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植木 秀登医学部附属病院 泌尿器科助教
研究活動情報
■ 受賞- 2026年09月 令和8年度神戸大学優秀若手研究者賞
- 2024年04月 第111回日本泌尿器科学会総会, Best Poster Award, RB1およびp53変異を有する治療関連神経内分泌前立腺がんにおけるゲノム解析と免疫組織化学的検証
- 2023年04月 第110回日本泌尿器科学会総会, 総会賞ポスター（腎腫瘍・基礎）, WT1経口がんワクチンはマウス腎癌モデルにおいて免疫チェックポイント阻害薬の抗腫瘍効果を増強する
- The global proliferation of robotic surgical platforms necessitates a framework for objective skill assessment using fundamental kinematic features that are theoretically extractable from any robotic system with 3D position tracking. Here, we demonstrated that fundamental three-dimensional movement patterns alone can accurately distinguish surgical expertise and show associations with clinical outcomes. A Random Forest classifier discriminated expertise with high case-wise accuracy (area under the curve 0.892 ± 0.075), and feature-importance analysis identified left-hand peak density as the principal discriminator. A small set of these fundamental indicators generalized to unseen surgeons in leave-one-surgeon-out validation, localizing the expertise-associated signal to a few interpretable kinematic measures. Kinematic patterns were correlated with clinical outcomes, and exploratory analysis revealed associations between movement features and blood loss. Individual learning curve analysis revealed heterogeneous adaptation patterns among experts transitioning to the new platform and identified distinct phenotypes with implications for personalized training. These findings show that fundamental kinematic analysis using only three-dimensional positional data can provide interpretable indicators of surgical performance that may extend across robotic systems providing coordinate data.2026年09月, NPJ digital medicine, 9(1) (1), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Robot-assisted partial nephrectomy (RAPN) is well-suited for managing complex renal tumors, including those located in the renal hilum. However, studies directly comparing RAPN outcomes for hilar and non-hilar tumors, particularly in terms of comprehensive measures, such as trifecta and pentafecta, are still limited. AIM: To evaluate whether tumor location in the renal hilum independently influences surgical and renal functional outcomes after RAPN, as assessed by trifecta and pentafecta criteria. METHODS: This single-center retrospective cohort study evaluated outcomes of RAPN for hilar and non-hilar renal tumors treated from April 2016 to June 2023. Eligible patients had tumors ≤ 7 cm, no metastasis, and at least one year of follow-up. Propensity score matching was applied. Primary endpoints were trifecta and pentafecta achievement. All procedures were performed under ischemia without early unclamping. Multivariate logistic regression identified predictors of outcome achievement. RESULTS: Of 350 patients, 324 met the inclusion criteria, consisting of 60 hilar and 264 non-hilar tumors. Trifecta achievement was similar between hilar (63.3%) and non-hilar groups (64.0%), with no significant differences in ischemia time, positive margins, or major complications. Pentafecta achievement rates were also similar (20.0% hilar vs 14.0% non-hilar, P = 0.237). Multivariate analysis identified R score, N score, and L score as predictors of pentafecta non-achievement. Surgeon experience and hilar tumor presence were predictors of pentafecta achievement. Hilar tumor location was not an independent determinant in the propensity-matched analysis, suggesting that the adjustment methods and sample size may have influenced the results. CONCLUSION: RAPN achieved comparable trifecta and pentafecta outcomes for hilar and non-hilar tumors, supporting its viability for complex hilar tumors when appropriate patient selection and surgical experience are ensured.2026年09月, World journal of nephrology, 15(3) (3), 119576 - 119576, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) alterations and ERBB2 (HER2) amplification are clinically actionable genomic events in metastatic urothelial carcinoma (mUC). However, their prevalence and overlap in metastatic-specific cohorts remain incompletely defined. We evaluated their nationwide distribution and co-occurrence using the Japanese C-CAT registry. METHODS: This retrospective study included patients with histologically confirmed mUC who underwent comprehensive genomic profiling with tissue-based FoundationOne assays between January 2019 and June 2025. FGFR3 positivity was defined as pathogenic mutations or fusions meeting companion diagnostic criteria, and HER2 positivity as ERBB2 amplification. Associations with clinicopathological variables were assessed using logistic regression. Co-occurrence was analyzed with Fisher's exact test. RESULTS: Among 1014 patients, FGFR3 alterations were identified in 157 (15.5%) and HER2 amplification in 150 (14.8%). Concurrent alterations occurred in 13 patients (1.3%). Under statistical independence, the expected co-occurrence rate was 2.3%; the observed frequency was significantly lower (P = 0.010; crude OR 0.47). In multivariable analysis, female sex (OR 0.58, 95% CI 0.36-0.93; P = 0.024) and upper tract origin (OR 0.57, 95% CI 0.39-0.84; P = 0.005) were independently associated with lower odds of HER2 amplification. HER2 amplification was independently associated with reduced odds of FGFR3 alterations (adjusted OR 0.49, 95% CI 0.27-0.88; P = 0.018). CONCLUSIONS: In this nationwide metastatic cohort, FGFR3 alterations and ERBB2 amplification were each detected in approximately 15% of cases and showed a significant but partial negative association. These findings clarify the molecular epidemiology of mUC and support comprehensive genomic profiling to guide biomarker-driven therapy.2026年09月, International journal of clinical oncology, 31(9) (9), 2025 - 2032, 英語, 国内誌研究論文（学術雑誌）
- Pancreatic ductal adenocarcinoma (PDAC) remains largely unresponsive to immune checkpoint inhibitors (ICI) due to its profoundly immunosuppressive tumor microenvironment. To overcome this resistance, we evaluated an oral WT1-targeted cancer vaccine using a recombinant Bifidobacterium longum strain (B. longum 420) engineered to display a partial WT1 antigen. Oral immunization with B. longum 420 activated WT1-associated cellular immunity, increasing IL-12-producing CD45+ cells and Th1/cytotoxic cytokine-producing T cells, and enhancing splenocyte cytotoxic activity against Pan02 cells. In a syngeneic Pan02 tumor model, the combination of B. longum 420 with anti-PD-1 and anti-CTLA-4 antibodies resulted in stronger antitumor effects and improved survival compared with each monotherapy, without marked body weight loss. An empty-vector control strain did not further enhance the efficacy of dual checkpoint blockade. Tumor analyses showed increased intratumoral CD8+ T cell density and expansion of effector, central memory, and PD-1+ Ki-67+ proliferating CD8+ subsets, together with treatment-dependent differences in intratumoral CD4+ T cell subset composition. These findings demonstrate that an oral WT1-targeted Bifidobacterium vaccine can potentiate dual checkpoint blockade and promote a more immunologically active T cell landscape in PDAC. To our knowledge, this is the first demonstration of this combination strategy in a syngeneic pancreatic cancer model.2026年09月, Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(54) (54), e24323, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: Enfortumab vedotin (EV) has shown survival benefits in advanced urothelial carcinoma (UC). However, patients with severe renal impairment, poor performance status, or anemia were excluded from pivotal trials. Evidence regarding real-world outcomes of EV in trial-ineligible populations remains limited. METHODS: We retrospectively investigated 180 patients with advanced UC treated with EV between December 2021 and December 2024 at Kobe University Hospital or affiliated institutions. Patients were classified as trial-eligible or trial-ineligible using modified EV-301 eligibility criteria based on three factors: estimated glomerular filtration rate < 30 mL/min/1.73 m2, Eastern Cooperative Oncology Group performance status ≥ 2, and hemoglobin < 9 g/dL. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events were evaluated. RESULTS: The median age was 73 years, and 73.3% of the patients were male. Eighty-two patients (45.6%) were trial-ineligible. Median PFS (8.0 vs. 5.0 months, p = 0.005) and OS (17.9 vs. 10.5 months, p = 0.001) were significantly longer in trial-eligible patients. ORR was also higher in the trial-eligible group (55.1% vs. 31.7%, p = 0.003). The incidence of all-grade and grade ≥ 3 adverse events was comparable. Subgroup analyses demonstrated significantly poorer PFS and OS in patients with Eastern Cooperative Oncology Group performance status ≥ 2 or hemoglobin < 9 g/dL. Outcomes did not differ according to renal function. CONCLUSIONS: Clinical outcomes following EV were poorer in trial-ineligible patients than in trial-eligible patients, while safety was comparable between the groups. Poor performance status and anemia were associated with worse survival outcomes, whereas severe renal impairment was not significantly associated with survival outcomes.2026年08月, International Journal of Urology, 33(8) (8), e70614, 英語, 国際誌研究論文（学術雑誌）
