Kiyohide Fujimoto

Introduction: Post‐transplant fractures are associated with increased mortality and reduced graft survival. Although computed tomography (CT)‐derived metrics, such as vertebral trabecular bone attenuation and abdominal aortic calcification have been reported as useful for assessing osteoporosis, their utility in predicting post‐transplant fractures in kidney transplant recipients (KTRs) has not been explored. This study examined pre‐transplant factors, including CT imaging parameters, associated with post‐transplant fractures using machine learning techniques. Methods: This retrospective study included 111 primary living‐donor KTRs who underwent preoperative CT at our hospital between 2009 and 2023. Aorto‐iliac calcification was quantified using the Agatston score. Vertebral trabecular bone CT attenuation values (Hounsfield units [HU]) were recorded at T12 to L5 levels. Machine learning with SHapley Additive exPlanations (SHAP) was used to identify the top predictors of fracture. Results: The median follow‐up period was 69 months. Twenty‐four recipients experienced fractures: hip ( n = 3), leg ( n = 6), arm ( n = 5), rib ( n = 3), and vertebrae ( n = 9). The L1 vertebral CT attenuation value and aortic segment calcification score emerged as the top predictors of fracture. Based on SHAP cutoffs (L1 CT = 104 HU; Agatston score = 504), recipients were categorized into Group 1: high L1/low calcification; Group 2: high L1/high calcification; and Group 3: low L1/high calcification. Compared to Group 1, fracture risk was higher in Group 2 (Subdistribution hazard ratio [SHR] 3.06; p = 0.034) and markedly higher in Group 3 (SHR 11.66; p < 0.0001). Conclusion: Pre‐transplant lower vertebral trabecular bone attenuation and higher aortic calcification on CT are strongly associated with post‐transplant fractures.

We aimed to evaluate the suitability of archival ureteroscopic (URS) biopsy specimens for fibroblast growth factor receptor 3 (FGFR3) biomarker analysis in upper urinary tract urothelial carcinoma. Thirty-six patients with upper urinary tract urothelial carcinoma who underwent diagnostic URS and radical nephroureterectomy (RNU) were included. Among the 36 RNU-derived tissue specimens, 33 (92%) yielded valid FGFR3 RNA test results; the remaining three (8.3%) showed test failure because of undetectable amplification by reverse transcriptase-polymerase chain reaction. Of the 33 RNU specimens with valid amplification, eight (24%) had FGFR3 alterations. Of these eight specimens, two (25%) were valid for FGFR3 RNA testing; one showed positive concordance with the paired RNU specimen, whereas the other did not. The remaining six specimens (75%) showed test failure. Correlation analysis of FGFR3 immunohistochemical staining scores demonstrated a moderate positive correlation between RNU and paired URS specimens (Spearman’s ρ = 0.47, P = 0.004). Our findings indicate that URS biopsy specimens are unsuitable for FGFR3 RNA testing but may be useful for protein-based biomarker analysis when RNU specimens are unavailable.

Aim: The aim of this multicenter study was to assess patient characteristics and short-term survival outcomes of first-line (1L) enfortumab vedotin plus pembrolizumab (EVP) as compared with conventional chemotherapy in locally advanced or metastatic urothelial carcinoma (la/mUC). Methods: The database included 642 patients with la/mUC diagnosed between January 2008 and December 2025 at 12 collaborating hospitals. Baseline characteristics and follow-up data, including overall and organ-specific objective tumor response according to the RECIST v1.1, progression-free survival, and duration of response, were compared among the 1L regimens. Treatment-related adverse events (TRAEs) were graded according to the CTCAE v5.0 in patients treated with 1L EVP. Results: The objective response and disease control rate were higher with 1L EVP than with chemotherapy (66% vs. 42% and 83% vs. 68%, respectively). The organ-specific response rate for liver metastatic lesions was 85%. Median progression-free survival (95% confidence interval) for 1L EVP, gemcitabine plus cisplatin, and gemcitabine plus carboplatin was 14.5 months (10.5–not determined), 10.5 months (8.4–13.3), and 9.2 months (6.7–14.2), respectively. In the safety analysis set including 40 patients, all-grade TRAEs occurred in 36 (90%) patients, including grade 1–2 events in 30 (75%) and grade 3–4 toxicities in 6 (15%). Grade 3–4 TRAEs included skin toxicity (7.5%), anorexia (5.0%), anemia (5.0%), gastrointestinal disorders (2.5%), renal dysfunction (2.5%), and interstitial lung disease (2.5%). The median number of administered EV cycles was 4 (range, 1–13), 5 (2–13), and 10 (4–13) in the overall, responder, and complete-response populations, respectively. EV dose modifications and interruptions were frequent in the initial 2 months but rare thereafter. Conclusions: This multicenter study provides real-world evidence on short-term outcomes and safety with 1L EVP, highlighting its impact on the evolving treatment landscape for la/mUC.

