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: BACKGROUND Besides clinical tumour size , other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery ( NSS ) . OBJECTIVE To propose an original , st and ardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications result ing from the surgery . DESIGN , SETTING , AND PARTICIPANTS We enrolled prospect ively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008 . INTERVENTION Open partial nephrectomy without vessel clamping . MEASUREMENTS All tumours were classified by integrating size with the following anatomical features : anterior or posterior face , longitudinal , and rim tumour location ; tumour relationships with renal sinus or urinary collecting system ; and percentage of tumour deepening into the kidney . We generated an algorithm evaluating each anatomical parameter and tumour size ( the preoperative aspects and dimensions used for an anatomical [ PADUA ] score ) to predict the risk of complications . RESULTS AND LIMITATIONS Overall rates of complication were significantly correlated to all the evaluated anatomical aspects , excluding clinical size and anterior or posterior location of the tumour . By multivariate analysis , PADUA scores were independent predictors of the occurrence of any grade complications ( hazard ratio [ HR ] for score 8 - 9 vs 6 - 7 : 14.535 ; HR for score ≥10 vs 6 - 7 : 30.641 ) . Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients . Further external validation of the PADUA score is needed . CONCLUSIONS The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS . The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help research ers evaluate the real comparability among patients undergoing NSS with different surgical approaches BACKGROUND The evidence for meat intake and renal cell carcinoma ( RCC ) risk is inconsistent . Mutagens related to meat cooking and processing , and variation by RCC subtype may be important to consider . OBJECTIVE In a large US cohort , we prospect ively investigated intake of meat and meat-related compounds in relation to risk of RCC , as well as clear cell and papillary RCC histologic subtypes . DESIGN Study participants ( 492,186 ) completed a detailed dietary assessment linked to a data base of heme iron , heterocyclic amines ( HCA ) , polycyclic aromatic hydrocarbons ( PAHs ) , nitrate , and nitrite concentrations in cooked and processed meats . Over 9 ( mean ) y of follow-up , we identified 1814 cases of RCC ( 498 clear cell and 115 papillary adenocarcinomas ) .  HRs and 95 % CIs were estimated within quintiles by using multivariable Cox proportional hazards regression . RESULTS Red meat intake [ 62.7 g ( quintile 5 ) compared with 9.8 g ( quintile 1 ) per 1000 kcal ( median ) ] was associated with a tendency toward an increased risk of RCC [ HR : 1.19 ; 95 % CI : 1.01 , 1.40 ; P-trend = 0.06 ] and a 2-fold increased risk of papillary RCC [ P-trend = 0.002 ] . Intakes of benzo(a)pyrene ( BaP ) , a marker of PAHs , and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine ( PhIP ) , an HCA , were associated with a significant 20 - 30 % elevated risk of RCC and a 2-fold increased risk of papillary RCC . No associations were observed for the clear cell subtype . CONCLUSIONS Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP . Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant . This study is registered at clinical trials.gov as NCT00340015 BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment BACKGROUND Currently two pretreatment prognostic models with limited accuracy ( 65 - 67 % ) can be used to predict survival in patients with localized renal cell carcinoma ( RCC ) . OBJECTIVE We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC . DESIGN , SETTING , AND PARTICIPANTS The data originated from a series of prospect ively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006 . Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers . MEASUREMENTS The probability of RCC-specific mortality was modeled using Cox regression . The significance of the predictors was confirmed using competing risks analyses , which account for mortality from other causes . RESULTS AND LIMITATIONS Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts , respectively . The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4 % at 5 yr after nephrectomy and 68.3 % at 10 yr after nephrectomy . All variables except gender achieved independent predictor status . In the external validation cohort the nomogram predictions were 88.1 % accurate at 1 yr , 86.8 % accurate at 2 yr , 86.8 % accurate at 5 yr , and 84.2 % accurate at 10 yr . CONCLUSIONS Our model substantially exceeds the accuracy of the existing pretreatment models . Consequently , the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC PURPOSE We report on a prospect i ve r and omized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy for renal tumor . MATERIAL S AND METHODS Between June 1999 and June 2001 , 102 consecutive eligible patients with a computerized tomography identified renal tumor were prospect ively r and omized to undergo either a transperitoneal ( group 