Gastroesophageal Reflux Disease (GERD) 2024-2025 PDF

uplogo UNIVERSITY OF PERUGIA DEPARTMENT OF MEDICINE Master’s Degree in Medical, Veterinary and Forensic Biotechnological Science Academic Year 2024-2025 Digestive System Diseases Ga...

uplogo UNIVERSITY OF PERUGIA DEPARTMENT OF MEDICINE Master’s Degree in Medical, Veterinary and Forensic Biotechnological Science Academic Year 2024-2025 Digestive System Diseases Gastroesophageal Reflux Disease (GERD) and Barrett’s Esophagus Monia Baldoni  ESOPHAGUS: ANATOMY  A muscular tube that connects the mouth to the stomach;  25 cm in length  Collapsed at rest,  Flat in upper 2/3 & rounded in lower 1/3  Starts at the lower edge of the cricoid cartilage (C6).  Descends along the front of the spine, through the posterior mediastinum, passes through the diaphragm and, entering the abdomen, terminates at the cardiac orifice of the stomach, opposite the eleventh dorsal vertebra.  ESOPHAGUS: ANATOMY  Tubular muscular organ about 18-26 cm in length in adults  In endoscopic view: 38-40 cm length from the incisor teeth 16-24 24-32 32-40  Conventionally divided into three parts: upper - middle - lower  Blood supply: Unusual! Arterial supply derived from vessels feeding mainly other organs – thyroid, trachea & stomach UES LES  VENOUS DRAINAGE  The upper third drains in into the inferior thyroid veins.  The middle third into the azygos veins.  The lower third into the left gastric vein, which is a tributary of the portal vein.  NB. Esophageal varices.  LYMPH DRAINAGE  The upper third is drained into the deep cervical nodes.  The middle third is drained into the superior and inferior mediastinal nodes.  The lower third is drained in the celiac lymph nodes in the abdomen. NERVE SUPPLY  The sympathetic supply is mediated by intermediated lateral T1-T10 spine and regulates blood vessel contraction (blood supply), esophageal sphincter tone, relaxation of the muscular wall and glandular function.  The parasympathetic supply is mediated by the ambiguous nucleus and the dorsal motor nucleus of the vagus nerves and provides motor innervation to the muscles and secretory-motor to the glands.  Inferior to the roots of the lungs, the vagus nerves join the sympathetic nerves to form the esophageal plexus.  The left vagus lies anterior to the esophagus.  The right vagus lies posterior to it.  NERVE SUPPLY Parasympathetic  Vagus – motor to muscular lyers & secretomotor to glands Sympathetic  From thoracic sympathetic chain  Contraction of sphincters (tone), wall relaxation, glands activity, blood flow Intramural  Combination of all innervation form plexuses & ganglia  In muscular layers (myenteric or Auerbach’s plexus)  In submucosa (Meissner plexus) Central Nervous System (CNS): Swallowing center  NERVE SUPPLY The afferent fibers of the Vagus do not play a direct role in the transmission of visceral pain to the encephalic trunk; are the spinal afferent fibers that act as nociceptors. Esophageal pain resembles that of cardiac origin due to the convergence of sensitive afferent fibers from the heart and esophageal neuron itself of the dorsal horn of the thoracic cervical spine. ESOPHAGEAL PATHOPHYSIOLOGY: FUNCTIONAL ANATOMY http://www.alphabeto.it/digestione/esofago.jpg Function: transport the bolus from the pharynx to the stomach, prevent the G-E reflux and allow belching and vomiting. Striated muscle (1|3, cervical esophagus) and smooth (2|3, thoracic esophagus), transition zone (4-6 cm). Functional areas: 1. Upper Esophageal Sphincter [UES] and junction pharyngo-esophageal 2. Esophageal Body 3. Lower Esophageal Sphincter [LES] and crural diaphragm (CD) esophago-gastric junction(EGJ) Yazaki E, Sifrim D. Dis Esophagus. 2012; 25:292-8 ESOPHAGUS DIVIDED INTO FUNCTIONAL SPHINCTERS  Upper Esophageal Sphincter (UES): It is a 2-4 mm zone of elevated pressure between pharynx & esophagus. It relates to cricopharyngeal muscle  Lower Esophageal Sphincter (LES): The LES is located at the junction between the esophagus and stomach, usually localized at or just below the diaphragmatic hiatus. Despite its distinct physiological function, it is not easily distinguished anatomically.  