Fluent Essays

For this assignment, you will review and reflect on the Prophylactic Hysterectomy article. This article can be applied to healthcare providers in the primary care and specialty settings.  Discussion of the article is based on the course objectives and weekly content, which emphasize the core learning objectives for an evidence-based primary care curriculum. Throughout your Nurse Practitioner program, discussions are used to promote the development of clinical reasoning through the use of ongoing assessments and diagnostic skills, and to develop patient care plans that are grounded in the latest clinical guidelines and evidence-based practice. Discuss any “take-away” thoughts from the article. What are the ethical dilemmas to consider with prophylactic surgeries? Discuss the screenings/interventions/options/education that you would provide to a patient that has a strong family history of ovarian cancer. What if the patient has no health insurance? What resources could you offer to assist the patient? Review Article Perioperative Management of Women Undergoing Risk-reducing Surgery for Hereditary Breast and Ovarian Cancer D1X XMariam M. AlHilli, D2X XMD, and D3X XZahraa Al-Hilli, D4X XMD From the Division of Gynecologic Oncology, Women’s Health Institute (Dr. AlHilli), Cleveland Clinic, Cleveland, Ohio, and Department of General Surgery, Digestive Diseases and Surgery Institute (Dr. Al-Hilli), Cleveland Clinic, Cleveland, Ohio ABSTRACT C The authors decla Corresponding au Euclid Avenue, A E-mail: [email protected] Submitted July 11 Available at www 1553-4650/$ — (http://creativeco https://doi.org/10 arriers of genetic mutations that predispose to cancer syndromes are often faced with complex decisions. For women with hereditary breast and ovarian cancer in particular, the decision to undergo risk-reducing mastectomy or bilateral salpingo- oophorectomy is burdensome from a physical and psychological perspective. Although risk-reducing surgery is the most effective preventative measure in reducing a genetic mutation carrier’s risk of breast or ovarian cancer, the success of these procedures requires a multidisciplinary approach that centers on careful counseling regarding the risks and benefits of risk- reducing surgery. The physical and psychological distress associated with risk-reducing surgery often makes a combined surgical approach attractive to some patients. In this review, we present the evidence surrounding the comprehensive surgi- cal care of women with hereditary breast and ovarian cancer syndromes and evaluate the perioperative factors that influence surgical management. Journal of Minimally Invasive Gynecology (2019) 26, 253−265 © 2018 Published by Elsevier Inc. on behalf of AAGL. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/) Keywords: R isk-reducing surgery; Risk-reducing mastectomy; Hereditary breast and ovarian cancer syndrome; BRCA; genetic screening re that they have no conflict of interest. thor: Mariam M. AlHilli, MD, Cleveland Clinic, 9500 81, Cleveland, OH 44195. ccf.org , 2018, Accepted for publication September 6, 2018. .sciencedirect.com and www.jmig.org see front matter © 2018 Published by Elsevier Inc. on behalf of AAGL. This is an open access article under the CC BY-NC-ND license. mmons.org/licenses/by-nc-nd/4.0/) .1016/j.jmig.2018.09.767 Approximately 5\% to 10\% of breast cancers are attrib- uted to deleterious mutations in BRCA1 or BRCA2 genes, which are key genes in DNA repair through homologous recombination [1]. The cumulative risk of breast cancer by 80 years of age is 67\% in BRCA1 carriers and 66\% in BRCA2 carriers [2,3]. After a diagnosis of breast cancer, BRCA mutation carriers continue to have a substantial risk of developing a new breast cancer. The likelihood of developing breast cancer in an unaffected BRCA mutation carrier is influenced by multiple factors such as the presence of affected family members with the gene mutation and age (calculated lifetime risk). A study by Van Den Broek et al [4] of 6294 women diagnosed with breast cancer under 50 years of age (including 271 women with BRCA1 or BRCA2 mutations) showed that the 10-year cumulative contralateral breast cancer risk was 5.1\% for noncarriers, 21.1\% for BRCA1 mutation carriers, and 