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1.  Balanced approach can help initial outcomes: analysis of initial 50 cases of a new liver transplantation program in East Asia 
To evaluate patient triage pattern and outcomes according to types of liver transplantation as part of a new liver transplant program developed in an East Asian country with a limited number of deceased donors.
Medical records of initial 50 liver transplantations were reviewed retrospectively.
Twenty-nine patients underwent deceased donor liver transplantation (DDLT) and 21 patients underwent living donor liver transplantation (LDLT). Mean model for end-stage liver disease scores of recipients of DDLT and LDLT were 24.9 ± 11.6 and 13.1 ± 5.4, respectively (P < 0.0001). Twenty-eight patients had HCCs and 17 of them (60.7%) underwent LDLT, which was 80.9% of LDLTs. There were 2 cases of perioperative mortality; each was from DDLT and LDLT, respectively. Median follow-up was 18 months. Overall patient and graft survival rates at 6 months, 1 and 2 years were 95.7%, 93.4%, and 89.8%, respectively. There was no significant difference in survival between DDLT and LDLT. Overall recurrence-free survival rates of hepatocellular carcinoma (HCC) patients at 6 month, 1, and 2 years were 96.3%, 96.3%, and 90.3%, respectively. There was no significant difference in recurrence-free survival between DDLT and LDLT.
As a new liver transplant program with limited resource and waiting list, patients with critical condition could undergo DDLT whereas relatively stable patients with HCCs were mostly directed to LDLT. We recommend a balanced approach between DDLT and LDLT for initiating liver transplant programs.
PMCID: PMC4091440  PMID: 25025023
Liver transplantation; Donor selection; Liver transplantation program; Outcome; Survival
2.  Use of right lobe graft with type IV portal vein accompanied by type IV biliary tree in living donor liver transplantation: report of a case 
Anatomic variations of the portal vein (PV) and bile duct (BD) are more common on the right lobe as compared with left lobe grafts in living donor liver transplantation (LDLT). We recently experienced a case of LDLT for hepatocellular carcinoma combined with liver cirrhosis secondary to hepatitis B virus and hepatitis C virus infection. The only available donor had right lobe graft with type IV PV associated with type IV BD. The patient underwent relaparotomy for PV stenting due to PV stenosis. Percutaneous transhepatic biliary drainage was done for a stricture at the site of biliary reconstruction. Thereafter, the patient was discharged in good health. Our experience suggests that, the use of right lobe graft with type IV PV accompanied by type IV BD should be the last choice for LDLT, because of its technical difficulty and risks of associated complications.
PMCID: PMC4062452  PMID: 24949326
Vascular complication; Postoperative complications; Anastomosis; Roux-en-Y
3.  Actionable Gene Expression-Based Patient Stratification for Molecular Targeted Therapy in Hepatocellular Carcinoma 
PLoS ONE  2013;8(6):e64260.
The effectiveness of molecular targeted agents is modest in hepatocellular carcinoma (HCC). Efficacy of molecular targeted therapies has been better in cancer patients with high expression of actionable molecules defined as cognate target molecules. However, patient stratification based on the actionable molecules dictating the effectiveness of targeted drugs has remained understudied in HCC.
Experimental Design & Results
Paired tumor and non-tumoral tissues derived from a total of 130 HCC patients were studied. Real-time RT-PCR was used to analyze the mRNA expression of actionable molecules in the tissues. mRNA levels of EGFR, VEGFR2, PDGFRβ, FGFR1, and mTOR were up-regulated in tumors compared to non-tumors in 35.4, 42.3, 61.5, 24.6, and 50.0% of patients, respectively. Up-regulation of EGFR was observed at early stage and tended to gradually decrease toward late stages (BCLC stage A: 41.9%; B: 30.8%; C: 17.6%). Frequency of VEGFR2 expression in tumors at stage C was lower than that in the other stages (BCLC stage A: 45.9%; B: 41.0%; C: 29.4%). PDGFRβ and mTOR were observed to be up-regulated in more than 50% of tumors in all the stages whereas FGFR1 was up-regulated in only about 20% of HCC irrespective of stages. A cluster analysis of actionable gene expression revealed that HCC can be categorized into different subtypes that predict the effectiveness of molecular targeted agents and combination therapies in clinical trials. Analysis of in vitro sensitivity to sorafenib demonstrated that HCC cells with up-regulation of PDGFRβ and c-Raf mRNA are more susceptible to sorafenib treatment in a dose and time-dependent manner than cells with low expression of the genes.
mRNA expression analysis of actionable molecules could provide the rationale for new companion diagnostics-based therapeutic strategies in the treatment of HCC.
