Comparison of contrast-enhanced ultrasonograpy with Gd-EOB-DTPA-enhanced MRI in the diagnosis of liver metastasis from colorectal cancer.

PURPOSE: To compare contrast-enhanced ultrasonography (CEUS) using Sonazoid with Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in the diagnosis of liver metastases in patients with colorectal cancer. METHODS: A total of 69 patients diagnosed with or suspected of having liver metastasis were enrolled. These hepatic lesions were diagnosed by histopathological examination after surgical resection or based on follow-up using various imaging modalities. The diagnostic accuracies of CEUS and EOB-MRI were compared. RESULTS: One hundred thirty-three lesions were detected. Of these lesions, 109 were diagnosed as liver metastases. Of the 133 lesions, 90.2% were detected on CEUS, and 98.5% on EOB-MRI. One hundred nine lesions were diagnosed as liver metastasis. The areas under the receiver operating characteristic curve for diagnosis were 0.906 and 0.851 on CEUS and EOB-MRI, respectively (p = 0.41). Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and overall accuracy were 90.8%, 84.5%, 97.1%, 67.1%, and 90.2%, respectively, for CEUS, and 95.4%, 70.8%, 93.7%, 77.3%, and 91%, respectively, for EOB-MRI. CONCLUSIONS: CEUS has a higher specificity and PPV for the diagnosis of liver metastasis than EOB-MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:138-144, 2017.

[Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival.

[Evaluation of Sorafenib for Hepatocellular Carcinoma with Low α-Fetoprotein by Arrival Time Parametric Imaging Using Contrast-Enhanced Ultrasonography with Sonazoid].

We aimed to determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS)with Sonazoid in the evaluation of early response to sorafenib for hepatocellular carcinoma (HCC). Thirteen ad- vanced HCC patients with low a / -fetoprotein (AFP) level (≤35 ng/mL) who received sorafenib for at least 4 weeks were enrolled in this study. CEUS was performed before and after treatment (2 weeks), and the images of the target lesion in the arterial phase were analyzed by AtPI. In the color mapping images obtained by AtPI, the mean arrival time of the contrast agent in the target lesion from the starting point (mean time: MT) was calculated. In each patient, differences between MT before and MT 2 weeks after treatment were compared. MT (+) and MT(-) groups were designated as such if the difference was 0 or greater(blood flow velocity of the lesion was reduced)and less than 0 sec(blood flow velocity of the lesion was increased), respectively. The overall survival was evaluated between the 2 groups. In the MT (+) group (7 patients) and MT (-) group (6 patients), the median survival times were 307 and 208 days, respectively, which was statistically significant. We suggest AtPI is useful for evaluating early response to sorafenib in advanced HCC patients with low AFP level.

[Efficacy of Sorafenib versus Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization].

We compared the benefits of sorafenib with that of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (ad-HCC) refractory to transcatheter arterial chemoembolization (TACE). We evaluated the patient characteristics, the median survival time (MST), and the prognostic factors in 17 patients in the sorafenib group and in 26 patients in the HAIC group. No significant difference was observed in the patient characteristics between the groups. The MST in the sorafenib group and HAIC group was 483 days and 284 days, respectively. A significantly longer survival time was noted in the sorafenib group (p=0.033). The prognostic factors were sorafenib therapy in all 43 patients(hazard ratio: 3.32 [95% CI: 1.36-8.10], p=0.008) and the longer treatment period of sorafenib in the sorafenib group(hazard ratio: 0.99 [95% CI: 0.984- 0.999], p=0.009). When compared with HAIC, sorafenib showed favorable treatment results in patients with ad-HCC refractory to TACE.

Comparison of Sorafenib and Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Study.

BACKGROUND/AIMS: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib vs hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma. METHODOLOGY: Forty-seven patients treated with sorafenib (sorafenib group) and 77 patients treated with HAIC (HAIC group) were investigated retrospectively using propensity score matching (PSM) to minimize selection bias. The cumulative survival rate was investigated before and after PSM in each of the sorafenib and HAIC groups. The cumulative survival rate was compared between the sorafenib and HAIC groups, and among the TNM stage by the Liver Cancer Study Group of Japan (LCSGJ TNM stage). RESULTS: No significant difference was noted in overall survival (OS) between the sorafenib and HAIC groups regardless of before or after PSM. On comparison of the cumulative survival rate between the groups by the same LCSGJ TNM stage, significant prolongation of OS was noted in stage IVB only in the sorafenib group (p = 0.032) after PSM. CONCLUSIONS: It may be better to actively introduce sorafenib for stage IVB, i.e., patients with extrahepatic metastasis.

