Abstract:Residual fimbrial tissue remains on the ovary after salpingectomy in a significant proportion of cases and could impact the level of risk-reduction that is obtained.
“…99 This was confirmed more recently in a study where tubes and ovaries were removed separately during surgery and examined histologically as two separate specimens; residual fimbrial tissue was found on the ovarian surface in 16% of cases. 100 This suggests that salpingectomy may not prevent all cases even when the origins are tubal. It highlights the importance and need for well-designed prospective trials to define more precisely the level of benefit.…”
Section: Risk-reducing Salpingectomy and Delayed Oophorectomy In Womementioning
There has been much progress in ovarian cancer screening and prevention in recent years. Improved tools that combine genetic and epidemiologic factors to predict an individual's ovarian cancer risk are set to become available for tailoring preventive and screening approaches. The increasing evidence on tubal origins of a proportion of ovarian cancer has paved the way to use of opportunistic bilateral salpingectomy at tubal ligation and hysterectomy in the general population. Clinical trials are in progress to estimate the long-term effects on endocrine function. In women at high risk, risk reducing salpingo-oophorectomy remains the standard of care with the current focus on management of resulting noncancer outcomes, especially sexual dysfunction in younger women. This has led to evaluation of early bilateral salpingectomy and delayed oophorectomy in this population. Meanwhile, modeling suggests that BRCA mutation carriers should consider using the oral contraceptive pill for chemoprevention. In the general population, the largest ovarian cancer screening trial to date, the UK Collaborative Trial of Ovarian Cancer Screening reported a stage shift with annual multimodal screening using the longitudinal CA 125 Risk of Ovarian Cancer Algorithm but not with annual transvaginal ultrasound screening. There was no definitive mortality reduction with either screening strategy compared with no screening. Further follow-up until December 2018 in now underway. Stage shift and higher rates of optimal cytoreduction were also reported during 3- to 4-monthly multimodal screening in the United Kingdom and U.S. high-risk screening trials. Although all agree that there is not yet evidence to support general population screening, recommendations for high-risk screening vary between countries. A key finding from the screening trials has been the better performance of longitudinal algorithms compared with a single cutoff for CA 125. A major focus of ovarian cancer biomarker discovery work has been tumor DNA markers in both plasma and novel specimens such as cervical cytology samples.
“…99 This was confirmed more recently in a study where tubes and ovaries were removed separately during surgery and examined histologically as two separate specimens; residual fimbrial tissue was found on the ovarian surface in 16% of cases. 100 This suggests that salpingectomy may not prevent all cases even when the origins are tubal. It highlights the importance and need for well-designed prospective trials to define more precisely the level of benefit.…”
Section: Risk-reducing Salpingectomy and Delayed Oophorectomy In Womementioning
There has been much progress in ovarian cancer screening and prevention in recent years. Improved tools that combine genetic and epidemiologic factors to predict an individual's ovarian cancer risk are set to become available for tailoring preventive and screening approaches. The increasing evidence on tubal origins of a proportion of ovarian cancer has paved the way to use of opportunistic bilateral salpingectomy at tubal ligation and hysterectomy in the general population. Clinical trials are in progress to estimate the long-term effects on endocrine function. In women at high risk, risk reducing salpingo-oophorectomy remains the standard of care with the current focus on management of resulting noncancer outcomes, especially sexual dysfunction in younger women. This has led to evaluation of early bilateral salpingectomy and delayed oophorectomy in this population. Meanwhile, modeling suggests that BRCA mutation carriers should consider using the oral contraceptive pill for chemoprevention. In the general population, the largest ovarian cancer screening trial to date, the UK Collaborative Trial of Ovarian Cancer Screening reported a stage shift with annual multimodal screening using the longitudinal CA 125 Risk of Ovarian Cancer Algorithm but not with annual transvaginal ultrasound screening. There was no definitive mortality reduction with either screening strategy compared with no screening. Further follow-up until December 2018 in now underway. Stage shift and higher rates of optimal cytoreduction were also reported during 3- to 4-monthly multimodal screening in the United Kingdom and U.S. high-risk screening trials. Although all agree that there is not yet evidence to support general population screening, recommendations for high-risk screening vary between countries. A key finding from the screening trials has been the better performance of longitudinal algorithms compared with a single cutoff for CA 125. A major focus of ovarian cancer biomarker discovery work has been tumor DNA markers in both plasma and novel specimens such as cervical cytology samples.
