Publications by authors named "Heung Up Kim"

51 Publications

The Intestinal Stem Cell Marker SMOC2 Is an Independent Prognostic Marker Associated With Better Survival in Gastric Cancer.

Anticancer Res 2021 Jul;41(7):3689-3698

Department of Pathology, Jeju National University School of Medicine and Jeju National University Hospital, Jeju, Republic of Korea;

Background/aim: SPARC-related modular calcium-binding protein 2 (SMOC2), a secreted matricellular protein, is reported to be involved in cancer progression such as cell cycle, angiogenesis, and invasion. In this study, we aimed to investigate the expression of SMOC2 in various gastric lesions and assessed its prognostic value in a large cohort of gastric cancer (GC) patients.

Patients And Methods: SMOC2 mRNA levels were measured by quantitative real-time PCR using 26 matched fresh-frozen GC samples. SMOC2 protein expression was determined by immunohistochemistry on tissue microarrays including 734 GC specimens and its correlations with clinicopathological features and survival were evaluated.

Results: The transcription level of SMOC2 was higher in GC samples compared to normal mucosa (p=0.006). Its expression levels were associated with the intestinal stem cell (ISC) marker, LGR5, but there were no correlations with EPHB2 and OLFM4 or the candidate cancer stem cell markers CD133 and CD44. SMOC2 expression was significantly increased in the intestinal metaplasia and was further increased in gastric adenomas and early gastric cancers (EGC). In total, 34% of GCs were positive for SMOC2, and SMOC2 positivity was higher in old (p=0.001) and male (p<0.001) patients, and in well-differentiated GC (p<0.001). SMOC2 expression had a negative association with perineural invasion (p<0.001) and tumor stage (p<0.001). In survival analysis, SMOC2-positive GC patients had much better clinical outcomes in overall survival rates (p<0.001) compared to SMOC2-negative GC patients. The prognostic impact of SMOC2 remained significant both in intestinal (p<0.001) and diffuse-type GC (p<0.001). Remarkably, a multivariate analysis demonstrated SMOC2 as an independent prognostic marker [hazard ratio (HR)=0.732, p=0.045] along with venous invasion (p=0.012), tumor stage (p<0.001) and CDX2 (p=0.028).

Conclusion: Our results suggest that SMOC2 can be a prognostic marker for better clinical outcomes in GC.
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http://dx.doi.org/10.21873/anticanres.15160DOI Listing
July 2021

Expression profile of intestinal stem cell and cancer stem cell markers in gastric cancers with submucosal invasion.

Pathol Res Pract 2021 Feb 2;218:153336. Epub 2021 Jan 2.

Department of Pathology, Jeju National University School of Medicine and Jeju National University Hospital, South Korea. Electronic address:

Cancer stem cells (CSCs) are believed to be responsible for tumor growth, invasion, and metastasis. Submucosal invasion, which greatly enhances metastasis risk, is a critical step in gastric cancer (GC) progression. To identify stem cell-related markers associated with submucosal invasion and lymph node (LN) metastasis in GCs, we investigated the expression of candidate CSC markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs that manifested submucosal invasion. We discovered that EPHB2 and LGR5 expression was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer, and the proportion of stem cell marker-positive cells substantially increased during submucosal invasion. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. Unexpectedly, no CSC markers showed any associations with LN metastasis, and only loss of EPHB2 expression was associated with increased LN metastasis. Treatment of RSPO2, a niche factor, along with Wnt 3a, to GC cells led to increased EPHB2 and LGR5 mRNA levels. RNA in situ hybridization confirmed specific RSPO2 expression in the smooth muscle cells of the muscularis mucosa, suggesting that RSPO2 is responsible for the increased expression of ISC markers in GC cells at the basal areas. In summary, no stem cell markers were associated with increased LN metastasis in early GCs. Conversely, isolated EPHB2 expression was associated with lower LN metastasis. EPHB2 and LGR5 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs, which was induced by a niche factor, RSPO2, from the muscularis mucosa.
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http://dx.doi.org/10.1016/j.prp.2020.153336DOI Listing
February 2021

SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers.

