Background: Throughout pregnancy maternal adipose tissue is metabolically active, producing adipocytokines involved in the process of insulin resistance. We explored the role of serum adipocytokines, including the newly identified adipocytokine visfatin, in the process of insulin resistance in normal pregnancy. Methods: We examined 80 pregnant nonobese, nondiabetic white women during the 3 trimesters of pregnancy. All study participants underwent anthropometric measurements, adipocytokine evaluation, and a 75-g oral glucose tolerance test. Homeostasis mathematical model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of -cell secretion were calculated. Results: Maternal weight, percentage total body fat, hip circumference, and indices of -cell secretion increased significantly during the 3 trimesters, and HOMA-R and ISI increased and decreased, respectively, in the 3rd trimester. During early pregnancy, insulin resistance, -cell secretion, and weight correlated positively with leptin. During the 1st trimester, visfatin correlated negatively with percentage
Corticotropin-releasing hormone (CRH), a 41 amino acid peptide, is an important regulatory molecule synthesized by neurons of the parvocellular and magnocellular hypothalamic paraventricular nuclei. It acts as the major physiologic corticotropin (ACTH) secretagogue. The CRH gene is located in humans on chromosome 8. The CRH hormone family has at least four ligands, two receptors (CRH-R1 and CRH-R2), and a binding protein (CRHbp). CRH is the principal regulator of the hypothalamic-pituitary-adrenal axis. Furthermore, CRH has been identified in most female reproductive tissues including the uterus, the placenta, and the ovary. CRH produced in the endometrium may participate in decidualization, implantation, and early maternal tolerance to semiallograft embryo. Placental CRH may participate in the physiology of pregnancy, in late pregnancy complications such as preterm labor and preeclampsia, and also in the onset of parturition. Ovarian CRH is involved in follicular maturation, ovulation, and luteolysis. Increased levels of unbound placental CRH may be responsible for the hypercortisolism of the second half of pregnancy. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period. This may explain the depressive states frequently observed in the postpartum period.
ObjectiveThis study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer.MethodsThis international, multicenter, retrospective study included 2453 patients diagnosed with vulvar cancer at 100 different institutions. Inclusion criteria were institutional review board approval from each collaborating center, pathologic diagnosis of invasive carcinoma of the vulva, and primary treatment performed at the participating center. Patients with intraepithelial neoplasia or primary treatment at non-participating centers were excluded. Global survival analysis and squamous cell histology subanalysis was performed.ResultsAfter excluding patients due to incomplete data entry, 1727 patients treated for vulvar cancer between January 2001 and December 2005 were registered for analysis (1535 squamous, 42 melanomas, 38 Paget’s disease and 112 other histologic types). Melanomas had the worse prognosis (p=0.02). In squamous vulvar tumors, independent factors for increase in local recurrence of vulvar cancer were: no prior radiotherapy (p<0.001) or chemotherapy (p=0.006), and for distant recurrence were the number of positive inguinal nodes (p=0.025), and not having undergone lymphadenectomy (p=0.03) or radiotherapy (p<0.001), with a HR of 1.1 (95% CI 1.2 to 1.21), 2.9 (95% CI 1.4 to 6.1), and 3.1 (95% CI 1.7 to 5.7), respectively. Number of positive nodes (p=0.008), FIGO stage (p<0.001), adjuvant chemotherapy (p=0.001), tumor resection margins (p=0.045), and stromal invasion >5 mm (p=0.001) were correlated with poor overall survival, and large case volume (≥9 vs <9 cases per year) correlated with more favorable overall survival (p=0.05).ConclusionsAdvanced patient age, number of positive inguinal lymph nodes, and lack of adjuvant treatment are significantly associated with a higher risk of relapse in patients with squamous cell vulvar cancer. Case volume per treating institution, FIGO stage, and stromal invasion appear to impact overall survival significantly. Future prospective trials are warranted to establish these prognostic factors for vulvar cancer.
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