Publications by authors named "Hee Jung Wang"

80 Publications

Strategy for Selective Middle Hepatic Vein Reconstruction in Living Donor Liver Transplantation Using Right Lobe Graft: A Retrospective Observational Study.

Transplant Proc 2021 Sep 24;53(7):2318-2328. Epub 2021 Aug 24.

Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea. Electronic address:

Background: The aim of this study was to verify the safety and feasibility of our selection criteria for middle hepatic vein (MHV) reconstruction in living donor liver transplantation (LDLT) using right lobe grafts.

Methods: A total of 153 LDLTs were performed using right lobe grafts in a tertiary hospital from 2006 to 2016. Among them, 52 cases without MHV reconstruction were compared with 101 recipients who underwent LDLT using right lobe graft with MHV reconstruction. Both groups were compared regarding indications for reconstruction, short-term and long-term complications, operative details, and outcomes.

Results: The two groups differed only in cold ischemic time (108.19 ± 49.81 minutes vs 146.37 ± 58.74 minutes) preoperatively. Short-term posttransplant outcomes, long-term overall survival, and long-term disease-free survival showed no significant differences between the 2 groups. After propensity score matching for both groups with and without MHV reconstruction to eliminate selection bias, the 2 groups were comparable.

Conclusions: We found that our selection criteria for performing MHV reconstruction in LDLT using right lobe graft were feasible and safe. A routine MHV reconstruction is not necessary if the right lobe graft graft-to-recipient weight ratio is ≥1.0, right hepatic vein draining territory volume is ≥0.8, and recipient Model for End-Stage Liver Disease score is <20.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2021.07.042DOI Listing
September 2021

TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659.

Liver Int 2021 Jul 30. Epub 2021 Jul 30.

Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Background & Aims: Noncoding RNAs (ncRNAs) play critical roles in hepatocellular carcinoma (HCC) progression. Here, by performing RNA-sequencing (RNA-Seq) profiling, we sought to identify novel ncRNAs that potentially drive the heterogeneous progression of liver cancers.

Methods: RNA-Seq profiles were obtained from 68 HCC specimens and 10 samples of adjacent non-tumour liver tissues. The functional significance of the potential driver ncRNAs was evaluated by cell experiments.

Results: TPRG1-AS1 was identified as a potential driver noncoding RNA that promotes heterogeneous liver cancer progression. TPRG1-AS1 induced tumour suppressor RNA-binding motif protein 24 (RBM24), suppressing tumour growth by activating apoptotic tumour cell death. In addition, we report that TPRG1-AS1 acts as a competing endogenous RNA (ceRNA) for RBM24, sponging miR-4691-5p and miR-3659 to interfere with their binding to RBM24.

Conclusions: We suggest that TPRG1-AS1 is a novel ceRNA sponging miR-4691-5p and miR-3659, resulting in RBM24 expression and suppression of liver cancer growth. Our results provide new insights into the functions of ncRNAs in heterogeneous HCC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15026DOI Listing
July 2021

USO1 isoforms differentially promote liver cancer progression by dysregulating the ER-Golgi network.

Carcinogenesis 2021 Jul 22. Epub 2021 Jul 22.

Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Alternative splicing of RNA transcripts plays an important role in cancer development and progression. Recent advances in RNA-seq technology have made it possible to identify alternately spliced events in various types of cancer; however, research on hepatocellular carcinoma (HCC) is still limited. Here, by performing RNA-Seq profiling of HCC transcripts at isoform level, we identified tumor-specific and molecular subtype-dependent expression of the USO1 isoforms, which we designated as a normal form USO1-N (XM_001290049) and a tumor form USO1-T (NM_003715). The expression of USO1-T, but not USO1-N, was associated with worse prognostic outcomes of HCC patients. We confirmed that the expression of USO1-T promoted an aggressive phenotype of HCC, both in vitro and in vivo. In addition, structural modeling analyses revealed that USO1-T lacks an ARM10 loop encoded by exon 15, which may weaken the dimerization of USO1 and its tethering to GM130. We demonstrated that USO1-T ensured unstacking of the Golgi and accelerated the trafficking from ER to Golgi and plasma membrane in multiple liver cancer cells. ERK and GRASP65 were found to be involved in the USO1-T mediated Golgi dysfunction. Conclusively, we provide new mechanophysical insights into the USO1 isoforms that differentially regulate the ER-Golgi network, promoting the heterogeneous HCC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgab067DOI Listing
July 2021

Risk Factors for Beyond Milan Recurrence After Hepatic Resection for Single Hepatocellular Carcinoma No Larger Than 5 Centimeters.

Liver Transpl 2021 08 14;27(8):1116-1129. Epub 2021 Jul 14.

Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea.