Sci Rep 2020 09 3;10(1):14591. Epub 2020 Sep 3.

Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Korea.

We aimed to investigate the expression profile of SPARC-related modular calcium-binding protein 2 (SMOC2) during colorectal cancer (CRC) progression and assess its prognostic impact in CRC patients. In our study, we showed that SMOC2 transcript level was higher in CRC samples than in normal mucosa (P = 0.017); this level was not associated with candidate cancer stem cell markers (CD44, CD166, CD133, and CD24) or intestinal stem cell markers (LGR5, ASCL2, and EPHB2) except for OLFM4 (P = 0.04). Immunohistochemical analysis showed that SMOC2-positive cells were confined to the crypt bases in the normal intestinal mucosa, hyperplastic polyps, and sessile serrated adenomas, whereas traditional serrated adenomas and conventional adenomas exhibited focal or diffuse distribution patterns. In total, 28% of 591 CRCs were positive for SMOC2, but SMOC2 positivity had negative correlations with lymphatic invasion (P = 0.002), venous invasion (P = 0.002), and tumor stage (P < 0.001). However, a positive association with nuclear β-catenin expression was seen. Furthermore, while upregulated SMOC2 expression was maintained during the adenoma-carcinoma transition, it decreased in cancer cells at the invasive front but did not decline further during lymph node metastasis. SMOC2 positivity showed no correlations with molecular abnormalities, including microsatellite instability, CpG island methylator phenotype, and mutations of KRAS and BRAF. In addition, we showed comprehensively that SMOC2 positivity is an independent prognostic marker for better clinical outcomes in a large cohort of CRC patients (P = 0.006). In vitro studies also demonstrated that induced SMOC2 expression in DLD1 cells exerts a suppressive role in tumor growth as well as in migration, colony, and sphere formation abilities. Taken together, our results suggest SMOC2 as a candidate tumor suppressor in CRC progression.
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http://dx.doi.org/10.1038/s41598-020-71643-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471277PMC
September 2020

Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Infection: A Nationwide Randomized Trial in Korea.

Gut Liver 2019 09;13(5):531-540

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for infection in the Korean population.

Methods: Patients with infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses.

Results: A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms.

Conclusions: The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.
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http://dx.doi.org/10.5009/gnl19136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743805PMC
September 2019

[Esophageal Foreign Body: Treatment and Complications].

Korean J Gastroenterol 2018 Jul;72(1):1-5

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

The most common cause of esophageal foreign bodies in adults is meat in Western countries and fish bones in Asian countries, including Korea. Although most ingested foreign bodies pass spontaneously through the esophagus without any clinical sequelae, some sharp foreign bodies, such as fish bones embedded in the esophagus, require treatment. Endoscopic management is the first choice in the treatment of esophageal foreign bodies because it is quite safe and effective. Major complications occur as a result of esophageal perforation; in particular, sharp foreign bodies, such as fish bones, are more likely to cause perforation. Complications include mediastinitis, paraesophageal abscess, pneumomediastinum, subcutaneous emphysema, pneumothorax, tracheoesophagal fistula, aortoesophageal fistula, aspiration, and asphyxia. Unnecessary delays should be avoided in endoscopic intervention for esophageal foreign bodies to prevent complications.
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http://dx.doi.org/10.4166/kjg.2018.72.1.1DOI Listing
July 2018

Endoscopic Submucosal Dissection of Early Gastric Cancer in Patients with Liver Cirrhosis.

Dig Dis Sci 2018 02 27;63(2):466-473. Epub 2017 Dec 27.

Department of Internal Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, South Korea.

Background And Objectives: Endoscopic submucosal dissection (ESD) has become widely accepted method for treating early gastric cancer (EGC), but little is known about its role in patients with liver cirrhosis (LC). The aims of this study were to evaluate the outcomes of ESD in treating EGC in patients with LC.