A case of sclerosing angiomatoid nodular transformation of the spleen: correlations between contrast-enhanced ultrasonography and histopathologic findings.

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized benign vascular lesion of the spleen. Detection of SANT as an incidentaloma has increased due to improvements in imaging techniques. However, a definitive diagnosis of SANT on CT or MRI remains difficult. We report the use of contrast-enhanced ultrasonography with Sonazoid in a case of SANT in a 50-year-old woman, with gross and microscopic pathologic correlations.

A case of solitary bile duct hamartoma with advanced gastric carcinoma: findings in contrast-enhanced ultrasonography.

Bile duct hamartomas (BDH), which are also known as von Meyenburg complexes, are benign neoplasms that involve cystic dilatation of the bile duct surrounded by fibrous stroma. However, multiple lesions develop in most cases of BDH, whereas a solitary lesion, as seen in our case, is relatively rare. We report here the co-existence of gastric carcinoma and BDH mimicking metastasis in a 30-year-old woman. A lesion measuring 13 × 9 mm with the appearance of a hyperechoic nodule with no pulsatile blood flow signals was observed on US and Doppler US in S4 of the liver. On contrast-enhanced ultrasonography (CEUS), the septum-like structure in the tumor was weakly enhanced at 17 s after administration of Sonazoid. There has been no description of solitary BDH findings on CEUS in the literature. We present the US findings of BDH, including those yielded by CEUS using Sonazoid, along with the microscopic pathological correlation.

Duct of Luschka diagnosed by sonography in a patient with bile duct carcinoma and intrahepatic bile duct dilatation.

The bile duct of Luschka (BDL) is an anatomic anomaly that is an important cause of bile leakage after bile duct surgery. We report a case of bile duct carcinoma with dilated BDL that was diagnosed by ultrasonography (US). An 83-year-old man presented with an obstructive jaundice. US on admission revealed the presence of a solid hypoechoic mass in the bile duct at the hepatic duct confluence and a branch of the bile duct, about 2-4 mm in diameter, distinct from the dilated right anterior hepatic duct slightly upstream of the tumor. This branch had a spiral structure, extended along the gallbladder bed on the surface of segment 5 (S5) of the liver, and emanated small branches that entered the hepatic parenchyma. There has been no previous report of delineation of BDL by preoperative US.

Right hepatic artery pseudoaneurysm complicating acute pancreatitis: a case report.

OBJECTIVE: To report a rare case of right hepatic artery pseudoaneurysm complicating acute pancreatitis based upon imaging findings obtained before and after the development of pseudoaneurysm. CLINICAL PRESENTATION AND INTERVENTION: A 32-year-old male with a history of acute pancreatitis 1 year prior was readmitted for acute pancreatitis. Computed tomography (CT) and angiography after admission revealed pseudoaneurysm of the right hepatic artery. Transcatheter arterial embolization with coils was used to successfully treat the pseudoaneurysm. A CT and angiography 1 year earlier did not reveal any pseudoaneurysm. CONCLUSION: This patient with a rare right hepatic artery pseudoaneurysm complicating acute pancreatitis was successfully treated with coil embolization.

Hepatic parenchymal hemodynamics of cholangitis with portal trunk thrombus using contrast-enhanced ultrasonography with Sonazoid: delineation of so-called central and peripheral zonal differentiation by arrival-time parametric imaging.

We carried out contrast-enhanced ultrasonography using Sonazoid for a patient who had portal thrombosis due to choledocholith and cholangitis, and the video images were analyzed by an offline procedure using arrival-time parametric imaging. Colors were changed with the time course from red to orange, yellow, green, light blue, and blue, with the time the contrast agent reached the right hepatic artery as the starting point. The central part of the liver was primarily colored blue, and the peripheral part primarily yellowish-green. In other words, we confirmed the central and peripheral zonal differentiation observed in the arterial phase of dynamic computed tomography by color mapping image of arrival-time parametric imaging. Particularly, real-time changes in the hemodynamics of the hepatic parenchyma could be captured by color mapping image using arrival-time parametric imaging.

