Clinical GI – Esophagus and Stomach PDF

Clinical GI – Esophagus and Stomach Leonard Mankin, MD, FACP Core Faculty Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW...

Clinical GI – Esophagus and Stomach Leonard Mankin, MD, FACP Core Faculty Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW [email protected]  Objectives Understand the mechanisms that contribute to Gastroesophageal Reflux Disease (GERD) and be familiar with treatment options Identify the common causes of dysphagia and understand workup and treatment Recognize the presentation of Peptic Ulcer Disease (PUD) and outline the major risk factors Understand the approach for investigating and treating PUD Identify the major causes for upper GI bleeding Recognize gastric motility disorders and understand their mechanism and treatment  Objectives I want you to learn and understand clinical medicine with emphasis on common entities I will try not to overwhelm you with too much information I wish to prepare you for board exams I plan to assess your knowledge with straightforward examination questions from lecture materials Outline Esophagus - Gastro-Esophageal Reflux Disease = GERD - Dysphagia Obstructive disorders Motility disorders Stomach - Peptic Ulcer Disease (PUD) - Upper GI Bleeding (UGIB) - Motility Disorders GERD Effortless regurgitation of stomach contents into the esophagus or mouth causing discomfort (heartburn, acid taste) GERD Most common GI complaint in outpatient clinics, about 9 million visits per year In US survey, 22% of respondents experienced GERD in last month Worse with delayed gastric emptying Worse with increased intra-abdominal pressure (e.g. ascites, pregnancy) 1. Gastroenterology 2018;154(2):267-276 2. Clin Gastroenterol Hepatol 2005;3(6):543-552 Lower Esophageal Sphincter (LES) dysfunction LES LES  GERD - symptoms Burning sensation (pyrosis) in retrosternal area, usually occurring after large meals and often after lying down at night Regurgitation of gastric contents with unpleasant taste in back of throat  GERD – A clinical diagnosis Diagnosis is based on classic symptoms and response to antacids or antisecretory therapy Testing is usually not necessary Reserve testing for refractory disease or “red flag” symptoms Red Flag symptoms Onset after age 60 Unexplained weight loss GERD for > 10 years Difficulty swallowing (dysphagia) or painful swallowing (odynophagia) Family hx of upper GI cancer Exertional symptoms - GERD is a common mimic for cardiac ischemia!  GERD – Tests for GERD Testing for refractory cases or “red flags”: - Ambulatory pH monitoring - Esophagogastroduodenoscopy (EGD) - Manometry - Upper GI series (esophogram) Ambulatory pH monitoring EGD EGD Normal LES EGD Normal LES GERD with stricture EGD Normal LES GERD with stricture Barrett’s esophagus GERD treatment GERD - Rx Step 1 = Lifestyle Step 2 = Meds Step 3 = Surgery  GERD Rx - Lifestyle Weight loss Stop smoking and drinking alcohol Eat smaller meals Avoid late night meals Avoid laying down after meals Elevate the head of the bed  GERD Rx – Foods to avoid Coffee (regular and decaf!) Chocolate Peppermint Soft drinks Fatty foods Spicy foods Tomatoes and citrus fruits/juices GERD - Pharmacotherapy  Step up vs. step down therapy Step-up therapy – progressive addition of agents from low to high potency until sx are controlled (antacids → H2 blockers → Proton Pump inhibitor (PPI)) Step-down therapy – start with PPI and then try to decrease therapy once under control. Use in patients with erosive esophagitis or more severe sx  GERD Rx - Antacids Available OTC and used PRN Neutralize stomach pH bringing rapid relief of heartburn sx Contain either magnesium trisilicate, aluminum hydroxide or calcium carbonate Safe in pregnancy  Antacids – Adverse effects Ca carbonate - Constipation - Milk-alkali syndrome (hypercalcemia, renal stones, AKI) - Rebound sx if used excessively Aluminum hydroxide - Constipation - Aluminum retention, especially in renal disease, can lead to osteomalacia Magnesium trisilicate - Diarrhea - Hypermagnesemia in renal disease  GERD Rx – Mucosal agents Enhance protective barrier in mucus layer of stomach Sucralfate – short duration and limited efficacy, mainly used during pregnancy Na alginate – polysaccharide from seaweed that forms a gum that absorbs acid GERD Rx – Histamine antagonists Histamine-2 Receptor Antagonists (e.g. ranitidine, famotidine, cimetidine) inhibit acid secretion by blocking H-2 receptors on gastric parietal cells Slower onset than antacids, but longer duration of action Adverse effects – potent Cytochrome P450 antagonists, esp. cimetidine GERD Rx – Proton Pump Inhibitors (PPIs) PPIs (e.g. omeprazole, esomeprazole, lansoprazole, pantoprazole) are the most potent inhibitors of gastric acid secretion Irreversibly bind the Hydrogen-Potassium ATPase pump Administer 30 minutes before the first meal of the day for maximal efficacy PPIs provide faster and better symptom relief than H2RAs  PPI – safety concerns Increased infection risk - C difficile - Pneumonia Malabsorption of vitamins/minerals - Magnesium hypomagnesemia - Calcium osteoporosis and fractures - Iron iron deficiency - B12 megaloblastic anemia Others: mortality, dementia, acute interstitial nephritis 2022 ACG Guidelines for PPI therapy Most patients with GERD can be managed without use of PPIs If GERD symptoms have resolved with an 8-week trial of PPI and the patient has no erosive esophagitis or Barrett esophagus, make efforts to discontinue or minimize dosage of PPI therapy Clevel Clin J Med 2022;89:700-703 GERD Rx – Potassium Channel Acid Blockers Blocks potassium channel of H+K+ ATPase pump. Advantages over PPIs: - Rapid onset of action - Neutralizes stomach acid after a single dose - Long half-life (daily dosing) - Not dependent on meals for activation Vonoprazan received FDA approval in July 2024 for treatment of GERD No RCTs comparing to PPIs yet Cost: $695 per 30-day supply1 1. www.drugs.com In 2015, sales of antacid meds topped $12 billion worldwide! N Engl J Med 2020;383:1961-1972  Clinical Case A 36-year-old woman presents with persistent heartburn sx and feelings of fullness in her chest What is the diagnosis? Hiatal Hernia and GERD  In the normal state, an increase in intra-abdominal pressure (e.g. cough, valsalva) results in equalization of pressure across the LES No Reflux With hiatal hernia, an increase in intra-abdominal pressure is not offset by pressure above the LES Reflux Surgical approaches to GERD  GERD Rx – Surgery Nissen Fundoplication - Wrapping fundus around lower esophagus and suturing, performed laparoscopically Transoral Incisionless Fundoplication (TIF) Magnetic Device insertion Transoral Incisionless Fundoplication (TIF) TIF makes an internal second flap below the G-E junction, creating a second barrier vs reflux Transoral Incisionless Fundoplication (TIF) A B C D Magnetic Sphincter Augmentation Magnetic Beads Magnetic Sphincter Augmentation Closed in resting state Expands with food bolus GERD - complications Esophageal stricture - May require balloon dilatation for dysphagia Hoarseness Chronic cough Aspiration – pneumonitis or pneumonia Barrett’s esophagus Adenocarcinoma Dysphagia  Normal Swallowing An incredibly complex process involving coordination of 6 cranial nerves, multiple muscle groups, subcortical and cortical nerve signals Three phases: 1. Oral – voluntary 2. Pharyngeal – voluntary and involuntary 3. Esophageal - involuntary J Am Geriatr Soc 2019;67:2643-2649 Definitions Dysphagia = difficulty swallowing Odynophagia = painful swallowing Globus = sensation that something is stuck in the throat  Solid vs Liquids? Dysphagia of solids - Implies a mechanical obstruction within the esophagus - May progress to dysphagia of solids + liquids Dysphagia of liquids and solids from the outset