Kyoto University Hospital

Tumor rupture is a rare complication of uterine leiomyosarcoma. We report a case of ruptured uterine leiomyosarcoma diagnosed after the onset of abdominal pain following endoscopic examination of the lower gastrointestinal tract. The patient was a 56-year-old woman who was diagnosed with anemia at 48 years of age when she was first referred to our medical team. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 48 × 50 mm mass in the anterior wall of the uterine body, which was diagnosed as a uterine fibroid. After 8 years of regular follow-up once or twice a year, the patient developed abdominal pain after undergoing lower gastrointestinal endoscopy, which was prompted by a positive fecal occult blood test result. Contrast-enhanced computed tomography (CT) showed that the uterine mass had enlarged to 90 × 69 mm. T2-weighted contrast-enhanced MRI demonstrated moderate signal intensity and restricted diffusion, whereas contrast-enhanced T1-weighted MRI revealed high signal intensity, suggestive of hemorrhage. The outlines of the tumor and uterus were interrupted cephalad to the lesion, raising the suspicion of rupture of a malignant uterine mesenchymal tumor. Therefore, total hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed. Intraoperatively, tumor rupture and adhesion of the ruptured tissue to the ileum were observed, necessitating partial ileectomy. Pathological examination of the resected specimen revealed irregularly proliferating spindle cells with marked nuclear atypia, 12 mitotic figures per 10 high-power fields, coagulative necrosis, and multinucleated giant cell infiltration. Another notable finding was the presence of ectopic osteosarcoma and chondrosarcoma.

Prenatal genetic testing in Japan has undergone major changes over the past 2 decades. Maternal serum screening (MSS), amniocentesis (AC), and chorionic villus sampling (CVS) have been the principal tools used to identify fetal chromosomal abnormalities. Recently, non-invasive prenatal testing (NIPT) has reshaped clinical decision-making. However, updated national-level data capturing trends in conventional prenatal testing methods are limited. We aimed to assess the current landscape of prenatal genetic testing in Japan. To update the national data, we compiled test volumes from five major high-volume laboratories that analysed prenatal genetic tests and conducted a supplemental nationwide questionnaire-based survey on ultrasound (US)-only screening between 2020 and 2023. Over this period, MSS declined from 34,887 cases in 2018 to 25,553 in 2023, AC from 16,454 in 2014 to 5620 in 2023, and CVS from 2149 in 2015 to 1167 in 2023, whereas US-only screening increased slightly to >10,000 cases annually. The chromosomal abnormality detection rate among AC cases increased from 8% during 2006-2014 to 20.0% in 2023, with trisomy 21 comprising 43.6% of the cases. During the same period, the proportion of mothers aged ≥35 years increased from 14.0% in 2003 to 30.4% in 2023, whereas the proportion of national live births decreased by 35.3%. Thus, declining test volumes cannot be attributed solely to demographic changes but also reflect the influence of NIPT uptake, improved pretest risk stratification, and changing reproductive decision-making supported by expanding genetic counselling. This study provides foundational data for future prenatal genetic testing practices and policies in Japan.

Summary: Driving Force for Innovation To tackle the growing health crises, including natural disasters and pandemics, an Open Ecosystem has been created at an academic center to accelerate challenge-driven research and human resource development for health security. Health Security here aims to prevent, prepare for, respond to, mitigate, recover from, and reconstruct to protect and improve people’s health during any crisis, whether of sudden onset or silent progression. Significant Findings: This ecosystem has three ecological cycles that reciprocally enhance performance for health security 1. Policy, Practice, and Academia The first is an interconnection of Policy, Practice, and Academia. For example, a memorandum of understanding is in place between the national headquarters of disaster medical assistance teams and academia to advance simultaneously solution-oriented R&D and expertise training for health security. Additional mechanisms are being developed for national/local authorities, as well as relevant organizations, to fuse academia with policy and practice. 2. Research, Education, and Social Contribution The second is a circulatory interconnection of the three functions of Research and Development, Human Resource Development, and Social Contribution, which encompasses on-site practices, advancing policies and social systems, and strengthening communities. 3. Transdisciplinary, Local/Global Boundary-Crossing Networks The third consists of three-layer networks: 1) transdisciplinary partnership of medicine, public health, disaster reduction engineering, public policy, law, economics, social psychology and other natural and socio-behavioral sciences; 2) networking with the national organizations of infection diseases, global health, public health, disaster medical assistance team headquarters, governments, universities and organizations; 3) global networks of national and international agencies and academic institutions around the world. Open Platform for Co-Creation Based on the above founding philosophies, the Centre for Health Security at Kyoto University was established in April 2024 as an open platform for individuals and organizations worldwide to collaborate and advance local and global health security activities.

