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PURPOSE: To examine the potential mediating role of psychological resilience in the relationship between frailty and Health related quality of life (HRQoL) among older cancer survivors. METHODS: This cross-sectional study recruited 314 older cancer survivors in Japan and Hong Kong. Questionnaires on frailty, psychological resilience, and HRQoL were administered. The associations among the variables were analyzed using multivariable linear regressions, and psychological resilience was tested as a mediator between frailty and global HRQoL using mediation analysis. RESULTS: Prefrail (β = -3.93, 95 %CI: -7.72, -0.14, p = 0.042) and frail (β = -11.77, 95 %CI: -19.33, -4.21, p = 0.002) participants showed significantly lower psychological resilience than robust individuals. Frailty was negatively associated with global HRQoL, physical, role, and cognitive functioning (β ranged from -17.22 to -14.00, all p < 0.001), and positively associated with fatigue (β = 21.48, 95 %CI: 11.49, 31.46, p < 0.001) and pain (β = 16.51, 95 %CI: 7.33, 25.69, p < 0.001) compared with robust group. Psychological resilience was positively associated with global HRQoL, emotional, cognitive, and social functioning (β ranged from 0.19 to 0.41, all p < 0.001), and negatively associated with insomnia (β = -0.51, 95 %CI: -0.73, -0.30, p < 0.001). Psychological resilience partially mediated the relationship of frailty and global HRQoL, accounting for 32.3 % and 21.9 % of the total effect in prefrail and frail groups, respectively. CONCLUSION: Psychological resilience served as a mediator in the association between frailty and HRQoL in older cancer survivors. Programs incorporating frailty-reducing and resilience-enhancing strategies may be helpful to improve HRQoL among older cancer survivors, particularly those who are pre-frail or frail.

DOI： 10.1016/j.ejon.2025.102993

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PURPOSE: To externally validate our surgical skill assessment system, which provides comprehensive real-time feedback based on motion capture (Mocap) metrics of laparoscopic instruments in simulation training environments. METHODS: Participants conducted periaortic tissue dissection (Dissection Task) and parenchymal closure of the kidney (Suturing Task) using porcine cadaveric organs. Surgical instrument movements were measured by the MoCap system, and all training sessions were video-recorded. Utilizing our previously developed machine-learning (ML) algorithm, participants received quantitative feedback based on their motion features immediately after the training, including three-tier classification results, which meant their skill levels being consistent with those with 0 ≤ to ≤ 9 surgical caseloads of laparoscopy (novice), 10 ≤ to ≤ 49 (intermediate), and ≥ 50 (experienced), and predicted Global Operative Assessment of Laparoscopic Skills (GOALS) scores. Automatically generated feedback comments were also provided through explainable artificial intelligence technology, and participants' satisfaction with this skill assessment system was also recorded. For the three-tier classifications, accuracy was calculated by comparison between estimated and actual surgical experience levels. The correlation and mean absolute error (MAE) were calculated between the algorithm-predicted and expert-evaluated mean GOALS scores. RESULTS: A total of 38 urologists, 4 junior residents, and 10 medical students voluntarily participated in the current training. Several participants repeatedly performed the training, and so 107 datasets were included in the present analysis. Validation analyses demonstrated overall classification accuracies of 67.3 and 56.9% for Dissection Task and Suturing Task, respectively, when excluding the subsequent data of repeaters. In terms of GOALS score prediction, the correlation coefficient and MAE were 0.86 and 2.51 ± 1.82 for Dissection Task, and 0.91 and 1.56 ± 1.20 for Suturing Task, respectively, when compared with experts' evaluations. Overall, 88% of the participants found the feedback easy to understand, and 75% of participants were satisfied with the evaluation. CONCLUSIONS: Our real-time feedback system was viewed favorably by the participants, and the ML algorithm was a reliable method, especially the predicted GOALS score. This system could facilitate objective performance assessment, enhance simulation-based training efficacy, and potentially accelerate surgical skill acquisition.

DOI： 10.1007/s00464-025-12018-3

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OBJECTIVES: To evaluate the effects of renal impairment at the time of second-line tyrosine kinase inhibitor (TKI) therapy initiation and rapid renal function decline during first-line immuno-oncology (IO) combination therapy on metastatic renal cell carcinoma (mRCC) patients treated with second-line TKIs. METHODS: This multicenter retrospective study included 243 mRCC patients treated with first-line IO combination therapy, followed by second-line TKI therapy. Patients were divided into three groups using the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) at the time of second-line TKI therapy initiation: eGFR ≥ 60, 30 ≤ eGFR < 60, and eGFR < 30. The eGFR slope during first-line IO combination therapy was calculated using eGFR measurements when initiating first-line and second-line therapies. Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of renal impairment and eGFR slope on progression-free survival (PFS) and overall survival (OS). RESULTS: The incidence rates of any grade and grade ≥ 3 adverse events were not significantly different among the three groups. Univariable analyses indicated that eGFR slope was not significantly associated with PFS or OS. Multivariable analyses suggested that moderate (30 ≤ eGFR < 60 mL/min/1.73 m2) and severe (eGFR < 30 mL/min/1.73 m2) renal impairment had no effects on shorter PFS, whereas severe renal impairment was independently and significantly associated with shorter OS. CONCLUSIONS: TKIs can be safely used as a second-line treatment after first-line IO combination therapy in mRCC patients with renal impairment without sacrificing oncological outcomes, except for in patients with severe renal impairment.

DOI： 10.1111/iju.70172

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Language：Japanese   Publisher：(一社)腎癌研究会  

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BACKGROUND: Circulating tumor DNA (ctDNA) is a promising tool for diagnosing and predicting cancer prognosis. However, its clinical utility in metastatic renal cell carcinoma (mRCC) remains unclear, particularly in terms of clinical prognosis. METHODS: We enrolled 124 patients with mRCC in the MONSTAR-SCREEN study (UMIN 000036749) between August 2019 and February 2022, a national observational ctDNA-based screening study, and performed ctDNA sequencing before and at the time of resistance to systemic therapy. RESULTS: ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were VHL (25.0%), PBRM1 (10.9%), TERT2 (8.7%), BAP1 (8.7%), and MTOR (7.6%). Patients receiving first-line therapy with tumor fraction (TF) < 1.2% showed significantly better progression-free survival than those with TF ≥ 1.2% (Hazard ratio (HR) = 0.467; 95% CI 0.229-0.979; p = 0.0425). BAP1 mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322-0.736; p = 0.0003). Serial ctDNA analysis showed that 46.8% of patients developed new ctDNA mutations at disease progression, which was linked to shorter time to progression (p = 0.046). CONCLUSIONS: Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.

DOI： 10.1038/s41416-025-02985-8

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INTRODUCTION: Effectiveness and safety of second-line tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) for whom first-line immuno-oncology (I-O) combination therapy was discontinued because of adverse events (AEs) remain to be determined. PATIENTS AND METHODS: Clinicopathological data were retrospectively collected from 34 institutions between August 2018 and January 2022 for 243 patients with mRCC who received second-line TKIs after first-line I-O combination therapy. Two patients who requested discontinuation of first-line I-O combination therapy were excluded. Oncological outcomes and safety were compared between patients who discontinued first-line I-O combination therapy because of progressive disease (Group PD) and AEs (Group AE). First- and second-line overall survival (OS) were defined as the time from the start of first- and second-line therapy to death, respectively. Propensity score matching was applied to adjust prognostic factors between the 2 groups. RESULTS: There were 179 patients in Group PD and 62 patients in Group AE. Objective response rate and disease control rate were similar between the 2 groups. Progression-free survival (PFS), second-line OS, and first-line OS were significantly longer in Group AE than in Group PD (median 13.6 months vs. 8.5 months, P = 0.005; median not reached [NR] vs. 19.5 months, P = .005; median NR vs. 30.8 months, P = .012, respectively). After propensity score matching, PFS and second-line OS were still significantly longer and first-line OS tended to be longer in Group AE than in Group PD. There were no significant differences in the occurrence of AEs of any grade, including severe grades of 3 or greater, between the 2 groups. CONCLUSION: Second-line TKIs are safe and at least as effective in patients with mRCC who discontinued first-line I-O combination therapy because of AEs as they are in patients who discontinued because of PD.

DOI： 10.1016/j.clgc.2025.102322

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PURPOSE: Bladder preservation therapy in combination with atezolizumab and radiation therapy trial, which was a multicenter, open-label, single-arm phase 2 study, showed a promisingly high interim clinical complete response (cCR) rate of 84.4% (38/45). In the present study, we aimed to identify potential tissue biomarkers for achieving cCR using bladder preservation therapy in combination with atezolizumab and radiation therapy. METHODS AND MATERIALS: We used tumor tissue samples of the bladder and blood samples collected from patients at baseline to analyze the tumor immune microenvironment at baseline using an integrated approach of immunophenotyping, genomic, and tumor-infiltrating lymphocyte (TIL) profiling. RESULTS: Immune phenotype analysis revealed that cCR rates of patients with the desert phenotype were as similarly high as patients with excluded/inflamed phenotypes (73.3% [11/15] vs 93.3% [14/15], P = .33) despite lower programmed death-ligand 1 expression levels in the desert phenotype. Genomic and TIL profiling then revealed that increased CD8+ and CD204+ TIL infiltration, high CD8:forkhead box protein P3 ratios in the stroma of the excluded/inflamed phenotypes, and gene alterations, such as CDK12, GNAS, NOTCH2, and AR1D1A, were associated with a high cCR rate (93.3%). Furthermore, the characteristics of these dual TILs, CD8-forkhead box protein P3 ratios, and gene alterations (especially FGFR3) bifurcated the desert phenotype into 2 subgroups with different cCR rates (100% [11/11] and 0% [0/4]). CONCLUSIONS: These potential subgroups, defined by combined molecular subclass and immune phenotype, could lead to the identification of good responders to atezolizumab plus radiation therapy for invasive bladder cancer. However, given the small cohort size and limited number of tumor samples, these findings should be viewed as hypothesis-generating and require further validation in larger studies.

DOI： 10.1016/j.ijrobp.2024.12.019

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Advanced/metastatic urothelial cancer (a/m UC) still has a poor prognosis despite the recent medical advances. Recent studies demonstrated that fibroblast growth factor receptor (FGFR) gene alterations (GAs) may be driver genes for UC; however, the proportion of UC genetic panel testing in Japan remains low. We clarified the proportion of patients with FGFR2/3 GAs, treatment patterns, and clinical outcomes in a/m UC patients in Japan. This study was a descriptive epidemiological study using the MONSTAR-SCREEN database, and 138 patients with a/m UC were evaluated. The primary endpoint was the proportion of patients with FGFR2/3 GAs. The secondary endpoints included treatment patterns, clinical outcomes, genomic status before and after treatment, etc. The proportion of FGFR GA-positive patients in a/m UC was 11.9%. The most common FGFR mutation variant and fusion gene were S249C (4.4%) and FGFR3-TACC3 fusion (3.7%), respectively. Fifty-one patients were tested two or more times; a few changes were observed in the FGFR GA status, regardless of the treatment regimen. Co-occurrence association was observed in FGFR1 with TET2, and in FGFR3 with CHEK2 or MLL2. During the first-, second-, and third-line treatment, median progression-free survival (PFS) of GA-positive patients was 7.3, 2.9, and 6.2 months, while for GA-negative patients, 6.9, 3.1, and 6.9 months, respectively. This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.

DOI： 10.1111/cas.70000

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OBJECTIVE: To validate multiple prognostic models in metastatic renal cell carcinoma patients who received second-line axitinib following first-line nivolumab plus ipilimumab therapy. METHODS: Five prognostic models (ACL, albumin, C-reactive protein, and lactate dehydrogenase; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; MSKCC, Memorial Sloan Kettering Cancer Center; ATP, axitinib treatment prediction; JMRC, Japanese metastatic renal cancer) to predict overall survival (OS) were validated and compared using data from 86 metastatic renal cell carcinoma patients who received second-line axitinib therapy following first-line nivolumab plus ipilimumab therapy at 34 hospitals affiliated with the Japan Urologic Oncology Group. RESULTS: The Karnofsky performance status, time from initial diagnosis to first-line therapy, and hemoglobin, platelet, albumin, and C-reactive protein levels correlated with OS in univariate Cox regression analyses. Among these factors, only albumin had a significant impact on OS in the multivariate analysis. The integrated area under the curve (AUC) of the ACL, IMDC, MSKCC, ATP, and JMRC models were 0.78, 0.76, 0.76, 0.69, and 0.70, respectively. The ACL model showed a higher value than the others in the time-dependent AUC. CONCLUSIONS: The accuracy of the five prognostic models (ACL, IMDC, MSKCC, ATP, and JMRC) created in the pre-immuno-oncology (IO) treatment cohort was maintained in the second-line axitinib group after nivolumab plus ipilimumab therapy. The ACL model demonstrated moderate accuracy in predicting OS with the fewest number of clinical variables.

DOI： 10.1093/jjco/hyaf018

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BACKGROUND: Axitinib is a widely used tyrosine kinase inhibitor (TKI) in metastatic renal cell carcinoma (mRCC) treatment. Here, we analyzed the characteristics of patients who did not respond to axitinib and evaluated alternative options for their treatment. METHODS: We retrospectively analyzed data for 449 patients with mRCC who were administered axitinib following another TKI as initial therapy. Patients with progressive disease (PD) at their first assessment were defined as showing early-PD. We analyzed the characteristics of patients at risk of early-PD and evaluated the relationship between the treatment following axitinib and their prognosis. RESULTS: Early-PD was diagnosed in 102 patients, and was more common in those who had not undergone nephrectomy (p < 0.001), those treated with a TKI for a short period (p < 0.001), and those in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor risk category for mRCC (p < 0.001). Multivariate analysis showed that these were independent risk factors for early-PD (all p < 0.001). Of those with early-PD, 52 changed to next-line treatment. The progression-free survival periods were 5.5 (95% confidence interval (CI) 2.4-8.6) months for patients administered TKIs, 4.2 (95% CI 0.3-8.1) months for those on nivolumab, and 2.2 (1.8-2.6) months for those on mammalian target of rapamycin inhibitors (p = 0.030). CONCLUSION: Patients who have not undergone nephrectomy, those previously treated with another TKI for a short period, and those in the IMDC poor risk category are more likely to experience early-PD when taking axitinib. Furthermore, TKIs are the best treatment for patients with early-PD who have previously been administered axitinib.

