Intravesical Instillation Of Pirarubicin Research Articles

Combined use of a 980‑nm diode laser and preoperative intravesical instillation of pirarubicin for the prevention of short‑term recurrence of non‑muscle invasive bladder cancer: A pilot study.

At present, transurethral resection of bladder tumors (TURBT) is the main surgical method for treating non-muscle invasive bladder cancer (NMIBC), but its postoperative recurrence needs to be prevented. The aim of the present study was to investigate the efficacy of a 980-nm diode laser combined with preoperative intravesical instillation of pirarubicin (THP) for the prevention of NMIBC recurrence. The data of 120 patients with NMIBC who underwent transurethral resection between May 2021 and July 2022 were retrospectively collected, and these patients were followed up. The patients were divided into four groups based on the surgical method used and preoperative intravesical instillation of THP as follows: i) 980-nm diode laser with THP (LaT); ii) 980-nm diode laser alone (La); iii) TURBT with THP (TUT); and iv) TURBT alone (TU). Clinicopathological variables, postoperative complications and short-term outcomes among the aforementioned groups were analyzed. The blood loss volume and the incidence of perforation and delayed bleeding were significantly lower in the LaT and La groups compared with those in the TUT and TU groups. The days of bladder irrigation, catheter extubation and postoperative hospitalization were significantly shorter in the LaT and La groups compared with the TUT and TU groups. The detection rate of suspicious lesions was significantly higher in the THP irrigation groups (LaT and TUT) compared with that in the saline irrigation groups (La and TU). Tumor diameter and number, 980-nm laser and THP irrigation were shown to be independent risk factors in the Cox regression analysis. In addition, the recurrence-free survival (RFS) rate of the LaT group was significantly higher than that of the other three groups. In conclusion, a 980-nm diode laser can effectively reduce intraoperative blood loss and the incidence of perforation, and accelerate postoperative recovery. Preoperative intravesical instillation of THP is conducive to identifying suspicious lesions. The combination of a 980-nm laser with preoperative THP intravesical instillation can significantly prolong RFS time.

Overnight Continuous Saline Bladder Irrigation After En Bloc Resection of Bladder Tumor Does Not Improve Oncological Outcomes in Patients Who Have Received Intravesical Chemotherapy.

ObjectiveTo evaluate the safety and efficacy of overnight continuous saline bladder irrigation (CSBI) for patients who have received thulium laser en bloc resection of bladder tumor (TmLRBT) combined with immediate intravesical chemotherapy previously.MethodsFrom October 2014 to June 2018, 235 patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included in this retrospective study. All patients received intravesical instillation of pirarubicin immediately after TmLRBT. The patients were divided into two groups according to the duration of postoperative bladder irrigation with normal saline. After immediate intravesical chemotherapy, patients in group 1 received overnight CSBI, while patients in group 2 did not receive overnight CSBI. Data on the time of initial tumor recurrence, recurrence-free survival (RFS) and progression-free survival (PFS) rates, and perioperative complications were collected and analyzed.ResultsOf 235 included patients (129 in group 1 and 106 in group 2), the median follow-up periods were 42 and 38 months, respectively. There were no significant differences in patients’ baseline characteristics between the two groups. The RFS rates of patients in group 1 were 90.7, 82.7, and 76.8% at the end of the first, third, and fifth years, while the corresponding RFS rates of patients in group 2 were 87.7, 78.9, and 73.3%, respectively. Four patients in group 1 and five patients in group 2 experienced tumor progression. No significant differences between the two groups were observed in the time of initial tumor recurrence, RFS, and PFS rates. Only Grade I complications occurred in the two groups, and no significant difference was reached between the two groups.ConclusionsFor patients with NMIBC who have previously received TmLRBT combined with immediate intravesical chemotherapy, overnight CSBI may not improve oncological outcomes and reduce perioperative complications.

