Faculty Bibliography

In a large, urban US public hospital, patients were found to present with more advanced stage differentiated thyroid carcinoma (DTC) than those in an affiliated, adjacent university hospital. Asians comprised the largest ethnic group (45%) in the public hospital. We conducted a qualitative study to understand experiences and challenges contributing to delays in diagnosis among Chinese patients with thyroid cancer. Five focus groups and 4 key informant interviews led by trained, bilingual Mandarin speakers were conducted. All adult, Mandarinspeaking patients treated for DTC in the public hospital (2000-2011) met inclusion criteria. A phenomenology approach was used to identify common themes. Seventeen out of 97 eligible patients participated (11 women, 6 men; average age 47). All participants were born in China, had lived in the United States for an average of 14 years (range: 5-22), and a majority reported not seeking regular medical care in China or the United States. Despite a history of an abnormal thyroid exam in over half, presentation to a physician was delayed by an average of 9 years (range: 2-17). Several challenges and barriers to accessing care were identified, with two main themes: misinformation and/or lack of information on thyroid cancer, and socioeconomic/cultural barriers in accessing the US healthcare system. All study participants reported an unawareness of thyroid cancer before diagnosis, and a majority expressed beliefs that such cancer was caused by contaminated seafood, living by the ocean, or consumption of salt. Socioeconomic constraints included language barriers, seeking care from unlicensed health practitioners, and prioritizing establishing a foothold in the United States over health and health-related needs. Nearly all patients denied using traditional Chinese medicine to treat their thyroid condition. These data underscore the importance of promoting preventative care and the need for targeted education to address significant misinformation on thyroid cancer in th!

OBJECTIVE: To examine genotypic and clinical differences between encapsulated, nonencapsulated, and diffuse follicular variant of papillary thyroid carcinoma (EFVPTC, NFVPTC, and diffuse FVPTC, respectively), to characterize the entities and identify predictors of their behavior. DESIGN: Retrospective medical chart review and molecular analysis. SETTING: Referral center of a university hospital. PATIENTS: The pathologic characteristics of 484 consecutive patients with differentiated thyroid cancer who underwent surgery by the 3 members of the New York University Endocrine Surgery Associates from January 1, 2007, to August 1, 2010, were reviewed. Forty-five patients with FVPTC and in whom at least 1 central compartment lymph node was removed were included. MAIN OUTCOME MEASURES: Patients with FVPTC were compared in terms of age, sex, tumor size, encapsulation, extrathyroid extension, vascular invasion, central nodal metastases, and the presence or absence of mutations in BRAF, H-RAS 12/13, K-RAS 12/13, N-RAS 12/13, H-RAS 61, K-RAS 61, N-RAS 61, and RET/PTC1. RESULTS: No patient with EFVPTC had central lymph node metastasis, and in this group, 1 patient (4.5%) had a BRAF V600E mutation and 2 patients (9%) had RAS mutations. Of the patients with NFVPTC, none had central lymph node metastasis (P > .99) and 2 (11%) had a BRAF V600E mutation (P = .59). Of the patients with diffuse FVPTC, all had central lymph node metastasis (P < .001), and 2 (50%) had a BRAF V600E mutation (P = .06). CONCLUSIONS: FVPTC consists of several distinct subtypes. Diffuse FVPTC seems to present and behave in a more aggressive fashion. It has a higher rate of central nodal metastasis and BRAF V600E mutation in comparison with EFVPTC and NFVPTC. Both EFVPTC and NFVPTC behave in a similar fashion. The diffuse infiltrative pattern and not just presence or absence of encapsulation seems to determine the tumor phenotype. Understanding the different subtypes of FVPTC will help guide appropriate treatment strategies.

Background: Healthcare disparities associated with insurance and socioeconomic status have been well characterized for several malignancies, such as lung cancer. To assess whether there are healthcare disparities in thyroid cancer, this study evaluated the stage on initial presentation of patients with differentiated thyroid cancer (DTC) in a public versus university teaching hospital. Methods: A retrospective chart review was performed to identify patients with a new diagnosis of DTC from January 1, 2007, to January 1, 2010, in a large public and adjoining university teaching hospital at a single academic medical center. Medical records were reviewed for demographics, pathology, and American Joint Committee on Cancer tumor-node-metastasis stage at initial presentation. Results: There were 49 cases of well-DTC (96% papillary and 4% Hurthle) in the public hospital and 370 cases (95% papillary, 2% Hurthle, and 3% follicular) in the university teaching hospital. Median age (years) at presentation was 50 in the public versus 48 in the university teaching hospital (p=0.39). Ninety-six percent of public hospital patients were from ethnic minorities compared with 16% of university teaching hospital patients (p<0.0001). Only 1 (2%) public hospital patient had private insurance compared with 85% of university teaching hospital patients. Tumor status (p=0.002) and stage (p=0.03) were more advanced and extrathyroidal extension (p=0.02) was more prevalent among public hospital patients compared with university teaching hospital patients. In a multivariable analysis, public hospital, male gender, increasing age, advanced tumor status, and the presence of lymphovascular invasion were the best predictors of more advanced disease stage. Public hospital patients were 3.4 times more likely to present with advanced DTC than university teaching hospital patients of the same age, gender, tumor status, and lymphovascular invasion status (95% confidence interval 1.29-8.95). Conclusions: In a public hospital, where the patient population is defined primarily by insurance status, patients were more likely to present with advanced-stage DTC than patients presenting to an adjacent university teaching hospital. These results suggest a disparity in the stage on initial presentation of DTC, possibly resulting in a delayed diagnosis of cancer.