DOI： 10.1007/s10147-025-02715-3

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PURPOSE: Genomic characterization of the predisposition of tumors to metastasize to specific sites has been performed in a few studies using mainly tissue-derived genomes. This nationwide prospective observational study investigated the association between genomic characteristics using circulating tumor DNA (ctDNA), and the synchronous and metachronous metastasis of tumors to specific target organs in advanced prostate cancer. METHODS: Patients with advanced prostate cancer undergoing systemic treatment were included. ctDNA was analyzed using the FoundationOne®Liquid CDx assay at enrollment. Associations between genomic characteristics and metastatic status were examined. RESULTS: Alterations in the genes MYC, APC, and BRCA2 and the DNA repair, MYC, and WNT pathways were associated with lung and liver metastasis. PTEN gene alterations and PI3K pathway alteration were associated with synchronous lung metastasis. RB1 gene alteration and RAS/RAF/MAPK pathway alteration were associated with synchronous liver metastasis. RB1 and BRCA2 gene alterations predicted metachronous lung metastasis, while TP53 and MYC gene alterations predicted metachronous liver metastasis. CONCLUSIONS: This study identifies genomic alterations in ctDNA associated with synchronous and metachronous metastases. These findings may be clinically helpful for treating, managing, and monitoring cancer.

DOI： 10.1016/j.jlb.2024.100282

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BACKGROUND: In Japan, since 2014, new treatments such as androgen receptor signaling inhibitors and cabazitaxel have become applicable for metastatic castration-resistant prostate cancer (mCRPC), leading to dramatic changes in treatment options. OBJECTIVE: This study aims to evaluate the impact of recent advancements in treatment options on the overall survival (OS) of patients diagnosed with de novo metastatic castration-sensitive prostate cancer (mCSPC) in Japan. METHODS: A retrospective analysis was conducted on 2450 Japanese men diagnosed with de novo mCSPC between 2008 and 2018. Patients were stratified into two groups based on the period of diagnosis: an earlier period (2008-2013) and a later period (2014-2018). OS was compared between earlier and later periods using Kaplan-Meier analysis in total and propensity score matched subpopulation as well as risk-stratified subgroups. RESULTS: Patients diagnosed in the later period exhibited significantly improved OS compared to those diagnosed in the earlier period. The risk score, calculated based on ISUP grade group, LDH levels, and ALP levels, was a poor prognostic factor. In the later period, compared to the earlier period, there was no improvement in OS in the favorable-risk group, but a significant improvement was observed in the poor-risk group. CONCLUSION: It was suggested that the introduction of novel androgen receptor signaling inhibitors and chemotherapy treatment regimens since 2014 has led to improved survival outcomes for patients with de novo mCSPC, particularly those with poor-risk profiles. The findings highlight the impact of recent advancements in treatment on the prognosis of patients with metastatic prostate cancer in Japan.

DOI： 10.1007/s10147-024-02681-2

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Nivolumab plus ipilimumab (NIVO+IPI) has a long-term response rate of 30% for patients with metastatic renal cell carcinoma (mRCC). However, 20% of patients develop primary resistant disease (PRD) to NIVO+IPI and show poor survival outcomes. In this study, we aimed to evaluate the effect of PRD as a second-line treatment in patients with mRCC. The data used in this multi-institutional, retrospective cohort were collected between August 2015 and January 2023. In total, 189 patients with mRCC were treated with NIVO+IPI and then with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Associations between PRD and progression-free survival of second-line treatment (PFS), progression-free survival 2 (PFS2), and overall survival (OS) were analyzed. The median age at NIVO+IPI initiation was 67 years in the male-dominant population (n = 140, 74.1%), and most patients had clear cell histology (n = 140, 74.1%). PRD was recorded in 42 (22.2%) of 189 patients during NIVO+IPI therapy. Patients who experienced PRD showed poor PFS (hazard ratio [HR], 1.788; 95% confidence interval [CI], 1.176-2.718; p = 0.007), PFS2 (HR, 4.127; 95% CI, 2.649-6.431; p < 0.001), and OS (HR, 3.330; 95% CI, 2.040-5.437; p < 0.001). Before starting second-line therapy, patients with PRD tended to have a poor performance status compared with non-PRD patients and a higher IMDC risk. Second-line drug therapy was not associated with treatment outcomes in patients with PRD. PRD in patients with mRCC receiving NIVO+IPI as first-line treatment was associated with poor clinical course, even with second-line therapy.

DOI： 10.1111/cas.16326

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BACKGROUND: Immune-combinations have recently become the standard first-line treatment for patients with metastatic renal cell carcinoma (mRCC). This study evaluated the applicability of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model in predicting outcomes for patients treated with either immune-oncologic drug doublet (IO-IO) or immune-oncologic drug tyrosine kinase inhibitor combinations (IO-TKI). A secondary objective to compare the effectiveness of IO-IO versus IO-TKI within the IMDC risk groups over a short follow-up period. METHODS: A retrospective analysis was conducted on 172 patients with mRCC treated with first-line immunotherapy combinations. Progression free survival (PFS), time to treatment failure 2 (TTF2), and overall survival (OS) were compared between IMDC risk categories. Model fit was assessed using the c-index. The inverse probability of treatment weighting (IPTW) method was used to adjust and compare outcomes between IO-IO and IO-TKI, except for IMDC favorable risk patients due to the small number of IO-IO cases. RESULTS: The IMDC risk model demonstrated a c-index of 0.684 (OS) for entire cohort, 0.600 (PFS), 0.596 (TTF2), and 0.624 (OS) for IO-IO, and 0.667 (PFS), 0.702 (TTF2), and 0.751 (OS) for IO-TKI. In the IMDC intermediate and poor risk groups after IPTW adjustment, PFS (HR 0.72), TTF2 (HR 0.67), and OS (HR 0.74) did not significantly differ between IO-IO and IO-TKI. Specifically, in the IMDC intermediate risk group, PFS (HR 0.79), TTF2 (HR 0.69), and OS (HR 0.65) were longer in IO-TKI, though the differences were not statistically significant. In the IMDC poor risk group, PFS (HR 0.76), TTF2 (HR 0.77), and OS (HR 1.03) were comparable. CONCLUSIONS: The impact of IMDC risk model on survival was modest in IO-IO, while remained statistically substantial in IO-TKI. Survival outcomes did not significantly differ between IO-IO and IO-TKI during the short follow-up period.

DOI： 10.1186/s12885-025-13504-6

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Language：Japanese  

We report a case of testicular cancer after kidney transplantation in a 29-year-old man. Twenty-two years after the surgery, computed tomography (CT) showed a retroperitoneal mass 3 cm in diameter. Positron emission tomography (PET) -CT revealed high FDG uptake in both the right testis and retroperitoneal mass. Regarding serum tumor markers, α fetoprotein (AFP) was slightly elevated to 12.5 ng/ml. He underwent right radical orchiectomy, and pathological examination revealed pure seminoma. After surgery, the serum AFP level remained high (12. 9 ng/ml), and we initially considered this nonseminoma patient to have a good prognosis according to International Germ Cell Consensus Classification. During three cycles of a combination regimen including bleomycin, etoposide, and cisplatin (BEP), we performed adjustment of immunosuppressive therapy, treatment for Cytomegalovirus infection (valganciclovir hydrochloride), and that for other adverse events associated with systemic chemotherapy. The chemotherapy schedule was delayed, and bleomycin (third course, day 15) was skipped due to adverse effects. After 3 cycles of BEP, the retroperitoneal lymph node metastasis shrunk from 3.0 to 1.5 cm in diameter. In contrast to the good radiological response, the serum AFP level gradually increased during the treatment to 102.6 ng/ml. Therefore, we did not consider the AFP elevation to have derived from residual cancer, and decided to perform close follow-up. During the 3-year follow-up, AFP decreased to around 20 ng/ml, and PET-CT did not show any uptake in the retroperitoneal mass or other sites.

DOI： 10.14989/ActaUrolJap_71_1_9

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2025&ichushi_jid=J01269&link_issn=&doc_id=20250204260003&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F2433%2F291608&url=http%3A%2F%2Fhdl.handle.net%2F2433%2F291608&type=%E4%BA%AC%E9%83%BD%E5%A4%A7%E5%AD%A6%EF%BC%9A%E4%BA%AC%E9%83%BD%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%83%85%E5%A0%B1%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80028_3.gif

Publishing type：Research paper (scientific journal)   Publisher：Institute of Electrical and Electronics Engineers (IEEE)  

DOI： 10.1109/tmrb.2025.3550666

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A man in his 40's presented with vomiting and numbness in the right thigh. Eight months earlier, he had undergone robot-assisted radical cystectomy and pelvic lymphadenectomy for bladder cancer. Computed tomography (CT) revealed a caliber change and a closed loop of the small intestine in the right pelvis, prompting emergency diagnostic laparoscopy. Intraoperative findings showed that the small intestine had herniated into the space between the right obturator nerve and pelvic wall, resulting in strangulated intestinal obstruction. The necrotic small intestine was resected and reconstructed, while preserving the obturator nerve. The hernia orifice was not repaired during the surgery. We encountered a rare case of an internal hernia involving the obturator nerve as the cord. In patients with abdominal distension and thigh symptoms following pelvic lymphadenectomy, internal hernia should be considered. The optimal approach for hernia repair involving the obturator nerve remains undetermined, necessitating a case-by-case approach.

DOI： 10.1111/ases.70030

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Language：Japanese  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

J-GLOBAL

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OBJECTIVE: To evaluate comorbidities in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. METHODS: This study enrolled TC survivors who visited any of the eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants answered questionnaires about their comorbidities. We analyzed the impact of treatment on comorbidities rate in TC survivors. RESULTS: A total of 509 TC survivors responded to the comorbidity questionnaires. Median age at the time of response was 43 years (IQR 35-51 years) and median follow-up period after treatment was 5.1 years (IQR 2.1-9.2 years). TC survivors were divided according to the number of cycles of chemotherapy into the following groups: None (n = 153); 1-2 cycles (n = 34); 3-4 cycles (n = 234); or ≥5 cycles (n = 88). The prevalence of kidney disease increased significantly with increasing number of cycles of chemotherapy (p < 0.05). The relative risk of cardiovascular disease in the groups with three or more cycles was 2.6 compared to the group without chemotherapy. CONCLUSION: The present study showed that the prevalence of kidney disease in TC survivors was increased with increasing number of cycles of chemotherapy.

DOI： 10.1111/iju.15622

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OBJECTIVES: To determine how the treatment decision-making process and posttreatment health-related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan. METHODS: We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12-item Short Form Survey. The decision-making process was assessed by patient evaluation of the decision-making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision-making processes. RESULTS: Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43-93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores. CONCLUSIONS: These findings underline the important influence of posttreatment HRQOL and decision-making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients.

DOI： 10.1111/iju.15602

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BACKGROUND: Advanced (Stage IV) prostate and renal cancer have poor prognosis, and several therapies have been developed, but many are very costly. This study investigated drug regimens used in patients with untreated Stage IV prostate cancer and renal cell carcinoma and calculated the monthly cost of each. METHODS: We surveyed first-line drugs administered to patients with untreated Stage IV prostate cancer and renal cancer at Japan Clinical Oncology Group affiliated centers from April 2022 to March 2023. Drug costs were calculated according to drug prices in September 2023. Individual drug costs were calculated or converted to 28-day costs. RESULTS: A total of 700 patients with untreated Stage IV prostate cancer were surveyed. Androgen deprivation therapy + androgen receptor signaling inhibitor was the most common regimen (56%). The cost of androgen deprivation therapy + androgen receptor signaling inhibitor was 10.6-30.8-fold compared with conventional treatments. A total of 137 patients with Stage IV renal cancer were surveyed. Among them, 91% of patients received immune-oncology drug-based regimen. All patients received treatments with a monthly cost of ≥500 000 Japanese yen, and 80.4% of patients received treatments with a monthly cost of ≥1 million Japanese yen, of combination treatments. The cost of immune-oncology drug-based regimen was 1.2-3.1-fold that of TKI alone. CONCLUSION: To the best of our knowledge, this is the first report of a survey of first-line drug therapy in untreated Stage IV prostate cancer and renal cell carcinoma stratified by age and treatment costs. Our results show that most Japanese patients received state-of-the-art, effective treatments with high financial burden.

DOI： 10.1093/jjco/hyae045

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PURPOSE: Our aim was to develop practical training for laparoscopic surgery using Thielembalmed cadavers. Furthermore, in order to verbalize experts' motion characteristics and provide objective feedback to trainees, we initiated motion capture analyses of multiple surgical instruments simultaneously during the cadaveric trainings. In the present study, we report our preliminary results. METHODS: Participants voluntarily joined the present cadaveric simulation trainings, and performed laparoscopic radical nephrectomy. After the trainings, scores for tissue similarity (face validity) and impression of educational merit (content validity) were collected from participants based on a 5-point Likert scale (tissue similarity: 5: very similar, 3: average, 1: very different; educational merit: 5: very high, 3: average, 1: very low). In addition, after the additional IRB approval, we started motion capture (Mocap) analyses of 6 surgical instruments (scissors, vessel sealing system, grasping forceps, clip applier, right-angled forceps, and suction), using an infrared trinocular camera (120-Hz location record). Mocap-metrics were compared according to the previous surgical experiences (experts: ≧50 laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test. RESULTS: A total of 9 experts, 19 intermediates, and 15 novices participated in the present study. In terms of face validity, the mean scores were higher than 3, other than for the Vena cava(mean score of 2.89). Participants agreed with the training value (usefulness for future skill improvement: mean score of 4.57). In terms of Mocap analysis, faster speed-related metrics (e.g., velocity, the distribution of tip velocity, acceleration, and jerk) in the scissors and vessel sealing system, a shorter path length of grasping forceps, and fewer dimensionless squared jerks, which indicated more purposeful motion of 4 surgical instruments (vessel sealing system, grasping forceps, clip applier and suction), were observed in the more experienced group. CONCLUSIONS: The Thiel-embalmed cadaver provides an excellent training opportunity for complex laparoscopic procedures with participants' high level of satisfaction, and may become a promising tool for a better objective understanding of surgical dexterity. In order to enrich formative feedback to trainees, we are now proceeding with Mocap analysis.