usually indicates a motility disorder  Causes of Dysphagia Obstructive Motility Disorders Esophagitis (+/- stricture) Achalasia - GERD Distal Esophageal Spasm - Eosinophilic esophagitis (DES) - Radiation and corrosives “Jackhammer” esophagus - Infections (candida, HSV) - Pills Systemic sclerosis Webs & rings Diverticula Benign tumors Malignancy Obstructive Causes of Dysphagia Esophageal Stricture - causes Chronic GERD is most common cause Radiation Chemical - Corrosive ingestion (lye) - Pills (esp. bisphosphonates!) Eosinophilic esophagitis Cancers Esophageal Stricture - Rx 5 cm stricture Balloon dilatation 1 month later  Eosinophilic Esophagitis Eosinophilic inflammation believed to be due to allergic response to food antigens Causes dysphagia and food impaction N Engl J Med 2015;373:1640-48  Eosinophilic Esophagitis - Dx Esophageal biopsy showing eosinophil- predominant inflammation EGD may reveal concentric rings (A) or small white eosinophilic abscesses (B) A B N Engl J Med 2015;373:1640-48  Eosinophilic Esophagitis - Rx Elimination diets (wheat, milk, nuts, soy, eggs and seafood) may help, but challenging Not an acid problem - PPIs are not helpful! Oral steroid sprays are effective Dilation in cases with significant esophageal narrowing N Engl J Med 2015;373:1640-48  Esophageal Webs and Rings Web = thin eccentric protrusion of the esophageal Web wall into the lumen Ring = concentric membrane of tissue that protrudes into ring the lumen  Plummer-Vinson syndrome Combination of atrophic glossitis, esophageal webs and iron deficiency anemia in Caucasian women Uncommon now (except on Board exams!), likely due to improved nutrition Associated with Esophageal SCCa – surveillance recommended Rx: Iron replacement  Esophageal Rings AKA “Schatzki’s ring” Common and usually benign May cause dysphagia of solids Dx: Barium esophagram > EGD Rx: Dilation if causing dysphagia  Esophageal diverticulum (Zenker’s) Saccular outpouching, usually found near the UES Posterior Splits through the cricopharygneus muscle posteriorly Presents with dysphagia, halitosis, throat gurgling, neck mass, regurgitation of food Zenker’s Diverticulum - Rx Zenker’s treated by cricopharyngeal myotomy with diverticulectomy Cricopharyngeus muscle Infectious Esophagitis Primarily seen in immunocompromised hosts (chemotherapy, transplant, AIDS) HSV, CMV and Candida most common HSV CMV Candida Esophageal Motility Disorders Achalasia A loss of normal peristalsis in the distal esophagus coupled by a failure of the LES to relax during swallowing Pathogenesis: Inflammatory degeneration of neurons in distal esophageal wall Usually congenital, but may be secondary to other diseases, esp. Chagas’ disease Causes dysphagia of solids and liquids Achalasia - Dx Manometry is gold standard, showing aperistalsis in distal 2/3 of esophagus and inability of LES to relax Esophagram may help, but low sensitivity and specificity EGD to rule out distal malignancy, termed “pseudoachalasia” w High-resolution Manometry  Type 1 Achalasia UES swallow Aperistalsis LES does not relax Time “Bird-beak” esophagus of achalasia Achalasia - Rx Treatment centers around reducing the resting pressure of the LES via: - Balloon dilatation - Surgical myotomy - Botulinum toxin injections - Oral nitrates There are no treatments to restore the nerve plexus of the distal esophagus, so swallowing will never return to normal  Distal Esophageal Spasm (DES) Simultaneous contractions in the distal esophagus result in abnormal transport of a food bolus Manometry is study of choice Esophagram may show corkscrew appearance on barium swallow May cause non-cardiac chest pain “Corkscrew Like angina, may be alleviated by Esophagus” sublingual nitroglycerin Hypercontractile Disorder “Jackhammer” or “Nutcracker” esophagus Very strong contractions of the distal esophagus with normal motility in response to a food bolus Like DES, can