Prophylactic Bilateral Salpingo-oophorectomy Research Articles

Prophylactic BSO in an Adolescent Patient With a SMARCA4 Mutation and a Family History of Small Cell Ovarian Carcinoma [8P

INTRODUCTION: Small cell carcinoma of the ovary hypercalcemic type is a rare malignancy that affects young women. Mutations in the SMARCA4 gene have been implicated as the main factor underlying oncogenesis and correlate strongly with disease presence. Several germline mutations with multiple affected family members have been described, although little is known about disease penetrance. METHODS: We describe our experience with a young asymptomatic patient found to have a SMARCA4 mutation and strong family history. RESULTS: A 15 year old female with two half-sisters diagnosed with SMARCA4 positive SCCOHT tested positive for the SMARCA4 gene mutation during screening of family members. The patient ultimately opted for prophylactic bilateral salpingo-oophorectomy. She underwent both genetic and reproductive endocrinology consultations preoperatively, but elected to forgo oocyte preservation. She is currently being treated with hormone replacement therapy. CONCLUSION: With recent advances in our understanding of the genetic basis of SCCOHT, identifying germline SMARCA4 mutation carriers at an early age will become more common. Management of these patients is challenging, given young age of disease onset, highly lethal course, and unknown gene penetrance. Prophylactic salpingo-oophorectomy is a reasonable therapeutic option, but requires aggressive management of subsequent surgical menopause and threatened fertility.

Potential adverse effects of prophylactic bilateral salpingo-oophorectomy on skin aging in premenopausal women undergoing hysterectomy for benign conditions.

This study aimed to assess the effects of hysterectomy and bilateral salpingo-oophorectomy (BSO)--compared with the effects of hysterectomy alone--on skin aging in premenopausal women undergoing hysterectomy for benign conditions. One hundred thirty-five premenopausal women who underwent hysterectomy with BSO were compared with a control group of women who underwent hysterectomy alone based on skin parameters (including wrinkling, laxity/sagging, and texture/dryness) and Skindex-29 questionnaire scores. The inclusion criteria were as follows: aged between 40 and 50 years, follicle-stimulating hormone level lower than 40 mIU/mL, undergoing hysterectomy with or without BSO for benign conditions, and not receiving estrogen or progesterone treatment. The exclusion criteria were as follows: adrenocortical hyperplasia or Cushing's syndrome; use of corticosteroids for autoimmune diseases; malignancy, connective tissue diseases (eg, Ehlers-Danlos syndrome), or dermatological diseases (eg, lichen sclerosus); or regular use of medications known to interfere with the condition of the skin. All skin parameters in the hysterectomy group and the hysterectomy with BSO group worsened on weeks 24 and 48. Laxity/sagging and texture/dryness scores on weeks 24 and 48 were significantly worse in the BSO group; laxity/sagging and texture/dryness scores continued to worsen between 24 and 48 weeks. Scores for the Skindex-29 questionnaire emotion and symptom subscales were significantly higher in the BSO group compared with the non-BSO group. Prophylactic BSO during hysterectomy is a significant independent risk factor for worsening skin laxity/sagging and texture/dryness in premenopausal women undergoing hysterectomy for benign conditions. Prophylactic BSO in the presence of dermatological conditions is also associated with reduced quality of life.

Primary peritoneal cancer in BRCA carriers after prophylactic bilateral salpingo-oophorectomy.

The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. Primary peritoneal cancer is an aggressive malignancy which, due to the absence of a specific screening test, cannot be diagnosed in its early stages. As a risk-reducing option, prophylactic bilateral salpingo-oophorectomy and mastectomy are often proposed in BRCA gene carriers. The effectiveness of a preventive surgical treatment is, however, unclear in the development of peritoneal cancer. An extensive electronic search was performed in PubMed, Scopus, and Cochrane databases. The total number of patients who underwent prophylactic bilateral salpingo-oophorectomy was 1,830, of whom 28 presented with peritoneal cancer (1.53%). The age of the included patients ranged from 48 to 61 years. BRCA-1 was present in 9 out of 28 patients and BRCA-2 in 2 patients, while the type of BRCA was unclear in 17 patients. Salpingo-oophorectomy was performed in 23 out of 28 patients, while oophorectomy was carried out in 5 patients. The interval from initial risk-reducing surgical treatment to the presentation of peritoneal cancer ranged from 12 to 84 months. Modification of the follow-up guidelines and increase in healthcare providers' awareness may reduce the risk of peritoneal cancer.

