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Introduction: Opportunistic salpingectomy during benign hysterectomy with ovarian preservation has become a preventive approach to epithelial ovarian cancer, particularly high-grade serous carcinoma, given evidence that it originates in the Fallopian tubes. However, the long-term impact of the procedure on ovarian function remains unknown. This study assessed whether opportunistic salpingectomy at benign hysterectomy affects ovarian function compared with no salpingectomy 1 year after surgery.

Material and Methods: This is a noninferiority substudy of the national register-based randomized controlled trial HOPPSA (Hysterectomy and OPPortunistic SAlpingectomy), registered at clinicaltrials.gov (NCT03045965) on 8 February 2017. Women under 55 years planned for a benign hysterectomy at the Sahlgrenska University Hospital were randomized to hysterectomy with opportunistic salpingectomy or hysterectomy-only. Blood samples were collected preoperatively and 1 year postoperatively and analyzed for anti-Müllerian hormone (AMH) by Access2 immunoassay. The primary outcome was absolute change in AMH over time in the per-protocol population. Secondary outcomes were the relative change in AMH and level of AMH 1 year after surgery. The difference between groups was estimated by analysis of covariance, adjusted for baseline AMH, age groups, operative route, and time from surgery to second sampling. Multiple imputation was applied on missing samples. The noninferiority margin was set to 0.125 μg/L.

Results: Between 16 August 2018 and 6 September 2023, 89 women were randomized to hysterectomy with opportunistic salpingectomy (n = 46) or hysterectomy-only (n = 43). After exclusions due to prior ovarian surgery or not receiving the allocated surgery, 37 women were analyzed in each group. Mean age was 45.1 and 46.3 years in respective groups and mean body mass index was 29.5 and 27.2 kg/m2. Baseline characteristics did not differ between the groups. Both groups had reduced AMH levels 1 year postoperatively. The adjusted mean difference in the reduction was −0.03 μg/L (95% CI −0.23 to 0.18), with 0.18 exceeding the predefined noninferiority limit.

Conclusions: Noninferiority was not demonstrated for opportunistic salpingectomy at hysterectomy compared with hysterectomy-only regarding ovarian function assessed by AMH. Absolute reduction in AMH levels appeared to be similar in both groups, with an unexpectedly large variability in AMH reduction suggesting a more pronounced decline in some individuals.

Background: Nanoparticle immunoassays for CA125 and CA15-3 glycovariants are promising tools for epithelial ovarian cancer (EOC) and borderline ovarian tumor (BOT) early detection.

Method: This retrospective population-based study utilized prospective (< 3 years) plasma samples from 110 cases and 440 controls. Sialyl-Thomsen-nouveau (STn) antibody and macrophage galactose-type lectin (MGL) to detect cancer antigen 125 (CA125) and 15 − 3 (CA15-3) glycoforms were evaluated, using CA125, CA15-3, and HE4 enzyme immunoassay (EIA) references. The area under the receiver operating characteristic curve (AUC), partial AUC (pAUC) at specificities 0.9–1.0, and sensitivity (SN) at 0.98 specificity (SP) for detecting EOC/BOT were calculated.

Results: The single marker with the highest point estimate for pAUC and SN at 98% SP was CA125EIA (pAUC 0.71 (0.66, 0.76), SN at 98% SP 0.29 (0.17–0.42 combinations)). The CA15-3STn + CA125EIA and CA125EIA + HE4EIA improved the detection rate point estimates and provided the highest pAUC values (CA125EIA + CA15-3STn: 0.75 (0.70–0.80); CA125EIA + HE4EIA: 0.71 (0.66–0.77)). For 0–<1, 1–<2 and 2–<3 years lag time, CA125EIA and the CA125 glycovariants provided similar pAUC and SN at 98% SP, with largely overlapping confidence intervals.

Conclusion: This case-control study, which used plasma samples collected up to three years before diagnosis of EOC or BOT, did not provide evidence of a higher discriminatory capacity of the glycovariant biomarkers compared with the clinically established biomarker CA125EIA in asymptomatic women. Increased plasma volumes and larger cohorts are suggested in future studies.

Importance Long-term follow-up studies regarding the safety of risk-reducing mastectomy (RRM) in terms of cancer risk and surgical complications among women with germline pathogenic variants (gPVs) in BRCA1 or BRCA2 (BRCA1/2) are scarce.

Objective To analyze cancer risk and surgical complications after RRM.

