EsophagealDiseases 1stEdition

An Atlas of Investigation and Management

ESOPHAGEALDISEASES

Michael F Vaezi, MD, PhD, MS(epi)Clinical Director

Division of Gastroenerology and HepatologyDirector Clinical Research

Director Swallowing and Esophageal MotilityVanderbilt University Medical Center

Nashville, Tennessee, USA

With contributions from:

Woosuk Park, MDClinical Fellow

Department of Gastroenterology and HepatologyThe Cleveland Clinic Foundation

Cleveland, Ohio, USA

Jason Swoger, MD, MPHResident

Department of Internal MedicineThe Cleveland Clinic Foundation

Cleveland, Ohio, USA

CLINICAL PUBLISHINGOXFORD

Clinical PublishingAn imprint of Atlas Medical Publishing LtdOxford Centre for InnovationMill Street, Oxford OX2 0JX, UK

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© Atlas Medical Publishing Ltd 2006

First published 2006

All rights reserved. No part of this publication may be reproduced, stored in a retrievalsystem, or transmitted, in any form or by any means, without the prior permission inwriting of Clinical Publishing or Atlas Medical Publishing Ltd.

Although every effort has been made to ensure that all owners of copyright materialhave been acknowledged in this publication, we would be glad to acknowledge insubsequent reprints or editions any omissions brought to our attention.

A catalogue record for this book is available from the British Library

ISBN 1 904392 55 5

The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the productinformation and clinical procedures with the most up-to-date published productinformation and data sheets provided by the manufacturers and the most recentcodes of conduct and safety regulations. The authors and the publisher do notaccept any liability for any errors in the text or for the misuse or misapplicationof material in this work.

Printed in Spain by TG Hostench S.A., Barcelona

Electronic ISBN 978 1 84692 563 4

Contents

Preface vi

Acknowledgement vi

Abbreviations vii

1 Normal esophageal anatomy and physiology 1Gross anatomy 1Anatomy of the esophageal wall 1Esophageal innervation 2Normal deglutition 2

2 Esophageal tesing 5Endoscopy 5Endoscopic ultrasound 10Barium swallow 13Esophageal manometry 14Ambulatory monitoring 17

3 Esophageal symptom assessment 31Typical symptoms 31Atypical symptoms 32Oropharyngeal dysphagia 33

4 Esophageal disease states 37Achalasia 37Non-achalasia motility disorders 47Webs and rings 52Strictures 58Neoplasms 62Gastroesophageal reflux disease (GERD) 69Extra-esophageal GERD 80Barrett’s esophagus 86Hiatal hernia 89Diverticula 94Foreign body 98Pill-induced injury 101Infectious esophagitis 103Caustic injury 108Upper gastrointestinal bleeding 110Varices 112

Gastroenterology Society Guidelines 115

Index 117

vi

Preface

This Atlas of Esophageal Diseases is intended to provide anoverview of the esophagus in health and disease. It is astarting point to familiarize doctors in training, as well asexperienced physicians and their staff, with both commonand rare diseases which may affect the esophagus. Patternrecognition is often key in establishing the correct diagnosis,and we believe that this atlas provides the basics for suchconcise and efficient diagnosis.

The atlas is organized to show normal esophagealanatomy and function initially, followed by the role foresophageal testing, and then to review diseases affecting the

esophagus from ‘A’ (achalasia) to ‘Z’ (Zenker’sdiverticulum). In each section the reader is provided withtables, figures, and appropriate references. The informationprovided is in summary and is not intended to be allinclusive. For more detailed information in each area werefer the readers to recent publications and reviews.

Michael F Vaezi, MD, PhD, MS(epi)Woosuk Park, MD

Jason Swoger, MD, MPH

Acknowledgement

We thank Dr Jason Vollweiler for his contributions to this atlas.

vii

Abbreviations

AC alternating currentACE angiotensin-converting enzymeACG American College of GastroenterologyAGA American Gastroenterological AssociationAIDS acquired immunodeficiency syndromeAPC argon plasma coagulatorASGE American Society of Gastrointestinal Endoscopybid twice dailyCMV cytomegalovirusCT computed tomographyDDx differential diagnosisDEA distal esophagueal amplitudeDES diffuse esophageal spasmDGER duodenogastroesophageal refluxEGD esophagogastroduodenoscopyEM esophageal manometryEMR endoscopic mucosal resectionENT ear, nose, and throatEUS endoscopic ultrasoundFNA fine-needle aspirationGEJ gastroesophageal junctionGERD gastroesophageal reflux diseaseGI gastrointestinalGVHD graft-versus-host diseaseH2RA histamine receptor antagonistHGD high grade dysplasiaHIV human immunodeficiency virusHPV human papilloma virusHSV herpes simplex virus

IEM ineffective esophageal motilityLES lower esophageal sphincterLPR laryngopharyngeal refluxLR reflux laryngitisMEN multiple endocrine neoplasiaMII multi-channel intraluminal impedanceNE nutcracker esophagusNERD non-erosive reflux diseaseNO nitric oxideNSAID non-steroidal anti-inflammatory drugPEG percutaneous gastrostomy (tube)PET positron emission tomographypo by mouthPPI proton-pump inhibitorqac before mealsqd once dailyqhs before sleepRF radio frequencySCC squamous cell carcinomaSCJ squamocolumnar junctionSCM squamocolumnar marginSIDS sudden infant death syndromeTBS timed barium swallowTIPS transhepatic intrajugular portosystemic shuntTLESR transient lower esophageal sphincter relaxationTNM tumor, nodes, and metastasisTPN total parenteral nutritionUES upper esophageal sphincterVIP vasoactive intestinal polypeptide

Normal esophagealanatomy and physiology

Chapter 1

Gross anatomy

The esophagus is a muscular tube connecting the pharynx tothe stomach, the proximal margin of which is the upperesophageal sphincter (UES). This is the functional unit thatcorrelates anatomically with the junction of the inferiorpharyngeal constrictor and cricopharyngeus muscles. Theesophagus extends distally for 18–26 cm within the posteriormediastinum as a hollow muscular tube to the loweresophageal sphincter (LES) (1.1), which is a focus oftonically contracted, thickened, circular smooth muscle2–4 cm long, that lies within the diaphragmatic hiatus.

Anatomy of the esophageal wall

The esophageal wall is comprised of four layers: mucosa,submucosa, muscularis propria, and adventitia; it has noserosa, making it unique to the rest of the gastrointestinal(GI) tract. Normal mucosa consists of stratified squamousepithelium, lamina propria, and muscularis mucosa, withlymphatic drainage beginning in the lamina propria (1.2).

The muscularis propria consists of both skeletal andsmooth muscle: the proximal 5–33% is skeletal muscle, themiddle 35–40% is mixed, and the distal 50–60% is smoothmuscle. Muscles are arranged into inner circular and outerlongitudinal layers (1.3).

1

1.1 Schematic view of the esophagus and its relationshipto neighboring structures. The proximal margin of theesophagus is the UES. The esophagus then extends for18–26 cm within the posterior mediastinum as a hollowmuscular tube to the LES.

Cm

16

23

27

31

35

39

UES

Aorta

LES

Cervicalesophagus

Thoracicesophagus

Abdominalesophagus

Distancefrom

incisors40 cm

Esophageal innervation

Smooth muscle portions are innervated by the vagus nerve,which controls peristalsis under physiologic conditions.Neural innervation is from the myenteric (Auerbach’s)plexus located between the two muscle layers, and fromMeissner’s plexus located in the submucosal (1.3). Themyenteric plexus is responsible for esophageal peristalsis,whereas Meissner’s complex is the site of afferentsensory input.

There are two main neurotransmitters within the myen-teric plexus (1.4): (1) acetylcholine produces excitatorystimulation, which mediates contraction of both longi-tudinal and circular muscle layers, with the largest effectproximally; (2) nitric oxide (NO) causes an inhibitory effect,predominantly on the circular layer, with the greatest effectdistally.

Normal deglutition

The UES, the esophageal body, and the LES act in acoordinated manner to allow swallowing. In theoropharyngeal/voluntary phase of swallowing, the foodbolus is propelled into the pharynx from the mouth. This isfollowed by the esophageal/involuntary phase, during whichthe bolus is propelled from pharynx to stomach by a rapidsequence of precisely coordinated events (1.5), as described

Normal esophageal anatomy and physiology2

1.2 Wall layers and lymphaticdrainage of the esophagus.Note the four wall layers:mucosa (stratified squamousepithelium, lamina propria, and muscularis mucosa),submucosa, muscularis propria,and adventitia. There is a richlymphatic supply, which beginsin the lamina propria.

1.3 Cross-sectional anatomy of the esophagus. Note theouter longitudinal layer and inner circular layer of smoothmuscle. Auerbach’s plexus, which is responsible forperistalsis, is located between the two muscle layers.Meissner’s plexus, responsible for sensation, is in thesubmucosa.

Meissner’s plexus(submucosal)

Auerbach’s plexus(mysenteric)

Circular muscle

Vagus nerve

Longitudinal muscle

Mucosa

Muscularispropria

Adventitia

Lamina propriaMuscularis mucosa

Submucosa

Normal esophageal anatomy and physiology 3

below. The phase begins as the larynx becomes elevated andthe epiglottis seals the airway. An immediate pharyngealcontraction then transfers the bolus through the relaxedUES into the esophagus. As the UES closes, progressivecircular contraction begins in the upper esophagus andproceeds distally along the esophageal body to propel the

1.4 Innervation of the esophagus. Thestriated muscle in the proximal one-thirdof the esophagus is innervated by thesomatic efferent cholinergic fibers of thevagus nerve originating from the nucleusambiguus. In the distal two-thirds, themyenteric plexus is innervated by thepre-ganglionic cholinergic vagus nervefibers from the dorsal motor nucleus.The myenteric plexus has two types ofpost-ganglionic neurons: excitatorycholinergic neurons, and inhibitorynitrinergic (NO) and vasoactive intestinalpolypeptide- (VIP) containing neurons.

bolus through the relaxed LES. Peristaltic pressures rangingfrom 30–180 mmHg are generated. The LES closes with aprolonged contraction, thus preventing movement of thebolus back into the esophagus. The mechanical effect ofperistalsis is a stripping wave that milks the esophagus cleanfrom its proximal to its distal end.

1.5 Normal esophageal peristalsis. The esophageal body and sphinctersare intricately coordinated. UESpressure (located at 19 cm) falls quicklyat swallow initiation (WS), followed byinitiation of esophageal body peristalsisand LES relaxation (located at 42 cm).The peristaltic pressure tends to belower in the proximal and mid-esophagus, and higher in the distalsmooth muscle portion of theesophagus.

WS

19 cm

22 cm

27 cm

32 cm

37 cm

42 cm

mmHg1501209060300

9060300

60300

60300

60300

60300

Aorticarch

Pharynx

UES

Esophagealbody

LES

Vagus nerve

Upper esophagus

Lower esophagus

Dorsal motor nucleus

Nucleus ambiguus

AchAch

Ach NO VIP

Ach

Striated muscle fiber

Smooth muscle fiber

Further reading

Goyal RK, Prasad M, Chang HY (2004). Functionalanatomy and physiology of swallowing and esophagealmotiliy. In The Esophagus, DO Castell, JE Richter (eds).Lippincott Williams and Wilkins, New York, pp 1-36.

Normal esophageal anatomy and physiology4

Esophageal testing

Chapter 2

Endoscopy

IndicationsEndoscopy is the technique of choice to detect structuralabnormalities of the esophagus and to evaluate the mucosa.The most common indications include dysphagia,symptoms of gastroesophageal reflux disease (GERD), andgastrointestinal (GI) bleeding.

EquipmentEndoscopy allows direct visualization of the esophagealmucosa and detect structural abnormalities. Endoscopesuse fiberoptic technology to capture and transmit the imagefrom the distal end of the endoscope (2.1). Four-way tipdeflection is permitted by the use of two control knobs, onewith up/down movement and the other with right/left

5

movement (2.2–2.4). Endoscopes are equipped withinternal channels for air, water, suction, and instruments(2.5, 2.6). The separate instrument channel allows thepassage of biopsy forceps and other instruments used fortreatment of upper GI disorders. Visualization is improvedwhen air is used to insufflate the esophagus and stomach,which are normally compressed.

Both small and large scopes are available (2.7, 2.8): the‘therapeutic’ endoscope contains a larger instrumentchannel that permits passage of ‘jumbo’ biopsy forceps andlarger coagulation devices, whereas ‘pediatric’ endoscopesmay be as small as 4 mm and allow transnasal or transoralendoscopy without sedation.

2.1 The typical forward-viewing endoscope used forexamination of the upper GI tract in an adult. Standardendoscopes range from 8–11 mm in diameter, and arefrom 100–160 cm in length. Controls allow formanipulation of viewing direction, air insufflation, suction, water spray, and taking still photos or video.

Esophageal testing6

2.2 Side view close up. The two control knobs allow forfour-way tip deflection. The outer/smaller dial is forright/left movement and the inner/larger dial for up/downmovement. The biopsy channel allows for insertion ofmultiple instruments including biopsy forceps, brushes,electrocautery probes, snares, and sclerotherapy needles.

2.3 Rotating the inner dial up with the thumb causes thetip of the endoscope to deflect downward.

2.4 Rotating the inner dial down in the opposite directioncauses the tip to deflect upward. Note the degree ofdeflection is not as great as when deflected downward.

2.5 Front view of the endoscopic controls. The twobuttons allow for suction, water spray, and air insufflation.The forefinger is used to press the top button for suction.The second finger is usually employed to cover thesecond button resulting in air insufflation. Pressing thisbutton will result in water spray.

Esophageal testing 7

2.6 End view of the endoscope. Note the three channelsfor suction, insufflation, and instruments. Two lightsources are also present. (1: video camera lens; 2: waterflush nozzle for lens cleaning; 3: auxillary water channel;4: light; 5: instrument channel.)

2.7 Upper GI endoscopes come in a variety of sizes. Thesmall caliber endoscope (right), or ‘pediatric’ endoscope,has a diameter of 5–6 mm. It is ideal for use in children,but is also useful in adults with strictures or narrowingsthat the standard caliber endoscope cannot pass. Thesesmaller instruments do have disadvantages, includingdecreased durability, poorer image quality, and smallerbiopsy sizes. The larger ‘therapeutic’ scope (left) allowsthe passage of larger tools and more effective suction.

2.8 End view of instrument channel of different sizeendoscopes. Note the decrease in size of the channelfrom the therapeutic endoscope (left) to the small caliberendoscope (right).

4

4

1

2

35

Esophageal testing8

TechniqueIn the United States, upper GI endoscopy is routinelyperformed under conscious sedation. Local anesthetic issprayed on the posterior pharynx and intravenous sedationadministered while the patient is in the left lateral decubitusposition (2.9). The endoscope is inserted into the posteriorpharynx where the pharynx and larynx can be examined forabnormalities (2.10). The endoscope is then advancedunder direct vision into the tonically closed upperesophageal sphincter. The patient is asked to swallow torelax the upper esophageal sphincter (UES) and theendoscope is advanced to the proximal esophagus, wherethe mucosa should normally be smooth and light pink(2.11, 2.12).

The area of the gastroesophageal junction (GEJ) iscarefully examined to identify specific landmarks (2.13),

and is defined by the proximal margin of the gastric folds.The squamocolumnar junction (SCJ) can be recognized bythe irregular Z-line demarcating the interface between thelight pink esophageal squamous mucosa and the redcolumnar mucosa gastric mucosa (2.14).

The diaphragmatic hiatus can be identified bydiaphragmatic contraction noted during patient respiration.The SCJ, the GEJ, and the diaphragmatic hiatus arenormally located at the same level, unless pathology ispresent. In patients with Barrett’s esophagus, the SCJ ismore proximal in the esophagus than the GEJ, whereas inpatients with hiatal hernia, the GEJ is more proximal thanthe diaphragmatic indentation. While in the stomach, theendoscope is ‘retroflexed’ to look back at the GEJ; this yieldsa better view of the gastric side of the junction (2.15).

2.9 The patient is placed in left lateral decubitus position forproper positioning. The endoscopist stands directly in front ofthe patient’s mouth with the view screens located directlyopposite. (Courtesy of John J Vargo, MD, Cleveland Clinic,Ohio, USA.)

2.10 An endoscopic view of normal appearing vocalcords. This landmark is identified as an endoscopicexam begins, after the endoscope is passedthrough the incisors and over the tongue. Patientswith extraesophageal reflux disease can presentwith symptoms, such as hoarseness, which can becaused by exposure of the vocal cords to gastricacid. Findings suggestive of reflux disease mayinclude erythema, edema, granulomas, ulcerations,and laryngeal carcinoma.


2.11 Endoscopic appearance of the mid-esophagusduring a normal examination. The squamousmucosa is pale and pink, without ulceration orinflammation. The lumen is of uniform caliber, andexpands uniformly with air insufflation. Landmarksseen as the esophagus is traversed includepulsation of left atrium and aorta along withindentation from left mainstem bronchus.

2.12 An esophageal inlet patch (arrow) is an areaof heterotropic gastric epithelium found in thecervical esophagus. Note the darker red gastricmucosa, in contrast to the pale, pink esophagealmucosa. This is a common finding on upperendoscopy, and does not cause any symptoms inthe patient. Inlet patches do not undergo malignanttransformation, and usually no further follow-up iswarranted.

2.13 Schematic diagram of the compositionof the normal gastroesophageal junction.Note the relationship of the squamocolumnarjunction to the diaphragm, which comprisesthe LES. The LES is the most importantbarrier protecting the esophagus from theregurgitation of gastric contents.

LES

Squamocolumnarjunction

Gastroesophagealjunction

Esophageal testing10

2.14 An endoscopic view of a normal SCJ. Themore proximal pale pink esophageal squamousmucosa meets the darker red gastric mucosa.The junction is irregular, and is called the ‘Z-line’.The location of the transition point more than 2 cm above the diaphragm signifies hiatalhernia. This junction is usually found at 38–40 cm from the incisor teeth in adults.

2.15 Gastric cardia on endoscopic retroflexion.Abnormalities to be noted include hiatal hernia,ulcers, gastric varices, and Mallory–Weiss tears.

Endoscopic ultrasound

IndicationsEndoscopic ultrasound (EUS) provides images of thedistinct layers of the esophageal wall and periluminalstructures (such as lymph nodes). The primary indicationsfor esophageal EUS are staging of esophageal cancer andevaluation of submucosal esophageal lesions.

EquipmentAn endoscope is used that has ultrasound transmission andreception capability at the tip of the instrument (2.16, 2.17).Linear echoendoscopes scan in the same plane as the longaxis of the endoscope, whereas radial echoendoscopes havea rotating mechanical ultrasound probe that scans in a circleat 90 degrees to the long axis of the endoscope.

TechniqueThe echoendoscope is inserted using a similar technique toa regular endoscope. Two video screens are used: onedisplays a standard endoscopic image, and the other theultrasound image (2.18). The endosonographic layers of theesophagus can then be delineated as five alternatinghyperechoic and hypoechoic bands that correspond to thehistologic layers (Table 2.1, 2.19). Structures adjacent to theesophagus including the aorta, spine, left lobe of the liver,left atrium, lungs, and lymph nodes can also be visualized(2.20–2.23). With a linear instrument, fine-needle aspiration(FNA) can be performed of adjacent lymph nodes. This iscritical for accurately staging esophageal cancer.


2.16 View of echoendoscopes. The radial echoendoscope(left) has a rotating mechanical ultrasound probe thatscans in a circle 90 degrees to the long axis of the scope.The linear echoendoscope (right) scans in the long axis ofthe scope.

2.17 Balloon insufflation. A small latex balloon is placedover the ultrasound transmitter. With the balloon filled withwater (A), better acoustic coupling can be achievedbetween the probe and the esophageal wall. This resultsin an improved ultrasound image. Note the light source ison which will provide an oblique endoscopic view.

2.18 Two video screens are utilized: one screen showsthe standard endoscopic image and the other theultrasound image. (Courtesy of John J Vargo, MD,Cleveland Clinic, Ohio, USA.)