Ultrasonography of intrahepatic bile duct adenoma with renal cell carcinoma: correlation with pathology.

Intrahepatic bile duct adenoma (BDA) is a relatively rare benign tumor. Most cases are incidentally discovered during surgery or autopsy. We report here the co-existence of renal cell carcinoma and BDA mimicking metastasis in a 30-year-old female. An isoechoic nodule with a hypoechoic rim sized 10 × 9 mm was observed by ultrasonography in S2 of the liver. On contrast-enhanced ultrasonography (CEUS), the mass was enhanced in the early vascular phase and a defect with a clear border appeared in the post-vascular phase. We present the ultrasonography findings of BDA, including those yielded by CEUS using Sonazoid, along with the gross and microscopic pathological correlation.

Diagnosis of hepatic hemangioma by parametric imaging using sonazoid-enhanced US.

BACKGROUND/AIMS: Comparison of Parametric Imaging (PI) using Sonazoid-enhanced ultrasonography (US) and microflow imaging (MFI) to determine the possibility of hepatic hemangioma diagnosis using PI. METHODOLOGY: Twenty-two hepatic hemangioma nodules (mean±SD diameter: 31.6±19.1mm) undergoing Sonazoid-enhanced US between February 2008 and March 2009. After Sonazoid-enhanced US, COMMUNE ultrasonographic image analysis software was used for analysis of tumor imaging dynamics in the vascular phase using PI and MFI. In PI, 0s was set as the time contrast agent reached the tumor. Imaging within the tumor after 0s was color-coded according to time, and the images were displayed in color. In MFI, 0s was set as the time contrast agent reached the tumor. The path of microbubbles as it flowed through blood vessels was superimposed on the original B-mode images. Three trained physicians used these methods to analyze tumor imaging dynamics. RESULTS: All physicians concluded all cases were hepatic hemangioma regardless of method used. However, compared to MFI, PI allowed determination of more detailed blood flow dynamics in high-flow hepatic hemangioma, where blood flow speed was faster than in normal hepatic hemangioma. CONCLUSIONS: It is possible to diagnose hepatic hemangioma using PI using sonazoid-enhanced US.

[Gastrointestinal hemorrhage associated with concurrent use of sorafenib and warfarin for hepatocellular carcinoma].

A 60-year-old man with liver cirrhosis caused by hepatitis C, who was receiving warfarin anticoagulation following acute myocardial infarction, was diagnosed with advanced hepatocellular carcinoma and multiple lung metastases, and began treatment with sorafenib 200 mg daily. From the treatment's start to 14 and 63 days later, sorafenib was increased to 400 mg and 600 mg, respectively. After increasing the quantity to 600 mg, he had an increase in PT-INR values and experienced a lower-extremity hemorrhage. For the patient with liver cirrhosis, who is receiving warfarin, PT-INR values might be elevated during the early period of sorafenib treatment dosage as for the increase in quantity. Therefore, when increasing dosage, a frequent measurement of PT-INR and a careful follow-up for PT-INR is necessary.

Predicting Therapeutic Efficacy of Transarterial Chemoembolization with Drug-Eluting Beads for Hepatocellular Carcinoma Using Contrast-Enhanced Ultrasound.

The aim of this study was to assess the usefulness of contrast-enhanced ultrasound (CEUS) for predicting the therapeutic efficacy of transarterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Thirty-two patients with HCC who underwent DEB-TACE were enrolled in this study. Enhancement patterns of vascular phase images on CEUS were compared before and within 3 days after DEB-TACE, and the patterns after DEB-TACE were classified as follows: Pattern A, no enhancement; Pattern B, peripheral ring enhancement; Pattern C, partial enhancement within or peripheral to tumors, and Pattern D, reduced or unchanged enhancement in the whole tumor. Enhancement patterns in all lesions and contrast-enhanced computed tomography (CECT) findings after DEB-TACE were compared statistically. The treatment response of DEB-TACE was evaluated using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) by CECT. The enhancement patterns on CEUS performed within 3 days after DEB-TACE were defined as Pattern A in 17 cases, B in 7, C in 13, and D in 2. The complete response rates at one month after treatment were 94.1% (16/17 lesions) for Pattern A, 85.7% (6/7) for B, 15.4% (2/13) for C, and 50% (1/2) for D. The response rates were significantly higher for lesions with Pattern A compared to those with Pattern C at one month (p = 0.009) and 12 months (p < 0.001) after treatment, and significantly higher for lesions with Pattern B compared to those with Pattern C at 12 months after treatment (p = 0.031). Comparisons between other patterns showed no significant differences. CEUS immediately after DEB-TACE may allow early assessment of therapeutic efficacy, with findings of no enhancement or peripheral ring enhancement suggesting a positive outcome.

