human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: INTRODUCTION Approximately 70 - 85 % of transitional bladder cell carcinomas are non-muscle-invasive . After an initial surgery , around 60 - 90 % will have a recurrence , being the highest risk period the first two years . Urothelium instability could be the main reason for recurrence in mid grade tumours , reason why a single dose of a chemotherapy after transurethral resection of the bladder ( TURB ) might be insufficient . That is why a deferred therapy in occasions associated with maintenance is recommended . PATIENTS AND METHODS A prospect i ve , controlled and r and omized study was performed . We included non-muscle-invasive mid risk bladder tumours . All patients had initially a TURB performed and were r and omized to receive a single dose of mitomycin C ( MMC ) , in the immediate postoperative period . RESULTS A total of 105 patients were included . Mean follow-up was 22 , 70 + /- 8 , 15 months . MMC was administered to 53 patients . Of these 66 , 0 % had no recurrence and 34.0 % had a non-muscle-invasive recurrence . Of the 52 patients in the non MMC group , 53.8 % had no recurrence and 44.2 % had a non-muscle-invasive recurrence and only 1 patient had a muscle-invasive progression . We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy . There was only one case of myelosuppression . DISCUSSION In mid risk non-muscle-invasive tumors , some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB . We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations Tumour cell implantation may be a factor in the aetiology of recurrent well-differentiated superficial bladder tumours . A prospect i ve trial is reported in which single dose intravesical thiotepa was administered to a group of r and omly selected patients immediately after cystodiathermy .  A control group of patients was treated by cystodiathermy alone and tumour recurrence in the 2 groups was compared . Significantly fewer patients in the thiotepa-treated group developed recurrent tumour and there was also a significantly reduced incidence of pure vault recurrence in this group . The beneficial effects of adjuvant thiotepa were apparent after 1 treatment . In this series of patients no benefit result ed from the continued use of adjuvant thiotepa once a patient developed a recurrent tumor PURPOSE We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary ( not recurrent ) superficial bladder cancer . MATERIAL S AND METHODS A total of 283 patients with stages Ta to T1 primary superficial , grade s 1 to 3 bladder cancer was r and omized into study groups 1-transurethral resection only , 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg . epirubicin .  Eligible for final analysis were 200 patients , including 66 in group 1 , 66 in group 2 and 68 in group 3 . Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence . RESULTS Group 3 had the most favorable outcome , since 45 of the 68 patients ( 66 % ) were without recurrence after 2 years compared to 24 of the 66 ( 37 % ) in group 2 and 26 of the 66 ( 40 % ) in group 1 ( log rank test p < 0.001 ) . Side effects were mostly mild and transient , and no differences were found among the groups . CONCLUSIONS A single 100 mg . dose of epirubicin given intravesically immediately after transurethral resection is safe , and significantly decreases the recurrence of primary superficial bladder cancer . A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose . The long-term effect of this treatment remains to be studied BACKGROUND Recurrence prophylaxis with intravesical gemcitabine ( GEM ) was effective and safe in patients with non-muscle-invasive bladder cancer ( NMIBC ) ; efficacy as single-shot instillation remains to be proved . OBJECTIVE To compare the efficacy of a single GEM instillation versus placebo ( PBO ) immediately after transurethral resection ( TUR ) of tumour in patients with histologically confirmed NMIBC ( pTa/pT1,G1 - 3 ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omised , PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC ( Ta/T1,G1 - 3 ) . Of 355 patients r and omised at 24 urologic centres , 328 underwent TUR and received instillation ( 92.4 % ; GEM/PBO : 166/162 ) . In case of nonmalignancy , carcinoma in situ ( CIS ) , > or = pT2 disease , or intraoperative complications , patients were discontinued . INTERVENTION We used a single , postoperative 30 - 40-min instillation of GEM ( 2000 mg/100 ml