What happens after menopause? (WHAM): A prospective controlled study of vasomotor symptoms and menopause-related quality of life 12 months after premenopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: To measure menopausal symptoms and quality of life up to 12 months after risk-reducing salpingo-oophorectomy (RRSO) and to measure the effects of hormone therapy. METHODS: Prospective observational study of 95 premenopausal women planning RRSO and a comparison group of 99 who retained their ovaries. Vasomotor symptoms and menopausal-related quality of life (QoL) were measured by the Menopause-Specific QoL Intervention scale at baseline, 3, 6 and 12 months. Chi-square tests measured differences in prevalence of vasomotor symptoms between RRSO vs the comparison group and by hormone therapy use. Change in QoL were examined with multilevel modelling. RESULTS: Three months after RRSO hot flush prevalence increased from 5.3% to 56.2% and night sweats from 20.2% to 47.2%. Symptoms did not worsen between 3 and 12 months and remained unchanged in the comparison group (p<0.001). After RRSO, 60% commenced hormone therapy. However, 40% of hormone therapy uses continued to experience vasomotor symptoms. After RRSO, 80% of non-hormone therapy users reported vasomotor symptoms. Regardless of hormone therapy use, 86% categorized their vasomotor symptoms as "mild" after RRSO. Following RRSO, Menopause-related QoL deteriorated but was stable in the comparison group (adjusted coefficient = 0.75, 95%CI = 0.55-0.95). After RRSO, QoL was better in hormone therapy users vs non-users (adjusted coefficient = 0.49, 95%CI = 0.20-0.78). CONCLUSIONS: Vasomotor symptoms increase by 3 months after RRSO but do not worsen over the next 12 months. Hormone Therapy reduces but does not resolve vasomotor symptoms and may improve QoL, but not to pre-oophorectomy levels.

Assessment of current follow-up for complete molar pregnancies: A single centre review.

BACKGROUND: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative ß-human chorionic gonadotropin (ß-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative ß-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable. AIM: To determine the trend in ß-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit. MATERIALS AND METHODS: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, ß-hCG at diagnosis, subsequent ß-hCG levels, incidence of GTN and treatment required. RESULTS: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative ß-hCG and completed their six months follow-up had a subsequent rise in ß-hCG. The median number of days from surgical evacuation to normalisation of ß-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative ß-hCG prior to further management. CONCLUSIONS: Consideration could be made to decreasing the period of ß-hCG monitoring for women who achieve a spontaneous negative ß-hCG following surgical evacuation of a CMP.

Uterus transplantation and pregnancy induction: Approved protocol at the Royal Prince Alfred Hospital.

Absolute uterine factor infertility (AUFI) is defined as the absence of a uterus or the presence of a non-functional uterus. Before the first live birth from a uterus transplant in 2014, the only fertility options for women with AUFI were surrogacy and adoption. In November 2019, our team was granted approval for the first uterus transplant trial in Australia using known living donors. Our program is based on that of our overseas collaborators in Dallas, Texas; this team will also be proctoring us for our first two cases.

Breast Cancer: Genetics and Risk Assessment.

As health care providers, we play a crucial role in the assessment of a patient's risk for hereditary breast cancer syndromes. The panorama of genetic assessment and testing has evolved dramatically since the identification of the BRCA genes. Next-generation sequencing technology has facilitated the development of multigene panels, but 1 consequence has been an increased identification of pathogenic variants at odds with a family history as well as variants of uncertain significance for which treatment guidelines are not defined. Progress in this field requires close collaboration between patients and clinicians with a thorough understanding in cancer genetics.

HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses - a prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population.

BACKGROUND: Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk. AIMS: To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI). MATERIALS AND METHODS: Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison. RESULTS: There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC-AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population. CONCLUSIONS: In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer.

Endometrial carcinomas with significant mucinous differentiation associated with higher frequency of k-ras mutations: a morphologic and molecular correlation study.

OBJECTIVES: K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation-associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation. METHODS: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant. RESULTS: K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05). CONCLUSION: The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.

Premalignant lesions: diagnosis, evaluation, and management.

