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King-Wah Chiu,
Tsung-Hui Hu,
Toshiaki Nakano,
Kuang-Den Chen,
Chia-Yun Lai,
Li-Wen Hsu,
Hui-Peng Tseng,
Ho-Ching Chiu, Yu-Fan Cheng,
Shigeru Goto,
Chao-Long Chen
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ABSTRACT: BACKGROUND: Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. The CYP3A4*18, CYP3A5*3, and MDR1-3435 variant alleles are very important, particularly in tacrolimus metabolism in organ transplant rejection.Aim: The aim of this study is o explore possible interactions among different CYP2C19 genotypes, namely, between homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers (HetEM), and poor metabolizers (PM), and the CYP3A4*18, CYP3A5*3, and MDR1-3435 variants in living donors and patients who received a living donor liver transplant (LDLT). METHODS: This prospective study enrolled 133 living donors and 133 corresponding recipients. On the basis of the HomEM, HetEM, and PM CYP2C19 genotypes, the distributions of CYP3A4*18 (exon 10; T878C), CYP3A5*3 (intron 3; A6986G), and MDR1-3435 (exon 26; C3435T) genotypes were analyzed for single nucleotide polymorphisms among donors and recipients. RESULTS: Among 102 HomEM genotypes, including 56 donors and 46 recipients, 91.2% of individuals harbored the T/T genotype of CYP3A4*18; 53.9% possessed G/G, and 34.3% had A/G genotypes of CYP3A5*3; and 38.2% had C/C and 50.0% had C/T genotypes at MDR1-3435. Among 130 HetEM genotypes, including 58 donors and 72 recipients, 97.7% of individuals possessed T/T genotype at CYP3A4*18; 50.0% harbored G/G and 41.5% had A/G genotypes at CYP3A5*3; and 40.0% had C/C and 49.2% had C/T genotypes at MDR1-3435. In 34 PMs, including 19 donors and 15 recipients, 88.2% had T/T genotypes at CYP3A4*18; 41.2% had G/G and 58.8% had A/G genotypes at CYP3A5*3; and 47.1% possessed C/C and 47.1% had C/T genotypes at MDR1-3435. On the basis of the CYP2C19 genotypes, no statistically significant distribution of genotypes were observed between donors and recipients for all genotypes of CYP3A4*18, CYP3A5*3, and MDR1-3435 (P >0.05). CONCLUSIONS: In conclusion, the CYP2C19 genotypes do not affect the expression of CYP3A4*18, CYP3A5*3, or MDR1-3435 variants, which are independently distributed among donors and recipients during LDLT.
Transplantation research. 04/2013; 2(1):6.
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Kuang-Den Chen,
Shigeru Goto,
Li-Wen Hsu,
Tzu-Yang Lin,
Toshiaki Nakano,
Chia-Yun Lai,
Yen-Chen Chang,
Wei-Teng Weng,
Yur-Ren Kuo,
Chih-Chi Wang, Yu-Fan Cheng,
Yen-Ying Ma,
Chih-Che Lin,
Chao-Long Chen
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ABSTRACT: Adipose-derived mesenchymal stem cells (adipose-derived MSCs, ASCs) possess the ability to differentiate into multiple tissue types and have immune-modulatory properties similar to those of MSCs from other origins. However, the regulation of the MSC-elicited immune-modulatory activity by specific microRNA (miRNA) mechanisms remains unexplored. Gene expression profiling with knowledge-based functional enrichment analysis is an appropriate approach for unraveling these mechanisms. This tool can be used to examine the transcripts and miRNA regulators that differentiate the rat tolerogenic orthotopic liver transplantation (OLT; DA liver into PVG) and rejection OLT (DA liver into LEW) models. In both models, the rejection reaction was observed on postoperative day 7∼14 (rejection phase) but was overcome only by the PVG recipients. Thus, the global gene expression patterns of ASCs from spontaneously tolerant (PVG) and acute rejecting (LEW) rats in response to LPS activation were compared. In this study, we performed miRNA enrichment analysis based on the analysis of pathway, gene ontology (GO) terms and transcription factor binding site (TFBS) motif annotations. We found that the top candidate, miR-27, was specifically enriched and had the highest predicted frequency. We also identified a greater than 3-fold increase of miR-27b expression in the ASCs of tolerant recipients (DA to PVG) compared to those of rejecting recipients (DA to LEW) during the rejection phase in the rat OLT model. Furthermore, our data showed that miR-27b knockdown has a positive influence on the allosuppressive activity that inhibits T-cell proliferation. We found that miR-27 knockdown significantly induced the expression of CXCL12 in cultured ASCs and the expression of CXCL12 was responsible for the miR-27b antagomir-mediated inhibition of T-cell proliferation. These results, which through a series of comprehensive miRNA enrichment analyses, might be relevant for stem cell-based therapeutic applications in immunosuppressive function using ASCs.
PLoS ONE 01/2013; 8(4):e60492. · 4.09 Impact Factor
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Tsan-Shiun Lin,
Chao-Long Chen,
Allan M Concejero,
Anthony Q Yap,
Yu-Hung Lin,
Chun-Yi Liu,
Yuan-Cheng Chiang,
Chih-Chi Wang,
Shih-Ho Wang,
Chih-Che Lin,
Chee-Chien Yong, Yu-Fan Cheng
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ABSTRACT: We describe our early and long-term experience with routine biliary reconstruction using microsurgical technique in living donor liver transplantation (LDLT). 177 grafts were primarily transplanted in 174 recipients (including 3 dual grafts). The minimum follow-up was 44 months. Biliary reconstructions were based on biliary anatomical variations in graft and recipient ducts. The recipients' demographics, graft characteristics, types of biliary reconstruction, biliary complications, and outcomes were evaluated. There were 130 right and 47 left lobe grafts. There were single duct in 71.8%, two in 26.0%, and three in 2.3% grafts. The complications were not significantly related to size and number of ducts, discrepancy between recipient and donor ducts, recipient age, ischemia time, and type of graft used. The overall biliary complication rate was 9.6%. Majority of complications occurred within the first year and only one developed a stricture at 20 months. No new complications were noted after 2 years. Excluding the learning curve phase of the first 15 cases, the overall biliary complication rate was 7.0% and complications that required intervention was 2.5%. The routine use of microsurgical biliary reconstruction decreases early and long-term biliary anastomotic complications in LDLT. © 2012 American Association for the Study of Liver Diseases.
Liver Transplantation 11/2012; · 3.39 Impact Factor
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Journal of vascular and interventional radiology: JVIR 05/2012; 23(5):724-5. · 1.81 Impact Factor
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Ting-Lung Lin,
Li-Wei Chiang,
Chao-Long Chen,
Shih-Hor Wang,
Chih-Che Lin,
Yueh-Wei Liu,
Chee-Chien Yong,
Tsan-Shiun Lin,
Wei-Feng Li,
Bruno Jawan, Yu-Fan Cheng,
Tai-Yi Chen,
Allan M Concejero,
Chih-Chi Wang
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ABSTRACT: For pediatric living donor liver transplantation, portal vein complications cause significant morbidity and graft failure. Routine intra-operative Doppler ultrasound is performed after graft reperfusion to evaluate the flow of portal vein. This retrospective study reviewed 65 children who had undergone living donor liver transplantation. Seven patients were detected with suboptimal portal vein flow velocity following vascular reconstruction and abdominal closure. They underwent immediate on-table interventions to improve the portal vein flow. Both surgical and endovascular modalities were employed, namely, graft re-positioning, collateral shunt ligation, thrombectomy, revision of anastomosis, inferior mesenteric vein cannulation, and endovascular stenting. The ultrasonographic follow-up assessment for all seven patients demonstrated patent portal vein and satisfactory flow. We reviewed our experience on the different modalities and proposed an approach for our future intra-operative management to improve portal vein flow at the time of liver transplantation.
Transplant International 03/2012; 25(5):586-91. · 2.92 Impact Factor
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ABSTRACT: In living donor liver transplantation (LDLT), the essential aims are to provide an adequate graft volume to the recipient and to keep a sufficient remnant liver volume in the donor. In some instances, these aims cannot be met by a single donor and LDLT using dual grafts from two donors is a good solution. From 2002 to 2009, five recipients in our hospital received dual graft LDLT. Two recipients received one right lobe and one left lobe grafts; the other three received two left lobe grafts. The mean final liver regeneration rate was 91.2%. Left lobe graft atrophy in the long term was observed in recipients who received a right and a left lobe grafts. The initial bigger volume graft in all recipients was noted to have better regeneration than the smaller volume grafts. Portal flow and bilateral grafts volume size discrepancy were considered as two major factors influencing graft regeneration in this study. We also noted that the initial graft volume correlated with portal flow in the separate grafts and finally contribute to individual graft regeneration. Because of compensatory hypertrophy of the other graft, recipients who experienced atrophy of one graft did not show signs of liver dysfunction.
Clinical Transplantation 03/2012; 26(2):E143-8. · 1.67 Impact Factor
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ABSTRACT: Living related liver transplantation (LRLT) may not be the only treatment for recurrent bleeding due to severe gastric varices secondary to left-side portal hypertension and splenic vein thrombosis. Splenectomy is the preferred long-term standard treatment for non-orthotopic liver transplantation patients, but additional treatments such as post-transplantation partial splenic arterial embolization to preserve the immunological function of the spleen and thus prevent the occurrence of post LRLT severe infection are suggested for these patients.
Hepato-gastroenterology 03/2012; 59(117):1586-8. · 0.66 Impact Factor
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ABSTRACT: Heroin users on methadone maintenance treatment (MMT) have elevated rates of co-morbid depression and are associated with have higher relapse rates for substance abuse. Structural abnormalities in MMT patients have been reported, but their impact on clinical performance is unknown. We investigated differences in gray matter volume (GMV) between 27 MMT patients and 23 healthy controls with voxel-based morphometry, and we correlated findings in the patients with Beck Depression Inventory scores, Beck Anxiety Inventory scores, and diminished cognitive functioning. MMT patients exhibited higher emotional deficits than healthy subjects. There was significantly smaller GMV in multiple cortices, especially in the left inferior frontal gyrus and left cerebellar vermis in the MMT group. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, left post-central gyrus, left insula, and right cerebellar declive correlated with higher depression scores. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, and left postcentral gyrus also correlated with higher anxiety scores, while smaller GMV in the cerebellum and bilateral insula was associated with impaired performance on tests of executive function. These results reveal that MMT patients have low GMV in brain regions that are hypothesized to influence cognition and emotion, and the GMV findings might be involved comorbid disorders in the MMT group.
Psychiatry Research 03/2012; 201(2):89-97. · 2.52 Impact Factor
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ABSTRACT: Chen H-L, Tsang LL-C, Concejero AM, Huang T-L, Chen T-Y, Ou H-Y, Yu C-Y, Chen C-L, Cheng Y-F. Segmental regeneration in right-lobe liver grafts in adult living donor liver transplant. Abstract: Our aim is to evaluate the relationship and impact of right-lobe (RL) liver grafts procured with or without the middle hepatic vein (MHV) trunk and MHV tributary reconstruction on segmental regeneration of these grafts in adult living donor liver transplantation (ALDLT). Patients underwent primary ALDLT using a RL liver graft were divided into three groups according to graft type: with MHV tributary reconstruction (group I), without MHV tributary reconstruction (group II), and with inclusion of the MHV trunk (group III). The overall graft volume and the volumes of the anterior and posterior segments of the grafts six months post-transplant, evaluated using computed tomography, were calculated as the regeneration indices. Optimal regeneration of the RL liver graft was achieved in the three groups of patients. There was no significant difference in the regeneration indices between groups I (149.4%) and III (143.6%). However, in group II (112.4%) without MHV or tributary reconstruction, the anterior regenerative index was lower than the other two groups and exhibited transient prolonged hyperbilirubinemia. Segmental graft regeneration is maximized by adequate venous drainage. Inclusion of the MHV trunk or MHV tributary reconstruction influences segmental liver regeneration and preclude transient hyperbilirubinemia in the early post-liver transplant phase.
Clinical Transplantation 02/2012; 26(5):694-8. · 1.67 Impact Factor
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ABSTRACT: Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from "without HE" or "minimal HE" to "overt HE", correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.
PLoS ONE 01/2012; 7(5):e36986. · 4.09 Impact Factor
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ABSTRACT: Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.
PLoS ONE 01/2012; 7(4):e33809. · 4.09 Impact Factor
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Toshiaki Nakano,
Chia-Yun Lai,
Shigeru Goto,
Li-Wen Hsu,
Seiji Kawamoto,
Kazuhisa Ono,
Kuang-Den Chen,
Chih-Che Lin,
King-Wah Chiu,
Chih-Chi Wang, Yu-Fan Cheng,
Chao-Long Chen
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ABSTRACT: The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.
PLoS ONE 01/2012; 7(5):e37202. · 4.09 Impact Factor
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ABSTRACT: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a 'small-world' network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI). Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions disturbed the functional network to further alter the global topology and efficiency of the whole brain network. These findings provide insights into the functional changes in the human brain in HE.
PLoS ONE 01/2012; 7(5):e35266. · 4.09 Impact Factor
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Li-Wen Hsu,
Shigeru Goto,
Toshiaki Nakano,
Kuang-Den Chen,
Chih-Chi Wang,
Chia-Yun Lai,
Chiung-Hui Hou,
Yen-Chen Chang, Yu-Fan Cheng,
King-Wah Chiu,
Chien-Chih Chen,
Shu-Hui Chen,
Chao-Long Chen
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ABSTRACT: Adipose-derived stem cells (ASCs) are of great interest for the development of novel cell therapies due to their ease of isolation and expansion, immunosuppressive activity, and multilineage differentiation potential. However, the mechanisms underlying the therapeutic potential of ASCs remain to be elucidated. Others and we have shown that nuclear proteins such as histone H1 and high mobility group box 1 (HMGB1) play important roles in the maturation of dendritic cells (DCs). Furthermore, we previously demonstrated translocation of histone H1 from the nucleus to the cytoplasm and activation of mitogen-activated protein kinases (MAPKs) in DCs. In the present study, we confirmed that histone H1 does not alter the immunophenotype and immunosuppression potential of ASCs, but that histone H1 enhanced wound healing and increased interleukin (IL)-6 expression. Moreover, histone H1 treated-ASCs showed up-regulation of MAPKs extracellular-regulated kinase 1/2 (ERK1/2) and sequential NF-κB translocation. Finally, we found that culture in differentiation media supplemented with histone H1 enhanced ASC osteogenesis. In contrast, inhibition of histone H1 by small interfering RNA (siRNA) reduced osteogenic differentiation markers including ALP. These results suggest that histone H1 may be useful for induction of mesenchymal stem cells in tissue engineering and future potential ASC therapies.
Journal of Cellular Physiology 12/2011; 227(10):3417-25. · 3.87 Impact Factor
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ABSTRACT: BACKGROUND: Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. METHODS: Forty-six patients with previously implanted coronary artery stents (n=87) underwent MDCT followed by CCA and IVUS within 24h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) ≤4.0mm(2) of IVUS as the reference standard were determined. RESULTS: Eight stents (9%) were judged non-evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA ≤4.0mm(2) was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. CONCLUSIONS: When ISAR with MLA ≤4.0mm(2) was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR.
International journal of cardiology 11/2011; · 7.08 Impact Factor
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ABSTRACT: The donor liver grafts with different allelic patterns do not affect CYP2C19 genotypes in the peripheral blood of living donor liver transplantation (LDLT) recipients.
This study investigated the influence of graft liver CYP2C19 genotypes on recipients who received the same or different CYP2C19 genotypes from donors after LDLT.
There were 30 donors and 30 recipients with the same CYP2C19 genotypes and 47 donors and 47 recipients with different CYP2C19 genotypes. Genomic DNA was isolated from the liver tissue of recipients. The CYP2C19 haplotypes were determined by polymerase chain reaction.
A homogenous phenomenon in the sequences of graft liver CYP2C19 genotypes was indicated because the recipients showed mixed patterns that were similar to that of the original donor after LDLT. A significant decrease in homozygous extensive metabolizer (HomEM) and an increase in poor metabolizer (PM) distribution were observed in recipients with different CYP2C19 genotypes from their donors compared with recipients with the same CYP2C19 genotype as their donors (P < 0·05).
Homogenous phenomenon of sequence changes in graft liver CYP2C19 from the different genotypes between the donors and the recipients may play a role in graft stability by causing decreased HomEM and increased PM after LDLT.
European Journal of Clinical Investigation 08/2011; 42(4):352-6. · 3.02 Impact Factor
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Hsien-Wen Hsu,
Leo Leung-Chit Tsang,
Anthony Yap,
Tung-Liang Huang,
Tai-Yi Chen,
Tsan-Shiun Lin,
Allan M Concejero,
Shin-You Ou,
Chun-Yen Yu,
Chao-Long Chen, Yu-Fan Cheng
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ABSTRACT: Exact knowledge of biliary anatomy is essential in living donor liver transplantation. The purpose of this study was to evaluate the accuracy of pretransplant magnetic resonance cholangiography (MRC) in depicting the biliary anatomy in comparison with intraoperative cholangiography (IOC).
From May 2006 to July 2009, 451 potential living liver donors underwent pretransplant evaluation at the Chang Gung Memorial Hospital-Kaohsiung Medical Center. Two hundred thirty-three donors underwent donor hepatectomy. Of these, only 203 donors with both preoperative MRC and IOC were included in this study.
Of the 451 potential donors, 218 (48.3%) were considered unsuitable for liver donation, hence was immediately disqualified after the initial evaluation for various reasons. Six of the 218 unsuitable donors (2.8%) were excluded due to complicated biliary anatomy. The overall accuracy rate of MRC for defining the biliary anatomy was 91.6%, with 84.9% sensitivity, 96% specificity, 88.2% positive predictive value, and 94.7% negative predictive value. There were 14 misidentified cases. The errors in MRC reading was largely attributed to the poor contrast between the biliary ducts and the surrounding tissues and organs. The concurrence between MRC and IOC were commendable (κ=0.9). No significant biliary complications were noted in the mismatch group.
MRC is essential for all pretransplantation evaluation with 91.6% accuracy rate.
Transplantation 07/2011; 92(1):94-9. · 4.00 Impact Factor
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ABSTRACT: The American Association for the Study of Liver Disease issued guidelines that proposed that hepatocellular carcinoma (HCC) can be diagnosed if a mass is larger than 2 cm in a cirrhotic liver and shows typical features of HCC at triphasic liver computed tomography (CT) or dynamic magnetic resonance imaging (MRI). In non-cirrhotic livers, the criteria were not applicable. The aim of the present study was to retrospectively analyze the sensitivity of imaging by samples of definite HCC postoperatively and test their application to diagnose HCC in non-cirrhotic livers.
From January 2006 to November 2008, a total of 343 pathologically-diagnosed HCC patients via surgical resection were reviewed. Among the 343 patients, 204 patients had undergone liver CT examination, and 80 patients underwent MRI examination; serum α-fetoprotein had been checked for all 343 patients prior to operation. The diagnostic sensitivity of HCC by imaging was evaluated and compared in patients with/without cirrhosis by ultrasound and histology.
The diagnostic sensitivity of HCC by single imaging was approximately 65-80% (liver CT or MRI). A higher sensitivity of HCC diagnosis was found in patients with ultrasound-diagnosed cirrhosis than non-cirrhosis, but the difference in sensitivity disappeared after histologically-cirrhotic validation. The results indicated that regardless of the presence or absence of cirrhosis (histology), a typical vascular pattern could diagnose HCC with equally high sensitivity.