Esophageal wall Endosonographic layer appearance

Superficial mucosa HyperechoicDeep mucosa HypoechoicSubmucosa HyperechoicMuscularis propria HypoechoicAdventitia Hyperechoic

Table 2.1 Endosonographic appearance ofesophageal wall layers

A

B

2.19 Schematic view of the esophageal wall and associated endoscopic ultrasound view.The endosonographic layers of the esophagus can be delineated as five alternatinghyperechoic and hypoechoic bands that correspond to the histologic layers. Theinnermost layer is hyperechoic and corresponds to the interface between the ultrasoundwaves and the superficial mucosa. The second layer is hypoechoic and corresponds tothe deep mucosa. The third layer is hyperechoic and corresponds to the submucosa. Thefourth layer represents muscularis propria and is depicted as a hypoechoic band. The fifthlayer is hyperechoic and represents the adventitia in the esophagus.


2.20 Normal endoscopic ultrasound, radial. (1: mucosaand muscularis mucosa; 2: submucosa; 3: inner circularsmooth muscle; 4: intermuscular connective tissue; 5: outer longitudinal muscle; 6: adventitia.)

2.21 Normal endoscopic ultrasound, linear. (Courtesy ofJohn J Vargo, MD, Cleveland Clinic, Ohio, USA.)

123

45

6


2.22 Endoscopic ultrasound of the LES. An echo-endoprobe with higher frequency (higher detail, lesspenetration) can allow detailed visualization of themusculature of the LES. Note the hypoechoic innercircular and outer longitudinal layers separated by a thinband of hyperechoic material (1: inner circular smoothmuscle; 2: outer longitudinal smooth muscle).

2.23 3-D Endoscopic ultrasound of the LES. Here theultrasound image is reconstructed to a longitudinal view.Again note the two layers of the muscularis propria (1: inner circular smooth muscle; 2: outer longitudinalsmooth muscle).

Barium swallow

IntroductionContrast studies enable radiographic examination of theesophagus and can be done alone, in combination withoropharyngeal evaluation, or as a part of an upper GI series.The following techniques are used for routine examination:• Double contrast.• Full-column.• Mucosal relief.• Fluoroscopic observation.

IndicationsIndications for a barium swallow include:• Dysphagia.• Odynophagia.• GERD.• Esophageal strictures.• Esophageal motility disorders.• Esophageal function testing.

Double contrastThis can be achieved by coating the esophagus with densebarium and subsequently distending it with gas (2.24).Double contrast is a good test for evaluating the esophagealmucosal surface to detect small neoplasms, esophagitis, anddiverticulosis. In some cases the gastroesophageal junctionmay not adequately distend, resulting in poor detection ofhiatal hernias, lower esophageal mucosal rings, and pepticstrictures.

Full-columnThis involves rapid filling of the esophagus with barium(2.25) while patient is in prone position and is a good testfor evaluating esophageal motility. It is also a usefultechnique to visualize hiatal hernias, lower esophagealmucosal rings, and peptic strictures (see figures from theappropriate sections), but may not detect small neoplasms,mild esophagitis, and esophageal varices.

1

2

1

2


2.24 Double contrast bariumswallow. Double contrast bariumswallow is performed by coatingthe esophagus with a densebarium and distending it with gas.This allows simultaneousexamination of the distendedesophagus and its mucosalsurface.

2.25 Full-column bariumswallow, obtained by rapidfilling of the esophagus withbarium while the patient is inthe prone position. Esophagealmotility may be assessed withfluoroscopy in the proneposition by observing multipleswallows of barium. It is a goodtest to visualize hiatal hernias,lower esophageal mucosalrings, and peptic strictures.However, it may not detectsmall neoplasms, mildesophagitis, and esophagealvarices.

Mucosal relief Imaging of the collapsed esophagus coated with densebarium allows good visualization of smooth, longitudinalesophageal folds. Irregularity of the thickening of these foldscan be due to small neoplasms, esophagitis, and esophagealvarices. Lesions that require esophageal distension are notseen well.

Fluoroscopic observationFluoroscopic observation provides a motion recording ofesophageal function and motility with each barium swallow,which facilitates evaluation of esophageal and oropharyngealfunctional disorders.

Esophageal manometry

IntroductionManometry can be used as a diagnostic test to evaluateesophageal motor function.

It measures intraluminal pressures and coordination ofthe pressure activity of the three functional regions of theesophagus: the lower esophageal sphincter (LES),esophageal body, and UES. The manometry probe consistsof a 4 mm polyvinyl catheter containing several small caliber

lumens that are perfused with water from a low complianceperfusion device (2.26). When a catheter port is occluded byan esophageal contraction, water pressure builds within thecatheter exerting a force, which is conveyed to an externaltransducer. The electrical signals from the transducers aretransmitted to a computer, which produces a graphic record.

IndicationsIndications for manometry are presented in Table 2.2, andinclude:• Evaluation of dysphagia in patients without evidence of

mechanical obstruction, such as strictures, or in whomachalasia is suspected.

• Defining the location of the LES for placement ofintraluminal devices, such as a pH probe, which requirespositioning relative to LES.

• Pre-operative evaluation for anti-reflux surgery in patientssuspected of having esophageal motility disorder such asachalasia.

• Other possible indications are:– Evaluation of dysphagia in patients treated for achalasia

or have undergone anti-reflux surgery.– Routine pre-operative assessment of esophageal

peristalsis prior to anti-reflux surgery.

Manometry is not indicated for making or confirming thediagnosis of GERD, or as the initial test for non-cardiacchest pain.

TechniqueManometry is performed after an overnight fast using around 4 mm polyvinyl catheter continuously perfused withdistilled water at a rate of 0.5 ml/min by a low compliance,

pneumohydraulic capillary infusion system (2.27). Thestationary pull-through technique is used to determine thelocation and length of the LES and UES.

Esophageal motility is then assessed by using 10 wetswallows (5 ml water each) with the distal recording sitepositioned 5 cm above the LES. Tables 2.3 and 2.4 demon-strate normal and pathological values for manometry andfigure 2.28 shows a typical esophageal manometric tracing.


Indicated

Evaluation of dysphagia in patientswithout evidence of mechanicalobstruction or if achalasia issuspected

Pre-op evaluation for anti-refluxsurgery in patients suspected ofhaving esophageal motility disorder,such as achalasia

Defining the location of LES forplacement of intraluminal devices,such as pH probe, which requirespositioning relative to LES

Possibly indicated

Evaluation of dysphagia in patientstreated for achalasia or undergoneanti-reflux surgery

Routine pre-op assessment ofesophageal peristalsis prior to anti-reflux surgery

Not indicated

As the initial test for non-cardiacchest pain

Diagnosis of GERD

Table 2.2 Indications for esophageal manometry

GERD: gastroesophageal reflux disease; LES: lower esophageal sphincter

2.26 Esophageal manometry probe, consisting of a 4 mmpolyvinyl catheter that contains several small caliber lumensthat are perfused with water from a low compliance perfusiondevice. When a catheter port is occluded by an esophagealcontraction, water pressure builds within the catheter exertinga force, which is conveyed to an external transducer. Theelectrical signals from the transducers are transmitted to acomputer, which produces a graphic record.


2.27 Esophageal manometry in a patient. The manometryprobe is inserted into the esophagus via nares. The catheteris then advanced to approximately 60 cm, which is wellwithin the stomach. At this point, the patient is placed supineon the left side and the catheter is calibrated. The stationarypull-through technique is then used. This involves slowlywithdrawing the catheter through the LES, esophagus, andUES. Resting LES pressure and relaxation are thusevaluated by a series of wet swallows.

LESP 10.0–45.0 mmHg

Esophageal body amplitude 30.0–180.0 mmHg

Esophageal body contraction duration 1.0–6.0 seconds

Distal onset velocity <8.0 seconds

UESP 30.0–118.0 mmHg

LESP: lower esophageal sphincter pressureUESP: upper esophageal sphincter pressure

Table 2.3 Normal values for esophageal manometry

2.28 Normal manometric tracing. The wet swallowinitiates a progressive peristaltic contraction in thebody of the esophagus with wave amplitudes of30–180 mmHg. The LES relaxes completely togastric baseline at the end of peristalsis.

Wet swallow

100

0

100

0100

0100

0100

0

LES

pre

ssur

e(m

mH

g)

Pro

xim

ales

opha

geal

pres

sure

(mm

Hg)

Dis

tal

esop

hage

alpr

essu

re(m

mH

g)

15 seconds

Ambulatory monitoring

24-hour pHIntroductionThis is an important tool in the diagnosis and managementof GERD as it can detect and quantify gastroesophagealreflux and correlate symptoms temporally with reflux.

IndicationsIndications for ambulatory pH monitoring are presented inTable 2.5 and include:

• To document abnormal acid exposure in patients withsuspected GERD but without endoscopic esophagitis.

• To evaluate the efficacy of medical or surgical therapiesfor GERD:

– In patients with GERD who are refractory to proton-pump inhibitor (PPI) therapy.

– In patients with anti-reflux surgery who have continuedreflux symptoms.

Other possible indications include:

• Evaluation of non-cardiac chest pain.• Evaluation of ear, nose and throat (ENT) manifestations

associated with GERD that are refractory to aggressivePPI therapy.

• Evaluation of reflux-induced asthma in an adult patientwith new-onset asthma. (A positive test does not provecausality.)

The test is not indicated to detect or confirm refluxesophagitis (reflux esophagitis is an endoscopic diagnosis),or for evaluation of non-acid reflux.


Diagnosis Criteria

Normal ≤20% ineffective; ≤10% simultaneous; average DEA <180 mmHg and >30 mmHg; normal LES resting pressure

Achalasia Isobaric simultaneous contractions or aperistalsis; poorly relaxing LES

Scleroderma Low amplitude or absent contraction in distal esophagus, with or without low LES pressure

DES ≥20% simultaneous normal amplitude esophageal contractions – intervening normal peristalsis

IEM ≥30% of swallows with amplitude <30 mmHg in either of the two distal sites at 5 and 10 cm above LES

Nutcracker esophagus Normal peristalsis with DEA >180 mmHg

Poorly relaxing LES Average LES residual pressure >8 mmHg

Hypertensive LES LES resting pressure >45 mmHg

Hypotensive LES LES resting pressure <10 mmHg

DEA: distal esophagueal amplitude; DES: diffuse esophageal spasm; IEM: ineffective esophageal motility; LES: lower esophageal sphincter

Table 2.4 Manometric criteria for esophageal motility disorders

EquipmentThe pH probe consists of 2.1 mm monocrystal line catheterswith antimony electrodes. There are three types of probe:• Single: has one pH sensor at the catheter tip; it measures

pH at the distal esophagus (5 cm above LES) (2.29).• Double: has two pH sensors 15 cm apart to detect pH at

the distal and proximal esophagus (2.29).• Triple: composed of two catheters; one catheter has two

pH sensors for hypopharyngeal and proximal esophagealpH monitoring and another catheter has one pH sensorfor the distal esophagus (2.30).

TechniqueThe pH probe is inserted into the esophagus via the naresand a distal electrode is positioned 5 cm above the proximalborder of the LES. LES location is usually determined priorto pH probe placement using esophageal manometry. ThepH electrodes are connected to a portable digital datarecorder (2.31) (Digitrapper Mark III Gold; SynecticsMedical AB, Stockholm, Sweden) worn around the waist,which stores pH data samples every 4 seconds for up to 24hours.

Patients are required to keep a diary of symptoms, mealtimes, time of lying down for sleep, and time of rising in themorning. They are instructed to perform normal dailyactivities, consume their usual diet without restrictions, andavoid taking naps during the daytime. Patients return on thefollowing day after a minimum of 18 hours to have the probesremoved and diaries reviewed. Data is analyzed using adedicated computer program (Gastrosoft, Irving, TX, USA).

Normal valuesA pH <4 is used as a cutoff for acid reflux, as this is the levelwhich is associated with the onset of heartburn (1) and hasbeen shown to best discriminate between normal andGERD cases (2). It has been found that esophageal pH isnormally <4.0 for a small percentage of the time (3)(Table 2.6, 2.32–2.35).


Indicated

Suspected GERD without endoscopicesophagitis

Assessment of efficacy of medical orsurgical therapies of GERD

Possibly indicated

Non-cardiac chest pain

ENT manifestation of GERDrefractory to PPI therapy

Reflux induced asthma

Not indicated

Detection of reflux esophagitis

Evaluation of non-acid reflux

Table 2.5 Indications for pH monitoring

ENT: ear, nose, and throat; GERD: gastroesophageal reflux disease; PPI: proton-pump inhibitor

pH electrode Body position % time pH <4.0

Proximal Total >1.1Upright >1.7Supine >0.6

Distal Total >5.5Upright >8.3Supine >3.0

Table 2.6 Normal values for pH monitoring


2.29 Single and double pH probes. A single pH probecontains one electrode which detects distal esophagealacid exposure at 5 cm above LES. The double pH probehas two electrodes 15 cm apart for acid exposuredetection at both distal and proximal esophagus.

2.30 Triple pH probe. It consists of three electrodes whichare used to detect acid exposure in the distal andproximal esophagus and in the hypopharynx.

2.31 A triple pH probe with portable data logger. The dataloggers use sampling rate of eight per minute with 0.1 pHunit resolution. There are input buttons on the data loggerto indicate events such as heart burn, meal time, supineposition, and so on.

2.32 A 24-h ambulatoryesophageal single probepH tracing in a normalsubject. Periods of mealsand supine position areindicated by horizontalbars. For the majority ofthe time, the esophagealpH is >4.0. (H: heartburn;M: meal; S: supine.) 11 am 3 pm 7 pm 11 pm 3 am 7 am 11 am

8

6

4

2

0

pH

SMH

MHH

M

Double

Single

Hypopharyngeal

Proximalesophageal

Distal esophageal


2.33 24-h ambulatoryesophageal single probe pHtracing in a gastroesophagealreflux disease (GERD)subject. Esophageal pHtracing shows markedlyincreased prevalence of distalpH >4.0 (>5.5%) consistentwith GERD. (C: chest pain; H: heartburn; M: meal; S: supine.)

2.34 pH tracing ofproximal and distal acidexposure. This tripleprobe pH tracing showsa pH drop to <4.0 inboth proximal and distalelectrodes but not inthe hypopharyngealelectrode. There is nohypopharyngeal acidexposure.

2.35 pH tracing ofhypopharyngeal acidexposure, shown by apH drop to <4.0 in allthree electrodes. This isin contrast with figure2.34 which does notshow hypopharyngealacid exposure.

9 am 1 pm 5 pm 9 pm 1 am 5 am 9 am

87654321

pH

SM M M

CCH H

Meal

Hypopharyngeal

Proximal

Distal

864208642086420

12:00/1 12:10/1 12:20/1 12:30/1 12:40/1 12:50/1 13:00/1

Meal

864208642086420

Hypopharyngeal

Proximal

Distal

20:30/1 20:40/1 20:50/1 21:00/1 21:10/1 21:20/1 21:30/1

Bravo wireless systemIntroductionBravo pH (Medtronic, Shoreview, MN, USA) is a wirelessambulatory pH monitoring system approved by the FDA,which consists of two components, a small pH capsule(2.36A) and a pager-sized receiver (2.36B)(4).

IndicationsThe indications for Bravo pH monitoring are the same as fortraditional 24-hour ambulatory esophageal pH monitoring.

TechniqueThe Bravo system comes in a pre-packaged assemblyconsisting of a pH capsule and a delivery system. Esophago-gastroduodenoscopy (EGD) is performed prior to Bravocapsule deployment, to determine the GEJ. The pH capsuledelivery system is then passed into the esophagus transorallyor transnasally and positioned so that the pH capsule is 6 cmabove the GEJ. After proper positioning, a vacuum isapplied which fills the suction chamber of the pH capsulewith the adjacent esophageal tissue. The safety pin isremoved and the locking pin is advanced which securelyattaches the Bravo capsule to the esophageal wall (2.37).

The capsule transmits pH data to the receiver via radiotelemetry signals. The pH monitoring is performed over24–48 hours and the patients are given the same instructions

as for standard pH monitoring. After the testing period, thepatient returns the receiver and the data is downloaded viaan infrared link to the computer and analyzed using adedicated software program.

The capsule is designed to slough off from the esophagealwall and pass through the GI tract.

InterpretationThe normal values are the same as traditional pHmonitoring (2.38, 2.39).

Bile refluxIntroductionBile reflux, or duodenogastroesophageal reflux (DGER),refers to regurgitation of duodenal contents through thepylorus into the stomach and subsequently into theesophagus. DGER may be important because factors otherthan acid, such as bile and pancreatic enzymes, may play arole in mucosal injury and symptoms in patients withGERD. Alkaline pH is a poor marker for DGER, which leadto the development of bilirubin monitoring.

IndicationsIndications for bile monitoring include detection of DGER.It has a limited clinical role as acid and bile reflux usuallyoccur together.


A B

2.36 A: Bravo pH capsule is 6 × 5.5 × 25 mm in size withantimony pH electrode and reference electrode located at thedistal tip of the capsule. An internal battery and transmitter arealso contained within the capsule. The pH capsule is placed 6 cm above the gastroesophagel junction determined by upperendoscopy. The pH capsule sends data using radio telemetry tothe external receiver. B: Bravo external receiver and pH capsule.

2.37 Bravo capsule deployed on the esophageallumen.


Reflux Table – Acid Reflux Analysis – Day 1

Total (Normal) Upright (Normal) Supine (Normal)

Fraction time pH <4 (%) 1.1 5.5 1.6 8.2 0.0 3.0



Fraction time pH <4 (%) 2.2 5.5 3.4 8.2 0.0 3.0

SI Table – Total SIP Table – Total

Total

HrtBrn 5.6

ChestP n/a

Regurg n/a

Cough n/a

Total

HrtBrn 64.3

ChestP 0.0

Regurg 0.0

Cough 0.0



Fraction time pH <4 (%) 17.6 5.5 27.1 8.2 5.9 3.0



Fraction time pH <4 (%) 21.9 5.5 26.5 8.2 16.6 3.0

SI Table – Total SIP Table – Total

Total

HrtBrn 50.0

ChestP n/a

Regurg n/a

Cough n/a

Total

HrtBrn 100.0

ChestP 0.0

Regurg 0.0

Cough 0.0

EquipmentA fiberoptic spectrophotometer (2.40) (Bilitec 2000,Synectics, Stockholm, Sweden) uses the optical propertiesof bilirubin to detect DGER. Bilirubin has a characteristicspectrophotometric absorption band at 450 nm. Absorptionnear this wavelength implies the presence of bilirubin and,therefore, DGER.

TechniqueAmbulatory bilirubin monitoring can be employed, similarto pH monitoring. Data is recorded as percent time thatbilirubin absorbance is >0.14, and can be analyzed for total,upright, and supine periods (2.41). Normal values forpercent total, upright, and supine times bilirubin is >0.14are 1.8%, 2.2%, and 1.6%, respectively.

This instrument may underestimate bile reflux in anacidic medium, so must be accompanied by simultaneouspH monitoring (2.42). A modified diet is necessary to avoidinterference and false readings, as the probe indiscriminatelyrecords any substance around 450 nm.

2.38 Normal 48-hr Bravo pHmonitoring. There is no increase in acid exposure in either day ofmonitoring.

2.39 48-hr Bravo pH monitoringshowing abnormal acid reflux. Thereis increased acid exposure in bothdays of monitoring. Additionally, thesymptom index correlates in 50% ofthe episodes of heartburn reported.

2.40 Bilitec 2000 monitor for duodenogastroesophagealreflux. The probe is a fiberoptic spectrophotometerdesigned for the detection of bilirubin in the distalesophagus.


M M MS

H H C C87654321

0.8

0.6

0.4

0.2

0.0


MMM

H H C C

S

pHB

iliru

bin

abso

rban

ce

S


11 am 3 pm 7 pm 11 pm 3 am 7 am

0.8

0.6

0.4

0.2

0Bili

rubi

n ab

sorb

ance

High episode Total Upright Supine Meal Post P Heart burnDuration (HH:MM) 19:54 12:54 07:00 00:20 06:00 00:12Number of episodes (#) 30 28 2 0 21 1Number of episodes longer

than 30 minutes (#) 0 0 0 0 0Longest episode (Min) 28 23 26 0 23 4Total time absorbance above 0.14 (Min) 181 128 53 0 97 4Fraction time absorbance above 0.14 (%) 15.2 16.2 12.7 0.0 26.8 33.3Median absorbance value – – – – – –

H HH

M M S M

2.42 Simultaneous pH and bile monitoring. Note that the episodes ofduodenogastroesophageal reflux correlating with meals (M) are associatedwith acid reflux as well. (C: chest pain; H: heartburn; S: supine.)

