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Rare Site Hepatocellular Carcinoma Metastasis
Transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEBs) have been introduced as a novel device which ensures more sustained and tumor-selective drug delivery and permanent embolization compared to conventional TACE with lipiodol. Studies highlighting the use of TACE with DEBs for the treatment of hepatocellular carcinoma (HCC) have shown similar or better results compared to conventional TACE with lipiodol. TACE with DEBs is increasingly being performed interchangeably with conventional TACE. This review assessed the characteristics, clinical outcomes and future direction of TACE with DEBs compared to conventional TACE.
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Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival.
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Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV.
In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study.
Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD,
Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.
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This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.
Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.
Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (
A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.
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Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.
130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.
Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (
ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
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The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.
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Low-dose metronomic chemotherapy involves the frequent administration of comparatively low doses of cytotoxic agents with no extended breaks, and it may be as efficient as and less toxic than the conventional maximum tolerated dose therapy. This study evaluated the feasibility and therapeutic efficacy of metronomic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) with major portal vein thrombosis (PVT).
Thirty consecutive HCC patients with major PVT with or without extrahepatic metastasis were prospectively allocated to metronomic chemotherapy consisting of epirubicin being infused through the correct hepatic artery at a dose of 30 mg/body surface area (BSA) every 4 weeks, and cisplatin (15 mg/BSA) and 5-fluorouracil (50 mg/BSA) every week for 3 weeks, with intervening 1 week breaks. The treatment response was assessed using response evaluation criteria in solid tumors (RECIST).
In total, 116 cycles of metronomic chemotherapy were administered to the 30 patients, with a median of 3 cycles given to individual patients (range, 1-15 cycles). Six patients (20.0%) achieved a partial response and six patients (20.0%) had stable disease. The median time to disease progression and overall survival were 63 days (range, 26-631 days) and 162 days (95% confidence interval; range, 62-262 days), respectively. Overall survival was significantly associated with baseline alpha-fetoprotein level (
Metronomic chemotherapy may be a safe and useful palliative treatment in HCC patients with major PVT.
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E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC.
Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients.
Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (
The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.
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Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.
The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.
Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The
objective
response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%,
High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.
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