Kobe University Hospital

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

Excessive production of immunoglobulin light chains can result in amyloid light-chain (AL) amyloidosis, which manifests as arthritis in approximately 3.7% of cases. Myeloma-associated amyloid arthropathy (MAA), a musculoskeletal manifestation of AL amyloidosis, often mimics rheumatoid arthritis (RA), making accurate diagnosis challenging. Musculoskeletal ultrasonography (MSKUS) has emerged as a valuable tool in the differential diagnosis of arthralgia; however, the specific sonographic features of AL amyloidosis-related arthritis remain poorly characterized. We present a case of AL amyloidosis-associated arthritis initially misdiagnosed and treated as seronegative RA. A comprehensive diagnostic workup-including MSKUS, magnetic resonance imaging, ultrasound-guided biopsy of the left shoulder joint, and systemic evaluations such as serum and urine protein electrophoresis and bone marrow examination-led to a definitive diagnosis of AL amyloidosis secondary to multiple myeloma. This case highlights the need to consider AL amyloidosis in the differential diagnosis of atypical arthritis, particularly in seronegative patients with poor response to RA therapies, involvement of non-classical joints, or systemic manifestations such as proteinuria or peripheral neuropathy. Although not diagnostic on its own, MSKUS may reveal atypical synovial changes suggestive of amyloid deposition and assist in guiding targeted biopsies, which remain essential for definitive diagnosis. Notably, this case demonstrated positive power Doppler signals, in contrast to previous reports, suggesting a broader spectrum of ultrasonographic findings in amyloid arthropathy than previously recognized.

Heart failure is a major public health issue, with an especially high burden in rapidly aging societies. As patients with heart failure increase, many present with multiple comorbidities, frailty, and complex social contexts, complicating their management. Comprehensive and context-oriented care provided by generalists is thus important in coordinating multidisciplinary management while addressing patients' overall health status and quality of life [1]. Close collaboration between generalists and specialists, who contribute disease-specific expertise, is important in providing high-quality care for patients with multimorbidity. Conferences for information sharing and joint decision-making are important for effective teamwork in places where this collaboration is required. For example, we hold weekly heart failure conferences at our hospital. They include discussion with cardiovascular specialists about all patients admitted to the Department of General Internal Medicine with heart failure, and it is thought to contribute to improved quality of care. Here, we propose “BRIDGE” (Figure 1), a practical mnemonic framework for successful generalist–specialist conferences based on our experience and discussions held during a recent symposium. “Balance” emphasizes valuing both generalist and specialist perspectives equally, recognizing that neither discipline should dominate, and that patient care is best supported by working cohesively. Collaboration across professional boundaries reportedly improves clinical outcomes [2]. “Respect” highlights the importance of mutual respect for differing roles, expertise, and responsibilities, which enables patient-centered discussions about the most appropriate attending physicians or department. Higher levels of mutual respect within teams have been associated with significantly lower rates of medical errors [3]. “Interaction” underscores the value of face-to-face communication and an atmosphere that encourages questions and opinions, because regular in-person discussions improve the quality of information sharing and reduce communication failures [4]. “Dedicated time” refers to securing protected and scheduled time for conferences despite clinical busyness. Our conferences are held every Tuesday at 13:00, and evidence from structured interdisciplinary rounds suggests that fixed, recurring meeting times contribute to continuity, trust-building, and improved clinical outcomes such as reduced length of stay in ICU [5]. “Goals and quality of life” emphasize that treatment objectives should extend beyond disease-oriented metrics and guidelines to incorporate patients' values and preferences, social contexts, and overall quality of life. Shared goal setting among generalists, specialists, and multidisciplinary teams facilitates patient-centered decision-making and may also reduce clinician burden [6]. Finally, “Education” highlights shared learning through the use of common templates and mutual teaching, leading to an overall improvement in team-based care. Generalists contribute insights into patient context and complexity, while specialists share advanced medical knowledge and treatment strategies. BRIDGE may become a practical and reproducible mnemonic framework to support effective collaboration between generalists and specialists and to enhance the quality of conferences in the era of increasing multi-morbidity. To facilitate implementation elsewhere, we have found starting with a small, regularly scheduled conference and using a simple shared template to be effective. Potential barriers include time constraints, hierarchical culture, and unclear role definitions. Future research should evaluate whether introducing the framework is associated with improvements in clinical outcomes, interprofessional collaboration scores, or clinician well-being across different healthcare settings. Yohei Kanzawa: writing – original draft, conceptualization, visualization. Yayoi Tetsuou Tsukada: writing – review and editing. Kenta Ishibashi: writing – review and editing. Masataka Ono: writing – review and editing. Yui Matsushima: writing – review and editing. Motohiro Shingu: writing – review and editing. Hideki Saito: writing – review and editing. Koichi Tamita: writing – review and editing. Naoto Ishimaru: writing – review and editing. We acknowledge proofreading and editing by Benjamin Phillis, a Board-Certified Editor in the Life Sciences (BELS), at Wakayama Medical University. The authors have nothing to report. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report.

