• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.51-61
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• 2002

Purpose: The most common causes of neonatal cholestasis are neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA). Since neonatal cholestasis presents with variable expression of same pathologic process and has similar clinical, biochemical, and histologic features between EHBA and idiopathic neonatal hepatitis (NH), differential diagnosis is often difficult. We reviewed the differences of clinical characteristics and laboratory data to find out any correlation between the results of $Tc^{99m}$ DISIDA scan and presence of acholic stool. Methods: Between June 1993 and January 2001, total 29 infants younger than 4 month-old underwent $Tc^{99m}$ DISIDA scan. Their biochemical tests and clinical course were reviewed retrospectively. Results: Patients who had negative intestinal activity on $Tc^{99m}$ DISIDA scan showed acholic stool and revealed higher serum direct bilirubin and urine bilirubin level. 18.2% of patients with acholic stool showed intestinal activity on $Tc^{99m}$ DISIDA scan and 81.8% of them did not. All the patients without acholic stool showed positive intestinal activity on $Tc^{99m}$ DISIDA scan. The result of $Tc^{99m}$ DISIDA scan and the presence of acholic stool showed high negative correlation (r :-0.858). Patients with acholic stool and negative intestinal activity on $Tc^{99m}$ DISIDA scan showed higher serum total bilirubin level. Patients without acholic stool and positive intestinal activity on $Tc^{99m}$ DISIDA scan showed higher serum level of ALT. Conclusion: Patients with acholic stool and negative intestinal activity showed high correlation, but 18.2% of patients with acholic stool showed positive intestinal activity. So operative cholangiogram or transcutaneous liver biopsy should be performed for confirmation.

• Journal of Life Science
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• v.23 no.9
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• pp.1126-1132
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• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.4
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• pp.590-595
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• 2008

The aim of our study was to research the effect of overfeeding on plasma parameters and mRNA expression of genes associated with hepatic lipogenesis in the Sichuan white goose and Landes goose. Fifty-four male Landes geese and 57 male Sichuan white geese were hatched on the same day under the same feeding conditions. After overfeeding for 14 days, (1) extrahepatic adipose tissues grew greatly in the Sichuan white geese, while more lipid accumulated in liver tissue in the Landes geese. (2) Sichuan white geese had a higher plasma concentration of triacylglycerols (TG), lipoproteins and insulin than the Landes geese. However, the Landes geese exhibited higher increase of plasma concentrations of TG, lipoproteins and insulin, with greater decrease of the diacylglycerol acyltransferase 2 (DGAT2) activity and DGAT2 mRNA level and a smller decrease of plasma glucose concentration. In addition, the mRNA level of MTP and LPL in liver was down- and up- regulated by overfeeding, respectively. (3) The correlations between the activity of LPL and the proportions of subcutaneous adipose tissue, abdominal adipose tissue, and liver weight, and the plasma concentration of VLDL were different in the two breeds. (4) The proportion of fatty liver weight was positively correlated to plasma concentrations of VLDL and TG in the overfed Sichuan white geese. Such a relationship did not exist in the Landes geese. (5) The activity of DGAT2 and its mRNA abundance in liver had significant negative correlations with the TG content in liver lipid and plasma insulin level in the Landes geese, while in the Sichuan white geese they had negative correlation (p>0.05) with TG concentration in liver lipid and had significant positive correlation with VLDL and TG concentrations in plasma.

• The Korean Journal of Nuclear Medicine
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• v.16 no.2
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• pp.71-80
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• 1982