Esophagus : Anatomy Esophagus is the narrowest region of alimentary tract except vermiform appendix. During its course it has three indentations: At 15-16 cm from incisor teeth is crico- pharyngeal sphincter (UES), normally closed At 25-27 cm aortic arch and left main bronchus At 40 cm where it pierces the diaphragm where a physiological sphincter is sited (LES)  THESE AREAS ARE WHERE MOST ESOPHAGEAL FOREIGN BODIES BECOME ENTRAPPED.  The most common site of esophageal impaction is at the thoracic inlet  Defined as the area between the clavicles on chest radiograph, this is the site of anatomical change from the skeletal muscle to the smooth muscle of the esophagus. The cricopharyngeus sling at C6 is also at this level and may "catch" a foreign body.  About 70% of blunt foreign bodies that lodge in the esophagus do so at this location.  Another 15% become lodged at the mid esophagus, in the region where the aortic arch and carina overlap the esophagus on chest radiograph.  The remaining 15% become lodged at the lower esophageal sphincter (LES) at the gastroesophageal junction. THE ESOPHAGUS IS A VERY THIN-WALLED ORGAN, MEASURING ABOUT 2 MM WIDE  The esophageal wall has four layers: From within outwards:  Mucosa,  Submucosa,  Muscle coat, Muscolaris propria  Outer most fibrous layer.  Unlike other areas of the gut, it does not have a distinct serosal covering, but is covered by a thin layer of loose connective tissue HISTOLOGY OF ESOPHAGUS  The esophageal mucosa consists of a stratified non-keratinized squamous epithelium Esophagus : Esophagogastric Junction Esophagus : Esophagogastric Junction Esophagus : Esophagogastric Junction  Esophageal Peristalsis Esophageal peristalsis can be initiated by deglutition "primary" peristalsis or local distention "secondary" peristalsis. Esophageal Deglutition distension Primary Secondary peristalsis peristalsis  Esophageal Peristalsis Deglutition is one of the most complex reflex neural activities. The initial phase is voluntary when food is chewed, mixed with saliva and formed into a bolus before being pushed to the posterior pharynx by the tongue. Receptors in the posterior pharynx are then activated to initiate the involuntary phase of deglutition, which involves carefully sequenced contraction of numerous head and neck muscles. The food bolus is rapidly pushed toward the esophagus by the pharyngeal constrictor muscles. The UES opens almost immediately upon activation of the deglutition reflex, allowing the food bolus to pass through. It then rapidly shuts to prevent the retrograde passage of the bolus. Once this oropharyngeal phase has served to propel the bolus into the esophagus, the esophageal phase of deglutition takes over. This involves two major phenomena, namely the sequential contraction of circular muscle of the esophageal body, which results in a peristaltic wave that pushes the food toward the stomach, and relaxation and opening of the LES - Primary peristalsis -  Esophageal Peristalsis Primary Peristalsis Spatiotemporal plot obtained during high-resolution manometry depicting esophageal pressure activity from the High-resolution esophageal manometry pharynx to the stomach.  SECONDARY PERISTALSIS Secondary peristalsis is a propagating esophageal contraction wave which is not Upper Esophageal induced by swallowing but by Sphincter (UES) stimulation of sensory receptors Secondary Peristalsis induced by distention (mechanoreceptors) in the of esophageal body esophageal body: local by gastric-reflux distention induced. This can Gastro- occur physiologically by food left esophageal behind after the primary reflux peristaltic wave has passed, or by refluxed contents from the stomach. Unlike primary peristalsis, secondary peristalsis is not accompanied by deglutition with associated Lower Esophageal Transient Release of the Lower Sphincter (LES) pharyngeal and upper Esophageal Sphincter (not