Hepatic resection (HR) is considered a treatment of choice for a single hepatocellular carcinoma (HCC) ≤5 cm in patients with preserved liver function. However, it is possible for these patients to develop a severe form of recurrence (beyond Milan recurrence [BMR] criteria). This recurrence could have been avoided if liver transplantation (LT) was performed primarily, as LT is believed to yield a more favorable oncological outcome compared with HR. The aim of this study was to determine the risk factors for BMR after HR and to verify whether primary LT can provide a more favorable outcome in patients with BMR risk factors. Data from 493 patients who underwent HR for HCC ≤5 cm between 1995 and 2016 were analyzed. Among them, 74 patients (15%) experienced BMR. The 10-year survival rate of patients with BMR was significantly low compared with that of patients without BMR (22.6% versus 79.8%; P < 0.01). In multivariate analysis, calculated hepatic venous pressure gradient ≥7 mm Hg and microvascular invasion were identified as the risk factors for BMR (P < 0.05). During the same period, 63 eligible patients underwent LT as a primary treatment for HCC ≤5 cm. No significant difference in long-term survival rate was observed when no risk factor for BMR was present in the HR and LT groups (85.5% versus 100%; P = 0.39). However, 10-year survival was poorer in the HR group in the presence of risk factors for BMR (60.6% versus 91.8%; P < 0.001). Among the patients with HCCs ≤5 cm, which are resectable and transplantable, LT is indicated when calculated hepatic venous pressure gradient ≥7 mm Hg and/or microvascular invasion is present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.26070DOI Listing
August 2021

A practical study of the hepatic vascular system anatomy of the caudate lobe.

Quant Imaging Med Surg 2021 Apr;11(4):1313-1321

Department of Surgery, Ajou University School of Medicine, Suwon, South Korea.

Background: This study aimed to examine the inflow and outflow vascular system of the caudate lobe and determine its relevance to hepatobiliary surgery.

Methods: A total of 41 cadaveric liver specimens were dissected in 2019 to evaluate the inflow and outflow vascular system of the caudate lobe.

Results: The Glisson's pedicles of the paracaval portion were mainly from the right pedicle in 14 cases (34.15%), mainly from the left pedicle in 22 cases (53.66%), and equally from the left and right pedicle in 5 cases (12.19%). Many thick branches of the portal vein were found behind the plane consisting of the hilar plate and Arantius ligament, but none of them were thicker than 1 mm in front of the plane. All of the veins of the caudate lobe drained into the inferior vena cava (IVC) via the anterior face. There was an avascular zone without short hepatic veins (SHVs) consisting of loose connective tissue between the retrohepatic IVC and caudate lobe, with its length and width being 45-97 mm and 6-15 mm, respectively.

Conclusions: The plane consisting of the hilar plate and Arantius ligament can be regarded as the boundary between the caudate lobe and the other lobes. There is an avascular zone without SHVs consisting of loose connective tissue between the retrohepatic IVC and caudate lobe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-20-780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930664PMC
April 2021

Bioelectrical impedance analysis for predicting postoperative complications and survival after liver resection for hepatocellular carcinoma.

Ann Transl Med 2021 Feb;9(3):190

Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.

Background: Bioelectrical impedance analysis provides information on body composition and nutritional status. However, it's unclear whether the preoperative edema index or phase angle predicts postoperative complication or mortality in patients with hepatocellular carcinoma (HCC). Thus, we investigated whether preoperative bioelectrical impedance analysis could predict postoperative complications and survival in patients with HCC.

Methods: Seventy-nine patients who underwent hepatectomy for hepatocellular carcinoma were prospectively enrolled and bioelectrical impedance analysis was performed before surgery. Postoperative ascites or acute kidney injury and patients' survival were monitored after surgery.

Results: Among 79 patients, 35 (44.3%) developed ascites or acute kidney injury after hepatectomy. In multivariate analysis, a high preoperative edema index (extracellular water/total body water) (>0.384) (odds ratio 3.96; 95% confidence interval: 1.03-15.17; P=0.045) and higher fluid infusion during surgery (odds ratio 1.36; 95% confidence interval: 1.04-1.79; P=0.026) were identified as significant risk factors for ascites or acute kidney injury after hepatectomy. Subgroup analyses showed that the edema index was a significant predictor of ascites or acute kidney injury in patients with cirrhosis. Tumor size was the only significant predictive factor for short-term survival after hepatectomy.

Conclusions: The preoperative edema index using bioelectrical impedance analysis can be used as a predictor of post-hepatectomy complication, especially in patients with liver cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-5194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940938PMC
February 2021

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

J Hepatobiliary Pancreat Sci 2021 Jan 12;28(1):1-25. Epub 2020 Dec 12.

Division of Public Health, Osaka Institute of Public Health, Higashinari, Japan.

Background: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors.

Methods: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations.

Results: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy.

Conclusions: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.868DOI Listing
January 2021

Mitochondrial Respiratory Defect Enhances Hepatoma Cell Invasiveness via STAT3/NFE2L1/STX12 Axis.

Cancers (Basel) 2020 Sep 15;12(9). Epub 2020 Sep 15.

Department of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea.

