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author:("Lee, Gin hyg")
1.  TLR3, TRIF and Caspase 8 determine double-stranded RNA-induced epithelial cell death and survival in vivo1 
Toll-like receptor 3 (TLR3) signaling is activated by double-stranded RNA (dsRNA), a virus-associated molecular pattern. Injection of dsRNA into mice induced a rapid, dramatic and reversible remodeling of the small intestinal mucosa with significant villus shortening. Villus shortening was preceded by increased caspase 3 and 8 activation and apoptosis of intestinal epithelial cells (IECs) located in the mid to upper villus with ensuing luminal fluid accumulation and diarrhea due to an increased secretory state. Mice lacking TLR3 or the adaptor molelcule TRIF mice were completely protected from dsRNA-induced IEC apoptosis, villus shortening and diarrhea. dsRNA induced apoptosis was independent of TNF signaling. Notably, NF-κB signaling through IκB kinase beta protected crypt IECs but did not protect villus IECs from dsRNA-induced or TNF-induced apoptosis. dsRNA did not induce early caspase 3 activation with subsequent villus shortening in mice lacking caspase 8 in IECs, but instead caused villus destruction with a loss of small intestinal surface epithelium and death. Consistent with direct activation of the TLR3-TRIF-caspase 8 signaling pathway by dsRNA in IECs, dsRNA-induced signaling of apoptosis was independent of non-TLR3 dsRNA signaling pathways, IL-15, TNF, IL-1, IL-6, IRF3, type I IFN receptor, adaptive immunity, as well as dendritic cells, NK cells, and other hematopoietic cells. We conclude that dsRNA activation of the TLR3-TRIF-caspase 8 signaling pathway in IECs has a significant impact on the structure and function of the small intestinal mucosa and suggest signaling through this pathway has a host protective role during infection with viral pathogens.
doi:10.4049/jimmunol.1202756
PMCID: PMC3551582  PMID: 23209324
2.  Intralesional Steroid Injection to Prevent Stricture after Near-Circumferential Endosopic Submucosal Dissection for Superficial Esophageal Cancer 
Clinical Endoscopy  2013;46(6):643-646.
Stricture frequently occurs after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma with near- or whole-circumferential mucosal defects, and post-ESD stricture is difficult to treat and usually requires multiple sessions of endoscopic balloon dilatation. Intralesional steroid injection has previously been used to prevent stricture; however, there have been few experiences with this method after near- or whole-circumferential ESD. We present a case of a single session of intralesional steroid injection performed immediately after near-circumferential ESD to prevent post-ESD stricture. After a follow-up period of 6 months, the patient showed good outcome without dysphagia.
doi:10.5946/ce.2013.46.6.643
PMCID: PMC3856266  PMID: 24340258
Injections, intralesional; Esophageal stenosis; Endoscopic submucosal dissection; Esophageal neoplasms
3.  The Feasibility of 18F-Fluorothymidine PET for Prediction of Tumor Response after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin in Patients with Resectable Esophageal Cancer 
Purpose
The aim of this study was to determine whether 18F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer.
Methods
This study was prospectively performed as a collateral study of “randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer”. 18F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET at baseline and 3–4 weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery.
Results
The 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline 18F-FLT and 18F-FDG PET were 85% and 100%, respectively. The tumor uptakes on 18F-FLT PET were lower than those of 18F-FDG PET. Among nine patients who completed second 18F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder.
Conclusion
The percent change of tumor uptake in 18F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.
doi:10.1007/s13139-011-0118-4
PMCID: PMC4042979  PMID: 24900033
18F-FLT; PET; Esophageal cancer; Induction chemotherapy; Tumor response
4.  Regression of Advanced Gastric MALT Lymphoma after the Eradication of Helicobacter pylori 
Gut and Liver  2012;6(2):270-274.
