Objective:To establish a new classification of biliary tumor thrombus(BTT).Methods:Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging ...Objective:To establish a new classification of biliary tumor thrombus(BTT).Methods:Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging systems.Univariate and multivariate analyses were used to determine factors affecting the overall survival(OS)to form the basis of our new classification for BTT.Results:All 6 international staging systems showed overlapping survival curves.Univariate followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of OS.Based on these data,a new BTT classification was defined as:TypeⅠ:intrahepatic BTT;and TypeⅡ:extrahepatic BTT involving a common bile duct or common hepatic duct.TypeⅠwas further subdivided into type Ia:BTT involving a second-order intrahepatic duct or above,and type Ib:BTT involving a first-order intrahepatic duct.TypeⅡwas further subdivided into typeⅡa and typeⅡb using a cut-off total bilirubin(TB)>300μmol/L.The numbers(percentages)of patients with typesⅠandⅡBTT were 69(34.2%)and 133(65.8%),respectively.The median OS of typeⅠpatients was significantly higher than that of typeⅡpatients(37.5 months vs.23.2 months;P=0.002).Using subgroup analyses,OS outcomes were significantly different between the subgroups of typeⅡb and type IIa,although there was no significant difference between the type Ia and type Ib subgroups(P=0.07).Conclusions:A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.展开更多
In the United States,80%-90%of primary hepatic tumors are hepatocellular carcinomas and 10%-15%are cholangiocarcinomas(CCA),both with high mortality rate,particularly CCA,which portends a worse prognosis.Traditional m...In the United States,80%-90%of primary hepatic tumors are hepatocellular carcinomas and 10%-15%are cholangiocarcinomas(CCA),both with high mortality rate,particularly CCA,which portends a worse prognosis.Traditional management with surgery has good outcomes in appropriately selected patients;however,novel ablative treatment options have emerged,such as radiofrequency ablation(RFA),which can improve the prognosis of both hepatic and biliary tumors.RFA is aimed to generate an area of necrosis within the targeted tissue by applying thermal therapy via an electrode,with a goal to completely eradicate the tumor while preserving surrounding healthy tissue.Role of RFA in management of hepatic and biliary tumors forms the focus of our current mini-review article.展开更多
Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced b...Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced biliary tumor disease were enrolled.They were divided into groups according to the order of admission,with 40 cases in each group.The control group received oxaliplatin combined with gemcitabine,and the experimental group received oxaliplatin combined with tiggio.Incidence of adverse reactions,time to disease progression,survival time and clinical efficacy were checked and assessed.Results:Compared with the incidence of adverse reaction of the experimental group,which was 5.00%(2/40),the incidence of adverse reaction of the control group was 25.00%(10/40).The chi-square value=6.2745,p-value=0.0122.The time to progression and survival time of patients in the experimental group were shorter than those of the control group,with significant differences between the groups(p<0.05);the clinical efficacy of the experimental group and the control group were 97.50%(39/40)and 77.50%(31/40)respectively,the comparative chi-square value=7.3143,p-value=0.0068.Conclusion:The combined treatment of oxaliplatin and Tiggio in the treatment of advanced biliary tract tumors has higher safety and reduces the incidence of adverse reactions.展开更多
Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage ...Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction： obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU （response rate 20%） and gemcitabine （response rate of 13%-60%）, so they have been selected for further development in multiple phase II clinical trials to explore their efficacy and safety in combination with other agents. In a phase III clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.展开更多
Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or co...Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.展开更多
Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory nature.Thus,the development of a model for effective drug screening is urgently needed.As the established therapeutic testing models ...Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory nature.Thus,the development of a model for effective drug screening is urgently needed.As the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug screening.Specifically,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural control.Interestingly,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo configuration.Over 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)monoculture.Further screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional hepatocytes.This study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.展开更多
Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor progno...Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.展开更多
Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic...Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).展开更多
基金supported by grants from Youth Project of Shanghai Municipal Health Commission(Grant No.20184Y0153)the Shanghai Young Physicians Training Program(Grant No.2018-15)+3 种基金the Medical Innovation Project of Health and Family Planning Commission of Fujian Province(Grant No.2018-CX-8)the Key Project of Natural Science Foundation of China(Grant No.81730097)a grant from the Science Fund for Creative Research Groups(Grant No.81521091)the National Natural Science Foundation of China(Grant Nos.81602523 and 81702335)。