Differences in Uptake of Risk Reduction Strategies Among Underserved Populations

Differences in Uptake of Risk Reduction Strategies Among Underserved Populations

A model for estimating ovarian cancer risk: Application for preventive oophorectomy

ObjectiveIt is important to identify women in the population who have a high risk of ovarian cancer and who might benefit from prophylactic bilateral salpingo-oophorectomy. The probability that a woman will develop ovarian cancer depends on her current age, her reproductive history and her genetic status. MethodsWe simulated the distribution of ovarian cancer risk for the 2011 Ontario female population. We generated (at random) individual risks of ovarian cancer to age 80 for 6,301,340 women, based on the published risk factors, mutation frequencies and population age-specific incidence rates (SEER database). Risk factors included parity, breastfeeding, oral contraceptives, tubal ligation and family history. Genetic factors included 11 single nucleotide polymorphisms (SNPs) and BRCA1/2 mutations. ResultsOf the 6,301,340 women simulated as the general population of Ontario, the (complete) model predicts that 65,805 women (1.0%) will develop ovarian cancer by age 80. There were 46,069 women (0.7%) with a risk of ovarian cancer above 5%. BRCA1/2 mutation carriers accounted for 67.4% of the women at greater than 5% risk (31,028 women). Among ovarian cancer patients at greater than 5% risk, a BRCA1/2 mutation was present in 89.2%. In contrast, SNPs contribute to a very small proportion of the ovarian cancer patients who were at greater than 5% risk. ConclusionsApproximately 12.9% of all ovarian cancers in Ontario occur in the 0.7% of women in the general population who have a lifetime ovarian cancer risk in excess of 5%, the majority of whom carry a mutation in BRCA1 or BRCA2.

The gynecological surveillance of women with Lynch syndrome in Sweden

ObjectiveWomen with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome. MethodsA retrospective nationwide study of 170 women with molecularly confirmed LS. Data including gynecological LS screening history, biopsy results (if any), genetic records, number of screening visits, results from screening including transvaginal ultrasound (TVUS), endometrial biopsy (EB), blood test for tumor marker cancer antigen (CA) 125, prophylactic surgery including age at procedure, and setting from which screening data were obtained from medical records. ResultsA total of 117 women were eligible for gynecological screening and of these, 86 patients attended screening visits. Of these, 41 underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy. Two patients (4.9%) were diagnosed with EC and two (4.9%) with precancerous lesions in conjunction with prophylactic surgery. Total incidence of gynecological cancer in the surveillance group (45 women) was 20% EC, 4% OC. Five patients had endometrial cancer or complex hyperplasia with atypia (n=2) detected by endometrial biopsy. Four additional cases were detected due to interval bleeding. Both cases of ovarian cancer were detected by transvaginal ultrasound in patients with ovarian cysts under surveillance. The youngest woman with endometrial cancer was diagnosed at 35years of age, before she was aware of her diagnosis of Lynch syndrome. ConclusionsGynecological surveillance of women with Lynch syndrome may lead to earlier detection of precancerous lesions, which might have some impact on the morbidity from endometrial cancer although further studies are needed to prove this. Prophylactic hysterectomy with or without bilateral salpingo-oophorectomy reduces the cancer incidence. A practical approach to surveillance in Lynch syndrome women would be to offer annual surveillance beginning at age 30years including probably both TVUS and EB in order to increase diagnostic yield with prospective data registry for follow-up studies. Prophylactic surgery could be performed at a suitable age after childbearing to obtain a balance between reducing the risk of cancer and minimizing long-term complications from premature menopause.

Single-port versus conventional multiport access prophylactic laparoscopic bilateral salpingo-oophorectomy in high-risk patients for ovarian cancer: a comparison of surgical outcomes.