Clinical application of drug sensitive gene detection in postoperative instillation for non-muscle invasive bladder cancer

BackgroundBladder cancer is the most common malignant tumor of the urinary system. One of the biological characteristics of NMIBC is the high recurrence rate after surgery. The implementation of this project aimed to investigate the role of pharmacogenomic testing-guided intravesical perfusion of chemotherapeutic agents in the postoperative perfusion therapy for non-muscle invasive bladder cancer.MethodFrom January 2015 to December 2016, 298 patients with non-muscle-invasive bladder cancer were enrolled in this prospective study. These patients received chemotherapy drugs after electrotherapy. According to the presence or absence of tumor susceptibility gene detection after surgery, they were divided into two groups, including the drug sensitive group(N = 44) and the control group(N = 254). The drug sensitive group received bladder infusion therapy with sensitive chemotherapy drugs based on drug sensitivity gene detection results. The control group received intravesical instillation of pirarubicin. The preoperative general data and tumor grade of patients were recorded. Cystoscopy was performed before and every 3 months after surgery. The chest CT, upper abdomen CT, renal function, and urinary routine tests were performed. Tumor recurrence, metastasis and tumor-related death were recorded and evaluated during follow-up.ResultsThe drug sensitive group, which selected high-sensitivity drugs for intravesical instillation therapy based on gene expression, has a significantly lower relapse rate (11.36% vs 37.40%, P < 0.05) and a significantly longer time to relapse (17.80 ± 7.20 month vs11.20 ± 6.10 month, P < 0.05) compared with the control group. There were no significant differences in the time of mortality and death time between two groups.ConclusionThe pharmacogenomic testing-directed bladder instillation of chemotherapeutic drugs may be more effective than empiric drug administration in reducing the recurrence rate of non-muscle-invasive bladder cancer.

The value of transurethral thulium laser en bloc resection combined with a single immediate postoperative intravesical instillation of pirarubicin in primary non-muscle-invasive bladder cancer.

The objective of this study was to evaluate which patients might benefit from a single immediate postoperative intravesical instillation (SII) compared to maintenance intravesical instillations (MII) in primary non-muscle-invasive bladder cancer (NMIBC) after transurethral en bloc resection of bladder tumors (ERBT). A total of 141 patients with primary NMIBC who underwent ERBT with thulium laser between January 2012 and May 2016 were retrospectively enrolled. All the patients were categorized into two groups based on the duration of postoperative intravesical instillation of pirarubicin (THP): single intravesical instillation (SII) group, patients received a single immediate postoperative intravesical instillation of THP (30mg), and maintenance intravesical instillations (MII) group, patients received a 1-year MII of THP (30mg). Prognosis and recurrence data of each group were analyzed. One hundred and four (73.8%) patients received MII, and other 37 (26.2%) patients received SII. There was no significant difference in recurrence-free survival (RFS) between the two groups (P = 0.105). Following recurrence risk-stratified analysis, patients with high recurrence risk who accepted SII had a significantly lower RFS rate than those who received MII (P = 0.027). However, there were no significant differences in RFS rate between the two groups in patients with low and intermediate recurrence risk. In the multivariate analysis, the number of tumors was found to be an independent prognostic factor for RFS in NMIBC patients [hazard ratio, 5.665; 95% confidence interval (CI), 2.577-12.454; P < 0.001]. SII seems not to be inferior to MII in patients with initial low-risk and intermediate-risk NMIBC after ERBT.

