The effect of chorionicity on maternal and neonatal outcomes in triplet pregnancies.

OBJECTIVE: Triplet gestations are associated with increased maternal, fetal, and neonatal complications particularly early and extreme preterm delivery. Identifying and interrupting the preterm delivery cascade could prevent the fetal, neonatal, and long-term childhood complications. The shared circulation and placental vascular anastomosis are responsible for the occurrence of twin-to-twin transfusion syndrome, selective fetal growth restriction as well as the higher risk of morbidity and mortality observed in mono and dichorionic compared to trichorionic triplet gestations. Thus, the aim of this study was to determine the effect of chorionicity on maternal, fetal, and neonatal outcomes of triplet pregnancies as it has not been fully ascertained. STUDY DESIGN: A retrospective population-based cohort study of 125 parturient with triplets' pregnancy who delivered at a single tertiary hospital. RESULTS: 98 trichorionic and 27 dichorionic gestations were included. Maternal demographic and obstetric characteristics as well as pregnancy and postpartum complications were similar in the two study groups. The median gestational age at delivery was lower among dichorionic than trichorionic triplet gestations (median 31 vs 33 weeks, p < 0.046). Early (<32 weeks) and extreme preterm delivery (<28 weeks) were more prevalent in the dichorionic than the trichorionic group (early - 56 % vs 34 %, p < 0.038; extreme - 33.3 % vs 8 %, p < 0.002). We found no difference in fetal or newborns' complications and characteristics between the groups. However, the rate of neonatal death was significantly higher in the dichorionic compared to trichorionic triplet gestations (22 % vs 7 %, p < 0.038). A multivariate logistic regression model to determine the variables that contribute to early preterm delivery in triplet gestations showed that women who experienced a past preterm delivery had an independently higher risk for early preterm delivery in the triplet gestation (adj. OR 5.91, 95 % CI 1.16-30.03). Neither maternal age nor chorionicity were found to be independent risk factors for early preterm delivery. CONCLUSIONS: Dichorionic triplet gestations exhibit a higher rate of early (<32 weeks) and extreme (<28 weeks) preterm delivery and are more prone to neonatal death compared to trichorionic gestations. Past preterm delivery is an independent risk factor for early preterm delivery in a triplet gestation.

Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for a small for gestational age neonate.

OBJECTIVE: The effect of severe maternal infectious morbidity on fetal growth during the second half of pregnancy is under debate. Preliminary evidence suggests that such association may be plausible. The objectives of this study were to determine: 1) The association between severe maternal infectious morbidity and adverse pregnancy outcome; and 2) The effect of maternal infection during pregnancy on fetal growth. STUDY DESIGN: This retrospective population - based cohort study included 4771 women who gave birth at our medical center during the study period. Parturients were allocated into two groups: 1) patients with severe maternal infection during the second half of pregnancy (n = 368); and 2) control group comprised of normal pregnant women who were matched to the study group by maternal age, gravidity and parity (n = 4403). RESULTS: The severe maternal infection group included women with pneumonia (n = 198), pyelonephritis (n = 131), and viral pneumonitis (n = 39). In comparison to the normal patients group: 1) having had pneumonia during the second half of pregnancy was associated with increased rates of fetal growth restriction, placental abruption, fetal demise (P < 0.001, for all comparisons) and preeclampsia (P = 0.041); 2) Pyelonephritis during the second half of gestation was associated with higher rates of fetal growth restriction (P < 0.001), placental abruption (P = 0.006) and labor induction (P = 0.039). As a group, women with severe maternal infection had higher rates of small for gestational age neonates compared to normal parturients (P < 0.001). Among women with infections, only those who had pyelonephritis (P = 0.032) or pneumonia (P = 0.008), had a higher rate of small for gestational age neonates than those in the control group. After adjustment to confounding factors, maternal infection (OR = 1.42, 95% CI 1.085-1.85) and previous delivery of a small for gestational age neonate (OR = 2.54, 95% CI 2.02-3.19), were independent risk factors for the delivery of a small for gestational age neonate. CONCLUSION: Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for the delivery of a small for gestational age neonate and is associated with adverse pregnancy outcomes. Both, pneumonia and pyelonephritis, during the second half of gestation affect fetal growth and are related to higher rates of small for gestational age neonates.

