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: AIMS To assess the effect of local hyperthermia on the systemic absorption of  mitomycin C ( MMC ) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder , and to establish the likely safety of this procedure . METHODS Group 1 ( n = 12 ) received 20 mg intravesical MMC plus local hyperthermia , group 2 ( n = 13 )  20 mg MMC alone , group 3 ( n = 16 )  40 mg MMC plus local hyperthermia and group 4 ( n = 10 ) 40 mg MMC alone . Patients in groups 1 , 2 , and 4 underwent post-tumour resection adjuvant treatment , whereas those in group 3 still had tumour present and were treated to eradicate it . Intravesical instillation lasted 60 min , with the solution ( 50 ml ) being replaced after the first 30 min . Blood sample s were taken before , and every 15 min during instillation . MMC concentrations in plasma and in urine were determined by h.p.l.c . RESULTS The highest MMC plasma concentration ( 67.9 ng ml(-1 ) ) occurred in a patient in group 3 . This value was well below the threshold concentration ( 400 ng ml-1 ) for myelosuppression . Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30 , 45 and 60 min compared with chemotherapy alone ( Group 1 vs 2 , P < or = 0.008 ) . Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered . Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients . CONCLUSIONS Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer . In the doses used , plasma MMC concentrations were always more than six times lower than those shown to cause toxicity For some time hyperthermia , alone or in combination with radiotherapy or chemotherapy , has proved to be a promising method for treating several kinds of solid tumors . After intensive laboratory investigations a new device , based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinical ly tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder . The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity . Endoscopic and histological evaluations proved that combined  local hyperthermia and chemotherapy can induce necrosis of transitional tumors . The overall response rate was 90.8 % , with 70.4 % complete and 20.4 % partial , leaving 4 patients ( 9.2 % ) nonrespondent . Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment . Further multicentric studies have been initiated PURPOSE To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment , after complete transurethral resection ( TURB ) of superficial transitional cell carcinoma ( TCC ) of the bladder . PATIENTS AND METHODS The study was design ed as a prospect i ve , multicentric , r and omized trial . Eighty-three patients suffering from primary or recurrent superficial ( Ta-T1 ) TCC of the bladder , after a complete TURB , were r and omly assigned to receive intravesical instillations of mitomycin C ( MMC ) alone , for 41 patients , and MMC in combination with local microwave-induced hyperthermia , for 42 patients . For the combined approach , a new system , Synergo101 - 1 ( Medical Enterprises , Amsterdam , the Netherl and s ) was used . The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence . The safety evaluation end points included subjective and objective side effects and clinical complications . For the efficacy end point , Kaplan-Meier analysis was employed , with the log-rank test for significance . Minimum follow-up time was 24 months . RESULTS Of the 83 r and omly assigned patients , 75 completed the study according to the protocol and had valid cystoscopy results . Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy . Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group . CONCLUSION In our series , endovesical thermochemotherapy appears to be more effective than st and ard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up , despite an increased but acceptable local toxicity BACKGROUND The purpose of this study was to evaluate the efficacy of combined local hyperthermia and intravesical mitomycin-C ( MMC ) in a selected group of patients with intermediate or high-risk recurrent transitional cell carcinoma ( TCC ) of bladder . PATIENTS AND METHODS Forty-seven patients with multiple or recurrent Ta or T1 TCC of the bladder were treated with intravesical MMC and local hyperthermia of the bladder wall . Patients were treated with either a prophylactic protocol ( 40 mg MMC ) after complete transurethral resection of all tumours or with an ablative protocol ( 80 mg MMC ) in patients with viable tumours . RESULTS Thirty-two patients were eligible for analysis . The prophylactic protocol was administered to 22 patients . After a mean follow-up of 289 days , 20 patients ( 91 % ) were recurrence free . Two patients ( 9 % ) had tumour recurrence after a mean period of 431 days . The ablative protocol was administered to 10 patients . Complete tumour ablation was achieved in eight patients ( 80 % ) after a mean follow up of 104.5 days . CONCLUSIONS Our efficacy and safety results confirm those reported in previously published studies , suggesting the promising value of this combined treatment modality for both prophylactic and ablative patients . The ablative protocol offers an alternative therapy for a selected patient population for whom no other treatment option exists PURPOSE The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study . MATERIAL S AND METHODS A total of 19 patients with multifocal , superficial grade s 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach . Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice . Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system , based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia . When possible , after treatment patients underwent transurethral resection of residual tumors and all suspicious areas . RESULTS After treatment transurethral resection appeared to be feasible and curative in 16 patients ( 84 % ) . Histological study revealed complete and partial responses in 9 ( 47 % ) and 7 ( 37 % ) cases , respectively . Due to extensive residual tumors radical cystectomy was performed in 3 patients ( 16 % ) . At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved . CONCLUSIONS Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible , safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed PURPOSE We evaluated the effectiveness of local bladder hyperthermia and intravesical chemotherapy compared to intravesical chemotherapy alone in the treatment of superficial transitional cell carcinoma . MATERIAL S AND METHODS A new system design ed to deliver simultaneously local bladder hyperthermia and intravesical chemotherapy has been developed at our institute . The system consists of a computerized 915 MHz . microwave source that directly heats the bladder walls ( within a temperature range of 42.5 to 45.5C ) using a transurethral catheter . From February 1989 to December 1993 , 52 patients 44 to 81 years old ( mean age 64.3 ) with superficial stages Ta to T1 , grade s 1 to 3 transitional cell carcinoma of the bladder were selected for neoadjuvant intracavitary treatment .  Tumors were left intact as marker lesions . Of the patients 29 were r and omly assigned to receive combined neoadjuvant intravesical chemotherapy and local hyperthermia ( group 1 ) , while 23 received intravesical chemotherapy alone ( group 2 ) . The treatment protocol included multiple sessions performed on an outpatient basis . Mitomycin C ( 40 mg . in 50 cc distilled water ) was used for intravesical chemotherapy in both groups . All patients underwent transurethral resection of residual tumors and of all suspicious areas 7 to 10 days after completion of treatment . Only a complete response was considered for statistical analysis . RESULTS A pathological complete response was documented in 19 cases ( 66 % ) in group 1 and 5 ( 22 % ) in group 2 ( chi-square p < 0.01 ) . CONCLUSIONS According to these preliminary data , microwave induced hyperthermia combined with local intravesical chemotherapy seems to be a feasible , safe and promising approach for neoadjuvant and minimally invasive treatment of superficial bladder cancer OBJECTIVES To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high- grade ( G3 ) superficial bladder cancer . METHODS Patients with G3 bladder tumors ( Stage Ta or T1 ) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall . The patients were treated with either a prophylactic protocol ( 40 mg mitomycin-C ) after complete transurethral resection of all tumors or with an ablative protocol ( 80 mg mitomycin-C ) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ . RESULTS Combined chemo-thermotherapy was administered to 52 patients with high- grade superficial bladder cancer ( 40 patients with Stage T1 tumor , 11 with Ta , and 3 with concomitant or isolated carcinoma in situ ) . At a median follow-up of 15.2 months ( mean 23 , range 6 to 90 ) , no stage progression to T2 or disease-related mortality had occurred . The bladder preservation rate was 86.5 % . The prophylactic protocol was administered to 24 patients . After a mean follow-up of 35.3 months , 15 patients ( 62.5 % ) were recurrence free . The bladder preservation rate was 95.8 % . The ablative protocol was administered to 28 patients . Complete ablation of the tumor was accomplished in 21 patients ( 75 % ) . After a mean follow-up of 20 months , 80.9 % of these patients were recurrence free . The bladder preservation rate for the ablative group was 78.6 % . CONCLUSIONS Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer . Ablation of high- grade bladder tumors is feasible , achieving a complete response in about three quarters of the patients Objective : To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas . To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to st and ard intravesical chemotherapy . Methods : Eighty patients suffering from single , recurrent , low – stage , low– grade superficial bladder tumor entered a prospect i ve nonr and omized study . Thirty – six of them were treated by means of mitomycin C instillation as a st and ard procedure . In 29 patients mitomycin C solution was administered in combination with local microwave – induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure . The treatment was scheduled as a short term neo – adjuvant regimen prior to transurethral resection . Feasibility and safety of the different procedures were evaluated on an out patients basis . The local toxicity induced by different approaches was defined and compared using a subjective question naire . Results : Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe . Local toxicity induced by thermo – 
