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Background and Aims: Trans-hepatic arterial chemo-embolization is the most commonly used treatment for unresectable hepatocellular carcinoma. The prognostic impact of tumor biomarkers has not therefore been evaluated in this treatment. Imbalance between matrix metalloproteinase-2 and tissue inhibitor metalloproteinase-2 is considered to play an important role in extracellular matrix remodeling and degradation. Higher serum levels of MMP-2 have been shown to predict a poor prognosis and shorter overall survival in HCC after TACE. The objective of this study was to evaluate the serum levels of MMP-2 and TIMP-2 in HCC patients before and after TACE to evaluate their clinical significance and usefulness as prognostic biomarkers., Methods: MMP-2 and TIMP-2 levels were measured by ELISA in 75 HCC patients and 30 healthy controls. Sera MMP-2 and TIMP-2 were correlated with clinico-pathological features., Results: The mean serum MMP-2 and TIMP-2 levels of HCC patients before TACE were 1700±71ng/mL and 89±45ng/mL respectively, significantly higher than that of the control group: 771±60ng/mL (p<0.0001, t-test) and 25.7±20ng/mL respectively (p<0.0001, t-test). A significant decrease of MMP-2 levels after 1 and 3months compared to baseline time was observed (p<0.0001), while with TIMP-2 a gradual increase in serum before and after TACE (p<0.01) was detected. No significant correlation between serum MMP-2 levels and other clinico-pathological features was observed. Patients with serum MMP-2 >1500ng/mL (median value) had worse overall and recurrence-free survival compared with those with serum MMP-2 levels <1500ng/mL before treatment., Conclusion: Higher serum MMP-2 levels and MMP-2/TIMP-2 ratio could predict poor prognosis after TACE, suggesting prognostic role of these biomarkers in HCC., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Radiofrequency thermal ablation (RFA) has been demonstrated to be useful for the treatment of liver neoplasms. The study aimed to evaluate the feasibility and safety of the combination of transarterial chemoembolization (TACE) and RFA, performed simultaneously to treat primary and secondary liver neoplasms., Patients and Methods: From July 2006 to October 2007, 34 patients (21 with HCC and 13 with liver metastases) underwent 37 sessions of treatment. The schedule consisted of: induction TACE (with epirubicin, mitomycin C and lipiodol, or with doxorubicin/irinotecan loaded on microspheres), percutaneous RFA and second TACE. Monopolar RFA was used on 52 nodules, whereas the bipolar multiprobe technique was used in 6 cases., Results: The treatment was well tolerated, with moderate hepatic and hematological toxicity. In total 51 nodules were evaluable for response, with technical success in 45/51 cases (88%)., Conclusion: Combined TACE plus RFA is feasible and safe; the preliminary data make it a promising procedure with regard to efficacy and support further investigation.

Background: New treatments are being investigated in patients with multiple or unresectable liver metastases, usually characterized by poor prognosis. Based on the predominant arterial blood supply of hepatic neoplasms, liver transarterial chemoembolization administers cytotoxic drugs in combination with the ischemic effect due to vascular occlusion. Mitomycin-C (MMC) is characterized by a high liver extraction rate and is potentiated by a hypoxic environment., Patients and Methods: This technique is performed by inducing a stop-flow of the hepatic artery, obtained by the placement of a balloon-catheter and followed by the infusion of MMC; in addition, in order to prevent iatrogenic lesions of the vascular wall, caused by the inflation of the balloon-catheter, a vascular stent is placed at the beginning of the procedure., Results: Thirty-one patients with liver metastases from various solid tumors were treated, while 47 sessions of treatment were performed. Toxicity was moderate; three cases of iatrogenic obstruction of the hepatic artery were observed, thus precluding further treatment., Conclusion: The feasibility and the good tolerability of this procedure make it an interesting option in the therapeutical strategy for patients with advanced metastatic liver disease, as well as in combination with systemic chemotherapy, ablative and cytoreductive treatments and/or free-flow liver perfusions with anticancer drugs.

Vascular endothelial growth factor (VEGF) is known to play a central role in tumour angiogenesis. However, no data have been published with regard to the clinical-biological significance of serum (S)-VEGF in hepatocellular cancer (HCC) patients undergoing to percutaneously radiofrequency thermal ablation (PRFA). The aim of this study was to assess the modifications of S-VEGF levels in a series of 28 HCC patients in hepatitis C virus-positive cirrhosis before and after PRFA, respectively. Samples of S were taken before, 2 and 5 days after PRFA respectively and VEGF levels were assessed by ELISA. No significant difference was found between pre- and post-VEGF levels (p= n.s.; by Wilcoxon test). We suggest that S-VEGF level is not useful as early predictive marker of response to PRFA.

13 patients affected by multifocal and/or large liver metastases from various solid tumors have been treated with stop-flow liver perfusion, to evaluate the safety and feasibility of hypoxic loco-regional infusion with Mitomycin C. The treatment was based on the hypoxic effect due to stop-flow, potentiating the cytotoxic activity of Mitomycin C, combined with the ischemic damage caused by the embolization of the vascular supply to the tumor. The schedule consisted in blocking arterial flow by an angiographic occlusion balloon catheter inflated in the hepatic artery, with previous placement of a vascular stent in order to prevent iatrogenic arterial lesions, and followed by the intraarterial administration of Mitomycin C; finally, arterial hepatic embolization was performed by a gelatine sponge. The study is ongoing with a median follow up of 8 months (range 2-12). Partial response was observed in 1/13 patients (8%), stable disease in 8/13 patients (61%), while progressive disease occurred in 4/13 patients (31%). Nine patients are still alive, and four patients died for hepatic progressive disease, three of them heavily pre-treated with multiple lines of chemotherapy for advanced disease. Toxicity was mild; main side effects were anaemia and thrombocytopenia(Grade 3 both in 1/15 treatments), while fever, nausea and vomiting and upper abdominal pain were short-lasting and easily manageable. No iatrogenic lesion of the hepatic arterial wall occurred. These preliminary data, although the small number of patients and the short follow up, show that the procedure is safe and feasible, with a interesting percentage of clinical responses. In addition, the placement of an arterial stent have demonstrated to protect vascular wall ensuring a regular blood flow, so allowing to perform repeated treatments in responsive patients. The good tolerability of this therapeutic modality suggests further investigation in order to determine its efficacy even in combination with systemic chemotherapy and other locoregional treatments such as termoablative procedures and/or intraarterial antiblastic perfusions in patients affected by metastatic liver disease.