인체 담도내 Helicobacter pylori 검출과 그 의의

Helicobacter pylori (이하 H. pylori로 약함) 감염은 위염, 위궤양, 십이지장궤양, 위암, 위의 MALT (mucosa associated lymphoid tissue) 림프종 등 광범위한 위장질환과 밀접하게 관련되어 있으나, H. pylori의 성장은 담즙에 의해 억제되기 때문에 간담도계 질환과는 관련이 없는 것으로 알려져 왔었다. 그러나 최근 mouse나 hamster 등의 담도내에서 몇가지 종류의 Helicobacter species (이하 spp.로 약함)가 발견되었고, 사람의 담즙내에서도 H. pylori의 부분적인 DNA 염기서열이 발견되어 사람의 담도내에서도 Helicobacter spp.가 생존할 가능성을 시사하고 있다. 본 연구에서는 우리나라 최초로 사람의 담즙, 담도 조직 및 담석 모두에서 H. pylori의 존재 유무를 알아보았고, 담즙의 성분 분석을 통해 H. pylori의 생존 여부가 담즙의 구성 성분과 연관이 있는지에 대해 연구하고자 하였으며 그 결과는 다음과 같았다. 1. 26 KDa 표면 단백항원에 대한 시발체(primer)로 PCR을 시행한 결과 43예(간내 담석증 30예, 담도암 9예, 양성 담도 협착 2예, 다발성 담도 유두종 1예, 담도 낭종암 1예)의 간내 담즙 중 4예(9.3%)에서 298 bp의 product를 확인할 수 있었고 이들은 모두 간내 담석 환자였다. 그러나 간내 담도 조직에서는 43예 모두에서 PCR 음성이었다. 또한 간내 담즙에서 urease A 유전자에 대한 시발체로 PCR을 시행한 결과 43예 중 5예(11.6%)에서 258 bp의 product를 확인할 수 있었고 이들 또한 모두 간내 담석 환자였으며, 간내 담도 조직에서 시행한 urease A 유전자에 대한 PCR 결과는 43예 중 1예(2.3%)에서만 양성이었다. 따라서 간내 담즙에서 26 KDa 표면 단백항원 또는 urease A 유전자의 시발체 어느 하나에 대해 양성을 보인 경우는 7예(16.3%)였으며, 두 시발체에 대해 모두 양성을보인 경우는 2예(4.7%)였다. 2. 담즙내에서 urease A 유전자에 대해 양성을 보인 5예의 PCR product를 직접 염기서열 분석법을 통해 비교분석하였다. 담도 조직에서 urease A 유전자에 대해 PCR 양성을 보인 1예의 염기서열 분석 결과는 같은 예의 담즙내 PCR product의 염기서열 분석 결과와 일치하였다. 3. 담낭 질환 환자군 23예와 대조군 8예의 담낭 담즙 및 담낭 조직에서 26 KDa 표면 단백항원 및 urease A 유전자에 대해 시행한 PCR 결과는 모두 음성이었다. 4. 간내 담석 7예에서 26 KDa 표면 단백항원 및 urease A 유전자에 대해 시행한 PCR 결과도 모두 음성이었다. 5. 담도 조직에서 시행한 CLO test , 병리조직학적 검사 및 담즙내의 H. pylori에 대한 배양검사는 전예에서 모두 음성이었다. 6. 경피경간 담도경(Percutaneous transhepatic cholangioscopy; PTCS)을 시행받은 군에서 간내 담즙의 pH는 담즙내 H. pylori PCR 양성군(n=7)에서 음성군(n=36)에 비하여 의미있게 낮았으나 (7.39±0.52 vs. 7.72±0.16, p<0.05), 콜레스테롤, 총 담즙산 및 인지질치는 유의한 차이가 없었다. 본 연구에서는 간내 담즙 43예 중 7예(16.3%)에서 H. pylori DNA를 검출하였으며, 이들은 모두 간내 담석 환자였다. 그러나 담도 조직에서는 간내 담도 조직 43예 중 1예(2.3%)에서만 H. pylori DNA가 검출되어 H. pylori의 담도 조직내 집락화(colonization) 가능성은 적을 것으로 보이며, 이는 간내 담석의 H. pylori에 대한 PCR이나 담즙의 H. pylori 배양에서 모두 음성의 결과를 보인 것으로 뒷받침 될 수 있다. 또한 담즙내 pH의 변화도 간내 담석에 동반된 담도염으로 인한 이차적 변화로 생각된다. 따라서 인체 담도계에서의 H. pylori의 생존 가능성은 적으며, 또한 담도 질환의 원인 인자로서의 역할을 할 가능성은 희박할 것으로 사료된다. ; Recently several authors have reported that H. pylori DNA could be found in the bile from patients with diseased bile duct, although its clinical significance is still unclear. The aim of this study was to investigate the existence of H. pylori in the biliary system of Koreans including bile, biliary epithelium and gallstones. The present study analyzed intrahepatic bile samples obtained via percutaneous tranhepatic biliary drainage tube from 43 cases (PTCS group; hepatolithiasis 30, cholangiocarcinoma 9 and others 4), gallbladder bile samples collected during cholecystectomy from 23 cases (CCT group; cholelithiasis 16 and gallbladder polyp 7) and gallbladder bile samples at incidental cholecystectomy from 8 cases (control group; stomach cancer 8). Furthermore, intrahepatic bile duct tissues were obtained by cholangioscopic biopsy from 43 cases (PTCS group) and gallbladder tissues were taken at operation from 31 