Application of contrast-enhanced intraoperative ultrasonography in the decision-making about hepatocellular carcinoma operation

AIM:To evaluate the detection and differentiation ability of contrast-enhanced intraoperative ultrasonography(CE-IOUS) in hepatocellular carcinoma(HCC) operations.METHODS:Clinical data of 50 HCC patients were retrospective analyzed.The sensitivity,specificity,false negative and false positive rates of contrast enhanced magnetic resonance imaging(CE-MRI),IOUS and CEIOUS were calculated and compared.Surgical strategy changes due to CE-IOUS were analyzed.RESULTS:Lesions detected by CE-MRI,IOUS and CEIOUS were 60,97 and 85 respectively.The sensitivity,specificity,false negative rate,false positive rate of CEMRI were 98.2%,98.6%,98.6%,60.0%,respectively;for IOUS were 50.0%,90.9%,1.8%,1.4%,respectively;and for CE-IOUS were 1.4%,40.0%,50.0%,9.1%,respectively.The operation strategy of 9(9/50,18.0%) cases was changed according to the results of CE-IOUS.CONCLUSION:Compared with CE-MRI,CE-IOUS performs better in detection and differentiation of small metastasis and regenerative nodules.It plays an important role in the decision-making of HCC operation.

Contrast-enhanced ultrasonography for the evaluation of liver fibrosis after biliary obstruction

AIM:To investigate perfusion change in contrastenhanced ultrasonography(CEUS) to evaluate liver fibrosis based on biliary obstruction using an animal model.METHODS:New Zealand white rabbits(3-4 kg) underwent bile duct ligation to form a biliary obstruction model.We performed liver CEUS and laboratory tests on the day before the operation(day 0) and every 7 postoperative days until the rabbits were sacrificed.After CEUS,signal intensity of liver parenchyma with a time-intensity curve was analyzed.Perfusion parameters were automatically calculated from regionof-interests,including peak signal intensity,mean transit time,area under the curve and time to peak.Histological grades of liver fibrosis were assessed according to the Metavir score system immediately after sacrifice.Generalized estimating equations were used to analyze the association between liver fibrosis grades and perfusion parameters for statistical analysis.The perfusion parameters were measured on the last day and the difference between day 0 and the last day were evaluated.RESULTS:From the nine rabbits,histological grades of liver fibrosis were grade 1 in one rabbit,grade 2 and 3 in three rabbits each,and grade 4 in two rabbits.Among the four CEUS parameters,only the peak signal intensity measured on the last day demonstrated a significant association with liver fibrosis grades(OR =1.392,95%CI:1.114-1.741,P =0.004).The difference in peak signal intensity between day 0 and the last dayalso demonstrated an association with liver fibrosis(OR =1.191,95%CI:0.999-1.419,P =0.051).The other parameters tested,including mean transit time,area under the curve,and time to peak,showed no significant correlation with liver fibrosis grades.CONCLUSION:This animal study demonstrates that CEUS can be used to evaluate liver fibrosis from biliary obstruction using peak signal intensity as a parameter.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography

Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted Sono VueTM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble Sono Vue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles Sono VueTM or general microbubble Sono Vue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results: Targeted ultrasound microbubble Sono Vue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles Sono Vue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased(P<0.05), and the total area under the curve of medulla increased(P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased(P<0.05). The peak intensity of the curve increased(P<0.05), and the total area under the curve increased(P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased(P<0.05), and the total area under the curve increased(P<0.05). Conclusions: Targeted microbubbles Sono VueTM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Double contrast-enhanced two-dimensional and three-dimensional ultrasonography for evaluation of gastric lesions