Mitochondrial respiratory defects have been implicated in cancer progression and metastasis, but how they control tumor cell aggressiveness remains unclear. Here, we demonstrate that a mitochondrial respiratory defect induces nuclear factor-erythroid 2 like 1 (NFE2L1) expression at the transcriptional level via reactive oxygen species (ROS)-mediated STAT3 activation. We identified syntaxin 12 (STX12) as an effective downstream target of NFE2L1 by performing cDNA microarray analysis after the overexpression and depletion of NFE2L1 in hepatoma cells. Bioinformatics analysis of The Cancer Genome Atlas Liver Hepatocellular carcinoma (TCGA-LIHC) open database ( = 371) also revealed a significant positive association ( = 0.3, = 2.49 × 10) between NFE2L1 and STX12 expression. We further demonstrated that STX12 is upregulated through the ROS/STAT3/NFE2L1 axis and is a key downstream effector of NFE2L1 in modulating hepatoma cell invasiveness. In addition, gene enrichment analysis of TCGA-LIHC also showed that epithelial-mesenchymal transition (EMT)-related core genes are significantly upregulated in tumors co-expressing NFE2L1 and STX12. The positive association between NFE2L1 and STX12 expression was validated by immunohistochemistry of the hepatocellular carcinoma tissue array. Finally, higher EMT gene enrichment and worse overall survival ( = 0.043) were observed in the NFE2L1 and STX12 co-expression group with mitochondrial defect, as indicated by low NDUFA9 expression. Collectively, our results indicate that NFE2L1 is a key mitochondrial retrograde signaling-mediated primary gene product enhancing hepatoma cell invasiveness via STX12 expression and promoting liver cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565734PMC
September 2020

F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus.

Ann Surg Treat Res 2020 Jul 29;99(1):8-17. Epub 2020 Jun 29.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Purpose: Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of F-fluorodeoxyglucose (F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT.

Methods: Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT.

Results: Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS.

Conclusion: SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2020.99.1.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332322PMC
July 2020

Mitoribosome Defect in Hepatocellular Carcinoma Promotes an Aggressive Phenotype with Suppressed Immune Reaction.

iScience 2020 Jun 7;23(6):101247. Epub 2020 Jun 7.

Departments of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea. Electronic address:

Mitochondrial ribosomes (mitoribosomes), the specialized translational machinery for mitochondrial genes, exclusively encode the subunits of the oxidative phosphorylation (OXPHOS) system. Although OXPHOS dysfunctions are associated with hepatic disorders including hepatocellular carcinoma (HCC), their underlying mechanisms remain poorly elucidated. In this study, we aimed to investigate the effects of mitoribosome defects on OXPHOS and HCC progression. By generating a gene signature from HCC transcriptome data, we developed a scoring system, i.e., mitoribosome defect score (MDS), which represents the degree of mitoribosomal defects in cancers. The MDS showed close associations with the clinical outcomes of patients with HCC and with gene functions such as oxidative phosphorylation, cell-cycle activation, and epithelial-mesenchymal transition. By analyzing immune profiles, we observed that mitoribosomal defects are also associated with immunosuppression and evasion. Taken together, our results provide new insights into the roles of mitoribosome defects in HCC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2020.101247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306587PMC
June 2020

Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker.

Liver Cancer 2020 Apr 18;9(2):182-192. Epub 2020 Feb 18.

Department of Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.

Background/aim: Uniform treatment of hepatocellular carcinoma (HCC) with molecular targeted drugs (e.g., sorafenib) results in a poor overall tumor response when tumor subtyping is absent. Patient stratification based on actionable gene expression is a method that can potentially improve the effectiveness of these drugs. Here we aimed to identify the clinical application of actionable genes in predicting response to sorafenib.

Methods: Through quantitative real-time reverse transcription PCR, we analyzed the expression levels of seven actionable genes (, , , , , , and ) in tumors versus noncancerous tissues from 220 HCC patients treated with sorafenib. Our analysis found that 9 responders did not have unique clinical features compared to nonresponders. A receiver operating characteristic curve evaluated the predictive performance of the treatment benefit score (TBS) calculated from the actionable genes.

Results: The responders had significantly higher TBS values than the nonresponders. With an area under the curve of 0.779, a TBS combining with , , and was the most significant predictor of response to sorafenib. When used alone, sorafenib had a 0.7-3% response rate among HCC patients, but when stratifying the patients with actionable genes, the tumor response rate rose to 15.6%. Furthermore, actionable gene expression is significantly correlated with tumor response.

Conclusions: Our findings on patient stratification based on actionable molecular subtyping potentially provide a therapeutic strategy for improving sorafenib's effectiveness in treating HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000504548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206603PMC
April 2020

Hepatitis B Prophylaxis after Liver Transplantation in Korea: Analysis of the KOTRY Database.

J Korean Med Sci 2020 Feb 17;35(6):e36. Epub 2020 Feb 17.

Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.

Methods: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.

Results: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.

Conclusion: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2020.35.e36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025905PMC
February 2020

Can we delineate preoperatively the right and ventral margins of caudate lobe of the liver?

Ann Surg Treat Res 2019 Sep 29;97(3):124-129. Epub 2019 Aug 29.

Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Jiangxi, China.

Purpose: Complete removal of the caudate lobe, which is sometimes necessary, is accomplished via isolated caudate lobectomy or hepatectomy that includes the caudate lobe. It is impossible, however, to confirm the right and ventral margins of the caudate lobe by preoperative imaging. This study was undertaken to determine whether we could identify the right and ventral margins of the caudate lobe preoperatively using Synapse 3D visualization software.

