Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.
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ABSTRACT: Purpose
To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.Methods
The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.Results
Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively.Conclusion
Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.
SUBMITTER: Dominguez-Valentin M
PROVIDER: S-EPMC8026395 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.
Dominguez-Valentin Mev M Crosbie Emma J EJ Engel Christoph C Aretz Stefan S Macrae Finlay F Winship Ingrid I Capella Gabriel G Thomas Huw H Nakken Sigve S Hovig Eivind E Nielsen Maartje M Sijmons Rolf H RH Bertario Lucio L Bonanni Bernardo B Tibiletti Maria Grazia MG Cavestro Giulia Martina GM Mints Miriam M Gluck Nathan N Katz Lior L Heinimann Karl K Vaccaro Carlos A CA Green Kate K Lalloo Fiona F Hill James J Schmiegel Wolff W Vangala Deepak D Perne Claudia C Strauß Hans-Georg HG Tecklenburg Johanna J Holinski-Feder Elke E Steinke-Lange Verena V Mecklin Jukka-Pekka JP Plazzer John-Paul JP Pineda Marta M Navarro Matilde M Vidal Joan Brunet JB Kariv Revital R Rosner Guy G Piñero Tamara Alejandra TA Gonzalez María Laura ML Kalfayan Pablo P Ryan Neil N Ten Broeke Sanne W SW Jenkins Mark A MA Sunde Lone L Bernstein Inge I Burn John J Greenblatt Marc M de Vos Tot Nederveen Cappel Wouter H WH Della Valle Adriana A Lopez-Koestner Francisco F Alvarez Karin K Büttner Reinhard R Görgens Heike H Morak Monika M Holzapfel Stefanie S Hüneburg Robert R von Knebel Doeberitz Magnus M Loeffler Markus M Rahner Nils N Weitz Jürgen J Pylvänäinen Kirsi K Renkonen-Sinisalo Laura L Lepistö Anna A Auranen Annika A Hopper John L JL Win Aung Ko AK Haile Robert W RW Lindor Noralane M NM Gallinger Steven S Le Marchand Loïc L Newcomb Polly A PA Figueiredo Jane C JC Thibodeau Stephen N SN Therkildsen Christina C Okkels Henrik H Ketabi Zohreh Z Denton Oliver G OG Rødland Einar Andreas EA Vasen Hans H Neffa Florencia F Esperon Patricia P Tjandra Douglas D Möslein Gabriela G Sampson Julian R JR Evans D Gareth DG Seppälä Toni T TT Møller Pål P
Genetics in medicine : official journal of the American College of Medical Genetics 20201201 4
<h4>Purpose</h4>To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.<h4>Methods</h4>The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.<h4>Results</h4>Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path ...[more]
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Project description:PurposeThis study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.MethodsThe Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.ResultsOverall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.ConclusionUptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.
| S-EPMC8916840 | biostudies-literature
Project description:IntroductionLittle is known about hysterectomy and bilateral salpingo-oophorectomy (BSO), which are associated with both health risks and benefits, among women Veterans.Purpose of the studyTo compare the prevalence of hysterectomy with or without BSO, and early hysterectomy, between postmenopausal Veterans and non-Veterans.Design and methodsWe used baseline data from the Women's Health Initiative Clinical Trial and Observational Study. Multinomial logistic regression models examined differences in the prevalence of hysterectomy (neither hysterectomy nor BSO, hysterectomy without BSO, and hysterectomy with BSO) between Veterans and non-Veterans. Generalized linear models were used to determine whether early hysterectomy (before age 40) differed between Veterans and non-Veterans. Analyses were stratified by birth cohort (<65, ≥65 years at enrollment).ResultsThe unadjusted prevalence of hysterectomy without BSO was similar among Veterans and non-Veterans in both birth cohorts (<65: 22% vs 21%; ≥65: 22% vs 21%). The unadjusted prevalence of hysterectomy with BSO was equivalent among Veterans and non-Veterans in the >65 cohort (21%), but higher among Veterans in the <65 cohort (22% vs 19%). In adjusted analyses, although no differences were observed in the >65 cohort, Veterans in the <65 cohort had higher odds of hysterectomy without BSO (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03, 1.36) and with BSO (OR 1.26, 95% CI 1.10, 1.45), as well as elevated risk of early hysterectomy (relative risk 1.32, 95% CI 1.19, 1.47), compared with non-Veterans.ImplicationsAging women Veterans may have higher prevalence of hysterectomy and BSO than non-Veterans. This information contributes to understanding the health needs and risks of women Veterans and can inform clinical practice and policy for this population.
