Rikiya Taoka - Academia.edu (original) (raw)

Papers by Rikiya Taoka

Research paper thumbnail of MP16-19 Use of Surgical Checklist During Transurethral Resection Increases Detrusor Muscle Collection Rate and Improves Recurrence-Free Survival in Patients with Non-Muscle Invasive Bladder Cancer

The Journal of Urology, Sep 1, 2021

Research paper thumbnail of MP32-15 MANAGEMENT Trends and Oncological Outcomes in Bladder Cancer Patients Undergoing Radical Cystectomy During 2013-2019 in Japan: A Multicenter Cohort Study

Research paper thumbnail of Real‐world treatment patterns and oncological outcomes in early relapse and refractory disease after bacillus Calmette‐Guérin failure in non‐muscle‐invasive bladder cancer

International Journal of Urology

Research paper thumbnail of Impact of non-muscle invasive bladder cancer treatment history on the efficacy of pembrolizumab for patients with metastatic urothelial carcinoma

Research paper thumbnail of Impact of carcinoma in situ on the outcome of intravesical Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer: a comparative analysis of large real-world data

International Journal of Clinical Oncology

This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus C... more This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC). This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression. At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression. Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.

Research paper thumbnail of Additional file 5 of Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maint... more Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maintenance induction BCG (iBCG) or iBCG plus maintenance BCG (mBCG) at 24 months. Landmark RFS at 6, 12, and 18 months among patients treated with non-maintenance iBCG or iBCG plus mBCG are plotted and compared between matched groups A and B (left panel) and between matched groups B and C (right panel). The P values, hazard ratios (HRs), and 95% confidence intervals (CIs) are shown in the figures.

Research paper thumbnail of Additional file 4 of Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

Additional file 4: Table S3. Comparison of variables according to patterns of intravesical BCG tr... more Additional file 4: Table S3. Comparison of variables according to patterns of intravesical BCG treatment: after propensity score matching.

Research paper thumbnail of Impact of histological variants on outcomes in patients with urothelial carcinoma treated with pembrolizumab: a propensity score matching analysis

BJU International, 2021

OBJECTIVES To assess the impact of histological variants on survival and response to treatment wi... more OBJECTIVES To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemoresistant urothelial cancer (UC). MATERIALS AND METHODS The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS Overall, 147 (19.5%) patients harbored any histological variant UC (VUC). After PSM, there were no significant differences in objective response rate (ORR, 24.5% vs 17.3%, p = 0.098) and disease control rate (DCR, 36.7% vs 30.2%, p = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, were associated with a similar risk of death (hazard ratio, 0.90; 95% confidence interval [CI], 0.68 to 1.20; p = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, p = 0.031), DCR (52.6%, p = 0.032), and OS (HR 0.37; 95% CI 0.15 to 0.90; p = 0.023) compared to patients with PUC. CONCLUSIONS The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemoresistant UC. The patients with sarcomatoid UC achieved favorable responses and survival rates compared to PUC.

Research paper thumbnail of The Paris system for reporting urinary cytology improves correlation with surgical pathology biopsy diagnoses of the lower urinary tract

Diagnostic Cytopathology, 2018

The current study seeks to compare both the original diagnoses (OD) and the updated Paris system ... more The current study seeks to compare both the original diagnoses (OD) and the updated Paris system diagnoses (PD) of urinary cytology specimens to the corresponding surgical pathology (biopsy) diagnoses (SD) to determine which diagnostic paradigm (OD vs PD) has a stronger correlation to the SD. Design: 56 cases from 34 patients that had a malignant SD associated with a corresponding cytology specimen from the same location within up to 90 days of the biopsy procedure were selected. We reviewed the cytology specimens and assigned a PD to each case. We then compared each OD and each PD to the corresponding SD. Correspondence was defined as when the SD had the same result or equal weight as either cytopathologic diagnosis.

