LR-M Observations on Contrast-Enhanced Ultrasound: Detection of Hepatocellular Carcinoma Using Additional Features in Comparison With Current LI-RADS Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) LI-RADS assigns category LR-M to observations that are definitely or probably malignant but that on imaging are not specific for hepatocellular carcinoma (HCC). A high percentage of LR-M observations represent HCC. OBJECTIVE. The purpose of this study was to retrospectively evaluate the utility of additional features, beyond conventional LI-RADS major features, for detecting HCC among LR-M observations on CEUS. METHODS. This retrospective study included 174 patients (145 men, 29 women; mean age, 53 years) at high risk of HCC who underwent CEUS from August 2014 to June 2016 that showed an LR-M observation according to CEUS LI-RADS version 2017. Two radiologists independently assessed CEUS images for major features and four additional features (chaotic vessels, peripheral circular artery, clear boundary of tumor enhancement, clear boundary of intratumoral unenhanced area). The diagnostic performance of four proposed criteria for the detection of HCC among LR-M observations was assessed. The impact of criteria based on the additional findings on detection of HCC was further explored. Histology or composite imaging and clinical follow-up were the reference standards. RESULTS. The 174 LR-M observations included 142 HCCs and 32 non-HCC lesions (20 intrahepatic cholangiocarcinomas, five combined hepatocellular-cholangiocarcinomas, seven benign lesions). Interreader agreement on the additional features ranged from κ = 0.65 to κ = 0.88. Two of the additional features had excellent PPV for HCC: chaotic vessels (94.8%) and peripheral circular arteries (98.1%). The presence of either of these two additional features had sensitivity of 50.7%, specificity of 90.6%, PPV of 96.0%, and NPV of 29.3% for HCC. Three other criteria incorporating variations of major LI-RADS features but not the additional features had sensitivities of 55.6-96.5%, specificities of 49.6-68.8%, PPVs of 87.8-90.6%, and NPVs of 25.0-75.0%. On the basis of criteria that included additional features, 75 of 174 LR-M observations were recategorized LR-5; 72 of the 75 were HCC. CONCLUSION. The presence of chaotic vessels and/or peripheral circular artery had high specificity and PPV for HCC among LR-M observations. Other explored criteria based on major features did not have higher specificity or PPV. CLINICAL IMPACT. Clinical adoption of the additional CEUS features could help establish the diagnosis of HCC noninvasively and avoid the need for biopsy of LR-M observations.

Application of ultrasound-guided biopsy and percutaneous radiofrequency ablation in 2 cases with phosphaturic mesenchymal tumor and literature review.

Tumor-induced osteomalacia (TIO) is a vanishingly rare paraneoplastic syndrome which is usually caused by phosphaturic mesenchymal tumors (PMTs). The conventional treatment for PMTs is total resection, and ultrasound-guided radiofrequency ablation (RFA) can also be used for the treatment of PMTs patients, especially for patients in whom complete resection may lead to serious complications. We report two cases with PMT who presented syndrome with progressive musculoskeletal complaints and performed ultrasound-guided biopsy and RFA. Ultrasound-guided RFA, which is a safe and effective minimally invasive treatment option, appears to be a valuable alternative to surgery for patients presenting with PMT. We are the first reported case of RFA guided by ultrasonography in the treatment of PMT.

NPTX1 inhibits colon cancer cell proliferation through down-regulating cyclin A2 and CDK2 expression.

Colon cancer is the third most common malignancy and one of the leading causes of cancer-associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated with tumor progression in some types of tumors. However, its expression and role in colon cancer has not been yet reported. Here we observed that NPTX1 was down-regulated in colon cancer. Additionally, we explored the functional significance of NPTX1 in colon cancer. We found that over-expression of NPTX1 inhibited colon cancer cell growth by performing MTT, colony formation, Edu corporation assays, and cell cycle analysis. In vivo mouse experiments also confirmed the anti-proliferative role of NPTX1 in colon cancer. Further mechanistic study showed that over-expression of NPTX1 inhibited the expression of cyclin A2 and CDK2 in colon cancer cells, thereby regulating the Rb-E2F signaling. In summary, these findings reveal that NPTX1 suppress the colon cancer cell growth and might serve as a useful potential target for treatment of colon cancer.

Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma.

TMEM16A plays an important role in cell proliferation in various cancers. However, less was known about the expression and role of TMEM16A in hepatocellular carcinoma. We screened the expression of TMEM16A in patients' hepatocellular carcinoma tissues, and also analyzed the biological function of hepatocellular carcinoma cells by knockdown of TMEM16A, as well as the expression of MAPK signaling proteins, including p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p-JNK, and cell cycle regulatory protein cyclin D1 in TMEM16A siRNA-transfected SMMC-7721 cells by Western blot. Our results showed that TMEM16A was overexpressed in hepatocellular carcinoma tissues. Inhibition of TMEM16A suppressed the cell proliferation, migration, and invasion, and cell cycle progression but did not influence the cell apoptosis. TMEM16A siRNA-suppressed cancer cell proliferation and tumor growth were accompanied by a reduction of p38 and ERK1/2 activation and cyclin D1 induction, and were not influenced by other tested MAPK signaling proteins. In addition, inhibition of TMEM16A suppressed tumorigenicity in vivo. TMEM16A is overexpressed in hepatocellular carcinoma, and that inhibition of TMEM16A suppressed MAPK and growth of hepatocellular carcinoma. TMEM16A could be a potentially novel therapeutic target for human cancers, including hepatocellular carcinoma.

[Evaluation of co-cultured CL-1 hepatocytes and hepatic stellate cells in rotatory cell culture system].

OBJECTIVE: To explore whether the function of the CL-1 hepatocytes, co-cultured with human hepatic stellate cells (HSC) on microcarriers was better than that cultured without HSC. METHODS: CL-1 hepatocytes were divided into 2 groups. The co-culture group was cultured with HSC in DMEM culture medium containing 10% fetal bovine serum, and HSC were not added in single-culture group. The cytomorphology was observed by inverted microscope and scanning electron microscopy. The effects of different culture method on the proliferation in vitro were analyzed by MTT assay. The function of hepatocytes was evaluated through measuring the concentration of ALT and albumin. RESULTS: The inverted microscope and the MTT staining results showed that the quantity and viability of the human hepatocyte (C3A) in bidirectional bioreactor group were much better than the RCMW group. The growth curve results showed that the density of the human hepatocyte (C3A) was firstly increased and then decreased in both groups, and the peak of the curve appeared in day 5. The density of human liver cells in the second generation of bi-directional rotation and perfusion microgravity bioreactor group was significantly higher than the RCMW group from day1 to day 7 (P<0.05). The functional results showed that the albumin and urea concentration, which reached the peak on day 5, also gone up firstly and then gradually gone down in both teams. And the albumin and urea concentration in bidirectional bioreactor group was significantly higher than RCMW group from day 1 to day7 (P<0.01). Besides, the concentration of ALT and AST in bidirectional bioreactor group was significantly lower than RCMW group from day 1 to day 7 (P<0.05). CONCLUSION: This study shows that this new culture method is advantageous in enhancing cell viability and function. It indicates that co-culturing hepatocytes with HSC has a good application prospect in the development of artificial liver technology.