Objective: Advanced ovarian clear cell carcinoma (OCCC) is associated with poor outcomes owing to chemoresistance. Bevacizumab (Bev) is increasingly being used to treat advanced ovarian cancer; however, its efficacy in OCCC remains unclear. This study evaluated the treatment outcomes of frontline bevacizumab chemotherapy in patients with OCCC. Methods: This retrospective multi-institutional study included patients diagnosed with advanced OCCC at eight institutions in Japan between 2008 and 2018. Patients were categorized into pre and post-market groups based on the Bev approval dates. Progressionfree survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate methods. Additionally, patients were classified into Bev-treated (Bev+) and non-Bev-treated (Bev−) groups, and their prognoses were compared. Results: A total of 96 patients were in the pre-market group and 82 in the post-market group. The post-market group had a significantly higher proportion of patients with poor performance status and patients who underwent interval debulking surgery (p<0.01 and p<0.01, respectively). Univariate analysis demonstrated a better PFS in the post-market group (p=0.041). In multivariate analysis, better PFS (hazard ratio [HR]=0.52; p=0.002) and OS (HR=0.47; p=0.002) were observed in the post-market group than in the pre-market group.Bev+ patients had significantly better PFS and OS than Bev− patients in univariate (p<0.001 and p<0.001, respectively) and multivariate analyses (PFS: HR=0.36; p<0.001 and OS:HR=0.21; p=0.001, respectively). Conclusion Incorporating Bev into frontline chemotherapy may improve outcomes in patients with advanced OCCC.

Methods: The study participants were 249 patients who underwent intradiscal condoliase injection for LDH at nine participating institutions, including 241 patients with initial LDH (group C) and eight with recurrent LDH (group R). Patient characteristics including age, sex, body mass index, disease duration, intervertebral LDH level, smoking history, and diabetes history were evaluated. Low back pain/leg pain Numerical Rating Scale (NRS) scores and the Oswestry Disability Index (ODI) were used to evaluate clinical symptoms before treatment and at 6 months and 1 year after treatment. Results: Low back pain NRS scores (before treatment and at 6 months and 1 year after treatment, respectively) in group C (4.9 → 2.6 → 1.8) showed significant improvement until 1 year after treatment. Although a tendency for improvement was observed in group R (3.5 → 2.8 → 2.2), no significant difference was noted. Groups C (6.6 → 2.4 → 1.4) and R (7.0 → 3.1 → 3.2) showed significant improvement in the leg pain NRS scores after treatment. Group C (41.4 → 19.5 → 13.7) demonstrated significant improvement in the ODI up to 1 year after treatment; however, no significant difference was found in group R (35.7 → 31.7 → 26.4). Conclusions Although intradiscal condoliase injection is less effective for LDH recurrence than for initial cases, it is useful for improving leg pain and can be considered a minimally invasive and safe treatment method.

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

Some serious infections due to Group A streptococci (Streptococcus pyogenes, GAS) manifest as primary peritonitis, which traditionally and commonly leads to the selection of laparotomy for initial treatment. We encountered a case in which laparoscopic surgery proved effective in treating primary peritonitis due to GAS. The patient was a 30-year-old woman transported via ambulance to our hospital with complaints of fever, abdominal pain, diarrhea, and vomiting on day 5 after a miscarriage. Diagnostic laparoscopy was performed under a presumptive diagnosis of acute generalized peritonitis. Accumulation of purulent ascites was found in the peritoneal cavity, but no primary lesion was identified. Peritoneal lavage and drainage were performed, and the surgery was concluded. Postoperatively, GAS were detected in blood, ascites, and vaginal discharge cultures, and primary peritonitis due to GAS was diagnosed. Antibiotics were switched to ampicillin sodium and clindamycin phosphate, and her condition started to improve. When primary peritonitis due to GAS is suspected, laparoscopic surgery can be considered for initial treatment.