10.8\% for BRCA2 mutation carriers (hazard ratio = 3.31 for BRCA carriers compared with noncarriers). Interestingly, the age of first cancer was a significant risk factor for contralateral breast cancer. In women with a gene mutation who were diagnosed with breast cancer before 41 years, the risk of contralateral breast cancer was 23.9\% compared with 12.6\% for those diagnosed between 41 and 49 years. This risk was found to be even lower in women with no family history of breast cancer. Approximately 3\% to 5\% of women assessed for hereditary breast cancer through multigene panel testing are found to have mutations in genes of moderate pene- trance such as PALB2, CHEK2, and ATM (Table 1). In relation to these breast cancer−related genes, providing accurate estimates for breast cancer risk based on age and life expectancy has been challenging because of the limited availability of data. Furthermore, the success of breast cancer screening may mitigate some of the increased risks. Risk-reducing surgery is currently not recommended for carriers of low to moderate http://creativecommons.org/licenses/by-nc-nd/4.0/ mailto:[email protected] www.sciencedirect.com www.jmig.org http://creativecommons.org/licenses/by-nc-nd/4.0/ https://doi.org/10.1016/j.jmig.2018.09.767 http://crossmark.crossref.org/dialog/?doi=10.1016/j.jmig.2018.09.767&domain=pdf Table 1 Hereditary Syndromes Associated with Breast and Ovarian Cancer 1 Genetic Mutation/Syndrome Estimated Breast Cancer Risk Up to Age 70 Years Estimated Ovarian Cancer Risk Up to Age 70 Years Management Recommendations BRCA1 »55\%−70\% »39\%−46\% Annual screening MRI (or mammogram with tomosynthe- sis) at age 25 years Discuss RRM RRSO by age 35−40 years Transvaginal ultrasound and CA 125 at age 30-35 years* BRCA2 »45\%−70\% »10\%−27\% Annual screening MRI (or mammogram with tomosynthe- sis) at age 25 years Discuss RRM RRSO by age 40−45 years Transvaginal ultrasound and CA 125 at age 30−35 years* BRIP1 No increased risk »7\%−10\% RRSO by age 45−50 years CDH1: hereditary diffuse gastric cancer Increased risk of lobular carcinoma »60\% No increased risk Annual screening mammogram Breast MRI with contrast at age 30 years Insufficient evidence for RRM CHEK2 »37\% No increased risk Annual screening mammogram Breast MRI with contrast at age 30 years Insufficient evidence for RRM MSH2, MLH1, MSH6, PMS2, EPCAM: Lynch syndrome Unknown risk MLH1 »11\%−20\% MSH2 »15\%−24\% MSH6 »1\% PMS2 »0\% RRSO by age 40 years or after completion of childbearing Transvaginal ultrasound and CA 125 at age 30−35 years* ATM »24\% No increased risk Annual screening mammogram Breast MRI with contrast at age 40 years Insufficient evidence for RRM PALB2 »35\%−70\% Unknown risk Annual screening mammogram Breast MRI with contrast at age 30 Insufficient evidence for RRM PTEN: Cowden syndrome; PTEN hamartoma tumor syndrome »50\% No increased risk Annual screening mammogram Breast MRI with contrast at age 30 years Discuss RRM RAD51C Unknown risk »5\%−12\% RRSO by age 50−55 years RAD51D Unknown risk »5\%−12\% RRSO by age 45−50 years STK11: Peutz-Jeghers syndrome »45\%−50\% »18\%−21\% risk of none- pithelial ovarian cancer Annual screening mammogram and breast MRI at age 25 Annual pelvic examination at age 18−20 years TP53: Li-Fraumeni syndrome »50\% No increased risk Annual breast MRI with contrast at age 20 years Breast MRI with contrast at age 30 years Discuss RRM CA 125 = cancer antigen 125; MRI = magnetic resonance imaging; RRM = risk-reducing mastectomy; RRSO = risk-reducing salpingo-oophorectomy. * If RRSO not performed, transvaginal ultrasound/CA 125 are offered. There is insufficient evidence (National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology 2018; Genetics/ Familial High-Risk Assessment: Breast and Ovarian Cancer). 