DOI： 10.1016/j.cpsurg.2024.101559

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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BACKGROUND: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. PATIENTS AND METHODS: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. RESULTS: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71-108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. CONCLUSIONS: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.

DOI： 10.1007/s00345-024-05240-6

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BACKGROUND: Tissue handling is one of the pivotal parts of surgical procedures. We aimed to elucidate the characteristics of experts' left-hand during laparoscopic tissue dissection. METHODS: Participants performed tissue dissection around the porcine aorta. The grasping force/point of the grasping forceps were measured using custom-made sensor forceps, and the forceps location was also recorded by motion capture system (Mocap). According to the global operative assessment of laparoscopic skills (GOALS), two experts scored the recorded movies, and based on the mean scores, participants were divided into three groups: novice (<10), intermediate (10≤ to <20), and expert (≤20). Force-based metrics were compared among the three groups using the Kruskal-Wallis test. Principal component analysis (PCA) using significant metrics was also performed. RESULTS: A total of 42 trainings were successfully recorded. The statistical test revealed that novices frequently regrasped a tissue (median total number of grasps, novices: 268.0 times, intermediates: 89.5, experts: 52.0, p < 0.0001), the traction angle became stable against the aorta (median weighted standard deviation of traction angle, novices: 30.74°, intermediates: 26.80, experts: 23.75, p = 0.0285), and the grasping point moved away from the aorta according to skill competency [median percentage of grasping force applied in close zone (0 to 2.0 cm from aorta), novices: 34.96 %, intermediates: 21.61 %, experts: 10.91 %, p = 0.0032]. PCA showed that the efficiency-related (total number of grasps) and effective tissue traction-related (weighted average grasping position in Y-axis and distribution of grasping area) metrics mainly contributed to the skill difference (proportion of variance of first principal component: 60.83 %). CONCLUSION: The present results revealed experts' left-hand characteristics, including correct tissue grasping, sufficient tissue traction from the aorta, and stable traction angle. Our next challenge is the provision of immediate and visual feedback onsite after the present wet-lab training, and shortening the learning curve of trainees.

DOI： 10.1016/j.sopen.2024.08.002

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Language：Japanese   Publisher：(一社)腎癌研究会  

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BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. METHODS: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. RESULTS: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002). CONCLUSION: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC.

DOI： 10.1007/s10147-024-02538-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture–based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.

DOI： 10.1371/journal.pone.0305693

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OBJECTIVE: To achieve patient-centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross-sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan. METHODS: Surveys from 83 patients and 165 physicians were analyzed. RESULTS: The top three most significant differences in expectations of systemic therapy between patients and physicians (patient-based physician value) were "Chance of achieving treatment-free status" (-30.1%, p < 0.001), "Longer survival" (+25.8%, p < 0.001), and "Chance of eliminating all evidence of disease" (-25.6%, p < 0.001). The top three most significant differences in concerns for systemic therapy between patients and physicians (patient-based physician value) were "Lack of efficacy" (+36.1%, p < 0.001), "Lack of knowledge of treatment" (-28.2%, p < 0.001), and "Daily activities affected by side effects" (+22.3%, p < 0.001). Diarrhea, fatigue/malaise, and nausea/vomiting were patients' most distressing adverse events; 50.6% of patients had difficulty telling their physicians about adverse events such as fatigue, anxiety, and depression. CONCLUSIONS: This study demonstrated a gap between patients with mRCC and physicians in their expectations and concerns for systemic therapy. Japanese patients with mRCC suffer from a number of adverse events, some of which are not shared with physicians. This study highlights the importance of communicating well with patients in clinical practice to achieve patient-centricity in systemic treatment for mRCC.

DOI： 10.1002/cam4.7196

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Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0-36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.

DOI： 10.3390/cancers16101904

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OBJECTIVES: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy. METHODS: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. RESULTS: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. CONCLUSIONS: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies.

DOI： 10.1111/iju.15396

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New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons' workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants' names, patients' backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey®. Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36-28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59-8.70), intraoperative complications (PE + 9.26, 95% CI 6.76-11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27-5.36) were associated with higher workloads. Regarding the surgeons' role, operator under supervision (PE + 12.46, 95% CI 9.86-15.06) showed the highest workloads. Surgeons' workloads decreased as the number of previous cases of the same procedure increased. Surgeons' workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees' high workloads and devise appropriate instructional interventions.

DOI： 10.1038/s41598-024-59596-1

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OBJECTIVE: To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. RESULTS: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. CONCLUSION: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP.

DOI： 10.1111/bju.16369

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BACKGROUND: Circulating tumor DNA (ctDNA) testing has emerged as a novel tool for cancer precision medicine. This study investigated the genomic profiling and clinical utility of ctDNA in metastatic prostate cancer. METHODS: This is a nation-wide prospective observational study. Patients treated with systemic treatment for metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC) were included. ctDNA was analyzed using FoundationOne Liquid®CDx at enrollment. In a subset of patients, ctDNA after disease progression and tissue prior to the initiation of treatment were examined using FoundationOne Liquid®CDx and FoundationOne®CDx, respectively. RESULTS: The frequency of AR alterations and homologous recombination repair (HRR) defect was higher in mCRPC compared with mCSPC. Tumor mutational burden was correlated between tissue and ctDNA at pre-treatment, as well as ctDNA between at pre-treatment and at post-treatment. Patients with HRR defect were associated with shorter time to castration resistance in androgen deprivation therapy/combined androgen blockade, but not in androgen receptor pathway inhibitor, compared with patients without HRR defect in mCSPC. Time to treatment failure in patients with AR amplification or AR mutation was shorter compared with patients without AR alterations in mCRPC. CONCLUSIONS: This study revealed valuable findings for the clinical care of metastatic prostate cancer. Especially, predictive factors such as HRR defect in mCSPC should be validated in the future.

DOI： 10.1038/s44276-024-00049-7

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We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).

DOI： 10.1038/s41598-024-55251-x

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OBJECTIVES: Previous studies suggested that living kidney donors do not have a higher risk of death or kidney failure than the general population. However, living kidney donor risk is controversial. Furthermore, only a few studies have evaluated long-term kidney function after kidney donation. METHODS: This study evaluated Japanese kidney donor' long-term outcomes, including mortality and kidney function. From 1965 to 2015, 230 donors (76 males, 154 females, and a median age of 54) were enrolled in this study. The median observation period was 11.0 (range, 0.3-41.0) years. RESULTS: In total, 215 donors were still alive, and 15 had died. Causes of death included malignancies, cardiovascular disease, pneumonia, suicide, gastrointestinal bleeding, and kidney failure. Actual donor survival rates at 10, 20, and 30 years were 95.3%, 90.7%, and 80.9%, respectively. These values were comparable to age- and gender-matched expected survival. Long-term kidney function after donation was evaluated in 211 donors with serum creatinine data. Two donors developed kidney failure 24 and 26 years post-donation, respectively. The percentage of donors whose estimated glomerular filtration rate (eGFR) remained ≥45 mL/min/1.73 m2 at 10, 20, and 30 years after donation were 84.2%, 73.0%, and 63.9%, respectively. Survival rates of donors with eGFR <45 mL/min/1.73 m2 were comparable to those in persons with eGFR >45 mL/min/1.73 m2 . CONCLUSION: Our findings revealed that kidney donors did not have a higher long-term risk of death than the general population. Although some donors showed decreased kidney function after donation, kidney function did not impact their survival.

DOI： 10.1111/iju.15395

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Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

DOI： 10.1038/s41598-023-48087-4

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OBJECTIVE: Several guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette-Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette-Guérin instillation in high-risk non-muscle-invasive bladder cancer patients. METHODS: This retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette-Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality. RESULTS: In the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73-0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76-1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64-1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56-1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35-0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55-0.97, P = 0.027) on univariate analysis. CONCLUSIONS: Second transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette-Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette-Guérin instillation, and so strongly recommend second transurethral resection in this patient population.

DOI： 10.1093/jjco/hyad155

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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OBJECTIVE: To evaluate sexual function after treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 (EORTC QLQ-TC26) questionnaire in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. METHODS: This study enrolled TC survivors who visited any of eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants completed the EORTC QLQ-TC26 questionnaires. We evaluated sexual function after treatment for TC using the EORTC QLQ-TC26 and analyzed the impact of treatment on sexual function in TC survivors. RESULTS: A total of 567 TC survivors responded to the EORTC QLQ-TC26. Median age at the time of response was 43 years (interquartile range [IQR] 35-51 years), and median follow-up period after treatment was 5.2 years (IQR 2.2-10.0 years). Sexual function, particularly ejaculatory function, was significantly lower after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) than after Surveillance or Chemotherapy groups (p < 0.05). In the PC-RPLND group, nerve-sparing procedure preserved postoperative ejaculatory function after RPLND compared with the non-nerve-sparing and offered improved ejaculatory function with time. On multivariate analysis, RPLND was a significant predictor of post-treatment ejaculatory dysfunction, particularly without nerve-sparing (odds ratio 3.0, 95% CI 1.2-7.7, p < 0.05). In addition, TC survivors with nerve-sparing RPLND had higher sexual activity than those without. CONCLUSION: This survey of the EORTC QLQ-TC26 showed that sexual function and activity in TC survivors after RPLND was reduced in the absence of nerve-sparing techniques.

DOI： 10.1111/iju.15262

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OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

DOI： 10.1016/j.urolonc.2023.08.008

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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A 23-year-old male was aware of pain around his left hip joint and visited a nearby orthopedic clinic. Swelling of the right testis was pointed out, and a testicular tumor was suspected. He was referred to the urology department of a local hospital. Blood analysis showed an increase of α-fetoprotein (AFP) (3,620 ng/ml). Computed tomographic (CT) -scan revealed a left iliac bone metastasis and morbid fracture. Right radical inguinal orchiectomy was performed. The pathological examination revealed mixed germ cell tumor (embryonic carcinoma and immature teratoma: 70%, seminoma: 30%). The diagnosis was non-seminomatous germ cell tumor, stage IIIc, and poor risk on the International Germ Cell Consensus Classification. After one cycle of a bleomycin, etoposide and cisplatinum (BEP) regimen, he was referred to our hospital. After a total of 4 cycles of BEP, AFP was normalized. Denosumab was also administered monthly. The CT-scan showed a reduction of bone metastasis and recovery of ossification. Bone biopsy did not show viable tumor cells. Because extirpation of the remaining mass would require resection of the left part of the pelvic bone with significant functional loss of the left limb, we performed close follow-up after an additional 2 courses of the etoposide and cisplatin regimen. The patient is currently alive without recurrence at 45 months after the last systemic chemotherapy.

DOI： 10.14989/ActaUrolJap_69_9_259

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Language：Japanese   Publisher：医学図書出版(株)  

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INTRODUCTION: Cabozantinib monotherapy is an option for treatment of advanced renal cell carcinoma (RCC). However, cabozantinib dose modification and discontinuation due to symptomatic adverse events (AEs) remains a challenge. The use of patient-reported outcomes (PROs) may help manage symptomatic AEs, which is reported to lead to improved quality of life (QOL), avoidance of drug discontinuation and better survival. This study aims to investigate the clinical benefits of PROs in patients with RCC receiving cabozantinib and the most appropriate medium for PRO monitoring (electronic [e]-PRO or paper-PRO). METHODS AND ANALYSIS: This study is being conducted at about 35 sites in Japan. Patients aged ≥18 years with unresectable or metastatic RCC initiating treatment with cabozantinib monotherapy are eligible and will be randomised to: (1) e-PRO monitoring, (2) paper-PRO monitoring or (3) usual care without PRO monitoring. Recruitment began in December 2021 (target sample size, 105). Patients start treatment with cabozantinib 60 mg once daily, and in the PRO groups, will record daily medication intake, weight, temperature, blood pressure and AEs. Endpoints include the proportion of patients with a ≥5-point deterioration on the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-19; primary endpoint), progression-free survival, QOL, dose adjustments, relative dose intensity, treatment-emergent AEs and frequency of interventions for AEs outside of the scheduled visits. Patient and physician opinions of the PRO monitoring systems and patient compliance with e-PRO/paper-PRO input are also being measured. ETHICS AND DISSEMINATION: The study is being conducted in compliance with the Declaration of Helsinki, the International Council for Harmonisation guidelines for Good Clinical Practice and the Clinical Trials Act. Written informed consent is being obtained from all patients, and the protocol has been approved by the Hokkaido University Hospital Certified Review Board (approval number, CRB021-005). The results will be presented at conferences and submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs011210055.

DOI： 10.1136/bmjopen-2022-070275

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OBJECTIVE: To determine the impact of postoperative complications on long-term survival outcomes in patients with bladder cancer undergoing radical cystectomy. METHODS: This retrospective multi-institutional study included 766 bladder cancer patients who underwent radical cystectomy between 2011 and 2017. Patient characteristics, perioperative outcomes, all complications within 90 days after surgery and survival outcomes were collected. Each complication was graded based on the Clavien-Dindo system, and grouped using a standardized grouping method. The Comprehensive Complication Index, which incorporates all complications into a single formula weighted by their severity, was utilized. Overall survival and recurrence-free survival (local, distant or urothelial recurrences) were stratified by Comprehensive Complication Index (high: ≥26.2; low: <26.2). A multivariate model was utilized to identify independent prognostic factors. RESULTS: The incidence of any and major complications (≥Clavien-Dindo grade III) was 70 and 24%, respectively. In terms of Comprehensive Complication Index, 34% (261/766) of the patients had ≥26.2. Patients with Comprehensive Complication Index ≥ 26.2 had shorter overall survival (4-year, 59.5 vs. 69.8%, respectively, log-rank test, P = 0.0037) and recurrence free survival (51.9 vs. 60.1%, respectively, P = 0.0234), than those with Comprehensive Complication Index < 26.2. The Cox multivariate model identified the age, performance status, pT-stage, pN-stage and higher CCI (overall survival: HR = 1.35, P = 0.0174, recurrence-free survival: HR = 1.26, P = 0.0443) as independent predictors of both overall survivial and recurrence-free survival. CONCLUSIONS: Postoperative complications assessed by Comprehensive Complication Index had adverse effects on long-term survival outcomes. Physicians should be aware that major postoperative complications can adversely affect long-term disease control.

