Young Women's Perspectives on Being Screened for Hereditary Breast and Ovarian Cancer Risk During Routine Primary Care.

PURPOSE: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. METHODS: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FINDINGS: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. CONCLUSION: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation.

Metabolomic Analysis of Vitamin E Supplement Use in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases.

Two-phase dual-signal-readout immunosensing platform based on multifunctional carbon nano-onions for ovarian cancer biomarker detection.

In order to detect early tumor markers and gain valuable time for treatment, there is an urgent need to develop a fast, cheap, and ultrasensitive multi-reading sensing platform. Herein, a solid/liquid two-phase dual-output biosensor was explored based on a sensitized sonochemiluminescence (SCL) strategy and a multifunctional carbon nano-onion (CNO) probe. It is clear that ultrasonic radiation caused the formation of hydroxyl radicals (˙OH), triggering the SCL signal of the emitter lucigenin (Luc2+). Meanwhile, titanium carbide nanodots and ethanol were used to enhance the SCL signal, and an astonishingly linear enhancement of the SCL intensity was produced with increasing ethanol concentration. More importantly, the CNOs, with their excellent photothermal properties and adsorption capacity, can output both the temperature signal and an enhanced SCL strength from the solid-liquid phase. Through inter-calibration of the signals from the two-phases, this biosensor shows excellent analytical performance for the detection of the ovarian cancer biomarker, human epididymis-specific protein 4, from 10-5 to 10 ng mL-1 with a low detection limit of 3.3 fg mL-1. This work not only provides a novel two-phase signal-output mode that broadens the scope of multiperformance joint applications of CNOs, but also enriches the quantitative detection of point-of-care testing.

A portable electrochemical immunosensor for ovarian cancer uses hierarchical microporous carbon material from waste coffee grounds.

A simple label-free electrochemical immunosensor for ovarian cancer (OC) detection was developed using a hierarchical microporous carbon material fabricated from waste coffee grounds (WCG). The analysis method exploited near-field communication (NFC) and a smartphone-based potentiostat. Waste coffee grounds were pyrolyzed with potassium hydroxide and used to modify a screen-printed electrode. The modified screen-printed electrode was decorated with gold nanoparticles (AuNPs) to capture a specific antibody. The modification and immobilization processes were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The sensor had an effective dynamic range of 0.5 to 50.0 U mL-1 of cancer antigen 125 (CA125) tumor marker with a correlation coefficient of 0.9995. The limit of detection (LOD) was 0.4 U mL-1. A comparison of the results obtained from human serum analysis with the proposed immunosensor and the results obtained from the clinical method confirmed the accuracy and precision of the proposed immunosensor.

Human-Centered Design Study to Inform Traceback Cascade Genetic Testing Programs at Three Integrated Health Systems.

INTRODUCTION: A traceback genetic testing program for ovarian cancer has the potential to identify individuals with hereditary breast and ovarian cancer and their relatives. Successful implementation depends on understanding and addressing the experiences, barriers, and preferences of the people served. METHODS: We conducted a remote, human-centered design research study of people with ovarian, fallopian tube, or peritoneal cancer (probands) and people with a family history of ovarian cancer (relatives) at three integrated health systems between May and September 2021. Participants completed activities to elicit their preferences about ovarian cancer genetic testing messaging and to design their ideal experience receiving an invitation to participate in genetic testing. Interview data were analyzed using a rapid thematic analysis approach. RESULTS: We interviewed 70 participants and identified five preferred experiences for a traceback program. Participants strongly prefer discussing genetic testing with their doctor but are comfortable discussing with other clinicians. The most highly preferred experience for both probands and relatives was to discuss with a knowledgeable clinician who could answer questions, followed by directed (sent directly to specific people) or passive (shared in a public area) communication. Repeated contact was acceptable for reminders. CONCLUSION: Participants were open to receiving information about traceback genetic testing and recognized its value. Participants preferred discussing genetic testing with a trusted clinician. Directed communication was preferable to passive communication. Other valued information included how genetic tests help their family and the cost of genetic testing. These findings are informing traceback cascade genetic testing programs at all three sites.

[Progress in diagnosis and treatment of ovarian metastases in rectal cancer].

