Background:Hepatic radiation injury severely restricts irradiation treatment for liver carcinoma.The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pent...Background:Hepatic radiation injury severely restricts irradiation treatment for liver carcinoma.The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MRI(EOB-MRI)in the assessment of liver function after external radiation therapy and to determine the relationship between focal liver reaction(FLR)and liver function.Methods:A total of 47 patients with liver malignancies who underwent external beam radiation therapy were enrolled.EOB-MRI was performed on each patient at approximately one month post-radiotherapy.The hepatobiliary(HPB)phase images from EOB-MRI were fused with the planning CT images,and the isodose lines from the patients’treatment plans were overlaid onto the fused images.The correlation of the EOB-MR image intensity distribution with the isodose lines was studied.We also compared liver function in patients between pre-treatment and post-treatment.Results:Decreased uptake of Gd-EOB-DTPA,which was manifested by well-demarcated focal hypointensity of the liver parenchyma or FLR to high-dose radiation,was observed in the irradiated areas of 38 patients.The radiotherapy isodose line of decreased uptake area of Gd-EOB-DTPA was 30–46 Gy.The median corresponding dose curve of FLR was 34.4 Gy.Nine patients showed the absence of decreased uptake area of Gd-EOB-DTPA in the irradiated areas.Compared to the 38 patients with the presence of decreased uptake area of Gd-EOB-DTPA,9 patients with the absence of decreased uptake area of Gd-EOB-DTPA showed significant higher levels of total bile acid,total bilirubin,direct bilirubin and alpha-fetoprotein(P<0.05).There were no significant differences in alanine transaminase,aspartate aminotransferase,gamma-glutamyl transpeptidase or albumin levels between the two groups(P>0.05).Conclusions:Visible uptake of Gd-EOB-DTPA by the liver parenchyma was significantly associated with liver function parameters.EOB-MRI can be a valuable imaging biomarker for the assessment of liver parenchyma function outside of radiation area.展开更多
Liver damage upon exposure to ionizing radiation(IR),whether accidental or therapeutic,can contribute to liver dysfunction.Currently,radiotherapy(RT)is used for various cancers including hepatocellular carcinoma(HCC);...Liver damage upon exposure to ionizing radiation(IR),whether accidental or therapeutic,can contribute to liver dysfunction.Currently,radiotherapy(RT)is used for various cancers including hepatocellular carcinoma(HCC);however,the treatment dose is limited by radiation-induced liver disease(RILD)with a high mortality rate.Furthermore,the precise molecular mechanisms of RILD remain poorly understood.Here,we investigated RILD pathogenesis using various knockout mouse strains subjected to whole-liver irradiation.We found that hepatocytes released a large quantity of double-stranded DNA(dsDNA)after irradiation.The cGAS-STING pathway in non-parenchymal cells(NPCs)was promptly activated by this dsDNA,causing interferon(IFN)-I production and release and concomitant hepatocyte damage.Genetic and pharmacological ablation of the IFN-I signaling pathway protected against RILD.Moreover,clinically irradiated human peri-HCC liver tissues exhibited substantially higher STING and IFNβexpression than non-irradiated tissues.Increased serum IFNβconcentrations post-radiation were associated with RILD development in patients.These results delineate cGAS-STING induced type 1 interferon release in NPCs as a key mediator of IR-induced liver damage and described a mechanism of innate-immunity-driven pathology,linking cGAS-STING activation with amplification of initial radiation-induced liver injury.展开更多
Background and Aims:There are no comparative studies on the efficacy of hepatic resection(HR)and CyberKnife stereotactic body radiation therapy(CK-SBRT)plus transhepatic arterial chemotherapy embolization(TACE)in the ...Background and Aims:There are no comparative studies on the efficacy of hepatic resection(HR)and CyberKnife stereotactic body radiation therapy(CK-SBRT)plus transhepatic arterial chemotherapy embolization(TACE)in the treatment of large hepatocellular carcinoma(HCC).Therefore,this study aimed to compare the efficacy of HR and CKSBRT+TACE in large HCC.Methods:A total of one hundred and sixteen patients were selected from November 2011 to December 2016.Among them,50 were allocated to the CKSBRT+TACE group and 66 were allocated to the HR group.The Kaplan-Meier method was applied to calculate overall survival(OS)and progression-free survival(PFS)rates.Propensity score matching was performed to control for baseline differences between the groups.Results:Thirtysix paired patients were selected from the CK-SBRT+TACE and HR groups.After propensity score matching,the 1-,2-and 3-year OS rates were 83.3%,77.8%and 66.7%in the HR group and 80.6%,72.2%and 52.8%in the CKSBRT+TACE group,respectively.The 1-,2-and 3-year PFS rates were 71.6%,57.3%and 42.3%in the HR group and 66.1%,45.8%and 39.3%in the CK-SBRT+TACE group,respectively(OS:p=0.143;PFS:p=0.445).Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS.Conclusions:CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion.Moreover,the liver injury occurrence rate was acceptable in both groups.展开更多