| S-EPMC5881615 | biostudies-literature
Project description:ImportanceThe link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.ObjectiveTo determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.Design, setting, and participantsThis multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression.Main outcomes and measuresIncidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database.ResultsAmong the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors.Conclusions and relevanceAlthough the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.
| S-EPMC5594920 | biostudies-literature
Project description:Congenital nephrogenic diabetes insipidus (NDI) primarily arises from an X-linked recessive inheritance caused by mutations in the AVPR2 gene, which is responsible for approximately 90% of cases. This condition has an incidence rate of 4-8 per million male live births, with females being much less frequently affected. Symptoms typically manifest shortly after birth, predominantly in males. The key clinical features of NDI include excessive urination (polyuria), compensatory excessive thirst (polydipsia), cognitive impairment, consistently low urine specific gravity, dehydration, and imbalances in electrolyte levels. This case study highlights an unusual occurrence of NDI in a 50-year-old Chinese woman attributed to a mutation in the AVPR2 gene. For more than a year, she had been suffering from excessive urination and severe thirst. The patient, who had undergone surgery for cervical cancer, developed polyuria and hypernatremia postoperatively. Initial laboratory analyses revealed normal blood sodium and chloride levels but reduced urine osmolality and specific gravity. Imaging assessments revealed no irregularities. To validate the diagnosis of NDI, she participated in a water deprivation and vasopressin test. Subsequent genetic tests revealed a thymine (T) to adenine (A) mutation, leading to a missense mutation in the AVPR2 gene. As part of her treatment, she was placed on a low-sodium diet and prescribed oral hydrochlorothiazide and indomethacin for 1 month, resulting in a marked improvement in her symptoms. To the best of our knowledge, this is the first documented case of NDI diagnosed postoperatively in an older female patient with AVPR2 heterozygosity. This case highlights an unusual instance of an X-linked recessive clinical presentation of NDI in an elderly female patient. This study also underscores the importance of conducting water deprivation, vasopressin tests, and genetic testing in establishing the underlying cause for individuals diagnosed with NDI.
| S-EPMC11518838 | biostudies-literature
Project description:ObjectiveTo estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions.MethodsAll patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000 person-years were calculated.ResultsOf 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).ConclusionsThe removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation.Level of evidenceII.
| S-EPMC4624417 | biostudies-literature
Project description:IntroductionRisk-reducing salpingo-oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer. Despite the solid recommendation, women frequently refuse surgery and uptake rates reported in the literature are diverse. This study analyses the uptake rate of RRSO in BRCA 1/2 PV-carriers referred to a specialised referral centre for first counselling and investigate personal factors linked to the decision.MethodsThis is a single-centre prospective study of BRCA1/2 PV-carriers referred for the first counselling to IRCCS Fondazione San Gerardo de' Tintori (Monza, Italy) between January 2010 and May 2023. Depending on individual characteristics, women were either proposed RRSO or surveillance, consisting of transvaginal ultrasound and CA125 measurement twice per year according to Regional guidelines. Women within the centre have access to a clinical psychologist, a nutritional consult and treatment of menopausal atrophy with diode vaginal laser. The primary endpoint of the study was the uptake rate of RRSO. The secondary objective was to evaluate the main reasons for refusing surgery.ResultsAmong the 287 women included, surgery was proposed to 205 women either at first counselling or during surveillance and was accepted by 197, with an uptake rate of 96.1%. 17.25% of women met the psychologist before or after surgery. The main reasons for refusing RRSO were fear of iatrogenic menopause and childbearing desire.ConclusionThis study shows a high uptake rate of RRSO in BRCA PV-carriers. We believe that the presence of a dedicated outpatient clinic with a multidisciplinary team contributes decisively to our results. Gynaecologic surveillance, as though not beneficial in terms of oncological prevention, may play a significant role in encouraging women with BRCA PV to opt for risk-reducing surgery.
| S-EPMC11612664 | biostudies-literature
Project description:Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.