This study evaluated changes in blood pressure and hypotension-related adverse drug reactions (ADRs) following oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) in patients undergoing transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis under blue light has demonstrated superior sensitivity compared with that of white light when 5-ALA is administered 4 to 8 h before TURBT (95.3% vs. 61.1%, p < 0.001); however, data regarding associated blood pressure change remain limited. In this study, blood pressure changes were monitored for 24 h after 5-ALA administration (20 mg/kg) and hypotension-related ADRs were assessed within 14 days post-dose. Both systolic and diastolic blood pressures reached their nadir at 2 h after 5-ALA administration. Absolute blood pressure values were lower in patients with ADRs, whereas the magnitude of blood pressure changes was not different between patients with and without ADRs. The incidence of hypotension, defined as systolic blood pressure ≤ 80 mmHg, was 2.1%, which was lower than that reported in previous retrospective studies (40.0–75.6%). Although hypotension-related ADRs occurred in 25.5% of patients, all events were non-serious and resolved without clinical sequelae. The lower incidence may partly reflect the exclusion criteria and medication restrictions applied in this protocol-controlled trial.

Aim: Intravesical Bacillus Calmette–Guérin (BCG) is the standard therapy for non-muscle invasive bladder cancer (NMIBC); however, many patients experience recurrence or progression. We examined how urinary immune signals and the urinary microbiome change across BCG and are related to outcomes. Methods: In this single-center prospective cohort study, adults with NMIBC underwent transurethral resection of bladder tumor (TURBT), followed by BCG induction. Urine was collected before TURBT, before BCG, after BCG induction, and three months later. Urine sediment mRNA (PD-L1, PD-L2, CD33, and CD204) was quantified using TaqMan ΔCt. The urinary microbiome was profiled using 16S rRNA gene sequencing, and diversity, composition, and taxon balance were evaluated using nonparametric tests, PERMANOVA, repeated-measures correlations, and mixed-effects models. We analyzed the relationship between the urinary microbiome and prognosis. Results: Twenty-three patients were analyzed; ten recurrences, eight progressions, and three deaths were observed. Relative to baseline, CD33 increased after BCG and after three months; PD-L2 increased immediately after BCG and returned to baseline by three months; PD-L1 and CD204 increased after BCG. Shannon alpha-diversity was unchanged, but total read count was higher at three months, with stable beta-diversity and dispersion. Higher PD-L1 expression was associated with lower Actinobacteria abundance in the bladder cancer microenvironment. A higher post-BCG Firmicutes/Bacteroidetes ratio was associated with worse prognosis, with the clearest signal for progression-free survival (PFS) observed in the univariate Cox models. Higher post-BCG Corynebacterium and Enterobacteriaceae abundance was associated with better PFS. Conclusions: BCG was associated with higher urinary PD-L1/PD-L2 and myeloid marker transcripts, while overall community structure remained stable. These exploratory data support that pre-BCG microbial features may be related to early response, and post-BCG profiles may reflect durability and survival. Urine immune-microbiome profiling could be a feasible, noninvasive adjunct for monitoring and risk stratification in NMIBC.