Research paper thumbnail of Photodynamic diagnosis-assisted transurethral resection using oral 5-aminolevulinic acid decreases residual cancer and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer

Photodiagnosis and Photodynamic Therapy

BACKGROUND 5-aminolevulinic acid is a protoporphyrin IX precursor used for photodynamic diagnosis... more BACKGROUND 5-aminolevulinic acid is a protoporphyrin IX precursor used for photodynamic diagnosis. We aimed to clarify the therapeutic benefits of orally administered 5-aminolevulinic acid for photodynamic diagnosis in transurethral resection for non-muscle-invasive bladder cancer in a real-world setting. METHODS From January 2009 to December 2020, patients with non-muscle-invasive bladder cancer who have undergone visually complete resection by initial transurethral surgery were included. Histopathologically confirmed residual and intravesical recurrent bladder cancer was retrospectively investigated and compared with transurethral resection using photodynamic diagnosis and conventional white light. RESULTS One hundred and fifteen patients who underwent photodynamic diagnosis-transurethral resection were compared with 346 patients who underwent white light-transurethral resection. The second transurethral resection revealed that the proportion of residual T1 and Ta bladder cancer was lower in the photodynamic diagnosis group than in the white light group (10.3% vs. 33.8%, P=0.001). Additionally, the proportion of intravesical recurrence was lower in the photodynamic diagnosis group than in the white light group (9.6% vs. 41.9%, P<0.001). Using 5-aminolevulinic acid-photodynamic diagnosis during transurethral resection of bladder tumor improved the cumulative intravesical recurrence-free survival (log-rank test: P<0.001). Furthermore, multivariate analyses indicated that not using 5-aminolevulinic acid-photodynamic diagnosis was an independent predictive factor for residual bladder cancer (odds ratio, 6.16; 95% confidence interval, 2.10-18.0; P<0.001) and intravesical recurrence (hazard ratio, 2.01; 95% confidence interval, 1.05-3.83, P=0.034). CONCLUSIONS Introducing 5-aminolevulinic acid-photodynamic diagnosis into transurethral resection reduces residual bladder cancer and improves the cumulative intravesical recurrence-free survival in patients with non-muscle-invasive bladder cancer, indicating its possible therapeutic benefits.

Research paper thumbnail of Chloride Ion Transport Blockade Enhances Cytocidal Effects of Sterile Water on Bladder Cancer Cells

Background:Bladder cancer is a major health concern worldwide. The conventional intravesical Baci... more Background:Bladder cancer is a major health concern worldwide. The conventional intravesical Bacillus Calmette–Guérin therapy has certain shortcomings; thereby, demanding novel alternatives. Although sterile water is a probable agent for such novel intravesical therapies, bladder cancer cell lines differ in their sensitivity to hypotonic shock due to sterile water. Therefore, we aimed to investigate whether Cl- channel blockers enhance the cytocidal effect of hypotonic shock on bladder cancer cells resistant to sterile water.Methods:Bladder cancer cell lines of varying grades (RT112, T24, and J82) were exposed to sterile water, and morphological changes were closely observed using microscopy. Sterile water-induced changes in cell membrane integrity and cell viability were analyzed to determine the effects of hypotonic shock. These effects were further analyzed using a Cl- channel blocker.Results:T24 and J82 cells started swelling immediately upon exposure to sterile water and ruptur...

Research paper thumbnail of Efficacy and toxicity of intravesical Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer

Current Urology, 2021

Abstract Objectives: This study aimed to compare the efficacy and toxicity of intravesical Bacill... more Abstract Objectives: This study aimed to compare the efficacy and toxicity of intravesical Bacillus Calmette-Guérin (BCG) therapy between elderly and younger patients with non-muscle-invasive bladder cancer (NMIBC). Material and methods: This retrospective study included 87 NMIBC patients who received intravesical BCG between January 2011 and December 2018. We compared the treatment outcomes of patients ≥75 and <75 years old. Our primary endpoint was intravesical recurrence-free survival after treatment. The secondary endpoint was the toxicity caused by intravesical BCG. Results: The elderly and younger patients included 38 and 49 patients with mean ages of 80.6 and 66.3 years (p < 0.01), respectively. Their baseline parameters were similar, aside from age. The elderly and younger patients’ 5-year recurrence-free survival rates were 59.4% and 51.6%, respectively, and were not significantly different (log-rank test, p = 0.72). Moderate to severe pain on micturition requiring prescription medications was observed more frequently in the elderly patients than in the younger patients (p < 0.01). No elderly patients required hospitalization for any adverse events. However, 3 (6.1%) younger patients were treated for urinary tract infection in the hospital. Conclusions: The efficacy and toxicity of intravesical BCG therapy for NMIBC patients are not associated with age. Therefore, elderly patients with high-risk NMIBC should be treated in the same manner as younger patients in clinical practice.

