Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells.

Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Clinical outcomes of early gastric cancer with lymphovascular invasion or positive vertical resection margin after endoscopic submucosal dissection.

BACKGROUND: In early gastric cancer (EGC) cases with lymphovascular invasion or positive vertical margins after endoscopic submucosal dissection (ESD), additional radical gastrectomy is performed on principle. However, an additional surgery is often difficult to consider if the surgical approach itself is challenging or the patient refuses surgery. In such cases, only close surveillance is performed without additional surgical procedures. This study aimed to examine the difference in clinical prognosis of EGC cases with lymphovascular invasion or positive vertical margins after ESD either with or without surgery. METHODS: We retrospectively studied 83 patients with lymphovascular invasion or positive vertical margins after ESD from July 2005 to November 2013. RESULTS: Of the 83 patients, 45 (54.2%) underwent radical additional gastrectomy (surgical group) and 38 (45.8%) were under close surveillance without surgical or endoscopic treatments (close surveillance group.) The cancer-free survival period was 78.3 ± 3.4 months in the surgical group and 64.5 ± 4.6 months in the close surveillance group. The recurrence rates did not significantly differ between the 2 groups, at 7.9% in the surgical group and 6.7% in the non-surgical group. CONCLUSIONS: Close surveillance may be suggested as an option for EGC patients for whom a surgical approach is difficult, who exhibit a positive vertical margin after ESD, and who have no lymphovascular or deep submucosa invasion after ESD.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving

Hedgehog signaling between cancer cells and hepatic stellate cells in promoting cholangiocarcinoma.

BACKGROUND: Aberrant Hedgehog (HH) signaling activation is important in cancer growth and mediates the interaction between cancer cells and the surrounding stromal cells. This study investigated the role of HH signaling on the growth of cholangiocarcinoma (CC), focusing on the interaction of CC cells with stromal cells. METHODS: To evaluate the interaction between human CC cells (SNU-1196, SNU-246, SNU-308, SNU-1079, and HuCCT-1) and stromal cells (hepatic stellate cell line, Lx-2), co-culture proliferation, migration, and invasion assays were performed. In vivo nude mice experiments were conducted using two groups-HuCCT-1 single implant xenograft (SX) and co-implant xenograft (CX) with HuCCT-1 and Lx-2. RESULTS: When HuCCT-1 cells were co-cultured with Lx-2 cells, the expression of HH signaling-related proteins increased in both HuCCT-1 and Lx-2 cells. Co-culture with Lx-2 cells stimulated the proliferation, migration, and invasion of CC cells, and these effects were mediated by HH signaling. Co-culture of HuCCT-1 and Lx-2 cells increased the secretion of several cytokines. In an ectopic xenograft model, Lx-2 co-implantation increased CC tumor growth and stimulated angiogenesis. Cyclopamine attenuated tumor growth in the CX group, but not in the HuCCT-1 mono-implant (SX) group. Cyclopamine treatment decreased CC cell proliferation, suppressed microvessel density, and increased tumor necrosis in the CX group, but not in the SX group. CONCLUSION: Hepatic stellate cells stimulate the proliferation, migration, and invasion of CC cells, promote angiogenesis through HH signaling activation, and render CC more susceptible to necrosis by HH inhibitor.

Feasibility and efficacy of stereotactic ablative radiotherapy for Barcelona Clinic Liver Cancer-C stage hepatocellular carcinoma.

The purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 35 patients between 2003 and 2011. Vascular invasion was diagnosed in 32 patients, extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions. The median survival time was 14 months. The 1- and 3-yr overall survival (OS) rate was 52% and 21%, respectively. On univariate analysis, CP class A and biologically equivalent dose ≥ 80 Gy(10) were significant determinants of better OS. Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients. In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate. We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy(10) is required for BCLC-C stage.

Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization.