AIM:To investigate the value of two-dimensional(2D) and three-dimensional(3D) double contrast-enhanced ultrasonography(DCUS) imaging for evaluation of gastric lesions.METHODS:2D and 3D DCUS imaging with both oral and intravenous administrations of contrast agents was used to assess gastroscopiclly-confirmed gastric lesions in 46 patients with benign and malignant diseases.Initially,liquid-based ultrasound contrast agent(Xinzhang) was given orally at dose of 500-600 mL for conventional ultrasound examination of the gastric lesions,and then a microbubble-based contrast agent(SonoVue) was injected intravenously at dose of 1.2-2.4 mL in bolus fashion to assess the perfusion pattern of the lesions using contrast imaging modes.The parameters derived from time-intensity curves including the arrival time(AT),time to peak(TTP),peak intensity(PI) and enhanced intensity(EI) were measured on the 2D DCUS imaging.3D DCUS of the lesions was acquired to demonstrate the value of this imaging mode.RESULTS:There were 22 cases with benign lesions including chronic gastritis(n = 5),gastric ulcer(n = 9),gastric polyps(n = 3),gastric stromal tumors(n = 5),and 24 cases with malignant lesions including gastric cancer(n = 20),gastric cardia carcinoma(n = 3) and post-operative recurrent gastric cancer(n = 1) in the study.The oral contrast-enhanced ultrasonography(CEUS) imaging of the stomach clearly demonstrated the anatomy of the stomach and morphologic features of gastric lesions.With optimal scanning window and imaging display under oral CEUS,intravenous CEUS clearly showed the perfusion of gastric lesions with various characteristic manifestations.Both 2D and 3D DCUS images clearly demonstrated normal gastric wall as a three-layer structure,from the inside out,hyperechoic mucosa,hypoechoic muscularis and hyperechoic serosa,respectively.There were statistical significant differences of AT(8.68 ± 2.06 vs 10.43 ± 2.75,P = 0.017),PI(34.64 ± 6.63 vs 29.58 ± 8.22,P = 0.023) and EI(29.72 ± 6.69 vs 22.66 ± 7.01,P = 0.001) between malignant lesions and normal gastric wall.However,no differences of AT,PI and EI between benign lesions and normal gastric wall tissue were found.3D DCUS could intuitively display morphological features and vascularities of the lesions with multiplanar and volume views.3D DCUS imaging provided comprehensive information complementary to 2D imaging.The crater or wellhead appearances and feeding vessels as well as distorted nourishing vasculature of gastric carcinoma were better seen with 3D imaging than 2D imaging.CONCLUSION:DCUS imaging can simultaneously display the anatomic and perfusion features of gastric lesions.3D DCUS can provide additional information to 2D DCUS for evaluation of gastric lesions.

Mass-forming pancreatitis: Value of contrast-enhanced ultrasonography

瞄准：在在集体形成的胰腺炎和胰腺的癌之间的鉴别诊断与第二代的造影剂估计提高对比的 ultrasonography (CEUS ) 的用途。方法：从我们的收音机病理数据库，我们检索了经历了 CEUS 的集体形成的胰腺炎或胰腺的癌影响的所有病人。我们由识别“ parenchymographic ”就在集体形成的胰腺炎和胰腺的肿瘤之间的鉴别诊断的可能性而言在 173 胰腺的群众的学习评估了 CEUS 的结果改进在 CEUS 的动态阶段期间，它为集体形成的胰腺炎被认为诊断。结果：在 CEUS， 94% 集体形成的胰腺炎显示出 intralesional parenchymography。CEUS 有 88.6% 的敏感的集体形成的胰腺炎的允许的诊断， 97.8% 的特性， 91.2% 的积极预兆的价值， 97.1% 的否定预兆的价值，和外套 96% 的精确性。CEUS 显著地在在集体形成的胰腺炎和胰腺的癌之间的鉴别诊断增加了诊断信心，与操作从 0.557 的特性曲线区域的接收装置(P = 0.1608 ) 为到 0.956 的基线美国(P 【 0.0001 ) 为 CEUS。结论：CEUS 与 96% 的诊断精确性允许集体形成的胰腺炎的诊断。CEUS 显著地在从胰腺的瘤认出集体形成的胰腺炎关于基础美国增加诊断信心。

Contrast-enhanced ultrasonography in peripheral lung consolidations: What's its actual role?

AIM:To evaluate the diagnostic accuracy of contrastenhanced ultrasonography(CEUS)in the differential diagnosis between neoplastic and non-neoplastic peripheral pleuro-pulmonary lesions.METHODS:One hundred patients with pleural or peripheral pulmonary lesions underwent thoracic CEUS.An 8 microliters/mL solution of sulfur hexafluoride microbubbles stabilized by a phospholipid shell(SonoVue)was used as US contrast agent.The clips were stored and independently reviewed by two readers,who recorded the following parameters:presence/absence of arterial enhancement,time to enhancement(TE),extent of enhancement(EE),pattern of enhancement(PE),presence/absence of wash-out,time to wash-out,and extent of wash-out.After the final diagnosis(based on histopathologic findings or follow-up of at least 15 mo)was reached,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),positive likelihood ratio(PLR),negative likelihood ratio(NLR)of each CEUS parameter in the differential diagnosis between neoplastic and nonneoplastic lesions were calculated.Furthermore,an arbitrary score based on the ratio between the PPVs of each CEUS parameter was calculated,to evaluate if some relationship could exist between overall CEUS behaviour and neoplastic or non-neoplastic nature of the lesions.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Differential diagnosis of benign and malignant branch duct intraductal papillary mucinous neoplasm using contrastenhanced endoscopic ultrasonography