Long-term Effect of Transurethral Resection of Bladder Tumor Combined with Intravesical Instillation of Pirarubicin on Immune Function in Superficial Bladder Cancer

This study was aimed to explore the long-term effects of transurethral resection of bladder tumor combined with intravesical instillation of pirarubicin on immune function in superficial bladder cancer. Eighty four patients with bladder cancer admitted to the Linzi District People's Hospital from March 2016 to March 2017 were selected as research subjects and divided into 2 groups according to the digital table. The control group was treated with transurethral resection of bladder tumor. The study group was given intravesical instillation of pirarubicin in addition to the treatment given to the control group. There was no significant difference in recurrence rate between the study group and the control group, 6 mo after operation. However, the recurrence rate in the study group was lower than that in the control group 1 y after operation and the recurrence time of the study group was significantly shorter than that of the control group. There was no significant difference in the incidence of postoperative complications between the study group and the control group and the levels of IgM, IgG and IgA in the study group were significantly higher than those in the control group. In addition the levels of CD4+, CD4+/CD8+ in the study group were significantly higher than those in the control group, while the CD8+ in the study group was significantly lower than that in the control group. In conclusion, transurethral resection of bladder tumor combined with intravesical instillation of pirarubicin is effective in the treatment of bladder cancer and should be further popularized in clinic.

Systemic Tumor Seeding Secondary to Peritonitis due to the Immediate Postoperative Intravesical Instillation of Pirarubicin After Intravesical Explosion Induced Bladder Perforation During Bipolar Transurethral Resection of Bladder Tumors

An 82-year-old man with multiple nonmuscle-invasive bladder cancer underwent transurethral resection (TUR) of bladder tumor by using the transurethral resection in saline (TURis) system. Intravesical explosion occurred during the resection of a tumor of the bladder dome, but no bladder perforation was detected. Immediate postoperative intravesical instillation of 30 mg pirarubicin in 30 mL saline was administered after the TURis. After this procedure, the patient complained of severe lower abdominal pain. A computed tomography (CT) scan after cystography revealed a collection of fluid in the abdominal cavity with signs of urine leakage. It was determined that instillation of pirarubicin led to leakage outside the bladder through a near perforation on the bladder that occurred during TURis. An indwelling 20 Fr Foley catheter was placed for 8 days. His condition improved without additional surgery. After the patient was discharged, gross hematuria appeared. A residual tumor was confirmed near the perforation area. Therefore, 3.5 months after the first TURis, he underwent a second TURis. Dyspnea appeared 1 month after the second TURis. Positron emission tomography and computed tomography (PET/CT) imaging revealed systemic tumor seeding. Five months after surgery, the patient died because of acute respiratory failure. J Med Cases. 2019;10(4):101-105 doi: https://doi.org/10.14740/jmc3277

Systemic Tumor Seeding Secondary to Peritonitis due to the Immediate Postoperative Intravesical Instillation of Pirarubicin After Intravesical Explosion Induced Bladder Perforation During Bipolar Transurethral Resection of Bladder Tumors

An 82-year-old man with multiple nonmuscle-invasive bladder cancer underwent transurethral resection (TUR) of bladder tumor by using the transurethral resection in saline (TURis) system. Intravesical explosion occurred during the resection of a tumor of the bladder dome, but no bladder perforation was detected. Immediate postoperative intravesical instillation of 30 mg pirarubicin in 30 mL saline was administered after the TURis. After this procedure, the patient complained of severe lower abdominal pain. A computed tomography (CT) scan after cystography revealed a collection of fluid in the abdominal cavity with signs of urine leakage. It was determined that instillation of pirarubicin led to leakage outside the bladder through a near perforation on the bladder that occurred during TURis. An indwelling 20 Fr Foley catheter was placed for 8 days. His condition improved without additional surgery. After the patient was discharged, gross hematuria appeared. A residual tumor was confirmed near the perforation area. Therefore, 3.5 months after the first TURis, he underwent a second TURis. Dyspnea appeared 1 month after the second TURis. Positron emission tomography and computed tomography (PET/CT) imaging revealed systemic tumor seeding. Five months after surgery, the patient died because of acute respiratory failure. J Med Cases. 2019;10(4):101-105 doi: https://doi.org/10.14740/jmc3277

Value of European Organisation for Research and Treatment of Cancer score system for predication of immediate postoperative intravesical instillation of pirarubicin after transurethral resection of non-muscle invasive bladder cancer

