Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention.

The current theory of carcinogenesis for the deadliest of 'ovarian' cancers-high-grade serous carcinoma (HGSC)-holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at-risk women with germ-line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a 'catastrophic' model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long-term follow-up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.

Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC).

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

Clinical and pathological outcomes of risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer.

BACKGROUND: To clarify the clinical as well as pathological outcomes in Japanese women with germline pathogenic BRCA1/2 variants who underwent risk-reducing salpingo-oophorectomy (RRSO). METHODS: This prospective study examined the rate of occult cancer and primary peritoneal cancer after RRSO at our institution in the period from 2011 to 2020. Clinical records of genetically confirmed patients with germline pathogenic BRCA1/2 variants who desired to undergo RRSO were reviewed. Specimens obtained during RRSO were pathologically diagnosed as per SEE-FIM protocol. All the participants underwent magnetic resonance imaging (MRI) about 1 month preoperatively. RESULTS: One hundred and seventeen women underwent RRSO during this period. Of these, the numbers of women with germline pathogenic BRCA1 and BRCA2 variants were 72 and 45, respectively. The mean observational time after RRSO was 35.8 months. Despite negative preoperative screening results, three (2.6%) serous tubal intraepithelial carcinoma and three (2.6%) invasive carcinomas were identified. Of the three invasive carcinomas cases, two were International Federation of Gynecology and Obstetrics (FIGO) stage I primary fallopian tube cancer, and the third case was double cancer (ovarian cancer and fallopian tube cancer) with FIGO stage IC3. CONCLUSIONS: The rate of occult neoplasms was similar to those reported by studies performed in other countries. Although women with occult cancer were diagnosed with FIGO stage I, the MRI performed 1 month preoperatively did not show any such malignant findings. Thus, RRSO is the only promising method that can improve the prognosis in women with germline pathogenic BRCA1/2 variants.

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience.

OBJECTIVES: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of ovarian, fallopian tube (FT), and peritoneal carcinoma (collectively OC). We describe rates of occult neoplasia in the largest single-institution prospective cohort of women undergoing RRSO, including those with mutations in non-BRCA homologous repair (HRR) genes. METHODS: Participants undergoing RRSO enrolled in a prospective tissue bank between 1999 and 2017. Ovaries and FTs were serially sectioned in all cases. Participants had OC susceptibility gene mutations or a family history suggesting OC risk. Analyses were completed in Stata IC 15.1. RESULTS: Of 644 women, 194 (30.1%) had mutations in BRCA1, 177 (27.5%) BRCA2, 27 (4.2%) other HRR genes, and 15 (2.3%) Lynch Syndrome-associated genes. Seventeen (2.6%) had occult neoplasms at RRSO, 15/17 (88.2%) in the FT. Of BRCA1 carriers, 14/194 (7.2%) had occult neoplasia, 8/194 (4.1%) invasive. One PALB2 and two BRCA2 carriers had intraepithelial FT neoplasms. Occult neoplasm occurred more frequently in BRCA1/2 carriers ≥45 years of age (6.5% vs 2.2%, chi square, p = .04), and 211/371 (56.9%) BRCA1/2 carriers had surgery after guideline-recommended ages. Four in 8 (50%) invasive and 2/9 (22%) intraepithelial neoplasms had positive pelvic washings. None with intraepithelial neoplasms developed recurrence or peritoneal carcinoma. CONCLUSIONS: BRCA1 carriers have the highest risk of occult neoplasia at RRSO, and the frequency increased with age. Women with BRCA1/2 mutations often have RRSO beyond recommended ages. One PALB2 carrier had FT intraepithelial neoplasia, a novel finding. Serial sectioning is critical to identifying occult neoplasia and should be performed for all risk-reducing surgeries.

Retrospective study of a 16 year cohort of BRCA1 and BRCA2 carriers presenting for RRSO: Prevalence of invasive and in-situ carcinoma, with follow-up.

