2013 년대한임상건강증진학회춘계합동학술대회 연수강좌 소강당 소화성궤양진단및치료 박영규 분당제생병원가정의학과 목차 1. 소화성궤양의정의와역학 2. 소화성궤양의병인 3. 소화성궤양의증상 4. 소화성궤양의진단 5. 소화성궤양의치료 6. 헬리코박터균과제균치료 - 조직학적인용어 소화성궤양의정의 - 위장관벽조직의결손이점막하층또는그이하까지발생한상태 - 위산과펩신으로인해발생한병변 - 결손이점막층까지만국한된경우는미란 (erosion) 으로정의 소화성궤양의유병율 Pathogenesis of peptic ulcer 1) 미국 H. Pylori positive 환자 : 2% 내외 2) 국내 - 대한상부위장관-헬리코박터학회 : 대략 10% ( 소화성궤양의진단가이드라인 ) - 국내다기관연구 : 18.0~20.2% 3) 아시아권 - 대만 : 6,457명의수검자대상으로한연구 10.9% 166
소화성궤양진단및치료 / 박영규 Acid Pepsin Bile H.Pylori Drug Alcohol Mucus Bicarbonate Blood flow PG NO ACID NO ULCER 공격인자 방어인자 H. pylori infection No acid, No ulcer Pathogenesis of peptic ulcer Hostile Factors Peptic ulcer and H. pylori H. pylori NSAIDs Other 92% 70% duodenal ulcer gastric ulcer H. pylori and duodenal ulcer recurrence Seroprevalence of Helicobacter pylori in South Korea 80 Probability of Remaining in Remission (%) antibiotics placebo P<0.001 70 60 50 40 30 20 10 66.9 69.4 59.6 61.9 64.3 56.5 Week after Treatment 0 Total Male Female 1998 2005 Hentschel E. NEJM. 1993 Seroprevalence of Helicobacter pylori in South Korea. Helicobacter 2007;12:333-40 167
2013 년대한임상건강증진학회춘계합동학술대회 Seroprevalence of Helicobacter pylori in South Korea NSAID-induced gastric ulcer (aspirin) 90 80 70 60 50 40 30 20 10 0 74 78.5 74 71 61.3 65.6 64.8 54.3 45.8 49.4 26.3 12.5 67 59.7 16-19 20-29 30-39 40-49 50-59 60-69 70-1998 2005 Seroprevalence of Helicobacter pylori in South Korea. Helicobacter 2007;12:333-40 H.Pylori induced 168
소화성궤양진단및치료 / 박영규 COX-1 & COX-2 Risk factors for NSAID-induced gastro-duodenal ulceration Established Advanced age History of ulcer Concomitant use of steroid High-dose NSAIDs Multiple NSAIDs Concomitant use of anticoagulant Serious or multisystem disease possible Concomitant infection with H. pylori Cigarette smoking Alcohol consumption Miscellaneous pathogenic factors of peptic ulcer Cigarette smoking Genetic predisposition Psychological stress Diet Specific chronic disorders Systemic mastocytosis, chronic pulmonary disease, CRF, LC, nephrolithiasis, antitrypsin deficiency. Symptoms Clinical Features of Peptic Ulcer Epigastric pain Duodenal ulcer 90 min to 3 h after a meal (hunger pain) 70% awakes the patient from sleep (between midnight and 3 A.M.) frequently relieved by antacids or food Gastric ulcer precipitated by food Nausea and weight loss occur more common 169
2013 년대한임상건강증진학회춘계합동학술대회 Symptoms The mechanism of abdominal pain in ulcer : unknown. - Acid-induced activation of chemical receptors in the duodenum - Enhanced duodenal sensitivity to bile acids and pepsin - Altered gastroduodenal motility Suggestion of ulcer complication Dyspepsia constant, not relieved by food or antacids, or radiates to the back penetrating ulcer (pancreas) Sudden onset of severe, generalized abdominal pain perforation Pain worsening with meals, nausea, and vomiting of undigested food gastric outlet obstruction Tarry stools or coffee ground emesis bleeding 감별진단 소화성궤양의진단 기능성위장관질환 (FGID) Functional dyspepsia(fd), Non-ulcer dyspepsia(nud) 위암같은소화기계질환 관상동맥질환 협심증, 심근경색 소화성궤양의진단을위해시행할수있는검사 Endoscopy UGIS 췌장질환 급성췌장염, 만성췌장염 담도계질환 급성담낭염, 만성담낭염 정신적질환 신경증, 신체화장애 UGIS 170