Research paper thumbnail of Adenoviral shRNA vector targeting ribonucleotide reductase M1 (RRM1) has a strong antitumor activity and decrease the drug resistance to GEM in RRM1-overexpressing bladder cells

Journal of Clinical Oncology, 2018

e24237Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible fo... more e24237Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides and involved in cell proliferation. It is also the primary c...

Research paper thumbnail of Retinal Nerve Fiber Layer Thickness Progression after Robotic-Assisted Laparoscopic Radical Prostatectomy in Glaucoma Patients

Journal of Ophthalmology, 2019

Purpose. To investigate the effect of the steep Trendelenburg position surgical procedure on the ... more Purpose. To investigate the effect of the steep Trendelenburg position surgical procedure on the retinal structure and function during robotic-assisted laparoscopic radical prostatectomy (RALP) in glaucoma patients. Methods. At 1 month and 1 day before and at 1 and 2 months after the RALP operation, 10 glaucoma patients underwent standard automated perimetry and optical coherence tomography. After placing patients in a supine position, intraocular pressure (IOP) was measured at 5 min after intubation under general anesthesia (T1), at 5 discrete time points (5, 30, 60, 120, and 180 min; T2-6) and at 5 min after returning to a horizontal supine position (T7). The Guided Progression Analysis software program was used to assess serial retinal nerve fiber layer (RNFL) thicknesses and visual field progression. Results. Eight additional patients were newly diagnosed in addition to the two previous glaucoma patients. Average IOP (mmHg) at each time point was as follows: T1 = 11.2 ± 3.8, T2 ...

Research paper thumbnail of Editorial Comment from Dr Taoka and Dr Sugimoto to Real‐world treatment patterns and clinical outcomes of Japanese patients with non‐muscle invasive bladder cancer receiving intravesical bacillus Calmette–Guérin treatment

International Journal of Urology

Research paper thumbnail of Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer

International Journal of Molecular Sciences

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (T... more D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viabili...

Research paper thumbnail of MP03-07 IMPACT of Prior Intravesical Bacillus Calmette-Guerin Therapy for Non-Muscle Invasive Bladder Cancer on the Efficacy of Pembrolizumab in Patients with Metastatic Urothelial Carcinoma

Journal of Urology

INTRODUCTION AND OBJECTIVE: This study aimed to determine whether prior intravesical bacillus Cal... more INTRODUCTION AND OBJECTIVE: This study aimed to determine whether prior intravesical bacillus Calmette-Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) affects the treatment outcomes of pembrolizumab in patients with urothelial carcinoma (UC). METHODS: In a multicenter retrospective study conducted under the Japan Urological Oncology Group framework, the clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. The best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed concerning the BCG usage using propensity score matching (PSM). The propensity score was estimated using a logistic regression model with four covariates, namely, PS, metastatic site, pretreatment Hb level, and NLR. (Kobayashi T, et al. Cancer Sci. 2021). RESULTS: A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 9.97 months), the OS in patients with a NMIBC history but not BCG (14.49 months, HR 0.68 [0.45e1.12], P[0.061) or those with a NMIBC history and BCG (12.13 months, HR 0.87 [0.64e1.17], P[0.356) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 32.1% vs. 27.5%, P[0.606) and disease control rate (DCR, 56.6% vs. 45.1%, P[0.241) of the 58 patients with a NMIBC history but not BCG did not differ from those of 58 matched patients without a NMIBC history. The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P[0.042), whereas DCR between the two groups did not differ significantly (55.8% vs. 54.4%, P[0.855). CONCLUSIONS: Our risk-adjusted analyses revealed that intravesical BCG therapy did not affect the treatment outcomes of pembrolizumab in metastatic UC patients. Source of Funding: None