In the present communication, the results will be reported on a clinical study of how well scintigraphic visualization of the hepatobiliary elements and several commonly used clinical liver function tests correlate each other in various diseases oft hepatobiliary system. The demonstrability of the biliary tract, gallbladder (GB) and duodenum was rather closely paralleled to serum bilirubin level and less closely to alkaline phosphatase and rather poorly to SGOT and SGPT. The biliary tree could not be visualized scintigraphically when bilirubin exceeded 10.5mg/dl. The usefulness of Tc-99m EHIDA [N-(2,6-diethylacetanilido) iminodiacetic acid, made by Amersham, England] hepatobiliary scintigraphy (Tc EHIDA HBS) in settling diagnostic controversy and ambiguity raised by oral cholecystography, intravenous cholangiography and ultrasonography in many hepatobiliary diseases is well known. The purpose of this investigation was to semiquantitatively evaluate the scintigraphic demonstrability of the hepatobiliary tract, GB and duodenum following intravenous injection of Tc-99m EHIDA in normal subjects and in patients with a disturbed liver function from various hepatobiliary diseases. The hepatobiliary scintigraphy was performed in 10 normal subjects and 39 patients with various hepatobiliary diseases (Table 1) at the Dept. of Radiology, St. Mary's Hospital Catholic Medical College, Seoul, Korea during 2 years period from September 1979. Scintigraphic examination was started at end of 3 minutes after intravenous injection of Tc-99m EHIDA in the amount of $50{\mu}Ci/kg$ and was continued until after 30 minutes at 5 minutes interval. The imaging was usually terminated when the tracer could be seen in the duodenum. Late scintigrams were obatained at 1 1/2, 3, 4 and 6 hours when reeded. Scintigrams were analyzed in terms of promptness and clarity of visualization of the biliary tree, GB and duodenum and demonstrability of these anatomical landmarks was correlated with the values of liver function tests. The demonstrability of the common hepatic duct, common bile duct, GB and duodenum was closely paralleled to the level of serum bilirubin when it is less than 10.5 mg/dl as shown in figure 1. However when the bilirubin exceeded 10.5 mg/dl the time of visualization between protracted reaching a flat curve or plateau around 10.5 mg/dl. The biliary tract could not be visualized when the bilirubin was higher than 10.5 mg/dl. The correlability between scintigraphic demonstration and serum alkaline phosphatase was less strong and between scintigraphic demonstration and SGOT and SGPT was rather poor. The present clinical study confirmed the usefulness and limitation of Tc-99m EHIDA hepatobiliary scintigraphy in visulizing and diagnosing the biliary system and duodenum when radiogrpahy and ultrasonography failed to provide useful informations. Scintigraphy was very helpful in the diagnosis of neonatal hepatitis, biliary atresia, cholecystitis and extrahepatic biliary obstruction. The hepatobiliary system and duodenum were visualized when serum bilirubin level was less than 10.5 mg/dl, SGOT 135 units, SGPT 114 units and alkaline phosphatase 52.2 KAU.

• The Korean Journal of Nuclear Medicine
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• v.20 no.2
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• pp.19-38
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• 1986

54 patients who had symptoms after biliary operation were studied by $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy for evaluation of clinical utility, with regional emphasis of recurrent pyogenic cholangitis (RPC) and intrahepatic stones. As expected, the most common disease was recurrent pyogenic cholangitis regardless of surgical anastomosis, 58% and next frequent disease was clonorhis sinensis infestation, 26%, stenosis of ampula vater 8%, and chronic hepatitis 4% (20% of patients had hepatitis but they showed clinically and scintigraphically dominallt combined disease feature). 87% of recurrent pyogenic cholangitis was associated with stones in intra or/and extrahepatic ducts and only 11.4% of RPC was found to be associated with Cs-infestation. The scintigraphic diagnosis of RPC was 81.6% and 78.6% of stones was detected by indirect visualization of scintigraphy findings and 71.7% of Cs-infestation was detected by scintigraphy. The characteristic bile flow pattern were described.

• Radiation Oncology Journal
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• v.32 no.1
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• pp.14-22
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• 2014

Purpose: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-na$\ddot{i}$ve patients with locally advanced hepatocellular carcinoma (HCC). Materials and Methods: Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 $Gy_{10}$ as the biologically effective dose using the ${\alpha}/{\beta}$ = 10 (range, 39 to 65.25 $Gy_{10}$). Results: At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). Conclusion: The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-na$\ddot{i}$ve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.37-44
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• 2016

Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.32-33
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• 2006

There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

• Applied Microscopy
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• v.22 no.2
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• pp.15-29
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• 1992

