Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifi...Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.展开更多
AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred...AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.展开更多
AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up s...AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.展开更多
Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellu...Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.展开更多
BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infectio...BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infection and immunological rejection on bile duct injury. This study was undertaken to assess biliary tract injury caused by relative warm ischemia (secondary warm ischemia time in the biliary tract) and reperfusion. METHODS: One hundred and two rats were randomly divided into 5 groups: group I (control); groups 11 to V, relative warm ischemia times of 0 minute, 30 minutes, I hour and 2 hours. In addition to the levels of serum alkaline phosphatase, and total bilirubin, pathomorphology assessment and TUNEL assay were performed to evaluate biliary tract damage. RESULTS: Under the conditions that there were no significant differences in warm ischemia time, cold perfusion time and anhepatic phase, group comparisons showed statistically significant differences. The least injury occurred in group H (portal vein and hepatic artery reperfused simultaneously) but the most severe injury occurred in group V (biliary tract relative warm ischemia time 2 hours). CONCLUSIONS: Relative warm ischemia is one of the factors that result in bile duct injury, and the relationship between relative warm ischemia time the bile injury degree is time-dependent. Simultaneous arterial and portal reperfusion is the best choice to avoid the bile duct injury caused by relative warm ischemia. (Hepatobiliary Pancreat Dis Int 2009; 8: 247-254)展开更多
Objective: To validate multi-slice three-dimensional spiral CT cholangiography (3-D CTC) in clinical di- agnosis of biliary diseases. Methods: This study included 146 patients with bili- ary diseases, involving 73 cas...Objective: To validate multi-slice three-dimensional spiral CT cholangiography (3-D CTC) in clinical di- agnosis of biliary diseases. Methods: This study included 146 patients with bili- ary diseases, involving 73 cases of biliary tumor, 87 cases of radioparent calculus, 12 cases of post cholan- gio-jejunostomy and one case of congenital choledo- chocyst. The data of thin-slice volumetric CT scan were sent to the workstation (GE Advantage Win- dows 3. 1). Rational 3-D CTC including maximum intensity projection, minimum intensity projection, surface shaded display, CT virtual endoscopy and ray sumption was performed. The diagnostic accura- cy of 3-D CTC was compared with that of conven- tional CT, ultrasonography and endoscopic retro- grade cholangiopancreaticography (ERCP). Results: Different biliary diseases showed distinct ima- ging manifestations on 3-D CTC, As a new technique for assessing the status of post cholangio-jejunosto- my, 3-D CTC was superior to conventional CT, ul- trasonography and ERCP in diagnosis of negative bil- iary calculus, extrahepatic cholangiocarcinoma, cancer embolus of the biliary duct, carcinoma of the pancreas head and periampullar carcinoma. It was also superior to conventional CT, ultrasonography or equal to ERCP in diagnosis of hilar cholangiocarcino- ma, but inferior to conventional CT and ultrasonog- raphy in diagnosis of gallbladder cancer. Conclusion: 3-D CTC as a non-invasive and sensitive technique for the diagnosis of biliary diseases with high diagnostic accuracy will greatly increase the de- tection rate of biliary diseases.展开更多
Surgeries for benign diseases of the extrahepatic bile duct(EHBD) are classified as lithotomy(i.e., choledocholithotomy) or diversion(i.e.,choledochojejunostomy). Because of technical challenges, laparoscopic approach...Surgeries for benign diseases of the extrahepatic bile duct(EHBD) are classified as lithotomy(i.e., choledocholithotomy) or diversion(i.e.,choledochojejunostomy). Because of technical challenges, laparoscopic approaches for these surgeries have not gained worldwide popularity. The right upper quadrant of the abdomen is advantageous for laparoscopic procedures,and laparoscopic choledochojejunostomy is safe and feasible. Herein, we summarize tips and pitfalls in the actual procedures of choledocholithotomy.Laparoscopic choledocholithotomy with primary closure of the transductal incision and transcystic C-tube drainage has excellent clinical outcomes;however, emergent biliary drainage without endoscopic sphincterotomy and preoperative removal of anesthetic risk factors are required. Elastic suture should never be ligated directly on the cystic duct. Interrupted suture placement is the first choice for hemostasis near the EHBD. To prevent progressive laceration of the EHBD, full-layer interrupted sutures are placed at the upper and lower edges of the transductal incision. Cholangioscopy has only two-way operation; using dedicated forceps to atraumatically grasp the cholangioscope is important for smart maneuvering. The duration of intraoperative stone clearance accounts for most of the operative time. Moreover, dedicated forceps are an important instrument for atraumatic grasping of the cholangioscope. Damage to the cholangioscope requires expensive repair. Laparoscopic approach for choledocholithotomy involves technical difficulties. I hope this document with the visual explanation and literature review will be informative for skillful surgeons.展开更多
文摘Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.