Methods: Ninety-four preoperative 3-dimensional (3D) computed tomographic images (1-mm slices) of the liver from candidate donors were examined. The images of the caudate lobe were subjected to a counter-staining method according to Synapse 3D to delineate their dimensions. We first examined whether the right margin of the caudate lobe exceeded the plane formed by the root of the right hepatic vein (RHV) and the right side of the inferior vena cava (IVC). Second, we determined whether the ventral margin of the caudate lobe exceeded the plane formed by the root of the middle hepatic vein (MHV) and the root of the RHV.

Results: For the right margin, 17 cases (18%) exceeded the RHV-IVC plane by a mean of 10.2 mm (range, 2.4-27.2 mm). For the ventral margin, 28 cases (30%) exceeded the MHV-RHV plane by a mean of 17.4 mm (range, 1.2-49.1 mm).

Conclusion: Evaluating the anatomy of caudate lobe using Synapse 3D preoperatively could be helpful for more precise anatomical resection of the caudate lobe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4174/astr.2019.97.3.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722294PMC
September 2019

Prognostic Analysis of Hepatocellular Carcinoma With Hepatitis C Virus Infection Using Epithelial-Mesenchymal Transition Gene Profiles.

J Surg Res 2020 01 14;245:302-308. Epub 2019 Aug 14.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan. Electronic address:

Background: Epithelial-mesenchymal transition genes have prognostic influence on hepatocellular carcinoma (HCC). Previously, the following four epithelial-mesenchymal transition-related genes were considered to be significantly influential: E-cadherin (CDH1), inhibitor of DNA binding 2 (ID2), matrix metalloproteinase 9 (MMP9), and transcription factor 3 (TCF3). A prognostic prediction model, NRISK4 = (-0.333 × [CDH1] - 0.400 × [ID2] + 0.339 × [MMP9] + 0.387 × [TCF3]) was constructed, but from patients with HCC with predominantly hepatitis B virus infection. We therefore aim to validate if this model also fits patients with HCC and hepatitis C virus (HCV) infection.

Methods: We collected HCC tissue samples from 67 patients with HCV infection. Discrimination of the NRISK4 was re-estimated using receiver operating curve analysis and we redefined the appropriate cutoff value. Using this cutoff value, patients were divided into two groups (high/low risk patients) and we compared their clinicopathological factors and prognosis.

Results: Area under the curve of NRISK4 prediction was 0.70 and an appropriate cutoff value was 3.19 in this cohort. Patients were divided into high- (n = 25) and low-risk (n = 42) patients for prognosis. There were no significant differences in tumor factors between the two groups. Cancer-specific survival rates at 5 y after surgery on high- and low-risk patients were 45% and 68%, respectively (P = 0.02). At 2 y after surgery, recurrence rates were 68% and 37% among high- and low-risk patients, respectively (P = 0.01). Aggressive recurrences were highly observed in the high-risk patients (P = 0.01).

Conclusions: NRISK4 model could also successfully validate prognosis of patients with HCC with HCV infection similarly to in the previous report of patients with hepatitis B virus infection, especially in the early period after surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2019.07.077DOI Listing
January 2020

Molecular classification of hepatocellular adenoma: A single-center experience.

Ann Hepatobiliary Pancreat Surg 2019 May 31;23(2):109-114. Epub 2019 May 31.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Backgrounds/aims: Hepatocellular adenoma (HCA) is a rare benign tumor that has a risk of malignant transformation into hepatocellular carcinoma (HCC) and bleeding. The aim of this study was to analyze the characteristics of HCA by performing molecular classification.

Methods: We retrospectively collected data from nine patients who were diagnosed with HCA from 1995 to 2016. The patients underwent liver surgery due to the existence of clinical symptoms. Immunohistochemical (IHC) staining was performed to classify the subgroups of HCA.

Results: Four patients with both β-catenin and inflammation were classified as β-IHCA. Two patients were defined as β-HCA. Two patients were classified as HHCA. Only one patient was defined as IHCA. None of the patients had unclassified HCA. Seven of nine patients had a malignant transformation. By comparing the characteristics of HCA between two groups, we found the mean tumor size in the malignant transformation group was greater than the non-malignant transformation group.

Conclusions: Taken together, the mean tumor size and activation of catenin β1 mutation status might be the risk factors for the malignant transformation of HCA into HCC. Moreover, IHCA without the catenin β1 mutation could also have a possibility of malignant transformation into HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14701/ahbps.2019.23.2.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558132PMC
May 2019

HDAC6 Suppresses Let-7i-5p to Elicit TSP1/CD47-Mediated Anti-Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma.

Hepatology 2019 10 21;70(4):1262-1279. Epub 2019 May 21.

Department of Pathology, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea.