Design, Setting, and Participants This nationwide cohort study investigated 1208 Swedish women with a confirmed gPV in BRCA1/2 without previous breast cancer identified through the Swedish Cancer Genetic Units between March 31, 1994, and January 2, 2019. Data were extracted from the National Patient Care Register, the Cancer Register, and the Cause of Death Register. Women were followed up from the date of RRM (RRM group) or genetic testing (no RRM group) until breast cancer diagnosis, death, emigration, or end of follow-up (December 31, 2023).

Main Outcomes and Measures Breast cancer incidence was calculated per 10 000 person-years, with women undergoing RRM contributing person-years to the no RRM group until RRM, and women with occult breast cancer contributing breast cancer cases to the no RRM group.

Results In the RRM group (507 women; median age at RRM, 39.7 years [range, 19.6-72.1 years]), 1 woman developed breast cancer, corresponding to a breast cancer incidence of 2 cases per 10 000 person-years. In the no RRM group (701 women; median age at genetic testing, 50.6 years [range, 4.3-93.6 years]), 112 women developed breast cancer, corresponding to a breast cancer incidence of 162 cases per 10 000 person-years. At RRM, 17 of 507 women (3.4%) received a diagnosis of occult breast cancer. In the RRM group, 296 of 507 women (58.4%) underwent simple mastectomy, 143 of 507 (28.2%) underwent nipple-sparing mastectomy, and 68 of 507 (13.4%) underwent skin-sparing mastectomy. Most women (382 of 507 [75.3%]) underwent implant-based breast reconstruction, with only 73 of 507 (14.4%) undergoing autologous tissue reconstruction with or without implants. Early major surgical postoperative complications associated with reoperation occurred in 19 of 507 women (3.7%).

Conclusions and Relevance In this cohort study of 1208 women with a gPV in BRCA1/2, the risk of developing breast cancer or early major surgical complications after RRM was very low. The low occurrence of primary breast cancer precluded meaningful statistical comparisons between different RRM techniques.

Importance Long-term follow-up studies regarding the safety of risk-reducing mastectomy (RRM) in terms of cancer risk and surgical complications among women with germline pathogenic variants (gPVs) in BRCA1 or BRCA2 (BRCA1/2) are scarce. Objective To analyze cancer risk and surgical complications after RRM. Design, Setting, and Participants This nationwide cohort study investigated 1208 Swedish women with a confirmed gPV in BRCA1/2 without previous breast cancer identified through the Swedish Cancer Genetic Units between March 31, 1994, and January 2, 2019. Data were extracted from the National Patient Care Register, the Cancer Register, and the Cause of Death Register. Women were followed up from the date of RRM (RRM group) or genetic testing (no RRM group) until breast cancer diagnosis, death, emigration, or end of follow-up (December 31, 2023). Main Outcomes and Measures Breast cancer incidence was calculated per 10 000 person-years, with women undergoing RRM contributing person-years to the no RRM group until RRM, and women with occult breast cancer contributing breast cancer cases to the no RRM group. Results In the RRM group (507 women; median age at RRM, 39.7 years [range, 19.6-72.1 years]), 1 woman developed breast cancer, corresponding to a breast cancer incidence of 2 cases per 10 000 person-years. In the no RRM group (701 women; median age at genetic testing, 50.6 years [range, 4.3-93.6 years]), 112 women developed breast cancer, corresponding to a breast cancer incidence of 162 cases per 10 000 person-years. At RRM, 17 of 507 women (3.4%) received a diagnosis of occult breast cancer. In the RRM group, 296 of 507 women (58.4%) underwent simple mastectomy, 143 of 507 (28.2%) underwent nipple-sparing mastectomy, and 68 of 507 (13.4%) underwent skin-sparing mastectomy. Most women (382 of 507 [75.3%]) underwent implant-based breast reconstruction, with only 73 of 507 (14.4%) undergoing autologous tissue reconstruction with or without implants. Early major surgical postoperative complications associated with reoperation occurred in 19 of 507 women (3.7%). Conclusions and Relevance In this cohort study of 1208 women with a gPV in BRCA1/2, the risk of developing breast cancer or early major surgical complications after RRM was very low. The low occurrence of primary breast cancer precluded meaningful statistical comparisons between different RRM techniques.

Importance: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking.

Objective: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements.

Design, Setting, and Participants: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025).

Main Outcomes and Measures: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1 - O/E).

Results: Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size.

Conclusions and Relevance: In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness.

Objective: To evaluate diagnostic accuracy of novel nanoparticle immunoassays across different histotypes of tubo-ovarian carcinoma (TOC) at diagnosis.

