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A novel prognostic factor for hepatocellular carcinoma: protein disulfide isomerase
Yu, Su Jong,Won, Jae-Kyung,Ryu, Han Suk,Choi, Won-Mook,Cho, Hyeki,Cho, Eun-Ju,Lee, Jeong-Hoon,Kim, Yoon Jun,Suh, Kyung-Suk,Jang, Ja-June,Kim, Chung Yong,Lee, Hyo-Suk,Yoon, Jung-Hwan,Cho, Kwang-Hyun The Korean Association of Internal Medicine 2014 The Korean Journal of Internal Medicine Vol.29 No.5
<P><B>Background/Aims</B></P><P>Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated.</P><P><B>Methods</B></P><P>We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment.</P><P><B>Results</B></P><P>PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (<I>p</I> = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (<I>p</I> = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; <I>p</I> = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (<I>p</I> = 0.015; HR, 1.865) and poor OS (<I>p</I> = 0.012; HR, 2.069).</P><P><B>Conclusions</B></P><P>Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.</P>
( Yuri Cho ),( Jeong Hoon Lee ),( Dong Hyeon Lee ),( Min Jong Lee ),( Jeong Ju Yoo ),( Won Mook Choi ),( Young Youn Cho ),( Yun Bin Lee ),( Eun Ju Cho ),( Su Jong Yu ),( Nam Joon Yi ),( Kwang Woong Le 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background/aims: Some patients with hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) have favorable tumor biology, and that these patients would have low risk of tumor recurrence after living donor liver transplantation (LDLT). This study was designed to develop a model of tumor recurrence after LDLT for HCC beyond the MC, so as to select the best candidates for LDLT in HCC beyond the MC. Methods: Consecutive patients who had undergone LDLT beyond the MC at Seoul National University Hospital between September 2001 and January 2013 were analyzed. Demographic, clinical, and tumor characteristics were evaluated and a model to predict recurrence after LDLT (MoRAL score) was created. Results: A total of 104 patients were included. The median follow-up was 52.7 (range, 1.6-157.5) months. Their 5-year overall survival and cumulative recurrence rates were 70.4% and 41.8%, respectively. In multivariate analysis, independent pretransplant risk factors for HCC recurrence were serum AFP (OR=1.003, P=0.013) and PIVKA-II (OR=1.001, P=0.050) levels. AFP reflected maximal tumor size and PIVKA-II reflected tumor number and type (nodular or diffuse/infiltrative) (all P<0.001). Using Cox proportional hazards model, MoRAL score ( )was derived (median, 108.3; range 33.7-3928.3). The concordance statistic of MoRAL (0.836) was superior to CLIP score (0.772), TNM stage (0.600), JIS stage (0.601) and T classification (0.626). The tumor recurrence after LDLT was significantly related to mortality (OR=21.6, P<0.001). Conclusions: A new model to predict tumor recurrence of HCC patients beyond the MC after LDLT based on objective parameters provides refined prognostication (Figure 1). External validation is warranted.
( Eun Ju Cho ),( Hyo Cheol Kim ),( Jeong Hoon Lee ),( Jeong Ju Yoo ),( Won Mook Choi ),( Young Youn Cho ),( Min Jong Lee ),( Yuri Cho ),( Dong Hyeon Lee ),( Yun Bin Lee ),( Su Jong Yu ),( Yoon Jun Kim 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Sorafenib is regarded as the standard treatment of care in Barcelona Clinic Liver Cancer (BCLC) stage C patients in the BCLC treatment algorithm. However, the modest survival warrants for a better treatment modality. This study aimed to investigate the feasibility of combined TACE and radiotherapy (TACE+RT) in comparison with sorafenib for locally advanced HCC. Methods: From 2007 to 2011, a total of 116 patients with locally advanced HCC without distant metastasis were retrospectively enrolled. 35 patients were treated with sorafenib and 67 patients underwent treatment with TACE+RT. Propensity score-matching generated a matched cohort composed of 54 patients. Overall survival was the primary endpoint for the analysis. Results: At baseline, the sorafenib treated group had a tendency for a tumor size ≥10 cm (74.3% vs. 59.7%, P<0.001), presence of lymph node metastasis (34.3% vs. 11.9%, P=0.007) and presence of main portal vein tumor thrombosis (45.7% vs. 25.4%, P=0.037). The overall survival in the TACE+RT group was significantly longer compared to the sorafenib group (3.3 months vs. 14.1 months, P<0.001). In the propensity scorematched cohort, baseline characteristic did not differ between the two groups. The TACE+RT group (n=27) showed prolonged overall survival compared to the sorafenib group (n=27) (6.7 months vs. 3.1 months, P<0.001). Multivariate analysis revealed that TACE+RT was the only independent prognostic factor associated with survival in the propensity score-matched cohort (HR=0.172, 95% CI 0.078-0.379; P<0.001). Conclusions: The overall survival of the combined treatment of TACE+RT was associated with a prolonged survival compared to the administration of sorafenib in locally advanced hepatocellular carcinoma patients.
( Eun Ju Cho ),( Jeong Hoon Lee ),( Il Young Lee ),( Moon Young Kim ),( Jeong Ju Yoo ),( Won Mook Choi ),( Young Youn Cho ),( Min Jong Lee ),( Yuri Cho ),( Dong Hyeon Lee ),( Yun Bin Lee ),( Su Jong Y 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure. In this study, we investigated which noninvasive fibrosis test most effectively reflects HVPG and predicts prognosis in patients with alcoholic liver disease (ALD). Methods: A total of 195 consecutive patients with ALD were included. Biochemical indices and liver stiffness assessed by transient elastography (TE) were compared with HVPG. Results: During a median follow-up period of 23.1 months, 51 patients died, including 21 liver-related deaths. The diagnostic values of liver stiffness in detecting clinically significant portal hypertension (CSPH; HVPG≥10 mmHg) was significantly higher (AUROC=0.87±0.03) than those of biochemical indices (i.e. APRI, FIB4, P2/MS and platelet count/spleen diameter ratio; all P<0.001). In multivariate analysis, liver stiffness was most significantly correlated to HVPG (P<0.001), whereas other biochemical indices were not. On the other hand, the prognostic values of liver stiffness for liver-related death (AUROC= 0.73±0.07) did not differ from those of FIB4 (0.78±0.04), HVPG (0.70±0.07) and APRI (0.69±0.04). In multivariate analysis, significant risk factors for liver-related death were Child score (hazard ratio [HR]=2.35, P<0.001), varices >F2 (HR=5.85; P=0.002) and FIB4 (HR=1.11, P=0.03), but not liver stiffness and HVPG. For all-cause death, age and FIB4 were independent predictors in compensated patients (P=0.02 and <0.001, respectively), whereas Child score was in decompensated patients (P<0.001). Conclusions: In patients with ALD, liver stiffness most accurately predicts CSPH, but did not improve the prognostic values of traditional risk factors for mortality, whereas FIB4 was independent predictor for liver disease-related death and allcause death.
Lee, Yun Bin,Jung, Eun Uk,Kim, Bo Hyun,Lee, Jeong-Hoon,Cho, Hyeki,Ahn, Hongkeun,Choi, Won-Mook,Cho, Young Youn,Lee, Minjong,Yoo, Jeong-Ju,Cho, Yuri,Lee, Dong Hyeon,Cho, Eun Ju,Yu, Su Jong,Park, Sung J American Society for Microbiology 2015 Antimicrobial Agents and Chemotherapy Vol.59 No.2
<P>Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (<I>P</I> = 0.562 and <I>P</I> = 0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.</P>