Acceptance and incorporation of widespread mammographic screening has led to an increase in the incidence of detection of "premalignant" breast lesions. Despite advances in our understanding of these diseases, their actual malignant potential remains somewhat unpredictable. Best current management of these diseases requires a multidisciplinary, coordinated approach between the disciplines of breast surgery, radiology, pathology, medical oncology, and radiation oncology at a minimum. Although this strategy has led to excellent outcomes, future advances in our understanding of the biologic determinants and behavior of these diseases will hopefully result in a more accurate assessment of the risk of progression to invasive breast cancer and allow us to individualize treatment more effectively.

A prospective controlled study of sexual function and sexually related personal distress up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) may impair sexual function, but the nature and degree of impairment and impact of estrogen therapy on sexual function and sexually related personal distress after RRBSO are uncertain. METHODS: Prospective observational study of 73 premenopausal women at elevated risk of ovarian cancer planning RRBSO and 68 premenopausal controls at population risk of ovarian cancer. Participants completed the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. Change from baseline in sexual function following RRBSO was compared with controls at 12 months according to estrogen therapy use. RESULTS: Baseline sexual function domains did not differ between controls and those who underwent RRBSO and subsequently initiated (56.2%) or did not initiate (43.8%) estrogen therapy. At 12 months, sexual desire and satisfaction were unchanged in the RRBSO group compared with controls. After RRBSO, nonestrogen therapy users demonstrated significant impairment in sexual arousal (ß-coefficient (95% confidence interval) -2.53 (-4.86 to -0.19), P < 0.03), lubrication (-3.40 (-5.84 to -0.96), P < 0.006), orgasm (-1.64 (-3.23 to -0.06), P < 0.04), and pain (-2.70 (-4.59 to 0.82), P < 0.005) compared with controls. Although sexually related personal distress may have been more likely after RRBSO, irrespective of estrogen therapy use, there was insufficient data to formally test this effect. CONCLUSIONS: The findings suggest premenopausal RRBSO adversely affects several aspects of sexual function which may be mitigated by the use of estrogen therapy. Further research is needed to understand the effects of RRBSO on sexual function and sexually related personal distress, and the potential for estrogen therapy to mitigate against any adverse effects.

Clinical characteristics and choices regarding risk-reducing surgery in BRCA mutation carriers.

BACKGROUND/AIMS: BRCA mutation carriers have a high lifetime risk of developing breast and ovarian malignancies. As genetic testing becomes widely available, preventative measures are a choice. We evaluated the characteristics of BRCA mutation carriers who chose prophylactic surgery (PS) compared to those who opted for surveillance. METHODS: A retrospective chart review of patients with a mutation in the BRCA1 or BRCA2 genes was performed. RESULTS: Ninety women were included, of whom 46 (51%) underwent PS. They were more likely to be a BRCA2 mutation carrier, parous, married, employed, and had a prior history of breast cancer. PS included 39 bilateral salpingo-oophorectomies and 13 mastectomies. Pathology was typically benign; however, 15% showed ductal carcinoma in situ of the breast, 8% reported infiltrating ductal carcinoma of the breast, 3% was adenocarcinoma of the fallopian tube, and 3% was adenocarcinoma of the ovary. CONCLUSION: It is notable that BRCA1 mutation carriers were less inclined to elect for PS. Evaluating the reasons for pursuing PS among women with a BRCA mutation is necessary and will require a larger data set. Long-term follow-up is required to describe the potential side effects of PS on quality of life.

Endometrial adenocarcinoma arising in a pelvic implant following uterine morcellation: A case report.

We report a unique case of a 60-year-old woman developing endometrial cancer in a uterine deposit 18 years after she had undergone laparoscopic subtotal hysterectomy with morcellation for benign pathology. She had used unopposed estrogen as menopausal hormone therapy. She presented with a pelvic mass that was causing pressure symptoms. On imaging, the mass had an enhancing vascular nodular component and appeared to abut normal ovaries and the residual cervix. She proceeded to laparotomy, where a 12 cm pelvic mass was found morbidly adherent to the bladder anteriorly and to the cervical stump. The pelvic mass was excised, and trachelectomy and bilateral salpingo-oophorectomy were performed. Adjacent to this mass was a separate, 5 cm adnexal mass, which was also excised. Histopathology of the smaller pelvic mass was consistent with endometrial adenocarcinoma grade 1, arising in complex endometrial hyperplasia with atypia surrounded by myometrium consistent with a uterine implant. This case highlights the need for consideration and discussion of possible risks of subtotal hysterectomy and morcellation of the uterus for benign disease. Furthermore, given the results in this patient, the use of unopposed estrogen in such patients is discouraged due to possible effects on any residual endometrium still present.

