Jun-Ichi Teranishi

Background and Aims: Apalutamide (APA) and enzalutamide (ENZ) are androgen receptor pathway inhibitors widely used for prostate cancer. Skin rash is a characteristic adverse event of APA, but how often it occurs in real‐world practice, the factors related to it, and possible differences by disease stage are not well understood. Methods: Using a Japanese nationwide claims database (Medical Data Vision), we identified patients with prostate cancer treated with APA (240 mg/day) or ENZ (160 mg/day) between April 2008 and August 2021. A skin‐related adverse event was defined as a case with both a skin‐related diagnosis and treatment for the skin event during therapy. Patients were classified as mCSPC or CRPC. We compared the rate and timing of skin rash between the two drugs and between disease stages, and examined associated clinical factors. Results: A total of 5524 patients were included (1264 APA and 4260 ENZ). The rate of skin rash was higher in the APA group than in the ENZ group (25.3% vs. 9.95%; p < 0.001), confirmed by Kaplan–Meier analysis. Within each drug, the rate did not differ significantly between mCSPC and CRPC. Most events occurred within the first month (median 29 days for APA and 22 days for ENZ). Age, body weight, BMI, and BSA were not associated with skin rash. After adjustment for age, body weight, BMI, and BSA, the risk remained about 2.6‐fold higher with APA (adjusted HR: 2.56, 95% CI: 2.18–3.01). Conclusion: Skin‐related adverse events requiring treatment were more common with APA than with ENZ, but they did not differ by disease stage for either drug and were not predicted by body size. Careful skin monitoring and early intervention are important for all patients from the start of APA or ENZ treatment, regardless of disease stage.

Objective: To examine how the age distribution of radical prostatectomy and radical cystectomy changed in Japan during the period in which robot‐assisted surgery spread. Methods: We used the National Database Open Data for fiscal years 2014 to 2024 (Japanese fiscal year, April to March). Procedures were identified by procedure code and classified as robot‐assisted or conventional. Rates per 100,000 population were calculated, and the rate in each age group was expressed relative to that in patients aged 70 to 74 years. Cells with fewer than 10 claims are suppressed in the source tables; sensitivity analyses imputed 0, 5 or 9 procedures into these cells. Results: Radical prostatectomy increased from 20,222 to 29,239 procedures and radical cystectomy from 3545 to 4793. Rates in patients younger than 75 years rose only about 1.2‐fold. For prostatectomy, the rate ratio in men aged 75 to 79 years rose from 0.40 to 0.93, while that in men aged 80 to 84 years reached only 0.22. For cystectomy, the ratio in patients aged 80 to 84 years rose from 0.74 to 0.95, while no clear increase was seen in patients aged 85 years or older (0.18 to 0.20, p = 0.791). In men aged 80 years or older, robot‐assisted prostatectomy increased from 94 to 1239 procedures, whereas conventional surgery changed from 64 to 97. These findings were unchanged when suppressed cells were imputed as 5 or 9. Conclusions: Between fiscal years 2014 and 2024, the age distribution of radical prostatectomy and radical cystectomy in Japan shifted toward older patients. The increase was concentrated in men aged 75 to 84 years for prostatectomy and in patients aged 80 to 84 years for cystectomy, and was accounted for mainly by robot‐assisted procedures.

Objectives: Lower urinary tract symptoms (LUTS) are common in men and have been linked to mental health, but their relationship with depressive symptoms across the adult age range, including young men, remains unclear. We examined the association between LUTS and depressive symptoms in Japanese men. Methods: Using an internet research panel, 4000 never‐smoking Japanese men were surveyed. LUTS were assessed with the Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), International Prostate Symptom Score (IPSS), and Quality of Life (QOL) index, and depressive symptoms with the Quick Inventory of Depressive Symptomatology, Japanese version (QIDS‐J). Scores were compared across QIDS‐J severity groups, and multivariable regression was used to adjust for age and household income. Results: Of 2568 respondents (mean age 46.6 years), more severe depressive symptoms were associated with younger age ( p < 0.001). ICIQ‐SF and IPSS increased with QIDS‐J severity (both p < 0.001) and remained independently associated after adjustment for age and income (IPSS adjusted β 0.32; ICIQ‐SF 0.13; both p < 0.001), whereas OABSS was not associated ( p = 0.193). The same pattern was observed in men aged 20–40 years. Conclusions: Greater depressive symptom severity was independently associated with higher IPSS and ICIQ‐SF scores, but not with OABSS, OAB, or UUI among Japanese male never‐smokers.