2.41 Bilitec tracing of a patient with duodenogastroesophageal reflux. Reflux is defined asbilirubin absorbance >0.14. This patient has several postprandial episodes of refluxassociated with heartburn (H). Also note the prolonged episode of duodenogastroesophagealreflux while supine (S). (M: meal.)


Intraluminal impedanceIntroductionMulti-channel intraluminal impedance (MII) is analternative technique available for the evaluation of GERD.Impedance is a measure of total resistance to the alternatingcurrent (AC) flow. Substances with high ionicconcentration, such as liquids, have high conductance andlow impedance. Conversely, substances with low ionicconcentration, such as air, have low conductance and highimpedance. A mixed (liquid and gas) bolus exhibits thecharacteristics of both (2.43)(5).

A typical MII catheter consists of multiple impedancemeasuring segments (i.e. multi-channel) mounted 5 cmapart on a 2.1 mm diameter polyvinyl catheter (SandhillScientific Inc., Denver, CO, USA) (2.44). Characteristicesophageal impedance tracing correlating with a liquid bolus

2.43 Relative impedance of various substances found inthe esophageal lumen. Impedance is a total resistance ofa substance to alternating current flow. Therefore, it is theopposite of conductance and is dependent on the ionicconcentration. Substances with high ionic concentrationhave high conductance and low impedance (e.g. liquid).Conversely, substances with low ionic concentration havelow conductance and high impedance (e.g. gas).

Air

Esophageal lining

Saliva

Food

Refluxate

Conductance

Impe

danc

e

2.44 Multi-channel intraluminalimpedance probe, consisting of fourimpedance-measuring segmentsspaced 5 cm apart. Each impedance-measuring segment consists of twoelectrodes 2 cm apart.

movement across the impedance-measuring segment wasvalidated with simultaneous video-fluoroscopy (2.45)(7).The direction of bolus movement is determined based onthe time sequence of bolus entry and exit through differentimpedance measuring segments (2.46, 2.47)(7).

Two variations of MII have been introduced for clinicaluse: combined MII and pH monitoring (MII-pH) andcombined MII and manometry (MII-EM). MII-pH permitsdifferentiation of the refluxate as either acid or non-acid andis useful for evaluation of GERD. On the other hand, MII-EM allows concurrent measurement of the esophagealcontraction and corresponding bolus movement and can beused for esophageal function testing.

1

2

3

4

5 cm

2 cm

UES

LES

2.45 Characteristic impedance tracing of aliquid bolus. At baseline, the esophagus is anarrow, empty tube and the impedance isdetermined by the electrical properties of theesophageal mucosa. As the bolus reachesthe impedance-measuring segment, theesophagus expands and the impedance risessharply due to the air in front of the bolushead. This is followed by a rapid drop inimpedance as the higher conductive liquidbolus passes the measuring segment. Bolusentry is considered to be at the 50% drop inimpedance from baseline, and bolus exit atthe 50% rise from the nadir. The impedancestays at nadir as long as the bolus is present on the impedance-measuring segment. Esophageal contractioncauses lumen narrowing and passage of bolus, resulting in transient impedance elevation (‘overshoot’) abovethe baseline before returning to baseline.


2.46 Impedance tracing ofantegrade bolus movement.Antegrade movement (orswallow) is shown by proximal todistal detection of bolus by theimpedance-measuring segments.

Entry Exit

Baseline

50%

Nadir

Esophagealcontraction

Boluspresence time

Impe

danc

e (o

hms)

1

2

3

4

5Time

1955

2131531

195921

2351497

213

Impedance at four sites (ohms)

UES

LES

2.48 Combined multi-channelintraluminal impedance and pH (MII-pH). Usually, impedance recording isperformed in combination with pHmonitoring. Combined they providecomplementary information of therefluxate: the composition of therefluxate (liquid, gas, or mixed) andpH (acid vs. non-acid). CombinedMII-pH catheter is a thin flexible 2.1 mm polyvinyl catheter (SandhillScientific Inc., Denver, CO, USA)similar to a standard pH catheter (A).On this catheter are six impedance-measuring segments (four distal and two proximal) and a pH sensor (B). It isplaced into the esophagus transnasally and positioned so that the pH sensoris 5 cm above LES. The impedance-measuring segments are located on thecatheter such that when properly placed in the esophagus, impedance at 3, 5, 7, 9, 15 and 17 cm above LES are measured.

Combined MII-pHMII-pH can characterize reflux events as liquid, gas, ormixed (liquid and gas) and acid, weak-acid, acid re-reflux,or non-acid (Table 2.7, 2.48–2.50)(7).

The results are interpreted based on the normal valuesestablished by Shay et al. (Table 2.8)(8). MII-pH is useful for


2.47 Impedance tracingof retrograde bolusmovement. Retrogrademovement (or reflux) is shown by distal toproximal detection ofbolus by the impedance-measuring segments.

A

B

the evaluation of typical and atypical gastroesophageal refluxsymptoms refractory to aggressive acid suppression therapy,and in elucidating the role of non-acid reflux in continuedreflux symptoms.

Time

1

2

3

4

5

1875

2291495

205920

2311501

220

Impedance at four sites (ohms)

17 cm

15 cm

9 cm7 cm5 cm3 cm

Distance above LES

pH electrode

Impedanceelectrode

LES

UES

UES

LES

2.49 A patient with MII-pH probe. The MII-pH test is performed similar to 24-hourambulatory pH monitoring. Patients are instructed to fast 4–6 hours before theMII-pH probe is placed. During the monitoring period, the patients are instructedto perform normal daily activities, consume a usual diet, and keep a diary ofsymptoms, meal times, time of lying down for sleep, time of rising in the morning,and time of acid-suppression medication. The patients return the following day tohave their probe removed and diaries reviewed. The MII-pH data are downloadedand analyzed using a dedicated computer program.


Acid reflux pH drop to <4.0 from baseline pH >4.0

Weak acid reflux pH drop by >1 unit but pH remains >4.0

Acid re-reflux Acid reflux when pH already <4.0

Non-acid reflux pH remains >4.0 and does not drop by >1 unit

Table 2.7 Multi-channel intraluminal impedance-pH classifications of reflux (7)

Total Acid Weak acid Non-acid Acid re-reflux

Distal Total 73 55 26 1 4Upright 67 52 24 1 4Recumbent 7 5 4 0 1

Proximal Total 31 28 12 1 2Upright 29 25 11 1 2Recumbent 3 2 1 0 0

(Shay et al. (2000). American Journal of Gastroenterology 99(6):1037–1043.)

Table 2.8 Multi-channel intraluminal impedance-pH normal values (number of reflux events)


2.50 MII-pH tracing of acid, non-acid, and gas reflux.Gastroesophageal reflux is shown by retrograde patternof the impedance recording. The proximal extent of therefluxate can also be determined by the most proximalimpedance-measuring segment that detects therefluxate. A: Acid reflux: impedance tracing showsretrograde pattern. The refluxate composition is liquidas shown by the decrease in impedance. In addition,pH drops to below 4.0 confirming that this is an acidreflux. B: Non-acid reflux: a similar liquid reflux but pHremains above 4.0. C: Gas reflux: a retrogradeimpedance pattern is seen. However, the impedancetracing shows marked increase in impedance consistentwith gas refluxate. The pH remains unchanged.

A B

C

Combined MII-EMMII-EM is useful for esophageal function testing as itprovides simultaneous assessment of esophageal motilityand corresponding functional bolus transit (2.51, 2.52).MII-EM classifications of swallows and normal values are

shown in Table 2.9 and Table 2.10 respectively. Theindications for MII-EM are similar to those for conventionalesophageal manometry (dysphagia, non-cardiac chest pain,GERD, pre-operative evaluation for anti-reflux surgery).

Impedance

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

Ohms

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

3 cm

5 cm

7 cm

9 cm

15 cm

17 cm

pH8

6

4

2

00 Sec 5

UES

LES

17 cm

15 cm

9 cm

7 cm

5 cm

3 cm

pH:5 cm

Impedance

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

Ohms

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

3 cm

5 cm

7 cm

9 cm

15 cm

17 cm

pH8

6

4

2

00 Sec 5

UES

LES

17 cm

15 cm

9 cm

7 cm

5 cm

3 cm

pH:5 cm

Impedance

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

300020001000

0

Ohms

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

0 5 Sec

3 cm

5 cm

7 cm

9 cm

15 cm

17 cm

pH8

6

4

2

00 Sec 5

UES

LES

17 cm

15 cm

9 cm

7 cm

5 cm

3 cm

pH:5 cm

pH2([H+]=12 meq/L)

pH7([H+]=0 meq/L)

pH2([H+]=12 meq/L)

2.51 Combined MII-EM. The MII-EM catheter is available as a 9 channel, 4.5 mm diameter flexible polyvinyl catheter with five pressure sensors (twocircumferential and three unidirectional) and four impedance measuringsegments (Sandhill Scientific Inc., Highlands Ranch, CO, USA). The twocircumferential pressure sensors are located 5 and 10 cm from the cathetertip and three unidirectional pressure sensors at 15, 20, and 25 cm from thetip. The four impedance measuring segments, consisting of two ringedelectrodes 2 cm apart each, are centered at 10, 15, 20, and 25 cm from thetip. The catheter is inserted transnasally and positioned in the esophageallumen using stationary pull-through technique so that the most distal pressuresensor is placed at the high pressure zone of LES. Thus, the remainder ofpressure sensors and impedance measuring segments are located 5, 10, 15,and 20 cm above LES.


2.52 A patient undergoing MII-EM. MII-EM is performed ina similar fashion as standard esophageal manometry withfew differences. Unlike manometry, 10 liquid swallows ofnormal saline, instead of water, are given since the formerhas standardized ionic concentration and knownimpedance characteristics. Additionally, 10 viscousswallows are performed with ‘apple sauce’ consistencymaterial with known impedance. The data are recordedand analyzed using dedicated computer software (InsightAcquisition and Bio View Analysis, Sandhill Scientific Inc.,Highlands Ranch, CO, USA).

Classification Criteria

Manometry

Normal Amplitudes at 5 and 10 cm above LES ≥30 mmHg and distal onset velocity <8 cm/sec

Simultaneous Amplitudes at 5 and 10 cm above LES ≥30 mmHg and distal onset velocity >8 cm/sec

Ineffective Amplitudes at 5 or 10 cm above LES <30 mmHg

Impedance

Complete bolus Bolus entry detected at 20 cm transit shown to have bolus exit at all

distal sites (15, 10, and 5 cm)

Incomplete bolus Bolus entry detected at 20 cm transit which does not have bolus exit

at any of the three distal sites

LES: lower esophageal sphincter

Table 2.9 Multi-channel intraluminal impedance-esophageal manometry classification of swallows (9)

20 cm

15 cm

10 cm

5 cm

UES

LES

1

2

3

4

5

Impedance

Pressure

Distanceabove LES

References

1 Johnson LF, Demeester TR (1974). Twenty-four-hourpH monitoring of the distal esophagus. A quantitativemeasure of gastroesophageal reflux. Am J Gastroenterol62:325–332.

2 Vitale GC, Cheadle WG, Sadek S, et al. (1984).Computerized 24-hour ambulatory esophageal pHmonitoring and esophagogastroduodenoscopy in thereflux patient. A comparative study. Ann Surg200:724–728.

3 Richter JE, Bradley LA, DeMeester TR, Wu WC (1992).Normal 24-hr ambulatory esophageal pH values.Influence of study center, pH electrode, age, and gender.Dig Dis Sci 37(6):849–856.

4 Pandolfino JE, Richter JE, Ours T et al. (2003).Ambulatory esophageal pH monitoring using a wirelesssystem. Am J Gastroenterol 98(4):740–749.

5 Sifrim D, Holloway R, Silny J, et al. (2001). Acid,nonacid, and gas reflux in patients with gastroesophagealreflux disease during ambulatory 24-hour pH-impedancerecordings. Gastroenterol 120(7):1588–1598.

6 Sifrim D, Silny J, Holloway RH, et al. (1999). Patterns ofgas and liquid reflux during transient lower oesophagealsphincter relaxation: a study using intraluminal electricalimpedance. Gut 44(1):47–54.

7 Tutuian R, Vela MF, Shay SS, et al. (2003). Multi-channel intraluminal impedance in esophageal functiontesting and gastroesophageal reflux monitoring. J ClinGastroenterol 37(3):206–215.

8 Shay S, Tutuian R, Sifrim D, et al. (2004). Twenty-fourhour ambulatory simultaneous impedance and pHmonitoring: a multicenter report of normal values from60 healthy volunteers. Am J Gastroenterol99(6):1037–1043.

9 Tutuian R, Vela MF, Balaji NS, et al. (2003). Esophagealfunction testing with combined multichannelintraluminal impedance and manometry: multicenterstudy in healthy volunteers. Clin Gastroenterol Hepatol1(3):174–182.

Further reading

Pandolfino JE, Kahrilas PJ (2005). AmericanGastroenterological Association medical positionstatement: Clinical use of esophageal manometry.Gastroenterol 128:207–208.

Pandolfino JE, Kahrilas PJ (2005). AGA Technical reviewon the clinical use of esophageal manometry. Gastroenterol128:209–224.

Park W, Vaezi MF (2005). Esophageal impedancerecording: Clinical Utility and Limitations. CurrGastroenterol Rep 7:182-189.

(1996). American Gastroenterological Association medicalposition statement: guidelines on the use of esophagealpH recording. Gastroenterol 110:1981–1996.


N=43 (95th percentile) Liquid bolus Viscous bolus

Total bolus head advance time (entry @ 20 cm → entry @ 5 cm) 5.0 sec 7.5 sec

Total bolus transit time (entry @ 20 cm → exit @ 5 cm) 12.5 sec 12.5 sec

Smooth muscle segmental transit time (entry @ 10 cm → exit @ 5 cm) 10.5 sec 8.5 sec

% complete bolus transit ≥80 ≥70

Table 2.10 Multi-channel intraluminal impedance-esophageal manometry normal values (9)

Esophageal symptomassessment

Chapter 3

Typical symptoms

Heartburn (pyrosis) and acid regurgitationDefinitionHeartburn is a substernal burning sensation, usuallyoccurring from 30 minutes to 2 hours post-prandial, thatcan radiate up to the neck and throat. Heartburn is usuallyworsened by lying down and bending over, and can awakenpatients from sleep. Large meals before sleeping areassociated with heartburn. Certain foods (alcohol, caffeine,coffee, chocolate, peppermint, tomatoes), as well ascigarettes and medications are also associated with anincreased risk of heartburn. Symptoms are usually improvedwith antacids. Heartburn is extremely prevalent, and occursin up to 33% of Americans on a monthly basis.

Acid regurgitation occurs when a small amount of acidicor bitter fluid that appears spontaneously and effortlessly inthe back of the throat or mouth. It is most common aftermeals, but it can also awaken patients from sleep and can beassociated with coughing or choking. It is separated from‘vomiting’ by an absence of retching and associated nausea.

DiagnosisThese are the classic symptoms of GERD and, in theabsence of warning signs (GI bleeding, weight loss, irondeficiency anemia, dysphagia), empiric therapy with acid-suppressive agents can be instituted. If symptoms do notimprove after a sufficient trial (up to 12 weeks), or warningsigns are present, further investigation is warranted. Upperendoscopy is often the first diagnostic test in the presence ofwarning signs, and pH monitoring is useful in associatingsymptoms with increased intraesophageal acid exposure.

31

Non-acid regurgitationDefinitionNon-acid regurgitation is described as food or fluid beingpresent in the mouth without a recognized associated‘vomiting’ episode. The food seems to effortlessly appear inthe mouth.

EtiologyThe contents that appear in the mouth can be undigestedfood, which is almost always associated with esophagealobstruction of some degree. This can be seen in associationwith strictures, rings, achalasia, or a pharyngeal pouch.

Water brashDefinitionWater brash is defined as a sudden filling of the mouth witha large amount of fluid, that is often clear and salty in taste.

EtiologyThis is caused by a reflex secretion (cholinergic) fromsalivary glands in the mouth, in response to stimulation fromdistal esophageal acid irritation. Water brash is oftenassociated with GERD, especially if acid regurgitation andheartburn are present.

HiccupDefinitionAn acute, involuntary lowering of diaphragm with glottisclosure – produces a characteristic sound.

EtiologyUremia, reflux, obstruction (achalasia or stricture).

OdynophagiaDefinitionThe symptom of odynophagia is best defined as thesensation of pain with swallowing. This symptom is stronglyassociated with an esophageal or pharyngeal abnormality,and is produced from local inflammation or neoplasm in themouth and pharynx. The symptom is described as burningor pain after swallowing, and can be associated with acidic,spicy, or hot or cold food.

EtiologyOdynophagia is most often associated with erosiveesophagitis of any etiology – pill-induced, infectious (CMV,HSV, Candida sp.), acid related, radiation, or caustic injury,and is commonly seen in patients with AIDS and patientsundergoing chemotherapy. When severe, cessation ofswallowing may occur.

DysphagiaDefinitionThe symptom of dysphagia, described by patients as adifficulty swallowing, is strongly associated with anesophageal abnormality. Patients describe the food ‘sticking’or ‘hanging up’ during its passage down the esophagus,during a swallow. Although pain may coexist, dysphagiamust be separated from odynophagia (pain with swallowing,see below). It is also important to differentiateoropharyngeal dysphagia from esophageal dysphagia.

EtiologyA detailed clinical history is often extremely helpful infinding an etiology. Dysphagia can be conceptualized asbelonging to two main groups: obstructive and motilityrelated (Table 3.1).

Esophageal symptom assessment32

Atypical symptoms

Globus DefinitionThe globus sensation is defined as the feeling of fullness, ora lump in the throat. Patients may also describe a ‘tickling’sensation in their throat. Globus is often a constantsymptom, and may improve with swallowing.

EtiologyIf pharyngeal, laryngeal, and neck physical and mechanicaletiologies are excluded, globus can be associated withmultiple esophageal etiologies. Possibilities include –hypertensive UES, altered visceral sensation, GERD, webs,diverticula, and dysmotility disorders (achalasia, ineffectiveesophageal motility).

Chest painChest pain, often qualitatively similar to ischemic chestpain, can be secondary to an esophageal abnormality. Thisis due to a shared embryologic sensory innervation. As thissymptom mimics the pain of myocardial ischemia, allevaluations must first definitively rule out a cardiac etiology.Like ischemic chest pain, it may be relieved by nitroglycerin.Esophageal chest pain is classically non-exertional, and canbe spontaneous, post-prandial, or occur at night.Symptoms may last for minutes to hours. It is oftenassociated with other esophageal symptoms, such asheartburn, regurgitation, and dysphagia. If thought to benon-cardiac, this chest pain is often secondary to anabnormal visceral nociception, an esophageal motordisorder, or GERD.

RespiratoryMultiple respiratory symptoms, such as asthma, bronchitis,and cough, have been associated with GERD. Thesesymptoms may be due to GERD as well as oropharyngealswallowing disorders. Continued acidic aspiration can leadto coughing, throat clearing, and hoarseness. Patients mayalso present with pneumonia from aspiration of gastriccontents.

DiagnosisClues in the history that will aid in diagnosis include thefollowing: • If the dysphagia presents with liquids, solids, or both: a

motility disorder may be indicated. Dysphagia to solidsonly is usually obstructive, and is usually progressive.

• If the dysphagia is progressive or intermittent: episodicdysphagia to liquids and solids can suggest a motordisorder, while intermittent dysphagia to solids suggests afixed esophageal ring or web. Progressive dysphagia(solids to solids and liquids) suggests an obstructiveetiology (stricture, neoplasm, or achalasia).

• If there associated heartburn: this may suggest a pepticstricture or scleroderma.

Other associated symptoms, such as pattern of onset,pain, weight loss, choking, and drugs, may narrow thedifferential diagnosis. If the progression of dysphagia israpid, and is associated with weight loss, esophagealcarcinoma must be suspected. The initial diagnosticmodality for dysphagia depends on the diagnostic suspicion.In those whom a motility disorder is suspected, bariumswallow should be the initial test. In those suspected ofhaving structural (obstructive) causes of dysphagia, upperGI endoscopy may be the better initial diagnostic modality.

