Hormonal Evaluation of Incidental Adrenal Masses: The Exception, Not the Rule.

BACKGROUND: Incidental adrenal masses (IAMs) occur in approximately 4% of patients undergoing abdominal CT scans for any indication. Hormonal evaluation is recommended for all IAMs. The purpose of this study was to identify the rate of IAMs in a screening population and to determine the adequacy of endocrine evaluation of newly identified IAMs based on established guidelines. METHODS: This was a retrospective analysis of 6913 patients undergoing a non-contrast screening CT colonography at a single academic medical center between June 2004 and July 2012. RESULTS: The prevalence of IAMs in this asymptomatic screening population was 2.1% (n = 148). Of those patients, 8.8% (n = 11) underwent some form of hormonal evaluation and only 6.4% (n = 8) patients had a "complete" workup. Cortisol, metanephrines, and an aldosterone-renin ratio were evaluated in 8.0%, 7.2%, and 4.0% of patients, respectively. Of the patients (n = 11) who underwent hormonal evaluation, 27.3% had functional masses and 36.4% underwent surgery. Of those who did not have hormonal evaluation, 42.1% (n = 48) had comorbidities that should have prompted hormonal evaluation based on established guidelines. Hormonal evaluation was not performed in 89.4% of patients with hypertension and 21.1% of patients with diabetes. 88.9% of patients on three or more antihypertensive medications did not undergo any hormonal evaluation. CONCLUSIONS: Compliance with IAM workup guidelines is poor, which may result in missed diagnosis of functional adrenal masses. Establishment of a robust protocol and education on appropriate workup for IAMs is necessary for adequate hormonal evaluation.

Is central lymph node dissection necessary for parathyroid carcinoma?

BACKGROUND: Parathyroid carcinoma is a rare cancer. Unlike other more common malignancies, the importance of lymph node (LN) status remains controversial. The purpose of this study was to determine the relative importance of LN metastases in disease-specific survival (DSS). METHODS: A retrospective review of the Surveillance, Epidemiology, and End Result database was performed on parathyroid carcinoma cases diagnosed between 1988 and 2010. RESULTS: We identified 405 parathyroid carcinoma patients. Among 114 patients with LNs examined at operation, only 12 (10.5%) had positive LNs. Sensitivity analysis found that a tumor size threshold of 3 cm best divided the cohort by DSS. Only tumors ≥ 3 cm and distant metastasis but not LN metastases were independent prognostic factors on multivariate analysis. When examining factors associated with LN status, only tumors ≥ 3 cm predicted LN metastasis. LN metastases were 7.5 times more likely in patients with tumors ≥ 3 cm than those with tumors <3 cm. CONCLUSION: Tumors ≥ 3 cm were associated with LN metastases in parathyroid carcinoma, but positive LN status was not associated with DSS. Tumor size can potentially risk stratify patients by their risk of LN metastases.

Novel approaches in anaplastic thyroid cancer therapy.

Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future.

Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells.

PURPOSE: The epidermal growth factor receptor (EGFR) is recognized as a key mediator of proliferation and progression in many human tumors. A series of EGFR-specific inhibitors have recently gained Food and Drug Administration approval in oncology. These strategies of EGFR inhibition have shown major tumor regressions in approximately 10% to 20% of advanced cancer patients. Many tumors, however, eventually manifest resistance to treatment. Efforts to better understand the underlying mechanisms of acquired resistance to EGFR inhibitors, and potential strategies to overcome resistance, are greatly needed. EXPERIMENTAL DESIGN: To develop cell lines with acquired resistance to EGFR inhibitors we utilized the human head and neck squamous cell carcinoma tumor cell line SCC-1. Cells were treated with increasing concentrations of cetuximab, gefitinib, or erlotinib, and characterized for the molecular changes in the EGFR inhibitor-resistant lines relative to the EGFR inhibitor-sensitive lines. RESULTS: EGFR inhibitor-resistant lines were able to maintain their resistant phenotype in both drug-free medium and in athymic nude mouse xenografts. In addition, EGFR inhibitor-resistant lines showed a markedly increased proliferation rate. EGFR inhibitor-resistant lines had elevated levels of phosphorylated EGFR, mitogen-activated protein kinase, AKT, and signal transducer and activator of transcription 3, which were associated with reduced apoptotic capacity. Subsequent in vivo experiments indicated enhanced angiogenic potential in EGFR inhibitor-resistant lines. Finally, EGFR inhibitor-resistant lines showed cross-resistance to ionizing radiation. CONCLUSIONS: We have developed EGFR inhibitor-resistant human head and neck squamous cell carcinoma cell lines. This model provides a valuable preclinical tool to investigate molecular mechanisms of acquired resistance to EGFR blockade.