Optimal application of stereotactic body radiotherapy and radiofrequency ablation treatment for different multifocal hepatocellular carcinoma lesions in patients with Barcelona Clinic Liver Cancer stage A4-B1: a pilot study.

BACKGROUND: In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4-B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4-B1 patients. METHODS: From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). RESULTS: The median follow-up duration was 31.3 months (range: 15.1-71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8-45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months' observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin-bilirubin grade, respectively. CONCLUSIONS: For patients with BCLC stage A4-B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

Use of intra-procedural fusion imaging combining contrast-enhanced ultrasound using a perflubutane-based contrast agent and auto sweep three-dimensional ultrasound for guiding radiofrequency ablation and evaluating its efficacy in patients with hepatocellular carcinoma.

Purpose: This study evaluated the usefulness of intraprocedural contrast-enhanced ultrasound (CEUS)/ultrasound (US) fusion imaging using a perflubutane-based contrast agent combined with preprocedural auto sweep three-dimensional US to obtain volume data for guidance and evaluation of the therapeutic efficacy of radiofrequency ablation (RFA).Methods: This uncontrolled clinical trial included 50 hepatocellular carcinomas (HCCs) with a mean diameter of 15.3 mm that had been treated by RFA. The efficacy of RFA was evaluated by CEUS/US fusion imaging during the procedure. If the ablation was deemed to be inadequate, further ablation was performed until adequate ablation was achieved. Contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) was performed a month after RFA, and the images obtained using each modality were reviewed to evaluate the efficacy of RFA.Results: Thirty-three of the 50 lesions were evaluated by CEUS/US fusion imaging as having been adequately ablated after the first RFA procedure. The ablation was evaluated as inadequate in the remaining 17 lesions, for which additional ablation was performed. Ninety-eight (49/50) of all HCCs were evaluated as having been eventually adequately ablated on intraprocedural CEUS/US fusion imaging. The concordance rate for evaluations between intraprocedural CEUS/US fusion imaging and CECT/CEMRI performed 1 month after RFA was 88% (44/50). The kappa value for agreement between the two methods of evaluation was 0.792.Conclusion: Intraprocedural fusion imaging combining CEUS and auto sweep three-dimensional US appears to be a useful modality for RFA guidance and evaluation of therapeutic efficacy of RFA in patients with HCC.

Intraprocedurally EOB-MRI/US fusion imaging focusing on hepatobiliary phase findings can help to reduce the recurrence of hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND & AIMS: To explore the ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI)/ultrasound (US) fusion imaging (FI) to improve the prognosis of radiofrequency ablation (RFA) by ablating the characteristic findings of hepatocellular carcinoma (HCC) in hepatobiliary phase (HBP) imaging. METHODS: We retrospectively recruited 115 solitary HCC lesions with size of (15.9 ± 4.6) mm. They were all treated by RFA and preoperative EOB-MRI. According to the modalities guiding RFA performance, the lesions were grouped into contrast enhanced US (CEUS)/US guidance group and EOB-MRI/US FI guidance group. For the latter group, the ablation scope was set to cover the HBP findings (peritumoral hypointensity and irregular protruding margin). The presence of HBP findings, the modalities guided RFA, the recurrence rate were observed. RESULTS: After an average follow-up of 377 days, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) were 14.8% and 38.4%, respectively. The lesions having HBP findings exhibited a higher recurrence rate (73.7%) than the lesions without HBP findings (42.9%) (p = 0.002) and a low overall recurrence-free curve using the Kaplan-Meier method (p = 0.038). Using EOB-MRI/US FI as guidance, there was no difference in the recurrence rate between the groups with and without HBP findings (p = 0.799). In lesions with HBP findings, RFA guided by EOB-MRI/US FI (53.8%) produced a lower recurrence rate than CEUS/US (84.0%) (p = 0.045). CONCLUSIONS: The intraprocedurally application of EOB-MRI/US FI to determine ablation scope according to HBP findings is feasible and beneficial for prognosis of RFA.

Comparison Between Low Mechanical Index and High Mechanical Index Contrast Modes of Contrast-Enhanced Ultrasonography: Evaluation of Perfusion Defects of Hypervascular Hepatocellular Carcinomas During the Post-Vascular Phase.