Oropharyngeal dysphagia

EpidemiologyOropharyngeal dysplasia is an extremely commoncondition, and increases in prevalence with age. It occurs inone-third of all stroke patients and is common in patientswith head injuries, Parkinson’s, and Alzheimer’s disease(20–40% prevalence). Up to 60% of nursing homeoccupants have feeding difficulties, with a substantialproportion having dysphagia. Consequences includemalnutrition, aspiration, choking, pneumonia, and death. Ittherefore carries a high morbidity, mortality, and cost.

EtiologySwallowing is a complex act, requiring interplay of multiplemuscles and neurological pathways in order for the bolus topass from the oral cavity into the esophagus. Table 3.2 liststhe common causes of oropharyngeal dysphagia. Commoncategories of underlying etiologies include central nervoussystem diseases, peripheral nervous system diseases,myogenic diseases (including drug-induced), metabolicabnormalities, infectious diseases, and structural disorders.

Clinical presentationOropharyngeal dysphagia can result from disturbance in anyaspect of the swallow response, and can be seen as delayedswallow initiation, aspiration, nasopharyngeal regurgitation,and excessive post-swallow residue. The patient can oftenaccurately localize the site of the dysfunction, as opposed tothe case in distal esophageal obstruction. Patients havedifficulty initiating a swallow, and have immediate coughing,choking, gagging, and nasal regurgitation.

Oral symptoms include drooling or spillage of food,sialorrhea, xerostomia, difficulty initiating swallowing,dysarthria, and piecemeal swallowing. Pharyngealsymptoms may include sensation of a bolus holding up inthe neck, post-nasal regurgitation, repeated swallowing toclear food, coughing and choking, and dysphonia. Othersymptoms include odynophagia and sore throat, dysphagia,and regurgitation of old food.

A neurological exam and evaluation of neurologicalsymptoms is often helpful in discovering the cause oforopharyngeal dysphagia, as neurological or neuromuscularfindings may assist in directing the physician to theunderlying primary etiology of the dysfunction.

Esophageal symptom assessment 33

Obstructive (mechanical)StricturesCarcinomaRingsWebsDiverticulaTumors – benignPill-induced injuryForeign bodyExternal compression – mediastinal, cervical osteoarthritis, vascular

Motility (neuromuscular)AchalaisaIneffective esophagealmotilityDiffuse esophagealspasmNutcracker esophagusSclerodermaHypertensive LESChagas’ disease

Table 3.1 Causes of dysphagia



Neuromuscular

Cerebrovascular accident

Parkinson’s disease

Brainstem tumors

Amyotrophic lateral sclerosis

Multiple sclerosis

Peripheral neuropathy (poliomyelitis)

Huntington’s chorea

Tabes dorsalis

Spinocerebellar degeneration

Syringobulbia

Amyloidosis

Botulism

Wilson’s disease

Progressive bulbar paralysis

Structural lesions

Zencker’s diverticulum

Retropharyngeal abscess

Cricopharyngeal bar

Thyromegaly or thyroid tumor

Cervical osteophyte or spur

Oropharyngeal carcinoma

Esophageal carcinoma

Esophageal web

High esophageal stricture

Inflammatory disease – tonsilar abscess, pharyngitis

Foreign body

Post-surgical change

Vascular anomalies

Cervical lymphadenopathy

Plummer–Vinson syndrome

Skeletal muscle disorders

Myasthenia gravis

Metabolic myopathies

Polymyositis

Muscular dystrophies – myotonic and oculopharyngeal

Inflammatory myopathies

Dermatomyositis

Scleroderma

Mixed connective tissue disease

Inclusion body myositis

Myxedema

Sarcoidosis

Systemic lupus erythamatosis

Hyperthyroidism

Stiff-man syndrome

Cranial nerve diseases

Rabies

Lead poisoning

Diabetes mellitus

Recurrent laryngeal nerve palsy

Transection or injury

Diphtheria

Other neurotoxins

Miscellaneous

Cricopharyngeal dysfunction

Decreased saliva – radiation, Sjögren’s syndrome,medications

Alzheimer’s disease

Depression

Table 3.2 Causes of oropharyngeal dysphagia

DiagnosisEvaluation by a speech pathologist can assist withinformation about language, cognitive dysfunction, and thestrength of the muscles involved in swallowing and speech.

Barium swallow contrast radiography can detectstructural causes of dysphagia, including cricopharyngealbar diverticula, neoplasm, webs, and stenoses (3.1–3.4).However, these films cannot accurately assess the mechanicsof swallowing. Videofluoroscopy is the best method ofassessment, as it allows replay of the act of swallowing,which enables assessment of the mechanisms and theseverity of dysfunction present to be established. Otherimportant information from this examination includes the

presence, timing, and severity of aspiration. Video-fluoroscopy does not allow for quantification of contractileforces or intrabolus pressure, or detection of incompleteupper esophageal sphincter (UES) opening.

Nasoendoscopy is the gold standard for identifying andbiopsying mucosal abnormalities. It is mandatory ifmalignancy is suspected in the differential diagnosis.

Manometry allows quantification of deglutitive forces,assesses UES relaxation, and assesses the coordination ofpharyngeal contraction and UES relaxation. Manometryfindings must be compared with appropriate age-specificstandards.

Esophageal symptom assessment 35

3.1 Barium study depicting a cricopharyngealbar. Hypertrophy and fibrosis of thecricopharyngeus muscle, coupled withincomplete relaxation, causes this defect ofthe posterior cervical esophagus. This musclecomprises the UES, and progression of thebar can lead to oropharyngeal dysphagia.Surgical myotomy is sometimes used forsymptomatic improvement in severe cases.

3.2 A patient with cervical dysphagia withesophageal web on barium swallow.

TreatmentResponse to treatment is variable and unpredictable, anddepends on factors including the underlying cause, theseverity and nature of mechanical dysfunction, the amountof cognitive dysfunction, and the prognosis of theunderlying etiology. It therefore involves a multidisciplinaryapproach.

Aims of treatment include identifying and treating theunderlying disease, along with attempting to circumvent orcompensate for the specific mechanical disturbances.Structural problems may be amenable to surgery, dilation,or myotomy. Speech pathology should be involved in orderto assess the risk for aspiration and to evaluate for possibleinstitution of non-oral feeding options.

Botulinum toxin injection may be of benefit inoropharyngeal dysphagia secondary to failed musclerelaxation, but further studies are needed before this therapycan be strongly recommended. Swallow therapy maneuversinclude dietary modification, changes in swallowing posture,and alterations in the techniques of swallowing. Thesechanges aim to strengthen swallowing muscles and modifythe mechanics of swallowing. Percutaneous gastrostomy(PEG) tubes may be necessary to reduce the risk ofaspiration, although studies have not shown a decrease inthe risk of aspiration pneumonia following initiation of PEGtube feeding.

Further reading

Cook IJ, Kahrilas PJ (1999). AGA technical review on themanagement of oropharyngeal dysphagia. Gastroenterol116:455–478.

Johnston BT, Castell DO (2004). Symptom overview andquality of life. In The Esophagus, DO Castell, JE Richter(eds). Lippincott Williams and Wilkins, New York, pp37–46.


3.3 High degree of stenosis in a patient withcervical dsyphagia.

3.4 Endoscopic view (A) and barium x-ray (B)for a patient post-esophagectomy and cervicaldysphagia.

A

B

Esophageal disease states

Chapter 4

Achalasia

DefinitionAchalasia is a primary esophageal motor disorder ofunknown cause, which is characterized by insufficient loweresophageal sphincter (LES) relaxation and aperistalsis.

Etiology The cause of achalasia remains unknown. Available datasuggest degenerative, autoimmune, infectious andhereditary factors as possible causes (1).

37

Esophageal motor innervation and normal physiology The proximal one-third of the esophagus (striated muscle)is innervated directly by the somatic efferent cholinergicfibers of the vagus nerve originating from the nucleusambiguus (4.1). The distal two-thirds of the esophagus(smooth muscle) are controlled by the myenteric plexus,which is innervated by the pre-ganglionic cholinergic vagusnerve fibers from the dorsal motor nucleus. The myenteric

4.1 Esophageal motor innervation.Thestriated muscle of the proximal esophagusis innervated directly by the somaticefferent cholinergic fibers of the vagusnerve originating from the nucleusambiguus. Smooth muscle of the distalesophagus is innervated by the pre-ganglionic vagus nerve fibers from thedorsal motor nucleus. The neurotransmitterreleased, acetylcholine, affects two types ofpost-ganglionic neurons in the myentericplexus: excitatory cholinergic neurons andinhibitory nitrinergic neurons.

Vagus nerve

Upper esophagus

Lower esophagus

Dorsal motor nucleus

Nucleus ambiguus

AchAch

Ach NO VIP

Ach

Striated muscle fiber

Smooth muscle fiber

plexus has two types of post-ganglionic neurons: (i)excitatory cholinergic neurons; and (ii) inhibitory nitrinergic(nitric oxide, NO) neurons and vasoactive intestinalpolypeptide- (VIP) containing neurons.

At baseline, the esophagus is in a contractile statemediated by excitatory cholinergic neurons. Deglutitioninduces inhibitory NO and VIP neuron excitation, resultingin esophageal and LES relaxation. Peristalsis results fromcoordinated relaxation and contraction mediated by theinhibitory and excitatory myenteric plexus neurons alongthe path of the esophagus.

Pathophysiology The hallmark of achalasia is the loss of inhibitory NO andVIP neurons in esophageal myenteric plexus. In earlyachalasia, there is inflammation of the myenteric plexus (T-cell lymphocytic infiltration) without the loss of ganglioncells (4.2). In later stages, loss of myenteric ganglion cellsand neural fibrosis ensues. In a selective manner, post-ganglionic inhibitory myenteric neurons containing NO andVIP are lost, whereas post-ganglionic excitatory cholinergicneurons are spared. The net result is unopposed cholinergicstimulation. This results in high basal LES pressure andfailure of LES relaxation. In addition, loss of latencygradient along the esophageal body, which is mediated bynitric oxide, results in aperistalsis.

EpidemiologyThe incidence is 1–2 per 200,000 (2). Both sexes areaffected equally, with onset usually in the third to fifthdecades, but can occur at any age.

Clinical presentationDysphagia to solids is present in nearly all achalasia patients.Dysphagia to liquids present in two-thirds of achalasiapatients. Regurgitation is found in 60–90% of achalasiapatients. It usually occurs shortly after a meal, or whilerecumbent. Undigested food is regurgitated.

Chest pain is found in one-third of achalasia patients. Itis located retrosternally and is typical of non-cardiac chestpain. Pain is precipitated by eating, which thus causesdecreased intake and weight loss.

Other symptoms include weight loss (associated withadvanced disease), pulmonary symptoms, and coughingspells secondary to aspiration.

DiagnosisDiagnosis of achalasia requires radiographic, manometric,and endoscopic evaluation.

Esophageal disease states38

4.2 Histology of achalasia. There is inflammation of themyenteric plexus with T-cell lymphocytes.

Esophageal disease states 39

4.3 Characteristicbarium esophagramof achalasia. Thereis poor emptying ofthe barium from theesophagus which isdilated. There is acharacteristic ‘bird’sbeak’ narrowing ofthe distalesophagus due to anon-relaxing LES.

4.4 End-stageachalasia (sigmoidesophagus). Theesophagus ismarkedly dilatedand tortuous,forming a sigmoidshape.

Radiographic studiesBarium esophagram (4.3, 4.4)This is the primary screening test for evaluation of achalasia,and has a 95% accuracy in diagnosing achalasia. Essentialfeatures are:

• ‘Bird’s beak’ narrowing of the LES with incompleteopening.

• Loss of primary peristalsis.• Delayed esophageal emptying.

Supportive features include a dilated or sigmoid-shapedesophagus, and epiphrenic diverticula.

Timed barium swallow (4.5)This provides objective evaluation of esophageal function. Itis performed as a primary evaluation of achalasia orassessment of response to pneumatic dilation (3, 4).

Three-on-one spot films are taken 1, 2, and 5 minutesafter ingestion of 100–250 ml low-density barium. Thevolume ingested is based on patient tolerance. The degree ofemptying is estimated qualitatively by comparing 1- and 5-minute films, or quantitatively estimated by measuring theheight and width for both films. On subsequent follow-upstudies, the same volume of barium is used for accurateserial assessment (3). In normal individuals, the esophagusis devoid of barium within 1 minute. The goal of therapy inachalasia is to normalize emptying by 5 minutes (3).

This technique has been shown to be a simple andreproducible method for objective assessment of esophagealfunction before and after treatment of achalasia (3).Additionally, it has been shown to be a reliable predictor ofresponse to pneumatic dilation therapy and is an importanttool in post-pneumatic dilation evaluation (4, 5).


4.5 Timed barium swallow (TBS) in two patients (A and B) with significant delay in esophageal emptying.TBS provides objective evidence of esophageal function and is most useful in diagnosing achalasia andassessing the response to therapies such as pneumatic dilation, or surgical myotomy. It is performed with 250 ml of barium. After the barium is ingested, an X-ray is taken in upright position at time 1, 2, and 5 minutes. The barium height and width at 1, 2, and 5 minutes are measured. In normal population, thebarium completely empties in 1 minute.

A B

Esophageal manometryThis is needed to confirm or establish the diagnosis ofachalasia, especially when an esophagram is inconclusive.Essential features are:

• Aperistalsis in the distal two-thirds of the esophagus(4.6).

• Simultaneous onset.• Isobaric (identical pressure tracings in all leads).• Abnormal LES relaxation with swallows.

Supportive features include hypertensive LES pressure(LES pressure >45 mmHg), and low amplitude esophagealcontractions (contraction amplitude <30 mmHg).

EndoscopyEndoscopy is necessary to rule out pseudoachalasiasecondary to malignancies at the esophagogastric junction.

A typical esophagus on endoscopy in an achalasia patientis dilated and tortuous. It is not uncommon to find retainedfood debris and secretions in the esophagus. The LESremains closed with air insufflation and appears puckered(4.7). The gastroesophageal junction (GEJ) and gastriccardia (4.8) are carefully examined for evidence of tumors.


4.6 Manometric findings in achalasia. Achalasia is definedmanometrically by aperistalsis and failure of LESrelaxation. The pressure tracing shows low amplitudesimultaneous contractions. Pressure tracings in all leadsare identical or isobaric. Isobaric contractions are due tothe esophagus being a closed chamber (dilatedesophagus closed by sphincters on both ends), wherepressure changes are detected by all manometric sites. Inaddition, LES does not relax with wet swallow.

Wet swallow100

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4.7 Upper endoscopy of an achalasia patient reveals acharacteristic puckered GEJ. Retained secretions andfood in the esophagus are also frequently seen.

4.8 Retroflexed view of the gastric cardia showsvery tight LES around the endoscope. There isno evidence of malignancy causingpseudoachalasia.

A B

Differential diagnosisVarious disorders with similar manometric and radiologicfeatures as achalasia (pseudoachalasia) should be consideredin making a diagnosis of achalasia (Table 4.1).

The most important cause of pseudoachalasia is malig-nant neoplasm. Tumors cause pseudoachalasia by encirclingor compressing the distal esophagus or infiltrating theesophageal myenteric plexus and impairing inhibitory LESinnervation. Clinical features that suggest malignancy are:

• Duration of symptoms <6 months.• Onset after age 60 years.• Excessive weight loss.• Difficulty with endoscope passage through GEJ during

esophagogastroduodenoscopy (EGD).• Computed tomography (CT) scan showing marked

(>1 cm) and/or asymmetric esophageal wall thickening.


Malignancy

• Gastric adenocarcinoma

• Esophageal squamous cell carcinoma

• Lymphoma

• Lung carcinoma

• Pancreatic carcinoma

• Prostatic carcinoma

• Anaplastic carcinoma

• Colon carcinoma

• Esophageal lymphangioma

• Pleural mesothelioma

Chronic intestinal pseudo-obstruction

Amyloidosis

Sarcoidosis

Chagas’ disease

Post-vagotomy

Pancreatic pseudocyst

Von Recklinghausen’s neurofibromatosis

Anderson–Fabry’s disease

Familial glucocorticoid deficiency syndrome

MEN type IIb

4.1 Disorders with manometric and radiologic features similar to achalasia

MEN: multiple endocrine neoplasia

Low risk

4.9 Achalasia treatment algorithm. (PD: pneumaticdilation.)

High risk

PD Surgery BotoxNitrates

Ca++ channelblockers

3.0 cm3.5 cm4.0 cm

3.5 cm4.0 cm

Males <40 years


Pneumatic Laparascopic Botulinum toxin Nifedipine/nitratesdilation myotomy

Response 60–90% at 1 year; 90% at 1 year; 90% at 1 month; 50–70% initially; 60% at 5 years 85% at 5 years 60% at 1 year <50% at 1 year

Complications 2–-5% perforation 10% symptomatic 20% rash, transient 30% headache, reflux chest pain hypotension

Advantages Good response Minimally invasive Low morbidity Rapidly initiatedrates surgery

Disadvantages Risk of perforation Risks associated Need frequent repeat Poor effect on with general injections within esophageal emptying; anesthesia; may 1 year; causes tachyphylaxisneed conversion to fibroinflammatory open procedure reaction at LES

LES: lower esophageal sphincter. (Adapted from Feldman M, Friedman LS, Sleisenger MH (2002). Sleisenger &Fordtran's Gastrointestinal and Liver Disease, 7th edn. Saunders, Philadelphia.)

4.2 Comparison of treatments for idiopathic achalasia

A B

TreatmentThere is no cure for achalasia. Treatment options include:

• Pneumatic dilation.• Surgical myotomy (Heller).• Botulinum toxin injection.• Medical therapy (calcium channel blockers, nitrates) (see

Table 4.2, 4.9).

Pneumatic dilationAll patients considered for pneumatic dilation should begood surgical candidates because of the 2–5% risk ofesophageal perforation. Pneumatic dilation uses air pressureto disrupt traumatically the circular muscle layer of the LES.Rigiflex balloon dilators are most commonly used and areavailable in three diameters (3.0, 3.5, and 4.0 cm) (4.10). A3.0 cm balloon is usually used for initial dilation. With

4.10 A: Rigiflex pneumatic dilator. B: Thedilator comes in three balloon sizes: 3.0, 3.5,and 4.0 cm. Pneumatic dilation uses airpressure to disrupt traumatically the circularmuscle layer of the LES. A 3.0 cm balloon isusually used for initial dilation. With symptomrecurrence, repeat dilations are performed ina stepwise graded fashion using larger sizedballoons.

symptom recurrence, repeat dilations are performed in astepwise graded fashion using larger sized balloons. Theballoon is positioned over a guidewire using eitherendoscopic or fluoroscopic control across the LES. Theballoon is then inflated until the balloon waist (formed bythe LES) is obliterated. The pressure applied is usually10–14 psi (4.11, 4.12). After dilation therapy, all patientsundergo gastrograffin esophagram followed by bariumesophagram to rule out perforation (4.13).

Studies have shown a 50–93% response rate withpneumatic dilation (6). A higher clinical response rate isseen with each successive dilation, with increasing balloonsize. A recent evidence showed that males <40 years old willlikely fail when a 3.0 cm balloon is used and that they maybeneift from the use of a 3.5 cm balloon as initial therapy.

Surgical therapy: Heller myotomy (4.14)The goal of myotomy is to reduce LES resting pressurewithout causing gastroesophageal reflux. Heller myotomy


4.11 The balloon is positioned over a guidewireusing either endoscopic or fluoroscopic controlacross the LES. Then, the balloon is inflateduntil the balloon waist detected on fluoroscopy(formed by the LES) is obliterated. The pressureapplied is usually 10–14 psi.

4.12 Pneumatic dilation is usually performed using fluoroscopiccontrol. When the balloon is inflated, a waist is formed secondary toa poorly relaxing LES. The balloon is slowly inflated further until thewaist is obliterated.

consists of anterior myotomy across the LES, which isperformed either laparoscopically (abdominal approach) oropen (transthoracic approach). The circular muscle fibersare divided down to the level of the mucosa and themyotomy extends to several centimeters above the LES and<1 cm onto the stomach. Anti-reflux surgery (Dorfundoplication) is usually performed concomitantly. Goodresponse rates are observed, from 80–90% (7).

Botulinum toxin injection (4.15)This can be performed on patients who are high risk forpneumatic dilation or surgical myotomy, such as the elderlyor those with other co-morbidities. Botulinum toxin inhibitsacetylcholine release from nerve terminals, thereby blockingexcitatory effects of the cholinergic neurons. It is initiallyeffective in about 85% of patients. However, the responseonly lasts about 6 months, with >50% symptom recurrencein 6 months.