Research paper thumbnail of Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells

International Journal of Molecular Sciences, 2021

RRM1—an important DNA replication/repair enzyme—is the primary molecular gemcitabine (GEM) target... more RRM1—an important DNA replication/repair enzyme—is the primary molecular gemcitabine (GEM) target. High RRM1-expression associates with gemcitabine-resistance in various cancers and RRM1 inhibition may provide novel cancer treatment approaches. Our study elucidates how RRM1 inhibition affects cancer cell proliferation and influences gemcitabine-resistant bladder cancer cells. Of nine bladder cancer cell lines investigated, two RRM1 highly expressed cells, 253J and RT112, were selected for further experimentation. An RRM1-targeting shRNA was cloned into adenoviral vector, Ad-shRRM1. Gene and protein expression were investigated using real-time PCR and western blotting. Cell proliferation rate and chemotherapeutic sensitivity to GEM were assessed by MTT assay. A human tumor xenograft model was prepared by implanting RRM1 highly expressed tumors, derived from RT112 cells, in nude mice. Infection with Ad-shRRM1 effectively downregulated RRM1 expression, significantly inhibiting cell gro...

Research paper thumbnail of Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma

Urologic Oncology: Seminars and Original Investigations, 2022

OBJECTIVE The aim of this study was to determine whether a history of treatment for non-muscle in... more OBJECTIVE The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC). MATERIALS AND METHODS The clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. Best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed with regard to the history of NMIBC treatment and BCG usage using propensity score matching (PSM). RESULTS A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 10.0 months), the OS from the initiation of pembrolizumab for patients with a NMIBC history (13.3 months, HR [95% CI] 0.79 [0.62-1.02], P = 0.073), those with a NMIBC history and BCG (12.1 months, HR 0.87 [0.64-1.17], P = 0.356), or those with a NMIBC history but not BCG (14.5 months, HR 0.68 [0.45-1.12], P = 0.061) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 24.5% vs. 31.0%, P = 0.222) and disease control rate (DCR, 56.1% vs. 52.1%, P = 0.501) of the 155 patients with an NMIBC history did not differ from those of 155 matched patients without an NMIBC history. Among those with an NMIBC history, the prior use of BCG did not affect OS (with vs. without BCG, 12.1 vs. 14.5 months, HR 1.29 [0.80-2.09], P = 0.295), ORR (24.5% vs. 34.0%, P = 0.298) or DCR (57.1% vs. 56.0%, P = 0.908). The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P = 0.042), whereas DCR between the 2 groups did not differ significantly (55.8% vs. 54.4%, P = 0.855). CONCLUSIONS Our risk-adjusted analyses revealed that a history of prior NMIBC treatment, including intravesical BCG therapy, did not affect the treatment outcomes of pembrolizumab in metastatic UC patients.

Research paper thumbnail of Transplant Prognosis in Kidney Transplant Recipients with Diabetes under Mycophenolic Acid-Focused Therapeutic Drug Monitoring

Journal of Personalized Medicine, 2021

Mycophenolate mofetil is a key immunosuppressant that is metabolized into mycophenolic acid (MPA)... more Mycophenolate mofetil is a key immunosuppressant that is metabolized into mycophenolic acid (MPA). The prognostic impact of MPA-focused therapeutic drug monitoring on allograft prognosis has not been determined in kidney transplant recipients with diabetes. In this study, we assessed the pharmacokinetics of MPA and allograft prognosis in recipients with diabetes. This study retrospectively analyzed 64 adult kidney transplant recipients. MPA blood concentration data (e.g., the time to the maximum concentration (Tmax), and the area under the concentration–time curve from 0 to 12 h (AUC0–12)) were collected at 3 weeks and 3 months after kidney transplantation. Of the 64 recipients, 15 had pre-existing diabetes. At 3 months after kidney transplantation, the Tmax of MPA was significantly longer in recipients with diabetes (mean (standard deviation): 2.8 (2.1) h) than in recipients without diabetes (1.9 (1.1) h, p = 0.02). However, the allograft estimated glomerular filtration rate and ac...