- 2026年08月, BJU International, 138(2) (2), 346 - 347, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The modified Glasgow Prognostic Score (mGPS) and systemic immune-inflammation index (SII) are useful prognostic markers for various malignancies. This study aimed to evaluate their prognostic significance in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel (CBZ). METHODS: We retrospectively reviewed the data of 344 patients with mCRPC who initiated CBZ treatment at Kobe University Hospital and affiliated institutions. The optimal SII cutoff value for predicting overall survival (OS) was determined using the maximally selected rank statistics (Maxstat) method. The prognostic significance of the mGPS and SII was assessed using Cox proportional hazards models. RESULTS: The median OS of the entire cohort was 15.9 months. The optimal SII cutoff value determined using the Maxstat method was 850.6. A multivariate analysis demonstrated that an mGPS ≥ 1 and an SII ≥ 850.6 were independent predictors of poorer OS, with hazard ratios of 2.10 (95% confidence interval [CI], 1.55-2.85; p < 0.001) and 1.58 (95% CI, 1.13-2.21; p = 0.008), respectively. Notably, among patients with an mGPS of 0, further stratification using the SII cutoff (mGPS 0/SII-low vs. mGPS 0/SII-high) significantly discriminated OS rates. CONCLUSION: mGPS and SII are significant prognostic biomarkers in patients with mCRPC treated with CBZ. Their combined assessment may provide improved risk stratification and support clinical decision-making in this population group.2026年07月, The Prostate, 86(14) (14), 1428 - 1434, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). This study evaluated the prognostic significance of early tumor shrinkage in patients with mRCC treated with first-line ICI-based combination therapies. METHODS: We retrospectively reviewed 169 mRCC patients who received nivolumab plus ipilimumab, pembrolizumab (or avelumab) plus axitinib, pembrolizumab plus lenvatinib, or nivolumab plus cabozantinib at Kobe University Hospital and its affiliated institutions. Patients were stratified into four groups according to early tumor shrinkage at the first imaging assessment after therapy initiation. The association between early tumor shrinkage and the overall survival (OS) was analyzed. RESULTS: The median early tumor shrinkage rate was 17.8%. Twenty-one patients (12.4%) had 50-100% shrinkage, 31 (18.3%) had 30-<50% shrinkage, 81 (47.9%) had 0-<30% shrinkage, and 36 (21.3%) showed progression. The median OS was 42.4 months. The corresponding median OS by shrinkage category above was not reached (NR), NR, 34.7 months, and 30.8 months, respectively (p = 0.023), with 2-year OS rates of 86.7%, 75.1%, 66.1%, and 60.5%, respectively. A univariate analysis identified a prior nephrectomy, International mRCC Database Consortium risk group, bone or liver metastasis, C-reactive protein level, histological subtype, and early tumor shrinkage as predictors of the OS. In the multivariate analysis, prior nephrectomy, bone or liver metastasis, histological subtype, and early tumor shrinkage remained independent. CONCLUSION: Early tumor shrinkage was independently associated with the OS, suggesting its potential as a prognostic indicator in patients with mRCC treated with first-line ICI-based combination therapy.2026年07月, International journal of clinical oncology, 31(7) (7), 1316 - 1325, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: Pembrolizumab plus lenvatinib (Pem-Len) and nivolumab plus cabozantinib (Nivo-Cabo) are effective first-line regimens for metastatic renal cell carcinoma (RCC); however, real-world data directly comparing these regimens are limited. We conducted a retrospective analysis to compare their clinical outcomes in Japanese patients. METHODS: Patients with metastatic RCC who received Pem-Len or Nivo-Cabo as first-line systemic therapy at Kobe University Hospital and affiliated institutions between August 2018 and September 2025 were included. Clinicopathological characteristics and treatment outcomes were compared between the two groups. RESULTS: A total of 139 patients received Pem-Len and 97 received Nivo-Cabo. Patients in the Nivo-Cabo group were significantly older than those in the Pem-Len group. After propensity score matching for prognostic factors, progression-free survival (PFS) was significantly longer in the Pem-Len group than in the Nivo-Cabo group (not reached vs. 15.9 months, P = 0.019), but there was no significant difference in overall survival between the groups (not reached vs. 31.5 months, P = 0.308). The incidence of grade ≥ 3 adverse events was comparable between the groups (51.8% vs. 55.4%, P = 0.756). CONCLUSION: In this real-world analysis, Pem-Len was associated with longer PFS than Nivo-Cabo in patients with metastatic RCC, with comparable safety profiles.2026年07月, International journal of clinical oncology, 31(7) (7), 1381 - 1388, 英語, 国内誌研究論文（学術雑誌）
- OBJECTIVES: The hinotori Surgical Robot System (HSRS) is the first surgical robotic system developed in Japan and has recently become more widely used worldwide. A key advantage of HSRS is that it can be modified without changing the platform model itself. This study aimed to determine the effect of HSRS modification on the learning curve for robotic-assisted radical prostatectomy (RARP). METHODS: Between December 2020 and February 2025, 482 RARP procedures using HSRS were performed by 21 cockpit surgeons. Among these, 320 cases performed by 16 surgeons at our hospital and affiliated institutions were analyzed. According to the timing of HSRS modification, cases were divided into two groups: Group A (before modification) and Group B (after the latest modification, including reduced arm floating sensation, fewer emergency stops due to arm collision, and addition of a hand-switch clutch function). The K-value, defined as the slope of the linear regression line for chronological changes in cockpit time excluding lymph node dissection (LND), was calculated and compared between groups. RESULTS: Of the 320 cases (median age 70 years, range 45-81), 143 were in Group A and 177 in Group B. The median K-value in Group B (-0.27495; range -1.7421 to 0.1002) was significantly better than in Group A (0.0691; range -0.237 to 5.3544; p = 0.0277). In Group B, cockpit time excluding LND decreased with experience, and K-values were not associated with prior case number (p = 0.5018). CONCLUSIONS: HSRS modification was associated with a more favorable learning curve for cockpit time in RARP.2026年07月, International Journal of Urology, 33(7) (7), e70577, 英語, 国際誌研究論文（学術雑誌）
- 2026年07月, JCO Oncology Advances研究論文（学術雑誌）
- OBJECTIVE: To evaluate the impact of Bacillus Calmette-Guérin (BCG) maintenance therapy intensity on outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and identify the critical period of maintenance efficacy. PATIENTS AND METHODS: This retrospective cohort study involved 150 patients with high-risk NMIBC who received BCG induction therapy between January 2010 and September 2022. The patients were classified by maintenance intensity within 1 year: adequate maintenance (AM; 5-9 of 9 planned instillations) or inadequate maintenance (IM; 0-4 instillations). The primary endpoint was conditional recurrence-free survival (CRFS), assessed at baseline (0 months) and at 6, 12, 18, and 24 months postinduction. CRFS was estimated, and multivariable Cox regression identified predictors of recurrence at each conditional time point. RESULTS: Of 150 patients, 77 (51.3%) received AM and 73 (48.7%) received IM. AM patients showed significantly better RFS, with 5-year rates of 85.9% vs. 63.9% for IM. The 5-year CRFS rates for AM remained consistently higher than IM at all time points (0, 6, 12, 18, and 24 months). In the multivariable analysis, IM was the only significant predictor of poorer RFS at baseline, 6, and 12 months, with this association diminishing at 18 and 24 months. CONCLUSION: Adequate BCG maintenance-defined as at least five instillations within the first year-significantly reduces early recurrence in high-risk NMIBC. The benefit of maintenance intensity is most pronounced during the first 12 months, underscoring the importance of adherence to an adequate BCG regimen to optimize outcomes.2026年06月, Urologic oncology, 44(6) (6), 53 - 60, 英語, 国際誌研究論文（学術雑誌）
- To compare perioperative, functional, and oncological outcomes of robot-assisted radical prostatectomy (RARP) performed using the hinotori Surgical System and the da Vinci Surgical System in a multi-institutional real-world setting. We retrospectively analyzed 2,066 patients who underwent RARP at 13 institutions. To ensure comparability, 1:2 propensity score matching was performed based on baseline clinicopathological variables, resulting in matched cohorts of 273 patients in the hinotori group and 546 in the da Vinci group. Perioperative, functional (urinary continence), and oncological (biochemical recurrence) outcomes were evaluated. Total operative time and console time were longer in the hinotori group than in the da Vinci group. In contrast, estimated blood loss, postoperative complications, and positive surgical margin rates were comparable between the two groups. No significant differences were observed in time to recovery of urinary continence within the first postoperative year or in biochemical recurrence-free survival. The 3-year biochemical recurrence-free survival rates were 96% in the hinotori group and 95% in the da Vinci group. Within the hinotori cohort, console time was significantly shorter in the later period of system adoption, suggesting a learning effect associated with accumulated experience. In this first multi-institutional comparison, hinotori-assisted RARP achieved perioperative, functional, and oncological outcomes comparable to those of the da Vinci, with operative efficiency improving as experience accumulated.2026年04月, Journal of robotic surgery, 20(1) (1), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: As no randomized study has compared abiraterone acetate (ABI) doublet and triplet therapy, the optimal target for the add-on of docetaxel (DTX) to ABI doublet therapy remains unclear. The present study explored patients who may benefit from add-on DTX using initial prostate-specific antigen (PSA) reduction after ABI doublet therapy. METHODS: We retrospectively reviewed 233 patients with CHAATED high-volume metastatic castration-sensitive prostate cancer (mCSPC) treated with ABI doublet therapy. Using the initial PSA half-life calculated by PSA reduction within 6 weeks of treatment (initial PSAT1/2), a subgroup of patients with a poor overall survival (OS) was explored. The optimal cutoff value of PSAT1/2 predicting a PSA decline < 90% after 12 weeks of ABI treatment was investigated using a receiver operating characteristic (ROC) analysis. RESULTS: A PSAT1/2 of 0.33 months was an ideal cutoff value for predicting a PSA decline < 90% after 12 weeks of ABI treatment. In addition to Grade Group 5 (hazard ratio [HR]: 3.06, p = 0.002) and an LDH ≥ 250 U/L (HR: 2.30, p = 0.017), an initial PSAT1/2 ≥ 0.33 months (HR: 3.39, p < 0.001) were identified as significant predictors of a poor OS in mCSPC treated with ABI doublet therapy. Only liver metastasis was significantly associated with an initial PSAT1/2 of ≥ 0.33 months. CONCLUSION: We showed that the initial PSAT1/2 of treatment was significantly prognostic in high-volume mCSPC patients treated with ABI doublet therapy. Our findings suggest that initial PSA reduction may help identify patients who will benefit from the addition of DTX. A prospective study is required to verify our hypotheses.2026年04月, The Prostate, 86(5) (5), 609 - 615, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Immune checkpoint inhibitors (ICI) have improved outcomes in mismatch repair–deficient/microsatellite instability–high colorectal cancer (CRC), yet only a subset of patients achieve durable benefit. The gut microbiota, particularly Enterococcus species, can modulate antitumor immunity and influence ICI efficacy. We investigated the probiotic potential of Enterococcus faecalis KU-EF-004, a non-antibiotic-resistant urinary isolate, as an adjunct to enhance ICI therapy in CRC. METHODS: MC38 tumor-bearing C57BL/6J mice received combination therapy with KU-EF-004 and anti-PD-1 or anti-CTLA-4 antibodies, and the therapeutic efficacy was compared with E. faecalis ATCC700802 strain and PBS-treated groups. Additionally, combination therapy with KU-EF-004 and either anti-PD-1 or anti-CTLA-4 antibodies was performed to evaluate which immune checkpoint inhibitor was associated with enhanced therapeutic effects. Dendritic cell activation in Peyer’s patches was assessed by flow cytometry, and gut microbiota changes were analyzed using 16S rRNA gene sequencing. RESULTS: KU-EF-004 markedly enhanced anti–CTLA-4 efficacy, reducing tumor growth and prolonging survival, whereas no benefit was observed with anti–PD-1. KU-EF-004 promoted dendritic cell activation and upregulated immune markers (CD80, CD86, IFN-γ, MHC II, IL-6, CD8a) in Peyer’s patches. 