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Abstract Background To evaluate the impact of intraoperative hypotension and hemodynamic instability on survival outcomes in patients with high-grade serous ovarian carcinoma (HGSOC). Methods We retrospectively identified patients with HGSOC, who underwent primary or interval debulking surgery between August 2013 and December 2019. We collected anesthesia-related variables, including the arterial blood pressure measurements (at 1-min intervals) during the surgery of patients. The cumulative duration of mean arterial blood pressure (MAP) readings under 65 mmHg and two performance measurements (median performance error [MDPE] and wobble) were calculated. We investigated associations between the factors indicating hemodynamic instability and prognosis. Results In total, 338 patients were included. Based on the cumulative duration of MAP under 65 mmHg, we divided patients into two groups: ≥30 min and

Abstract Background The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. Methods This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. Discussion We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. Trial registration ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

Abstract Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P

Abstract Background Preventing Loss of Independence through Exercise (PLIÉ) is an integrative group movement program developed for adults with mild-to-moderate dementia attending day programs. However, many older adults with dementia ultimately require assistance with their activities of daily living and become residents in nursing homes or other long-term care facilities with their complex comorbidities and unique needs. We conducted a post-implementation evaluation of PLIÉ at a San Francisco Veterans Affairs (VA) nursing home to assess reach and effectiveness among residents, staff, and family members who participated in ≥ 1 PLIÉ class from 9/2018 to 6/2019. Methods Post-implementation number of classes offered and mean attendance; anonymous satisfaction surveys (5-point Likert scales); qualitative content analysis of open-ended survey responses and clinical progress notes. Results Forty-five PLIÉ classes were offered over 9 months. Residents attended an average of 13 ± 12 classes with an average class size of 14 residents, 4 staff members, and 2 family members. Most survey respondents rated the program overall as “very good” or “excellent” (100 % residents, n = 15; 87 % staff, n = 14; 100 % family members, n = 8). Respondents reported improvements in themselves and/or others in four domains: (1) physical, (2) psychological, (3) social, and (4) cognitive. Physical improvements among veterans included mobility, strength, and energy. Psychological improvements included feelings of happiness/well-being, enjoyment, and self-empowerment. Social improvements included connection, social skills, and social support. Cognitive improvements included engagement, communication ability, and focus/attention. Responses were similar among resident, staff, and family member surveys and clinical progress notes. Participants frequently reported improvements in multiple domains (e.g., “The veterans are more alert and engaged, many are smiling and laughing.”). Negative comments were primarily related to logistics, suggesting that the class occur more frequently. Conclusions PLIÉ was successfully implemented in a VA nursing home with high attendance and satisfaction among residents, staff, and family members. Participants reported clinically meaningful physical, psychological, social, and cognitive benefits. Other long-term care facilities could potentially benefit from implementing PLIÉ to increase quality of life in residents with dementia.

Abstract Background To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy. Methods In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups. Results The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84–1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72–2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery. Conclusions More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy.

Abstract Background Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. Methods This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. Discussion We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. Trial registration This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248 ).

Abstract Objective To evaluate impact of germline BRCA mutational status on prognosis in patients with advanced ovarian cancer. Methods A total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study. We compared patients’ clinicopathological characteristics and survival outcomes after primary treatment according to germline BRCA mutational status. Treatment-related factors that might affect patients’ survival outcome were also investigated. Results Germline BRCA1/2 mutations were observed in 51 women (39.8%). There were no differences in age and serum CA-125 levels at the time of HGSOC diagnosis, use of neoadjuvant chemotherapy (NAC), extent of debulking surgery, and overall survival (OS) between the BRCA mutation and wild-type BRCA groups. In contrast, the BRCA mutation group displayed longer progression-free survival (PFS) (median, 22.9 vs. 16.9 months, P = 0.001). Multivariate analyses identified germline BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted HR, 0.502; 95% CI, 0.318–0.795; P = 0.003). In the wild-type BRCA group, patients who received NAC as the primary treatment had shorter PFS compared to those who received primary debulking surgery (PDS) (median, 14.2 vs. 16.9 months, P = 0.003). However, in the BRCA mutation group, PFS did not differ between the NAC and PDS groups (P = 0.082). Conclusions In advanced-stage HGSOC, patients with germline BRCA1/2 mutations have better prognosis with longer PFS than those lacking BRCA mutations. Prognosis after NAC was different according to the BRCA mutational status.