소화성궤양진단및치료 / 박영규 상부위장관내시경 (= 위내시경 ) 검사 1 검사의민감도와정확도가우수 2 촬영영상이시각적이어서환자에게설명하기가용이 ( 의사도이해하기가편함 ) 3 악성종양을감별하기위한조직검사 4 헬리코박터균검사가능등의장점 헬리코박터파이로리검사 Invasive Method Invasive Sensitivity(%) Specificity(%) Advantage Disadvantage Non-invasive Method Non-invasive Sensitivity(%) Specificity(%) Advantage Disadvantage Rapid urease test 80-95 95-100 Histology 90-95 95-98 Culture 80-90 100 Inexpensive rapid results Excellent sensitivity and specificity Excellent specificity antibiotic sensitivities Low sensitivity in Post-treatment Expensive infrastructure and trained personnel Expensive difficult to perform low sensitivity 양성자펌프억제제 (PPI) 는최소 1~2주 Inexpensive 항생제는최소 2~4주중지후검사시행 Serologic test 80-95 80-95 widely available Urea breath test Stool antigen test 90-95 86-95 90-95 90-95 Very good NPV active H. pylori infection Useful before and after therapy active H. pylori infection Useful before and after therapy PPV depend on prevalence Not useful after H. pylori Therapy Reimbursement and availability Polyclonal test less well validated Unpleasantness American College of Gastroenterology guideline on the management of Helicobacter pylori infection. The American Journal of Gastroenterology 2007;102:1808-25. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. The American Journal of Gastroenterology 2007;102:1808-25. Hemorrhage complication Perforation obstruction 171
2013 년대한임상건강증진학회춘계합동학술대회 Treatment: medical Treatment of Peptic Ulcers Acid Neutralizing / Inhibitory Drugs Antacids H 2 Receptor Antagonists Proton Pump Inhibitors Cytoprotective agent Bismuth Sucralfate Prostaglandin Analogues Therapy of H. pylori Therapy of NSAID-Related Gastric or Duodenal Injury. Treatment: antacids Rarely used as the primary therapeutic agent For symptomatic relief of dyspepsia Aluminum hydroxide: constipation Magnesium hydroxide: loose stools Commonly used antacids (e.g., Maalox, Mylanta) combination of both aluminum and magnesium hydroxide in order to avoid these side effects Calcium carbonate and sodium bicarbonate Treatment: H 2 receptor antagonist Cimetidine, ranitidine, famotidine, and nizatidine Different potency, all will significantly inhibit basal and stimulated acid secretion to comparable levels when used at therapeutic doses Renal excretion: reduce dose in renal impairment Adverse effects uncommon, but Cimetidine serum aminotransferases, creatinine, and serum prolactin (gynaecomastia), confusion, psychosis Be careful!!! Cimetidine inhibits Cytochrome P450 isoenzymes: inhibits metabolism of warfarin, phenytoin, carbamazepine, prednisolone, theophylline careful monitoring Ranitidine, famotidine, nizatidine produce clinically insignificant inhibition Treatment: PPI Covalently bind and irreversibly inhibit H+,K+- ATPase Potently inhibit all phases of gastric acid secretion Onset of action : 2 and 6 h after administration Duration of inhibition lasting up to 72 to 96 h 172
소화성궤양진단및치료 / 박영규 PPI vs H 2 RA : Effect on persistent or recurrent bleeding of peptic ulcer without (top) and with (bottom) adjunct endoscopic therapy Treatment: sucralfate (Ulcermin ) Binding primarily to sites of active ulceration providing a physicochemical barrier Trophic effect by binding growth factors enhance prostaglandin synthesis stimulate mucous and bicarbonate secretion Enhance mucosal defense and repair SE: Constipation (2 to 3%). Gisbert. Aliment Pharmacol Ther 2001;15(7):917-926 질문 : 위궤양이위암으로발전하는가? 소화성궤양의치료에서고려할사항 양성위궤양이위암으로발전하지는않는다. 양성위궤양과위암의공통적인위험인자가있다. 위암이처음에양성위궤양으로잘못진단되어지는수가있다. Long-term treatment for prevention of recurrent bleeding from peptic ulcer - Hp eradication vs antisecretory treatment 헬리코박터제균치료 Gisbert. Aliment Pharmacol Ther 2004;19(6):617-629 173