16S rRNA sequencing revealed increased microbial diversity and enrichment of Lactobacillus species following combined KU-EF-004 and anti–CTLA-4 treatment. CONCLUSION: These findings identify E. faecalis KU-EF-004 as a promising probiotic candidate to augment immune checkpoint blockade efficacy in colorectal cancer.2026年03月, BMC immunology, 27(1) (1), 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: This study aims to determine the impact of the number of relevant factors for high-complexity tumors on perioperative outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: The 308 patients who underwent RAPN for renal hilar, completely endophytic, or clinical T1b tumors were defined as the complex tumor group (CTG), and the other 752 were defined as the non-complex tumor group (NCTG). The CTG patients were further classified on the basis of their number of relevant factors for high-complexity tumors into the one-factor and multiple-factor subgroups. Perioperative outcomes were compared for each group. RESULTS: The median times using the robotic system were 187 and 167 min (p = 0.0006), median warm ischemic times (WITs) were 24 and 20 min (p < 0.0001), Grade 3 or higher complication rates were 6.2% and 2.5% (p = 0.0038), median preserved renal function rates at 1 month postoperatively were 78.9% and 85.2% (p < 0.0001), and trifecta achievement rates were 55.2% and 76.9% (p < 0.0001), respectively. RFS was significantly worse in CTG than in NCTG (5-year RFS was 92.6% and 97.4%, respectively). In the one- and multiple-factor subgroups, the median times using the robotic system were 184 and 222 min (p = 0.0003), median WITs were 23 and 28 min (p = 0.0002), median preserved renal function rates at 1 month postoperatively were 80.1% and 73.1% (p = 0.0036), and trifecta achievement rates were 59.9% and 37.9% (p = 0.0014), respectively. CONCLUSIONS: RAPN for high-complexity tumors may show different perioperative outcomes depending on the number of relevant factors. Recurrence appears to be more frequent in high-complexity tumors.2026年03月, International Journal of Urology, 33(3) (3), e70434, 英語, 国際誌研究論文（学術雑誌）
- Background: Enfortumab vedotin plus pembrolizumab (EVP) has become a first-line standard for metastatic or unresectable urothelial carcinoma. However, EVP is associated with distinct toxicities, particularly cutaneous adverse events, and prophylactic systemic corticosteroids were not permitted in pivotal trials. Therefore, the safety and early effectiveness of EVP with routine dexamethasone premedication in real-world practice remain unclear. Methods: This multicenter retrospective study included consecutive patients with metastatic or unresectable urothelial carcinoma who received first-line EVP at five institutions in Japan between September 2024 and September 2025. All patients received routine intravenous dexamethasone premedication before enfortumab vedotin administration. Safety and early clinical outcomes were evaluated, with exploratory subgroup analyses according to clinical trial eligibility and EVITA criteria. Results: Seventy-seven patients were included, with a median age of 75 years, and more than half would have been ineligible for pivotal clinical trials. Cutaneous toxicity was the most frequent adverse event (52.0%), whereas grade ≥3 skin reactions were uncommon (3.9%). With a median follow-up of 6.7 months, the objective response rate was 73.0%. The 6-month progression-free survival and overall survival rates were 73.9% and 78.7%, respectively. Early progression-free survival was generally maintained across subgroups stratified by clinical trial eligibility and EVITA category, with no evidence of excess early progression. Conclusions: In this real-world multicenter cohort, first-line EVP with routine dexamethasone premedication was feasible, with manageable toxicity and encouraging early clinical activity, including in patients with comorbidities commonly encountered in routine clinical practice. Longer follow-up and prospective comparative studies are warranted to clarify long-term outcomes and the impact of dexamethasone on efficacy and toxicity.2026年02月, Cancers, 18(5) (5), 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: To identify independent prognostic factors for recurrence and develop a practical risk stratification system in patients with clinical T1 (cT1) clear-cell renal cell carcinoma (ccRCC) following curative-intent surgery. METHODS: This retrospective multi-institutional study analyzed 1081 consecutive patients with cT1N0M0 ccRCC who underwent partial or radical nephrectomy at 14 Japanese tertiary centers (2016-21). We evaluated six established prognostic factors based on prior literature: pathological T3 upstaging, tumor size, nuclear grade, tumor necrosis, surgical approach, and venous invasion. Cox proportional hazards regression was performed to identify independent predictors of recurrence-free survival. RESULTS: During a median follow-up of 48 months, 66 patients (6.1%) developed recurrence. Multivariable Cox regression identified two independent prognostic factors: pathological T3 upstaging (HR 4.67, 95% CI 2.40-9.08, P <.001) and tumor necrosis (HR 2.51, 95% CI 1.22-5.13, P = .012). Tumor size showed borderline significance (HR 1.22 per cm, 95% CI 1.00-1.49, P = .055). Based on the significant factors, patients were stratified into low-risk (91.1%, no upstaging/necrosis) and high-risk (8.9%, upstaging or necrosis present) groups with recurrence rates of 4.3% and 25.0%, respectively (log-rank P <.001). The 5-year recurrence-free survival rates were 95.2% and 73.4% for low- and high-risk groups, respectively. CONCLUSIONS: Pathological T3 upstaging and tumor necrosis were identified as the only independent predictors of recurrence in cT1 ccRCC. This simplified two-tier risk stratification effectively distinguishes a small high-risk subset (9% of patients) with 25% recurrence rate from the low-risk majority, enabling tailored surveillance strategies and appropriate selection for adjuvant therapy trials.2026年02月, Japanese Journal of Clinical Oncology, 56(5) (5), 646 - 653, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Cabazitaxel (CBZ) is the mainstay of treatment for metastatic castration-resistant prostate cancer (mCRPC). In the present study, we developed a nomogram to predict the individual survival probability after CBZ treatment in patients with mCRPC. METHODS: We retrospectively analyzed 345 patients with mCRPC who started CBZ treatment between September 2019 and March 2024 and randomly divided them into a development cohort (n = 230) and a validation cohort (n = 115). We investigated several potential risk factors for poor overall survival (OS) using the Cox proportional hazard model and developed a nomogram to predict the 1-year survival probability. The accuracy and discrimination ability of the nomograms were evaluated according to Harrell's concordance index (C-index) and calibration plot. RESULTS: We developed a nomogram predicting the 1-year survival probability with predictors including ECOG-PS ≥ 2, presence of liver metastasis, an initial PSA ≥ 30 ng/mL, a PSADT ≤ 3 months, radiological progression of disease during docetaxel, Hb ≤ 12 g/dL, and LDH ≥ 250 U/L. C-indices of our Cox hazard model at internal validation and external validation were 0.72 and 0.67, respectively. The model was adequately calibrated, and its predictions were correlated with the observed outcomes in both cohorts. The OS was significantly different among the risk groups defined by the total points calculated from the nomogram in both cohorts. CONCLUSION: Our validated nomogram, which is predictive of the survival outcome after CBZ treatment in patients with mCRPC, may help in individual clinical decision-making.2025年12月, International Journal of Urology, 32(12) (12), 1792 - 1799, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: The efficacy of local therapy for oligometastatic prostate cancer has been increasingly reported; however, there is little evidence regarding the treatment of patients with castration-resistant disease compared with that for those with castration-sensitive disease. In this retrospective study, we examined data of patients with oligoprogressive castration-resistant prostate cancer (CRPC) treated with progressive site-directed therapy (PSDT) and investigated the prognosticators of treatment efficacy. METHODS: The cohort comprised 35 patients with oligoprogressive CRPC who underwent radiotherapy in the form of PSDT. Oligoprogression was defined as the presence of five or fewer affected sites. Radiation was administered to all lesions without interruption or modification of systemic therapy. The endpoints were prostate-specific antigen (PSA) response, progression-free survival (PFS), and cancer-specific survival (CSS). RESULTS: The most common site was bone (57.1%), and the prostate was a site in 10 (28.6%) patients. Twenty patients (57.1%) achieved a PSA response of ≥ 50%. The median PFS and CSS were 8.0 months (95% confidence interval [CI], 2.3-22.8) and 28.7 months (95% CI, 17.6-not reached), respectively. Multivariate analysis identified time to oligoprogression from the initiation of the most recent systemic treatment ≥ 1 year as a favorable prognostic factor of PFS (hazard ratio [HR], 0.35; 95% CI, 0.13-0.94; p = 0.038). One patient (2.9%) developed urinary frequency (Grade 2). CONCLUSIONS: PSDT for oligoprogressive CRPC may achieve good disease control in patients who evidenced time to oligoprogression ≥ 1 year after the initiation of the most recent systemic treatment.2025年12月, International Journal of Urology, 32(12) (12), 1784 - 1791, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本癌治療学会, 2025年10月, 日本癌治療学会学術集会抄録集, 63回, EN2 - 9, 英語進行性尿路上皮癌を対象としたB440経口がんワクチンの第一相医師主導治験
