Contrast-enhanced ultrasound (CEUS) prediction of focal liver lesions in patients after liver transplantation in comparison to histopathology results

Abstract

PURPOSE: To investigate the value of contrast-enhanced ultrasound (CEUS) in histologic prediction of focal liver lesions after liver transplantation.

MATERIALS AND METHODS: 10 focal liver lesions in 10 patients after liver transplantation were scanned using CEUS and the CEUS results were compared with the histopathological results.

RESULTS: Among 10 focal liver lesions, 7 proofed to be histopathological benign and 3 lesions proofed to be histopathological malignant. All lesions (100%) were correctly report as benign or malignant in the report of the CEUS examination.

CONCLUSION: CEUS can be helpful in the differentiation of benign and malignant focal liver lesions in patients after liver transplantation and can be used in clinical management of focal liver lesions.

Keywords

CEUS (Contrast-enhanced,ultrasound)histopathology liver transplantation focal liver lesions

1 Introduction

Fundamental B-mode ultrasound is the first-choice imaging modality for liver evaluation by physicians almost all around the world. It is a fast, cost-effective, secure and almost universally available imaging modality with no harmful effect to patients [1]. With contrast-enhanced ultrasound (CEUS) an imaging modality has been established into clinical routine that can be easily used to characterize focal liver lesions and that has already shown in several studies that it can accurately differentiate between benign and malignant focal liver lesions with comparable sensitivity and specificity to other imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI) and a good correlation to histopathology [2 –5].

The recurrence of HCC after liver transplantation is one of the main prognosis predictors in patients after liver transplantation and estimated recurrence rates range between 15–20%, which makes a live-long postoperative surveillance of these patients inevitable [6]. Postoperative radiological monitoring includes all available imaging options including fundamental B-mode ultrasound, CEUS, MRI and CT. Unfortunately, fundamental B-mode ultrasound shows a limited accuracy in the detection as well as in the characterization of liver lesions [7, 8]. Several patients after liver transplantation show comorbidities that makes it not possible to follow them up using MRI and/or CT, e.g. chronic renal failure, allergic reaction to MRI or CT contrast agents, metal implants or hyperthyroidism making postoperative imaging a challenge. With the introduction of ultrasound contrast agents a major breakthrough was possible for these patients, as these contrast agents do not rely on thyroid or renal function [9 –12]. CEUS can visualize the microvascular dynamic perfusion patterns of focal liver lesions and can thereby provide information about potential malignancy, which is crucial for postoperative patient management [7].

This retrospective study investigates the value of CEUS in histologic prediction of focal liver lesions after liver transplantation. A high diagnostic accuracy in the prediction of malignant lesion can be seen as an important factor for follow-up.

2 Materials and methods

We retrospectively analysed our imaging database regarding imaging series in patients after liver transplantation and with unclear focal liver lesions. Additionally, we evaluated if there were any histopathological information in correlation to our CEUS examination. All study data were collected in compliance with the principles of the Helsinki/Edinburgh Declaration of 2002. The local ethics committee approved this study and the authors followed the ethical guidelines for publication in Clinical Hemorheology and Microcirculation [13]. Oral and written informed consent of all patients was obtained prior to each CEUS examination.

We found 10 patients with suspicious focal liver lesions after liver transplantation and an additional histopathological result with imaging studies between January 2010 and November 2015. From the patient record file we evaluated the initial date of liver transplantation, which ranged from November 1998 to May 2015. In 7 cases hepatitis was the original cause for liver transplantation and in 3 cases auto-immune disorders with hepatic complications were the cause for the liver transplantation. 4 out 10 patients were female (40%). Mean patient age at the time of the liver transplantation was 41 years (Min: 18; Max: 52; SD±12.7 years). Mean patient age at the time of the CEUS examination was 46.5 years Min: 18; Max: 68; SD±16.6 years). The mean time difference between the CEUS examination and the histopathological result was 4 weeks (SD±7.2 weeks).

High-end ultrasound machines with specialized examination protocols accessible at the day of the examinations were used (Siemens Acuson Sequoia and Siemens S2000, EPIQ 7, Philips Ultrasound). The Sequoia and S2000 systems were used with C4-1 and C6-1 HD transducers and the EPIQ 7 systems was used with the C9-2 transducer. All examinations were completed by one individual radiologist with more than 10 years of practice.

SonoVue^® (Bracco, Milan, Italy) was the ultrasound contrast agent of choice in all examinations and was intravenously bolus-injected through a 20–22 G needle followed by a up to 10 ml Saline-solution flush-injection. Mean examination time fluctuated between 2–6 minutes for the whole examination.

We retrospectively evaluated to initially acquired and digitally stored cine video clips of these examinations and the initially written report and matched these results with the histopathological result.

3 Results

CEUS was successfully possible in all patients and imaging data sets could be retrieved successfully in all patients and none of these data sets had to be discarded due to inappropriate image quality. In all cases the histopathological result could be obtained from the patient record file and the histopathological result showed a conclusive result in all of the examined 10 cases. No adverse reaction was reported in any of the analysed cases after the exposition to SonoVue®. The average doses for diagnostic image quality given to the patients ranged from 1.4 to 2.0 ml with a maximum of 4.8 ml and minimum of 1.0 ml. Single-dose contrast media flush-injection was adequate for most examinations, if required the flush-injections were repeated to gather additional imaging series or to add diagnosticconfidence.

The histopathological results of these 10 patients reported a malignant lesion in 3 cases (30%), all being an HCC and reported 7 benign lesions (70%). All malignant and benign lesions were correctly interpreted using the dynamic perfusion pattern information gathered through the CEUS examination (100%). Examples of these dynamic perfusion patterns are depicted for two patients as imaging series, both shown to be a HCC (Figs. 1–8).

Fig.1

Hyperechoic lesion in the liver in a patient after liver transplantation. The lesion can clearly be visualized in fundamental B-mode ultrasound.

Fig.2

Same patient as in Fig. 1. The suspicious lesion does not show major vascularization using color Doppler.

Fig.3

Same patient as in Figs. 1 and 2. Contrast-enhanced ultrasound of the same lesion in side-by-side mode with B-mode ultrasound shows an early hypervascularization of the suspicious lesion compared to the surrounding liver tissue, suggestive of an arterial hypervascularized tumour entity.

Fig.4

Same patient as in Figs. 1–3. Side-by-side contrast-enhanced ultrasound and B-mode ultrasound of the same lesions shows a wash-out of the lesion in the late venous phase almost 3 minutes after contrast media injection. The dynamic perfusion pattern of this lesion is in line with an arterial hypervascularized hepatocellular carcinoma that was histopathologically proven later on.

Fig.5

MRI/ultrasound image fusion in a patient with a suspicious lesion seen on a postoperatively on MRI. The suspicious lesion is marked with T₁ and image fusion was used for guidance purposes to clearly depict the lesion in fundamental B-mode ultrasound and to add diagnostic confidence.

Fig.6

Same patient as in Fig. 5. Image fusion of the same patient using a side-by-side mode with color Doppler mode. No major vascularization of the suspicious lesion can be depicted.

Fig.7

Same patient as in Figs. 5 and 6. Image fusion with side-by-side contrast-enhanced ultrasound mode shows an early hypervascularization of the suspicious lesion in the arterial phase almost 10 sec. after contrast agent injection suggestive of an arterial hypervascularized tumour.

Fig.8

Same patient as in Figs. 5–7. Image fusion with side-by-side contrast-enhanced ultrasound mode shows a pathological wash-out in the late venous phase after a bit more than two and a half minutes in line with a dynamic perfusion pattern of a hepatocellular carcinoma. This diagnosis was later on confirmed by the histopathological result.

4 Discussion

This study resonates with numerous other studies regarding the diagnostic accuracy of CEUS in the evaluation of focal liver lesions and shows the important advantage of being a dynamic examination with the possibility to evaluate microcirculation and vascularization patterns of focal lesions [14 –18]. In the hand of a skilled examiner, CEUS is a feasible imaging modality for the follow-up and management of focal liver lesions after liver transplantation with special benefits for patient sub-groups that cannot be followed-up using other radiological imaging modalities due to contraindications to MRI and/or CT. With the advanced experience of CEUS and its expanded clinical use the number of CT and MRI scans can significantly be decreased adding benefits for the patients and the reducing the economic burden for the health system.

Limiting to this study was the small sample size evaluated in this study with only 10 patients with appropriate imaging data sets and histopathological results. Even in a university hospital setting it was difficult to find patients that could be included into this study, with most patients receiving MRI or CT follow-up examinations in cases with unclear focal liver lesions. As this study suggests, this might be not extensively necessary and could be reduced in future times.

5 Conclusion

CEUS can be helpful in the differentiation of benign and malignant focal liver lesions in patients after liver transplantation and can be used in clinical management of focal liver lesions.

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