AIM: To elucidate the role of contrast-enhanced endoscopic ultrasonography(CE-EUS) in the diagnosis of branch duct intraductal papillary mucinous neoplasm(BD-IPMN).METHODS: A total of 50 patients diagnosed with BDIPMN by computed tomography(CT) and endoscopic ultrasonography(EUS) at our institute were included in this study. CE-EUS was performed when mural lesions were detected by EUS. The diagnostic accuracy for identifying mural nodules(MNs) was evaluated by CT, EUS, and EUS combined with CE-EUS. In the patients who underwent resection, the accuracy of measuring MN height with each imaging modality was compared. The cut-off values to diagnose malignant BD-IPMNs based on MN height for each imaging modality were determined using receiver operating characteristic curve analysis.RESULTS: Fifteen patients were diagnosed with BD-IPMN with MNs and underwent resection. The remaining 35 patients were diagnosed with BD-IPMN without MNs and underwent follow-up monitoring. The pathological findings revealed 14 cases with MNs and one case without. The accuracy for diagnosing MNs was 92% using CT and 72% using EUS; the diagnostic accuracy increased to 98% when EUS and CE-EUS were combined. The accuracy for measuring MN height significantly improved when using CE-EUS compared with using CT or EUS(median measurement error value, CT: 3.3 mm vs CE-EUS: 0.6 mm, P < 0.05; EUS: 2.1 mm vs CE-EUS: 0.6 mm, P < 0.01). A cut-off value of 8.8 mm for MN height as measured by CE-EUS improved the accuracy of diagnosing malignant BDIPMN to 93%. CONCLUSION: Using CE-EUS to measure MN height provides a highly accurate method for differentiating benign from malignant BD-IPMN.

Clinical value of contrast-enhanced ultrasonography in the characterization of focal liver lesions:a prospective multicenter trial

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is increasingly accepted in clinical settings for diagnostic imaging of focal liver lesions (FLLs). This study aimed to assess the efficacy of CEUS in the characterization of FLLs in comparison with final diagnosis based on gold standard assessment. METHODS: The study was approved by the local ethics committee and participating patients provided written informed consent. A total of 148 patients with 164 FLLs were studied. Unenhanced ultrasonography (US) and CEUS were performed using fundamental and harmonic imaging, respectively. Contrast enhancement was assessed during the arterial, portal and late vascular phases after intravenous administration of contrast (SonoVue (R), Bracco, Italy). Sensitivity, specificity and diagnostic accuracy of US and CEUS were compared in identifying the lesion as benign, malignant or indeterminate and its actual tumor type. Final diagnosis was established by biopsy (129/164), MR imaging (11/164) or medical history (24/164). RESULTS: When compared to the gold standard, the number of indeterminate diagnoses was reduced from 56.7% (93/164) as assessed by fundamental imaging to 6.1% (10/164) after SonoVue (R) enhanced US examination. Sensitivity and specificity improved from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively (P<0.01). Diagnostic accuracy of CEUS was 88% in contrast to 41% of baseline US. CONCLUSION: SonoVue (R) enhanced US improves the characterization of FLLs and may limit the need for further investigations.