Methods: The multicenter retrospective study identified 43 patients with chronic hepatitis B (CHB)-related cirrhosis undergoing ESD for treating EGC. The patients (LC group) were subdivided into two groups based on their Child-Pugh classification (CP-class): 32 with CP-class A (LC-A) and 11 with CP-class B (LC-B). The patients were compared to 47 non-cirrhotic CHB patients who underwent ESD (CHB group). Eight patients had a past history of hepatocellular carcinoma (HCC) prior to ESD, but no patients had viable HCC when ESD was performed.

Results: Procedural outcomes (en bloc, lateral/basal margins resection) and post-procedural complications (bleeding or perforation) did not differ significantly between the LC and CHB groups or between the LC-A and LC-B groups. No patients experienced worsening of the Child-Pugh score 1 month after ESD compared with the baseline score. During a median observation period of 66 months, the recurrence rates of gastric cancers were similar between the LC and CHB groups (5-year recurrence rates: 2.4 vs. 2.3%, p = 0.925), and all recurrent gastric cancers were completely resected by additional ESD. The overall mortality rate was increased in the LC group (5-year mortality rates: 17.9 vs. 5.7%, p = 0.034), and 8 of 10 deaths were attributed to liver-related diseases (such as HCC, complications of portal hypertension, hepatic failure).

Conclusions: ESD is feasible in patients with EGC and comorbid LC, even those with CP-class B cirrhosis. Their prognosis depends on LC-related diseases and not recurrent EGC.
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http://dx.doi.org/10.1007/s10620-017-4814-5DOI Listing
February 2018

Ophthalmologic manifestations in patients with inflammatory bowel disease.

Intest Res 2017 Jul 12;15(3):380-387. Epub 2017 Jun 12.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Background/aims: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), has been reported to have various ophthalmologic manifestations. The aim of this study was to evaluate the prevalence of ophthalmologic manifestations associated with IBD in Korea.

Methods: Sixty-one patients were examined between May 2013 and October 2014. We performed complete ophthalmologic examinations.

Results: Findings included 36 patients with CD and 25 with UC. The mean age of the patients was 34±16 years and disease duration was 45.3±23.9 months. Ophthalmologic manifestations were positive in 44 cases. Primary complication was diagnosed in 5 cases, as follows; iritis in 2 cases, episcleritis in one case, iritis with optic neuritis in 1 case, and serous retinal detachment in 1 case, without secondary complications. The most common coincidental complication was dry eye syndrome (DES), in 35 patients (57.4%). The prevalence of DES in the control group was 21.3%. The proportion of DES in patients with IBD was significantly higher than in the control group (=0.002).

Conclusions: Ophthalmologic manifestations were high (72.1%) in IBD patients. Clinically significant primary ocular inflammation occurred in 8.2% of patients. The most common complication was DES. There was a higher rate of DES in patients with IBD compared to the control group. Evaluation of the eye should be a routine component in patients with IBD.
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http://dx.doi.org/10.5217/ir.2017.15.3.380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478763PMC
July 2017

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series.

Clin Endosc 2017 May 11;50(3):297-300. Epub 2017 Apr 11.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS)-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.
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http://dx.doi.org/10.5946/ce.2016.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5475510PMC
May 2017

A Case of Infection Diagnosed by Colonoscopy.

Korean J Parasitol 2017 Feb 28;55(1):65-69. Epub 2017 Feb 28.

Department of Parasitology, Jeju National University School of Medicine, Jeju 63241, Korea.

A case of infection detected by small bowel series and colonoscopy is described. The patient was a 42-year-old Korean man accompanied by discharge of movable proglottids via anus. He used to eat raw pig liver but seldom ate beef. Small bowel series radiologic examinations showed flat tape-like filling defects on the ileum. By colonoscopy, a moving flat tapeworm was observed from the terminal ileum to the ascending colon. The tapeworm was identified as by mitochondrial DNA sequencing. The patient was prescribed with a single oral dose (16 mg/kg) of praziquantel.
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http://dx.doi.org/10.3347/kjp.2017.55.1.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365257PMC
February 2017

The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study.

J Gastric Cancer 2016 Sep 30;16(3):182-190. Epub 2016 Sep 30.

Department of Surgery, Samsung Medical Center, Seoul, Korea.

Purpose: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy.

