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1.  Balloon dilation itself may not be a major determinant of post-endoscopic retrograde cholangiopancreatography pancreatitis 
World Journal of Gastroenterology : WJG  2014;20(45):16913-16924.
Endoscopic retrograde cholangiopancreatography (ERCP) is the essential first modality for common bile duct (CBD) stone therapy. The conventional endoscopic treatment for CBD stones is stone removal after endoscopic sphincterotomy (EST). Stone removal after papillary stretching using balloon dilation instead of the conventional method has been widely adopted. There are many reports regarding endoscopic papillary balloon dilation (EPBD) utilizing a small balloon (< 10 mm) instead of EST for the removal of small CBD stones. In contrast, two cases of mortality due to post-ERCP pancreatitis (PEP) were reported after an EPBD clinical trial in the Western world, and the psychological barrier caused by these incidences hinders the use of this technique in Western countries. Endoscopic papillar large balloon dilation (EPLBD), which is used to treat large CBD stones, was not widely adopted when first introduced due to concerns about perforation and severe pancreatitis from the use of a large balloon (12-20 mm). However, as experience with this procedure accumulates, the occurrence of PEP with EPLBD is confirmed to be much lower than with EPBD. This report reviews whether EPBD and EPLBD, two procedures that use balloon dilation but differ in terms of indications and concept, contribute to the occurrence of PEP.
PMCID: PMC4258560  PMID: 25493004
Post-endoscopic retrograde cholangiopancreatography pancreatitis; Endoscopic papillary balloon dilation; Endoscopic papillary large balloon dilation; Common bile duct stone
2.  Endoscopic Treatment of Pancreatic Calculi 
Clinical Endoscopy  2014;47(3):227-235.
Chronic pancreatitis is a progressive inflammatory disease that destroys pancreatic parenchyma and alters ductal stricture, leading to ductal destruction and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of chronic pancreatitis that requires treatment to relieve abdominal pain and improve pancreas function. Endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although lingering controversies have hindered a consensus recommendation. Many comparative studies have reported that surgery is the superior treatment because of reduced duration and frequency of hospitalization, cost, pain relief, and reintervention, while endoscopic therapy is effective and less invasive but cannot be used in all patients. Surgery is the treatment of choice when endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is present. However, in patients with the appropriate indications or at high-risk for surgery, endoscopic therapy in combination with ESWL can be considered a first-line treatment. We expect that the development of advanced endoscopic techniques and equipment will expand the role of endoscopic treatment in PDS removal.
PMCID: PMC4058540
Pancreatitis, chronic; Calculi; Endoscopy; Surgery; Lithotripsy
3.  Endoscopic Papillary Large Balloon Dilation: Guidelines for Pursuing Zero Mortality 
Clinical Endoscopy  2012;45(3):299-304.
Since endoscopic papillary large balloon dilation (EPLBD) is used to treat benign disease and as a substitute for conventional methods, such as endoscopic sphincterotomy plus endoscopic mechanical lithotripsy, we should aim for zero mortality. This review defines EPLBD and suggests guidelines for its use based on a review of published articles and our large-scale multicenter retrospective review.
PMCID: PMC3429757  PMID: 22977823
Endoscopic papillary large balloon dilation; Endoscopic sphincterotomy; Mechanical lithotripsy
4.  Development of Single-Stranded DNA Aptamers for Specific Bisphenol A Detection 
Oligonucleotides  2011;21(2):85-91.
The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 1015 random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4′-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol–gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules.
PMCID: PMC3125561  PMID: 21413891
5.  Endoscopic removal of a migrated cystogastrostomy double pigtail stent through a pancreatico-duodenal fistula tract 
A common complication of pancreatitis is pseudocyst formation. Endoscopic drainage is a widely used treatment for pancreatic pseudocysts, and offers a definitive solution in approximately 75% of cases. Drainage-related complications may be related directly to the procedure or may occur later as stents and drains migrate or erode into adjacent structures. Procedure-related complications included bleeding, pancreatitis, and infection while stent-related complications may involve dislocation or clogging with subsequent infection. This report is the first description of the successful endoscopic removal of a migrated cystogastrostomy double pigtail stent through a pancreatico-duodenal fistula tract that developed more than six years after the stent was originally misplaced into a pseudocyst.