esophageal sphincter motor associated with swallowing) function. On the other hand, secondary peristalsis in the smooth muscle esophagus is largely an intrinsic neuromuscular reflex. Gastroesophageal Reflux Disease (GERD) THE MONTREAL DEFINITION OF GASTRO- ESOPHAGEAL REFLUX DISEASE (GERD) GERD is a condition which develops when the reflux of stomach content causes troublesome symptoms and/or complications Esophageal Extra-esophageal Syndromes Syndromes Symptomatic Syndromes with Established Proposed Syndromes Esophageal Injury Association Association Typical reflux Reflux esophagitis Reflux cough Sinusitis syndrome Reflux stricture Reflux laryngitis Pulmonary Reflux chest fibrosis pain syndrome Barrett's Reflux asthma esophagus Pharyngitis NERD (Non Reflux dental Adenocarcinoma erosions Recurrent otitis Erosive Reflux media Disease)  Epidemiology ❖ An accurate epidemiologic evaluation is not easy because many GERD patients have light symptoms ❖  Prevalence in industrialized countries ❖ GERD affects ~20% (between 10 to 30%) of total population ❖ Age: prevalence of GERD increases with age, older patients are more likely to develop less symptomatic but more severe disease. Most cases in IV-V decade of life  Prevalence of GERD Population-based studies suggest that GERD is a common condition with a prevalence of 10–30% in Western Europe and North America. GERD is less commonly seen in the Asia-Pacific region  Prevalence of GERD The prevalence of GERD and GERD-related disorders has been steadily increasing in the US, Western Europe, Australia and Asia. An opposing trend time was observed between 1970 and 1995 in the prevalence of peptic ulcer disease and GERD. The rates of peptic ulcer and gastric cancer fell while at the same time the rates of GERD and esophageal adenocarcinoma rose significantly.  Gender distribution along the GERD spectrum Esophageal adenocarcinoma Women Barrett’s Men Erosive Esophagitis Women Men GERD Symptoms Men Women Men Women  Pathogenesis Imbalance between: ❖ Esophageal protective mechanisms Competence of LES (resting tone), esophageal peristalsis (acid clearance), proper gastric emptying, mucosal resistance (integrity of epithelium and of tight junction), buffering activity of saliva. ❖ Aggressive factors Characteristics of refluxate: volume, presence of HCL, pepsin, bile, pancreatic enzyme. GERD pathophysiology  GERD pathophysiology Although GERD is an acid-related disease, its main cause is not an increase in acid secretion, which is usually normal, but the impaired function of the natural anti- reflux barrier at the gastro-esophageal junction Concept: acidic reflux, mildly acidic reflux, alkaline reflux  GERD pathophysiology Esophageal protective mechanisms The gastro-esophageal junction is an anatomically and functionally complex structure that comprises: ▪ Lower Esophageal Sphincter (LES), and its intraabdominal location ▪ Crural diaphragm and phrenoesophageal ligament ▪ The acute angle of His Esophageal mucosal barrier ▪ Mucus, bicarbonates, stratified epithelium  Esophagogastric Junction The lower esophageal sphincter and the crural diaphragm constitute the intrinsic and extrinsic sphincter, respectively. The two sphincters are anatomically superimposed on each other and are anchored by the phrenoesophageal ligament.  GERD pathophysiology Lower Esophageal Sphincter (LES) 2-4 cm of “functionally thickened” smooth muscle at gastroesophageal junction High pressure resting tone ~20 mmHg (10-40 mmHg) ▪ Swallow-associated LES relaxation ▪ Transient LES relaxation  Esophagogastric Junction The smooth muscles of the esophagus are organized into two distinct layers, the circular and the longitudinal, and these layers continue into the LES. If one examines autopsy specimens, both of these muscle layers are not thicker in the LES as compared to the esophagus. The thickness of the LES muscles changes in a dynamic fashion with the change in LES tone, that is, it increases and decreases with the increase and decrease in the LES pressure, respectively, and it is for this reason that autopsy studies fail to show LES as a distinct anatomic structure, because with the loss of muscle tone in the autopsy specimen the LES looks no different than the esophagus.  