Research paper thumbnail of MP16-19 Use of Surgical Checklist During Transurethral Resection Increases Detrusor Muscle Collection Rate and Improves Recurrence-Free Survival in Patients with Non-Muscle Invasive Bladder Cancer

The Journal of Urology, Sep 1, 2021

Research paper thumbnail of MP32-15 MANAGEMENT Trends and Oncological Outcomes in Bladder Cancer Patients Undergoing Radical Cystectomy During 2013-2019 in Japan: A Multicenter Cohort Study

Research paper thumbnail of Real‐world treatment patterns and oncological outcomes in early relapse and refractory disease after bacillus Calmette‐Guérin failure in non‐muscle‐invasive bladder cancer

International Journal of Urology

Research paper thumbnail of Impact of non-muscle invasive bladder cancer treatment history on the efficacy of pembrolizumab for patients with metastatic urothelial carcinoma

Research paper thumbnail of Impact of carcinoma in situ on the outcome of intravesical Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer: a comparative analysis of large real-world data

International Journal of Clinical Oncology

This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus C... more This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC). This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression. At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression. Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.

Research paper thumbnail of Additional file 5 of Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maint... more Additional file 5: Fig. S2. Landmark analysis of recurrence among patients treated with non-maintenance induction BCG (iBCG) or iBCG plus maintenance BCG (mBCG) at 24 months. Landmark RFS at 6, 12, and 18 months among patients treated with non-maintenance iBCG or iBCG plus mBCG are plotted and compared between matched groups A and B (left panel) and between matched groups B and C (right panel). The P values, hazard ratios (HRs), and 95% confidence intervals (CIs) are shown in the figures.

Research paper thumbnail of Additional file 4 of Non-maintenance intravesical Bacillus Calmette–Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study

Additional file 4: Table S3. Comparison of variables according to patterns of intravesical BCG tr... more Additional file 4: Table S3. Comparison of variables according to patterns of intravesical BCG treatment: after propensity score matching.

Research paper thumbnail of Impact of histological variants on outcomes in patients with urothelial carcinoma treated with pembrolizumab: a propensity score matching analysis

BJU International, 2021

OBJECTIVES To assess the impact of histological variants on survival and response to treatment wi... more OBJECTIVES To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemoresistant urothelial cancer (UC). MATERIALS AND METHODS The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS Overall, 147 (19.5%) patients harbored any histological variant UC (VUC). After PSM, there were no significant differences in objective response rate (ORR, 24.5% vs 17.3%, p = 0.098) and disease control rate (DCR, 36.7% vs 30.2%, p = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, were associated with a similar risk of death (hazard ratio, 0.90; 95% confidence interval [CI], 0.68 to 1.20; p = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, p = 0.031), DCR (52.6%, p = 0.032), and OS (HR 0.37; 95% CI 0.15 to 0.90; p = 0.023) compared to patients with PUC. CONCLUSIONS The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemoresistant UC. The patients with sarcomatoid UC achieved favorable responses and survival rates compared to PUC.

Research paper thumbnail of The Paris system for reporting urinary cytology improves correlation with surgical pathology biopsy diagnoses of the lower urinary tract

Diagnostic Cytopathology, 2018

The current study seeks to compare both the original diagnoses (OD) and the updated Paris system ... more The current study seeks to compare both the original diagnoses (OD) and the updated Paris system diagnoses (PD) of urinary cytology specimens to the corresponding surgical pathology (biopsy) diagnoses (SD) to determine which diagnostic paradigm (OD vs PD) has a stronger correlation to the SD. Design: 56 cases from 34 patients that had a malignant SD associated with a corresponding cytology specimen from the same location within up to 90 days of the biopsy procedure were selected. We reviewed the cytology specimens and assigned a PD to each case. We then compared each OD and each PD to the corresponding SD. Correspondence was defined as when the SD had the same result or equal weight as either cytopathologic diagnosis.