DOI： 10.1093/jjco/hyad079

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OBJECTIVES: Current prognostic models for metastatic renal cell carcinoma (mRCC) are likely inaccurate due to recent treatment advances and improved survival outcomes. The JEWEL study used a data set from patients who received tyrosine kinase inhibitors (TKIs) to explore the prognostic impact of the tumor immune environment in the absence of immune checkpoint inhibitor intervention. METHODS: The primary analysis population comprised 569 of the 770 Japanese patients enrolled in the ARCHERY study who received first-line TKIs. Multivariable Cox proportional hazard models were used to identify factors associated with the primary (overall survival [OS]) and secondary outcomes (treatment duration) using 34 candidate explanatory variables. RESULTS: Median OS was 34.1 months (95% CI, 30.4-37.6) in the primary analysis population. A considerable negative prognostic impact (descriptive p ≤ 0.0005) on OS was seen with lactate dehydrogenase (LDH) >1.5 × upper limit of normal (adjusted HR [aHR], 3.30; 95% CI, 2.19-4.98), Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (aHR, 2.14; 95% CI, 1.56-2.94), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 4 (aHR, 1.89; 95% CI, 1.43-2.51), C-reactive protein (CRP) level ≥0.3 (aHR, 1.78; 95% CI, 1.40-2.26), and age ≥75 years (aHR, 1.65; 95% CI, 1.24-2.18) in the multivariable analysis. PD-L1 and immunophenotype affected OS in univariable analyses but were not selected in the multivariable model as explanatory variables. CONCLUSIONS: JEWEL identified sex, age, ECOG PS, liver and bone metastases, CRP levels, WHO/ISUP grade, LDH, and albumin levels as key prognostic factors for OS after first-line TKI therapy for mRCC.

DOI： 10.1111/iju.15244

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New clinical issues have been raised through an interval of 7 years from the previous version (2016). In this study, we update the "Clinical Practice Guidelines for tuberous sclerosis complex-associated renal angiomyolipoma" as a 2023 version under guidance by the Japanese Urological Association. The present guidelines were cooperatively prepared by the Japanese Urological Association and Japanese Society of Tuberous Sclerosis Complex; committee members belonging to one of the two societies or specializing in the treatment of this disease were selected to prepare the guidelines in accordance with the "Guidance for preparing treatment guidelines" published by Minds (2020 version). The "Introduction" consisted of four sections, "Background Questions (BQ)" consisted of four sections, "Clinical Questions (CQ)" consisted of three sections, and "Future Questions (FQ)" consisted of three sections (total: 14 sections). Concerning CQ, an agreement was confirmed through voting by the committee members based on the direction and strength of recommendation, accuracy of evidence, and recommendation comments. The present guidelines were updated based on the current evidence. We hope that the guidelines will provide guiding principles for the treatment of tuberous sclerosis complex-associated renal angiomyolipoma to many urologists, becoming a foundation for subsequent updating.

DOI： 10.1111/iju.15213

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BACKGROUND: Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment. METHODS: CONTACT-03 was a multicentre, randomised, open-label, phase 3 trial, done in 135 study sites in 15 countries in Asia, Europe, North America, and South America. Patients aged 18 years or older with locally advanced or metastatic renal cell carcinoma whose disease had progressed with immune checkpoint inhibitors were randomly assigned (1:1) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus cabozantinib (60 mg orally once daily) or cabozantinib alone. Randomisation was done through an interactive voice-response or web-response system in permuted blocks (block size four) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk group, line of previous immune checkpoint inhibitor therapy, and renal cell carcinoma histology. The two primary endpoints were progression-free survival per blinded independent central review and overall survival. The primary endpoints were assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT04338269, and is closed to further accrual. FINDINGS: From July 28, 2020, to Dec 27, 2021, 692 patients were screened for eligibility, 522 of whom were assigned to receive atezolizumab-cabozantinib (263 patients) or cabozantinib (259 patients). 401 (77%) patients were male and 121 (23%) patients were female. At data cutoff (Jan 3, 2023), median follow-up was 15·2 months (IQR 10·7-19·3). 171 (65%) patients receiving atezolizumab-cabozantinib and 166 (64%) patients receiving cabozantinib had disease progression per central review or died. Median progression-free survival was 10·6 months (95% CI 9·8-12·3) with atezolizumab-cabozantinib and 10·8 months (10·0-12·5) with cabozantinib (hazard ratio [HR] for disease progression or death 1·03 [95% CI 0·83-1·28]; p=0·78). 89 (34%) patients in the atezolizumab-cabozantinib group and 87 (34%) in the cabozantinib group died. Median overall survival was 25·7 months (95% CI 21·5-not evaluable) with atezolizumab-cabozantinib and was not evaluable (21·1-not evaluable) with cabozantinib (HR for death 0·94 [95% CI 0·70-1·27]; p=0·69). Serious adverse events occurred in 126 (48%) of 262 patients treated with atezolizumab-cabozantinib and 84 (33%) of 256 patients treated with cabozantinib; adverse events leading to death occurred in 17 (6%) patients in the atezolizumab-cabozantinib group and nine (4%) in the cabozantinib group. INTERPRETATION: The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials. FUNDING: F Hoffmann-La Roche and Exelixis.

DOI： 10.1016/S0140-6736(23)00922-4

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OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.

DOI： 10.1111/iju.15206

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Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

DOI： 10.1111/cas.15837

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：日本老年泌尿器科学会  

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Language：Japanese   Publisher：(公社)日本医学放射線学会  

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BACKGROUND: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. METHODS: Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. RESULTS: In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. CONCLUSIONS: Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.

DOI： 10.1007/s10147-022-02283-w

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DOI： 10.4322/acr.2023.433

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AIMS: The treatment landscape of renal cell carcinoma has changed with the introduction of targeted therapies. While the clinical benefit of cabozantinib is well-established for Japanese patients who have received prior treatment, the economic benefit remains unclear. The objective of this study was to assess the cost-effectiveness of cabozantinib compared with everolimus, axitinib, and nivolumab in patients with advanced renal cell carcinoma who have failed at least one prior therapy in Japan. METHODS: A cost-effectiveness model was developed using a partitioned survival approach and a public healthcare payer's perspective. Over a lifetime horizon, clinical and economic implications were estimated according to a three-health-state structure: progression-free, post-progression, and death. Key clinical inputs and utilities were derived from the METEOR trial, and a de novo network meta-analysis and cost data were obtained from publicly available Japanese data sources. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were estimated. Costs and health benefits were discounted annually at 2%. RESULTS: Cabozantinib was more costly and effective compared with everolimus and axitinib, with deterministic incremental cost-effectiveness ratios of \5,375,559 and \2,223,138, respectively. Compared to nivolumab, cabozantinib was predicted to be less costly and more effective. Sensitivity and scenario analyses demonstrated that the key drivers of cost-effectiveness results were the estimation of overall survival and treatment duration, relative efficacy, drug costs, and subsequent treatment costs. LIMITATIONS: METEOR was an international trial but did not enroll any patients from Japan. Efficacy and safety data from METEOR were used as a proxy for the Japanese population following validation by clinical experts, and alternative assumptions specific to clinical practice in Japan were evaluated in scenario analyses. CONCLUSIONS: In Japan, cabozantinib is a cost-effective alternative to everolimus, axitinib, and nivolumab for the treatment of patients with advanced renal cell carcinoma who have received at least one prior line of therapy.

DOI： 10.1080/13696998.2023.2242197

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Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/SII55687.2023.10039340

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Other Link： https://dblp.uni-trier.de/db/conf/sii/sii2023.html#EbinaAHHFIKKKKMOMTSCSK23

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The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

DOI： 10.1038/s41598-022-25669-2

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BACKGROUND: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. METHODS: Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. EXPECTED OUTCOME: Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. TRIAL REGISTRATION: The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.

DOI： 10.1186/s12885-022-10398-6

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OBJECTIVES: Most testicular cancer (TC) survivors have long-term survival. However, the association between financial toxicity (FT), which is an economic side effect of cancer treatment, and the quality of life (QOL) of TC survivors is still unclear. Thus, the impact of FT on the QOL of TC survivors was examined in a multi-institutional cross-sectional study. METHODS: We recruited TC survivors from eight high-volume institutions in Japan between January 2018 and March 2019. A total of 562 participants completed the EORTC QLQ-C30, EORTC QLQ-TC26 and the questionnaires on demographics, including annual income. Financial difficulty in the EORTC QLQ-C30 and low income were used to assess financial distress (FD) and financial burden (FB), respectively. FT was defined as FD and FB. The QOL scores were compared, and a multivariate logistic regression analysis for FT was performed. RESULTS: With severe FD, TC survivors had more treatment side effects, physical limitations, and anxiety concerning employment and future. The TC survivors who reported low income were worried about their jobs and the future. The QOL of the survivors with FT exhibited high impairment, except for sexual activity. In particular, the TC survivors with FT were physically limited and anxious concerning the future. The multivariate logistic regression analysis revealed that four or more chemotherapy cycles were substantial risk factors for FT (4 cycles, odds ratio (OR) = 4.17; ≥5 cycles, OR = 6.96). CONCLUSIONS: TC survivors who received multi-cycle chemotherapy were prone to experience FT, resulting in a decline in their health-related QOL.

DOI： 10.1111/iju.15039

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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OBJECTIVES: This study analyzes the relationship between biglycan expression in prostate cancer and clinicopathological parameters to clarify the potential link between biglycan and prognosis and progression to castration-resistant prostate cancer (CRPC). METHODS: We retrospectively analyzed 60 cases of prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy in Hokkaido University Hospital. RESULTS: Biglycan was expressed in the tumor stroma but not in tumor cells. There was no significant relationship with biochemical recurrence (p = 0.5237), but the expression of biglycan was 36.1% in the group with progression to CRPC. This indicates a significant relationship with progression to CRPC (p = 0.0182). Furthermore, the expression of biglycan-positive blood vessels was significantly higher (15.9%) in the group with biochemical recurrence than in the group without biochemical recurrence (8.5%) (p = 0.0169). The biglycan-positive vessels were 28.6% in the group with progression to CRPC, which was significantly higher than that in the group without progression to CRPC (p < 0.0001). CONCLUSION: This is the first study to show that stroma biglycan is a useful prognostic factor for prostate cancer.

DOI： 10.1111/iju.15080

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis.

DOI： 10.1016/j.pathol.2022.07.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

INTRODUCTION: We report a case of laparoscopic adrenalectomy in a salvage setting after multiple chemotherapies for neuroendocrine carcinoma. CASE PRESENTATION: A 49-year-old man was diagnosed with unknown primary carcinoma with single brain metastasis, and right supraclavicular and mediastinal lymph node metastases. After stereotactic radiotherapy of the brain metastasis and systemic chemotherapy, lymphadanectomy was performed. The pathologic diagnosis was neuroendocrine carcinoma. At 11 months after surgery, computed tomography revealed right adrenal metastasis. Local radiotherapy initially resulted in complete remission. However, adrenal recurrence was noted 10 months later. Laparoscopic adrenalectomy was performed with curative intent. The patient is currently alive without recurrence at 20 months after the operation. CONCLUSION: Adrenalectomy can become a treatment option if other metastases are well-controlled with systemic therapy. Surgical elimination of oligometastases can offer long-term disease control in selected patients as part of a multimodal approach.

DOI： 10.1002/iju5.12511

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/iju5.12511

Language：English   Publisher：Japanese Council of IFToMM  

This paper describes details of the development of skill evaluation system for laparoscopic surgical procedure. The measurement experiment was conducted for 70 surgeons, and the participants perform 2 tasks: tissue dissection around the aorta and renal parenchymal suturing/knotting using porcine cadaver. In the experiments, the movement of surgical instruments were recorded by motion capture (MoCap) system, and the motion indices were calculated. The participants grouped into three classes (novices, intermediates, and experts) according to their level of experience. Three classification algorithms: support vector machine (SVM), principal component based SVM (PCA-SVM), gradient boosting decision tree (GBDT) were utilized for developing the model of classifier. The accuracy of each model was assessed by nested and repeated k-fold cross validation. Regarding 3-class classification, the GBDT method resulted highest accuracy (the median of the accuracy is A_med = 68.6 %) in the dissection tasks. In the suturing/knotting tasks, PCA-SVM resulted highest accuracy (A_med = 58.4 %). Regarding 2-class classification (experts vs. intermediates/novices), the GBDT method resulted A_med = 72.9 % in the dissection task, and the PCA-SVM method resulted A_med = 69.2 % in the suturing task. This result shows the MoCap based skill evaluation system in wet-lab training could be a practical way to objectively assess trainees' surgical competence.

DOI： 10.57272/jciftomm.5.0_73

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A 62-year-old woman presented with a tumor in the right kidney. A right partial nephrectomy was performed, and the tumor was diagnosed as clear cell renal cell carcinoma (RCC) on histopathological examination. A right ovarian tumor was detected on follow-up computed tomography (CT) 5 years after partial nephrectomy and pathology proved RCC metastasis. RCC rarely metastasizes to the ovaries. There is limited information on the radiological features of ovarian metastasis in RCC. In this case report, we presented the CT and magnetic resonance images of ovarian metastasis of RCC. In addition, we also presented a literature review with special emphasis on the imaging features of ovarian metastasis of RCC.

DOI： 10.1016/j.radcr.2022.03.110

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OBJECTIVES: There is no consensus about the follow-up schedule after 5-year cancer-free periods. In this study, we aimed to elucidate the risk factors for the recurrence in patients with non-muscle-invasive bladder cancer who remained cancer free for more than 5 years. METHODS: Data from six Japanese institutions were retrospectively reviewed. Among the patients with non-muscle-invasive bladder cancer who were treated with transurethral resection of bladder tumor between 1990 and 2013, those who had no recurrence for more than 5 years were included in this study. The Kaplan-Meier method and Cox hazards model were used to estimate recurrence-free survival and to determine the pathologic and clinical factors affecting late recurrence. RESULTS: In total, 434 patients were enrolled in this study. Of these patients, 55 patients (12.7%) experienced late recurrence. The median follow-up time was 8.9 years (interquartile range 6.9-11.3 years). Prior history of bladder cancer before the most recent transurethral resection was a significant predictor for late recurrence (hazard ratio 1.99 [95% confidence interval 1.13-3.47], P = 0.019), although other clinical factors including tumor grade, pathologic stage, tumor multiplicity, and current risk classification systems were not associated with late recurrence. CONCLUSIONS: Late recurrence after a long tumor-free period is not rare and it was not predicted by current risk classification systems. Only prior history of bladder cancer was a significant predictor for late recurrence in this study.