Bilateral salpingo-oophorectomy (BSO) in carriers of BRCA1 and BRCA2 mutations is widely recommended as part of a risk-reduction strategy for ovarian or breast cancer due to an underlying genetic predisposition. BSO is also performed as a therapeutic intervention for patients with hormone-positive premenopausal breast cancer. BSO may be performed via a minimally invasive approach with the use of three to four 5 mm and/or 12 mm ports inserted through a skin incision. To further reduce the morbidity associated with the placement of multiple port sites and to improve cosmetic outcomes, single-port laparoscopy has been developed with a single access point from the umbilicus. The purpose of this study was to evaluate the surgical outcomes associated with reducing the risks of salpingo-oophorectomy performed in a single port, while comparing multiport laparoscopy in women with a high risk for ovarian cancer. Single-port laparoscopy–BSO is feasible and safe, with favorable surgical and cosmetic outcomes when compared to conventional laparoscopy.

Abstract P1-11-03: Receipt of Risk Reduction strategies among an underserved population of BRCA mutation carriers

Abstract Introduction: Risk reduction strategies for women with deleterious BRCA mutations include risk-reducing mastectomy (RRM) or screening with annual mammograms and MRIs, chemoprevention and prophylactic bilateral salpingo-oophorectomy (RRBSO). The objective of the study was to describe the receipt of various risk reduction strategies in an underserved and largely understudied minority population of BRCA mutation carriers. Methods: Positive BRCA mutation carriers detected in our center between October 2005 and January 2014 were included in the study. Participants who had bilateral mastectomies prior to genetic testing were excluded from the analysis of breast cancer reduction strategies. Women age 40 or older, with at least one ovary intact at baseline and no history of ovarian malignancy or metastatic cancer were included in the analysis of uptake of RRBSO. Compliance with annual screening mammogram and MRI was defined as receipt of 2 screening mammograms and 2 MRIs within 2 years of the disclosure of the test results. Medical records were reviewed to collect demographic data, personal history of cancer and receipt of mammography, MRI, RRM and RRBSO. Results: Of the 87 BRCA mutation carriers, 84 were women and 3 were men. 35% were Caucasian, 31% were African American and 26% were Hispanic. Seventy percent were uninsured and 24% had public insurance. The mean age at the time of testing was 44 years (range: 18-71 years). BRCA1 positivity was seen in 54% and BRCA2 positivity was seen in 46%. Of the 84 total women, 6 had bilateral mastectomies prior to testing and 11 were lost to follow up. Of the remaining 67 women, 53 (79%) had a personal history of breast and/or ovarian cancer (affected) and 14 (21%) had no personal history of breast or ovarian cancer (unaffected). Among the 53 affected women, 14 (26%) received RRMs. The median duration from disclosure to RRM was 91.5 days (IQR: 22- 442 days). Among the 39 affected that did not undergo RRM, 31 had follow up care at our institution for at least 2 years after disclosure, during which 25 (81%) had at least 2 screening mammograms and 13 (42%) had at least 2 screening MRIs. Among the 14 unaffected women, 0 women underwent RRM (0%). Eleven unaffected women had follow up care at our institution for at least 2 years after testing, during which 5 (45%) had at least 2 mammograms and 3 (27%) had at least 2 MRIs. Of the 40 women eligible for RRBSO, 5 (13%) women were lost to follow up. Among the 35 remaining, 22 (63%) underwent RRBSO. Twenty-one out of the 22 who underwent RRBSO had a previous history of cancer. The median duration between disclosure to RRBSO was 167 days (IQR: 88-448 days). Thirteen women (37%) have not yet received the recommended RRBSO after a median follow up of 976 days (IQR:465-1591 days). Conclusions:Among a diverse group of medically underserved minority women who tested positive for a deleterious BRCA mutation, the receipt of surgical risk reduction strategies and MRI screening is low, especially among women who do not have a personal history of cancer. Additional studies are needed in this population to examine the factors associated with acceptability and compliance with standard of care recommendations as well as institutional barriers to receipt of these risk reduction strategies. Citation Format: Romy Thekkekara, Christina Seelaus, Maria O"Connell, Elizabeth Marcus, Pamela S Ganschow. Receipt of Risk Reduction strategies among an underserved population of BRCA mutation carriers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-03.

Opportunistic salpingectomies for the prevention of a high-grade serous carcinoma: a statement by the Kommission Ovar of the AGO.

