Study on the value of serum miR-106b for the early diagnosis of hepatocellular carcinoma

AIM To investigate the short-term outcomes and risk factors indicating postoperative death of patients with lesions adjacent to the hepatocaval confluence.METHODS We retrospectively analyzed 54 consecutive patients who underwent hepatectomy combined with inferior vena cava(IVC)and/or hepatic vein reconstruction(HVR)from January 2012 to January 2016 at our liver surgery center.The patients were divided into5 groups according to the range of IVC and hepatic vein involvement.The patient details,indications for surgery,operative techniques,intra-and postoperative outcomes were compared among the 5 groups.Univariate and multivariate analyses were performed to explore factors predictive of overall operative death.RESULTS IVC replacement was carried out in 37(68.5%)patients and HVR in 17(31.5%)patients.Type I2H2 had the longest operative blood loss,operative duration and overall liver ischemic time(all,p0.05).Three patients of Type I3H1 with totally occluded IVC did not need IVC reconstruction.Total postoperative morbidity rate was40.7%(22 patients)and the operative mortality rate was 16.7%(9 patients).Factors predictive of operative death included IVC replacement(p=0.048),duration of liver ischemia(p=0.005)and preoperative liver function being Child-pugh B(p=0.025). CONCLUSION IVC replacement,duration of liver ischemia and preoperative poor liver function were risk factors predictive of postoperative death.We should be cautious about IVC replacement,especially in Type I2H2.For Type I3H1,it was unnecessary to replace IVC when the collateral circulation was established.     

Surgical management of liver diseases invading the hepatocaval confluence based on IH classification: The surgical guideline in our center

AIM To investigate the short-term outcomes and risk factors indicating postoperative death of patients with lesions adjacent to the hepatocaval confluence.METHODS We retrospectively analyzed 54 consecutive patients who underwent hepatectomy combined with inferior vena cava(IVC)and/or hepatic vein reconstruction(HVR)from January 2012 to January 2016 at our liver surgery center.The patients were divided into5 groups according to the range of IVC and hepatic vein involvement.The patient details,indications for surgery,operative techniques,intra-and postoperative outcomes were compared among the 5 groups.Univariate and multivariate analyses were performed to explore factors predictive of overall operative death.RESULTS IVC replacement was carried out in 37(68.5%)patients and HVR in 17(31.5%)patients.Type I2H2 had the longest operative blood loss,operative duration and overall liver ischemic time(all,p0.05).Three patients of Type I3H1 with totally occluded IVC did not need IVC reconstruction.Total postoperative morbidity rate was40.7%(22 patients)and the operative mortality rate was 16.7%(9 patients).Factors predictive of operative death included IVC replacement(p=0.048),duration of liver ischemia(p=0.005)and preoperative liver function being Child-pugh B(p=0.025). CONCLUSION IVC replacement,duration of liver ischemia and preoperative poor liver function were risk factors predictive of postoperative death.We should be cautious about IVC replacement,especially in Type I2H2.For Type I3H1,it was unnecessary to replace IVC when the collateral circulation was established.     

The influence of perioperative blood transfusion on intrahepatic recurrence after curative resection of hepatocellular carcinoma

OBJECTIVE: This study retrospectively evaluated the association between perioperative blood transfusion and intrahepatic recurrence in patients with hepatocellular carcinoma (HCC) who had undergone curative hepatic resections. METHODS: Hepatic resection was performed with curative intent in 195 patients with primary HCC between 1985 and 1996. Patients who had received perioperative blood transfusion (transfused group: n = 117) and those who had no perioperative blood transfusion (nontransfused group: n = 78) were compared in terms of conventional prognostic variables and cancer-free survival by the univariate and multivariate analyses. RESULTS: The 1-, 3-, and 5-yr cancer-free survival rates in the nontransfused and transfused groups were 83.4% and 67.9%, 43.0% and 36.7%, and 23.1% and 24.6%, respectively (p = 0.175). Multivariate analysis of prognostic factors in all patients revealed that vascular invasion, tumor size (> or =5 cm), and Child's class were independent factors for intrahepatic recurrence. Further analyses in various stratified groups showed that perioperative blood transfusion was an independent predictor of prognosis in HCC patients with portal vein invasion (RR: 2.8, p = 0.0038). The 1-, 3-, and 5-yr survival rates in the nontransfused and transfused groups with portal vein invasion were 71.9% and 41.6%, 54.5% and 10.9%, and 26% and 0%, respectively (p = 0.0003). CONCLUSIONS: We conclude that perioperative blood transfusions enhance the risk of intrahepatic recurrence of HCC in patients with portal vein invasion. As well, the more difficult surgery and the increased manipulation of the liver that occur in these cases create a greater possibility of tumor dissemination.     