be a source of non-cardiac chest pains relieved by nitroglycerin DES and Jackhammer Esophagus - Rx If GERD present PPI therapy If chest discomfort peppermint oil (Altoids®), diltiazem, TCAs, or NTG to lessen smooth muscle contractions Refractory sx botulinum toxin Systemic Sclerosis (scleroderma) Multisystem connective tissue disease Esophageal involvement in 50-80% Loss of smooth muscle in distal 2/3 of esophagus with destruction of nerves leads to aperistalsis and dysphagia Unlike achalasia, LES becomes incompetent, leading to gastric reflux and possible Barrett’s and/or stricture Disorders of the Stomach Peptic Ulcer Disease (PUD) A mucosal defect in the stomach or duodenum that extends through the muscularis mucosa layer PUD - presentation Up to 70% are asymptomatic Symptomatic PUD usually presents with tenderness in epigastrium/RUQ/LUQ Gastric ulcer pains with eating Duodenal ulcer pains several hours after eating and at night PUD - complications 1. Bleeding – most common complication, often presents with hematemesis of bright red blood or digested blood “coffee ground emesis,” and/or melena 2. Gastric outlet obstruction 3. Penetration/fistulization 4. Perforation When I was a medical student… PUD affected about 10% of adults It was felt to be a problem of excess acid from stress and unhealthy habits Treatments at the time targeted acid suppression, ranging from antacids to vagotomy to partial gastrectomy And then along came two superheroes… Drs. Barry Marshall and Robin Warren  Timeline 1979 – Warren, a pathologist, notices colonies of bacteria in biopsies of patients with gastric ulcers and stomach cancers 1981 – Marshall, a third-year internal medicine resident in need of a research project, was given a list of 20 patients with this strange bacteria on bx One of the patients on the list, an 80-year-old Russian man, was Dr. Marshall’s patient suffering from “gastric angina.” Marshall treated him with tetracycline and his symptoms disappeared Helicobacter pylori H pylori H pylori  Timeline 1982 – They recruited 100 patients with GI symptoms undergoing EGD. They cultured each subject for H pylori, but none grew Finally, an excited call from the microbiologist came when samples 34 and 35 were accidentally left culturing over the weekend and grew out H pylori 100% of patients diagnosed with DU had H. pylori 1983 – The duo presented their results at the national meeting of the Royal College of Australian Physicians …  Timeline 1982 – They recruited 100 patients with GI symptoms undergoing EGD. They cultured each subject for H pylori, but none grew Finally, an excited call from the microbiologist came when samples 34 and 35 were accidentally left culturing over the weekend and grew out H pylori 100% of patients diagnosed with DU had H. pylori! 1983 – The duo presented their results at the national meeting of the Royal College of Australian Physicians … they were scorned and ridiculed!  Timeline 1984 – Unable to get approval for a human study, Marshall underwent a baseline EGD with biopsy, and then drank a cloudy flask filled with H pylori that he had obtained from one of his successfully treated patients Over two weeks, Marshall developed severe abdominal pains, nausea and vomiting  Timeline He underwent repeat EGD, with a second biopsy that confirmed the presence of diffuse gastritis and overwhelming infection with H pylori He subsequently treated himself with bismuth and metronidazole and his symptoms completely resolved  Timeline 1985 – Scientific paper by Marshall and Warren accepted by Australian Medical Journal 1985-1992 – several papers published clearly linking H pylori and PUD 1994 – The NIH recognized H pylori as the primary cause of PUD 1994 – WHO classified H pylori as a carcinogen responsible for certain types of gastric cancer 2005 – Warren and Marshall are awarded the Nobel Prize in Physiology or Medicine PUD