DOI： 10.1111/iju.14936

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The rapidly increasing pool of older patients being diagnosed with and surviving their cancer is creating many challenges. Regarding localized renal cell carcinoma, surgery is considered as gold standard treatment options even in older men, whereas active surveillance and ablation therapy are alternative options for a proportion of these patients. With regard to advanced disease, anti-vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) and immune check point inhibitor are standard treatment modalities, although treatment choice from multiple regimens and prevention of adverse events need to be considered. Better assessment techniques, such as comprehensive geriatric assessment to meet the unique needs of older patients, are a central focus in the delivery of high-quality geriatric oncology care. Through this process, shared decision-making should be adopted in clinical care to achieve optimal goals of care that reflect patient and caregiver hopes, needs and preferences. It is necessary to continue investigating oncological outcomes and complications associated with treatment in this population to ensure appropriate cancer care. In this narrative review, we completed a literature review of the various treatments for renal cell carcinoma in older patients that aimed to identify the current evidence related to the full range of the treatments including active surveillance, surgery, ablation therapy and systemic therapy. Prospectively designed studies and studies regarding geriatric assessment were preferentially added as references. Our goals were to summarize the real-world evidence and provide a decision framework that guides better cancer practices for older patients with renal cell carcinoma.

DOI： 10.1093/jjco/hyac047

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BACKGROUND: Our aim was to build a skill assessment system, providing objective feedback to trainees based on the motion metrics of laparoscopic surgical instruments. METHODS: Participants performed tissue dissection around the aorta (tissue dissection task) and renal parenchymal closure (parenchymal-suturing task), using swine organs in a box trainer under a motion capture (Mocap) system. Two experts assessed the recorded movies, according to the formula of global operative assessment of laparoscopic skills (GOALS: score range, 5-25), and the mean scores were utilized as objective variables in the regression analyses. The correlations between mean GOALS scores and Mocap metrics were evaluated, and potential Mocap metrics with a Spearman's rank correlation coefficient value exceeding 0.4 were selected for each GOALS item estimation. Four regression algorithms, support vector regression (SVR), principal component analysis (PCA)-SVR, ridge regression, and partial least squares regression, were utilized for automatic GOALS estimation. Model validation was conducted by nested and repeated k-fold cross validation, and the mean absolute error (MAE) was calculated to evaluate the accuracy of each regression model. RESULTS: Forty-five urologic, 9 gastroenterological, and 3 gynecologic surgeons, 4 junior residents, and 9 medical students participated in the training. In both tasks, a positive correlation was observed between the speed-related parameters (e.g., velocity, velocity range, acceleration, jerk) and mean GOALS scores, with a negative correlation between the efficiency-related parameters (e.g., task time, path length, number of opening/closing operations) and mean GOALS scores. Among the 4 algorithms, SVR showed the highest accuracy in the tissue dissection task ([Formula: see text]), and PCA-SVR in the parenchymal-suturing task ([Formula: see text]), based on 100 iterations of the validation process of automatic GOALS estimation. CONCLUSION: We developed a machine learning-based GOALS scoring system in wet lab training, with an error of approximately 1-2 points for the total score, and motion metrics that were explainable to trainees. Our future challenges are the further improvement of onsite GOALS feedback, exploring the educational benefit of our model and building an efficient training program.

DOI： 10.1007/s00423-022-02505-9

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Introduction: Granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma is rare, with a poor prognosis. Advanced urothelial carcinoma is currently treated with immune checkpoint inhibitors, whose efficacy for granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma remains unclear. Case presentation: A 66-year-old male diagnosed with clinical stage T3N1M0 urothelial carcinoma of the right ureter with giant hydronephrosis underwent right radical nephroureterectomy. Local recurrence, leukocytosis, and elevated serum granulocyte colony-stimulating factor levels were observed approximately 3 months after surgery. Chemotherapy was started but failed to control the disease. Therefore, pembrolizumab was chosen as the second-line treatment. After this treatment, the blood leukocyte count rapidly normalized, and a clinically favorable response was achieved. There was no recurrence 10 months after the beginning of pembrolizumab treatment, which is still ongoing. Conclusion: Pembrolizumab may be a treatment option for advanced granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma.

DOI： 10.1002/iju5.12406

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OBJECTIVES: We examined the outcomes of eight weekly bacillus Calmette-Guérin induction therapy after second transurethral resection, and investigated risk factors for intravesical recurrence or disease progression in high-risk non-muscle-invasive bladder cancer patients. METHODS: This retrospective study included 146 high-risk non-muscle-invasive bladder cancer patients who received eight weekly bacillus Calmette-Guérin instillations without a maintenance schedule between 2000 and 2019. Intravesical recurrence-free and progression-free survival rates were evaluated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify risk factors. RESULTS: Pathological T staging in the first transurethral resection was pTa in 56 patients (38.4%), pT1 in 75 (51.4%) and primary carcinoma in situ in 15 (10.2%). A total of 109 (83.2%) with pTa-1 disease underwent second transurethral resection before bacillus Calmette-Guérin induction therapy, and residual disease was detected in 54 (49.5%). The completion rate of eight instillations was 82.2%. The 2- and 5-year intravesical recurrence-free survival rates were 80.7% and 75.2%, whereas the 2- and 5-year progression-free survival rates were 85.7% and 82.0%. Recurrent tumors (hazard ratio 6.5830, P = 0.0007) and residual tumors at the second transurethral resection (hazard ratio 4.0337, P = 0.0021) were risk factors for intravesical recurrence. Multiple tumors (hazard ratio 5.8056, P = 0.0302), pT1 disease (hazard ratio 3.7351, P = 0.0447) and residual tumors at second transurethral resection (hazard ratio 3.2552, P = 0.0448) were associated with disease progression. CONCLUSIONS: Accurate disease staging and disease elimination by second transurethral resection followed by eight weekly bacillus Calmette-Guérin instillations achieved good disease control. Our protocol (without a maintenance schedule) after thorough surgical resection has potential as a treatment option in the current bacillus Calmette-Guérin shortage.

DOI： 10.1111/iju.14761

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Language：Japanese  

A 57-year-old man visited the urology department with a painful mass on the dorsal side of the penis. Magnetic resonance imaging sagittal image showed a small nodule. Leukemia recurrence was suspected due to his history of treatment for acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation. No recurrence was identified by bone marrow biopsy ; however, two months later, the recurrence of leukemia was strongly suspected because the tumor grew over time and blasts were found in the peripheral blood. A biopsy of the penile tumor and bone marrow was performed, leading to the diagnosis of granulocytic sarcoma. Patients with a history of leukemia may be preceded by a single recurrence to extramedullary organs, even if blood and bone marrow findings suggest remission.

DOI： 10.14989/ActaUrolJap_68_2_63

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OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.

DOI： 10.1111/iju.14793

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Language：Japanese  

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DOI： 10.3390/uro2010004

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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OBJECTIVES: With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. METHODS AND MATERIALS: We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. RESULTS: The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391). CONCLUSIONS: Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints.

DOI： 10.1016/j.urolonc.2021.09.014

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OBJECTIVES: During the past 2 decades, in order to improve perioperative and oncological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. MATERIALS AND METHODS: A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. RESULTS: A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. CONCLUSIONS: Surgical complications related to RC still remain significant problems, despite the recent improvements in surgical techniques and perioperative care. NAC did not increase the complications.

DOI： 10.1016/j.urolonc.2021.09.005

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Introduction: We report a rare case of primary renal leiomyosarcoma with a tumor thrombus in the inferior vena cava. Case presentation: A 54-year-old woman presented with right flank pain and abdominal distension. Physical examination findings were unremarkable. Abdominal computed tomography revealed a heterogeneously enhancing right solid renal mass with a thrombus in the renal vein extending into the inferior vena cava. Magnetic resonance imaging demonstrated a renal tumor with a thrombus about 4 cm below the hepatic vein. Chest computed tomography and bone scintigraphy were negative. The patient underwent right radical nephrectomy and vena cava thrombectomy. Histophathologic evaluation of the resected tumor confirmed the diagnosis of leiomyosarcoma. She underwent no adjuvant therapy. Seven months after surgery, the patient died following a 2-month history of multiple pulmonary and hepatic metastases. Conclusion: This report highlights the importance of considering the possibility of renal leiomyosarcoma invasion to the inferior vena cava, similar to renal cell carcinoma.

DOI： 10.1002/iju5.12396

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BACKGROUND: The quality of transurethral resection of bladder tumor (TURBT) markedly varies among surgeons and may have a considerable impact on treatment outcomes. The importance of a surgical checklist for TURBT has been suggested in order to standardize the procedure and improve surgical and oncological outcomes. In the present study, we verified the usefulness of a checklist for managing patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: This retrospective study included 201 NMIBC patients diagnosed with Ta, T1, or Tis between October 2011 and February 2021. After September 2016, TURBT was performed with a checklist. We analyzed the intravesical recurrence-free survival (RFS) rate and the presence or absence of the detrusor muscle in resected specimens before and after the introduction of the checklist. Survival rates were compared using the Log-rank test. A multivariate analysis with Cox proportional hazards modeling was performed to verify risk factors for intravesical recurrence. RESULTS: Ninety-nine patients who underwent TURBT with the checklist (checklist group) were compared with 102 patients who underwent TURBT without the checklist (non-checklist group). When the analysis was narrowed down to 9 critical items, we observed a mean number of 9 documented items per operative report (98.0% completion) after implementation of the checklist. Two-year intravesical RFS rates in the checklist and non-checklist groups were 76.7 and 69.5%, respectively (p = 0.1059). The Cox proportional multivariate analysis showed that the rate of intravesical recurrence was slightly lower in the checklist group (hazard ratio 0.7376, 95% CI 0.4064-1.3388, P = 0.3170). CONCLUSION: The introduction of a checklist is recommended for the standardization of TURBT and increasing the quality of operative reporting, and it may also improve oncological outcomes.

DOI： 10.1371/journal.pone.0276816

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We report a case of bladder cancer in a 54-year-old woman who underwent renal transplantation for chronic renal failure. Six years after the transplantation, she was diagnosed with muscle-invasive bladder cancer with multiple lung metastases. She received gemcitabine/cisplatin therapy for Stage IV bladder cancer, and the dose of the immunosuppressants was reduced to prevent adverse effects. Since lung metastatic lesions disappeared after four courses of chemotherapy and no new lesions were found, we performed radical cystectomy and right nephroureterectomy with ileal conduit construction. Although she was followed closely without therapy, multiple lung metastases appeared 6 months after the radical cystectomy. Gemcitabine/carboplatin therapy was administered, and the lung metastasis improved slightly until the end of the 4th course, but aggressive growth was observed after the 5th course. She switched to palliative treatment without requesting additional treatment and died of cancer 1 year and 9 months after total cystectomy.There is no evidence-based treatment strategy for advanced bladder cancer after kidney transplantation. It is necessary to recognize that the patient had renal dysfunction and was in an immunosuppressed state. Thus, it is crucial to select appropriate drug and surgical treatments for each patient.

DOI： 10.5980/jpnjurol.113.37

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The purpose of this study was to characterize the motion features of surgical devices associated with laparoscopic surgical competency and build an automatic skill-credential system in porcine cadaver organ simulation training. Participants performed tissue dissection around the aorta, dividing vascular pedicles after applying Hem-o-lok (tissue dissection task) and parenchymal closure of the kidney (suturing task). Movements of surgical devices were tracked by a motion capture (Mocap) system, and Mocap-metrics were compared according to the level of surgical experience (experts: ≥50 laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test and principal component analysis (PCA). Three machine-learning algorithms: support vector machine (SVM), PCA-SVM, and gradient boosting decision tree (GBDT), were utilized for discrimination of the surgical experience level. The accuracy of each model was evaluated by nested and repeated k-fold cross-validation. A total of 32 experts, 18 intermediates, and 20 novices participated in the present study. PCA revealed that efficiency-related metrics (e.g., path length) significantly contributed to PC 1 in both tasks. Regarding PC 2, speed-related metrics (e.g., velocity, acceleration, jerk) of right-hand devices largely contributed to the tissue dissection task, while those of left-hand devices did in the suturing task. Regarding the three-group discrimination, in the tissue dissection task, the GBDT method was superior to the other methods (median accuracy: 68.6%). In the suturing task, SVM and PCA-SVM methods were superior to the GBDT method (57.4 and 58.4%, respectively). Regarding the two-group discrimination (experts vs. intermediates/novices), the GBDT method resulted in a median accuracy of 72.9% in the tissue dissection task, and, in the suturing task, the PCA-SVM method resulted in a median accuracy of 69.2%. Overall, the mocap-based credential system using machine-learning classifiers provides a correct judgment rate of around 70% (two-group discrimination). Together with motion analysis and wet-lab training, simulation training could be a practical method for objectively assessing the surgical competence of trainees.

DOI： 10.1371/journal.pone.0277105

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BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly being used to treat malignancies. Some patients experience immune-related adverse events (irAEs), which may affect any organ/tissue. IrAEs are occasionally fatal and usually have nonspecific symptoms. We developed a three-step application (https://irae-search.com/) to provide healthcare professionals with information on the diagnosis, treatment options, and published reports for 38 categories of irAEs encountered in clinical practice. METHODS: IrAEs reported in ≥5 cases were identified from articles published between October 2018 and August 2020 by searching Japanese (SELIMIC, JAPIC-Q Service, and JMED Plus) and international (MEDLINE, EMBASE, Derwent Drug File) databases. The cases' symptoms were entered into the application to identify irAEs, which were verified using the reported diagnosis, to evaluate the application's sensitivity and specificity. RESULTS: Overall, 1209 cases (1067 reports) were analyzed. The three most common categories of irAEs were pituitary or adrenal disorders (14% of cases), skin disorders (13%), and diabetes mellitus (10%). The top three primary diseases were lung cancer (364 cases), melanoma (286 cases), and renal cell carcinoma (218 cases). The average sensitivity was 90.8% (range 44.4%-100.0%) initially, and improved to 94.8% (range 83.3%-100.0%) after incorporating the symptoms reported in published cases into the application's logic for two irAE categories. The average specificity was 79.3% (range 59.1% [thyroid disorders]-98.2% [arthritis]). CONCLUSION: irAE Search is an easy-to-use application designed to help healthcare professionals identify potential irAEs in ICI-treated patients in a timely manner to facilitate prompt management/treatment. The application showed high sensitivity and moderate-to-high specificity for detecting irAEs.