Oligohydramnios is an independent risk factor for perinatal morbidity among women with pre-eclampsia who delivered preterm.

PURPOSE: The purpose of this study is to determine the relationship between oligohydramnios and adverse maternal and neonatal outcomes in a unique cohort of preterm pre-eclamptic patients. MATERIALS AND METHODS: A retrospective matched case-control study comparing 81 preterm parturients (28 0/7 and 36 6/7 weeks) with pre-eclampsia and oligohydramnios to 81 preterm pre-eclamptic patients with a normal amniotic fluid index (AFI). RESULTS: About 4.8 percent of all our preterm pre-eclamptic patients had oligohydramnios. Patients in the study group showed a trend toward being older than 35 years (18.5%% versus 27.2%) and were more likely more likely to be primi-parous, and have previously delivered a small for gestational age (SGA) or a dead fetus (p = .012, .039, and .032). Severity of pre-eclampsia, including HELLP and eclampsia as well as gestational age at delivery did not differ statistically between the study groups (p = .47, .516). Growth restricted fetuses were more common in the study group (p < .001) but oliguria was more prevalent in patients without oligohydramnios (p = .046). Post-partum complications, pre-eclampsia during the puerperium, admission to intensive care units, and MgSO4 treatment were more common in the control group (p = .028, .012, .008). But study group patients had more cesarean sections (p = .011). Neonates of study group parturients had lower fetal weight, were more likely to be SGA, and experience fetal distress during labor (p = .001, .001, and .03). Following delivery, they were more likely to have anemia and stay longer in neonatal intensive care unit (NICU) (p = .017, .017). A multivariate logistic regression analysis showed that oligohydramnios, but not the severity of pre-eclampsia, significantly affected Composite Neonatal Outcome {Apgar scores at 1 & 5 min (<5 and <7, respectively), neonatal death, umbilical cord pH <7.1, fetal distress (category III fetal heart rate tracing), fetal anemia, fetal hypoglycemia}. CONCLUSIONS: Oligohydramnios is an independent risk factor for early neonatal morbidity in preterm pre-eclamptic patients. AFI <5 cm can be used as one component in the educated decision for delivery of these patients. Brief rationale The significance of oligohydramnios in pregnancies complicated by preterm delivery, preeclampsia or both is controversial. By comparing two relatively large, almost similar, cohorts of preterm preeclamptic parturient with and without oligohydramnios we demonstrated that Amniotic Fluid Index <5 cm is associated with a significant neonatal morbidity. This question was not previously addressed in proper manner aside one, much smaller, study that was under powered to address this topic. We innovate by illustrating the significance of oligohydramnios and its association with subsequent neonatal morbidity. Thus, we conclude that the presence of oligohydramnios in women with preterm preeclampsia can be a factor in the decision for or against conservative management of these patients.

Postoperative radiation rates in stage IIA1 cervical cancer: Is surgical treatment justified? An Israeli Gynecologic Oncology Group Study.

OBJECTIVES: Data on the outcome of stage IIA1 cervical cancer is limited, as these tumors comprise a small percentage of early tumors. NCCN guidelines suggest consideration of surgical management for small tumors with vaginal involvement. Our objective was to evaluate the risk of adjuvant radiotherapy in stage IIA1 cervical cancer and its associated features, in order to improve selection of patients for surgical management. METHODS: A retrospective cohort study comparing surgically treated cervical cancer patients with stage IB1 and stage IIA1 disease. Women treated between 2000 and 2015 in ten Israeli medical centers were included. Patient and disease features were compared between stages. The relative risk (Fisher's exact test) of receiving post-operative radiation was calculated and compared for each risk factor. A general linear model (GLM) was used for multivariable analysis. RESULTS: 199 patients were included, of whom 21 had stage IIA1 disease. Most features were comparable for stage IB1 and stage IIA1 disease, although patients with vaginal involvement were more likely to have close surgical margins (23.8% vs 8.5%, p = 0.03). Patients with stage IIA1 disease were more likely to receive radiation after surgery (76% vs. 46%, RR = 1.65 (1.24-2.2), p = 0.011). Vaginal involvement as well as depth of stromal invasion, LVSI and lymph node metastases were independent predictors of radiation on multivariable general linear modeling. CONCLUSIONS: Cervical cancer patients with vaginal involvement are highly more likely to require postoperative radiation. We recommend careful evaluation of these patients before surgical management is offered.