Incidence in U.S. 1992 - 2015 Medicine; Published 2016 DOI:10.16966/2381-8689.123  H pylori - stats 44% of the world’s population, roughly 3.5 billion people, are infected with H pylori Higher rate in developing countries (51%) compared to developed countries (35%) Gastroenterology 2024;166:605-619  H pylori prevalence 2014 https://www.helico.com/epidemiology.html H pylori and disease PUD Gastritis/Non-ulcer dyspepsia Cancers - Gastric adenocarcinoma - Gastric Mucosa-Associated Lymphoid Tissue Lymphoma (MALTOMA) N Engl J Med 2019; 380:1158-1165 PUD – 4 proven etiologies H pylori NSAIDs Gastrinoma Crohn disease of stomach  PUD and H pylori 90% of those with ulcers are infected with H pylori Only ~1% of those infected with H pylori develop ulcers each year Other factors clearly play into an individual’s susceptibility to ulcers Gastroenterology 2017;153:420-429 PUD – other risk factors Smoking – prevalence of ulcer disease is twice that of nonsmokers Alcohol – heavy drinkers (≥ 6 drinks/d) have four-fold increased risk Genetics – Associations with multiple genes encoding for pro-inflammatory cytokines Do certain foods give you ulcers?  Diet and PUD No specific foods are causally linked to PUD Large prospective study of diet and incidence of duodenal ulcer: - Protective effects of diets high in fruits, vegetables and fiber - No association between fat or protein consumption and DU Am J Epidemiol 1997;145:42-50 Does drinking coffee cause ulcers? No correlation between coffee consumption and ulcer risk! Does stress cause ulcers?  Stress and ulcer disease Psychogenic stress, social problems and depression appear to increase risks for PUD PUD complication rates increase after natural disasters or societal catastrophes May be secondary to altered behaviors as well as altered physiology  Clinical Scenario A 24-year-old medical student reports ongoing abdominal pains, nausea and early satiety that has worsened during their GI pathophysiology course Pains have persisted x 3 months despite trials of antacids, H2 blockers and a proton pump inhibitor Denies use of tobacco, alcohol or NSAIDs Denies N/V, diarrhea, bloody stools, or weight loss You suspect PUD - What test(s) would you consider next? Dyspepsia workup – who gets EGD? Dyspepsia workup – Next step If EGD not done, then testing for H pylori should be performed What is the best test for H pylori infection? 4 Tests for H. pylori 1) Serum IgG antibody testing - Confirms exposure, but not necessarily active infection 2) Urea breath test* Sensitivity/Specificity > 92% 3) Stool antigen testing* 4) Direct biopsy from EGD* * Taking a PPI decreases the sensitivity N Engl J Med 2019; 380:1158-1165 What is a urea breath test? Developed by Warren and Marshall Radioactive Carbon 14 is attached to a urea molecule and given by mouth H pylori hydrolyzes urea, aerosolizing radiolabeled CO2 that can be detected in the patient’s breath in 15-20 minutes How do you treat H pylori?  H pylori treatments PCAB = potassium channel acid blocker Am J Gastroenterol 2024;119:1730-1753 Confirmation of cure Repeat testing for H pylori with a urea breath test or stool antigen is advised about 1 month after completion of antibiotics Patients should not be taking a PPI during repeat testing N Engl J Med 2019; 380:1158-1165  Are there unintended consequences of H pylori eradication?  H pylori and the esophagus Pangastritis from H pylori raises stomach pH Eradication of H pylori is associated with doubling of reflux esophagitis The marked decrease in H pylori infection in the US and Western Europe mirrors the dramatic rise in esophageal adenocarcinoma Gastroenterology 1997;112(5):1442-1447 https://www.cancer.gov/types/esophageal/hp/esophageal-screening-pdq#_71_toc Clinical scenario A 32-year-old man with 6 months of abdominal pains treated with antacids, now experiences sudden onset worsening mid-epigastric pains. He is writhing in pains on the gurney! Presumptive Diagnosis?  