De novo Hepatocellular Carcinoma after Liver Transplantation

Liver transplantation is the definitive therapy for patients with advanced liver disease and its complications. Patients who are transplanted with a diagnosis of hepatocellular carcinoma (HCC) are at risk of recurrent cancer, and these patients are monitored on a regular basis for recurrence. In contrast, de novo HCC following liver transplantation is a very rare complication, and recipients without HCC at the time of transplantation are not screened. We describe the clinical features of de novo HCC over a decade after achieving a sustained viral response with treatment of hepatitis C and two decades after liver transplantation. Our case highlights the necessity of screening for HCC in the post-transplant patient with advanced liver disease even after viral clearance.     

Combined Transcatheter Arterial Embolization and Expanded Liver Resection for Hepatocellular Carcinoma with Multiple Intrahepatic Metastasis

After repeated transcatheter arterial embolization, a patient with hepatocellular carcinoma with multiple intrahepatic metastases in the entire lobe was successfully treated by extended right lobectomy with resection of the retrohepatic inferior vena cava under extracorporeal venovenous bypass.     

Transcatheter Arterial Embolization for Spontaneous Rupture of Hepatocellular Carcinoma

For the last 6 yr, we had 47 cases of spontaneous rupture of hepatocellular carcinoma causing hemorrhage into the peritoneal cavity. Thirty-three cases were treated by supportive care and 14 cases by emergency transcatheter arterial embolization. Fourteen cases underwent emergency transcatheter arterial embolization and abdominal pain developed in 71.4%, shock in 50.0% and bloody ascites in all cases and the hematocrit of bloody ascites ranged between 1.0% and 40%. On hepatic angiogram, the mean tumor extent rate was 47.9% and the extravasation of the contrast material was noted in 35.7%. The mean survival time of 14 cases that underwent emergency transcatheter arterial embolization was 98.5 days and 13.0 days in 33 cases with supportive care. The former was significantly longer than the latter.     

Clinical Course and Survival after Liver Transplantation for Hepatitis B Virus Infection Complicated by Hepatocellular Carcinoma

Objectives and Methods : The outcome after liver transplantation for HBsAg-positive liver disease complicated by hepatocellular carcinoma is not clearly defined, and in the present study we analyzed the clinical course in 39 patients transplanted for hepatitis B virus (HBV)-re-lated liver disease (group 1) compared with 16 patients with chronic HBV and hepatocellular carcinoma (group 2) and 52 patients with primary hepatocellular carcinoma seronegative for HBsAg (group 3). Results : Despite similar pretransplant viral serology, HBV recurred more often in patients with tumor (group 2) than in nontumor cases (group 1), with 1-yr actuarial cumulative reinfection rates of 85.4% versus 65.0%, respectively ( p < 0.05). In group 2 cases, we observed a more aggressive pattern of HBV-related graft injury with a higher frequency of graft loss (56.3% vs . 12.8%, p < 0.001). Long-term outcome was worse in the group 2 cases, with 5-yr actuarial survival rates of 16.7% compared with 73.2% and 28.2% for groups 1 and 3, respectively. In group 2, recurrence of HBV in the graft, rather than tumor recurrence, was the principal cause of the high mortality observed (56.2% vs. 12.5%), which, in some cases, may have been potentiated by adjuvant chemotherapy. Conclusion : The poor outcome of patients transplanted for HBsAg-positive cirrhosis and hepatocellular carcinoma is due to HBV reinfection of the graft, rather than tumor recurrence. Antiviral agents in association with hepatitis B immunoglobulin would be the most promising approach to improving survival in this patient population.     

Doxorubicin-loaded Drug-eluting beads Versus Conventional Transarterial Chemoembolization for Nonresectable Hepatocellular Carcinoma

Background/Aims:To compare the efficacy and safety profile of doxorubicin-loaded drug-eluting beads (DEB) to the conventional TACE (C-TACE) in the management of nonresectable hepatocellular carcinoma (HCC).Results:Thirty-five patients (51 procedures) in the DEB-TACE group and 19 patients (25 procedures) in the c-TACE group were included in the analysis. The median follow up time was 61 days (range 24–538 days) in the DEB-TACE group and 86 days (range 3–152 days) for the c-TACE group patients. Complete response (CR), objective response (OR), disease control (DC), and progressive disease (PD) rates were 11%, 24%, 53%, and 47%, respectively, in the DEB = TACE group compared with 4%, 32%, 64%, and 36%, respectively, in the c-TACE group. Mean ALT change from baseline was minimal in the DEB-TACE patients compared with c-TACE group (7.2 vs 79.4 units, P = 0.001). Hospital stay was significantly shorter in the DEB-TACE group (7.8 days vs 11.4 days; P = 0.038). The 2-year survival rate was 60% for the c-TACE patients and 58% for the DEB-TACE (P = 0.4).Conclusions:DEB-TACE compared with c-TACE is associated with lesser liver toxicity benefit, better tolerance, and shorter hospital stay. The two modalities however had similar survival and efficacy benefits.     