Objectives: Drug treatment for overactive bladder (OAB) is changing, with an increasing share of β3‐adrenoceptor agonists relative to anticholinergics, but it is not known how far this change has progressed in older people, who are most vulnerable to the risks of anticholinergics. We examined the use of these drugs in Japan by age and sex, and analyzed changes in anticholinergic burden using a large database. Methods: We analyzed outpatient prescriptions of two β3‐adrenoceptor agonists and six anticholinergics from FY2017 to FY2024, using the sex‐ and age‐stratified tables of the NDB Open Data of Japan. Dispensed tablets were converted into patient‐days, and the β3‐adrenoceptor agonist share was calculated. Anticholinergic burden was measured as ACB‐weighted prescription volume (patient‐days multiplied by the anticholinergic cognitive burden score). Because FY2021–FY2022 was a period of nationwide generic supply disruption, FY2018 and FY2024 were used as endpoints when estimating change over time. Results: The β3‐adrenoceptor agonist share rose from 36.2% to 64.9%, but anticholinergic use fell only slightly (3.10 × 10 ⁸ to 2.94 × 10 ⁸ tablets; −5.0%). In FY2024, the β3‐adrenoceptor agonist share was higher in men than in women in every age group, and the difference widened with age (+1.2 percentage points at 50–54 years and +14.2 at ≥ 90 years). ACB‐weighted prescription volume was higher in women than in men, and the female‐to‐male ratio rose with age (1.1 at 65–74 years, 1.6 at 75–84 years, and 2.8 at ≥ 85 years). Between FY2018 and FY2024, prescription volume fell by about 20% at 65–74 and 75–84 years, but the fall was smallest in women aged ≥ 85 years (−11.3%). Conclusions: The β3‐adrenoceptor agonist share for OAB has continued to increase in Japan, but this change appears slower in older women, in whom anticholinergic exposure remains high.

Background and Objective: Lower urinary tract symptoms (LUTS) are highly prevalent in women, yet care‐seeking is very low, and a large treatment gap remains despite the availability of effective treatments. Previous studies, mainly from Western populations, suggest that symptom bother, as well as symptom severity, is associated with medical care‐seeking; however, quantitative data in Asian and particularly Japanese women are scarce, the influence of bother on the separate care indicators is unclear, and the willingness to pay (WTP) for treatment has rarely been quantified. We therefore examined the factors associated with medical care‐seeking, including symptom bother, and the WTP, in Japanese women. Methods: We conducted a nationwide web‐based survey of 1800 Japanese women aged 40 years or older, covering the OABSS, ICIQ‐UI SF, symptom bother (0–10), separate care indicators (consulting, visiting, treatment, and current treatment), reasons for not seeking care, and WTP. Factors associated with visiting a clinic were assessed with multivariable logistic regression. Results: Among symptomatic women, only 12.9% had visited a clinic. Both symptom bother and measured symptom severity were independently associated with visiting (bother ≥ 5, adjusted OR 5.19, 95% CI 3.08–8.76; OABSS ≥ 6, adjusted OR 2.24, 95% CI 1.23–4.07), while age, marital status, children, housing, and income were not significant. The most common reason for not seeking care was “thought it was just aging” (65.1%), and WTP rose with bother. Conclusions: In Japanese women, symptom bother was independently associated with medical care‐seeking (visiting a clinic) for LUTS, as was symptom‐score severity.

Background: Androgen deprivation therapy (ADT) is the base of treatment for prostate cancer, and gonadotropin‐releasing hormone (GnRH) drugs are given as depot injections. Long‐acting formulations may reduce the number of injections and the drug cost, but this impact has not been quantified in real practice. Methods: We used the National Database Open Data of Japan from fiscal year (FY) 2017 to FY2024, and studied leuprorelin, goserelin, and degarelix in men aged 40 years or older. Patient‐years were estimated by weighting the dispensed quantity by the period that each formulation covers. Descriptive statistics (patient numbers, drug, and formulation shares) were based on all products, whereas the analyses of the number of administrations and drug cost were restricted to originator products. Shapley value decomposition was used to divide the change in injections and in drug cost into factors. Results: In total, 2 276 025 patient‐years were analyzed. The share of each drug did not change greatly, but a clear shift to long‐acting formulations was seen. The 6‐month formulation of leuprorelin exceeded the 3‐month formulation in FY2021 and was used more often in older patients. The number of patients increased by 12.9% (from 269 328 to 304 181 patient‐years; +10.0% for originator products, used for the administration and cost analyses), but injections decreased by 21.5%, from 1 275 081 to 1 000 324. Injections per patient per year decreased from 4.97 to 3.55. The shift to long‐acting formulations was the main factor for this decrease (−383 932 injections), and it also reduced the drug cost by 7.7 billion JPY per year. Conclusions: The shift to long‐acting GnRH formulations was associated with a reduction in injections of about one in five, even though the number of patients increased and was estimated to account for part of the reduction in drug cost. Because the oncological effect is similar among GnRH drugs, a further shift to long‐acting formulations may lower the burden on patients and on health care.

