1. #1014 Ulcer Disease Update January 25 to 28 Hagop S. Mekhjian, MD Professor of Internal Medicine Division of Digestive Diseases Medical Director, OSU Hospitals E. Christopher Ellison, MD Zollinger Professor of Surgery and Interim Chair, Department of Surgery The Ohio State University Medical Center

2. 1 Hagop S. Mekhjian, MD Professor of Internal Medicine Division of Digestive Diseases Medical Director, OSU Hospitals

3. Profile 55 year old Physician 2 melanic stools Fine otherwise History Mild coronary artery disease Using beta blocker Takes 1 aspirin / day 55 year old Physician 2 melanic stools Fine otherwise History Mild coronary artery disease Using beta blocker Takes 1 aspirin / day 2

4. Profile Examination Vital signs stable Hemoglobin 10.5g Symptoms No pain or indigestion Evaluation Performed fiber optic endoscopy Showed active duodenal ulcer Biopsy positive for H. pylori Examination Vital signs stable Hemoglobin 10.5g Symptoms No pain or indigestion Evaluation Performed fiber optic endoscopy Showed active duodenal ulcer Biopsy positive for H. pylori 2 A

5. Profile Treatment Immediately started on omeprazole Placed on amoxicillin and clarithromycin for 14 days Follow up Follow up 6 weeks later Duodenal ulcer completely healed Asymptomatic Normal hemoglobin Treatment Immediately started on omeprazole Placed on amoxicillin and clarithromycin for 14 days Follow up Follow up 6 weeks later Duodenal ulcer completely healed Asymptomatic Normal hemoglobin 2 B

6. Peptic Ulcer Disease 500,000 new cases per year 4 million recurrences 4 million physician visits $5 - 10 billion annual cost Decreased mortality Increasing costs 9,000 deaths >130,000 operations 500,000 new cases per year 4 million recurrences 4 million physician visits $5 - 10 billion annual cost Decreased mortality Increasing costs 9,000 deaths >130,000 operations 3

7. Hospitalization and Mortality Trends Decreased for uncomplicated duodenal ulcer Bleeding or perforation hospitalization unchanged Increase in elderly (NSAIDS) Mortality 1 per 100,000 population - 3-4 fold decrease Decreased for uncomplicated duodenal ulcer Bleeding or perforation hospitalization unchanged Increase in elderly (NSAIDS) Mortality 1 per 100,000 population - 3-4 fold decrease 4

8. Epidemiology H. pylori Nonsteroidals Genetics - familial - Incidence (20-50% vs controls 10%) All genetic markers likely relate to susceptibility of infection with H. pylori H. pylori Nonsteroidals Genetics - familial - Incidence (20-50% vs controls 10%) All genetic markers likely relate to susceptibility of infection with H. pylori 5

9. Peptic Ulcer Other Associations Zollinger Ellison Syndrome Systemic mastocytosis MEN I COPD CRF Cirrhosis Kidney stones Alpha-antitrypsin deficiency Zollinger Ellison Syndrome Systemic mastocytosis MEN I COPD CRF Cirrhosis Kidney stones Alpha-antitrypsin deficiency 6

10. Pathophysiology of Gastric Ulcers NSAIDS H. pylori Bile reflux Gastric motility NSAIDS H. pylori Bile reflux Gastric motility 7

11. Smoking and Peptic Ulcer Increased incidence Co-factor with H. pylori Increased complication COPD increased risk Increased incidence Co-factor with H. pylori Increased complication COPD increased risk 8

12. Etiologic Role of H. Pylori Peptic Ulcer Natural history of H. pylori gastritis - 11% peptic ulcer in 10 years - 1% controls Association - age independent - 90% duodenal ulcer; H. pylori positive - 70-90% gastric ulcer; H. pylori positive Treatment outcome of H. pylori - Eradicates recurrent duodenal ulcer and gastric ulcer - Reduction in re-bleeding Natural history of H. pylori gastritis - 11% peptic ulcer in 10 years - 1% controls Association - age independent - 90% duodenal ulcer; H. pylori positive - 70-90% gastric ulcer; H. pylori positive Treatment outcome of H. pylori - Eradicates recurrent duodenal ulcer and gastric ulcer - Reduction in re-bleeding 9