Arterial-phase contrast-enhanced ultrasonography for evaluating anti-angiogenesis treatment: A pilot study

AIM:To verify whether arterial-phase contrast-enhanced ultrasonography(CEUS) of tumor parenchymal tissue is useful for evaluation of anti-angiogenesis agents.METHODS:Rabbits with liver tumor were subjected to CEUS,and images of the nodular maximal diameter in vascular phase were recorded.Image analysis was performed to plot the time intensity curve(TIC) at the tumor parenchyma,which set the diameter of the region of interest of intensity measurement.The TIC was calculated to obtain the time to peak intensity(TPI) and the magnitude of PI.Rabbits were randomly assigned to a treatment group with sorafenib and a control group.Two weeks later,the same ultrasound examination was repeated followed by pathological testing to assess the effect of sorafenib on the liver tumor.RESULTS:In four rabbits in the treatment group,the rate of change of tumor size was decreased comparedwith that of the control(the rate 2.3 vs 7.9,P = 0.02).The TPI of the treatment group elongated significantly(the rate 3.1 vs 1.1,P = 0.07 for SonoVue,2.0 vs 0.88,P = 0.09 for Sonazoid).The magnitude of PI showed no significant changes.In pathological examination,capillary diameters in the treatment group were significantly smaller than those in the control group(26.4 vs 42.8 μm,P = 0.013).CONCLUSION:Analysis of the TIC in the arterial phase of tumor tissue could evaluate the efficacy of antiangiogenesis drug treatment in liver tumor.

Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography(CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma.METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled.In the primary analysis, patients with successful EUSfine needle aspiration(FNA) were included. The lymph nodes were assessed by several standard EUS variables(short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel(CIV) presence] and CH-EUS variable(heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUSFNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection.RESULTS: One hundred and nine patients(143 lymph nodes) fulfilled the criteria. The short axis cutoff ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS.CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

Evaluation of hepatocellular carcinoma using contrast-enhanced ultrasonography:correlation with microvessel morphology

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is an important technique for depiction and assessment of tumor vascularity. This study aimed to explore the relationship between the morphological characteristics of tumor microvessels and enhancement patterns on CEUS in hepatocellular carcinoma (HCC). METHODS: Eighty patients with HCC underwent CEUS using SonoVue before hepatectomy. Contrast-enhanced ultrasonographic enhancement patterns and quantitative parameters were recorded. The tumor tissue sections were immunostained with human CD34 monoclonal antibody. The patients were classified into a point-line type group (n=36) and a loop-strip type group (n=44) according to microvessel morphology. The microvascular density (MVD) in the different types of microvessels was calculated. The relationship between enhancement patterns of HCC lesions and morphological characteristics of tumor microvessels was analyzed. RESULTS:TS: The mean MVD in HCC was 22.4 +/- 3.5 per 0.2 mm(2) in the point-line group, and 19.6 +/- 6.7 per 0.2 mm(2) in the loop-strip group, and there was no significant difference between them (t=0.948, P=0.354). In the portal vein phase, hypoenhancement was significantly more frequent in HCC (chi(2)=4.789, P=0.029) in the loop-strip group (40/44, 90.9%) than in the point-line group (26/36, 72.2%). The time to hypoenhancement in the loop-strip group (mean 64.84 +/- 26.16 seconds) was shorter than that in the point-line group (mean 78.39 +/- 28.72 seconds) (t=2.247, P=0.022). The time to hypoenhancement was correlated with MVD in the loop-strip group (r=-0.648, P=0.001). CONCLUSIONS: The enhancement patterns on CEUS are related to tumor microvascular morphology, and the type of microvascular morphology influences CEUS characterization. CEUS, an important noninvasive imaging technique, is used to evaluate microvascular morphology and angiogenesis, providing valuable information for antiangiogenic therapy in HCC. (Hepatobiliary Pancreat Dis Jut 2010; 9:605-610)

Contrast-enhanced ultrasonographic findings of hepatic paragonimiasis

AIM: To investigate the features of hepatic paragonimiasis on contrast-enhanced ultrasound (CEUS) imag- ing. METHODS: Fifteen patients with hepatic paragonimiasis who were admitted to our hospital between March 2008 and August 2012 were enrolled to this study. The conventional ultrasound and CEUS examinations were performed with a Philips IU22 scanner with a 1-5-MHz convex transducer. After conventional ultrasound scanning was completed, the CEUS study was performed. Pulse inversion harmonic imaging was used for CEUS. A bolus injection of 2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent (SonoVue) was administered. CEUS features were retrospectively reviewed and correlated with pathological findings. RESULTS: In total, 16 lesions were detected on CEUS. The mean size of the lesions was 4.4 ± 1.6 cm (range, 1.7-6.6 cm). Subcapsular location was found in 12 lesions (75%). All the lesions were hypoechoic. Six lesions (37.5%) were of mixed content, seven (43.8%) were solid with small cystic areas, and the other three (18.8%) were completely solid. Ten lesions (62.5%) were rim enhanced with irregular tract-like nonenhanced internal areas. Transient wedge-shaped hyperenhancement of the surrounding liver parenchyma was seen in seven lesions (43.8%). Areas with hyperor iso-enhancement in the arterial phase showed contrast wash-out and appeared hypoenhanced in the late phase. The main pathological findings included: (1) coagulative or liquefactive necrosis within the lesion, infiltration of a large number of eosinophils with the formation of chronic eosinophilic abscesses and sporadic distribution of Charcot-Leyden crystals; and (2) hyperplasia of granulomatous and fibrous tissue around the lesion. CONCLUSION: Subcapsular location, hypoechogenicity, rim enhancement and tract-like nonenhanced areas could be seen as the main CEUS features of hepatic paragonimiasis.

