• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.262-266
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• 1999

Obstruction of the extrahepatic bile ducts is the most common cause of conjugated hyperbilirubinemia in early infancy. More than 90% of such obstructive lesions are accounted for by extrahepatic biliary atresia. A rare lesion is obstruction of the common duct by impacted, thickened secretions and bile. Bile plug syndrome is defined as extrahepatic obstruction of the bile ducts by bile sludge in term infants without anatomic abnormalities, congenital chemical defects of bile, or hepatocellular lesions. Obstruction of extrahepatic ducts by plugs of biliary material apperas to be due to the inspissation and precipitation of bile and mucus within the lumen of the ducts. Cholestasis and precipitation of bile develop in association with abnormal composition of bile in cystic fibrosis, hepatocellular damage, prolonged erythroblastic jaundice, altered biliary dynamics with total parenteral nutrition, gut dysfunction, diuretic therapy, exchange transfusions and perinatal hemolysis. In those cases, the term inspissated bile syndrome is used. The clinical and laboratory findings in bile plug syndrome are identical to those observed in biliary atresia and choledochal cyst. The diagnosis can be suspected based on the findings of clinical and laboratory examinations together with hepatobiliary imaging, ultrasonography, radionuclide scan and liver biopsy. We experienced a case of spontaneous resolution of bile plug syndrome in a 4-year-old girl. We report this case with brief review related literatures.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• Journal of Korean Neurosurgical Society
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• v.65 no.1
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• pp.57-63
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• 2022

Objective : To study the factors relating to operative treatment for spinal metastasis in Thailand during 2005-2014 and to determine the hospital costs, mortality rate, and incidence of perioperative complication. Methods : Inpatient reimbursement data from 2005 to 2014 was reviewed from three national healthcare organizations, including the National Health Security Office, the Social Security Office, and the Comptroller General's Department. The search criteria were secondary malignant neoplasm of bone and bone marrow patients (International Classification of Diseases 10th revision, Thai modification codes [ICD 10-TM], C79.5 and C79.8) who underwent spinal surgical treatment (ICD 9th revision, clinical modification procedure with extension codes [ICD 9-CM], 03.0, 03.4, 03.09, and 81.0) during 2005-2014. Epidemiology, comorbidity, and perioperative complication were analyzed. Results : During the study period, the number of spinal metastasis patients who underwent operative treatment was significantly increased from 0.30 to 0.59 per 100000 (p<0.001). More males (56.14%) underwent surgical treatment for spinal metastasis than females. The most common age group was 45-64 (55.1%). The most common primary tumor sites were the unknown origin, lung, breast, prostate, and hepatocellular/bile duct. Interestingly, the proportion of hepatocellular/bile duct, breast, and lung cancer was significantly increased (p<0.001). The number of patients who had comorbidity or in-hospital complication significantly increased over time (p<0.01); however, the in-hospital mortality rate decreased. Conclusion : During the last decade, operative treatment for spinal metastasis increased in Thailand. The overall in-hospital complication rate increased; however, the in-hospital mortality rate decreased.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.91-95
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• 2014

Objectives : This study was carried out to evaluate whether the water extract from cause the cellular damage in HepG2 cell line. It was reported that Dictamnus dasycarpus Turcz(DDT) intake induce poisoning symptoms in human population. These symptoms was closely related to liver toxicity, however, mechanisms for liver toxicity caused by DDT have not been elucidated exactly. Here, hepatotoxicity caused by DDT was evaluated using HepG2 cell line. Methods : Water extract of DDT was treated into HepG2 cell with various doses such as 0, 0.1, 0.5, 1.0 and $5.0mg/m{\ell}$. In order to cell viability, both MTT and LDH assay were carried out. Also, apoptosis array kit was used to identify whether cell death caused by DDT is due to apoptosis or not. In addition, reactive oxygen species (ROS) was measured after treatment of water extract. Results : We found out significant changes in the apoptosis related factors of hepatocyte. The cell viability of HepG2 treated with DDT water extract was decreased in dose-dependent. Also most of the apoptosis related factors were significantly increased. We found out that Caspase 3, Cytochrome C and ROS had increased in dose-dependent. In addition, other apoptosis related factors Bcl 2 and Bax, which were also constant changes. However, there was no significance. Conclusions : These results suggest that water soluble extract of DDT is expected to have oral toxicity, including hepatocellular damage Therefore, it is suggested that DDT could cause various side effects and toxicity of clinical conditions.