PMCID: PMC3234702  PMID: 22163088
pseudocyst; pigtail stent; migration; fistula
6.  Structural Diversity Repertoire of Gene Silencing Small Interfering RNAs 
Nucleic Acid Therapeutics  2011;21(3):125-131.
Since the discovery of double-stranded (ds) RNA-mediated RNA interference (RNAi) phenomenon in Caenorhabditis elegans, specific gene silencing based upon RNAi mechanism has become a novel biomedical tool that has extended our understanding of cell biology and opened the door to an innovative class of therapeutic agents. To silence genes in mammalian cells, short dsRNA referred to as small interfering RNA (siRNA) is used as an RNAi trigger to avoid nonspecific interferon responses induced by long dsRNAs. An early structure–activity relationship study performed in Drosophila melanogaster embryonic extract suggested the existence of strict siRNA structural design rules to achieve optimal gene silencing. These rules include the presence of a 3′ overhang, a fixed duplex length, and structural symmetry, which defined the structure of a classical siRNA. However, several recent studies performed in mammalian cells have hinted that the gene silencing siRNA structure could be much more flexible than that originally proposed. Moreover, many of the nonclassical siRNA structural variants reported improved features over the classical siRNAs, including increased potency, reduced nonspecific responses, and enhanced cellular delivery. In this review, we summarize the recent progress in the development of gene silencing siRNA structural variants and discuss these in light of the flexibility of the RNAi machinery in mammalian cells.
PMCID: PMC3198623  PMID: 21749289
7.  Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey 
AIM: To investigate prevalence of Clonorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea.
METHODS: Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire.
RESULTS: Of 3080 patients with gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients (37.2%) had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non-infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis.
CONCLUSION: Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.
PMCID: PMC2653299  PMID: 19115472
Clonorchis sinensis; Epidemiology; Cholangiocarcinoma; Korea; Multicenter study; Clonorchiasis
8.  Induction and characterization of taxol-resistance phenotypes with a transiently expressed artificial transcriptional activator library 
Nucleic Acids Research  2004;32(14):e116.
Phenotype-based functional genomic methods are useful for the identification of genes that are related to a particular biological function or disease. Essential to this approach is the ability to regulate the expression of selected genes. Artificial transcription factors (ATFs) are key molecular tools that selectively regulate gene expression in vivo. Here, we use an ATF library to identify genes that participate in rendering a cell resistant to the drug Taxol, a potent anti-cancer drug that binds to tubulin and inhibits cell division. The library, which encodes ATFs that activate (rather than inhibit) transcription, was introduced into a HeLa cell line, and Taxol-resistant cells were selected. After eight rounds of selection, we identified two ATFs that significantly increased the level of Taxol resistance (TR) in HeLa cells. Gene expression microarray experiments using these ATFs identified 37 co-regulated genes, including genes already known to participate in TR. This study demonstrates that ATF libraries can be used to induce phenotypic alterations in eukaryotic cells and then identify specific genes that are associated with the phenotype of choice.
PMCID: PMC514398  PMID: 15304545
9.  Specific SR protein-dependent splicing substrates identified through genomic SELEX 
Nucleic Acids Research  2003;31(7):1955-1961.
The Drosophila pre-mRNA splicing factor B52 (SRp55) is essential for fly development, but splicing of RNAs of specific genes tested previously is normal in B52-null animals, presumably due to partial functional redundancy with other SR proteins. To identify B52-dependent splicing substrates in vivo, we selected genomic sequence fragments whose transcripts bind B52. Almost all of the corresponding genes having a known function encode either transcription factors or components of signal transduction pathways, with the B52- binding fragments located to not only exonic but also intronic regions. Some pre-mRNAs from these genes showed splicing defects in the B52-null mutant. These results indicate that B52 has unique functions in the removal of some introns during development, and plays a critical role in cellular regulatory networks.
PMCID: PMC152802  PMID: 12655012
10.  Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice 
Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.
PMCID: PMC4274398  PMID: 25523099
11.  Contrast-enhanced endoscopic ultrasonography: advance and current status 
Ultrasonography  2014;33(3):161-169.