1 , 50 patients ) or retroperitoneal ( group 2 , 52 patients ) laparoscopic radical nephrectomy with intact specimen extraction . Exclusion criteria for the study included body mass index greater than 35 or a history of prior major abdominal surgery in the quadrant of interest . Both groups were matched regarding age ( 63 versus 65 years , p = 0.69 ) , BMI ( 29 versus 28 , p = 0.89 ) , American Society of Anesthesiologists class ( 2.7 versus 2.8 , p = 0.37 ) , laterality ( right side 46 % versus 48 % , p = 0.85 ) and mean tumor size ( 5.3 versus 5.0 cm , p = 0.73 ) . RESULTS All 102 procedures were technically successful without the need for open conversion . Compared to the transperitoneal approach , the retroperitoneal approach was associated with a shorter time to renal artery control ( 91 versus 34 minutes , p < 0.0001 ) , shorter time to renal vein control ( 98 versus 45 minutes , p < 0.0001 ) and shorter total operative time ( 207 versus 150 minutes , p = 0.001 ) . However , the transperitoneal and retroperitoneal approaches were similar in terms of estimated blood loss ( 180 versus 242 cc , p = 0.13 ) , hospital stay ( 43 versus 45 hours , p = 0.55 ) , intraoperative complications ( 10 % versus 7.7 % , p = 0.30 ) , postoperative complications ( 20 % versus 13.5 % , p = 0.14 ) and postoperative analgesia requirements ( 27 versus 26 mg MSO4 equivalent p = 0.13 ) . Pathology revealed renal cell carcinoma in 84 % and 75 % of cases , respectively , with no positive surgical margin in any case . CONCLUSIONS Laparoscopic radical nephrectomy can be performed efficiently and effectively with the transperitoneal or the retroperitoneal approach . While renal hilar control and total operative time may be quicker with retroperitoneoscopy , the approaches are similar in terms of other patient outcomes evaluated BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability .  Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) PURPOSE Laparoscopic partial nephrectomy is an increasingly performed , minimally invasive alternative to open partial nephrectomy . We compared early postoperative outcomes in 1,800 patients undergoing open partial nephrectomy by experienced surgeons with the initial experience with laparoscopic partial nephrectomy in patients with a single renal tumor 7 cm or less . MATERIAL S AND METHODS Data on 1,800 consecutive open or laparoscopic partial nephrectomies  were collected prospect ively 
    Output:
    
agent
The 2014 guideline has been up date d by a multidisciplinary panel using the highest method ological st and ards , and provides the best and most reliable contemporary evidence base for RCC management .
***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: BACKGROUND Besides clinical tumour size , other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery ( NSS ) . OBJECTIVE To propose an original , st and ardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications result ing from the surgery . DESIGN , SETTING , AND PARTICIPANTS We enrolled prospect ively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008 . INTERVENTION Open partial nephrectomy without vessel clamping . MEASUREMENTS All tumours were classified by integrating size with the following anatomical features : anterior or posterior face , longitudinal , and rim tumour location ; tumour relationships with renal sinus or urinary collecting system ; and percentage of tumour deepening into the kidney . We generated an algorithm evaluating each anatomical parameter and tumour size ( the preoperative aspects and dimensions used for an anatomical [ PADUA ] score ) to predict the risk of complications . RESULTS AND LIMITATIONS Overall rates of complication were significantly correlated to all the evaluated anatomical aspects , excluding clinical size and anterior or posterior location of the tumour . By multivariate analysis , PADUA scores were independent predictors of the occurrence of any grade complications ( hazard ratio [ HR ] for score 8 - 9 vs 6 - 7 : 14.535 ; HR for score ≥10 vs 6 - 7 : 30.641 ) . Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients . Further external validation of the PADUA score is needed . CONCLUSIONS The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS . The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help research ers evaluate the real comparability among patients undergoing NSS with different surgical approaches BACKGROUND The evidence for meat intake and renal cell carcinoma ( RCC ) risk is inconsistent . Mutagens related to meat cooking and processing , and variation by RCC subtype may be important to consider . OBJECTIVE In a large US cohort , we prospect ively investigated intake of meat and meat-related compounds in relation to risk of RCC , as well as clear cell and papillary RCC histologic subtypes . DESIGN Study participants ( 492,186 ) completed a detailed dietary assessment linked to a data base of heme iron , heterocyclic amines ( HCA ) , polycyclic aromatic hydrocarbons ( PAHs ) , nitrate , and nitrite concentrations in cooked and processed meats . Over 9 ( mean ) y of follow-up , we identified 1814 cases of RCC ( 498 clear cell and 115 papillary adenocarcinomas ) .  