Tumor lysis syndrome after sorafenib for hepatocellular carcinoma: a case report.

We encountered a patient who developed marked renal impairment and hyperuricemia in a short period after sorafenib administration, which suggested tumor lysis syndrome (TLS). A 79-year-old woman with hepatitis C-related liver cirrhosis was found to have intermediate hepatocellular carcinoma (HCC) according to Barcelona Clinic Cancer staging classification. Pre-treatment laboratory tests showed mild renal impairment. On the 10th day of sorafenib intake, the creatinine and uric acid levels rose to 2.99 and 16.1 mg/dl, respectively, and arterial blood gas analysis showed respiratory compensated metabolic acidosis, which suggested grade I clinical TLS according to the diagnostic criteria of TLS as defined by Cairo-Bishop. TLS is a group of metabolic abnormalities that arise from the rapid breakdown of many tumor cells upon the initiation of malignant tumor chemotherapy, resulting in the release of intracellular metabolites that exceed the ability of the kidney to excrete them. TLS occurs more rarely in solid tumors, including HCC, than in hematologic malignancies. Sorafenib is administered to patients with renal impairment at recommended doses. However, the drug may cause TLS or severe renal impairment in advanced HCC patients with preexisting mild renal impairment, necessitating reduced-dose therapy and careful follow-up after the start of therapy to facilitate early diagnosis and treatment. This is a very rare complication developed in a short period treated with sorafenib as a single-agent for an advanced HCC.

Recurrence incidence of small HCC in cirrhosis patients by ablation versus injection.

BACKGROUND/AIMS: The incidence of local recurrence of hypervascular hepatocellular carcinoma (HCC) (15 mm or less) was compared retrospectively between a group treated with radiofrequency ablation (RFA) using cool-tip (Radionics, USA) 10-mm electrodes and a group treated with percutaneous ethanol injection (PEI). METHODOLOGY: There were 23 patients who were treated for a total of 25 tumors during a 3-year period at our hospital. Ten of the tumors (11.1 +/- 2.7mm) were treated with RFA using cool-tip 10-mm electrodes and 15 tumors (10.6 +/- 2.7 mm) were treated with PEI. After treatment, progression was evaluated in enhanced CT scans every 3-6 months to confirm presence or absence of local recurrence. RESULTS: The number of recurrences, mean observation period, and mean recurrence period in the RFA group were 2 (20%), 6.6 months, and 6 months. The number of recurrences, mean observation period, and mean recurrence period in the PEI group were 2 (13.3%), 19.1 months, and 18 months. The period between treatment and recurrence tended to be longer in the PEI group than in the RFA group to be significant p < 0.05. CONCLUSIONS: The results suggest that PEI treatment is more effective in local treatment of hypervascular HCC with tumor diameters of 15 mm or less.

Evaluation of local recurrence after treatment for hepatocellular carcinoma by contrast-enhanced ultrasonography using Sonazoid: comparison with dynamic computed tomography.

PURPOSE: To evaluate the effectiveness of contrast-enhanced ultrasonography (CEUS) using Sonazoid for the diagnosis of the local recurrence after treatment for hepatocellular carcinoma (HCC) by comparing it with dynamic CT. METHODS: Seventy-one patients with 87 HCC lesions (mean +/- SD; 19.5 +/- 9.6 mm) underwent CEUS using Sonazoid and dynamic CT after radiofrequency ablation (n = 55), transcatheter arterial chemoembolization (n = 22), or radiofrequency ablation combined with transcatheter arterial chemoembolization (n = 10). Two hepatologists (observer 1; 10 years of experience, and 2; 20 years of experience) reviewed the CEUS and dynamic CT images independently and evaluated presence or absence of the local recurrence. Diagnostic performance for the local recurrence was assessed using receiver operating characteristic curve analysis. RESULTS: The Az value for dynamic CT was significantly lower in observer 1 than 2 (p < 0.05). The sensitivity of CEUS was 79% in observer 1 and 83.9% in observer 2, and that of dynamic CT was 83.9% and 90.3%, respectively. The specificity of CEUS was 96%, and that of dynamic CT was 92%, in both observers. CONCLUSION: This study suggests that CEUS using Sonazoid is less affected by the observer's experience and is more accurate in the diagnosis of local recurrence after treatment for HCC than dynamic CT.

