Gwyn Richardson

Use of BRCA Mutation Test in the U.S., 2004–2014

INTRODUCTION BRCA mutation testing has been used for screening women at high risk of breast and ovarian cancer and for selecting the best treatment for those with breast cancer. To optimize the infrastructure and medical resources allocation for genetic testing, it is important to understand the use of BRCA mutation testing in the U.S. health system. METHODS This retrospective cohort study included 53,254 adult women with insurance claims for BRCA mutation testing between 2004 and 2014 from ClinformaticsTM Data Mart Database. Data analysis was performed in 2016. This study assessed trends in the use of BRCA mutation testing in women with previously diagnosed breast or ovarian cancer and those without (unaffected women). RESULTS Between 2004 and 2014, of those receiving BRCA testing, the proportion of BRCA tests performed in unaffected women increased significantly (p<0.001), from 24.3% in 2004 to 61.5% in 2014. An increase in the proportion of BRCA tests used in unaffected women was found in each characteristic subgroup. In 2014, most subgroups had a proportion surpassing 50%, except for those aged 51-65 years and those without a family history of breast cancer. There was a much lower proportion of those aged 20-40 years among tested women with previously diagnosed breast or ovarian cancer than in unaffected women (17.6% vs 41.7%, p<0.001). CONCLUSIONS During the past decade, the role of BRCA testing has gradually shifted from being used primarily in cancer patients to being used in unaffected women in the U.S.

Work related stress among gynecologic oncologists

OBJECTIVE Up to one third of oncologists experience burnout. The objective was to determine correlates of work related stress in gynecologic oncologists (GOs). METHODS Using an online tool, we surveyed 273 members of the International Gynecologic Cancer (IGCS) Society (60% from North America) to examine demographic, psychological and spiritual correlates of work related stress (WRS) and burnout. Measures of death anxiety (DA) and locus of control (LOC) were also administered. RESULTS WRS did not correlate with religion, religiosity, race, or gender, but did correlate with DA (r=0.23, p=0.0006). WRS was also associated with younger age (p=0.01) and fewer years out of training (p=0.0286), higher scores on LOC Chance (r=0.18, p=0.007), higher scores on Powerful Other (r=0.30, p<0.0001), and lower scores on LOC Internality (r=-0.30, p<0.0001). CONCLUSION Responses from younger and less experienced GOs, correlate with higher WRS scores especially if their LOC is weighted toward chance and powerful others. Responses of GOs with these two characteristics also correlate with higher DA scores and reports of difficulty talking about death.

Should high-risk adolescents have Papanicolaou tests?

The current American College of Obstetricians and Gynecologists guidelines state that cervical cancer screening should begin at age 21 years, regardless of sexual or obstetric history. However, previous studies have demonstrated that there is a small but significant subset of high‐risk adolescents with extensive sexual and obstetric history who harbor a significant squamous cervical lesion. The objective of the current study was to use histologic and demographic data from adolescents (aged <21 years) who received Papanicolaou (Pap) tests to determine whether they benefited from early cervical cancer screening.

A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women: Testosterone therapy ameliorates cancer-related muscle loss

Cancer cachexia negatively impacts cancer‐related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.

The prognostic significance of thromboembolic events in patients treated for invasive cervical carcinoma

