Instillation Of Chemotherapy Research Articles

Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola™) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer.

Background:Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk.Objective:To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo.Methods:Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively.Results:Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60±30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity.Conclusions:Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60±30-minutes time interval which requires further study.

Post-Operative Immediate Single Instillation of Chemotherapy as Prevention of Recurrence after Transurethral Resection of Intermediate-High Risk Non-Muscle-Invasive Bladder Cancer

We retrospectively evaluated the efficacy of immediate single instillation (SI) of pirarubicine hydrochloride (THP) in the chemoprevention of intermediate and high risk patients with non-muscle-invasive bladder cancer (NMIBC). The study population consisted of 256 intermediate and high risk patients with NMIBC who underwent Bacillus Calmette-Guerin (BCG) induction therapy or delayed intravesical chemotherapy between 1999 and 2014. We introduced SI of 30 mg THP in 30 ml normal saline for all cases in 2010, and thus earlier cases could be considered as historical controls. As BCG induction therapy, patients received 80 mg of BCG Tokyo strain 2 weeks after transurethral resection of bladder tumor (TURBT), and the instillations were repeated weekly for 8 weeks. On the other hand, as delayed intravesical chemotherapy, patients received 30 mg THP in 30 ml normal saline over a period of 6 months starting 2 weeks after TURBT. The instillation schedule was once a week for 1 month, every other week for 1 month and once a month for 4 months. The patients were followed with cystoscopy and urine cytology every 3 months for the first 2 years and every 6 months thereafter. The 3-, and 5-year non-recurrence rates were 80. 3 and 80.3%, respectively, in the single immediate instillation group and 69.7 and 64.5%, respectively, in the control group. Univariate analysis revealed a significant difference between the SI group and the control group (P=0. 025). Multivariate analysis showed that there was an independent and significant recurrence risk factor in selecting chemotherapy instead of BCG in additional intravesical instillation therapy and not to perform SI. Limitations of our study are its retrospective and nonrandomized nature with a limited number of patients.

Hexvix plus Chemo

While photodynamic diagnosis during transurethral resection of bladder tumor seems warranted only in seemingly high-risk cases, early intravesical instillation of chemotherapy is warranted in all low-risk cases. According to the latest randomized controlled trial, data may make sense also in intermediate- and high-risk cases.

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.

Safety and efficacy of thulium transurethral en block resection with fiber laser “Urоlaz” for treatment of non-muscle-invasive bladder cancer

Background. The high recurrence rate after conventional transurethral resection (cTUR) for bladder cancer (BC) requires search for more effective methods of surgical treatment. Objective: to evaluate the feasibility, safety, and efficacy of cTUR versus thulium laser en bloc resection of bladder tumors using new fiber laser “Urolaz”. Materials and methods. 129 patients, who underwent surgical treatment for BC between 2015–2017 in urological department of I.M. Sechenov First Moscow State Medical University were included in the study. The cTUR were performed for 58 patients, 71 patients underwent thulium laser en bloc resection of bladder tumors. Results. The presence of detrusor muscle in specimen was 58.62 % in cTUR group and 91.55 % in thulium laser en bloc resection group respectively. Obturator nerve reflex, bladder perforation, and bleeding in thulium laser en bloc resection group were absent, therefore immediate instillation of chemotherapy was made in all these cases. Recurrence rate after 12 and 18 months after surgery in the group of en bloc resection was statistically lower compared to the cTUR group. Conclusion. The results, obtained in our study shows that thulium en bloc resection using thulium fiber laser “Urolaz” is feasible, effective and safe procedure for patients with BC. Thulium en bloc resection has a number of advantages over the cTUR: absence of obturator nerve reflex, high quality of specimen for pathological examination (presence of detrusor muscle in specimen was 91.55 %) and low recurrence rate.

Re: Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients

Abstract Background The efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non–muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. Objective To compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participants Between 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysis Primary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ 2 test in SPSS. Results and limitations A total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p =0.11), 20% and 32% in the IMR group (3-yr follow-up, p =0.037), and 28% and 35% in the HIR group (3-yr follow-up, p =0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24–30) in the immediate and 36% (95% CI, 33–39) in the delayed instillation group ( p p p =0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. Conclusions An immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summary A single instillation of chemotherapy after the resection of non–muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.

Down-regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer.

Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non‐muscle‐invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down‐regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p‐AMPK and p‐STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan‐Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down‐regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti‐bladder cancer activities. On the other hand, down‐regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L−1, 50 μL), the combination with metformin (60 mmol L−1, 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down‐regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.

Conditional analyses of recurrence and progression in patients with TaG1 non–muscle-invasive bladder cancer

ObjectiveTo determine conditional recurrence-free survival (RFS) and progression-free survival (PFS) and improve decision-making toward surveillance protocols and scheduling. Furthermore, evaluating the evolution of predictors for disease recurrence over time, because TaG1 non–muscle-invasive bladder cancer harbors a risk of disease recurrence and progression. Material and methodsThe retrospective multicenter design study includes 1,245 TaG1 bladder cancer patients with median follow-up of 62.7 (interquartile range: 34.3–91.1) months. Conditional RFS and PFS estimates were calculated using the Kaplan-Meier method. Multivariable Cox regression model was calculated proportional for the prediction of recurrence and progression (covariables: age, tumor size, multiple tumors, prior recurrence, and immediate postoperative instillation of chemotherapy). ResultsAfter 3 months without event, the conditional RFS and PFS (to ≥pT2) rates for 5 additional years without event were 57.5% and 93.4%, respectively. Given a 1-, 2-, 3-, and 5-year survival, the conditional RFS rates for 5 additional years without event improved by +9.8 (67.3%), +5.2 (72.5%), +6.5 (79.0%), +2.0 (81.0%), and +1.0% (82.0%), respectively. In contrast, the 5-year conditional PFS rates were more or less stable with 94.3% after 1 year to 94.1% after 5 years. Multivariable analyses showed decreasing impact of risk parameters on RFS estimates over time. Based on these findings, we suggest a risk stratification to individualize follow-up for intermediate risk TaG1. Main limitation was the retrospective design. ConclusionsConditional-survival analyses demonstrates that the patient risk profile changes over time. RFS rates rise with increasing survival whereas PFS rates were stable. The impact of prognostic features decreases over time. Our findings can be used for patient counseling and planning of personalized follow-up.

Reduce bladder cancer recurrence in patients treated for upper urinary tract urothelial carcinoma: The REBACARE-trial.

BackgroundFollowing radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22–47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy.AimTo reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy.MethodsAdult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines.ResultsThe primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences.ConclusionsA single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation.

Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30mg/50mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71months. The overall recurrence rate was 39 and 31%, respectively (p=0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p=0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p=0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

Low-Grade, Multiple, Ta Non-muscle-Invasive Bladder Tumors: Tumor Recurrence and Worsening Progression.

Nearly half of newly diagnosed cases of bladder cancer are low grade, noninvasive, and papillary tumors. The standard treatment for non-muscle-invasive bladder cancer (NMIBC) has been transurethral resection of the bladder tumor (TUR-BT) with or without adjuvant intravesical instillation (IVI) of chemotherapy or Bacillus Calmette-Guerin (BCG) therapy. NMIBC is known to be associated with high rates of recurrence and risk of progression. In this study, we have retrospectively analyzed the clinical outcome of initially diagnosed multiple low-grade Ta tumors, with a special focus on tumor recurrence and worsening progression (WP) pattern. We retrospectively reviewed 42 patients with primary, multiple, low-grade Ta bladder cancer. We defined WP as confirmed high-grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinico-pathological factors and tumor recurrence as well as WP pattern were analyzed. Tumor recurrence and WP occurred in 23 (54.76%) and 8 (19.04%) patients during follow-up (median follow-up: 57.38months), respectively. WP to high grade/stage was seen in 8 patients. Multivariate analysis demonstrated that use of tobacco (p < 0.0001) and absence of IVI (p < 0.0001) were significant risk factors for tumor recurrence. The 5-year recurrence-free survival rate for non-tobacco users (74.0%) was significantly higher than that for tobacco users (42.5%, p = 0.0001), and also higher for patients receiving intravesical instillation (84.2 vs. 30.0% without IVI, p = 0.0001). Recurrence is common in patients with low-grade, Ta bladder cancer, especially in the setting of multiplicity. Recurrences occurred in 54.76% of patients and WP occurred in 19.04% of patients. Use of tobacco and non-use of IVI were strongly associated with high recurrence rate.

Processing techniques and safety analysis for transurethral resection of bladder lesions

Objective To evaluate the processing techniques and safety of ureteral stent after transurethral resection (TUR) of bladder lesions involving the ureteral orifice. Methods From January 2010 to August 2016, 42 cases of non-muscle invasive bladder tumor and 18 cases of glandular cystitis including 44 male and 16 female aged from 32 to 81 years(mean 55 years) were treated by TUR. Twenty-three cases of bladder tumor had single tumor and 19 cases had multiple tumors, and 37 cases were primary and 5 cases were recurrent. All the patients without preoperative hydronephrosis revealed by imageological examination.The lesions were resected into the deep muscle layer and involved ureteral orifice were resected during the procedure and after that a Double-J ureteral stent was placed in all cases.When looked for the ureteral orifice, we followed the ureteral peristalsis step by step, and found " concentric circles" muscle tissue.Then we used the guide wire as a guide for ureteral stenting. All the patients received one immediate intravesical instillation of 50 mg pirarubicin after TUR, and further scheme of adjuvant intravesical instillation was made according to the pathological diagnosis. Ureteral stents were removed 8~10 weeks after TUR, imageological examination were performed every three months. Results The operations were successful without complications. No serious adverse reaction occurred in adjuvant intravesical instillation chemotherapy. During the follow-up period of 4~60 months, no ureteral stricture and hydronephrosis occurred in all patients with ureteral stent, and the resected ureteral orifices recovered well with normal appearance and ejecting urine. Conclusions The ureteral orifice usually need to be removed during TUR for bladder lesions, and the way we following the ureteral peristalsis to resect the ureteral orifice is effective.Ureteral stenting after TUR of bladder lesions involving the ureteral orifice can prevent stricture at the ureterovesical junction without increasing the risk of tumor cell seeding along the upper urinary tract. Key words: Cystectomy; Urethra; Electrosurgery; Ureter

Discrepancy Between European Association of Urology Guidelines and Daily Practice in the Management of Non–muscle-invasive Bladder Cancer: Results of a European Survey

BackgroundThe European Association of Urology (EAU) non–muscle-invasive bladder cancer (NMIBC) guidelines are meant to help minimise morbidity and improve the care of patients with NMIBC. However, there may be underuse of guideline-recommended care in this potentially curable cohort. ObjectiveTo assess European physicians’ current practice in the management of NMIBC and evaluate its concordance with the EAU 2013 guidelines. Design, setting, and participantsInitial 45-min telephone interviews were conducted with 20 urologists to develop a 26-item questionnaire for a 30-min online quantitative interview. A total of 498 physicians with predefined experience in treatment of NMIBC patients, from nine European countries, completed the online interviews. Outcome measurements and statistical analysisDescriptive statistics of absolute numbers and percentages of the use of diagnostic tools, risk group stratification, treatment options chosen, and follow-up regimens were used. Results and limitationsGuidelines are used by ≥87% of physicians, with the EAU guidelines being the most used ones (71–100%). Cystoscopy (60–97%) and ultrasonography (42–95%) are the most used diagnostic techniques. Using EAU risk classification, 40–69% and 88–100% of physicians correctly identify all the prognostic factors for low- and high-risk tumours, respectively. Re-transurethral resection of the bladder tumour (re-TURB) is performed in 25–75% of low-risk and 55–98% of high-risk patients. Between 21% and 88% of patients received a single instillation of chemotherapy within 24h after TURB. Adjuvant intravesical treatment is not given to 6–62%, 2–33%, and 1–20% of the patients with low-, intermediate-, and high-risk NMIBC, respectively. Patients with low-risk NMIBC are likely to be overmonitored and those with high-risk NMIBC undermonitored. Our study is limited by the possible recall bias of the selected physicians. ConclusionsAlthough most European physicians claim to apply the EAU guidelines, adherence to them is low in daily practice. Patient summaryOur survey among European physicians investigated discrepancies between guidelines and daily practice in the management of non–muscle-invasive bladder cancer (NMIBC). We conclude that the use of the recommended diagnostic tools, risk-stratification of NMIBC, and performance of re-TURB have been adopted, but adjuvant intravesical treatment and follow-up are not uniformly applied.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Analysis of the efficacy of transurethral thulium-Yag laser resection of bladder tumor in the treatment of non-muscle invasive bladder cancer