文摘Objective:To establish a new classification of biliary tumor thrombus(BTT).Methods:Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging systems.Univariate and multivariate analyses were used to determine factors affecting the overall survival(OS)to form the basis of our new classification for BTT.Results:All 6 international staging systems showed overlapping survival curves.Univariate followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of OS.Based on these data,a new BTT classification was defined as:TypeⅠ:intrahepatic BTT;and TypeⅡ:extrahepatic BTT involving a common bile duct or common hepatic duct.TypeⅠwas further subdivided into type Ia:BTT involving a second-order intrahepatic duct or above,and type Ib:BTT involving a first-order intrahepatic duct.TypeⅡwas further subdivided into typeⅡa and typeⅡb using a cut-off total bilirubin(TB)>300μmol/L.The numbers(percentages)of patients with typesⅠandⅡBTT were 69(34.2%)and 133(65.8%),respectively.The median OS of typeⅠpatients was significantly higher than that of typeⅡpatients(37.5 months vs.23.2 months;P=0.002).Using subgroup analyses,OS outcomes were significantly different between the subgroups of typeⅡb and type IIa,although there was no significant difference between the type Ia and type Ib subgroups(P=0.07).Conclusions:A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.
文摘In the United States,80%-90%of primary hepatic tumors are hepatocellular carcinomas and 10%-15%are cholangiocarcinomas(CCA),both with high mortality rate,particularly CCA,which portends a worse prognosis.Traditional management with surgery has good outcomes in appropriately selected patients;however,novel ablative treatment options have emerged,such as radiofrequency ablation(RFA),which can improve the prognosis of both hepatic and biliary tumors.RFA is aimed to generate an area of necrosis within the targeted tissue by applying thermal therapy via an electrode,with a goal to completely eradicate the tumor while preserving surrounding healthy tissue.Role of RFA in management of hepatic and biliary tumors forms the focus of our current mini-review article.
文摘Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced biliary tumor disease were enrolled.They were divided into groups according to the order of admission,with 40 cases in each group.The control group received oxaliplatin combined with gemcitabine,and the experimental group received oxaliplatin combined with tiggio.Incidence of adverse reactions,time to disease progression,survival time and clinical efficacy were checked and assessed.Results:Compared with the incidence of adverse reaction of the experimental group,which was 5.00%(2/40),the incidence of adverse reaction of the control group was 25.00%(10/40).The chi-square value=6.2745,p-value=0.0122.The time to progression and survival time of patients in the experimental group were shorter than those of the control group,with significant differences between the groups(p<0.05);the clinical efficacy of the experimental group and the control group were 97.50%(39/40)and 77.50%(31/40)respectively,the comparative chi-square value=7.3143,p-value=0.0068.Conclusion:The combined treatment of oxaliplatin and Tiggio in the treatment of advanced biliary tract tumors has higher safety and reduces the incidence of adverse reactions.
文摘Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction： obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU （response rate 20%） and gemcitabine （response rate of 13%-60%）, so they have been selected for further development in multiple phase II clinical trials to explore their efficacy and safety in combination with other agents. In a phase III clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.
文摘Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.
文摘Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory nature.Thus,the development of a model for effective drug screening is urgently needed.As the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug screening.Specifically,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural control.Interestingly,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo configuration.Over 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)monoculture.Further screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional hepatocytes.This study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.
文摘Cholangiocarcinoma(CCA)are a heterogeneous group of tumors in terms of aetiology,natural history,morphological subtypes,molecular alterations and management,but all sharing complex diagnosis,management,and poor prognosis.Several mutated genes and epigenetic changes have been detected in CCA,with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets.Accessing tumoral components and genetic material is therefore crucial for the diagnosis,management and selection of targeted therapies;but sampling tumor tissue,when possible,is often risky and difficult to be repeated at different time points.Liquid biopsy(LB)represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples.Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated,allowing a real-time monitoring of the tumor genetic profile or the response to therapy.In this review,we analysis the current evidence on the possible roles of LB(circulating DNA,circulating RNA,exosomes,cytokines)in the diagnosis and management of patients affected by CCA.
文摘Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).