PMCID: PMC3681850  PMID: 23785399
4.  Biliary phytobezoar resulting in intestinal obstruction 
Phytobezoar is the most common type of bezoar. It is composed of indigestible vegetable matter and is usually found in the stomach. Biliary phytobezoar is extremely rare and difficult to diagnose preoperatively. The pathogenesis is not clear, and there have been only a few reports of biliary bezoars associated with sphincteric impairmentat the ampulla of Vater. Here, we present a report of biliary bezoar that resulted in jejunal obstruction. We were unable to identifythe bezoar in the extrahepatic bile duct until it obstructed the small bowel lumen. To our knowledge, this is the first report of small bowel obstruction resulting frommigration of a biliary bezoar.
PMCID: PMC3542761  PMID: 23326176
Phytobezoar; Biliary; Intestinal obstruction; Choledochoduodenal; Fistula; Multidetector-row computed tomography
5.  Liver abscess developed after cadaveric liver transplantation due to ligation of an accessory right hepatic artery of the donor graft 
It is important that extrahepatic arteries are identified precisely at the time of graft procurement. We present a case where the accessory right hepatic artery of the liver was ligated leading to postoperative liver abscess formation in the liver graft. A forty-seven-year-old female patient diagnosed with liver cirrhosis underwent orthotopic cadaveric liver transplantation due to altered mentality. The donor graft showed a variant of the hepatic artery anatomy where an accessory right hepatic artery arose from the superior mesenteric artery. This artery was accidentally transected during procurement. Since the back bleeding test using perfusion fluid was good, the artery was ligated. Postoperative abdominal computed tomography scan revealed a 6 cm low attenuating lesion in the liver. The patient underwent conservative treatment. We believe that even small accessory arteries (1 to 2 mm) should be reconstructed whenever possible to avoid postoperative complications such as liver abscess.
PMCID: PMC3467392  PMID: 23091798
Liver abscess; Liver transplantation; Postoperative complications; Hepatic artery
6.  Increasing effect of body weight perception on suicidal ideation among young Korean women: Findings from the Korea National Health and Nutrition Examination Survey 2001 and 2005 
To examine the prevalence of actual and perceived overweight and to compare the mediating effect of perceived overweight on the relationship between actual overweight and suicidal ideation among young Korean women between 2001 and 2005.
Data were gathered from the 2001 and 2005 Korean National Health and Nutrition Examination Surveys involving a nationally representative sample of young women (568 in 2001 and 385 in 2005) aged 20–29 years.
Over the 5-year period, the prevalence of actual overweight (body mass index ≥23 kg/m2) and perceived overweight increased by 10.5% and 22.8%, respectively. The discrepancy between actual and perceived body weights was much wider in 2005 than in 2001. After controlling for covariates (age, marital status, educational attainment, employment status, smoking status, alcohol consumption, and regular exercise), overweight women were more likely to think about suicide than their normal-weight counterparts in both periods. However, in both periods, the association between overweight and suicidal ideation became nonsignificant when perceived weight was considered. In both periods, a self-perception of overweight was associated with an increased risk of suicidal ideation, but the association was much stronger in 2005 than in 2001.
This study suggests a need for educational programs or effective treatments to help young women who perceive themselves as overweight to reduce the potential risk of suicidal ideation in later life.
PMCID: PMC3064415  PMID: 21448318
body mass index; perceived body weight; body weight; body image; suicidal ideation
7.  Early Initiation of Alcohol Drinking, Cigarette Smoking, and Sexual Intercourse Linked to Suicidal Ideation and Attempts: Findings from the 2006 Korean Youth Risk Behavior Survey 
Yonsei Medical Journal  2009;51(1):18-26.
This study examined the association between early initiation of problem behaviors (alcohol drinking, cigarette smoking, and sexual intercourse) and suicidal behaviors (suicidal ideation and suicide attempts), and explored the effect of concurrent participation in these problem behaviors on suicidal behaviors among Korean adolescent males and females.
Materials and Methods
Data were obtained from the 2006 Korean Youth Risk Behavior Survey, a nationally representative sample of middle and high school students (32,417 males and 31,467 females) in grades seven through twelve. Bivariate and multivariate logistic analyses were conducted. Several important covariates, such as age, family living structure, household economic status, academic performance, current alcohol drinking, current cigarette smoking, current butane gas or glue sniffing, perceived body weight, unhealthy weight control behaviors, subjective sleep evaluation, and depressed mood were included in the analyses.