OBJECTIVES: Carriers of BRCA1 and BRCA2 mutations are at increased risk of high grade serous carcinoma and are therefore offered risk-reducing salpingo-oophorectomy (RRSO) by 40-45 years. Most of these carcinomas are believed to arise in the fallopian tube from serous tubal intraepithelial carcinoma (STIC). We conducted a retrospective study on the prevalence of high grade serous carcinoma and STIC in BRCA1/2 carriers presenting for RRSO, and their follow-up. METHODS: Consecutive BRCA1/2 carriers presenting for an RRSO at Erasmus MC (2000-2016) were studied. SEE-FIM pathology protocol was followed from 2010 onwards. For the cases with carcinoma and/or STIC, the histology was reviewed and immunohistochemistry (p53 & MIB-1) was performed. Next Generation Targeted Sequencing (NGTS) for TP53 mutation was used to establish clonality in 2 cases. RESULTS: Of the 527 included patients, 68% were BRCA1, 31.6% were BRCA2, and 0.4% carried both mutations. The prevalence of high grade serous carcinoma was 2.3% (12/527); 59% of these were of tubal origin. High grade serous carcinoma was more common in patients operated on after the recommended age (p = 0.03). Isolated STIC was present in 0.8% (4/527). Two BRCA1 carriers with isolated STIC at RRSO developed peritoneal serous carcinoma >7 years later. Identical TP53 mutations in the peritoneal serous carcinoma and the preceding STIC established their clonal origin. CONCLUSIONS: High grade serous carcinoma is more common in BRCA1/2 carriers presenting for RRSO after the recommended age, and is more often of tubal origin. Longer follow up of patients with STIC at RRSO should be considered.

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Objective: To update the 2013 US Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013, to March 6, 2019, for updates; January 1, 1994, to March 6, 2019, for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction and Synthesis: Data on study methods, setting, population characteristics, eligibility criteria, interventions, numbers enrolled and lost to follow-up, outcome ascertainment, and results were abstracted. Two reviewers independently assessed study quality. Main Outcomes and Measures: Cancer incidence and mortality; discriminatory accuracy of risk assessment tools for BRCA1/2 mutations; benefits and harms of risk assessment, genetic counseling, genetic testing, and risk-reducing interventions. Results: For this review, 103 studies (110 articles; N = 92 712) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies (n = 43 813) of 8 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve, 0.68-0.96). Twenty-eight studies (n = 8060) indicated that genetic counseling was associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies (n = 4322) showed that breast cancer worry and anxiety were higher after testing for women with positive results and lower for others; understanding of risk was higher after testing. In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Mastectomy was associated with 90% to 100% reduction in breast cancer incidence (6 studies; n = 2546) and 81% to 100% reduction in breast cancer mortality (1 study; n = 639); oophorectomy was associated with 69% to 100% reduction in ovarian cancer (2 studies; n = 2108); complications were common with mastectomy. Conclusions and Relevance: Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.

The Use of Opportunistic Salpingectomy at the Time of Benign Hysterectomy.

STUDY OBJECTIVE: To delineate the use of opportunistic salpingectomy over the study period, to examine factors associated with its use, and to evaluate whether salpingectomy was associated with perioperative complications. DESIGN: A retrospective cross-sectional study (Canadian Task Force classification II-2). SETTING: The Michigan Surgical Quality Collaborative. PATIENTS: Women undergoing ovarian-conserving hysterectomy for benign indications from January 2013 through April 2015. INTERVENTIONS: The primary outcome was the performance of opportunistic salpingectomy with ovarian preservation during benign hysterectomy. The change in the rate of salpingectomy was examined at 4-month intervals to assess a period effect over the study period. Multivariate logistic regression was performed to evaluate independent effects of patient, operative, and period factors. Perioperative outcomes were compared using propensity score matching. MEASUREMENTS AND MAIN RESULTS: There were 10 676 (55.9%) ovarian-conserving hysterectomies among 19 090 benign hysterectomies in the Michigan Surgical Quality Collaborative in the study period. The rate of opportunistic salpingectomy was 45.8% (n = 4890). Rates of opportunistic salpingectomy increased over the study period from 27.5% to 61.6% (p < .001), demonstrating a strong period effect in the consecutive 4-month period analysis. Salpingectomy was more likely with the laparoscopic approach (odds ratio = 3.48; 95% confidence interval, 3.15-3.85) and among women younger than 60 years of age (odds ratio = 1.60; 95% CI, 1.34-1.92). There was substantial variation in salpingectomy across hospital sites, ranging from 3.6% to 79.9%. Salpingectomy was associated with a 12-minute increase in operative time (p < .001), but there were no differences in the estimated blood loss or perioperative complications. CONCLUSION: The rates of salpingectomy increased significantly over the study period. The laparoscopic approach and younger age are associated with an increased probability of salpingectomy. Salpingectomy is not associated with increased blood loss or perioperative complications.

Distinctive psychological and social experiences of women choosing prophylactic oophorectomy for cancer prevention.

Women known to have significantly elevated ovarian cancer risk due to genetic mutations or family history can reduce this risk by surgically removing both ovaries and fallopian tubes (RRBSO, risk-reducing bilateral salpingo-oophorectomy). We used interpretive phenomenological analysis (IPA) to explore the psychosocial experiences of women who chose RRBSO for cancer prevention. We extended the traditional use of IPA to compare the experiences of women who chose RRBSO for cancer prevention to those of women who underwent similar gynecologic surgery for benign indications. The analysis resulted in three superordinate themes describing women's psychosocial experiences related to RRBSO: (a) psychological facets of cancer risk (b) social support and (c) shared medical decision making. Findings illustrate that women choosing RRBSO for cancer prevention experience heightened psychosocial challenges before and after surgery compared to women undergoing surgery for benign indication. Furthermore, they may need distinct types of information and support from healthcare providers.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

STUDY OBJECTIVE: To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. DESIGN: A prospective study (Canadian Task Force classification II-1). SETTING: A gynecologic oncology referral center. PATIENTS: Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). INTERVENTIONS: Minimally invasive risk-reduction surgery. MEASUREMENTS AND MAIN RESULTS: Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). CONCLUSION: Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery.

Role of Fallopian Tubes in the Development of Ovarian Cancer.

Ovarian cancer is the leading cause of death from gynecologic malignancy and the fifth cause of cancer death in women in the United States. The most common and lethal histologic subtype of epithelial ovarian cancer is high-grade serous carcinoma (HGSC), which generally presents at an advanced stage. HGSC may be associated with BRCA1 and BRCA2 mutations. Historically, HGSC was believed to originate from the ovarian epithelial cells. However, more recent evidence supports the idea that most ovarian cancers originate in the fallopian tube epithelium in both high-risk women and in the general population. Serous tubal intraepithelial carcinomas may ultimately evolve into ovarian or peritoneal cancer. As a result, prophylactic salpingectomy with conservation of the ovaries has become an increasingly more common practice for premenopausal women undergoing risk-reducing surgery. Because the fallopian tube is now recognized as the most common potential site of origin of ovarian carcinoma, there is ongoing research to explore molecular and genetic factors that may be critical in the development of this disease. Further research is needed to identify novel opportunities for early detection and screening of ovarian cancer with the ultimate goal of increasing overall survival.

No. 344-Opportunistic Salpingectomy and Other Methods of Risk Reduction for Ovarian/Fallopian Tube/Peritoneal Cancer in the General Population.

OBJECTIVE: This guideline reviews the potential benefits of opportunistic salpingectomy to prevent the development of high grade serous cancers (HGSC) of the ovary/fallopian tube/peritoneum based on current evidence supporting the fallopian tube origin of disease. INTENDED USERS: Gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers. TARGET POPULATION: Adult women (18 and older): OPTIONS: Women considering hysterectomy who wish to retain their ovaries in situ have traditionally also retained their fallopian tubes. In addition, women undergoing permanent surgical sterilization have usually undergone tubal ligation using various methods rather than undergoing surgical removal of the entire fallopian tube. EVIDENCE: For the sections "Evidence Supporting the Hypothesis That HGSC Originates in the Fallopian Tube" and "Current Literature on the Effects and Safety of Opportunistic Salpingectomy," relevant studies were searched in PubMed, Medline, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials: "high grade serous cancers ovary," "fallopian tube," "peritoneum," "opportunistic salpingectomy," "epithelial ovarian cancers," "origin," "tubal carcinoma in situ," "BRCA mutation," "prophylactic salpingectomy," "inflammation," "clear cell," and "endometrioid." The initial search was performed in March 2015 with a final literature search in March 2016. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. The total number of studies identified was 458, and 56 studies were included in this review. For the section "Other Factors Influencing the Risk of Developing "Ovarian" Cancers" a general Medline search was carried out using the terms "ovarian neoplasm" and "prevention." The search included papers published from December 2005 to March 2016. Meta-analyses were preferentially selected except where no such review was found. Additional searches for each subheading were also conducted (e.g., "ovarian neoplasm" and "tubal ligation.") Additional significant articles were identified through cross-referencing the identified reviews. For the search for "ovarian neoplasm" and "prevention," 10 meta-analyses were identified. For the search for "ovarian neoplasm" and "tubal ligation," an additional 4 meta-analyses were identified. VALIDATION METHODS: The content and recommendations were drafted and agreed on by the principal authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (Table 1). The interpretation of strong and weak recommendations is described in Table 2. The summary of findings is available on request. BENEFITS, HARMS, AND/OR COSTS: The addition of opportunistic salpingectomy to a planned hysterectomy or permanent sterilization did not increase rates of hospital readmission (OR 0.91, 95% CI 0.75 to 1.10 and OR 0.8, 95% CI 0.56 to 1.21, respectively) or blood transfusions (OR 0.86, 95% CI 0.67 to 1.10 and OR 0.75, 95% CI 0.32 to 1.73, respectively) but did increase the overall operating time (by 16 minutes and 10 minutes, respectively) in a retrospective review of 43 931 women. The risk of repeat surgery for tubal pathology among women with retained fallopian tubes after hysterectomy was at least doubled (OR 2.13, 95% CI 1.88 to 2.42 in a population-based study of 170 000 women). If general gynaecologists were to consider removal of fallopian tubes at the time of every hysterectomy and sterilization procedure with referral of all patients with HGSC for hereditary cancer counselling and genetic testing, experts project a potential reduction in the rate of HGSC by 40% over the next 20 years. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SPONSORS: This guideline was developed with resources funded by the Society of Gynecologic Oncology of Canada and SOGC. SUMMARY STATEMENTS: RECOMMENDATIONS.

Incidence and Characteristics of Unsuspected Neoplasia Discovered in High-Risk Women Undergoing Risk Reductive Bilateral Salpingooophorectomy.

OBJECTIVE: Risk reducing salpingooophorectomy is recommended to women with a BReast CAncer susceptibility gene (BRCA) 1 or 2 germline mutation to reduce the risk of ovarian cancer. The incidence of unsuspected neoplasia varies in the literature. The purpose of this study was to identify the rate of unsuspected neoplasia in a high-risk Australian population, discuss their management, and assess the clinical outcome. METHOD: This is a retrospective review of all women undergoing risk reductive salpingooophorectomy between January 2006 and December 2014. The medical, operative, and pathology results were reviewed. The specimens were assessed using the Sectioning and Extensively Examining the Fimbriated End protocol to the fallopian tube, and the ovary was also examined using 2 to 3 mm sectioning. RESULTS: During the study period, 138 patients underwent risk-reducing salpingooophorectomy for a known BRCA 1 or 2 germline mutation or a high-risk personal or family history of ovarian cancer. Five patients with neoplasia were identified, 2 with invasive tubal carcinoma and 3 with serous tubal intraepithelial carcinoma (STIC), giving an overall incidence of 3.62%. Invasive tubal carcinoma occurred in 1 woman with a BRCA 1 mutation and 1 woman with a BRCA 2 mutation. The incidence of carcinoma in women with either a BRCA 1 or 2 germline mutation was subsequently 2.78%. STIC occurred in 2 women with a BRCA 1 germline mutation and 1 woman carrying a BRCA 2 germline mutation. The incidence of STIC in women with either a BRCA 1 or 2 germline mutation was subsequently 4.17%. Of the patients with STIC, all 3 remain disease free at an average follow-up period of 79.33 months. CONCLUSIONS: In this retrospective review, we found the incidence of neoplasia within a high-risk Australian population undergoing risk-reducing bilateral salpingo-oophorectomy to be 3.62%. The incidence of STIC was 2.17%. During our follow-up period, all patients with STIC remained disease free.

A new strategy for prophylactic surgery in BRCA women: Combined mastectomy and laparoscopic salpingo-oophorectomy with immediate reconstruction by double DIEP flap.

BACKGROUND: Prophylactic surgery remains the most effective modality for reducing both breast and ovarian cancer rate in woman at high risk, such as BRCA1 or BRCA2. Autologous breast reconstruction with bilateral deep inferior epigastric perforator (DIEP) flap allows predictable and durable results. However, existing two-step approach separating salpingo-oophorectomy and reconstruction could even make DIEP flap impossible, or make insufflation more difficult during laparoscopy. Other authors described one-step procedure but with open laparotomy. The goal of this study was to verify the feasibility of a simultaneous procedure, including laparoscopic salpingo-oophorectomy. METHODS: We included BRCA mutation careers scheduled for simultaneous laparoscopic salpingo-oophorectomy, and bilateral breast reconstruction with DIEP flaps. The first step of the procedure was laparoscopic salpingo-oophorectomy and ports had to be strategically placed to avoid interference with the following procedure. The second step was bilateral breast reconstruction with DIEP flaps. We reviewed medical charts. Surgical procedure was analyzed for duration, revisions and surgical complications. RESULTS: During 1-year period, eight patients agreed to a simultaneous procedure. All of them were BRCA positive, mean age was 38.3years (range, 39-50), and mean BMI was 28.3kg/m(2) (range, 21-33). The mean duration of the entire procedure was 524minutes (range, 405-630) and the mean hospital stay 9.2 days (range, 8-14). There was 100% flap survival. No abdominal wall dehiscence occurred. CONCLUSION: One-step procedure for prophylactic surgery of ovarian and breast hereditary malignancies is feasible. First salpingo-oophorectomy with open laparoscopy then bilateral immediate or delayed breast reconstruction with DIEP flaps can be performed.

[Salpingectomy in ovarian cancer prevention: Evidence behind the hypothesis and surgical implications]. / Salpingectomía como opción de reducción de riesgo de cáncer de ovario.

Background: Over the last decade, evidence suggests the fallopian tubes are the origin of most of the high grade ovarian serous carcinomas. This type of carcinoma represents at least 50% of all the cases of epithelial ovarian cancer. Salpingectomy may lower the risk of high grade serous carcinoma. Removing the two fallopian tubes should be considered a strategy for risk reduction in patients who decide tubal sterilization or in patients with hysterectomy for benign disease. There are ongoing protocols that evaluate the ovarian hormonal production impact after prophilactic salpingectomy. In patients with BRCA1 and BRCA2 mutations, salpingo-oophorectomy is recommended usually between 35 to 40 years of age for BRCA 1 and between 40 and 45 years of age for BRCA 2. The oopherectomy done whithin these decades has the consequences and side effects of premature menopause, some physicians have suggested doing a two step procedure: perform a salpingectomy as soon as the patient has decided to have permanent birth control, and doing the ophoorectomy at the onset of menopause. The oncological safety of this approach is still under evaluation and is not recommended outside a protocol.

Role of salpingectomy at the time of urogynecologic surgery.

PURPOSE OF REVIEW: This article reviews the current literature about prophylactic bilateral salpingectomy and provides guidelines for clinicians in regard to the inclusion of salpingectomy at the time of urogynecologic surgery. RECENT FINDINGS: After the Nurses' Health Study showed that all-cause mortality was increased in women undergoing oophorectomy at the time of hysterectomy for benign indications, there was a shift in focus toward ovarian conservation at the time of gynecologic surgery. As there has been continued interest in the fallopian tube as the origin of ovarian cancer, a move toward prophylactic salpingectomy has occurred. This strategy has become widely accepted in high-risk women, but is not universal in either premenopausal or postmenopausal women who are primarily served by the urogynecologic community. SUMMARY: Current literature supports that, if easily accessible, the fallopian tubes should be removed at the time of urogynecologic surgery. In premenopausal women, salpingectomy does not likely affect ovarian reserve, but this possibility should be discussed with patients. If inaccessible (i.e., at the time of a midurethral sling), there should not be additional surgery performed to access the fallopian tubes. In addition, the pathologic evaluation of the fallopian tubes should include complete examination of the fimbriae and a representative section of the nonfimbriated portion.

Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.

DESCRIPTION: Update of the 2005 U.S. Preventive Services Task Force (USPSTF) recommendation on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility. METHODS: The USPSTF reviewed the evidence on risk assessment,genetic counseling, and genetic testing for potentially harmful BRCA mutations in asymptomatic women with a family history of breast or ovarian cancer but no personal history of cancer or known potentially harmful BRCA mutations in the family. The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery. POPULATION: This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer. RECOMMENDATION: The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2). Women with positive screening results should receive genetic counseling and, if indicated after counseling, BRCA testing. (B recommendation)The USPSTF recommends against routine genetic counseling or BRCA testing for women whose family history is not associated with an increased risk for potentially harmful mutations in the BRCA1 or BRCA2 genes. (D recommendation).

Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation.