Background: Avelumab maintenance therapy was approved in Japan in February 2021 for patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) without disease progression after platinum-based chemotherapy (PBC). We report subgroup analyses from the JAVEMACS chart review study of avelumab maintenance therapy in Japan by characteristics of first-line (1L) PBC. Methods: This multicenter, retrospective study collected data from medical charts of patients with la/mUC who received avelumab maintenance after 1L PBC. Protocol-specified subgroups defined by 1L PBC characteristics (PBC regimen, number of PBC cycles, and best overall response to PBC) were analyzed. Results: Between February 2021 and December 2023, 350 patients received avelumab maintenance. Patient characteristics were generally similar across subgroups defined by 1L PBC characteristics. In patients who received 1L gemcitabine + cisplatin ( n = 196) or gemcitabine + carboplatin ( n = 116), median overall survival (OS) was not reached (95% CI, 31.2 months-not estimable [NE]) and 24.3 months (95% CI, 19.5–30.6 months), respectively. In patients who received 1–3 cycles ( n = 68), 4 cycles ( n = 205), 5/6 cycles ( n = 61), or ≥ 7 cycles ( n = 16) of 1L PBC, median OS was 25.0 months (95% CI, 15.2 months-NE), not reached (95% CI, 29.3 months-NE), 31.2 months (95% CI, 18.0 months-NE), and 23.6 months (95% CI, 19.3 months-NE), respectively. In patients with complete response ( n = 32), partial response ( n = 180), or stable disease ( n = 138) as best response to 1L PBC, median OS was not reached (95% CI, 30.6 months-NE), 31.2 months (95% CI, 22.6 months-NE), and 26.5 months (95% CI, 20.2 months-NE), respectively. Across all subgroups, enfortumab vedotin was the most common second-line treatment after discontinuation of avelumab. Conclusions: Results from these descriptive subgroup analyses from JAVEMACS suggest that real-world outcomes with avelumab maintenance therapy are generally consistent regardless of 1L PBC regimen, number of 1L PBC cycles, or best response to 1L PBC. These findings further support the use of avelumab maintenance therapy as a standard of care for patients with la/mUC without disease progression after 1L PBC. Trial registration: NCT06412848.

Objectives: Hypofractionated radiotherapy for prostate cancer has recently gained attention, with growing evidence supporting the clinical use of hypofractionation. This retrospective study aimed to compare the outcomes of hypofractionated radiotherapy with conventional fractionation. Methods: Between 2012 and 2021, patients with low‐ or intermediate‐risk prostate cancer treated at our institution were included. Patients were divided into two groups: the conventional group (78.0 Gy in 39 fractions over 8 weeks) and the hypofractionated group (51.6 Gy in 12 fractions over 2.5 weeks). Survival outcomes and toxicities were compared between the two groups. Results: A total of 96 patients were included: 54 in the conventional group and 42 in the hypofractionated group. The median follow‐up time was 110.5 months (IQR: 78.3–125.0) in the conventional group and 73.5 months (IQR: 57.8–83.5) in the hypofractionated group. Only one patient in the conventional group experienced biochemical recurrence. There were no significant differences in acute grade ≥ 2 urinary or bowel toxicity between the two groups. Grade ≥ 2 late urinary toxicity was more frequent in the hypofractionated group (16.7% vs. 7.4%, p = 0.16), while grade ≥ 2 late bowel toxicity was more frequent in the conventional group (16.7% vs. 4.8%, p = 0.07). Conclusions: Hypofractionated radiotherapy demonstrated comparable oncological outcomes and an acceptable toxicity profile to those of conventionally fractionated radiotherapy in patients with low‐ to intermediate‐risk prostate cancer.

Pelvic organ prolapse (POP) is a condition in which the bladder, uterus, or rectum prolapses from the vagina. Assessing the presence or absence of POP is important when examining for lower urinary tract dysfunction (LUTD) in women. However, reports on changes in LUTD before and after robot-assisted sacrocolpopexy (RSC) are scarce. This study aimed to explore the progression of LUTD after RSC for POP. Patients with POP who underwent RSC at the Department of Urology, Nara Medical University, between July 1, 2021, and September 30, 2024, were enrolled. Patient background, perioperative uroflowmetry results, treatment efficacy, and safety were retrospectively evaluated. In total, 23 patients were included in the study, with a median age of 74.0 years at the time of surgery. The total international prostate symptom score and quality of life scores were significantly lower at 4 weeks after surgery than at baseline and continued to decrease at 12 and 24 weeks. The maximum flow rate was significantly higher at 4 weeks after surgery than at baseline and continued to increase at 12 and 24 weeks. The post-void residual urine volume was significantly lower at 4 weeks after surgery than at baseline and continued to decrease at 12 and 24 weeks. Postoperative complications included urinary incontinence (grade II and IIIb) in two patients and intestinal obstruction (grade IIIb) in one patient. Two cases of stage II recurrence were identified, but after consultation with the patients, no reoperation was performed. RSC appears to be a clinically useful option for pelvic organ prolapse with concomitant lower urinary tract dysfunction, providing meaningful postoperative functional improvement with an acceptable safety profile. Larger comparative studies with longer follow up are needed to confirm durability and better define patient selection and complication prevention.