DOI： 10.1371/journal.pone.0265230

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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OBJECTIVE: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment. CONCLUSIONS: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.

DOI： 10.1111/iju.14645

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Introduction: Thyroid storm is a rare life-threating condition. We report a case of thyroid storm after radical nephrectomy for renal cell carcinoma with inferior vena cava tumor thrombus. Case presentation: A 76-year-old man with a left renal tumor and tumor thrombus extending into the inferior vena cava underwent left radical nephrectomy and thrombectomy. After the surgery, his postoperative course rapidly deteriorated, including central nervous system disturbance, fever, tachycardia, congestive heart failure, and hepatic manifestation. Thyroid function test revealed perioperative hyperthyroidism. Corticosteroids and inorganic iodide improved his condition, suggesting that he developed thyroid storm after surgery. He was discharged 5 months after surgery and has been free from disease recurrence for more than 2 years. Conclusion: Thyroid storm after surgery is rare. However, this postoperative complication is important because it is fatal if not diagnosed and treated properly.

DOI： 10.1002/iju5.12341

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Language：Japanese   Publisher：(一社)日本移植学会  

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DOI： 10.1007/s00464-020-08038-w

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BACKGROUND: Our aim was to characterize the motions of multiple laparoscopic surgical instruments among participants with different levels of surgical experience in a series of wet-lab training drills, in which participants need to perform a range of surgical procedures including grasping tissue, tissue traction and dissection, applying a Hem-o-lok clip, and suturing/knotting, and digitize the level of surgical competency. METHODS: Participants performed tissue dissection around the aorta, dividing encountered vessels after applying a Hem-o-lok (Task 1), and renal parenchymal closure (Task 2: suturing, Task 3: suturing and knot-tying), using swine cadaveric organs placed in a box trainer under a motion capture (Mocap) system. Motion-related metrics were compared according to participants' level of surgical experience (experts: 50 ≤ laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test, and significant metrics were subjected to principal component analysis (PCA). RESULTS: A total of 15 experts, 12 intermediates, and 18 novices participated in the training. In Task 1, a shorter path length and faster velocity/acceleration/jerk were observed using both scissors and a Hem-o-lok applier in the experts, and Hem-o-lok-related metrics markedly contributed to the 1st principal component on PCA analysis, followed by scissors-related metrics. Higher-level skills including a shorter path length and faster velocity were observed in both hands of the experts also in tasks 2 and 3. Sub-analysis showed that, in experts with 100 ≤  cases, scissors moved more frequently in the "close zone (0  ≤ to < 2.0 cm from aorta)" than those with 50-99 cases. CONCLUSION: Our novel Mocap system recognized significant differences in several metrics in multiple instruments according to the level of surgical experience. "Applying a Hem-o-lok clip on a pedicle" strongly reflected the level of surgical experience, and zone-metrics may be a promising tool to assess surgical expertise. Our next challenge is to give completely objective feedback to trainees on-site in the wet-lab.

DOI： 10.1007/s00464-020-07940-7

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The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.

DOI： 10.1111/cas.15038

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DOI： 10.1016/j.jgo.2020.12.012

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PURPOSE: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. PATIENTS AND METHODS: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. RESULTS: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. CONCLUSIONS: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.

DOI： 10.1093/jjco/hyaa264

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Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.

DOI： 10.1111/cas.14722

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OBJECTIVE: To evaluate the health-related quality of life (QOL) of testicular cancer (TC) survivors using the Japanese version of the EORTC QLQ-TC26 questionnaire in a multi-institutional, cross-sectional study. METHODS: This study recruited TC survivors who were followed after treatment for TC at eight high-volume institutions between January, 2018 and March, 2019. The participants completed the EORTC QLQ-TC26 questionnaire and mailed the completed questionnaires to a central institution. The QOL scores were assessed according to therapeutic modality (watchful waiting, WW; chemotherapy, CT; and CT followed by retroperitoneal lymph node dissection, CT+RPLND) and follow-up period and compared using analysis of variance and Student's t-test. RESULTS: A total of 567 TC survivors responded to the questionnaire. The median age at response was 43 years (IQR 35-51 years), and the median follow-up was 5.2 years (IQR 2.2-10.0 years). As for treatment side effects and physical limitations, the scores of the CT+RPLND group were significantly higher than those of the WW group, especially within one year after treatment. In addition, TC survivors in the CT+RPLND group reported high impairment related to job and education problems and future perspective less than 5 years after treatment. Even TC survivors in the WW group were anxious about job and education issues within one year after treatment. CONCLUSION: TC survivors were anxious about not only cancer recurrence, but also their jobs and education. TC patients should be given appropriate information on QOL after treatment for TC to attenuate post-treatment anxiety and improve their health-related QOL.

DOI： 10.1016/j.urology.2021.02.039

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OBJECTIVE: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors. METHODS: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated. RESULTS: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains. CONCLUSIONS: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.

DOI： 10.1111/iju.14422

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：British Institute of Radiology  

<sec><title>Objectives:</title> The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer.

</sec><sec><title>Methods:</title> A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV.

</sec><sec><title>Results:</title> The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years.

</sec><sec><title>Conclusions:</title> Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated.

</sec><sec><title>Advances in knowledge:</title> Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.

</sec>

DOI： 10.1259/bjro.20210064

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DOI： 10.3233/BLC-200359

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A woman with a diagnosis of tuberous sclerosis complex (TSC) presented with TSC2 gene mutation and various manifestations, including epilepsy, renal angiomyolipomas (AML), and pathologically confirmed multifocal micronodular pneumocyte hyperplasia (MMPH). With oral administration of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, MMPH and AML were markedly reduced. Further, after starting treatment with everolimus, serum levels of surfactant protein (SP)-A and SP-D, which reflect type II pneumocyte hyperplasia, decreased to the normal range. At the time of writing of this manuscript, 6 years after starting everolimus, MMPH lesions did not relapse and SP-A/D remained the low levels. This is the first case of everolimus efficacy shown for histologically confirmed MMPH in genetically determined TSC patient, with time course of serum SP-A and SP-D.

DOI： 10.1016/j.rmcr.2021.101526

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OBJECTIVES: This study investigated the relapse pattern and oncologic outcomes after laparoscopic nephroureterectomy with template-based lymph node dissection (LND) in patients with clinically node-negative (cN0) upper urinary tract urothelial carcinoma. The frequency of lymph node metastasis, including micrometastases, was also evaluated. METHODS AND MATERIALS: A total of 105 patients with cTa-3N0M0 upper urinary tract urothelial carcinoma were analyzed, all of whom underwent regional LND during laparoscopic nephroureterectomy. Of those patients, 96 (91%) underwent complete LND in accordance with an anatomical template-based rule. We collected patient characteristics, pathological data, and follow-up data from medical charts. Micrometastases were assessed by pan-cytokeratin immunohistochemistry. Nonurothelial recurrence-free survival and cancer-specific survival were estimated using the Kaplan-Meier method. RESULTS: The median number of lymph nodes removed was 12 (range, 1-59). Lymph node metastasis was identified by routine pathological examination in 7 (7/105, 6.7%) patients. Pan-cytokeratin immunohistochemistry revealed micrometastases in 5 additional patients (pNmicro +: 5/105, 4.8%). Nonurothelial disease recurrence was observed in 21 (20%) patients at a median of 10 months (range: 1-33) after surgery. Distant metastasis was dominant (15/105, 14.3%), followed by locoregional recurrence (5/105, 4.8%) and both (1/105, 0.95%). The 5-year nonurothelial recurrence-free survival rates were 84.8% for pN0, 53.3% for pNmicro+, and 19.1% for pN+ (3-sample log-rank test, P < 0.0001). The 5-year cancer-specific survival rates were 95.0% for pN0, 53.3% for pNmicro+, and 23.8% for pN+ (P < 0.0001). CONCLUSIONS: Our observation showed that template-based LND could contribute to precise disease staging and better local disease control probably by eliminating nodal disease, compared with previous studies. The survival impact and ideal management of pNmicro+ disease should be evaluated in a larger cohort.

DOI： 10.1016/j.urolonc.2020.05.013

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INTRODUCTION: We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. METHODS: The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. RESULTS: This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12-66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach's alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = - 0.19). A missing value percentage of > 15% was associated with old age (p < 0.05). The mean domain scores differed significantly among distinct clinically relevant treatment groups. CONCLUSIONS: Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

DOI： 10.1007/s10147-020-01770-2

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OBJECTIVES: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy. METHODS: This phase II, open-label, single-arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end-point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end-points included clinical benefit rate (complete or partial response, or ≥8-week stable disease), progression-free survival, overall survival and safety. RESULTS: Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1-43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8-34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7-95.2%). The 6-month estimated progression-free survival was 72.3% (95% confidence interval 53.3-84.6%); the median progression-free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events. CONCLUSIONS: The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.

DOI： 10.1111/iju.14329

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Objectives: To evaluate the association between the use of local radiotherapy (RT) with the survival of patients with de novo metastatic prostate cancer and symptomatic local events (SLEs). Patients and methods: Patients were initially diagnosed with metastatic prostate cancer between 2008 and 2017 at 30 institutes in Japan. Prostate-specific antigen (PSA) progression-free survival (PSA-PFS) under initial androgen deprivation therapy and overall survival (OS) was compared between patients receiving local RT (RT group) and no RT (no-RT group) by multivariate Cox proportional hazard analyses. The occurrence rate of grade ≥2 SLEs was compared by multivariate logistic regression analyses. Propensity score matching (PSM) analyses were performed to compare PSA-PFS and OS of the groups in the high and low metastatic burden cohort. Results: Two hundred and five (7%) of 2829 patients received RT before PSA progression. Median PSA-PFS and OS were significantly longer in the RT group than in the no-RT group and the difference was significant in multivariate analyses (HR = 0.44, 95% CI = 0.33-0.57 and HR = 0.40, 95% CI = 0.27-0.60, respectively). The occurrence rate of grade ≥2 SLEs was significantly lower in the RT group (2%) than the no-RT group (9%) and the difference was significant in multivariate analyses (HR = 0.28, 95% CI = 0.10-0.76). Using PSM analyses, PSA-PFS and OS remained significantly different (HR = 0.64, 95% CI = 0.46-0.89 and HR = 0.47, 95% CI = 0.30-0.72, respectively), between the RT (n = 182) and the no-RT (n = 182) groups. The difference in OS was significant in the high metastatic burden cohort (HR = 0.55, 95% CI = 0.37-0.81). Conclusions: Addition of local RT to standard treatment for de novo metastatic prostate cancer patients tends to have the potential to extend survival, even in patients with high metastatic burden, and to reduce SLEs.

DOI： 10.1002/bco2.35

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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OBJECTIVE: To evaluate the association of the MyProstateScore (MPS) urine test on the decision to undergo biopsy in men referred for prostate biopsy in urology practice. METHODS: MPS testing was offered as an alternative to immediate biopsy in men referred to the University of Michigan for prostate biopsy from October 2013 through October 2016. The primary endpoint was the decision to perform biopsy. The proportion of patients undergoing biopsy was compared to predicted risk scores from the Prostate Cancer Prevention Trial risk calculator (PCPTrc). Analyses were stratified by the use of multiparametric magnetic resonance imaging (mpMRI). The associations of PCPTrc, MPS, and mpMRI with the decision to undergo biopsy were explored in a multivariable logistic regression model. RESULTS: Of 248 patients, 134 (54%) proceeded to prostate biopsy. MPS was significantly higher in biopsied patients (median 29 vs14, P < .001). The use of biopsy was strongly associated with MPS, with biopsy rates of 26%, 38%, 58%, 90%, and 85% in the first through fifth quintiles, respectively (P < .001). MPS association with biopsy persisted upon stratification by mpMRI. On multivariable analysis, MPS was strongly associated with the decision to undergo biopsy when modeled as both a continuous (odds ratio [OR] 1.05, 95%; confidence interval [CI] 1.04-1.08; <.001) and binary (OR 7.76, 95%; CI 4.14-14.5; P < .001) variable. CONCLUSION: Many patients (46%) undergoing clinical MPS testing as an alternative to immediate prostate biopsy were able to avoid biopsy. Increasing MPS was strongly associated with biopsy rates. These findings were robust to use of mpMRI.

DOI： 10.1016/j.urology.2020.07.042

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PURPOSE: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). METHODS: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. RESULTS: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. CONCLUSION: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. STUDY REGISTRATION: Clinical trial registry-UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11).

DOI： 10.1007/s00345-020-03494-4

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OBJECTIVES: To develop a wet laboratory training model for learning core laparoscopic surgical skills and evaluating learners' competency level outside the operating room. METHODS: Participants completed three tasks (task 1: tissue dissection around the aorta; task 2: tissue dissection and division of the renal artery; task 3: renal parenchymal closure). Each performance was video recorded and subsequently evaluated by two experts, according to the Global Operative Assessment of Laparoscopic Skills and task-specific metrics that we developed (Assessment Sheet of Laparoscopic Skills in Wet Lab score). Mean scores were used for analyses. The subjective mental workload was also assessed (NASA Task Load Index). RESULTS: The 54 participants included 32 urologists, eight young trainees and 14 medical students. A total of 13 participants were categorized as experts (≥50 laparoscopic surgeries), eight as intermediates (10-49) and 33 as novices (0-9). There were significant differences in the Global Operative Assessment of Laparoscopic Skills and Assessment Sheet of Laparoscopic Skills in Wet Lab scores among the three groups in all three tasks. Higher NASA Task Load Index scores were observed in novices, and there were significant differences in tasks 1 (Kruskal-Wallis test, P = 0.0004) and 2 (P = 0.0002), and marginal differences in task 3 (P = 0.0745) among the three groups. CONCLUSIONS: Our training model has good construct validity, and differences in the NASA Task Load Index score reflect previous laparoscopic surgical experiences. Our findings show the ability to assess both laparoscopic surgical skills and mental workloads, which could help educators comprehend trainees' level outside the operating room. Given the decreasing opportunity to carry out pure laparoscopic surgeries because of the dissemination of robotic surgery, especially in urology, our model can offer practical training opportunities.