Objective To evaluate the efficacy and safety of transurethral thulium-Yag laser(Tm-Yag Laser) resection of bladder tumor in the treatment of non-muscle invasive bladder cancer(NMIBC). Methods The clinical data of 186 patients who underwent transurethral resection with pathologically identified of NMIBC were retrospectively analyzed.76 cases and 110 cases were in the transurethral resection of bladder cancer Tm-Yag Laser group and TURBT group, respectively. The operative time, intraoperative blood loss, incidence of obturator nerve reflex, days for urethral catheterization, duration of hospitalization after surgery, detection rate of muscle layer in postoperative pathologic examination and recurrence between the two groups were compared. All patients were followed up for 24 months. Regularly gemcitabine intravesical instillation chemotherapy and cystoscopy were performed postoperation. Results The operative time [(27.08±5.56) min vs. (25.55±5.37) min, P>0.05] and intraoperative blood loss [(14.23±4.05) mL vs. (15.10±3.24) mL, P>0.05] showed no differences between the two groups. The incidence of obturator nerve reflex in Tm-Yag laser group was lower than that in TURBT group (0.0% vs. 5.5 %, χ2=4.28, P=0.038). The days for urethral catheterization [(3.48±1.05) d vs. (4.02±1.14) d, t=3.328, P=0.001] and the duration of hospitalization after surgery [(4.47±1.08) d vs. (5.02±1.13) d, t=3.350, P=0.001] in Tm-Yag laser group were significantly shorter than those in TURBT group. In Tm-Yag laser group, the detection rate of muscle layer in postoperative pathologic examination was higher than that in TURBT group(χ2=14.96, P=0.001). The total rate of tumor recurrence in Tm-Yag laser group was significantly lower than that in TURBT group(13.2 % vs. 25.5%, χ2=4.18, P=0.041). Conclusion Transurethral Tm-Yag laser is safe and effective in the treatment of NMIBC. It can avoid the incidence of complications and reduce tumor recurrence rate, which is worthy of promotion. Key words: Urinary bladder neoplasms; Laser therapy

Value of an Immediate Intravesical Instillation of Mitomycin C in Patients with Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised Study in 2243 patients

BackgroundThe efficacy of an immediate single chemotherapy instillation after transurethral resection of a bladder tumour (TURBT) in patients with non–muscle-invasive bladder cancer (NMIBC) remains a topic of debate. Evidence is even more scarce when an immediate instillation is followed by adjuvant instillations. ObjectiveTo compare the effect of a mitomycin C (MMC) instillation within 24h to an instillation 2 wk after TURBT in patients with NMIBC with or without adjuvant instillations. Design, Setting, and participantsBetween 1998 and 2003, 2844 NMIBC patients were randomised for immediate versus delayed MMC instillation after TURBT. Patients were categorised in low-risk (LOR), intermediate-risk (IMR), and high-risk (HIR) groups. Total numbers of instillations in these groups were 1, 9, and 15, respectively. Outcome measurements and statistical analysisPrimary end point was 3-yr recurrence risk for the IMR and HIR groups and 5-yr risk for the LOR group. Secondary outcomes were time to recurrence and incidence of adverse events. Analyses were performed with the log-rank test, Cox-regression, and χ2 test in SPSS. Results and limitationsA total of 2243 patients were eligible on an intention-to-treat basis. Recurrence risks were 43% and 46% in the LOR group (5-yr follow-up, p=0.11), 20% and 32% in the IMR group (3-yr follow-up, p=0.037), and 28% and 35% in the HIR group (3-yr follow-up, p=0.007), for an immediate and a delayed instillation, respectively. For all patients, the recurrence risk was 27% (95% confidence interval [CI], 24–30) in the immediate and 36% (95% CI, 33–39) in the delayed instillation group (p<0.001) with a 27% reduction in relative recurrence risk (hazard ratio: 0.73, 95% CI, 0.63–0.85, p<0.001). The incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p=0.08). The risk groups in our study differ slightly from the current guidelines, which is a limitation of our study. ConclusionsAn immediate, single instillation after TURBT reduces the recurrence risk in NMIBC patients, independent of the number of adjuvant installations. Patient summaryA single instillation of chemotherapy after the resection of non–muscle-invasive bladder cancer reduces the recurrence risk, even if patients are treated with an adjuvant schedule of instillations.

The clinical efficacy of transurethral plasma needle electrode en bloc resection of bladder cancer