- UNLABELLED: Patients with advanced nodal involvement (cN2 or cN3) in urothelial carcinoma (UC) typically have poor outcomes after radical surgery. Clinical evidence on how to manage these patients following immunotherapy is limited. Major neoadjuvant trials such as KEYNOTE-B15 and NIAGARA excluded patients with multiple or bulky nodal metastases, leaving a significant gap in evidence. We present a case of a 76-year-old man with cT1 bladder cancer, concomitant distal ureteral UC (≤ cT2), and multiple enlarged right pelvic lymph nodes (cN2). After six cycles of enfortumab vedotin plus pembrolizumab (EVP), he achieved a radiologic complete response (CR) and resolution of hydronephrosis. He then underwent robot-assisted right nephroureterectomy with extended pelvic lymph node dissection using the da Vinci Xi surgical system. Pathology revealed no residual cancer in either the primary site or lymph nodes (ypT0, ypN0), with marked fibrosis suggesting a strong treatment response. There were no surgical complications, and systemic therapy was stopped after surgery. To our knowledge, this is the first reported case of pathologic complete response following EVP and robotic nephroureterectomy in a patient with node-positive UC. This case supports the potential role of surgery in select patients with excellent responses to systemic therapy who were initially considered unresectable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-025-00785-8.2025年10月, International cancer conference journal, 14(4) (4), 407 - 411, 英語, 国際誌研究論文（学術雑誌）
- Introduction This study was performed to investigate the relationship between changes in urination-related quality of life (QOL) after brachytherapy and preoperative findings, including urinary function, urination scores, and patient background. Methods This retrospective study included 193 patients with localized prostate cancer who underwent brachytherapy at our institution. Urination-related QOL was assessed using the urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) score, measured before treatment and 3, 6, and 12 months after treatment. Changes in EPIC scores from baseline were analyzed, and preoperative urination-related parameters - including prostate volume, maximum urinary flow rate, voiding volume, age, International Prostate Symptom Score (IPSS), and Overactive Bladder Symptom Score (OABSS) - were compared with post-treatment QOL outcomes. Results The urination-related EPIC score was lowest at three months post-treatment but gradually improved toward baseline levels. Patients with a preoperative voiding volume of <192 mL showed significantly greater declines in EPIC scores at 3, 6, and 12 months post-treatment. Additionally, those with an IPSS of <7 or an OABSS of <3 had significantly greater declines at six months, but these differences were not observed at 12 months. Prostate volume, maximum urinary flow rate, and age did not significantly impact changes in EPIC scores. Conclusion Preoperative voiding volume was significantly associated with changes in post-treatment urination-related QOL. These findings suggest that preoperative urination-related parameters may help predict post-treatment QOL, highlighting the importance of evaluating pretreatment urinary function when selecting treatments for patients with localized prostate cancer.2025年09月, Cureus, 17(9) (9), e91946, 英語, 国際誌研究論文（学術雑誌）
- Objectives The hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan) offers advanced capabilities for performing complex urological surgeries. However, despite its growing adoption, limited data are available on surgeons' subjective impressions of its usability and the process of skill acquisition. This study aimed to assess surgeons' perceptions of the difficulty of key surgical steps during robot-assisted radical prostatectomy (RARP) using the hinotori system. Methods We included facilities that perform 20 or more RARP procedures annually using the hinotori system. In November 2024, an anonymous online survey was conducted among urologists at these facilities to collect information on their overall RARP experience and specific experience with the hinotori system. Surgeons used a five-point Likert scale to rate the difficulty of seven surgical steps. Although this approach is unique, several steps, such as bladder neck dissection, nerve sparing, and vesicourethral anastomosis, are also considered technically demanding in studies with other robotic systems. Statistical analyses were performed to assess differences based on experience levels. Results We received 58 survey responses, representing a cumulative experience of over 800 RARP cases performed using the hinotori system. Bladder takedown was perceived as the least difficult step, whereas bladder neck dissection, nerve sparing, vesicourethral anastomosis, and pelvic lymph node dissection were rated as more challenging. Stratification by experience showed that surgeons with 40 or more hinotori RARP cases perceived bladder takedown (p = 0.033), nerve sparing (p = 0.024), and vesicourethral anastomosis (p = 0.001) as being easier. Conclusion Surgeons' prior experience with other robotic systems influenced the perceived difficulty of procedures using the hinotori system, particularly for complex steps such as nerve-sparing and vesicourethral anastomosis.2025年08月, Cureus, 17(8) (8), e90487, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: To develop and evaluate a convolutional neural network (CNN)-based model for recognising surgical phases in robot-assisted laparoscopic radical prostatectomy (RARP), with an emphasis on model interpretability and cross-platform validation. METHODS: A CNN using EfficientNet B7 was trained on video data from 75 RARP cases with the hinotori robotic system. Seven phases were annotated: bladder drop, prostate preparation, bladder neck dissection, seminal vesicle dissection, posterior dissection, apical dissection, and vesicourethral anastomosis. A total of 808 774 video frames were extracted at 1 frame/s for training and testing. Validation was performed on 25 RARP cases using the da Vinci robotic system to assess cross-platform generalisability. Gradient-weighted class activation mapping was used to enhance interpretability by identifying key regions of interest for phase classification. RESULTS: The CNN achieved 0.90 accuracy on the hinotori test set but dropped to 0.64 on the da Vinci dataset, thus indicating cross-platform limitations. Phase-specific F1 scores ranged from 0.77 to 0.97, with lower performance in the phase of seminal vesicle dissection, and apical dissection. Gradient-weighted class activation mapping visualisations revealed the model's focus on central pelvic structures rather than transient instruments, enhancing interpretability and insights into phase classification. CONCLUSIONS: The model demonstrated high accuracy on a single robotic platform but requires further refinement for consistent cross-platform performance. Interpretability techniques will foster clinical trust and integration into workflows, advancing robotic surgery applications.2025年07月, BJU international, 136(5) (5), 891 - 901, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: To identify prognostic factors that guide adjuvant therapy decisions, we investigated factors predicting recurrence in patients with high-risk clear cell renal cell carcinoma (RCC) after nephrectomy. METHODS: We retrospectively reviewed patients with non-metastatic, high-risk clear cell RCC who underwent radical or partial nephrectomy at our institution and affiliated centers between January 2016 and March 2024. Multivariate analysis using the Cox proportional hazards model was performed to identify clinicopathological factors associated with recurrence. On the basis of these factors, we developed a risk stratification model. RESULTS: A total of 338 patients were included. The 5-year recurrence-free survival (RFS) rate was 54.3%. Multivariate analysis identified a body mass index of ≤ 22 kg/m2 (Hazard Ratio [HR]: 2.61), rhabdoid differentiation (HR: 5.14), anemia (HR: 1.97), hypercalcemia (HR: 2.67), and C-reactive protein ≥ 0.5 mg/dL (HR: 1.72) as independent predictors of recurrence. RFS was significantly different between patients with varying numbers of risk factors: 3-year RFS rates were 22.6% for those with 3-4 factors, 47.9% for those with two, 75.5% for those with one, and 83.6% for those with none. CONCLUSION: We identified independent predictors of recurrence in patients with nephrectomy-treated clear cell RCC. Patients stratified according to a risk score based on these factors had different recurrence rates, suggesting that this score could assist in guiding adjuvant therapy decisions.2025年07月, International journal of clinical oncology, 30(9) (9), 1849 - 1857, 英語, 国内誌研究論文（学術雑誌）