Cervical cancer prevention: Asian-American women's knowledge and participation in screening practices.

OBJECTIVE: The purpose of this study was to compare cervical cancer knowledge and prevention strategy participation among Chinese-American women compared with Southeast-Asian-American women. METHODS: We performed a cross-sectional survey of Chinese and Southeast Asian women in Rhode Island. Anonymous surveys were administered following informed consent. The survey included demographics and questions related to health care practices, cervical cancer, and the human papilloma virus (HPV). Categorical variables were compared by Fisher's exact test. Mean scores of correct answers on the knowledge questions were compared by Student's t-test and analysis of variance. RESULTS: Ninety-six Chinese women and 132 Southeast Asian women were included in the analysis. Sixty-seven percent of Chinese women had at least a college education compared with 37% of Southeast Asian women (p < .0001). Nineteen percent of Chinese women reported annual household incomes of greater than $100,000 compared with 3% of Southeast Asian women (p = .0003). Twenty percent of Southeast Asian women did not have health insurance compared with 10% of Chinese women (p = .06). Among both groups, 25% of participants either never had a pap test or did not know if they ever had a pap test. There was a greater lack of knowledge about the relationship between HPV and cervical cancer among Chinese (mean 2.9 out of 8 questions) compared with Southeast Asian (mean 3.6 out of 8 questions; p = .02). CONCLUSIONS: Regardless of ethnic subgroup, education, or income, all participants had a poor knowledge of cervical cancer and HPV. This study supports the need for improvement in cervical cancer prevention education among all Asian women.

Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient.

Ovarian cancer is the most fatal gynecologic malignancy. Women often present late and though median survival has improved, a majority of women will succumb to their disease. The incidence of ovarian cancer among female-to-male transsexuals is not known. We report only the second case of ovarian cancer in a female-to-male transsexual while on androgen supplementation therapy. Staining of his tumor for androgen receptors showed abundant expression. Androgen supplementation in this population may be associated with an increased risk of both ovarian cancer and of endometrial cancer. Consideration for bilateral salpingo-oophorectomy as part of gender reassignment surgery should be given, especially in this poorly studied group of patients whose overall risk of ovarian cancer remains unknown.

Two for good measure: six versus eight cycles of carboplatin and paclitaxel as adjuvant treatment for epithelial ovarian cancer.

INTRODUCTION: Although the standard of care for advanced epithelial ovarian cancer (EOC) is six cycles (6C) of platinum-taxane (PT), there have been no studies on the optimal duration of treatment in the era of adjuvant taxanes. At our center, some women receive eight cycles (8C) of PT, based on physician judgment. We were interested in evaluating the outcomes of women treated with 8C of PT for EOC as compared to a cohort who received 6C. METHODS: We retrospectively identified women with Stage III or IV EOC between 1998 and 2003 who received 6C or 8C of PT. The endpoints were disease-free (DFS) and overall survival (OS). CA-125 response was defined as a decrease in CA-125 of 50% in four serial samples or of 75% over three samples. RESULTS: One hundred and twenty-two women met criteria for inclusion; 84 received 6C, and 38 received 8C. Comparing the cohorts receiving 6C versus 8C, 71% versus 26% were optimally debulked (P < 0.01). 79 patients were evaluable by CA-125 (52 6C/27 8C), and all responded. 88% receiving 6C and 81% receiving 8C normalized their CA-125 at end of treatment (P = 0.20). The proportion with a normal CA-125 at Cycle 2 was 29% versus 12%, respectively (P = 0.15) and, at Cycle 4, was 88% versus 36%, respectively (P < 0.01). DFS was 13 months with 6C and 8 months with 8C (P = 0.01). OS was 31 versus 23.5 months (P = 0.02), respectively. When the survival analysis is restricted to suboptimal debulked patients only, the DFS is 12.5 versus 8 months (P = 0.02), and OS is 32 versus 26.5 months (P = 0.15), respectively. CONCLUSIONS: Two further cycles of PT did not improve DFS or OS for patients with advanced EOC. Patients who do not achieve remission after 6C are unlikely to benefit from additional chemotherapy using the same agents and should be considered for clinical trials involving novel agents with different mechanisms of action.