Research paper thumbnail of Photodynamic diagnosis-assisted transurethral resection using oral 5-aminolevulinic acid decreases residual cancer and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer

Photodiagnosis and Photodynamic Therapy

BACKGROUND 5-aminolevulinic acid is a protoporphyrin IX precursor used for photodynamic diagnosis... more BACKGROUND 5-aminolevulinic acid is a protoporphyrin IX precursor used for photodynamic diagnosis. We aimed to clarify the therapeutic benefits of orally administered 5-aminolevulinic acid for photodynamic diagnosis in transurethral resection for non-muscle-invasive bladder cancer in a real-world setting. METHODS From January 2009 to December 2020, patients with non-muscle-invasive bladder cancer who have undergone visually complete resection by initial transurethral surgery were included. Histopathologically confirmed residual and intravesical recurrent bladder cancer was retrospectively investigated and compared with transurethral resection using photodynamic diagnosis and conventional white light. RESULTS One hundred and fifteen patients who underwent photodynamic diagnosis-transurethral resection were compared with 346 patients who underwent white light-transurethral resection. The second transurethral resection revealed that the proportion of residual T1 and Ta bladder cancer was lower in the photodynamic diagnosis group than in the white light group (10.3% vs. 33.8%, P=0.001). Additionally, the proportion of intravesical recurrence was lower in the photodynamic diagnosis group than in the white light group (9.6% vs. 41.9%, P<0.001). Using 5-aminolevulinic acid-photodynamic diagnosis during transurethral resection of bladder tumor improved the cumulative intravesical recurrence-free survival (log-rank test: P<0.001). Furthermore, multivariate analyses indicated that not using 5-aminolevulinic acid-photodynamic diagnosis was an independent predictive factor for residual bladder cancer (odds ratio, 6.16; 95% confidence interval, 2.10-18.0; P<0.001) and intravesical recurrence (hazard ratio, 2.01; 95% confidence interval, 1.05-3.83, P=0.034). CONCLUSIONS Introducing 5-aminolevulinic acid-photodynamic diagnosis into transurethral resection reduces residual bladder cancer and improves the cumulative intravesical recurrence-free survival in patients with non-muscle-invasive bladder cancer, indicating its possible therapeutic benefits.

Research paper thumbnail of Chloride Ion Transport Blockade Enhances Cytocidal Effects of Sterile Water on Bladder Cancer Cells

Background:Bladder cancer is a major health concern worldwide. The conventional intravesical Baci... more Background:Bladder cancer is a major health concern worldwide. The conventional intravesical Bacillus Calmette–Guérin therapy has certain shortcomings; thereby, demanding novel alternatives. Although sterile water is a probable agent for such novel intravesical therapies, bladder cancer cell lines differ in their sensitivity to hypotonic shock due to sterile water. Therefore, we aimed to investigate whether Cl- channel blockers enhance the cytocidal effect of hypotonic shock on bladder cancer cells resistant to sterile water.Methods:Bladder cancer cell lines of varying grades (RT112, T24, and J82) were exposed to sterile water, and morphological changes were closely observed using microscopy. Sterile water-induced changes in cell membrane integrity and cell viability were analyzed to determine the effects of hypotonic shock. These effects were further analyzed using a Cl- channel blocker.Results:T24 and J82 cells started swelling immediately upon exposure to sterile water and ruptur...

Research paper thumbnail of Efficacy and toxicity of intravesical Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer

Current Urology, 2021

Abstract Objectives: This study aimed to compare the efficacy and toxicity of intravesical Bacill... more Abstract Objectives: This study aimed to compare the efficacy and toxicity of intravesical Bacillus Calmette-Guérin (BCG) therapy between elderly and younger patients with non-muscle-invasive bladder cancer (NMIBC). Material and methods: This retrospective study included 87 NMIBC patients who received intravesical BCG between January 2011 and December 2018. We compared the treatment outcomes of patients ≥75 and <75 years old. Our primary endpoint was intravesical recurrence-free survival after treatment. The secondary endpoint was the toxicity caused by intravesical BCG. Results: The elderly and younger patients included 38 and 49 patients with mean ages of 80.6 and 66.3 years (p < 0.01), respectively. Their baseline parameters were similar, aside from age. The elderly and younger patients’ 5-year recurrence-free survival rates were 59.4% and 51.6%, respectively, and were not significantly different (log-rank test, p = 0.72). Moderate to severe pain on micturition requiring prescription medications was observed more frequently in the elderly patients than in the younger patients (p < 0.01). No elderly patients required hospitalization for any adverse events. However, 3 (6.1%) younger patients were treated for urinary tract infection in the hospital. Conclusions: The efficacy and toxicity of intravesical BCG therapy for NMIBC patients are not associated with age. Therefore, elderly patients with high-risk NMIBC should be treated in the same manner as younger patients in clinical practice.