U leiomyomata, or myomas, are one of the most common benign tumors of the reproductive tract, affecting more than 70% of women in their lifetime. Definitive surgical treatment of myoma is hysterectomy while myomectomy is the treatment for those women who have symptomatic myomas and desire uterine or fertility preservation. Leiomyomas can arise from any tissue including the broad ligament, the incidence of broad-ligament leiomyoma is <1%. Myomectomy of large broad ligament fibroid presents certain challenges due to anatomical distortion, leading to higher incidence of ureteric injury and excessive bleeding. Still most of the myomectomies are done abdominally, this is due to the complexity and the necessity of extensive suturing for the desired multilayered uterine closure, which is technically hard to do laparoscopically. The introduction of robotic surgery has allowed more surgeons to perform complex laparoscopic procedures.Results: Seven hundred sixty-six patients were diagnosed with invasive cervical cancer during study period. Records were available on 747 patients for mean follow up of 33 months. The incidence of thromboembolic events in cervical cancer patients was 9.0%. Incidence of thromboembolic events was higher in patients with advanced stage. There was no statistically significant difference when accounted by race, smoking history or tumor histology. As expected in patient with advanced stage, treatment modality was related to increased incidence of thromboembolic events. Survival analysis data showed that patients with thromboembolic events had a significantly poorer survival than patients without thromboembolic events.Study design, size and duration: Four hundred fifty patients with genital endometriosis, stages I-III, aged 18 to 44 years, before first laparoscopy: Patients were randomly assigned to 1 of 3 treatment groups, hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focused on the endometriosis stage, recurrence of symptoms, and pregnancy rate.G trophoblastic tumors are developed in all ages of the pregnant with high metastasis and the mechanism has been poorly understood. In this investigation we proposed that HIF-1α/VEGF axis in the development and metastasis of gestational trophoblastic tumors. Expressions of HIF-1α and VEGF proteins in normal pregnancy villi (N; 20 cases), hydatidiform mole (HM; 35 cases), invasivemole (IM; 14 cases) and carcinomas (C; 14 cases) have been examined and compared. We showed positive staining in all the four groups for both HIF-1α (N 5.0%, HM 28.6%, IM 78.6% and C 85.7%) and VEGF (N 25.0%, HM 37.1%, IM 71.4% and C 78.6%). Statistical analyses indicated significant differences between N and IM or C and between HM and IM or C. There was no significant difference between N and HM or between IM and C. Expressions of both HIF-1α and VEGF from stage I/II groups were significantly lower than from III/IV groups, but not significantly lower in patients of less than 40 years old than the patients of more than 40. This indicated a correlation of HIF-1α/ VEGF to clinical stage, but not ages. We further revealed a positive relationship between HIF-1α and VEGF in the invasivemole and choriocarcinoma group.Methods: In a retrospective study, data were analyzed for patients treated for cervical cancer at a center in Beijing, China, between December 2011 and September 2013. Patients were subdivided into those with early-stage disease (FIGO stage IA2– IB1) who were treated by robotic surgery (group 1), and those with LACC (stage IB2–IIB) who were treated by robotic surgery after neo-adjuvant chemotherapy (NACT). Therapeutic outcomes and complications were compared.Cervical cancer has a major impact on the lives of Indian women with an estimated 122,844 new cases of cervical cancer in the year 2012, which accounted for 23% of all the cancers in females . 80% of our patients come for treatment with a locally advanced stage of the disease. Further, it has been established that cervical cancer spreads in a progressive but predictable pattern and many patients with locally advanced carcinoma of cervix harbour para-aortic metastasis AIMMethods: A cross-sectional study was conducted among young-adult females (between ages 25 and 45) in Sharjah. A total of 492 females were selected based on a non-probability convenience sampling method. Data were collected through interviewbased questionnaires then analysed using SPSS20. The total knowledge was calculated by averaging the total score (correct answers/total questions (66)) of each participant.

Bilateral salpingectomy: An opportunity for cancer prevention

D a significant improvement in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. The Nitric Oxide (NO) donors synthetic compounds that release NO, in vivo and/or in vitro, have been considered as a potential anti-cancer agent. The effect of NO donors on the biological activity of ovarian cancer cells in the presence or absence of cisplatin was determined. Two members of NONOates family with different half-live time were used. Various ovarian cancer cell lines as well as cancer cells isolated from ascites of patients with advanced stage of diseases were used in these studies. We found that NO donors inhibited the ovarian cancer cells growth mainly by induction their apoptosis. Moreover, NO donors decreased the activity of signaling proteins (STAT3 and AKT) involved in uncontrolled proliferation of ovarian cancer cells. We also found that NO donors have low ability to inhibit the production and secretion of pro-metastatic factors. Our study showed that NO donors significantly enhanced the susceptibility of ovarian cancer cells to cytotoxicity of cisplatin. We demonstrated that NO donors increased the number of late apoptotic\necrotic ovarian cancer cells treated with cisplatin. We also found that none of NO donors or their combination with cisplatin affects the expression of genes (ABCB1, BIRC5 and PTEN) involved in the drug resistance. The obtained results show that NO donors have a high potential of being a supporting compounds in the ovarian cancer therapies.H breast/ovarian cancers are responsible for 5-10% of breast cancers and 7-10% of ovarian cancers. Breast cancer is one of the most common cancers in Indian women. Women carrying BRCA1 or BRCA2 mutations have a lifetime risk of between 60% and 85% for development of breast cancer, and 26% and 54% for development of ovarian cancer for BRCA1, and between 10% and 23% for BRCA2. In this study, 61 breast and/or ovarian cancer patients with a positive family history of breast and/or ovarian cancer were screened for BRCA1/2 mutations. For mutation screening, conformation sensitive gel electrophoresis was used, followed by DNA sequencing, were heteroduplexes were detected. In the BRCA1 gene, 15 mutations were identified; (mutation frequency, 24.6%) and in the BRCA2 gene, two mutations were detected (mutation frequency, 3.28%). Of the BRCA1 mutations identified, 3 were novel mutations and 3 more were previously reported mutations. The mutation, 185delAG was found in 10 patients at a very high frequency of 16.4%. This mutation is detected in high proportion in Ashkenazi Jewish population (18% in breast/ovarian cancers and 1% in general population). A large number of polymorphisms were also detected in BRCA2 gene, which were normal population variants. The mutation spectrum of BRCA1/2 in other Indian studies also indicate a higher incidence of 185delAG mutation, and the important studies shall be reviewed. Haplotype analysis was carried out, and it was found to be different from Ashkenazi Jewish population. The possibility of founder mutation status need to be considered for BRCA1 185delAG mutation.Methods: 152 patients were selected from my private practice in a retrospective observational study, 98 of them having been diagnosed with venous thrombosis and 54 of them having been diagnosed with cancer. The diagnosis of ovarian varicose veins and varicocele were made through eco-color-Doppler, considering the minimum diameter of the veins (4.0; 5.0 and 6.0 mm) next to the ovaries and next to the testicles (2.0; 2.5 and 3.0 mm), with a reflux of 0.5 s.