BA


4.13 Esophageal perforation a patientwith post-pneumatic dilation.

4.14 Open Heller myotomy. Heller myotomy consists of anteriormyotomy across the LES. The circular muscle fibers are divided downto the level of mucosa. The myotomy extends to several centimetersabove LES and <1 cm onto the stomach. Anti-reflux surgery (Dorfundoplication) is usually performed concomitantly.

4.15 A: Botulinum toxin injection isperformed on patients who are highrisk for pneumatic dilation or surgicalmyotomy, such as the elderly or thosewith other co-morbidities. Botulinumtoxin inhibits acetylcholine release fromnerve terminals, thereby blocking theexcitatory effects of the cholinergicneurons. B: It is injected at about 1 cmabove the gastroesophageal junction(large arrow). The LES is highlightedby the smaller arrows at the puckeredGEJ. Botulinum toxin is initiallyeffective in about 85% of patients.However, the response only lasts about6 months with >50% symptomrecurrence in 6 months.

A B

Other pharmacologic optionsCalcium-channel blockers and long-acting nitrates reduceLES pressure. The clinical response is not complete and isshort lasting, with decreased efficacy over time. Therefore,medical therapy is recommended for those who are notcandidates for pneumatic dilation or surgical myotomy andwho fail to respond to botulinum toxin injection.

Complications Complications are related to retention and stasis in theesophagus. They include esophagitis secondary to irritationof the mucosal lining, aspiration of esophageal contents(nocturnal coughing spells or aspiration pneumonia), andesophageal squamous cell carcinoma (SCC).

References 1 Park W, Vaezi MF (2005). Etiology and pathogenesis of

achalasia: the current understanding. Am J Gastroenterol100(6):1404–1414.

2 Howard PJ, Maher L, Pryde A, et al. (1992). Five yearprospective study of incidence , clinical features, anddiagnosis of achalasia in Edinburgh. Gut 33:1011.


SummaryDefinition: primary esophageal motor disorder.Etiology: unknown.Pathophysiology: loss of inhibitory neurons in myenteric

plexus required for LES relaxation. Aperistalsis alsooccurs.

Symptoms: dysphagia, regurgitation, chest pain, weightloss, pulmonary symptoms and coughing.

Diagnosis: contrast radiography (barium esophagram),esophageal manometry and endoscopy.

DDx: pseudoachalasia due to neoplasia.Treatment: pneumatic dilation, surgical myotomy,

botulinum injection, medical therapy (calciumchannel blockers, nitrates).

Complications: esophagitis, aspiration of esophagealcontents, SCC.

3 de Oliveira JM, Birgisson S, Doinoff C et al. (1997).Timed barium swallow: a simple technique for evaluatingesophageal emptying in patients with achalasia. AJR169:473–479.

4 Vaezi MF (2001). Quantitative methods to determineefficacy of treatment in achalasia. GastrointestinalEndoscopy Clinics of America 11(2):409–424.

5 Vaezi MF, Baker ME, Achkar E et al. (2002). Timedbarium oesophagram: Better predictor of long termsuccess after pneumatic dilation in achalasia thansymptom assessment. Gut 40:765–770.

6 Vaezi MF, Richter JE (1998). Current therapies forachalasia: comparison and efficacy. J Clin Gastroenterol27:21-35.

7 Vantrappen G, Hellemans J (1980). Treatment ofachalasia and related motor disorders. Gastroenterol79:144.

Further readingVaezi MF, Richter JE (1999). Diagnosis and management of

achalasia. Am J Gastroenterol 94:3406–3412.


Non-achalasia motility disorders

IntroductionEsophageal motility disorders are associated with abnormalmanometric motility patterns primarily in patients with non-cardiac chest pain and non-obstructive dysphagia (Table4.3). Their clinical significance is unclear (1), and they areassociated with poor correlation between manometricfindings and symptoms. In some cases, treatment mayreduce symptoms but manometric findings are unchanged.In one study of 1,161 adult patients with chest pain ordysphagia, motility abnormality was found in 33% (2).Motility abnormality was more common in patients withsymptoms of dysphagia than chest pain (53% and 28%respectively)(2).

Clinical presentationEsophageal motility disorder should be considered inpatients presenting with dysphagia, chest pain, orodynophagia. For symptoms of dysphagia, structural lesions

must first be ruled out with barium esophagram or upperendoscopy. Cardiac chest pain cannot be distinguished fromesophageal chest pain. Therefore, heart disease must beexcluded before non-cardiac chest pain is entertained.Odynophagia is rare in primary esophageal motility disorder.It is usually due to infectious, pill-induced, or refluxesophagitis and work-up should be performed to rule outsuch causes.

Diagnosis• Barium esophagram is sensitive and specific in detecting

motility disorder when carefully performed withvideofluoroscopy.

• EGD has little role in the evaluation of esophagealdysmotility. It is used in conjunction with barium studiesto rule out structural lesions or esophagitis.

• Manometry is necessary in order to characterize anddefine esophageal motility disorder.

Functional defect Diagnosis Manometric criteria

Aperistalsis Achalasia Isobaric simultaneous contractions; poorly relaxing LES

Scleroderma Low amplitude or absent contraction in distal esophagus, with or without low LES pressure

Incoordinated motility DES ≥20% simultaneous esophageal contractions

Hypercontractile NE Normal peristalsis with DEA >180 mmHg

Hypertensive LES LES resting pressure >45 mmHg

Hypocontractile IEM ≥30% of swallows with amplitude <30 mmHg in either of the two distalsites at 5 and 10 cm above LES

Hypotensive LES LES resting pressure <10 mmHg

DEA: distal esophageal amplitude: DES: diffuse esophageal spasm; IEMD: ineffective esophageal motility; LES: lower esophageal sphincter; NE: nutcracker esophagus

4.3 Manometric diagnosis of motility disorders

Diffuse esophageal spasm (DES)Etiology and pathophysiologyThe etiology of DES is unknown. Suggested mechanisms ofdisease include a hypersensitivity response to cholinergicand hormonal stimulation, mediated by defects in neuralinhibition.

Clinical presentationRecurrent chest pain is indistinguishable from cardiac chestpain and is relieved with nitroglycerin. It is associated withmeals but rarely exertionally induced. Dysphagia isintermittent and non-progressive.

DiagnosisManometry is the only way to diagnose DES accurately.The diagnostic criteria are the presence of normal peristalsisintermixed with simultaneous contractions in ≥20% of wetswallows (4.16)(3).

Finding from barium swallows are variable and areusually normal. Therefore, normal radiographic study doesnot rule out the diagnoses. Tertiary activity producesesophageal coiling appearance (‘corkscrew’) (4.17). TheLES region is usually normal.

Natural historyPatients with DES have an excellent prognosis in general.Transition to achalasia occurs in approximately 3–5% (4).

TreatmentTreatment consists of medications that relax the esophagus,including nitrates and calcium channel blockers. They areusually not effective.


4.16 Manometric finding in DES. There are repetitive simultaneous contractions inthe esophageal body, but some normal peristalsis is maintained. LES relaxation isnormal and complete.

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Wet swallow Wet swallow

Nutcracker esophagusEtiologyThe cause of nutcracker esophagus (NE) is unknown.However, findings of infrequent transition to achalasiasuggests it may be an early part of a spectrum of disease thatresults in achalasia (5). Some believe it may be a functionaldisorder similar to irritable bowel syndrome and associatedwith increased visceral pain perception (6).

Clinical presentationChest pain is the most common (90%) symptom. Dysphagiais less frequent. These patients usually present togastroenterologists after cardiac chest pain is ruled out bytheir internist and cardiologist.

DiagnosisManometry is required to diagnose NE. Diagnostic criteriarequire that all contractions are peristaltic and that thecontraction amplitude is ≥180 mmHg (4.18). Patients withNE may present later as normal or with differentmanometric tracing, such as DES (7).

Radiographic findings are usually normal, since allpatients have normal peristalsis by definition.


4.17 Barium esophagram in DES. The barium swallowstudy shows characteristic ‘corkscrew’ appearance.

4.18 Manometric finding in NE. NE is diagnosedmanometrically as high amplitude (≥180 mmHg)peristaltic contractions with wet swallows.

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Hypertensive lower esophageal sphincter Hypertensive LES is defined by a resting LES pressure>45 mmHg. As part of a peristaltic sequence, LES relaxationoccurs with normal residual pressure (4.19). Of unknownetiology, it is typically seen in patients with symptoms ofchest pain. Dysphagia can also be seen. Barium swallow isusually normal with normal esophageal function.

Ineffective esophageal motility (4.20)The manometric abnormality is characterized by ahypocontractile esophagus, which is defined as distalesophageal contraction amplitude <30 mmHg in ≥30% ofwet swallows. It is commonly associated with gastro-esophageal reflux disease (GERD).


4.19 Manometric finding inhypertensive LES. The restingpressure of the LES is>45 mmHg. As part of theperistaltic sequence, LESrelaxation occurs with normalresidual pressure.

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4.20 Manometry tracing of apatient with ineffectiveesophageal motility showingnormal weak amplitude peristalticcontractions (A) and non-transmitted (NT) esophagealcontraction in distal esophagus(B). (Adapted from Dig Dis Sci[1997] 42: 9.)

A B

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SW SW SW SW12 14 57 55

26 23 78 82

NT NT18 17

Treatment (Table 4.4)GERD should be treated if present. Sublingual nitrates aregiven as needed if symptoms are mild and intermittent. Forunexplained chest pain in patients with depressive or anxietycomponent, trazodone 50–100 mg three times daily orimipramine 50 mg at bed time is recommended. Calcium-channel blockers are prescribed in those who are refractoryto the above treatment: diltiazem 60–90 mg three timesdaily, or nifedipine 10– 20 mg three times daily. For severelyrefractory patients with LES dysfunction, botulinum toxin,pneumatic dilation, or myotomy should be considered.


Nitrates Nitroglycerin 0.4 mg sublingually before meals or as neededIsosorbide 10–30 mg orally 30 minutes before meals

Viceral analgesic Imipramine 50 mg orally at bedtime

Sedatives/antidepressants Alprazolam 2–5 mg orally four times dailyTrazadone 50 mg orally three or four times daily

Calcium-channel blockers Nifedipine 10–30 mg orally four times dailyDiltiazem 60–90 mg orally four times daily

Smooth muscle relaxant Hydralazine 25–50 mg orally three times dailyBotulinum toxin 80 U (injected into LES using endoscopy)

Dilation 50–60 French bougiePneumatic dilation


Table 4.4 Therapeutic options for esophageal motility disorders

References1 Richter JE (2001). Oesophageal motility disorders. Lancet

358:823–828.2 Katz PO, Dalton CB, Richter JE, et al. (1987).

Esophageal testing of patients with noncardiac chest painand/or dysphagia. Results of a three year experience with1161 patients. Ann Intern Med 106:593.

3 Richter JE, Castell DO (1984). Diffuse esophagealspasm: Reappraisal. Ann Intern Med 100:242.

4 Rhoton AJ, et al. (1992). The natural history of diffuseesophageal spasm (DES): a long term follow-up study.Am J Gastroenterol 87:A1256.

5 Anggiansah A, Bright NF, McCullagh M, et al. (1990).Transition from nutcracker esophagus to achalasia. DigDis Sci 35:1162.

6 Richter JE, Obrecht WF, Bradley LA, et al. (1986).Psychological comparison of patients with nutcrackeresophagus and irritable bowel syndrome. Dig Dis Sci31:131.

7 Narducci F, et al. (1985). Transition from nutcrackeresophagus to diffuse esophageal spasm. Am JGastroenterol 80:242.

Webs and rings

Table 4.5 shows the similarities and differences betweenesophageal webs and the two types of esophageal rings (Aand B). Although the terms ‘web’ and ‘ring’ are often usedinterchangeably, there do exist several importantdifferences, and an accurate distinction should be made indescribing these lesions.

Proximal webDefinitionA proximal web is a thin, transverse membrane of squamousmucosal epithelium occurring anywhere in the esophagus,though most often in the proximal esophagus.

EpidemiologyThe prevalence of webs is not well described, although anestimate is 1–8% of the population. Webs have been foundin 5–15% of patients with benign causes of dysphagia who

undergo endoscopic evaluation. They can be locatedanywhere in the esophagus, but typically occur in the post-cricoid area of the upper esophagus, located on the anteriorcervical wall. The prevalence of webs increases with age, andsymptomatic rings are more common in women.

PathophysiologyThe cause of webs is unclear, and most are classified asbeing idiopathic. GERD has been suggested as a possiblecause. Several other conditions have been associated withwebs, but the cause and effect relationship is uncertain.These conditions include thyroid disease, duplication cyst,Zenker’s diverticula, chronic graft-versus-host disease(GVHD), blistering skin diseases (pemphigoid andepidermolysis bullosa), psoriasis, Stevens–Johnsonsyndrome, and laryngeal carcinoma.


Characteristic Esophageal web Mucosal (B ring) Muscular (A ring)

Location Posterior cricoid region along Schatzki’s ring, 1.5 cm proximal to anterior wall squamocolumnar junction – squamocolumnar junction –

associated with hiatal hernia at upper LES

Histology Mucosa and submucosa Mucosa and submucosa Hypertrophied muscle covered by epithelium covered by squamous covered by squamous

and columnar epithelium epithelium

Symptoms Intermittent solid food Intermittent solid food Usually asymptomatic – dysphagia dysphagia – size dependent solid food dysphagia if

symptomatic

Imaging Thin projection off anterior Thin, transverse, Smooth, symmetrical surface of post-cricoid circumferential ridge narrowingesophagus

Treatment Bougie or balloon dilation Maloney dilation – Maloney dilation – 50–60 French 50–60 French


Table 4.5 Webs and rings

Clinical presentationThe majority of all rings and webs are asymptomatic. Themost common complaints of patients with esophageal webswho do experience symptoms are solid food or pill-induceddysphagia. The proximal location of the web leads to asensation of choking while eating.

DiagnosisThe diagnosis of webs is difficult, and they are often missedduring endoscopic evaluation as well as on radiographicexamination. The most sensitive test for diagnosis is abarium esophagram, and the radiologist must focus on theproximal esophagus to detect the webs (4.21). Webs willappear as a thin membranous filling defect just below theupper esophageal sphincter (UES), and they are bestvisualized on lateral images. Webs are 2–3 mm thick, and lie

at the lower border of the cricoid cartilage. They may beunilateral or circumferential. Endoscopy is less reliable, butwebs may be seen as a thin, eccentric lesion with normalappearing mucosa (4.22) compromising the esophageallumen. The webs may impinge on the passage of the scopedepending on their size. The passage of the scope may alsodisrupt the webs without the endoscopist being aware.

Treatment The most common treatment is Savary dilation over aguidewire, with most physicians using dilators 15 mm orgreater in diameter. Webs may persist even followingsymptom relieving therapy. Other methods of treatmentinclude endoscopic biopsy, balloon dilation, laser ablation,and surgery.


4.21 Bariumesophagramshowing a proximalesophageal web(arrow). This is themost sensitive testto detect this lesion.The most commonlocation for thislesion is theposterior cricoidarea of the upperesophagus.

4.22 Endoscopic appearance of a proximalesophageal web. The web appears to be a thin,eccentric lesion. The mucosa is normal inappearance. If located proximally, it is possible tofracture the web during passage through the UESwithout being aware of its presence.

Plummer–Vinson or Patterson-Kelly syndromeThis syndrome is a triad of esophageal web, iron-deficiencyanemia, and dysphagia.

The webs are typically hypopharyngeal or in the upperesophagus, may be single or multiple, and may be associatedwith stricture formation. It is more common in the middle-aged, and in white women.

Ringed esophagusThis is a rare condition that most often occurs in youngmales, with most patients being younger than 30 years.Clinical presentation is often a complaint of long-standingsolid food dysphagia, usually going back to early childhood.Patients may present with an acute food impaction, afterspending years accommodating their chronic dysphagia.

Proposed etiologies include GERD, congenitalabnormalities, and possible allergic conditions (eosinophilicesophagitis) (4.23, 4.24). Endoscopy shows multiple

esophageal rings, often associated with an area of esophagealnarrowing. The esophageal mucosa appears normalthroughout.

Treatment is with mechanical bougienage and a con-sideration of acid suppressive therapy. It is not uncommonto require multiple dilations, and these patients are atincreased risk of painful, deep mucosal tears.

Schatzki’s ringsA prevalence of 0.2–14% in the general population has beenreported, with an increase in incidence with increasing age(most occur after the age of 40 years). The rings are locatedat the GEJ, at the distal margin of the LES, and arecomposed of annular membranes of mucosa andsubmucosa. Due to their location, the proximal aspect isusually squamous mucosa, with gastric columnar mucosadistally (4.25). By definition, there is a hiatal hernia presentwith all Schatzki’s rings. Schatzki’s rings are the most


4.23 Endoscopy depicting a ringed esophagus.This rare condition is most prevalent in young men,and presents with dysphagia. There are multipleesophageal rings seen on endoscopy, andtreatment includes dilation and possible addition ofan acid suppressive agent. Complications, such asdeep mucosal tears, are more common withtreatment of this condition.


A B

4.25 Schematic figure to show the difference in appearance of esophageal ‘A’ rings(A) and ‘B’ rings (Schatzki’s ring) (B). The ‘A’ ring is located proximal to the SCJ, andis an annular ring composed of hypertrophied muscle. The ‘B’ ring, or Schatzki ring,is located at the SCJ, and is always located in association with a hiatal hernia. Thisring is composed of normal esophageal epithelium, but may have a columnarmucosa on the gastric side.

4.24 Histology from an esophageal biopsy in a patientwith eosinophilic esophagitis. This condition is mostcommon in young males, and patients present withchronic solid food dysphagia. Associated conditions areoften present, and include allergies, asthma, and atopy.Endoscopy will show multiple mucosal rings, and anarrow, slender esophagus. The demonstration ofeosinophils on biopsy is necessary in order to make the diagnosis.

common cause of intermittent solid food dysphagia, whichmay be slowly progressive over years. Other clinicalpresentations include food impaction and, rarely,perforation.

The presence of symptoms depend on luminal diameter:if <13 mm the patient will have symptoms; if >20 mm thepatient will almost never have symptoms. Symptoms arevariable at diameters between 13 and 20 mm. Pathogenesisis controversial, and proposed etiologies include congenitalabnormalities and GERD.

For diagnosis the most sensitive test is the bariumesophagram (4.26), and yield may be enhanced by using abarium bolus (tablet, marsh mallow). Most rings can also beseen on endoscopy (4.27) using patience, air insufflation, orthe Valsalva maneuver.

Treatment is only necessary if the patient is symptomatic.In these cases, mechanical bougienage is the treatment ofchoice, usually using a single pass with a large bore (48 F)dilator. It is not uncommon to have recurrent symptomsrequiring repeat dilation. Acid suppressive therapy may beused considering the possible association with GERD.


4.26 Esophagramshowing a Schatzki’sring after bariumswallow (arrow).Notice the presenceof the hiatal hernia.Presence ofdysphagia isdependent on thediameter of the ring,with nearly allpatients havingsymptoms if <13 mm.

4.27 An endoscopic view of a Schatzki’s ring, depicting a significant narrowing of the esophageallumen (A: esophageal view (arrows); B: retroflex gastric view). Endoscopists may use air insufflationto identify these rings better during the examination.

A B

‘A’ ringAn ‘A’ ring is a muscular ring located in the lower esophagusat the proximal margin of the LES, approximately 2 cmproximal to the squamocolumnar margin (SCM) (4.25).This ring is composed of hypertrophic bands of circularmuscle, covered with normal squamous epithelium. Theincidence increases with age, with most symptomaticpatients being older than 40 years of age. These rings arerarely symptomatic, but can lead to intermittent solid fooddysphagia.

Diagnosis is made by barium swallow, which shows asmooth, symmetrical narrowing of the distal esophagus(4.28). This may also be seen on endoscopy. As with otherrings, treatment is with large-bore dilation (>50 F), andshould only be considered if the patient is symptomatic.

Further readingCastell DO, Richter JE (eds) (2003). The Esophagus, 4th

edn. Lippincott, Williams, and Wilkins, Philadelphia.Tobin RW (1998). Esophageal rings, webs, and diverticula.