Hepatocellular Carcinoma Simulating Amebic Liver Abscess: Report of a Case and Analysis of Current Diagnostic Methods

Radiological and serological tests are valuable tools commonly used in diagnosing amebic liver abscess. The limitations in sensitivity and specificity of the various imaging procedures should be recognized in order to avoid misinterpretation of test results. Serodiagnostic methods present potential pitfalls primarily because of their frequent inability to differentiate previous disease from active infection, and must therefore be interpreted carefully.     

Transarterial Therapy: An Evolving Treatment Modality of Hepatocellular Carcinoma

Liver cancer is the fifth most common cancer in men, the seventh most common in women, and the third most common cause of death from cancer worldwide. Only 30-40% of liver cancer patients present early enough to undergo curative treatments such as surgery or liver transplantation. Local treatment with radiofrequency ablation or ethanol injection is often reserved for non-surgical candidates with early stages of disease. Transarterial embolization has become a widely accepted treatment for asymptomatic patients with unresectable lesions. This review discusses in details the three major forms of transarterial therapies: Bland embolization, chemoembolization, and radioembolization.     

Chemo-embolization for Unresectable Hepatocellular Carcinoma with Different Sizes of Embolization Particles

The purpose of this study was to evaluate the size responses and vascular responses to three different sizes of Embosphere (EMBS) embolization particles used for chemo-embolization in patients with unresectable hepatocellular carcinoma (HCC). Forty-seven patients with biopsy proven HCC treated with TACE using EMBS (Biosphere Medical, Rockland, MA, USA) were included in this study. EMBS are non-resorbable tris-acryl gelatin defined-size microspheres. Sixteen patients were treated with 40–120 micron (40-μm), 13 patients with 100–300 (100-μm), and 18 patients with 300–500 (300-μm) EMBS particles. We measured the two-dimensional area and vascularity of the tumor index lesion on initial and subsequent CTs after treatment. Lesions were classified into four grades based on the degree of vascularity measured in 25% increments. Size of tumor after one treatment decreased by an average (avg) of 18% for 40–120-μm particles, 38% for 100–300-μm particles, and 17% for 300–500-μm particles. After three treatments, size decreased by an avg of 46% for 40–120-μm particles, 76% for 100–300-μm particles, and 46% for 300–500-μm particles. Vascularity decrease was also measured after the first and third treatments, and defined as a decrease of one or more grades in tumor vascularity. Results were as follows (% of patients with decrease). For 40–120-μm particles: 1 and 3 treatments, 53% and 88% of patients. For 100–300-μm particles: 1 and 3 treatments, 60% and 88% of patients. For 300–500-μm particles: 1 and 3 treatments, 50% and 57% of patients. It was concluded the 100–300-μm EMBS particles produce slightly higher responses.     

Hepatocellular Carcinoma: A Multivariate Analysis of Prognostic Features in Patients Treated with Hepatic Arterial Embolization

The prognosis after hepatic arterial chemoembolization was retrospectively analyzed in relation to therapeutic modalities, stage of tumor, and degree of liver cirrhosis in 150 patients with solitary tumors of hepatocellular carcinoma. The analyses of life-table methods revealed that adjunct hepatectomy, tumor size, bilirubin, albumin, globulin, and the 15-min retention rate of indocyanine green are statistically significant prognostic factors for hepatic arterial chemoembolization. Results of Cox's proportional hazard analyses disclosed that adjunct hepatectomy (p = 0.0001), serum albumin level (p = 0.0032), and stage of tumor (p = 0.0194) are statistically significant and independent prognostic factors. These findings suggest that the prognosis after hepatic arterial chemoembolization depends on the hepatic functional reserve and stage of tumor in patients with hepatocellular carcinoma, and adjunct hepatectomy improves the prognosis in these patients.     

Combination of Radiofrequency Ablation with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis

Background

Recent studies suggest that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have a synergistic effect for hepatocellular carcinoma (HCC).

Aims

The aim of this meta-analysis was to compare the effectiveness of combination of RFA and TACE with that of RFA alone in patients with HCC.

Methods

Randomized controlled trials and retrospective cohort studies comparing RFA plus TACE with RFA alone for HCC were included into this meta-analysis. Study quality was rated with a standardized scale and the strength of evidence was also rated by using the grading of recommendations assessment, development, and evaluation system (GRADE system).

Results

Meta-analyses showed that the combination of RFA and TACE was obviously associated with higher survival rates (odds ratio [OR]_1-year = 2.14, 95 % confidence interval [95 % CI] 1.57–2.91, P < 0.001; OR_3-year = 1.98, 95 % CI 1.28–3.07, P = 0.001; OR_5-year = 2.70, 95 % CI 1.42–5.14, P = 0.003). The overall quality of evidence was judged to be low by using the GRADE system.