Both male and female preteen initiators of each problem behavior were at greater risk for suicidal behaviors than non-initiators, even after controlling for covariates. More numerous concurrent problematic behaviors were correlated with greater likelihood of seriously considering or attempting suicide among both males and females. This pattern was more clearly observed in preteen than in teen initiators although the former and latter were engaged in the same frequency of problem behavior.
Early initiation of alcohol drinking, cigarette smoking, and sexual intercourse, particularly among preteens, represented an important predictor of later suicidal ideation and suicide attempts in both genders. Thus, early preventive intervention programs should be developed and may reduce the potential risks for subsequent suicidal behaviors.
PMCID: PMC2799971  PMID: 20046509
Alcohol drinking; cigarette smoking; sexual intercourse; suicidal ideation; attempted suicide; life experience
8.  Effectiveness of Sodium Picosulfate/Magnesium Citrate (PICO) for Colonoscopy Preparation 
Annals of Coloproctology  2014;30(5):222-227.
Bowel preparation with sodium phosphate was recently prohibited by the U.S. Food and Drug Administration. Polyethylene glycol (PEG) is safe and effective; however, it is difficult to drink. To identify an easy bowel preparation method for colonoscopy, we evaluated three different bowel preparation regimens regarding their efficacy and patient satisfaction.
In this randomized, comparative study, 892 patients who visited a secondary referral hospital for a colonoscopy between November 2012 and February 2013 were enrolled. Three regimens were evaluated: three packets of sodium picosulfate/magnesium citrate (PICO, group A), two packets of PICO with 1 L of PEG (PICO + PEG 1 L, group B), and two packets of PICO with 2 L of PEG (PICO + PEG 2 L, group C). A questionnaire survey regarding the patients' preference for the bowel preparation regimen and satisfaction was conducted before the colonoscopies. The quality of bowel cleansing was scored by the colonoscopists who used the Aronchick scoring scale and the Ottawa scale.
The patients' satisfaction rate regarding the regimens were 72% in group A, 64% in group B, and 45.9% in group C. Nausea and abdominal bloating caused by the regimens were more frequent in group C than in group A or group B (P < 0.01). Group C showed the lowest preference rate compared to the other groups (P < 0.01). Group C showed better right colon cleansing efficacy than group A or group B.
Group A exhibited a better result than group B or group C in patient satisfaction and preference. In the cleansing quality, no difference was noted between groups A and C.
PMCID: PMC4213938  PMID: 25360429
Sodium picosulfate magnesium citrate; Satisfaction; Bowel preparation; Polyethylene glycols; Colonoscopy
9.  Directed Evolution of Human Heavy Chain Variable Domain (VH) Using In Vivo Protein Fitness Filter 
PLoS ONE  2014;9(6):e98178.
Human immunoglobulin heavy chain variable domains (VH) are promising scaffolds for antigen binding. However, VH is an unstable and aggregation-prone protein, hindering its use for therapeutic purposes. To evolve the VH domain, we performed in vivo protein solubility selection that linked antibiotic resistance to the protein folding quality control mechanism of the twin-arginine translocation pathway of E. coli. After screening a human germ-line VH library, 95% of the VH proteins obtained were identified as VH3 family members; one VH protein, MG2x1, stood out among separate clones expressing individual VH variants. With further screening of combinatorial framework mutation library of MG2x1, we found a consistent bias toward substitution with tryptophan at the position of 50 and 58 in VH. Comparison of the crystal structures of the VH variants revealed that those substitutions with bulky side chain amino acids filled the cavity in the VH interface between heavy and light chains of the Fab arrangement along with the increased number of hydrogen bonds, decreased solvation energy, and increased negative charge. Accordingly, the engineered VH acquires an increased level of thermodynamic stability, reversible folding, and soluble expression. The library built with the VH variant as a scaffold was qualified as most of VH clones selected randomly were expressed as soluble form in E. coli regardless length of the combinatorial CDR. Furthermore, a non-aggregation feature of the selected VH conferred a free of humoral response in mice, even when administered together with adjuvant. As a result, this selection provides an alternative directed evolution pathway for unstable proteins, which are distinct from conventional methods based on the phage display.
PMCID: PMC4043505  PMID: 24892548
10.  Primary Hepatic Marginal Zone B Cell Lymphoma : A Case Report and Review of the Literature 
The Indian Journal of Surgery  2012;75(Suppl 1):331-336.
Primary hepatic lymphoma (PHL) is a very rare malignancy, and constitutes about 0.016 % of all cases of non-Hodgkin’s lymphoma and is often misdiagnosed. The optimal therapy is still unclear and the outcomes are uncertain. Among PHLs, a primary hepatic low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is extremely rare.
