Population-Based Results in the Management of Sinonasal and Ventral Skull Base Malignancies.

Population-based cancer registries allow for data collection on the scale of large populations, outside the limits of a single institution, and facilitate study of rare entities. The SEER database has been used to study more than 7000 cases encompassing a wide variety of relatively rare sinonasal malignant histologies. Clinically useful parameters have been gleaned from these analyses. Important limitations, such as omission of chemotherapy data, surgical approach used, type of radiation administered, and selection and confounding bias, should be considered. Nevertheless, population-based analyses yield readily generalizable and clinically relevant information regarding the management of sinonasal malignancies for the practicing clinician.

Epithelial-Myoepithelial Carcinoma of the Salivary Glands: An Analysis of 246 Cases.

OBJECTIVE: Epithelial-myoepithelial carcinoma (EMC) is a rare neoplasm of the salivary glands. In this study, we aim to examine the demographic, clinicopathologic, and survival features of EMC using a population-based approach. STUDY DESIGN AND SETTING: Retrospective cohort study. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Result (SEER) database (1973-2010) was queried for EMC of the major salivary glands. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: In total, 246 cases were available for frequency analysis and 207 for survival analysis. Mean ± SD age at diagnosis was 63.8 ± 15.4 years. EMC affected females more frequently (57.3%). Distant metastases were present at diagnosis in only 4.5% of cases. Overall disease-specific survival (DSS) at 60, 120, and 180 months was 91.3%, 90.2%, and 80.7%, respectively. Patients with low-grade histology had significantly better survival at 180 months relative to those with high-grade tumors (90.6% vs 0.0%, P = .0246). When stratified by tumor size, patients with lesions >4 cm had the worst survival at 180 months (58.8%, P = .0003). All but 9 of the 207 cases available for survival analysis underwent surgery. A total of 85 patients (41.1%) received radiotherapy in addition to surgery. No survival benefit was noted for patients who received radiotherapy compared with those who did not (P = .4832). CONCLUSION: This report represents the largest series of EMC to date. Despite being regarded as a low-grade, indolent tumor, a significant fraction of our cohort underwent radiotherapy in addition to surgery, with no apparent added survival benefit.

N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses.

BACKGROUND: Intraperitoneal adhesions occur in more than 94% of patients after abdominal surgery. Mechanisms that decrease oxidative stress and upregulate peritoneal fibrinolysis reduce adhesions. N-acetyl-l-cysteine (NAC) is a clinically relevant antioxidant whose effect on peritoneal fibrinolysis and ability to decrease adhesions has not been established. The aims of this study were to determine if NAC reduces adhesions and to characterize its potential mechanism(s) of action. METHODS: Male Wistar rats (n = 92) received 0.9% saline (OP Control), intraperitoneal NAC (150 mg/kg, OP + NAC), or oral NAC (1200 mg/kg) twice daily on preoperative day 1, day of operation, and postoperative day 1. Adhesions were induced on the day of operation using our previously described ischemic button model. Animals were killed on postoperative day 7 for adhesion scoring. Peritoneal tissue and fluid from the intraperitoneal NAC group were measured at 24 hours for fibrinolytic activity, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), total glutathione, and 8-isoprostane (8-IP). The effect of NAC on tPA and PAI-1 production was tested in vitro in human mesothelial cells. The effect of NAC on intestinal wound healing was measured using colonic anastomotic burst pressures. RESULTS: Intraperitoneal NAC reduced adhesions by 53% (P < .001) compared to OP Controls without affecting anastomotic wound healing. NAC increased the tPA/PAI-1 protein ratio and peritoneal fibrinolytic activity by 69% and 127%, respectively, compared to OP Controls (P < .05). NAC did not restore total glutathione levels in peritoneal adhesion tissue but decreased 8-IP by 46% and 65% (P < .05) in peritoneal tissue and fluid, respectively, compared to OP Controls. Human mesothelial cells incubated with NAC exhibited a concentration-dependent increase in the tPA/PAI-1 ratio, which supported in vivo observations (P < .05). Oral NAC did not decrease adhesions. CONCLUSION: NAC administered intraperitoneally decreased adhesion formation while upregulating peritoneal fibrinolytic activity and antioxidant defenses without affecting normal anastomotic wound healing. These data suggest a potential new therapeutic use for NAC in adhesion prevention.

Androgen deficiency and atherosclerosis: The lipid link.

The relationship between androgen deficiency and atherosclerosis is complex, poorly understood, and remains controversial. The aim of this review is to evaluate the data in the literature to determine if androgen deficiency modulates lipid profiles and contributes to atherosclerosis development or progression. Studies in animals and humans suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Although the effects of androgen deficiency on high-density lipoprotein cholesterol (HDL-C) remains controversial, recent data suggest that androgen therapy is associated with increased levels of HDL-C and may improve reverse cholesterol transport. Animal studies suggested that androgen deprivation adversely affect lipid profiles and this was reversed by androgen treatment. Furthermore, androgen treatment of hypogonadal men significantly improved lipid profiles. Emerging data indicate that androgens play an important role in lipid metabolism. Therefore androgens are critical in the prevention and progression of atherosclerosis. Androgen deficiency contributes to increased TGs, TC, LDL-C and reduced HDL-C while androgen treatment results in a favorable lipid profile, suggesting that androgens may provide a protective effect against the development and/or progression of atherosclerosis.