DOI： 10.1111/iju.14315

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BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.

DOI： 10.1007/s10147-020-01692-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Association for Cancer Research (AACR)  

Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. However, whether TEC phenotypes are altered by anticancer drugs remains to be clarified. Here, we show that ABCB1 expression increases after chemotherapy in urothelial carcinoma cases. The ratio of ABCB1-positive TEC before and after first-line chemotherapy in urothelial carcinoma tissues (n = 66) was analyzed by ABCB1 and CD31 immunostaining. In 42 cases (64%), this ratio increased after first-line chemotherapy. Chemotherapy elevated ABCB1 expression in endothelial cells by increasing tumor IL8 secretion. In clinical cases, ABCB1 expression in TEC correlated with IL8 expression in tumor cells after first-line chemotherapy, leading to poor prognosis. In vivo, the ABCB1 inhibitor combined with paclitaxel reduced tumor growth and metastasis compared with paclitaxel alone. Chemotherapy is suggested to cause inflammatory changes in tumors, inducing ABCB1 expression in TEC and conferring drug resistance. Overall, these findings indicate that TEC can survive during chemotherapy and provide a gateway for cancer metastasis. Targeting ABCB1 in TEC represents a novel strategy to overcome cancer drug resistance. SIGNIFICANCE: These findings show that inhibition of ABCB1 in tumor endothelial cells may improve clinical outcome, where ABCB1 expression contributes to drug resistance and metastasis following first-line chemotherapy.

DOI： 10.1158/0008-5472.CAN-19-3791

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The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

DOI： 10.1111/cas.14449

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DOI： 10.1093/jjco/hyz197

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OBJECTIVE: Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system. METHODS: Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival. RESULTS: The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]. CONCLUSIONS: Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy.

DOI： 10.1093/jjco/hyz211

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Language：Japanese   Publisher：(株)メディカ出版  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

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OBJECTIVE: To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. METHODS: Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan-Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. RESULTS: Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). CONCLUSIONS: In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.

DOI： 10.1093/jjco/hyz152

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Language：Japanese   Publisher：(株)メディカ出版  

J-GLOBAL

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J06733&link_issn=&doc_id=20200210100007&doc_link_id=%2Fao7hnyuc%2F2020%2F002501%2F009%2F0042-0047%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao7hnyuc%2F2020%2F002501%2F009%2F0042-0047%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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A 66-year-old man was referred to our hospital for an incidentally detected 40-mm mass located at the inter-aortocaval area around the renal hilum. Positron emission tomography CT revealed high accumulation (SUVmax 12.382) without distant metastasis. Bilateral testes were normal by ultrasonography and physical examination, but the serum AFP level was increased to 1161 ng/mL. The pathology based on trans-duodenal needle biopsy demonstrated a yolk sac tumor; therefore, we diagnosed him with retroperitoneal primary germ cell tumor. Due to old age, the potential toxicity of systemic chemotherapy, and no significant signs of invasion to adjacent organs, we performed surgical resection. Although the AFP level decreased to 13.2 ng/mL postoperatively, it increased to 553 ng/mL 2 months after surgery without clinical recurrence on imaging studies. Four cycles of a VIP regimen (VP-16, ifosfamide, and CDDP) were performed, and the AFP level normalized to 2.4 ng/mL. The patient is now disease-free 1 year and 6 months after surgery.

DOI： 10.1007/s13691-019-00384-4

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Background: Virtual reality simulators allow trainees to perform repeated practice and provide objective dexterity metrics regarding their performance, which means that virtual reality-based surgical training is becoming a vital part of initial learning of basic laparoscopic surgical skills. However, its educational role in learning advanced procedures remains undetermined. We evaluated the validity of the laparoscopic radical nephrectomy module of the LapVision virtual reality simulator. Methods: Urologists, medical students, and a junior resident voluntarily participated in the present study, and they performed training with a laparoscopic left radical nephrectomy module. For construct validation, dexterity metrics calculated in the simulator and the mean score of Global Operative Assessment of Laparoscopic Skills evaluated by 2 experts' video review were compared according to the certification of Japanese Endoscopic Surgical Skill Qualification or previous surgical experience. Results: Ten experts (≥ 50 laparoscopic surgeries), 9 intermediates (11-49), and 14 novices (0-10) voluntarily participated in the present study. Regarding the construct validity, there was a significant difference in the total number of errors, blood loss, and Global Operative Assessment of Laparoscopic Skills score among the groups for both the Endoscopic Surgical Skill Qualification status and previous surgical experience. Conclusion: The present study demonstrated good construct validity for the LapVision nephrectomy module. Furthermore, global skill assessment was possible by experts' reviews, which indicates the usefulness of the virtual reality procedural module as a skill assessment tool. Virtual reality-based procedural simulation has marked potential to become a vital part of integrated laparoscopic training programs.

DOI： 10.1016/j.sopen.2019.08.003

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Language：Japanese   Publisher：(一社)腎癌研究会  

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PURPOSE: To determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire. METHODS: For each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated. RESULTS: Assuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p < 0.0167). CONCLUSIONS: The urethral position with a Foley catheter is different from the urethral position with a thin and soft guide-wire in a significant proportion of the patients. This should be taken into account for the PRV of the urethra to ensure precise radiotherapy such as in urethra-sparing radiotherapy.

DOI： 10.1186/s13014-019-1424-8

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Purpose: Robot-assisted laparoscopic radical prostatectomy (RARP) requires a steep head-down tilt and pneumoperitoneum, which may cause an increase in cerebral blood volume (CBV). With a new near-infrared time-resolved spectroscopy device, the tNIRS-1, we can measure the absolute value of the cerebral hemoglobin concentration and hence calculate CBV and cerebral oxygen saturation (rSO2). Using this device, we evaluated the time course of CBV during surgery and also evaluated the changes in rSO2 simultaneously. Materials and Methods: We performed a prospective observational study of 21 patients scheduled for RARP. We evaluated CBV and rSO2 by using the tNIRS-1 at 10 time points during surgery. Results: The CBV was 2.92 ± 0.38 mL ·100 g-1 after the end of anesthetic preparation. It significantly increased to 3.05 ± 0.44 mL ·100 g-1 after the head-down tilt and was around 3.1 mL ·100 g-1 until 120 minutes after the head-down tilt. However, just before the return to the horizontal position, it decreased to 2.93 ± 0.46 mL ·100 g-1 and then decreased more after the return to the horizontal position. Changes in rSO2 over time were within only 3%, and no significant differences from the control value were observed. Conclusions: The increase in CBV was <10% despite the steep head-down tilt and pneumoperitoneum, and it was compensated for at around the end of surgery. Clinically significant changes in rSO2 were not observed during the surgery.

DOI： 10.1089/end.2019.0217

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

1997〜2010年までの間に20施設で膀胱癌に対して腸管利用尿路変向の開腹膀胱全摘除術(開腹RC)を施行した668例(男性528例、女性140例、年齢中央値65歳)を対象に、周術期重度合併症の術前予測因子を検討した。その結果、男性、心血管疾患既往、同時NUx(同時腎尿管全摘除術)が周術期重度合併症の有意な予測因子となったものの、この3つの因子を用いたモノグラムではAUC 0.58と十分な予測精度を持つには至らなかった。

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Radical cystectomy (RC) is the gold standard for managing muscle-invasive and high-risknon-muscleinvasive bladder cancer, but is accompanied by non-negligible operative risk. The aim of this study is to identify preoperative variables to predict major perioperative complications after RC and to develop a nomogram using the cohort from multiple institutions in Japan. We retrospectively reviewed 668 patients who underwent open RC with ileal conduit or neobladder at Hokkaido University hospital and 20 affiliated institutions between 1997 and 2010. Complications occurring within 90 days of surgery were graded using modified Clavien classification system. We defined modified Clavien grade 3 or more as major complications and performed univariate and multivariate logistic regression analyses. Predictive accuracy of the nomogram was evaluated with the area under the receiver operating characteristics curve (AUC). A total of 528 men and 140 women were included in this study. There were a total of 160/668 patients (24%) with major perioperative complications. A multivariate model identified gender (OR : 1. 63, p=0. 04), cardiovascular comorbidity (OR : 1.48, p=0.03) and simultaneous nephroureterectomy (OR : 2.81, p=0. 01) as independent predictors. Using these 3 variables, a nomogram was developed with the AUC of 0.58. Predictive performance of our nomogram showed only fair performance ; but at least, we identified male, cardiovascular comorbidity and simultaneous nephroureterectomy as independent predictors of perioperative major complications.

DOI： 10.14989/ActaUrolJap_65_12_495

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DOI： 10.1093/jjco/hyz084

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BACKGROUND: Robot-assisted radical cystectomy is becoming a common treatment for bladder carcinoma. However, in comparison with open radical cystectomy, its cost-effectiveness has not been confirmed. Although few published reviews have compared total costs between the two surgical procedures, no study has compared segmental costs and explained their impact on total costs. METHODS: A systematic review was conducted based on studies on the segmental costs of open, laparoscopic, and robot-assisted radical cystectomy using PubMed, Web of Science, and Cochrane Library databases to provide insight into cost-effective management methods for radical cystectomy. The segmental costs included operating, robot-related, complication, and length of stay costs. A sensitivity analysis was conducted to determine the impact of the annual number of cases on the per-case robot-related costs. RESULTS: We identified two studies that compared open and laparoscopic surgeries and nine that compared open and robotic surgeries. Open radical cystectomy costs were higher than those of robotic surgeries in two retrospective single-institution studies, while robot-assisted radical cystectomy costs were higher in 1 retrospective single-institution study, 1 randomized controlled trial, and 4 large database studies. Operating costs were higher for robotic surgery, and accounted for 63.1-70.5% of the total robotic surgery cost. Sensitivity analysis revealed that robot-related costs were not a large proportion of total surgery costs in institutions with a large number of cases but accounted for a large proportion of total costs in centers with a small number of cases. CONCLUSIONS: The results show that robot-assisted radical cystectomy is more expensive than open radical cystectomy. The most effective methods to decrease costs associated with robotic surgery include a decrease in operating time and an increase in the number of cases. Further research is required on the cost-effectiveness of surgeries, including quality measures such as quality of life and quality-adjusted life years.

DOI： 10.1186/s12894-019-0533-x

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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A 62-year-old man was referred to our department for elevation of plasma ACTH and cortisol levels during nivolumab administration for renal cell carcinoma. Although his ACTH and cortisol levels had been maintained within their reference ranges, they were elevated to 232.7 pg/mL and 21.9 μg/dL, respectively, after eight courses of nivolumab without any subjective symptoms or Cushing's sign. He was hospitalized for endocrinological investigation. ACTH and cortisol returned to their normal ranges (29.18 pg/mL and 11.4 μg/dL, respectively) in the early morning on day 1, but fell down sharply to 3.7 pg/mL and 1.6 μg/dL, respectively, in the early morning on day 2 without subjective symptoms or vital sign changes. Brain magnetic resonance imaging showed no abnormality in his pituitary gland. ACTH response to CRH was apparently normal, but cortisol did not respond to increased ACTH. A rapid ACTH stimulation test showed slightly reduced response of cortisol to exogenous ACTH (1-24). These findings and his clinical course suggested secondary adrenal insufficiency arising from nivolumab-induced hypophysitis. In previous reports, most cases of immune checkpoint inhibitor (ICI)-induced hypophysitis were diagnosed based on adrenal insufficiency symptoms or hyponatremia with low ACTH and cortisol. The ACTH elevation observed in the present case may reflect destruction of the pituitary gland, suggesting that this finding may be important for early detection of ICI-induced hypophysitis. Our case underlines the necessity of close monitoring for subsequent onset of adrenal insufficiency when ACTH elevation is observed during ICI administration.

DOI： 10.1507/endocrj.EJ19-0076

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Language：English   Publisher：(一社)日本癌治療学会  

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DOI： 10.1111/iju.14073

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DOI： 10.1038/s41598-019-50577-3

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A 45-year-old woman visited a local clinic with left-flank abdominal pain. Abdominal computed tomography (CT) revealed a tumor 20 cm in diameter in the left adrenal gland. She was referred to our hospital for further treatment. No endocrinological abnormality was detected on either serum or urine examination. CT and haematology findings led to a preoperative diagnosis of primary adrenal carcinoma, and we performed a left adrenalectomy. Histopathological examination revealed a paraganglioma with intact adrenal gland. Therefore we diagnosed this case as primary retroperitoneal paraganglioma. Six months after the surgery, she developed peritoneal dissemination including bilateral ovarian metastases. After cytoreductive metastasectomy, she received 131I-meta-iodobenzylguanidine (MIBG) radiotherapy. During the following five-year follow-up, MIBG radiotherapy in conjunction with cytoreductive metastasectomy (3 surgeries and 6 sessions of 131I-MIBG radiotherapy) was performed, aiming at disease control. Five years after the initial surgery, liver, lung, and intra-peritoneal dissemination progressed. Thereafter, she developed severe diarrhea, hypokalemia, and metabolic acidosis with an elevated level of vasoactive intestional peptide, which was consistent with water diarrhea, hypokalemia, achlorhydria (WDHA) syndrome. Despite intensive treatments such as with a somatostatin analogue, she died two months after the onset of this syndrome.

DOI： 10.14989/ActaUrolJap_65_6_277

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Since the 2000s, there have been dramatic advances in the treatment of metastatic renal cell carcinoma (mRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. The first VEGF inhibitors approved for mRCC were sorafenib and sunitinib. Subsequently, two mTOR inhibitors (everolimus and temsirolimus) and other VEGF inhibitors (pazopanib and axitinib) were approved. Overall survival (OS) of mRCC patients has significantly increased during this period. Two novel VEGF inhibitors have recently been approved overseas, including cabozantinib and lenvatinib. Additionally, the recent advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment of mRCC. The PD-1 inhibitor nivolumab improved the OS rate of patients with mRCC following VEGF inhibitors. Moreover, the CheckMate 214 trial demonstrated the benefit of nivolumab plus ipilimumab combination therapy in OS and objective response rate in treatment-naive intermediate- and poor-risk mRCC. In this review, current evidence related to the clinical use of targeted therapies and checkpoint inhibitors for the treatment of patients with mRCC is discussed. In addition, we review ongoing trials investigating combinations of checkpoint inhibitors with targeted agents and the identification of biomarkers to guide patient selection and enable individualization of therapy.

