Liver, Pancreas and Biliary Tract
Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography—A prospective study

https://doi.org/10.1016/j.dld.2011.01.001Get rights and content

Abstract

Background

Outcome of patients with hepatocellular carcinoma is influenced by their histological grade. Invasive biopsy of the lesions is the gold standard in this regard.

Aims

We therefore analysed the diagnostic accuracy of contrast enhanced ultrasound for non-invasive grading of hypervascular hepatocellular carcinoma in liver cirrhosis.

Methods

According to the tumour perfusion kinetics on contrast enhanced ultrasound two grading groups were prospectively defined: well-differentiated hepatocellular carcinoma (US-G1) and higher grade hepatocellular carcinoma (US-G2/G3). Immediately after contrast enhanced ultrasound-grading, biopsies of hepatocellular carcinoma-lesions (n = 95, 1.2–12.5 cm) were obtained and analysed for tumour grading (G). Descriptive statistics, sensitivity, specificity positive and negative predictive values, diagnostic likelihood ratios and interoperator reproducibility were calculated (κ).

Results

Histologically 77 (81.1%) patients had G2–G3 and 18 (18.9%) had G1 tumours. Higher grade hepatocellular carcinoma showed more often a washout in the portal or late phase (p < 0.0001). The sensitivity, specificity, positive predictive values and negative predictive values of contrast enhanced ultrasound for grading of hepatocellular carcinoma for all patients were 94% (CI: 72–99%), 95% (CI: 88–99%), 81% and 99% and for patients with tumours < 5 cm 100%(95% CI: 79–100), 96% (95% CI: 80–99), 92% and 100%. Positive and negative diagnostic likelihood ratios’ were 18 and 26 and 0.06 and 0, respectively. κ = 0.941 (p < 0.001).

Conclusions

Contrast enhanced ultrasound has a high diagnostic value and reproducibility for non-invasive grading of hypervascular hepatocellular carcinoma >1 cm in patients with liver cirrhosis.

Introduction

In the majority of cases, hepatocellular carcinoma (HCC) originates from liver cirrhosis [1]. The molecular events leading to the development of HCC in a cirrhotic liver are currently incompletely understood. They may even differ according to various aetiologies [2]. The same variability is seen in the morphological appearance making the detection of HCC in a cirrhotic liver a challenge for all imaging modalities.

Hepatocarcinogenesis is a multistep process [2]. It is assumed that many HCC develop from high grade dysplastic nodules [3] with a further progression from well differentiated to poorly differentiated HCC. The histopathological grade of HCC is a well established prognostic factor [4]. Furthermore, grading of HCC is also considered as an important issue in the planning of the therapeutic strategy. Patients with high grade HCC, for example, show a higher rate of HCC recurrence after resective surgery and orthotopic liver transplantation (OLT) [5], [6]. Also the therapeutic results after radiofrequency ablation are influenced by the histological grade of HCC [7].

Therefore, it is of great clinical interest to diagnose HCC at an early stage and to gain information regarding the tumour grade. There have been attempts to correlate CT and MRI findings with the grading of HCC [8], [9]. However, to detect HCC at an early stage an imaging modality with a very high temporal and spatial resolution is needed. The method must be able to detect tumour neovascularisation as well as the changing pattern of vascularity in a tumour during the course of time. Amongst the available imaging modalities, contrast enhanced ultrasound (CEUS) is reported to have the highest potential to fulfil these criteria [10], [11].

Some pilot studies have reported the enhancement characteristics of HCC using CEUS as well as their correlation to histopathological grade [4], [12], [13]. Therefore, the aim of our study was to analyse prospectively the diagnostic value of CEUS in grading of HCC.

Section snippets

Patients and methods

This study was approved by the local ethics committee and written informed consent was obtained from each patient.

The patients were recruited prospectively between August 2005 and December 2008. As part of our standard work-up all patients with incidentally detected liver tumours or new masses after operation (out patients, interdisciplinary tumour board and liver transplant unite) receive an ultrasound examination. 1523 patients with liver tumours received an ultrasound examination during this

Descriptive statistics

The clinical data of the patients are demonstrated in Table 1. Forty-one percent of the patients had large-multinodular HCC. Though the exact determination of tumour size is difficult, all of them showed more than 50% of the liver parenchyma infiltrated by the tumour. This high large-multinodular rate is related to our referral centre. Most patients are referred to us at an end stage tumour state. The percentage of HCC < 2 cm in the group of patients with G1 differentiation was higher than the

Discussion

Here we present a prospective study evaluating the non-invasive grading of hypervascular HCC with CEUS.

In a retrospective authors demonstrated that moderately differentiated HCC shows classic CEUS enhancement features, whilst well and poorly differentiated tumours account for most of the atypical variations [13]. Others showed that the enhancement and washout time of primary malignancies of the liver are related to pathologic types and grades [12]. Nicolau et al. reported that tumour

Conflict of interest statement

None declared.

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