Objective: To assess value of immediate postoperative intravesical instillation of pirarubicin after transurethral resection (TURBT)of non-muscle invasive bladder cancer. Methods: 484 patients diagnosed with non-muscle-invasive bladder cancer admitted to the Second Affiliated Hospital of Kunming Medical University were divided into two groups after transurethral resection of bladder tumor. 285 patients received postoperative intravesical instillation of pirarubicin within 6 hours after the surgery, 199 patients received first instillation of pirarubicin at 10 days after the surgery, after that, all the patients received routine bladder perfusion chemotherapy. Patients who received intravesical instillation of pirarubicin within 6 hours were defined as immediate intravesical instillation group and the other patients as the control group. Based on the European Organisation for Research and Treatment of Cancer risk tables, scores of recurrence and progression of patients were calculated and then stratified into risk groups accordingly. Recurrence and progression rates of the immediate intravesical instillation group were analyzed and then compared with the corresponding reference of the risk tables. Results: The 1-year and 5-year recurrence rate of patients with EORTC table scoring 0 in the immediate intravesical instillation group were significantly lower than that of the EORTC reference group (5.3% and 14.0% vs 15.0% and 31.0%, P<0.05). 1-year recurrence free rate between the immediate intravesical instillation group and the control group in patients scoring 1-4 was significantly different (81.3% vs 76.7%, P=0.014). However, 1-year recurrence free rate of the immediate intravesical instillation group was comparable with that of the control group in patients scoring 5-9, 10-17(P>0.05), which is quite close to the EORTC reference. The probability rates of 1-year and 5-year progression of the 285 patients who received immediate intravesical instillation group did not show significant difference with the EORTC reference. On multivariate analysis, previous recurrence, tumor grade G2-3, tumor multiplicity, delay of immediate intravesical instillation were independent risk factors of recurrence(P<0.05). Conclusions: With the help of EORTC recurrence risk table stratifying the patients into different risk groups, our study showed that delay of immediate postoperative intravesical instillation of chemotherapy after TURBT was an independent risk factor of post-surgery recurrence of tumor. Moreover, patients with EORTC scoring 1-4 might obtain greatest benefits.

The clinical study of thulium laser combined with intravesical instillation of pirarubicin in the treatment of non-muscle invasive bladder cancer

Objective To investigate the clinical efficacy of transurethral thulium laser enucleation combined with intravesical instillation of pirarubicin in the treatment of non-muscle invasive bladder cancer. Methods The clinical data of 67 cases of non-muscle invasive bladder cancer who were treated in our hospital from January 2014 to January 2015 were analyzed retrospectively. Including 56 cases single tumor and 11 cases multiple tumors, the tumor diameter ranged from 0.5 to 2.7 cm [mean (2.1±0.4)cm]. All patients were treated by transurethral thulium laser enucleation combined with immediate postoperative instillation of pirarubicin and maintenance instillation of pirarubicin. Regular cystoscopy after operation and long-term follow-up was performed. Results All the operations were successfully enucleationed tumor with once time. The average time of tumor enucleation was (17.3 ± 6.8)min, the intraoperative blood loss was no more than 10 mL. There was no dilutional hyponatremia, bladder perforation, obturator nerve reflex were found in all patients. Postoperative complications included 7 cases of mild hematuria, 2 cases of urinary tract infection, 1 case of urethral stricture, and all patients were cured by symptomatic treatment. Followed up for 6 to 24 months with a mean of (13.6±3.4)months. Five cases were lost to follow up, 8 cases (12.9%) had recu-rrence, 1 case (1.6%) had progression, 13 patients had grade I adverse reactions during intravesical instillation of pirarubicin. Conclusions The transurethral thulium laser enucleation combined with intravesical instillation of pirarubicin for treatment of non-muscle invasive bladder cancer is safe and effective, it is worthy of clinical application. Key words: Urinary Bladder Neoplasms; Thulium; Epirubicin

MP13-08 THE COMPARISON ONE IMMEDIATE POSTOPERATIVE INTRAVESICAL CHEMOTHERAPY WITH SHORT-TERM ADJUVANT INTRAVESICAL CHEMOTHERAPY AFTER TURBT IN LOW- AND INTERMEDIATE RECURRENT RISK OF NON-MUSCLE-INVASIVE BLADDER CANCER- A RANDOMIZED PROSPECTIVE STUDY IN JAPAN.