Histone deacetylase 6 (HDAC6) uniquely serves as a tumor suppressor in hepatocellular carcinogenesis, but the underlying mechanisms leading to tumor suppression are not fully understood. To identify comprehensive microRNAs (miRNAs) regulated by HDAC6 in hepatocellular carcinogenesis, differential miRNA expression analysis of HDAC6-transfected Hep3B cells was performed. Using integrative analyses of publicly available transcriptome data and miRNA target prediction, we selected five candidate miRNAs and, through in vitro functional validation, showed that let-7i-5p specifically suppressed thrombospondin-1 (TSP1) in hepatocellular carcinoma (HCC). Ectopic expression of antisense let-7i-5p (AS-let-7i-5p) inhibited in vitro tumorigenesis of HCC cells. In addition, treatments of partially purified TSP1 from culture cell media (ppTSP1) and recombinant TSP1 (rTSP1) exhibited similar effects with AS-let-7i-5p treatment on the same HCC cells, whereas TSP1 neutralizing antibody treatment significantly attenuated these effects. Notably, treatments of HDAC6 plasmid, AS-let-7i-5p, ppTSP1, and rTSP1 significantly suppressed in vitro angiogenesis and metastatic potential of HCC cells, but the co-treatment of TSP1 antibody specific to cluster of differentiation 47 (CD47) binding domain successfully blocked these effects in the same cells. Furthermore, we demonstrated that recovery of HDAC6 elicited let-7i-5p suppression to de-repress TSP1 expression; therefore, it occupied the CD47 receptor to block CD47-SIRPα-mediated anti-phagocytosis of macrophage in HCC. We also observed that HCC-derived exosomal let-7i-5p suppressed TSP1 of recipient hepatocyte cells. Treatments of HDAC6 plasmid, AS-let-7i-5p, and rTSP1 suppressed tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. Conclusion: Our findings suggest that the HDAC6-let-7i-5p-TSP1 regulatory pathway suppresses neoplastic and antiphagocytic behaviors of HCC by interacting with cell surface receptor CD47 in HCC and neighboring cells of tumor microenvironment, providing a therapeutic target for the treatment of liver malignancy and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30657DOI Listing
October 2019

The 7th/8th American Joint Committee on Cancer and the Modified Union for International Cancer Control Staging System for Hepatocellular Carcinoma.

Yonsei Med J 2019 Feb;60(2):140-147

Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Purpose: Although many staging systems have been proposed for hepatocellular carcinoma (HCC), there is no globally accepted system due to the extreme heterogeneity of the disease. We aimed to compare the results of the 7th/8th American Joint Committee on Cancer (AJCC) and the modified Union for International Cancer Control (mUICC) staging systems in patients with HCC.

Materials And Methods: We collected data from 792 patients who underwent hepatic resection at our center. The Kaplan-Meier method was used to determine disease-free survival and overall survival. To evaluate homogeneity, '-2 log likelihood' was calculated using Cox proportional hazards regression. To measure discriminatory ability, the linear trend chi method and the Cochran-Armitage test for trend were used. The ability to accurately predict survival was verified by cross-validation analysis.

Results: Kaplan-Meier curves for disease-free survival and overall survival showed mUICC to be superior to the 7th/8th AJCC. The homogeneity test indicated that mUICC was the best for both disease-free survival and overall survival. In the discriminatory ability test, the chi-square value of mUICC was the best for disease-free survival, while the 7th AJCC had the best value for overall survival. In the cross-validation analysis, all three staging systems had significant predictive power.

Conclusion: mUICC seemed to be superior to the 7th/8th AJCC after analyzing the data of our surgical patients, although the geographic heterogeneity of HCC might result in differences between the staging systems. We believe that, while the three staging systems allow for the clear stratification of patients into prognostic groups, mUICC may be more appropriate in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2019.60.2.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342718PMC
February 2019

Surgical Outcomes of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Korea-Japan Multicenter Study.

Ann Surg 2020 05;271(5):913-921

Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Objective: To identify optimal surgical methods and the risk factors for long-term survival in patients with hepatocellular carcinoma accompanied by macroscopic bile duct tumor thrombus (BDTT).

Summary Background Data: Prognoses of patients with hepatocellular carcinoma accompanied by BDTT have been known to be poor. There have been significant controversies regarding optimal surgical approaches and risk factors because of the low incidence and small number of cases in previous reports.

Methods: Records of 257 patients from 32 centers in Korea and Japan (1992-2014) were analyzed for overall survival and recurrence rate using the Cox proportional hazard model.

Results: Curative surgery was performed in 244 (94.9%) patients with an operative mortality of 5.1%. Overall survival and recurrence rate at 5 years was 43.6% and 74.2%, respectively. TNM Stage (P < 0.001) and the presence of fibrosis/cirrhosis (P = 0.002) were independent predictors of long-term survival in the Cox proportional hazards regression model. Both performing liver resection equal to or greater than hemihepatectomy and combined bile duct resection significantly increased overall survival [hazard ratio, HR = 0.61 (0.38-0.99); P = 0.044 and HR = 0.51 (0.31-0.84); P = 0.008, respectively] and decreased recurrence rate [HR = 0.59 (0.38-0.91); P = 0.018 and HR = 0.61 (0.42-0.89); P = 0.009, respectively].

