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: Objectives : No established therapy exists for unresectable intrahepatic cholangiocarcinoma ( ICC ) . We conducted a phase I/II study to ascertain the recommended dose ( RD ) of hepatic arterial infusion using gemcitabine ( GEM ) for ICC and to assess the efficacy and safety . Methods : For patients with unresectable ICC , GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1 , 8 , and 15 every 4 weeks for 5 cycles . In phase I , dosage for levels 1 , 2 , and 3 was set at 600 , 800 , and 1000 mg/m2 , respectively , and was increased in 3 to 6 patients at a time . Maximum tolerated dose was defined as a dosage result ing in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients , and RD was estimated during the first cycle . In the phase II , more RD patients were added to assess tumor response and toxicity . Results : During the phase I , 16 patients were enrolled .  Maximum tolerated dose was not reached . Assuming RD at 1000 mg/m2 , the phase II enrolled a total of 13 patients . The following Grade 3 toxicities were observed : neutropenia 20 % , increased gamma-glutamyl transpeptidase 8 % , increased aspartate aminotransferase 4 % , increased alanine aminotransferase 4 % , increased bilirubin 4 % , nausea 4 % , and fatigue 4 % . The tumor response rate was 7.7 % ( complete response 0 , partial response 1 , stable disease 8 , and progressive disease 4 ) . Conclusion : Whereas the toxicity of hepatic arterial infusion with 1000 mg/m2 GEM for ICC was tolerable , expected efficacy could not be obtained , thus suggesting only minimal activity BACKGROUND The benefits of preoperative biliary drainage , which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head , are unclear . METHODS In this multicenter , r and omized trial , we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head . Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter ( 2.3 to 14.6 mg per deciliter ) were r and omly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks , followed by surgery , or surgery alone within 1 week after diagnosis . Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retro grade cholangiopancreatography . The primary outcome was the rate of serious complications within 120 days after r and omization . RESULTS We enrolled 202 patients ; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage ; 6 patients were excluded from the analysis . The rates of serious complications were 39 % ( 37 patients ) in the early-surgery group and 74 % ( 75 patients ) in the biliary-drainage group ( relative risk in the early-surgery group , 0.54 ; 95 % confidence interval [ CI ] , 0.41 to 0.71 ; P<0.001 ) . Preoperative biliary drainage was successful in 96 patients ( 94 % ) after one or more attempts , with complications in 47 patients ( 46 % ) . Surgery-related complications occurred in 35 patients ( 37 % ) in the early-surgery group and in 48 patients ( 47 % ) in the biliary-drainage group ( relative risk , 0.79 ; 95 % CI , 0.57 to 1.11 ; P=0.14 ) . Mortality and the length of hospital stay did not differ significantly between the two groups . CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications . ( Current Controlled Trials number , IS RCT N31939699 . The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002 . This is the first up date since then and is based on a comprehensive review of the recent literature , including data from r and omised controlled trials , systematic review s , meta-analyses , cohort , prospect i ve and retrospective studies PURPOSE Intrahepatic cholangiocarcinomas ( IHC ) are rare tumors for which large r and omized studies regarding the use of radiation are not available . The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients . METHODS AND MATERIAL S This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance , Epidemiology , and End Results ( SEER ) data base . The primary endpoint was overall survival ( OS ) . RESULTS Patients received either surgery alone ( 25 % ) , radiation therapy alone ( 10 % ) , surgery and adjuvant radiation therapy ( 7 % ) or no treatment ( 58 % ) . The median age of the patient population was 73 years ( range , 22 - 102 years ) ; 52 % of patients were male and 81 % were Caucasian .  Median OS was 11 ( 95 % confidence interval [ CI ] , 9 - 13 ) , 6 ( 95 % CI , 5 - 6 ) , 7 ( 95 % CI , 6 - 8 ) , and 3 months for surgery and adjuvant radiation therapy , surgery alone , radiation therapy alone , and no treatment , respectively . The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy ( p = 0.014 ) and radiation therapy alone and no treatment ( p < 0.0001 ) . Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS ( HR = 0.40 ; 95 % CI , 0.34 - 0.47 ) , followed by surgery alone ( hazard ratio [ HR ] , 0.49 ; 95 % CI , 0.44 - 0.54 ) and radiation therapy alone ( HR , 0.68 ; 95 % CI , 0.59 - 0.77 ) compared with no treatment , on multivariate analysis . Propensity score adjusted hazard ratios ( controlling for age , race/ethnicity , stage , and year of diagnosis ) were also significant ( surgery and adjuvant radiation therapy vs. surgery alone ( HR , 0.82 ; 95 % CI , 0.70 - 0.96 ) ; radiation therapy alone vs. no treatment ( HR , 0.67 ; 95 % CI , 0.58 - 0.76 ) ) . CONCLUSIONS The study results suggest that adjuvant and definitive radiation treatment prolong survival , although cure rates remain low . Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC Background Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer ( BTC ) has been established recently . However , overall prognosis is still poor , and additional therapeutic approaches are needed for patients with locally advanced , irresectable and /or pretreated tumors .  Hepatic arterial infusion ( HAI ) of chemotherapy represents a safe and well-established treatment modality , but data on its use in patients with BTC are still sparse . Methods Patients with irresectable BTC predominant to the liver were included in a prospect i ve , open phase II study investigating HAI provided through interventionally implanted port catheters . Intraarterial chemotherapy consisted of biweekly oxaliplatin ( O ) 85 mg/m2 and folinic acid ( F ) 170 mg/m2 with 5-FU ( F ) 600 mg/m2 . Results Between 2004 and 2010 , 37 patients were enrolled . A total of 432 cycles of HAI were applied with a median of 9 ( range 1–46 ) cycles . Objective response rate was 16 % , and tumor control was achieved in 24 of 37 ( 65 % ) patients . Median progression-free survival was 6.5 months ( range 0.5–26.0 ; 95 % CI 4.3–8.7 ) , median overall survival was 13.5 ( range 0.9–50.7 ; 95 % CI 11.1–15.9 ) months . The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients . Conclusions Using a minimal invasive technique , repetitive HAI with OFF is feasible and results in clinical ly relevant tumor control with low toxicity in patients with liver predominant advanced BTC OBJECTIVE To assess safety , feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres ( DSM-TACE ) in the treatment of patients with advanced hepatocellular carcinoma ( HCC ) dismissing or ineligible for multikinase-inhibitor chemotherapy administration ( Sorafenib ) due to unbearable side effects or clinical contraindications . PATIENTS AND METHODS Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospect i ve single-center pilot study . DSM-TACE was performed via a lobar approach , based on extent and distribution of the disease ( 1 treatment session for every lobe involved , with a 2-week interval in case of bilobar disease ) . Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after " complete treatment " and every 3 months thereafter . RESULTS Eleven treatments were performed , and technical success was achieved in all patients . No intra/peri-procedural death/major complications occurred . No signs of liver failure or systemic toxicity were detected . At one month follow-up , 5 partial responses ( 83.3 % ) and 1 progression disease ( 16.6 % ) with an overall disease control ( ODC ) of 83.3 % were observed . In two patients with ODC and residual viable tumor higher than 50 % , a repeated DSM-TACE treatment was performed . During the mean follow-up of 11 months ( range : 4 - 14 months ) , an ODC of 66.6 % was obtained . Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3 % and 66.6 % , respectively . CONCLUSIONS DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects PURPOSE To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma ( ICC ) refractory to st and ard chemotherapy after yttrium-90 ( (90)Y ) radioembolization therapy .  MATERIAL S AND METHODS In an institutional review board-approved prospect i ve correlative study , 21 consecutive patients with ICC refractory to st and ard chemotherapy underwent (90)Y radioembolization therapy .  Target and overall Response Evaluation Criteria In Solid Tumors ( RECIST ) , modified RECIST ( mRECIST ) , and European Association for the Study of the Liver ( EASL ) treatment responses were assessed . The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies . Conventional definitions for complete and partial response were applied ; these responses comprised objective response . Restaging imaging was obtained at 1- and 3-month intervals until patient death . Survival analyses by Kaplan-Meier and log-rank proportional models including application of the l and mark method to avoid lead-time bias were performed from the day of treatment . Significance was set at P < .05 . RESULTS Median overall survival ( OS ) from the time of (90)Y therapy was 16.3 months ( 95 % confidence interval , 7.2 - 25.4 mo ) . Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders ( P < .001 ) . Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria ( P = .005 and P = .001 , respectively ) at 3 months . RECIST was not found to correlate with survival at 1- or 3-month follow-up . CONCLUSIONS Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS . RECIST did not correlate with survival BACKGROUND AND OBJECTIVES Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected . METHODS Review of a prospect i ve hepatobiliary data base identified 130 patients .  Survival was compared using the log-rank test . RESULTS Seventy-nine patients ( 61 % ) were resected while 51 ( 49 % ) patients were not . Forty-two patients ( 54 % ) had an R0 resection . There was no difference in mean age ( 69 vs. 67 ; P = 0.8 ) , 