Correlation between Enhanced Intensity of Atherosclerotic Plaque at Contrast-enhanced Ultrasonography and Density of Histological Neovascularization

Summary： The feasibility of contrast-enhanced ultrasonography in the assessment of atherosclerotic plaque neovascularization and its relation to histological findings were investigated. Abdominal aortic atherosclerotic plaque model was induced in 25 New Zealand white rabbits by a combination of high cholesterol-rich diet and balloon aortic denudation. Standard and contrast-enhanced ultrasonography was performed at the 16th week of the model induction period. The plaques were classified as echogenic plaques or echolucent plaques according to their echogenicity at standard ultrasonography. The maxi- mum thickness of plaque was measured in the longitudinal section. Time intensity curve was used to quantify the enhanced intensity of the plaque. Animals were euthanized and abdominal aortas were har- vested for histological staining of CD31 to evaluate the neovascularization density of atherosclerotic plaque. The results showed that the echolucent plaques had higher enhanced intensity during con- trast-enhanced ultrasonography and higher neovascularization density at CD31 staining than the echo- genic plaques. The enhanced intensity of atherosclerotic plaque and its ratio to lumen were well corre- lated with histological neovascularization density （r=0.75, P〈0.001; r=0.68, P〈0.001, respectively）. However, the maximum thickness of plaque was not correlated with neovascularization density （r=0.235, P=0.081）. These findings demonstrated that the enhanced intensity in the plaque and ratio of enhanced intensity to that in the lumen of abdominal aorta may be more accurate in the evaluation of plaque neovascularization than maximum thickness. Our study indicates that contrast-enhanced ultra- sonography provides us a reliable method for the evaluation of plaque neovascularization.

A case of eosinophilic cholangitis:Imaging findings ofcontrast-enhanced ultrasonography, cholangioscopy, andintraductal ultrasonography

A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient's biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient's eosinophil count was over 1000/mm3. Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.

Current status and future applications of contrast-enhanced endoscopic ultrasonography

Endoscopic ultrasonography(EUS) is currently an in-tegral investigation of many gastrointestinal disorders.It has been shown to have a higher efficacy thanconventional computed tomography in detection andcharacterization of small lesions especially in the pan-creas. Much effort has been put to further improvethe sensitivity, specificity and overall accuracy of EUS.One of the major advances is the utilization of contrastagents for better delineation of the vascularity and tis-sue perfusion of the target lesion. This article describesthe basic principles of ultrasound contrast agents andthe different modalities used in contrast-enhanced EUS(CE-EUS) including contrast-enhanced Doppler EUS(CED-EUS) and contrast-enhanced harmonic EUS(CEH-EUS). In addition, the current applications of contrastenhanced EUS in different gastrointestinal conditionswere discussed. Furthermore, the future developmentof hybrid approaches combining CE-EUS with other im-aging modalities and the potential therapeutic aspectof using it as a vector for drug delivery were also dis-cussed.

Contrast-enhanced ultrasonography in the evaluation of incidental focal liver lesions: A cost-effectiveness analysis