BACKGROUND: To determine whether a 'lay' rater could assess clinical reasoning, interrater reliability was measured between physician and lay raters of patient notes written by medical students as part of an 8-station objective structured clinical examination. METHODS: Seventy-five notes were rated on core elements of clinical reasoning by physician and lay raters independently, using a scoring guide developed by physician consensus. Twenty-five notes were rerated by a 2nd physician rater as an expert control. Kappa statistics and simple percentage agreement were calculated in 3 areas: evidence for and against each diagnosis and diagnostic workup. RESULTS: Agreement between physician and lay raters for the top diagnosis was as follows: supporting evidence, 89% (kappa = .72); evidence against, 89% (kappa = .81); and diagnostic workup, 79% (kappa = .58). Physician rater agreement was 83% (kappa = .59), 92% (kappa = .87), and 96% (kappa = .87), respectively. CONCLUSIONS: Using a comprehensive scoring guide, interrater reliability for physician and lay raters was comparable with reliability between 2 expert physician raters

BACKGROUND: Single nucleotide polymorphisms (SNPs) may function as modifiers of the RET proto-oncogene, resulting in the expression of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). We present 2 non-related Italian-American families (Family 1, n = 107; Family 2, n = 31) with the RET V804M mutation. We have correlated the presence of specific SNPs and the rare RET V804M mutation to MTC, C-cell hyperplasia (CCH), and PTC. METHODS: Sequencing was performed on exons 10, 11, and 13-16 of the RET proto-oncogene. The presence of MTC, CCH, and PTC were correlated to specific SNPs. RESULTS: In both families, 3 SNPs in exon 11 (G691S), exon 13 (L769L), and exon 15 (S904S) were detected in 100% of patients with overt MTC. The SNP L769L was present in all patients including patients with PTC, MTC, and CCH. CONCLUSION: SNP analysis revealed a similar pattern between the 2 families. SNPs in exon 11 (G691S) and exon 15 (S904S) appear to influence the development of MTC. A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation

BACKGROUND: The 2009 ATA Guidelines state 'lobectomy alone may be sufficient treatment for small (<1 cm), low risk, unifocal, intrathyroidal papillary carcinomas in the absence of . . . nodal metastases.' We determined how often these criteria are satisfied, and whether tumor size alone can dictate operative management. METHODS: Medical records of 346 patients with well-differentiated thyroid cancer (WDTC) who underwent thyroidectomy from January 1, 2007 to November 10, 2009, were reviewed. There were 130 patients with tumors </=1 cm and negative lateral nodes. Pathology reports were reviewed to identify adverse features including multifocality, extrathyroidal extension, vascular invasion, and central node metastases. RESULTS: Eighty-four percent underwent total thyroidectomy and 16% central node dissection. All but 2 patients had papillary cancer. Sixty-one percent with cancers 6-10 mm (group 1) had adverse pathologic features compared with 32% with cancers <6 mm (group 2). Multifocality was most common: 55% in group 1 versus 32% in group 2 (P = .004). Positive central nodes were identified in 23% of group 1 versus 4% of group 2 (P = .004). Of patients in group 1, 88% had positive or suspicious fine-needle aspiration biopsy (FNAB) preoperatively. CONCLUSION: We recommend that total thyroidectomy be considered as the initial operation for thyroid tumors 6-10 mm in size in which the preoperative FNAB is diagnostic or suspicious for WDTC

Transplantation of functional adrenal cortex cells could reduce morbidity and increase the quality of life of patients with adrenal insufficiency. Our aim was to determine whether adrenal extracellular matrix (ECM) scaffolds promote adrenocortical cell endocrine function and proliferation in vitro. We seeded decellularized porcine adrenal ECM with primary human fetal adrenocortical (HFA) cells. Adrenocortical function was quantified by cortisol secretion of HFA-ECM constructs after stimulation with adrenocorticotropic hormone. Proliferation was assessed by adenosine triphosphate assay. HFA-ECM construct morphology was evaluated by immunofluorescence microscopy and scanning electron microscopy. Adrenal HFA-ECM constructs coated with laminin were compared to uncoated constructs. Laminin coating did not significantly affect HFA morphology, proliferation, or function. We demonstrated HFA cell attachment to adrenal ECM scaffolds. Cortisol production and HFA cell proliferation were significantly increased in HFA-ECM constructs compared to controls (p < 0.05), and cortisol secretion rate per cell is comparable to that of human adult and fetal explants. We conclude that adrenal ECM supports endocrine function and proliferation of adrenocortical cells in vitro. Adrenal ECM scaffolds may form the basis for biocompatible tissue-engineered adrenal replacements.

BACKGROUND: "Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis. METHODS: All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARgamma gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome. RESULTS: From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic-histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false-positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001). CONCLUSIONS: By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and "suspicious for follicular neoplasm" categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high-risk and low-risk categories.