Conclusions: Clinical outcomes were mostly influenced by tumor stage and underlying liver function, and the impact of BDTT to survival seemed less prominent than vascular invasion. Therefore, an aggressive surgical approach, including major liver resection combined with bile duct resection, to increase the chance of R0 resection is strongly recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003014DOI Listing
May 2020

A Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A-Related Acute Liver Failure.

Hepatology 2019 08 17;70(2):621-629. Epub 2019 Feb 17.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30262DOI Listing
August 2019

Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer.

Oncogene 2018 08 3;37(32):4443-4454. Epub 2018 May 3.

Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Gene mutations play critical roles during cancer development and progression, and therefore represent targets for precision medicine. Here we recapitulated the pharmacogenomic data to delineate novel candidates for actionable mutations and therapeutic target drugs. As a proof-of-concept, we demonstrated that the loss-of-function of SULF2 by mutation (N491K) or inhibition enhanced sorafenib sensitivity in liver cancer cells and in vivo mouse models. This effect was mediated by deregulation of EGFR signaling and downstream expression of LCN2. We also report that the liver cancer patients non-responding to sorafenib treatment exhibit higher expression of SULF2 and LCN2. In conclusion, we suggest that SULF2 plays a key role in sorafenib susceptibility and resistance in liver cancer via deregulation of LCN2. Diagnostic or therapeutic targeting of SULF2 (e.g., OKN-007) and/or LCN2 can be a novel precision strategy for sorafenib treatment in cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-018-0291-3DOI Listing
August 2018

Longterm Analysis of Biliary Complications After Duct-to-Duct Biliary Reconstruction in Living Donor Liver Transplantations.

Liver Transpl 2018 08;24(8):1050-1061

Department of Hepatobiliary Surgery and Liver Transplantation, Ajou University School of Medicine, Suwon, Korea.

Biliary complication (BC) is still regarded as the Achilles' heel of a living donor liver transplantation (LDLT). This study aims to evaluate the longterm outcomes of the duct-to-duct (DD) biliary reconstruction using 7-0 suture and to identify the risk factors of BCs after LDLTs. Data of 140 LDLTs between 2006 and 2015 were analyzed. All biliary reconstructions were performed as DD anastomoses using 7-0 suture: 102 for the right lobe, 20 for the left lobe, and 18 for right posterior sector grafts. BC was defined as a bile leakage (BL) or a biliary stricture (BS), and the median follow-up time after LDLT was 65 months. A total of 19 recipients (13.5%) developed BCs (8 BLs and 16 BSs) after LDLT. The survival rates between recipients with and without BCs were 83% and 86.7%, respectively (P = 0.88). In univariate analyses, the risk factors for BC were small diameter of the graft's bile duct, long warm ischemic time, small graft-to-recipient weight ratio, and no use of external biliary stent (EBS). The graft's bile duct diameter ≤ 3 mm and no use of EBS were determined as independent risk factors (hazard ratios of 9.74 and 7.68, respectively) in multivariate analyses. The 116 recipients with EBS had no BL, 11 had BSs (9%), while 24 without EBS had 8 BLs (33%) and 5 BSs (21%). After a propensity score match between the recipients with and without EBS, the EBS group (24) developed only 1 BS (4%). In conclusion, DD anastomosis using 7-0 suture combined with EBS could provide favorable longterm outcomes after LDLT, which should thus be considered the surgical technique of choice for LDLTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25074DOI Listing
August 2018

Highlights of the Third Expert Forum of Asia-Pacific Laparoscopic Hepatectomy; Endoscopic and Laparoscopic Surgeons of Asia (ELSA) Visionary Summit 2017.

Ann Hepatobiliary Pancreat Surg 2018 Feb 26;22(1):1-10. Epub 2018 Feb 26.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The application of laparoscopy for liver surgery is rapidly increasing and the past few years have demonstrated a shift in paradigm with a trend towards more extended and complex resections. The development of instruments and technical refinements with the effective use of magnified caudal laparoscopic views have contributed to the ability to overcome the limitation of laparoscopic liver resection. The Endoscopic and Laparoscopic Surgeons of Asia (ELSA) Visionary Summit 2017 and the 3 Expert Forum of Asia-Pacific Laparoscopic Hepatectomy organized hepatobiliary pancreatic sessions in order to exchange surgical tips and tricks and discuss the current status and future perspectives of laparoscopic hepatectomy. This report summarizes the oral presentations given at the 3 Expert Forum of Asia-Pacific Laparoscopic Hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14701/ahbps.2018.22.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845605PMC
February 2018

High spatial resolution navigated 3D T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA for evaluation of biliary anatomy in living liver donors.

Abdom Radiol (NY) 2018 07;43(7):1703-1712

Department of Radiology, Ajou University School of Medicine and Graduate School of Medicine, Ajou University Hospital, 164, World-cup Ro, Yeongtong-gu, Suwon, 16499, South Korea.

Purpose: To determine the feasibility of high-resolution navigated three-dimensional (3D) T1-weighted hepatobiliary MR cholangiography (Nav T1 MRC) using Gd-EOB-DTPA for biliary visualization in living liver donors and to assess added value of 3D T1-weighted hepatobiliary MRCs in improving the confidence and diagnostic accuracy of biliary anatomy in complementary to T2-weighted MRCs.