13. Peptic Ulcer Clinical Presentation Abdominal discomfort - Epigastric - Nocturnal - Relief by food or antacids Bleeding or perforation initial presentation - 10% Abdominal discomfort - Epigastric - Nocturnal - Relief by food or antacids Bleeding or perforation initial presentation - 10% 10

14. Peptic Ulcer Diagnosis Endoscopy gold standard Single contrast x-rays worthless Double contrast x-rays valuable Endoscopy gold standard Single contrast x-rays worthless Double contrast x-rays valuable 11

15. Diagnosis of Helicobacter Pylori Endoscopy Duodenal ulcer highly predictive Antral nodularity specific (96%), but insensitive (32%), “plucked chicken” Biopsy - two antral, antral and angle ~ 100% sensitivity Prior therapy important Endoscopy Duodenal ulcer highly predictive Antral nodularity specific (96%), but insensitive (32%), “plucked chicken” Biopsy - two antral, antral and angle ~ 100% sensitivity Prior therapy important 12

16. Diagnosis of Helicobacter Pylori Histology is Gold Standard Highly reproducible readings Giemsa stain 96% specific Acute or chronic inflammation always presents Immunohistochemical stains highly reliable Histology is Gold Standard Highly reproducible readings Giemsa stain 96% specific Acute or chronic inflammation always presents Immunohistochemical stains highly reliable 13

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18. Treatment of Helicobacter Pylori Resistance to metronidazole high - South Korea 95% Resistance to clarithromycin ~ 10% Resistance to tetracycline rare Resistance to metronidazole high - South Korea 95% Resistance to clarithromycin ~ 10% Resistance to tetracycline rare 15

19. Cure for H. Pylori BMT for 14 Days Pepto-Bismol 2 tabs 4 x day Metronidazole 250 mg 4 x day Tetracycline 500 mg 4 x day plus H 2 RA for 4 weeks Pepto-Bismol 2 tabs 4 x day Metronidazole 250 mg 4 x day Tetracycline 500 mg 4 x day plus H 2 RA for 4 weeks 16

20. Cure for H. Pylori OAC for 14 Days Omeprazole 20 mg 2 x day Amoxicillin 1 gram 2 x day Clarithromycin 500 mg 2 x day Omeprazole 20 mg 2 x day Amoxicillin 1 gram 2 x day Clarithromycin 500 mg 2 x day 17

21. Cure for H. Pylori LAC for 14 Days Lansoprazole 30 mg 2 x day Amoxicillin 1 gram 2 x day Clarithromycin 500 mg 2 x day Lansoprazole 30 mg 2 x day Amoxicillin 1 gram 2 x day Clarithromycin 500 mg 2 x day 18

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23. Peptic Ulcer Complications Hemorrhage 15% Perforation 7% Penetration ? Gastric outlet obstruction 2% Hemorrhage 15% Perforation 7% Penetration ? Gastric outlet obstruction 2% 20

24. NSAIDS and Bleeding Ulcers Gastric ulcers 10 - 20 x increase Duodenal ulcers 5 - 15 x increase * Increase risk proportional to daily dose of NSAID Gastric ulcers 10 - 20 x increase Duodenal ulcers 5 - 15 x increase * Increase risk proportional to daily dose of NSAID 21

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30. Risk Factors for GI Bleeding Age > 60 years Co-morbid medical illness Hematochezia or red blood aspirate Hypotension or shock Transfusion > 6 units of blood Rebleeding in hospitals Age > 60 years Co-morbid medical illness Hematochezia or red blood aspirate Hypotension or shock Transfusion > 6 units of blood Rebleeding in hospitals 27

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33. E. Christopher Ellison, MD Zollinger Professor of Surgery and Interim Chair, Department of Surgery The Ohio State University Medical Center 30

34. Profile Mr. Tidball Presented 18 years ago with ulcer Partial removal of stomach Condition Did well initially Then developed disphagia Early satiety caused vomiting Mr. Tidball Presented 18 years ago with ulcer Partial removal of stomach Condition Did well initially Then developed disphagia Early satiety caused vomiting

35. Profile Mr. Tidball Diagnostic tests UGI series Endoscopy Fasting serum gastrin level Diagnosis Gastric stasis with a marginal ulcer Mr. Tidball Diagnostic tests UGI series Endoscopy Fasting serum gastrin level Diagnosis Gastric stasis with a marginal ulcer 31

