Yung Sang Lee

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.

Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma.

Background Bile duct injuries after transarterial chemoembolization (TACE) have been reported; however, the exact pathogenic mechanisms and clinical implications of the injuries remain to be clarified. Study A total of 950 consecutive patients with hepatocellular carcinoma (HCC) were studied. Among them, 807 were treated with TACE and the remaining 143 were treated with transarterial chemoinfusion (TACI) of cisplatin. Results None of 143 patients with HCC treated with TACI were found to have any radiographic evidence of biliary injury. In contrast, of the 807 patients treated with TACE, 17 (2%) developed biliary complications. Of all complications, 12 (71%) were subcapsular bilomas; 3 (17%), focal strictures of the common hepatic duct or common bile duct; and 2 (12%), diffuse mild dilatation of the intrahepatic bile ducts. Interestingly, 2 of the 12 bilomas were found in the lobe that was not embolized with gelatin sponge particles. The median numbers of TACE tended to be greater in the patients with focal stricture than in those with bilomas (6.0 vs. 2.5;p = 0.08). All 3 patients with focal strictures and 4 of the 12 patients with bilomas had associated serious bacterial infections at presentation. Conclusions Bilomas seem to be caused by iodized oil rather than gelatin sponge particles; focal strictures of large bile ducts seem to be caused by gelatin sponge particles. We suggest that adjustments in the amounts of iodized oil or gelatin sponge particles and in the sites of embolization may reduce ischemic biliary injuries after TACE.

Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization1

Background and Aims: The aim of this study was: (i) to define the characteristics of hepatocellular carcinoma (HCC) associated with recurrences following initial remission by transcatheter arterial chemoembolization (TACE); (ii) to evaluate the patterns of recurrences; and (iii) find a better surveillance method of detecting recurrent HCC.

Nodular regenerative hyperplasia of the liver in Budd–Chiari syndrome: CT and MR features

We report the imaging findings of spiral computed tomography (CT), magnetic resonance (MR) imaging, and MR angiography in a patient with nodular regenerative hyperplasia of the liver associated with Budd–Chiari syndrome. Spiral CT showed multiple enhancing nodules during the hepatic arterial and portal venous phases. MR images showed multiple hyperintense nodules on T1-weighted images and hypointense or isointense nodules on T2-weighted images. MR angiography showed thrombotic occlusion of three hepatic veins, suggesting Budd–Chiari syndrome.

Close correlation of p53 mutation to microvascular invasion in hepatocellular carcinoma.

Mutation of p53 is a poor prognostic indicator of hepatocellular carcinoma (HCC). Although poor histologic differentiation of HCC has been associated with p53 mutations, the exact reasons for unfavorable clinical outcomes in patients with HCC remain to be clarified. In this study, we evaluate the association between p53 mutation and histopathologic features of HCCs, as well as tumor recurrences and survival. We examined 20 HCCs and surrounding liver tissues from patients who underwent surgical resection, and we performed direct sequencing of p53 gene. p53 mutations were found in 9 of 20 HCCs; none were found in the surrounding liver tissue. p53 mutations were frequent in large, multinodular, and poorly differentiated HCCs. Five of 9 with p53 mutation (in contrast, none of 11 with wild-type mutation) showed microvascular invasions. Hepatocellular carcinoma recurred in 6 of 9 with p53 mutation, in contrast to only 2 of 11 with wild-type mutation. The 1-year survival rate with p53 mutation was significantly lower than that with wild-type. In conclusion, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions, which may result in micrometastasis, followed by frequent recurrences.