Late preterm and early term: when to induce a growth restricted fetus? A population-based study.

PURPOSE: (1) Compare fetal and neonatal morbidity and mortality associated with induction of labor (IOL) versus expectant management (EM) in women with isolated fetal growth restriction (FGR) between 340/7 and 386/7 weeks; (2) Determine optimal gestational age for delivery of such fetuses. MATERIALS AND METHODS: A retrospective population based cohort study of 2232 parturients with isolated FGR, including two groups: (1) IOL (n = 1428); 2) EM (n = 804). RESULTS: IOL group had a lower stillbirth and neonatal death rates (p = .042, p < .001), higher 1 and 5 min Apgar scores and a higher vaginal delivery rate compared to the EM group. In the late preterm period, EM was associated with increased rate of low 1 and 5 min Apgar scores, nonreassuring fetal heart rate tracing (NRFHR), stillbirth and neonatal death rate (p = .001, p = .039). In the early term cohort, EM was associated with a higher rate of NRFHR and low 1 min Apgar scores (p = .003, p = .002). IOL at 37 weeks protected from stillbirth but not from adverse composite neonatal outcomes. CONCLUSIONS: IOL of FGR fetuses at 37 weeks had a protective effect against stillbirth. In addition, at late preterm, it is associated with lower rates of stillbirth, neonatal death, and NRFHR.

Robotic surgery for ovarian cancers: individualization of the surgical approach to select ovarian cancer patients.

BACKGROUND: While well-accepted treatment for endometrial and cervical cancers, the role of robotic surgery in the management of primary and recurrent ovarian cancers remains an area of active study and debate. METHODS: Narrative review of the pertinent literature on the use of robotics in the treatment of ovarian cancers. RESULTS: The available evidence may indicate the feasibility of robotics for primary and secondary debulking of ovarian cancers. The use of robotics can be considered for the surgical treatment of patients requiring primary tumour excision, alone or with one additional major procedure, and patients with isolated recurrences. However, most of the publications are underpowered, retrospective, fail to provide sufficient data on long-term oncological outcomes and are published by highly skilled minimally invasive surgeons. CONCLUSIONS: Robot-assisted surgery may provide a tool to individualize the surgical approach to select ovarian cancer patients. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

OBJECTIVE: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. METHODS: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. RESULTS: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. CONCLUSIONS: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

Neo-adjuvant chemotherapy for advanced stage endometrial carcinoma: a glimmer of hope in select patients.

PURPOSE OF REVIEW: The objective of this review is to conduct a critical appraisal of the published literature on the use of neo-adjuvant chemotherapy followed by interval debulking in the treatment of stage IVb endometrial carcinoma patients. METHODS: Narrative review of the pertinent literature on the application of neo-adjuvant chemotherapy and interval surgery in the treatment of advanced stage endometrial cancers. RESULTS: Advanced stage endometrial carcinoma patients are treated by aggressive cytoreduction followed by adjuvant chemotherapy or by chemotherapy alone. The prognosis of patients that cannot undergo surgery is extremely poor. Preoperative reduction of tumor burden by chemotherapy can facilitate surgery in patients previously considered to have an unresectable disease, identify patients with chemo-sensitive tumors that are more likely to benefit from surgery, and enable a less aggressive surgery thus reducing morbidity. However, only 106 cases of neo-adjuvant chemotherapy were documented in the last two decades, majority (76) were described in retrospective case reports and case series. The available data may indicate feasibility of neo-adjuvant treatment in select patients. Compared to patients that had primary surgery, neo-adjuvant setting was associated with improved or equivalent survival and maximal debulking rates and reduced postoperative morbidity. CONCLUSIONS: Until further progress is reached, consideration can be given to recommending neo-adjuvant chemotherapy followed by interval debulking to patients with poor performance status or those patients who the surgeon believes would have suboptimal debulking if surgery was attempted.

Minimally invasive surgery for endometrial cancer.