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.

Evaluation of family history in individuals with heterozygous BRCA pathogenic variants diagnosed with breast or ovarian cancer in a single center in Italy.

BACKGROUND: BRCA1 and BRCA2 gene mutations are responsible for 5% of breast cancer (BC) and 10-15% of ovarian cancer (EOC). The presence of a germline mutation and therefore the identification of subjects at high risk of developing cancer should ideally precede the onset of the disease, so that appropriate surveillance and risk-reducing treatments can be proposed. In this study, we revisited the family history (FH) of women who tested positive for BRCA mutations after being diagnosed with BC or EOC. METHODS: The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®), and the Italian Association of Medical Oncology (AIOM) guidelines were applied to the FH of 157 women who were referred to San Gerardo Hospital for genetic counseling. RESULTS: Almost 85% of women had an FH of BRCA-related cancer. 63.7% and 52.2% of women could have undergone genetic testing according to NCCN and AIOM testing criteria (p < .05) before tumor diagnosis. An FH of EOC was the most frequent NCCN criterion, followed by BC diagnosed <45 years old. Sixty-five percent of deceased women could have undergone genetic testing before developing cancer. CONCLUSIONS: FH is a powerful tool to identify high-risk individuals eligible for genetic counseling and testing. Testing of healthy individuals should be considered when an appropriately affected family member is unavailable for testing.

Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

Modular and Noncontact Wireless Detection Platform for Ovarian Cancer Markers: Electrochemiluminescent and Photoacoustic Dual-Signal Output Based on Multiresponse Carbon Nano-Onions.

An electrochemiluminescent (ECL)-photoacoustic (PA) dual-signal output biosensor based on the modular optimization and wireless nature of a bipolar electrode (BPE) was constructed. To further simplify the detection process, the BPE structure was designed as three separate units: anode ECL collection, cathode catalytic amplification, and intermediate functional sensing units. Specifically, the anode unit was placed with Eosin Yellow, a cheap and effective ECL reagent, and the cathode unit was a laser-induced polyoxometalate-graphene electrode, which was helpful to enhance the anode ECL signal. The intermediate functional sensing unit consisted of a temperature-sensitive conductive film. Further, using a carbon nano-onion nanocomposite with excellent absorption performance in the near-infrared region as a signal tag not only leads to changes in the electrical conductivity of the film through heat transfer and thus affects the ECL signal but also produces a strong PA response. With this design, PA and ECL signals can be output simultaneously. This work not only realizes multiple modularization processes in the design of sensors but also implements the diversification of signal output modes, which will enrich the joint research field of ECL detection technology and other new detection methods.

Efficacy of Clinical Guidelines in Identifying All Japanese Patients with Hereditary Breast and Ovarian Cancer.

Clinical screening using the National Comprehensive Cancer Network (NCCN) testing criteria may fail to identify all patients with hereditary breast and ovarian cancers. Thus, this study aimed to evaluate the strategy of expanding target patients for genetic testing among Japanese patients. We reviewed the medical records of 91 breast cancer patients who underwent genetic testing. Among 91 patients, eight were diagnosed with pathogenic or likely pathogenic variants: BRCA1 (n = 4) and BRCA2 (n = 4). Among 50 patients meeting the testing criteria of the guidelines, 6 (12%) were diagnosed with pathogenic or likely pathogenic variants. The sensitivity and specificity of screening using the testing criteria were 75% and 47%, respectively. Expanding the NCCN criteria to include all women diagnosed with breast cancer aged ≤65 years achieved 88% sensitivity but 8% specificity. The expansion of the NCCN criteria could benefit Japanese patients; however, larger studies are necessary to change clinical practice.

Tyrosine kinase inhibitor treatment and long-term follow-up for metastatic malignant struma ovarii.