Materials And Methods: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected.

Results: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients.

Conclusions: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.
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http://dx.doi.org/10.5230/jgc.2016.16.3.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065948PMC
September 2016

Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of in Peptic Ulcer Disease.

Gut Liver 2017 Mar;11(2):226-231

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Background/aims: The resistance rate of is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line eradication in peptic ulcer disease.

Methods: Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed.

Results: The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655).

Conclusions: Levofloxacin-based third-line eradication showed efficacy similar to that of previously reported first/second-line therapies.
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http://dx.doi.org/10.5009/gnl16099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347646PMC
March 2017

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

Clin Mol Hepatol 2016 Sep 30;22(3):390-395. Epub 2016 Aug 30.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.
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http://dx.doi.org/10.3350/cmh.2015.0050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066381PMC
September 2016

Oroesophageal Fish Bone Foreign Body.

Authors:
Heung Up Kim

Clin Endosc 2016 Jul 26;49(4):318-26. Epub 2016 Jul 26.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Fish bone foreign body (FFB) is the most frequent food-associated foreign body (FB) in adults, especially in Asia, versus meat in Western countries. The esophageal sphincter is the most common lodging site. Esophageal FB disease tends to occur more frequently in men than in women. The first diagnostic method is laryngoscopic examination. Because simple radiography of the neck has low sensitivity, if perforation or severe complications requiring surgery are expected, computed tomography should be used. The risk factors associated with poor prognosis are long time lapse after FB involvement, bone type, and longer FB (>3 cm). Bleeding and perforation are more common in FFB disease than in other FB diseases. Esophageal FB disease requires urgent treatment within 24 hours. However, FFB disease needs emergent treatment, preferably within 2 hours, and definitely within 6 hours. Esophageal FFB disease usually occurs at the physiological stricture of the esophagus. The aortic arch eminence is the second physiological stricture. If the FB penetrates the esophageal wall, a life-threatening aortoesophageal fistula can develop. Therefore, it is better to consult a thoracic surgeon prior to endoscopic removal.
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http://dx.doi.org/10.5946/ce.2016.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977739PMC
July 2016

[How to Use Scoring Systems for Upper Gastrointestinal Bleeding?].

Authors:
Heung Up Kim

Korean J Gastroenterol 2016 Jan;67(1):1-3

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http://dx.doi.org/10.4166/kjg.2016.67.1.1DOI Listing
January 2016

[Clinical Efficacy of Dynamic Contrast-enhanced Multidetector-row Computed Tomography in Patients with Obscure Gastrointestinal Bleeding].

Korean J Gastroenterol 2016 Apr;67(4):198-206

Department of Radiology, Jeju National University School of Medicine, Jeju, Korea.

Background/aims: Obscure gastrointestinal bleeding (OGIB) accounts for 5% of all gastrointestinal (GI) bleeding cases. Dynamic contrast-enhanced multidetector-row CT (DCE-MDCT) is not generally recommended in OGIB patients due to its low sensitivity. However, it can be used to quickly and simply diagnose OGIB according to some guidelines. The aim of this study was to evaluate the clinical efficacy of DCE-MDCT in OGIB patients.

Methods: We retrospectively analyzed the medical records of 362 patients who underwent DCE-MDCT between March 2009 and January 2014. A total of 45 patients diagnosed with OGIB were included in this study. Their baseline characteristics and treatment procedure were analyzed retrospectively. The positive rates of DCE-MDCT for the detection of bleeding and associated factors were assessed.

Results: The mean age of the patients was 59 years, and males represented 51.1%. Melena was the most common symptom (44.4%). Positive rate of DCE-MDCT findings was 20.0% (9/45). Among these patients, intraluminal contrast extravasation was found in 5 patients (55.6%) and intraluminal hematoma or mass lesions were found in 2 patients each (22.2%). Thirty nine patients (86.7%) underwent conservative management, and 6 patients (13.3%) underwent specific treatment, such as endoscopic treatment, embolization, or surgery. Patients who showed positivity in DCE-MDCT more frequently received specific treatment compared with those who were negative (44.4% vs. 5.6%, p=0.010).