Angle of His The intrinsic LES in humans is composed of at least two muscles. The circular muscle forms only a partial ring (or semicircular clasp), and the gastric sling muscle runs on the left lateral aspect to complete this portion of the sphincter The presence and location of the sling muscle have also been linked to the maintenance of the acute angle of His at the greater curve aspect of the gastroesophageal junction, and the formation of a flap valve function that could also serve as an anti-reflux mechanism https://www.youtube.com/watch?v=ojyFodct9kA GERD pathophysiology ▪ ↓ Esophageal clearance ▪ LES: ↓ Resting tone ↑ Transient LES relaxation ▪ ↓ Gastric emptying ▪↑ intragastric pressure GERD pathophysiology A vicious circle is created…..  GERD pathophysiology  The main mechanism that lowers the barrier is Transient Lower Esophageal Sphincter Relaxation, TLESR, a reflex that occurs independent of swallowing, is not accompanied by peristaltic activity, and persisting longer than post-deglutitive LES relaxation.  In normal conditions, TLESR is a protective mechanism against gastric overdistention, but in GERD TLESR is much more frequent and facilitates long-lasting reflux episodes.  Transient LES Relaxations Physiologic record of a spontaneous, transient Manometric recordings made with relaxation of the LES an electrode sleeve sensor (inset) at pressure recording ports at various locations (from the pharynx to the stomach). The vertical arrow indicates the onset of relaxation, which occurs in the absence of a swallow as shown by the absence of a pressure wave or contraction in the pharynx. There is complete LES relaxation for more than 20 seconds (horizontal line at the bottom of the tracing for the LES). Relaxation is associated with inhibition of the crural diaphragm, as indicated by the loss of inspiratory pressure oscillations at the level of the sphincter and loss of inspiratory DEMG. The contribution of the LES is shown in pink, and that of the crural diaphragm in brown. Reflux (indicated by a decrease in esophageal pH) occurs after complete relaxation of the sphincter and crural diaphragm and is associated with an increase in intraesophageal pressure.  Hiatal hernia Definition: It’s a dislocation of the proximal stomach into the chest, through the diaphragmatic hiatus, so that the LES becomes separated from the crural diaphragm Sliding hiatal hernia is a further pathogenetic mechanism in GERD, since it may reduce the competence of GE junction and facilitate the presence of acid near the diaphragm, inside the thoracic cavity, where the pressure is lower than abdomen. Hiatal hernia IS NOT synonymous with GERD, GERD requires a dysfunctional LES Hiatal hernia  Hiatal hernia The presence of a hiatal hernia, particularly if it is large (≥5 cm) is associated with increased severity of GERD. The prevalence of hiatal hernia increases with the severity of esophageal mucosal involvement. 20-30% in NERD patients 95% in patients with long segment Barrett’s esophagus Displacement of LES from the crural diaphragm into the chest: reduces LES basal pressure loss of the intra-abdominal LES segment reduced threshold for TLESR in response to gastric distension  GERD risk factors ❖ Hiatal hernia ❖ High Body mass index (BMI) ❖ Diet (coffee, chocolate, alcohol, large fatty meal, peppermint, citrus, etc…) ❖ Smoke ❖ Drugs ❖ Surgery  MEDICATIONS MAY AGGRAVATE GERD SYMPTOMS Impairment of LES function:  beta-adrenergic agonists Damage to the esophageal  theophylline mucosa:  anticholinergics  acetylsalicylic acid and  progesterone other NSAIDs  tricyclic antidepressants  tetracycline  alpha-adrenergic  quinidine antagonists  bisphosphates.  diazepam  calcium channel blockers.  