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria were a greatest tumor dimension (LD sum) <10 cm, inoperable HCC, and incomplete response after TACE. Prescribed SBRT doses were up to 60 gray (Gy) in 3 fractions, but doses were reduced until normal tissue constraints were allowed. RESULTS: Between May 2008 and February 2011, 50 patients were enrolled in this phase 2 trial, of which 47 patients were evaluable. Forty-one patients had Child-Pugh class A disease (A5/A6 were 32/9), 6 patients had class B7 disease, and 5 patients had portal vein tumor thrombosis. All patients underwent TACE 1 to 5 times before SBRT. SBRT doses ranged from 42 to 60 Gy in 3 fractions (median dose, 57 Gy), and the median LD sum was 29 mm (range, 13-78 mm). Eighteen patients (38.3%) achieved complete remission within 6 months of completing of SBRT, and 18 patients (38.3%) had a partial response. The 2-year local control rate was 94.6%, the overall survival rate was 68.7%, and the progression-free survival rate was 33.8%. Three patients (6.4%) experienced grade 3 gastrointestinal toxicity, and 2 patients (4.3%) experienced grade 4 gastric ulcer perforation. CONCLUSIONS: This trial demonstrated that SBRT after incomplete TACE for inoperable HCC achieves promising rates of response and local control. On the basis of these study results, a modified, multi-institutional, phase 2 trial to reduce gastrointestinal toxicity is recommended.

Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.

BACKGROUND/AIM: Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment. METHODS: This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles. RESULTS: The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001). CONCLUSION: This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.

Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: To evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of localized hepatocellular carcinoma (HCC) in the absence of another standard treatment option. METHODS: The authors reviewed the details of 38 patients with inoperable HCC (diameter <10 cm) treated by SBRT in a prospectively registered database at their institution. All patients had been treated by transcatheter arterial chemoembolization before SBRT, which had been finally deemed ineffective. SBRT dosages (33-57 Gy in three or four fractions) were administered according to tumor volumes, which ranged from 11 to 464 ml (median, 40.5 ml). RESULTS: Two-year overall survival and local progression-free survival rates were 61.4% and 66.4%, respectively. The local response rate was 63% at 3 months after SBRT. A high radiation dose was found to be independently related to survival. A decline in liver function was observed in six patients (16%) and Grade 3 musculoskeletal toxicity in one patient (2.7%). CONCLUSIONS: This study showed that SBRT can be safely administered to select HCC patients, and these results suggest that this technique should be considered a salvage treatment. A further well-controlled large-scale study and longer follow-up are needed to determine optimal dose-fraction schedules and characterize late complications.

Pilot study of stereotactic body radiotherapy for huge hepatocellular carcinoma unsuitable for other therapies.

AIMS: To determine the feasibility and efficacy of stereotactic body radiotherapy (SBRT) for huge hepatocellular carcinoma unsuitable for other therapies. METHODS: Six patients with very large hepatocellular carcinomas (>10 cm) unsuitable for surgical resection or that failed to respond to transcatheter arterial chemoembolization (TACE) were treated by SBRT. Doses ranged from 32 Gy to 40 Gy in four fractions. Survival, response, and toxicities were evaluated. RESULTS: After a median follow-up of 25.9 months (range 8.1-56 months), three patients had died and three were alive. Overall, treatment was well tolerated and no dose-limiting toxicity or radiation-induced liver disease was observed. The median survival was 10 months (range 3-56 months) and the median progression-free duration was 6 months (range, 2-21 months). Partial response was achieved by four patients, stable disease by one, and one patient had disease progression. One patient with a partial response who underwent lobectomy after SBRT was alive 56 months post-SBRT. CONCLUSION: This study suggests that SBRT can be delivered safely at 32-40 Gy in four fractions to huge hepatocellular carcinoma. Furthermore, combinations of SBRT with other modalities such as surgery or TACE might prolong survival.

Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma.

PURPOSE: The poor prognosis of hepatocellular carcinoma (HCC) is, in part, due to the high rate of recurrence even after "curative resection" of tumors. Therefore, it is axiomatic that the development of an effective prognostic prediction model for HCC recurrence after surgery would, at minimum, help to identify in advance those who would most benefit from the treatment, and at best, provide new therapeutic strategies for patients with a high risk of early recurrence. EXPERIMENTAL DESIGN: For the prediction of the recurrence time in patients with HCC, gene expression profiles were generated in 65 HCC patients with hepatitis B infections. RESULT: Recurrence-associated gene expression signatures successfully discriminated between patients at high-risk and low-risk of early recurrence (P=1.9 x 10(-6), log-rank test). To test the consistency and robustness of the recurrence signature, we validated its prognostic power in an independent HCC microarray data set. CD24 was identified as a putative biomarker for the prediction of early recurrence. Genetic network analysis suggested that SP1 and peroxisome proliferator-activated receptor-alpha might have regulatory roles for the early recurrence of HCC. CONCLUSION: We have identified a gene expression signature that effectively predicted early recurrence of HCC independent of microarray platforms and cohorts, and provided novel biological insights into the mechanisms of tumor recurrence.

