Changes in cytokine and sequestosome-1 levels during twin pregnancy progression: Association with outcome.

BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions. OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome. STUDY DESIGN: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined. RESULTS: IL-1ß (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1ß concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1ß in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1ß level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05). CONCLUSION: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.

Does atenolol use during pregnancy cause small for gestational age neonates? A meta-analysis.

OBJECTIVES: Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature. METHODS: We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic. RESULTS: Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %. CONCLUSIONS: Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol.

Hispanic race is a risk factor for COVID-19 during pregnancy: data from an urban New York City hospital.

There are limited studies on predisposing factors for COVID-19 positivity in asymptomatic pregnant women. The literature published to date on asymptomatic COVID-19 pregnant carriers does not focus on pregnancy or pre-pregnancy comorbidities. We wanted to identify risk factors for COVID-19 in asymptomatic pregnant women. We performed a retrospective chart review of 263 asymptomatic pregnant women admitted to labour and delivery at New York City Health + Hospitals/Lincoln.We analysed the association between race, body mass index (BMI), smoking, indication for admission, gravidity, parity, pre-pregnancy comorbidity, pregnancy comorbidity via uni- and multivariate statistical tests. Only Hispanic race was significant in the univariate analysis (p = .049). At the post-hoc analysis, Hispanics had a higher proportion of COVID-19 cases compared to non-Hispanic Blacks (p = .019). No variables were significantly associated with COVID-19 positivity in the multivariate analysis.Hispanic race appears to be a risk factor for asymptomatic COVID-19 infection during pregnancy. We speculate that the cultural and socioeconomic reality of Hispanic women living in our community leads to more exposure opportunities and therefore, a higher infection rate.Impact statementWhat is already known on this subject? Little is known on the role of comorbidities and risk factors that can favour COVID-19 infection during pregnancy.What do the results of this study add? We found that Hispanic pregnant asymptomatic women had a higher rate of COVID-19 in comparison to non-Hispanic Black women. Pre-pregnancy comorbidities such as pregestational diabetes, hypertension and asthma were not associated with COVID-19 positivity.What are the implications of these findings for clinical practice and/or further research? The reasons why the Hispanic race is more affected by COVID-19 during pregnancy is unclear. The social environment of Hispanic women living in our community, such as their tendency to live in multigenerational and multi-family households, might contribute to a higher infection rate. More resources might be dedicated in the future to Hispanic-dense neighbourhoods.

Preeclampsia: state of art and future perspectives. A special focus on possible preventions.

Preeclampsia (PE) is characterised by the new onset of hypertension after the 20th week of pregnancy, with or without proteinuria or hypertension that leads to end-organ dysfunction. Since the only definitive treatment is delivery, PE still represents one of the leading causes of preterm birth and perinatal mobility and mortality. Therefore, any strategies that aim to reduce adverse outcomes are based on early primary prevention, prenatal surveillance and prophylactic interventions. In the last decade, intense research has been focussed on the study of predictive models in order to identify women at higher risk accurately. To date, the most effective screening model is based on the combination of anamnestic, demographic, biophysical and maternal biochemical factors. In this review, we provide a detailed discussion about the current and future perspectives in the field of PE. We will examine pathogenesis, risk factors and clinical features. Moreover, recent developments in screening and prevention strategies, novel therapies and healthcare management strategies will be discussed.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Twins Compared with Singletons.

OBJECTIVES: It is well known that twin pregnancies confer a high degree of adverse perinatal outcomes. Fetal growth restriction, preterm labor/delivery, and hypertensive disorders of pregnancy are among the causal etiologies associated. Hematologic parameters, specifically, the neutrophil:lymphocyte ratio (NLR), the platelet:lymphocyte ratio (PLR), and some of the routine complete blood cell count components denote a peculiar inflammatory and immunologic profile and have been used as clinical markers for specific obstetric syndromes. To our knowledge, no study has ever evaluated NLR/PLR in twins as a distinct population from singletons. Our primary objective was to analyze NLR/PLR in twins compared with singletons. Our secondary objective was to compare white blood cells, neutrophils, lymphocytes, and platelets between twins and singletons. METHODS: We conducted a retrospective case-control study comparing NLR/PLR markers in twin gestations (dichorionic/diamniotic and monochorionic/dichorionic) versus singleton pregnancies, from January 2019 to April 2020. We excluded pregnancies with potential confounding factors such as human immunodeficiency virus, chronic hypertension, smoking, pregestational diabetes mellitus, or cases with miscarriage/intrauterine fetal demise. We included twin pregnancies (two fetuses) as cases and singletons as controls. RESULTS: We recruited 29 twins and 29 singletons, matched for age, body mass index, and parity. NLR was statistically significantly higher in the first trimester in twins compared with singletons (3.3 vs 2.7, P < 0.01) and the platelet value was lower in the second trimester in twins compared with singletons (199 vs 251, P = 0.01). CONCLUSIONS: We speculate that a decrease in NLR from the first to the second trimester and a decrease in platelet in the second trimester reflect both the physiologic inflammatory/immune reaction of early pregnancy and denote a vital response for the development of normal placentation in twin gestations.