Lens culinaris agglutinin-reactive alpha-fetoprotein as a prognostic marker in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization

Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is known to be a useful marker for the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that positive AFP-L3 results after treatment predicts tumor recurrence and poor clinical outcome. This study was to evaluate the role of pretreatment AFP-L3 as a prognostic marker for response to transcatheter arterial chemoembolization (TACE) and survival in patients with HCC. Forty-six patients with HCC who underwent TACE were analyzed. Agglutinin-reactive AFP was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting. Agglutinin-reactive AFP results larger than 24.4% were considered to be positive. Agglutinin-reactive AFP fractions were positive in 32 patients. Agglutinin-reactive AFP-positive patients had poorer performance status, larger tumors, frequent portal vein thrombosis, and higher levels of serum AFP. The partial response rate to TACE was lower in AFP-L3–positive patients than in AFP-L3–negative ones (37.5% vs. 78.6%, p = 0.01). Tumor size and AFP-L3 were two independent predictive factors for response to TACE. The 2-year survival rate was lower in AFP-L3–positive patients than in AFP-L3–negative ones (21.2% vs. 78.6%, p = 0.01). Child-Pugh class, AFP-L3, the presence of portal vein thrombosis, and response to TACE were independent prognostic factors for survival. In conclusion, pretreatment status of AFP-L3 could be considered a useful marker for predicting clinical outcome in patients with HCC who underwent TACE.

Characteristic clinical features of hepatocellular carcinoma associated with Budd-Chiari syndrome: evidence of different carcinogenic process from hepatitis B virus-associated hepatocellular carcinoma.

Objective Budd–Chiari syndrome (BCS) is a known risk factor for hepatocellular carcinoma (HCC). Considering the pathophysiological mechanism of BCS, BCS-associated HCC may have a different carcinogenic process to hepatitis B virus (HBV)-associated HCC, resulting in different characteristic clinical features. Methods The clinical, radiological and histopathological characteristics of 15 HCCs associated with BCS were analysed and compared with 211 HBV-associated HCCs. Results HCC associated with BCS showed a female predominance in contrast to a male predominance in HCC associated with HBV infection. Child classes of BCS-associated HCC patients were not different from the classes of HBV-associated HCC. BCS tended to be associated with the single nodular type of HCC. Only one BCS-associated HCC patient had portal vein invasion at the time of diagnosis, compared with 96 patients with HBV-associated HCC. No HCC patients with BCS showed biliary invasion, compared with 47 HBV-associated HCC patients. The median survival period of HCC patients associated with BCS was 58 months, which was much longer than the median survival period of 10 months in HBV-associated HCC. All of the three BCS-associated HCCs available for histological examination were well differentiated. Conclusions Patients with HCC associated with BCS seemed to survive for much longer periods than those with HBV due to the low invasiveness of the tumour. Such unique clinical features may be evidence of different carcinogenic processes in BCS-associated and HBV-associated HCC.

Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine.

Fibrosing cholestatic hepatitis (FCH) is a rare and extremely severe form of hepatitis B virus (HBV) infection. This condition was originally described in HBV‐infected recipients after a liver transplantation. Recently, FCH has been reported not only in liver transplant recipients, but also in other immunosuppressed patients. It is characterized clinically by cholestatic hepatic dysfunction, and pathologically by severe periportal fibrosis, cholestasis, widespread balloon degeneration of hepatocytes, and only a mild infiltration of inflammatory cells. Without treatment, FCH is universally fatal within a few months of diagnosis. There have been only two isolated case reports of FCH with long‐term patient survival, and one case report with treatment failure after lamivudine therapy. Because of the rarity of this clinical entity, the therapeutic efficacy of lamivudine in patients with FCH cannot be evaluated systematically. Here, we present four patients with HBV‐related FCH treated with lamivudine. One received antineoplastic therapy for acute lymphoblastic leukemia, and the other three were renal graft recipients. Two patients who developed FCH after a renal transplantation survived with an improvement in liver function and were followed up for 20 and 30 months, respectively, and were found to be in good health. However, the other two patients died of sepsis, possibly as a consequence of the immunosuppression with hepatic failure despite lamivudine treatment. Our experience suggests that lamivudine can alter the grave natural history of FCH.

Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using 18F-FDG PET/CT

This study aimed to evaluate the metabolic characteristics of lipiodolized hepatocellular carcinomas (HCCs) and the diagnostic accuracy of 18F-FDG PET/CT in assessing the viability of lipiodolized HCCs. Methods: Thirty-six patients (age range, 32–73 y) with 38 lipiodolized HCCs who had undergone transcatheter arterial chemoembolization (TACE) with lipiodol before 18F-FDG PET/CT (2–434 d) and 55 patients (age range, 36–77 y) with 57 treatment-naïve HCCs who had not been treated with TACE were retrospectively studied. All patients underwent hepatic lobectomy or transplantation within 1 mo after PET/CT and multiphasic contrast-enhanced CT. 18F-FDG uptake by lipiodolized and naïve HCCs was compared and correlated with tumor size, pathologic grade, serum α-fetoprotein (AFP) concentration, and time interval between TACE and PET/CT. The diagnostic accuracy of PET/CT and contrast-enhanced CT in evaluating the viability of lipiodolized HCC was compared. Results: Histologic examination showed 30 viable and 8 nonviable lipiodolized HCCs. Of the 30 viable tumors, 19 showed increased, 10 similar, and 1 decreased 18F-FDG uptake. Of the 8 nonviable HCCs, 3 showed increased and 5 decreased 18F-FDG uptake. Uptake by viable lipiodolized HCCs was correlated with tumor size (P < 0.05) but not correlated with pathologic grade, AFP concentration, or interval between TACE and PET/CT. In contrast, 18F-FDG uptake by naïve HCCs was significantly correlated with tumor size and pathologic grade (P < 0.05 for each comparison). When lipiodolized HCCs with 18F-FDG uptake that was greater than or similar to that in the surrounding normal liver were considered viable, the diagnostic sensitivity of PET/CT and contrast-enhanced CT in the early postembolic period (<3 mo) was 100% and 94%, respectively, and that in the late postembolic period was 93% and 79%, respectively. The specificity of 18F-FDG PET/CT and contrast-enhanced CT was 63% and 100%, respectively, in the acute period. Three viable lipiodolized HCCs with high AFP concentration were true-positives on PET/CT but false-negatives on contrast-enhanced CT images. Conclusion: After TACE, 18F-FDG uptake in lipiodolized HCCs was not correlated with pathologic grade, in contrast to uptake in treatment-naïve HCCs. 18F-FDG PET/CT showed a high diagnostic sensitivity in assessing the viability of lipiodolized HCCs, with moderate specificity. This method may be useful in determining the viability of lipiodolized HCCs in patients with increased serum AFP concentration or normal results on contrast-enhanced CT images.

Clinical Implications of Arrest-Defective Protein 1 Expression in Hepatocellular Carcinoma: A Novel Predictor of Microvascular Invasion

Objective: The associations between arrest-defective protein 1 (ARD1) gene expression and the clinicopathological characteristics and clinical outcomes of 94 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) were investigated. Methods: ARD1 mRNA levels in HCC and corresponding non-cancerous tissues were quantified by real-time PCR. The gene expression of the tumor relative to that in the non-tumor tissues was calculated using the 2–ΔΔCT method. The subjects were classified into high expression (2–ΔΔCT > 1, n = 38) and low expression (2–ΔΔCT ≤ 1, n = 56) groups. Results: The HCCs did not differ from matched liver tissues in terms of ARD1 mRNA levels. The high expression group had more often microvascular invasion than the low expression group (32 vs. 14%; p = 0.045). The two groups did not differ significantly in terms of other patient or tumor variables. The median follow-up period was 92.1 months. The 5-year recurrence-free and overall survival rates were 34 and 76% for the high expression group, respectively, which were similar to the rates of the low expression group (46 vs. 73%, p = 0.98 and p = 0.52, respectively). Conclusions: Intratumoral ARD1 mRNA overexpression was involved in the microvascular invasion process in patients with HCC, although it did not associate strongly with postresectional outcomes.