- INTRODUCTION AND OBJECTIVES: This study assessed the prognostic value of maximal evaluable lesion size (MLS) in predicting the efficacy and outcomes of nivolumab plus ipilimumab (NIVO+IPI) therapy for metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively analyzed 99 mRCC patients treated with NIVO + IPI. Patients were divided into larger-MLS (≥ 35 mm) and smaller-MLS (< 35 mm) groups based on the median MLS. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared, and predictive factors for PFS and OS were identified. RESULTS: The median follow-up period was 29.5 months. In the larger-MLS group (50 patients), the number of patients who did not undergo cytoreductive nephrectomy, as well as the number of patients in whom the kidney, lymph node, and lung were identified as an organ of MLS origin, was significantly higher compared to the smaller-MLS group. ORR was 40% in the larger-MLS group and 32.7% in the smaller-MLS group (p = 0.4315). However, PFS and OS were significantly worse in the larger-MLS group (p = 0.0016 and p = 0.0002, respectively). Multivariate analysis identified Karnofsky performance status (KPS) < 80%, non-clear cell histology, and larger MLS as independent predictors of worse PFS and OS. A prognostic model integrating MLS, KPS, and histology stratified patients effectively, with ≥ 2 risk factors predicting significantly worse OS (p < 0.0001). CONCLUSIONS: MLS is a key prognostic factor in mRCC patients treated with NIVO+IPI. A risk model incorporating MLS, KPS, and histology can aid in patient stratification and treatment decisions.2025年07月, International Journal of Urology, 32(7) (7), 850 - 858, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: Prostate cancer patients receiving androgen deprivation therapy (ADT) have increased risks of decreased bone mineral density (BMD). However, there are no established guidelines for assessing BMD in patients with bone metastases. The aim of this study was to assess the effects of ADT on bone health by comparing longitudinal changes in BMD between prostate cancer patients with and without bone metastases. METHODS: A single-center observational study was conducted from February 2020 to January 2023 at Kobe University Hospital. BMD at the lumbar vertebrae, total hip, and femoral neck was measured at baseline, 6, and 12 months using dual-energy X-ray absorptiometry. Bones were classified into Metastatic Site (with metastases), Non-metastatic Sites (from patients with bone metastases), and Control (patients without metastases) groups. All patients received luteinizing hormone-releasing hormone antagonists or agonists plus oral ARSI or bicalutamide for 1 year. RESULTS: Among the 78 patients, 35, 110, and 245 bones were classified into the Metastatic Site group, Non-metastatic Sites group, and Control group, respectively. The Metastatic Site group exhibited significantly higher T-scores compared with the other groups (P < 0.001). Repeated measures analysis revealed a statistically significant reduction in T-scores over time across all groups (P < 0.001). However, no significant interaction was observed between group classification and time (P = 0.817). CONCLUSION: The present study demonstrates that BMD changes at non-metastatic sites in patients with bone metastases are similar to those in patients without metastases. Monitoring BMD at non-metastatic sites may provide valuable insights into ADT's effects on bone health in prostate cancer patients.2025年04月, International journal of clinical oncology, 30(4) (4), 797 - 804, 英語, 国内誌研究論文（学術雑誌）
- OBJECTIVE: This study aims to evaluate the efficacy and safety of routine corticosteroid premedication with dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving enfortumab vedotin (EV) for previously treated advanced urothelial carcinoma (UC). Furthermore, we assessed the impact of this strategy on treatment continuity and the incidence of dermatologic toxicities. METHODS: We retrospectively analyzed 48 patients with unresectable or metastatic UC who received EV at our institution. All patients received 6.6 mg of intravenous dexamethasone prior to each EV infusion (1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle). Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs version 5.0. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and factors influencing time to cutaneous toxicity onset were analyzed using Cox proportional hazards regression. RESULTS: The median PFS was 4.6 months (95% CI: 3.5-10.8), and the median OS was 14.8 months (95% CI: 7.4-20.0). Grade 1-2 nausea was observed in six patients (14.6%), with no Grade ≥ 3 nausea reported. Dermatologic toxicity occurred in 13 patients (31.7%), all Grade 1-2, and none required systemic corticosteroid therapy. Patients with normal serum albumin levels experienced significantly earlier cutaneous toxicity onset compared with those with abnormal levels (p = 0.015). Treatment continuity was largely maintained, with minimal severe AEs leading to discontinuation. However, the study's single-center, retrospective design and small sample size may limit the generalizability of these findings, warranting further prospective validation. CONCLUSION: Routine dexamethasone premedication in patients receiving EV was feasible and associated with a low incidence of severe nausea and cutaneous toxicity. While these findings suggest a potential role for corticosteroids in CINV control and cutaneous toxicity mitigation, the retrospective design and absence of a control group preclude definitive conclusions. Further prospective studies are needed to clarify the impact of corticosteroid premedication in this setting.2025年03月, International urology and nephrology, 57(9) (9), 2867 - 2875, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND/AIM: This study aimed to investigate the genomic features of small cell neuroendocrine prostate cancer (SCPC) in Japanese patients, assess their relationships with platinum-based chemotherapy efficacy, and evaluate the potential treatment eligibility for therapies using cancer genomic profiling. PATIENTS AND METHODS: This retrospective study included 21 patients diagnosed with SCPC between 2018 and 2022. An expert pathologist reviewed the biopsy specimens according to the World Health Organization prostate cancer classification. Biopsy samples from primary or metastatic lesions were analyzed using FoundationOne® CDx to identify genomic mutations, focusing on DNA damage repair (DDR) mutations and other clinically relevant alterations. Platinum-based chemotherapy efficacy was assessed using progression-free survival (PFS) and overall survival (OS) outcomes. RESULTS: DDR mutations were detected in eight (38.1%) patients, and BRCA mutations were present in three (14.3%) cases. TP53 and RB1 mutations were identified in 15 (71.4%) and 12 (57.1%) cases, respectively. Three (14.8%) patients were identified with microsatellite instability-high or tumor mutational burden-high, making them eligible for immune checkpoint inhibitor treatment. PFS/OS rates suggested that the presence of these mutations did not significantly impact platinum-based chemotherapy efficacy. Six (28.6%) patients were eligible for treatments approved for prostate cancer in Japan as of 2024. CONCLUSION: This study is the first to reveal the SCPC genomic landscape in Japanese patients. Although genomic mutations, including DDR mutations, were not predictive of platinum-based chemotherapy efficacy, active genomic testing may improve access to targeted therapies for this challenging malignancy, especially where treatment options are limited.2025年03月, Anticancer research, 45(3) (3), 1137 - 1147, 英語, 国際誌研究論文（学術雑誌）
- Muscle-invasive bladder cancer (MIBC), a highly heterogeneous disease, shows genomic instability and a high mutation rate, making it difficult to treat. Recent studies revealed that cancer stem cells (CSCs) play a critical role in MIBC frequent recurrence and high morbidity. Previous research has shown that Cyclooxygenases-2 (COX-2) is particularly highly expressed in bladder cancer cells. In recent years, the development of oncolytic adenoviruses and their use in clinical trials have gained increased attention. In this study, we composed a conditionally replicative adenovirus vector (CRAd-synNotch) that carries the COX-2 promotor driving adenoviral E1 gene, the synNotch receptor therapeutic gene, and the Ad5/35 fiber gene. Activation of the COX-2 promoter gene causes replication only within COX-2 expressing cancer cells, thereby leading to tumor oncolysis. Also, CD44 and HIF signals contribute to cancer stemness and maintaining CSCs in bladder cancer, and the transduced synNotch receptor inhibits both CD44 and HIF signals simultaneously. We performed an in vivo study using a mouse xenograft model of T24 human MIBC cells and confirmed the significant antitumor activity of CRAd-synNotch. Our findings in this study warrant the further development of CRAd-synNotch for treating patients with MIBC.2025年03月, Cancer Gene Therapy, 32(3) (3), 306 - 317, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: This is a multicenter, open-label, single-arm clinical trial to evaluate the safety and efficacy of oral cancer vaccine B440 in patients with PD-1/PD-L1 inhibitor-resistant advanced urothelial cancer. METHODS: The trial will be performed at three university hospitals in Japan. The target number of patients will be 12. The patients will be treated orally with B440 once daily for 5 days followed by 2 days for four consecutive courses (4 weeks, 20 treatments). The low-dose group will receive 800 mg (4 capsules) per dose and the high-dose group will receive 1,600 mg (8 capsules) per dose. The primary outcome will be the number and incidence of DLT cases the start of treatment and Day 28. Secondary outcomes are the presence or absence of a response, the best overall response and PFS. DISCUSSION: If this trial shows B440 to be safe and effective, it may lead to a late phase randomized controlled trial in advanced urothelial cancer. Ultimately, we hope to provide a new treatment option for such patients. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCT2051220143. Registered on December 27, 2022.2025年02月, BMC cancer, 25(1) (1), 195 - 195, 英語, 国際誌研究論文（学術雑誌）
- INTRODUCTION: Ureteropelvic junction obstruction (UPJO) in patients with a duplicated collecting system is rare, and evidence on robot-assisted laparoscopic pyeloplasty (RALP) and technical strategies for end-to-side pyeloureterostomy in such cases remains limited. MATERIALS AND SURGICAL TECHNIQUE: We present technical refinements used during RALP in a patient with an incomplete duplicated collecting system. First, an open-ended ureteral catheter was used to guide accurate ureteral incision and secure anastomosis. Second, the dorsal pelvis of the lower pole was anastomosed to the larger-caliber common ureter rather than the narrow upper pole ureter. To ensure a tension-free anastomosis, the kidney and pelvis were mobilized as needed. Third, an M-shaped traction technique was applied during posterior wall suturing: the lateral stay suture was tied, while the medial one was left untied and retracted with a bulldog clamp to create a groove, enhancing lumen visibility and enabling continuous posterior suturing under direct vision. DISCUSSION: This case demonstrates the feasibility of end-to-side pyeloureterostomy for UPJO with incomplete duplication using robotic techniques. Key modifications-catheter-assisted incision, anatomical mobilization, and M-shaped traction-allowed for precise anastomosis. Further case accumulation is needed to validate these strategies for similar anatomical variations.2025年, Asian journal of endoscopic surgery, 18(1) (1), e70151, 英語, 国内誌研究論文（学術雑誌）
