| BackgroundPrimary hepatocellular carcinoma is one of the common malignant tumors in China. Some of the patients with HCC could be treated by surgery, which results in long term resolution of symptoms and long term survival. Nevertheless, most patients could not be candidates for surgery, because of the late diagnosis of HCC. Even after the surgery, patients with HCC seldom could achieve long term survival. With regard to hepatocellular carcinoma presented with obstructive jaundice, the reported prognosis were worse than HCC without vascular and bile duct invasion. HCC with bile duct invasion may have progressive nature of malignant tumor. Even though the HCC presented with obstructive jaundice has the similar symptoms with cholangiocarcinoma, but it is quit different from cholangiocarcinoma in pathogenesis, biological behavior, pathology, clinical manifestation, treatment and prognosis. Therefore, it is very important to identify the differential diagnosis between HCC presented with obstructive jaundice and cholangiocarcinoma.For most of the patients who diagnosed with HCC presented with obstructive jaundice, they lost the opportunity to be cured by surgical resection. In such cases, an alternative way for decompression of bile duct could be performed, for example, endoscopic or percutaneous biliary drainage. Palliative antitumor therapies may be used as the first choice.In previous study, the characteristics of the hepatocellular carcinoma presented with obstructive jaundice in pathology and biological behavior has been described. First, tumor growing within bile ducts often was not tightly adherent to the bile duct wall. The underlying ductal epithelium was well preserved microscopically. It implies that the invasion of the tumor to the bile duct was not so progressive. Second, the surgeons often found out the necrosis of tumor and blood clots in the exploration of common bile duct. The tumor thrombus could be removed easily. It is different to cholangiocarcinoma which invade bile duct wall and leads to irregular thickening of bile duct wall as stricture and distortion of bile duct lumen. Third, it could be proved directly or indirectly that HCC and bile duct tumor thrombus both are hypervascular tumor. The surgeon always found hemobilia and blood clots in the exploration of the bile duct. And, the characteristic findings of HCC and bile duct tumor thrombus were early enhancement at hepatic arterial phase and rapid washout of contrast material at portal venous phase.All the characteristics mentioned above implied that the comprehensive treatment of interventional vascular approach could be effective for the treatment of the HCC presented with obstructive jaundice. But in the past few decades, the comprehensive treatment of interventional approach to treat HCC with obstructive jaundice seldom reported. In this study, the comprehensive treatment of interventional approach includes the percutaneous transhepatic cholangial drainage using catheter and the subsequent transcatheter arterial chemoembolization. After the intrahepatic tumor and bile duct tumor thrombus were treated effectively with TACE, the biliary catheter could be removed without recurrence of obstructive jaundice after the cholangiography shows no obstruction in the lumen of bile duct. This study investigate the efficacy and safety of comprehensive treatment of interventional approach which includes percutaneous transhepatic cholangial drainage with catheter with subsequent transarterial chemoembolization in treating hepatocellular carcinoma with obstructive jaundice, and identify which factors predict the prognosis.ObjectiveTo investigate the efficacy, safety, survival and prognostic factors of comprehensive treatment of interventional approach which include percutaneous transhepatic cholangial drainage with catheter with subsequent transarterial chemoembolization in treating hepatocellular carcinoma with obstructive jaundice.Materials and methods1. Clinical application of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approachesThis retrospective study evaluated patients with hepatocellular carcinoma with obstructive jaundice between September1,2007and January31st,2013. A total of26patients underwent comprehensive and sequential treatment of OJHCC using interventional approaches. The study population consisted of22men (84.6%) and4women (15.4%), with an overall mean of49±12years of age. The coexisted liver diseases were hepatitis B (n=23,88.5%) and alcohol abuse (n=3,11.5%). There are17patients had been treated with surgery, TACE, radiofrequency ablation, systemic chemotherapy or other anti-tumor therapy before the obstructive jaundice occurred.9patients were newly diagnosed with hepatocellular carcinoma with obstructive jaundice without previous therapy. The preoperative evaluation of liver function was based on the Child-Pugh classification.23patients with Child-Pugh Class B, and3patients with Child-Pugh Class C. According to the Lau classification of hepatocellular carcinoma with obstructive jaundice, the obstruction was classified as type1and type2in12patients (46.0%), and type3in14patients (54.0%).Kaplan-Meier method was used to estimate the survival rate and median survival time and to plot the survival curve. Log-rank test was used to compare the survival curves between intervals more than30days group and intervals less than30days group. Paired t test was used to compare conjugated bilirubin and unconjugated bilirubin. Paired t test was used to