Female sexual dysfunction post radical cystectomy and urinary diversion.

OBJECTIVES: To evaluate the impact of radical cystectomy and urinary diversion on female sexual function. MATERIALS AND METHODS: A Medline search was conducted according to the PRISMA statement for all English full-text articles published between 1980 and 2016 and assessing female sexual function post radical cystectomy and urinary diversion. Eligible studies were subjected to critical analysis and revision. The primary outcomes were the reporting methods for female sexual dysfunction (FSD), manifestations of FSD, and factors associated with FSD, postoperative recoverability of FSD, and awareness level regarding FSD. RESULTS: From the resulting 117 articles, 11 studies were finally included in our systematic review, with a total of 361 women. Loss of sexual desire and orgasm disorders were the most frequently reported (49% and 39%). Dyspareunia and vaginal lubrication disorders were reported in 25% and 9.5%, respectively. The incidence of sexual dysfunction was 10% in 30 patients receiving genital- or nerve-sparing cystectomy vs. 59% receiving conventional cystectomy. CONCLUSION: Although female sexual function is an important predictor of health-related quality of life post radical cystectomy and urinary diversion, the available literature is not enough to provide proper information for surgeons and patients.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Preservation of the internal genital organs during radical cystectomy in selected women with bladder cancer: a report on 15 cases with long term follow-up.

PURPOSE: To prospectively present the technique, functional and oncological outcome of internal genitalia sparing cystectomy for bladder cancer in 15 selected women. PATIENTS AND METHODS: Between January 1995 and December 2010, 305 women underwent orthotopic neobladder after radical cystectomy. Of these, 15 cases with a mean age of 42 years underwent genitalia sparing. Inclusion criteria included stage (T2b N0 Mo or less, as assessed preoperatively, unifocal tumors away from the trigone, sexually active young women and internal genitalia free of tumor. Cystectomy with preservation of the uterus, vagina and ovaries and Hautmann neobladder were performed. Oncological, functional, urodynamic and sexual outcome using Female Sexual Function Index (FSFI) were evaluated. RESULTS: Definitive histopathology showed advanced stage not recognized preoperatively in 2 patients, who developed local recurrence and bony metastasis after 3-4 months. A third patient developed bony metastasis after 15 months. No recurrence developed in the retained genital organs. The remaining 12 patients remained free of disease with a mean follow-up of 70 months. Among women eligible for functional evaluation, daytime and nighttime continence were achieved in 13/13 (100%) and 12/13 (92)%, respectively. Chronic urinary retention was not noted. The urodynamic parameters were comparable to those in other patients without genital preservation. Sexual function (FSFI) was better in these patients than in others without genital preservation. CONCLUSIONS: Genital sparing cystectomy for bladder cancer is feasible in selected women. It provides a good functional outcome, better sexual function and the potential for fertility preservation. So far, the oncological outcome is favorable.

Oncological outcome after radical cystectomy and orthotopic bladder substitution in women.

AIM: The pathological outcome after radical cystectomy and orthotopic bladder substitution in women and the possibility of genital sparing are studied in a prospective way. METHODS: Between January 1995 and June 2003, 180 women with bladder cancer (mean age 50.6 years) underwent orthotopic neobladder reconstruction. Histopathologic assessment of the cystectomy specimens was performed. Involvement of the internal genitalia by primary or secondary cancer was evaluated by preoperative CT or MRI. Histopathological evaluation of these organs was made in the cystectomy specimens. RESULTS: Mean follow-up was 57 months. At follow-up, isolated urethral recurrence developed in two patients. Local pelvic recurrence developed in 30 patients, distant metastasis in 14 and both in nine. Uterine infiltration, which was suspected by preoperative CT, was confirmed by definitive histopathology after radical cystectomy in only two cases; otherwise there were no primary or secondary malignancies of the internal genitalia. Isolated recurrence of bladder cancer in the vaginal remnant during follow-up after cystectomy was not noted in any woman. CONCLUSIONS: The rate of urethral recurrence and oncological failure after orthotopic bladder substitution in women is low and acceptable and thus justifies the continued performance of this type of diversion. Proper selection of cases is mandatory. In women with absence of malignant involvement of the internal genitalia on preoperative imaging, the risk of secondary malignant involvement of these organs in cystectomy specimens is very low. Therefore, preservation of the uninvolved gynecologic organs during radical cystectomy in premenopausal women with unifocal, organ-confined tumor above the bladder base, is justified.

Sliding hernia containing the ureter--a rare cause of graft hydroureteronephrosis: a case report.

Obstructive uropathy following renal transplantation is frequently reported. However, ureteral obstruction due to its incorporation in a sliding hernia is a rare event. Herein, we report a case of late graft hydroureteronephrosis secondary to a sliding hernia containing the transplanted ureter. The diagnosis was confirmed with the aid of magnetic resonance urography and antegrade urography. Following hernioplasty, a decrease of serum creatinine level was achieved with significant decompression of the system.

Critical evaluation of the factors influencing erectile function after renal transplantation.

A total of 400 male renal transplant recipients (RTR) were investigated. Data on medical, sexual history, clinical examination and laboratory variables were collected. The severity of erectile dysfunction (ED) was assessed using the International Index of Erectile Function questionnaire. Univariate and multivariate logistic regression analyses were used to determine prognostic variables, which have independent impact on erectile function. ED was detected in 35.8% of the whole group. Current erectile function as compared to pretransplant status was improved, deteriorated or remained static in 44, 12.5 and 43.5% of the evaluated transplant recipients, respectively. After logistic regression analysis, age, hemoglobin level and presence of DM and/or peripheral neuropathy had significant and independent negative impact on erectile function. We concluded that renal transplantation has varying effects on erectile function. ED is highly prevalent among RTR and its pathogenesis is multifactorial.

Renal transplantation in children with abnormal lower urinary tract.

OBJECTIVE: This retrospective study reports the outcomes as well as pre- and posttransplant urologic treatments of renal transplantation for children with an abnormal lower urinary tract (LUT). METHODS: Between March 1981 and December 2001, 195 children (< or =18 years of age) received live-donor kidney transplants. The 15 recipients (14 boys and 1 girl, mean age 13.5 +/- 3 years) who had lower urinary tract disorders included posterior urethral valves (PUV) with valve bladder (n=12) and neuropathic bladders secondary to meningomyelocele (n=3). These children were evaluated by voiding cystourethrogram, cystourethroscopy, and cystometry. The children with PUV were maintained on clean intermittent catheterization (CIC) and a detrusor relaxant at least 3 months before transplantation. Augmentation ileocystoplasty or continent cutaneous diversion were used in three patients. The graft and patient survivals as well as complications in this cohort was compared with a group of children with normal LUT, who underwent renal transplantation during the same period. RESULTS: One child died in the early posttransplant period due to rupture of the external iliac artery. Follow-up ranged from 6 months to 16 years (mean=4.5 years). During the same period the graft and patient survival rates were comparable between the group of children with versus without abnormal LUT. Furthermore, mean serum creatinine and creatinine clearance values were also comparable. The group with an abnormal LUT showed a higher incidence of urinary fistula (3/14) and recurrent UTI and/or bacteremia (4/14). CONCLUSIONS: Renal transplantation is feasible with good results for children with abnormal LUT. Pre- and posttransplant urologic management is critical for a successful outcome. However these children display a high incidence of urologic and infectious complications.

Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index.

OBJECTIVES: To assess the prognostic factors that could be used to predict tumour recurrence and progression, and to construct and validate a predictive index. PATIENTS AND METHODS: Between June 1991 and December 2000, 533 patients (418 men and 115 women; mean age 55.4 years) underwent complete transurethral resection of histologically confirmed pTa and pT1 transitional cell carcinoma of the bladder, after which 377 (test series) were randomized into two subsequent studies, of six groups, to receive adjuvant intravesical sequential bacillus Calmette-Guérin (BCG) and epirubicin, BCG alone, epirubicin (50 or 80 mg), adriamycin 50 mg or no adjuvant therapy. Factors potentially affecting tumour recurrence or progression were assessed using univariate and multivariate analysis, i.e. tumour stage, histological grade, DNA ploidy, history of recurrence, multiplicity, size, tumour configuration, associated carcinoma in situ, recurrence at the first 3-month check cystoscopy and the use of adjuvant therapy. The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). The algebraic sum of the regression coefficients of the factors with independent and significant association with disease-free survival for each case represented a proportional hazard score (PHS). The PI was validated in another series of 156 patients (validation series) in whom the same regression coefficients for the same significant factors as the test series were used to categorize it into three risk groups. Kaplan-Meier survival curves were plotted to compare the different risk categories in both test and validation series. RESULTS: The mean (sd, range) follow-up in the test and validation series were 58 (19, 5-96) and 28.3 (14.9, 2-94) months, respectively. In the test series, tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration, cystoscopy result and the type of adjuvant therapy had independent significance for recurrence on multivariate analysis. For progression, the cystoscopy result, DNA ploidy and grade were the only independent and significant predictors. The ranges of PHS for the factors affecting recurrence-free and progression-free survival were 0.0-7.14 and 0.0-5.84, respectively, which were divided equally into three risk categories with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.001). The three categories in the validation series were significantly different from each other and each was comparable with that in the test series. CONCLUSIONS: Tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration and type of adjuvant therapy affected independently the rate of recurrence after resecting superficial bladder tumour. Recurrence at the 3-month cystoscopy, histological grade and DNA ploidy were the only predictors of progression to muscle-invasion. The PI dividing the patients into three risk groups with different treatment and follow-up strategies for recurrence and progression was reproducible in a validation series.

Sequential intravesical immunochemotherapy for stages Ta and T1 transitional cell carcinoma of the bladder : an update

Objectives: To present an update of our experience with sequential immuno-chemotherapy using bacillus Calmette-Guerin (BCG) and epirubicin in superficial bladder tumors. In addition; the question of whether to start with BCG or epirubicin is answered. Methods: Between January 1993 and December 2001; 156 patients with histologically proven Ta and T1 bladder transitional cell carcinoma were included in a prospective randomized study. Following transurethral resection of the bladder tumor (TURBT); patients were randomly assigned to 1 of 2 groups. Patients in group 1 received weekly doses of 150 mg BCG alternating with 50 mg epirubicin for 6 weeks. Maintenance was carried out by a monthly dose of BCG alternating with epirubicin; to complete 1 year of treatment. Patients in group 2 received the same protocol; but with a reversed order with epirubicin being used initially. Results: 149 patients; 114 men and 35 women with a mean age of 55 years; were evaluable. 7 patients were excluded due to severe side effects. Mean and median follow-up was 42.8 and 43 months; respectively. In the whole series recurrence rate was 18.1; recurrence rate per year was 0.06; mean interval to first recurrence was 29 months and progression rate was 12. Side effects developed in 40 patients (25.6) and were mostly in the form of mild cystitis (26 patients). The 2 groups of therapy were comparable regarding recurrence rate; recurrence rate per year; progression rate and side effects. Conclusions: The sequential therapy is effective in recurrence prophylaxis of superficial bladder tumors. The side effects were less frequent than in our historical controls treated with BCG alone. It does not matter to start with epirubicin or BCG in this regimen

Effects of selective autonomic and pudendal denervation on the urethral function and development of retention in female dogs.

PURPOSE: This trial is an experimental approach to the possible causes of continence and voiding problems after urethra sparing radical cystectomy and orthotopic bladder substitution in women. MATERIALS AND METHODS: Between January 1996 and January 1999 we included 24 mongrel female dogs in this 4-phase study of 6 dogs each. The effects of autonomic denervation of the urethra (phase 1) and urethral transection just distal to the bladder neck (phase 2) on the urethral pressure profile were recorded. In phase 3 the effects of autonomic denervation, urethral transection and pharmacological manipulation of the denervated transected urethra on the urethral pressure profile were studied in succession. In phase 4 the effects of pudendal nerve transection and pharmacological blockade were recorded. In the 12 phases 2 and 3 dogs the transected urethra was re-anastomosed to the bladder neck. Acute experiments were repeated after 2 and 6 months, urethrocystoscopy was done and post-void residual urine was estimated. Two of the latter dogs were sacrificed 6 months after the acute experiment and the urethras were histopathologically examined. RESULTS: Autonomic denervation resulted in a 46% to 48% decrease in mean maximal pressure in the proximal urethra in phases 1 and 3 (p <0.001) with no significant effect on the distal urethra. Urethral transection in phase 2 did not affect the urethral pressure profile. Phentolamine injection after urethral denervation and transection in phase 3 produced a further reduction of 11.3% and 46.3% in mean resting pressure in the proximal and distal urethra, respectively, while succinyl choline produced a 38.1% further decrease in the distal urethra. Unilateral and bilateral pudendal denervation reduced pressure in the distal urethra significantly but not in the proximal urethra. When phentolamine was given thereafter, a further decrease of 38% and 2.4% resulted in resting pressure values in the proximal and distal urethra, respectively. The change in distal urethral pressure was marginally significant after succinyl choline injection (p = 0.05). Results were reproducible after 2 and 6 months. The proximal urethra remained patent with no post-void residual urine after autonomic denervation. There was no significant urethral fibrosis after realignment of the transected urethra in the 2 sacrificed phases 2 and 3 dogs. CONCLUSIONS: From this study we concluded that autonomic denervation reduced pressure in the proximal urethra by less than 50%. Continuity of the urethra with the bladder is not necessary for proper urethral function. After autonomic denervation the proximal urethra remained patent with no subsequent fibrosis. In addition, no post-void residual urine was noted. Bilateral pudendal denervation did not completely block activity of the distal urethra. The nonneuromuscular components had a small role in the creation of urethral closure function.

Urological complications after living-donor renal transplantation.

OBJECTIVE: To determine the incidence and management of urological complications after 1200 consecutive live-donor renal transplantations, all of which were carried out in one centre; the possible risk factors and the effect on patient and graft survival were also assessed. PATIENTS AND METHODS: Data were retrieved from an electronic database; the incidence of urological complications was determined, and correlated with relevant risk factors by univariate and multivariate analysis. The effect on patient and graft survival was assessed using Kaplan-Meier statistics. RESULTS: There were 100 complications in 96 patients (8%); urinary leaks occurred in 37, ureteric strictures in 23 and lymphoceles causing ureteric obstruction in 17. Percutaneous needle biopsy was complicated by haematuria and clot anuria in six patients. Late complications included 11 cases of stones, four of bladder malignancy and two of haemorrhagic cystitis. There was evidence that the age of the recipients (< 10 years), method of establishing urinary continuity (uretero-ureteric anastomosis) and a high dose of steroids had an independent positive effect on the incidence of urological complications. However, their development did not influence graft or patient survival. CONCLUSION: When there is meticulous attention to the technical details, renal transplantation should incur few urological complications. Early intervention with percutaneous drainage reduces morbidity and the likelihood loss of graft function. Proper and prompt management should not affect the graft and/or the patient's survival.

Live-donor renal transplantation at the Urology & Nephrology Center of Mansoura: 1976-1998.

Based on more than 1,200 living donor transplants performed at the Urology & Nephrology Center at Mansoura University between 1976-1998, we report: 1. The overall graft survival rate was 75.8% and 51.9% at 5 and 10 years, respectively, with a projected half-life of 10.7 years. 2. Three factors acted as independent variables that significantly influenced graft survival: the number of HLA mismatches, the number of acute rejection episodes and the presence of posttransplant hypertension. a. Grafts with 2 or fewer HLA-A, -B and -DR mismatches had a significantly better survival rate. b. The incidence and the number of early acute rejection episodes had a significant negative impact on graft survival. c. A significant reduction in graft survival was associated with hypertension uncontrolled by or newly developed after transplantation. 3. Bilharziasis had no impact on the outcome. 4. Despite improvements in tissue matching and immunosuppression, an important proportion of grafts is still lost following living-donor kidney transplantation. 5. Efforts must be directed to identify better regimens, which can provide adequate immunosuppression and minimal nephrotoxicity.

A magnetic device for increasing the urethral resistance to flow: an experimental study in female dogs.

