Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study

Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.