cases (CCT and control group). H. pylori in the bile and the bile duct tissue smaples were examined by PCR with 26 KDa surface protein antigen and urease A gene primer. In 7 cases of hepatolithiasis, gallstones were collected and DNA was extracted from the inner side of the stones for subsequent H. pylori PCR. To further verify the specificity of PCR analysis, partial sequences of the PCR products from the positive samples were analyzed by direct sequencing. The chemical composition and pH of intrahepatic bile were analyzed. PCR was positive in 4/43 (9.3%) by using 26 KDa surface protein antigen primer and 5/43 (11.6%) by using urease A gene primer in the bile from PTCS group. All PCR positive cases were seropositive for H. pylori and they were the patients with intrahepatic duct stones. H. pylori DNA was detected in only one bile duct tissue sample (2.3%) from a patient with intrahepatic duct stones in PTCS group. PCR of gallbladder bile and tissue was negative in CCT and control group. H. pylori DNA was not detected in 7 cases of intrahepatic duct stones by PCR. As a result of direct sequencing of PCR products, several mutations were identified in the urease A gene. Upon analysis of intrahepatic bile, pH was significantly lower in cases with H. pylori PCR positive (n=7) than PCR negative cases (n=36) (7.39±0.52 vs. 7.72±0.16, p<0.05), while cholesterol, total bile acid and phospholipid were similar between the two. In conclusion, it is the least likely that H. pylori live in the human biliary tree. And there is little possibility that H. pylori have a pathogenic role in human biliary diseases.논문개요 ------------------------------------------------------------ ⅷ I. 서론 ------------------------------------------------------------- 1 II. 연구대상 및 방법 ------------------------------------------------ 3 A. 연구대상 -------------------------------------------------------- 3 B. 방법 ------------------------------------------------------------ 3 1. 담즙, 담도 조직 및 담석의 채취 --------------------------------- 3 2. H. pylori 감염의 확인 ------------------------------------------ 5 3. DNA 추출 ------------------------------------------------------- 5 4. 중합효소 연쇄반응 ---------------------------------------------- 6 5. 직접 염기서열 분석 --------------------------------------------- 6 6. 담즙의 성분 분석 ----------------------------------------------- 8 7. 통계 처리 ------------------------------------------------------ 8 III. 결과 ----------------------------------------------------------- 9 A. H. pylori 감염 -------------------------------------------------- 9 B. 중합효소 연쇄반응 ----------------------------------------------- 9 C. Helicobacter urease A 유전자의 직접 염기서열 분석 --------------- 16 D. 담즙의 성분 분석 ------------------------------------------------ 16 IV. 고찰 ------------------------------------------------------------ 19 V. 결론 ------------------------------------------------------------- 23 참고문헌 ------------------------------------------------------------ 25 영문초록 ------------------------------------------------------------ 3