    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: Objectives : No established therapy exists for unresectable intrahepatic cholangiocarcinoma ( ICC ) . We conducted a phase I/II study to ascertain the recommended dose ( RD ) of hepatic arterial infusion using gemcitabine ( GEM ) for ICC and to assess the efficacy and safety . Methods : For patients with unresectable ICC , GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1 , 8 , and 15 every 4 weeks for 5 cycles . In phase I , dosage for levels 1 , 2 , and 3 was set at 600 , 800 , and 1000 mg/m2 , respectively , and was increased in 3 to 6 patients at a time . Maximum tolerated dose was defined as a dosage result ing in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients , and RD was estimated during the first cycle . In the phase II , more RD patients were added to assess tumor response and toxicity . Results : During the phase I , 16 patients were enrolled .  Maximum tolerated dose was not reached . Assuming RD at 1000 mg/m2 , the phase II enrolled a total of 13 patients . The following Grade 3 toxicities were observed : neutropenia 20 % , increased gamma-glutamyl transpeptidase 8 % , increased aspartate aminotransferase 4 % , increased alanine aminotransferase 4 % , increased bilirubin 4 % , nausea 4 % , and fatigue 4 % . The tumor response rate was 7.7 % ( complete response 0 , partial response 1 , stable disease 8 , and progressive disease 4 ) . Conclusion : Whereas the toxicity of hepatic arterial infusion with 1000 mg/m2 GEM for ICC was tolerable , expected efficacy could not be obtained , thus suggesting only minimal activity BACKGROUND The benefits of preoperative biliary drainage , which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head , are unclear . METHODS In this multicenter , r and omized trial , we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head . Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter ( 2.3 to 14.6 mg per deciliter ) were r and omly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks , followed by surgery , or surgery alone within 1 week after diagnosis . Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retro grade cholangiopancreatography . The primary outcome was the rate of serious complications within 120 days after r and omization . RESULTS We enrolled 202 patients ; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage ; 6 patients were excluded from the analysis . The rates of serious complications were 39 % ( 37 patients ) in the early-surgery group and 74 % ( 75 patients ) in the biliary-drainage group ( relative risk in the early-surgery group , 0.54 ; 95 % confidence interval [ CI ] , 0.41 to 0.71 ; P<0.001 ) . Preoperative biliary drainage was successful in 96 patients ( 94 % ) after one or more attempts , with complications in 47 patients ( 46 % ) . Surgery-related complications occurred in 35 patients ( 37 % ) in the early-surgery group and in 48 patients ( 47 % ) in the biliary-drainage group ( relative risk , 0.79 ; 95 % CI , 0.57 to 1.11 ; P=0.14 ) . Mortality and the length of hospital stay did not differ significantly between the two groups . CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications . ( Current Controlled Trials number , IS RCT N31939699 . The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002 . This is the first up date since then and is based on a comprehensive review of the recent literature , including data from r and omised controlled trials , systematic review s , meta-analyses , cohort , prospect i ve and retrospective studies PURPOSE Intrahepatic cholangiocarcinomas ( IHC ) are rare tumors for which large r and omized studies regarding the use of radiation are not available . The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients . METHODS AND MATERIAL S This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance , Epidemiology , and End Results ( SEER ) data base . The primary endpoint was overall survival ( OS ) . RESULTS Patients received either surgery alone ( 25 % ) , radiation therapy alone ( 10 % ) , surgery and adjuvant radiation therapy ( 7 % ) or no treatment ( 58 % ) . The median age of the patient population was 73 years ( range , 22 - 102 years ) ; 52 % of patients were male and 81 % were Caucasian .  Median OS was 11 ( 95 % confidence interval [ CI ] , 9 - 13 ) , 6 ( 95 % CI , 5 - 6 ) , 7 ( 95 % CI , 6 - 8 ) , and 3 months for surgery and adjuvant radiation therapy , surgery alone , radiation therapy alone , and no treatment , respectively . The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy ( p = 0.014 ) and radiation therapy alone and no treatment ( p < 0.0001 ) . Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS ( HR = 0.40 ; 95 % CI , 0.34 - 0.47 ) , followed by surgery alone ( hazard ratio [ HR ] , 0.49 ; 95 % CI , 0.44 - 0.54 ) and radiation therapy alone ( HR , 0.68 ; 95 % CI , 0.59 - 0.77 ) compared with no treatment , on multivariate analysis . Propensity score adjusted hazard ratios ( controlling for age , race/ethnicity , stage , and year of diagnosis ) were also significant ( surgery and adjuvant radiation therapy vs. surgery alone ( HR , 0.82 ; 95 % CI , 0.70 - 0.96 ) ; radiation therapy alone vs. no treatment ( HR , 0.67 ; 95 % CI , 0.58 - 0.76 ) ) . CONCLUSIONS The study results suggest that adjuvant and definitive radiation treatment prolong survival , although cure rates remain low . Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC Background Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer ( BTC ) has been established recently . However , overall prognosis is still poor , and additional therapeutic approaches are needed for patients with locally advanced , irresectable and /or pretreated tumors .  Hepatic arterial infusion ( HAI ) of chemotherapy represents a safe and well-established treatment modality , but data on its use in patients with BTC are still sparse . Methods Patients with irresectable BTC predominant to the liver were included in a prospect i ve , open phase II study investigating HAI provided through interventionally implanted port catheters . Intraarterial chemotherapy consisted of biweekly oxaliplatin ( O ) 85 mg/m2 and folinic acid ( F ) 170 mg/m2 with 5-FU ( F ) 600 mg/m2 . Results Between 2004 and 2010 , 37 patients were enrolled . A total of 432 cycles of HAI were applied with a median of 9 ( range 1–46 ) cycles . Objective response rate was 16 % , and tumor control was achieved in 24 of 37 ( 65 % ) patients . Median progression-free survival was 6.5 months ( range 0.5–26.0 ; 95 % CI 4.3–8.7 ) , median overall survival was 13.5 ( range 0.9–50.7 ; 95 % CI 11.1–15.9 ) months . The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients . Conclusions Using a minimal invasive technique , repetitive HAI with OFF is feasible and results in clinical ly relevant tumor control with low toxicity in patients with liver predominant advanced BTC OBJECTIVE To assess safety , feasibility and effectiveness of transarterial chemoembolization with degradable-starch-microspheres ( DSM-TACE ) in the treatment of patients with advanced hepatocellular carcinoma ( HCC ) dismissing or ineligible for multikinase-inhibitor chemotherapy administration ( Sorafenib ) due to unbearable side effects or clinical contraindications . PATIENTS AND METHODS Six consecutive advanced HCC patients dismissing Sorafenib because of unbearable side effects or worsened clinical conditions were enrolled in our prospect i ve single-center pilot study . DSM-TACE was performed via a lobar approach , based on extent and distribution of the disease ( 1 treatment session for every lobe involved , with a 2-week interval in case of bilobar disease ) . Tumor response based on mRECIST criteria was evaluated on MD-CT performed at 1 month after " complete treatment " and every 3 months thereafter . RESULTS Eleven treatments were performed , and technical success was achieved in all patients . No intra/peri-procedural death/major complications occurred . No signs of liver failure or systemic toxicity were detected . At one month follow-up , 5 partial responses ( 83.3 % ) and 1 progression disease ( 16.6 % ) with an overall disease control ( ODC ) of 83.3 % were observed . In two patients with ODC and residual viable tumor higher than 50 % , a repeated DSM-TACE treatment was performed . During the mean follow-up of 11 months ( range : 4 - 14 months ) , an ODC of 66.6 % was obtained . Progression-free survival was 5.5 months with a cumulative 6-month and 1-year overall survival rates of 83.3 % and 66.6 % , respectively . CONCLUSIONS DSM-TACE seems to be a promising option for advanced HCC patients ineligible for Sorafenib administration or dismissing it due to progressive disease or unbearable side effects PURPOSE To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma ( ICC ) refractory to st and ard chemotherapy after yttrium-90 ( (90)Y ) radioembolization therapy .  MATERIAL S AND METHODS In an institutional review board-approved prospect i ve correlative study , 21 consecutive patients with ICC refractory to st and ard chemotherapy underwent (90)Y radioembolization therapy .  Target and overall Response Evaluation Criteria In Solid Tumors ( RECIST ) , modified RECIST ( mRECIST ) , and European Association for the Study of the Liver ( EASL ) treatment responses were assessed . The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies . Conventional definitions for complete and partial response were applied ; these responses comprised objective response . Restaging imaging was obtained at 1- and 3-month intervals until patient death . Survival analyses by Kaplan-Meier and log-rank proportional models including application of the l and mark method to avoid lead-time bias were performed from the day of treatment . Significance was set at P < .05 . RESULTS Median overall survival ( OS ) from the time of (90)Y therapy was 16.3 months ( 95 % confidence interval , 7.2 - 25.4 mo ) . Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders ( P < .001 ) . Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria ( P = .005 and P = .001 , respectively ) at 3 months . RECIST was not found to correlate with survival at 1- or 3-month follow-up . CONCLUSIONS Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS . RECIST did not correlate with survival BACKGROUND AND OBJECTIVES Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected . METHODS Review of a prospect i ve hepatobiliary data base identified 130 patients .  Survival was compared using the log-rank test . RESULTS Seventy-nine patients ( 61 % ) were resected while 51 ( 49 % ) patients were not . Forty-two patients ( 54 % ) had an R0 resection . There was no difference in mean age ( 69 vs. 67 ; P = 0.8 ) , 
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