文摘AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.
文摘AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.
基金Supported by The National Institutes of Health grants,R01 DK070195 and R01 AA12916,to Jaeschke Hthe "Training Program in Environmental Toxicology",T32 ES007079-26A2 from the National Institute of Environmental Health Sciences
文摘Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.
文摘BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infection and immunological rejection on bile duct injury. This study was undertaken to assess biliary tract injury caused by relative warm ischemia (secondary warm ischemia time in the biliary tract) and reperfusion. METHODS: One hundred and two rats were randomly divided into 5 groups: group I (control); groups 11 to V, relative warm ischemia times of 0 minute, 30 minutes, I hour and 2 hours. In addition to the levels of serum alkaline phosphatase, and total bilirubin, pathomorphology assessment and TUNEL assay were performed to evaluate biliary tract damage. RESULTS: Under the conditions that there were no significant differences in warm ischemia time, cold perfusion time and anhepatic phase, group comparisons showed statistically significant differences. The least injury occurred in group H (portal vein and hepatic artery reperfused simultaneously) but the most severe injury occurred in group V (biliary tract relative warm ischemia time 2 hours). CONCLUSIONS: Relative warm ischemia is one of the factors that result in bile duct injury, and the relationship between relative warm ischemia time the bile injury degree is time-dependent. Simultaneous arterial and portal reperfusion is the best choice to avoid the bile duct injury caused by relative warm ischemia. (Hepatobiliary Pancreat Dis Int 2009; 8: 247-254)
文摘Objective: To validate multi-slice three-dimensional spiral CT cholangiography (3-D CTC) in clinical di- agnosis of biliary diseases. Methods: This study included 146 patients with bili- ary diseases, involving 73 cases of biliary tumor, 87 cases of radioparent calculus, 12 cases of post cholan- gio-jejunostomy and one case of congenital choledo- chocyst. The data of thin-slice volumetric CT scan were sent to the workstation (GE Advantage Win- dows 3. 1). Rational 3-D CTC including maximum intensity projection, minimum intensity projection, surface shaded display, CT virtual endoscopy and ray sumption was performed. The diagnostic accura- cy of 3-D CTC was compared with that of conven- tional CT, ultrasonography and endoscopic retro- grade cholangiopancreaticography (ERCP). Results: Different biliary diseases showed distinct ima- ging manifestations on 3-D CTC, As a new technique for assessing the status of post cholangio-jejunosto- my, 3-D CTC was superior to conventional CT, ul- trasonography and ERCP in diagnosis of negative bil- iary calculus, extrahepatic cholangiocarcinoma, cancer embolus of the biliary duct, carcinoma of the pancreas head and periampullar carcinoma. It was also superior to conventional CT, ultrasonography or equal to ERCP in diagnosis of hilar cholangiocarcino- ma, but inferior to conventional CT and ultrasonog- raphy in diagnosis of gallbladder cancer. Conclusion: 3-D CTC as a non-invasive and sensitive technique for the diagnosis of biliary diseases with high diagnostic accuracy will greatly increase the de- tection rate of biliary diseases.
文摘Surgeries for benign diseases of the extrahepatic bile duct(EHBD) are classified as lithotomy(i.e., choledocholithotomy) or diversion(i.e.,choledochojejunostomy). Because of technical challenges, laparoscopic approaches for these surgeries have not gained worldwide popularity. The right upper quadrant of the abdomen is advantageous for laparoscopic procedures,and laparoscopic choledochojejunostomy is safe and feasible. Herein, we summarize tips and pitfalls in the actual procedures of choledocholithotomy.Laparoscopic choledocholithotomy with primary closure of the transductal incision and transcystic C-tube drainage has excellent clinical outcomes;however, emergent biliary drainage without endoscopic sphincterotomy and preoperative removal of anesthetic risk factors are required. Elastic suture should never be ligated directly on the cystic duct. Interrupted suture placement is the first choice for hemostasis near the EHBD. To prevent progressive laceration of the EHBD, full-layer interrupted sutures are placed at the upper and lower edges of the transductal incision. Cholangioscopy has only two-way operation; using dedicated forceps to atraumatically grasp the cholangioscope is important for smart maneuvering. The duration of intraoperative stone clearance accounts for most of the operative time. Moreover, dedicated forceps are an important instrument for atraumatic grasping of the cholangioscope. Damage to the cholangioscope requires expensive repair. Laparoscopic approach for choledocholithotomy involves technical difficulties. I hope this document with the visual explanation and literature review will be informative for skillful surgeons.