Long-term follow-up (LTFU) outpatient clinics play a primary role in screening, preventing, and addressing late effects after hematopoietic cell transplantation (HCT). Following the 2018 nationwide survey, which led to the development of standardized nationwide tools to deliver information to HCT survivors, we re-evaluated changes in the current status of LTFU clinics. We targeted 267 HCT centers certified by the Japanese society for transplantation and cellular therapy. Several questionnaire categories were retained from the 2018 survey to compare results (e.g., LTFU clinic establishment and institutional practices for late-effect screening). The response rate was high in both adult (90%) and pediatric HCT centers (88%), and the establishment rate of post-HCT LTFU clinics increased to 82% (adult, 90%; pediatric, 64%). Pediatric centers were more likely to continue follow-up of patients who received HCT beyond 5 years post-HCT. Regarding transitional medical care for long-term survivors at non-HCT institutions, only a few HCT centers conducted routine transitions to specific referral facilities. We observed significant changes in recommendations for secondary cancer screenings compared to 2018, with a substantial decrease in the proportions of "not routinely included as a screening issue." In the future, it is essential to create a sustainable follow-up system, establish networks with non-HCT facilities, and educate patients to encourage behavioral changes for lifelong health screenings.

The concurrent presence of valvular heart disease and malignancy poses significant therapeutic challenges, particularly in patients of advanced age. Balloon aortic valvuloplasty (BAV) represents one potential option for addressing critical aortic valve disease before oncological intervention, though optimal patient selection criteria remain debated. We present a 90-year-old woman in whom echocardiographic evaluation prior to planned gingival cancer surgery revealed hemodynamically significant aortic valve narrowing. Following multidisciplinary consultation with cardiologists and anesthesiologists, BAV was performed 48 hours prior to the oncological procedure. The valve intervention produced sufficient hemodynamic improvement to permit definitive tumor resection with adequate surgical margins, including prophylactic lymph node clearance. Hospital discharge occurred approximately four weeks postoperatively without major adverse events. To the best of our knowledge, this is the first documented instance of a gingival malignancy resection following BAV. Our experience suggests that BAV may enable curative cancer surgery in carefully selected elderly patients with critical valvular disease who would otherwise face prohibitive operative risk. Nonetheless, additional evidence is necessary to define the appropriate role and safety profile of this staged therapeutic approach.

Currently, hormonal therapyis the main treatment option for advanced prostate cancer; however, a certain number of cases progress to metastatic, castration-resistant prostate cancer. Therefore, we designed in vitro and in vivo studies of a new molecular targeted therapy using alpha-tomatine (α-tomatine), a glycoalkaloid extracted from tomatoes, for the growth inhibition of both castration-sensitive human LNCaP and castration-resistant mouse TRAMP-C2 and metastatic human C4-2B prostate cancer cell lines. In vitro, α-tomatine supplementation showed a dose-dependent decrease in the proliferation potential of all prostate cancer cells at concentrations ranging from 1.0 to 5.0 μg/mL, as well as a decrease in migration and invasion abilities at concentrations ranging from 1.0 to2.5 μg/mL, which was sustained throughout the 72 hours post-treatment (p <0.050). Furthermore, flow cytometry demonstrated that α-tomatine at 2.5 μg/mL enhanced the incidence of apoptosis in TRAMP-C2 cells at 48 hours post-treatment (p <0.010). In vivo, TRAMP-C2 cells were subcutaneously implanted in C57BL/6 mice. Then, at a 10-mm diameter, single-time intratumoral injection of 1.0 µg/body α-tomatine was performed. Longitudinal follow-up identified a time-dependent tumor growth inhibition at 3-4 (p< 0.050), 5-7 (p < 0.010), and 8-10 (p < 0.001) days after the administration of α-tomatine. In summary, α-tomatine has the potential to block the proliferation, migration, and invasion of both castration-sensitive and castration-resistant prostate cancer (CRPC) types, even with metastatic cell lines. Further investigation is warranted to clarify the pharmacological action and molecular mechanism of α-tomatine's effects on prostate cancer cells.

