A Nomogram Based on Contrast-Enhanced Ultrasound to Predict the Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to establish and validate a contrast-enhanced ultrasound (CEUS) nomogram for pre-operative microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC), and compare it with the nomogram based on gadopentetate dimeglumine-enhanced magnetic resonance imaging (Gd-MRI). METHODS: A total of 251 patients with a single HCC were enrolled in this prospective study, including 176 patients in the training cohort and 75 patients in the validation cohort. Contrast-enhanced ultrasound (CEUS) with Sonazoid and Gd-MRI was performed pre-operatively. Post-operative histopathology was the gold standard for MVI. Univariate and multivariate logistic regression was performed to determine independent risk factors for MVI. Nomograms based on CEUS and Gd-MRI were established, and their discrimination, calibration and decision curve analysis were evaluated and compared. RESULTS: Multivariate logistic regression revealed that arterial circular enhancement, non-enhancing area and thick ring-like enhancement in the post-vascular phase were independent risk factors for MVI. The areas under the receiver operating characteristic curve of the nomogram were 0.841 (0.779-0.892) and 0.914 (0.827-0.966) in the training and validation cohorts, with no significant difference compared with the Gd-MRI nomogram (p = 0.294, 0.321). The C-indexes were 0.821 and 0.870 in the training and validation cohorts. Decision curve analysis revealed that the CEUS nomogram had better clinical applicability than the Gd-MRI nomogram when the threshold probability was between 0.35 and 0.95. CONCLUSION: The CEUS-based nomogram was available for predicting MVI in HCC, and its predictive performance was not inferior to that of Gd-MRI.

Ring-like enhancement on Contrast-Enhanced ultrasound may correlate well with histopathological capsule of Hepatocellular Carcinoma: Comparison with the enhancing capsule on Gadopentetate-enhanced MRI.

PURPOSE: To evaluate the correlation of ring-like enhancement (RE) on contrast-enhanced ultrasound with Sonazoid (S-CEUS) with the fibrous capsule of HCC, and compared it with the enhancing capsule on Gadopentetate-enhanced MRI (Gd-MRI). METHOD: Consecutive patients with pathologically-proven resected HCCs from January 2021 to December 2021 were reviewed in this retrospective study. Preoperatively, the RE on the S-CEUS and the enhancing capsule on Gd-MRI were evaluated for each lesion. We analyzed the correlation of the presence, integrity, and thickness of imaging features with the histopathological fibrous capsule. The diagnostic performance to recognize the capsule between two modalities was compared by the McNemar test. RESULTS: Ninety-one patients (mean age, 58.30 ± 11.13 years; 82 men) with ninety-seven HCCs (mean size, 4.67 ± 2.70 cm) were reviewed. The RE on S-CEUS correlated with the presence of the fibrous capsule (P = 0.006). The sensitivity, specificity, and accuracy were 92.05 %, 44.44 %, and 82.47 %, respectively, which was not different from Gd-MRI (P = 0.388). The integrity of RE in the post-vascular phase correlated with the integrity of the fibrous capsule (P = 0.018), whose diagnostic performance was not statistically different from Gd-MRI (P > 0.999). The thickness shown both on S-CEUS and Gd-MRI was thicker than that in histopathology (P < 0.001), and the thickness on Gd-MRI was not statistically different from that in the vascular phase of S-CEUS (P = 0.563), but thinner than that in the post-vascular phase (P = 0.001). CONCLUSIONS: Compared with the Gd-MRI, RE on S-CEUS had a similarly well correlation with the presence and integrity of fibrous capsule of HCC.

Intraarterial contrast-enhanced ultrasound to predict the short-term tumour response of hepatocellular carcinoma to Transarterial chemoembolization with Lipiodol.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective locoregional therapy in hepatocellular carcinoma (HCC). However, it is difficult to predict the tumour response (TR) of TACE intraprocedurally. The aim of this study was to predict the TR after TACE (1-3 months) in HCC patients using intraprocedural intraarterial contrast enhanced ultrasound (IA-CEUS). METHODS: In this case-control study, consecutive patients who received TACE in our hospital from September 2018 to May 2019 were enrolled. IA-CEUS was performed before and after TACE. Postoperative contrast-enhanced liver MRI was performed 1-3 months after TACE as the gold standard. According to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), ultrasonic manifestations were compared between the complete remission (CR) group and non-CR group by univariate and multivariate analyses. A logistic predictive model was established and validated, and its diagnostic efficiency was evaluated. RESULTS: Forty-four patients with sixty-one lesions were enrolled in the study. Multivariate analysis identified, the risk factors as a large lesion diameter (OR: 1.84; 95% confidence interval [CI]: 1.009, 3.080; P = 0.020), a larger dimension of non-enhancing area in superior mesenteric artery (SMA)-CEUS than the size in B-mode ultrasound preoperatively (OR: 3.379; 95% CI: 1.346,8.484; P = 0.010), presence of corona enhancement in hepatic artery (HA)-CEUS postoperatively (OR: 6.642; 95% CI: 1.214, 36.331; P = 0.029), and decreased corona enhancement thickness (per centimetre) postoperatively (OR: 0.025; 95% CI: 0.006,0.718; P = 0.025). The area under the receiver operating characteristic curve (AUROC) of the predictive model was 0.904 (95% CI: 0.804, 0.966; P < 0.001). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 81.08, 91.67, 85.25, 93.75, and 75.86%, respectively. Leave-one-out cross-validation (LOOCV) showed that the accuracy was 77.05%. CONCLUSIONS: Intraprocedural IA-CEUS can be used to predict the TR in HCC patients after TACE.

Application value of contrast-enhanced transrectal ultrasound in differential diagnosis of benign and malignant prostate nodules / 中华医学超声杂志（电子版）

Objective To investigate the application value of contrast-enhanced transrectal ultrasound (CE-TRUS) in differential diagnosis of prostate benign and malignant lesions. Methods A retrospective analysis of patients with prostate lesions detected by CE-TRUS from January 2014 to December 2016 in Southwest Hospital of Third Military Medical University was performed. Seventy-two cases of prostate disease with 88 lesions were confirmed by transrectal prostate biopsy under ultrasound guidance. The age of patients with benign and malignant lesions, serum prostate specific antigen (PSA), and the size of prostate and prostate inner gland were compared by independent sample t test. Pathologic results of transrectal prostate biopsy under ultrasound guidance were used as diagnostic gold standard, and the sensitivity, specificity and accuracy of CE-TRUS in diagnosis of benign and malignant prostate lesions were calculated. Results Sixty- seven lesions in 52 patients were benign prostatic diseases, and 21 lesions in 20 patients were prostate cancer in this study. The size of prostate and prostate inner gland were not different between patients with prostate cancer and benign prostatic diseases [(58.33±34.99) cm3vs (57.14±24.42) cm3, t=0.185, P=0.854; (34.98±19.96) cm3vs (33.89±17.65) cm3, t=0.213, P=0.832]. Most of prostate cancer lesions were in prostate outer gland area (15/21), and contrast-enhanced ultrasound imaging showed contrast enhancement increased mostly in arterial phase and faded faster than the surrounding tissues (16/21). However, most of prostate benign lesions were in prostate inner gland (47/67), and contrast-enhanced ultrasound imaging showed contrast enhancement was mostly equal with the surrounding tissue in arterial phase and faded the same as the surrounding tissues in venous phase (47/67). Pathologic results of transrectal prostate biopsy under ultrasound guidance were used as diagnostic gold standard, the sensitivity of CE-TRUS in diagnosis of benign and malignant prostate lesions was 85.71%, the specificity was 91.04%, and the accuracy was 89.77%. Two lesions were in prostate inner and outer gland border areas in the three missed prostate cancer lesions, and Gleason scores were all medium and high differentiated group. Six prostate benign lesions were diagnosed as malignant lesions, five lesions were confirmed prostate hyperplasia with chronic prostatitis and one was confirmed granulomatous inflammation with coagulation necrosis by transrectal prostate biopsy under ultrasound guidance. Conclusion CE-TRUS can effectively identify prostate benign and malignant lesions, and provides reliable information for accurate diagnosis of prostate cancer.

Effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastructure and migration of colon cancer cells / 中华消化外科杂志

Objective To investigate the effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastmcture and migration of colon cancer cells.Methods The experimental study was conducted.Colon cancer cells inn vitro (Lovo ceils) were cultured and divided into 4 groups,ceils in the A group were not treated and cells in the B,C and D groups were treated by microbubbles combined with different mechanical index ultrasound irradiation (mechanical index were 0.20,0.80 and 1.45).The changes of ultrastructure and migration of cells were observed using laser scanning confocal microscope and MilliceIl-PCF cell culturechamber method,respectively.Measurement data with normal distribution were represented as (x)±s.Comparisons among groups were analyzed by the one-way ANOVA.Pairwise comparisons were done by the t test.Results (1)Effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastructure of Lovo cells:Lovo cells in the A group showed big nucleus,less plasma,regular arrangement,jagged-like or more irregular varicosity surrounding nucleus,twisted euchmmatin,expansion of nucleus cisternal space,homogeneous distribution and normal development of granular soil and clear mitochondrial ridge-like structures.Lovo cells in the B group showed big nucleus with regular arrangement,obvious nucleolus margination,endoplasmic reticulum dilatation,normal development of mitochondrion and clear mitochondrial ridge-like structures.Lovo cells in the C group showed broadening nucleus space,abnormal nucleus with karyopycnosis,chromatin condensation,a few remaining or obvious dilatation of rough endoplasmic reticulum,typically consisting of different fragments or bubbles,cytoplasmic vacuoles changes and decreasing mitochondrial ridge-like structures.Lovo cells in the D group showed big and irregular nucleus,nucleolus margination,obvious endoplasmic reticulum dilatation,fewer mitochondrion with extended cell area and swelling shape,rare mitochondrial ridge-like structures with disordered or broken arrangement,even disappearing.(2) Effects of the microbubbles combined with different mechanical index ultrasound irradiation on migration of Lovo cells:Millicell-PCF cell culture chamber method showed that number of migration of Lovo cells were respectively 63±7,61±4,21±3 and 19±5 in the A,B,C and D groups,with a statistically significant difference (F=55.040,P＜0.05).There were no statistically significant difference in migration of Lovo cells between group A and B (t =1.571,P＞0.05) and between group C and D (t =2.013,P＞0.05).There were statistically significant differences in migration of Lovo cells between group A and C or D (t=7.861,10.652,P＜0.05) and between group B and group C or D (t=7.161,10.453,P＜0.05).Conclusion Microbubbles combined with high mechanical index ultrasound irradiation can make the ultrastructural alterations in the cancer cells,resulting in tumor cell degeneration and death,ultimately inhibit tumor cell migration and metastasis.

Establishment of a keloid model in nude mice with human keloid-derived fibroblasts / 中华皮肤科杂志

Objective To establish a simple and efficient method for developing a keloid model in nude mice with human keloid-derived fibroblasts.Methods Twenty-seven female BALB/c nude mice were randomly divided into five groups with 5,5,5,8 and 4 mice in group A,B,C,D and E respectively.The mice in group A,B and C were inoculated with 0.1 ml of suspension containing human keloid-derived fibroblasts at concentrations of 1.0 × 104,3.0 × 104 and 5.0 × 104 per microliter Matrigel,respectively,at the right axillary fossa.The tumors that formed in one mouse in group C were taken out,and cut into several parts measuring 5 mm × 5 mm × 5 mm in size,which were then subcutaneously transplanted into the right axillary fossa of mice in group D.The mice in group E were subcutaneously injected with 100 μl of Matrigel and served as the control group.The formation of tumor in mice was observed by naked eyes,and the size of tumors was measured until day 30 after tumor formation in group A,B and C as well as after tumor transplantation in group D.Mice were sacrificed on day 30 after tumor formation,and histopathologic examination was performed to analyze histological features of transplanted tumors and pathological changes in visceral organs such as heart,liver,spleen,lung and kidney.Results The tumor formation rate was consistently 100％ in group A,B and C,and the time required for tumor formation was (90.20 ± 3.96),(61.00 ± 2.92) and (39.60 ± 3.20) days in group A,B and C respectively.There was a significant difference in tumor volume on the 30th day after tumor formation between group A,B and C ((288.34 ± 25.29) vs.(1 370.63 ± 105.24) vs.(1 940.98 ± 184.37) mm3,F =138.74,P ＜ 0.05).The size of implanted tumor mass in group D firstly increased,then gradually decreased,but began to continuously increase since the 14~ day,and tumor finally formed in 7 out of 8 mice.There was no evidence of tumor formation in group E.Histopathologic examination showed uniform histological manifestations,which were similar to those of human scar,in tumor tissues from mice in group A,B,C and D.Neither pathological changes nor metastases were observed in visceral organs of these mice.Conclusion Keloid-bearing nude mouse model can be established by subcutaneous inoculation with human keloidderived fibroblasts,or by subcutaneous transplantation of tumor masses of a certain size that have formed in nude mice.

Effectiveness of dosing technology and coating material excipient's application on solid drug's moisture-proof improvement / 中成药

AIM: To investigate the effectiveness of dosing technology and excipient application on solid drug's moisture-proof property and to provide a method improving the solid drug's moisture-proof property. METHODS: Based on the analysis of the moisture absorbing process and the absorbing mechanics,a new concept "active moisture absorbance site"(AMAS) was defined and mathematic model was constituted.Two constants as: initial AMAS concentration C_0,moisture resistance coemcient K,were proposed to indicate the drugs moisture-proof ability. The CI WU JIA extracts and SHUANG HUANG LIAN extracts were used to conduct experiments, which were designed to investigate the improvement of the drug's moisture resistance ability when varying the AMAS's concentration and/or its space distribution. RESULTS: Reducing the amount of moisture absorbance excipients in each dosage of solid drug can lower the drug's moisture absorbance ability,and applying a thin film coating material outside the drug can also slow the drug's moisture absorbance rate. CONCLUSION: The proposed mathematic model is useful for finding a way to improve the drug's moisture resistance;experimental data shows that the drug's moisture-proof property would be improved by reducing the amount of moisture absorbance excipient in each dosage and improving the moisture distribution resistance through a certain dosing technology,such as film coating technology.