OBJECTIVES: We evaluated the detection rates for perfusion defects in hypervascular hepatocellular carcinomas comparing the low mechanical index (MI) and high MI contrast modes during the post-vascular phase (PVP) of contrast-enhanced ultrasonography. METHODS: Seventy-eight patients with 84 hypervascular hepatocellular carcinomas (mean diameter, 23.4 ± 11.2 mm) were selected for this retrospective study. All the patients underwent whole-liver scanning using conventional ultrasonography before injection of a perflubutane-based contrast agent (Sonazoid), and all the detected nodules were classified as either hypoechoic or hyperechoic nodules. Next, hypoechoic and hyperechoic nodules were evaluated using contrast-enhanced ultrasonography, and the presence of a perfusion defect was assessed for each nodule using both the low MI (0.2-0.3) and the high MI (0.7-1.2) contrast modes during the PVP (10 minutes after injection). The data were analyzed using the McNemar test. RESULTS: Forty-four nodules were classified as hypoechoic nodules, and the remaining 40 nodules were classified as hyperechoic nodules using conventional ultrasonography. The detection rate for perfusion defects determined using the high MI contrast mode was higher than that determined using the low MI contrast mode in hyperechoic nodules during the PVP (low MI, 58% [23 of 40]; high MI, 90% [36 of 40]; P < .0001). However, no significant difference was observed between the low MI and the high MI contrast modes in hypoechoic nodules (low MI, 80% [35 of 44]; high MI, 89% [39 of 44]; P = .125). CONCLUSION: Compared with the low MI contrast mode, the high MI contrast mode was more sensitive for detecting perfusion defects in hypervascular hepatocellular carcinomas in patients with hyperechoic nodules during the PVP.

Use of vessel patterns on contrast-enhanced ultrasonography using a perflubutane-based contrast agent for the differential diagnosis of regenerative nodules from early hepatocellular carcinoma or high-grade dysplastic nodules in patients with chronic liver disease.

OBJECTIVE: We evaluated the use of tumor vessel patterns observed during arterial-phase contrast-enhanced ultrasonography (US) to differentiate regenerative nodules (RN) from early hepatocellular carcinoma (HCC) or high-grade dysplastic nodules (HGDN) in patients with chronic liver disease. SUBJECTS AND METHODS: Pathologically confirmed lesions (83 early HCC, 6 HGDN, and 13 RN with mean maximal diameters of 15.4, 15.3, and 16.2 mm, respectively) were enrolled in this retrospective study. We performed contrast-enhanced US using a perflubutane-based contrast agent. We then classified the tumor vessels observed during the arterial phase of contrast-enhanced US into two patterns: peripheral vessels (centripetal pattern) and central vessels (centrifugal pattern). RESULTS: Eighty-one (97.6%) of the 83 early HCC exhibited various enhancement patterns (hypovascular, 44.6%; isovascular, 25.3%; and hypervascular, 27.7%) and a peripheral vessel pattern, while the remaining 2 lesions (2.4%) exhibited hypovascular enhancement and a central vessel pattern. All 6 HGDN lesions were hypovascular with a peripheral vessel pattern. Twelve (92.3%) of the 13 RN were hypovascular with a central vessel pattern, and the remaining one (7.7%) was hypervascular with a central vessel pattern. When lesions exhibiting a central vessel pattern during arterial-phase contrast-enhanced US were diagnosed as RN, the sensitivity, specificity, and accuracy of these diagnoses were 100%, 97.8%, and 98.0%, respectively. CONCLUSION: The tumor vessel patterns observed during arterial-phase contrast-enhanced US may be useful for differentiating RN from early HCC or HGDN in patients with chronic liver disease.

Pathological Appearance of Focal Liver Reactions after Radiotherapy for Hepatocellular Carcinoma.

