Search

Objective: The objective of this study was to evaluate the efficacy and safety of dose-dense gemcitabine and cisplatin (ddGC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC)., Methods: Patients with locally advanced MIBC (cT2aN0M0-cT4N1M0) who received ddGC between December 2017 and December 2023 were included. Regimens of ddGC with pegfilgrastim were administered every 2 weeks for 4 cycles, followed by radical cystectomy. The pathological complete response (CR) (pT0N0) and objective response (OR) (

Background: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting., Methods: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting., Results: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01)., Conclusions: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC.

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., (Copyright © 2022. Published by Elsevier B.V.)

Background: The Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS., Methods: A total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation., Results: After implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08-4.77; P = 0.03)., Conclusion: In instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit., (© 2022. The Author(s).)

Introduction: We examined the prevalence, pathological findings, and oncological outcomes of incidental bladder cancer found on cystoscopy among patients eligible for prostate biopsy (PB)., Methods: We retrospectively reviewed 803 patients who underwent cystoscopy prior to PB between January 2010 and September 2020. In cases of bladder tumor-like findings on cystoscopy, biopsy or transurethral resection of the bladder tumor was performed. The primary and secondary outcomes were the prevalence of incidental bladder cancer and pathological and oncological outcomes of incidental bladder cancer, respectively., Results: Incidental findings were observed in 31/803 patients (3.9%). Bladder tumor-like findings were found in 24/803 patients (3%), while 9/803 patients (1.1%) were pathologically diagnosed with urothelial carcinoma. The stage and grade of incidental bladder cancer were pTa in 8/9 patients and pT1 in 1/9 and low grade in 8/9 and high in 1/9, respectively. The median tumor size of the papillary pedunculated type was 0.5 cm. At 26-month median follow-up, no recurrence was observed., Conclusion: Cystoscopy during PB may yield incidental bladder cancer findings, although the prevalence is very low. Incidental bladder cancer was of low stage and grade, which seemed unrelated to survival. Moreover, performing routine cystoscopy in conjunction with PB is not recommended as it may lead to overdiagnosis of low-risk bladder cancer., (© 2021 S. Karger AG, Basel.)

Objective: To elucidate the therapeutic benefits of using a surgical checklist during transurethral resection for non-muscle-invasive bladder cancer., Methods: A nine-item surgical checklist was established in January 2016 to assess disease risk and resection adequacy, and it was prospectively implemented into clinical practice. Patients diagnosed with non-muscle-invasive bladder cancer who underwent complete resection from January 2009 to August 2019 were included in this study. The presence of detrusor muscle in the transurethral resection specimen and the intravesical recurrence-free survival were compared between patients who underwent transurethral resection before and after surgical checklist implementation., Results: A total of 125 patients who underwent transurethral resection after surgical checklist implementation were reviewed and compared with 125 patients who underwent transurethral resection before surgical checklist implementation. The use of the surgical checklist led to an increase in the proportion of transurethral resection specimens containing detrusor muscle (92% vs 69.6%, P < 0.01) and a decrease in the recurrence rate (19.2% vs 49.6%, P < 0.01). Multivariate analysis showed that transurethral resection without a surgical checklist was an independent predictive factor influencing the absence of detrusor muscle in the transurethral resection specimen (odds ratio 4.78, P < 0.01) and intravesical recurrence (hazard ratio 1.92, 95% confidence interval 1.14-3.23; P = 0.01). Kaplan-Meier plots showed that the recurrence-free survival rate was significantly lower when the surgical checklist was not used (log-rank test result P < 0.01)., Conclusions: This study shows the therapeutic benefits of surgical checklist in improving the quality of resection during transurethral resection and reducing the recurrence rate in patients with non-muscle-invasive bladder cancer., (© 2021 The Japanese Urological Association.)

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 growth in both RRM1 highly expressed tumor cells. In vivo, Ad-shRRM1 treatment had pronounced antitumor effects against RRM1 highly expressed tumor xenografts ( p < 0.05). Moreover, combination of Ad-shRRM1 and GEM inhibited cell proliferation in both cell lines significantly more than either treatment individually. Cancer gene therapy using anti-RRM1 shRNA has pronounced antitumor effects against RRM1 highly expressed tumors, and RRM1 inhibition specifically increases bladder cancer cell GEM-sensitivity. Ad-shRRM1/GEM combination therapy may offer new treatment options for patients with GEM-resistant bladder tumors.

Objectives: To clarify the potential therapeutic benefit of a second transurethral resection for high-grade Ta bladder cancer., Methods: From January 2009 to August 2019, 521 patients with bladder tumors underwent initial transurethral resection procedures at Kagawa University Hospital. Patients diagnosed with high-grade Ta bladder cancer considered to have been resected completely were included in this study. Recurrence and progression rates were compared between patients who received a second transurethral resection and those who did not., Results: We identified 97 eligible patients, including 22 patients who received a second transurethral resection. In terms of clinical characteristics, the proportion of patients with bladder cancer and upper urinary tract tumor history was lower in the second transurethral resection group than in the no second transurethral resection group (P < 0.01 and P = 0.03, respectively). The histopathological findings of 22 transurethral resection procedures were no cancer in 13 (59.2%), Ta in six (27.2%) and carcinoma in situ in three patients (13.6%). After the second transurethral resection, one patient (4.6%) had recurrent high-grade T1 bladder cancer. The no second transurethral resection group showed a 44% recurrence rate (33 patients), including five patients (6.7%) with progression, and consequently, had a higher rate of recurrence than in the second transurethral resection group (P < 0.01). Multivariate analysis showed that no second transurethral resection was the independent predictive factor influencing recurrence (hazard ratio 8.662, P = 0.04). The Kaplan-Meier curve showed that a second transurethral resection significantly decreased the recurrence rate than that of patients without a second transurethral resection (P < 0.01)., Conclusions: A second transurethral resection can reduce the recurrence rate in high-grade Ta bladder cancer, showing a possible therapeutic benefit of this procedure., (© 2020 The Japanese Urological Association.)

Background: The incidence of atypical oncologic failure in patients with bladder cancer, including peritoneal carcinomatosis, and recurrences at the port site and soft tissue after laparoscopic and robot-assisted radical cystectomy are not well characterized., Methods: We retrospectively reviewed the records of 52, 51, and 12 patients who underwent open, laparoscopic, and robot-assisted radical cystectomy, respectively, for bladder cancer from 2007 to 2018 at our institution. We identified techniques associated with atypical oncologic failure., Results: The median follow-up period was 29 months. Among the 115 patients, 29 (25%) experienced oncological recurrences, and 7 (6%), 12 (10%), and 23 (20%) had atypical, local, and distant recurrences, respectively. The laparoscopic and robot-assisted radical cystectomy groups had significantly higher incidences of total atypical oncologic failure than the open radical cystectomy group (p = 0.013), including six, one, and two patients with peritoneal carcinomatosis, port site carcinomatosis, and soft tissue involvement, respectively. All 7 patients with atypical oncologic failure died of cancer; the median time from surgery to death was 9.3 months. All these patients were cT ≧ 3 and had grade 3 disease. In three patients (43%), the pathological tissue contained variants other than urothelial carcinoma. Five (71%) were among the initial twenty patients. Four patients (57%) had histories of intraoperative urine spillage or bladder perforation during transurethral resection., Conclusions: Patients with cT ≧ 3 stage, with pathological variants other than urothelial carcinoma, and those undergoing procedures that lead to extravesical dissemination should avoid laparoscopic radical cystectomy when the procedures are first introduced.