Endoscopic ultrasonography (EUS) technology has undergone a great deal of progress along with the color and power Doppler imaging, three-dimensional imaging, electronic scanning, tissue harmonic imaging, and elastography, and one of the most important developments is the ability to acquire contrast-enhanced images. The blood flow in small vessels and the parenchymal microvasculature of the target lesion can be observed non-invasively by contrast-enhanced EUS (CE-EUS). Through a hemodynamic analysis, CE-EUS permits the diagnosis of various gastrointestinal diseases and differential diagnoses between benign and malignant tumors. Recently, mechanical innovations and the development of contrast agents have increased the use of CE-EUS in the diagnostic field, as well as for the assessment of the efficacy of therapeutic agents. The advances in and the current status of CE-EUS are discussed in this review.
PMCID: PMC4104959  PMID: 25038805
Endosonography; Image enhancement; Ultrasonography; Contrast media; Microbubbles
12.  RNA Interference-Mediated Simultaneous Silencing of Four Genes Using Cross-Shaped RNA 
Molecules and Cells  2013;35(4):320-326.
The structural flexibility of RNA interference (RNAi)-triggering nucleic acids suggests that the design of unconventional RNAi trigger structures with novel features is possible. Here, we report a cross-shaped RNA duplex structure, termed quadruple interfering RNA (qiRNA), with multiple target gene silencing activity. qiRNA triggers the simultaneous down-regulation of four cellular target genes via an RNAi mechanism. In addition, qiRNA shows enhanced intracellular delivery and target gene silencing over conventional siRNA when complexed with jetPEI, a linear polyethyleneimine (PEI). We also show that the long antisense strand of qiRNA is incorporated intact into an RNA-induced silencing complex (RISC). This novel RNA scaffold further expands the repertoire of RNAi-triggering molecular structures and could be used in the development of therapeutics for various diseases including viral infections and cancer.
PMCID: PMC3887895  PMID: 23563800
polyethyleneimine (PEI); quadruple interfering RNA (qiRNA); RNA interference; small interfering RNA (siRNA)
13.  DICER1 loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88 
Cell  2012;149(4):847-859.
Alu RNA accumulation due to DICER1 deficiency in the retinal pigmented epithelium (RPE) is implicated in geographic atrophy (GA), an advanced form of age-related macular degeneration that causes blindness in millions of individuals. The mechanism of Alu RNA-induced cytotoxicity is unknown. Here we show that DICER1 deficit or Alu RNA exposure activates the NLRP3 inflammasome and triggers TLR-independent MyD88 signaling via IL-18 in the RPE. Genetic or pharmacological inhibition of inflammasome components (NLRP3, Pycard, Caspase-1), MyD88, or IL-18 prevents RPE degeneration induced by DICER1 loss or Alu RNA exposure. These findings, coupled with our observation that human GA RPE contains elevated amounts of NLRP3, PYCARD and IL-18, and evidence of increased Caspase-1 and MyD88 activation, provide a rationale for targeting this pathway in GA. Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements.
PMCID: PMC3351582  PMID: 22541070
14.  Correction: Ionizing Radiation Induces Stemness in Cancer Cells 
PLoS ONE  2013;8(3):10.1371/annotation/15587a16-d9c2-446b-9601-924c2db5c5d9.
PMCID: PMC3613426
15.  Selection and Optimization of Asymmetric siRNA Targeting the Human c-MET Gene 
Molecules and Cells  2011;32(6):543-548.
The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3’ end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic.
PMCID: PMC3887682  PMID: 22058018
asiRNA; cancer; c-MET; RNA interference; siRNA
16.  Ionizing Radiation Induces Stemness in Cancer Cells 
PLoS ONE  2012;7(8):e43628.
The cancer stem cell (CSC) model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation–induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.
PMCID: PMC3424153  PMID: 22928007
17.  A Comparative Study on the Efficacy of Covered Metal Stent and Plastic Stent in Unresectable Malignant Biliary Obstruction 
Clinical Endoscopy  2012;45(1):78-83.
The placement of self expandable metal stent (SEMS) is one of the palliative therapeutic options for patients with unresectable malignant biliary obstruction. The aim of this study was to compare the effectiveness of a covered SEMS versus the conventional plastic stent.
We retrospectively evaluated 44 patients with unresectable malignant biliary obstruction who were treated with a covered SEMS (21 patients) or a plastic stent (10 Fr, 23 patients). We analyzed the technical success rate, functional success rate, early complications, late complications, stent patency and survival rate.
There was one case in the covered SEMS group that had failed technically, but was corrected successfully using lasso. Functional success rates were 90.5% in the covered SEMS group and 91.3% in the plastic stent group. There was no difference in early complications between the two groups. Median patency of the stent was significantly prolonged in patients who had a covered SEMS (233.6 days) compared with those who had a plastic stent (94.6 days) (p=0.006). During the follow-up period, stent occlusion occurred in 11 patients of the covered SEMS group. Mean survival showed no significant difference between the two groups (covered SEMS group, 236.9 days; plastic stent group, 222.3 days; p=0.182).
The patency of the covered SEMS was longer than that of the plastic stent and the lasso of the covered SEMS was available for repositioning of the stent.
PMCID: PMC3363115  PMID: 22741136
Malignant biliary obstruction; Self-expandable metal stent; Plastic stent
18.  Clinical Outcomes and Risk Factors of Rebleeding Following Endoscopic Therapy for Nonvariceal Upper Gastrointestinal Hemorrhage 
Clinical Endoscopy  2011;44(2):93-100.
Rebleeding after endoscopic therapy for non-variceal upper gastrointestinal hemorrhage (NGIH) is the most important predictive factor of mortality. We evaluated the risk factors of rebleeding in patients undergoing endoscopic therapy for the NGIH.
Between January 2003 and January 2007, 554 bleeding events in 487 patients who underwent endoscopic therapy for NGIH were retrospectively enrolled. We reviewed the clinicoendoscopical characteristics of patients with rebleeding and compared them with those of patients without rebleeding.
The incidence of rebleeding was 21.7% (n=120). In the multivariate analysis, initial hemoglobin level ≤9 g/dL (p=0.002; odds ratio [OR], 2.433), inexperienced endoscopist with less than 2 years of experience in therapeutic endoscopy (p=0.001; OR, 2.418), the need for more 15 cc of epinephrine (p=0.001; OR, 2.570), injection therapy compared to thermal and injection therapy (p=0.001; OR, 2.840), and comorbidity with chronic renal disease (p=0.004; OR, 2.908) or liver cirrhosis (p=0.010; OR, 2.870) were risk factors for rebleeding following endoscopic therapy.
Together with patients with low hemoglobin level at presentation, chronic renal disease, liver cirrhosis, the need for more 15 cc of epinephrine, or therapy done by inexperienced endoscopist were risk factors for the development of rebleeding.
PMCID: PMC3363058  PMID: 22741119
Gastrointestinal hemorrhage; Risk factors; Endoscopy; Therapy
19.  DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration 
Nature  2011;471(7338):325-330.
Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.
PMCID: PMC3077055  PMID: 21297615
20.  The Increase in Balloon Size to Over 15 mm Does Not Affect the Development of Pancreatitis After Endoscopic Papillary Large Balloon Dilatation for Bile Duct Stone Removal 
Digestive Diseases and Sciences  2010;56(5):1572-1577.
Endoscopic papillary large balloon dilatation (EPLBD) after endoscopic sphincterotomy (EST) has recently become widely used for common bile duct (CBD) stone removal, but many clinicians remain concerned about post-procedural pancreatitis with increasing the balloon size to over 15 mm.
We aimed to evaluate the safety and efficacy of EPLBD with a relatively large balloon (15–20 mm) after EST and to evaluate the factors related to post-EPLBD pancreatitis.
A retrospective review was undertaken of the endoscopic database of 101 patients with CBD stones who underwent EPLBD using a larger balloon size of over 15 mm (15–20 mm). Clinical parameters, endoscopic data, and outcomes were analyzed.