Objective To summarize the clinical experience and analyze the efficacy of transurethral plasma needle electrode en bloc resection for bladder cancer. Methods From February 2015 to August 2016, a total of 26 patients, including 21 males and 5 females, with bladder cancer received transurethral plasma needle electrode en bloc resection of bladder tumor. Their age ranged from 42 to 75 years, mean (56±13)years. The size of tumor ranged from 1 to 4 cm, mean (2.3±1.6)cm. The solitary tumor was found in 19 cases and multiple tumors were found in 7 cases, including 2 tumors in 5 cases, 3 tumors in 2 cases. In 6 cases, the tumor located in the lateral bladder wall. All the pre-operative biopsy showed the urethelial carcinoma in all cases, No bladder extravasion or upper urinary tumor was noticed in the CTU before surgery.By using the electrode needle tip inserted into the bladder mucosa, blunt release or cut the tumor bases until the deep muscularis or the serosal layer, complete removal of the tumor. The specimen was removed from the bladder and sent to the pathological examination.The operation time, the volume of blood loss during operation, surgical complications, pathological diagnosis and the wounds recovery were recorded and analyzed. Results All surgeries were undergone successfully. Totally 35 tumors were resected with diameter of 1.0-4.0 cm, mean (2.3±1.6)cm. The estimated blood loss was less than 10 ml. The operative duration ranged from 20 to 50 min, mean (30±16)min. The duration for removing the single tumor ranged from 5 to 25 min. No obturator nerve reflex were observed during surgery. No blood loss and complications occurred after operation. All patients received 30 mg pirarubicin bladder instillation chemotherapy immediately and no adverse reaction was noticed. Postoperative pathological stages of enrolled cases were distributed as 33 cases of T1G1 staging, 2 cases of T1G3 staging. No positive margin was observed. 3 months after operation, cystoscopy showed that the wound healed well. A total of 26 cases followed up for 3-10 months (mean 6.0±2.3 months). No one developed recurrence. Conclusions Transurethral plasma needle electrode en bloc resection of bladder tumor would reduce the incidence of complications and obturator nerve reflex. It can provide sufficient specimens for histological diagnosis. Key words: Bladder tumor; Transurethral resection of bladder tumor; Plasma needle electrode; The en bloc resection.

Post-Operative Single Immediate Intravesical Instillation Chemotherapy as Prophylaxis for Reccurence after Transurethral Resection of Low Risk Non-Muscle-Invasive Bladder Cancer

We evaluated the efficacy of single-dose instillation of pirarubicine hydrochloride (THP) in the chemoprophylaxis of non-muscle-invasive bladder cancer(NMIBC). In a retrospective study, 135 evaluable patients were assigned to three groups after transurethral resection of bladder tumors (TURBT). In group 1, patients received no adjuvant therapy after TURBT. In group 2, patients received a single-dose of 30 mg THP in 30 ml normal saline immediately after TURBT. In group 3, patients received 30 mg THP in 30 ml normal saline 2 weeks after TURBT , and the instillations were repeated for 4 weeks, then every other week twice and successively monthly for 6 months. Patients were followed with cystoscopy and urine cytology every 3 months for the first 2 years and every 6 months thereafter. The 3- and 5-year non-recurrence rates were 66.9%, and 66.0%, respectively, in group 1, 85.6%, and 85.6%, respectively, in group 2, and 93.6%, and 77.9%, respectively, in group 3. There was a significant difference only between group 1 and group2 (P ＝0.048). With respect to the recurrence per month, there was a significant difference between the 3 groups (P＝0.014) for the first 2 years. However, there was no significant difference thereafter. Limitations of our study are its retrospective and nonrandomized nature with a limited number of patients.

Bladder cancer in 2016: News in diagnosis, treatment, and risk group assessment.

2016 has been a good year for research in non-muscle-invasive bladder cancer. Topics to see progress include risk assessment of patients treated with BCG maintenance, the role of repeat transurethral resection of the bladder (TURB), a prospective study of white-light versus narrow-band imaging, a meta-analysis regarding single instillation chemotherapy, and the effect of the use of fluorescence-guided TURB on progression.

Positively charged polypeptide nanogel enhances mucoadhesion and penetrability of 10-hydroxycamptothecin in orthotopic bladder carcinoma

Bladder cancer (BC) has become a serious public health problem due to its continuously rising incidence, high recurrence rate, and poor quality of life. Intravesical instillation of chemotherapy, one of common and important treatment strategy for BC, is restricted partially due to the short residence time and the low penetration ability of current antineoplastic agent formulations in clinic. Herein, a positively charged disulfide-core-crosslinked polypeptide nanogel of poly(l-lysine)–poly(l-phenylalanine-co-l-cystine) (PLL–P(LP-co-LC)) was synthesized. 10-Hydroxycamptothecin (HCPT) was loaded into the core via a facile diffusion to obtain loading nanogel (i.e., NG/HCPT). The reduction-responsive cationic polypeptide nanogel not only showed a high drug-loading efficiency, a prolonged residence time, and an improved tissue penetration capability, but also demonstrated an ability to accurately and rapidly release HCPT in bladder cancer cells. NG/HCPT exhibited superior cytotoxicity against human T24 bladder cancer cells compared to that of free HCPT in vitro. Moreover, the positively charged loading nanogel exhibited significantly enhanced antitumor efficacy and reduced side effects toward orthotopic bladder cancer model in vivo. Overall, the smart polypeptide nanogel with enhanced residence and permeability provides a promising drug delivery platform for local chemotherapy of BC.