Plasma Fibrinogen-Like 1 as a Potential Biomarker for Radiation-Induced Liver Injury.

Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.

Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma.

Hypoxia stimulates hepatocellular carcinoma (HCC) cell growth via hexokinase (HK) II induction, and alternatively, HK II inhibition induces apoptosis by activating mitochondrial signaling. This study was to investigate whether the induction of HK II by hypoxia is associated with enhanced mitochondrial stability and to confirm the apoptosis-inducing efficacy of HK II inhibitor in an in vivo model of HCC. Mitochondrial stability was examined by treating isolated mitochondria with deoxycholate, a permeability-enhancing agent. Alteration of permeability transition pore complex composition was analyzed by immunoprecipitation and immunoblotting. An in vivo model of HCC was established in C3H mice i.d. implanted with MH134 cells. The antitumor efficacy of i.p. given 3-bromopyruvate (3-BrPA), a HK II inhibitor, was evaluated by measuring tumor volumes and quantifying apoptosis using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and (99m)Tc-hydrazinonicotinamide-Annexin V scans. Hypoxia enhanced mitochondrial stability, and this was inhibited by 3-BrPA treatment. In particular, HK II levels in permeability transition pore complex immunoprecipitates were reduced after 3-BrPA treatment. In mice treated with 3-BrPA, mean tumor volumes and tumor volume growth were found to be significantly reduced. Moreover, percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were significantly increased in 3-BrPA-treated mice, and this apoptosis-inducing efficacy was reflected in vivo by (99m)Tc-hydrazinonicotinamide-Annexin V imaging. Our results show that hypoxia enhances mitochondrial stability via HK II induction and that HK II inhibitor treatment exhibits an in vivo antitumor effect by inducing apoptosis. Therefore, HK II inhibitors may be therapeutically useful for the treatment of advanced infiltrative hypovascular HCCs, which are growing in a hypoxic environment.

Lack of association between serum leptin levels and hepatic steatosis, fibrosis or response to antiviral therapy in Korean chronic hepatitis C patients.

BACKGROUND/AIMS: Leptin has been recently implicated in the development of hepatic steatosis and fibrosis in chronic hepatitis C (CHC) infection. The serum levels of leptin are known to be strongly affected by anthropometric parameters such as body mass index (BMI) and total body fat, which show differences between races or ethnicities. In this study, we examined whether serum leptin levels are correlated with clinical, virological, and histological features, and with response to antiviral therapy in Korean CHC patients. METHODOLOGY: We evaluated correlations between serum leptin level and age, sex, BMI, fasting glucose, alanine aminotransferase, genotype, hepatitis C virus RNA titer, steatosis, fibrosis, and response to antiviral therapy after 24 weeks completing 24 weeks of interferon-alpha based therapy in 47 Korean CHC patients. RESULTS: Of the variables examined, only female sex and a BMI > 25kg/m2 were identified as independent variables related to a higher leptin level by multivariate analysis. Baseline leptin levels and leptin changes before/after antiviral therapy were not correlated with response to therapy. CONCLUSIONS: In Korean CHC patients, serum leptin levels were found to be correlated with anthropometric parameters, but not with virological or histological features. In addition, serum leptin levels did not predict response to antiviral therapy.

The usefulness of colonoscopy as a screening test for detecting colorectal polyps.

BACKGROUND/AIMS: Colonic polyps are the most common lesions encountered during screening colonoscopy. The purpose of this study is to evaluate the usefulness of colonoscopy to detect colonic polyps in adults. METHODOLOGY: From January 2003 to September 2005, a total of 4,629 adults underwent colonoscopic screening as a part of a health evaluation program. We analyzed the completed questionnaires, and the colonoscopic and pathologic findings. RESULTS: Complete colonic evaluation was possible in 4,491 (97.0%) subjects, and 804 (17.9%) had adenomatous polyps, including 153 subjects (3.4%) with advanced adenomas. There were no significant complications such as bowel perforation or massive bleeding requiring transfusion in relation to the procedure. There was a trend toward an increased prevalence of adenomatous polyps with age. Among the subjects with polyps, 72.1% of the subjects had distal polyps and the relative risk for proximal polyp, according to the distal findings, was 5.4 (95% CI: 4.5-6.3) for adenomatous polyp, 5.1 (95% CI 3.6-7.0) for advanced adenoma as compared to the finding of no adenomatous polyp. CONCLUSIONS: Colonoscopy performed by experienced colonoscopists as a screening test is feasible for detecting subjects with colorectal polyps.

