Introduction:BRCA2 alterations and high tumor mutational burden (TMB-H) are responsible for prostate cancer; however, their co-occurrence is uncommon, and evidence for PARP inhibition in the castration-sensitive setting remains limited. We describe a case of metastatic castration-resistant prostate cancer (CRPC) harboring both biomarkers, showing a marked response to olaparib. Case Presentation:A 74-year-old man presented with urinary retention. Initial prostate-specific antigen (PSA) level was 11 ng/mL. Follow-up MRI revealed bilateral PI-RADS 5 lesions with seminal-vesicle invasion. Biopsy confirmed adenocarcinoma (Gleason score 5 + 5 = 10). Staging revealed osseous and 30-mm right internal iliac nodal metastasis. Genomic profiling identified a pathogenic BRCA2 mutation and near-threshold TMB. Chemohormonal therapy was discontinued early owing to severe infection, and olaparib was initiated. Over 3 months, MRI showed further regression of the primary lesion and nodal disease, and PSA and SCC decreased. Conclusion:In metastatic CRPC harboring a BRCA2 mutation and near-threshold TMB, olaparib produced clear radiological and serological responses.
BACKGROUND:Stabilising inpatient volume is essential for acute care hospitals to sustain operations. Despite Japan's high national bed supply, Nerima Ward in Tokyo has a low bed-to-population ratio, limiting acute care access. At our 224-bed hospital, ambulance acceptance and admissions remained stagnant despite regional demand, suggesting a capacity mismatch. The aim of this study was to evaluate whether centralising admission coordination improves hospital admissions and operational efficiency, while ensuring that staff workload remains manageable and patient safety is maintained. METHODS:We conducted a single-centre, observational before-and-after study using monthly data from January 2024 to July 2025. Outcomes included inpatient numbers, ambulance arrivals/admissions, discharges, bed occupancy, length of stay and surgeries. Nursing overtime and patient safety indicators served as balancing measures. Changes before and after the intervention were compared using the Welch t-test. The core intervention was centralised admission coordination. Multivariable regression identified predictors of inpatient volume and statistical process control (SPC) with moving range charts assessed process stability. RESULTS:After the operational change, mean monthly inpatients increased significantly (+49.3, p=0.003), a relative increase of approximately 10%. Ambulance-based admissions (+29.0, p<0.001), arrivals (+60.1, p=0.001) and discharges (+39.6, p=0.018) also rose significantly. Bed occupancy remained stable, as the increase in admissions balanced the shorter length of stay. Regression analysis identified ambulance-based admissions (β=+1.24, p<0.001) and surgeries (β=+1.09, p=0.002) as independent predictors of inpatient volume (adjusted R2=0.725). SPC demonstrated a sustained process shift in ambulance admissions, indicating stable systemic improvement. Although nursing overtime increased modestly (+1.14 hours/month, p<0.001), patient safety indicators, including falls and severe adverse events, remained stable. CONCLUSIONS:Enhancing emergency care capacity-primarily through increased ambulance acceptance and centralised coordination-substantially boosted inpatient volume and improved acute care access. These gains were achieved without imposing excessive additional workload or compromising patient safety.
Current colorectal cancer mouse models either lack colon specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. Here we report the identification of NOX1 and NPY1R as cell-surface markers enriched in LGR5+ stem cells predominantly within the caecum and exclusively within the middle and distal colorectum, respectively. Selective dysregulation of Wnt signalling in NOX1+ or NPY1R+ stem cells using CreERT2 mouse lines drives colon cancer initiation, predominantly within the caecum and rectum respectively, establishing these stem cell populations as important sources of colon cancer. Selective conditional activation of Wnt signalling and oncogenic Kras in combination with loss of TRP53 in these stem cell compartments resulted in the development of advanced, invasive cancers. This study establishes CreERT2 drivers as valuable tools for studying stem cell contributions to colon cancer.
