Reproductive effects of irisin: Initial in vitro studies.

The recently discovered myo- and adipokine irisin affects insulin sensitivity in classical insulin target tissues (adipose tissue, skeletal muscle and liver), but the reproductive effects of this hormone, if any, remain largely unexplored. We hypothesized that irisin may have effects on the hypothalamic-pituitary-gonadal axis. To test this hypothesis, we used murine pituitary mPit12 and human ovarian granulosa cells. GnRH treatment resulted in significant (up to 2.5-fold, p<0.0005) and dose-dependent stimulation of LH production by the mPit12 cells. Treating these cells with irisin alone showed a significant stimulatory effect on LH synthesis only at irisin concentration of 100ng/ml. When used together with GnRH, irisin abolished the stimulatory effect of GnRH on LH production. Human ovarian granulosa cells were treated with insulin, irisin or a combination of both and the estradiol (E2) production was measured. Both insulin or irisin stimulated granulosa cell E2 production (1.4-fold, p<0.05 and 2.5-fold, p=0.0002, respectively), but when insulin and irisin were used in combination, this stimulatory effect on E2 production was abolished. We conclude that irisin may have reproductive axis effects in the pituitary and in the ovary. Further studies are needed to confirm these initial observations and to explore the mechanisms of irisin effects in the reproductive system.

Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung cancer.

BACKGROUND: The optimal surgical technique for lobectomy in lung cancer is not well defined. Proponents of video-assisted thoracic surgery (VATS) hypothesize that less trauma leads to quicker recovery, whereas those who advocate thoracotomy claim it as an oncologically superior procedure. However, a well-balanced comparison of the two procedures is lacking in the literature. METHODS: All patients who underwent lobectomy for clinical stage 1A lung cancer by computed tomographic and positron emission tomographic scan were identified from a prospective database. Patient characteristics were compared by the Student t test, Pearson chi(2), and Fisher exact test. A propensity score-matched analysis was performed. Survival was assessed by Kaplan-Meier and Cox proportional hazards analysis. Complications were assessed by a multivariate logistic regression model evaluating age, sex, comorbidities, pulmonary function, tumor size, nodal status, surgeon, and histologic characteristics. RESULTS: From May 2002 to August 2007, 398 patients underwent an attempt at VATS lobectomy and 343 underwent thoracotomy. An "intent-to-treat" analysis was performed. There was 1 postoperative death in each group. Survival by Cox model was no different for VATS versus thoracotomy (hazard ratio 0.72; P = .12), whereas age (hazard ratio 1.03; P < .001), larger tumor size (hazard ratio 1.34; P < .001), and higher nodal stage (hazard ratio 1.92; P < .001) were associated with worse survival. Logistic regression demonstrated fewer complications for VATS lobectomy (odds ratio 0.73; P = .06), whereas age (odds ratio 1.04; P < .001) and tumor size (odds ratio 1.2; P < .020) correlated with a greater number of complications. Patients undergoing VATS lobectomy demonstrated a 2-day shorter length of stay than patients undergoing thoracotomy (P < .001). Propensity score-matched analysis supported these findings. CONCLUSIONS: VATS lobectomy and thoracotomy demonstrated similar 5-year survivals. However, VATS lobectomy was associated with fewer complications and shorter length of hospital stay.

The impact of lymph node station on survival in 348 patients with surgically resected malignant pleural mesothelioma: implications for revision of the American Joint Committee on Cancer staging system.

OBJECTIVES: The propensity of malignant pleural mesothelioma to metastasize to N1 or N2 nodes and their corresponding prognostic value is unclear. The American Joint Committee on Cancer staging system groups N1 and N2 disease together as stage III. The goal of this study was to define the prognostic value of specific nodal stations. METHODS: Patients with malignant pleural mesothelioma who underwent resection were identified from an institutional database. Nodal stations were defined by the American Joint Committee on Cancer lung cancer node map classification. Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. RESULTS: From 1990 to 2006, 348 patients were identified: 279 men and 69 women with a median age of 67 years (range 26-85 years). Extrapleural pneumonectomy was performed in 223 cases, and pleurectomy/decortication was performed in 125 cases. Survival differences (P < .01) were observed between 2 groups: N0 or N1(+) (median survival = 19 months) and N2(+), N2/N1(+) and internal thoracic(+) (median survival = 10 months). Survival was influenced by the number of involved N2 stations (0, 1, 2, or more: P < .001). Multivariate analysis grouping all N2 and internal thoracic(+) versus N1(+) and N0 demonstrated a hazard ratio for survival of 1.7 (P < .0001) controlling for T3/T4 status (hazard ratio = 1.3, P < .01), non-epithelioid histology (hazard ratio = 1.7, P < .0001), extrapleural pneumonectomy (1.1, P = .4), and male gender (hazard ratio 1.4, P < .01). CONCLUSION: This study confirms a preferential pattern of drainage of malignant pleural mesothelioma to N2 rather than N1 lymph nodes, but suggests that N1 only nodal involvement should be classified as lower stage disease. Multiple N2 nodal site involvement could potentially be classified as higher stage disease than single station N2. Our results emphasize the need for larger, confirmatory multicenter studies that could lead to revision of the current staging system.