Non-Clinical Variables Influencing Cesarean Section Rate According to Robson Classification.

Background and Objectives: The incidence of cesarean section (CS) has progressively increased worldwide, without any proven benefit to either the mother or the newborn. The aim of this study was to evaluate the association between CS rates and both clinical and non-clinical variables, while applying the Robson classification system. Materials and Methods: This is a retrospective observational study of pregnant women delivering at a tertiary care hospital between 2012 and 2017, either under public or private healthcare. The overall CS rate, and the elective and non-elective CS rate, divided by classes of Robson, were determined. The rate of vaginal deliveries and CSs was compared between the public and private setting. The distribution of incidence of non-elective CSs and their main indications were analyzed between daytime and nighttime. Results: 18,079 patients delivered during the study period: 69.2% delivered vaginally and 30.8% by CS. Robson class 5 was the most frequent (23.4%), followed by class 2B (16.8%). Of the 289 private practice deliveries, 59.2% were CSs. The CS rate was significantly higher in private compared to public practice: 59.2% and 30.4%, respectively (OR 3.32, 95% CI 2.62 ± 4.21). When only considering elective CSs, a statistically significant difference was found in Robson class 5 between private and public practice, with the latter having more CSs (94.2% and 83.8%, respectively (p = 0.046)). The rate of non-elective CS was significantly lower during nighttime than during daytime (17.2% vs. 21.5%, p < 0.01). During daytime, the higher incidence of CS occurred between 4:00 and 4:59 pm, and during nighttime between 9:00 and 9:59 pm. Failed induction was significantly more common as an indication to CS during daytime when compared to nighttime (p = 0.01). Conclusions: This study identified two non-clinical variables that influenced the CS rate: the type of healthcare setting (private vs. public) and the time of the day. We believe that these indications might be related more to the practitioner attitude, rather than objective delivery complications.

Risk Factors for Neonatal/Maternal Morbidity and Mortality in African American Women with Placental Abruption.

Background and Objectives: Risk factors for neonatal/maternal morbidity and mortality in placental abruption have been incompletely studied in the current literature. Most of the research overlooked the African American population as mostly Caucasian populations are selected. We aimed to find which risk factor influence the neonatal and maternal outcome in cases of placental abruption occurring in African American pregnant women in an inner-city urban setting. Materials and Methods: We performed a retrospective cohort study at St. Joseph's Regional Medical Center, NJ United States of America (USA), between 1986 and 1996. Inclusion criteria were African American race, singleton pregnancy with gestational age over 20 weeks and placental abruption. Maternal age, gravidity, parity, gestational age at delivery/occurrence of placental abruption and mode of delivery were collected. Risk factors for placental abruption such as placenta previa, hypertensive disorders of pregnancy, cigarette smoking, crack/cocaine and alcohol use, mechanical trauma, preterm premature rupture of membranes (PPROM), and premature rupture of membranes (PROM) were recorded. Poor neonatal outcome was considered when anyone of the following occurred: 1st and 5th minute Apgar score lower than 7, intrauterine fetal demise (IUFD), perinatal death, and neonatal arterial umbilical cord pH less than 7.15. Poor maternal outcome was considered if any of the following presented at delivery: hemorrhagic shock, disseminated intravascular coagulation (DIC), hysterectomy, postpartum hemorrhage (PPH), maternal intensive care unit (ICU) admission, and maternal death. Results: A population of 271 singleton African American pregnant women was included in the study. Lower gestational age at delivery and cesarean section were statistically significantly correlated with poor neonatal outcomes (p = 0.018; p < 0.001; p = 0.015) in the univariate analysis; only lower gestational age at delivery remained significant in the multivariate analysis (p = < 0.001). Crack/cocaine use was statistically significantly associated with poor maternal outcome (p = 0.033) in the univariate analysis, while in the multivariate analysis, hemolysis, elevated enzymes, low platelet (HELLP) syndrome, crack/cocaine use and previous cesarean section resulted significantly associated with poor maternal outcome (p = 0.029, p = 0.017, p = 0.015, p = 0.047). PROM was associated with better neonatal outcome in the univariate analysis, and preeclampsia was associated with a better maternal outcome in the multivariate analysis. Conclusions: Lower gestational age at delivery is the most important risk factor for poor neonatal outcome in African American women with placental abruption. Poor maternal outcome correlated with HELLP syndrome, crack/cocaine use and previous cesarean section. More research in this understudied population is needed to establish reliable risk factors and coordinate preventive interventions.