254 Journal of Minimally Invasive Gynecology. Vol 26, No 2, February 2019 penetrance genes. However, the available data do sup- port risk-reducing mastectomy (RRM) for carriers of BRCA1, BRCA2, PTEN, and TP53 mutations. Ovarian Cancer Risk Carriers of BRCA1 or BRCA2 mutations have a cumula- tive lifetime risk of ovarian cancer of 15\% to 40\% [1]. Women with a BRCA1 mutation have a 39\% to 46\% risk for ovarian, fallopian tube, or primary peritoneal cancer (referred to cumulatively as ovarian cancer) by age 70. Women with mutations in BRCA2 have a 10\% to 27\% risk of ovarian cancer [5,6]. Additionally, up to 25\% of women with ovarian cancer may harbor germline mutations in homologous recombination genes (e.g., RAD51C, RAD51D, and BRIP1) other than BRCA1 and BRCA2 [3]. Table 1 shows other genes associated with hereditary ovarian cancer and management recommendations. Given the substantial risk of identifying a genetic mutation in a patient diagnosed with ovarian cancer, genetic testing is currently recommended for all women with epithelial ovarian cancer [1,6]. AlHilli and Al-Hilli Perioperative Management of Women Undergoing Risk-reducing Surgery 255 Approach to the Management of Women with Hereditary Breast and Ovarian Cancer Genetic Risk Evaluation and Testing Criteria for genetic risk evaluation for hereditary breast and ovarian cancer (HBOC) include a personal history of ovarian cancer; a personal history of breast cancer in the setting of a known mutation in the family; breast cancer diagnosed ≤ 50 years of age; triple-negative breast cancer; 2 breast primaries in a single individual; breast cancer with multiple family members with breast, ovarian, or prostate cancer; family history of male breast cancer; Ashkenazi Jewish descent; family history of multiple primary cancers; and a first- or second-degree relative with breast cancer ≤ 45 years of age [1]. Genetic counseling is a key component in the manage- ment of women with HBOC. The primary goal of genetic counseling is to formally assess a patient’s personal and family history with respect to hereditary cancers and to provide an estimate of the likelihood that an inherited genetic mutation is present [1,6]. The patient’s knowledge, concerns, goals, and needs are evaluated at the time of genetic consultation and before genetic testing. Education regarding differential diagnosis, inheritance patterns and penetrance, possible outcomes of testing, screening, pre- vention, and risk-reducing strategies is initiated at that time [6]. Post-test counseling is an important aspect of patient management and education. Details of the results, their sig- nificance, and impact of recommendations should be discussed; family members are to be informed, and testing and resources should be provided [1]. At this time, most centers offer genetic testing through commercially developed multigene panel tests instead of single gene testing unless a specific inherited genetic mutation has been previously identified in a family mem- ber. Multigene panel tests are based on next-generation sequencing and allow the simultaneous evaluation of multiple genes including those with moderate penetrance [16]. This approach has some limitations including uncer- tainty regarding the management of genes of intermediate penetrance, variants of uncertain significance, and individu- als with negative testing but strong family histories [1]. Breast Cancer Screening Recommendations for breast cancer screening for women with HBOC include breast awareness, clinical breast examinations, and breast imaging. In general, breast awareness and regular monthly self-breast examinations start at the age of 18 years. Clinical breast examinations begin at 25 years of age. Between the ages of 25 and 29 years, annual breast magnetic resonance imaging (MRI) with contrast is performed (this should be performed on days 7−15 of the menstrual cycle) or annual mammograms if MRI is not available. Between the ages of 30 and 75 years, annual mammography is recommended, alternating every 6 months with annual breast MRI. Tomo- synthesis can be considered with or without 2-dimensional mammography, particularly in women with increased breast density, because it is superior to mammography in the detection of abnormalities within the breast. However, this is not routinely performed or may not be widely avail- able. Screening beyond 75 years is unclear and is consid- ered on a case-by-case basis based on patient current health and life expectancy [1]. Mammography has a sensitivity and specificity of 77\% to 95\% and 94\% to 97\%, respectively [7]. The most recent update for the US Preventive Services Task Force included a review of 8 randomized trials of mammographic screen- ing [8]. Mammographic screening was found to reduce the risk of breast cancer mortality for women between 39 and 69 years old. A reduction in cancer mortality of 15\% was observed for women aged 39 to 49 years (relative risk [RR] = 0.85; 95\% confidence interval [CI], 0.75−0.96). Data regarding women aged 70 years or older are lacking. In comparison with mammography, MRI screening has been shown to have a higher sensitivity. However, it is important to note that MRI screening may be associated with higher false-positive rates and a higher cost. Ovarian Cancer Screening In comparison with breast cancer screening, there are no screening tests that have been deemed effective in improv- ing the detection of ovarian or fallopian tube cancer [9]. Studies that evaluate ovarian cancer screening strategies have not shown an improvement in survival [1]. The cur- rently available screening modalities including transvaginal ultrasound and cancer antigen 125 (CA 125) have not been shown to reduce mortality related to ovarian cancer [10,11]. Other large prospective studies in high-risk women have suggested the possibility of early detection of ovarian cancer through screening with transvaginal ultrasound and CA 125 (using the risk of ovarian cancer algorithm) [12]. However, the impact on mortality in these patients has not been established. As such, risk-reducing surgery is the rec- ommended strategy for reduction in ovarian cancer risk in carriers of genetic mutations. Based on National Compre- hensive Cancer Network guidelines, performing CA 125 and pelvic ultrasound starting at age 30 to 35 years is left to the provider’s discretion [1]. Chemoprophylaxis Breast cancer risk reduction elements include lifestyle modification, surgical prophylaxis, and chemopreven- tion. Risk-reducing chemoprevention agents include the selective estrogen receptor modulators tamoxifen and raloxifene and the aromatase inhibitors anastrozole and exemestane. (The latter 2 are yet to be Food and Drug Administration approved for breast cancer risk reduction purposes.) Tamoxifen is used for premenopausal 256 Journal of Minimally Invasive Gynecology. Vol 26, No 2, February 2019 women, whereas all 4 can be used for postmenopausal woman; this choice will be influenced by patient comor- bidities and risk considerations. The challenge with che- moprevention recommendations in gene mutation carriers is the limited data available on the use of these agents for risk reduction in this cohort. Studies have shown that the use of tamoxifen was associated with an approximately 45\% to 60\% reduction in the risk of con- tralateral breast cancer in affected women with BRCA1 and 2 mutations [13,14]. The National Surgical Adju- vant Breast and Bowel Project Breast Cancer Prevention Trial (P-1) was a randomized trial evaluating the role of tamoxifen for the prevention of breast cancer in unaf- fected women considered to be high risk for the disease [15]. BRCA2 patients, who typically develop estrogen receptor−positive tumors, achieved a 62\% reduction in breast cancer risk with the use of tamoxifen compared with placebo. On the other hand, BRCA1 mutation car- riers did not achieve risk reduction with tamoxifen, likely because of the propensity for developing estrogen receptor−negative tumors in these patients. It is impor- tant to interpret chemoprevention benefit data in muta- tion carriers with caution because of the small number of patients included in studies. In addition, little is known about the role of chemoprevention in non-BRCA gene mutation carriers. With regard to ovarian cancer risk reduction, the use of combined oral contraceptive pills has been shown to be associated with a 40\% to 50\% reduction in the risk of ovarian cancer [16]. In a case-control study by Narod et al [17], the use of oral contraceptives was associated with a significant reduction in the risk of ovarian cancer in both BRCA1 and BRCA2 mutation carriers [5]. This risk decreased with increasing duration of the use of oral contraceptives. As such, the use of combined oral contraceptives is considered to be a potential chemo- preventive strategy in women with BRCA mutations [16]. Data on the effect of oral contraception on breast cancer risk among BRCA1/2 mutation carriers have been conflicting. Some