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Frailty in patients with ovarian cancer and the role of healthcare access, race, and ethnicity

ObjectiveOvarian cancer has poor 5-year survival, particularly among non-Hispanic (NH) Black patients. Efforts to identify patients at high-risk of functional limitations and frailty may improve outcomes. In this study, we examined how healthcare access (HCA) and race/ethnicity relate to frailty among patients with ovarian cancer. MethodsWe identified Hispanic, NH Black, and NH White patients diagnosed at ages ≥6 5 years with ovarian cancer between 2009 and 2015 using SEER-Medicare. Log-binomial regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between HCA and race/ethnicity with pre- or post-diagnosis frailty, adjusting for age and comorbidities. ResultsA total of 6041 patients with ovarian cancer were included, including 91.8% NH White, 6.6% NH Black, and 1.7% Hispanic. Pre-diagnosis, 14.7% of patients were defined as frail (NH White: 14.3%; NH Black: 17.9%; Hispanic: 20.8%). Post-diagnosis, frailty prevalence increased to 58.8% (NH White: 58.2%; NH Black: 65.2%; Hispanic: 70.2%). No statistically significant associations were observed between race/ethnicity and pre- or post-diagnosis frailty in fully adjusted models. After adjustment for patient characteristics and healthcare accessibility and availability, higher healthcare affordability was associated with a decreased prevalence of pre-diagnosis frailty (PR: 0.91, 95% CI: 0.8 5, 0.98). ConclusionsPatients with ovarian cancer have a high prevalence of frailty after diagnosis, particularly NH Black and Hispanic patients. Improving healthcare affordability may prevent or help manage frailty in Medicare patients, improve receipt of cancer treatment, and increase cancer survival.

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SVIL promotes ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions through the TGF-β/Smad pathway

ObjectiveOvarian cancer is the malignant tumor with the highest mortality rate in gynecology. We aimed to identify novel genes that promote ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions. MethodsWe screened SVIL as a hypoxia-associated target in ovarian cancer and explored the related molecular mechanisms. We assessed the effects of SVIL on ovarian cancer progression and metastasis in clinical samples and cellular hypoxia models. Further, we investigated the relevant pathways of SVIL and confirmed the effects of SVIL on ovarian cancer progression by using nude mouse in situ tumor models. ResultsWe found that SVIL was significantly highly expressed in the hypoxic environment of ovarian cancer, and SVIL expression correlated with patient prognosis.CCK8, Wound-healing assay, Transwell assay, Western Blot, and apoptosis assays revealed that knockdown of SVIL inhibited the activation of the TGFβ1/smad2/3 pathway, which attenuated the progression and epithelial-mesenchymal transition(EMT) of ovarian cancer and alleviated cisplatin resistance by increasing cisplatin-induced apoptosis. Furthermore, in a nude mouse ovarian cancer in situ model, we found that the knockdown of SVIL significantly inhibited tumor growth and metastasis. ConclusionSVIL highly expressed in the hypoxic microenvironment can increase ovarian cancer progression and cisplatin resistance by activating TGFβ1/smad2/3 pathway. Our study demonstrated that SVIL may be a novel target for the treatment of ovarian cancer.

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Body composition and peri- and postoperative complications in patients with gynaecological malignancies: A systematic review

BackgroundIn general abdominal surgery, the ratio of fat to muscle mass, or body composition measures, shows a stronger association with complications than body mass index. These studies include male and female patients. Women have a different body composition than men. Therefore, findings from general abdominal surgery cannot be extrapolated to women with cancer. The aim of this systematic review is to summarise the evidence on the association between body composition and peri- and postoperative complications in patients with gynaecological cancer. MethodsPubmed, Embase and the Cochrane Central databases were searched in June 2023. Studies were eligible if they included patients undergoing surgery for gynaecological cancer and reported on the association between body composition (muscle or fat mass) and surgical complications. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale. A best-evidence synthesis was used to summarise the level of evidence. ResultsFifteen studies were included that assessed muscle mass (n = 9) or fat mass (n = 6). We found strong evidence that there was no association between visceral fat and length of hospital stay. We found moderate evidence that a higher amount of good quality muscle was associated with a lower risk of postoperative complications. We found moderate evidence that there was no association between muscle or fat mass (i.e., muscle- or subcutaneous fat) and postoperative complications or fat mass and intraoperative complications. There was insufficient evidence for an association between visceral fat and intraoperative or postoperative complications, and for an association between muscle mass or -quality and length of hospital stay. There was high heterogeneity in the methods used to measure body composition, hampering meta-analyses. ConclusionThe association between body composition, particularly adipose tissue and muscle quality, and complications suggests that these measures may be of interest in determining postoperative risk in women undergoing surgery for gynaecological cancer.