J Clin Gastroenterol 27(4):285–295.


SummaryDefinition: a transverse membrane of squamous

mucosal epithelium anywhere in the esophagus,usually proximally.

Etiology: unknown, possible association with GERD.Pathophysiology: partially occlude lumen.Symptoms: dysphagia (solid food or pill-induced),

majority are asympomatic.Diagnosis: contrast radiography (barium esophagram).

Endoscopy is less reliable. Treatment: dilation (Savary), endoscopic biopsy, laser.

4.28 The ‘A’ ring is most often detected on bariumswallow, and is rarely symptomatic. The location isapproximately 2 cm proximal to the SCJ.

Strictures

DefinitionAn esophageal stricture is any loss of lumen area within theesophagus.

Clinical presentationThe predominant clinical symptom is dysphagia whichusually is most prevalent when the luminal diameter is<15 mm (normal is 20 mm). Less severe strictures can causeintermittent dysphagia to large food pieces, such as meatand bread.


CausesThere are multiple intrinsic and extrinsic causes foresophageal strictures (Table 4.6). Intrinsic strictures aremost common, with acid/peptic disease accounting for amajority of the cases. (Rings/webs and neoplasms arediscussed in separate sections.)

DiagnosisStrictures may be diagnosed by barium swallow orendoscopy (4.29–4.32). Barium swallow is particularlyuseful to assess for the presence of subtle strictures or rings.Endoscopy is usually necessary to allow biopsy for diagnosisand for treatment.

Intrinsic

Acid peptic

Pill-induced

Chemical/lye

Post-nasogastric tube

Infectious esophagitis

Sclerotherapy

Radiation-induced

Esophageal/gastric malignancies

Surgical anastomotic

Congenital

Systemic inflammatory disease

Epidermolysis bullosa

Extrinsic

Pulmonary/mediastinal malignancies

Anomalous vessels and aneurysms

Metastatic submucosal infiltration (breast cancer, mesothelioma, adenocarcinoma of gastric cardia)

Table 4.6 Etiology of esophageal strictures


4.29 Aortic arch causing external compression ofthe proximal esophagus. The aortic arch normallycauses minor narrowing in the proximal esophagus.Occasionally, this can results in symptoms and isknown as ‘dysphagia lusoria’.

4.30 Bariumesophagram of a pepticstricture (arrow). Pepticstrictures usually occurin the distal esophagusand are associated withintermittent orprogressive dysphagia.Strictures are treatedwith gentle dilation andPPI therapy. PPIs aresuperior to H2 blockersin preventing therecurrence of acid-related strictures.

4.31 Endoscopic photograph of a tight radiation-induced stricture. Initially the standard upper GIendoscope was unable to pass through thenarrow lumen.

4.32 Bariumesophagram of thestricture in 4.31 (arrow).Note the residual lumenis only severalmillimeters in width.Stricture length can alsobe determined easilybased on this bariumstudy.

TreatmentThe hallmark for treating benign stricture disease isesophageal dilation (4.33–4.35), and there are severaldifferent types of dilators (4.36, 4.37). To minimize the riskof perforation, the ‘rule of threes’ applies: no more thanthree sequential dilators should be passed per session. Thegoal is to obtain an objective diameter of >15 mm.

Complications from stricture dilation are uncommon:perforation (0.5%), bleeding (0.3%), and bacteremia(20–50%).

Refractory stricturesRefractory strictures are defined by lack of response to twoor more dilations. Causes include ongoing insults from pillsor non-steroidal anti-inflammatory drugs (NSAIDs) (see


4.33 Endoscopic photo of balloon dilation. A‘through-the-scope’ balloon has been passedunder fluoroscopic guidance through the stricture.Balloon insufflation creates radial force to dilatethe stricture.

4.34 Fluoroscopic image of the dilation in 4.33.The balloon expands fully and there is noresidual ‘waist’.

Pill-induced injury. below), uncontrolled acid reflux, andinadequate lumen diameter with dilations.

Treatment is by elimination of offending agents (pills)and acid suppression with proton-pump inhibitors (PPIs).Gentle dilation to 15 mm is used. Intralesion steroidsinjected before dilation are safe and probably effective.Removable plastic stents are a recent advance (4.38).Surgery is extremely rare for benign disease.

Further readingFerguson DD (2005). Evaluation and management of

benign esophageal strictures. Dis Esophagus 18(6):359-64.Richter JE (1999). Peptic strictures of the esophagus.

Gastroenterol Clin North Am 28(4):875–891.


4.35 Endoscopic image post-dilation. The lumenis now larger, allowing for passage of the upperendoscope.

4.36, 4.37 There are several different types of dilatorsavailable (in addition to the ‘through-the-scope’ balloonsas in 4.33). 4.36 Mercury-filled Maloney dilators (top).4.37 Wire-guided rigid Savary–Gilliard dilators. Choice ofdilator often depends on the anatomy of the stricture andoperator expertise. In general, Maloney bougies are usedin uncomplicated, short, straight strictures. The wire-guided Savary–Gilliard and TTS balloons are best suitedfor long, tight, or tortuous strictures.

4.38 Plastic stent in an esophageal stricture.Removable plastic stents are now available foruse in refractory benign strictures.

Neoplasms

EpidemiologyApproximately 12,000 cases of esophageal carcinoma occureach year in the US.

Two main culprits are adenocarcinoma and SCC, withover 50% of cases being adenocarcinoma. The diseasesshare similar presentations but their epidemiology is quitedifferent (Table 4.7).

Clinical presentationPatients typically present with rapidly progressing solid fooddysphagia caused by mechanical obstruction. Up to 75% ofpatients experience weight loss. Other symptoms includeodynophagia, iron deficiency, or hoarseness from recurrentlaryngeal nerve injury.


Squamous cell carcinoma Adenocarcinoma

Gender Males Males

Ethnicity African Americans Caucasians

Risk factors Tobacco/alcohol, achalasia, caustic injury HPV GERD; Barrett’s

Site Mid-esophagus Distal esophagus

GERD: gastroesophageal reflux disease; HPV: human papilloma virus

Table 4.7 Epidemiology of esophageal cancer

SCC is locally aggressive and complications related tolocal invasion are common and include tracheoesophagealfistulas and recurrent laryngeal nerve injury with vocal cordparalysis. Distant metastases occur in the lung, liver, bone,and brain. Adenocarcinoma, while not as locally invasive,will often have lymphatic and liver metastases secondary tothe rich lymphatic supply in the lamina propria.

DiagnosisEndoscopy with biopsy is usually diagnostic (4.39–4.42).


4.39 Endosocopic photo of an ulcerated mid-esophageal mass. Biopsy confirmed the presenceof esophageal SCC.

4.40 Endoscopic photo of a large mass present atthe GEJ. Biopsy confirmed adenocarcinoma.

4.41 Endoscopic photo of a nodule arising at theproximal end of Barrett’s esophagus. Biopsydocumented adenocarcinoma within the nodule.

4.42 Retroflexed view of the GEJ. An ulceratedadenocarcinoma is seen. Tumors located at theGEJ can mimic the signs and symptoms ofachalasia and is known as ‘pseudoachalasia’.

depth of tumor invasion (4.44–4.48) and lymph nodemetastases. EUS has the added advantage of allowing fine-needle aspiration (FNA) of suspicious lymph nodes (4.49,

4.50). CT scan and PET scans are important for identifyingdistant metastases.


TreatmentOutcome and treatment will depend upon the stage of themalignancy, so rigorous staging is used (Table 4.8, 4.43).Staging usually includes CT scan, endoscopic ultrasound(EUS), and positron emission tomography (PET) scan.EUS is the most accurate technique for identifying the

4.43 Tumor, nodes, and metastasis (TNM) classification of esophageal cancer. T class is based on the depth of tumor invasion. T1 tumors are limited to thesubmucosa, T2 tumors extend to the muscularis propria, T3 tumors extend throughthe muscularis propria into the adventitia, and T4 tumors invade adjacent structures(i.e. aorta). N class is based on the present or absence of involved lymph nodes.Early lymph node metastases are common secondary to the rich lymphatic supply ofthe esophageal wall.

HGD

Aorta

N1

N0

T1 intramucosal

T1 submucosal

T2

T3 T4

Epithelium

Basement membraneLamina propria

Muscularis mucosa

Submucosa

Muscularis propria

Periesophageal tissue


Primary tumor (T) Regional lymph nodes (N)

TX: Primary tumor cannot be assessed NX: Lymph nodes cannot be assessed

T0: No evidence of primary tumor N0: No lymph node metastasis

Tis: Carcinoma in situ N1: Lymph node metastasis

T1a Tumor invades lamina propria

T1b: Tumor invades submucosa Distant metastasis (M)

T2: Tumor invades muscularis mucosa MX: Distant metastasis cannot be assessed

T3: Tumor invades adventitia M0: No distant metastasis

T4: Tumor invades adjacent structures M1: Distant metastasis

Table 4.8 TNM staging classification of esophageal cancer

4.44 EUScorrelates to thelayers of theesophageal wall.(1: submucosa;2: aorta.)

4.45 EUS of T1 tumor. The tumorextends into the third hyperechoiclayer (submucosa but not beyond).

2

1

T1T2

T3

EpitheliumBasement membrane

Lamina propriaMuscularis mucosa

Submucosa

Muscularis propria

Periesophageal tissue


4.46 EUS of T2 tumor. Thetumor extends to the fourthhypoechoic layer, themuscularis propria.

4.47 EUS of T3 tumor. Thetumor now invades throughthe fourth hypoechoic layerand into the fifthhyperechoic layer,adventitia.

4.48 EUS of T4 tumor.The tumor now invadesthe aorta.


4.49 EUS of multiple enlarged abdominal lymph nodes.EUS is the most accurate technique for determining lymphnode involvement.

4.50 FNA of an enlarged lymph node. EUS with FNA allows sampling of suspiciousnodes which increases the accuracy of staging.

Staging is based on the TNM classification (Table 4.8,4.43). Patients with early stage disease, namely T1 or T2,without nodal or metastatic disease can be treated withsurgery alone. Patients with more advanced disease, T3 orN1, may benefit from neoadjuvant chemotherapy/radiationbefore surgical resection. Those with late stage diseasereceive palliative treatment. Palliative endoscopic measuresinclude repeated dilation, laser/photodynamic ablation,esophageal stent placement (4.51, 4.52), and percutaneousgastrostomy (PEG) tube placement.

PrognosisEsophageal cancer is usually identified at a late, incurablestage. Five-year survival rates for SCC are <10% and are<15% for adenocarcinoma. Survival is stage-dependent with5-year survival rates for T1 lesions and T4 lesions of 46%and 7% respectively.

Benign neoplasmsBenign neoplasms of the esophagus are rare and includeleiomyoma (4.53), granular cell tumors, and papillomas.Many of these lesions present as submucosal masses.

Further readingWang KK, Wongkeesong M, Buttar NS (2005). American

Gastroenterological Association technical review on therole of the gastroenterologist in the management ofesophageal carcinoma. Gastroenterol 128(5):1471–1505.


4.51 Tracheoesophageal fistula. This patienthad a proximal SCC and symptoms suggestiveof aspiration. Endoscopy diagnosed the T-Efistula (smaller ‘lumen’ to the upper left). T-Efistula is a common complication of SCC. Thispatient was managed with an endoscopicallyplaced metal stent.

4.52 Endoscopic view after metal stent deployment.

Gastroesophageal reflux disease (GERD)

IntroductionGERD is defined as chronic symptoms or mucosal damagecaused by the abnormal reflux of gastric contents into theesophagus (1). Reflux esophagitis refers to a subset ofGERD that has endoscopic or histopathologic characteristicchanges in the esophageal mucosa.

Non-erosive reflux disease (NERD) refers to patient withtypical GERD symptoms who have normal upperendoscopy. Barrett’s esophagus is a complication of chronicGERD and is defined as intestinal columnar metaplasiacharacterized by mucin-containing goblet cells. GERDpatients can be subdivided as follows (4.54)(2):

• NERD: 50%.• Reflux esophagitis: 30–40%.• Barrett’s esophagus: 10–20%.

EpidemiologyThere is a 58.7% prevalence of symptoms of heartburn oracid regurgitation, based on a population-based study ofOlmsted County, Minnesota (3). GERD is equally prevalentin men and women; however, there is male predominancefor esophagitis (2–3:1) and Barrett’s metaplasia (10:1)(4).Pregnancy is associated with the highest incidence ofGERD, with 48–79% of pregnant woman complaining ofheartburn (5). White races are more frequently affected thanother races, with a low prevalence in Africa and Asia andhigh rates in North America and Europe (6).

Clinical presentation Esophageal and extra-esophageal symptoms of GERD arepresented in Table 4.9. Typical symptoms include heartburnor pyrosis, acid regurgitation, and dysphagia orodynophagia. Heartburn presents as an intermittent,restrosternal burning discomfort that may radiate towardsthe neck. Aggravating factors include meals (usually within60 minutes of eating), exercise, and lying down. Heartburnis typically relieved with antacids or by drinking water.

Acid regurgitation presents with the sensation of sour orburning fluid in the mouth or throat. It is due to effortlessreturn of esophageal or gastric contents into the pharynx.

Dysphagia or odynophagia usually presents in the settingof chronic heartburn due to impaired peristalsis, pepticstrictures, and/or erosive esophagitis.


SummarySquamous cell carcinoma (SCC) and adenocarcinoma.Symptoms: rapidly progressing solid food dysphagia,

weight loss, odynophagia, iron deficiency, hoarseness.Diagnosis: endoscopy with biopsy.Treatment: depends on tumor stage; surgery alone for

early disease (T1 and T2), combined withchemo/radiotherapy for T3 or N1. Late stage disease– palliative treatment.

Prognosis: fairly poor as identified late. 5-year survival:SCC < 10%, adenocarcinoma <15%.

4.53 Endoscopic ultrasound of a leiomyoma. Notethe mass arises from the second hypoechoic layer(muscularis mucosa) which is highly suggestive ofleiomyoma. FNA can be performed for diagnosticpurposes.


4.54 Patients with GERD symptoms may have endoscopically normal (NERD [A]) orabnormal (GERD [B], Barrett’s [C]) findings.

A B C

Esophageal

Heartburn

Acid regurgitation

Odynophagia

Dysphagia

Non-cardiac chest pain

Water brash

Extra-esophageal

Cough

Wheezing

Hoarseness

Throat clearing

Globus

Tracheal stenosis

Aspiration pneumonia

Pulmonary fibrosis

Apnea (infants)

Table 4.9 Symptoms of gastroesophageal reflux disease

Atypical symptoms include:

• Posterior laryngitis.• Asthma.• Cough.• Chest pain.• Dental erosions.

Etiology and pathophysiology Table 4.10 lists the common causes of GERD. GERD canoccur when there is transient or permanent impairment ofthe antireflux barrier between the stomach and theesophagus (7). This can be caused by LES incompetence

(hypotensive LES) (Table 4.11), transient LES relaxation(TSLER)(8), hiatal hernia, and scleroderma.

TSLER is a primary mechanism for gastroesophagealreflux in healthy persons and in those with mild GERD, andoccurs as short periods of relaxation of the LES that is notassociated with swallowing. Those with severe GERD andrelated complications usually have more permanentstructural defects, such as hiatal hernia. An increasedgastroesophageal pressure gradient, due to delayed gastricemptying (diabetic gastroparesis, intestinal pseudo-obstruction, collagen vascular disease), pregnancy, andobesity can result in GERD.

Another cause is prolonged esophageal acid clearance,

which can be due to impaired esophageal emptying in thecase of abnormal peristalsis (ineffective esophageal motility),re-reflux of acid due to hiatal hernia or impaired salivaryfunction. This results in reduced neutralization of acid bysalivary bicarbonate and is observed in smokers (9) andSjögren’s syndrome.

Breakdown of esophageal tissue resistance may beinvolved in the etiology of GERD. This occurs when

gastroduodenal contents, such as acid, pepsin, and bile,damage the intercellular junction of the esophagealepithelium. As a result, there is increased permeabilityallowing hydrogen ion penetration. Consequentacidification of the cytosol leads to cell edema and death.Acid hypersecretion, such as that in Zollinger–Ellisonsyndrome, is also a causal factor of GERD.


Barrier defect

TLESR

Hiatal hernia

Hypotensive LES

Scleroderma

LES disruption (status post myotomy, balloon dilatation)

Increased gastroesophageal pressure gradient

Delayed gastric emptying (diabetic gastroparesis,intestinal pseudo-obstruction)

Pregnancy

Obesity

Tight fitting clothes

Poor esophageal clearance

Ineffective esophageal motility

Re-reflux due to hiatal hernia

Impaired salivary function

Cigarette smoking

Sjögren’s syndrome

Increased gastric acid production

Zollinger–Ellison syndrome

Table 4.10 Causes of gastroesophageal reflux

LES: lower esophageal sphincter; TLESR: transient lower esophageal sphincter relaxation

Increases resting LESP Decreases resting LESP

Food Protein Fat, chocolate, ethanol, peppermint

Medications Metoclopramide, domperidone, cisapride Nitrates, calcium channel blockers, morphine, meperidine, barbiturates, diazepam

Neural agents α-adrenergic agonists, β-adrenergic α-adrenergic antagonists, β-adrenergic agonists, cholinergic agonists antagonists, cholinergic antagonists, serotonin

Hormones Gastrin, motilin, substance P Secretin, cholecystokinin, glucagon, gastric inhibitory polypeptide, progesterone

LESP: lower esophageal sphincter pressure

Table 4.11 Substances that affect lower esophageal sphincter pressure


4.55 Histopathology of GERD. The esophageal biopsy ofGERD shows squamous cell hyperplasia and numerousinflammatory cells (predominantly eosinophils) (arrows).(Courtesy of Mary Bronner M.D., Department of AnatomicPathology, Cleveland Clinic, Ohio.)

HistopathologyThe normal esophagus is lined with non-cornified stratifiedsquamous epithelium. At the squamocolumnar junction, thesquamous epithelium is in continuity with the columnarcells of the stomach. Reactive epithelial cell changes are seenin GERD even though upper endoscopy may be normal.These include hyperplasia of the basal zone and elongationof the papillae, as well as increased mitotic figures andincreased vascularization of the epithelium. When there isendoscopic evidence of esophagitis, epithelial cell injury isevident and there is inflammatory cell infiltrate (neutrophilicor eosinophilic) (4.55).

Differential diagnosis Table 4.12 presents the differential diagnosis for GERD.

Diagnosis There is no diagnostic gold standard for detecting GERD.Classic symptoms of acid regurgitation and heartburn arespecific but not sensitive for the diagnosis of GERD, asdetermined by abnormal 24-hour pH monitoring.

Therefore, if only heartburn and/or acid regurgitation ispresent, empiric antisecretory therapy (PPI) can be started.The diagnosis of GERD is confirmed by the resolution ofsymptoms with antisecretory therapy. Further diagnostictesting (such as upper endoscopy) should be performed incases of therapy failure, extremely chronic GERD (to ruleout Barrett’s) or if certain ‘alarm signs’ are present, such asdysphagia, odynophagia, weight loss, or GI bleeding.

If chest pain is present, coronary artery disease should beruled out with appropriate tests.

Table 4.13 lists the tests used in the diagnosis of GERD,and their advantages and disadvantages. Upper endoscopyis the technique of choice to evaluate esophageal mucosa insuspected GERD. It allows detection and management ofcomplications of GERD and also exclusion of otherdiseases. Endoscopy is diagnostic for GERD if refluxesophagitis or Barrett’s esophagus is present. The severity ofreflux esophagitis is characterized by grading systems:

• Los Angeles classification (Table 4.14, 4.56, 4.57).• Savary–Miller classification (Table 4.15).