This study aimed to identify the key determinants of vascular networks (VN) morphology, with a particular focus on the role of endothelial cell body area expansion. We introduced a quantitative metric, the cell body area expansion (CBE) score, to assess endothelial cell (EC) enlargement during the early stage of self-organizing vascular network formation. The CBE score positively correlated with both VN connectivity and vessel diameter. Notably, VNs formed in the absence of growth factors exhibited reduced connectivity accompanied by lower CBE scores, while protrusion formation remained unaffected. Additionally, comparative analysis of multiple EC types revealed that cells forming wider vascular branches consistently showed higher CBE score. A mathematical model further supported these findings, demonstrating that greater CBE leads to VNs with enhanced connectivity and larger branch diameters. STATEMENT OF SIGNIFICANCE: The on-chip vascular network, a luminal network structure formed by endothelial cells within a microfluidic device, has attracted significant attention as a promising platform for vascular disease modeling and coculture with spheroids and organoids. However, the complexity of the vascular formation process poses challenges in optimizing network formation. This study identifies cell body expansion (CBE) as a key determinant of vascular network morphology through time lapse observations and image analysis of the formation process. Furthermore, mathematical modelling provided consistent supporting results. These findings provide valuable insights into vascular network formation and serve as a framework for designing vascular networks with desired connectivity and diameter.

Lung transplant (LTx) recipients are at a higher risk of infection and mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The course of coronavirus disease 2019 (COVID-19) in Japanese LTx recipients remains unknown. This study aimed to clarify the incidence, outcomes, and clinical characteristics of COVID-19 in LTx recipients in Japan over a 3-year period. This single-center retrospective study enrolled all LTx recipients who underwent LTx at Kyoto University Hospital between June 2008 and December 2022 and who were followed up during the COVID-19 pandemic from March 2020 to June 2023. Among 230 LTx recipients, 64 (27.8%) developed SARS-CoV-2 infection and one (1.6%) died due to COVID-19. No significant differences in baseline characteristics, except for hypertension, were observed between the LTx recipients with and without COVID-19. Disease severity decreased as variants of concern transitioned but remained high even after 2022. Unilateral LTx, advanced age, and diabetes mellitus were associated with COVID-19 severity. The incidence of COVID-19 in LTx recipients was similar to that in the general Japanese population, whereas the disease severity in LTx recipients remained high even after the Omicron era. Continuous development of preventive and early therapeutic interventions is required for these vulnerable groups.

Self-expanding metal stents (SEMS) are widely used as a bridge to surgery in obstructive colon cancer, offering short-term benefits by reducing postoperative complications and avoiding emergency stoma creation. Additionally, early initiation of systemic chemotherapy may improve oncological outcomes. However, the safety and feasibility of preoperative chemotherapy following SEMS placement remain unclear. This study aims to evaluate the safety and efficacy of neoadjuvant CAPOX chemotherapy after SEMS placement in patients with obstructive colon cancer. This is a prospective, multicenter, single-arm Phase II trial involving patients with clinical stage II or III obstructive colon cancer. Eligible patients undergo successful SEMS placement followed by two cycles of CAPOX chemotherapy prior to elective surgery. The primary endpoint is the incidence of severe perioperative complications, defined as a composite of stent-related adverse events and Clavien - Dindo Grade III or higher postoperative complications. Secondary endpoints include chemotherapy-related adverse events, pathological response, and 2-year relapse-free survival. A total of 75 patients are planned for enrollment across 16hospitals in Japan over 1.5 years. The study is registered in the Japan Registry of Clinical Trials (jRCTs051240077).