2013 년대한임상건강증진학회춘계합동학술대회 2007 American College of Gastroenterology Guideline Established Active peptic ulcer disease Confirmed history of peptic ulcer disease Gastric MALT lymphoma (low grade) After endoscopic resection of early gastric cancer Uninvestigated dyspepsia (depending upon H. pylori prevalence) Controversial Indications Non-ulcer dyspepsia Gastro-esophageal reflux disease Persons using NSAIDs Unexplained iron deficiency anemia Populations at higher risk for gastric cancer Indications 2009 대한 Helicobacter 및상부위장관연구학회 Definite indication 증거수준권고등급 H. pylori 에감염된소화성궤양환자위의저악성도 B-세포 MALT 림프종조기위암 높음 높음 Highly recommended indication 위암의가족력이있는경우 중등도 중등도 Possible indication 조직학적검사위축성위염이있거나 Serum pepsinogen I/II ratio 가 3 이하인경우 H. pylori 양성인 dyspepsia 환자장기간 NSAID 를복용해야하는환자 H. pylori 에감염된환자의배우자나자녀역류성식도질환으로장기간 PPI 유지요법을해야하는환자 H. pylori 치료를원하는사람 매우낮음 매우낮음 X X X X? Treatment regimen (First-Line) Regimen Duratio n 2005 Maastricht III Consensus Report Eradicat ion rate Comment PPI + AMX + CLA or MET 7-14 14 day treatment is more effective than 7 days In populations with less than 15-20% clarithromycin resistance PPI + CLA + MET Bismuth containing quadruple therapy 10-14 Alternative In populations with less than 40% metronidazole resistance Regimen Treatment regimen (First-Line) Durati on Eradicati on rate Comment 2007 American college of gastroenterology PPI + AMX + CLA 10 14 70-85% Consider in nonpenicillin allergic patients who have not previously received a macrolide PPI + CLA + MET 10 14 70-85% Consider in penicillin allergic patients who have not previously received a macrolide or are unable to tolerate bismuth quadruple Therapy Bismuth containing quadruple therapy PPI + AMX 1000 mg (BID) followed by: PPI + CLA 500mg (BID) + Tinidazole 500 mg (BID) 10 14 70-85% Consider in penicillin allergic patients 5 5 > 90% Requires validation in North America Antibiotic resistance among H. pylori isolates in Korea 2 개이상항생제에대한내성비율 1987 1994 2003 66.2 1987 1994 2003 24 33 47.7 61.1 52.9 1987 1994 2003 33.3 32.3 33.8 The Effects of Resistance of Amoxicillin and Clarithromycin on the Eradication Rate Amoxicillin Clarithromycin No. of patients Success(%) Failure(%) 18.5 21.5 21.5 Susceptible Susceptible 31 97 3 13.8 12.3 13.9 Resistant Susceptible 5 40 60 5.6 5.9 5.9 2.8 0 0 0 0 0 0 0 0 Amoxicillin Clarithromycin Metronidazole Tetracycline Azithromycin Ciprofloxacin Levofloxacin Moxifloxacin Susceptible Resistant 5 0 100 Resistant Resistant 2 0 100 Antibiotic resistance of Helicobacter pylori isolated from Korean patients. Korean J Gastroenterol 2006; 47: 337-49. 174
소화성궤양진단및치료 / 박영규 Treatment regimen (Second-Line) regimen duration Eradication Rate comment 2009 대한 Helicobacter 및상부위장관연구학회 PPI (BID) + Denol 120mg (QID) + MET 0.5g (TID) + TET 0.5g (QID) 7-14 2005 Maastricht III Consensus Report PPI + Bismuth + MET + TET 7 - Minimum for 7 days Remain the best second choice PPI + AMX or TET + MET If Bismuth is not available 2007 American college of gastroenterology PPI + Bismuth + MET + TET 7 68% Accessible, cheap but high pill count and frequent mild side effects Levofloxacin triple therapy PPI + AMX 1 g (BID) + LVF 500 mg (QD) 10 87% Requires validation in North America 175