We present a case of primary hepatic lymphoma (MALT lymphoma) treated with surgical resection and adjuvant chemotherapy. A 38-year-old Korean man, who was diagnosed with chronic hepatitis B 20 years ago, was admitted for liver biopsy after liver lesions were detected on follow-up computed tomography scan (CT). Liver biopsy revealed the diagnosis of marginal zone B-cell malignant lymphoma (MALT lymphoma). The preoperative clinical staging was IE, given that no additional foci of lymphoma were found anywhere else in the body. The patient underwent left hemihepatectomy. Subsequently, the patient received two cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) regimen.
After 15 months of follow-up, the patient is alive and well without any evidence of disease recurrence.
Although the prognosis is variable, good response to early surgery combined with postoperative chemotherapy can be achieved in strictly selected patients.
PMCID: PMC3693344  PMID: 24426608
Primary hepatic lymphoma; MALT lymphoma; Chronic hepatitis B; Surgery; Adjuvant chemotherapy
11.  Clinicopathological Analysis of Hepatocellular Adenoma According to New Bordeaux Classification: Report of Eight Korean Cases 
Korean Journal of Pathology  2013;47(5):411-417.
Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. A subtype classification of HCA (hepatocyte nuclear factor 1α [HNF1α]-mutated, β-catenin-mutated HCA, inflammatory HCA, and unclassified HCA) has recently been established based on a single institutional review of a HCA series by the Bordeaux group.
We used histologic and immunohistochemical parameters to classify and evaluate eight cases from our institution. We evaluated the new classification method and analyzed correlations between our results and those of other reports.
Seven of our eight cases showed histologic and immunohistochemical results consistent with previous reports. However, one case showed overlapping histologic features, as previously described by the Bordeaux group. Four cases showed glutamine synthetase immunohistochemical staining inconsistent with their classification, indicating that glutamine synthetase staining may not be diagnostic for β-catenin-mutated HCA. HNF1α-mutated HCA may be indicated by the absence of liver fatty acid binding protein expression. Detection of amyloid A may indicate inflammatory HCA. HCA with no mutation in the HNF1α or β-catenin genes and no inflammatory protein expression is categorized as unclassified HCA.
Although the new classification is now generally accepted, validation through follow-up studies is necessary.
PMCID: PMC3830987  PMID: 24255628
Adenoma, liver cell; Subtype; Hepatocyte nuclear factor 1-alpha; Beta catenin; Serum amyloid A protein
12.  Colloid Carcinoma of the Extrahepatic Biliary Tract with Metastatic Lymphadenopathy Mimicking Cystic Neoplasm: A Case Report 
Iranian Journal of Radiology  2013;10(2):90-93.
The patient is a previously healthy 52-year-old woman who presented with dyspepsia for two months. Multiple imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed diffuse bile duct dilatation with an obstructive lesion of the distal extrahepatic biliary duct (EHD) as well as two masses in the peripancreatic area. The peripancreatic masses appeared cystic with posterior acoustic enhancement on ultrasound, low density on CT imaging, and high signal intensity on T2-weighted MRI. The lesion in the distal EHD exhibited similar characteristics on CT and MRI. A Whipple procedure was performed and histological specimens showed malignant cells with large mucin pools that was consistent with a diagnosis of colloid carcinoma of the EHD with metastatic lymphadenopathies.
Colloid carcinoma, also called mucinous carcinoma, is classified as a histologic variant of adenocarcinoma. Because the colloid carcinoma of the biliary tree is exceedingly rare, the imaging characteristics and the clinical features of colloid carcinoma remain relatively unknown. We report a case of colloid carcinoma of the common bile duct and its accompanied metastatic lymphadenopathies with characteristic imaging findings reflecting abundant intratumoral mucin pools.
PMCID: PMC3767013  PMID: 24046786
Adenocarcinoma, Mucinous; Bile Ducts, Extrahepatic; Lymphatic Diseases; Ultrasonography
13.  Effect of HX108-CS supplementation on exercise capacity and lactate accumulation after high-intensity exercise 
In the present study, we determined the effects of HX108-CS (mixed extract of Schisandra chinensis and Chaenomeles sinensis) supplementation on lactate accumulation and endurance capacity. Furthermore, we examined CK (creatine kinase), LDH (lactate dehydrogenase) activity to determine whether the HX108-CS affected markers of skeletal muscle injury in vivo and in vitro.
