Ming-De Lu

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

ObjectiveWe assessed the usefulness of contrast-enhanced ultrasound (CEUS) in the differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).MethodsThe 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.ResultsIn 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).ConclusionCEUS improves the diagnostic performance significantly in the differentiation between ICC and HCC.

A novel cell encapsulation method using photosensitive poly(allylamine alpha-cyanocinnamylideneacetate)

A photosensitive alpha-cyanocinnamylideneacetyl group was coupled to poly(allylamine) to obtain a photosensitive polymer. This photosensitive poly(allylamine alpha-cyanocinnamylideneacetate) can cross-link upon light exposure. Microcapsules were fabricated from alginate in contact with Ca+2 ion, followed by coating with the photosensitive poly(allylamine alpha-cyanocinnamylideneacetate). The microcapsules, thus formed, can be strengthened significantly by the light-induced cross-linking of poly(allylamine alpha-cyanocinnamylideneacetate). Only 16 capsules (out of 50) prepared from the photosensitive poly(allylamine alpha-cyanocinnamylideneacetate) fractured after 48 h of agitation. For microcapsules prepared from the unmodified poly(allylamine), 32 capsules fractured. The photo cross-linked capsular membrane was permeable to cytochrome C, moderately permeable to myoglobin, and least permeable to serum albumin. IW32 (a mouse leukaemia cell line) cells were entrapped and cultured within these microcapsules. The cells proliferated to a density of about 9 x 10(6) cells/ml in the capsules after 7 days of cultivation.A photosensitive alpha-cyanocinnamylideneacetyl group was coupled to poly(allylamine) to obtain a photosensitive polymer. This photosensitive poly(allylamine) can cross-link upon light exposure. Microcapalpha-cyanocinnamylideneacetate sules were fabricated from alginate in contact with Ca+2 ion, followed by coating with the photosensitive poly(allylamine alpha-cyanocinnamylideneacetate). The microcapsules, thus formed, can be strengthened significantly by the lightinduced cross-linking of poly(allylamine alpha-cyanocinnamylideneacetate). Only 16 capsules (out of 50) prepared from the photosensitive poly(allylamine alphacyanocinnamylideneacetate) fractured after 48 h of agitation. For microcapsules prepared from the unmodified poly(allylamine), 32 capsules fractured. The photo cross-linked capsular membrane was permeable to cytochrome C, moderately permeable to myoglobin, and least permeable to serum albumin. IW32 (a mouse leukaemia cell line) cells were entrapped and cultured within these microcapsules. The cells proliferated to a density of about 9 x 106 cells/ml in the capsules after 7 days of cultivation.

Renal Cell Carcinoma and Renal Angiomyolipoma Differential Diagnosis With Real-time Contrast-Enhanced Ultrasonography

Objective. The purpose of this study was to evaluate the usefulness of contrast‐enhanced ultrasonography (CEUS) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML). Methods. One hundred nineteen patients with 126 renal lesions (33 RAMLs and 93 RCCs) who had undergone CEUS were retrospectively studied. All of the lesions were histopathologically or clinical proved. Contrast‐enhanced ultrasonography was performed using low–acoustic power modes and a sulfur hexafluoride–filled microbubble contrast agent. The baseline sonograms and CEUS images were retrospectively analyzed in consensus by 2 radiologists. The tumor echogenicity, enhancement patterns, and degree of enhancement at different phases were evaluated. The diagnostic efficacy of CEUS in differentiating the two diseases was computed and compared. Results. On CEUS, the features of wash‐out from hyperenhancement or isoenhancement to hypoenhancement over time (observed in 3.0% of RAMLs and 71.0% of RCCs; P < .001), heterogeneous enhancement (observed in 12.1% of RAMLs and 74.2% of RCCs; P < .001), and an enhanced perilesional rim (observed in 3.0% of RAMLs and 79.6% of RCCs; P < .001) achieved significant difference between RCCs and RAMLs. Early wash‐out and heterogeneous enhancement or peritumoral rim enhancement yielded the highest diagnostic capability in differentiating RCC from RAML. The corresponding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88.2% (82 of 93), 97.0% (32 of 33), 98.8% (82 of 83), 74.4% (32 of 43), and 90.5% (114 of 126), respectively. Conclusions. The CEUS features of early wash‐out, heterogeneous enhancement, and an enhanced peritumoral rim highly suggest RCC, whereas homogeneous enhancement and prolonged enhancement are characteristic manifestations of RAML. Contrast‐enhanced ultrasonography is valuable in differentiating RCC from RAML.

Imaging of Peripheral Cholangiocarcinoma With Low-Mechanical Index Contrast-Enhanced Sonography and SonoVue Initial Experience

Objective. The purpose of this study was to investigate the imaging findings of peripheral cholangiocarcinoma with low‐mechanical index (MI) contrast‐enhanced sonography. Methods. Eighteen nodules of peripheral cholangiocarcinoma proved by pathologic examination in 18 patients were evaluated with contrast‐enhanced sonography. A low‐MI real‐time contrast‐enhanced sonographic mode (ie, contrast pulse sequencing) and a sulfur hexafluoride‐filled microbubble contrast agent (SonoVue [BR1]; Bracco SpA, Milan, Italy) were used. Results. On contrast‐enhanced sonographic images, all 18 nodules (100%) of peripheral cholangiocarcinoma showed inhomogeneous enhancement during the arterial phase, and the emergence of nodule enhancement was earlier in 3 nodules (16.7%), simultaneous in 13 (72.2%), and later in 2 (11.1%), respectively, when compared with the adjacent liver tissue. During the arterial phase, 8 nodules (44.4%) showed irregular peripheral rimlike hyperenhancement, 2 (11.1%) showed inhomogeneous hyperenhancement, and 8 (44.4%) showed inhomogeneous hypoenhancement. In portal and late phases, all 18 nodules (100%) showed hypoenhancement. When contrast‐enhanced sonography was added for analysis, the confidence levels of the investigators were improved in 15 (83.3%) of 18 nodules, and 17 (94.4%) of 18 peripheral cholangiocarcinomas were correctly characterized. Conclusions. The imaging findings of peripheral cholangiocarcinoma had some characteristics on low‐MI contrast‐enhanced sonography. Knowledge of these characteristics might be beneficial for improving the diagnostic performance of sonography in evaluating this entity.

Real-time contrast-enhanced ultrasound imaging of infected focal liver lesions.

Objective. The purpose of this study was to investigate the features of infected focal liver lesions on contrast‐enhanced ultrasound (CEUS) imaging. Methods. Thirty‐two hepatic abscesses, 15 infected granulomas, and 6 inflammatory pseudotumors in 53 patients were evaluated with real‐time CEUS before awareness of the definitive diagnosis. A 2.4‐mL dose of a sulfur hexafluoride–filled microbubble contrast agent was administered by intravenous bolus injection. Results. The numbers of abscesses with hyperenhancement, isoenhancement, and hypoenhancement in the arterial phase were 26 (81.3%), 5 (15.6%), and 1 (3.1%), respectively. Thirty (93.8%) lesions were irregularly rim enhanced with nonenhanced areas; enhanced septa were shown in 22 (68.8%) lesions; and transient hyperenhancement of liver parenchyma around the lesion was shown in 20 (62.5%). In 31 abscesses with hyperenhancement or isoenhancement in the arterial phase, 25 (80.6%) showed contrast wash‐out and changed in appearance to hypoenhancement in the late phase. As for infected granulomas and inflammatory pseudotumors, 16 (76.2%) lesions showed hyperenhancement or isoenhancement in the arterial phase, and all of them were hypoenhanced in the portal and late phases. Conclusions. Most infected focal liver lesions showed more rapid contrast wash‐out than the surrounding liver parenchyma, which is similar to malignant lesions. Abscesses typically showed features of rim enhancement, enhanced internal septa, nonenhanced central necrotic areas, and transient hyperenhanced liver parenchyma around the lesions. The CEUS appearance of infected granulomas and inflammatory pseudotumors was variable, and a biopsy was necessary for definitive diagnosis.

Evaluation of the vascular architecture of hepatocellular carcinoma by micro flow imaging : Pathologic correlation

The purpose of this study was to evaluate micro flow imaging (MFI) in depicting the vascular architecture of hepatocellular carcinoma (HCC) and the correlation between pathologic differentiation and the intratumoral vascular architecture pattern.

Diagnostic performance of contrast-enhanced ultrasound for complex cystic focal liver lesions: blinded reader study

The study was aimed at evaluating the diagnostic performance of contrast-enhanced ultrasound (CEUS) in characterizing complex cystic focal liver lesions (FLLs). Sixty-seven complex cystic FLLs in 65 patients were examined with conventional ultrasound (US) and real-time CEUS. The US and CEUS images were reviewed by a resident radiologist and a staff radiologist independently. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance, and the interobserver agreement was analysed. The results showed that complete non-enhancement throughout three phases of CEUS or sustained enhancement in the portal and late phases were exhibited in most benign lesions. Conversely, hypo-enhancement in the late phase was seen in all malignancies. After ROC analysis, the areas (Az) under the ROC curve were 0.774 at US versus 0.922 at CEUS (P = 0.047) by the resident radiologist, and 0.917 versus 0.935 (P = 0.38) by the staff radiologist. A significant difference in Az between the resident and the staff radiologists was found for US (0.774 versus 0.917, P = 0.044), whereas not found for CEUS (0.922 versus 0.935, P = 0.42). Interobserver agreement was improved after CEUS (κ = 0.325 at US versus κ = 0.774 at CEUS). Real-time CEUS improves the capability of discrimination between benign and malignant complex cystic FLLs, especially for the resident radiologist.

Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

Objective To assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases. Methods This study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed. Results Among the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS. Conclusion CEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy.

Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: an experiment in vivo.

Background Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. Purpose To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. Material and Methods Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5× 106 cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1a and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. Results Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P < 0.05). By comparing the control group with the RFA group, we found that insufficient RFA promoted HIF-1α and VEGFA expression (P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P < 0.05). Conclusion Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.

Unusual benign focal liver lesions: findings on real-time contrast-enhanced sonography.

This presentation aims to provide an overview of the manifestations of some unusual benign focal liver lesions (FLLs) on low–acoustic power contrast‐enhanced sonography (CES) with a sulfur hexafluoride contrast agent.