Research paper thumbnail of Adenoviral shRNA vector targeting ribonucleotide reductase M1 (RRM1) has a strong antitumor activity and decrease the drug resistance to GEM in RRM1-overexpressing bladder cells

Journal of Clinical Oncology, 2018

e24237Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible fo... more e24237Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides and involved in cell proliferation. It is also the primary c...

Research paper thumbnail of Retinal Nerve Fiber Layer Thickness Progression after Robotic-Assisted Laparoscopic Radical Prostatectomy in Glaucoma Patients

Journal of Ophthalmology, 2019

Purpose. To investigate the effect of the steep Trendelenburg position surgical procedure on the ... more Purpose. To investigate the effect of the steep Trendelenburg position surgical procedure on the retinal structure and function during robotic-assisted laparoscopic radical prostatectomy (RALP) in glaucoma patients. Methods. At 1 month and 1 day before and at 1 and 2 months after the RALP operation, 10 glaucoma patients underwent standard automated perimetry and optical coherence tomography. After placing patients in a supine position, intraocular pressure (IOP) was measured at 5 min after intubation under general anesthesia (T1), at 5 discrete time points (5, 30, 60, 120, and 180 min; T2-6) and at 5 min after returning to a horizontal supine position (T7). The Guided Progression Analysis software program was used to assess serial retinal nerve fiber layer (RNFL) thicknesses and visual field progression. Results. Eight additional patients were newly diagnosed in addition to the two previous glaucoma patients. Average IOP (mmHg) at each time point was as follows: T1 = 11.2 ± 3.8, T2 ...

Research paper thumbnail of Editorial Comment from Dr Taoka and Dr Sugimoto to Real‐world treatment patterns and clinical outcomes of Japanese patients with non‐muscle invasive bladder cancer receiving intravesical bacillus Calmette–Guérin treatment

International Journal of Urology

Research paper thumbnail of Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer

International Journal of Molecular Sciences

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (T... more D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viabili...

Research paper thumbnail of MP03-07 IMPACT of Prior Intravesical Bacillus Calmette-Guerin Therapy for Non-Muscle Invasive Bladder Cancer on the Efficacy of Pembrolizumab in Patients with Metastatic Urothelial Carcinoma

Journal of Urology

INTRODUCTION AND OBJECTIVE: This study aimed to determine whether prior intravesical bacillus Cal... more INTRODUCTION AND OBJECTIVE: This study aimed to determine whether prior intravesical bacillus Calmette-Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) affects the treatment outcomes of pembrolizumab in patients with urothelial carcinoma (UC). METHODS: In a multicenter retrospective study conducted under the Japan Urological Oncology Group framework, the clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. The best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed concerning the BCG usage using propensity score matching (PSM). The propensity score was estimated using a logistic regression model with four covariates, namely, PS, metastatic site, pretreatment Hb level, and NLR. (Kobayashi T, et al. Cancer Sci. 2021). RESULTS: A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 9.97 months), the OS in patients with a NMIBC history but not BCG (14.49 months, HR 0.68 [0.45e1.12], P[0.061) or those with a NMIBC history and BCG (12.13 months, HR 0.87 [0.64e1.17], P[0.356) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 32.1% vs. 27.5%, P[0.606) and disease control rate (DCR, 56.6% vs. 45.1%, P[0.241) of the 58 patients with a NMIBC history but not BCG did not differ from those of 58 matched patients without a NMIBC history. The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P[0.042), whereas DCR between the two groups did not differ significantly (55.8% vs. 54.4%, P[0.855). CONCLUSIONS: Our risk-adjusted analyses revealed that intravesical BCG therapy did not affect the treatment outcomes of pembrolizumab in metastatic UC patients. Source of Funding: None

