Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective：Only 44 of the 82 university medical schools in Japan have rehabilitation medicine departments, although rehabilitation medicine is one of the 19 basic specialties recognized by the Japanese Medical Specialty Board, and many medical doctors are concerned regarding selecting rehabilitation medicine as a basic specialty without sufficient education in the field. The “Let's Become a Physiatrist” Seminar has been organized since 2017 to eliminate such concerns, and this study aimed to investigate how these results are manifested in the number of majors.Methods：We examined the number of past attendees and tracked how many of them became rehabilitation medicine majors.Results：The number of seminar attendees over a 5-year period was 589. The number of on-demand viewers in FY2020 and FY2021, which were held via the web, was 554. A total of 116 of the 471 physicians who began specialty training in rehabilitation medicine after the seminar was planned attended or web viewed the seminar accounting for 24.63％．This percentage has been increasing each year, with 36.81％ of the majors who applied in 2022 attending the seminar, and the number of multiple attendees also increased. The number of majors has increased significantly doubling to 144 in 2022 compared with 74 in 2018.Conclusion：In many cases, the seminar helped the attendees learn more about physiatrists and develop their thoughts while attending multiple times. Thus, they started their majors. Five years have passed since we started planning this seminar, and we believe that the results are now coming to fruition.

Objective：Only 44 of the 82 university medical schools in Japan have rehabilitation medicine departments, although rehabilitation medicine is one of the 19 basic specialties recognized by the Japanese Medical Specialty Board, and many medical doctors are concerned regarding selecting rehabilitation medicine as a basic specialty without sufficient education in the field. The “Let's Become a Physiatrist” Seminar has been organized since 2017 to eliminate such concerns, and this study aimed to investigate how these results are manifested in the number of majors.Methods：We examined the number of past attendees and tracked how many of them became rehabilitation medicine majors.Results：The number of seminar attendees over a 5-year period was 589. The number of on-demand viewers in FY2020 and FY2021, which were held via the web, was 554. A total of 116 of the 471 physicians who began specialty training in rehabilitation medicine after the seminar was planned attended or web viewed the seminar accounting for 24.63％．This percentage has been increasing each year, with 36.81％ of the majors who applied in 2022 attending the seminar, and the number of multiple attendees also increased. The number of majors has increased significantly doubling to 144 in 2022 compared with 74 in 2018.Conclusion：In many cases, the seminar helped the attendees learn more about physiatrists and develop their thoughts while attending multiple times. Thus, they started their majors. Five years have passed since we started planning this seminar, and we believe that the results are now coming to fruition.

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. Methods: This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

Objective: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. Methods: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). Results: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. Conclusion: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.

We began providing comprehensive cardiac rehabilitation for congestive heart failure (CHF) in 2014 at our institution, using an original pamphlet and heart failure notebook to provide life guidance for CHF. However, the life guidance rate was lower in 2017 (61%) than it was in 2014 (77%). The objective of this study was to investigate the awareness of life guidance among nurses. We administered a questionnaire survey regarding life guidance to 28 nurses in December 2018. Among the 27 respondents, 26 nurses (96%) had high motivation and 21 (80%) felt a sense of accomplishment. Responses to the “most important point in life guidance” were “understanding living condition” by 14 nurses, “heart failure notebook” by 9 nurses, and “guidance using the pamphlet” by 6 nurses. Fifteen nurses (58%) felt that the guidance had become routine in nature, and 5 nurses (19%) were worried about their instruction. The nurses were motivated to provide life guidance, but they also felt that the guidance had become routine because they had been providing the same guidance for many years. We consider that the factors related to the lower life guidance rate are the routine/repetitive nature of the guidance and concerns about instruction. Going forward, we need to review the content of the guidance and the teaching approach.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.