Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common cancers worldwide. Surgery, percutaneous ablation and liver transplantation are the only curative treatment modalities for HCC. However, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options for patients with advanced HCC are required. In advanced HCC, according to current international guidelines, sorafenib, a molecular targeted agent, is the standard treatment. However, alternative treatment modalities are required because of the low response rates and unsuitability of molecular agents in real practice. In various treatment modalities, mostly in Asia, hepatic arterial infusion chemotherapy(HAIC) has been applied to advanced HCC with a view to increasing the therapeutic efficacy. HAIC provides direct drug delivery into the tumor feeding vessels and also minimizes systemic toxicities through a greater first-pass effect in the liver. However, the sample sizes of studies on HAIC have been small and large randomized trials are still lacking. In this article, we describe the treatment efficacy of HAIC for advanced stage HCC and discuss future therapeutic possibilities.

Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma:An intricate pathway

The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma(HCC)are still ill-defined;however,there is increasing evidence that the gradual accumulation of mutations,genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci,nodules,and finally,overt HCC.As well as many other neoplasias,liver cancer is considered an"inflammatory cancer",arising from a context of inflammation,and characterized by inflammation-related mechanisms that favor tumor cell survival,proliferation,and invasion.Molecular mechanisms that link inflammation and neoplasia have been widely investigated,and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species.The latter,in turn,probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation,and ultimately leading to cancer.The relationship amongst chronic liver injury,free radical production,and development of HCC is explored in the present review,particularly in the light of the complex network that involves oxidative DNA damage,cytokine synthesis,telomere dysfunction,and microRNA regulation.

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after surgery.In patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC recurrence.It is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis B.However,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established.There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon.Interferon treatment reduces the overall incidence of HBV-related HCC in sustained re-sponders.However,side effects may limit its long-term clinical application.Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases.They may also improve the outcome after curative resection for HBV-related HCC.There are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC recurrence.After all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma

AIM: To explore the role of SF/HGF-Met autocrine and parscrine in metastasis of hepatocellular carcinoma (HCC).METHODS: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4 HCC cell lines, including HepG2, Hep3B,SMMC7721 and MHCC-1, the last cell line had a higher potential of metastasis. Sf/hgf cDNA was transfected by the method of Lipofectin into SMMC7721. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve.RESULTS: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC7721 changed into elongated morphology, and the abilities of proliferation ( P < 0.05) and mobility increased. Such bio-activity could he blocked by c-met antibody ( P< 0.05).CONCLUSION: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC.

Clostridium perfringens infection after transarterial chemoembolization for large hepatocellular carcinoma

We report an unusual case of Clostridium perfringens liver abscess formation after transcatheter arterialchemoembolization(TACE) for large hepatocellular carcinoma.Severe deterioration in liver and renal function accompanied with hemocytolysis was found on the 2nd day after TACE.Blood culture found Clostridium perfringens and abdominal computed tomography revealed a gas-containing abscess in the liver.Following antibiotics administration and support care, the infection was controlled and the liver and renal function turned normal.The 2nd TACE procedure was performed 1.5 mo later and no recurrent Clostridium perfringens infection was found.

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here,a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy,the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2,CK8,CK18,CEA(polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3,CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors(GISTs).The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here,we report the clinicopathological features of our case,along with a review of the few cases present in the literature.

Liver Transplantation for Hepatitis B Virus-related Hepatocellular Carcinoma in Hong Kong

Hepatocellular carcinoma(HCC)is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide.Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis,and liver transplantation is the treatment of choice.Liver transplanta-tion has been shown to produce superior oncological benefits,when compared to hepatectomy for HCC.New developments in the context of patient selection criteria,modification of organ allocation,bridging therapy,salvage liver transplanta-tion and pharmaceutical breakthrough have improved the survival of HCC patients.In this article,we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.