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Serum miRNA improves the accuracy of a multivariate index assay for triage of an adnexal mass

ObjectiveTo determine whether a multimodal assay combining serum microRNA with protein biomarkers and metadata improves triage assessment of an adnexal mass. MethodsSerum samples from 468 training subjects (191 cancer cases and 277 benign adnexal mass controls or healthy controls) were analyzed for seven protein biomarkers and 180 miRNA. Circulating analyte data were combined with age and menopausal status (metadata) into a neural network model to classify samples as cases or controls. Forward regression with ten-fold cross-validation minimized the dimensionality of the model while maximizing linear separation between cases and controls. Model validation proceeded using both internal (44 cases and 56 controls) and external validation sets (51 cases and 59 controls). ResultsThe total study population comprised 678 subjects, including 286 cases and 392 controls. Overall, 290 (43%) of the subjects were premenopausal. A panel of 10 miRNA delivered optimal performance when combined with protein and metadata features. The combined model improved the Receiver Operator Characteristic Area Under the Curve (ROC AUC) on the internal (AUC = 0.9; 95% CI 0.81–0.95) and external validation sets (AUC = 0.95; 95% CI 0.90–0.98) compared to miRNA alone or proteins plus metadata (without miRNA). On external validation, the combined model offered 92% sensitivity at 80% specificity overall, with 80% and 100% sensitivity for early and late-stage cancers, respectively, including 78% sensitivity for early-stage, serous ovarian cancers and 82% sensitivity for early-stage, non-serous cancers. ConclusionsA multimodal assay combining miRNA with protein biomarkers, age, and menopausal status improves surgical triage of an adnexal mass.

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Investigating the timing and site of recurrence for ovarian clear cell carcinoma: Analysis of the JGOG/GCIG trial-JGOG 3017-A3

BackgroundThis study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery. MethodsYielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks. ResultsThe peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months. DiscussionThe incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important.

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Postoperative urinary retention by void trial methodology following radical hysterectomy for cervical cancer

ObjectivesRadical hysterectomy is the standard of care for management of early-stage cervical cancer and is associated with postoperative urinary retention. No clear consensus exists regarding optimal voiding trial methodology for mitigating postoperative urinary retention. Our objective was to evaluate the association between type of postoperative voiding trial and risk of urinary retention after radical hysterectomy for cervical cancer. MethodsWe conducted a retrospective analysis of patients undergoing radical hysterectomy for apparent early-stage cervical cancer (FIGO 2018 Stage IA2-IB2) between January 2014 and February 2023. We compared incidence of urinary retention and perioperative outcomes based on method of postoperative voiding trial (timed, autofill, or backfill). Multivariate logistic regression was used to determine association of type of void trial with absence of urinary retention within 30 days postoperatively. ResultsOf the 115 patients identified, 48 (41.8%) patients completed a timed void trial, 40 (34.7%) an autofill void trial, and 27 (23.5%) a backfill void trial. 44.3% of patients developed postoperative urinary retention with no differences based on void trial (p = 0.17). Urinary retention was more likely to resolve by 7 (p = 0.012) and 30 days (p = 0.01) for patients undergoing backfill voiding trials, compared to other trials. In multivariate models, backfill void trial was associated with absence of 30-day urinary retention, compared to other trials (aOR 15.1; 95% C.I. 1.5–154.9). ConclusionsRates of urinary retention following radical hysterectomy do not differ based on postoperative void trial methodology. A backfill void trial following radical hysterectomy may lead to increased rates of resolution of postoperative urinary retention.