The mean age of the subjects was 69 years. All patients had a dilated CBD of over 11 mm (mean = 22.6 mm). The mean size of balloon used in EPLBD was 17.1 ± 1.9 mm (range 15–20 mm). Mechanical lithotripsy was required in seven patients (6.9%). The rate of complete stone removal in the first session was 92.1%. Post-procedural pancreatitis developed in five cases (5.4%), but none were graded as severe. The smaller dilatation of the CBD, longer cannulation time, and longer time for stone removal were associated with post-procedural pancreatitis, but larger size of balloon did not affect the development of post-EPLBD pancreatitis.
EPLBD with a large balloon of over 15 mm with EST is an effective and safe procedure with a very low probability of severe post-procedural pancreatitis. Post-EPLBD pancreatitis was not associated with larger balloon size, but was associated with longer procedure time and smaller dilatation of the CBD.
PMCID: PMC3082046  PMID: 20945093
Common bile duct (CBD) stone; Endoscopic papillary large balloon dilatation (EPLBD); Large balloon; Post-EPLBD pancreatitis
21.  Biliary Stricture after Adult Right-Lobe Living-Donor Liver Transplantation with Duct-to-Duct Anastomosis: Long-Term Outcome and Its Related Factors after Endoscopic Treatment 
Gut and Liver  2010;4(2):226-233.
Biliary stricture is the most common and important complication after right-lobe living-donor liver transplantation (RL-LDLT) with duct-to-duct biliary anastomosis. This study evaluated the efficacy and long-term outcome of endoscopic treatment for biliary stricture after LDLT, with the aim of identifying the factors that influence the outcome.
Three hundred and thirty-nine adults received RL-LDLTs with duct-to-duct biliary anastomosis between January 2000 and May 2008 at Kangnam St. Mary's Hospital. Endoscopic retrograde cholangiography (ERC) was performed in 113 patients who had biliary stricture after LDLT. We evaluated the incidence of post-LDLT biliary stricture and the long-term outcome of endoscopic treatment for biliary stricture. The factors related to the outcome were analyzed.
Biliary strictures developed in 121 (35.7%) patients, 95 (78.5%) of them within 1 year of surgery. The mean number of ERCs performed per patient was 3.2 (range, 1 to 11). The serum biochemical markers decreased significantly after ERC (p<0.001). Stent insertion or stricture dilatation during ERC was successful in 90 (79.6%) patients. After a median follow-up period of 33 months from the first successful treatment with ERC, 48 (42.5%) patients achieved treatment success and 12 (10.6%) patients remained under treatment. The factors related to the outcome of endoscopic treatment were nonanastomotic stricture and stenosis of the hepatic artery (p=0.016).
Endoscopic treatment is efficacious and has an acceptable long-term outcome in the management of biliary strictures related to RL-LDLT with duct-to-duct biliary anastomosis. Nonanastomotic stricture and stenosis of the hepatic artery are correlated with a worse outcome of endoscopic treatment.
PMCID: PMC2886928  PMID: 20559526
Biliary stenting; Biliary stricture; Duct-to-duct biliary anastomosis; Endoscopic retrograde cholangiography; Liver transplantation
22.  bZIPDB : A database of regulatory information for human bZIP transcription factors 
BMC Genomics  2007;8:136.
Basic region-leucine zipper (bZIP) proteins are a class of transcription factors (TFs) that play diverse roles in eukaryotes. Malfunctions in these proteins lead to cancer and various other diseases. For detailed characterization of these TFs, further public resources are required.
We constructed a database, designated bZIPDB, containing information on 49 human bZIP TFs, by means of automated literature collection and manual curation. bZIPDB aims to provide public data required for deciphering the gene regulatory network of the human bZIP family, e.g., evaluation or reference information for the identification of regulatory modules. The resources provided by bZIPDB include (1) protein interaction data including direct binding, phosphorylation and functional associations between bZIP TFs and other cellular proteins, along with other types of interactions, (2) bZIP TF-target gene relationships, (3) the cellular network of bZIP TFs in particular cell lines, and (4) gene information and ontology. In the current version of the database, 721 protein interactions and 560 TF-target gene relationships are recorded. bZIPDB is annually updated for the newly discovered information.
bZIPDB is a repository of detailed regulatory information for human bZIP TFs that is collected and processed from the literature, designed to facilitate analysis of this protein family. bZIPDB is available for public use at .