OBJECTIVE: To test a new magnetic device for increasing the urethral resistance to flow in a dog model, and thus provide a potential mechanical device for the treatment of incontinence in women. MATERIALS AND METHODS: The study comprised 12 female mongrel dogs; three dogs were used to study the effect on urethral resistance of inserting a vaginal magnet (control experiment) and five were assessed in a urodynamic study. With the animals under general anaesthesia, the bladder and the urethra were exposed by a low midline incision. One magnet, embedded in a silicon layer, was placed on the anterior side of the urethra 3 cm distal to the bladder neck and fixed with a few sutures. To increase the urethral resistance as required, a second magnet was inserted into the vagina and the device activated. Urethral pressure profiles and leak-point pressures were recorded in the anaesthetized animals under resting conditions and after the urethra was compressed between the magnets. Recordings were also made after pharmacological blockade of the urethral musculature. In four additional dogs, chronic experiments were conducted to evaluate the effect of continuous compression of the urethra and the vaginal wall for 14 days. RESULTS: Urethral compression between the magnets resulted in a doubling of the maximal pressure in the proximal urethra and in a threefold increase of the leak-point pressure. After pharmacological denervation of the urethra the differences between the control pressures and those after activating the device were even greater, although not significantly so. After 2 weeks of continuous compression of the vaginal wall and the urethra between the magnets there was no detectable tissue damage. CONCLUSION: These results suggest that the magnetic device can efficiently increase urethral pressure and that prolonged compression caused no apparent damage to the urethra or vagina. It may therefore be a useful potential method of providing urinary continence in women.

Sequential bacillus Calmette-Guerin and epirubicin versus bacillus Calmette-Guerin alone for superficial bladder tumors: a randomized prospective study.

PURPOSE: This study was designed to find a new therapeutic modality that may have the same efficacy and lower toxicity than bacillus Calmette-Guerin (BCG) for the treatment of superficial transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between January 1993 and July 1997 a prospective randomized trial was conducted on 139 patients with stages pTa and pT1 bladder transitional cell carcinoma to compare the prophylactic efficacy and toxicity of sequential BCG and epirubicin (group 1) versus BCG alone (group 2). Group 1 comprised 69 patients who received alternating doses of 150 mg. BCG and 50 mg. epirubicin (1 drug at a time), while 70 patients in group 2 received 150 mg. BCG at each instillation. Treatment was continued for 6 weeks followed by 10 monthly instillations. RESULTS: Therapy was discontinued permanently in 3 group 1 and 12 group 2 patients due to severe side effects, and they were excluded from the study. Among the 124 evaluable patients (96 men and 28 women, mean age 58.2 years) mean followup was 30.4 months (range 12 to 50). Recurrence and progression rates were statistically comparable in both groups. Interval to first recurrence with or without progression was longer in group 1 than in group 2 (log rank p = 0.05). Toxicity and complications were significantly lower with sequential treatment than with BCG alone at rates of 27.3% (18 patients) and 70.7% (41), respectively (p = 0.001). CONCLUSIONS: Sequential BCG and epirubicin are comparable to BCG alone in efficacy and superior in terms of toxicity.

Orthotopic bladder substitution in women: functional evaluation.

PURPOSE: Orthotopic bladder substitution following cystectomy in women has recently been introduced at some specialized centers. Studies of such a procedure should consider the oncological and functional outcomes. We analyzed only the functional results of orthotopic bladder substitution since followup is too short (about 2 years) for a valid oncological assessment. MATERIALS AND METHODS: From October 1994 to November 1997, 60 women with a mean age of 48.3 years underwent standard radical cystectomy and orthotopic diversion (ileal W-neobladder with subserous tunnel in 47 and hemi-Kock reservoir in 13). The oncological criterion was organ confined invasive bladder cancer. RESULTS: There was no perioperative mortality. Postoperative complications included fatal pulmonary embolism in 1 woman, deep vein thrombosis in 2, prolonged ileus in 1 and fistula of the vaginal pouch in 3, which was repaired successfully. Cancer recurred in the pelvis in 2 cases and as distant metastases in 5. Of the patients 43 had been followed for a mean of 20.2 months (range 6 to 36), and 32 were continent day and night, 1 was totally incontinent, 2 had daytime stress incontinence and 6 had nighttime incontinence. Six women had difficulty emptying the pouch spontaneously with concomitant residual urine due to acute angulation between the urethra and pouch. CONCLUSIONS: Orthotopic bladder substitution after standard radical cystectomy in select women provides a satisfactory functional outcome. Failure of complete emptying seems to be due to anatomical rather than functional reasons.

Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study.