DOI： 10.1093/jjco/hyz013

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OBJECTIVE: To evaluate the association between the RENAL nephrometry score (RNS) and tumor proliferative activity assessed by immunohistochemistry in patients with localized renal cell carcinoma. METHODS: The current study included 145 pathological T1 (pT1) clear cell renal cell carcinomas (ccRCC). Tumor proliferative activity was assessed with the Ki67 index and microvessel density (MVD). RNS was retrospectively assessed in the present study. We divided patients into 3 groups according to RNS (RNS 4-6: low-complexity, 7-9: moderate complexity, and 10-12: high-complexity tumors) and compared the Ki67 index as well as MVD among the 3 groups. The association between the Ki67index/MVD and each component (R, E, N, A, L, h) was also evaluated. RESULTS: There were 56 low, 84 moderate, and 5 high-complexity tumors. The median Ki67 index of all tumors was 5.34% (interquartile range: 3.28-8.57). The median Ki67 index of low, moderate, and high-complexity tumors was 3.97%, 6.39%, and 11.27%, respectively, with a significant difference among the 3 groups (Kruskal-Wallis test, P = 0.0004). On the other hand, the median MVD of low, moderate, and high-complexity tumors was 14.11%, 14.42%, and 21.22%, respectively, and there were no significant differences among the 3 groups. In terms of each RNS component, there were significant differences in the Ki67 index among the 3 groups in N (P = 0.0101) and L (P = 0.0280) components, respectively. CONCLUSIONS: The revealed association between RNS and the Ki67 index in pT1 clear cell renal cell carcinomas further supports the previous findings that the anatomy of renal cell carcinoma is associated with the malignant potential of localized clear cell renal cell carcinoma, which may provide additional information for treatment decision.

DOI： 10.1016/j.urolonc.2019.02.005

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OBJECTIVES: To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. METHODS: A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. RESULTS: Of 277 eligible patients, 266, 170 and 77 received first-, second- and third-line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first-line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second-line treatment, tyrosine kinase inhibitor-tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor-mammalian target of rapamycin inhibitor (14.1%) and cytokine-tyrosine kinase inhibitor (14.1%). With a median follow-up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first-line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first-line tyrosine kinase inhibitors for ≥6 months. CONCLUSIONS: The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real-world setting in Japan. Tyrosine kinase inhibitor-tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first-line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options.

DOI： 10.1111/iju.13830

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Objective: To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. Methods: We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan-Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Results: A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan-Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. Conclusion: Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.

DOI： 10.1093/jjco/hyy128

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Axitinib was approved for use in Japan as a salvage therapy for patients with metastatic renal cell carcinoma (RCC) in 2012. We retrospectively evaluated the cases of 32 RCC patients that were treated with Axitinib as a 2nd- or further-line therapy between November 2012 and March 2017. Overall survival (OS), progression-free survival (PFS), and adverse events were assessed. The median OS and PFS from the initiation of Axitinib were 29 and 11 months, respectively. Nineteen patients received Axitinib as a 2nd-line treatment, in whom the median OS and median PFS were 22 and 10 months, respectively, while the median OS and PFS were 29 and 15.5 months, respectively, amongthe 13 patients who received Axitinib as a 3rd- or further-line treatment, which suggested that Axitinib is effective in the 3rd-line and further-line settings. A Cox multivariate model revealed that bone metastasis was a significant adverse factor for OS. Common grade 3 or higher adverse events included hypertension (28%), diarrhea (7%), and proteinuria (7%). Although the present study demonstrated the efficacy and safety of salvage Axitinib treatment in patients who had recurrent disease after the initial systemic therapy, further large-scale studies should be warranted to make clear its clinical effectiveness in these patients.

DOI： 10.14989/ActaUrolJap_64_9_353

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Objective: Urinary extracellular vesicles (EV) could be promising biomarkers for urological diseases. In this retrospective feasibility study, we conducted biomarker screening for early stage bladder cancer using EV mRNA analysis. Methods: Biomarker candidates were identified through RNA-seq analysis of urinary EV from patients with non-muscle invasive bladder cancer (N=3), advanced urothelial cancer (N=3), no residual tumor after TURBT (N=2), and healthy and disease controls (N=4). Diagnostic performance was evaluated by RT-qPCR in a larger patient group including bladder cancer (N=173), renal pelvis and ureter cancer (N=33), no residual tumor and non-cancer disease control (N=36). Results: Urinary EV SLC2A1, GPRC5A and KRT17 were overexpressed in pT1 and higher stage bladder cancer by 20.6-fold, 18.2-fold and 29.5-fold, respectively. These genes allowed detection of non-muscle invasive bladder cancer (AUC: 0.56 to 0.64 for pTa, 0.62 to 0.80 for pTis, and 0.82 to 0.86 for pT1) as well as pT2 and higher muscle invasive bladder cancer (AUC: 0.72 to 0.90). Subgroup analysis indicated that these markers could be useful for the detection of cytology-negative/-suspicious and recurrent bladder cancers. Conclusion: Three urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation.

DOI： 10.18632/oncotarget.25998

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Objectives: The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Methods: Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. Results: The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. Conclusions: The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

DOI： 10.1093/jjco/hyy094

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DOI： 10.1111/iju.13584

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DOI： 10.1007/s12032-018-1090-y

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DOI： 10.1371/journal.pone.0197252

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DOI： 10.1016/S0140-6736(17)32365-6

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Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell-like populations with high aldehyde dehydrogenase (ALDH) activity (ALDHhigh TEC). ALDHhigh TEC have proangiogenic properties compared with ALDHlow TEC. However, the association between ALDHhigh TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor-conditioned medium (tumor CM). The ALDHhigh population increased along with upregulation of stem-related genes such as multidrug resistance 1, CD90, ALP, and Oct-4. Tumor CM also induced sphere-forming ability in HMVEC. Platelet-derived growth factor (PDGF)-A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDHhigh TEC were resistant to fluorouracil (5-FU) in vitro and in vivo. ALDHhigh TEC showed a higher grade of aneuploidy compared with that in ALDHlow TEC. These results suggested that tumor-secreting factor increases ALDHhigh TEC populations that are resistant to 5-FU. Therefore, ALDHhigh TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance.

DOI： 10.1111/cas.13388

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DOI： 10.1111/cas.13388

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Objective: To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians. Methods: A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between ≥80-year (n = 86) and <80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications. Results: American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the ≥80-year group compared with <80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (≥80-year group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively). The ≥80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications. Conclusions: In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory.

DOI： 10.1093/jjco/hyx062

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DOI： 10.1016/j.urology.2016.10.054

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DOI： 10.1016/j.juro.2017.02.2273

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DOI： 10.1016/j.juro.2017.02.378

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DOI： 10.1016/j.urology.2016.10.051

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Despite an increasing number of prostate cancer survivors in Japan, the current delivery of prostate cancer survivorship care is insufficient and lacks a multidisciplinary approach. We carried out a study to characterize prostate cancer survivorship care in Japan, examine the Japanese workforce available to deliver survivorship care, introduce a conceptual framework for survivorship and identify opportunities to improve Japanese survivorship care. We systematically searched PubMed for prostate cancer survivorship care studies, including those from Japan. We also searched the internet for prostate cancer guidelines relevant to survivorship care. We found 392 articles, of which 71 were relevant, read in detail and reported here. In Japan, survivorship care is mostly provided by urologists. Primary care as a specialty does not exist in Japan, and there are no independent nurse practitioners or physician assistants to assist with survivorship care. Japanese quality of life studies characterize the long-term effects of prostate cancer treatment, but routine use of patient-reported outcomes is not common in Japan. In the USA, in light of a growing comprehensive awareness of challenges facing survivors and their providers, the American Cancer Society prostate cancer survivorship care guidelines serve as a tool for optimizing the management of long-term treatment effects and coordination of care. In order to deliver high-quality survivorship care in Japan, urologists need to establish collaborations with other disciplines within the delivery system. A multidisciplinary guideline for prostate cancer survivorship care in Japan appears warranted.

DOI： 10.1111/iju.13186

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DOI： 10.1016/j.urology.2016.05.044

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DOI： 10.1111/iju.13186

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DOI： 10.1016/j.juro.2016.02.946

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DOI： 10.1016/j.juro.2015.10.137

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DOI： 10.3233/BLC-150043

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PURPOSE: To determine the appropriate template of regional lymph node dissection (LND) at the time of laparoscopic nephroureterectomy (LNU) for patients with clinically node- negative urothelial carcinoma of the upper urinary tract. PATIENTS AND METHODS: This prospective study included 45 patients undergoing LND with LNU in accordance with our prospective rules regarding the area of LND. Perioperative, pathologic, and follow-up data were collected. Micrometastasis in lymph nodes (LNs) was later evaluated by immunohistochemistry (IHC). Recurrence-free survival (RFS) was calculated with the Kaplan-Meier method. RESULTS: The median number of LNs removed was 14 (range 1-33). One patient with pT3 disease had node metastasis based on routine pathologic examination, and IHC revealed micrometastases in two additional patients (pT2 in one and pT3 in one). Therefore, 15% (3/20) of patients with ≥pT2 disease had node disease. After surgery, six patients experienced minor complications (Grade 1 or 2), and Grade 5 gastrointestinal bleeding after aspiration pneumonia developed in one elderly male patient on the 45th postoperative day, which was not considered to be associated with LND. At the last follow-up, lung metastasis developed in four patients (pT1 in one, pT2 in one, and pT3 in two), and presacral lymph node metastasis developed in one patient with a lower ureteral tumor (pT2), which was not included in our prospective template for a lower ureteral tumor. LN recurrence within/ near the LND area was not observed in patients with pelvic/upper ureteral carcinoma. The 2-year nonurothelial RFS rate was 84%. CONCLUSIONS: We consider that the present template represents regional LNs for patients with clinically node-negative pelvic/upper ureteral carcinoma, while presacral LNs may be incorporated into the regional LND template for patients with clinically node-negative lower ureteral carcinoma.

DOI： 10.1089/end.2014.0369

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DOI： 10.1089/end.2014.0381

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DOI： 10.7314/APJCP.2015.16.14.5687

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DOI： 10.3892/or.2013.2620

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DOI： 10.1038/bjc.2013.535

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DOI： 10.1111/pin.12031

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INTRODUCTION: Nephron-sparing surgery (NSS) has become the standard treatment for small renal cell carcinoma because of its comparable oncological outcome and superior patient survival compared to total nephrectomy. However, the precise chronological course of recovery from initial kidney damage and the factors responsible for it remain unknown. MATERIALS AND METHODS: Seventy-one patients who underwent NSS were enrolled. To elucidate the chronological changes in kidney function that occur after NSS, the estimated glomerular filtration rate (eGFR) was calculated at different two points, the early (7 days after surgery) and late time points (more than 12 months after surgery), and compared with the preoperative eGFR. Perioperative factors were applied to a multivariate regression model to investigate the factors that most affect patient recovery from nephron damage. RESULTS: eGFR was decreased at the early time point but had partially recovered at the late time point. Male gender, ischemic time, and tumor size were found to be significant predictors of the initial drop in eGFR. The only significant factor that prevented later functional recovery was the presence of DM. CONCLUSION: Several perioperative factors significantly influence early kidney damage; however, the presence of DM is the only factor affecting the risk of long-term chronic kidney damage.

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PURPOSE: To evaluate postoperative renal function and risk factors for the loss of renal function in patients who had undergone radical cystectomy. MATERIALS AND METHODS: A retrospective single institutional study evaluated 70 patients, including 54 men and 16 women who underwent radical cystectomy. The median follow-up period was 34.5 months (range, 12 to 228 months). In this cohort, four types of urinary diversions were studied, including ileal neobladder (n = 24), ileocecal neobladder (n = 12), ileal conduit (n = 25), and cutaneous ureterostomy (n = 9). Postoperative changes in renal function were reviewed, and the estimated serum creatinine-based glomerular filtration rate (eGFR) was calculated. The variables analyzed were age, a prior history of hypertension or diabetes mellitus, pre-operative renal function, type of urinary diversion, the postoperative occurrence of acute pyelonephritis, and the presence of chemotherapy. RESULTS: The mean eGFR was 74.6 (range, 15.2 to 155.1) mL/min/1.73 m² before surgery and 63.6 (range, 8.7 to 111.5) mL/min/1.73 m² at the last follow-up. The 10-year renal deterioration-free interval was 63.8%. Multivariate analysis showed that a postoperative episode of acute pyelonephritis [Odds Ratio (OR), 3.21; 95% Confidence Interval (CI), 1.14 to 9.02; P = .03] and the presence of chemotherapy (OR, 3.27; 95% CI, 1.33 to 8.01; P = .01) were significant adverse factors. CONCLUSION: Twenty-four (34.2%) patients demonstrated reduced renal function during the follow-up period. Postoperative episodes of acute pyelonephritis and the presence of chemotherapy were found to be significant adverse factors.

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DOI： 10.1371/journal.pone.0034045

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Language：English   Publisher：(一社)日本癌学会  

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DOI： 10.1111/j.1349-7006.2012.02261.x

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DOI： 10.1111/j.1440-1827.2012.02792.x

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DOI： 10.1016/j.ajpath.2011.11.035

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DOI： 10.1038/bjc.2012.59

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DOI： 10.1016/j.juro.2010.05.027

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DOI： 10.1111/j.1464-410X.2009.08836.x

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DOI： 10.1111/j.1399-0012.2009.01006.x

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DOI： 10.1016/S0022-5347(09)61250-7

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DOI： 10.1111/j.1442-2042.2008.02221.x

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Language：Japanese   Publisher：Japanese Urological Association  

DOI： 10.5980/jpnjurol.100.12

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J01175&link_issn=&doc_id=20090130090003&doc_link_id=1390001205057949440&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001205057949440&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

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DOI： 10.1111/j.1464-410X.2008.07673.x

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DOI： 10.1111/j.1464-410X.2006.06108.x

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Language：Japanese   Publisher：(一社)日本医学教育学会  

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