GERD aetiology Idiopathic (>80% of patients) Secondary causes: ▪ Obesity/overweight ▪ Scleroderma, Systemic Lupus Erythematosus ▪ Pregnancy:  estrogen and progesterone  intra-abdominal pressure  GERD diagnosis Identify symptoms that are related to Gastroesophageal reflux Identify esophageal inflammation  GERD symptoms Esophageal Typical Atypical Chest pyrosis (heartburn) Dysphagia Acid regurgitation Non-cardiac chest pain resembling myocardial infarction Odynophagia  GERD symptoms Esophageal Typical Sensation of discomfort or Heartburn burning behind the sternum rising up to the neck, made worse after meals, the supine body position and eased by antacids. Regurgitation The perception of spontaneous flow of refluxed gastric content into the mouth or hypopharynx occurring in the absence of extrinsic muscular phenomena of vomiting  GERD symptoms Extra-esophageal Pharyngeal Laryngeal Pulmonary Sore throat Hoarseness Chronic bronchitis Dysphonia Chronic cough Globus sensation Chronic posterior Wheezing and laryngitis asthma The clinical spectrum of GERD N.E.R.D. (Non Erosive Reflux Disease) In more than the 50% of patients affected by GERD there are symptoms caused by gastroesophageal reflux in absence of macroscopic mucosal lesions, in the other cases GERD is characterized by: Erosive esophagitis and chronic complications The clinical spectrum of GERD 35% NON EROSIVE REFLUX DISEASE = NERD COMPLICATED GERD ESOPHAGITIS 60% 5%  The clinical spectrum of GERD GERD is characterized by a wide variety of clinical symptoms and different degrees of mucosal damage G-E reflux without Symptomatic symptoms G-E reflux GERD with and without Erosive mucosal Barrett’s mucosal Esophagitis damage Esophagus damage (EE) (normal and (NERD) life!) Adenocarcinoma  The clinical spectrum of GERD MILD SEVERE Non-Erosive Erosive Stenosis Reflux Disease Esophagitis Ulcer (NERD) (ERD) Barrett’s esophagus Adenocarcinoma  The clinical spectrum of GERD GERD symptom frequency or severity does not correlate with the extent of esophageal mucosal involvement in patients with erosive esophagitis. Heartburn severity and intensity are similar in patients with erosive esophagitis and NERD. In the elderly patient with GERD, heartburn and acid regurgitation are less frequent than in younger subjects. In contrast, atypical symptoms such as vomiting, anorexia, dysphagia, respiratory symptoms, belching, dyspepsia, hoarseness, and postprandial fullness are more common presentations in elderly. GERD: clinical presentations Typical Atypical symptoms symptoms Complications Heartburn Chest pain Esophageal erosions Dysphagia and ulcers Acid Hoarseness Stenosis regurgitation (laryngitis) Asthma, Barrett’s chronic cough, esophagus dyspnoea Tooth decay Adenocarcinoma  GERD Stenosis/Barrett Gastroenterologist Adenocarcinoma Atypical symptoms General Esophagitis NERD practitioner MILD symptoms 10% of population Self-medication GERD and the risk of esophageal complications 30-35% of patients with acid-related diseases have an esophagitis Patients with acid-related diseases have a higher prevalence for esophageal complications Esophageal ulceration 2 - 7 % Barrett‘s esophagus 10 - 15 % Esophageal stricture 4 - 20 % The risk of malignancy in patients with Barrett‘s esophagus may be up to 30 - 40 times that of the general population GERD: diagnostic modalities - Effectiveness of Proton Pump Inhibitors (PPIs) therapy - Esophagus-Gastroduodenoscopy (EGD) - PH impedance monitoring - High-resolution esophageal Manometry - But before ….  GERD: diagnostic modalities Take a good history! ‘A burning Sensitivity 96% feeling (PPV 87%) rising from your for GERD stomach or compared lower with endoscopy/ chest towards 24-hour pH your neck’ monitoring https://www.youtube.com/watch?v=kXJLbFCeroc  GERD diagnosis ❖ Effectiveness of Proton Pump Inhibitors (PPIs) therapy (only for young people) in case of typical mild symptoms and in absence of alarm symptoms such as dysphagia, odynophagia, weight loss or bleeding. A short course (1–2 weeks) of high-dose PPI given twice daily for the diagnosis of GERD in patients with typical symptoms of GERD, PPI test: If symptoms disappear with therapy and then return when medication is stopped, GERD can be assumed, and no further testing is required.  