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Efficacy and safety of minimally invasive surgery versus open laparotomy for epithelial ovarian cancer: A systematic review and meta-analysis

ObjectiveTo examine the efficacy and safety of minimally invasive surgery (MIS) and conventional abdominal surgery for epithelial ovarian cancer (EOC), stratified by treatment type. MethodsA systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Several academic databases, including PubMed/MEDLINE, Cochrane Database, and Ichushi were searched by the Japan Medical Library Association on November 11, 2023, using the keywords “epithelial ovarian cancer”, “minimally invasive surgery”, “laparoscopic”, and “robot-assisted”. Articles describing MIS treatment for EOC compared with conventional abdominal surgery were independently assessed by two authors. The primary outcomes were survival and perioperative adverse events. ResultsAfter screening 1114 studies, 35 articles were identified, including primary staging surgery (PSS) for early-stage EOC EOC (n = 20) and neoadjuvant chemotherapy following interval debulking surgery (NACT-IDS; n = 10) and upfront primary debulking surgery (PDS; n = 5) for advanced-stage EOC. These studies included 29,888 patients (7661 undergoing MIS and 22,227 undergoing abdominal surgery). Patients receiving MIS and abdominal surgery had similar overall survival (PSS: odds ratio [OR] 1.02, 95% confidence interval [CI] 0.75–1.37; NACT-IDS: OR 0.93, 95%CI 0.25–3.44 and PDS: OR 0.66, 95%CI 0.36–1.22, all P > 0.05). MIS showed perioperative complication rates comparable to those of abdominal surgery (intraoperative and postoperative, all treatment types P ≥ 0.05). However, the rate of lymph node dissection in early-stage EOC (PSS: OR 0.49, 95%CI0.26–0.91) and multivisceral resections in advanced-stage EOC (NACT-IDS: OR 0.27 95%CI 0.16–0.44 and PDS: OR 0.27, 95%CI 0.16–0.44) was lower in MIS than in abdominal surgery (all P < 0.05). ConclusionMIS did not negatively impact the survival and perioperative complications of patients with EOC compared to abdominal surgery. While MIS is a viable option, varied case selection and surgical procedures suggest potential bias, requiring further validation studies.

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Quality of life among borderline ovarian tumor survivors: A comparison with survivors of early-stage ovarian cancer and a cancer-free population: A cross-sectional population-based PROFILES study

ObjectiveThis study assessed the health-related quality of life (HRQo) of women surviving a borderline ovarian tumor (BOT) in comparison with early-stage ovarian cancer survivors treated surgically alone and with a matched cancer-free population. MethodsSurvivors of BOT and ovarian cancer were invited in two Dutch cross-sectional, population-based studies. Ovarian cancer survivors with tumor stage I who were treated surgically only were included. A random sample from the cancer-free population was matched on sex, age and education to the sample of BOT survivors. The EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 were completed by the cancer-free population and the BOT and ovarian cancer survivors in study 1 and 2. The Hospital Anxiety and Depression Scale (HADS) was only completed by the cancer-free population and the survivors of BOT and ovarian cancer in study 1. BOT survivors were compared to early-stage ovarian cancer survivors and the general population using linear regression analyses and effect sizes regarding clinical importance. Results83 BOT (42%), 88 early-stage ovarian cancer survivors (52%), and 82 women from the general population were included. In most HRQoL domains, BOT survivors were not significantly different from early-stage ovarian cancer survivors and the cancer-free population, except that BOT survivors reported significantly less insomnia than early-stage ovarian cancer survivors and more dyspnea than the cancer-free population (small clinical difference). ConclusionIn general, BOT survivors' HRQoL lies between the HRQoL of early-stage ovarian cancer survivors and of the cancer-free population, but clinical effect sizes between the groups were mostly only trivial.

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