Conclusions: Although DCE-MDCT showed a low positive rate (20.0%), positive findings of DCE-MDCT could lead to specific treatment. Positive DCE-MDCT findings play a useful role in the management of patients with OGIB.
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http://dx.doi.org/10.4166/kjg.2016.67.4.198DOI Listing
April 2016

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis.

Clin Mol Hepatol 2016 Mar 28;22(1):183-7. Epub 2016 Mar 28.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
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http://dx.doi.org/10.3350/cmh.2016.22.1.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825159PMC
March 2016

Eradication Rates of Helicobacter pylori in Korea Over the Past 10 years and Correlation of the Amount of Antibiotics Use: Nationwide Survey.

Helicobacter 2016 Aug 16;21(4):266-78. Epub 2015 Oct 16.

Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The efficacy of proton-pump inhibitor-amoxicillin-clarithromycin therapy for H. pylori eradication has decreased over time.

Objective: We assessed the trend of H. pylori eradication rates over the last 10 years and the relationship between the eradication rates and the amount of macrolide antibiotic use in a country with a high prevalence of H. pylori infection.

Methods: This vast nationwide multicenter study was conducted with 34,139 adults treated for H. pylori infection from January 2001 to December 2010. The defined daily dose per km(2) (DSD) of macrolide antibiotics was calculated (n = 141,019) using the Health Insurance Review & Assessment data base from 2008 to 2010 in the two cities which had the lowest (Jeju city) or highest (Chuncheon city) eradication rate.

Results: The eradication rates of proton-pump inhibitor-amoxicillin-clarithromycin therapy ranged 84.9-87.5% from 2001 to 2007, and those of 2008 to 2010 ranged 80.0-81.4% with a decreasing trend (p < 0.0001). The decreasing trend of eradication rates for the overall first-line therapy was observed only in three of the seven geographic areas in Korea (p < 0.0001). The DSD of macrolide antibiotics was significantly higher in Jeju than Cheunchon city (0.85 vs 0.52, p < 0.0001).

Conclusions: H. pylori eradication rates with clarithromycin-containing triple therapy in Korea showed a decreasing trend over the past 10 years, although the trend varied among geographic areas. This difference may be associated with the amount of macrolide antibiotic use.
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http://dx.doi.org/10.1111/hel.12279DOI Listing
August 2016

Diagnostic and Treatment Approaches for Refractory Peptic Ulcers.

Authors:
Heung Up Kim

Clin Endosc 2015 Jul 24;48(4):285-90. Epub 2015 Jul 24.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.
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http://dx.doi.org/10.5946/ce.2015.48.4.285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522418PMC
July 2015

Primary intestinal lymphangiectasia with generalized warts.

World J Gastroenterol 2015 Jul;21(27):8467-72

Soon Jae Lee, Hyun Joo Song, Sun-Jin Boo, Soo-Young Na, Heung Up Kim, Department of Internal Medicine, Jeju National University School of Medicine, Jeju 690-767, South Korea.

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient.
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http://dx.doi.org/10.3748/wjg.v21.i27.8467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507119PMC
July 2015

Erratum.

Clin Mol Hepatol 2015 Mar;21(1):104

[This corrects the article on p. 355 in vol. 20, PMID: 25548741.][This corrects the article on p. 368 in vol. 20, PMID: 25548743.].
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http://dx.doi.org/10.3350/cmh.2015.21.1.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379191PMC
March 2015

[Additional polyp detection rate using colonoscopic retroflexion in right colon].

Korean J Gastroenterol 2015 Feb;65(2):90-8

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Background/aims: There have been several studies showing that retroflexion (RF) in the right colon (RC) could reduce the polyp miss rate of proximal colon during colonoscopy. This study was conducted to evaluate the additional benefit of RF technique in the RC.

Methods: Patients who underwent colonoscopy from May 2008 to April 2011 were enrolled in the study. Data were obtained by retrospectively reviewing the medical records. RF was attempted in every patients undergoing colonoscopy since May 2008 except in cases of small RC vault, co-morbidity, severe diverticulosis, failed RF despite two trials, complaints of severe abdominal pain, or time burden. At first, RC was examined under direct vision. It was then examined by RF to detect missed polyps during the initial observation. Finally, the RC was re-examined with direct view.

Results: The cumulative RF success rate in the RC was 78.84% (1,805 of 2,319). The RF success rate increased with the number of cases (50% at 160 cases, 70% at 400 cases, and reached near 90% over 1,000 cases). Few polyps (4.88%) were detected only with RF and the additional adenoma detection rate was 3.32%. The additional polyp/adenoma detection rates were higher in the old age group (p<0.01). There were no RF associated perforation or severe complication.

Conclusions: Using RF examination, additional 4.88% of polyps could be detected in the RC. This technique could be a useful and safe method to detect hidden polyp during colonoscopy.
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http://dx.doi.org/10.4166/kjg.2015.65.2.90DOI Listing
February 2015

Protease-activated receptors modulate excitability of murine colonic smooth muscles by differential effects on interstitial cells.

J Physiol 2015 Mar 4;593(5):1169-81. Epub 2015 Feb 4.

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

Protease-activated receptors (PARs) are G protein-coupled receptors activated by proteolytic cleavage at their amino termini by serine proteases. PAR activation contributes to the inflammatory response in the gastrointestinal (GI) tract and alters GI motility, but little is known about the specific cells within the tunica muscularis that express PARs and the mechanisms leading to contractile responses. Using real time PCR, we found PARs to be expressed in smooth muscle cells (SMCs), interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor α positive (PDGFRα(+)) cells. The latter cell-type showed dominant expression of F2r (encodes PAR1) and F2rl1 (encodes PAR2). Contractile and intracellular electrical activities were measured to characterize the integrated responses to PAR activation in whole muscles. Cells were isolated and ICC and PDGFRα(+) cells were identified by constitutive expression of fluorescent reporters. Thrombin (PAR1 agonist) and trypsin (PAR2 agonist) caused biphasic responses in colonic muscles: transient hyperpolarization and relaxation followed by repolarization and excitation. The inhibitory phase was blocked by apamin, revealing a distinct excitatory component. Patch clamp studies showed that the inhibitory response was mediated by activation of small conductance calcium-activated K(+) channels in PDGFRα(+) cells, and the excitatory response was mediated by activation of a Cl(-) conductance in ICC. SMCs contributed little to PAR responses in colonic muscles. In summary, PARs regulate the excitability of colonic muscles; different conductances are activated in each cell type of the SMC-ICC-PDGFRα(+) cell (SIP) syncytium. Motor responses to PAR agonists are integrated responses of the SIP syncytium.
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http://dx.doi.org/10.1113/jphysiol.2014.285148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358678PMC
March 2015

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

Clin Mol Hepatol 2014 Dec 24;20(4):355-60. Epub 2014 Dec 24.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Background/aims: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection.

Methods: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels.

Results: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥ 5.1 × 10(7) IU/mL and ALT ≥ 5 × ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure.

Conclusions: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.
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http://dx.doi.org/10.3350/cmh.2014.20.4.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278066PMC
December 2014

Partial purification and properties of a cysteine protease from citrus red mite Panonychus citri.

Korean J Parasitol 2014 Feb 19;52(1):117-20. Epub 2014 Feb 19.

Department of Parasitology, Jeju National University School of Medicine, Jeju 690-767, Korea.

Several studies have reported that the citrus red mites Panonychus citri were an important allergen of citrus-cultivating farmers in Jeju Island. The aim of the present study was to purify and assess properties of a cysteine protease from the mites acting as a potentially pathogenic factor to citrus-cultivating farmers. A cysteine protease was purified using column chromatography of Mono Q anion exchanger and Superdex 200 HR gel filtration. It was estimated to be 46 kDa by gel filtration column chromatography and consisted of 2 polypeptides, at least. Cysteine protease inhibitors, such as trans poxy-succinyl-L-leucyl-amido (4-guanidino) butane (E-64) and iodoacetic acid (IAA) totally inhibited the enzyme activities, whereas serine or metalloprotease inhibitors did not affect the activities. In addition, the purified enzyme degraded human IgG, collagen, and fibronectin, but not egg albumin. From these results, the cysteine protease of the mites might be involved in the pathogenesis such as tissue destruction and penetration instead of nutrient digestion.
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http://dx.doi.org/10.3347/kjp.2014.52.1.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948988PMC
February 2014

Long-term follow up of endoscopic resection for type 3 gastric NET.