New Frontiers in IVF: mtDNA and autologous germline mitochondrial energy transfer.

Many infertility specialists support the existence of a relationship between the levels of mitochondrial DNA and the quality of the blastocysts. Despite the extensive use of pre-implantation genetic testing for aneuploidy, a significant percentage of euploid embryos do not implant even though the endometrium is normal. Mitochondrial DNA may be used as a new test in evaluating embryonic vitality.Ovarian aging leads to a decrease in the quantity and quality of oocytes and aged oocytes have a reduced number of mitochondria. Mitochondria are the energy factories of the cells and their lacked could leads to lower fertilization rates and poor embryonic development. Various strategies have been tested to increase the mitochondria quantity and thus improve the quality of oocytes used in in vitro fertilization. Results of ovarian rejuvenation techniques such as autologous mitochondrial transplantation have been controversial. In this review, we describe the state of the art concerning the use of mitochondrial DNA and autologous mitochondrial transplantation as new possibilities to increase success in vitro fertilization.

Insulin-like growth factor binding protein-1 predicts preterm premature rupture of membranes in twin pregnancies.

PURPOSE: Mechanisms leading to preterm premature rupture of membranes (PPROM) remain incompletely defined. Based on the elevated occurrence of PPROM in twin gestations and recent studies of the involvement of insulin-like growth factor binding protein-1 (IGFBP-1) in the inhibition of collagen production we hypothesized that serum IGFBP-1 levels might be predictive of susceptibility to PPROM in women with twins. METHODS: In this prospective study peripheral blood was obtained from 58 women with twin gestations prior to 20 weeks gestation and sera analyzed by ELISA for concentrations of IGFBP-1. Demographic and clinical outcome data were subsequently obtained and associations between IGFBP-1 and PPROM were analyzed by the Mann-Whitney test and receiver operator curve (ROC) analysis. RESULTS: Eight of our subjects developed PPROM. They did not differ from the other women in demographics, medical history or current pregnancy outcome parameters. However, median IGFBP-1 levels were higher in women who subsequently developed PPROM (59.3 ng/ml) than in the other women (46.6 ng/ml) (p = 0.042). Using a cutoff value of 53.9 ng/ml the circulating IGFBP-1 level predicted development of PPROM with a sensitivity of 74%, specificity of 75%, a negative predictive value of 97% and a positive predictive value of 20%. CONCLUSIONS: Pending validation in larger studies the findings suggest that determination of serum IGFBP-1 levels in women with twin pregnancies may predict the later development of PPROM.

Body of Evidence in Favor of Adopting 130/80 mm Hg as New Blood Pressure Cut-Off for All the Hypertensive Disorders of Pregnancy.

The American College of Cardiology/American Heart Association (ACC/AHA) updated its guideline redefining the classification of hypertension and the blood pressure cut-off in 2017. The current cut-offs for stage 1 hypertension of 130 mm Hg systolic blood pressure or 80 mm Hg diastolic blood pressure replace the previous cut-offs of 140 mm Hg systolic blood pressure or 90 mm Hg diastolic blood pressure which were based on the ACC/AHA guidelines from 1988. However, the blood pressure cut-off for the obstetric population still remains as 140/90 mm Hg despite the scarcity of evidence for it. Recent American College of Obstetricians and Gynecologists (ACOG) bulletins for pregnant women have not reflected the new ACC/AHA change of guideline. We reviewed a mounting body of evidence prompting the implementation of the new ACC/AHA guidelines for the obstetric population. These studies examined maternal and fetal outcomes applying the new ACC/AHA guidelines during antepartum or postpartum care.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Complete Blood Count Components in the First Trimester Do Not Predict HELLP Syndrome.