PUD and NSAIDs NSAIDs block production of prostaglandins essential for the formation of a healthy mucus in the stomach lining Risk of NSAID-induced PUD increases with: - Duration and dosage of NSAID - Age - Concomitant corticosteroid use Ann Intern Med 2013;159:ITC2-1 Prevention of NSAID-induced GIB Minimize use of NSAIDs Avoid use in high-risk patients: - Prior PUD or GI bleeding - Age > 65 - On aspirin or other blood thinners - On glucocorticoids Am J Gastroenterol 2009;104:728-738 Prevention of NSAID-induced GIB Three proven strategies to decrease risk: 1. Proton pump inhibitors (e.g. omeprazole, pantoprazole, rabeprazole) * 2. Misoprostol (Prostaglandin E analog) 3. Switch non-selective NSAID to a selective NSAID (celecoxib) H2-blockers do not reduce GIB risk! * PPI is by far the preferred method! Stress Ulcers Extreme stress in hospitalized patients leads to ulcers PPI recommended as prophylaxis for: - Burns - Head or spinal trauma - Mechanical ventilation - Severe coagulopathy Ann Intern Med 2013;159:ITC2-1  Chronic Gastritis Inflammation of gastric mucosa that does not extend through the muscularis mucosa Two types: Type A = Autoimmune Type B = chronic H. pylori infection  Chronic Gastritis - Autoimmune T-cells destroy oxyntic cells, and autoantibodies target parietal cells and intrinsic factor Three Major manifestations: 1. Loss of parietal cells lead to achlorhydria, elevated gastrin levels and iron deficiency 2. Loss of intrinsic factor and lack of acid leads to B-12 deficiency (pernicious anemia) 3. Increased risk of cancers (adenocarcinoma and carcinoid tumors) Upper GI Bleeding GI Bleeding ½ million hospitalizations/year at a cost of $4.5 billion 50% are from an upper GI source (Esophagus, stomach, duodenum) Ligament of Treitz is the official dividing point N Eng J Med 2016;374:2367-2376 Upper GI Bleeding - causes Duodenal Ulcers Gastric Ulcers Gastritis Esophageal varices Mallory-Weiss tears AV malformations Esophageal rupture Upper GI Bleeding - causes Duodenal Ulcers ~50% of all bleeds Gastric Ulcers ~50% due to NSAIDs Gastritis Esophageal varices Mallory-Weiss tears AV malformations Esophageal rupture  Esophageal Varices Ectatic blood vessels due to portal HTN ~ 50% of pts with cirrhosis have varices ~ 12% have initial bleed/year ~ 60% rebleed within 1 year of initial bleed ~ 15-20% mortality with each bleed! N Engl J Med 2010;362:823-832 World J Gastrointest Pharmacol Ther 2019:DOI: 10.4292/wjgpt.v10.i1.1  Esophageal Varices - Strategies 1. Screening – all patients with cirrhosis 2. Prevention of bleed – non-selective beta- blockers (e.g. propranolol, nadolol) 3. Treatment of acute bleed - Endoscopic hemostasis - Drugs that reduce pressure (vasopressin, somatostatin, octreotide) - Placement of shunt (TIPS) N Engl J Med 2010;362:823-832 Mallory-Weiss Tears Longitudinal tear(s) of the gastric mucosa secondary to severe retching Usually seen in association with heavy alcohol use leading to vomiting Rx: Acid suppression, anti- emetics, endoscopic therapy for active bleeding  Esophageal Rupture Full-thickness tear of the wall of the lower esophagus, usually iatrogenic (endoscopy, dilatation procedures, surgery) 10-15% due to vomiting (Boerhaave’s) Dx: Free air on CXR or CT Very high mortality rate! - 100% mortality without surgery - 25% mortality with surgery + antibiotics  Esophageal Rupture Pneumopericardium Subcutaneous emphysema BMC Emerg Med 2009;9:24 Angiodysplasia = AV malformation Aberrant blood vessels on the mucosal surface may be located throughout the GI tract, and can easily bleed Dieulafoy’s Lesion Congenital condition resulting in large, tortuous submucosal artery in the GI tract (~75% in proximal stomach) Dx: Identification of a large (usually bleeding) artery in the absence of ulcer disease, alcohol or NSAIDs Dieulafoy’s Lesion GE Junction Dieulafoy’s lesion