Reproductive Factors and Non-Hodgkin Lymphoma Risk in the California Teachers Study

BACKGROUND:Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype. METHODOLOGY/PRINCIPAL FINDINGS:Women in the California Teachers Study cohort provided detailed data in 1995-1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68-1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54-1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype. CONCLUSIONS:Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL

Recent breast cancer incidence trends according to hormone therapy use: the California Teachers Study cohort

Abstract Introduction Recent, international declines in breast cancer incidence are unprecedented, and the causes remain controversial. Few data sources can address breast cancer incidence trends according to pertinent characteristics like hormone therapy use history. Methods We used the prospective California Teachers Study to evaluate changes in self-reported use of menopausal hormone therapy (HT) between 1995 to 1996 and 2005 to 2006 and age-adjusted breast cancer incidence among 74,647 participants aged 50 years or older. Breast cancer occurrence was determined by linkage with the California Cancer Registry. Results During 517,286 woman years of follow up, 565 in situ and 2,668 invasive breast cancers were diagnosed. In situ breast cancer incidence rates in this population did not change significantly from 2000 to 2002 to 2003 to 2005, whereas rates of invasive breast cancer declined significantly by 26.0% from 528.0 (95% confidence intervals (CI) = 491.1, 564.9) per 100,000 women in 2000 to 2002 to 390.6 (95% CI = 355.6, 425.7) in 2003 to 2005. The decline in invasive breast cancer incidence rates was restricted to estrogen receptor-positive tumors. In 1996 to 1999 and 2000 to 2002 invasive breast cancer incidence was higher for women who reported current HT use especially estrogen-progestin (EP) use at baseline than for never or past users; but by 2003 to 2005 rates were comparable between these groups. For women who were taking EP in 2001 to 2002,75% of whom had stopped use by 2005 to 2006, incidence had declined 30.6% by 2003 to 2005 (P = 0.001); whereas incidence did not change significantly for those who never took HT (P = 0.33). Conclusions Few data resources can examine prospectively individual HT use and breast cancer diagnosis. Stable in situ breast cancer rates imply consistent levels of screening and suggest recent declines in invasive breast cancer to be explained predominantly by changes in HT use

Progesterone receptor gene polymorphisms and risk of endometriosis: results from an international collaborative effort

Objective To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism (SNP) and the PROGINS allele. Design Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies. Setting An international ovarian cancer consortium including studies from the Australia, Europe and the United States, Patients 5,812 White female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies. Interventions None. Main Outcome Measures Genotypes for the +331C/T SNP and PROGINS allele and a history of endometriosis. Results The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (OR=0.65; 95% CI: 0.43–0.98, p=0.042), whereas there was no association between the PROGINS allele and endometriosis (OR=0.94, 95% CI 0.76, 1.16). Conclusions Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced PR-A to PR-B ratio and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease

Twin gestation in a uterus didelphys with only one functional cervix: A case report

Introduction: Twin gestation in a uterus didelphys with one fetus in each uterine cavity is rare and presents unique challenges in antepartum and intrapartum care. Case Presentation: A 35-year-old woman with a uterus didelphys became pregnant with twins, with one fetus in each uterus, after intrauterine insemination of a single visible cervix. Multiplanar ultrasonography showed the presence of one complete cervix and a second hypoplastic cervix; it was unclear whether she could deliver both twins vaginally. Her pregnancy was complicated by fetal growth restriction of twin B. At 38 weeks, the patient underwent scheduled cesarean section and delivered two viable twins. Conclusion: Determining the precise anatomy of Mullerian duct anomalies, including the cervix and vagina, is important for obstetrical management. Keywords: Twin gestation, Uterus didelphys, Hypoplastic cervix, Mullerian duct anomalies, Cervical anomalie

49 Panniculectomy to facilitate minimally invasive hysterectomy is effective for severely obese patients undergoing gynecological oncological surgery

Objectives: The prevalence of obesity (BMI ≥30) in US women approximates 40%. Severely obese women (BMI ≥40) have increased rates of perioperative morbidity and mortality. Minimally invasive surgical (MIS) options have improved perioperative outcomes but become limited for patients with severely elevated BMI, particularly ≥60. Contrary to previously published conclusions, utilizing panniculectomy at the time of surgical staging can make laparoscopic surgery feasible in this patient population. Methods: Retrospective review of patients undergoing concurrent panniculectomy and total laparoscopic hysterectomy (TLH). Twenty-one patients between 2009–2022 were identified through surgical logs. Data was collected regarding successful completion of laparoscopy as well as intraoperative and postoperative complications within 30 days of surgery. Results: Average preoperative BMI was 53.3 (range 41–79). A laparoscopic procedure was scheduled in all 21 patients. Laparoscopy was successfully completed in 20/21 cases (95%). One case required conversion from laparoscopic hysterectomy to laparotomy. Mean blood loss was 238ml (range 100–500 ml). The median weight of pannus resection was 6.6 kg (range 4.2–38.5 kg). One patient required intraoperative blood transfusion due to operative losses as the pannus removed was >38 kg. Median operative time was minutes 214 (range 169–322 mins). 90% of patients were discharged by post operative day 2 (range day 1–5). Two-thirds of patients were discharged without need for home health services. No patients required readmission within 30 days following surgery and no patients required ICU admission. There were no events of venous thromboembolism, bowel obstruction or surgical site complications occurred. Conclusions: Our pilot data demonstrates utilizing panniculectomy at the time of hysterectomy is successful in facilitating laparoscopic surgery for severely obese patients. No major complications were seen during admission or in the 30-day postoperative period, and the additional inpatient stay is minimal. The current data is the basis of ongoing research regarding long-term effects of combined panniculectomy and laparoscopic hysterectomy, with specific attention to hypertension, diabetes, weight management and patient quality of life

Novel three-dimensional in vitro models of ovarian endometriosis

Background: Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures. Methods: A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR. Results: In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions. Conclusions: To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches

Evidence of a genetic link between endometriosis and ovarian cancer.

ObjectiveTo evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer.DesignPooled genetic analysis.SettingUniversity hospital.Patient(s)Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies.Intervention(s)None.Main outcome measure(s)Endometriosis-associated genetic variation and ovarian cancer.Result(s)There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected.Conclusion(s)By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions