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Objective@#This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. @*Materials and Methods@#This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. @*Results@#The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. @*Conclusion@#2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.
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Objective@#This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. @*Materials and Methods@#This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. @*Results@#The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. @*Conclusion@#2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.
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PURPOSE: Hepatocellular carcinoma (HCC) is an aggressive disease with high recurrence rate. However, current staging systems were lack of predictive capacity for HCC recurrence. We aimed to develop prognostic nomograms based on inflammation-related markers for HCC patients underwent hepatectomy. MATERIALS AND METHODS: We recruited 889 surgically treated patients from two medical centers. Independent prognostic factors were identified by cox regression analyses. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were established, and validated internally and externally. The performance, discrimination, and calibration of nomograms were assessed, and compared with existed staging systems. RESULTS: Neutrophil to lymphocyte ratio (NLR) and gamma-glutamyl transpeptidase to platelet ratio (GPR) were the two inflammation-related factor that independently correlated with survival. NLR, GPR, international normalized ratio (INR), microvascular invasion, satellite lesions, tumour number, tumour diameter, and macrovascular invasion were used to construct nomogram for RFS while GPR, total bilirubin, INR, α-fetoprotein, microvascular invasion, satellite lesions, tumour diameter, and macrovascular invasion were for OS. In the training cohort, the C-index of nomogram was 0.701 (95% confidence interval [CI], 0.669 to 0.732) for RFS and 0.761 (95% CI, 0.728 to 0.795) for OS. These results received both internal and external validation with C-index of 0.701 (95% CI, 0.647 to 0.755) and 0.707 (95% CI, 0.657 to 0.756) for RFS, and 0.706 (95% CI, 0.640 to 0.772) and 0.708 (95% CI, 0.646 to 0.771) for OS, respectively. The nomograms showed superior accuracy to conventional staging systems (p<0.001). CONCLUSION: The nomograms based on inflammation-related markers are of high efficacy in predicting survival of HCC patients after hepatectomy, which will be valuable in guiding postoperative interventions and follow-ups.
Subject(s)
Humans , Bilirubin , Blood Platelets , Calibration , Carcinoma, Hepatocellular , Cohort Studies , Discrimination, Psychological , Follow-Up Studies , gamma-Glutamyltransferase , Hepatectomy , Inflammation , International Normalized Ratio , Lymphocytes , Neutrophils , Nomograms , RecurrenceABSTRACT
Objective To determine the correlation between intravoxel incoherent motion (IVIM) parameters and both histologic inflammatory and fibrotic grades of Crohn disease (CD) in adults. Methods Prospectively, 17 patients (77 lesions) with a clinical and pathological diagnosis of CD in the first affiliated hospital of sun yat-sen university from July 2015 to June 2016 underwent MRE 15 days before surgery. All patients underwent T2WI, IVIM and enhanced MRI and calculated IVIM parameters include diffusion-related coefficient (D), perfusion-related coefficient (D*) and perfusion-related fraction (f). Histological intestinal inflammation and fibrosis was scored using the surgical histopathology as reference standard and further divided into mild-moderate (score 1 to 2) and severe (score 3 to 4) groups. Intestinal microvessel density (MVD) were also analyzed. Differences in IVIM parameters among different histological inflammation and fibrosis grades were assessed with the Kruskal-Wallis test. The Wilcoxon test was used for assessing differences in f between mild-moderate and severe fibrosis. The bivariate correlations between IVIM parameters and histological inflammation and fibrosis grades were analyzed using partial correlation . The bivariate correlations between IVIM parameters and MVD were analyzed using Spearman rank correlation. The areas under the receiver operating characteristics curves (AUROC) were analyzed to evaluate the efficacy for distinguishing severe from mild-moderate fibrosis. Results Of 77 surgical specimens, there were 41 mild-moderate and 36 severe inflammatory bowel segments, along with 22 mild-moderate and 55 severe fibrotic bowel segments. Positive correlation was shown between histologic inflammatory and fibrotic scores (r=0.592, P<0.01). MVD (42.7 ± 39.9)/HP presented weak positive correlation with histologic inflammatory scores (r=0.332, P=0.003) while no correlation with histologic fibrotic scores (r=0.129, P=0.262) was presented. Neither the D nor the D* values significantly correlated with histologic inflammation or fibrosis (P>0.05) while the f value significantly correlated with both histologic inflammation and fibrosis (P<0.05). Significant correlation was present between the f value and histologic inflammatory and fibrotic scores, respectively (r=-0.280, -0.520;P<0.05). There was significant difference in the f value between mild-moderate and severe fibrosis(Z=-5.255,P<0.01). The AUROC for the f value to distinguish between patients with mild-moderate fibrosis and severe fibrosis were 0.885. Using a threshold fractional perfusion of 0.33, the sensitivity and specificity values were 95.5％ and 81.8％, respectively. No correlation between f, D and D*value with histologic fibrotic scores (r=0.129, P=0.262) was presented. Conclusion The f value derived from IVIM could help to evaluate the severity of intestinal inflammation and fibrosis CD in adults.