We studied five pathological specimens from five patients at 1.5, 3.0, 4.0, 13.5, and 14.0 months after radiotherapy for HCC. Four needle biopsies were obtained to investigate liver parenchyma of focal liver reaction (FLR) around treated HCC, when patients had newly developed HCC or local recurrence appeared in the liver. Liver resection was performed in one case where insufficient radiotherapy effect for HCC was suspected. In all patients, FLR was recognized as a hypervascular area around the HCC on enhanced CT and enhanced Gd-EOB-DTPA (EOB-MRI). Liver specimens were analyzed to assess the pathological characteristics of FLR. FLR was recognized as prolonged liver enhancement in enhanced CT and EOB-MRI. From pathological understanding, sinusoidal dilatation with degeneration and desquamation was caused by direct endothelial cell injury following radiotherapy. Hepatocytes and endothelium fell off, and so the portal tract came close, and hepatic arteries increase simultaneously, resulting in FLR around HCC after radiotherapy. In conclusion, the prolapse of hepatocytes and sinusoidal endothelium induced neovascularization of hepatic arteries due to the repair mechanisms; in addition, these prolapse may shorten the distance between each portal region and the hepatic arteries flowing through the portal region become more prominent in FLR.

Added Value of Ultrasound-Based Multimodal Imaging to Diagnose Hepatic Sclerosed Hemangioma before Biopsy and Resection.

Imaging methods have the overwhelming advantage of being non-invasive in the diagnosis of hepatic lesions and, thanks to technical developments in the field of ultrasound (US), radiation exposure can also be avoided in many clinical situations. In particular, contrast-enhanced US (CEUS) outperforms other radiological methods in regard to real-time images, repeatability, and prompt reporting and demonstrates relatively few contraindications and adverse reactions. In this study, we reported in detail a rare benign tumor: hepatic sclerosed hemangioma (HSH). We described US-based multimodal imaging (B-flow imaging, US elastography, and Sonazoid CEUS) features of this HSH case. Furthermore, by summarizing the recently published literature on the imaging diagnosis of HSH, we offered readers comprehensive knowledge of conventional imaging methods (CT, MRI) and CEUS in the diagnosis of HSH and preliminarily discussed their mechanism of pathology-based diagnosis. Our multimodal imaging approach may provide a diagnostic strategy for HSH, thus avoiding unnecessary biopsy or resection.

Use of Contrast-Enhanced Ultrasound with Sonazoid for Evaluating the Radiotherapy Efficacy for Hepatocellular Carcinoma.

Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16-82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity (p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.

The value of hepatobiliary phase in EOB-MRI in predicting hypervascularization outcome of non-hypervascular hypointense lesions in high-risk patients for hepatocellular carcinoma.

PURPOSE: To estimate the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) in predicting hypervascularization outcome of non-hypervascular hypointense hepatic lesions in high-risk patients for hepatocellular carcinoma (HCC). METHODS: Under the premise of non-hyperenhance in arterial phase (AP) and hypointensity in hepatobiliary phase (HBP) of EOB-MRI, 29 fresh lesions from 22 patients with chronic viral hepatitis (median (range) age: 69(57-82) years) were prospectively enrolled. During continuously followed-up by EOB-MRI, lesional vascularity in AP, the signal intensity (SI) ratios of lesions-to-parenchyma in HBP images (post-contrast ratio) and adjusted enhancement with reference of unenhanced images (EOB enhancement ratio) were examined. RESULTS: After 644 (220-2912) days of follow-up, 20 lesions changed into hyperenhancement in AP of EOB-MRI (hypervascularized group), while nine remained non-hyperenhanced (maintained non-hypervascular group). There is no statistical difference of post-contrast ratio at the initial detection. The post-contrast ratios in hypervascularized group were different between each follow-up time point when followed-up ≥ three (P < 0.01) and four (P < 0.05) times, and exposed a linear downward trend with time. Between the hypervascularized and maintained non-hypervascular groups, there were significant differences in the post-contrast ratio at endpoint for three-times' follow-up (P < 0.001); and at the second (P = 0.037), third follow-up time points (P = 0.005), endpoint (P = 0.005) for four-times' follow-up. EOB enhancement ratio showed inter-group difference only at endpoint for three-times' follow-up (P = 0.008). CONCLUSION: For non-hypervascular, HBP hypointense hepatic lesions, decreasing trend of SI in HBP may early predict unfavorable hypervascularized outcome.

Comparison of Sonazoid contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid MRI for the histological diagnosis of hepatocellular carcinoma.

