Advances in the systemic treatment of neuroendocrine tumors in the era of molecular therapy.

Neuroendocrine tumors (NETs) are heterogeneous in underlying tumor biology and clinical presentations. They are generally classified according to their degree of differentiation and sites of origin. Moreover, NETs are further characterized by their secreted bioactive neuroamine. The treatment paradigm used to be surgical intervention in early disease and mostly palliative nature in the metastatic setting. With an increase in the understanding of the molecular signaling pathways involved in tumor growth, there are various emerging treatment options for patients with advanced NETs. Somatostatin analogs have both anti-tumor effects as well as symptom palliation associated with the secreted neuropeptides. Peptide-radio-receptor treatment (PRRT) using radio-labeled peptides which binds to somatostatin receptor is a useful anti-tumor treatment but limited by general availability. Sunitinib, a multi-targeted tyrosine kinase inhibitor, has recently been shown to improve the survival of pancreatic NETs patients. Similarly, the use of an mTOR inhibitor--everolimus, either alone or in combination with somatostatin analogs have demonstrated encouraging efficacy in treating advanced NETs. The success of these two agents in pancreatic NETS supports the notion that targeting angiogenesis and/or PI3K/AKT/mTOR pathway is an important strategy for making therapeutic advances in this disease. There are now many ongoing trials in exploring the role of other novel agents in treating patients with pancreatic NETs or carcinoid. The major plaguing problem in this era is the differential response to biological agents amongst NETs of different anatomical origins. Pancreatic NETs are generally more responsive to both chemotherapy and targeted agents than NETs of other sites. Thus, the development of potential predictive and prognostic biomarkers to tailor various molecular therapies to different NETs populations is a major unmet need.

Survival after surgical treatment for primary hyperparathyroidism.

BACKGROUND: Reports have suggested that patients with primary hyperparathyroidism (pHPT) are at increased risk for premature death, even when they reach normocalcemia. This study addresses factors that may be of relevance for long-term outcome. METHODS: Between 1980 and 1984, 1052 patients (27% men and 73% women; median age, 59 years) underwent initial cervical exploration for pHPT. Long-term follow-up was obtained with regard to overall survival and cause of death. By using univariate and multivariate (Cox) survival analysis, subgroups of patients were compared. RESULTS: Median follow-up was 12 years (range, 0 to 15 years). Overall, survival was not decreased compared with the expected survival of a gender- and age-matched midwest population. Survival was better in patients with a history of kidney stones (p = 0.044), without osteoporosis (p = 0.004), and without muscle weakness (p = 0.013). CONCLUSIONS: Decreased long-term survival was not evident in this study. Age at the time of initial surgical treatment and the degree of endocrine activity of the diseased glands appear to be the most important independent prognostic factors for survival. Comparison of these data to prior Scandinavian data is not justified, principally because of the less advanced stage of disease in this study.