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Purpose To study the malignant transformation after treating rat oval cell line ( WB-F344 ) with chemical carcinogen N-methyl-N′-nitro-N-nitrosoguanidine ( MNNG) . Methods WB-F344 cells were cultured with MNNG for severe times. The biological characteristics of induced cells were detected through the following methods:to check proliferation activity by flow cytometry analysis, to examine malignant transformation degree of induced cells by soft agar assay and tumor formation in NOD/SCID mice, and to investi-gate the transcriptional and protein levels of hepatocellular carcinoma marker GGT, GST-P by real time-PCR. Results Oval cells in-duced by MNNG showed changes in biological characteristics and malignant molecular markers. Conclusion Hepatic oval cells model is successfully established, which can be confirmed by tumor formation in NOD/SCID mice.
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[Objective] To investigate the expression of NF-κB and IL-lra in gastric cancer, and to explore their correlation with the clinicopathological parameters and prognosis of gastric cancer (GC). [Methods] Expression of NF-κB and IL-1ra was detected by immunohistochemistry in tissue microarry of 359 cases of GC. [Results] The expression rates of NF-κB in the patients with metastasis of lymph node, TNM Ⅲ-Ⅳ stage, and poorly differentiated of histology were 80.2%, 80.0%, and 79.2%, respectively. The expression rates of IL-1ra in the patients with tumor size ≤3 cm, early stage, non-metastasis of lymph node, and TNM Ⅰ-Ⅱ stage were 61.7%, 75.0%, 66.4%, and 61.9%, respectively. The 5-year survival rate of the cases with non-expressed NF-κB was statistically higher than that of the cases with expressed NF-κB(P=0.036). The 5-year survival rate of the patients with negative expression of NF-κB and positive expression of IL-1ra was statistically higher than the others (P=0.021). [Conclusions] NF-κB is the adverse predictors of prognosis of gastric cancer. IL-1ra maybe play a protective role in early gastric cancer stage, but it is necessary to study deeply and get more evidences.
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AIM: To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients. METHODS: Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4~+T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software. RESULTS: In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%±0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%±2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%±2.23%) than newly HIV-1 infected patients (3.22%±1.01%, P<0.05) and patients in progression to AIDS(5.21%±1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4~+T cell absolute counts but elevated plasma viral load. CONCLUSION: Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.
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[Objective] To investigate the expression of MICA mRNA and protein in osteosarcoma and give a more comprehensive understanding to its immune evasion.[Methods] RT-PCR was used to analyze MICA mRNA in 11 osteosarcoma tissues and 5 osteosarcoma cell lines.MICA expression was examined in 66 paraffin-embedded osteosarcoma tissues and 6 paraffin-embedded normal bone tissues by immunohistochemistry,and MICA protein in 9 fresh osteosarcoma tissues was detected by Western blot too.MICA surface expression was estimated by flow cytometry.[Results] Nine of eleven (81.8%) osteosarcoma specimens and all of the five cell lines consistently expressed MICA mRNA.Up-regulation of MICA expression was found in osteosarcoma (34/66,51.6%),compared with normal bone tissues (0/6,0%).The cell lines Saos-2,MG63,and HOS showed positive surface MICA expression,while the U2OS and OS732 showed very limited expression.[Conclusion] MICA mRNA and protein predominantly expressed on osteosarcoma tissues and cell lines.