Eupatilin attenuates bile acid-induced hepatocyte apoptosis.

BACKGROUND: In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against experimentally induced gastrointestinal, pancreatic, and hepatic damage. This study was undertaken to examine if eupatilin modulates bile acid-induced hepatocyte apoptosis. METHODS: Huh-BAT cells, a human hepatocellular carcinoma cell line stably transfected with a bile acid transporter, were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored in bile duct-ligated rats. RESULTS: Eupatilin significantly reduced bile acid-mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8 cleavage. Eupatilin diminished the bile acid-induced activation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile acid-induced c-Jun N-terminal kinase activation was found to be responsible for attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte apoptosis in bile duct-ligated rats. CONCLUSIONS: Eupatilin attenuates bile acid-induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation. Therefore, eupatilin might be therapeutically efficacious in a variety of human liver diseases associated with cholestasis.

Anti-apoptotic N-cadherin signaling and its prognostic implication in human hepatocellular carcinomas.

N-cadherin signaling has recently been implicated in the progression of certain epithelial tumors by promoting invasion and dissemination of cancer cells. N-cadherin has also been reported to exert an anti-apoptotic effect. In this study, we attempted to evaluate the participation of this adhesion molecule in the progression of human hepatocellular carcinomas (HCCs) by analyzing its anti-apoptotic signaling as well as its prognostic implication in HCC patients. N-cadherin was found to be expressed in human HCCs. We established a stable human HCC cell line expressing a truncated N-cadherin, NCaddeltaC, with a dominant-negative action. NCaddeltaC-expressing cells were more susceptible to bile acid-induced apoptosis than control cells. N-cadherin was found to complex with procaspase-8, and this association was diminished in NCaddeltaC-expressing cells, leading to enhanced procaspase-8 recruitment to death-inducing signaling complex following bile acid treatment. A clinicopathological analysis in patients who had undergone surgical resection for HCC revealed that tumoral N-cadherin up-regulation was significantly related to poor recurrence-free and overall survival. Our findings implicate N-cadherin signaling as contributing to HCC progression by exerting anti-apoptotic effects. Thus, we suggest that the selective interruption of this signaling may have therapeutic potential.

Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: This study aimed to evaluate the effect of stereotactic ablative radiotherapy (SABR) after incomplete transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients. METHODS: The study enrolled 178 HCC patients initially treated with TACE between 2006 and 2011. Patients were included if they had Barcelona Clinic Liver Cancer stage 0 or A, ≤3 nodules with a total sum of longest diameter ≤10 cm, Child-Turcotte-Pugh score of ≤7, no major vessel invasion, and no extra-hepatic metastases. RESULTS: Twenty-four patients achieved a complete response to TACE (group 1). Among those with incomplete response, 47 patients received other curative treatments (group 2), 37 received SABR (group 3), and 70 received non-curative treatments (group 4). The 2-year overall survival (OS) rates for groups 1, 2, 3, and 4 were 88 %, 81 %, 73 %, and 54 %, respectively. The corresponding 5-year OS rates were 50 %, 58 %, 53 %, and 28 %, respectively. CONCLUSIONS: Patients treated with SABR after incomplete TACE had similar survival outcomes to those achieving complete response to TACE or receiving curative treatments. However, patients receiving non-curative treatments had significantly lower survival rates than the other groups. Therefore, if SABR was indicated at the initial diagnosis, it might be recommended after TACE failure.

HBV reactivation in a HBsAg-negative patient with multiple myeloma treated with prednisolone maintenance therapy after autologous HSCT.

Hepatitis B virus (HBV) reactivation has previously occurred in hepatitis B surface antigen-negative patients with malignant lymphoma who received rituximab-based combination chemotherapy. However, few reports have described cases of HBV reactivation in patients with multiple myeloma thus far. We report a case of HBV reactivation in a patient with multiple myeloma treated with chemotherapy, autologous hematopoietic stem cell transplantation, and maintenance steroid therapy. For the HBV reactivation, the patient was treated with the antiviral agent entecavir. The clinical symptoms and laboratory findings improved after 3 months. Further studies should target the identification of patients at high risk of HBV reactivation in multiple myeloma treated with autologous hematopoietic stem cell transplantation and steroid therapy for maintenance and establish viral prophylaxis strategies, especially in Korea, in which HBV infection is endemic.