Hepatic resection followed by IFN-alpha and 5-FU for advanced hepatocellular carcinoma with tumor thrombus in the major portal branch

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) invading the major branches of the portal vein (Vp3) is extremely poor. Recently, we reported the efficacy of combination therapy with subcutaneous interferon (IFN)-alpha and intra-arterial 5-FU for intractable HCC with Vp3. In this study, this therapy was applied for resectable advanced HCC (Vp3) as a postoperative adjuvant. METHODOLOGY: Patients with HCC and tumor thrombi either in the major or first branch of portal vein were included (n=30). Fifteen consecutive patients with HCC and Vp3 were treated with at least 3 cycles of a combination therapy consisting of continuous arterial infusion of 5-FU (300 mg/mm3/day, 5 days/week, for the initial 2 weeks) and subcutaneous injection of IFN (5 MIU, 3 times/week, 4 weeks) as a postoperative adjuvant therapy following hepatic resection. Another 15 patients who underwent hepatic resection with no IFN/5-FU chemotherapy acted as controls. RESULTS: The results were as follows in the IFN/5-FU adjuvant treatment group; disease-free survival (n=11, 5-55 months), survival with recurrence (n=2, 9, 48 months), cancer death (n=1, 18 months), death from other causes but no recurrence (n=l, 22 months). The 1-year survival rate was 100% in patients treated with IFN/5-FU, and 41% in those without IFN/5-FU historical controls (n=15). There was a significant difference in disease-free and overall survival rates between the two groups (p = 0.0033 and 0.0031). CONCLUSIONS: Combination therapy with subcutaneous IFN and intra-arterial perfusion of 5-FU seems to be a promising postoperative adjuvant treatment modality for resectable HCC with Vp3.     

Nine-year experience of doxorubicin-eluting beads chemoembolization for hepatocellular carcinoma

BACKGROUND: Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efifcacy and sur-vival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment.
METHODS: This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of com-puted tomography and serum alpha-fetoprotein (AFP). Mul-tivariate analysis was used to determine the factors affecting tumor response.
RESULTS: The median post-treatment to pre-treatment AFP level was 0.8 for a DEB session (n=258) and 1.0 for a cTACE session (n=452), showing a signiifcantly greater decrease in AFP after DEB (P<0.05). More patients in the DEB group achieved objective response (complete and partial) compared with those in the cTACE group (P<0.05). Objective tumor re-sponse after DEB vs cTACE was 34.8% vs 15.4% in 0-3 months (P=0.001), 37.1% vs 20.0% in 3-6 months (P<0.05), and 50.0%vs 30.0% in 6-12 months (P=0.093). DEB predicted a 3.604 times odds of achieving at least one objective tumor response in a patient when compared to cTACE (P<0.0001). The median survival from ifrst transcatheter therapy of patients having undergone at least once DEB was 12.53 months, while those having received cTACE only was 10.53 months (P=0.086). A tendency of improved survival appeared to maintain until >80 months after the ifrst TACE session in the DEB group.
CONCLUSION: DEB is a safe alternative to cTACE in HCC pa-tients with better therapeutic efifcacy.     

Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma

BACKGROUND/AIMS: Solitary small-sized HCCs tend to be considered as less aggressive cancer, and non-surgical treatments have recently been preferred. The aim of this study was to clarify the clinicopathological features and the prognostic factors of small-sized HCCs and to evaluate the significance of hepatic resection for them. METHODOLOGY: Eighty patients with HCC up to 2cm in diameter who had undergone hepatic resection were enrolled in this study. We investigated the clinicopathological features and evaluated the prognostic factors by univariate and multivariate analyses. RESULTS: The overall survival rates at 3, 5 and 10 years were 83%, 69% and 36%, respectively, and the corresponding disease-free survival rates were 63%, 41% and 10%. Well-differentiated, moderately differentiated and poorly differentiated HCC were detected in 29%, 65% and 6% of the patients, respectively. Furthermore, microscopic portal vein invasion (vp), hepatic vein invasion (vv) and intrahepatic metastasis (im) were positive in 15%, 4% and 10% of the patients, respectively. Multivariate analysis revealed that Child-Pugh classification (p=0.005) and vp (p=0.0008) were independent prognostic factors for survival rate and that platelet count (p=0.002) and tumor differentiation (p=0.0016) were independent prognostic factors for disease-free survival rate. CONCLUSIONS: Even solitary small-sized (up to 2cm in diameter) HCC already have the characteristics of advanced HCC. When hepatic function is well preserved, hepatic resection should be the first choice for local control, especially in cases of moderately to poorly differentiated HCC, because the frequency of microscopic vascular invasion is high.     