The prevalence of colorectal neoplasia in patients with gastric cancer: A korean association for the study of intestinal disease (KASID) study

GOALS: The goal of this study was to determine the prevalence of colorectal neoplasia, using colonoscopy surveillance, in a cohort of patients with gastric cancers. BACKGROUND: The association between gastric cancer and colorectal cancer has been conflicting. STUDY: A total of 543 patients (males, 362; females, 181) with gastric cancer were matched with 2 persons from the population without a diagnosis of gastric cancer as confirmed by endoscopy according to age (±2y), sex, date of colonoscopy examination (±2wk), and endoscopist. Main Outcome was the prevalence of colorectal neoplasia diagnosed by colonoscopy. RESULTS: A significantly higher colorectal cancer prevalence was found in the gastric cancer group, that is, 19 of 543 (3.5%) versus 14 of 1086 (1.3%; P<0.001). The odds of developing colorectal cancer were higher in the presence of gastric cancer (odds ratios, 3.46; 95% confidence interval: 1.51-7.91). Four of the 119 (3.4%) gastric cancer patients below 50 years of age had colorectal cancer in contrast with no cases in the matched controls. The prevalence of colorectal adenoma was higher in the gastric cancer group, with a prevalence of 215 in 543 (39.6%) versus 311 in 1086 (28.6%; P<0.001). The risk of adenoma was also greater among gastric cancer patients (odds ratios, 1.76; 95% confidence interval: 1.34-2.25). CONCLUSIONS: Our data reveal a higher prevalence and risk of colorectal cancer in patients diagnosed with gastric cancer, particularly in patients below 50 years of age. Additional studies are needed to explore the geographical differences in the association between gastric cancer and colon cancer. Copyright © 2010 by Lippincott Williams & Wilkins

What is the optimal timing of bowel preparation for video capsule endoscopy?

[No abstract available

A case of oral ingestion of elemental mercury

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Importance of a Diversity Committee in Advancing the Korean Society of Gastroenterology: A Survey Analysis

Background/Aims: The numbers of women, young doctors, and foreigners in the medical field have increased continuously. On the other hand, the environment for these minority groups has not improved, particularly in Eastern countries. The authors aimed to increase the awareness of the importance of a Diversity Committee in the Korean Society of Gastroenterology (KSG) by an analysis of a survey. Methods: From January to February in 2019, a survey was conducted on physicians and a few medical students by googling. The questionnaire consisted of the target doctors of the Diversity Committee, purpose, specific activities, and expected effects of Diversity Committee to the KSG. The participants requested to respond with yes/no or a 5-point scale. Results: A total of 202 participants completed the questionnaire, and 93.5% (189/202) were medical specialists. The proportion of males was 61.9% (125/202), and 39.6% (80/202) and 36.1% (73/202) participants were in their 30s and 40s, respectively. A total of 174 participants (86.1%) agreed with the necessity of a Diversity Committee, and 180 participants (89.1%) answered this committee would help advance the KSG with significant differences between males and females (80.8% vs. 94.8%, p=0.006; 84.8% vs. 96.1%, p=0.011). Similarly, there were significant differences in the responses according to sex in most questions. Conclusions: Most participants of the survey expected a contribution of the Diversity Committee to the advancement of the KSG. On the other hand, in most of the priorities of the target, purpose, specific activities, and expected effects of the Diversity Committee, there was a difference in the perceptions between males and females. Therefore, continuous efforts are needed to reduce the differences within the KSG

Bowel preparation for capsule endoscopy: A prospective randomized multicenter study