基金supported by grants from the Project of Health Commission of Zhejiang province(2014KYA075)Natural Science Foundation of Zhejiang province(2014C33199)
文摘Background:Hepatic radiation injury severely restricts irradiation treatment for liver carcinoma.The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MRI(EOB-MRI)in the assessment of liver function after external radiation therapy and to determine the relationship between focal liver reaction(FLR)and liver function.Methods:A total of 47 patients with liver malignancies who underwent external beam radiation therapy were enrolled.EOB-MRI was performed on each patient at approximately one month post-radiotherapy.The hepatobiliary(HPB)phase images from EOB-MRI were fused with the planning CT images,and the isodose lines from the patients’treatment plans were overlaid onto the fused images.The correlation of the EOB-MR image intensity distribution with the isodose lines was studied.We also compared liver function in patients between pre-treatment and post-treatment.Results:Decreased uptake of Gd-EOB-DTPA,which was manifested by well-demarcated focal hypointensity of the liver parenchyma or FLR to high-dose radiation,was observed in the irradiated areas of 38 patients.The radiotherapy isodose line of decreased uptake area of Gd-EOB-DTPA was 30–46 Gy.The median corresponding dose curve of FLR was 34.4 Gy.Nine patients showed the absence of decreased uptake area of Gd-EOB-DTPA in the irradiated areas.Compared to the 38 patients with the presence of decreased uptake area of Gd-EOB-DTPA,9 patients with the absence of decreased uptake area of Gd-EOB-DTPA showed significant higher levels of total bile acid,total bilirubin,direct bilirubin and alpha-fetoprotein(P<0.05).There were no significant differences in alanine transaminase,aspartate aminotransferase,gamma-glutamyl transpeptidase or albumin levels between the two groups(P>0.05).Conclusions:Visible uptake of Gd-EOB-DTPA by the liver parenchyma was significantly associated with liver function parameters.EOB-MRI can be a valuable imaging biomarker for the assessment of liver parenchyma function outside of radiation area.
基金supported by the National Nature Science Foundation of China(No.81773220 and U1505229).
文摘Liver damage upon exposure to ionizing radiation(IR),whether accidental or therapeutic,can contribute to liver dysfunction.Currently,radiotherapy(RT)is used for various cancers including hepatocellular carcinoma(HCC);however,the treatment dose is limited by radiation-induced liver disease(RILD)with a high mortality rate.Furthermore,the precise molecular mechanisms of RILD remain poorly understood.Here,we investigated RILD pathogenesis using various knockout mouse strains subjected to whole-liver irradiation.We found that hepatocytes released a large quantity of double-stranded DNA(dsDNA)after irradiation.The cGAS-STING pathway in non-parenchymal cells(NPCs)was promptly activated by this dsDNA,causing interferon(IFN)-I production and release and concomitant hepatocyte damage.Genetic and pharmacological ablation of the IFN-I signaling pathway protected against RILD.Moreover,clinically irradiated human peri-HCC liver tissues exhibited substantially higher STING and IFNβexpression than non-irradiated tissues.Increased serum IFNβconcentrations post-radiation were associated with RILD development in patients.These results delineate cGAS-STING induced type 1 interferon release in NPCs as a key mediator of IR-induced liver damage and described a mechanism of innate-immunity-driven pathology,linking cGAS-STING activation with amplification of initial radiation-induced liver injury.
基金This study protocol was supported by a grant from the Beijing Municipal Science and Technology Commission Fund(Z171100001017181).
文摘Background and Aims:There are no comparative studies on the efficacy of hepatic resection(HR)and CyberKnife stereotactic body radiation therapy(CK-SBRT)plus transhepatic arterial chemotherapy embolization(TACE)in the treatment of large hepatocellular carcinoma(HCC).Therefore,this study aimed to compare the efficacy of HR and CKSBRT+TACE in large HCC.Methods:A total of one hundred and sixteen patients were selected from November 2011 to December 2016.Among them,50 were allocated to the CKSBRT+TACE group and 66 were allocated to the HR group.The Kaplan-Meier method was applied to calculate overall survival(OS)and progression-free survival(PFS)rates.Propensity score matching was performed to control for baseline differences between the groups.Results:Thirtysix paired patients were selected from the CK-SBRT+TACE and HR groups.After propensity score matching,the 1-,2-and 3-year OS rates were 83.3%,77.8%and 66.7%in the HR group and 80.6%,72.2%and 52.8%in the CKSBRT+TACE group,respectively.The 1-,2-and 3-year PFS rates were 71.6%,57.3%and 42.3%in the HR group and 66.1%,45.8%and 39.3%in the CK-SBRT+TACE group,respectively(OS:p=0.143;PFS:p=0.445).Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS.Conclusions:CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion.Moreover,the liver injury occurrence rate was acceptable in both groups.