PURPOSE OF REVIEW: To critically appraise the pertinent literature on traditional laparoscopy and robotically assisted laparoscopy for the treatment of endometrial cancer. RECENT FINDINGS: Multiple retrospective and prospective studies on traditional laparoscopy and retrospective studies on robotically assisted laparoscopy for the treatment of uterine cancers have shown reduced blood loss, shorter length of hospital stay and decreased incidence and severity of postoperative surgical complications compared with laparotomy. Minimally invasive techniques maintain equivalent oncologic results with regard to the number of dissected lymph nodes and overall and disease-free survival rates.Compared with traditional laparoscopy, robotic surgery has a lower rate of conversion to laparotomy, lower blood loss and presents significant ergonomic advantages for the surgeon facilitating execution of complex oncologic procedures. Minimally invasive techniques are particularly advantageous in obese patients, reducing perioperative and postoperative abdominal wound complications. SUMMARY: A thorough review of the literature indicates that minimally invasive approach has a number of established advantages over laparotomy that makes it the surgical treatment option of choice in endometrial carcinoma patients.

Primary rhabdoid tumor of the ovary: When large cells become small cells.

•The third case of pure primary malignant rhabdoid tumor of the ovary (MRTO) is described•SMARCA4 and SMARCB1 genetic analysis and immunohistochemistry are necessary for correct diagnosis of MRTO•MRTO and small cell carcinoma of the ovary, hypercalcemic type are essentially the same and should be treated as such.

Para-aortic and Pelvic Radiotherapy, an Effective and Safe Treatment in Advanced-stage Uterine Cancer.

AIM: The present, was a feasibility study of extended-field (EF) external-beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) given sequentially following complete staging and adjuvant chemotherapy for patients with advanced-stage endometrial carcinoma (EC). PATIENTS AND METHODS: A cohort study was carried out in 38 patients with stage IIIC and IVB EC treated by surgery, six cycles of paclitaxel-carboplatin chemotherapy followed by EF EBRT and VBT. RESULTS: A total of 60% of the patients had non-endometrioid histology, 45% had both pelvic and para-aortic lymph node metastases. Two patients experienced recurrence in the previously irradiated field. Five-year overall and progression-free survival were 77% and 72.5%, respectively. Grade 1 diarrhea and grade 1 cystitis were the most common acute and delayed side-effects. CONCLUSION: EF EBRT and VBT following complete staging and adjuvant chemotherapy is a safe and effective treatment for patients with advanced-stage EC. Compared to historical data, our study suggests an improved progression-free and overall survival with acceptable acute and delayed side-effects.

Prolonged pegylated liposomal doxorubicin treatment for recurrent pelvic cancers: a feasibility study.

We conducted a proof of concept study evaluating prolonged treatment with pegylated liposomal doxorubicin for recurrent ovarian, tubal and peritoneal carcinoma. Thirteen consecutive patients received an average of 22.6 cycles of pegylated liposomal doxorubicin, with an average cumulative dose of 1409 mg/m(2) . Progression-free survival at 18 months was 61.5%, and was longer than the previous progression-free survival in 10 of the 13 patients. Overall 5-year survival was 78.8%. Despite prolonged use and relatively large cumulative doses of pegylated liposomal doxorubicin, most of the patients had mild to moderate side-effects, none of the patients had detectable cardio-toxic side-effects, and a positive impact on the performance status was noticed. Thus, in our group of patients, continued pegylated liposomal doxorubicin treatment was associated with a longer progression-free interval and allowed improved performance status with manageable toxicity.

Minimally invasive surgery for endometrial cancer: a comprehensive review.

PURPOSE OF REVIEW: The objective of this article is to review the recently published literature on the use of minimally invasive surgical approaches for patients with endometrial cancer. METHODS: Narrative review of the pertinent literature on traditional laparoscopy and robotically assisted laparoscopy for the treatment of endometrial cancer. RESULTS: Multiple studies have shown that minimally invasive surgical approaches for the treatment of endometrial cancer reduce blood loss, length of hospital stay and the incidence and severity of post-operative surgical complications compared with laparotomy. Minimally invasive techniques maintain equivalent oncologic results with regard to the number of dissected lymph nodes and overall and disease-free survival rates. Robotically assisted laparoscopy compared to traditional laparoscopy reduced the conversion rate to laparotomy, further reduces intra-operative blood lose and has significant ergonomic advantages for the surgeon. Laparoscopic and robotic surgery techniques are particularly advantageous in obese patients, reducing peri-operative and post-operative abdominal wound complications. CONCLUSIONS: A thorough review of the literature indicates that minimally invasive approach has a number of established advantages over laparotomy that makes it the surgical treatment option of choice in endometrial carcinoma patients.

Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

Expression of IL-18, IL-18 binding protein, and IL-18 receptor by normal and cancerous human ovarian tissues: possible implication of IL-18 in the pathogenesis of ovarian carcinoma.

Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P = 0.0007), IL-18BP levels were significantly higher in normal ovarian tissues (P = 0.04), and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P = 0.036). Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P = 0.025), while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

Distinct expression and localization of TNF system in ovarian carcinoma tissues: possible involvement of TNF-α in morphological changes of ovarian cancerous cells.

BACKGROUND/AIM: It has been previously shown that epithelial ovarian carcinoma tissues express high levels of tumor necrosis alpha (TNF-α), interleukin (IL)-6, IL-1α and IL-1ß. The aim of the present study was to evaluate the localization of TNF-α and its receptors (TNFR1 and TNFR2) in different types of ovarian carcinoma tissues and the possible role of TNF in the pathogenesis of epithelial ovarian carcinoma. MATERIALS AND METHODS: Total RNA was extracted from normal and cancerous ovarian tissues and mRNA was analyzed with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemical staining was performed with use of antibodies against human (ah)TNFR1 and TNF2. RESULTS: TNF-α mRNA and TNFR2 mRNA levels were significantly higher in ovarian carcinoma tissues than in normal ovarian tissues, whereas TNFR1 mRNA levels were similar. TNFR1 and TNFR2 were mainly localized in the epithelial neoplastic cells of the tumor. Knocking-down TNF-α activity with αhTNF-a altered ovarian carcinoma cell morphology (with more branches) in vitro. CONCLUSION: Our study indicates a possible role of TNF-α in epithelial ovarian carcinoma pathogenesis through TNFR2, which affects morphological changes, which may be involved ovarian cancer pathogenesis.

Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells.

BACKGROUND: Thalidomide inhibits TNF-α production in lipopolysaccharide-stimulated monocytes. The aim of this study was to evaluate the effect of thalidomide on TNF-α, IL-6 and MMP secretion in epithelial ovarian carcinoma cells. MATERIALS AND METHODS: SKOV-3 cells and primary epithelial ovarian carcinoma cells were cultured in the presence of various concentrations of thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF-α and IL-6 levels were determined in the supernatants of the cell cultures by ELISA, and MMP activity was examined by gelatin zymography. RESULTS: Thalidomide did not significantly affect the proliferation and growth of SKOV-3 cells. However, it decreased significantly the capacity of SKOV-3 cells and primary epithelial ovarian carcinoma cells to secrete TNF-α. Thalidomide also significantly decreased the capacity of SKOV-3 cells, but not primary epithelial ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma cells. CONCLUSION: Our study suggests that thalidomide distinctly affected TNF-α, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and primary ovarian cancer cells. This might suggest a different susceptibility of these two types of cells to thalidomide, and/or that the mechanisms of secretion of the factors examined are differently regulated in these cells. Our results may deepen our understanding the mechanism/s of action of thalidomide in ovarian carcinoma cells. The results might have important implications in future therapeutic strategies that will incorporate thalidomide and other cytokine inhibitors in the treatment of epithelial ovarian carcinoma.

The rate of the predominant Jewish mutations in the BRCA1, BRCA2, MSH2 and MSH6 genes in unselected Jewish endometrial cancer patients.