- OBJECTIVES: We aimed to investigate the prognostic significance of tumor size in metastatic renal cell carcinoma (mRCC) by comparing the effectiveness of dual immune checkpoint inhibitor (IOIO) and immune checkpoint inhibitor combined with tyrosine kinase inhibitor (IOTKI) therapies. METHODS: This retrospective observational study included patients with mRCC diagnosed between October 2014 and February 2024 who received IOIO or IOTKI treatment at Kobe University Hospital and 5 affiliated hospitals. Clinical and imaging data were collected, and target lesions were measured according to RECIST v.1.1 criteria. Time-dependent ROC curve analysis was performed to evaluate the prognostic value of tumor size, nephrectomy status, and IMDC risk criteria for progression-free survival (PFS) and overall survival (OS). RESULTS: The study included 180 mRCC patients, consisting of 99 receiving IOIO therapy and 81 receiving IOTKI therapy. Time-dependent AUC analysis showed that tumor size had a higher predictive ability for PFS and OS in the IOIO group than the IOTKI group. In multivariate analysis, tumor size was a significant independent prognostic factor for PFS (HR: 1.010, 95% CI: 1.004-1.016, P < 0.001) in the IOIO group. Moreover, the AUC for tumor size was consistently superior in predicting outcomes compared to nephrectomy status and IMDC risk classification in the IOIO group. Kaplan-Meier curves indicated that tumor size effectively stratified PFS in both nephrectomized and non-nephrectomized cases. CONCLUSION: Tumor size significantly impacts the prognosis of mRCC patients treated with IOIO therapy, demonstrating greater predictive ability than nephrectomy status and IMDC risk classification. These findings suggest that tumor volume should be considered a critical factor in treatment decision-making for renal cancer, particularly in patients undergoing IOIO therapy.Elsevier BV, 2025年01月, Urologic Oncology: Seminars and Original Investigations, 43(1) (1), 63.e19 - 63.e27, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND/OBJECTIVES: Extended pelvic lymph node dissection is a crucial surgical technique for managing intermediate to high-risk prostate cancer. Accurately predicting lymph node metastasis before surgery can minimize unnecessary lymph node dissections and their associated complications. This study assessed the efficacy of various machine learning models for predicting lymph node metastasis in a cohort of Japanese patients who underwent robot-assisted laparoscopic radical prostatectomy. METHODS: Data from 625 patients who underwent extended pelvic lymph node dissection or standard dissection with lymph node metastasis between October 2010 and February 2023 were analyzed. Four machine learning models-Random Forest, Light Gradient-Boosting Machine, Logistic Regression, and Support Vector Machine-were used to predict lymph node metastasis. Their performance was assessed using receiver operating characteristic curves, a decision curve analysis, and predictive values at different thresholds. RESULTS: Lymph node metastasis was observed in 34 patients (5.4%). The Light Gradient-Boosting Machine had the highest AUC of 0.924, followed by the Random Forest model with an AUC of 0.894. The decision curve analysis indicated substantial net benefits for both models, particularly at low threshold probabilities. The Light Gradient-Boosting Machine demonstrated superior accuracy, achieving 95.6% at the 0.05 threshold and 96.7% at the 0.10 threshold, outperforming other models and conventional nomograms in the validation dataset. CONCLUSION: Machine learning models, especially Light Gradient-Boosting Machine and Random Forest, show significant potential for predicting lymph node metastasis in prostate cancer, thereby aiding in reducing unnecessary surgical interventions.2024年12月, Cancers, 16(23) (23), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The standard treatment for non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is complete surgical resection; however, this procedure is complex and carries high complication rates and perioperative mortality. Previous studies have explored preoperative multimodal therapy to reduce surgical difficulty, but limited evidence prevents guideline recommendations. This study aimed to investigate the impact of neoadjuvant therapy on the prognosis of patients with RCC and IVC thrombus without distant metastasis. METHODS: Data from 2006 to 2024 on RCC patients with IVC thrombus undergoing radical nephrectomy plus IVC thrombus resection were collected. Patients received neoadjuvant therapy, including tyrosine kinase inhibitors or immune checkpoint inhibitors, followed by surgery. Tumor size and thrombus height were assessed by computed tomography. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier curves. Multivariate analysis was used to identify factors predicting DFS. RESULTS: Thirty-one patients who did not receive neoadjuvant chemotherapy therapy (NAC-Naive group) and 19 patients who received neoadjuvant chemotherapy therapy (NAC group) were analyzed. The NAC group showed significant reductions in primary renal tumor size and neutrophil-to-lymphocyte ratio compared to the NAC-Naive group just before nephrectomy. The NAC group had significantly improved DFS and OS. Median DFS and OS were not reached in the NAC group compared to 26.3 months and 73.5 months, respectively, in the NAC-Naive group. The NAC group had a 2-year recurrence-free survival rate of 70.9% compared to 50.6% in the NAC-Naive group. Multivariate analysis identified a preoperative tumor size of 10 cm or larger and lack of neoadjuvant therapy as poor prognostic factors for DFS. CONCLUSION: Neoadjuvant therapy significantly improves the prognosis of RCC patients with IVC thrombus. This therapy reduces surgical invasiveness and has a mid- to long-term preventive effect on recurrence. These findings support the potential benefit of neoadjuvant systemic therapy in improving outcomes for this patient population.Elsevier BV, 2024年11月, Urologic Oncology: Seminars and Original Investigations, 43(3) (3), 178 - 185, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本癌治療学会, 2024年10月, 日本癌治療学会学術集会抄録集, 62回, PSP2 - 5, 英語国産手術支援ロボット"hinotori"を用いた先端AI解析研究
- ABSTRACT Background This study aimed to investigate the perioperative outcomes of robot‐assisted laparoscopic pyeloplasty (RLP) using the recently launched hinotori surgical robot system. Methods This retrospective study compared the perioperative outcomes of 11 consecutive patients who underwent RLP with the hinotori surgical robot system from October 2022 to March 2024 (hinotori group) and 30 consecutive patients who underwent RLP with the da Vinci system from March 2019 to September 2022 (da Vinci group). Results The patient characteristics of the groups were similar. The median operative times in the hinotori and da Vinci groups were 236.0 and 231.5 min, respectively (p = 0.480). The success rates were 100.0% and 96.7%, respectively (p = 1.000). Clavien‐Dindo grade ≥ 3 complications occurred in one patient (9.1%) in the hinotori group and one patient (3.3%) in the da Vinci group (p = 0.470). Conclusions The perioperative outcomes in the hinotori group were not inferior to those in the da Vinci group.Wiley, 2024年09月, The International Journal of Medical Robotics and Computer Assisted Surgery, 20(5) (5), e2673, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The diagnosis of treatment-related neuroendocrine prostate cancer (t-NEPC) often involves a pathological assessment and immunohistochemistry (IHC) for neuroendocrine markers. Genomic alterations in RB1 and TP53 are frequently observed in NEPC and are believed to play a crucial role in the transformation of adenocarcinoma to NEPC. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of patients with t-NEPC to better understand their prognosis and diagnostic utility. METHODS: This retrospective study reviewed the records of patients diagnosed with t-NEPC at Kobe University Hospital between October 2018 and December 2022. Clinical data, including age, serum neuroendocrine marker levels, and treatment history, were collected. IHC was performed for conventional neuroendocrine markers (synaptophysin, chromogranin A, and CD56) and RB1 and p53 expression. Next-generation sequencing (NGS) was conducted using FoundationOne® CDx to identify mutations in RB1 and TP53. RESULTS: This study included 20 patients with t-NEPC. The median time from ADT initiation to development was 42.8 months. IHC revealed RB1 loss in 75% of cases and p53 abnormalities in 75% of cases. NGS identified RB1 mutations in 55% and TP53 mutations in 75% of cases. The concordance between NGS and IHC results was high, with 70% (14/20) agreement for RB1/RB1 and 80% (16/20) for p53/TP53. The immunostaining and genomic analysis of RB1/RB1 and p53/TP53 showed abnormal findings for the four negative cases for conventional neuroendocrine markers. CONCLUSIONS: This study indicated high concordance between IHC and NGS findings for RB1/RB1 and p53/TP53 in t-NEPC. We provide a comprehensive benchmark of NGS performance compared with IHC, and these findings may help increase the diagnostic sensitivity of t-NEPC.2024年09月, The Prostate, 84(16) (16), 1506 - 1514, 英語, 国際誌研究論文（学術雑誌）
- Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell line to improve antigen uptake and then determined the anti-tumor effect in tumor-bearing mice. DC2.4 cells were pulsed with the cell lysate of EL4, a murine lymphoma cell line, and VP-R8 to generate the DC2.4 vaccine. For the in vivo study, DC2.4 cells pulsed with EL4 lysate and VP-R8 were subcutaneously injected into the inguinal lymph node to investigate the anti-tumor effect against EL4 and EL4-specific T cell immune responses. VP-R8 significantly improved antigen uptake into DC2.4 compared to conventional keyhole limpet hemocyanin (p < 0.05). The expression of MHC class I, MHC class II, and CD86 in DC2.4 cells significantly increased after pulsing tumor lysates with VP-R8 compared to other treatments (p < 0.05). The intra-lymph node injection of DC2.4 pulsed with both VP-R8 and EL4 lysate significantly decreased tumor growth compared to DC2.4 pulsed with KLH and lysates (p < 0.05) and induced tumor-infiltrating CD8T cells. The DC2.4 vaccine also remarkably increased the population of IFN-gamma-producing T cells and CTL activity against EL4 cells. In conclusion, we demonstrated that VP-R8 markedly enhances the efficiency of dendritic cell-based vaccines in priming robust anti-tumor immunity, suggesting its potential as a beneficial additive for dendritic cell-based immunotherapy.2024年05月, International journal of molecular sciences, 25(11) (11), 英語, 国際誌研究論文（学術雑誌）
- INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for meta-static non-clear-cell renal cell carcinoma (nccRCC). METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared. RESULTS: The first-line regimen was ICI-ICI in 26 cases and ICI-TKI in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between groups (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535), nor above grade 3 (p=0.3786) between the ICI-ICI and ICI-TKI groups. CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.2024年05月, Canadian Urological Association journal = Journal de l'Association des urologues du Canada, 18(5) (5), E162-E166, 英語, 国際誌研究論文（学術雑誌）
- The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.2023年11月, Oncology letters, 26(5) (5), 470 - 470, 英語, 国際誌研究論文（学術雑誌）
- INTRODUCTION: The performance of robot-assisted laparoscopic pyeloplasty has recently been increasing in frequency. However, patients with duplicated renal pelvises and ureters can present challenges. CASE PRESENTATION: A 71-year-old woman presented with flank pain and was diagnosed with ureteropelvic junction obstruction with an incomplete duplicated collecting system. Preoperative imaging did not reveal the details of the stenosis. Therefore, three reconstructive procedures were prepared: The Anderson-Hynes procedure, end-to-side pyeloureterostomy, and upper pole ureter to lower pole pyeloplasty with the Anderson-Hynes procedure for the lower pole. These procedures were determined by the length of the intact ureter and the presence of crossed vessels. During the surgery, the crossing vein was severed, allowing successful reconstruction with Anderson-Hynes anastomosis. CONCLUSION: Preoperative evaluation and preparation of multiple surgical techniques are crucial in robot-assisted laparoscopic pyeloplasty for incomplete duplicated collecting systems.2023年11月, IJU case reports, 6(6) (6), 357 - 361, 英語, 国際誌研究論文（学術雑誌）
- 2023年10月, Clinical genitourinary cancer, 21(5) (5), 613.e1-613.e6, 英語, 国際誌研究論文（学術雑誌）
- Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60-70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.2023年06月, Scientific reports, 13(1) (1), 9994 - 9994, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.2023年06月, Japanese journal of clinical oncology, 53(6) (6), 522 - 529, 英語, 国際誌研究論文（学術雑誌）
- Triple-negative breast cancer (TNBC) is known as the most difficult molecular subtype of breast cancer to treat. Recent studies revealed that cancer stem cells (CSCs) play a critical role in TNBC recurrence and metastasis. In this study, we developed a recombinant replication-deficient adenoviral vector (Ad-CD44-N-HIF-3α4), which contains a gene encoding a synthetic Notch (synNotch) receptor composed of the extracellular domain of CD44 (CD44-ECD) and the hypoxia-inducible factor (HIF)-3α4 connected by the Notch core regulatory region. CD44 is a transmembrane glycoprotein and known as a CSC marker in breast cancer and other malignancies. HIF-3α4 is a dominant-negative regulator of HIF-1α and HIF-2α and inhibits hypoxia-inducing effect. Both CD44 and HIF signals contribute cancer stemness and maintaining CSCs in breast cancer. The CD44-ECD in the synNotch receptor acts as the CD44 decoy receptor, and after a ligand such as a hyaluronic acid binds to the CD44-ECD, HIF-3α4 is released from the Notch core domain. We performed an in vivo study using a mouse xenograft model of MDA-MB-231, a highly invasive TNBC cell, and confirmed the significant antitumor activity of the intratumoral injections of Ad-CD44-N-HIF3α4. Our findings in this study warrant the further development of Ad-CD44-N-HIF3α4 for the treatment of patients with TNBC.2023年, Frontiers in oncology, 13, 1147668 - 1147668, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVE: In renal cell carcinoma with inferior vena cava (IVC) thrombus, adhesion to, or invasion into, the IVC wall will often increase the level of surgical difficulty and even necessitate resection of the IVC. It will generally be difficult to perform an accurate preoperative assessment using the standard imaging modalities of contrast-enhanced computed tomography and standard magnetic resonance imaging (MRI). Cine MRI is an MRI sequence that captures motion to produce detailed information on both the anatomy and the dynamic motion. In the present study, we evaluated the accuracy of preoperative cine MRI for determining the need for IVC wall resection, with validation of the imaging findings according to the intraoperative findings. METHODS: A total of 15 patients who had undergone radical nephrectomy and tumor thrombectomy from May 2018 to April 2020 met the inclusion criteria. The primary outcome of interest was the need for IVC resection because of adhesion or invasion of a venous tumor thrombus. Cine MRI was used to evaluate the blood flow between the tumor thrombus and the IVC wall and the presence of tumor thrombus mobility during free respiration. The sensitivity and specificity were calculated for preoperative cine MRI for determining the need for IVC wall resection. The Fisher exact test was used to determine the association between intraoperative IVC wall resection and the cine MRI findings. Furthermore, receiver operating characteristic curves and the area under the curve were used to compare the accuracy of conventional MRI and cine MRI. RESULTS: Of the 15 patients, 8 (53.3%) had undergone IVC resection. We found that the absence of both dynamic blood flow and tumor thrombus mobility on cine MRI could reliably predict for IVC resection with 100% (95% confidence interval, 51.8%-100%) sensitivity and 85.7% (95% confidence interval, 42.1%-1.00%) specificity. The area under the receiver operating characteristic curve was 0.821 for conventional MRI and 0.929 for cine MRI. CONCLUSIONS: In the preoperative setting, cine MRI could be a helpful examination modality to predict for the need for IVC wall resection for patients with renal cell carcinoma with venous tumor thrombus.2022年07月, Journal of vascular surgery. Venous and lymphatic disorders, 10(4) (4), 908 - 915, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: Two methods are used to identify sarcopenia by calculating skeletal muscle area on computed tomography: the skeletal muscle index (SMI) and the psoas muscle index (PMI). Programmed death (PD)-1 inhibitors are helpful in treating metastatic renal cell carcinoma (mRCC). However, there remains insufficient information regarding a clear and easy-to-use biomarker for predicting the response to PD-1 inhibitors in patients with mRCC. Therefore, we investigated the influence of sarcopenia on clinical outcomes in patients with mRCC undergoing treatment with nivolumab. MATERIALS AND METHODS: This study evaluated 96 patients with RCC who received nivolumab. The SMI and PMI were calculated for each patient and normalized for stature by use of the following formulas: SMI (cm²/m²)=([skeletal muscle cross-sectional area at the level of L3]/[height]²) and PMI (cm²/m²) = ([left-right sum of the psoas muscle areas at the level of L3]/[height]²). The relationship of the clinical variables with progression-free survival and overall survival (OS) was examined using a Cox proportional hazards model. RESULTS: According to the SMI-based definition of sarcopenia, 74.0% of patients had sarcopenia. However, according to the PMI-based definition of sarcopenia, only 34.3% of patients were diagnosed with sarcopenia. Multivariate analysis identified sarcopenia based on PMI (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.04-7.26; p<0.001) and International Metastatic RCC Database Consortium poor risk status (HR, 1.90; 95% CI, 1.03-3.50; p=0.041) as significant and independent prognostic factors of OS. CONCLUSIONS: PMI-based sarcopenia is a significant prognostic factor for OS in patients with RCC who receive nivolumab therapy.2022年07月, Investigative and clinical urology, 63(4) (4), 415 - 424, 英語, 国際誌研究論文（学術雑誌）
- Recently, robot-assisted laparoscopic partial nephrectomy (RAPN) has become a commonly performed surgical treatment for small renal tumors, but for difficult cases, such as those presenting with multiple tumors, there are few institutions with experience. We herein report two cases of unilateral multifocal renal cell carcinoma that were successfully treated with RAPN. Case 1: A 65-year-oldwoman was incidentally identified to have two right kidney tumors on imaging. RAPN under cold ischemia was performed. Pathological examinations revealed both tumors to be clear cell carcinoma. Case 2: A 56-year-oldman was incidentally found to have two left kidney tumors on imaging. RAPN under zero-ischemia and warm ischemia was performed. Pathological examinations revealed both tumors to be clear cell carcinoma. In both cases, no recurrence has been observed, and the decrease that occurred in the renal function was mild during the one-and-a half year follow-up.2022年07月, Hinyokika kiyo. Acta urologica Japonica, 68(7) (7), 245 - 249, 日本語, 国内誌研究論文（学術雑誌）