Parametric imaging using contrast-enhanced ultrasound with Sonazoid for hepatocellular carcinoma.

PURPOSE: To clarify the usefulness of parametric imaging using contrast-enhanced ultrasound (CE-US) with Sonazoid by comparing parametric images of hepatocellular carcinoma (HCC) with histopathological findings. METHODS: Two patients with HCCs underwent CE-US with Sonazoid before surgical resection. A single focus point was set at the lower margin of the tumor, and a bolus intravenous injection of Sonazoid (0.5 ml) was administered. Images of the ideal scanning plane were displayed in real-time mode for the early vascular phase. We analyzed these images using prototype PC software. The software watches, pixel by pixel, the increase in the intensity due to the inflow of the microbubbles, and displays colors if the intensity becomes larger than a certain threshold. Parametric images were compared with histopathological findings. RESULTS: The level of blood flow in the tumor could be visually evaluated using a single image by expressing the detailed hemodynamics of the tumor in terms of differences in color using a time axis appropriate for each case. CONCLUSIONS: Parametric imaging is a very useful way of facilitating straightforward visualization of the level of blood flow within HCC and the distribution of histopathological findings in single static images.

Evaluation of the hemodynamic status of focal hepatic lesions 20 mm or less in diameter by contrast-enhanced ultrasonography using Sonazoid.

OBJECTIVE: To clarify the validity of the evaluation of the hemodynamics of hepatic lesions < or =20 mm in diameter using contrast-enhanced ultrasonography (CE-US) with Sonazoid. METHODS: Sixty-two hepatic lesions in 55 patients with chronic hepatitis or cirrhosis due to hepatitis C virus were studied. We evaluated by quantitative analysis the time intensity curve (TIC) on hepatic lesion and parenchyma in the early vascular phase and Kupffer imaging in the post-vascular phase. RESULTS: TIC patterns were classified into those with a maximum slope (Max slope) steeper in the hepatic lesion than in the parenchyma (Pattern I), those with a Max slope similar in the hepatic lesion and parenchyma (Pattern II), and those with a Max slope gentler in the hepatic lesion than in the parenchyma (Pattern III). The blood flow was considered to be higher, the blood flow velocity to be faster, and the contrast agent to reach the lesion more rapidly in Pattern I lesions than in the hepatic parenchyma. Pattern III lesions showed that the velocity of arterial blood influx was slow. CONCLUSION: Our study suggested the possibility that the TIC allows a detailed evaluation of the hemodynamics of hepatic lesions.

Analysis of patients with rapid aggressive tumor progression of hepatocellular carcinoma after percutaneous radiofrequency ablation.

BACKGROUND/AIMS: Rapid aggressive tumor progression of hepatocellular carcinoma is one of the major complications after radiofrequency ablation. We statistically analyzed hepatocellular carcinoma patients with rapid aggressive tumor progression after radiofrequency ablation regarding patient characteristics, computed tomography findings, radiofrequency ablation methods, and the course of clinical and imaging changes and outcomes. METHODOLOGY: We defined the tumor not detected by previous CT and US rapidly increased more than double in compared with the ablated area as rapid aggressive tumor progression. Ten hundred seventy three lesions of 538 patients underwent ultrasound-guided radiofrequency ablation in our hospital between April 1999 and March 2008. Of these patients, the risk factors for rapid aggressive tumor progression of 7 with 7 lesions were analyzed. RESULTS: The rate of rapid aggressive tumor progression was 0.65%. Subcapsular lesions, a pretreatment Protein Induced by Vitamin K Absence-II level > or = 40mAU/ml, and initial treatment for hepatocellular carcinoma were significantly identified as risk factors. CONCLUSIONS: There is possibility that portal vein invasion by hepatocellular carcinoma is an important factor involved in rapid aggressive tumor progression after radiofrequency ablation from the results of this study. In our opinion, these hepatocellular carcinomas need to be sufficiently ablated.