case-control studies have reported a modest increased risk of breast cancer among BRCA1 but not BRCA2 mutation carriers, whereas others have reported no increased risk [17,18]. However, at least 2 meta-analyses showed no increased risk of breast cancer in women with a BRCA1/2 mutation who used oral con- traception [19,20]. Risk-reducing Surgical Options for Women with HBOC Risk-reducing salpingo-oophorectomy (RRSO) has been shown to reduce the risk of ovarian cancer by 96\%, breast cancer by 50\% to 75\%, and all-cause mortality in unaf- fected women [5,21−23]. Therefore, RRSO is the most effective strategy for decreasing the incidence of ovarian cancer and mortality in high-risk women with hereditary mutations. For women identified to have a BRCA1 mutation, national guidelines recommend RRSO between the ages of 35 to 40 years because risk begins to increase in these patients in their late 30s [6,16]. Carriers of the BRCA2 mutation have a later age of onset of ovarian can- cer, and RRSO is recommended between ages 40 and 45 years in these patients. Prospective studies of women with BRCA1 and BRCA2 mutations show that approxi- mately 60\% of women will opt for RRSO [24]. RRM reduces the risk of breast cancer by 90\% to 97\%. RRM can occur in conjunction with or as an alternative to high-risk screening. Bilateral RRM (BRRM) may be con- sidered in women without a personal history of breast can- cer. On the other hand, women with a diagnosis of breast cancer continue to carry an elevated risk for breast cancer in the affected or contralateral breast. Therefore, these patients may consider contralateral RRM (CRRM). In general, women with a confirmed genetic mutation in BRCA1 or BRCA2 or other genes with an elevated risk for breast or ovarian cancer are offered risk-reducing surgery. Women with negative genetic testing but a first-degree rela- tive with epithelial ovarian cancer are estimated to have a risk of 5\% of developing ovarian cancer and also qualify for RRSO. In the absence of a pathogenic mutation, an ele- vated risk based on family history assessment of breast and/ or ovarian cancer risk is an appropriate indication for risk- reducing surgery [3] (Fig. 1). RRSO Preoperative Counseling Investigations into the psychosocial impact of risk- reducing surgery show that surgery is associated with a sig- nificant decline in psychological morbidity and anxiety without an increase in negative body impact or a decrease in sexual functioning [9]. Nevertheless, the decision to undergo RRSO is complex and requires early consultation with a gynecologic oncologist as well as a provider with expertise in genetic counseling and testing [6]. At the time of counseling, a thorough discussion on the impact of RRSO on reproduction, breast and ovarian cancer risk, and the long-term risk of premature menopause (including oste- oporosis, cardiovascular disease, and sexual concerns) must be had. A review of the impact of this intervention on qual- ity of life is of high importance [1]. In addition, hormone replacement therapy (HRT) is encouraged in women with- out contraindications for estrogen and/or progesterone replacement. This strategy of HRT after surgical meno- pausal minimizes and ameliorates the potential detrimental consequences of surgical menopause [3]. Although con- cerns have been raised about a possible increase in breast cancer risk with the use of HRT in premenopausal women, it is important to discuss with patients that HRT has been deemed to be safe in women with BRCA1 mutations, and an increase in the risk of breast cancer among women taking HRT has not been observed in prospective studies [22,25]. Fig. 1 Evaluation and management of women with suspected or confirmed hereditary breast and ovarian cancer syndrome. Personal history of high grade epithelial ovarian cancer Personal history of breast cancer: - ≤50 years - Triple negative breast cancer - Two breast cancer primaries - Family history of breast or ovarian or other cancers - Male breast cancer Ashkenazi Jewish descent First or second degree family member with breast cancer ≤45 years Family history of breast or ovarian cancer Family history of multiple cancers Referral for consulta�on with a gene�cs counselor Gene�c tes�ng if indicated Hereditary breast and