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 / AIMS Hepatocellular carcinoma ( HCC ) remains a disease with a poor prognosis . Several different therapies have been recommended for use as adjuvant treatment for this disease . One of the most promising therapies is targeted locoregional immuno-chemotherapy . MATERIAL S AND METHODS From 1990 to 1996 , 91 patients who were eligible for liver resection were treated in a prospect i ve r and omized study . Forty-two patients received resection alone ( Group A ) and 49 received resection plus chemoembolization and targeted locoregional immuno-chemotherapy ( Group B ) . RESULTS The mortality rate for these two groups was significantly different ( 13 % vs 4 % ) favoring Group B. Overall survival was also significantly different ( 18 months vs 36.3 months ) again favoring Group B. CONCLUSIONS Although prognosis is still miserable for HCC , the approach of targeted locoregional immuno-chemotherapy can offer new hope of improved resectability and survival 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 To clarify whether pre‐operalive transcatheter arterial embolization ( TAE ) improves survival after hepatectomy , a prospect i ve r and omized comparative study was done . Of a total of 115 registered patients having solitary hepatocellular carcinoma ( HCC ) 2 to 5 cm in diameter , 18 ( 15.7 % ) were excluded after r and omization . As a result , 97 patients were chosen as subjects and divided into two groups : hepatectomy with ( group A : n = 50 ) and without ( group B : n=47 ) pre‐operative TAE . The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years . The r and omization appeared to have provided well‐balanced groups of patients and the clinico‐pathological characteristics of the two groups were quite similar . The necrotic part of the cancerous lesions , as confirmed by operative specimens , amounted to 74.8 ±33.4 % ( mean±SD ) in group A and 6.8 ±7.2 % in group B ( P<0.01 ) . However , the cancer‐free survival rates after hepatectomy in both groups showed little difference ( 39.1±7.0 ( % ±SE ) and 31.1±0.1 , respectively ) . We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre‐operative TAE does not improve post‐operative survival BACKGROUND Postsurgical recurrence of hepatocellular carcinoma ( HCC ) is frequent and fatal . Adoptive immunotherapy is active against HCC . We assessed whether postoperative immunotherapy could lower the frequency of recurrence . METHODS Between 1992 and 1995 , we did a r and omised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy  ( n=76 ) or  no adjuvant treatment  ( n=74 ) . Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months . Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat . FINDINGS 76 patients received 370 ( 97 % ) of 380 scheduled lymphocyte infusions ( mean cell number per patient 7.1x10(10 ) [ SD 2.1 ] ; CD3 and HLA-DR cells 78 % [ 16 ] ) , and none had grade 3 or 4 adverse events . After a median follow-up of 4.4 years ( range 0.2 - 6.7 ) , adoptive immunotherapy decreased the frequency of recurrence by 18 % compared with controls ( 45 [ 59 % ] vs 57 [ 77 % ] ) [ corrected ] patients . Time to first recurrence in the immunotherapy group was significantly longer than that in the control group ( 48 % [ 37 - 59 ] vs 33 % [ 22 - 43 ] at 3 years , 38 % [ 22 - 54 ] vs 22 % [ 11 - 34 ] at 5 years ; p=0.008 ) . The immunotherapy group had significantly longer recurrence-free survival ( p=0.01 ) and disease-specific survival ( p=0.04 ) than the control group . Overall survival did not differ significantly between groups ( p=0.09 ) . INTERPRETATION Adoptive immunotherapy is a safe , feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy , we conducted a prospect i ve r and omized controlled trial of interferon ( IFN ) in patients with chronic liver disease caused by hepatitis C virus ( HCV ) . Twenty eligible patients with cirrhosis were r and omized into two groups : 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy . One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy . None of the patients in either group lost HCV-RNA until the end of the observation . Although 7 ( 70.0 % ) of 10 patients in the nontreatment group showed tumor recurrence , only 1 ( 10.0 % ) of 10 patients with IFN therapy developed tumor recurrence during a median observation period of 25.0 months . Cumulative recurrence rates of the treated and untreated groups were 0 % and 62.5 % at the end of the first year , and 0 % and 100 % at the second year , respectively ( log-rank test , P = .0004 ) . In conclusion , intermittent administration of IFN suppressed tumor recurrence after treatment with surgery or ethanol injection in patients with HCV-related chronic liver disease OBJECTIVE To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma . DESIGN A r and omized controlled trial . SETTING A tertiary referral center . PATIENTS During a 54-month period , 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution . Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study . The median follow-up time was 28.3 months . INTERVENTION Thirty patients received a combination of intravenous epirubicin hydrochloride ( 8 doses of 40 mg/m2 each at 6-week intervals ) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin ( 3 courses with a maximum dose of 20 mL each at 2-month intervals ) . Thirty-six patients had no adjuvant treatment . MAIN OUTCOME MEASURES Recurrence rate and disease-free survival . RESULTS A total of 138 courses of intravenous epirubicin was given to the 30 patients . Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group , because the hepatic artery in 1 patient was thrombosed . Six patients ( 20 % ) had chemotherapy-related complications with no mortality . Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences ( P=.01 ) . Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases ( 11 patients vs 5 patients ; P=.03 ) . The respective disease-free survival rates at 1 , 2 , and 3 years were 50%,36 % , and 18 % for the treatment group and 69 % , 53 % , and 48 % for the control group ( P=.04 ) . CONCLUSION In a group of patients who underwent curative resection of hepatocellular carcinoma , postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome Vascular invasion and intrahepatic metastasis by hepatocellular carcinoma are important factors predisposing to tumor recurrence . Recurrences of this malignancy occur frequently in residual liver , and its prevention is one of the most important factors in obtaining better surgical survival .  Fifty patients who underwent hepatectomy for invasive hepatocellular carcinoma with vascular invasion and /or intrahepatic metastases were studied to evaluate the effect of adjuvant bolus hepatic arterial infusion of iodized poppyseed oil ( Lipiodol ) containing anticancer drugs in preventing recurrence and in prolonging survival . Patients were assigned to two treatment groups . Twenty-three of the fifty patients received adjuvant bolus infusion of Lipiodol containing doxorubicin and mitomycin C , whereas 27 patients received no therapy . The disease-free survival rate for the patients who received adjuvant therapy was significantly better ( p < 0.05 ) than that for those who did not when measured at 172 , 516 , 688 and 860 days after hepatectomy , and the disease-free survival curve for patients with adjuvant therapy was significantly ( p = 0.0237 ) better than that without adjuvant therapy . The cumulative survival rates and curves were not significantly different between the two groups . While adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs was effective in improving disease-free survival , the effect was not satisfactory . Further trials of adjuvant chemotherapy are required to improve the surgical survival of hepatocellular carcinoma patients Objective : This study was aim ed at evaluating the effects of interferon (IFN)-α on survival rate after resection of hepatocellular carcinoma . Methods : In a r and omized , controlled trial by the University Hospital , Medical Center and affiliated hospital in Osaka , Japan , 30 men were after surgery r and omly allocated to an IFN-α group  ( 15 patients ) and to a control group . Patients in the IFN group received 6 MIU of IFN-α intramuscularly daily for 2 weeks , then three times a week for 14 weeks , and finally twice a week for 88 weeks . The incidence of recurrence and survival rate were then studied . Results : The response to IFN was sustained viral response ( SVR ) in 2 patients , biochemical response ( BR ) in 6 , partial response ( PR ) in 5 , and no response ( NR ) in 2 . In the control , 8 of the 15 patients demonstrated continuous abnormally high levels of ALT . At the end point of the study , intrahepatic recurrence was detected in 9 of the IFN group and in 13 of the control ( p = 0.065 , log-rank test ) . The cumulative survival rate was higher in the IFN group than in the controls ( p = 0.041 ) . Conclusion : Postoperative IFN therapy improves the outcome after resection of hepatitis C virus-related hepatocellular carcinoma Transcatheter arterial chemoembolization ( TACE ) improves the treatment of hepatocellular carcinoma ( HCC ) by causing tumour necrosis and shrinkage . Fifty‐two patients with resectable large HCC ( defined as a maximal tumour diameter of 10 cm or more ) were prospect ively r and omized into two groups : group 1 comprised 24 patients who had 1–5 sessions of TACE before operation ; group 2 consisted of the other 28 patients , on whom surgery was performed without delay . Tumour volume was reduced to a mean(s.d . ) of 42·8(15·3 ) per cent in 16 patients in group 1 , but remained unchanged in four and increased in size in a further four . Patients in group 
