Kazuhide Makiyama

Prostate cancer is common in older men, and the treatment decision depends strongly on the patient’s general condition and comorbidities. However, the medication background of men who reach prostate biopsy has rarely been described. We used a large Japanese administrative claims database (Medical Data Vision) to profile the medications of men who underwent prostate needle biopsy between April 2008 and June 2019. We examined the number of medications and the drug classes in relation to body mass index (BMI) and age. We identified 67,812 men, all aged 60 years or older. The mean number of medications was lowest at BMI 20–25 and increased toward both low and high BMI, showing a U-shaped pattern (minimum 1.44 drugs at BMI 22.0–22.5); the increase was driven mainly by high BMI. This pattern was consistent across age strata, and in a negative binomial regression adjusted for age the quadratic term of BMI remained significant (p < 0.001), with an adjusted minimum at BMI 20.5. The composition of drug classes differed by body size: metabolic drugs (antihypertensive/cardiovascular, dyslipidemia, diabetes, and hyperuricemia drugs) were more common at high BMI, whereas gastrointestinal and analgesic drugs were relatively more common at low BMI, and all classes increased with age. In conclusion, among men undergoing prostate biopsy, the number of medications was lowest at BMI 20–25 and the qualitative medication profile differed by BMI. These findings describe the medication background of this population and may inform the design of future risk-stratified or prospective studies.

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.

Introduction: Malignant ureteral obstruction (MUO) caused by urological, gynecological, and gastrointestinal cancer requires a nephrostomy or ureteral stenting to preserve the renal function and prevent pain and urinary tract infections. Recent investigations have revealed the importance of low skeletal muscle mass as a poor prognostic factor in various solid malignancies. This study investigated the importance of a low psoas muscle index (PMI) as a prognostic factor for MUO patients who have undergone nephrostomy. Materials and Methods: A total of 89 percutaneous nephrostomies were created from July 2008 to March 2016 in our institutions. Fifty‐seven of these patients had MUO. The psoas muscle volume was calculated at the L3 level using axial computed tomography images obtained prior to nephrostomy. The PMI was calculated using the following formula: (left psoas muscle area at the level of L3 [mm ² ]) / (body height [m]) ² . Results: In these 57 patients, 41 cases (71.9%) were male, and 16 (28.1%) were female. The median (mean ± SD) age was 70 (69.0 ± 9.6) years old in males and 68 (66 ± 13.5) years old in females. A low PMI was associated with a significantly poorer overall survival in male MUO patients (log‐rank p = 0.018), whereas no significant difference was observed in female patients ( p = 0.861). In the multivariate Cox proportional hazards regression analysis, a low PMI was identified as an independent predictor of poor overall survival (HR: 2.29, 95% CI: 1.05–5.03, p = 0.038). Conclusion: Among male patients who underwent percutaneous nephrostomy, a low PMI was associated with poor overall survival, suggesting its utility as a prognostic indicator in this population.