You have accessJournal of UrologyBladder Cancer: Non-Invasive I1 Apr 2016MP13-08 THE COMPARISON ONE IMMEDIATE POSTOPERATIVE INTRAVESICAL CHEMOTHERAPY WITH SHORT-TERM ADJUVANT INTRAVESICAL CHEMOTHERAPY AFTER TURBT IN LOW- AND INTERMEDIATE RECURRENT RISK OF NON-MUSCLE-INVASIVE BLADDER CANCER- A RANDOMIZED PROSPECTIVE STUDY IN JAPAN. Yoshio Naya, Takumi Shiraishi, Masakatsu Oishi, Takashi Ueda, Hiroyuki Nakanshi, Yasuyuki Naitoh, Terukazu Nakamura, Fumiya Hongo, Kazumi Kamoi, Koji Okihara, Kazuya Mikami, Tsuyoshi Iwata, and Osamu Ukimura Yoshio NayaYoshio Naya More articles by this author , Takumi ShiraishiTakumi Shiraishi More articles by this author , Masakatsu OishiMasakatsu Oishi More articles by this author , Takashi UedaTakashi Ueda More articles by this author , Hiroyuki NakanshiHiroyuki Nakanshi More articles by this author , Yasuyuki NaitohYasuyuki Naitoh More articles by this author , Terukazu NakamuraTerukazu Nakamura More articles by this author , Fumiya HongoFumiya Hongo More articles by this author , Kazumi KamoiKazumi Kamoi More articles by this author , Koji OkiharaKoji Okihara More articles by this author , Kazuya MikamiKazuya Mikami More articles by this author , Tsuyoshi IwataTsuyoshi Iwata More articles by this author , and Osamu UkimuraOsamu Ukimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2489AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We conducted a randomized, prospective, multicenter study comparing one immediate postoperative intravesical chemotherapy with short-term adjuvant intravesical chemotherapy after transurethral resection of bladder tumor (TURBT) in non-muscle invasive bladder carcinoma (NMIBC) with low or intermediate recurrent risk. The objective is to evaluate the efficacy of intravesical chemotherapy using pirarubicin for patients with low or intermediate risk. METHODS This study was approved by the ethics committees of Kyoto Prefectural University of Medicine in September 2010. The recurrent risk was stratified using EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Between October 2010 and January 2015, 216 patients was enrolled in this study and 97 patients were excluded from this study after TURBT for their high recurrent risk of NMIBC. Remaining 109 with low or intermediate recurrent risk of NMIBC were randomized to one immediate postoperative intravesical instillation of pirarubicin (THP) 30mg (Group A), or additional intravesical chemotherapy of THP 30mg weekly for 8 weeks (Group B). The patients were examined by cystoscopy and urine cytological examination every 3 months after TURBt to determine bladder tumor recurrence. RESULTS The 2-year recurrence free rate were 65.3% for Group A and 87.2% for Group B, respectively (log rank test, p = 0.038). In patients with intermediate recurrent risk, the 2year recurrence free rate were 62.3% in Group A and 86.8% in group B, respectively (log rank test, p = 0.0261). In patients with recurrent score between 5 and 9, the 2-year recurrence free rate were 91.7% in Group A and 25.0% in Group B (log rank test, p=0.0052). There was no patient with progression during this period. Adverse events were documented in 0% and 24.4% in Group A and Group B, respectively. There was no patient with severe adverse event (Grade 3 or more). CONCLUSIONS Additional instillation of THP 30mg weekly for 8 weeks reduced the risk of tumor recurrence without severe toxicity in NMIBC patients with intermediate recurrent risk. Our data provide a rationale for adjuvant intravesical chemotherapy after TURBT in NMIBC patients with intermediate recurrent risk. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e137 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yoshio Naya More articles by this author Takumi Shiraishi More articles by this author Masakatsu Oishi More articles by this author Takashi Ueda More articles by this author Hiroyuki Nakanshi More articles by this author Yasuyuki Naitoh More articles by this author Terukazu Nakamura More articles by this author Fumiya Hongo More articles by this author Kazumi Kamoi More articles by this author Koji Okihara More articles by this author Kazuya Mikami More articles by this author Tsuyoshi Iwata More articles by this author Osamu Ukimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP13-10 THE INCIDENCE OF LATE BLADDER TUMOR RECURRENCE OF UPPER TRACT UROTHELIAL CARCINOMA AND OPTIMAL CYSTOSCOPIC FOLLOW-UP: A MULTICENTER STUDY