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37. Ulcer Disease Indications for Surgery Bleeding Perforation Obstruction Intractability Indications for Surgery Bleeding Perforation Obstruction Intractability 33

38. Ulcer Disease Operations Truncal vagotomy and pyloroplasty Truncal vagotomy and antrectomy - Billroth I - Billroth II Subtotal gastrectomy Highly selective vagotomy Operations Truncal vagotomy and pyloroplasty Truncal vagotomy and antrectomy - Billroth I - Billroth II Subtotal gastrectomy Highly selective vagotomy 34

39. Truncal Vagotomy 35

40. Antrectomy 36

41. Reconstruction After Antrectomy Billroth I Billroth II 37

42. Highly Selective Vagotomy 38

43. Duodenal Ulcer Disease Bleeding Endoscopic therapy - Injection - Heater probe - Clips Operation if - UNSTABLE - Rebleeding - > 6 units PRBC A major indication for surgery Endoscopic therapy - Injection - Heater probe - Clips Operation if - UNSTABLE - Rebleeding - > 6 units PRBC A major indication for surgery 39

44. Bleeding Duodenal Ulcer Method of Ligation 40

45. Perforated Ulcer Clinical presentation Free air on AAS (absent in 25%) Operative vs. non-operative treatment - Operation in most cases - NG decompression, antibiotics if “sealed” Mortality rate high if >24 hours between onset of symptoms and surgery Clinical presentation Free air on AAS (absent in 25%) Operative vs. non-operative treatment - Operation in most cases - NG decompression, antibiotics if “sealed” Mortality rate high if >24 hours between onset of symptoms and surgery 41

46. Duodenal Ulcer Disease Gastric Outlet Obstruction NG decompression Correct electrolytes Nutrition H-2 antagonist Proton pump inhibitor NG decompression Correct electrolytes Nutrition H-2 antagonist Proton pump inhibitor 42

47. Recurrent Ulcer Operation Incidence Vagotomy & Pyloroplasty 10 - 15% Vagotomy & Antrectomy 0 - 2% Subtotal Gastrectomy 2 - 5% Highly selective Vagotomy 10 - 20% Operation Incidence Vagotomy & Pyloroplasty 10 - 15% Vagotomy & Antrectomy 0 - 2% Subtotal Gastrectomy 2 - 5% Highly selective Vagotomy 10 - 20% 43

48. Recurrent Ulcer Etiology and Treatment Exclude ZES, PTH, etc Aggressive medical Rx Tailor operation - Revagotomy - Re-resection Exclude ZES, PTH, etc Aggressive medical Rx Tailor operation - Revagotomy - Re-resection 44

49. Postgastrectomy Syndromes Dumping syndrome Alkaline reflux gastritis Gastric stasis Loop syndromes Gastric remnant carcinoma Dumping syndrome Alkaline reflux gastritis Gastric stasis Loop syndromes Gastric remnant carcinoma 45

50. Dumping Syndrome Early Fluid shifts - Intravascular space - Bowel lumen Enteric peptides (Vasodilation) - Neurotensin - Serotonin - VIP - Motilin Fluid shifts - Intravascular space - Bowel lumen Enteric peptides (Vasodilation) - Neurotensin - Serotonin - VIP - Motilin 46

51. Dumping Syndrome Treatment Dietary modification - Consult dietician - Reduce carbohydrates Somatostatin (50-100 mcg subq TID ) - Reduces intestinal hypermotility - Increases fluid and electrolyte absorption - Inhibits enteric peptide secretion Acarbose (alpha glucosidase inhibitor 50-100 mg ac) reduces postprandial hyperglycemia Surgical treatment is roux-en-Y or pyloroplasty closure Dietary modification - Consult dietician - Reduce carbohydrates Somatostatin (50-100 mcg subq TID ) - Reduces intestinal hypermotility - Increases fluid and electrolyte absorption - Inhibits enteric peptide secretion Acarbose (alpha glucosidase inhibitor 50-100 mg ac) reduces postprandial hyperglycemia Surgical treatment is roux-en-Y or pyloroplasty closure 47

52. Post-Gastrectomy Syndromes Alkaline Reflux Gastritis Epigastric pain and bilious vomiting Incidence 15-20% Diagnosis - EGD & Bx ETIOLOGY - Decreased emptying - Poor clearance of bile - Bile irritation - Inflammatory infiltrate - Helicobacter pylori Epigastric pain and bilious vomiting Incidence 15-20% Diagnosis - EGD & Bx ETIOLOGY - Decreased emptying - Poor clearance of bile - Bile irritation - Inflammatory infiltrate - Helicobacter pylori 48

53. Alkaline Gastritis Combination Therapy Protect mucosa- sulcralfate Improve gastric emptying - Metaclopramide or cisapride - Erythomycin Bile salt binding - Aluminum hydroxide antacids - Cholestyramine Alter bile composition - Ursodeoxycholic acid Surgical treatment - Roux-en-Y Protect mucosa- sulcralfate Improve gastric emptying - Metaclopramide or cisapride - Erythomycin Bile salt binding - Aluminum hydroxide antacids - Cholestyramine Alter bile composition - Ursodeoxycholic acid Surgical treatment - Roux-en-Y Roux-en-Y 49

54. Gastric Stasis Uncommon condition (5 cases / year) Symptoms - Early satiety, vomiting, recurrent bezoars Etiology - Obstruction (recurrent ulcer, efferent loop) - Atony - Roux syndrome Treatment - Prokinetic agents - Completion gastrectomy (improves 50-70%) Uncommon condition (5 cases / year) Symptoms - Early satiety, vomiting, recurrent bezoars Etiology - Obstruction (recurrent ulcer, efferent loop) - Atony - Roux syndrome Treatment - Prokinetic agents - Completion gastrectomy (improves 50-70%) 50

55. Loop Syndromes Complication of Gastrojejunostomy Afferent loop syndrome - Nausea, non bilious vomiting, pain (episodic bilious emesis that relieves postprandial pain) - Caused by kink, herniation, volvulous - Diagnosis > US, CT, MRCP - Treatment > jejunojenostmy or BRII to BRI Efferent loop obstruction - Bilious vomiting, bezoars - Diagnosis > GI contrast studies, EGD - Treatment adhesiolysis, revision +/- resection Afferent loop syndrome - Nausea, non bilious vomiting, pain (episodic bilious emesis that relieves postprandial pain) - Caused by kink, herniation, volvulous - Diagnosis > US, CT, MRCP - Treatment > jejunojenostmy or BRII to BRI Efferent loop obstruction - Bilious vomiting, bezoars - Diagnosis > GI contrast studies, EGD - Treatment adhesiolysis, revision +/- resection 51

56. Gastric Remnant Carcinoma Etiology (P53, K-ras mutations) Enterogastric reflux H. pylori, EB virus N-nitrosocompounds Etiology (P53, K-ras mutations) Enterogastric reflux H. pylori, EB virus N-nitrosocompounds Incidence 0.8% >20 years postop Etiology Differentiate from loop syndromes, new ulcer EGD critical in dx. Requires completion gastrectomy Incidence 0.8% >20 years postop Etiology Differentiate from loop syndromes, new ulcer EGD critical in dx. Requires completion gastrectomy 52

57. Summary Mr. Tidball Surgical Procedure Completion gastrectomy with a Roux-en-Y esophagojejunostomy Necessary in a small number of patients who have had previous stomach surgery for ulcer disease Indications Gastric stasis with a marginal ulcer Mr. Tidball Surgical Procedure Completion gastrectomy with a Roux-en-Y esophagojejunostomy Necessary in a small number of patients who have had previous stomach surgery for ulcer disease Indications Gastric stasis with a marginal ulcer 53

58. Summary Mr. Tidball Prognosis Excellent Currently 2 months post-op and has gained nearly 10 pounds Vitamin B-12 regularly No other medications required Mr. Tidball Prognosis Excellent Currently 2 months post-op and has gained nearly 10 pounds Vitamin B-12 regularly No other medications required 53 A

59. Press: # (pound) + 71 on your phone keypad to speak with Dr. Mekhijian, and Dr. Ellison Visit OMEN OnLine http://omen.med.ohio-state.edu Visit OMEN OnLine http://omen.med.ohio-state.edu Questions on this subject? 54

60. #1015 Approach to Chronic Cough February 1 to 4 Jeffrey E. Weiland, MD Associate Professor of Clinical Internal Medicine Division of Pulmonary and Critical Care Medicine The Ohio State University Medical Center Ruairi Fahy, MD Clinical Instructor of Internal Medicine Division of Pulmonary and Critical Care Medicine The Ohio State University Medical Center NEXT WEEK