GERD diagnosis ❖ Endoscopy : The gold standard procedure for diagnosing erosive esophagitis, GERD complications, and Barrett’s esophagus. Allows an assessment of the degree of esophageal mucosal injury, and tissue sampling can be performed if necessary. Also indicated in case of: Severe symptoms Atypical symptoms PPIs non responders Barrett’s follow up GERD Erosive esophagitis Endoscopic evaluation of erosive esophagitis Lateral spreading of Length of mucosal mucosal erosion is the erosion is not a most reliable criterion reliable criterion and in predicting severity adds a rather difficult of GERD estimation maneuver to the endoscopic classification effort Endoscopic evaluation of erosive esophagitis Simultaneous erosion of Defining mucosal different mucosal fold is fold damage is the most reliable easier with soft parameter to classify insufflation erosive reflux esophagitis during EGD THE LOS ANGELES (LA) CLASSIFICATION SYSTEM FOR THE ENDOSCOPIC ASSESSMENT OF REFLUX ESOPHAGITIS Grade A Grade B One (or more) mucosal One (or more) mucosal break no longer than 5mm, break more than 5 mm long, that does not extend that does not extend between the tops of two between the tops of two mucosal folds mucosal folds Grade C Grade D One (or more) mucosal break that is continuous between the One (or more) mucosal break tops of two or more mucosal which involves at least 75% of folds,but which involves less the esophageal circumference than 75% of the circumference THE LOS ANGELES (LA) CLASSIFICATION SYSTEM FOR THE ENDOSCOPIC ASSESSMENT OF REFLUX ESOPHAGITIS Grade A Grade B Grade C Grade D  GERD: diagnosis 24-Hour Esophageal pH Monitoring Most accurate test for measuring pattern, frequency, and duration of reflux episodes Documents correlation between reflux episodes and symptoms Reflux is traditionally assessed by means of catheter-based or wireless pH monitoring and identified by pH drops below 4.0 units. The total percentage of time with pH 5 minutes Mean duration of esophageal reflux Evaluating the relationship between symptoms and Reflux Symptom Index (DeMeester score) Symptom Association Probability PH impedance monitoring This method now is the "gold standard" for measuring gastroesophageal reflux, allowing a more comprehensive characterization of reflux episodes, including physical properties (i.e., liquid, gas, mixed), chemical properties (i.e., acid or nonacid), height of the refluxate, bolus presence, and acid presence and clearance. Is based on measuring the resistance to alternating current (i.e., impedance) and pH of the content of the esophageal lumen A 2.1-mm diameter combined, Multichannel Intraluminal Impedance, MII-pH catheter is passed transnasally into the esophagus and stomach and then positioned so that the esophageal pH electrode is located 5 cm above the proximal border of the LES. Data are recorded with a sample frequency of 50 Hz and stored on the flash card of a data logger  PH impedance monitoring Combined Multichannel Intraluminal Impedance and pH (MII-pH) Monitoring  PH impedance monitoring The conductivity of the empty esophageal lumen is relatively Impedance-measuring allows us to determine stable (values around 2000 to 4000 Ohms). The appearance of a the direction of bolus movement liquid bolus in the impedance-measuring segment is recognized a: Drops in impedance starting proximally and as a rapid drop in impedance. The presence of gas in the moving distally are indicative of antegrade impedance-measuring segment is recognized by a rise in bolus movement as seen during swallowing. impedance typically above 5000 Ohms. The presence of a mixed b: Drops in impedance starting distally and bolus is recognized by impedance changes indicating air and moving proximally are indicative of retrograde liquid presence bolus movement as seen during reflux.  