of saline ) or PBO ( 100 ml of saline ) followed by continuous bladder irrigation for > or = 20 h. A second TUR ( no instillation ) and adjuvant bacillus Calmette-Guérin ( BCG ) instillations were allowed . MEASUREMENTS Primary outcome was recurrence-free survival ( RFS ) . Secondary outcomes included type of recurrence and adverse events . To detect a difference in RFS , 191 recurrences were required ( 80 % power , log-rank-test , alpha = 0.050 ) . RESULTS AND LIMITATIONS Two hundred forty-eight patients ( 69.9 % , GEM , PBO : 124 , 124 ) had histologically confirmed pTa/pT1 G1 - 3 Gx tumour and were eligible for efficacy ( GEM : 76.6 % male ; median age : 65 yr ; PBO : 83.1 % male ; median age : 67 yr ) . Treatment groups were balanced ( pTa : 75.0 % , 71.0 % ; G1-G2 : 85.5 % , 87.9 % ; recurrent tumour : 24.2 % , 21.0 % ; BCG : 10.5 % , 16.9 % ) . After a median follow-up of 24 mo , there were only 94 recurrences and 11 deaths . The study was terminated early based on predefined decision criteria . RFS was high in both groups ( 12-mo RFS [ 95 % confidence interval ( CI ) ] : GEM : 77.7 % [ 68.8 - 84.3 ] ; PBO : 75.3 % [ 66.3 - 82.3 ] ) . There was no significant group difference ( hazard ratio [ HR ] : 0.946 [ 0.64 - 1.39 ] , log-rank test , p=0.777 ) . CONCLUSIONS In this study of NMIBC , the immediate single instillation of GEM 2000 mg/100 ml of saline after TUR was not superior to PBO in terms of RFS . Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups PURPOSE We studied whether a single instillation of epirubicin  after transurethral bladder tumor resection would influence the interval to and size of the first recurrence . MATERIAL S AND METHODS A total of 404 patients from 13 hospitals were r and omized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors . RESULTS Of 155 evaluable patients in the epirubicin group 79 ( 51.0 % ) had recurrence compared to 95 of 152 ( 62.5 % ) in the placebo group ( p = 0.04 ) . Of the recurrences 63.3 % were small ( 1 to 5 mm ) . Tumor size was unknown in 5 patients . Of 79 patients with recurrence in the epirubicin arm 33 ( 42.9 % ) vs 29 ( 31.5 % ) of 95 in the placebo arm had larger ( more than 5 mm ) first recurrences ( p = 0.12 ) . Approximately half of the patients with first recurrences were treated as out patients and the other half spent a total of 145 days in the hospital with no difference between the groups . CONCLUSIONS We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence . Furthermore , our data may indicate that only small recurrences are prevented , which could easily be fulgurated using local anesthesia at followup cystoscopy . The benefit of single instillations can be question ed if this finding is confirmed by others OBJECTIVE To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours . PATIENTS AND METHODS In a prospect i ve r and omized 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 A total of 431 eligible patients with solitary , primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a r and omized multicenter trial to compare a single intravesical instillation of 80 mg . epirubicin with water given immediately after resection , with respect to the disease-free interval and recurrence rate . The interval to initial recurrence was significantly better in favor of the epirubicin group . After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined . Toxicity was mainly restricted to bladder irritation in plus or minus 10 % of the cases . Pathology review brought considerable changes in T category from stages T1 to Ta ( 53 % ) . Changes in grade were less pronounced but nevertheless important The influence of the instillation of thiotepa or doxorubicin hydrochloride into the bladder at the end of transurethral surgical treatment on the recurrence of bladder cancer  was evaluated . We studied in a r and omized , double-blind , controlled fashion 89 patients with transitional cell epithelioma ( carcinoma in situ or papillary carcinoma ) whose tumors were considered to have been completely removed . Of these patients 28 ( the control group ) received a placebo ( sterile water ) , 30 received thiotepa and 31 received doxorubicin . By 3 to 4 months postoperatively 71 per cent of the control group , and 30 and 32 per cent , respectively , of the patients treated with thiotepa and doxorubicin had recurrences ( p less than 0.01 ) . Additional treatment during the followup interval was ineffective in all 