Neck Dissection Followed by Definitive Radiotherapy for Small Upper Aerodigestive Tract Squamous Cell Carcinoma,with Advanced Neck Disease: An Alternative Treatment Strategy

Treatment options for patients with small upper aerodigestive tracts squamous cell carcinoma (T1, T2) with advanced neck disease (N2, N3) is a topic that generates controversy in terms of thereuptic stratagies. We present the retrospective analysis of 109 patients treated, between 1991 and 2008, by “Neck dissection first approach” for N2, N3 neck node, followed by external beam radiotherapy (RT) with or without chemotherapy for the operated neck and the primary, deemed radiocurable. 94 patients completed the planned treatment and formed the material for this study. The primary (tumor) stage was as follows: T1 (29) and T2 (65) commonly arising from oropharynx; the neck nodes were predominantly N2a (n = 54), followed by N2b (n = 26) and N3 (n = 14) disease. Complete nodal clearence was achieved in 89 patients, with no major post operative complications. With a median follow up of 24 months disease free survival of 70% and overall survival of 61% at 5 years. Recurrence at primary site was noted predominantly with pyriform fossa tumors (n = 8), followed by base of tongue (n = 5) and were T2 lesions. Failure in the neck was seen in predominantly N3 nodes, R1 resection and failure to comply with adjuvant treatment. Neck dissection first approach is a valid treatment option that allows a good control of the disease in the neck, where it often fails if only RT is administered, along with preserving the pharyngolaryngeal function. Care should be excercised so that there should be no delay in initiating the RT following surgery.     

Over-nutrition, obesity and insulin resistance in the development of β-cell dysfunction

The incidence of type 2 diabetes mellitus (DM2) has increased dramatically over the last several decades, largely driven by equally worrisome growing rates of obesity. Chronic diabetic complications are leading causes of morbidity and mortality worldwide. Key players in the pathophysiology of DM2 are insulin resistance and β cell dysfunction, which in turn is a result of both β cell functional abnormality as well as reduced β cell mass. The mechanisms implicated are multifactorial and include genetic and environmental factors related to obesity. Glucose homeostasis is critically dependent on a finely regulated balance between insulin sensitivity and output in the pancreas, and insulin resistance demands a corresponding rise in insulin output in order to maintain normal glycemia. However, this compensation is lost in individuals predisposed to DM2, resulting in overt hyperglycemia. Furthermore, insulin resistance related to excess adiposity is linked to several abnormalities which impact β cell function and viability. These include glucotoxicity, lipotoxicity, increased oxidative stress, and inflammation. In addition, insulin signaling in the β cell is essential to its own functionality and viability, and obesity-related abnormalities in insulin signaling are known to induce failure of insulin secretion and hyperglycemia. Insulin resistance in the β cell arises from defects in phosphorylation/activation of insulin receptor substrates (IRS) proteins, which result in impairment in glucose sensing, glucose stimulated insulin secretion, and also in increased loss of β cells. This review intends to provide an update on the main characteristics and mechanisms that link obesity and insulin resistance to β cell dysfunction in the pathogenesis of DM2.