GERD: diagnosis High Resolution Manometry: is a gastrointestinal motility diagnostic system that measures intraluminal pressure activity in the gastrointestinal tract using a series of closely spaced pressure sensor. High Resolution esophageal Manometry (HRM) is a new approach of measuring pressures in the esophageal body and presentation of the results. This method consists of measuring multiple pressures simultaneously. It measures pressure events along the entire length of the esophagus simultaneously. This allows detailed assessment of all relevant data for the whole esophagus. High-resolution esophageal manometry A commercially available high-resolution catheter has 36 solid-state circumferential sensors spaced at 1 cm intervals along the entire intracorporal portion of the catheter assembly. This arrangement facilitates pressure assessment of the entire esophagus, from the cricopharyngeus to the LES, without the need for catheter pull-through manoeuvres. HRM is simpler and more precise than older methods. Also determines a 50% reduction in procedure time. High-resolution esophageal manometry components Monitor display Catheters with circumferentially oriented, pressure-sensing elements analysis software High-resolution esophageal manometry This figure shows a pressure topography plot during a normal swallow, measured using a 36-channel high- resolution manometry system. Time is on the horizontal axis and length along the esophagus is on the vertical axis. Pressure magnitude is encoded in color corresponding to the scale shown at the bottom. High-pressure regions are denoted by the red end of the spectrum while the low- pressure regions are by the blue end  GERD: therapy Lifestyle modification ✓ Avoid alcohol, caffeine, tobacco cessation ✓ Avoid eating before lying down ✓ Avoid spicy food, citrus, carbonated beverages ✓ Elevate the head of the bed ✓ Weight loss, strong recommendation for patients with BMI>25 or patients with recent weight gain ✓ Reduce meals size ✓ Decrease fatty meals  GERD: therapy Medical therapy ANTIACID: Magnesium hydroxide and Aluminium hydroxide +/- Alginic acid H2 receptor antagonists (H2RAs): Ranitidine (not more), Famotidine Proton Pump Inhibitors(PPIs): Omeprazole, Pantoprazole, Rabeprazole, Lansoprazole, Esomeprazole PROKINETICS: Domperidone, Metoclopramide, Levosulpiride DRUGS FOR THE REDUCTION OF TLESRs (agonist of GABA-B) Baclofene  Pharmacology of Antacids and Antisecretory agents GERD: therapy George Sachs, Distinguished Professor of Medicine and Physiology at UCLA (1935-2019) Fellenius E, Berglindh T, Sachs G, et al. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature. 1981;290:159–161. Phenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet David A.Katzka∗John E.Pandolfino‡Peter J.Kahrilas‡ Clinical Gastroenterology and Hepatology Volume 18, Issue 4, April 2020, Pages 767-776 Risks linked to the PPI use  GERD: therapy Surgical treatment GERD refractory to medical therapy GERD: complications Peptic Barrett’s esophagus stricture (10-15%) (4-20%) GERD Bleeding Ulceration < 2% (5%) GERD: complications Endoscopic dilation + PPI  Barrett’s Esophagus Erosive Esophagitis Barrett’s Esophagus  Barrett’s Esophagus Barrett’s esophagus is a pathological alteration of the distal esophagus mucosa. It is characterized by the replacement of the normal stratified squamous epithelium by simple columnar epithelium with goblet cells (Intestinal metaplasia) just above the gastroesophageal junction. Long Barrett: > 3 cm Short Barrett: 1-3 cm Esophago-Gastro- Duodenoscopy (EGDS) is the Gold Standard to diagnose Barrett's Esophagus (BE)  Wilder Tileston, American Pathologist, in 1906 first described Norman Rupert Barrett, columnar epithelium 1903-1979, born in in esophagus, and Australia, was a thoracic related this mucosal surgeon in Saint Thomas’ alteration to Hospital, London. He gastroesophageal thought that “the lower reflux. esophagus lined by columnar epithelium” was a “congenital short esophagus” In 1953 P. R. Allison and A. Johnstone argued that he wasn’t right and