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein

AIM To compare the therapeutic effect andsignificances of multimodality treatment forhepatocellular carcinoma (HCC) with tumorthrombi in portal vein (PVTT).METHODS HCC patients (n=147) with tumortrombi in the main portal vein or the first branchof portal vein were divided into four groups bythe several therapeutic methods. There wereconservative treatment group in 18 out ofpatients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI)group in 18 patients (group B), in whompostoberative chemoembolization was doneperiodically; group of removal of HCC with PVTTin 79 (group C) and group of transcatheterhepatic arterial chemoembolization (TACE) orHAI and/or portal vein infusion (PVI) afteroperation in 32 (group D).RESULTS The median survival period was 12months in our series and the 1-, 3-, and 5-yearsurvival rates were 44.3%, 24.5% and 15.2%,respectively. The median survival times were 2,5, 12 and 16 months in group A, B, C and D,respectively. The 1-, 3- and 5-year survival rateswere 5.6%, 0% and 0% in group A; 23.2%,5.6% and 0% in group B; 53.9%, 26.9% and16.6% in group C; 79.3%, 38.9% and 26.8% ingroup D, respectively. Significant differenceappeared in the survival rates among the groups (P<0.05).CONCLUSION Hepatic resection with removalof tumor thrombi and HCC should increase thecurative effects and be encouraged for theprolongation of life span and quality of life forHCC patients with PVTT, whereas the besttherapeutic method for HCC with PVTT is withregional hepatic chemotherapy orchemoemblization after hepatic resection withremoval of tumor thrombi.     

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM: To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).METHODS: From April 2002 to November 2006, 92 consecutive patients with spontaneous rupture of BCLC stage A or B HCC undergoing hepatic resection were included in a case group. A control arm of 184 cases (1:2 ratio) was chosen by matching the age, sex, BCLC stage and time of admission among the 2904 consecutive patients with non-ruptured HCC undergoing hepatic resection. Histological confirmation of HCC was available for all patients and ruptured HCC was confirmed by focal discontinuity of the tumor with surrounding perihepatic hematoma observed intraoperatively. Patients with microvascular thrombus in the hepatic vein branches were excluded from the study. Clinical data and survival time were collected and analysed.RESULTS: Sixteen patients were excluded from the study based on exclusion criteria, of whom 3 were in the case group and 13 in the control group. Compared with the control group, more patients in the case group had underlying diseases of hypertension (10.1% vs 3.5%, P = 0.030) and liver cirrhosis (82.0% vs 57.9%, P < 0.001). Tumors in 67 (75.3%) patients in the case group were located in segments II, III and VI, and the figure in the control group was also 67 (39.7%) (P < 0.001). On multivariate analysis, hypertension (HR = 7.38, 95%CI: 1.91-28.58, P = 0.004), liver cirrhosis (HR = 6.04, 95%CI: 2.83-12.88, P < 0.001) and tumor location in segments II, III and VI (HR = 5.03, 95%CI: 2.70-6.37, P < 0.001) were predictive for spontaneous rupture of HCC. In the case group, the median survival time and median disease-free survival time were 12 mo (range: 1-78 mo) and 4 mo (range: 0-78 mo), respectively. The 1-, 3- and 5-year overall survival rates and disease-free survival rates were 66.3%, 23.4% and 10.1%, and 57.0%, 16.8% and 4.5%, respectively. Only radical resection remained predictive for overall survival (HR = 0.32, 95%CI: 0.08-0.61, P = 0.015) and disease-free survival (HR = 0.12, 95%CI: 0.01-0.73, P = 0.002).CONCLUSION: Tumor location, hypertension and liver cirrhosis are associated with spontaneous rupture of HCC. One-stage hepatectomy should be recommended to patients with BCLC stages A and B disease.     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.     

Predictors of hepatic venous trunk invasion and prognostic factors in patients with hepatocellular carcinomas that had come into contact with the trunk of major hepatic veins

Purpose

In this study, we tried to identify the preoperative predictors of hepatic venous trunk invasion and the prognostic factors in patients with hepatocellular carcinoma (HCC) that had come into contact with the trunk of a major hepatic vein over a distance of 1.0?cm or more.

Methods

Forty patients who had such HCCs resected were entered into this study and predictors of hepatic venous trunk invasion and prognostic factors were evaluated by univariate and multivariate analyses.