Metastatic malignant struma ovarii (MMSO) is a very rare disease (in the United States, less than one case in 10 million females annually). However, this incidence rate is due to a paucity of data regarding diagnosis, treatment, and follow-up. Herein, we describe the case of a 14-year-old female who presented with MMSO, which later metastasized and was followed up on for over 10 years. The patient underwent right oophorectomy surgery and was then treated with a combination of radioactive iodine followed by iodine scans to detect the absorption of radioiodine in the metastatic sites, and radiation therapy to treat skeletal lesions. She subsequently received treatment with the tyrosine kinase inhibitors (TKIs), sorafenib and then lenvatinib, as treatments for advanced disease, thereby achieving long-term disease stability. This case report, which adds to the limited data available on MMSO treatment, suggests that patients treated with a combination of radioactive iodine, radiation therapy, and TKIs can result in good responses and long-term overall survival.

Novel Interactive Tool for Breast and Ovarian Cancer Risk Assessment (Bright Pink Assess Your Risk): Development and Usability Study.

BACKGROUND: The lifetime risk of breast and ovarian cancer is significantly higher among women with genetic susceptibility or a strong family history. However, current risk assessment tools and clinical practices may identify only 10% of asymptomatic carriers of susceptibility genes. Bright Pink developed the Assess Your Risk (AYR) tool to estimate breast and ovarian cancer risk through a user-friendly, informative web-based quiz for risk assessment at the population level. OBJECTIVE: This study aims to present the AYR tool, describe AYR users, and present evidence that AYR works as expected by comparing classification using the AYR tool with gold standard genetic testing guidelines. METHODS: The AYR is a recently developed population-level risk assessment tool that includes 26 questions based on the National Comprehensive Cancer Network (NCCN) guidelines and factors from other commonly used risk assessment tools. We included all women who completed the AYR between November 2018 and January 2019, with the exception of self-reported cancer or no knowledge of family history. We compared AYR classifications with those that were independently created using NCCN criteria using measures of validity and the McNemar test. RESULTS: There were 143,657 AYR completions, and most participants were either at increased or average risk for breast cancer or ovarian cancer (137,315/143,657, 95.59%). Using our estimates of increased and average risk as the gold standard, based on the NCCN guidelines, we estimated the sensitivity and specificity for the AYR algorithm-generated risk categories as 100% and 89.9%, respectively (P<.001). The specificity improved when we considered the additional questions asked by the AYR to define increased risk, which were not examined by the NCCN criteria. By race, ethnicity, and age group; we found that the lowest observed specificity was for the Asian race (85.9%) and the 30 to 39 years age group (87.6%) for the AYR-generated categories compared with the NCCN criteria. CONCLUSIONS: These results demonstrate that Bright Pink's AYR is an accurate tool for use by the general population to identify women at increased risk of breast and ovarian cancer. We plan to validate the tool longitudinally in future studies, including the impact of race, ethnicity, and age on breast and ovarian cancer risk assessment.

Mainstreaming Genetic Testing for Epithelial Ovarian Cancer by Oncology Providers: A Survey of Current Practice.

PURPOSE: With limitations in early detection and poor treatment response, ovarian cancer is associated with significant morbidity and mortality. Up to 25% of epithelial ovarian cancer (EOC) is related to a hereditary predisposition. Current National Comprehensive Cancer Network guidelines recommend that all individuals diagnosed with EOC be offered germline genetic testing. Although this would ideally be performed by genetics professionals, a shortage of genetic counselors can affect timely access to these services. This study sought to investigate the current genetic testing practices of oncology providers to determine the feasibility of oncologist-led genetic testing for patients with EOC. METHODS: A survey was distributed to members of the Society of Gynecologic Oncologists with questions regarding timing, frequency, and type of cancer genetic testing, referrals to genetics professionals, confidence with aspects of genetic testing, and any barriers to these processes. RESULTS: We received 170 evaluable responses. Eighty-five percent of providers always ordered genetic testing for patients with EOC. Most providers ordered germline multigene panel testing (95.8%), generally at diagnosis (64.5%). Provider confidence with the genetic testing process was generally high and significantly differed by providers' testing practices, namely, respondents who reported always ordering genetic testing tended to be more confident in ordering testing (P = .008), interpreting results (P = .005), and counseling a patient (P = .002). Patient disinterest and concerns for insurance coverage were commonly cited as barriers to testing and referrals. CONCLUSION: The findings from this study suggest that oncologist-led genetic testing for patients with EOC, with referrals to genetics professionals when appropriate, has the potential to be a viable alternative service delivery model to increase access to genetic testing for patients diagnosed with EOC.