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 : We examined the utility of distal perfusion (DP) in open stent grafting (OSG) for the treatment of thoracic aortic aneurysm. Methods : Fifty patients who underwent OSG were categorized into two groups (the Non-DP group and the DP group) based on the presence or absence of distal perfusion in OSG. There was no statistically significant difference between the two groups with regard to patient characteristics. Results : There was no statistically significant difference between the two groups with regard to operation time, but, cardiopulmonary bypass time (178±22 min vs. 193±18 min ; p <0.01) and aortic cross clamp time (84±23 min vs. 106±19 min ; p<0.01) were significantly longer in the DP group. Lower-body circulatory arrest time (46±11 min vs. 20±5 min ; p<0.001) was significantly longer in the Non-DP group. Postoperative paraplegia and paraparesis occurred in one case each in the Non-DP group, whereas permanent spinal cord ischemia did not occur in the DP group. Postoperative intubation time (72.6±40.1 h vs. 40.1±34.7 h ; p<0.05) was significantly longer in the Non-DP group. There were two in-hospital deaths due to stroke and respiratory failure in the Non-DP group, and one in-hospital death due to respiratory failure in the DP group. The postoperative maximum value of BUN (38.5±15.6 mg/dl vs. 30.8±9.8 mg/dl ; p<0.05) and s-Cr (1.9±1.0 mg/dl vs. 1.3±0.4 mg/dl ; p<0.01) were significantly higher in the Non-DP group. Conclusion : DP in OSG was an effective method for prevention of spinal cord ischemia, and for protection of respiratory and renal function.

To assess the changes in attitudes toward smoking after the smoking-prevention classes presented by Kumamoto Tobacco-Free Forum, this study administered a questionnaire survey to first-year junior high school students before and after a smoking-prevention class at a junior high school. The questionnaire that was used to pre and post comparison comprised thirteen items, ten from the Kano Test for Social Nicotine Dependence (KTSND-Youth) and three as follows: “I think I will be a smoker in the future,” “I think I will smoke about once,” and “What do you think of people around you who smoke tobacco?” The results of this pre- and post-class questionnaire indicate that attitudes toward seven items improved in a statistically significant way. These included four from KTSND-Youth: “Smokers cannot stop even if they want to,” “Smoking is adult-like and cool,” “Smoking is enjoys taste and a fragrance,” and “If it’s a place with an ashtray, it’s okay to smoke.” The smoking-prevention classes significantly decreased total KTSND-Youth scores. Furthermore, the analysis has clarified that the KTSND-Youth items: “Smoking is adult-like and cool” and “Doctor and school teachers say, ‘Tobacco is no good too much”, as well as the item “What do you think of people around you who smoke tobacco?” are significantly influencing factors for the item “I will be a smoker in the future.” These results indicate that the smoking-prevention classes presented by Kumamoto Tobacco-Free Forum were effective for decline in social nicotine dependence of the first-year students in junior high school.

Objective: Hypertriglyceridemia or elevated serum triglyceride (TG) is a leading risk factor for developing atherosclerotic cardiovascular diseases.This clinical study was designed to test the potential of polyphenol-rich extract from Rosa rugosa petals (PE) for improving hypertriglyceridemia and other types of dyslipidemia. Methods: An open-label clinical study was conducted on 19 male and female adult subjects with elevated serum TG (120–399 mg/dL), who were intervened the study diet containing (in a daily dose) 200 mg of PE once daily for sss4 weeks.The serum levels of TG and cholesterols were measured at baseline and week-4.The efficacy was evaluated by comparing the measurements at these two timepoints. Results: A significant decrease (P < 0.05) in serum TG, as well as in serum total cholesterol and non HDL-cholesterol, and a marginally significant decrease (P = 0.070) in serum LDL-cholesterol were observed, while serum HDL-cholesterol was virtually not changed.The study diet was well tolerated without any untoward side effect. Conclusions: The PE-containing diet appears to have benefits in improving hypertriglyceridemia and hypercholesterolemia.