ovarian cancer confirmed Ovarian cancer risk managementBreast cancer risk management Breast cancer high-risk screening Risk –reducing mastectomy when sufficient evidence to recommend Offer screening with transvaginal ultrasound and CA125 age 30-35 Risk-reducing salpingo- oophorectomy between 35-40 years (BRCA1 muta�on carriers) and 40-45 (BRCA2 muta�on carriers) or a�er comple�on of childbearing AlHilli and Al-Hilli Perioperative Management of Women Undergoing Risk-reducing Surgery 257 Rebbeck et al [21] showed that the short-term use of HRT until the average age of menopause in premenopausal women undergoing RRSO generally did not increase the risk of breast cancer. A strategy of limiting HRT duration to the age of 51 years (the average age of menopause) is gener- ally recommended. In a decision analytic model developed by Armstrong et al [26], RRSO was found to be associated with an increase in life expectancy in patients with a BRCA1/2 mutation regardless of HRT use. A decrement in life expectancy was noted when HRT was continued for life versus when HRT was stopped at age 50 years [26]. Patients should be counseled about the risk of detec- tion of occult ovarian, fallopian tube, or primary perito- neal carcinoma at the time of risk-reducing surgery, which would necessitate surgical staging [9,27]. Furthermore, women who opt for RRSO before the completion of childbearing should be counseled about alternative reproductive options and referred appropri- ately to a reproductive endocrinology specialist. They should be informed about the option of undergoing embryo or ovarian cryopreservation as well as preim- plantation genetic diagnosis [1]. 258 Journal of Minimally Invasive Gynecology. Vol 26, No 2, February 2019 Decision Regarding Concurrent Hysterectomy Counseling regarding the risks and benefits of con- current hysterectomy at the time of RRSO is an impor- tant point of discussion. Hysterectomy is currently offered electively to women undergoing RRSO. Women with a gynecologic indication for hysterectomy includ- ing those with a known history of Lynch syndrome are likely to benefit from the addition of hysterectomy. Pre- menopausal women without a personal history of breast cancer who undergo RRSO are also offered hysterec- tomy to simplify hormone replacement [9]. The use of estrogen alone after hysterectomy is considered to be safer than combined estrogen and progesterone with regard to breast cancer risk [28]. It has been suggested that concurrent hysterectomy at the time of RRSO may provide long-term survival bene- fits when the risk of uterine cancer is taken into consid- eration [16]. Data regarding the increased risk of uterine serous carcinoma among BRCA mutation carriers are conflicting. BRCA1 mutation carriers have been pro- posed to be at highest risk. In a prospective review of 1083 women with BRCA mutations who underwent RRSO with uterine conservation, an increased risk of serous endometrial carcinoma was noted in BRCA1 mutation carriers (observed:expected risk ratio = 22.2; 95\% CI, 6.1−56.9; p < .001) [29,30]. However, at this time, the decision to perform hysterectomy at the time of RRSO is individualized after balancing the surgical risks and benefits of the procedure. Delayed Oophorectomy Delayed oophorectomy has been proposed to avoid premature menopause. The performance of risk-reducing salpingectomy alone in genetic mutation carriers who wish to preserve fertility and ovarian function is based on the accepted paradigm that serous tubal intraepithe- lial carcinoma is a precursor lesion for invasive carci- noma [31]. Although retrospective studies in low-risk women suggest a 35\% to 42\% reduction in the risk of ovarian cancer after salpingectomy, this is not consid- ered to be sufficient evidence to recommend salpingec- tomy in high-risk women [1]. Furthermore, carriers of BRCA1/2 mutations who undergo salpingectomy may not receive the benefit of a reduction of breast cancer risk (by 50\%) if oophorectomy is delayed [1]. Other concerns include the possibility that serous tubal intrae- pithelial carcinoma lesions may represent metastases from ovarian primary lesions in about 50\% of cases [3]. Furthermore, 70\% of occult carcinomas are found to originate in the fallopian tubes, which implies