Factors influencing genetic counseling and testing for hereditary breast and ovarian cancer syndrome in a large US health care system.

Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.

Dietary phytoestrogen intake and lung cancer risk: an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.

Phytoestrogens (PEs) have estrogen-like activity and were found to lower incidences of several hormone-dependent cancers. Emerging evidence suggests that estrogen may play a role in lung cancer carcinogenesis. We aim to evaluate dietary PE intake and lung cancer risk using data from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. A total of 1706 lung cancer cases were identified. The association between lung cancer risk and PE intake (in quartiles) was calculated using the Cox proportional hazard models adjusting for potential confounders. Stratified analyses by smoking status, sex and histology were also performed. The highest quartile of total PE intake was associated with a reduced risk of lung cancer compared with the lowest quartile [hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.73-0.99 for >1030 µg/day versus <290 µg/day] (P trend = 0.56). Similar patterns were observed among ever smokers (HR = 0.84, 95% CI: 0.71-0.98), non-small cell histology (HR = 0.84, 95% CI: 0.72-0.99), male (HR = 0.84, 95% CI: 0.69-1.03) and female (HR = 0.80, 95% CI: 0.64-0.99 for 510-1030 µg/day, HR = 0.84, 95% CI: 0.67-1.06 for >1030 µg/day versus <290 µg/day) subjects with no significant linear trend observed. Despite a lower consumption compared with the Asian population, increased PE intake still appears to decrease lung cancer risk in a Caucasian-dominant population. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of PEs on lung carcinogenesis and the interaction between PEs, smoking and endogenous estrogens.

Implications of Multigene Panel Testing on Psychosocial Outcomes: A Comparison of Patients With Pancreatic and Breast or Ovarian Cancer.

PURPOSE: National Comprehensive Cancer Network guidelines for germline genetic testing have included pancreatic cancer in the context of additional family cancer history for many years but this was not recommended for patients with pancreatic ductal adenocarcinoma (PDAC) independent of a family history until 2019. This hypothesis-generating study reports the results from multigene panel testing for PDAC patients at an academic medical center. PATIENTS AND METHODS: This prospective longitudinal feasibility study examined responses to genetic counseling and multigene panel testing among PDAC and breast or ovarian cancer (BrOv) patients between October 2016 and November 2017. Pre- and post-test surveys assessed perceptions of genetic risk and testing, recall, comprehension, and emotional reactions to results using open-ended and closed-ended items. RESULTS: Forty-six BrOv and 33 PDAC patients were enrolled, and 44 BrOv and 31 PDAC participants underwent genetic testing. Seven pathogenic variants were identified in six BrOv participants (13.6%), and three pathogenic variants were identified in three PDAC participants (9.7%). The majority of both cohorts expressed similar attitudes about the importance of genetic testing for their personal and family medical management and expressed accurate understanding of implications of their results. Although sample size was small, there were no significant differences between the BrOv and PDAC cohorts for positive or negative emotions. CONCLUSION: This study points to high rates of positive emotions and low rates of negative emotions following genetic test results, suggesting that the emotional reactions to genetic test results are similar for patients with BrOv and PDAC, despite poor prognosis with PDAC diagnoses. Because of the unique needs of the PDAC population following diagnosis, a multidisciplinary approach to germline genetic testing following diagnosis may result in best patient and family member outcomes.

Ovarian cancer surveillance in the clinical follow up of women with known BRCA1 or BRCA2 pathogenic variants in a large health care system.

OBJECTIVE: To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up. METHODS: Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed. RESULTS: There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance. CONCLUSIONS: Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.

Role of hsa­miR­105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer.

