記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia. CASE PRESENTATION: This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20-60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood-Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N-H scale were observed, but two participants experienced resumption of menstruation. CONCLUSION: Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. TRIAL REGISTRATION: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040 .

DOI： 10.1186/s13256-025-05562-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson's trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms.

DOI： 10.1038/s41598-025-18391-2

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8–9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1–1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (≥3), and longer warm ischemic time (WIT) (≥7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option.

DOI： 10.3390/jcm14176102

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the long-term survival of kidney transplant recipients has significantly improved, malignant neoplasms remain one of the leading causes of death in this population. The recipients face a 1.8-fold increased risk of developing malignant neoplasms compared with the general population. This risk increases with time after transplantation. Tacrolimus (TAC) is preferred over cyclosporine A (CyA) in terms of efficacy against organ rejection, but evidence on the risk of malignant neoplasms is lacking. We aimed to describe the incidence and types of malignant neoplasms in kidney transplant recipients and evaluate the association between malignant neoplasms development and the type of prescribed CNI. METHODS: This retrospective cohort study was conducted using the Japanese National Database of Health Insurance Claims, including data covering 99% of kidney transplant patients in Japan. Patients who underwent kidney transplantation and were prescribed TAC or CyA between April and June 2011 were included. The primary outcome included the incidence of malignant neoplasms, and secondary outcomes included overall survival and graft survival. RESULTS: A total of 7,590 patients were included, with 11.0% developing malignant neoplasms during the follow-up period. The most common malignant neoplasms were in the digestive organs and urinary tract. No statistically significant difference in malignant neoplasms incidence was observed between TAC and CyA users (hazards ratio: 0.97, 95% CI: 0.84 to 1.12; estimated average treatment effect: -24.05, 95% CI: -184.90 to 136.80). The patient and graft survival rates were also comparable between the groups. CONCLUSIONS: This large study suggests that TAC is not associated with an increased risk of malignant neoplasms compared to CyA in the late post-transplant period. CLINICAL TRIAL NUMBER: Not applicable.

DOI： 10.1186/s12882-025-04405-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This study investigated the correlation between body mass index (BMI, kg/m2) and clinical outcomes in patients with advanced renal cell carcinoma (RCC) treated with ipilimumab and nivolumab. PATIENTS AND METHODS: A total of 113 patients with advanced RCC, treated with first-line ipilimumab and nivolumab were analyzed. Patients were divided into two groups based on their BMI at treatment initiation: the high BMI (BMI ≥25) and the low BMI group (BMI <25). The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR) were analyzed to compare the two groups. RESULTS: Patient characteristics for the high BMI (n=30) and the low BMI (n=83) were as follows: median age at treatment initiation (70 years for both groups), percentage of male patients (77% vs. 82%), International Metastatic RCC Database Consortium (IMDC) poor-risk category (23% vs. 33%), the presence of liver metastasis (7% vs. 8%). The ORR was 53% (16/30) in the high BMI and 37% (29/77) in the low BMI (p=0.01). The median OS was not estimated in the high BMI and 33 months in the low BMI (p=0.049). Multivariable analysis identified IMDC poor-risk status with a hazard ratio (HR) of 2.31 and the presence of liver metastasis with an HR of 4.83 as independent factors affecting OS. CONCLUSION: A higher ORR for the combination of ipilimumab and nivolumab was observed in patients with high BMI compared to those with low BMI. IMDC poor risk and the presence of liver metastasis significantly influenced the prognosis of patients with advanced RCC treated with the combination.

DOI： 10.21873/anticanres.17635

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

With the advancement of modern ureteroscopes and laser technology, kidney-sparing surgery(KSS)has an expanding role for patients with upper tract urothelial carcinoma(UTUC), although radical nephroureterectomy remains the gold standard. Patients with UTUC are generally elderly and often have major medical comorbidities. As such, KSS is recommended for patients with imperative indications, such as bilateral disease, renal insufficiency, or a solitary kidney, while maintaining renal function, resulting in the avoidance of potential long-term cardiovascular morbidity and hemodialysis. In addition, KSS is also advocated for low-risk patients(elective indication)based on the risk stratifications recommended by each guideline. The big issue of risk stratifications is their narrow indications at the cost of providing accuracy, but the current elective indications have been updated and expanded year by year. KSS includes endoscopic management through antegrade or retrograde access to the upper tract and segmental ureterectomy. Thulium: YAG laser in combination with Ho: YAG laser is recently used for KSS due to the advantages of its shallow penetration depth in tissue, with a reduced risk of upper urinary tract perforation. The concern regarding KSS is a high recurrence rate. Adjuvant intracavitary instillation to the upper tract has the potential to reduce the risk of recurrence. The phase Ⅲ trial assessing a mitomycin-containing reverse thermal gel (JelmytoTM)revealed the promising result despite their use not being approved in Japan. Therefore, KSS is assumed to have an increasing demand for patients with UTUC in our aged society and is expected to be widely utilized nationwide.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

For small renal tumors, nephron-preserving treatment, including partial nephrectomy or ablation therapy, is recommended. According to major guidelines, ablation therapies are advised for patients who are deemed not suitable to undergo surgery due to an advanced age or the presence of comorbidities. However, compared with surgery, ablation therapy can result in superior safety and functional outcomes. The present review discusses the factors affecting decision-making as regards treatment options for small renal tumors. When determining an appropriate treatment option, tumor locations, as well as the condition and preferences of the patient, are considered. Scoring systems, such as the RENAL Nephrometry Score can assist in guiding treatment decisions. However, surgery may be the preferred approach for tumors near major vessels and collecting systems. For endophytic tumors, partial nephrectomy can be challenging due to the difficulty in visualizing intra-parenchymal tumors during the procedure, whereas ablation therapies may be inferior to partial nephrectomy. Although treatment selection for small renal tumors can be affected by tumor location, partial nephrectomy remains the gold standard for numerous cases.

DOI： 10.3892/mi.2025.247

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery. PATIENTS AND METHODS: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ≤7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging. RESULTS: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (κ=0.62). CONCLUSION: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.

DOI： 10.21873/invivo.14077

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.urolonc.2024.09.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.

DOI： 10.1016/j.dmpk.2021.100407

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. METHODS: We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. RESULTS: The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. CONCLUSION: ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.

DOI： 10.1016/j.transproceed.2021.03.043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To analyze the effect and impact of low-dose rituximab induction therapy on cytomegalovirus infection in living-donor renal transplantation. METHODS: A total of 92 recipients undergoing living-donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor-specific anti-human leukocyte antigen antibody-positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus. RESULTS: There were 59 patients in the rituximab group and 17 in the non-rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus-seronegative recipients of renal allografts from cytomegalovirus-seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5-year survival rates of death-censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups. CONCLUSIONS: Low-dose rituximab induction therapy is effective in immunological high-risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.

DOI： 10.1111/iju.14382

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jiac.2018.11.013

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会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：幕張メッセ  

ワークショップ9 腎移植医療における腹腔鏡・ロボット手術

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会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：佐賀  

シンポジウム4 『慢性腎不全の治療；保存期治療～ 移植まで』

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会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：岡山（オンライン学会）  

シンポジウム２：初心にかえって、TURBTの手技徹底検証！

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