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: INTRODUCTION Approximately 70 - 85 % of transitional bladder cell carcinomas are non-muscle-invasive . After an initial surgery , around 60 - 90 % will have a recurrence , being the highest risk period the first two years . Urothelium instability could be the main reason for recurrence in mid grade tumours , reason why a single dose of a chemotherapy after transurethral resection of the bladder ( TURB ) might be insufficient . That is why a deferred therapy in occasions associated with maintenance is recommended . PATIENTS AND METHODS A prospect i ve , controlled and r and omized study was performed . We included non-muscle-invasive mid risk bladder tumours . All patients had initially a TURB performed and were r and omized to receive a single dose of mitomycin C ( MMC ) , in the immediate postoperative period . RESULTS A total of 105 patients were included . Mean follow-up was 22 , 70 + /- 8 , 15 months . MMC was administered to 53 patients . Of these 66 , 0 % had no recurrence and 34.0 % had a non-muscle-invasive recurrence . Of the 52 patients in the non MMC group , 53.8 % had no recurrence and 44.2 % had a non-muscle-invasive recurrence and only 1 patient had a muscle-invasive progression . We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy . There was only one case of myelosuppression . DISCUSSION In mid risk non-muscle-invasive tumors , some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB . We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations Tumour cell implantation may be a factor in the aetiology of recurrent well-differentiated superficial bladder tumours . A prospect i ve trial is reported in which single dose intravesical thiotepa was administered to a group of r and omly selected patients immediately after cystodiathermy .  A control group of patients was treated by cystodiathermy alone and tumour recurrence in the 2 groups was compared . Significantly fewer patients in the thiotepa-treated group developed recurrent tumour and there was also a significantly reduced incidence of pure vault recurrence in this group . The beneficial effects of adjuvant thiotepa were apparent after 1 treatment . In this series of patients no benefit result ed from the continued use of adjuvant thiotepa once a patient developed a recurrent tumor PURPOSE We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary ( not recurrent ) superficial bladder cancer . MATERIAL S AND METHODS A total of 283 patients with stages Ta to T1 primary superficial , grade s 1 to 3 bladder cancer was r and omized into study groups 1-transurethral resection only , 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg . epirubicin .  Eligible for final analysis were 200 patients , including 66 in group 1 , 66 in group 2 and 68 in group 3 . Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence . RESULTS Group 3 had the most favorable outcome , since 45 of the 68 patients ( 66 % ) were without recurrence after 2 years compared to 24 of the 66 ( 37 % ) in group 2 and 26 of the 66 ( 40 % ) in group 1 ( log rank test p < 0.001 ) . Side effects were mostly mild and transient , and no differences were found among the groups . CONCLUSIONS A single 100 mg . dose of epirubicin given intravesically immediately after transurethral resection is safe , and significantly decreases the recurrence of primary superficial bladder cancer . A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose . The long-term effect of this treatment remains to be studied BACKGROUND Recurrence prophylaxis with intravesical gemcitabine ( GEM ) was effective and safe in patients with non-muscle-invasive bladder cancer ( NMIBC ) ; efficacy as single-shot instillation remains to be proved . OBJECTIVE To compare the efficacy of a single GEM instillation versus placebo ( PBO ) immediately after transurethral resection ( TUR ) of tumour in patients with histologically confirmed NMIBC ( pTa/pT1,G1 - 3 ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omised , PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC ( Ta/T1,G1 - 3 ) . Of 355 patients r and omised at 24 urologic centres , 328 underwent TUR and received instillation ( 92.4 % ; GEM/PBO : 166/162 ) . In case of nonmalignancy , carcinoma in situ ( CIS ) , > or = pT2 disease , or intraoperative complications , patients were discontinued . INTERVENTION We used a single , postoperative 30 - 40-min instillation of GEM ( 2000 mg/100 ml of saline ) or PBO ( 100 ml of