INTRODUCTION AND OBJECTIVES: We conducted a randomized, prospective, multicenter study comparing one immediate postoperative intravesical chemotherapy with short-term adjuvant intravesical chemotherapy after transurethral resection of bladder tumor (TURBT) in non-muscle invasive bladder carcinoma (NMIBC) with low or intermediate recurrent risk. The objective is to evaluate the efficacy of intravesical chemotherapy using pirarubicin for patients with low or intermediate risk. METHODS: This studywas approved by the ethics committees of KyotoPrefectural University ofMedicine inSeptember 2010. The recurrent risk was stratified using EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Between October 2010 and January 2015, 216 patients was enrolled in this study and 97 patients were excluded from this studyafter TURBT for their high recurrent riskofNMIBC. Remaining 109 with low or intermediate recurrent risk of NMIBC were randomized to one immediate postoperative intravesical instillation of pirarubicin (THP) 30mg (GroupA), or additional intravesical chemotherapy of THP 30mg weekly for 8 weeks (Group B). The patients were examined by cystoscopy and urine cytological examination every 3 months after TURBt to determine bladder tumor recurrence. RESULTS: The 2-year recurrence free rate were 65.3% for Group A and 87.2% forGroupB, respectively (log rank test, p1⁄4 0.038). In patients with intermediate recurrent risk, the 2year recurrence free rate were 62.3% inGroupAand86.8% in groupB, respectively (log rank test, p1⁄4 0.0261). In patients with recurrent score between 5 and 9, the 2-year recurrence free ratewere91.7% inGroupAand25.0% inGroupB (log rank test, p1⁄40.0052). There was no patient with progression during this period. Adverse events were documented in 0% and 24.4% in Group A and Group B, respectively. There was no patient with severe adverse event (Grade 3 or more). CONCLUSIONS: Additional instillation of THP 30mg weekly for 8 weeks reduced the risk of tumor recurrence without severe toxicity in NMIBC patients with intermediate recurrent risk. Our data provide a rationale for adjuvant intravesical chemotherapy after TURBT in NMIBC patients with intermediate recurrent risk.

Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study.

To verify the efficacy and safety of intravesical instillation of pirarubicin combined with hyaluronic acid after TURBT in non-muscle invasive bladder cancer patients. We conducted a prospective study recruiting 127 eligible patients from 2008 to 2010. Patients were randomly assigned to Group A (pirarubicin combined with hyaluronic acid) and Group B (pirarubicin alone). Patients' demographics, treatment efficacy on recurrence, visual analog scale score, and postoperative complications were evaluated and analyzed during observation. After the first month of intravesical chemotherapy, a perceptible relief of pelvic pain and urinary symptoms was detectable in Group A when compared with Group B (Fig. 2; P = 0.04). From objective analysis, the clinicians observed a consistent better improvement in Group A than in Group B on clinical conditions (P = 0.02). Frequency, urgency, and odynuria are relieved effectively in Group A (21/64 32.9%) and in Group B (41/63 65.1%), with significant difference observed (P = 0.001). No statistical evidence of benefit was observed in terms of recurrence. No obvious hyaluronic acid-related adverse event was observed. As compared to intravesical instillation of pirarubicin alone, the administration of pirarubicin combined with HA for prevention from postoperative recurrence was satisfactory and safe. The relief of pelvic pain and urinary symptoms is more rapid and more durable.