BACKGROUND: This study aimed to compare the value of Sonazoid contrast-enhanced ultrasound (SCEUS) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) for histological grading diagnosis, especially for early hepatocellular carcinoma (eHCC). METHODS: A total of 163 histopathologically confirmed HCC lesions were retrospectively collected, including 71 eHCCs (27 hypervascular, 44 non-hypervascular) and 92 advanced HCCs (adHCC) (73 hypervascular, 19 non-hypervascular). We performed SCEUS to evaluate the lesions' vascularity during the portal phase (PP) and the echogenicity during the post-vascular phase (PVP). EOB-MRI was used to determine the signal intensity between lesions and the surrounding liver parenchyma on unenhanced T1-weighted images (pre-contrast ratio) in the hepatobiliary phase (HBP) (post-contrast ratio). RESULTS: For the PP and PVP of SCEUS (for all lesions), the pre-and post-contrast ratios of EOB-MRI (for all hypervascular lesions) showed statistical differences in the diagnosis of some (but not all) histological grades. For the diagnosis of eHCC, isoechogenicity in the PVP achieved the best diagnostic efficacy [area under the receiver operating characteristic curve (AUC) =0.892]. Whether used independently or in a combination of any form, all indicators failed to produce a higher diagnostic efficacy than PVP. Post- (≥0.610) and pre-contrast ratios (≥0.981) yielded acceptable diagnostic efficacy, with, respectively, accuracy levels of 69.3% and 75.5% and AUC values of 0.719 and 0.736. For eHCC diagnosis, the post-contrast ratio (≥0.625) and combined diagnosis using pre- (≥0.907) and post-contrast ratios (≥0.609) revealed the highest sensitivity (92.6%) for hypervascular lesions and perfect specificity (100%) for non-hypervascular lesions. CONCLUSIONS: Unenhanced T1-weighted images and the HBP of EOB-MRI [regardless of the vascularity in the arterial phase (AP)], and the PP and PVP of SCEUS showed their value in the histological grading diagnosis of HCC. In particular, isoechogenicity in the PVP may have promising diagnostic utility for eHCC.

Application of new ultrasound techniques for focal liver lesions.

Ultrasonography (US) has the overwhelming advantages of not entailing radiation exposure and being a noninvasive, real-time, convenient, easy-to-perform, and relatively inexpensive imaging modality. It is used as the first-line imaging modality for screening, detection, and diagnosis of focal liver lesions (FLLs) [small hepatocellular carcinomas (HCCs), in particular]. However, with the increasing demand for accurate and early diagnosis of small HCCs, newer radiologic methods need to be explored to overcome certain limitations of US. For example, the imaging is easily negatively affected by the presence of gas, rib cage, and subcutaneous fat, and is insensitive for capturing the subtle but vital information on the blood flow. It was in response to this need that new promising technologies such as contrast-enhanced ultrasound and fusion imaging were introduced for the detection of liver lesions. This paper presents an overview of the epidemiology and mechanisms of the development of HCCs, with an emphasis on the application of US in the diagnosis and treatment of FLLs. The aim of this article is to provide the state-of-the-art developments in the imaging diagnosis of FLLs and evaluation of ablation treatment of early HCCs. By keeping abreast of these recent advances, we hope that doctors and researchers working in the field of diagnosis/treatment of liver diseases will be able to discriminate benign FLLs such as regenerative nodules and focal nodular hyperplasia from HCCs, so as to avoid unnecessary repeated tumor biopsies and overtreatment. In particular, we expect that small HCCs or precancerous nodules (such as dysplastic nodules) can be accurately diagnosed and appropriately treated even at an early stage.

Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma.

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001-0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

Central vascular structures as a characteristic finding of regenerative nodules using hepatobiliary phase gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI and arterial dominant phase contrast-enhanced US.