The detection of premalignant cells in the epithelium of the fallopian tube has resulted in revolutionary theories regarding the origin of epithelial ovarian cancer (EOC). Serous tubal intra-epithelial carcinomas (STIC) have been detected in patients with BRCA 1 or 2 mutations and are considered as the most likely precursors of the high-grade serous ovarian cancer (HGSOC), which is the most common histological subtype in patients with EOC. A bilateral salpingo-oophorectomy is associated with a significant reduction in risk of developing EOC. According to various national guidelines, prophylactic bilateral salpingo-oophorectomy should be performed in the age group 40-45 years. As in patients with BRCA mutations, the prophylactic removal of the fallopian tubes is also performed in women without an increased genetic risk, for example, in surgical treatments of benign conditions. There is a current debate as to whether prophylactic or so-called opportunistic salpingectomy will influence the overall incidence of EOC in the coming years. Opponents of this theory warn of a higher surgical morbidity and the higher risk of a premature menopause through impaired vascular supply to the ovaries. The value of opportunistic salpingectomies has not yet been clarified since there are currently no systematic risk-benefit evaluations. This review will attempt to give an overview of the current body of evidence regarding the risks and benefits of opportunistic salpingectomies.

Factors Associated with Prophylactic Bilateral Salpingo-oophorectomy in Women under 50 Years of Age

Factors Associated with Prophylactic Bilateral Salpingo-oophorectomy in Women under 50 Years of Age

Serous tubal intraepithelial carcinoma: an incidental finding at the time of prophylactic bilateral salpingo-oophorectomy.

Background. Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion for high-grade pelvic serous carcinoma. The incidence of STIC is estimated to occur in 0.6% to 6% of women who are BRCA positive or have a strong family history of breast or ovarian cancer. Case. A 56-year-old woman underwent robotic-assisted sacrocolpopexy, rectocele repair, and concurrent bilateral salpingo-oophorectomy for recurrent stage 3 pelvic organ prolapse and reported family history of ovarian cancer. Histopathologic examination of her left fallopian tube revealed STIC. Conclusion. We report this rare occurrence of STIC in a patient undergoing surgery primarily for pelvic organ prolapse and having a family history of ovarian cancer. Possible management options include observation with annual physical exam and CA-125, surgical staging, or empiric chemotherapy. However, due to the lack of consensus regarding management options, referral to a gynecologic oncologist is recommended.

A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome.

Lynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes. To evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified. Systematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed. Inconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing. The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI and BRAF testing [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing). The absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation. Results suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL. This study is registered as PROSPERO CRD42012002436. The National Institute for Health Research Health Technology Assessment programme.

A pilot study of BRCA mutation carriers' knowledge about the clinical impact of prophylactic-oophorectomy and views on fertility consultation: a single-center pilot study.

BRCA mutation carriers will experience early surgically induced menopause following prophylactic bilateral salpingo-oophorectomy (PBSO). This pilot study aimed to investigate their (1) knowledge about the clinical impact of PBSO; (2) views on fertility consultation (FC)/fertility preservation (FP) treatment; and (3) difficulties in conceiving compared to non-carriers. A cross-sectional, single institution web-survey was performed at a university-based IVF center. Women aged 18-50years who were screened for BRCA gene mutations from 2005 to 2013 were recruited via mail. Forty-one BRCA-positive and 110 BRCA-negative women completed the survey (response rate: 50%). The knowledge about the reproductive impact of PBSO was limited, with the majority of women in this highly educated sample only identifying the correct response 64% of the time. Among BRCA mutation carriers, 24 (59%) had positive views about FC/FP treatments. A larger proportion of women with no children at the time of BRCA testing, and those who were non-white tended to have positive views toward FP. Women with, versus without, BRCA mutations were more likely to have difficulty in conceiving (p = 0.08). This well-educated group had limited knowledge about the reproductive clinical impact of PBSO, or the benefit of a FP before PBSO. Most women with BRCA mutations were interested in FC/FP treatment if they had not completed childbearing at the time of screening. Targeted referrals for FC at the time of BRCA screening may help women improve knowledge and allow improved decision-making about reproductive options.