described 7 patients who presented reflux esophagitis involving an “esophagus lined with gastric mucous membrane” and refuted Barrett’s contention that the tubular, intra- thoracic, columnar-lined viscus was the stomach. The eponym Barrett’s esophagus was kept, whether justified or not. During endoscopy, the following must be recognized: 1. diaphragmatic pinch 2. the gastro-esophageal junction 3. The squamocolumnar junction. The diaphragmatic pinch coincides with the passage point of esophagus through the diaphragm (if >2 cm from the two junctions it indicates a sliding hiatal hernia) The gastro-esophageal junction (GEJ) is the apical point of the gastric folds. The squamocolumnar junction (z-line) is easily recognizable by the pale pink color of the squamous epithelium while the columnar one has a bright light red color. In the normal esophagus the GEJ coincides with the squamocolumnar junction, whereas when the latter is at last 1 cm from the GEJ it suggest the presence of a BE Barrett’s Esophagus: Prague C&M criteria 16 14 M = Maximal length 12 10 8 C =Circumferential 6 extent 4 Identify 2 gastroesophageal 0 junction Distance from gastroesophageal Identify Hiatal junction hernia Barrett’s Esophagus ❖ Barrett's esophagus occurs as a result of chronic, pathologic reflux of gastro-duodenal contents into the esophagus. ❖ The diagnosis is made by endoscopy with biopsy. ❖ Histologically, Barrett's esophagus is a metaplastic change in the distal esophagus (intestinal metaplasia IM). ❖ Barrett's esophagus is classified histologically as either non- dysplastic IM, low-grade dysplasia (IM-LGD) or high- grade dysplasia (IM-HGD) The prevalence of Barrett's esophagus in the adult population is 0.4% to 1.6%, although recent reports from gastroenterology-selected populations suggest a higher prevalence Barrett’s Esophagus EGDS  BIOPSY PROTOCOL  Minimum of 8 biopsies provides adequate assessment of Intestinal Metaplasia  Starting distally 1-2cm above GEJ, 4 quadrant random biopsies should be done every 2cm while advancing proximally  Targeted biopsies of visible lesions (should be done before random biopsies)  Ideally, erosive esophagitis should be healed prior to biopsies for BE to avoid missing short segments of columnar epithelium Barrett’s Esophagus Biopsy protocol  SCREENING FOR BE  Screening for BE in unselected population of patients with gastro esophageal reflux symptoms is not recommended  Screening should be considered in patients with chronic GERD (> 13 years) and multiple risk factors including at least 3 of the following:  Age 50 or older  White race  Male sex  Obesity  Hiatal Hernia  Threshold of multiple risk factors should be lowered in those with a first degree relative with Barrett’s or esophageal adenocarcinoma  SURVEILLANCE  What is the risk of esophageal cancer with Barrett’s esophagus?  Less than 1 percent of people with Barrett’s esophagus develop esophageal adenocarcinoma each year  Aim of surveillance is to detect cancer or pre-cancer at a stage when intervention may be curative  Surveillance correlates with earlier staging and improved survival from cancer  Endoscopic monitoring with the histopathological assessment of dysplasia is the only current method of surveillance  High Resolution Endoscopy should be used for surveillance  Barrett’s Esophagus Surveillance ❖ Patients with BE should receive PPI therapy once or twice a day ❖ Endoscopic surveillance should employ four-quadrant biopsies at 2 cm intervals in patients without dysplasia and 1 cm intervals in patients with prior dysplasia ❖ Mucosal abnormalities should be sampled separately and before ❖ Surveillance interval depends on the degree of mucosal dysplasia Barrett’s Esophagus Surveillance Algorithm  ESOPHAGITIS BARRETT’S ESOPHAGUS (METAPLASIA) DYSPLASIA ADENOCARCINOMA Barrett’s esophagus treatment  PPI reduce incidence of dysplasia in BE El-Serag HB, Aguirre TV, Davis S et al. Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett’s esophagus. Am J Gastroenterol 2004;99:1877–83. SUMMARY