Pill-induced esophagitis

Esophageal motor disorders

Gastritis

Peptic ulcer disease

Non-ulcer dyspepsia

Biliary colic

Coronary artery disease

Table 4.12 Differential diagnosis of gastroesophageal reflux disease

Test Advantages Disadvantages

Empiric PPI therapy Diagnostic and therapeutic; low cost; May mask underlying disease; disease no referral needed to the specialist severity unknown; poor diagnostic accuracy

with atypical reflux symptoms

Endoscopy Visual establishment of severity of Often normal; costlyesophagitis; screening for Barrett’s

Ambulatory 24/48-hour Diagnosis of ‘acid’ reflux; quantifies Low sensitivity with catheter-based system;esophageal pH monitoring acid reflux events and allows improved sensitivity with the wireless 48-hour

symptom correlation; when used on- device; costlytherapy, monitors therapy efficacy

Barium esophagram Good test for defining anatomy Often normal; non-specific

Esophageal manometry Measures LESP; pre-op evaluation Limited use in GERD managementfor anti-reflux surgery

Esophageal impedance Identifies non-acid reflux events; Role of non-acid reflux in GERD is not defineduseful in evaluating for non-acid reflux in patients who are refractory to high dose PPI therapy

GERD: gastroesophageal reflux disease; LESP: lower esophageal sphincter pressure; PPI: proton-pump inhibitor

Table 4.13 Diagnostic tests for gastroesophageal reflux disease

Grade Pathology

A One or more mucosal breaks <5 mm and not contiguous with adjacent mucosal fold tops

B One or more mucosal breaks >5 mm and not contiguous with adjacent mucosal fold tops

C Mucosal breaks contiguous between tops of two or more folds but involving <75% of esophageal circumference

D Mucosal breaks contiguous between tops of two or more folds and involving ≥75% of esophageal circumference

Table 4.14 Los Angeles classification of esophagitis


Grade Pathology

I One of more non-confluent lesions with erythema or reddish spots

II Confluent but not circumferential erosive and edematous lesions in the distal esophagus

III Circumferential erosions in the distal esophagus

IV Chronic complications, such as ulcers, strictures, or Barrett’s metaplasia

Table 4.15 Savary–Miller classification of esophagitis

4.56 Los Angeles classification of esophagitis.

4.57 Endoscopic view of esophagitis. A: Los Angeles grade A; B: Los Angeles grade B; C: Los Angeles grade D.

A B C

Grade A Grade B

Grade C Grade D


Ambulatory 24-hour pH monitoring has limited use inthe diagnosis of GERD as results are normal in 25% oferosive esophagitis and 33% of NERD (10). However, it isa useful test to quantitate esophageal acid exposure andcorrelate symptoms to reflux events. A barium esophagramis useful in identifying strictures and esophageal ulcers but itis not a good test for detecting esophagitis or Barrett’smetaplasia.

TreatmentThe goals of therapy in GERD should be to relievesymptoms, heal esophagitis, prevent recurrence ofsymptoms, and prevent complications. Therapies arepresented in Table 4.16. Modifying the patient’s lifestyle maybe of benefit, especially for mild GERD. They should beadvised to avoid fatty foods, alcohol, caffeine, etc, avoidrecumbency for 3 hours after meals, elevate their bed, stop

Table 4.16 Treatment for gastroesophageal reflux disease

Treatment

Lifestyle modifications

H2RAs

PPI

Promotility agents

Endoscopic

Surgical

Method

Diet: avoid large meals, high fat diets,avoid meals at bedtime. Avoid caffeine,alcohol, smoking, mints, chocolate;weight loss; elevate head of bed 6 inches; sleep on left side rather thanright; avoid tight fitting clothes; smokingcessation

Cimetidine 400 mg po qac, qhsRanitidine 150 mg po bidFamotidine 20–40 mg po bidNizatidine 150 mg po bid

Omeprazole 20–40 mg po, qd-bidLansoprazole 15–30 mg po qd-bidRabeprazole 20 mg po qd-bidPantoprazole 40 mg po qd-bidEsomeprazole 20–40 mg po qd-bid

Metoclopramide 5–15 mg qac, qhs(Cisapride)

Radiofrequency ablation (Stretta);endoscopic suturing (Bard EndoCinch);endoscopic injection; gatekeeper refluxrepair system

Fundoplication: Nissen, Toupet, Dor

Comments

All patients with GERD should beadvised. There is minimal data to supportefficacy of lifestyle modification. It is likelyto be suitable only for mild GERD

Most effective acid suppressive occursduring fasting and during sleep. Efficacyis limited by tachyphylaxis andinadequate suppression of acid related to meals

Better acid suppression than H2RAs.Should be administered 30 minutesbefore meals for optimal acidsuppression. Rebound hypersecretionoccurs with discontinuation due tosecondary hypergatrinemia

Metoclopramide side-effects: tremor,parkinsonism, depression, tardivediskinesia; cisapride is not available dueto cardiotoxic effects (prolonged QT)

Currently, only Stretta is FDA approvedfor endoscopic therapy of GERD

bid: twice daily; GERD: gastroesophageal reflux disease; po: by mouth, qac: before meals; qd: once daily; qhs: before sleep

smoking, wear loose fitting clothes, and lose weight. Acidsuppressive therapy can be used to provide symptomaticrelief and heal esophagitis. Histamine receptor antagonists(H2RAs) in standard divided doses have been shown toachieve complete symptom relief in approximately 60% ofpatients and to heal esophagitis in about 50%. PPIs aresuperior to H2RAs in both symptom relief and healingesophagitis, with a success rate of up to 90% (11).

Because GERD is a chronic relapsing disease for mostpatients, with almost universal recurrence, maintenancetherapy may be required in many patients. Long-term use ofPPIs is superior to H2RAs, with remission maintained at80% and 50% respectively (12). ‘Step down’ therapy isrecommended in clinical practice. Patients are initiallytreated with PPIs; when clinical response is achieved,H2RAs and PPIs are used as needed.

Prokinetic drugs, such as metoclopramide and cisapride,have been used with minimal effect, and their use is alsolimited by significant side-effects.

Anti-reflux surgery may be required. Basic methods offundoplication (4.58, 4.59) involve pulling down the GEJinto the abdominal cavity and the fundus of the stomach iswrapped around the distal esophagus. The net result is thecreation of an artificial valve and prevention of the LESsliding back into the thorax. The procedure can be

performed either with open or laparoscopic laparotomy.There are multiple variations to this procedure:

• Nissen: complete fundoplication; the wrap encircles theentire (360°) esophagus (4.58, 4.59).

• Toupet: posterior partial fundoplication; the wrapencircles two-thirds (270°) of the esophagus posteriorly.

• Dor: anterior partial fundoplication; the wrap encirclesone-third (120°) of the esophagus anteriorly; usuallyperformed with Heller myotomy in achalasia.

Complete fundoplication provides better acid refluxcontrol than partial (13).

Indications include persistent symptoms refractory tomedical therapy, severe esophagitis by endoscopy, benignstricture, Barrett’s esophagus (without dysplasia orcarcinoma), and recurrent pulmonary symptoms associatedwith GERD. Patients with large hiatal hernia withpredominant regurgitation symptoms should also beconsidered for surgery.

The ideal candidate is the patient with typical symptomsthat respond completely to antisecretory therapy.

Patients who are refractory to acid suppression therapyon high dose PPIs are poor candidates and surgery shouldbe considered with caution. In this setting, ongoing


4.58 Nissen fundoplication. A: The mobilized fundus is brought behind the esophagus. Tightness of the wrap is usuallycontrolled by passing a 56F to 60F bougie into the esophageal lumen (not shown). B–D: Left and right fundal wrap isapproximated and sutured. The esophageal muscle wall is also sutured to hold the wrap in place (circle). Before the wrapis sutured, the crura is approximated behind the esophagus.

A B C D


4.59 Endoscopic view of the Nissenfundoplication. The retroflexed view of thegastric cardia shows fundus wrapped aroundthe esophagus.

4.60 Endoscopic radiofrequency (RF) ablation therapy(Stretta). The instrument consists of a balloon surroundedby four curved metal needle electrodes. A: After the GEJis measured using the standard EGD, the Stretta catheteris inserted into the esophagus and positioned at the GEJ.B: The balloon is inflated deploying the four needleelectrodes. Each electrode delivers RF energy to achievetarget temperature of 85°C for 90 seconds, resulting in aring of lesions. C: The catheter is rotated and repositionedlinearly to create several rings of lesions 2 cm above andbelow gastric cardia. D: The net result is nerve ablationand scarring at the GEJ which acts as a reflux barrier.

A B

C D

esophageal acid exposure while on medication should bedocumented. If acid is well controlled on therapy, non-acidreflux may cause symptoms and this should be investigatedby impedance monitoring. Otherwise, surgery is notrecommended in those who are unresponsive to high dosePPIs and who have no evidence of esophageal acid exposurewhile on therapy.

Complications of fundoplication include acute peri-operative complications, such as pneumonia, sepsis, woundinfection, pulmonary embolism, pneumothorax, esophagealor gastric perforation, spleen damage, and death. Technicalfailures can occur, such as transdiaphragmatic herniation,fundoplication disruption, slipped or misplaced fundo-plication, too tight or loose wrap, or twisted fundoplication.Symptomatic failures are those patients with persistent orrecurrent heartburn, dysphagia, chest pain, nausea, gas-bloat syndrome, and inability to belch or vomit.

Endoluminal therapies include radiofrequency (RF)ablation of the GEJ (Stretta) (4.60), in whichradiofrequency energy delivers heat to the GEJ which causesnerve tissue to ablate and scar tissue form. It results inreduction of transient LES relaxation. Scarring at the GEJfunctions as an additional barrier to reflux. Otherendoluminal therapies include endoscopic suturing of theGEJ (Bard EndoCinch) (4.61), endoscopic injection of theGEJ (4.62), and gatekeeper reflux repair system (4.63).


4.61 Endoscopic suturing of the GEJ (Bard EndoCinch). The Bard EndoCinch sewing capsule isattached to the standard EGD scope and inserted into the esophagus via an overtube to theGEJ. A, B: Suction is applied to the capsule drawing the adjacent tissue into the capsule. Theneedle with pre-loaded suture is then advanced and the endoscope is removed. C, D: In theoriginal technique, half-stitches were hand-tied and pushed with knot-pusher and the suture cutusing a separate guillotine catheter. Further refinements have been made and the newcinch/cutting catheter (not shown) is used to place a cinch tag and cut the suture in one step.

4.62 Endoscopic injection of the GEJ. A, B: Using a standard endoscope and injectioncatheter under fluoroscopic guidance, a liquid polymer dissolved in solvent is injectedinto the LES in four quandrants. C, D: The solvent separates away and the polymersolidifies into a spongy material, enhancing the LES barrier against reflux.

A B C D

A B C D


References1 Devault KR, Castell DO (1999). Updated guideline for

the diagnosis and treatment of gastroesophageal refluxdisease. Am J Gastroenterol 94:1434–1442.

2 Achem SR (1999). Endoscopy-negative gastroesophagealreflux disease: the hypersensitive esophagus. GastroenterolClin North Am 28:893–904.

3 Locke GR III, Talley NJ, Fett SL, et al. (1997).Prevalence and clinical spectrum of gastroesophagealrefulx: A population-based study in Olmsted County,Minnesota. Gastroenterol 112:1448–1456.

4 Wienbeck M, Barnert J (1989). Epidemiology of refluxdisease and reflux esophagitis. Scand J GastroenetrolSuppl 156:7–13.

5 Bainbridge ET, Temple JG, Nicholas SP, et al. (1983).Symptomatic gastroesophageal reflux in pregnancy: Acomparative study of white Europeans and Asians inBirmingham. Br J Clin Pract 37:53–57.

6 Sonnenberg A, El-Serag HB (1999). Clinicalepidemiology and natural history of gastroesophagealreflux disease. Yale J Biol Med 72:81–92.

7 Orlando RC (2002). Pathogenesis of gastroesophagealdisease. Gastroenterol Clin North Am 31:S35–S44.

8 Mittal RK, Holloway RH, Penagini R, et al. (1995).Transient lower esophageal sphincter relaxation.Gastroenterol 109:601–610.

9 Kahrilas PJ, Gupta RR (1989). The effect of cigarettesmoking on salivation and esophageal acid clearance. JLab Clin Med 114:431–438.

10 Fass R, Fennerty MB, Vakil N (2001). Nonerosive refluxdisease – current concepts and dilemmas. Am JGastroenterol 96:303–314.

11 Chiba N, De Gara CJ, Wilkinson JM, et al. (1997).Speed of healing and symptom relief in grade II to IVgastroesophageal reflux disease: a metaanalysis.Gastroenterol 112:1798–1810.

12 Vigneri S, Termini R, Leandro G, et al. (1995). Acomparison of five maintenance therapies for refluxesophagitis. N Engl J Med 333:1106–1110.

13 Sonnenberg A (2004). Review article: anti-reflux surgeryand endoluminal therapies. Alimentary Pharmacolology &Therapeutics 20(Suppl 5):81–88.

Further readingDeVault KR, Castell DO (2005). Updated guidelines for

the diagnosis and treatment of gastroesophageal refluxdisease. Am J Gastroenterol 100(1):190–200.

A B C D E

4.63 Gatekeeper reflux repair system. A, B: A gatekeeper overtube is positioned over the LES and suction is applied,drawing adjacent tissue into the overtube. C, D: A radiopaque removable hydrogel (Polyacrylonitril) is injected into thesubmucosa via the delivery sheath. E: Submucosal placement of the gatekeeper narrows the esophageal lumen,enhancing the barrier effect of the LES.

Extra-esophageal GERD

IntroductionPatients with GERD may present with symptoms other thanheartburn and regurgitation.

Extra-esophageal symptoms include asthma, chest pain,chronic cough, laryngitis, and dental erosions. In mostpatients, esophagitis or Barrett’s esophagus is not present.Response to anti-reflux surgery and acid suppression is lesspredictable. An empiric trial of PPIs bid is indicated as theinitial treatment as there is no definitive diagnostic goldstandard for GERD (4.64). If treatment fails, a fullevaluation with ambulatory pH monitoring isrecommended.


Edema and hyperemia of larynx

Hyperemia and lymphoid hyperplasia of posterior larynx (cobblestoning)

Interarytenoid changes

Granuloma

Contact ulcers

Laryngeal polyps

Reinke’s edema

Tumors

Subglottic stenosis

Posterior glottic stenosis

Strictures

Apnea

Sudden infant death syndrome (SIDS)

Table 4.17 Potential laryngopharyngeal signs associated with gastroesophageal reflux disease

LaryngitisThere is increasing evidence that GERD causes laryngealsigns and symptoms, so called reflux laryngitis (LR) orlaryngopharyngeal reflux (LPR). GERD may causesignificant laryngeal changes including erythema, edema,pharyngeal ulcerations, vocal cord nodules and polyps,granulomas, or even leukoplakia and cancer, but thesefindings are not specific for GERD (Table 4.17, 4.65–4.69).The most specific laryngeal lesions for GERD-inducedinjury are vocal cord lesions and arytenoid medial wallerythema and edema. Overall, only 50% of patients withlaryngoscopic signs of GERD have abnormal esophagealacid exposure on pH monitoring (4.70). PPIs should be firstline of therapy, initially twice daily and then tapering to oncedaily in responders.


Extra-esophageal manifestations of GERD

Laryngitis Asthma Cough Chest pain

Symptom assessment

Non-responders Responders

Empiric trials with PPIs bid x3–4 months

24-hr pH/impedanceon medication

Step down therapy

Normal Abnormal

Reflux most likely not cause of symptoms

Look for another cause

Intensify anti-refluxtherapy

Consider laparscopicfundoplication

Taper PPI to qd;consider H2-blocker,

or prn PPIs

4.64 Treatment algorithm for extra-esophageal manifestations of GERD. (bid: twice daily; prn: as needed; qd: once daily.)


4.65 Laryngeal signs of GERD: vocal cordnodule (arrow).

4.66 Interarytenoid bar (arrow).

4.67 Laryngeal signs of GERD: artynoid medial wallerythema (arrow).

4.68 Laryngeal signs of GERD: vocal cord erythema(arrow).


4.69 Vocal cord leukoplakia (arrow).

4.70 Hypopharyngeal acid exposure is shown by a pH drop to <4.0 in all three electrodes.Only 50% of patients with laryngoscopic signs of GERD have abnormal acid exposure onpH monitoring.

Meal

864208642086420

Hypopharyngeal

Proximal

Distal

20:30/1 20:40/1 20:50/1 21:00/1 21:10/1 21:20/1 21:30/1

AsthmaApproximately 70–80% of asthma patients have GERD.There are two pathophysiological mechanisms: proximalesophageal reflux leading to microaspiration/bronchospasm,and vagally-mediated esophageal–bronchial reflex, resultingin bronchospasm. Treatment of GERD improvesrespiratory symptoms in 69% and reduces asthmamedication use by 62%.

Chest painNon-cardiac chest pain may be due to pulmonary,muscoskeletal, or esophageal etiologies. The most commonesophageal cause is GERD, accounting for 40–60% ofpatients. The most cost effective initial option is a trial ofPPIs for 3 months.

Chronic coughGERD is the third most common cause of chronic coughafter post-nasal drip and asthma (4.71). Patients withchronic cough from GERD have normal chest radiographs,are non-smokers, are not taking medications (such as

angiotensin-converting enzyme [ACE] inhibitors) known tocause cough, and have had no response to treatment forasthma and post-nasal drip. PPIs twice daily are the bestinitial management, and a GERD-related cough can take3 months to resolve. A pH study can be helpful as it allowstemporal correlation between reflux events and cough. Ifcough precedes the pH drop, this suggests secondary reflux.

Dental erosionsDental erosion is a loss of tooth structure resulting from achemical rather than bacterial cause (4.72). Chronicexposure to acid can lead to a loss of enamel and toothsubstance. Reported prevalence of dental erosions inpatients with GERD is 17–68%.

Further readingVaezi MF, Hicks DM, Abelson TI, Richter JE (2003).

Laryngeal signs and symptoms and gastroesophagealreflux disease: a critical assessment of cause and effectassociation. Clin Gastroenterol Hepatol 1:333–44.


SummaryDefinition: chronic symptoms or mucosal damage caused by

reflux of gastric contents into the esophagus.Pathophysiology: impaired anti-reflux barrier at LES,

increased gastroesophageal pressure gradient, prolongedacid clearance, reduced esophageal tissue resistance, acidhypersecretion.

Symptoms: heartburn (pyrosis), acid regurgitation, dysphagiaor odynophagia, atypical symptoms (asthma, cough, chestpain, dental erosions).

Diagnosis: no gold standard. pH monitoring or empirical PPItherapy. Endoscopy to examine mucosa.

Treatment: lifestyle modification, acid suppressive therapy(PPIs, H2RAs), anti-reflux surgery (fundoplication).


4.72 Dental erosions secondary to GERD.

4.71 Causes of chronic cough. GERD is the third most common causeafter post-nasal drip and asthma. (Data derived from Irwin RS, CurleyFJ, French CL et al. (1990) Chronic cough. The spectrum andfrequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis, 141:640–647.)

%

100

75

50

25

0P

MD

Ast

hma

GE

RD

Chr

onic

bron

chiti

s

Bro

nchi

ecta

sis

Mis

cella

neou

s

1+2+

3

41%

24% 21%

5% 4% 5%

86%

Barrett’s esophagus

DefinitionNormal stratified squamous epithelium of the distalesophagus is replaced with intestinal columnar metaplasia(4.73). Barrett’s metaplasia can be divided into short-segment and long-segment, based on the length of Barrett’smetaplasia of greater or less than 3 cm (4.74, 4.75).

EpidemiologyIt is estimated that 6–12% of patients with GERD will haveBarrett’s esophagus, with the highest risk in older Caucasianmales. It is a significant outcome of chronic GERD and pre-disposes to the development of esophageal adenocarcinoma.There are no specific symptoms related to Barrett’sesophagus, but it is associated with more severe GERD.However, secondary to impaired acid sensitivity, somepatients are no worse than uncomplicated GERD, so it isrecommended that patients with prolonged GERDsymptoms undergo endoscopic screening.

DiagnosisBarrett’s esophagus is suspected endoscopically when thepale pink-appearing squamous mucosa of the distalesophagus is replaced to various lengths with salmon pinkcolumnar mucosa. Thus the SCJ is displaced proximal tothe GEJ. It is confirmed when intestinal metaplasia is notedon biopsy (4.76).


TreatmentThe risk of adenocarcinoma increases by approximately0.5% per year, thus it is recommended that patients undergocontinued endoscopic surveillance to detect the develop-ment of dysplasia and adenocarcinoma (Table 4.18).Current endoscopic surveillance guidelines suggest four-quadrant biopsies at 2 cm intervals along the entire length ofBarrett’s every 3 years. Surveillance biopsies are examinedfor the presence of dysplasia. Surveillance intervals arebased on the presence and degree of dysplasia as outlined inthe updated guidelines of the American College ofGastroenterology (ACG) (Table 4.18). Several endoscopicmethods can be used as alternatives to surgery for high gradedysplasia or intramucosal cancer. These include argonplasma coagulation (4.77), photodynamic therapy, cryo-ablation, and endoscopic mucosal resection (4.78).