We provide evidence that the sensitivity of HCC diagnosis by imaging is not influenced by the cirrhotic background. Further study is needed to validate the specificity and accuracy.
Journal of Gastroenterology and Hepatology 04/2011; 26(4):745-50. · 2.87 Impact Factor
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ABSTRACT: A prospective trial of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with osteoporotic vertebral compression fracture (VCF).
To investigate the relationship between intraosseous clefts and bone marrow perfusion using DCE-MRI in patients with osteoporotic VCF before vertebroplasty.
The nonhealing cleft may be responsible for persistent pain and progressive vertebral collapse after acute injury. If localized kyphosis increased, there is risk of neuropathy appearing as a complication. Even after receiving vertebroplasty, it was reported to be at increased risk for subsequent cemented vertebral refracture and new adjacent vertebral fractures. DCE -MRI has been used for the evaluation of bone marrow perfusion. However, there are few reports on the evaluation of osteoporotic VCF and intraosseous cleft formation.
Forty subjects referred for evaluation of VCF underwent DCE-MRI. Bone marrow perfusion, as measured using the DCE-MRI time-intensity curve from a noninjured vertebrae was developed using two distinct parameters including peak enhancement ratio and enhancement slope. The ratio of the well-enhanced and the poorly enhanced zone of each injured vertebra were calculated. Multiple logistic regression analysis was used to evaluate the relationships between baseline clinical factors, parameters of DCE-MRI and presence or absence of intraosseous clefts.
Twenty-nine injured vertebrae (72%) had intraosseous clefts. Lower PER of the noninjured vertebrae was associated with higher poorly enhanced zone ratio of the injured vertebrae (γ = -0.362, P = 0.017). Multivariate logistic regression analysis identified only lower PER (hazard ratio, 0.000; 95% confidence interval, 0.000-0.096; P = 0.009) was associated with the presence of intraosseous clefts. A peak enhancement ratio value less than 0.57 had a sensitivity of 80% and specificity of 90% for predicting intraosseous clefts.
In patients with osteoporotic VCF before vertebroplasty, decreased bone marrow perfusion, as measured by DCE-MRI, was associated with intraosseous cleft formation.
Spine 01/2011; 36(15):1244-50. · 2.08 Impact Factor
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Kuang-Den Chen,
Li-Wen Hsu,
Shigeru Goto,
Chin-Wei Yeh,
Toshiaki Nakano,
Chia-Yun Lai,
Yen-Chen Chang,
Chiung-Hui Hou,
Chih-Chi Wang, Yu-Fan Cheng,
King-Wah Chiu,
Chih-Che Lin,
Chao-Long Chen
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ABSTRACT: The Shc isoforms is known to mediate immune responses and has been indicated as a negative regulator of autoimmunity and lymphocyte activation. We aimed to evaluate the immune-regulatory role of Shc in rat bone marrow-derived DCs in the maturation process triggered by LPS.
We found that, in response to LPS, expression of Shc proteins was induced and that neutralization of Shc inhibited the LPS-induced transient phosphorylation of p52Shc on pTyr239/240 in DCs of Lewis (LEW; RT1(l)) rats. Moreover, the significantly enhanced expression of IL-10 and the surface level of costimulatory molecule CD80, as well as suppressed expression of IL-6 and IL-12 in the Shc-silenced DCs were also observed. Similar IκB phosphorylation occurred in Shc-silenced DCs primed by LPS, indicating Shc is not associated with NF-κB pathway. We further demonstrate that Shc blockade on LPS-treated DCs results in significant increase of the overall STAT3 phosphorylation and the relative levels of phospho-STAT3 in the nuclear fraction. STAT3 activation by LPS with or without Shc blockade was totally abolished by SU6656, a selective Src family kinases inhibitor, underscoring the critical role of Src-mediated activation.
We conclude that Shc blockade in LPS-primed DC leads to the development of tolerogenic DC via Src-dependent STAT3 activation and that adaptor protein Shc might play a pivotal role in mediating immunogenic and tolerogenic properties of DCs.
BMC Immunology 01/2011; 12:32. · 2.53 Impact Factor
