Prognostic factors in patients with uterine sarcoma: the SARCUT study.

OBJECTIVE: Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different prognostic factors on overall survival and disease-free survival of patients with uterine sarcoma. METHODS: This international multicenter retrospective study included 683 patients diagnosed with uterine sarcoma at 46 different institutions between January 2001 and December 2007. RESULTS: The 5-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma was 65.3%, 78.3%, 52.4%, and 89.5%, respectively, and the 5-year disease-free survival was 54.3%, 68.1%, 40.3%, and 85.3%, respectively. The 10-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma and adenosarcoma was 52.6%, 64.8%, 52.4%, and 79.5%, respectively, and the 10-year disease-free survival was 44.7%, 53.3%, 40.3%, and 77.5%, respectively. The most significant factor associated with overall survival in all types of sarcoma except for adenosarcoma was the presence of residual disease after primary treatment. In adenosarcoma, disease stage at diagnosis was the most important factor (hazard ratio 17.7; 95% CI 2.86 to 109.93). CONCLUSION: Incomplete cytoreduction, tumor persistence, advanced stage, extra-uterine and tumor margin involvement, and the presence of necrosis were relevant prognostic factors significantly affecting overall survival in uterine sarcoma. The presence of lymph vascular space involvement and administration of adjuvant chemotherapy were significantly associated with a higher risk of relapse.

Prognostic factors in patients with vulvar cancer: the VULCAN study.

OBJECTIVE: This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer. METHODS: This 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. RESULTS: After 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). CONCLUSIONS: Advanced 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.

Tumor to Tumor Metastasis from Adenocarcinoma Not Otherwise Specified of the Parotid Gland to Uterine Leiomyoma: Presentation of a Unique Case.

Salivary gland adenocarcinoma not otherwise specified (NOS) is a malignant epithelial tumor composed of ductal/glandular structures with or without cystic formation. Histologically it is classified as high grade with relevant biological behavior. Although both minor and major glands may be involved, the majority (60%) implicate the parotid gland. Location, regional lymph node status, and histological grade are some of the factors that predict the progress of the disease and the development of metastases. Long follow-up is considered the standard option as distant metastases (DM) may occur despite regional control. Primary sites of DM, besides lymph nodes, include bone, lung, and liver. Herein we report a unique case of a 68-year-old female with a previous history of high-grade adenocarcinoma NOS of her right parotid gland. On her biannual follow-up examination, MRI revealed an abnormal increase in the size of a known uterine leiomyoma of the posterior uterine wall. Positron emission tomography-CT (PET-CT) showed increased uptake in the uterus and lungs. On frozen section, adenocarcinoma was found at the center of the leiomyoma. Histological and immunohistochemical findings were consistent with secondary involvement by the salivary gland adenocarcinoma NOS. Treatment consisted of cyclophosphamide, adriamycin, and cisplatin with poor outcome. The patient was lost to follow-up. Review of the literature indicates that no similar case has been reported in the English literature.

Maternal chronic stress correlates with serum levels of cortisol, glucose and C-peptide in the fetus, and maternal non chronic stress with fetal growth.

INTRODUCTION: During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus. MATERIALS AND METHODS: Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day. RESULTS: In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores<40. 2nd trimester: STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negatively with U/S fetal biparietal head diameter, while serum cortisol correlated positively with abdominal circumference. Maternal serum IL6, CRH and cortisol all correlated positively with birth waist circumference. 3rd trimester: Women with STAI state scores ≥40 had fetuses with larger U/S abdominal and smaller head circumferences compared to those of women with STAI scores <40. Women with STAI trait scores ≥40 had greater levels of cord blood cortisol, glucose, and c-peptide compared to women with STAI scores <40. STAI state scores ≥40 correlated positively with maternal CRH and U/S fetal abdominal circumference, and negatively with fetal head circumference and biparietal diameter. STAI trait scores correlated positively with cord blood c-peptide, glucose, insulin and cortisol. Maternal serum levels of CRH correlated positively with U/S fetal abdominal circumference and cord blood cortisol, and negatively with fetal head circumference and biparietal head diameter. Maternal serum levels of both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter. CONCLUSIONS: Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively.

Recent Trends in HPV Infection and Type Distribution in Greece.

BACKGROUND/AIM: This study gives an insight into recent trends for Human papillomavirus (HPV)-specific infection and its fluctuation over the years 2011-2016. MATERIALS AND METHODS: A total of 2,417 Caucasian women between the age of 18 and 71 years underwent their annual gynaecologic examination at the Outpatient Gynaecological Clinic in the study period. RESULTS: Overall HPV prevalence was 43.9%, and high-risk HPV accounted for 31.3%. HPV16 was the most common high-risk type followed by HPV51 and HPV31. HPV positivity was higher in those with low- and high-grade squamous intraepithelial lesions (HSILs) than in women with a normal cytological test. HPV infection was highest in 2011.The prevalence of single infections remained higher than multiple infections over the entire study period. HPV16 prevalence was very high in the first years of the study and HPV18 exhibited highest prevalence in 2011. Younger women exhibited a significant increase in HPV infection from 2014. Overall HPV infection decreased over the study period. CONCLUSION: These data suggest that HPV vaccination might reduce the frequency of HSILs and cervical cancer and are useful for the development of a national screening programme.

Cytological Features of the Large Cell Variant of Small Cell Ovarian Carcinoma in Young Patients with Hypercalcemia: Histological Findings and Review of the Literature.

OBJECTIVE: To present the cytological features of a very rare and lethal ovarian neoplasm occurring in the young. STUDY DESIGN: We reviewed the cytological findings as they presented in touch imprints obtained from an ovarian mass sent to our department for frozen section investigation. RESULTS: Smears were highly cellular. The cells were of intermediate size with a moderate amount of microvacuolated, pale, or eosinophilic cytoplasm with indistinct cell borders. The nuclei were of round or oval shape with mild to moderate atypia and indistinct nucleoli. CONCLUSIONS: The diagnosis of small cell carcinoma of the ovary can be challenging even histologically. Cytology can be an invaluable adjunct to hematoxylin-eosin sections both pre- or intraoperatively. Although it is a very rare occurrence and cytological results are almost absent in the literature, our case can make cytopathologists more acquainted with the cytological features of this rare tumor entity especially in association with a characteristic clinical profile. Furthermore, the cytological features of small cell carcinoma of the ovary, large cell variant, have only rarely been described in the literature.

In pregnancy increased maternal STAI trait stress score shows decreased insulin sensitivity and increased stress hormones.

INTRODUCTION: Chronic or acute stressors influence maternal and fetal Hypothalamus-Pituitary-Adrenal Axes (HPA) during pregnancy. In this study, the effect of maternal stress into maternal insulin sensitivity was investigated during pregnancy. MATERIALS AND METHODS: Eighty-two pregnant women [aged 27.1±2.5 (mean±SD) yrs; BMI=25±2.2kg/m2] had at the 2nd and 3rd trimesters anthropometry, fasting blood samples (cortisol, Corticotropin Releasing Hormone (CRH), active amylin, Interleukin (IL6)), Oral Glucose Tolerance Test (OGTT) for glucose and insulin, state-trait anxiety inventory (STAI) trait and state questionnaires (for stress assessment). RESULTS: Maternal cortisol, CRH and STAI state score increased significantly from 2nd to 3rd trimester. At these trimesters women with STAI trait scores ≥40 had greater serum cortisol and CRH concentrations and lower insulin sensitivity index (ISI) values than those with scores <40 while STAI trait score predicted negatively ISI. At the 2nd trimester maternal CRH concentrations correlated positively with maternal STAI state, Homeostatic Model Assessment Insulin Resistance (HOMAR), 1st and 2nd phase insulin secretion and negatively with ISI. STAI trait correlated negatively with ISI. STAI state correlated positively with maternal systolic blood pressure and HOMAR. At the 3rd trimester STAI trait correlated negatively and positively with ISI and STAI state, respectively, while STAI state correlated positively with HOMAR. In women with STAI state scores ≥40, these scores correlated positively with maternal CRH. CONCLUSIONS: In normal pregnant women, enhanced long-term stress is associated with decreased insulin sensitivity. Both long- and short- term stress are associated with enhanced maternal HPA axis and increased placental CRH secretion.

Peritoneal Keratin Granulomatosis Associated with Endometrioid Adenocarcinoma of the Uterine Corpus in a Woman with Polycystic Ovaries: A Potential Pitfall-A Case Report and Review of the Literature.

Peritoneal keratin granulomatosis is a rare condition included under granulomatous lesions of the peritoneum. It can be secondary to neoplasms of the female genital tract and can mimic carcinomatosis intraoperatively. A case of a 40-year-old woman with a history of polycystic ovaries and a chief complaint of vaginal bleeding is presented. She was diagnosed with endometrioid adenocarcinoma with squamous differentiation in endometrial curettings. Intraoperatively, many peritoneal nodules were found, interpreted as peritoneal carcinomatosis. The woman underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, bilateral pelvic lymphadenectomy, and appendicectomy. Multiple biopsies were taken, as well as peritoneal washings. Microscopic examination revealed multiple keratin granulomas on the serosal surface of the ovaries, fallopian tubes, appendix, and omentum. Lymph node metastasis was not found. Peritoneal keratin granulomas (PKGs) have been reported in cases of endometrioid adenocarcinoma with squamous differentiation of the uterine corpus, ovary, and atypical adenomyoma. It should be noted that the prognosis of cases of peritoneal keratin granulomas without viable tumor cells is favourable and that the histologic examination is essential for its diagnosis. We report a case of PKG in a patient with endometrial carcinoma with squamous differentiation, being the first in a woman with polycystic ovaries.

Neonatal birth waist is positively predicted by second trimester maternal active ghrelin, a pro-appetite hormone, and negatively associated with third trimester maternal leptin, a pro-satiety hormone.

INTRODUCTION: In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth. METHODS: Forty-two normal and thirty eight overweight women (mean±SD; age: 26.9±2.5years; pre-pregnancy BMI 26±2.2kg/m(2)) were seen during each of the three trimesters, had blood sampling and a 75g oral glucose tolerance test. At birth, neonates underwent anthropometry and cord blood sampling for c-peptide, glucose, insulin. RESULTS: During all three trimesters maternal weight correlated positively with percent total neonatal body fat while during the second and third trimesters it correlated positively with birth weight. The second trimester maternal active ghrelin levels correlated positively with neonatal waist and were its best positive predictor. The third trimester maternal active ghrelin levels correlated positively with neonatal waist and negatively with percent total neonatal body fat, fetal cord blood insulin levels and were the best negative predictor of the latter. The third trimester maternal leptin levels correlated negatively with neonatal waist. CONCLUSIONS: During pregnancy circulating maternal active ghrelin, a pro-appetite hormone, is associated with neonatal visceral energy storage (as expressed by neonatal waist). By inhibiting glucose-driven maternal insulin secretion, ghrelin might ensure adequate fasting glucose and nutrient supplies to the fetus while limiting overall fetal adipose tissue deposition.

First trimester maternal BMI is a positive predictor of cord blood c-peptide levels while maternal visfatin levels is a negative predictor of birth weight.

OBJECTIVE: The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-peptide and birth weight in pregnancy was investigated. DESIGN: Seventy non-diabetic pregnant Caucasian women were recruited. Anthropometry and measurements of fasting adipocytokines (visfatin, leptin, adiponectin), insulin and glucose were performed in each of the three trimesters. At birth, birth weight and cord blood c-peptide, glucose, insulin, visfatin, leptin, adiponectin and IL6 in each neonate were measured. RESULTS: First trimester maternal BMI correlated positively with cord blood c-peptide (p=0.035, r=0.74) and negatively with cord blood visfatin (p=0.049, r=-0.67). First trimester HOMAR was negatively correlated with cord blood visfatin (p=0.037, r=-0.90) and negatively with cord blood leptin (p=0.031, r=0.90). First trimester maternal BMI was a positive predictor of cord blood c-peptide (p=0.007). First trimester maternal visfatin levels were negative predictors of birth weight (p=0.017). CONCLUSIONS: We conclude that first trimester maternal BMI and serum visfatin seem to be strongly associated with fetal insulin secretion and final birth weight, respectively, suggesting a role of early-pregnancy maternal adipose tissue in the pregnancy metabolic environment.

Pulsatile interleukin-6 leads CRH secretion and is associated with myometrial contractility during the active phase of term human labor.

OBJECTIVE: Our objective was to investigate IL-6 and CRH secretion during the active phase of human labor and to define their potential involvement in myometrial contractility. STUDY DESIGN: Twenty-two primigravid women were studied for 90 minutes during the active phase of term labor by serial plasma sampling every 3 minutes for measurement of IL-6 and CRH concentrations. Uterine contractions, measured by cardiotocograph, were evaluated in Montevideo units. Basic, quantitative, pulsatility, and time cross-correlation statistical analyses were performed. RESULTS: By linear regression analysis, a positive correlation was observed between IL-6 and CRH total mean area under the curve above 0 (r = 0.76184, P = .006). Mean number of pulses was 2.00 ± 0.70 and 3.33 ± 1.29 for IL-6 and CRH, respectively. There was a significant positive correlation between IL-6 and CRH over time, peaking at the 12-minute interval, with IL-6 leading CRH. Also, there was a significant positive correlation between myometrial contractility expressed in Montevideo units and IL-6 concentrations over time, starting at +51 minutes and ending at +57 minutes with myometrial contractility leading IL-6. No significant correlation was found between myometrial contractility and CRH concentrations over time. CONCLUSION: IL-6 and CRH are both secreted in a pulsatile fashion during the active phase of human labor. The time-integrated concentrations of the two hormones are positively correlated, with IL-6 leading CRH secretion. It appears, thus, that proinflammatory mediators may be direct and/or indirect promoters of placental CRH release. Furthermore, the secretion of IL-6, which is a myokine, seems to be associated positively with uterine contractility. Additional studies are needed to elucidate the combined effect of inflammation, placental CRH release, and/or the receptors of the latter in parturition.

The role of adipocytokines in insulin resistance in normal pregnancy: visfatin concentrations in early pregnancy predict insulin sensitivity.

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 beta-cell secretion were calculated. RESULTS: Maternal weight, percentage total body fat, hip circumference, and indices of beta-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, beta-cell secretion, and weight correlated positively with leptin. During the 1st trimester, visfatin correlated negatively with percentage body fat and was the best positive predictor of 2nd trimester ISI. In the 2nd trimester, serum visfatin was the best negative predictor of percentage body fat. CONCLUSIONS: During normal pregnancy of nonobese, nondiabetic women, adipose tissue increases, accompanied by a significant progressive increase of insulin resistance. Visfatin concentrations in the 1st trimester positively predict insulin sensitivity during the 2nd trimester. Body fat mass during 1st trimester of pregnancy is negatively associated with insulin sensitivity during the 2nd trimester and perhaps should be kept under control.

"Reproductive" corticotropin-releasing hormone.

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.

Isolated colonic leukocytoclastic vasculitis causing segmental megacolon: report of a rare case.

We report the case of a 44-year-old white man who presented with progressively worsening crampy abdominal pain and distention. Deterioration of his clinical picture along with leukocytosis and radiographic evidence of severe colonic dilation rendered exploratory laparotomy necessary. Greatly distended and inflamed transverse and descending colon were evident and an extended left colectomy was performed. Characteristic changes of leukocytoclastic vasculitis in the serosal and muscular layers of the resected colon were demonstrated at histopathologic examination. Systemic leukocytoclastic vasculitis, usually coexisting with Henoch-Schonlein purpura, commonly affects the small bowel with clinical evidence of ischemia or bleeding. Colon involvement is infrequently reported in the context of systemic disease. Isolated colonic leukocytoclastic vasculitis without extraintestinal manifestations is rare. A previously unreported case of localized leukocytoclastic vasculitis of the left colon resulting in the impressive presentation of megacolon, without the presence of any precipitating factor or associated systemic disease is presented here, with an overview of the related literature.