BACKGROUND: Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer. PURPOSE: To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. DATA SOURCES: MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists. STUDY SELECTION: English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality. DATA EXTRACTION: Individual investigators extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability by using established criteria. DATA SYNTHESIS: Five referral models accurately estimated individual risk for BRCA mutations. Genetic counseling increased the accuracy of risk perception and decreases the intention for genetic testing among unlikely carriers and cancer-related worry, anxiety, and depression. No trials evaluated the effectiveness of intensive screening or risk-reducing medications in mutation carriers, although false-positive rates, unneeded imaging, and unneeded surgeries were higher with screening. Among high-risk women and mutation carriers, risk-reducing mastectomy decreased breast cancer by 85% to 100% and breast cancer mortality by 81% to 100% compared with women without surgery; risk-reducing salpingo-oophorectomy decreased breast cancer incidence by 37% to 100%, ovarian cancer by 69% to 100%, and all-cause mortality by 55% to 100%. LIMITATION: The analysis included only English-language articles;efficacy trials in mutation carriers were lacking. CONCLUSION: Studies of risk assessment, genetic counseling, genetic testing, and interventions to reduce cancer and mortality indicate potential benefits and harms that vary according to risk.

Quantitative analysis of γ-H2AX and p53 nuclear expression levels in ovarian and fallopian tube epithelium from risk-reducing salpingo-oophorectomies in BRCA1 and BRCA2 mutation carriers.

Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Increased lifetime ovarian cancer risk among BRCA1/BRCA2 mutation carriers can be substantially decreased by risk-reducing salpingo-oophorectomy (RRSO), which also provides material for molecular research on early pathogenesis of serous ovarian cancer. RRSO studies have suggested fallopian tube as a primary site of serous high-grade ovarian cancer. In this study, the nuclear expression levels of γ-H2AX and p53 using immunohistochemical (IHC) study was quantitatively assessed in ovarian and fallopian tube epithelium derived from RRSOs in 29 BRCA1 and BRCA2 mutation carriers and in 1 patient with a strong family history of breast and ovarian cancer but showing an unknown BRCA status. Both p53 and γ-H2AX nuclear staining levels were significantly higher in BRCA1/2 mutation-positive fallopian tube epithelium compared with the control fallopian tube epithelium (P<0.006 and P=0.011, respectively). Nuclear expression levels of p53 and γ-H2AX were similar between the BRCA1/2 mutation-positive ovarian epithelium and controls. Both γ-H2AX and p53 showed significantly higher nuclear expression levels in BRCA1/2 mutation-positive fallopian tube epithelium compared with BRCA1/2 mutation-positive ovarian epithelium (P<0.0001 and P<0.0001, respectively). BRCA1/2 mutation-positive fallopian tube epithelium showed a positive correlation between the γ-H2AX and p53 nuclear expression levels (Pearson r=0.508, P=0.003). Our results of quantitative nuclear p53 and γ-H2AX expression levels in ovarian and fallopian tube epithelium derived from RRSO in high-risk patients support the previously suggested role of fallopian tube epithelium serving as a possible site of initial serous ovarian carcinogenesis.

Potential effect of the risk of ovarian cancer algorithm (ROCA) on the mortality outcome of the Prostate, Lung, Colorectal and Ovarian (PLCO) trial.

Recently, the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial reported no mortality benefit for annual screening with CA-125 and transvaginal ultrasound (TVU). Currently ongoing is the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which utilizes the risk of ovarian cancer algorithm (ROCA), a statistical tool that considers current and past CA125 values to determine ovarian cancer risk. In contrast, PLCO used a single cutoff for CA125, based on current levels alone. We investigated whether having had used ROCA in PLCO could have, under optimal assumptions, resulted in a significant mortality benefit by applying ROCA to PLCO CA125 screening values. A best-case scenario assumed that all cancers showing a positive screen result earlier with ROCA than under the PLCO protocol would have avoided mortality; under a stage-shift scenario, such women were assigned survival equivalent to Stage I/II screen-detected cases. Updated PLCO data show 132 intervention arm ovarian cancer deaths versus 119 in usual care (relative risk, RR = 1.11). Forty-three ovarian cancer cases, 25 fatal, would have been detected earlier with ROCA, with a median (minimum) advance time for fatal cases of 344 (147) days. Best-case and stage-shift scenarios gave 25 and 19 deaths prevented with ROCA, for RRs of 0.90 (95% CI: 0.69-1.17) and 0.95 (95% CI: 0.74-1.23), respectively. Having utilized ROCA in PLCO would not have led to a significant mortality benefit of screening. However, ROCA could still show a significant effect in other screening trials, including UKCTOCS.