New systemic therapies for locally advanced and metastatic thyroid cancer

Thyroid cancer affects one in 100 people over their lifetime. Differentiated and medullary thyroid cancer, refractory to traditional therapy, respond poorly to chemotherapeutic agents. However, tyrosine kinase inhibitors provide new hope for stabilizing disease in patients with advanced progressive disease. There are multiple tyrosine kinase inhibitors under study for thyroid cancer and currently four drugs that are US FDA approved. Nonetheless, use of these drugs should be selective given a significant adverse event profile and diseases with a typically indolent course. This review will cover molecular mechanisms in thyroid cancer as they are relevant to targeted therapies and review available evidence for the safety and efficacy of therapies currently approved and under study for thyroid cancer. </jats:p

Surgery for lymph node metastases of medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells, and can commonly spread to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the only effective option for curative therapy, reduction in tumor burden or effective palliation. In patients undergoing preventative operations for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is above 40 pg/ml. Systematic removal of at-risk or involved lymph node compartments should be performed in all patients with palpable primary tumors and recurrent disease, and a ‘berry-picking’ approach should be avoided. </jats:p

Adrenal myelolipoma: Operative indications and outcomes

Background: Adrenal myelolipoma (AM) is a benign lesion for which adrenalectomy is infrequently indicated. We investigated operative indications and outcomes for AM in a large single-institution series. Subjects and Methods: A retrospective cohort study of prospectively collected data was conducted. Patients (≥16 years of age) who underwent adrenalectomy in the Division of General Surgery at Barnes-Jewish Hospital (1993–2010) were grouped by operative indication (myelolipoma versus other pathology) and compared using nonparametric tests (α<0.05). Results: Sixteen patients (4.0%) had myelolipomas resected out of 402 patients who underwent adrenalectomy. Fourteen patients with suspected AM underwent adrenalectomy, 13 (93%) of whom had AM confirmed on pathology. Indications for adrenalectomy were abdominal or flank pain, large tumor size (>8 cm), atypical radiologic appearance, and/or inferior vena cava compression. Three patients with suspected other adrenal lesions had AM confirmed on final pathology. Operative approach was laparoscopic in 15 cases and open in 1 case of a 21-cm lesion. Patients who underwent laparoscopic adrenalectomy for AM (n=15) or other adrenal pathology (n=343) were similar with respect to age, gender, American Society of Anesthesiologists classification, prior abdominal operation, tumor side, operative time, conversion rate, estimated blood loss, intraoperative complications, hospital length of stay, and 30-day morbidity. However, patients with resected AM had a higher body mass index (36.5±8.1 kg/m(2) versus 30.1±7.5 kg/m(2); P<.01) and a larger preoperative tumor size (8.4±3.0 cm versus 3.1±1.7 cm; P<.01). Conclusions: Laparoscopic adrenalectomy may be appropriate for patients with a presumptive diagnosis of AM and abdominal or flank pain, large tumor size, and/or uncertain diagnosis after imaging. Outcomes and morbidity following LA for AM and other adrenal pathology appear comparable

Metastatic disease to the breast: the Washington University experience

<p>Abstract</p> <p>Background</p> <p>Metastases to the breast occur rarely, but may be increasing in incidence as patients live longer with malignant diseases. The aim of this study is to characterize metastatic disease to the breast and to describe the management and prognosis of patients who present with this diagnosis.</p> <p>Methods</p> <p>A retrospective review of our institution's pathology and breast cancer databases was performed in order to identify patients with breast malignancies that were not of primary breast origin. Chart review provided additional information about the patients' primary malignancies and course of illness.</p> <p>Results</p> <p>Between 1991 and 2006, eighteen patients with metastatic disease to the breast of non-hematologic origin were identified and all had charts available for review. Among the 18 patients with disease metastatic to the breast, tissues of origin included 3 ovarian, 6 melanoma, 3 medullary thyroid, 3 pulmonary neuroendocrine, 1 pulmonary small cell, 1 oral squamous cell, and 1 renal cell. Overall mean survival after diagnosis of metastatic disease to the breast was 22.4 months. Treatment of metastases varied and included combinations of observation, surgery, radiation, and chemotherapy. Five patients (27.8%) required a change in management of their breast disease for local control.</p> <p>Conclusion</p> <p>Due to the variable course of patients with metastatic disease, a multi-disciplinary approach is necessary for each patient with disease metastatic to the breast to determine optimal treatment. Based on our review, many patients survive for long periods of time and local treatment of metastases to the breast may be beneficial in these patients to prevent local complications.</p

BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma

The BRAF mutation occurs commonly in papillary thyroid carcinoma (PTC). Previous investigations of its utility to predict recurrence-free survival (RFS) and disease-specific survival (DSS) have reported conflicting results and its role remains unclear. The purpose of this retrospective study was to determine the incidence of the BRAF mutation and analyze its relationship to clinicopathologic risk factors and long-term outcomes in the largest, single-institution American cohort to date. BRAF mutational status was determined in 508 PTC patients using RFLP analysis. The relationships between BRAF mutation status, patient and tumor characteristics, RFS, and DSS were analyzed. The BRAF mutation was present in 67% of patients. On multivariate analysis, presence of the mutation predicted only for capsular invasion (HR, 1.7; 95% CI, 1.1–2.6), cervical lymph node involvement (HR, 1.7; 95% CI, 1.1–2.7), and classic papillary histology (HR, 1.8; 95% CI 1.1–2.9). There was no significant relationship between the BRAF mutation and RFS or DSS, an observation that was consistent across univariate, multivariate, and Kaplan–Meier analyses. This is the most extensive study to date in the United States to demonstrate that BRAF mutation is of no predictive value for recurrence or survival in PTC. We found correlations of BRAF status and several clinicopathologic characteristics of high-risk disease, but limited evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that BRAF is minimally prognostic in PTC. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association