Hormone therapy in oophorectomized BRCA1/2 mutation carriers

BRCA1/2 mutation carriers have greatly elevated lifetime risks of breast, ovarian, and fallopian tube cancers. Bilateral prophylactic salpingo-oophorectomy is recommended to prevent cancer in these women. As it is often performed before natural menopause, it may be accompanied by menopausal symptoms, impaired quality of life, and increased cardiovascular risk. In this review, we describe the indications, timing, and implications of salpingo-oophorectomy for BRCA-positive women, with a special focus on the risks and benefits of hormone therapy (HT). Furthermore, retrospective and prospective trials of HT in BRCA mutation carriers undergoing prophylactic salpingo-oophorectomy are debated. Hormonal deprivation after prophylactic salpingo-oophorectomy may negatively impact health and quality of life; most women experience menopausal symptoms shortly after surgical operation. Literature data suggest that HT generally reduces vasomotor symptoms related to surgical menopause, improving sexual functioning without affecting survival. Despite the limitations of retrospective and prospective observational studies, short-term HT seems to improve quality of life and does not seem to have an adverse effect on oncologic outcomes in BRCA1 and BRCA2 mutation carriers without a personal history of breast cancer. Therefore, randomized and larger trials are urgently needed.

Dealing with Uncertainty in Genetic Testing

Testing for BRCA1 and BRAC2 deleterious mutations, and the subsequent decisions about prophylactic surgery, have an important effect on the psychological well-being of an individual. Studies have found that over time, the psychological well-being of at-risk women who test positive returns to baseline, and women at high risk who are tested and are found to be negative for the mutations have an improvement in their psychological state. However, at-risk women who decline testing were noted to have an increase in depression. Family dynamics play a role in each individual’s experience with BRCA testing. For women who test positive for BRCA mutations, choosing whether to have a prophylactic mastectomy and bilateral salpingo-oophorectomy are decisions that may affect self-image and psychological well-being. Multiple sources for psychological support are available for women who undergo the process of testing and decision-making about prophylactic treatment options. [ Psychiatr Ann . 2014; 44(7):329–333.]

Genetics, biomarkers, hereditary cancer syndrome diagnosis, heterogeneity and treatment: a review.

Molecular genetic pathways that drive the phenotypic and genotypic heterogeneity of hereditary colorectal cancer also can affect response to chemotherapy and chemoprevention. These mutations also can alter patients' response to therapy. Environmental differences can affect this highly complex conundrum. We will use Lynch syndrome as a model to explore this issue. However, to begin with, after more than a century of documentation, we must ask what is meant by the eponym "Lynch syndrome". Germline mutations may act as drivers of chemoprevention and chemotherapy and therein may act positively or conversely they may have a negative effect in terms of inhibiting the inactivation of cancer-causing germline mutations. A relatively new field of hereditary cancer therapeutics has significantly impacted cancer care, from the standpoint of the sensitivity or resistance to a particular form of chemotherapy and/or chemoprevention. The question for the diagnostician and therapist must always concern what is the best possible management approach for the patient, particularly when he or she harbors a cancer-causing germline mutation, which, in this case, causes Lynch syndrome. Continued molecular genetic research might yield a more tailored effective treatment for Lynch syndrome. The ultimate goal of such hereditary oncologic research is to better understand the mutation's therapeutic task, namely, its potential to benefit the patient in terms of its treatment goal, thereby fulfilling the essence of personalized medicine. However, this goal may be exceedingly complicated. For example, in the natural clinical and molecular genetic history of hereditary forms of cancer, there will be a predominance of early-onset cancers of multiple anatomic sites. In our Lynch syndrome model, these will be most commonly colorectal, endometrial, and ovarian cancer. Attention must initially be focused upon cancer's early age of onset coupled with the tendency to multiple primary cancers so that, in the case of CRC, colonoscopic screening must be initiated by age 20-25 years and repeated every other year until age 40 years and then annually thereafter. However, screening will be of limited efficacy in the gynecologic cancers (endometrial and ovarian) so that once the family is completed, particularly by age 35-40 years, careful attention must be given to the option of prophylactic hysterectomy and bilateral salpingo-oophorectomy. Given issues of tumor heterogeneity, selected Lynch syndrome families may show an excess of urologic cancers or cancers of the small bowel, and highly targeted screening should be given serious consideration for these as well as cancers of other anatomic sites in such high-risk, cancer-prone patients.