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
doi:10.5009/gnl.2012.6.2.270
PMCID: PMC3343168  PMID: 22570759
Marginal zone B-cell lymphoma; Stomach
5.  Genetic Evaluation of ALADIN Gene in Early-Onset Achalasia and Alacrima Patients 
Background/Aims
ALADIN gene has been known to cause achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. A considerable proportion of achalasia patients has been known to show alacrima (decreased secretion of tear). However, the genetic mechanism between achalasia and alacrima has not been defined yet. We postulated that ALADIN gene may be involved in the occurrence of early-onset achalasia; thus, we investigated the correlation of ALADIN gene in early-onset achalasia patients.
Methods
From 1989 to 2007, patients who were diagnosed as primary achalasia before age 35 were enrolled. All of the enrolled patients were asked for (1) blood sampling for DNA, (2) Shirmer test and (3) dysphagia questionnaires.
Results
The ALADIN gene in exon 1, 2, 10, 11 and 12 from 19 patients was investigated (M:F = 12:7). The mean age of patients at diagnosis was 27 ± 5 (15-35) years old. Eight out of 19 (42%) showed alacrima by the positive Shirmer test. In spite of thorough exam in the genetic study, there was no definite abnormal genetic finding in this study.
Conclusions
A considerable number of achalasia patients showed alacrima. Due to the limitation of this study, it is difficult to conclude that early-onset achalasia may have significant correlations with the ALADIN gene.
doi:10.5056/jnm.2011.17.2.169
PMCID: PMC3093009  PMID: 21602994
AAAS protein; Esophageal achalasia; Human; Shirmer test
6.  Low Levels of Pepsinogen I and Pepsinogen I/II Ratio are Valuable Serologic Markers for Predicting Extensive Gastric Corpus Atrophy in Patients Undergoing Endoscopic Mucosectomy 
Gut and Liver  2010;4(4):475-480.
Background/Aims
The levels of pepsinogen (PG) I and the PGI/II ratio are useful serologic markers for chronic atrophic gastritis. This study evaluated the performance and clinical implications of these markers in patients undergoing endoscopic mucosectomy.
Methods
We enrolled 142 consecutive patients with early gastric tumors and Helicobacter pylori infection who were eligible for mucosectomy. Chronic gastritis and atrophy were assessed using four defined biopsy procedures. Serum PGs were measured by an enzyme immunoassay. Optimal diagnostic cut-offs and performance were determined using receiver operating characteristic curves.
Results
The PGI level and the PGI/II ratio decreased with corpus-dominant gastritis and as atrophy advanced toward the corpus greater curvature (GC). For the presence of corpus GC atrophy, the areas under the PGI and PGI/II-ratio curves were 0.82 and 0.77, respectively. The optimal cut-off levels were 59.3µg/L for PGI (sensitivity, 83.3%; specificity, 78.4%) and 3.6µg/L for PGI/II ratio (sensitivity, 70.0%; specificity, 78.4%). Using these serologic cut-off levels, we found that the frequency of corpus tumor location differed significantly (32.9% vs 11.1% for PGI <59.3 and ≥59.3µg/L, respectively; and 31.1% vs 14.8% for PGI/II ratio <3.5 and ≥3.5, respectively; p<0.05).
Conclusions
A low PGI level and PGI/II ratio are valuable serologic markers for predicting corpus GC atrophy, and have clinical implications with respect to the corpus location of tumors in mucosectomy patients.
doi:10.5009/gnl.2010.4.4.475
PMCID: PMC3021602  PMID: 21253295
Pepsinogens; Atrophic gastritis; Stomach neoplasia; Helicobacter pylori; Endoscopy
7.  Benign Bronchoesophageal Fistula in Adults: Endoscopic Closure as Primary Treatment 
Gut and Liver  2010;4(4):508-513.
Background/Aims
Benign bronchoesophageal fistula (BEF) is a rare condition that is usually treated surgically; however, less invasive endoscopy procedures have been attempted to overcome the disadvantages of surgery. The aim of this study was thus to determine the results of endoscopic management as a primary treatment in patients with BEF.
