Improvement of prognosis for unresectable biliary tract cancer

AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan,were retrospectively analyzed.These patients were divided into three groups based on the year beginning chemotherapy:Group A(2000-2003),Group B(2004-2006),and Group C(2007-2009).The data were fixed at the end of December 2011.Overall survival and time-to-progression were analyzed and compared chronologically.RESULTS:No patient characteristics were significantly different among the three groups.The gallbladder was involved in about half of the patients in each group,and metastatic biliary tract cancer was present in three quarters of the enrollees.In Group A,5-fluorouracilbased chemotherapies were primarily selected as firstline chemotherapy,and only 24% were treated with second-line chemotherapy.In Group B,gemcitabine or S-1 monotherapy was mainly introduced as firstline chemotherapy,and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy.In Group C,the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy,and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy.The median timeto-progressions were 4.4 mo,3.5 mo and 5.9 mo in Groups A,B and C,respectively(4.4 mo vs 3.5 mo vs 5.9 mo,P < 0.01).The median overall survivals were 7.1,7.3,and 11.7 mo in Groups A,B and C(7.1 mo vs 7.3 mo vs 11.7 mo,P = 0.03).Induction rates of all three drugs(gemcitabine,platinum analogs,and fluoropyrimidine) in Groups A,B and C were 4%,2% and 27%(4% vs 2% vs 27%,P < 0.01).CONCLUSION:The prognosis of unresectable biliary tract cancer has improved recently.Using three effective drugs(gemcitabine,platinum analogs,and fluoropyrimidine) may improve the prognosis of this cancer.

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

AIM:To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).METHODS:Between December 2006 and June 2008,a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled.Liver stiffness was obtained noninvasively by using Fibroscan (Echosens,Paris,France).The date of blood transfusion was obtained by interview.Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement (LSM).Patients were stratified into four groups based on the duration of infection (17-29 years;30-39 years;40-49 years;and 50-70 years).The difference in liver stiffness between patients with and without HCC was assessed in each group.Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS:A total of 524 patients underwent LSM.Eight patients were excluded because of unsuccessful measurements.Thus 516 patients were included in the current analysis (225 with HCC and 291 without).The patients were 244 men and 272 women,with a mean age of 67.8 ± 9.5 years.The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in nonHCC group).The patients who developed HCC in short duration of infection were male dominant,having lower platelet count,with a history of heavier alcohol consumption,showing higher liver stiffness,and receiving blood transfusion at an old age.Liver stiffness was positively correlated with duration of infection in patients without HCC (r=0.132,P=0.024) but not in patients with HCC (r=-0.103,P=0.123).Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001).The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001),duration of infection (P=0.0015),and heavy alcohol consumption (P=0.043) CONCLUSION:Although liver stiffness gradually increases over time,HCC develops in patients with high stiffness value regardless of the duration of infection.

Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers

Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade.New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs.Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival,although the effect was minimal.Little or no improvement in survival with recent moleculartargeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer.Recently,the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time.For biliary tract cancer,gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy.Further improvement in survival is expected by the addition of cetuximab.