Exercise capacity was measured by an exhaustive swimming test using ICR mice divided into four groups; one group received distilled water (DW) (Control group, n = 10), and the other groups received three different dosages of HX108-CS (10, 50 and 100 mg/kg, n = 10 per group) solution in water orally. Then, for the time-dependent measurements of blood lactate, CK, and LDH, Sprague–Dawley rats were divided into two groups; one received DW (Control group, n = 10), and the other group received HX108-CS (100 mg/kg, n = 10) solution in the same way as mice. Before the exercise test, the animals were given either DW or HX108-CS for 2 weeks. High-intensity treadmill exercise was performed for 30 minutes. Blood samples were collected and analyzed during and after exercise. For the in vitro experiment, C2C12 cells were treated with HX108-CS to examine its effect on lactate production, CK, and LDH activity.
Blood lactate concentration was significantly lowered immediately after treadmill exercise in HX108-CS group; however, there were no significant differences in activities of CK and LDH between HX108-CS and control during treadmill exercise and recovery phase. Furthermore, treatment with 100 mg/kg of HX108-CS led to a significant increase in the time to exhaustion in swimming test, and concurrently blood lactate concentration was significantly decreased in 50 and 100 mg/kg treated group. Moreover, our results of in vitro experiment showed that HX108-CS suppressed lactate production, CK, and LDH activity in a dose-dependent manner.
These results suggest that supplementation with HX108-CS may enhance exercise capacity by lowering lactate accumulation. This may in part be related to an amelioration of skeletal muscle injury.
PMCID: PMC3659049  PMID: 23587302
HX108-CS; Schisandra chinensis; Chaenomeles sinensis; Endurance capacity; Exercise capacity; Lactate accumulation
14.  Functional 3D Human Primary Hepatocyte Spheroids Made by Co-Culturing Hepatocytes from Partial Hepatectomy Specimens and Human Adipose-Derived Stem Cells 
PLoS ONE  2012;7(12):e50723.
We have generated human hepatocyte spheroids with uniform size and shape by co-culturing 1∶1 mixtures of primary human hepatocytes (hHeps) from partial hepatectomy specimens and human adipose-derived stem cells (hADSCs) in concave microwells. The hADSCs in spheroids could compensate for the low viability and improve the functional maintenance of hHeps. Co-cultured spheroids aggregated and formed compact spheroidal shapes more rapidly, and with a significantly higher viability than mono-cultured spheroids. The liver-specific functions of co-cultured spheroids were greater, although they contained half the number of hepatocytes as mono-cultured spheroids. Albumin secretion by co-cultured spheroids was 10% higher on day 7, whereas urea secretion was similar, compared with mono-cultured spheroids. A quantitative cytochrome P450 assay showed that the enzymatic activity of co-cultured spheroids cultured for 9 days was 28% higher than that of mono-cultured spheroids. These effects may be due to the transdifferentiation potential and paracrine healing effects of hADSCs on hHeps. These co-cultured spheroids may be useful for creating artificial three-dimensional hepatic tissue constructs and for cell therapy with limited numbers of human hepatocytes.
PMCID: PMC3517565  PMID: 23236387
15.  Metastatic hepatocellular carcinoma to the parotid gland: Case report and review of the literature 
Hepatocellular carcinoma, the most frequent primary hepatic tumor, metastasizes in more than 50% of cases. However, parotid gland metastatic HCCs are very uncommon. We report a patient in whom the finding of a left parotid mass revealed metastatic HCC.
A thirty-six-year-old male presented with a round palpable left neck mass that persisted for 3 months. He had received right hemihepatectomy for hepatocellular carcinoma (HCC). Preoperative evaluation revealed a benign tumor of the parotid gland. We performed superficial parotidectomy. Metastatic hepatocellular carcinoma of the parotid gland was diagnosed.
Although HCC metastases to the oral cavity have been reported, to date, only 4 cases HCC metastasis to the parotid gland have been reported. Although clinicians and cytopathologists alike both agree that salivary gland fine needle aspiration biopies (FNABs) are highly useful and safe diagnostic alternatives to biopsies and resections, we believe that in specific clinical situations, awareness of potential diagnostic pitfalls in salivary gland FNAB is a necessary part of the microscopic interpretations of these lesions.
Although rare, since HCC can metastasize to the parotid gland, high suspicion should be maintained in a patient presenting with a parotid mass with a history of HCC. In addition, since potential diagnostic pitfalls in salivary gland fine-needle aspiration (FNA) biopsies exist, incisional or excisional biopsy may be necessary for definite diagnosis of metastatic HCC to the parotid gland.
PMCID: PMC3537927  PMID: 23123420
HCC, hepatocellular carcinoma; FNA, fine-needle aspiration; Metastatic hepatocellular carcinoma; Parotid gland; Fine-needle aspiration

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