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and other components of the routine complete blood count (CBC) were found to be sensitive biomarkers of preeclampsia and other inflammatory obstetric conditions in previous studies, with conflicting results. We speculated that the same associations existed with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome in the first trimester of pregnancy. Materials and Methods: We conducted a retrospective case-control study at a tertiary care hospital in NY (USA), in the time frame between January 2016 and December 2018. Our population consisted of pregnant women in the first trimester: We compared patients with HELLP syndrome (cases) with healthy patients (controls) matched by age, body mass index (BMI), parity, and race. Patients with preeclampsia, infection, and fever were excluded. Venous blood samples were obtained as part of the routine work-up during the first prenatal visit in the first trimester, which includes a CBC. The main outcomes were NLR and PLR, and the secondary outcomes were hemoglobin, RDW, platelet count, MPV, neutrophils, and lymphocytes. Results: There were 10 patients in each group (Table 1). There were no differences in NLR and PLR levels and other CBC components between the two groups (Table 2). Conclusions: In our study NLR, PLR, and other CBC components did not predict HELLP syndrome. We speculate that HELLP syndrome has a sudden increase of tissue inflammation in the third trimester that is not manifested during the early phases of placentation. Larger studies are needed to evaluate the true ability of NLR, PLR, and CBC components to predict HELLP syndrome in the first trimester.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Routine Complete Blood Count Components in HELLP Syndrome: A Matched Case Control Study.

Background and objective: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are new readily available inflammatory markers that have been analyzed in pregnancy-induced hypertensive disorders such as preeclampsia. Studies on the NLR/PLR ratio in hemolysis, elevated liver enzymes, low-platelet count (HELLP) syndrome are limited in the current literature. We compared NLR/PLR and other complete blood count (CBC) components between women with HELLP syndrome and women with healthy pregnancies. Methods: We conducted a retrospective matched case-control study at a tertiary care hospital in NY (USA) in the time frame between January 2016 and December 2018. The study compared pregnant women with HELLP syndrome (cases) to women with healthy pregnancies in the third trimester (controls), matched by age, body mass index (BMI), parity, and race. Patient with preeclampsia, infection, and fever were excluded. Venous blood samples were obtained as part of the routine work-up at admission for delivery, which included a CBC. The main outcomes were NLR and PLR. The secondary outcomes were hemoglobin, red cell distribution width (RDW), platelet count, mean platelet volume (MPV), neutrophils, lymphocytes. Results: There were 14 patients in each group. They were matched by age, race, BMI, and parity. NLR (5.8 vs. 3.6, p-value = 0.002) and neutrophil count (10.7 vs. 6.8, p-value = 0.001) were higher in women with HELLP compared to controls. PLR (34 vs. 130.2, p-value < 0.001) and platelet count (71 vs. 223, p-value < 0.001) were lower in the study group compared to controls. Conclusions: NLR was higher, and PLR was lower in women with HELLP syndrome. These inflammatory markers can be incorporated into the diagnostic algorithm for HELLP syndrome. Future studies are needed to evaluate their ability to predict HELLP syndrome.

Unique Associations between Insulin-Like Growth Factor Binding Protein-1, Insulin-Like Growth Factor-1 and T Cell Immunoglobulin Mucin 3 in Successful Twin Pregnancies Conceived with Donor Oocytes.

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.

Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects.

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.

The Role of Hsp70 in the Regulation of Autophagy in Gametogenesis, Pregnancy, and Parturition.

Induction of the 70 kDa heat shock protein (hsp70) and autophagy are two major mechanisms that promote cell homeostasis during the rapid cell growth and differentiation characteristic of reproduction. Hsp70 insures proper assembly, conformation, and intracellular transport of nascent proteins. Autophagy removes from the cytoplasm proteins, other macromolecules, and organelles that are no longer functional or needed and recycles their components for synthesis of new products under nutritionally limiting conditions. Hsp70 inhibits autophagy and so a proper balance between these two processes is essential for optimal germ cell production and survival and pregnancy progression. A marked inhibition in autophagy and a concomitant increase in hsp70 at term is a trigger for parturition. Excessive external or endogenous stress that induces a high level of hsp70 production can lead to a non-physiological inhibition of autophagy, resulting in altered spermatogenesis, premature ovarian failure, and complications of pregnancy including preeclampsia, intrauterine growth restriction, and preterm birth.