The gallbladder is known to have the function of the storage and the concentration of the bile produced by the liver. This function is carried out by the removal of water and inorganic electrolytes. Extrahepatic cholestasis or the impairment of excretion of the bile leads to the distension and loss of the function of the gallbladder. The purpose of this study was to examine the ultrastructural characteristics of the normal gallbladder epithelial cells, and their structural changes induced by the ligation of common bile duct of the rabbit. Common bile duct ligation was performed under ether anesthesia. The rabbits were sacrificed on the 1st, 3rd, 5th, 7th and 14th day, respectively after operations. The tissue blocks of the gallbladder were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde prior to fixation in 1% osmium tetroxide, and embedded in the araldite mixture, and observed with JEM 100 CX-II electron microscope. The results were as follows: 1. The normal gallbladder epithelium of adult rabbit demonstrated two cell types, the ordinary epthelial cell and the dark cell. The dark cells have electron dense cytoplasm, and were found much infrequently, whereas ordinary epthelial cells were found quite numerous. 2. The ordinary epthelial cells of normal gallbladder were provided with the regular microvilli at the free surface and the images of pinocytotic activities in the apical cytoplasm, and exhibit highly convoluted lateral surfaces with elaborated microfolds. These figures of the cells suggest that they are resorptive in functional activity. 3. In the early stages (1st, 3rd, 5th day groups) following the ligation, the apical cytoplasm of some cells is protruding from the free surface and lost their microvilli. Numerous mucous granules filled in the apical and supranuclear cytoplasm compactly. 4. In the late stages (7th, 14th day groups) following the ligation, many light cells containing mumerous mucous granules are seen, between the ordinary epthelial cells. Mucous granules are fused each other, and are discharged into the lumen from the apical cytoplasm. The lateral membranes are straight or undulating without any interdigitations. From the above results, it was concluded that in the cholestasis induced by the common bile duct ligation, there is a tendency for the mucosal epithelium of the rabbit gallbladder to have secretory rather than an absorptive function.

• Journal of Yeungnam Medical Science
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• v.7 no.2
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• pp.197-202
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• 1990

Mechanical obstruction of the common hepatic duct includes the following causes ; choledocholithiasis, sclerosis, cholangitis, pancreatic carcinoma, cholangiocarcinoma, postoperative stricture, primary hepatic duct carcinoma, enlarged cystic duct lymph nodes, and metastatic nodal involvement of the porta hepatis. Partial mechanical obstruction of the common hepatic duct caused by impaction of stones and inflammation surrounding the vicinity of the neck of the gallbladder had been reported on the "syndrome del conducto hepatico" in 1948 by Mirizzi. Nowadays, this disease was named by Mirizzi syndrome. Mirizzi syndrome is a rare entity of common hepatic duct obstruction that results from an inflammatory response secondary to a gallstone impacted in the cystic duct or neck of the gallbladder. It results from an almost parallel course and low insertion of the cystic duct into the common hepatic duct. In a varient of Mirizzi's syndrome, the cause of the common hepatic duct obstruction was a primary cystic duct carcinoma rather than gallstone disease. A 71-year-old man was admitted with a four-day history of right upper quadrant abdominal pain. Past medical history was unremarkable. On physical examination, the patient had a temperature of $38^{\circ}C$, icteric sclera and right upper quadrant tenderness. Pertinent laboratory findings included WBC 18,000/$cm^2$;albumin 2.6g/dl(normal 3.9-5.1) ; SGOT 183u/L(normal 0-50) ; SGPT167u/L(normal 0-65) ; bilirubin, 8.2mg/dl(normal 0-1) with the direct bilirubin, 4.4mg/dl(normal 0-0.4). Ultrasonography revealed a dilated extrahepatic biliary tree. ERCP showed that the superior margin was angular and more consistent with a calculus causing partial CHD obstruction(Mirizzi syndrome). At surgery a diseased gallbladder containing calculi was found. In addition, there was two calculi partially eroding through the proximal portion of the cystic duct and compressing the common hepatic duct. A cholecystectomy and excision of common bile duct was performed, with Roux-en-Y hepaticojejunostomy. The postoperative course was uneventful.