Intravesical Seeding of Upper Urinary Tract Urothelial Carcinoma Cells During Nephroureterectomy: An Exploratory Analysis from the THPMG Trial

The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells. Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed. Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium. Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial

We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Mechanism of intravesical instillation of pirarubicin for preventing recurrence of non-muscle invasive bladder cancer

To evaluate the apoptosis-inducing effect of intravesical instillation of pirarubicin (THP) on bladder cancer and normal bladder tissue, and explore the mechanism of such treatment for preventing recurrence of non-muscle invasive bladder cancer. Forty patients with primary non-muscle invasive bladder cancer were treated in our hospital from January 2006 to October 2008. The patients were divided into three groups, including 15 cases treated by intravesical instillation of THP (30 mg/50 ml, 0.5 hours) at 1 hour, 15 cases at 24 hours before transuretheral resection of bladder tumor (TUR-BT), and 10 cases in control group who received TUR-BT only. The THP uptake of the tumor and normal bladder tissues was observed by fluorescence microscopy, the apoptosis was assessed with TUNEL staining, and immunohistochemistry was used to detect the expression of bcl-2 and bax. Seldom fluorescence of THP in normal bladder tissues and some diffuse fluorescence reaching the muscular layer in the tumor area were observed after THP instillation at 1 hour before TUR-BT. The fluorescence of THP could still be observed in the tumor tissues at 24 hours after THP instillation. The apoptosis indexes (AI) of tumors in the chemotherapy groups were significantly higher than that in the control group (P < 0.01). There was a correlation between bcl-2/bax ratio and AI. Pirarubicin can be uptaken by bladder cancer tissue selectively and induces apoptosis of tumor cells. The changes of expression of bcl-2 and bax and decreasing of the bcl-2/bax ratio may be an important mechanism of action of the intravesical instillation of THP for preventing recurrence of non-muscle invasive bladder cancer.

The absorption of pirarubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

To assess the validity of the prophylactic use of pirarubicin ([2'R]-4-O-tetrahydropyranyl-doxorubicin) immediately after transurethral resection of bladder tumour (TURBT), using pharmacodynamic studies. The study included 20 consecutive patients with superficial bladder cancer. Pirarubicin (30 mg/50 mL or 30 mg/100 mL, 10 patients each) was instilled immediately after TURBT and retained in the bladder for 1 h. Blood samples were obtained before and at 15, 30, 60 and 120 min after the instillation. After retaining the drug for 1 h all the intravesical fluid was collected and assayed for pirarubicin. The plasma pirarubicin concentration in those receiving either dose was below detectable levels at any time after instillation. The mean recovery rate of pirarubicin in the drained fluid was 73%. The intravesical instillation of pirarubicin immediately after TURBT caused no detectable plasma concentration and few systemic side-effects.

Cooperative Study of Therapy of Superficial Bladder Cancer by Intravesical Instillation of Pirarubicin

Intravesical instillation therapy with (2"R)-4'-O-tetrahydropyranyl adriamycin [pirarubicin (THP)], a new anthracycline agent, was performed to examine its direct effect on superficial bladder cancer in a six-center cooperative Phase II study. There were 50 evaluable cases, for which a response rate of 50% was obtained. The main side effects that occurred were bladder irritation symptoms such as pollakisuria (50%) and pain on urination (38%). Intravesical pirarubicin instillation therapy was administered to eight cases that had not responded to doxorubicin therapy or that had experienced recurrence after such therapy. For six evaluable cases, the response rate was 50%, and the incidence of side effects was 88%.