• BMB Reports
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• v.55 no.6
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• pp.281-286
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• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Molecules and Cells
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• v.45 no.12
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• pp.935-949
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• 2022

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

• Korean Journal of Radiology
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• v.22 no.8
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• pp.1279-1288
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• 2021

Objective: To assess the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 treatment response algorithm (TRA) for the evaluation of hepatocellular carcinoma (HCC) treated with transarterial radioembolization. Materials and Methods: This retrospective study included patients who underwent transarterial radioembolization for HCC followed by hepatic surgery between January 2011 and December 2019. The resected lesions were determined to have either complete (100%) or incomplete (< 100%) necrosis based on histopathology. Three radiologists independently reviewed the CT or MR images of pre- and post-treatment lesions and assigned categories based on the LI-RADS version 2018 and the TRA, respectively. Diagnostic performances of LI-RADS treatment response (LR-TR) viable and nonviable categories were assessed for each reader, using histopathology from hepatic surgeries as a reference standard. Inter-reader agreements were evaluated using Fleiss κ. Results: A total of 27 patients (mean age ± standard deviation, 55.9 ± 9.1 years; 24 male) with 34 lesions (15 with complete necrosis and 19 with incomplete necrosis on histopathology) were included. To predict complete necrosis, the LR-TR nonviable category had a sensitivity of 73.3-80.0% and a specificity of 78.9-89.5%. For predicting incomplete necrosis, the LR-TR viable category had a sensitivity of 73.7-79.0% and a specificity of 93.3-100%. Five (14.7%) of 34 treated lesions were categorized as LR-TR equivocal by consensus, with two of the five lesions demonstrating incomplete necrosis. Interreader agreement for the LR-TR category was 0.81 (95% confidence interval: 0.66-0.96). Conclusion: The LI-RADS version 2018 TRA can be used to predict the histopathologic viability of HCCs treated with transarterial radioembolization.

• Journal of the Korean Society of Radiology
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• v.85 no.2
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• pp.409-414
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• 2024

Hepatoid adenocarcinoma (HAC) is a rare form of adenocarcinoma that is diagnosed based on immuno-histochemical findings reminiscent of hepatocellular carcinoma (HCC). The clinical characteristics of HAC include increased levels of serum alpha-fetoprotein and a poor prognosis due to early liver metastasis. In particular, diagnosing liver metastasis of HAC can be challenging owing to radiological findings similar to those of HCC. Although HAC can occur in various organs, the stomach is the most common site. We present the case of a 64-year-old femalewho presented with multiple tumors in the liver. During subsequent examination, rectal cancer was identified and diagnosed as HAC through a biopsy. Herein, we report this case along with a literature review.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.3
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• pp.211-219
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• 2022

Backgrounds/Aims: Historically, incidence and survival analysis and annual traits for primary liver cancer (LC) has not been investigated in a population-based study in Korea. The purpose of the current study is to determine incidence, survival rate of patients with primary LC in Korea. Methods: We conducted a retrospective cohort study using Korea Central Cancer Registry based on the Korea National Cancer Incidence Database. Statistical analysis including crude rate and age-standadized rate (ASR) of incidence and mortality was performed for LC patients registered with C22 code in International Classification of Diseases, tenth revision from 1999 to 2019. Subgroup analysis was performed for hepatocellular carcinoma (HCC, C22.0) and intrahepatic cholangiocarcinoma (IHCC, C22.1). Results: The crude incidence rate of HCC (21.0 to 22.8 per 100,000) and IHCC (2.3 to 5.6 per 100,000) increased in the observed period from 1999 to 2019. The ASR decreased in HCC (20.7 to 11.9 per 100,000) but remained unchanged in IHCC (2.4 to 2.7 per 100,000). The proportion of HCC patients diagnosed in early stages (localized or regional Surveillance, Epidemiology, and End Results or SEER stage) increased significantly over time. As expected, 5-yeat survival rate of HCC was greatly improved, reaching 42.4% in the period between 2013 and 2019. This trait was more prominent in localized SEER stage. On the other hand, the proportion of IHCC patients diagnosed in localized stage remained unchanged (22.9% between 2013 and 2019), although ASR and 5-year survival rate showed minor improvements. Conclusions: A great improvement in survival rate was observed in patients with newly diagnosed HCCs. It was estimated to be due to an increase in early detection rate. On the contrary, detection rate of an early IHCC was stagnant with a minor improvement in prognosis.