saline ) followed by continuous bladder irrigation for > or = 20 h. A second TUR ( no instillation ) and adjuvant bacillus Calmette-Guérin ( BCG ) instillations were allowed . MEASUREMENTS Primary outcome was recurrence-free survival ( RFS ) . Secondary outcomes included type of recurrence and adverse events . To detect a difference in RFS , 191 recurrences were required ( 80 % power , log-rank-test , alpha = 0.050 ) . RESULTS AND LIMITATIONS Two hundred forty-eight patients ( 69.9 % , GEM , PBO : 124 , 124 ) had histologically confirmed pTa/pT1 G1 - 3 Gx tumour and were eligible for efficacy ( GEM : 76.6 % male ; median age : 65 yr ; PBO : 83.1 % male ; median age : 67 yr ) . Treatment groups were balanced ( pTa : 75.0 % , 71.0 % ; G1-G2 : 85.5 % , 87.9 % ; recurrent tumour : 24.2 % , 21.0 % ; BCG : 10.5 % , 16.9 % ) . After a median follow-up of 24 mo , there were only 94 recurrences and 11 deaths . The study was terminated early based on predefined decision criteria . RFS was high in both groups ( 12-mo RFS [ 95 % confidence interval ( CI ) ] : GEM : 77.7 % [ 68.8 - 84.3 ] ; PBO : 75.3 % [ 66.3 - 82.3 ] ) . There was no significant group difference ( hazard ratio [ HR ] : 0.946 [ 0.64 - 1.39 ] , log-rank test , p=0.777 ) . CONCLUSIONS In this study of NMIBC , the immediate single instillation of GEM 2000 mg/100 ml of saline after TUR was not superior to PBO in terms of RFS . Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups PURPOSE We studied whether a single instillation of epirubicin  after transurethral bladder tumor resection would influence the interval to and size of the first recurrence . MATERIAL S AND METHODS A total of 404 patients from 13 hospitals were r and omized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors . RESULTS Of 155 evaluable patients in the epirubicin group 79 ( 51.0 % ) had recurrence compared to 95 of 152 ( 62.5 % ) in the placebo group ( p = 0.04 ) . Of the recurrences 63.3 % were small ( 1 to 5 mm ) . Tumor size was unknown in 5 patients . Of 79 patients with recurrence in the epirubicin arm 33 ( 42.9 % ) vs 29 ( 31.5 % ) of 95 in the placebo arm had larger ( more than 5 mm ) first recurrences ( p = 0.12 ) . Approximately half of the patients with first recurrences were treated as out patients and the other half spent a total of 145 days in the hospital with no difference between the groups . CONCLUSIONS We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence . Furthermore , our data may indicate that only small recurrences are prevented , which could easily be fulgurated using local anesthesia at followup cystoscopy . The benefit of single instillations can be question ed if this finding is confirmed by others OBJECTIVE To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours . PATIENTS AND METHODS In a prospect i ve r and omized 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 A total of 431 eligible patients with solitary , primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a r and omized multicenter trial to compare a single intravesical instillation of 80 mg . epirubicin with water given immediately after resection , with respect to the disease-free interval and recurrence rate . The interval to initial recurrence was significantly better in favor of the epirubicin group . After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined . Toxicity was mainly restricted to bladder irritation in plus or minus 10 % of the cases . Pathology review brought considerable changes in T category from stages T1 to Ta ( 53 % ) . Changes in grade were less pronounced but nevertheless important The influence of the instillation of thiotepa or doxorubicin hydrochloride into the bladder at the end of transurethral surgical treatment on the recurrence of bladder cancer  was evaluated . We studied in a r and omized , double-blind , controlled fashion 89 patients with transitional cell epithelioma ( carcinoma in situ or papillary carcinoma ) whose tumors were considered to have been completely removed . Of these patients 28 ( the control group ) received a placebo ( sterile water ) , 30 received thiotepa and 31 received doxorubicin . By 3 to 4 months postoperatively 71 per cent of the control group , and 30 and 32 per cent , respectively , of the patients treated with thiotepa and doxorubicin had recurrences ( p less than 0.01 ) . Additional treatment during the followup interval was ineffective in all 
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