compare the TBIL, AST, ALT, ALB, PT, SCr, BUN before and after PTCD. Paired t test was used to compare the above items before and after TACE. And the independent t test was used to compare the increase of TBIL three days after TACE between TBIL>100μmol/L group and TBIL<100μmol/L group.2. Analyses of efficacy and prognostic factors of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approachesThis retrospective study evaluated patients with hepatocellular carcinoma with obstructive jaundice between September1,2007and January31st,2013. The baseline patient characteristics of two groups showed no difference. A total of54patients underwent percutaneous biliary drainage with or without subsequent TACE. The study population consisted of47men (87%) and7women (13%), with an overall mean of54±12years of age. The54patients were divided into two groups. The CPTCD group consisted of30patients who were treated with percutaneous biliary drainage and supportive treatment. Another group consisted of24patients who were treated with CPTCD with subsequent TACE, and finally the biliary catheter could be removed. The coexisted liver diseases were hepatitis B (n=48,88.9%) and alcohol abuse (n=6,11.1%). There are30patients had been treated with surgery, TACE, radiofrequency ablation, systemic chemotherapy or other anti-tumor therapy before the obstructive jaundice occurred.24patients were newly diagnosed with hepatocellular carcinoma with obstructive jaundice without previous therapy. The preoperative evaluation of liver function was based on the Child-Pugh classification.46patients with Child-Pugh Class B, and8patients with Child-Pugh Class C. According to the Lau classification of hepatocellular carcinoma with obstructive jaundice, the obstruction was classified as type1and type2in23patients (42.6%), and type3in31patients (57.4%).Kaplan-Meier method was used to estimate the survival rate and median survival time and to plot the survival curve. Log-rank test was used to compare the survival curves between CPTCD group and CPTCD with subsequent TACE group. The effects of covariates on survival time, age, gender, TBIL before PTCD, Child-Pugh class, BCLC stage, type of obstruction, portal vein tumor thrombosis, tumor size, number of tumor and treatment, were assessed using Cox proportional hazards model. A log-rank analysis was performed to identify which factors predict the prognosis.Results1. Clinical application of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approaches(1)Technical success and complications of comprehensive and sequential treatment of OJHCC using interventional approachesA total of26patients underwent CPTCD and the technical success rate was100%. Among them,21patients underwent CPTCD by one catheter (2with8.5F catheter,10with10.2F catheter,9with12F),5patients underwent PTCD by two catheters (2with8.5F catheter,6with10.2F catheter,2with12F). The mean TBIL before CPTCD was345.61±121.69μmol/L. The average duration from the first drainage procedure to TACE was30.5±10.9(range9-54days). After TACE were performed, the biliary catheter was pulled out after a median of3.5months (2-27months).After CPTCD,7patients with hemobilia were observed. Three patients(38.5%) had blood clot blocked the catheter, and required an additional larger biliary catheter. Three patients with hemobilia were managed successfully by conservative treatment. One patient was treated with arterial embolization. Three patients (11.5%) with biliary infection and bacteremia, they were cultured with two cases of Escherichia coli and one with Enterococcus faecalis.The average number of TACE during the follow-up period was3(range2-7). The volume of lipiodol used in TACE ranged from8to20ml. A total of36times of percutaneous ablation were performed in26patients. The volume of lipiodol used in percutaneous ablation ranged from3to10ml. The mean TBIL before TACE was76.5±37.8μmol/L. The mean TBIL increased to91.6±41.6μmol/L3days after TACE. The median concentration of AFP was decreased from4221.85ug/L to120.65 ug/L.The concentration of AFP after TACE was significantly lower than AFP before TACE (P<0.05, mean of17463±29017ug/L). The values of TBIL, AST, ALT and PT after TACE were significantly higher than the values before TACE. There was no significant difference between SCr and BUN three days after TACE. There was no significant difference in the increase of TBIL, AST, ALT, PT, SCr, BUN three days after TACE between TBIL>100μmol/L group and TBIL<100μmol/L group.26patients underwent a total of81times of TACE and36times of percutaneous lipiodol emulsion injection.77times of fervescence (95.1%), the temperature ranged from37.3℃to41.0℃. The fervescence lasted for2-6days. Nausea, vomiting and anorexia, gastrointestinal reaction occurred for46cases after TACE (61.8%), pain were observed in71cases after TACE(87.7%),81cases of postoperative injury of liver function (100%)were observed. All symptoms discussed above were managed by conservative treatment.(2) Survival of OJHCC patientsComplete response (CR) occurred in three patients. Partial response (PR) occurred in thirteen patients. Stable disease (SD) occurred in three patients. Progressive disease (PD) occurred in seven patients. The median survival time was16months (range from7to78months).The1-year survival rate after were77.9%.19patients reached the end point before January31st,2014, including eight patients died of hepatic encephalopathy, six patients died of upper gastrointestinal bleeding, three patients died of infectious, one patient died of hepatic failure and one patient died of heart failure. Seven patients are still alive. During the follow up, tumor progression were found in three patients and another four patients were still tumor free survived.The survival time was significantly different between intervals more than30days group and intervals less than30days group (P<0.01).The median survival time in intervals less than30days group was significantly longer than intervals more than30days group.