that one third of occult carcinomas that arise outside of the fallo- pian tubes would not be prevented with salpingectomy. Therefore, despite its feasibility, bilateral salpingectomy alone is not considered the standard of care with regard to risk reduction because the role of this procedure in BRCA mutation carriers has not been adequately vali- dated. Prospective studies are currently underway including the TUBA study (NCT02321228), which explores the impact of bilateral salpingectomy with delayed oophorectomy on quality of life as well as ovar- ian and breast cancer risk [3,32]. Intraoperative Considerations As described by the Society of Gynecologic Oncology and the American College of Obstetrics and Gynecology, the opti- mal technique for RRSO involves a systematic approach [33]. This process involves minor modifications in comparison with standard bilateral salpingo-oopherectomy (BSO) per- formed for other indications. A laparoscopic approach is gen- erally undertaken [9]. An abdominal survey is performed, and all peritoneal surfaces are inspected. Peritoneal washings are routinely obtained [6,34]. To ensure complete removal of the adnexa, the retroperitoneal space is entered. If adhesions between the ovary and pelvic side wall are encountered, they must be resected along with the ovary [9]. Prevention of ovar- ian remnant syndrome is of high importance in this patient population. The fallopian tubes are removed at their insertion point in the uterus if hysterectomy is not performed. The importance of complete removal of the fallopian tube is attributed to the high rate of occurrence of fallopian tube can- cers among BRCA mutation carriers [35]. These patients have a 120-fold increased risk of fallopian tube cancer compared with the general population [9]. The ovarian vessels are ligated at the pelvic brim. Postoperatively, meticulous histologic evaluation of the fallopian tubes and ovaries with sectioning in 2 to 3 mm is performed. This protocol, known as Sectioning and Exten- sively Examining the Fimbriated End of the fallopian tube, has been shown to increase the detection of serous carcinoma that arises in the fimbriated end of the fallopian tube in 50\% of patients regardless of BRCA status [22,36,37]. Box 1 describes best practice recommendations for RRSO. Adher- ence to these guidelines may impact prognosis and minimize the risk of missing an occult malignancy. In a retrospective study of 263 patients undergoing RRSO performed by gen- eral gynecologists compared with gynecologic oncologists, it was found that gynecologic oncologists are more likely to adhere to best practice guidelines and a meticulous RRSO technique [34,38]. Particularly, gynecologic oncologists were more likely to perform pelvic washings, include a description of the upper abdomen in the operative report, use a retroperi- toneal approach, and undergo careful pathologic examination of the specimens. In order to maximize the benefit from RRSO, referral of women desiring RRSO to surgeons with specialized training in pelvic surgery and those with expertise in caring for high-risk women is advocated. AlHilli and Al-Hilli Perioperative Management of Women Undergoing Risk-reducing Surgery 259 Box 1 Best Practice Recommendations for Risk-reducing Bilateral Sal- pingo-oophorectomy Preoperative � Pelvic ultrasound and cancer antigen 125 at least within 6 months of surgery � Counseling regarding reproductive desires, menopausal symp- toms, cancer risk, and hormone replacement Intraoperative � Abdominal and pelvic survey and close evaluation of peritoneal surfaces, bowel, and pelvic organs � Pelvic washings (50 mL normal saline instilled and aspirated) � Complete removal of the fallopian tube at isthmus � Ligation of ovarian vessels at pelvic brim (at least 2 cm proximal to ovary) � Removal of all peritoneum around ovaries/fallopian tubes, espe- cially if adhesions present Postoperative � Histologic evaluation and processing using the Sectioning and Extensively Examining the Fimbriated End of the fallopian tube approach (2- to 3-mm sections) � Referral to genetics and gynecologic or surgical oncology if occult malignancy or serous tubal intraepithelial carcinoma is diagnosed Risk of Occult Malignancy at the Time of RRSO The detection of …