PURPOSE: We performed a prospective, randomized, controlled study to compare intravesical epirubicin and doxorubicin as adjuvant therapy after endoscopic resection of superficial bladder tumor. MATERIALS AND METHODS: We randomly allocated 253 eligible patients to 4 study arms. Seven to 14 days after transurethral bladder tumor resection instillation of the intravesical agent was instituted, including 50 and 80 mg. epirubicin in study arms 1 and 2, respectively, and 50 mg. doxorubicin in arm 3. Control arm 4 included patients who underwent transurethral bladder tumor resection alone. Instillation was repeated weekly for 8 weeks and monthly thereafter to complete 1 year of treatment. All patients were followed every 3 months by cystourethroscopy, urine cytology and deoxyribonucleic acid flow cytometry for 12 to 48 months (mean 30.1). RESULTS: Rates of recurrence were significantly lower in the chemotherapy groups than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.02). In arms 1 to 4 recurrence rates were 25, 17.6, 36.7 and 65.6%, respectively. Recurrence rates per 100 patient months were 0.83, 0.60, 1.18 and 2.73, respectively, which were significant statistically, and lower after chemotherapy in general and epirubicin in particular (p < 0.05). Mean interval to first recurrence was 16, 15.4, 18.9 and 6.3 months, respectively, with a significant difference between the chemotherapy and control groups (p < 0.05). Progression to muscle invasive disease occurred in 7 (10.9%), 3 (4.4%), 6 (10%) and 5 patients (8.2%), respectively, in arms 1 to 4 (p > 0.05). We studied the relationships among different risk factors, and patterns of recurrence and progression. For pT1 tumors recurrence rates in arms 1 to 4 were 26.3, 17.8, 39.3 and 70.9%, respectively, which were significantly lower in the chemotherapy group than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.01). Toxic and untoward side effects developed in 10 (15.6%), 16 (23.5%) and 25 (41.7%) patients in chemotherapy arms 1 to 3, respectively, with a marginal insignificant difference between low and high dose epirubicin (p = 0.3), and significantly lower toxicity rates in arms 1 and 2 than in 3 (p = 0.002). A contracted bladder developed in 2.1% of all patients who received chemotherapy. CONCLUSIONS: This study demonstrates that epirubicin has better efficacy and lower toxicity than doxorubicin when used as an intravesical agent.

Single-dose versus multiple instillations of epirubicin as prophylaxis for recurrence after transurethral resection of pTa and pT1 transitional-cell bladder tumours: a prospective, randomized controlled study.

OBJECTIVE: To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours. PATIENTS AND METHODS: In a prospective randomized and controlled study, 168 evaluable patients were assigned to three groups after transurethral resection of bladder tumour (TURBT) and histological confirmation of its superficial nature (pTa and pT1). The groups were comparable for tumour stage, grade and other tumour characteristics. In group 1, patients received a single dose of 50 mg epirubicin in 50 mL normal saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal saline 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and thereafter monthly to complete one year of treatment: group 3 (control group) received no adjuvant therapy after TURBT. The patients were assessed by cysto-urethroscopy, urine cytology and DNA flow cytometry 8 weeks after resection and then every 3 months during the first 2 years and 6 monthly thereafter during the next 2 years. Intravenous urography was performed annually and when otherwise indicated. RESULTS: The recurrence rate was significantly lower in the patients treated with epirubicin than in the control group (24, 25 and 52%, respectively; P < 0.001). In those receiving epirubicin, the rates of recurrence were statistically comparable (P = 0.9). Patients who had a large tumour burden showed slightly lower recurrence rates with single-dose epirubicin than with delayed maintenance therapy but the difference was statistically insignificant. Patients with a history of bladder tumours before treatment had lower recurrence rates with maintenance treatment than with a single dose (34.6 and 22.6% in groups 1 and 2, respectively); again this difference was statistically insignificant. Patients with grade 3 tumours showed a marginal difference in favour of maintenance therapy. The rates of progression amongst the three groups were 5.5, 3.4 and 9.3%, respectively, with no significant differences. The overall toxicity rates were comparable in the two treated groups (22 and 25%). CONCLUSION: With the possible exception of grade 3 tumours, single-dose immediate epirubicin is as effective as delayed maintenance therapy, with the advantage of being more cost-effective.