World J Gastroenterol 2013 Dec;19(46):8703-8

Yong Hwan Kwon, Seong Woo Jeon, Department of Internal Medicine, Kyungpook National University Hospital, Daegu 702-210, South Korea.

Aim: To clarify the short and long-term results and to prove the usefulness of endoscopic resection in type 3 gastric neuroendocrine tumors (NETs).

Methods: Of the 119 type 3 gastric NETs diagnosed from January 1996 to September 2011, 50 patients treated with endoscopic resection were enrolled in this study. For endoscopic resection, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) was used. Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively.

Results: EMR was performed in 41 cases and ESD in 9 cases. Pathologically complete resection was performed in 40 cases (80.0%) and incomplete resection specimens were observed in 10 cases (7 vs 3 patients in the EMR vs ESD group, P = 0.249). Upon analysis of the incomplete resection group, lateral or vertical margin invasion was found in six cases (14.6%) in the EMR group and in one case in the ESD group (11.1%). Lymphovascular invasions were observed in two cases (22.2%) in the ESD group and in one case (2.4%) in the EMR group (P = 0.080). During the follow-up period (43.73; 13-60 mo), there was no evidence of tumor recurrence in either the pathologically complete resection group or the incomplete resection group. No recurrence was reported during follow-up. In addition, no mortality was reported in either the complete resection group or the incomplete resection group for the duration of the follow-up period.

Conclusion: Less than 2 cm sized confined submucosal layer type 3 gastric NET with no evidence of lymphovascular invasion, endoscopic treatment could be considered at initial treatment.
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http://dx.doi.org/10.3748/wjg.v19.i46.8703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870517PMC
December 2013

Endoscopic resection for duodenal carcinoid tumors: a multicenter, retrospective study.

J Gastroenterol Hepatol 2014 Feb;29(2):318-24

Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.

Background And Aim: Gastrointestinal carcinoid tumors < 10 mm in diameter and limited to the submucosal layer demonstrate a low frequency of lymph node and distant metastasis, and are suitable for endoscopic treatment. The aim of this study was to assess the efficacy, safety, and long-term prognosis of endoscopic resections for the treatment of duodenal carcinoid tumors.

Methods: This study included a total of 41 duodenal carcinoid tumors in 38 patients between January 2006 and December 2011. The indications for endoscopic resection were lesions ≤ 10 mm in diameter, confined to the submucosal layer, and without lymph node or distant metastasis. Endoscopic resection was accomplished using endoscopic mucosal resection (EMR), EMR with a ligation device (EMR-L), EMR after circumferential precutting, or endoscopic submucosal dissection (ESD).

Results: EMR was performed in 18 tumors, EMR-L in 16, EMR after circumferential precutting in 3, and ESD in 4. En-bloc resection was performed in 39 tumors (95%), and endoscopic complete resection was achieved in 40 (98%); pathological complete resection was achieved in 17 tumors (41%). The endoscopic complete resection rate did not differ according to the resection method, but the pathological complete resection rate was higher for ESD than for EMR and EMR-L. Intraprocedural bleeding was noted in five cases, with no occurrence of perforation. Recurrence was not observed during the mean follow-up period of 17 months (range 1-53 months).

Conclusion: Endoscopic resection appears to be a safe and effective treatment for duodenal carcinoid tumors measuring ≤ 10 mm in diameter and confined to the submucosal layer.
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http://dx.doi.org/10.1111/jgh.12390DOI Listing
February 2014

Prevalence and risk factors of Helicobacter pylori infection in Korea: nationwide multicenter study over 13 years.

BMC Gastroenterol 2013 Jun 24;13:104. Epub 2013 Jun 24.