- BACKGROUND: Ureteroscopy for middle ureteral stones is often difficult from an anatomical view. This study aimed to evaluate the pelvic anatomy in three dimensions and investigate the relationship between the pelvic anatomy and potential semi-rigid ureteroscopic approach for treating middle ureteral stones. METHODS: From a total of 967 patients who underwent ureteroscopy from December 2017 to January 2021, 124 patients who had middle ureteral stones were included in this retrospective cohort study. The pelvic transverse diameter, pelvic vertical diameter, pelvic depth, and lumbosacral angle were measured through preoperative non-contrast computed tomography to define the shape of the pelvic cavity. The relationship between the reachability of the middle ureteral stone using a semi-rigid ureteroscope and the aforementioned anatomical factors, as well as treatment outcomes, was examined retrospectively. RESULTS: The lumbosacral angle and female sex were significant predictors of the possibility of a semi-rigid ureteroscopic approach to middle ureteral stones [odds ratio =1.08; 95% confidence interval (CI): 1.03-1.14; P=0.003, and odds ratio =3.23; 95% CI: 1.12-9.32; P=0.03, respectively]. The cutoff value of the lumbosacral angle was 149.9°, with a sensitivity of 55.1% and a specificity of 72.7%. The time to reach the stone was longer in the lumbosacral angle <150° group than in the lumbosacral angle ≥150° group (P=0.049). CONCLUSIONS: In this study, gradual lumbosacral angle and female sex are positive predictors of the reachability of the middle ureteral stone with a semi-rigid ureteroscope.2022年04月, Translational andrology and urology, 11(4) (4), 451 - 459, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20-30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab. PATIENTS AND METHODS: A total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed. RESULTS: Patients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%). CONCLUSION: PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.2022年03月, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 24(3) (3), 568 - 577, 英語, 国際誌研究論文（学術雑誌）
- (一社)西日本泌尿器科学会, 2021年11月, 西日本泌尿器科学会総会抄録集, 73回, 166 - 166, 英語The efficacy of pre-operative cine MRI to evaluate the adhesion of renal cancer thrombus to the wall of inferior vena cava(和訳中)
- 日本老年泌尿器科学会, 2021年04月, 日本老年泌尿器科学会誌, 34(1) (1), 123 - 123, 日本語
- OBJECTIVES: To investigate the findings of preoperative magnetic resonance imaging associated with the occurrence of transient urinary incontinence after holmium laser enucleation of the prostate. METHODS: At a single institution, 360 patients underwent holmium laser enucleation of the prostate between January 2014 and December 2018. Of those, we retrospectively evaluated 237 who underwent preoperative magnetic resonance imaging and for whom postoperative evaluations were available for >3 months after holmium laser enucleation of the prostate. We carried out preoperative magnetic resonance imaging, and measured the periurethral sphincter complex, levator ani thickness, membranous urethral length and minimal residual membranous urethral length. Logistic regression analysis was carried out to assess the variables associated with incontinence. RESULTS: Transient urinary incontinence occurred after holmium laser enucleation of the prostate in 68 patients (28.7%); 46 (67.6%) of whom recovered within 3 months. Multivariate analysis showed that the membranous urethral length was independently associated with postoperative urinary incontinence at 1 and 3 months after surgery. The operative time was also independently associated with postoperative transient urinary incontinence at 1 month after surgery. CONCLUSION: Preoperative membranous urethral length and operative time are independent predictors of transient urinary incontinence after holmium laser enucleation of the prostate. These findings should be considered by surgeons before surgery.2020年10月, International journal of urology : official journal of the Japanese Urological Association, 27(10) (10), 893 - 898, 英語, 国際誌研究論文（学術雑誌）
- 2020年, Japanese Journal of Endourology, 日本語研究論文（学術雑誌）
- When resecting small tumors or tumors with an irregular margin, a marking technique is conducted prior to the surgery. CT-guided marking techniques are common in pulmonary surgery, but it is rarely used in abdominal or urological surgery. We performed a marking technique for a small tumor that was undetectable by ultrasound using CT guidance prior to laparoscopic resection.A 63 year-old woman, two years after total hysterectomy for uterine stromal sarcoma, underwent combined right kidney resection and retroperitoneal tumor resection for a giant recurrence. Two months after the surgery, micro recurrence was observed in the vicinity of the right intestinal psoas muscle which upon follow up, the tumor size increased to 1 cm. Surgical resection of the small recurrent tumor was planned. Since it was difficult to detect by ultrasound, preoperative CT-guided marking was performed. Retroperitoneal laparoscopic resection was performed the following day. The histopathological diagnosis was endometrial stromal sarcoma.2020年, Nihon Hinyokika Gakkai zasshi. The japanese journal of urology, 111(1) (1), 34 - 37, 日本語, 国内誌研究論文（学術雑誌）
- A 74 year-old man presented with complaints of dysuria and miction pain. Since the prostate volume was 43.5 ml, the patient was scheduled for surgical treatment of benign prostatic hyperplasia. However, prostate cancer was suspected from the magnetic resonance imaging findings and a prostate biopsy was performed. No malignant findings were observed in the pathological results, but numerous plasma cells stained positive for IgG4. Abdominal computed tomography showed pancreatic head enlargement with surrounding inflammatory changes and elevated serum IgG4 was also observed. The patient was diagnosed with IgG4-related disease (pancreatitis/prostatitis). Dysuria improved with induction of 30 mg prednisolone. The patient no longer needed to take the α1 blocker and 5α reductase inhibitor. The international prostate symptom score and urine flow measurement indicated that the patient remained in good condition at 18 months since the start of treatment.2019年09月, Hinyokika kiyo. Acta urologica Japonica, 65(9) (9), 381 - 384, 日本語, 国内誌研究論文（学術雑誌）
- Background: CT-guided marking technique is rarely used in abdominal or urologic surgery. We developed and performed a marking technique for a small tumor, undetectable by ultrasound, using CT guidance before laparoscopic resection of the tumor. Case Presentation: A 73-year-old woman with a history of breast cancer underwent right colectomy with D3 lymph node dissection for ascending colon cancer. Five years after the operation, a solitary tumor was found in the right pararenal region of the retroperitoneal space on enhanced abdominal CT. The tumor was 20 mm in diameter and undetectable by ultrasound, so we performed a marking technique using CT guidance before the operation. Placing the patient in a prone position on the CT table, a 22-gauge needle was inserted into the Gerota's fascia percutaneously and a mixed fluid containing India ink and Iopamidol was injected para to the tumor by the radiologist. During the surgery, the marker was clearly identified and the cutting line was determined to ensure a sufficient surgical margin. The tumor was laparoscopically resected as planned. The histopathologic diagnosis was adenocarcinoma, compatible with metastasis of colon cancer. The postoperative course was uneventful and the patient remained free of disease at 10 months after surgery. Conclusion: When resecting small tumors or tumors with an irregular margin, a marking technique is conducted before the surgery. But, preoperative CT-guided marking has not been applied generally for resection of intraabdominal lesion yet. CT-guided marking can be effective when performing minimally invasive and curable surgery on small tumors. This is the first report of an effective CT-guided marking before retroperitoneal laparoscopic tumorectomy. We believe that this technique provides an important therapeutic option for small tumors that may be undetectable by ultrasound.2018年, Journal of endourology case reports, 4(1) (1), 120 - 123, 英語, 国際誌研究論文（学術雑誌）
- 2017年, Jpn J Urol Surg腎原発孤立性線維性腫瘍 （solitary fibrous tumor）の1例研究論文（学術雑誌）
- (一社)日本癌治療学会, 2024年10月, 日本癌治療学会学術集会抄録集, 62回, P17 - 7, 英語機械学習を用いた限局性前立腺癌患者におけるリンパ節転移の予測モデルの開発
- (一社)日本泌尿器科学会総会事務局, 2021年12月, 日本泌尿器科学会総会, 109回, PP02 - 09, 日本語ニボルマブを使用した腎細胞癌患者の予後と骨格筋量との関連についての検討
- (一社)西日本泌尿器科学会, 2021年11月, 西日本泌尿器科学会総会抄録集, 73回, 166 - 166, 英語術前cine MRIによる腎癌血栓の下大静脈壁への癒着評価の有効性(The efficacy of pre-operative cine MRI to evaluate the adhesion of renal cancer thrombus to the wall of inferior vena cava)
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2026年04月01日 - 2029年03月31日ロボット手術操作ログのXYZ座標によるAI技能評価と転帰予測の統合
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2025年04月01日 - 2028年03月31日癌幹細胞を標的とする腫瘍溶解性ウイルスを用いた筋層浸潤性膀胱癌に対する新規治療法
- 日本医療研究開発機構（AMED）, 令和7年度「メディカルアーツ研究事業」, データ利活用・ライフコースプロジェクト, 神戸大学, 2025年04月 - 2028年03月, 研究代表者手術支援ロボットにおける術中操作ログのAI解析による、次世代型 手術技術評価・教育システムの開発研究
- 2025年度日本癌治療学会/KFCR公募型若手研究助成, 神戸大学医学部附属病院, 2026年07月 - 2027年06月, 研究代表者転移性尿路上皮癌における腸内細菌叢を基軸とした免疫応答予測バイオマーカーの開発
- 2026年04月 - 2027年03月, 研究代表者2026年度 神戸大学GAPファンドプログラム（うりぼーファンド）ディープテック型起業枠
- 2026年04月 - 2027年03月, 研究代表者NEDO NEP開拓コース「Front-Runner（FR）」
- 日本泌尿器内視鏡・ロボティクス学会 第2回 教育コンテンツ作成事業助成, 2026年06月 - 2026年11月術中情報のAI解析による教育システム開発
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2023年04月01日 - 2026年03月31日腎癌WT1経口ワクチンによる免疫チェックポイント阻害薬の制癌性増強作用の解明マウス腎癌モデルを用いて、WT1表層発現したビフィズス菌の投与による抗腫瘍効果の評価を行った。具体的には、平均腫瘍体積、腫瘍内の浸潤リンパ球解析、免疫染色での評価を行った。いずれも、WT1表層発現したビフィズス菌の投与で免疫反応の活性化による抗腫瘍効果を発揮したことを示唆する所見が得られた。平均腫瘍体積では、PBS投与群に対してWT1表層発現したビフィズス菌と免疫チェックポイント阻害薬の併用群は有意に腫瘍の発育が抑制された。腫瘍内の浸潤リンパ球解析でも、併用群においてCD8陽性細胞の浸潤を認めた。WT1表層発現したビフィズス菌の単剤投与群では、CD4陽性細胞が多く浸潤している初見も得られ、一部Treg細胞の関与による治療抵抗性を示唆する所見もあった。
- 日本泌尿器科内視鏡学会, 第5回ロボット支援手術研究助成金B, 2024年11月 - 2025年11月手術操作ログを用いたAIモデルの実装
- 日本泌尿器科学会, 第18回日本泌尿器科学会ヤングリサーチグラント, 2024年04月 - 2025年04月腎癌におけるWT1経口がんワクチンの臨床応用を目指したトランスレーショナル・リサーチ 〜臨床標本を用いたWT1発現率と腫瘍浸潤リンパ球についての探索研究〜
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2022年04月01日 - 2025年03月31日癌幹細胞を標的とした前立腺癌に対する新規遺伝子治療法の開発現在までに我々は、癌遺伝子治療薬としてウイルスベクターに搭載する治療遺伝子として、癌幹細胞マーカーとして知られるCD44のデコイ（おとり）レセプターと低酸素誘導因子（hypoxia inducible factor; HIF）の阻害因子であるHIF-3α4をNotch core domainで結合させたCD44-N-HIF3α4融合遺伝子を創出し、強力な抗腫瘍効果を有することを確認している。今回、本治療遺伝子を代表的な腫瘍融解性ウイルス（OV）である制限増殖型Ad（Conditionally replicating adenovirus; CRAd）に搭載した新規OV、CRAd-CD44-N-HIF3α4を開発する。本研究期間前までに作製していた治療遺伝子CD44-N-HIF3α4を搭載した制限増殖型アデノウイルスベクターCRAｄの再評価を実施したところ、治療遺伝子の導入効率が低かったことから再度、改良したCRAdベクターを作製した。今回のベクター ではアデノウイルスのファイバーを改変することによりアデノウイルス受容体（ＣＡＲ）を発現しない細胞にも感染することができ、感染効率も上昇した。また再作製したCRAdの遺伝子発現を確認し、In vitroでの細胞増殖抑制効果を確認した。また、本ＣＲＡｄはＣＯＸ２を高発現する腫瘍細胞のみに特異的に増殖する設計になっているが、これに関してもＩn Vitro実験で本CRAｄがＣＯＸ２高発現細胞株に特異的に増殖することを確認した。マウス膀胱癌Xenograftモデルを用いたＩｎ vivoモデルで本CRAdの抗腫瘍効果を確認した。
- 鈴木泌尿器医学振興財団 令和５年度助成金, 2024年04月 - 2025年03月転移性腎細胞癌におけるWT1発現と予後の検討
- 日本泌尿器科学会、欧州泌尿器科学会, - 2025年03月2025 JUA-EAU Academic Exchange Programme
- 日本泌尿器科学会、アジア泌尿器科学会, - 2022年11月UAA Young Urologist’s Fellowship 2022
- 日本化薬株式会社, 日本化薬 医学・薬学に関する研究活動への支援, 2022年04月マウス腎細胞癌に対する経口がんワクチン（B420）および免疫チェックポイント阻害薬併用療法の有効性の検討