AIM To determine whether contrast-enhanced ultrasonography(CEUS) as the first-line method is more costeffective in evaluating incidentally discovered focal liver lesions(FLLs) than is computed tomography(CT) and magnetic resonance imaging(MRI). METHODS Between 2010 and 2015, our prospective study enrolled 459 patients with incidentally found FLLs. The biological nature of FLLs was assessed by CEUS in all patients. CT or MRI examinations were added in unclear cases. The sensitivity and specificity of CEUS were calculated. The total costs of CEUS examinations and of the added examinations performed in inconclusive cases were calculated. Afterwards, the theoretical expenses for evaluating incidentally discovered FLLs using CT or MRI as the first-line method were calculated. The resultswere compared. RESULTS The total cost of the diagnostic process using CEUS for all enrolled patients with FLLs was 75884 USD. When the expenses for additional CT and MRI examinations performed in inconclusive cases were added, the total cost was 90540 US dollar(USD). If all patients had been examined by CT or MR as the first-line method, the costs would have been 78897 USD or 384235 USD, respectively. The difference between the cost of CT and CEUS was 3013 USD(4%) and that between MRI and CEUS was 308352 USD(406.3%). We correctly described 97.06% of benign or malignant lesions, with 96.99% sensitivity and 97.09% specificity. Positive predictive value was 94.16% and negative predictive value was 98.52%. In cases with 4 and more lesions, malignancy is significantly more frequent and inconclusive findings significantly less frequent(P < 0.001).CONCLUSION While the costs of CEUS and CT in evaluating FLLs are comparable, CEUS examination is far more costeffective in comparison to MRI.

Evaluation of Carotid Plaque Neovascularization in Patients with Diabetes Mellitus by Contrast-enhanced Ultrasonography

This study investigated the relationship between carotid plaque neovascularization and diabetes mellitus（DM） by using contrast-enhanced ultrasonography. Contrast-enhanced ultrasonography was performed in 104 patients with carotid plaque thicker than 2.0 mm. There were 36 patients with DM and 68 patients without DM. The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery in patients with DM were significantly greater than those in patients without DM. Our study demonstrated that the enhanced intensity in patients with DM is greater than that their counterparts without DM, suggesting that carotid plaque in DM patients may have more neovessels and may be more vulnerable.

Contrast-enhanced intraoperative ultrasonography equipped with late Kupffer-phase image obtained by sonazoid in patients with colorectal liver metastases

AIM: To find occult metastases during hepatectomy in patients with colorectal cancer liver metastases (CRCLM), contrast-enhanced intraoperative ultrasonography (CE-IOUS) was performed using a new microbubble agent, sonazoid, which provides a parenchyma-specific contrast image based on its accumulation in the Kupffer cells. METHODS: Eight patients with CRCLM underwent CE- IOUS using sonazoid before hepatectomy. The liver was investigated during a late Kupffer-phase imaging, which is a valuable characteristic of sonazoid. RESULTS: CE-IOUS using sonazoid provided the early vascular- and sinusoidal-phase images for 10 min followed by the late Kupffer-phase image up to 30 min after the injection of sonazoid. IOUS did not provide new findings of metastatic lesion in the 8 patients. However, during the late Kupffer-phase image of sonazoid, a metastatic lesion was newly found in two of the 8 patients. These newly detected lesions were removed by an additional hepatectomy and histopathologically diagnosed as a metastasis. CONCLUSION: CE-IOUS using sonazoid can allow surgeons to investigate the whole liver with enough time and to find new metastases intraoperatively.

Usefulness of contrast-enhanced ultrasonography in determining treatment efficacy and outcome after pancreatic cancer chemotherapy

AIM:To investigate if contrast-enhanced ultrasonography(CE-US) is useful for determining treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy by assessing changes in intratumor hemodynamics using CE-US with a contrast agent.METHODS:The subjects were 34 patients with unresectable advanced pancreatic cancer treated by chemotherapy.CE-US was assessed after every treatment(course) completion under the same conditions,and patients were divided into two groups according to the intratumor enhancement pattern:Vascular rich(R) group and vascular poor(P) group.RESULTS:After the second course of treatment,R group in intratumor hemodynamics had 18 patients,and P group had 16 patients.The reduction rates of serum CA19-9 level after chemotherapy which decreased to half or less of the baseline level were 2/15(0.1%) in P group,but 11/16(69%) in R group(P = 0.006).When the mean number of courses of chemotherapy and outcome were compared,P group had a mean number of courses of 4.9(R group,10.2) and mean survival time(MST) of 246 d(R group,402 d),showing that outcome was significantly better in R group(P=0.006).CONCLUSION:CE-US revealed that the change in intratumor blood flow correlated with both serum CA19-9 level and outcome.Patients with serum CA19-9 that decreased to less than half the baseline level,and patients with an abundant intratumor blood flow,had a significantly better outcome.Thus,CE-US is potentially useful for evaluating treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy.