Focal liver lesions in cirrhosis: Role of contrast-enhanced ultrasonography

Contrast-enhanced ultrasound (CEUS) represents a great innovation for the evaluation of focal liver lesions (FLLs). The main advantage of CEUS is the real-time imaging examination and the very low toxicity in patients with renal failure. Liver cirrhosis has been recognized as a major risk factor for the onset of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). HCC in liver cirrhosis develops as the last step of a complex that leads to the gradual transformation from regenerative nodule through dysplastic nodule to HCC. In patients with liver cirrhosis, a surveillance program is recommended consisting of ultrasound (US) for detecting small focal lesions. A wide spectrum of benign and malignant lesions other than HCC may be found in the cirrhotic liver and their differentiation is important to avoid errors in staging diseases that may preclude potentially curative therapies. Several published studies have explored the value of CEUS in liver cirrhosis and they have been shown to have excellent diagnostic and prognostic performances for the evaluation of non-invasive and efficient diagnosis of FLLs in patients at high risk for liver malignancies. The purpose of this article is to describe and discuss CEUS imaging findings of FLLs including HCC and ICC, all of which occur in cirrhotic livers with varying prevalence.     

Detection and characterization of focal liver lesions with contrast-enhanced ultrasonography in patients with hepatitis C-induced liver cirrhosis

Background: Hepatitis C virus (HCV)-associated liver cirrhosis provides a major preneoplastic condition for hepatocellular carcinoma (HCC). Ultrasonography (US) is usually used for screening of HCC, but needs improvement.

Purpose: To assess whether use of a second-generation ultrasound contrast agent can improve characterization of focal liver lesions and detection of HCC in HCV-infected patients with liver cirrhosis.

Material and Methods: In total, 96 US studies in 49 HCV-infected patients with liver cirrhosis were performed. The patients were first examined with a baseline US. After this, a diagnostic decision was made and recorded. The patients were then re-examined with contrast-enhanced ultrasound (CEUS), and the diagnostic triage was repeated. The patients were followed up for at least 1 year.

Results: On baseline US, indeterminate focal lesions were found in 27 examinations. After CEUS, a confident diagnosis of HCC was made in eight of these examinations. In an additional eight US examinations, diagnosis of regenerative/dysplastic noduli was established. In one patient with no detectable focal lesion at baseline examination, an indeterminate malignant lesion was detected with CEUS. This lesion was further investigated with computed tomography and diagnosed as HCC.

Conclusion: Our study indicates that the use of CEUS significantly improves diagnostic confidence. CEUS improves the detection of HCC in patients with HCV-induced liver cirrhosis. Also, CEUS makes it possible to rule out malignancy in many cases where baseline US shows indeterminate focal lesions. In low-endemic countries, the use of CEUS in screening for HCC may be considered.     

Management of hepatocellular carcinoma: The role of contrast-enhanced Tultrasound简

Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third cause of cancer death worldwide. Contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. On the basis of the Guideline and Good Clinical Practice Recommendations for CEUS in the liver-update 2012 and related literature about the management of HCC, we summarize the main roles and applications of CEUS in the management of HCC, including HCC surveillance, diagnosis, CEUS-guided treatment, treatment response evaluation and follow-up. The diagnostic algorithm for HCC is also suggested. Meanwhile, the comparisons between CEUS and contrast enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) in these areas are made. Although CEUS is subject to the same limitation as ordinary US and is inferior to CECT/CEMRI in some aspects, CEUS has proved to be of great value in the management of HCC with inherent advantages, such as sufficient high safety profile making it suitable for patients with renal failure or allergic to iodine, absence of radiation, easy reproducibility and high temporal resolution. The tremendous application of CEUS to the diagnosis and treatment of HCC provides more opportunities for patients with HCC diagnosed at different stages.     

Contrast-enhanced ultrasound: The evolving applications

Contrast-enhanced ultrasound (CEUS) is a major breakthrough for ultrasound imaging in recent years. By using a microbubble contrast agent and contrast-specific imaging software, CEUS is able to depict the micro- and macro-circulation of the targeted organ, which in turn leads to improved performance in diagnosis. Due to the special dual blood supply system in the liver, CEUS is particularly suitable for liver imaging. It is evident that CEUS facilitates improvement for characterization of focal liver lesions (FLLs), detection of liver malignancy, guidance for interventional procedures, and evaluation of treatment response after local therapies. CEUS has been demonstrated to be equal to contrast-enhanced computed tomography or magnetic resonance imaging for the characterization of FLLs. In addition, the applicability of CEUS has expanded to non-liver structures such as gallbladder, bile duct, pancreas, kidney, spleen, breast, thyroid, and prostate. The usefulness of CEUS in these applications is confirmed by extensive literature production. Novel applications include detecting bleeding sites and hematomas in patients with abdominal trauma, guiding percutaneous injection therapy and therefore achieving the goal of using interventional ultrasonography in managing splenic trauma, assessing the activity of Crohn's disease, and detecting suspected endoleaks after endovascular abdominal aneurysm repair. Contrast-enhanced intraoperative ultrasound (US) and intracavitary use of CEUS have been developed and clinically studied. The potential use of CEUS involves sentinel lymph node detection, drug or gene delivery, and molecular imaging. In conclusion, the advent of CEUS has greatly enhanced the usefulness of US and even changed the status of US in clinical practice. The application of CEUS in the clinic is continuously evolving and it is expected that its use will be expanded further in the future.     

Contrast-enhanced ultrasound in the biliary system: Potential uses and indications

Conventional ultrasound (US) is the first-line imaging investigation for biliary diseases. However, it is lack of the ability to depict the microcirculation of some lesions which may lead to failure in diagnosis for some biliary diseases. The use of contrast-enhanced US (CEUS) has reached the field of bile duct disease in recent years and promising results have been achieved. In this review, the methodology, image interpretation, enhancement pattern, clinical usefulness, and indications for CEUS in the biliary system are summarized. CEUS may be indicated in the biliary system under the following circumstances: (1) Where there is a need to make a characterization of intrahepatic cholangiocarcinoma (ICC); (2) For differentiation diagnosis between ICC and other tumors (i.e. hepatocellular carcinoma or liver metastasis) or infectious diseases; (3) For differentiation diagnosis between biliary cystadenoma and biliary cystadenocarcinoma; (4) To detect malignant change in Caroli's disease; (5) To depict the extent of Klatskin's tumor with greater clarity; (6) To make a distinction between gallbladder cholesterol polyp, adenoma and polypoid cancer; (7) To make a distinction between chronic cholecystitis with thickened wall and gallbladder cancer; (8) For differentiation diagnosis between motionless sludge and gallbladder cancer; (9) For differentiation diagnosis between common bile duct cancer and sludge or stone without acoustic shadowing; and (10) In patients who are suspected of having a drop of their percutaneous transhepatic cholangiodrainage tube, US contrast agent can be administered to through the tube detect the site of the tube.     

Focal liver lesions in cirrhosis: value of contrast-enhanced ultrasonography compared with Doppler ultrasound and α-fetoprotein levels

Purpose

This study aimed to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in characterising focal liver lesions in cirrhosis and to validate its use in lesions discovered during surveillance for hepatocellular carcinoma (HCC).

Materials and methods

Between 2003 and 2006, 128 cirrhotic patients with focal liver lesions at baseline ultrasonography (US) were studied by power colour Doppler US (Doppler US) and CEUS. Serum alpha-fetoprotein (AFP) levels were assessed in all patients. Fine-needle biopsy or other reference modalities such as computed tomography (CT), magnetic resonance imaging (MRI) or digital subtraction angiography (DSA) were used as the gold standard. The accuracy of baseline US, Doppler US, AFP levels, combined US and AFP levels and combined US, Doppler US and CEUS in characterising focal liver lesions was assessed. Diagnostic performance was compared using the McNemar test.

Results

A total of 207 focal liver lesions (101 benign and 106 malignant) were identified in 128 patients. CEUS sensitivity and specificity for lesion characterisation were 96.2% and 97.0%, respectively, whereas its positive and negative predictive values were 97.1% and 96.1%. CEUS accuracy was 96.6%, higher than that of US (72.0%), Doppler US (70.0%), AFP levels (65.7%), combined US and Doppler US (70.0%) and combined US and AFP levels (90.3%). The differences between US and CEUS were statistically significant (p<0.05).

Conclusions

CEUS can characterise focal liver lesions with 96.6% accuracy, a value higher than US, Doppler US, AFP levels, combined US and AFP levels and combined US and Doppler US. CEUS should therefore be used to characterise focal liver lesions detected during HCC surveillance of cirrhotic patients.     

Pretreatment Evaluation with Contrast-Enhanced Ultrasonography for Percutaneous Radiofrequency Ablation of Hepatocellular Carcinomas with Poor Conspicuity on Conventional Ultrasonography

Objective

To determine whether pretreatment evaluation with contrast-enhanced ultrasonography (CEUS) is effective for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) with poor conspicuity on conventional ultrasonography (US).

Materials and Methods

This retrospective study was approved by the institutional review board and informed consent was waived. From June 2008 to July 2011, 82 patients having HCCs (1.2 ± 0.4 cm) with poor conspicuity on planning US for RFA were evaluated with CEUS prior to percutaneous RFA. We analyzed our database, radiologic reports, and US images in order to determine whether the location of HCC candidates on planning US coincide with that on CEUS. To avoid incomplete ablation, percutaneous RFA was performed only when HCC nodules were identified on CEUS. The rate of technical success was assessed. The cumulative rate of local tumor progression was estimated with the use of the Kaplan-Meier method (mean follow-up: 24.0 ± 13.0 months).

Results

Among 82 patients, 73 (89%) HCCs were identified on CEUS, whereas 9 (11%) were not. Of 73 identifiable HCCs on CEUS, the location of HCC on planning US corresponded with that on CEUS in 64 (87.7%), whereas the location did not correspond in 9 (12.3%) HCCs. Technical success was achieved for all 73 identifiable HCCs on CEUS in a single (n = 72) or two (n = 1) RFA sessions. Cumulative rates of local tumor progression were estimated as 1.9% and 15.4% at 1 and 3 years, respectively.

Conclusion

Pretreatment evaluation with CEUS is effective for percutaneous RFA of HCCs with poor conspicuity on conventional US.     

Contrast ultrasound in hepatocellular carcinoma at a tertiary liver center: First Indian experience

AIM: To assess the role of contrast enhanced ultrasonography in evaluation of hepatocellular carcinoma (HCC) at the first Indian tertiary liver center. METHODS: Retrospective analysis of contrast enhanced ultrasound (CEUS) examinations over 24 mo for diagnosis, surveillance, characterization and follow up of 50 patients in the context of HCC was performed. The source and indication of referrals, change in referral rate, accuracy and usefulness of CEUS in a tertiary liver center equipped with a 64 slice dual energy computer tomography (CT) and 3 tesla magnetic resonance imaging (MRI) were studied. Sonovue (BR1, Bracco, Italy, a second generation contrast agent) was used for contrast US studies. Contrast enhanced CT/MRI or both were performed in all patients. The findings were taken as a baseline reference and correlation was done with respect to contrast US. Contrast enhanced MRI was performed using hepatocyte specific gadobenate dimeglumine (Gd-BOPTA). Iomeron (400 mg; w/v) was used for dynamic CT examinations. RESULTS: About 20 (40%) of the examinations were referred from clinicians for characterization of a mass from previous imaging. About 15 (30%) were performed for surveillance in chronic liver disease; 5 (10%) examinations were performed for monitoring lesions after radiofrequency ablation (RFA); 3 (6%) were post trans-arterial chemoembolization (TACE) assessments and 3 (6%) were patients with h/o iodinated contrast allergy. About 2(4%) were performed on hemodynamically unstable patients in the intensive care with raised alpha fetoprotein and 2(4%) patients were claustrophobic. The number of patients referred from clinicians steadily increased from 12 in the first 12 mo of the study to 38 in the last 12 mo. CEUS was able to diagnose 88% of positive cases of HCC as per reference standards. In the surveillance group, specificity was 53.3% vs 100% by CT/MRI. Post RFA and TACE specificity of lesion characterization by CEUS was 100% in single/large mass assessment, similar to CT/MRI. For non HCC lesions such as regenerative and dysplastic nodules, the specificity was 50% vs 90% by CT/MRI. The positive role of CEUS in imaging spectrum of HCC included a provisional urgent diagnosis of an incidentally detected mass. It further led to a decrease in time for further management. A confident diagnosis on CEUS was possible in cases of characterization of an indeterminate mass, in situations where the patient was unfit for CT/MRI, was allergic to iodinated contrast or had claustrophobia, etc.CEUS was also cost effective, radiation free and an easy modality for monitoring post RFA or TACE lesions. CONCLUSION: CEUS is a valuable augmentation to the practice of ultrasonography, and an irreplaceable modality for confounding cases and interpretation of indeterminate lesions in imaging of HCC.     

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.     

Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

Objective

To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions.

Method

Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT.

Results

(1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05).

Conclusion

CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the diagnostic consistency among doctors. The performances of CEUS are similar to that of CECT in the diagnosis of pancreatic carcinoma and focal pancreatitis.     