PMCID: PMC1891292  PMID: 17535445
23.  A Phase II Study of Capecitabine Combined with Gemcitabine in Patients with Advanced Gallbladder Carcinoma 
Yonsei Medical Journal  2005;46(4):526-531.
Capecitabine and gemcitabine are used in the treatment of a variety of solid tumors including pancreatic and biliary tract carcinomas. The authors evaluated survival, response, and toxicity associated with using a combination of capecitabine and gemcitabine to treat patients with unresectable or metastatic gallbladder adenocarcinoma (GBC). Eligible patients had histologically- or cytologically-confirmed GBC, no prior systemic therapy with capecitabine or gemcitabine, Karnofsky Performance Status 70%, serum total bilirubin up to three times normal, and measurable disease. Treatment consisted of gemcitabine 1000 mg/m2 IV on Days 1 and 8 concurrent with administration of capecitabine 1000 mg/m2 PO BID on Days 1 through 14, on a 3-week cycle. Tumor response was assessed by the response evaluation criteria in solid tumors (RECIST criteria) and survival was calculated from initiation of CapGem therapy. A total of 24 patients were enrolled. Median age at the time of diagnosis was 62 years (range, 41-78 years). Fourteen patients had undergone prior surgery. Results showed that eight patients achieved partial response (33%) with an additional 10 patients achieving stable disease (42%). The overall median time to disease progression was 6.0 months (95% CI, 3.8-8.1 months) and overall survival was 16 months (95% CI, 13.8-18.3 months). The one-year survival rate was 58%. No Grade 4 toxicity was seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable nausea, hand-foot syndrome and anorexia were the most common toxicities. Our study shows that CapGem is an active and well-tolerated chemotherapy regimen in patients with advanced GBC.
PMCID: PMC2815838  PMID: 16127778
Capecitabine; gemcitabine; gallbladder cancer
24.  Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study 
Yonsei Medical Journal  2005;46(3):399-407.
Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the posttreatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0→4.2, p=0.000); lactulose group (11.3→5.0, p=0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.
PMCID: PMC2815818  PMID: 15988813
Hepatic encephalopathy; rifaximin; lactulose; liver cirrhosis
25.  The Diagnostic Value of Endoprobe for Small Esophageal Leiomyomas Derived from the Muscularis Mucosae 
Yonsei Medical Journal  2005;46(1):61-65.
Esophageal leiomyoma derived from the muscularis mucosae (MM) is a rare condition, and the optimal modality for diagnosis and treatment is controversial. Endoscopic ultrasonography can provide an accurate image of esophageal layer structure, providing information on lesion suitability for potential endoscopic therapy. We attempted to investigate the diagnostic value of a transendoscopic balloon-tipped miniature ultrasonic endoprobe for small esophageal leiomyomas derived from MM. We resected 7 small esophageal leiomyomas derived from MM by endoscopic mucosal resection (EMR), all of which were diagnosed by a balloon-tipped endoprobe. The endosonographic and pathologic features of 7 cases of small esophageal leiomyomas derived from MM were compared. The balloon-tipped endoprobe clearly showed all 7 small esophageal leiomyomas derived from MM, even those under 5 mm in size (smallest lesion, 3.0 mm). The endosonographic characteristics of small esophageal leiomyomas derived from MM were a hypoechoic mass with smooth, regular, and a well-defined outer margin and homogenous inner echogram arising from the second hypoechoic layer. Complete resections were possible in all 7 cases by EMR without any complications. Tumor size was 3.0 - 13.5 mm (mean 7.8 mm) in maximum diameter. In all cases, endosonographic findings by endoprobe were exactly concordant with pathologic finding in determining the tumors depth in the esophageal wall, tissue origin and characteristics, growth pattern, and size. We detail the balloon-tipped endoprobe is a simple, convenient, and very useful in making accurate diagnosis of small esophageal leiomyomas derived from the MM and the appropriate applications of EMR.
PMCID: PMC2823058  PMID: 15744806
Endoscopic ultrasonography; leiomyoma; esophagus

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