HRs and 95 % CIs were estimated within quintiles by using multivariable Cox proportional hazards regression . RESULTS Red meat intake [ 62.7 g ( quintile 5 ) compared with 9.8 g ( quintile 1 ) per 1000 kcal ( median ) ] was associated with a tendency toward an increased risk of RCC [ HR : 1.19 ; 95 % CI : 1.01 , 1.40 ; P-trend = 0.06 ] and a 2-fold increased risk of papillary RCC [ P-trend = 0.002 ] . Intakes of benzo(a)pyrene ( BaP ) , a marker of PAHs , and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine ( PhIP ) , an HCA , were associated with a significant 20 - 30 % elevated risk of RCC and a 2-fold increased risk of papillary RCC . No associations were observed for the clear cell subtype . CONCLUSIONS Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP . Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant . This study is registered at clinical trials.gov as NCT00340015 BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment BACKGROUND Currently two pretreatment prognostic models with limited accuracy ( 65 - 67 % ) can be used to predict survival in patients with localized renal cell carcinoma ( RCC ) . OBJECTIVE We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC . DESIGN , SETTING , AND PARTICIPANTS The data originated from a series of prospect ively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006 . Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers . MEASUREMENTS The probability of RCC-specific mortality was modeled using Cox regression . The significance of the predictors was confirmed using competing risks analyses , which account for mortality from other causes . RESULTS AND LIMITATIONS Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts , respectively . The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4 % at 5 yr after nephrectomy and 68.3 % at 10 yr after nephrectomy . All variables except gender achieved independent predictor status . In the external validation cohort the nomogram predictions were 88.1 % accurate at 1 yr , 86.8 % accurate at 2 yr , 86.8 % accurate at 5 yr , and 84.2 % accurate at 10 yr . CONCLUSIONS Our model substantially exceeds the accuracy of the existing pretreatment models . Consequently , the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC PURPOSE We report on a prospect i ve r and omized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy for renal tumor . MATERIAL S AND METHODS Between June 1999 and June 2001 , 102 consecutive eligible patients with a computerized tomography identified renal tumor were prospect ively r and omized to undergo either a transperitoneal ( group 1 , 50 patients ) or retroperitoneal ( group 2 , 52 patients ) laparoscopic radical nephrectomy with intact specimen extraction . Exclusion criteria for the study included body mass index greater than 35 or a history of prior major abdominal surgery in the quadrant of interest . Both groups were matched regarding age ( 63 versus 65 years , p = 0.69 ) , BMI ( 29 versus 28 , p = 0.89 ) , American Society of Anesthesiologists class ( 2.7 versus 2.8 , p = 0.37 ) , laterality ( right side 46 % versus 48 % , p = 0.85 ) and mean tumor size ( 5.3 versus 5.0 cm , p = 0.73 ) . RESULTS All 102 procedures were technically successful without the need for open conversion . Compared to the transperitoneal approach , the retroperitoneal approach was associated with a shorter time to renal artery control ( 91 versus 34 minutes , p < 0.0001 ) , shorter time to renal vein control ( 98 versus 45 minutes , p < 0.0001 ) and shorter total operative time ( 207 versus 150 minutes , p = 0.001 ) . However , the transperitoneal and retroperitoneal approaches were similar in terms of estimated blood loss ( 180 versus 242 cc , p = 0.13 ) , hospital stay ( 43 versus 45 hours , p = 0.55 ) , intraoperative complications ( 10 % versus 7.7 % , p = 0.30 ) , postoperative complications ( 20 % versus 13.5 % , p = 0.14 ) and postoperative analgesia requirements ( 27 versus 26 mg MSO4 equivalent p = 0.13 ) . Pathology revealed renal cell carcinoma in 84 % and 75 % of cases , respectively , with no positive surgical margin in any case . CONCLUSIONS Laparoscopic radical nephrectomy can be performed efficiently and effectively with the transperitoneal or the retroperitoneal approach . While renal hilar control and total operative time may be quicker with retroperitoneoscopy , the approaches are similar in terms of other patient outcomes evaluated BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability .  Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) PURPOSE Laparoscopic partial nephrectomy is an increasingly performed , minimally invasive alternative to open partial nephrectomy . We compared early postoperative outcomes in 1,800 patients undergoing open partial nephrectomy by experienced surgeons with the initial experience with laparoscopic partial nephrectomy in patients with a single renal tumor 7 cm or less . MATERIAL S AND METHODS Data on 1,800 consecutive open or laparoscopic partial nephrectomies  were collected prospect ively 
    Output:
    