Background/Aims: The ability to visualize the small bowel mucosa by capsule endoscopy is limited. Moreover, studies involving small-bowel preparation with purgative drugs have failed to establish which preparations produce better images and higher diagnostic yields. The aim of this study was to evaluate the efficacies and diagnostic yields of different bowel preparations. Methods: A cohort of 134 patients with suspected small bowel disease was randomly assigned to 3 groups. Patients in group A (n=44) fasted for 12 h before being administered an M2A capsule (Given Imaging, Yoqneam, Israel). Patients in group B (n=45) were asked to drink two doses of 45 mL of sodium phosphate (NaP) with water during the afternoon and evening on the day before the procedure and to drink at least 2 L of water thereafter. Patients in group C (n=45) drank 2 L of a polyethylene glycol (PEG) lavage solution the evening before the procedure. Results: Overall cleansing of the small bowel was adequate in 43% of patients in group A, 77% of those in group B, and 56% of those in group C (group A vs group B, p=0.001). Diagnoses for obscure gastrointestinal bleeding were established in 9 patients (39%) in group A, 16 patients (69%) in group B, and 14 patients (50%) in group C. No significant difference in diagnostic yield was observed between groups. Conclusions: Bowel preparation with NaP for capsule endoscopy improved small-bowel mucosal visualization when compared to 12-h overnight fasting

Effect of Helicobacter pylori eradication on the development of reflux esophagitis and gastroesophageal reflux symptoms: A nationwide multi-center prospective study

Background/Aims: A two-year, prospective, nationwide multicenter study was undertaken to evaluate the effect of Helicobacter pylori eradication on the development of reflux esophagitis (RE) and gastroesophageal reflux disease (GERD) symptoms in the Korean population. Methods: In total, 1,489 subjects without RE were enrolled at the outpatient clinics of 12 tertiary hospitals nationwide, and 452 subjects underwent follow-up (F/U) for 2 years to evaluate the development of RE and GERD symptoms. Results: RE was found in 33 subjects (7.3% of 452 subjects) and 14 subjects (7.3% of 192 subjects) during the first and second year of F/U, respectively. H. pylori status was not associated with the development of RE. RE was found in six (9.0%) of 67 H. pylorinegative patients, in 26 (11.2%) of 233 eradicated subjects and in eight (7.0%) of 114 noneradicated subjects (p=0.532). Multivariate analysis showed that age ≥60 years (odds ratio [OR], 7.11; 95% confidence interval [CI], 1.92 to 26.41), alcohol consumption (OR, 4.43; 95% CI, 1.03 to 19.19) and F/U cholesterol levels ≥200 mg/dL (OR, 5.03; 95% CI, 1.32 to 19.17) were significant risk factors for the development of RE. There was no significant difference in the development of GERD symptoms or weight according to H. pylori status during the 2-year F/U. Conclusions: Eradication of H. pylori did not affect the development of reflux esophagitis or GERD symptoms among patients in outpatient gastroenterology clinics in South Korea

Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatmentnaive patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection

Quality indicators for small bowel capsule endoscopy

Capsule endoscopy (CE) enables evaluation of the entire mucosal surface of the small bowel (SB), which is one of the most important steps for evaluating obscure gastrointestinal bleeding. Although the diagnostic yield of SB CE depends on many clinical factors, there are no reports on quality indicators. Thus, the Korean Gut Image Study Group (KGISG) publishes an article titled, “Quality Indicators for Small Bowel Capsule Endoscopy” under approval from the Korean Society of Gastrointestinal Endoscopy (KSGE). Herein, we initially identified process quality indicators, while the structural and outcome indicators are reserved until sufficient clinical data are accumulated. We believe that outcomes of SB CE can be improved by trying to meet our proposed quality indicators. © 2017 Korean Society of Gastrointestinal Endoscopy

Long-Term Recurrence Rates of Peptic Ulcers without Helicobacter pylori

Background/Aims: The purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without Helicobacter pylori. Methods: We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a H. pylori-negative group (HP-negative group), and a group of patients with untreated H. pylori (HP noneradicated group). We compared the recurrence rates of PUD in these two groups and analyzed the factors that affected ulcer recurrence. Results: Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease. Conclusions: The 5-year cumulative probability of PUD recurrence without H. pylori infection after a long-term follow-up was 36.4% and the factors that affected recurrence were elder, male, and comorbid chronic kidney disease