(17months, IQR:12.9-21.1versus14months, IQR:12.1-15.9; P=0.025) 2. Analyses of efficacy and prognostic factors of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approaches(1) Technical success of comprehensive and sequential treatment of OJHCC using interventional approachesA total of54patients underwent percutaneous transhepatic cholangial drainage and the technical success rate was100%.24patients who were treated with percutaneous transhepatic cholangial drainage with catheter with subsequent transarterial chemoembolization underwent a total of76TACE. After the Percutaneous transhepatic cholangial drainage,13patients with hemobilia were observed in13of a total of54patients. Five patients (38.5%) had blood clot blocked the catheter, and required an additional larger biliary catheter. The remaining patients with hemobilia were managed successfully by conservative treatment. Six patients (11.1%) with biliary infection and bacteremia,5patients were cultured with4cases of Escherichia coli and1with Enterococcus faecalis.In CPTCD with subsequent TACE group,24patients underwent a total of76times of TACE.73patients with fervescence (96.1%), the temperature ranged from37.3℃to41.0℃, average temperature was38.5±1.02℃.The fervescence lasted for2-6days. Nausea, vomiting and anorexia, gastrointestinal reaction occurred in47cases after TACE (61.8%), pain were observed in69cases after TACE(90.8%),76cases of postoperative injury of liver function (100%)were observed. All the symptom discussed above were managed by conservative treatment.(2) Survival analysis44patients reached the end point before January31st,2014. In PTCD group, eleven patients died of hepatic encephalopathy, eight patients died of upper gastrointestinal bleeding, two patients died of infectious. In CPTCD with TACE group, seven patients died of hepatic encephalopathy, six patients died of upper gastrointestinal bleeding, two patients died of infectious, one patient died of hepatic failure and one patient died of heart failure. Ten patients are still alive. During the follow up, tumor progression were found in five patients and another five patients were still tumor free survived. Seven patients are still alive.The survival time was significantly different between two groups (P<0.01).The median survival time in CPTCD with subsequent TACE group was significantly longer than PTCD group.(16months, IQR:12.7-19.3versus4months, IQR:3.2-4.8; P<0.01) The1-,3-year survival rates after in CPTCD with subsequent TACE were77.9%and11.2%.(3) Prognostic factors associated with survival in hepatocellular carcinoma with obstructive jaundice using Cox proportional hazards regression.Clinical characteristics in54patients were used as covariant, age, gender, TBIL before PTCD, Child-Pugh class, BCLC stage, type of obstruction, portal vein tumor thrombosis, tumor size, number of tumor and treatment. Survival time was used as dependent variable. The multivariate analysis showed that TACE (P<0.001, HR=75.301),BCLC stage(P=0.043, HR=1.744) tumor size(P<0.001, HR=3.414) and portal vein tumor thrombosis (P=0.033, HR=2.050), which are known as prognostic factors, were associated with shorter survival.Conclusions1. Clinical application of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approachesIn this study, the application of Comprehensive Treatment of Interventional approach which includes percutaneous transhepatic cholangial drainage with catheter with subsequent transarterial chemoembolization in hepatocellular carcinoma with obstructive jaundice has been presented. After effective biliary drainage, the intrahepatic tumor or the bile duct tumor thrombus could be treated with subsequent TACE. The decrease in tumor size and necrosis of the bile duct tumor thrombus allows the pulling out of the biliary catheter without the recurrence of obstructive jaundice. The cholangiography shows the obstructed lumen of the bile duct could reopen. We can concluded as follow.(1) In this study, PTCD using catheter was mainly used for rapid decrease of TBIL.(2) It is not necessary to wait for the serum total bilirubin decreased to the normal level in patients with obstructive jaundice caused by hepatocellular carcinoma. It is still be safe to perform TACE even the TBIL reached to100μmol/L.(3)The comprehensive treatment mainly using TACE was effective for OJHCC.(4)In the patients who were treated with subsequent transarterial chemoembolization, the decrease in tumor size and necrosis of the bile duct tumor thrombus allows the removal of the biliary catheter without the recurrence of obstructive jaundice during the follow up.2. Analyses of efficacy and prognostic factors of comprehensive and sequential treatment of hepatocellular carcinoma with obstructive jaundice using interventional approachesThe multivariate analysis showed that TACE, BCLC stage, tumor size and portal vein tumor thrombosis, which are known as prognostic factors, were associated with shorter survival. |
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