Abdominal virtual ultrasonographic images reconstructed by multi-detector row helical computed tomography

BACKGROUND: Three-dimensional (3D) images can be generated using thin sections from multi-detector row computed tomography (CT) and computer software, simulating images obtained using conventional ultrasonography (US). This software allows easy diagnosis of abdominal lesions and subsequent treatment of focal liver lesions such as hepatocellular carcinoma (HCC). The present study used newly developed virtual US software for diagnose and treatment of hepatobiliary disease. METHODS: The software was used to create virtual US images in 10 subjects. Radiofrequency ablation (RFA) was performed by virtual US in seven patients with HCC. RESULTS: Slices were easily reconstructed from various angles, and each slice was continuously animated as with conventional US in all subjects. Moreover, when seven patients with HCC were examined using virtual US, HCC nodules were visualized and could be treated with RFA. CONCLUSIONS: Virtual US should prove useful for visualization of HCC nodules that cannot be seen under conventional US. Virtual US is a useful tool for US-guided treatment of HCC.     

Contrast enhanced ultrasound of hepatocellular carcinoma

Sonazoid (Daiichi Sankyo, Tokyo, Japan), a second-generation of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent, has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography (US) in Japan since January 2007. Sonazoid-enhanced US has two phases of contrast enhancement: vascular and late. In the late phase of Sonazoid-enhanced US, we scanned the whole liver using this modality at a low mechanical index (MI) without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma (HCC) lesions which cannot be detected by conventional US as perfusion defects in the late phase. Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow into the defects. High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions. Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoid-enhanced three dimensional (3D) US. Fusion images combining US with contrast-enhanced CT or contrast-enhanced MRI have made it easy to detect typical or atypical HCC lesions. By these methods, Sonazoid-enhanced US can characterize liver tumors, grade HCC lesions histologically, recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization, and guide ablation therapy for unresectable HCC. This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions, especially HCC.     

Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

Objective

We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU).

Subjects and methods

Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period.

Results

Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively.

Conclusion

CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.     

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Patients with liver cirrhosis are at increased risk of hepatocellular carcinoma (HCC). Conventional or baseline ultrasound (BUS) is often used as the first-line tool for HCC surveillance or detection, but the accuracy of BUS in HCC detection or differentiation from other focal liver lesions (FLLs) is limited. Contrast-enhanced ultrasound (CEUS) represents a recent revolution in the field of ultrasonography and it has become increasingly important in the detection and evaluation of FLLs. In CEUS, HCC typically exhibits arterial hyper-enhancement and portal-venous washout represented by hypo-enhanced lesions in the portal venous and late phases. The detection rate of HCC was significantly higher with CEUS compared with BUS. Even regenerative or some dysplastic nodules may exhibit arterial hyper-enhancement as they are differentiated from HCC by its iso-enhancing pattern in portal and late phases. The contrast-enhancement patterns of other different types of benign and malignant FLLs, as well as their detection rates with CEUS, were also discussed.     

射频消融联合其他介入综合技术治疗原发性肝癌研究进展

原发性肝癌（HCC）死亡率居全球第三位,而中国肝癌患者的年发病及死亡病例数均超过全球总数的50%。目前,手术仍是唯一有可能治愈HCC的首选方法,但绝大多数患者发现时已为肝癌中晚期,失去了手术机会。近年来介入微创治疗已成为不可手术切除肝癌治疗的研究热点之一,主要包括：肝动脉化疗栓塞（TACE）、局部消融治疗、放射性粒子组织间近距离放疗及体外高能聚焦超声波等。由于介入微创治疗方式多样,如何合理有序的联合应用仍是当前的研究热点。本文重点综述以射频消融为基础的各种介入综合技术手段联合应用治疗肝癌的新进展。     

Contrast-enhanced US of hepatocellular carcinoma

PURPOSE: To evaluate the capabilities of contrast-enhanced ultrasound (CEUS) in the characterization of hepatocarcinoma (HCC) in terms of accuracy as compared to spiral CT and diagnostic gain as compared to conventional and Doppler US. MATERIALS AND METHODS: Forty-three patients with viral hepatopathy or cirrhosis diagnosed with HCC (6 histologically and 37 cytologically proven) were retrospectively studied. Between January 2002 and May 2003, all patients were evaluated with CEUS after detection of at least one suspicious nodule on US. CEUS features of HCCs were retrospectively compared with those on conventional and Doppler US, and spiral CT. RESULTS: HCCs varied between 1.2 cm and 18 cm in diameter; 14/43 were small' (< or = 2 cm). In 18/43 patients, HCC was multifocal. Doppler US revealed 24/43 hypervascular nodules. On CEUS, 37/43 (86%) showed contrast enhancement in the arterial phase, 13/37 (35%) with negative colour and power Doppler US examination; in 6/37 (16%) contrast enhancement in the arterial phase was not visible on spiral CT. On CEUS, 6/43 hypovascular HCCs were characterized as malignant in the sinusoidal phase. On CEUS, the sinusoidal phase revealed additional nodules not visible on baseline US in 3/18 multifocal HCCs. CONCLUSIONS: CEUS diagnosis of HCC in cirrhotic liver is possible with a combination of the arterial phase, which shows tumoral hypervascularity in the microcirculation, and the sinusoidal phase, which allows to confirm the malignancy of the nodule.     

Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound

Objective

We assessed the usefulness of contrast-enhanced ultrasound (CEUS) in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).

Methods

The CEUS enhancement patterns of 50 ICCs were retrospectively analysed and compared with 50 HCCs. Two readers independently reviewed the baseline ultrasound (BUS) and CEUS images and the diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis. Time–intensity curves (TIC) were plotted for quantification analysis.

Results

In the arterial phase, peripheral rim-like hyperenhancement, heterogeneous hyperenhancement, homogeneous hyperenhancement and heterogeneous hypoenhancement were found in 25, 10, 3 and 12 of the ICCs versus 2, 29, 19 and 0 of the HCCs (P?<?0.001), respectively. The diagnostic performance of both readers in terms of the area under the ROC curve (0.745 vs. 0.933 for reader 1, and 0.803 vs. 0.911 for reader 2), sensitivity (28% vs. 90%, and 44% vs. 82%) and accuracy (64% vs. 90%, and 71% vs. 90%) improved significantly after CEUS (all P?<?0.05). The interobserver agreement increased from κ?=?0.575 at BUS to κ?=?0.720 after CEUS. TICs demonstrated that the intensities of the peripheral and central portions of the ICCs were lower than those of HCCs (both P?<?0.05).

Conclusion

CEUS improves the diagnostic performance significantly in the differentiation between ICC and HCC.     

Contrast enhanced ultrasound: Should it play a role in immediate evaluation of liver tumors following thermal ablation?

Purpose

To compare the accuracy of immediate CEUS with results of 24-h CEUS and MDCT in early evaluation of liver tumors following thermal ablation, using the combined results of a 3 month follow-up MDCT and CEUS as a reference standard.

Subjects and methods

From our database, we selected patients who underwent a thermal ablation immediately followed by CEUS (within 5–10 min) between February 2009 and February 2011. There were 92 patients (median age 73 years), two of whom had repeat ablation during the study period for a total of 94 tumors. Sixty tumors were treated with radiofrequency and 34 with microwave ablation. All patients underwent CEUS and CT examinations at 24 h. For patients with more than one treated tumor in the same session, the lesion imaged post-procedural and at 24-h with CEUS in all vascular phases was selected. All measurements of the necrotic zone, as an avascular zone, were performed during the portal-venous phase. Immediate post-procedural CEUS and 24 h CEUS and MDCT were blindly reviewed by two radiologists. One radiologist blindly reviewed the follow-up imaging. The mean diameters of the necrotic zone at post-procedural CEUS, and CEUS and MDCT at 24 h were compared and diagnostic accuracy to detect residual tumor calculated for each index tests compared to 3-months follow-up imaging.

Results

The mean diameter of the necrotic zone was: 29 ± 9 mm at post-procedural CEUS, 34 ± 10 mm at 24 h CEUS and 35 ± 11 mm at 24 h MDCT. Mean diameter of the necrotic zone was significantly smaller at post-procedural CEUS compared to either CEUS or MDCT at 24 h (p < 0.001 for all).With a 95% confidence interval, the sensitivity was 25% (11–47%) for immediate CEUS, 20% (8–42%) for CEUS at 24-h, and 40% (22–61%) for CT at 24-h. Specificity was 96% (89–99%) for immediate CEUS, 97% (91–99%) for CEUS at 24-h, and 97% (91–99%) for CT at 24-h.

Conclusions

Diagnostic accuracy of post-procedural CEUS in early evaluation of liver tumors following thermal ablation is comparable to both CEUS and MDCT performed at 24 h. Therefore, post-procedural CEUS can be used to detect and retreat residual viable tissue in the same ablation session.     

Role of Contrast-Enhanced Ultrasound as a Second-Line Diagnostic Modality in Noninvasive Diagnostic Algorithms for Hepatocellular Carcinoma

ObjectiveTo investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations.Materials and MethodsWe prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar''s test.ResultsThe sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, p = 0.06 by EASL; 86.1%, p < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 0.04). There were no false-positive cases for HCC on CEUS.ConclusionThe addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.     

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

PurposeTo investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).MethodsThirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS).ResultsThe median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups.ConclusionsThe novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.