Pure natural orifice transluminal endoscopic surgery (NOTES) involving peroral endoscopic salpingo-oophorectomy (POESY)

ObjectiveNatural orifice transluminal endoscopic surgery (NOTES) is a surgical approach that uses natural orifices to gain access to areas of the body. In the present article, we describe the first transgastric pure NOTES salpingo-oophorectomy, which we call peroral endoscopic salpingo-oophorectomy (POESY). MethodsA woman with BRCA1 mutation presented for prophylactic bilateral salpingo-oophorectomy. We offered her the transgastric approach, having performed more than 25 transgastric appendectomies. After gastroscopic incision in the corpus wall, we advanced the gastroscope into the abdominal cavity. Salpingo-oophorectomy was performed with the help of an intrauterine manipulator and a transvaginally introduced 5-mm trocar. The posterior colpotomy was dilated and the specimens were extracted. The gastrotomy was closed with an over-the-scope clip, and the colpotomy with a running suture. ResultsThe gastroscope provided excellent optical control and good tissue preparation. Prophylactic bilateral salpingo-oophorectomy was performed successfully via POESY. The patient recovered quickly and was discharged on the third day, with an uneventful follow-up. ConclusionThe present case demonstrates the feasibility of transgastric access. The gastroscope provided excellent optical control and good tissue preparation. Therefore, we expect an increasing role of transgastric procedures for diseases in the pelvic region, particularly if new endoscopic platforms with better means of instrumentation and tissue management become available.

Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome

ObjectiveThe primary aim of this study was to determine the prevalence of occult gynecologic malignancy at the time of risk reducing surgery in patients with Lynch Syndrome. A secondary aim was to determine the prevalence of occult gynecologic malignancy at the time of surgery for non-prophylactic indications in patients with Lynch Syndrome. MethodsA retrospective review of an Inherited Colorectal Cancer Registry found 76 patients with Lynch syndrome (defined by a germline mutation in a DNA mismatch repair gene) or hereditary nonpolyposis colorectal cancer (HNPCC) (defined by Amsterdam criteria) who had undergone hysterectomy and/or salpingo-oophorectomy for a prophylactic or non-prophylactic indication. Indications for surgery and the prevalence of cancer at the time of each operation were reviewed. Results24 of 76 patients underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy for Lynch syndrome or HNPCC. In 9 of these patients, a benign indication for surgery was also noted. 4 of 24 patients (17%, 95% CI=5–38%) were noted to have cancer on final pathology. 20 of 76 patients (26%) undergoing operative management for any indication were noted to have occult malignancy on final pathology. ConclusionsPatients should be counseled about the risks of finding gynecologic cancer at the time of prophylactic or non-prophylactic surgery for Lynch syndrome and HNPCC, and the potential need for additional surgery.

Alternatives to risk-reducing surgery for ovarian cancer

BRCA1 and BRCA2 mutation carriers have an 18%–60% and 11%–27% lifetime risk of developing ovarian carcinoma, respectively. Prophylactic bilateral salpingo-oophorectomy reduces the risk of this malignancy by up to 96%. Gynecological screening programs with periodical trans-vaginal ultrasound and serum CA125 assay have been widely used in women at hereditary high risk of ovarian carcinoma, but clinical results have been conflicting. These surveillance protocols have often fallen short of expectations because of the advanced stage of ovarian carcinoma in the identified screened women. Several investigations have been addressed to the detection of additional tumor markers able to generate more reliable screening tools. The combined serum assay of leptin, prolactin, osteopontin, CA125, macrophage inhibiting factor and insulin-like growth factor-II appears to have a significant better diagnostic reliability compared with serum CA125 alone in discriminating healthy individuals from ovarian carcinoma patients, and therefore, it could have a role in the screening of women at high risk for this malignancy. As far as chemoprevention is concerned, oral contraceptives significantly reduce the ovarian carcinoma risk also in BRCA mutation carriers, whereas the efficacy of fenretinide is still under investigation.

Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines

J. Balmana1, F. Balaguer2, A. Cervantes3 & D. Arnold4, on behalf of the ESMO Guidelines Working Group* Department of Medical Oncology, Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona; Department of Gastroenterology, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona; Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain; Department of Medical Oncology, Tumor Biology Clinic, Albert Ludwigs University, Freiburg, Germany;