Methods: Twenty-nine right liver donors underwent 3D T2 MRC, 2D T2 MRC, breath-hold T1-weighted hepatobiliary MRC (BH T1 MRC), and Nav T1 MRC. Two readers independently reviewed and compared 3D/2D MRC set, added BH T1 MRC set, and added Nav T1 MRC set for biliary diagnostic accuracy and confidence. For each MRC, biliary segments visualization and image quality were scored.

Results: Both BH T1 MRC and Nav T1 MRC improved accuracy and specificity in biliary diagnosis when added to 3D/2D T2 MRC-alone set, though without statistical significance (R1, 82.8% to 93.1%; R2, 82.8% to 89.7%). The added Nav T1 MRC set showed the highest diagnostic confidence with both readers. Both readers scored Nav T1 MRC with the highest visualization scores for branching ducts and overall ducts.

Conclusion: Combining T1-weighted hepatobiliary MRCs to 3D/2D T2 MRC set improved accuracy for biliary anatomy diagnosis; time-efficient BH T1 MRC in axial and coronal planes should be considered as a key MRC sequence complementary to T2 MRCs. Given excellent biliary visualization and superior diagnostic confidence, Nav T1 MRC in selected subjects with breath-hold difficulties and inconclusive or complex biliary variations may assist in reaching a correct biliary diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-018-1474-7DOI Listing
July 2018

Prognostic Prediction Models for Resection of Large Hepatocellular Carcinoma: A Korean Multicenter Study.

World J Surg 2018 08;42(8):2579-2591

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

Background: We developed a prognostic prediction model (PPM) using 4 factors for hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication of α-fetoprotein (AFP), des-γ-carboxy prothrombin, and tumor volume (TV) (ADV score) is a surrogate marker for post-resection prognosis. This study intended to validate the predictive power of 4-factor PPM and to develop new ADV score-based PPM.

Methods: A total of 526 patients who underwent HR for solitary HCC ≥ 8 cm were selected from 9 Korean institutions between 2008 and 2014.

Results: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively. Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and 70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor recurrence and patient survival included AFP ≥ 100 ng/mL, hypermetabolic FDG-positron emission tomography (PET), microvascular invasion and satellite nodules, which comprised 4 factors of the PPM. Five subgroups based on the number of involved risk factors exhibited significant differences in tumor recurrence and patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster prognostic analysis. Patient grouping according to combination of ADV7log and FDG-PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence and patient survival, comparable to those of the 4-factor PPM.

Conclusions: Two PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of early HCC recurrence and long-term survival outcomes in patients who underwent HR for large HCC. We believe that these PPMs can guide surgical treatment for large HCCs from preoperative HR planning to post-resection follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-018-4468-2DOI Listing
August 2018

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma.

World J Surg Oncol 2017 Dec 19;15(1):225. Epub 2017 Dec 19.

Department of Surgery, School of Medicine, Ajou University, 164 World cup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Background: The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection.

Methods: A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI).

Results: The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival.

Conclusions: McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-017-1292-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738148PMC
December 2017

A Multicenter Phase III Study to Evaluate the Efficacy and Safety of Hepabulin, a New Hepatitis B Immunoglobulin, in Liver Transplantation Recipients with Hepatitis B.

Ann Transplant 2017 Dec 12;22:740-748. Epub 2017 Dec 12.

Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.

BACKGROUND This study was performed to evaluate the effects and stability of the new hepatitis B immunoglobulin (HBIG), Hepabulin, in patients undergoing liver transplantation for hepatitis B. MATERIAL AND METHODS A total of 87 patients undergoing liver transplantation for hepatitis B-related liver disease were enrolled in this multicenter, phase III, open-label, single-arm study. Seventy (80.5%) of the 87 enrolled patients completed the study during the 52-week study period. Hepabulin (10,000 units) was intravenously injected intraoperatively, daily for 1 week, weekly for 1 month, and then once per month. Hepabulin was used as monotherapy without antiviral agents. Hepatitis B recurrence was defined as conversion from negativity for surface antigen after HBIG administration to positivity. RESULTS There were no cases of hepatitis B recurrence during the 52-week observation period. A total of 876 adverse events (AEs) that occurred during the study period were observed in 83 (95.4%) of 87 patients, and serious AEs were seen in 119 cases in 44 (50.6%) of the 87 patients. None of the AEs showed a relationship with this drug. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) rapidly disappeared within 1 week after HBIG administration, but hepatitis B virus (HBV) DNA persisted for up to 8 weeks after surgery, which was related to HBV viral load. Hepatitis B surface antibody (HBsAb) was correlated with HBIG (Hepabulin) dose. CONCLUSIONS The new HBIG, Hepabulin, was shown to be safe and effective in preventing the recurrence of HBV after liver transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248297PMC
http://dx.doi.org/10.12659/aot.905898DOI Listing
December 2017

Comparison of anatomic and non-anatomic hepatic resection for hepatocellular carcinoma.

