 30.6 / 8.0 kg/m, p 0.05) and were more often African American (42.5% versus 34.7%, p 0.05). Conclusion: Thyroid lobectomy is optimal therapy when benign NTD is limited to one lobe, as evidenced by a 2% recurrence rate and maintenance of euthyroidism in 72% of patients. When NTD is bilateral, total thyroidectomy is indicated to eliminate recurrence, underscoring the importance of routine preoperative ultrasound. Young age, African American race and increased BMI are risk factors for recurrent NTD and warrant more aggressive follow up.

Hypothesis Patients receiving neoadjuvant chemoradiotherapy followed by surgery (CRS) undergo downstaging of their tumor and have improved survival when compared with patients undergoing surgery followed by adjuvant chemoradiotherapy (SCR). Design Retrospective study. Setting Tertiary-care university medical center. Patients One hundred twenty-three patients with squamous cell carcinoma and adenocarcinoma of the esophagus underwent Ivor-Lewis esophagectomy from January 1, 1990, through December 31, 2001. Of these, 31 received CRS; 27, SCR; and 65, surgery alone. Interventions Patients were candidates for neoadjuvant or adjuvant therapy if they had locally advanced disease (T3/T4 N0 or any T stage with N1). Neoadjuvant and adjuvant therapies were nonrandomized and based on the preference of the treating oncologist and surgeon. Main Outcome Measurements Pathological downstaging was analyzed in the patients receiving CRS. Operative mortality, postoperative morbidity, median survival, and overall survival were compared between the CRS and SCR groups. Results Pathological downstaging (as characterized by TNM staging) was observed in 20 (64%) of the patients receiving CRS. Complete pathological responses occurred in 5 (16%) of the patients undergoing CRS. No 30-day mortality was observed in either treatment group. No statistical difference in survival was observed between groups, although a trend suggested improved survival with neoadjuvant therapy (3-year survival in CRS and SCR groups was 45% and 22%, respectively; P = .15). Complete pathological responders in the CRS group had a 1-year survival of 80% compared with 29% in nonresponders ( P = .25). No statistical differences were observed between groups in relation to blood loss, length of hospital stay, mortality, or morbidity. Conclusions Neoadjuvant chemoradiotherapy effectively downstages cancer in patients with locally advanced esophageal disease. Morbidity and operative mortality were not significantly different between patients receiving neoadjuvant and adjuvant therapy. The difference in overall survival between the 2 groups did not reach statistical significance, although a trend at 3 years was observed.