Methods
We retrospectively analyzed data from 368 patients with BEF who were treated at a tertiary care, academic medical center between January 2000 and August 2009.
Results
Benign causes were found for only 18 of the 368 patients. Of these, seven were treated endoscopically and the others by surgery or other methods. The first endoscopy procedures failed in all seven patients, with second trials of endoscopy performed in four patients at a median of 8 days (range, 3 to 11 days) after the first procedure. The second endoscopic procedure was successful in two out of four patients; one patient showed no recurrence of the fistula, whereas the second patient experienced a recurrence after 24 months. All patients underwent successful surgical procedures after the failure of endoscopic treatment, with no further recurrences.
Conclusions
Although we observed a low rate of success for primary endoscopic treatment of benign BEF, the invasive nature of surgery suggests the need for a prospective study with a large number of patients to evaluate the efficacy of less invasive procedures such as endoscopic treatment.
doi:10.5009/gnl.2010.4.4.508
PMCID: PMC3021607  PMID: 21253300
Esophageal fistula; Endoscopy; Fibrin glue
8.  The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole 
Gut and Liver  2010;4(2):201-206.
Background/Aims
The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies.
Methods
A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C13-urea breath test.
Results
Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795).
Conclusions
The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.
doi:10.5009/gnl.2010.4.2.201
PMCID: PMC2886925  PMID: 20559522
Helicobacter pylori; CYP2C19; Proton pump inhibitor; Lansoprazole; Rabeprazole
9.  Clinicopathologic Characteristics of Barrett's Cancer in Korea 
Gut and Liver  2008;2(3):193-198.
Background/Aims
The incidence of Barrett's cancer is increasing in Western countries, but there have been only a few case reports of this condition in Korea. The aim of this study was to elucidate the endoscopic and pathologic characteristics of Barrett's cancer in a single center in Korea.
Methods
We retrospectively reviewed the demographic, endoscopic, and pathologic characteristics of six patients with Barrett's cancer, defined as a tumor centered above the esophagogastric junction and surrounded by Barrett's esophagus.
Results
All six patients were male, and three (50%) were symptomatic. Barrett's cancer had developed from short-segment Barrett's esophagus in all patients. All tumors were located on the right side of the lower esophagus and showed hyperemic mucosal changes. Three patients were treated surgically and three by endoscopic resection. All cases had pathologic evidence of Barrett's cancer.
Conclusions
Early detection of Barrett's cancer requires meticulous endoscopic observations of subtle mucosal color and morphological changes around the esophagogastric junction.
doi:10.5009/gnl.2008.2.3.193
PMCID: PMC2871641  PMID: 20485646
Barrett esophagus; Esophageal neoplasms
10.  Meta-Analysis of First-Line Triple Therapy for Helicobacter pylori Eradication in Korea: Is It Time to Change? 
Journal of Korean Medical Science  2014;29(5):704-713.
Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin, and clarithromycin, is the recommended first-line treatment for Helicobacter pylori infection. However, the eradication rate of triple therapy has declined over the past few decades. We analyzed the eradication rate and adverse events of triple therapy to evaluate current practices in Korea. A comprehensive literature search was performed up to August 2013 of 104 relevant studies comprising 42,124 patients. The overall eradication rate was 74.6% (95% confidence interval [CI], 72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by per-protocol analysis. The eradication rate decreased significantly from 1998 to 2013 (P < 0.001 for both intention-to-treat and per-protocol analyses). Adverse events were reported in 41 studies with 8,018 subjects with an overall incidence rate of 20.4% (95% CI, 19.6%-21.3%). The available data suggest that the effectiveness of standard triple therapy for H. pylori eradication has decreased to an unacceptable level. A novel therapeutic strategy is warranted to improve the effectiveness of first-line treatment for H. pylori infection in Korea.
Graphical Abstract
doi:10.3346/jkms.2014.29.5.704
PMCID: PMC4024949  PMID: 24851029
Helicobacter pylori; Eradication; Triple Therapy

Results 1-10 (10)