UGI bleeding - prognosis Worse outcomes with the following: - heart rate - Blood pressure - Hemoglobin - BUN - Syncope - Advanced age - Poor heart or liver function N Eng J Med 2016;374:2367-2376 Math problem A 36-year-old alcoholic man presents to the ED after vomiting up 1.5 liters of blood 30 minutes prior. His hematocrit 3 days ago was 45. Assuming he began with 6 liters of blood, what will his hematocrit be on his initial blood draw in the ED? Answer His hematocrit should remain at 45 Recalibration of his hematocrit will not occur until his fluid status is corrected with IV fluids Bottom line – initial Hb/Hct does not accurately depict the degree of severity of a GI bleed! UGI Bleeding – Initial Rx Stabilize with maximal IV fluids Transfuse RBCs for Hb < 7g/dl EGD within 24 hours! - Length of stay - Need for surgery - Mortality PPI therapy UGI Bleeding – Subsequent Rx Testing and Rx for H pylori - 26% of H pylori-associated bleeding ulcers will rebleed within 1 year if H pylori is not eradicated Discontinue NSAIDs if possible - If NSAID must be continued, consider COX-2 inhibitor (celecoxib) + PPI Clinical scenario A confused man presents to the Emergency Department with complaint of large black stools What is your first step in evaluation and management?  Pts with CAD and GI bleeding – when to restart aspirin? Pts taking ASA for 20 prevention - RCT compared prompt resumption of ASA after GI bleeding vs holding ASA for 8 weeks - Immediate resumption of ASA resulted in sig. decrease in mortality at 8 weeks (1% vs 13%) - Bottom line – continue ASA if high CV risk Ann Intern Med 2010;152:1-9 What about use of aspirin for primary prevention of CV disease? Low dose aspirin has been used for the last couple decades as a means for lowering CV risk 3 RCTs (n=47,140) of ASA vs placebo for primary prevention found that benefits of ASA for lowering CV risk were equally balanced by increased risk of major bleeding N Engl J Med 2018;379:1572-1574 Aspirin is no longer recommended for primary prevention of CV disease for most people N Engl J Med 2018;379:1572-1574 Clinical scenario A 26-year-old man has severe dyspepsia that is refractory to combined H-2 blockers and maximal dose PPI He has had 2 prior hospitalizations for upper GI bleeds An EGD reveals multiple gastric and duodenal ulcers Dx? Zollinger-Ellison Syndrome Gastric acid hypersecretion due to gastrin- producing tumor in the pancreas or duodenum causing refractory PUD sx - Ulcers (90%) - GI Bleeds - Refractory GERD - Diarrhea Dx: gastrin level with low stomach pH Exceedingly rare! (0.5-2 per million) Zollinger-Ellison Syndrome Z-E is associated with Multiple Endocrine Neoplasia (MEN 1) in 20-30% of cases Remember the “3 P’s” - Parathyroid tumors - Pituitary (anterior) tumors - Pancreatic tumors Menetrier Disease Disease of abnormally enlarged mucosal folds of the stomach which results in decreased acid production, excess mucus production and severe protein loss Dx: EGD with biopsy Rx: high protein diet + experimental drugs Menetrier’s Disease of stomach  22-year-old woman with anxiety and recent hair loss complains of abdominal pains and non-bilious emesis x 6 months Gastric Motility Disorders Gastroparesis Delay in transition of food from stomach to intestines, not due to obstruction Patients complain of nausea, vomiting, abdominal pain, bloating and early satiety Gastroparesis – common causes Idiopathic in half of cases Diabetes mellitus - autonomic dysfunction Medications - Opioids, anticholinergics, dopamine agonists Post-surgical - injury to the vagus nerve Neurologic (e.g. multiple sclerosis) Gastroparesis - Dx EGD or upright abdominal xray to rule out mechanical obstruction Scintigraphy - Patient eats radiolabeled food, and then measure movement of the radiotracer through the stomach and intestines over 2- 4 hours Normal Scintigraphy Gastroparesis Gastroparesis Rx - Lifestyle Liquids better tolerated Avoid fatty or acidic foods, insoluble fibers (roughage), and carbonated drinks Avoid tobacco and ETOH Gastroparesis Rx - Medications Promotility agents - Metoclopramide is first line - enhances gastric antral contractions Many adverse effects including dystonic reactions, Parkinsonism, QT prolongation! - Others: Domperidone, erythromycin Antiemetic agents (diphenhydramine, ondansetron) 20-year-old man with abdominal pains and constipation x 20 days Dx: ? Sudden loss of consciousness (LOC) 28-year-old was brought to the hospital, unconscious with respiratory depression, hypoxemia and pinpoint pupils Revived with IV naloxone In ICU, had 4 further episodes of LOC requiring additional doses of naloxone, and finally a naloxone continuous drip Lancet 2019;393:e35 Lancet 2019;393:e35 Lancet 2019;393:e35 A few practice questions for you A 53-year-old man with gurgling in his throat and regurgitation has the following barium swallow. What is the most likely diagnosis? a. Achalasia b. Nutcracker esophagus c. Esophageal web d. Schatzki’s ring e. Zenker’s diverticulum A 53-year-old man with gurgling in his throat and regurgitation has the following barium swallow. What is the most likely diagnosis? a. Achalasia b. Nutcracker esophagus c. Esophageal web d. Schatzki’s ring e. Zenker’s diverticulum A 28-year-old medical student suffers from severe heartburn and requests a medication. Which of the following best pairs the medication with its common side effect? a. Mg trisilicate Constipation b. Omeprazole Hypercalcemia c. Ranitidine P450 interactions d. Al hydroxide Milk alkali syndrome e. Sucralfate Fetal defects A 28-year-old medical student suffers from severe heartburn and requests a medication. Which of the following best pairs the medication with its common side effect? a. Mg trisilicate Constipation b. Omeprazole Hypercalcemia c. Ranitidine P450 interactions d. Al hydroxide Milk alkali syndrome e. Sucralfate Fetal defects A 46-year-old woman has painful swallowing and a 15 lb weight loss. Her esophagram is shown. Which of the following is true regarding her condition? a. Peristalsis will be increased in her middle esophagus on manometry b. She should undergo EGD to rule out a distal mass c. Dilation of her distal esophagus will be curative d. Her lower esophageal pressures will be diminished e. She should undergo botulinum toxin injections to her middle esophagus A 46-year-old woman has painful swallowing and a 15 lb weight loss. Her esophagram is shown. Which of the following is true regarding her condition? a. Peristalsis will be increased in her middle esophagus on manometry b. She should undergo EGD to rule out a distal mass c. Dilation of her distal esophagus will be curative d. Her lower esophageal pressures will be diminished e. She should undergo botulinum toxin injections to her middle esophagus A 26-year-old man presents emergently with abdominal pains and coffee ground emesis. He is a heavy drinker. He is hypotensive and tachycardic. Which of the following is true regarding his GI bleeding? a. Angiodysplasia is the most likely cause b. He should be admitted and placed on an IV propranolol drip for presumed varices c. His initial hemoglobin will determine his need for transfusion d. He should be treated with omeprazole for 48 hours prior to an endoscopy e. Elevated BUN levels suggest a worse prognosis A 26-year-old man presents emergently with abdominal pains and coffee ground emesis. He is a heavy drinker. He is hypotensive and tachycardic. Which of the following is true regarding his GI bleeding? a. Angiodysplasia is the most likely cause b. He should be admitted and placed on an IV propranolol drip for presumed varices c. His initial hemoglobin will determine his need for transfusion d. He should be treated with omeprazole for 48 hours prior to an endoscopy e. Elevated BUN levels suggest a worse prognosis