Background/Objectives: Endoscopic submucosal dissection (ESD) is a state-of-the-art en bloc resection for early gastro-intestinal cancers and precursors developed and validated in Japan. Western expertise with this complex technique remains limited. Tutored training might be optimal for patients and ESD learning. We established ESD tutoring courses led by experienced Japanese experts to provide (i) optimal long-term curative outcomes and low complication rates for patients and (ii) hands-on training on difficult lesions for European endoscopists under direct expert supervision. Methods: Prospective data from 2011 to 2015 (follow-up to 12/2024) were analyzed. A total of 118 neoplasms (50% HGIEN and cancer) in 101 patients (median age 68 [37-91] years; 38% with significant comorbidities) were treated with expert or tutored ESD. Japanese experts performed 28 ESDs, while 22 trained beginners conducted 90 supervised procedures on difficult lesions during 5 live and 20 tutoring events (1-4 days each). Results: Analysis of the complete data showed curative and en bloc resection rates of 88% and 95%, respectively, with no recurrence after R0 resections during a median follow-up of 9.8 [1.5-14.9] years. Long-term survival remained recurrence-free after endoscopic resection of 3 recurrent adenomas (at R1/Rx) and curative surgery/2nd ESD for 5 non-curative ESDs. Adverse events occurred in 9.3% without emergency surgery or 30-day mortality. Comparing expert-only vs. tutored ESD procedures, beginners correctly applied curative ESD indications in 94% of 118 neoplasms. Experts resected larger lesions (22 cm2) at a rate of 9.3 cm2/h in 121 min. Tutored beginners achieved a 75% [25-100] self-completion rate on 33% smaller lesions in 112 min. Conclusions: ESD tutoring courses led by Japanese experts ensure excellent patient outcomes and standardized procedural training. This model may foster professional ESD performance across European referral centers.

ABSTRACTBackgroundTranexamic acid (TXA) is sometimes used to relieve sore throat discomfort from acute upper‐respiratory tract infection (URTI), but its clinical effect has not been demonstrated in robust randomized controlled trials.MethodsThe tranexamic acid for URTI study is a randomized double‐blinded clinical trial that was conducted between November 2023 and March 2025. Patients with URTI and a sore throat (18–65 years old) were randomized to receive either 1 g placebo (lactose) or 1 g preparation of 50% TXA. Randomization was stratified according to age (< 45 vs. ≥ 45 years) and baseline sore throat visual analog scale (VAS) score (< 50 vs. ≥ 50). Change in the proportion of patients with sore throat score more than a moderate level within a 2‐h period after taking TXA was the primary outcome. We also examined the difference in sore throat VAS scale score between before and 2 h after TXA was taken. Data were analyzed using analysis of covariance, controlling for stratification factors.ResultsWe analyzed the 17 participants assigned to each group (total = 34). The groups were not significantly different in the proportion of patients whose sore throat had a moderate or greater impact on their day‐to‐day life (TXA 41.2% vs. placebo 47.1%; p = 1.00). Similarly, they did not significantly differ in mean change of sore throat score on VAS within 30 min (TXA 17.3 vs. placebo 13.1; p = 0.49). No side effects were reported.ConclusionTXA was not significantly better than a placebo at relieving acute URTI‐associated sore throat.Trial RegistrationUMIN000056394