J Hepatobiliary Pancreat Sci 2017 Nov 19;24(11):616-626. Epub 2017 Oct 19.

Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan.

Background: The aim of the present study was to compare the prognostic impact of anatomic resection (AR) versus non-anatomic resection (NAR) on patient survival after resection of a single hepatocellular carcinoma (HCC).

Methods: To control for confounding variable distributions, a 1-to-1 propensity score match was applied to compare the outcomes of AR and NAR. Among 710 patients with a primary, solitary HCC of <5.0 cm in diameter that was resectable by either AR or NAR from 2003 to 2007 in Japan and Korea, 355 patients underwent NAR and 355 underwent AR of at least one section with complete removal of the portal territory containing the tumor.

Results: Overall survival (OS) was better in the AR than NAR group (hazard ratio 1.67, 95% confidence interval 1.28-2.19, P < 0.001) while disease-free survival showed no significant difference. Significantly fewer patients in the AR than NAR group developed intrahepatic HCC recurrence and multiple intrahepatic recurrences. Patients with poorly differentiated HCC who underwent AR had improved disease-free survival and OS.

Conclusions: Anatomic resection decreases the risk of tumor recurrence and improves OS in patients with a primary, solitary HCC of <5.0 cm in diameter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.502DOI Listing
November 2017

Conditional Survival Analysis Demonstrates that Recurrence Risk of Surgically Treated Hepatocellular Carcinoma Evolves with Time.

J Gastrointest Surg 2017 08 23;21(8):1237-1244. Epub 2017 May 23.

Department of Surgery, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon, 16499, South Korea.

Objective: The study aim was to investigate long-term change in tumor recurrence risk in patients with hepatocellular carcinoma (HCC) after hepatic resection. Recurrence probability over time was estimated by conditional survival (CS) analysis.

Patients And Methods: Early-stage HCC patients with hepatic resection were selected for inclusion from our surgery database. Variables predictive of tumor recurrence were identified by univariate and multivariate analyses. Five-year recurrence-free CS probability was calculated for all patients and for risk groups stratified by independent predictors.

Results: In this series of 436 patients, tumor size >5 cm, microvascular invasion, positive resection margin, liver cirrhosis, and a indocyanine green retention ratio at 15 min (ICG-R15) >20% were independently predictive of tumor recurrence. The estimated 5-year recurrence-free CS probability improved with each additional year of recurrence-free survival, and the improvement was significantly greater in the high-risk than in the low- or intermediate-risk groups.

Conclusion: CS provides added value during follow-up of early-stage HCC patients treated by surgical resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-017-3437-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517592PMC
August 2017

Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype.

Oncotarget 2017 Apr;8(14):22903-22916

Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells. Transcriptome analysis also revealed that the recurrent HCCs reprogram their transcriptomes to acquire aggressive phenotypes. Network analysis revealed CXCL8 (IL-8) and SOX4 as common downstream targets of the mutants. In conclusion, we suggest that the mutations of GOLGB1 and SF3B3 are potential key drivers for the acquisition of an aggressive phenotype in recurrent HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.14248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410272PMC
April 2017

Low levels of circulating microRNA-26a/29a as poor prognostic markers in patients with hepatocellular carcinoma who underwent curative treatment.

Clin Res Hepatol Gastroenterol 2017 Mar 7;41(2):181-189. Epub 2016 Nov 7.

Department of Gastroenterology, Ajou University School of Medicine, Worldcup-ro 164, Yeongtong-Gu, Suwon 16499, South Korea. Electronic address:

Background/aims: We evaluated the prognostic implication of circulating microRNA (miR)-21, miR-26a, and miR-29a in hepatocellular carcinoma (HCC) patients who underwent curative treatment.

Methods: The study included 120 hepatitis B virus-related HCC patients who underwent hepatic resection (n=63) or radiofrequency ablation (n=57). MiR-21, miR-26a, and miR-29a expression levels in pretreatment plasma and several clinical variables were analyzed to identify prognostic bio-markers.

Results: Old age, low albumin level, low platelet count, advanced tumor stage (modified Union for International Cancer Control stages III, IV), low miR-26a (hazard ratio [HR]=1.72; 95% confidence interval [CI]=1.04-2.83; P=0.035), and low miR-29a (HR=1.75; 95% CI=1.04-2.94; P=0.035) were identified as independent risk factors for predicting poor disease-free survival. Low miR-21, miR-26a, and miR-29a were associated with poor liver transplantation (LT)-free survival in the univariate analysis. Multivariate Cox regression analysis showed that low miR-26a (HR=3.41; 95% CI=1.32-8.82; P=0.011) and low miR-29a (HR=2.75; 95% CI=1.10-6.85; P=0.030), low platelet count, and advanced tumor stage were significantly associated with poor LT-free survival. Remarkable correlation was found between miR-26a and miR-29a (Spearman's rho=0.734, P<0.001).

Conclusion: Pretreatment levels of circulating miR-26a and miR-29a are independent prognostic markers for poor disease-free survival and LT-free survival in hepatitis B virus-related HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2016.09.011DOI Listing
March 2017
-->