    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: BACKGROUND / AIMS Hepatocellular carcinoma ( HCC ) remains a disease with a poor prognosis . Several different therapies have been recommended for use as adjuvant treatment for this disease . One of the most promising therapies is targeted locoregional immuno-chemotherapy . MATERIAL S AND METHODS From 1990 to 1996 , 91 patients who were eligible for liver resection were treated in a prospect i ve r and omized study . Forty-two patients received resection alone ( Group A ) and 49 received resection plus chemoembolization and targeted locoregional immuno-chemotherapy ( Group B ) . RESULTS The mortality rate for these two groups was significantly different ( 13 % vs 4 % ) favoring Group B. Overall survival was also significantly different ( 18 months vs 36.3 months ) again favoring Group B. CONCLUSIONS Although prognosis is still miserable for HCC , the approach of targeted locoregional immuno-chemotherapy can offer new hope of improved resectability and survival 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 To clarify whether pre‐operalive transcatheter arterial embolization ( TAE ) improves survival after hepatectomy , a prospect i ve r and omized comparative study was done . Of a total of 115 registered patients having solitary hepatocellular carcinoma ( HCC ) 2 to 5 cm in diameter , 18 ( 15.7 % ) were excluded after r and omization . As a result , 97 patients were chosen as subjects and divided into two groups : hepatectomy with ( group A : n = 50 ) and without ( group B : n=47 ) pre‐operative TAE . The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years . The r and omization appeared to have provided well‐balanced groups of patients and the clinico‐pathological characteristics of the two groups were quite similar . The necrotic part of the cancerous lesions , as confirmed by operative specimens , amounted to 74.8 ±33.4 % ( mean±SD ) in group A and 6.8 ±7.2 % in group B ( P<0.01 ) . However , the cancer‐free survival rates after hepatectomy in both groups showed little difference ( 39.1±7.0 ( % ±SE ) and 31.1±0.1 , respectively ) . We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre‐operative TAE does not improve post‐operative survival BACKGROUND Postsurgical recurrence of hepatocellular carcinoma ( HCC ) is frequent and fatal . Adoptive immunotherapy is active against HCC . We assessed whether postoperative immunotherapy could lower the frequency of recurrence . METHODS Between 1992 and 1995 , we did a r and omised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy  ( n=76 ) or  no adjuvant treatment  ( n=74 ) . Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months . Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat . FINDINGS 76 patients received 370 ( 97 % ) of 380 scheduled lymphocyte infusions ( mean cell number per patient 7.1x10(10 ) [ SD 2.1 ] ; CD3 and HLA-DR cells 78 % [ 16 ] ) , and none had grade 3 or 4 adverse events . After a median follow-up of 4.4 years ( range 0.2 - 6.7 ) , adoptive immunotherapy decreased the frequency of recurrence by 18 % compared with controls ( 45 [ 59 % ] vs 57 [ 77 % ] ) [ corrected ] patients . Time to first recurrence in the immunotherapy group was significantly longer than that in the control group ( 48 % [ 37 - 59 ] vs 33 % [ 22 - 43 ] at 3 years , 38 % [ 22 - 54 ] vs 22 % [ 11 - 34 ] at 5 years ; p=0.008 ) . The immunotherapy group had significantly longer recurrence-free survival ( p=0.01 ) and disease-specific survival ( p=0.04 ) than the control group . Overall survival did not differ significantly between groups ( p=0.09 ) . INTERPRETATION Adoptive immunotherapy is a safe , feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy , we conducted a prospect i ve r and omized controlled trial of interferon ( IFN ) in patients with chronic liver disease caused by hepatitis C virus ( HCV ) . Twenty eligible patients with cirrhosis were r and omized into two groups : 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy . One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy . None of the patients in either group lost HCV-RNA until the end of the observation . Although 7 ( 70.0 % ) of 10 patients in the nontreatment group showed tumor recurrence , only 1 ( 10.0 % ) of 10 patients with IFN therapy developed tumor recurrence during a median observation period of 25.0 months . Cumulative recurrence rates of the treated and untreated groups were 0 % and 62.5 % at the end of the first year , and 0 % and 100 % at the second year , respectively ( log-rank test , P = .0004 ) . In conclusion , intermittent administration of IFN suppressed tumor recurrence after treatment with surgery or ethanol injection in patients with HCV-related chronic liver disease OBJECTIVE To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma . DESIGN A r and omized controlled trial . SETTING A tertiary referral center . PATIENTS During a 54-month period , 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution . Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study . The median follow-up time was 28.3 months . INTERVENTION Thirty patients received a combination of intravenous epirubicin hydrochloride ( 8 doses of 40 mg/m2 each at 6-week intervals ) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin ( 3 courses with a maximum dose of 20 mL each at 2-month intervals ) . Thirty-six patients had no adjuvant treatment . MAIN OUTCOME MEASURES Recurrence rate and disease-free survival . RESULTS A total of 138 courses of intravenous epirubicin was given to the 30 patients . Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group , because the hepatic artery in 1 patient was thrombosed . Six patients ( 20 % ) had chemotherapy-related complications with no mortality . Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences ( P=.01 ) . Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases ( 11 patients vs 5 patients ; P=.03 ) . The respective disease-free survival rates at 1 , 2 , and 3 years were 50%,36 % , and 18 % for the treatment group and 69 % , 53 % , and 48 % for the control group ( P=.04 ) . CONCLUSION In a group of patients who underwent curative resection of hepatocellular carcinoma , postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome Vascular invasion and intrahepatic metastasis by hepatocellular carcinoma are important factors predisposing to tumor recurrence . Recurrences of this malignancy occur frequently in residual liver , and its prevention is one of the most important factors in obtaining better surgical survival .  Fifty patients who underwent hepatectomy for invasive hepatocellular carcinoma with vascular invasion and /or intrahepatic metastases were studied to evaluate the effect of adjuvant bolus hepatic arterial infusion of iodized poppyseed oil ( Lipiodol ) containing anticancer drugs in preventing recurrence and in prolonging survival . Patients were assigned to two treatment groups . Twenty-three of the fifty patients received adjuvant bolus infusion of Lipiodol containing doxorubicin and mitomycin C , whereas 27 patients received no therapy . The disease-free survival rate for the patients who received adjuvant therapy was significantly better ( p < 0.05 ) than that for those who did not when measured at 172 , 516 , 688 and 860 days after hepatectomy , and the disease-free survival curve for patients with adjuvant therapy was significantly ( p = 0.0237 ) better than that without adjuvant therapy . The cumulative survival rates and curves were not significantly different between the two groups . While adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs was effective in improving disease-free survival , the effect was not satisfactory . Further trials of adjuvant chemotherapy are required to improve the surgical survival of hepatocellular carcinoma patients Objective : This study was aim ed at evaluating the effects of interferon (IFN)-α on survival rate after resection of hepatocellular carcinoma . Methods : In a r and omized , controlled trial by the University Hospital , Medical Center and affiliated hospital in Osaka , Japan , 30 men were after surgery r and omly allocated to an IFN-α group  ( 15 patients ) and to a control group . Patients in the IFN group received 6 MIU of IFN-α intramuscularly daily for 2 weeks , then three times a week for 14 weeks , and finally twice a week for 88 weeks . The incidence of recurrence and survival rate were then studied . Results : The response to IFN was sustained viral response ( SVR ) in 2 patients , biochemical response ( BR ) in 6 , partial response ( PR ) in 5 , and no response ( NR ) in 2 . In the control , 8 of the 15 patients demonstrated continuous abnormally high levels of ALT . At the end point of the study , intrahepatic recurrence was detected in 9 of the IFN group and in 13 of the control ( p = 0.065 , log-rank test ) . The cumulative survival rate was higher in the IFN group than in the controls ( p = 0.041 ) . Conclusion : Postoperative IFN therapy improves the outcome after resection of hepatitis C virus-related hepatocellular carcinoma Transcatheter arterial chemoembolization ( TACE ) improves the treatment of hepatocellular carcinoma ( HCC ) by causing tumour necrosis and shrinkage . Fifty‐two patients with resectable large HCC ( defined as a maximal tumour diameter of 10 cm or more ) were prospect ively r and omized into two groups : group 1 comprised 24 patients who had 1–5 sessions of TACE before operation ; group 2 consisted of the other 28 patients , on whom surgery was performed without delay . Tumour volume was reduced to a mean(s.d . ) of 42·8(15·3 ) per cent in 16 patients in group 1 , but remained unchanged in four and increased in size in a further four . Patients in group 
    Output:
    