Incidental Collision Tumor of Hepatocellular Carcinoma and Neuroendocrine Carcinoma

The composite tumors of the liver are very rare,including the coexistence of HCC(hepatocellular carcinoma)with NEC(neuroendocrine carcinoma).The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics,behaviors and treatments.Herein is described an incidental collision tumor of HCC-NEC,along with a review of the literature focusing on their clinicopathological findings and prognosis.The tumor presented here was found incidentally in the hepatectomy specimen of a 56-yearold man who had undergone liver transplantation for rapidly progressive liver failure because of alcoholic hepatitis and cirrhosis.Imaging and laboratory examinations did not demonstrate tumor-related findings.During macroscopic examination,two sharply defined and distinctive areas(1.7 cm and 0.6 cm dimension respectively)were detected among the cirrhotic nodules.The characteristic histopathological features and immunohistochemical findings allowed a diagnosis of HCCNEC to be made.There was no evidence of recurrence and metastasis after 10months following surgery.The present case and review revealed that these tumors are frequently found in older ages and males.Although serum markers are valuable in the discrimination of malignant tumors,their absence cannot completely rule out composite HCC-NEC.Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry.The NEC component might influence the treatment strategy and eventually the outcome of the patient.In conclusion,the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors,especially in patients with the chronic liver disease.

Three decades of hepatitis B control with vaccination

Hepatitis B virus(HBV) continues to represent a major health problem and can lead to acute liver failure, acute hepatitis, chronic carriership, chronic hepatitis of HBV, liver cirrhosis, liver cancer, liver transplantation and death. There is a marked difference in the geographic distribution of carriers. More than 240 million people worldwide are chronic HBV carriers. Mother-to-child transmission remains the most important mechanism of infection in countries with a high prevalence of HBV. Percutaneous/parenteral transmission and unsafe sexual practices are important mode of spread transmission of HBV in other countries. Vaccination against HBV is the gold measure for primary prevention and control of the disease. Currently, 179 countries have added HBV vaccination to their routine vaccination programs with great results. Neonatal immunization with HBV vaccine has been one of the most highly effective measures in public health and the first anti-cancer program to be launched. In this paper we review the achievements for the last three decades.

Saikosaponin-b regulates the proliferation and apoptosis of HepG2 cells by targeting the MACC1/c-Met/Akt signaling pathway

OBJECTIVE Metastasis-associated in colon cancer-1(MACC1)is an oncogene that has been newly identified.It promotes tumor proliferation and invasion via the MET pathway.Our study investigated the effects of Saikosaponin-b(SS-b)on the proliferation and apoptosis of HepG2 cells and its regulation on MACC1/c-Met/Akt signaling pathway.METHODS HepG2 cells were treated with SS-b(10-800 g·L^(-1))for 48 h in vitro.The CCK-8 assay was used to assess cell proliferation,and cell apoptosis was determined by Hoechst33258 staining,AnnexinⅤ/PI staining and caspase 3 assay.RT-PCR was used to examine the expression of MACC1,c-MET and hepatocyte growth factor(HGF)mR NA.MACC1 protein was detected by Western blot and immunohistochemistry.The protein expressions of p-cMET,c-MET,p-AKT,AKT,p-BAD,BAD were measured by Western blot.RESULTS SS-b inhibited the growth of HepG2 cells in dose-dependent way and induced cell apoptosis significantly.HepG2 cells showed karyopyknosis,fragmentation and fluorescence highlight in SS-b treatment group.FCM results showed that apoptosis rate of HepG2 cells increased with SS-b concentration.The immunofluorescence results showed that the MACC1 expression decreased significantly in HepG2 cells treated with SS-b.The expression levels of MACC1,c-MET and HGF mR NA in HepG2 cells were significantly inhibited by SS-b.SS-b also significantly decreased the protein expressions of MACC1,p-c-MET and p-AKT while increased the expression of p-BAD and caspase 3 in HepG2 cells(P<0.05).CONCLUSION SS-b inhibited the proliferation and induced the apoptosis of HepG2 cells by targeting the MACC1/c-Met/Akt signaling pathway.