Prevalence of lymph node metastasis and prognostic significance of lymphadenectomy in apparent early-stage malignant ovarian sex cord-stromal tumors.

OBJECTIVE: The aim of this retrospective population-based study was to investigate the prevalence of lymph node metastasis in patients with apparent early stage malignant sex cord-stromal tumors (SCSTs) and the effect of regional lymph node sampling/lymphadenectomy (LND) on their survival. METHODS: A cohort of patients diagnosed with malignant SCSTs between 1988 and 2012 was drawn from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Overall and Cancer Specific Survival, stratified by performance of LND, were calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank and Breslow tests. A multivariate Cox proportional analysis was performed to determine the effect of LND on overall mortality. RESULTS: A total of 1156 patients with SCST met the inclusion criteria; 1000 (86.5%) and 156 (13.5%) patients had apparent stage I and II disease, respectively. LND was performed in 572 (49.5%) patients. Lymph node metastases were pathologically confirmed in 19 patients (3.3%). Five-year cancer specific survival (CSS) was similar, 92.7% and 94.7%, for patients who did or did not undergo LND, respectively. According to multivariate analysis overall mortality did not differ between the two groups after controlling for age, histology and apparent stage. CONCLUSIONS: Regional lymphatic mode metastasis in patients with apparent early stage SCSTs is uncommon and lymphadenectomy did not confer a survival benefit in this cohort.

Epidemiology of Second Primary Tumors in Women With Ovarian Cancer.

OBJECTIVE: The last large study of second primary tumors (SPTs) in women with ovarian cancer was published in 1996, prior to major changes in the differential diagnosis and treatment. The present study reports on the incidence of SPTs in a contemporary cohort of patients with a diagnosis of ovarian cancer. METHODS: Ovarian cancer patients with a diagnosis of an ovarian malignancy between 1992 and 2012 were identified and characterized from 13 registries of the Surveillance, Epidemiology, and End Results database. RESULTS: Of 41,073 women with a diagnosis of an ovarian malignancy between 1992 and 2012, 1831 (4.5%) developed a microscopically confirmed SPT. There was no significant difference in the risk of developing an SPT at all sites between women with an ovarian cancer and the general population. There was an elevated risk of site-specific SPTs of the small intestine, vagina, thyroid gland, and acute nonlymphocytic leukemia in ovarian cancer patients compared with the general Surveillance, Epidemiology, and End Results population. Conversely, the risk of lung and non-Hodgkin lymphoma was significantly decreased in women with ovarian cancer. An elevated risk of SPTs was observed in women with mucinous, endometrioid, and germ cell tumors. White women had an overall decreased risk of developing a second primary solid tumor, whereas American Indian and Asian/Pacific Islander women had an overall increased risk of an SPT at any site. CONCLUSIONS: The incidence of SPTs in women with ovarian cancer was not significantly different as compared with the general population. However, divergent rates of SPTs in relation to histology, latency, age, and race were observed.

Malignant Transformation of Vaginal Endometriosis - A Review of Literature.

BACKGROUND: The study aimed to examine all available evidence regarding primary vaginal cancer arising from endometriosis from an evidence-based perspective. METHODS: A literature search in Medline and EMBASE databases was conducted. The following key words were employed: 'vaginal cancer' AND 'endometriosis malignant transformation' OR 'endometriosis'. RESULTS: A total of 23 eligible studies were identified and included in the present review providing information for 37 patients. Endometrioid adenocarcinoma (17 cases) was the most common histological subtype followed by endometrial stromal sarcoma (6 cases). The majority of patients received cancer-directed surgery while adjuvant treatment was commonly employed for patients with sarcomas. CONCLUSION: Vaginal cancer arising from endometriosis is exceedingly rare. The mainstay of treatment is surgical excision. Mean follow-up of patients was relative short. Tumor recurrence was often observed, and the outcome was less favorable for patients with non-epithelial tumors.