OBJECTIVE: We investigated the characteristic findings of regenerative nodules (RNs) for differentiating early hepatocellular carcinoma (HCC) from high-grade dysplastic nodules (HGDNs) using magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; EOB-MRI) and contrast-enhanced ultrasonography (CEUS) in patients with chronic liver disease. SUBJECTS AND METHODS: Pathologically confirmed lesions (100 early HCCs, 7 HGDNs, and 20 RNs with a maximum diameter of more than 1 cm and mean maximal diameters of 15.5, 15.1, and 14.8 mm, respectively) were enrolled in this retrospective study. The signal intensities of these lesions during the hepatobiliary phase of EOB-MRI were investigated, and findings characteristic of RNs using this modality were also evaluated using CEUS. RESULTS: Ninety-eight of the 100 early HCCs that were hypo-intense (n = 95), iso-intense (n = 2), or hyper-intense (n = 1) and the seven HGDNs that were hypo-intense (n = 6) or hyper-intense (n = 1) during the hepatobiliary phase of EOB-MRI exhibited centripetal vessels during the arterial dominant phase of CEUS, although one early HCC that was hypo-intense exhibited both centrifugal and centripetal vessels. Eighteen of the 20 RNs and one early HCC that were hyper-intense with a small central hypo-intensity and the remaining two RNs that were hyper-intense on EOB-MRI exhibited centrifugal vessels during the arterial dominant phase of CEUS. The small central hypo-intense area corresponded to central vascular structures in the lesion, such as the hepatic artery and portal vein running from the center to the periphery, when viewed using CEUS. CONCLUSION: Central vascular structures may be a characteristic finding of RNs when observed during the hepatobiliary phase of EOB-MRI and the arterial dominant phase of CEUS.

Low mechanical index contrast mode versus high mechanical index contrast mode: which is a more sensitive method for detecting Sonazoid microbubbles in the liver of normal subjects?

PURPOSE: Using the low mechanical index (MI) contrast mode and the high MI contrast mode of contrast-enhanced ultrasonography, we evaluated which method is more sensitive for detecting Sonazoid microbubbles in the liver of normal subjects. METHODS: Thirteen normal subjects received an intravenous bolus injection of 0.2 mL of Sonazoid. We defined the intensity difference as the intensity post-injection minus the intensity pre-injection. We evaluated the intensity difference at the portal vein using both the low MI (0.21-0.23) and the high MI (0.7-1.2) at 1 min, at every 10 min between 10 to 60 min, and at every 30 min between 60 to 300 min post-injection. The intensity difference at the liver parenchyma was also evaluated at eight points (1, 10, 30, 60, 120, 180, 240, and 300 min) using the low MI and at three points (1, 10, and 300 min) using the high MI. RESULTS: The intensity differences at the portal vein measured using high MI were significantly higher than those measured using the low MI at each point between 1 and 240 min (P < 0.01) and at 270 min post-injection (P < 0.05). The intensity differences at the liver parenchyma measured using the high MI were also significantly higher than those measured using the low MI at each time point (P < 0.01). CONCLUSION: Compared with the low MI, the high MI is more sensitive for detecting Sonazoid microbubbles in the liver of normal subjects.

Differential diagnosis of gallbladder diseases with contrast-enhanced harmonic gray scale ultrasonography.

OBJECTIVES: We evaluated the usefulness of contrast-enhanced harmonic gray scale ultrasonographic findings for differential diagnosis of gallbladder diseases. METHODS: We evaluated contrast-enhanced harmonic gray scale ultrasonographic images from 33 patients with 35 polypoid gallbladder disease lesions larger than 10 mm in diameter, consisting of 12 biliary sludge lesions, 8 cholesterol polyps, 1 inflammatory polyp, 2 adenomas, and 12 carcinomas. After a galactosepalmitic acid contrast agent was injected, lesions were scanned by contrast-enhanced harmonic gray scale ultrasonography in 2 phases: early vascular and late vascular. RESULTS: None of the biliary sludge lesions (n = 12) showed either tumor vessels or tumor enhancement. Lesions showing tumor vessels and tumor enhancement on contrast-enhanced harmonic gray scale ultrasonography were diagnosed as cholesterol polyp, inflammatory polyp, adenoma, or carcinoma. Three (38%) of the 8 cholesterol polyps showed dotted-type tumor vessels. Branched-type tumor vessels were observed in 5 (62%) of the 8 cholesterol polyps, the 1 (100%) inflammatory polyp, both (100%) adenomas, and 3 (25%) of the 12 carcinomas. Tortuous-type tumor vessels were observed in 9 (75%) of the 12 carcinomas. Lesions with tumor enhancement and tortuous-type tumor vessels on contrast-enhanced harmonic gray scale ultrasonography were diagnosed as carcinomas, and the sensitivity, specificity, and accuracy of this diagnosis with the current modality were 75% (9/12), 100% (23/23), and 91% (32/35), respectively. CONCLUSIONS: Evaluation of tumor vessels on contrast-enhanced harmonic gray scale ultrasonography may be a useful modality for differentiating gallbladder carcinoma from other polypoid gallbladder disease lesions.