Abstract Background The purpose of this study was to investigate the role of malignant ascites tumor microenvironment in ovarian cancer progression and chemoresistance. Methods A total of 45 patients with ovarian cancer and three benign ascites were collected at the time of clinical intervention. Ascites cholesterol levels were quantitated using cholesterol quantitation kit and recurrence free survival (RFS) of ovarian cancer patients were collected. The sensitivity of ovarian cancer cells to cisplatin (CDDP) and paclitaxel (PAC) were assessed by viability assay, flow cytometry and protein expression. Receiver operating characteristics (ROC) curve and Youden index analysis were applied to calculate the optimal cut-off values for ascites cholesterol. Kaplan-Meier curve were applied to compare RFS between high and low ascites cholesterol levels in ovarian cancer patients. Results Here we show that cholesterol is elevated in malignant ascites and modulates the sensitivity of ovarian cancer cells to CDDP and PAC by upregulating the expression of drug efflux pump proteins, ABCG2 and MDR1, together with upregulation of LXRɑ/β, the cholesterol receptor. Transfection of LXRɑ/β siRNA inhibited cholesterol-induced chemoresistance and upregulation of MDR1. In addition, the cholesterol level in malignant ascites was negatively correlated with number of CDDP-induced apoptotic cell death, but not with that of PAC-induced apoptotic cell death. Cholesterol depletion by methyl beta cyclodextrin (MβCD) inhibited malignant ascites-induced chemoresistance to CDDP and upregulation of MDR1 and LXRɑ/β. For patients with ovarian cancer, high cholesterol level in malignant ascites correlated with short RFS. Conclusions High cholesterol in malignant ascites contributes to poor prognosis in ovarian cancer patients, partly by contributing to multidrug resistance through upregulation of MDR1 via activation of LXRɑ/β.

Abstract Background Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC. Methods In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified. Results Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P

Abstract Background Most activities of daily life (ADL) require cooperative bimanual movements. A unilateral stroke may severely impair bimanual ADL. How patients with stroke (re)learn to coordinate their upper limbs (ULs) is largely unknown. The objectives are to determine whether patients with chronic supratentorial stroke could achieve bimanual motor skill learning (bim-MSkL) and to compare bim-MSkL between patients and healthy individuals (HIs). Methods Twenty-four patients and ten HIs trained over 3 consecutive days on an asymmetrical bimanual coordination task (CIRCUIT) implemented as a serious game in the REAplan® robot. With a common cursor controlled by coordinated movements of the ULs through robotic handles, they performed as many laps as possible (speed constraint) on the CIRCUIT while keeping the cursor within the track (accuracy constraint). The primary outcome was a bimanual speed/accuracy trade-off (biSAT), we used a bimanual coordination factor (biCO) and bimanual forces (biFOP) for the secondary outcomes. Several clinical scales were used to evaluate motor and cognitive functions. Results Overall, the patients showed improvements on biSAT and biCO. Based on biSAT progression, the HI achieved a larger bim-MSkL than the patients with mild to moderate impairment (Fugl-Meyer Assessment Upper Extremity (FMA-UE): 28–55, n = 15) but not significantly different from those with minimal motor impairment (FMA-UE: 66, n = 9). There was a significant positive correlation between biSAT evolution and the FMA-UE and Stroke Impact Scale. Conclusions Both HI and patients with chronic stroke training on a robotic device achieved bim-MSkL, although the more impaired patients were less efficient. Bim-MSkL with REAplan® may be interesting for neurorehabilitation after stroke. Trial registration: ClinicalTrial.gov identifier: NCT03974750. Registered 05 June 2019. https://clinicaltrials.gov/ct2/show/NCT03974750?cond=NCT03974750&draw=2&rank=1

Abstract Background Myocardial injury after non-cardiac surgery (MINS) has recently been accepted as a predictor of mortality. However, sex differences in the incidence of MINS and survival thereafter are not fully understood. This study aimed to compare the incidence of MINS and mortality among male and female patients. Methods This single-center study was conducted using the database of a large tertiary referral hospital. Consecutive patients with cardiac troponin (cTn) detected within 30 days after non-cardiac surgery performed between January 2010 and June 2019 were grouped according to sex. The incidence of MINS and mortality of patients with MINS were compared between men and women. Results Of the 33,311 patients, 18,546 (55.7%) were men and 14,765 (44.3%) were women. In a multivariable analysis, women showed a significantly lower incidence of MINS than did men (17.9% vs. 14.2%; odds ratio, 0.76; 95% confidence interval [CI], 0.71–0.81; P