Introduction: Pheochromocytoma crisis complicated by catecholamine‐induced cardiomyopathy is a life‐threatening condition requiring careful preoperative management. Although metyrosine has recently been approved in Japan for the perioperative management of pheochromocytoma, clinical experience remains limited. Case Presentation: A 46‐year‐old man presented with pheochromocytoma crisis complicated by reverse Takotsubo cardiomyopathy and was diagnosed with bilateral pheochromocytomas. Given the preceding life‐threatening crisis, severe cardiac dysfunction, marked catecholamine excess, and bilateral disease, he was considered at high perioperative risk. Metyrosine was added to conventional α‐adrenergic blockade before one‐stage bilateral adrenalectomy. Metyrosine was well tolerated, and total urinary metanephrine decreased by approximately 76% without symptomatic hypotension. Although intraoperative blood pressure fluctuations still occurred, bilateral adrenalectomy was completed successfully. Conclusion: This case supports the feasibility of preoperative metyrosine administration in a high‐risk patient. Although its effect on intraoperative hemodynamic stability remains uncertain, metyrosine may be considered as an adjunct to conventional α‐adrenergic blockade in carefully selected patients.

Objectives: To determine whether the seasonality of urinary stone surgery and its association with ambient temperature differ between surgical procedures and to compare the time lag between temperature and each procedure. Subjects and methods: We used the nationwide open data of the National Database of health insurance claims in Japan for fiscal years 2019–2024 (April 2019 to March 2025, 72 months). We counted monthly inpatient surgeries for extracorporeal shock wave lithotripsy (ESWL), ureteroscopic lithotripsy (URS), percutaneous nephrolithotomy (PCNL) and transurethral cystolitholapaxy and expressed them as a seasonal index of surgeries per business day normalized to a mean of 1 within each fiscal year. Observed monthly mean temperatures for 12 representative meteorological stations were correlated with the index at lags of −1 to +4 months. Results: A total of 71 791 ESWL, 320 863 URS, 71 272 cystolitholapaxy and 20 387 PCNL procedures were performed. Volume rose from summer to autumn and was lowest in winter for ESWL, URS and cystolitholapaxy. In the same month, the correlation with temperature was strongest for ESWL ( r = 0.83, 95% CI 0.74–0.89), followed by URS ( r = 0.43, 0.22–0.60) and cystolitholapaxy ( r = 0.35, 0.13–0.54), whereas PCNL showed no association ( r = 0.05, −0.19–0.27). The correlation peaked at 1 month for ESWL ( r = 0.87), at 2 months for URS ( r = 0.69) and cystolitholapaxy ( r = 0.52) and at 3 months for PCNL, where it was not significant at any lag. PCNL showed significant month‐to‐month variation that was not explained by temperature. Conclusion: The seasonality of urinary stone surgery and the time lag relative to ambient temperature differ by procedure, being shortest for ESWL and longer for procedures requiring anaesthesia and hospitalization, while PCNL shows no association with temperature.

Introduction: Overactive bladder (OAB) is a prevalent condition, particularly among women, and is associated with substantial economic and quality‐of‐life burdens. Although stress urinary incontinence during and after pregnancy is well documented, the association between childbirth and OAB symptoms remains unclear. This study aimed to investigate the relationship between childbirth history and OAB symptoms among Japanese women using a large‐scale internet‐based survey. Methods: A total of 4800 Japanese women aged 40 years and older were recruited through an online survey platform. Participants were stratified by age and completed the Overactive Bladder Symptom Score (OABSS) questionnaire. Subjects were grouped based on childbirth history (parous vs. nulliparous), and OABSS scores were compared between the groups. Subgroup analyses were conducted for women aged 40–60 years and for parous women based on delivery mode (vaginal vs. cesarean). Results: The OABSS total score and scores for nocturia, urgency, and urgency incontinence were significantly higher in the parous group compared to the nulliparous group (all p < 0.001). These trends persisted in the 40–60‐year‐old subgroup. No significant differences in OABSS scores were found between women who had vaginal deliveries and those who had cesarean sections. BMI showed minimal correlation with OABSS, while symptom severity increased with age. Conclusion: A history of childbirth may be associated with more severe OAB symptoms among Japanese women, independent of age. These findings highlight childbirth as a potential risk factor for OAB and underscore the need for long‐term urinary health monitoring in women.

Background: Cytomegalovirus (CMV) infection remains a common complication after kidney transplantation, particularly among high‐risk donor‐seropositive/recipient‐seronegative (D+/R−) recipients. Valganciclovir is the standard first‐line therapy; however, its use may be limited by hematological toxicity or impaired graft function. Maribavir is a recently approved antiviral agent with a distinct mechanism of action. Case Presentation: We report four high‐risk kidney transplant recipients in whom maribavir was introduced because continued valganciclovir therapy was difficult owing to cytopenia or renal dysfunction. After switching therapy, CMV viral loads decreased in all cases, and hematological abnormalities improved following discontinuation of valganciclovir. One patient developed a drug‐induced skin eruption, while no other serious adverse events were observed. No CMV recurrence or graft dysfunction occurred during follow‐up. Conclusion: These cases highlighted practical clinical considerations for managing CMV infection when standard antiviral therapy cannot be safely continued.