Objectives: Primary urethral carcinoma is an extremely rare malignancy, and evidence on its treatment and prognosis remains limited. This study aimed to clarify the treatment patterns, clinical outcomes, and prognostic factors for primary urethral carcinoma in Japan. Methods: This retrospective study across 10 institutions included 57 Primary urethral carcinoma cases between 2004 and 2022. Recurrence‐free survival and overall survival were estimated using the Kaplan–Meier method, and overall survival–related factors were evaluated using univariate Cox regression analysis. Results: The cohort comprised 24 men (42%) and 33 women (58%), with a median tumor size of 30 mm (interquartile range, 15–48 mm). Stage distribution was ≤ I in 17 (30%), II in 10 (18%), III in 8 (14%), and IV in 21 (38%) patients. Urothelial carcinoma, including cases with divergent differentiation, was the predominant histological subtype, identified in 17 men (71%) and 14 women (42%). The median follow‐up time was 17.1 months (interquartile range, 6.4–37.7 months). Overall survival did not differ significantly between Stage I and Stage II disease ( p = 0.499), whereas it was significantly shorter in patients with Stage III and Stage IV disease compared with Stage I ( p = 0.030 and p < 0.001, respectively). Previous urinary catheter placement, urethral diverticulum, and elevated lactate dehydrogenase (> 220 IU/L) were significantly associated with poorer overall survival. Conclusions: Stage ≤ II Primary urethral carcinoma has favorable survival following definitive treatment, Stage III–IV disease showed poor outcomes, necessitating multimodal perioperative strategies (chemotherapy and/or radiotherapy).

Introduction: In real‐world practice in Japan, standard treatment for metastatic hormone‐naïve prostate cancer (mHNPC) is androgen deprivation therapy (ADT), administered as monotherapy, combined androgen blockade (CAB), ADT plus androgen receptor pathway inhibitors (ARPIs), or ADT plus docetaxel. In a previous interim analysis of the large‐scale, longitudinal, multicentre, J‐ROCK registry study of real‐world clinical and patient‐reported outcomes, ADT plus ARPI or ADT plus docetaxel was used more frequently than ADT/CAB in patients (aged ≥ 20 years) with newly diagnosed LATITUDE‐criteria high‐risk mHNPC. Methods: This post hoc analysis of the J‐ROCK study evaluated prostate‐specific antigen (PSA) response, progression‐free survival (PFS), time to castration‐resistant prostate cancer (CRPC), overall survival (OS) and safety in patients with high‐risk mHNPC who received ADT/CAB (cohort 1) or ADT plus ARPI (cohort 2B) in subgroups were defined according to the following known prognostic factors at baseline: age, Gleason Grade Group (GGG), alkaline phosphatase (ALP), hemoglobin (Hb) and lactate dehydrogenase (LDH). Results: This analysis included 947 evaluable patients (371 in cohort 1 and 576 in cohort 2B). PSA response rates remained similar among age and GGG subgroups in both cohorts, but were reduced in cohort 2B patients with elevated ALP, low Hb, and elevated LDH. Time to CRPC and OS were longer in cohort 2B than in cohort 1, regardless of prognostic factors. Among patients with poor prognosis (older, high GGG, low Hb, elevated LDH), OS decline occurred earlier in cohort 1 versus cohort 2B. A trend towards a plateau in the time to CRPC curve was observed in both cohorts, even in patients with poor prognosis. Safety data were not affected by prognostic factors or treatment. Conclusions: These findings suggest that novel ADT plus ARPI regimens for LATITUDE‐criteria high‐risk mHNPC may improve real‐world outcomes compared with ADT monotherapy or CAB, particularly among patients with poor prognosis.