    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: AIMS To assess the effect of local hyperthermia on the systemic absorption of  mitomycin C ( MMC ) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder , and to establish the likely safety of this procedure . METHODS Group 1 ( n = 12 ) received 20 mg intravesical MMC plus local hyperthermia , group 2 ( n = 13 )  20 mg MMC alone , group 3 ( n = 16 )  40 mg MMC plus local hyperthermia and group 4 ( n = 10 ) 40 mg MMC alone . Patients in groups 1 , 2 , and 4 underwent post-tumour resection adjuvant treatment , whereas those in group 3 still had tumour present and were treated to eradicate it . Intravesical instillation lasted 60 min , with the solution ( 50 ml ) being replaced after the first 30 min . Blood sample s were taken before , and every 15 min during instillation . MMC concentrations in plasma and in urine were determined by h.p.l.c . RESULTS The highest MMC plasma concentration ( 67.9 ng ml(-1 ) ) occurred in a patient in group 3 . This value was well below the threshold concentration ( 400 ng ml-1 ) for myelosuppression . Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30 , 45 and 60 min compared with chemotherapy alone ( Group 1 vs 2 , P < or = 0.008 ) . Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered . Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients . CONCLUSIONS Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer . In the doses used , plasma MMC concentrations were always more than six times lower than those shown to cause toxicity For some time hyperthermia , alone or in combination with radiotherapy or chemotherapy , has proved to be a promising method for treating several kinds of solid tumors . After intensive laboratory investigations a new device , based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinical ly tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder . The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity . Endoscopic and histological evaluations proved that combined  local hyperthermia and chemotherapy can induce necrosis of transitional tumors . The overall response rate was 90.8 % , with 70.4 % complete and 20.4 % partial , leaving 4 patients ( 9.2 % ) nonrespondent . Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment . Further multicentric studies have been initiated PURPOSE To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment , after complete transurethral resection ( TURB ) of superficial transitional cell carcinoma ( TCC ) of the bladder . PATIENTS AND METHODS The study was design ed as a prospect i ve , multicentric , r and omized trial . Eighty-three patients suffering from primary or recurrent superficial ( Ta-T1 ) TCC of the bladder , after a complete TURB , were r and omly assigned to receive intravesical instillations of mitomycin C ( MMC ) alone , for 41 patients , and MMC in combination with local microwave-induced hyperthermia , for 42 patients . For the combined approach , a new system , Synergo101 - 1 ( Medical Enterprises , Amsterdam , the Netherl and s ) was used . The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence . The safety evaluation end points included subjective and objective side effects and clinical complications . For the efficacy end point , Kaplan-Meier analysis was employed , with the log-rank test for significance . Minimum follow-up time was 24 months . RESULTS Of the 83 r and omly assigned patients , 75 completed the study according to the protocol and had valid cystoscopy results . Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy . Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group . CONCLUSION In our series , endovesical thermochemotherapy appears to be more effective than st and ard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up , despite an increased but acceptable local toxicity BACKGROUND The purpose of this study was to evaluate the efficacy of combined local hyperthermia and intravesical mitomycin-C ( MMC ) in a selected group of patients with intermediate or high-risk recurrent transitional cell carcinoma ( TCC ) of bladder . PATIENTS AND METHODS Forty-seven patients with multiple or recurrent Ta or T1 TCC of the bladder were treated with intravesical MMC and local hyperthermia of the bladder wall . Patients were treated with either a prophylactic protocol ( 40 mg MMC ) after complete transurethral resection of all tumours or with an ablative protocol ( 80 mg MMC ) in patients with viable tumours . RESULTS Thirty-two patients were eligible for analysis . The prophylactic protocol was administered to 22 patients . After a mean follow-up of 289 days , 20 patients ( 91 % ) were recurrence free . Two patients ( 9 % ) had tumour recurrence after a mean period of 431 days . The ablative protocol was administered to 10 patients . Complete tumour ablation was achieved in eight patients ( 80 % ) after a mean follow up of 104.5 days . CONCLUSIONS Our efficacy and safety results confirm those reported in previously published studies , suggesting the promising value of this combined treatment modality for both prophylactic and ablative patients . The ablative protocol offers an alternative therapy for a selected patient population for whom no other treatment option exists PURPOSE The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study . MATERIAL S AND METHODS A total of 19 patients with multifocal , superficial grade s 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach . Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice . Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system , based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia . When possible , after treatment patients underwent transurethral resection of residual tumors and all suspicious areas . RESULTS After treatment transurethral resection appeared to be feasible and curative in 16 patients ( 84 % ) . Histological study revealed complete and partial responses in 9 ( 47 % ) and 7 ( 37 % ) cases , respectively . Due to extensive residual tumors radical cystectomy was performed in 3 patients ( 16 % ) . At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved . CONCLUSIONS Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible , safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed PURPOSE We evaluated the effectiveness of local bladder hyperthermia and intravesical chemotherapy compared to intravesical chemotherapy alone in the treatment of superficial transitional cell carcinoma . MATERIAL S AND METHODS A new system design ed to deliver simultaneously local bladder hyperthermia and intravesical chemotherapy has been developed at our institute . The system consists of a computerized 915 MHz . microwave source that directly heats the bladder walls ( within a temperature range of 42.5 to 45.5C ) using a transurethral catheter . From February 1989 to December 1993 , 52 patients 44 to 81 years old ( mean age 64.3 ) with superficial stages Ta to T1 , grade s 1 to 3 transitional cell carcinoma of the bladder were selected for neoadjuvant intracavitary treatment .  Tumors were left intact as marker lesions . Of the patients 29 were r and omly assigned to receive combined neoadjuvant intravesical chemotherapy and local hyperthermia ( group 1 ) , while 23 received intravesical chemotherapy alone ( group 2 ) . The treatment protocol included multiple sessions performed on an outpatient basis . Mitomycin C ( 40 mg . in 50 cc distilled water ) was used for intravesical chemotherapy in both groups . All patients underwent transurethral resection of residual tumors and of all suspicious areas 7 to 10 days after completion of treatment . Only a complete response was considered for statistical analysis . RESULTS A pathological complete response was documented in 19 cases ( 66 % ) in group 1 and 5 ( 22 % ) in group 2 ( chi-square p < 0.01 ) . CONCLUSIONS According to these preliminary data , microwave induced hyperthermia combined with local intravesical chemotherapy seems to be a feasible , safe and promising approach for neoadjuvant and minimally invasive treatment of superficial bladder cancer OBJECTIVES To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high- grade ( G3 ) superficial bladder cancer . METHODS Patients with G3 bladder tumors ( Stage Ta or T1 ) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall . The patients were treated with either a prophylactic protocol ( 40 mg mitomycin-C ) after complete transurethral resection of all tumors or with an ablative protocol ( 80 mg mitomycin-C ) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ . RESULTS Combined chemo-thermotherapy was administered to 52 patients with high- grade superficial bladder cancer ( 40 patients with Stage T1 tumor , 11 with Ta , and 3 with concomitant or isolated carcinoma in situ ) . At a median follow-up of 15.2 months ( mean 23 , range 6 to 90 ) , no stage progression to T2 or disease-related mortality had occurred . The bladder preservation rate was 86.5 % . The prophylactic protocol was administered to 24 patients . After a mean follow-up of 35.3 months , 15 patients ( 62.5 % ) were recurrence free . The bladder preservation rate was 95.8 % . The ablative protocol was administered to 28 patients . Complete ablation of the tumor was accomplished in 21 patients ( 75 % ) . After a mean follow-up of 20 months , 80.9 % of these patients were recurrence free . The bladder preservation rate for the ablative group was 78.6 % . CONCLUSIONS Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer . Ablation of high- grade bladder tumors is feasible , achieving a complete response in about three quarters of the patients Objective : To assess the feasibility and safety of two novel methods for intravesical chemotherapy administration in patients suffering from superficial bladder carcinomas . To draw preliminary considerations concerning the ablative effect on marker lesion using novel approaches compared to st and ard intravesical chemotherapy . Methods : Eighty patients suffering from single , recurrent , low – stage , low– grade superficial bladder tumor entered a prospect i ve nonr and omized study . Thirty – six of them were treated by means of mitomycin C instillation as a st and ard procedure . In 29 patients mitomycin C solution was administered in combination with local microwave – induced hyperthermia and in 15 patients the mitomycin C solution was administered according to the electromotive drug procedure . The treatment was scheduled as a short term neo – adjuvant regimen prior to transurethral resection . Feasibility and safety of the different procedures were evaluated on an out patients basis . The local toxicity induced by different approaches was defined and compared using a subjective question naire . Results : Both intravesical chemotherapy administered in combination with hyperthermia and according to the electromotive drug technique appeared to be feasible and safe . Local toxicity induced by thermo – 
    Output:
    