Results and Conclusions

A combined resection of the HCC and the venous trunk was performed in 29 patients. Hepatic venous trunk invasion was observed in 12 patients, including 2 with inferior vena cava tumor thrombus. A stepwise logistic regression analysis indicated that tumors larger than or equal to 7?cm in diameter and tumors showing a poorly differentiated histological grade were independent predictors of hepatic venous trunk invasion. The survival of patients without venous trunk invasion was significantly better than that for patients with venous trunk invasion (P = 0.048). A univariate analysis revealed that Child–Pugh classification B (P = 0.002), a high des-γ-carboxy prothrombin concentration (≧400?mAU/ml, P = 0.023), a large HCC (≧5.0?cm in diameter, P = 0.002), the presence of portal vein invasion (P < 0.001), the presence of venous trunk invasion (P = 0.048), the presence of intrahepatic metastasis (P < 0.001), and poorly differentiated HCC (P = 0.006) correlated with a worse overall survival after hepatic resection. In a multivariate analysis, however, only the presence of intrahepatic metastasis (P = 0.037, relative risk 8.25) was an independent predictor of poor overall survival.

Conclusions

Large tumors (≥7?cm in diameter) and poorly differentiated HCCs were more likely to be associated with hepatic venous trunk invasion and intrahepatic metastasis was an independent prognostic factor in patients with HCC that had come into contact with the trunk of a major hepatic vein.

     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Clinical outcome of esophageal varices after hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with major portal vein tumor thrombus

Aim: To analyze the clinical outcome of esophageal varices (EV) after hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombus (Vp3/4). Methods: The study subjects were 45 consecutive patients who received HAIC for HCC with Vp3/4 between January 2005 and December 2009. HAIC comprised the combination therapy of intra‐arterial 5‐FU with interferon‐α (5‐FU/IFN) in 23 patients and low‐dose cisplatin plus 5‐FU (FP) in 22. Radiotherapy (RT) was also provided in 19 patients for portal vein tumor thrombosis. Aggravation rate for EV and overall survival rate were analyzed. Results: The aggravation rates for EV were 47% and 64% at 12 and 24 months, respectively. The survival rates were 47% and 33% at 12 and 24 months, respectively. The response rates to 5‐FU/IFN and FP were 35% and 41%, while the disease control rates in these two groups were 57% and 50%, respectively. There were no significant differences in the objective response and disease control between 5‐FU/IFN and FP. Multivariate analysis identified size of EV (F2/F3) (HR = 7.554, P = 0.006) and HCC disease control (HR = 5.948, P = 0.015) as significant and independent determinants of aggravation of EV, and HCC disease control (HR = 12.233, P < 0.001), metastasis from HCC (HR = 11.469, P = 0.001), ascites (HR = 8.825, P = 0.003) and low serum albumin (HR = 4.953, P = 0.026) as determinants of overall survival. RT for portal vein tumor thrombosis tended to reduce the aggravation rate for EV in patients with these risk factors. Conclusions: Hepatocellular carcinoma disease control was the most significant and independent factor for aggravation of EV and overall survival in HCC patients with major portal vein tumor thrombosis treated with HAIC.     

Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis

OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection is higher than in patients with hepatitis B virus (HBV)-related HCC in Japan, the long-term prognosis and prognostic factors of HCV-related HCC after hepatic resection are poorly understood. METHODS: The surgical outcome of HCV-related HCC in 172 consecutive patients who underwent hepatic resection between 1989 and 1997 was retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 23.2%, and 11 patients among that group had hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median overall survivals including hospital death after surgery were 41 months and 33 months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free survival rates after hepatic resection were 33%, 20%, and 15%, respectively. Multivariate analysis revealed that serum alpha-fetoprotein (AFP) of > or = 1000 ng/ml and the presence of vascular invasion were independent unfavorable prognostic factors affecting overall survival and that AFP of > or = 1000 ng/ml was an independently significant factor of poor disease-free survival. CONCLUSIONS: We found the postresection survival of patients with HCV-related HCC should be stratified by the high value of AFP and the presence of vascular invasion. AFP may be the most powerful predictor of the long-term prognosis and recurrence in such patients.     

Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein

Background and Aim: Fucosylated alpha‐fetoprotein (AFP‐L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP‐L3 under low AFP (≤ 20 ng/mL). The aim of this study was to elucidate the role of AFP‐L3 in HCC patients with low AFP conditions. Methods: One hundred and ninety six consecutive newly developed HCC patients with low AFP (≤ 20 ng/mL) were examined for serum AFP‐L3 expression by a newly‐developed micro‐total analysis system that could stably measure AFP‐L3 in low AFP circumstances, and its clinical importance was analyzed. Results: Positivity of AFP‐L3 in HCC patients was 13.3% at a cut‐off level of 10%. Five‐year survivals of HCC patients with AFP‐L3 (< 10%) and AFP‐L3 (≥ 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des‐gamma carboxy prothrombin were observed in the high AFP‐L3 (≥ 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR] = 3.24, 95% confidence interval [CI] = 1.27–8.26), the presence of ascites (RR = 3.44, 95% CI = 1.22–9.34), multiple tumor number (RR = 3.06, 95% CI = 1.33–7.17), and high AFP‐L3 (RR = 8.36, 95% CI = 2.79–25.5) were risk factors for survival. High AFP‐L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048). Conclusions: AFP‐L3 is a strong prognostic factor for survival even in HCC patients with low AFP (≤ 20 ng/mL).     

Histological evaluation of intracapsular venous invasion for discrimination between portal and hepatic venous invasion in hepatocellular carcinoma

Background and Aim:  Histological criteria for intracapsular venous invasion (IVI) that would allow its discrimination between portal and hepatic venous invasion in hepatocellular carcinoma (HCC) have not been established.
Methods:  We evaluated IVI immunohistochemically to discriminate between portal and hepatic venous invasion in 89 resected specimens from patients with HCC. IVI was defined as the microscopic involvement of the vessels within the fibrous capsule of HCC. The hepatic venous system was subdivided into the central vein and the sublobular/hepatic vein. Immunohistochemical analysis with the D2-40 monoclonal antibody revealed lymphatic vessels.
Results:  In non-neoplastic liver tissues, the portal veins ( n  = 4355) were accompanied by lymphatic vessels (99.7%), bile ductules (100%) and arteries (96%), whereas the central veins ( n  = 3932) and sublobular/hepatic veins ( n  = 662) were rarely accompanied by lymphatic vessels (0% and 17%, respectively) and bile ductules (12% and 33%, respectively). In total, 29 IVI foci were detected; three foci were clearly visible within vessels that contained a distinct layer of connective tissue fibers, signifying sublobular/hepatic venous invasion. As the remaining 26 foci were accompanied by lymphatic vessels (26/26 [100%]), bile ductules (21/26 [81%]) and arteries (10/26 [38%]), these foci were considered to reflect intracapsular portal venous invasion rather than venous invasion of the central vein. Intracapsular portal venous invasion was significantly associated with extratumoral portal venous invasion ( P  < 0.001).
Conclusions:  D2-40 immunoreactivity for the histological evaluation of IVI in HCC allows discrimination between portal and hepatic venous invasion for cases in which portal venous invasion predominates.     

Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection:a matched study

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear.
METHODS: We compared the prognoses of 110 HCC patients without BDTT (group A) to 22 cases with BDTT (group B). The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Addi-tionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors.
RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively (P=0.043). The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gamma-glutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage III-IV was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage I-II after R0 resection (hazard ratio=6.056,P=0.014). Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage III-IV were independent risk fac-tors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection (31.0 vs 4.0 months,P=0.007).
CONCLUSIONS: R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.     

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

BACKGROUND: Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he-patocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are dififcult to differentiate by observing only their hemodynamics changes. The present study aimed to investi-gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nod-ules using CT perfusion and receiver operating characteristic (ROC) curves.
METHODS: Male Wistar rats were randomly divided into con-trol (n=20) and experimental (n=70) groups. Diethylnitrosa-mine (DEN) was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion (HPP), hepatic arterial frac-tion (HAF), hepatic arterial perfusion (HAP), hepatic blood volume (HBV), hepatic blood lfow (HBF), mean transit time (MTT) and permeability of capillary vessel surface (PS) data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats (control, pre-carcinoma and early HCC groups) using the Kruskal-Wallis test and analyzed with ROC curves. Histo-logical examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.
RESULTS: For HPP, HAF, HBV, HBF and MTT, there were signiifcant differences among the three groups (P<0.05). HAF had the highest areas under the ROC curves: 0.80 (control vs pre-carcinoma groups) and 0.95 (control vs early HCC groups) with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 (control vs pre-carcinoma groups) and 0.92 (control vs early HCC groups) with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively.
CONCLUSIONS: CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.     

Intra‐arterial 5‐fluorouracil/interferon combination therapy for hepatocellular carcinoma with portal vein tumor thrombosis and extrahepatic metastases

Background and Aims: We investigated the efficacy of intra‐arterial 5‐fluorouracil (5‐FU) and systemic interferon (IFN)‐α (5‐FU‐IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. Methods: We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non‐meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5‐FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. Results: For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non‐meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non‐meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC‐related disease. Conclusions: The efficacy of 5‐FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited.     

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.