A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Optimization of hepatobiliary phase imaging in gadoxetic acid-enhanced magnetic resonance imaging: a narrative review.

Background and Objective: Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) is widely used in clinical practice. Its unique hepatobiliary phase (HBP) has been used to improve the detection and identification of hepatic lesions and has also been used to evaluate hepatic function and fibrosis. At the early stage of its clinical practice, the HBP was typically collected empirically with a delay of 20 minutes after intravenous administration to image the liver with sufficient enhancement for diagnosis. However, numerous methods and consensus statements for optimizing HBP acquisition have been proposed. This review details the methods and consensus statements on optimizing HBP collection. Methods: The electronic literature search was performed using the databases PubMed, MEDLINE, Cochrane, and Embase without limit on publication period to identify published reports on optimizing HBP imaging in Gd-EOB-DTPA-enhanced MRI. Articles with low relevance to the topics were excluded. Key Content and Findings: Recently, an increasing number of investigations suggest that collecting HBP after 20 min is too drawn-out for patients with normal liver function but is too short for patients with cirrhosis. Previous studies demonstrated that liver enhancement is closely related to liver function in Gd-EOB-DTPA-enhanced MRI. Therefore several reports have proposed various HBP delay times at different liver function levels. These delay times could be evaluated by laboratory indicators, such as prothrombin (PT) activity, total bilirubin, direct bilirubin, and the model for end-stage liver disease. Other investigations have found that the initial visualization time of the intrahepatic bile duct (IHD) in Gd-EOB-DTPA-enhanced MRI to also be related to liver enhancement and function. Therefore, initial visualization of the IHD is considered necessary for adequate HBP and has been employed in HBP acquisition in recent reports. Conclusions: Optimizing HBP acquisition according to individual hepatic function is a good strategy and was followed in most of the investigations included in our review. Obtaining adequate HBP in the shortest possible time is the target condition in Gd-EOB-DTPA-enhanced MRI. However, a more concise and efficient HBP acquisition strategy is still expected to be developed in the future.

[Research of factors related to invasion and metastasis in choroidal melanoma].

OBJECTIVE: To investigate the expression of factors related to invasion and metastasis in choroidal melanoma and to determine their relationships with malignant features. METHODS: The expression of Connexin43 (Cx43), epithelial cadherin (E-cadherin), phosphatidylinositol 3-kinase (PI3K) and connective tissue growth factor (CTGF) in choroidal melanoma and nevi were detected by immunohistochemistry, and the correlation between these factors and clinicopathological features were analyzed. RESULTS: Positive rates of Cx43, E-cadherin, PI3K and CTGF were 74.07% (20/27), 44.4% (12/27), 74.07% (20/27) and 66.67% (18/27) in choroidal melanoma tissues, respectively; and 33.33% (5/15), 86.67% (13/15), 33.33% (5/15) and 20.00% (3/15) in the nevi tissues, respectively. There were significant differences in the expression of these markers between the two groups (χ(2) = 5.060, P = 0.024; χ(2) = 5.490, P = 0.019; χ(2) = 5.060, P = 0.024; χ(2) = 6.637, P = 0.010). The expression rates of Cx43 protein were 40% (4/10), 88.89% (8/9) and 100% (8/8) in spindle, mixed and epithelioid cell type, respectively. The expression of these data was related to histological type (χ(2) = 9.874, P = 0.007). The expression rates of PI3K protein were 42.86% (3/7), 75% (9/12) and 100% (8/8), in small, medium and large tumors, respectively, and their expression were co-related to the tumor size (χ(2) = 6.357, P = 0.042). Positive rates of Cx43, E-cadherin, PI3K and CTGF were 50% (6/12), 83.33% (10/12), 50% (6/12) and 41.66% (5/12), respectively, in choroidal melanoma tissues without sclera invasion and were 93.33% (14/15), 40% (6/15), 93.33% (14/15) and 86.67% (13/15), respectively, in choroidal melanoma tissues with violation involved the sclera. There were significant differences of the expression of these markers between the two groups (χ(2) = 4.457, P = 0.016; χ(2) = 3.546, P = 0.028; χ(2) = 4.457, P = 0.016; χ(2) = 4.218, P = 0.019). CONCLUSION: Increased expression of Cx43, PI3K and CTGF and decreased expression of E-cadherin are involved in the processes of invasion and metastasis of choroidal melanoma.

Expression and significance of factors related to angiogenesis in choroidal melanoma.

AIM: TO INVESTIGATE EXPRESSION OF FACTORS RELATED TO ANGIOGENESIS: HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma and its clinical significance. METHODS: Fifty samples of choroidal melanoma and 15 samples of melanocytic nevi of the eyelid identified by pathology were collected. Immunohistochemistry SP method was used to examine the expression of HIF-1α, iNOS, COX-2 and VEGF in these samples. The comparison among groups was done by SPSS 13.0 software. RESULTS: The positive expression rates of HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma group were significantly higher than those in eyelid nevi group (χ(2)=6.5542, 7.7224, 8.5828, 15.1749). The positive expression rate of VEGF was associated with the tumor size (χ(2)=10.9194), but was not associated with pathological type (χ(2)=2.0712) and the situation of scleral invasion (χ(2)=5.4289). The positive expression rate of HIF-1α was associated with the tumor size (χ(2)=7.1216) and pathological type (χ(2)=9.0889), but was not associated with the situation of scleral invasion (χ(2)=3.3586). The positive expression rate of iNOS was associated with the tumor size (χ(2)=9.5503), but was not associated with pathological type (χ(2)=1.9450) and the situation of scleral invasion (χ(2)=2.3810). The positive expression rate of COX-2 was associated with the tumor size (χ(2)=7.2970), but was not associated with pathological type (χ(2)=1.8421) and the situation of scleral invasion (χ(2)=0.4018). The expression of HIF-1α, iNOS and COX-2 were significantly associated with the expression of VEGF (r=0.9429, 1, 0.9857). The expression of COX-2 was significantly associated with the expression of iNOS (r=0.9857). The expression of HIF-1α was significantly associated with the expression of COX-2 (r=0.9857). The expression of HIF-1α was significantly associated with the expression of iNOS (r=0. 9429). CONCLUSION: The expression of HIF-1α, iNOS and COX-2 protein in choroidal melanoma were higher and may relate to angiogenesis and stimulate tumor growth. Determination of HIF-1α, iNOS and COX-2 may be helpful for the diagnosis and therapy of this tumor.

Expression of connexin 43 and E-cadherin in choroidal melanoma.

AIM: To investigate the expression of connexin 43 and epithelial cadherin (E-cadherin) in choroidal melanoma, to explore the clinical and pathological implications of expression of these proteins, and to determine their relations with malignant features. METHODS: The expression of connexin 43 and E-cadherin in choroidal melanoma were detected by immunohistochemistry and correlated with clinicopathological features. RESULTS: Positive rates of connexin 43 in choroidal melanomas and benign pigmented nevus tissues were 75% and 40% respectively with significant differences between the two groups (χ(2)=5.607, P=0.009). Positive rates of E-cadherin in choroidal melanomas and benign pigmented nevus tissues were 40% and 75% respectively with significant differences between the two groups (χ(2)=5.214, P=0.010). Significant overexpression of connexin 43 and reduction of E-cadherin expression was associated with the invasion to the sclera, and there were respectively significant differences between without and with scleral invasion groups (χ(2)=2.880, P=0.040; χ(2)=2.778, P=0.046). Overexpression of connexin 43 were correlated with tumor cell types and the expression of connexin 43 and E-cadherin may be correlated with each other. CONCLUSION: The increased expression of connexin 43 and the decreased expression of E-cadherin may be involved in the process of invasion of choroidal melanoma. The overepression of connexin 43 and reduction of E-cadherin may contribute to the development of choroidal melanoma.

[Production and characterization of gold labeled monoclonal antibody against MC-LR].

OBJECTIVE: Production of the gold labeled monoclonal antibody against MC-LR. Study the simple mechanism of the conjugation by the spectral analysis. METHODS: Production and purification monoclonal antibodies against MC-LR by hybridoma technology. Production the 20nm colloidal gold and label the monoclonal antibody. Study the gold--McAb conjugate by the spectroanalysis. RESULTS: Monoclonal antibody produced by the hybridoma cells were tested for subtypes and designated as IgG2a for 8C11. The titers of antibody in ascites was 108.The IC50 for MC-LR was around 3ng/ml. The IgG molecule weight was 1.5 x 10(5). The structure of the antibody was altered to more tighter and stabler. CONCLUSION: Product the gold labeled monoclonalantibody against MC-LR conjugate successfully and keep the antige-binding determinant.

[Production purification and characterization of polyantibodies against microcystin-LR].

OBJECTIVE: Production and characterization the polyantibodies against MCYST-LR. METHODS: microcystin-LR (MC-LR) was conjugated to KLH, then immune the rabbit by the routine method. Purify the antiserum by centrifugal and saturated sulfuric ammonium precipitated methods. Count the affinity constant and measure the titers, IC50 Value and the sensitivity. RESULTS: The titers of the antiserum is over 25600. IC50 value is about from 0.1 ng/ml to 1 ng/ml. The across-reactivity ratio to MC-LW and MC-LR is about from 0.1% to 20%.

[Therapeutic effect and pathology changing of eyelid xanthelasma by Bleomycin A5].

OBJECTIVE: To investigate the effects of Bleomycin A5 on the pathology and ultrastructure of eyelid xanthelasmas. METHODS: Twenty-five randomly selected outpatients from our hospital received 0.2 ml of a 0.4% Bleomycin A5 solution. The drug was directly injected into the tumor every 10 days. In other 5 cases (double up-eyelids xanthelasma), one eye received 0.2 ml of 0.4% Bleomycin A5 injection once and another eye was used as controlling. After one month, operations were performed to remove double up-eyelids xanthelasma tissues, one half of the tissues were investigated by histochemistry; the other half was cut into 1.0 mm x 1.0 mm x 1.5 mm pieces and investigated by electron microscopy. RESULTS: The clinical investigation demonstrated that 25 cases of the Bleomycin treated tumors disappeared completely and the skin color recovered. The eyelids kept their normal morphology and function. Histopathologic investigation of the Bleomycin treated groups showed fibroblasts hyperplasia and sparse foam cells in shallow derma. In the control group, there are large foam cells in shallow layer of derma. The ultrastructure of the treated specimens showed fat droplets decrease in foam cells in contrary to the control group. CONCLUSIONS: Bleomycin A5 can rapidly inhibit the proliferation of foam cells and induce xanthelasma disappearance. Bleomycin A5 is an easy and safe method to treat eyelid xanthelasma and can be widely used in clinical work.

[Preparation and characterization of immunogen against microcystin LR].

OBJECTIVE: To prepare Microcystins-LR (MC-LR) conjugates with the carrier protein for developing a new immune assay for MC-LR. METHODS: MC-LR was coupled to BSA or KLH by "activated ester" and "water-soluble carbodimide". Measure the combine ratio of MC-LR with KLH or BSA by the UV scanning or the Bradford's method. RESULTS: The results are 9.1 and 9.4. New Zealand rabbits was immunized by MC-LR-KLH. The titer of the polyantibodies was over 25,600 measured by id ELISA. CONCLUSION: MC-LR-KLH was proved the suitable immunogen against MC-LR.