| S-EPMC8932494 | biostudies-literature
Project description:Background: Colpectomy entails the surgical removal of the vaginal epithelium. It may be performed in trans-masculine individuals as gender-affirming surgery. Vaginal colpectomy is a complex procedure with potentially severe complications. As alternative, robotic-assisted laparoscopic colpectomy combined with robotic-assisted laparoscopic hysterectomy and possible bilateral salpingo-oophorectomy (RAC+) can be performed. Aim: To compare surgical outcomes of robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy with a vaginal colpectomy after previous hysterectomy in trans masculine patients. Methods: A single-center retrospective cohort study included 310 transgender men who underwent either robotic-assisted colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy (RAC+) (n = 140) or vaginal colpectomy (n = 170) between January 2006 and December 2019. Surgical details and clinical outcomes were collected from all patients. Results: The median intra-operative blood loss was 100 mL (50-200) in RAC + and 300 mL (200-450) in vaginal colpectomy (p < 0.01). The median duration of hospital stay was 2 days (1-2) in the RAC + group and 3 days (2-4) in the vaginal group (p < 0.01). In the RAC + group 63 (45%) peri-operative complications were reported, compared to 93 (54.7%) in the vaginal group [OR 0.7 (0.4-1.1)]. The main difference was found in intra-operative complications (RAC+ 0.7% vs. vaginal 10.6%). Furthermore, the total number of complications graded 3a and higher was significantly lower in the RAC + group [OR 0.3 (0.2-0.7)]. Conclusion: Although RAC + entailed a more extensive procedure, compared to vaginal colpectomy, RAC + had a lower risk of severe peri-operative complications, requiring re-intervention; intra-operative blood loss was lower and hospital stay shorter. Both routes of colpectomy are complex procedures with potentially severe complications. Future studies are needed to study whether robot-colpectomy could be a safe alternative to vaginal colpectomy in patients with a previous hysterectomy.
| S-EPMC11500588 | biostudies-literature
Project description:ObjectivesThe vaginal surgical approach has not become the standard of care, despite its advantages. The Hominis™ Surgical System is a humanoid shaped robot-assisted system that was designed specifically for robotic vaginal natural orifice transluminal endoscopic surgery (RvNOTES). We aimed to present our experience with the first RvNOTES bilateral salpingo-oophorectomy (BSO) performed by the Hominis system.Study designA two-center prospective study of BSO by RvNOTES in women with nonmalignant indications conducted between August and December 2018. Women older than 18 years were offered to participate. Exclusion criteria included a history of abdominal malignancy, pelvic or abdominal irradiation, Crohn's disease, pelvic inflammatory disease, severe infections in the lower abdomen, active diverticulitis, deep infiltrating recto-vaginal endometriosis, and an active vaginal infection. The primary outcome of the study was the rate of conversion to open or laparoscopic approaches. Secondary outcomes included intra- and postoperative adverse events, operative time, estimated blood loss, length of hospital stay, and 6-week follow-up assessment.ResultsEight women aged 50-70 years with BMI of 19-30 kg/m2 were recruited. All the procedures were completed successfully without conversions to open surgery. No intraoperative complications were observed. Median blood loss was 10 mL (range: 10-50). The median duration of the procedure was 45 min (range: 38-91), and decreased over the study period. Surgeons' usability assessment was very favorable, with a median of 5 on a 1-5 scale. The median visual analog scale (VAS) score was 1 (range: 1-3).ConclusionsThis is the first documentation of a surgery performed via the vagina using robotic instrumentation developed for this purpose. The disruptive technology of RvNOTES, with its fast learning curve, will make gynecological surgeries accessible to more women.
| S-EPMC7379144 | biostudies-literature
Project description:IntroductionWomen after risk-reducing salpingo-oophorectomy (RRSO) can have impaired sexual functioning, but whether there is an association between hormone levels and sexual functioning is unclear.AimTo determine whether hormone levels are associated with sexual functioning in women after RRSO.MethodsThis is a retrospective cohort study of 198 sexually active and 91 inactive women after RRSO. Participants completed the Sexual Activity Questionnaire, questionnaires concerning hormone replacement therapy (HRT), quality of life, care from partner, body image, and comorbidity and provided blood samples. Associations between sexual functioning scores and covariates were examined by linear regression. Variables associated with sexual activity were examined by logistic regression.Main outcome measuresAssociations with sexual pleasure and sexual discomfort scores were expressed by multivariable regression coefficients and associations with sexual activity were expressed by odds ratios.ResultsNone of the hormone levels were associated with sexual pleasure in contrast to age (P = .032), current use of systemic HRT (P = .002), and more care form partner (P < .001). Increased free androgen index (P = .016), more care from partner (P = .017), systemic HRT (P = .002), and no history of cardiovascular disease (P = .001) were associated with less sexual discomfort. The odds ratio of being sexually active increased with younger age, no breast cancer, better quality of life, and more care from partner.ConclusionsOur results indicate that other factors than hormone levels are important for sexual functioning, although systemic HRT can have a positive impact on sexual functioning in women who have undergone RRSO. Testosterone therapy could improve women's sexual functioning after RRSO; however, the inverse association between free androgen levels and sexual discomfort should be addressed in future studies. Johansen N, Liavaag AH, Mørkird L, Michelsen TM. Hormone Levels and Sexual Functioning After Risk-Reducing Salpingo-Oophorectomy. Sex Med 2018;6:143-153.
| S-EPMC5960032 | biostudies-literature