OBJECTIVES: The genes associated with familial Endometrial Cancer (EC) are largely unknown. While EC is an integral part of Hereditary Non-Polyposis Colon Cancer, there is an ongoing debate if EC is indeed overrepresented in hereditary breast/ovarian cancer families. METHODS: Unselected Jewish women with EC who were diagnosed from January 1982 to January 2008 were genotyped for the predominant mutations in Jewish individuals in BRCA1 (185delAG, 5382InsC, Tyr978X) BRCA2 (6174delT), MSH2 (A636P, 324delCA) and MSH6 (c.3984_3987dup). RESULTS: Overall, 289 Jewish women with EC were included, the majority (217-75%) were Ashkenazim. Mean age at diagnosis was 62.6 ± 12 years, the most common histopathology was type I (endometrioid carcinoma) (80.4% of participants) with 29 having type II (Uterine papillary serous and clear cell cancer) Most patients (85.4%) had stage 1 disease by the FIGO staging. Five women (1.7%-2.3% of the Ashkenazim) carried either the BRCA1*185delAG (n = 4) or BRCA2*6174delT (n = 1) mutations, a rate similar with that of the general Ashkenazi population. Notably, none of 34 women with type II EC carried any BRCA1/BRCA2 mutations. Four (1.8%) and three (1.4%) of the 217 Ashkenazim patients harbored the c.3984_3987dup, A636P, MSH6 and MSH2 mutations, respectively, and 1/72 (1.4%) of the non-Ashkenazi patients harbored the 324delCA MSH2 mutation. Three of 42 (7.1%) women with EC diagnosed < 50 years carried either BRCA1 MSH6 or MSH2 mutations. CONCLUSIONS: Our data do not support screening for BRCA1/2 mutations in consecutive EC patients.

The effect of alcohol, THC and their combination on perceived effects, willingness to drive and performance of driving and non-driving tasks.

BACKGROUND: Driving under the influence of drugs (DUID) is one of the main causes of car accidents. Alcohol and marijuana are the most popular drugs among recreational users. Many classify these drugs as "Light" drugs and therefore allow themselves to drive after consuming them. OBJECTIVE: The study had two main objectives: 1) to investigate the effect of alcohol (BAC=0.05%), THC (13 mg) and their combination on driving and non-driving tasks. 2) to investigate the extent to which people are willing to drive based on their subjective sensations and their perceived effects of the drugs. METHOD: 7 healthy men and 5 healthy women, ages 24-29, all recreational users of alcohol and marijuana, completed 5 experimental sessions. Sessions included: drinking and smoking placebo, drinking alcohol and smoking placebo, drinking placebo and smoking THC, drinking alcohol and smoking THC, drinking placebo and smoking placebo 24 hours after drinking alcohol and smoking THC. Three types of measures were used: subjective perceptions (with questionnaires), performance parameters of the driving and non-driving tasks (arithmetic task and a secondary target detection task) and physiological changes (heart rate). RESULTS: Overall, the combination of alcohol and THC had the most intense effect after intake. This effect was reflected in performance impairments observed in the driving and non-driving tasks, in the subjective sensations after intake, and in the physiological measures. Despite significant differences in the size of the effects after the various treatments, there were no differences in the distances subjects were willing to drive while under the influence on each of the treatments.

Expression of IL-10 in human normal and cancerous ovarian tissues and cells.

IL-10 is an 18-kd polypeptide that has been shown to be secreted by multiple cell types, including T and B cells, monocytes and some human tumors. However, which cell population is responsible for the elevated IL-10 levels in the serum and ascites of ovarian cancer patients, whether ovarian carcinoma cells produce IL-10, and how IL-10 influences the development and progression of ovarian carcinoma are issues that remain unclear. The aim of our study was to examine IL-10 production and secretion by ovarian carcinoma tissues and cells, and to determine its possible role in the cell and tumor micro-environment. The mean IL-10 protein levels expressed in normal ovarian tissue homogenates were significantly higher compared to cancerous ovarian tissue (p = 0.002). Yet, the IL-10 mRNA expression was significantly higher in cancerous ovarian tissues as compared to normal tissues (p = 0.021). The IL-10 receptor mRNA expression levels of the cancerous ovarian tissue homogenates were slightly, but not significantly, higher than the normal tissues. IL-10 immunostaining revealed that in both normal and cancerous ovarian tissues, IL-10 expression could be detected mainly in epithelial cells. In normal ovarian tissues, similar levels of IL-10R were demonstrated in epithelial and stromal cells. However, in cancerous ovarian tissues, epithelial cells expressed higher levels of IL-10R than the stroma. Primary normal and cancerous ovarian cell cultures and SKOV-3 cells secreted similar amounts of IL-10 after 24 hours of incubation. Our results suggest that epithelial cells are the main source of IL-10 in the ovary. Nevertheless, the target cells for IL-10 are different in normal and cancerous ovarian cells. Thus, IL-10 and its receptor could be involved in the pathogenesis of ovarian carcinoma.