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: R and omized controlled clinical trials are conducted to determine whether differences of clinical importance exist between selected treatment regimens . When statistical analysis of the study data finds a P value greater than 5 % , it is convention to deem the assessed difference nonsignificant . Just because convention dictates that such study findings be termed nonsignificant , or negative , however , it does not necessarily follow that the study found nothing of clinical importance . Subject sample s used in controlled trials tend to be too small . The studies therefore lack the necessary power to detect real , and clinical ly worthwhile , differences in treatment . Freiman et al. found that only 30 % of a sample of 71 trials published in the New Engl and Journal of Medicine in 1978 - 79 with a P value greater than 10 % were large enough to have a 90 % chance of detecting even a 50 % difference in the effectiveness of the treatments being compared , and they found no improvement in a similar sample of trials published in 1988 . It is therefore wrong and unwise to interpret so many negative trials as providing evidence of the ineffectiveness of new treatments . One must instead seriously question whether the absence of evidence is a valid justification for inaction . Efforts must be made to look for quantification of an association rather than just a P value , especially when the risks under investigation are small . The authors cite a recent trial comparing octreotide and sclerotherapy in patients with variceal bleeding  , as well as the overview of clinical trials evaluating fibrinolytic treatment for preventing reinfa rct ion after acute myocardial infa rct ion as examples Objective A Phase II study was conducted at Indiana University to evaluate the safety and efficacy of combined weekly Gemcitabine ( GEM ) with external beam radiotherapy ( RT ) in unresectable , locally advanced pancreatic cancer ( LAPC ) . Methods Eligible patients had biopsy-proven LAPC without evidence of metastatic disease . In part A of the treatment plan , patients received GEM 600 mg/m2 IV weekly , with concurrent RT ( 50.4 Gy in 28 fractions , 1.8 Gy/d , 5 days per week ) . Part B of the treatment plan began approximately 4 weeks after completing part A : patients without disease progression received weekly GEM 1000 mg/m2 on days 1 , 8 , and 15 of a 28-day cycle for 6 cycles or until disease progression . Results From April 2001 to June 2003 , of 28 patients evaluated , 24 ( 86 % ) completed part A. About 22 patients had grade 3 toxicities , primarily hematologic ( 43 % ) and gastrointestinal ( 36 % ) . Three patients ( 11 % ) had grade 4 toxicities ( one each for hyperbilirubinemia , infection , and dyspnea ) . The median follow-up was 10 months ( 1–63 months ) for all enrolled patients . Six patients ( 21 % ) had a radiologic partial response , 16 ( 57 % ) had stable disease , 5 ( 18 % ) had progressive disease , and 1 patient ( 4 % ) had an unevaluable response at last follow-up . Four patients ( 14 % ) underwent surgical resection ( 2 with R0 resection ) . Median time to progression was 6 months ( 0–36 months ) . Median survival time was 10.3 months ( 95 % confidence interval , 7.9–14.6 months ) . The 1- and 2-year actuarial survival rates were 30 % and 11 % . At last analysis , all but 2 patients died . Conclusion The activity and toxicity profile of combination GEM and RT indicates that this can be safely administered for patients with LAPC OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Objectives : The antitumor activity and toxicity of a multi-step treatment were evaluated in patients with locally advanced , inoperable , or incompletely resected pancreatic ( Pa ) and biliary tree ( Bt ) adenocarcinomas ( ADKs ) . Methods : Fifty-four patients , 63 % with Pa and 37 % with Bt ADK , received 3 courses of cisplatin-gemcitabine induction chemotherapy . Progression-free ( PF ) patients were given consolidation radiotherapy with concurrent capecitabine . PF patients had , as maintenance immunotherapy ( MI ) , interleukin 2 ( 1.8 × 106 IU ) and 13-cis-retinoic acid ( 5 mg/kg ) . Results : Thirty-eight patients , 27 with Pa and 11 with Bt ADKs , PF after cisplatin/gemcitabine  , were treated with consolidation radiotherapy with concurrent capecitabine . Fourteen PF patients , 7 with Pa and 7 with Bt ADK , received MI . Median PF and overall survivals ( OS ) for all 54 patients were 6.8 and 12.1 months , respectively . Patients treated with MI had a median PF survival of 16.2 months , whereas median OS had not been reached yet , after a median follow-up of 27.5 months . Toxicity : Grade s 3 and 4 hematological and gastrointestinal in 30 % and 37 % of patients , respectively ; grade s 1 and 2 autoimmune reactions in 28 % of patients . Conclusions : These results support the efficacy and safety of a multi-step sequential treatment in patients with locally advanced , inoperable or incompletely resected Pa and Bt ADKs Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled .  The PFS  in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy  demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Objectives : Dendritic cell ( DC ) therapy frequently induces a measurable immune response . However clinical responses are seen in a minority of patients , presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes ( CTLs ) capable of eradicating tumor cells . To increase therapeutic efficacy of DC-based vaccination , we have undertaken the first clinical trial involving a combination therapy of gemcitabine ( GEM ) with immunotherapy for patients with inoperable locally advanced pancreatic cancer . Methods : Patients ( n = 5 ) received the treatment course , which consisted of intravenous GEM administration at 1000 mg/m2 ( day 1 ) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor , followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody ( CD3-LAKs ) ( day 4 ) , at 2-week intervals . Results : No serious treatment-related adverse events were observed during the study period . Three of the 5 patients demonstrated effective responses to this clinical trial ; 1 had partial remission and 2 had long stable disease more than 6 months . In the patient with partial remission , it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs . Conclusion : This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs BACKGROUND Though the outcome of resection for locally invasive pancreatic cancer is still poor , it has gradually improved in Japan , and the 5-year survival is now about 10 % . However , the advantage of resection over radiochemotherapy has not yet been confirmed by a r and omized trial . We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter r and omized design . METHODS Patients with pancreatic cancer who met our preoperative criteria for inclusion ( pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery , or without distant metastasis ) underwent laparotomy . Patients with operative findings consistent with our criteria were r and omized into a radical resection group and a radiochemotherapy group ( 200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy ) without resection . The 2 groups were compared for mean survival , hazard ratio , 1-year survival , quality of life scores , and hematologic and blood chemical data . RESULTS Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group . There was 1 operative death . The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival ( 62 % vs 32 % , P=.05 ) , mean survival time ( > 17 vs 11 months , P < .03 ) , and hazard ratio ( 0.46 , P=.04 ) . There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection . CONCLUSIONS Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection BACKGROUND / AIMS To evaluate , the early and long-term results of mono-bloc spleno-pancreatic and vascular resection for advanced carcinoma of the head of the pancreas , with portal-mesenteric venous invasion . METHODOLOGY In a prospect i ve , r and omized trial , fifty-six patients with advanced carcinoma of the head of the pancreas with vascular invasion were studied . Patients were r and omly divided in two groups A and B. Group A patients underwent an en-bloc spleno-pancreatic and vascular resection . Group B patients underwent a palliative gastro-biliary bypass . Patients in both groups were subjected to adjuvant locoregional chemoimmunotherapy , through an arterial catheter introduced into the superior mesenteric artery via a jejunal arterial branch . RESULTS The 2- and 5-year survival rates for Group A patients were 81.8 % and 18.5 % . The respective percentages for disease-free survival were 60.6 % and 0 % . Two-year survival for group B was nil . CONCLUSIONS Mono 
    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: R and omized controlled clinical trials are conducted to determine whether differences of clinical importance exist between selected treatment regimens . When statistical analysis of the study data finds a P value greater than 5 % , it is convention to deem the assessed difference nonsignificant . Just because convention dictates that such study findings be termed nonsignificant , or negative , however , it does not necessarily follow that the study found nothing of clinical importance . Subject sample s used in controlled trials tend to be too small . The studies therefore lack the necessary power to detect real , and clinical ly worthwhile , differences in treatment . Freiman et al. found that only 30 % of a sample of 71 trials published in the New Engl and Journal of Medicine in 1978 - 79 with a P value greater than 10 % were large enough to have a 90 % chance of detecting even a 50 % difference in the effectiveness of the treatments being compared , and they found no improvement in a similar sample of trials published in 1988 . It is therefore wrong and unwise to interpret so many negative trials as providing evidence of the ineffectiveness of new treatments . One must instead seriously question whether the absence of evidence is a valid justification for inaction . Efforts must be made to look for quantification of an association rather than just a P value , especially when the risks under investigation are small . The authors cite a recent trial comparing octreotide and sclerotherapy in patients with variceal bleeding  , as well as the overview of clinical trials evaluating fibrinolytic treatment for preventing reinfa rct ion after acute myocardial infa rct ion as examples Objective A Phase II study was conducted at Indiana University to evaluate the safety and efficacy of combined weekly Gemcitabine ( GEM ) with external beam radiotherapy ( RT ) in unresectable , locally advanced pancreatic cancer ( LAPC ) . Methods Eligible patients had biopsy-proven LAPC without evidence of metastatic disease . In part A of the treatment plan , patients received GEM 600 mg/m2 IV weekly , with concurrent RT ( 50.4 Gy in 28 fractions , 1.8 Gy/d , 5 days per week ) . Part B of the treatment plan began approximately 4 weeks after completing part A : patients without disease progression received weekly GEM 1000 mg/m2 on days 1 , 8 , and 15 of a 28-day cycle for 6 cycles or until disease progression . Results From April 2001 to June 2003 , of 28 patients evaluated , 24 ( 86 % ) completed part A. About 22 patients had grade 3 toxicities , primarily hematologic ( 43 % ) and gastrointestinal ( 36 % ) . Three patients ( 11 % ) had grade 4 toxicities ( one each for hyperbilirubinemia , infection , and dyspnea ) . The median follow-up was 10 months ( 1–63 months ) for all enrolled patients . Six patients ( 21 % ) had a radiologic partial response , 16 ( 57 % ) had stable disease , 5 ( 18 % ) had progressive disease , and 1 patient ( 4 % ) had an unevaluable response at last follow-up . Four patients ( 14 % ) underwent surgical resection ( 2 with R0 resection ) . Median time to progression was 6 months ( 0–36 months ) . Median survival time was 10.3 months ( 95 % confidence interval , 7.9–14.6 months ) . The 1- and 2-year actuarial survival rates were 30 % and 11 % . At last analysis , all but 2 patients died . Conclusion The activity and toxicity profile of combination GEM and RT indicates that this can be safely administered for patients with LAPC OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Objectives : The antitumor activity and toxicity of a multi-step treatment were evaluated in patients with locally advanced , inoperable , or incompletely resected pancreatic ( Pa ) and biliary tree ( Bt ) adenocarcinomas ( ADKs ) . Methods : Fifty-four patients , 63 % with Pa and 37 % with Bt ADK , received 3 courses of cisplatin-gemcitabine induction chemotherapy . Progression-free ( PF ) patients were given consolidation radiotherapy with concurrent capecitabine . PF patients had , as maintenance immunotherapy ( MI ) , interleukin 2 ( 1.8 × 106 IU ) and 13-cis-retinoic acid ( 5 mg/kg ) . Results : Thirty-eight patients , 27 with Pa and 11 with Bt ADKs , PF after cisplatin/gemcitabine  , were treated with consolidation radiotherapy with concurrent capecitabine . Fourteen PF patients , 7 with Pa and 7 with Bt ADK , received MI . Median PF and overall survivals ( OS ) for all 54 patients were 6.8 and 12.1 months , respectively . Patients treated with MI had a median PF survival of 16.2 months , whereas median OS had not been reached yet , after a median follow-up of 27.5 months . Toxicity : Grade s 3 and 4 hematological and gastrointestinal in 30 % and 37 % of patients , respectively ; grade s 1 and 2 autoimmune reactions in 28 % of patients . Conclusions : These results support the efficacy and safety of a multi-step sequential treatment in patients with locally advanced , inoperable or incompletely resected Pa and Bt ADKs Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled .  The PFS  in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy  demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Objectives : Dendritic cell ( DC ) therapy frequently induces a measurable immune response . However clinical responses are seen in a minority of patients , presumably due to insufficient expansion of antigen-specific cytotoxic T lymphocytes ( CTLs ) capable of eradicating tumor cells . To increase therapeutic efficacy of DC-based vaccination , we have undertaken the first clinical trial involving a combination therapy of gemcitabine ( GEM ) with immunotherapy for patients with inoperable locally advanced pancreatic cancer . Methods : Patients ( n = 5 ) received the treatment course , which consisted of intravenous GEM administration at 1000 mg/m2 ( day 1 ) and the endoscopic ultrasound-guided fine-needle injection of OK432-pulsed DCs into a tumor , followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody ( CD3-LAKs ) ( day 4 ) , at 2-week intervals . Results : No serious treatment-related adverse events were observed during the study period . Three of the 5 patients demonstrated effective responses to this clinical trial ; 1 had partial remission and 2 had long stable disease more than 6 months . In the patient with partial remission , it has been shown that DC-based vaccination combined with GEM administration induces tumor antigen-specific CTLs . Conclusion : This combined therapy was considered to be synergistically effective and may have a role in the therapy of pancreatic cancer for inducing tumor antigen-specific CTLs BACKGROUND Though the outcome of resection for locally invasive pancreatic cancer is still poor , it has gradually improved in Japan , and the 5-year survival is now about 10 % . However , the advantage of resection over radiochemotherapy has not yet been confirmed by a r and omized trial . We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter r and omized design . METHODS Patients with pancreatic cancer who met our preoperative criteria for inclusion ( pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery , or without distant metastasis ) underwent laparotomy . Patients with operative findings consistent with our criteria were r and omized into a radical resection group and a radiochemotherapy group ( 200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy ) without resection . The 2 groups were compared for mean survival , hazard ratio , 1-year survival , quality of life scores , and hematologic and blood chemical data . RESULTS Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group . There was 1 operative death . The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival ( 62 % vs 32 % , P=.05 ) , mean survival time ( > 17 vs 11 months , P < .03 ) , and hazard ratio ( 0.46 , P=.04 ) . There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection . CONCLUSIONS Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection BACKGROUND / AIMS To evaluate , the early and long-term results of mono-bloc spleno-pancreatic and vascular resection for advanced carcinoma of the head of the pancreas , with portal-mesenteric venous invasion . METHODOLOGY In a prospect i ve , r and omized trial , fifty-six patients with advanced carcinoma of the head of the pancreas with vascular invasion were studied . Patients were r and omly divided in two groups A and B. Group A patients underwent an en-bloc spleno-pancreatic and vascular resection . Group B patients underwent a palliative gastro-biliary bypass . Patients in both groups were subjected to adjuvant locoregional chemoimmunotherapy , through an arterial catheter introduced into the superior mesenteric artery via a jejunal arterial branch . RESULTS The 2- and 5-year survival rates for Group A patients were 81.8 % and 18.5 % . The respective percentages for disease-free survival were 60.6 % and 0 % . Two-year survival for group B was nil . CONCLUSIONS Mono 
    Output:
    