Method: This multicenter observational study consisted of consecutive patients (n = 1,312) having surgery due to suspected ovarian pathology. Serum were analyzed with Sialyl-Thomsen-nouveau (STn) antibody and Macrophage-Galactose-Lectin (MGL) for the detection of cancer antigen 125 (CA125) and 15-3 (CA15-3) glycoforms using CA125 enzyme immunoassay (EIA), CA15-3EIA and HE4EIA as references. Receiver operating characteristics (ROC) were applied and sensitivity at 75 % and 98 % specificity were calculated across histotypes.

Result: TOC was present in 596 patients and 716 had benign disease. CA125STn showed higher sensitivity at 98 % specificity compared with CA125EIA for high grade serous ovarian carcinoma (HGSC) (0.85 vs 0.62, p < 0.001), HGSC early-stage (0.66 vs 0.24, p = 0.003), and HGSC late-stage (0.90 vs 0.69, p < 0.001). CA15-3STn showed higher sensitivity at 98 % specificity compared to CA125EIA for mucinous ovarian carcinoma (0.50 vs 0.16, p = 0.038). No improvements were found for low grade serous carcinoma (LGSC), endometrioid and clear cell histotypes. The best performing combined biomarker test was CA125STn + HE4EIA with higher sensitivity at 98 % specificity for HGSC (0.93 vs 0.86, p < 0.001) and HGSC late-stage (0.97 vs 0.91p < 0.001) compared with CA125EIA + HE4EIA.

Conclusion: The STn glycovariants of CA125 and CA15-3 have improved sensitivity at high specificity for high grade serous and mucinous ovarian carcinoma and often perform better than the commonly used biomarker CA125EIA.

The resemblance between fallopian tube cells and serous borderline ovarian tumors (BOTs) suggests a potential origin link, with salpingitis proposed as a contributing factor in the pathogenesis of BOT. This study aimed to explore the potential association between pelvic inflammatory disease (PID) and the risk of developing BOT. A national population-based case–control study in Sweden included women with BOT between 1999 and 2020 and 10 matched controls. Data from nationwide registers were analyzed using conditional logistic regression, adjusting for age, residential district, educational level and parity. Among 4782 cases and 45,167 controls, 2.0% of cases and 1.3% of controls had a history of PID. Previous PID was associated with an increased risk of BOT overall (aOR, 1.48; 95% CI, 1.19–1.85). Significant association was observed with serous tumors (aOR, 1.76; 95% CI, 1.36–2.29), while not with mucinous tumors (aOR, 0.95; 95% CI, 0.60–1.49). A dose–response relationship between number of PID episodes and serous BOT risk was noted (Ptrend <.001). This study demonstrates that PID is associated with increased risk of serous BOT, with a dose response relationship. The study highlights the potential serious implications of upper reproductive tract infections and inflammation. This underscores the need for further investigation of biological mechanisms and possible impact of PID on serous BOT development.

Introduction: The evidence on complication rates after gynecological surgery is based on multiple types of studies, and the level of evidence is generally low. We aimed to validate the registration of complications in the Swedish National Quality Register of Gynecological Surgery - GynOp, by cross-linkage to multiple national registers. 

Material and methods: A national register-based study using prospectively collected data was conducted, including women who had surgery of the uterus or adnexa for benign indications from January 1, 2017, to December 31, 2020. In Sweden, complications after gynecological surgery are registered in GynOp, and if the complication has rendered any interaction with healthcare, also in national health registers. The GynOp register, the National Patient Register, the Prescribed Drugs Register and the Cause of Death Register were cross-linked. Complications in GynOp and complications according to ICD10 were analyzed, as well as cause of death if occurring within three months of surgery and prescription of antibiotics ≤30 days. Comparisons between the registries were descriptive. 

Results: During the study period 32 537 surgeries were performed, whereof 26 214 (80.6%) minimally invasive. Complications were reported in GynOp for 569 women (1.7%) at surgery, 1045 (3.2%) while admitted, and 3868 (13.7%) from discharge to three months after surgery. In comparison, according to the Patient Register 2254 women (6.9%) had postoperative complications within three months of discharge (difference of 6.8 percentage points (95% confidence interval 7.2, 6.2)). Furthermore, 4117 individuals (12.7%) had a prescription of antibiotics ≤30 days which could indicate a postoperative infection. The rates of hemorrhage, wound dehiscence and thrombosis were comparable between GynOp and the Patient Register while diagnoses not leading to contact with specialized care had higher rates in the quality register. The coverage of complications was 79.1% in GynOp and 46.1% in the Patient Register, using the total number of complications from both registers as the denominator. 

Conclusion: A higher frequency of complications is captured in GynOp than in the National Patient Register. Patient reported outcomes assessed by a physician are beneficial in identifying complications indicating the importance of structured pre-defined follow-up over a set period.