Research paper thumbnail of Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells

International Journal of Molecular Sciences, 2021

RRM1—an important DNA replication/repair enzyme—is the primary molecular gemcitabine (GEM) target... more RRM1—an important DNA replication/repair enzyme—is the primary molecular gemcitabine (GEM) target. High RRM1-expression associates with gemcitabine-resistance in various cancers and RRM1 inhibition may provide novel cancer treatment approaches. Our study elucidates how RRM1 inhibition affects cancer cell proliferation and influences gemcitabine-resistant bladder cancer cells. Of nine bladder cancer cell lines investigated, two RRM1 highly expressed cells, 253J and RT112, were selected for further experimentation. An RRM1-targeting shRNA was cloned into adenoviral vector, Ad-shRRM1. Gene and protein expression were investigated using real-time PCR and western blotting. Cell proliferation rate and chemotherapeutic sensitivity to GEM were assessed by MTT assay. A human tumor xenograft model was prepared by implanting RRM1 highly expressed tumors, derived from RT112 cells, in nude mice. Infection with Ad-shRRM1 effectively downregulated RRM1 expression, significantly inhibiting cell gro...

Research paper thumbnail of Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma

Urologic Oncology: Seminars and Original Investigations, 2022

OBJECTIVE The aim of this study was to determine whether a history of treatment for non-muscle in... more OBJECTIVE The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC). MATERIALS AND METHODS The clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. Best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed with regard to the history of NMIBC treatment and BCG usage using propensity score matching (PSM). RESULTS A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 10.0 months), the OS from the initiation of pembrolizumab for patients with a NMIBC history (13.3 months, HR [95% CI] 0.79 [0.62-1.02], P = 0.073), those with a NMIBC history and BCG (12.1 months, HR 0.87 [0.64-1.17], P = 0.356), or those with a NMIBC history but not BCG (14.5 months, HR 0.68 [0.45-1.12], P = 0.061) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 24.5% vs. 31.0%, P = 0.222) and disease control rate (DCR, 56.1% vs. 52.1%, P = 0.501) of the 155 patients with an NMIBC history did not differ from those of 155 matched patients without an NMIBC history. Among those with an NMIBC history, the prior use of BCG did not affect OS (with vs. without BCG, 12.1 vs. 14.5 months, HR 1.29 [0.80-2.09], P = 0.295), ORR (24.5% vs. 34.0%, P = 0.298) or DCR (57.1% vs. 56.0%, P = 0.908). The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P = 0.042), whereas DCR between the 2 groups did not differ significantly (55.8% vs. 54.4%, P = 0.855). CONCLUSIONS Our risk-adjusted analyses revealed that a history of prior NMIBC treatment, including intravesical BCG therapy, did not affect the treatment outcomes of pembrolizumab in metastatic UC patients.

Research paper thumbnail of Transplant Prognosis in Kidney Transplant Recipients with Diabetes under Mycophenolic Acid-Focused Therapeutic Drug Monitoring

Journal of Personalized Medicine, 2021

Mycophenolate mofetil is a key immunosuppressant that is metabolized into mycophenolic acid (MPA)... more Mycophenolate mofetil is a key immunosuppressant that is metabolized into mycophenolic acid (MPA). The prognostic impact of MPA-focused therapeutic drug monitoring on allograft prognosis has not been determined in kidney transplant recipients with diabetes. In this study, we assessed the pharmacokinetics of MPA and allograft prognosis in recipients with diabetes. This study retrospectively analyzed 64 adult kidney transplant recipients. MPA blood concentration data (e.g., the time to the maximum concentration (Tmax), and the area under the concentration–time curve from 0 to 12 h (AUC0–12)) were collected at 3 weeks and 3 months after kidney transplantation. Of the 64 recipients, 15 had pre-existing diabetes. At 3 months after kidney transplantation, the Tmax of MPA was significantly longer in recipients with diabetes (mean (standard deviation): 2.8 (2.1) h) than in recipients without diabetes (1.9 (1.1) h, p = 0.02). However, the allograft estimated glomerular filtration rate and ac...