Seoul National University Hospital, Healthcare System Gangnam Center, Healthcare Research Institute, Seoul, Korea.

Background: The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors.

Methods: This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated.

Results: After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area.

Conclusions: A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.
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http://dx.doi.org/10.1186/1471-230X-13-104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702482PMC
June 2013

[Clarithromycin-resistant Helicobacter pylori associated with 23S rRNA point mutations in Jeju Island].

Korean J Gastroenterol 2013 May;61(5):252-8

Department of Internal Medicine, Jeju National University School of Medicine, National Biobank of Korea, Jeju National University Hospital, Jeju, Korea.

Background/aims: The point mutations in 23S rRNA gene accounts for the majority of the clarithromycin resistance of Helicobacter pylori. This study aimed to investigate the association between the clarithromycin-resistance of H. pylori and the failure of primary H. pylori eradication therapy in Jeju Island.

Methods: Between April 2011 and October 2012, 6,937 patients underwent endoscopy, and H. pylori infection was evaluated in 2,287 patients (33.0%). Total of 110 patients with H. pylori infection were treated with proton pump inhibitor (PPI)-based triple therapy. The result of eradication was evaluated with urea breath test, histology and PCR which were conducted 4 weeks from the last dose of medicine.

Results: The patients who had point mutations were 33 (26.0%). A2142G and A2143G mutations were observed in 10 patients (7.9%) and 23 patients (18.1%). Among 110 patients treated with PPI-based triple therapy, the success rate of the eradication therapy was 52.7% (58/110) and 70.7% (58/82) by intention-to-treat and per-protocol analysis, respectively. Fifteen of the 24 patients who failed the eradication therapy showed point mutations; 1 patient (4.2%) showed A2142G mutation and 14 patients (58.3%) showed A2143G mutation. Patients with A2143G mutation H. pylori showed higher failure rate of 87.5%. Patients with A2142G mutation H. pylori showed similar failure rate compared to those of the patients with wild type H. pylori.

Conclusions: In Jeju Island, the frequency of 23S rRNA point mutations is similar (26.0%) with other regions of Korea (15.8-31.3%). A2143G mutation is associated with the failure of H. pylori eradication.
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http://dx.doi.org/10.4166/kjg.2013.61.5.252DOI Listing
May 2013

Prevalence and risk factors of atrophic gastritis and intestinal metaplasia: a nationwide multicenter prospective study in Korea.

Gut Liver 2013 May 13;7(3):303-10. Epub 2013 May 13.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Background/aims: Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions.

Methods: In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured.

Results: The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively).

Conclusions: A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.
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http://dx.doi.org/10.5009/gnl.2013.7.3.303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661962PMC
May 2013

Management of Asymptomatic Erosive Esophagitis: An E-Mail Survey of Physician's Opinions.

Gut Liver 2013 May 9;7(3):290-4. Epub 2013 Apr 9.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: The management of asymptomatic erosive esophagitis is controversial. We surveyed physicians' opinions on asymptomatic erosive esophagitis using e-mail.

Methods: All members of the Korean Society of Neurogastro-enterology and Motility were invited to answer the questionnaire on the treatment and follow-up of patients with asymptomatic erosive esophagitis by e-mail.

Results: A total of 73 members answered the questionnaire (response rate, 18%). As initial management, 41% of respondents chose pharmacologic treatment, whereas 59% chose nonpharmacologic treatment. In the case of pharmacologic treatment, proton pump inhibitors were the preferred medication. The most common treatment duration was 4 weeks (43%), followed by 8 weeks (38%), and 6 months (11%). Sixty-two percent of the respondents recommended follow-up endoscopy annually, whereas 29% chose no endoscopic follow-up. Thirty-four percent of the respondents answered that they would talk about reflux-related sleep disturbances. Only 25% of the respondents explained the possibility of Barrett's esophagus or esophageal adenocarcinoma to their patients.

Conclusions: There are substantial practice variations in the management of asymptomatic erosive esophagitis in Korea.
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http://dx.doi.org/10.5009/gnl.2013.7.3.290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661960PMC
May 2013
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