ABSTRACT
Insulin resistance and obesity are suggested to have a key role in the molecular pathogenesis of various disorders, including several malignancies. Moreover, insulin resistance has recently been found to be associated with cutaneous and uveal melanoma, while a variable positive correlation between obesity and the risk of cutaneous melanoma was also found at least in men. The present trial aims at confirming whether insulin resistance, assessed with the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI), is a risk factor for cutaneous melanoma. One hundred and thirty patients diagnosed with cutaneous melanoma and 130 age-, sex-, and skin phototype-matched controls were evaluated. At the univariate and multivariate analysis, the diagnosis of cutaneous melanoma was inversely related with insulin resistance (HOMA-IR) and positively with BMI (p = 0.0014 and p = 0.008, respectively). Consistently, insulin sensitivity (QUICKI) and BMI resulted positively associated with the diagnosis of cutaneous melanoma (p = 0.0001 and p = 0.0026, respectively). The results obtained are partially in agreement with those reported in the literature. By comparing our data with those generated by other studies, inconsistencies in key features among subgroups of different trials have emerged, possibly affecting final correlations. Based on insulin resistance/sensitivity, fasting insulinemia/glycemia, and BMI values collected from patients who participated in the present trial, two nomograms potentially assessing the risk of cutaneous melanoma have been generated. Molecular aspects sustain a role for insulin resistance in the carcinogenesis of cutaneous melanoma, but clinical data remain uncertain. Larger, well-balanced, correlative trials are still needed to define the potential role of insulin resistance in the carcinogenesis of cutaneous melanoma.
ABSTRACT
OBJECTIVE: Surgery for extracranial carotid artery disease has been challenged by carotid angioplasty stenting because the latter is less invasive and avoids surgical trauma. In fact, the magnitude of the perioperative stress response evoked by carotid endarterectomy (CEA) has never been evaluated. Our aim was to determine the degree of surgical trauma caused by CEA and to define differences related to the use of locoregional or general anesthesia. METHODS: We prospectively studied 113 consecutive CEAs performed on 109 patients admitted at a community institutional center. Patients were stratified for demographics and risk factors and operated on under locoregional (LA) or general anesthesia (GA) depending on both the surgeon preference and patient's compliance. Selective carotid shunting was performed for patients who manifested neurologic deficits under LA or had stump pressure values =30 mm Hg under GA. Markers of the stress response, including cortisol, adrenocorticotropic hormone, prolactin, and C-reactive protein, were measured intraoperatively, before and after carotid artery cross-clamping (CACC), and postoperatively up to the third day after surgery. Hemodynamic variability was assessed during surgery and for 24 hours postoperatively. Operative times were also measured. Surgeons were considered as independent variables for stress response. Statistics were run by means of nonparametric tests and univariate and multivariate analysis with a linear regression model. RESULTS: CEA was performed under GA in 63 cases (55.8%) and under LA in 50 (44.2%). The two groups were comparable in terms of demographics and risk factors. Intraoperatively, cortisol and adrenocorticotropic hormone levels were significantly higher in the LA group (both P <.001). CACC increased the intraoperative cortisol levels in both the GA (P =.019) and the LA groups (P =.006). However, in patients who underwent carotid shunting, this effect was abolished (GA group, P =.779; LA group, P = 1.0). During the early postoperative period there was no difference between the two groups. On postoperative day 1 the stress response was abolished in both groups. Prolactin levels increased intraoperatively in both the LA and GA groups and returned within preoperative values on postoperative day 1. Prolactin levels were higher in the GA group (P =.003 intraoperatively and P <.001 postoperatively). C-reactive protein significantly increased in both GA and LA groups on postoperative days 1 and 2 and started to decrease on day 3 with no differences between the two groups at any time. Hemodynamic variability and considered risk factors including individual surgeon were not significant variables. Gender-related differences were found only in prolactin secretion. The length of surgery had an impact for procedures that lasted >120 minutes. Three patients experienced an intraoperative neurologic event and had higher post-CACC cortisol values as compared to asymptomatic patients. CONCLUSIONS: Intraoperative surgical stress was higher under LA and was blunted by carotid shunting under both LA and GA. Within 2 hours after surgery the anesthetic modality no longer had any impact on surgical trauma. The stress response to CEA, regardless of the type of anesthesia, was abolished within 24 hours. Intraoperative stress response, namely hypercortisolemia, directly correlated with subclinical and clinical cerebral hypoperfusion/ischemia during CACC. Hence, attenuation of the stress response to CEA might decrease the incidence of cerebral ischemic events.
Subject(s)
Endarterectomy, Carotid , Perioperative Care , Stress, Psychological/drug therapy , Adrenocorticotropic Hormone/metabolism , Aged , Aged, 80 and over , Anesthesia, General , Anesthesia, Local , Biomarkers/blood , C-Reactive Protein/metabolism , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/surgery , Carotid Artery, Internal/surgery , Combined Modality Therapy , Female , Humans , Hydrocortisone/metabolism , Italy/epidemiology , Male , Postoperative Complications/etiology , Postoperative Complications/mortality , Prolactin/metabolism , Prospective Studies , Risk Factors , Sex Factors , Statistics as Topic , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Surgical Instruments , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: The aim of our study was to evaluate human papillomavirus (HPV) infection as a risk factor for cutaneous squamous cell carcinoma (SCC) in immunocompetent individuals. DESIGN: Hospital-based case-control study. SETTING: Referral center for dermatologic diseases for central and southern Italy. PARTICIPANTS: Consecutive patients with histologically confirmed cutaneous SCC (n = 46) and control subjects (n = 84) chosen by frequency matching (age and sex) among patients admitted with unrelated diseases. MAIN OUTCOME MEASURE: Infection with epidermodysplasia verruciformis-related HPV types, blindly assessed by serologic testing (viruslike particle enzyme-linked immunosorbent assay). Information was obtained on known potentially confounding risk factors (family history, history and signs of sun exposure, and pigmentary traits) and on history of HPV-related lesions and diseases, assessed by interview and examination by a dermatologist. RESULTS: Positive serologic findings for HPV type 8 were associated with SCC (odds ratio, 3.2; 95% confidence interval, 1.3-7.9) independently of other risk factors, whereas positive serologic findings for HPV type 15 were negatively associated with SCC (odds ratio, 0.4; 95% confidence interval, 0.2-0.9). Other variables significantly associated with the tumor were family history of skin cancer, professional or recreational sun exposure, light eye color, high number of solar keratoses and seborrheic keratoses on the body surface, and residency in radon-emitting buildings. CONCLUSIONS: Positive serologic findings for HPV type 8 are associated with SCC occurrence in immunocompetent individuals. Viral infection could act as a cofactor in the tumor development, along with genetic predisposition, solar radiation, and other environmental exposures. If confirmed, these findings could open new perspectives for treatment and prevention of SCC.