More than 70% of patients with epithelial ovarian cancer (EOC), one of the leading cause of gynecological cancer­related deaths worldwide, are diagnosed at an advanced stage of the disease. Currently, the mainstay for treatment of advanced EOC is tumor debulking surgery followed by combined platinum­ and paclitaxel (PTX)­based chemotherapy. However, most patients eventually develop chemoresistance, which remains a major obstacle to successful treatment. Herein, by using clinical specimens and experimentally induced cell models, we found that the expression levels of hsa­miR­105 were significantly decreased in PTX­resistant EOC tissues and cell lines. Follow­up functional experiments demonstrated that repression of hsa­miR­105 conferred resistance to paclitaxel in EOC cells, whereas restoration of hsa­miR­105 expression in situ via intratumoral injection of hsa­miR­105 micrON™ agomir potentiated in vivo sensitivity to PTX and thereafter significantly inhibited tumor growth in a PTX­challenged xenograft model. Mechanistically, hsa­miR­105 exerted its tumor suppressor function by directly inhibiting the zinc and ring finger 2 (ZNRF2) signaling pathway. Importantly, aberrant expression of hsa­miR­105 in both tumor and circulating samples predicted a poor post­chemotherapy prognosis in EOC patients. These findings collectively suggest that hsa­miR­105 may act as a potent tumor suppressor miRNA during the progression of EOC, likely affecting cell proliferation, invasiveness and chemosensitivity to PTX, and functioning at least in part via inhibition of ZNRF2 signaling. The stability and availability and ease in measurement of circulating hsa­miR­105 make it a valuable diagnostic/prognostic biomarker candidate for chemotherapy of EOC.

Ovarian Leydig cell tumor and postmenopausal hirsutism with signs of virilisation.

A 71-year-old woman was referred to the endocrinology clinic to investigate postmenopausal hirsutism with 10 years of evolution. She had history of regular menses and menopause with 50 years old. Physical examination showed a male pattern facies, deepening of the voice, androgenic alopecia and hirsutism with a score of 23 according to the modified Ferriman-Gallwey scale. Testosterone and androstenedione were increased. Transvaginal ultrasound, abdominal and pelvic CT showed uterine fibroids with no pathological findings in the adrenals or ovaries. Since she had postmenopausal vaginal bleeding, uterine fibroids and suspicion of an ovarian source for her hyperandrogenism, total hysterectomy and bilateral oophorectomy were performed. Histopathological diagnosis was a Leydig cell tumour located in left ovary and endometrial carcinoma. Improvement of hirsutism was started to notice 1 month after the surgery and she was referred to the oncology clinic for adjuvant treatment.

Impact of Previous Gynecologic Surgical Procedures on Outcomes of Non-Gynecologic Peritoneal Malignancies Mimicking Ovarian Cancer: Less Is More?

BACKGROUND: Non-gynecologic rare peritoneal surface malignancies (PSMs) often are misdiagnosed as disseminated ovarian cancer and initially treated by gynecologic surgeons. This study aimed to assess whether these previous maneuvers (i.e., full surgical staging and/or cytoreductive attempts) affect outcomes after the definitive surgery performed in a tertiary center. METHODS: The study reviewed 298 women affected by non-gynecologic PSM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after previous gynecologic surgery. Prior surgery was categorized as limited surgery (pLS: abdominal exploration with biopsy plus adnexectomy and/or appendectomy) or extended surgery (pES: full surgical staging or cytoreductive attempts including hysterectomy with bilateral salpingo-oophorectomy). RESULTS: Of the 298 patients, 143 had pLS and 153 had pES. Morbidity was similar between the groups (P = 0.143), but the pES group had more severe urinary tract injuries (19 vs. 3; P < 0.001), longer operating time (585.9 vs. 506.7; P = 0.027), and more patients needing more than two anastomoses (41 vs. 26; P = 0.033). Age older than 55 years (odds ratio [OR] 2.42; P = 0.009) and number of anastomoses (OR 3.17; P = 0.002) correlated with severe morbidity; pES correlated with urinary tract grades 3 and 4 injuries (OR 7.9; P = 0.001). The 5-year cumulative incidence of locoregional relapse was significantly higher in the pES group (0.41 vs. 0.27; P = 0.012; median follow-up period, 69 months). The multivariate analysis identified a Peritoneal Carcinomatosis Index (PCI) higher than 20 and pES as independent risk factors. CONCLUSION: For women undergoing CRS±HIPEC for non-gynecologic PSM, the risk for locoregional relapse and severe postsurgical urinary tract complications is increased by pES. Therefore, prior full surgical staging or cytoreductive attempts without definitive gynecologic histology should be avoided. Prophylactic ureteral stenting and stricter oncologic follow-up assessment must be considered in this scenario.