Conclusions

The combination of TACE with RFA can improve the overall survival rate and provides better prognosis for patients with HCC, but more randomized controlled trials using large sample size are needed to provide sufficient evidence.     

Combination of Radiofrequency Ablation with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis

Background

Recent studies suggest that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have a synergistic effect for hepatocellular carcinoma (HCC).

Aims

The aim of this meta-analysis was to compare the effectiveness of combination of RFA and TACE with that of RFA alone in patients with HCC.

Methods

Randomized controlled trials and retrospective cohort studies comparing RFA plus TACE with RFA alone for HCC were included into this meta-analysis. Study quality was rated with a standardized scale and the strength of evidence was also rated by using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE system).

Results

Meta-analyses showed that the combination of RFA and TACE was obviously associated with higher survival rates (OR_1-year = 2.06, 95 % CI 1.46–2.91, P < 0.001; OR_3-year = 1.93, 95 % CI 1.18–3.15, P = 0.009; OR_5-year = 1.87, 95 % CI 1.23–2.83, P = 0.003). The overall quality of the evidence was judged to be low by using the GRADE system.

Conclusions

The combination of TACE with RFA can improve the overall survival rate and provides better prognosis for patients with HCC, but more randomized controlled trials using large sample sizes are needed to provide sufficient evidence.     

Primary Liver Tumors Other than Hepatocellular Carcinoma: Clinical and Molecular Pearls

Purpose of Review

Liver tumors, excluding hepatocellular carcinoma and metastatic disease, are rare. However, it is important to understand how to distinguish these lesions from hepatocellular carcinoma. They run the spectrum of benign to malignant, some aggressive with relatively few therapeutic options. The goal of this paper is to review the most recent literature to provide current insights into diagnosis, treatment, and pathogenesis of these tumor types.

Recent Findings

Recent literature has focused on oncogenomics and putative targets for therapeutic intervention. Several ongoing studies are elucidating molecular pathways and evaluating novel therapies in these rare tumors and we focus on these findings, particularly in intrahepatic cholangiocarcinoma and fibrolamellar HCC. While these advances are promising, surgical resection continues to be associated with the greatest survival benefit for rare malignant tumors of the liver.

Summary

Clinicians must be aware of rare liver tumors to distinguish them from hepatocellular carcinoma and to develop a differential diagnosis in complicated or atypical presentations. In these rare tumors, advances in understanding tumor biology hold the promise of expanding diagnostic and therapeutic possibilities.

     

Predictors of Mortality in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Background/Aim

Transarterial chemoembolization (TACE) is the recommended treatment for patients with Barcelona stage B hepatocellular carcinoma; however, community practice varies from these American Association for the Study of Liver Diseases guidelines. In this study, we sought to assess factors determining outcome after TACE and examine adherence to guidelines.

Methods

From January 2006 to December 2012, 308 patients with newly diagnosed HCC were treated at the Veterans Affairs (VA) Ann Arbor Healthcare System. Of these, 109 patients underwent TACE. The primary outcome measured mortality. Kaplan–Meier analysis was used to determine the cumulative probability of death. Cox regression was used to assess the predictors of mortality.

Results

The median age of the 109 patients was 60 years (48–90), 97 % were males and 82 % had chronic HCV infection. The median size of the largest lesion was 4 cm, 51 % were multifocal, and portal vein thrombosis was present in 3.6 %. Sixty-two patients died after median 333 days from the index TACE treatment. Median overall survival from index TACE was 11.2 months. Unadjusted 1-, 2-, and 3-year survival was 64, 35, and 24 %, respectively. CTP score (B vs. A: HR 2.51, p = 0.002; C vs. A: HR 7.96, p < 0.0001) and presence of complete response to TACE (HR 0.51, p = 0.004) were independent predictors of mortality. Barcelona stage (p = 0.88) and performance status as measured by ECOG (p = 0.98) were not associated with mortality after TACE.

Conclusions

In this community based, single VA center study, we found a significant number of patients beyond Barcelona stage B were treated with TACE. Advanced TNM stage, poor liver synthetic function and achieving CR with TACE were better predictors of mortality than guideline-directed decisions based on Barcelona stage. These factors may be useful to guide future patient selection for TACE.     

Juvenile Hepatocellular Carcinoma in a Healthy Liver

Primary hepatocellular carcinoma (HCC) in patients ＜30 years old is extremely rare. In younger patients, HCC develops against a background of persistent hepatitis B virus infection. We herein report a 23-year-old woman with HCC with all-negative hepatitis virus markers developing in an apparently healthy liver. Imaging studies showed a 50-mm hypervascular mass in segment 4 of the left liver lobe, compatible with HCC. The patient underwent surgical resection. A histological examination showed the presence of poorly differentiated HCC. The patient was diagnosed with HCC developing in a healthy liver. This is an extremely rare case of non-B non-C HCC.