“…The degree of risk reduction obtained may be compromised by the presence of microscopic residual fimbrial tissue that persists on the ovarian surface in up to 16% of women after salpingectomy. 51 The degree of risk reduction for salpingectomy alone is currently unknown and cannot, at present, be recommended as surgical prophylaxis in women at high risk who are above the target age for definitive risk-reducing surgery.…”
varian cancer has the highest mortality of all female reproductive cancers, largely owing to the absence of early symptoms and lack of effective screening, resulting in diagnosis at an advanced stage. Hereditary breast and ovarian cancers include specifically identified genetic variants that greatly increase the lifetime risk of breast and ovarian cancer. BRCA1 and BRCA2 (BRCA 1/2) pathogenic germline variants account for most hereditary breast and ovarian cancer syndromes. Given the substantial lifetime risk and high mortality of ovarian cancer in women with BRCA1/2 pathogenic variants, risk reduction is a priority, and a risk-reducing salpingo-oophorectomy can decrease the lifetime risk of ovarian cancer by about 80%. 1 Gynecologic management associated with reducing the risk of ovarian cancer in this population includes medical and surgical prophylaxis, important contraception and fertility considerations, and the management of iatrogenic premature menopause, as detailed in the recently published Society of Obstetrician and Gynaecologists of Canada (SOGC) clinical practice guideline. 1 We discuss the gynecologic management of women with a BRCA1/2 pathogenic variant who are at high risk of ovarian cancer, based on evidence outlined in Box 1. These women with a BRCA1/2 pathogenic variant are also at substantially increased risk of breast cancer and require specific management, 5,6 but this is outside the scope of this review and will not be covered. What are BRCA 1/2 pathogenic variants? Pathogenic germline variants in BRCA1/2 substantially increase a woman's lifetime risk of breast and ovarian cancer, in addition to other cancers such as prostate and pancreatic cancer and melanoma. BRCA1/2 genes code for tumour suppressor proteins that function to maintain DNA integrity. BRCA1/2 pathogenic variants are inherited in an autosomal dominant fashion, and the prevalence in the general population ranges from 1/400 to 1/800, but can be as high as 1/40 in women of Ashkenazi Jewish descent. 7,8 Women with BRCA1 and BRCA2 pathogenic variants have a cumulative lifetime risk of ovarian cancer of 39%-44% and 11%-17%, respectively, 9,10 and this is greatly increased above the 1.4% lifetime risk of ovarian cancer in the average Canadian woman. 11 The risk of ovarian cancer begins to rise above the population risk after age 40 years in women with BRCA1, and after age 50 in women with BRCA2; this finding forms the basis for the approach to risk reduction outlined below. Given the histopathologic similarity between high-grade serous
“…For instance, the close proximity of tubal mucosa to ovarian surface epithelium allows FTSECs to form adhesions with the mesothelium and grow directly on the surface of the ovary [46]. Recent evidence [112] suggests that individuals who underwent salpingectomy (removal of Fallopian tubes), for reasons other than ovarian cancer, possessed microscopic tubal tissue on the surface of the ovary, indicating the possibility that fallopian tube mucosa naturally comes in contact with the ovarian surface. Thus, it is conceivable to think that malignant outgrowths adhere to ovarian mesothelium before release.…”
Epithelial ovarian cancer (EOC) comprises multiple disease states representing a variety of distinct tumors that, irrespective of tissue of origin, genetic aberrations and pathological features, share common patterns of dissemination to the peritoneal cavity. EOC peritoneal dissemination is a stepwise process that includes the formation of malignant outgrowths that detach and establish widespread peritoneal metastases through adhesion to serosal membranes. The cell biology associated with outgrowth formation, detachment, and de novo adhesion is at the nexus of diverse genetic backgrounds that characterize the disease. Development of treatment for metastatic disease will require detailed characterization of cellular processes involved in each step of EOC peritoneal dissemination. This article offers a review of the literature that relates to the current stage of knowledge about distinct steps of EOC peritoneal dissemination, with emphasis on the cell biology aspects of the process.
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