Background: s/Aims: Patients with hepatocellular carcinoma (HCC) and histologically confirmed F4 cirrhosis often have limited hepatic reserve, making major hepatectomy difficult. Although laparoscopic liver resection is increasingly performed, its perioperative safety in this setting remains unclear. This study compared laparoscopic and open partial hepatectomy in these patients using propensity score matching (PSM). Methods: Among 298 patients who underwent hepatectomy for HCC between 2006 and 2023, 112 with histologically confirmed F4 cirrhosis who underwent partial hepatectomy were included (laparoscopic, n = 60; open, n = 52). PSM was performed using previous liver resection, difficulty score, tumor size, tumor number, and platelet count, yielding 32 matched pairs. Outcomes included operative time, blood loss, transfusion requirements, complications, hospital stay, posthepatectomy liver failure (PHLF), R0 resection rate, and 30-day mortality. Results: After matching, intraoperative blood loss was significantly lower in the laparoscopic group than in the open group (50 mL vs. 295 mL, p < 0.001). Operative time, transfusion rate, complication rate, R0 resection rate, and 30-day mortality were comparable between groups. Hospital stay was significantly shorter in the laparoscopic group (13 vs. 22 days, p < 0.001). Grade A PHLF occurred in one patient in the open group, with no significant between-group difference. Conclusions In patients with HCC and histologically confirmed F4 cirrhosis, laparoscopic partial hepatectomy was associated with less blood loss and shorter hospital stay than open surgery, without increasing perioperative morbidity. It may be a safe option in carefully selected patients undergoing limited liver resection.

Objective: To investigate the effects of social restrictions imposed during the coronavirus disease 2019 (COVID-19) pandemic on postoperative functional recovery in patients who underwent surgery for degenerative musculoskeletal disorders. Methods: This longitudinal prospective cohort study included 291 patients categorized into pre-pandemic (surgery in 2018), early pandemic (2019), and late-pandemic (2020) groups based on their 1-year recovery period. The primary outcome was improvement in locomotive syndrome (LS) status 1 year after surgery. We analyzed the association between social limitations and LS improvement using multivariate logistic and segmented regression analyses. Results: The late-pandemic group exhibited the lowest LS improvement rate (50.6%) and the highest prevalence of postoperative social contact limitations (61.0%). Multivariate analysis identified the absence of postoperative social contact limitation as a highly potent independent predictor of LS improvement (odds ratio, 10.01; 95% confidence interval, 5.40–19.34; p<0.01). Segmented regression analysis revealed a time lag: social contact limitations peaked in March 2020, whereas the decline in LS improvement rates began in October 2020. Conclusion Prolonged social restrictions negatively impacted functional recovery, particularly during the late phase of the pandemic. Social participation, specifically direct social contact, could be a critical and independent component of postoperative rehabilitation. These findings underscore the need to integrate psychosocial assessments into standard postoperative care to optimize patient outcomes.

Objective: To examine back muscle activity and fatigue behavior in female patients with degenerative thoracolumbar kyphosis (DTK) using high-density surface electromyography (HDSEMG) and evaluate the effects of using a soft spinal orthosis. Methods: Seven female participants with DTK (mean age: 73.6 years) were assessed during static standing and a weighted holding task with and without a soft spinal orthosis. HDSEMG signals were obtained from the lumbar erector spinae using a 64-electrode array. Time to fatigue (TTF), spatial displacement, and directional consistency of muscle activation were analyzed using the spatial center of activity (SCoA) and circular variance (CV). Results: Orthosis use significantly reduced the sagittal vertical axis and low back pain. TTF was significantly prolonged during the weighted holding task with the orthosis (p=0.012), indicating delayed fatigue onset. SCoA displacement was significantly reduced in both tasks (p<0.001), whereas CV analysis demonstrated improved directional consistency of muscle activation. Conclusion HD-SEMG revealed early fatigue onset and unstable muscle activation patterns in patients with DTK, particularly during load-bearing tasks performed without orthotic support. Orthosis used improved endurance and neuromuscular efficiency by reducing spatial and directional variability in muscle recruitment. These findings underscore the utility of HDSEMG for elucidating the neuromuscular pathophysiology of DTK and support the use of spinal orthoses as a conservative treatment approach.

Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

Hydromorphone is known for its low bioavailability. Currently, there is no recommended conversion ratio when changing from injectable to oral hydromorphone for patients with hepatic impairment. Its overdose may result in serious side effects, particularly respiratory depression, necessitating careful attention to dosage. In the present case, a patient with hepatic impairment developed respiratory depression following a switch from continuous subcutaneous administration of hydromorphone to an oral extended-release form. The prescribed oral dose of hydromorphone was four times higher than the injectable dosage, based on the standard conversion ratio typically considered equivalent in drug potency. However, increased bioavailability due to hepatic impairment is believed to have caused the patient’s respiratory depression. Therefore, in such cases, it is imperative to cautiously monitor dosage due to significant fluctuations in the conversion ratio, which varies based on individual circumstances.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.