Further readingFalk GW (2002). Barrett’s esophagus. Gastroenterol

122(6):1569–1591.Sampliner RE (2002). Updated guidelines for the diagnosis,

surveillance, and therapy of Barrett’s esophagus. Am JGastroenterol 97:1888–1895.

Sharma P, McQuaid K, Dent J, et al. (2004). A criticalreview of the diagnosis and management of Barrett’sesophagus: the AGA Chicago Workshop. Gastroenterol127(1):310–330.

Dysplasia Confirmation Intervention

None 2 EGDs with 4-quadrant biopsies every 2 cm Surveillance endoscopy every 2–3 years

Low grade Highest grade on repeat EGD with biopsy Surveillance endoscopy every year until no dysplasiaremains low grade

High grade Repeat EGD with 4-quadrant biopsies Focal HGD surveillance-endoscopy every 3 monthsevery 1 cm Expert pathologist confirmation Multifocal HGD-esophagectomy, ablation therapy, or

esophageal mucosal resection

EGD: esophagogastroduodenoscopy; HGD: high grade dysplasia

Table 4.18 Management of Barrett’s metaplasia


4.73 Schematic diagram of Barrett’s esophagus. The SCJis proximal to the GEJ.

4.74 Short-segment Barrett’s esophagus. ‘Tongues’of red columnar mucosa extending <3 cm abovethe GEJ. Dysplasia and cancer are more commonin patients with long-segment Barrett’s esophagus,but patients with short-segment Barrett’s are also atincreased risk.

4.75 Long-segment Barrett’s esophagus. Thecolumnar mucosa extends >3 cm above the GEJ.Islands of normal squamous mucosa are presentwithin the Barrett’s metaplasia.

4.76 Histology of a distal esophageal biopsy,demonstrating goblet cells (arrows) diagnostic of Barrett’smetaplasia. Alcian blue stain could be used if there isdifficulty identifying goblet cells by routine H&E stain.

SCJ

Columnar-lined esophagus

GEJ


4.77 A–C: Argon plasma coagulator (APC) ablation of Barrett’s esophagus. The patient was a non-surgical candidate withhigh grade dysplasia. APC is used to ablate the mucosa and the patient is followed with close surveillance.

A B C

4.78 A–C: Nodule arising in Barrett’s esophagus. Biopsies show high grade dysplasia at the nodule only. The nodule isthen resected with a cap-assisted endoscopic mucosal resection (EMR) technique. A large amount of tissue can beremoved with EMR.

A B C

Hiatal hernia

IntroductionHiatal hernia is a prolapse of stomach or other abdominalcontents through the diaphragmatic esophageal hiatus intothe thorax. Hiatal hernia is usually asymptomatic, but canpotentially result in life-threatening conditions. Prevalence isestimated from 0.8–2.9% of all patients undergoing upperendoscopy (1). There are four types of hiatal hernia, whichcan be grouped as esophageal or paraesophageal (Table 4.19).


Sliding

Type I Herniation of gastric cardia into the posterior mediastinum; most common type (95%); usually asymptomatic but can cause symptomatic GERD; usually an acquired condition

Paraesophageal

Type II Herniation of gastric fundus; due to localized defect of phrenoesophageal membrane and laxity of gastrosplenic and gastrocolic ligaments; stomach is fixed at GEJ; stomach may rotate around its longitudinal axis resulting in organoaxial volvulus, or infrequently rotate around its transverse axis resulting in mesenteroaxial volvulus

Type III Combination of types I and II hernias; due to progressive enlargement of type II

Type IV Herniation of other intra-abdominal organs, such as colon, spleen, pancreas, and small intestine; due to a large defect in the phrenoesophageal membrane

GEJ: gastroesophageal junction; GERD: gastroesophageal reflux disease

Table 4.19 Types of hernia

EtiologyIt is thought to be an acquired condition due to multiplefactors compromising the integrity of the hiatus. Some ofthese factors may include:

• Age-related degeneration.• Repeated mechanical stresses of inspiration, vomiting,

postural change, swallowing, heavy lifting.• Increased abdominal pressure due to obesity or

pregnancy.

Other possible causes are trauma, congenital malforma-tions, or iatrogenic.

Type I or sliding hiatal herniaType I hernia involves an upward herniation of the gastriccardia through the esophageal hiatus into the posteriormediastinum (4.79–4.81). This is the most common type ofhiatal hernia (95% of all hiatal hernias). It is usuallyasymptomatic but there is increased likelihood of gastro-esophageal reflux and patients often present with GERDsymptoms.

It is caused by widening of the muscular hiatus and laxityof phrenoesophageal membrane.

Type II herniaThis is caused by a localized defect in the phrenoesophagealmembrane. The gastric fundus is herniated while the GEJremains fixed. The hernia gets progressively worse overtime, so that the entire stomach may eventually herniate.

Rotation of the herniated stomach around its longitudinalaxis (organoaxial volvulus) may occur as a result of stomachbeing fixed at the GEJ. The stomach may also infrequentlyrotate around its transverse axis, resulting in mesenteroaxialvolvulus.

Types III and IV hiatal herniasThese are variations of type II hernia. Type III hiatal herniais a combination of both types I and II hernias and occursdue to progressive enlargement of the type II hernia.

Type IV hiatal hernia is due to a large defect in thephrenoesophageal membrane. As a result, other intra-abdominal organs, such as colon, spleen, pancreas, andsmall bowel, may enter the hernia sac.


4.79 Type I and type II hiatal hernia. In type I (or sliding) hernia, thegastric cardia is upwardly herniated through the esophageal hiatus intothe posterior mediastinum. It is secondary to widening of the muscularhiatus and laxity of phrenoesophageal membrane. Type II hiatal herniais caused by a localized defect in the phrenoesophageal membrane.The gastric fundus is herniated while the GEJ is fixed.

Type I hiatal hernia Type II hiatal hernia

Phrenoesophagealmembrane


A B

4.80 A: Barium upper GI image of type Ihiatal hernia. The barium study shows alarge herniation of the stomach through the esophageal hiatus. B, C: Barium upperGI image of large type II paraesophagealhernia (arrows, herniated gastric fundus;arrowhead, GEJ).

C


Sliding

Type I Observation if aymptomatic; if GERD symptoms start PPI therapy; consider surgery if PPI therapy fails

Paraesophageal

Types II, III, IV Surgery is indicated due to increased risk of catastrophic complications

GERD: gastroesophageal reflux disease; PPI: proton-pump inhibitor

Table 4.20 Treatment of hiatal hernia

4.81 Barium upper GI image of a large hiatal herniawith mesenteroaxial volvulus.

Associated conditionsGERDThere is a 50–94% prevalence of hiatal hernia in patientswith GERD (2). The LES becomes incompetent in thesetting of hiatal hernia due to the loss of diaphragmaticcontribution. Additionally, hiatal hernia impairs esophagealemptying.

BleedingBleeding is usually subtle and may be asymptomatic;massive bleeding is rare (2). Bleeding sites include theesophagus, esophogastric junction, or hiatal hernia sac. Riskfactors for bleeding include NSAID use. Hiatal herniaincreases the risk of developing a Mallory–Weiss tear.Cameron lesions can occur, which are linear gastric erosivechanges in the hernia sac. They are usually found at or nearthe diaphragm, and may cause obscure bleeding evidencedby iron deficiency anemia. They are not associated withHelicobacter pylori.

Incarceration and volvulusTwo types of gastric volvulus can occur (4.82): organoaxial(rotation of stomach on its longitudinal axis) andmesenteroaxial (rotation of stomach on its transverse axis).Volvulus may result in obstruction, necrosis, and perforationwhich can be catastrophic.


4.82 Endoscopic retroflexed view of hiatal hernia.The diaphragmatic hiatus is easily visualized inthe retroflexed view allowing easier visualizationof the hernia.

SummaryDefinition: a prolapse of stomach or other abdominal contents through the diaphragmatic

esophageal hiatus into the thorax.Etiology: acquired condition due to multiple factors, such as age, mechanical stresses,

increased intra-abdominal pressure.Type I: most common, usually asymptomatic or GERD symptoms.Type II: due to localized defect in phrenoesophageal membrane.Types III and IV are variations of type II.Symptoms and sequelae: GERD, bleeding, incarceration and volvulus (especially types II-IV),

Schatzki’s ring.Treatment: Type I – as for GERD, PPIs +/- surgery; type II–IV – surgical treatment even if

asymptomatic.

Schatzki’s ringHiatal hernia can be associated with a mucosal loweresophageal ring (B ring), located within 3 mm proximal tothe SCJ.

TreatmentTreatment of hiatal hernia is described in Table 4.20. Type Ihiatal hernia can be managed by observation, ifasymptomatic. If there are GERD symptoms, medicaltreatment should be initiated first with PPIs. Surgicaltreatment may be needed if medical therapy fails (seeGERD section for more detail).

Enlarging type II, III, and IV hiatal hernias have a highrisk of serious complications of incarceration, necrosis, andperforation. Therefore, they should be treated surgicallyeven if asymptomatic.

References1 Pridie RB (1966). Incidence and colincidence of hiatus

hernia. Gut 7:188–189.2 Johnson DA, Ruffin WK (1996). Hiatal hernia.

Gastrointest Endosc Clin N Am 6(3):641–66.

Diverticula

Definition An esophageal diverticulum is a sac that protrudes from theesophageal wall. A true diverticulum contains all layers ofthe wall of the esophagus, while a false diverticulum onlyconsists of mucosa and submucosa that have herniatedthrough a weak area of the esophageal wall (4.83).

Zenker’s diverticulum A Zenker’s diverticulum is located proximal to theesophagus above the UES, and is, in reality, ahypopharyngeal diverticulum. These protrusions occur inan area called Killian’s triangle, an area of relative weakness,which is located between the cricopharyngeal sphincter andthe inferior pharyngeal constrictor muscle (4.84). Theformation of this diverticulum is related to incompleterelaxation of the UES, increased UES resting pressure, orincoordination between the UES and the hypopharynx.GERD has also been implicated as a possible cause ofZenker’s diverticula. Zenker’s are false diverticula, involvingonly the mucosa and submucosa.

The incidence of Zenker’s increases with age, possiblysecondary to an increase in tissue elasticity. The prevalencereaches 50% in the seventh and eighth decades of life, andis higher in women. Many of these diverticula areasymptomatic, and are incidentally discovered during aradiologic study. Symptoms typical of a Zenker’s includeoropharyngeal dysphagia, regurgitation of undigested food,intermittent solid food dysphagia, halitosis, excessivesalivation, cough, and aspiration pneumonia.

The best diagnostic test for this diverticulum is a bariumswallow, with special attention to the oropharyngeal phaseof swallowing. The diverticulum protrudes posteriorly, andmay best be seen on lateral and oblique views. Endoscopydoes not add to the diagnosis, and may lead to perforationof the diverticulum.

Treatment should only be offered to patients who aresymptomatic secondary to large diverticula; smallasymptomatic diverticula may be followed with serialbarium studies.


Treatment includes open surgical resection of thediverticulum, with division of the cricopharyngeus muscles.Another treatment option is a diverticulopexy, whichinvolves suspension of the diverticulum in a cranialdirection. Endoscopic therapeutic maneuvers are beginningto emerge, including the use of lasers and stapling devices.

Mid-esophageal diverticulaThese diverticula, also known as traction diverticula, andare formed secondary to external pulling of the esophagealwall by adjacent inflammatory or fiberoptic tissue (as can beseen in tuberculosis mediastinitis). These formations arelocated in the middle third of the esophagus, and are theonly true diverticula seen in the esophagus. A pulsion typediverticulum also occurs in the mid-esophagus, which is afalse diverticulum formed due to abnormal forces applied tothe esophageal wall resulting in an outpouching.

Most traction diverticula are asymptomatic, and tend tobe small. Patients may present with chest pain anddysphagia, but this usually occurs in subjects with a motilitydisorder.

Complications are rare, and include rupture, aspiration,exsanguinations, fistula formation, and carcinoma.Diagnosis is often made incidentally during a barium studycarried out for other reasons. As with Zenker’s diverticula,endoscopy does not add to the diagnosis.

Treatment is not required for most mid-esophagealdiverticula, as they are asymptomatic and uncomplicated. Ifnecessary, the standard treatment is diverticulectomy withor without myotomy, but the presence of a motility disordermust be ruled out prior to surgery.


4.83 Schematic diagram showing the three majortypes of diverticula. A false diverticula is secondaryto the herniation of mucosa and submucosathrough the muscular wall. True diverticula containall the layers of the esophageal wall. The mostproximal diverticulum, a Zencker’s diverticulum,forms in an area of weakness known as Killian’striangle. Mid-esophageal diverticulum is the onlytrue diverticulum in the esophagus, and is a tractiondiverticulum formed as a result of pulling of theesophageal wall by inflammatory or fibrotic tissue.The epiphrenic diverticulum, located near thediaphragm, is often secondary to achalasia oranother motility disorder.

4.84 A barium swallow esophagram showinga Zencker’s diverticulum. These occurbetween the cricopharyngeal sphincter andthe inferior pharyngeal constrictor muscle.Treatment, which consists of surgicalresection, is only offered to patients withlarge, symptomatic diverticula.

Zenker’sdiverticulum

Mid-esophagealdiverticulum

Epiphrenicdiverticulum

Epiphrenic diverticulaThese outpouchings are located in the distal esophagus,near the LES and the diaphragmatic hiatus (4.85). Thisterm is usually use for diverticula in the distal 3–4 cm of theesophagus. Epiphrenic diverticula are almost always theresult of a motility disorder, such as achalasia or diffuseesophageal spasm, or incoordination between the distalesophagus and the LES. Epiphrenic diverticula can occur inall age groups, with a range in a large case series of 18–88years. The incidence of epiphrenic diverticula is low, with afrequency estimated to be only 20% that of Zenker’sdiverticula.

The majority of epiphrenic diverticula are asymptomatic,but symptoms, when present, may include chest pain orregurgitation. Symptoms also depend on the associatedmotor abnormality. Diagnosis of these diverticula includesmanometric testing to rule out an associated motilitydisorder. As with other diverticula, diagnosis is made bybarium esophagram, and multiple views aid in defining thesize of the pouch and the location of the mouth. A modifiedbarium swallow is useful in identifying an associated motorabnormality.

One aspect of treatment of epiphrenic diverticula includesmanagement of the underlying motility disorder. This willaim to avoid further enlargement of the diverticulum.Surgical treatment of an epiphrenic diverticulum isdiverticulotomy, with or without myotomy, if thediverticulum is symptomatic.

Intraluminal pseudodiverticulaEsophageal intramural pseudodiverticula are most oftenseen as multiple small outpouchings on barium esophagramor upper endoscopy (4.86, 4.87). These are not actualdiverticula, rather they are composed of dilated submucosalglands. The etiology of these diverticula is unclear, althoughit has been postulated that they are due to extensive chronicinflammation leading to dilated ducts, which then developsmall cysts. Other associations, with GERD, esophagealstrictures, candidiasis, motility disorders, and esophagealcarcinoma, have also been described.


4.85 A, B: Endoscopic views of an epiphrenic diverticulum. These are seen in close proximity to theLES, and these diverticula are often asymptomatic.

A B

The prevalence is unknown, but it is thought to be a rarecondition. On radiological evaluations for all causes, twoseries have found prevalences of 0.09% and 0.15%. Mostcases occur in the sixth and seventh decades of life, andoccur in both males and females.

Patients present with dysphagia, mostly to solid foods,and which may be acute in onset. These diverticula areassociated with strictures, and usually occur proximal to thenarrowing.

Diagnosis is made on barium esophagram, and they arebest seen with a double air contrast technique. They mayalso be noted as pinpoint openings in the esophageal wall onendoscopy. Treatment is with esophageal dilation, oftenachieving symptomatic relief for several years. Serialdilations may be required in some patients.

Further readingCassivi SD, Deschamps C, Nichols FC, et al. (2005).

Diverticula of the esophagus. Surg Clin North Am85(3):495–503.


SummaryDefinition: a sac that protrudes from the esophageal

wall, and contains all the layers of the wall.Zenker’s: false diverticula above UES, involving mucosa

and submucosa only.Mid-esophageal: secondary to adjacent inflammatory or

fiberoptic tissue.Epiphrenic: distal, near LES.Intraluminal pseudodiverticula: not true diverticula,

but dilated submucosal glands.Symptoms: often asymptomatic, dysphagia,

regurgitation, and chest pain. Diagnosis: barium esophagram.Treatment: surgical resection if symptomatic.

4.86 Esophageal pseudodiverticula(arrowhead) are seen on bariumesophagram as multiple small out-pouchings in the wall of the esophagus.These are not diverticula, but are ratherdilated submucosal glands.

4.87 Pseudodiverticula (arrow) seen atendoscopy. Although the cause of these lesionsis not clear, they are associated with strictures,acid reflux, and esophageal cancer. The numberof pseudodiverticula in a single patient can number from a few to dozens.

Castell DO, Richter JE (eds) (2003). The Esophagus, 4thedn. Lippincott, Williams, and Wilkins, Philadelphia.

Foreign body

EpidemiologyThe annual incidence of food impaction has been estimatedto be 13/100,000. Foreign bodies cause significantmorbidity and mortality, with 1,500 deaths per yearattributed to foreign bodies. Children tend to ingest objectssuch as coins, toys, safety pins, button batteries, marbles,screws, and pen caps. Adults tend to have problems withimpaction of meat and bones. Special populations at risk offoreign body ingestion include psychiatric patients andprisoners. Food impaction in adults tends to increase withadvancing age, secondary to the use of dentures. Men tendto have problems more than women, and impaction tends tobe more common in overweight individuals.

PathophysiologyMost foreign bodies are lodged at levels of naturalnarrowing – cricopharyngeus, thoracic inlet, aortic arch,tracheal bifurcation, and LES. Studies have shown that88–97% of adults with meat impaction had distalesophageal disease (stricture, esophagitis, or hiatal hernia).In adults, 63–75% of foreign bodies are impacted at theLES, 8–10% at the aortic arch, and 35–40% at the UES.

Clinical presentationCommon symptoms following ingestion of a foreign bodyinclude dysphagia, odynophagia, foreign body sensation,and excessive salivation. In children, respiratory symptomsmay be more common than GI symptoms. Other symptomsthat should raise concern include stridor, persistent cough,drooling, and refusal to take feedings.

In adults, a life-threatening situation can occur when foodbecomes lodged at the level of the UES, which may causeacute airway obstruction and death from asphyxiation. Thisresponds to the Heimlich maneuver. Physical findings areusually rare, and may include pharyngeal erythema or oralabrasions. Subcutaneous emphysema may indicateperforation. The presence of a penetrating foreign body maypresent with hematemesis and shock, secondary to anaortoesophageal fistula.


DiagnosisA thorough history may assist in discovering the type ofobject, the size, the timing of the event, and any prioresophageal pathology. The most important step inmanagement is determining the exact location of the foreignbody. Plain radiographs can localize objects as well as giveinsight into size and shape (4.88). They can also giveinformation about complications, such as perforation,aspiration, or pleural effusion. CT scans are of particularvalue in evaluating foreign bodies present in the cervicalesophagus, even after plain films and endoscopy have beennegative. CT scans can also show pseudoaneurysms,abscesses, or inflammatory changes in adjacent structures.Endoscopy plays an essential role in diagnosis, as it can helpto show location, type of object, configuration, and can alsoprovide a means of therapy (4.89). It may also identify othermucosal changes not seen on radiography. Diagnostic andtherapeutic endoscopy should be performed as early aspossible in situations of foreign body ingestion. There is norole for barium studies, unless being used to confirmdisimpaction.

TreatmentImportant information for the physician to consider in themanagement of foreign bodies includes location, type andnature of object, size of object, timing of ingestion,associated symptoms, number of objects, stability of object,radiologic evaluation, previous esophageal pathology, andsafety of retrieving the object.

Endoscopic removal is the only safe way to remove bodiesthat are sharp; it should be remembered that the leadingedge of the object has the potential for perforation.

Button batteries should be removed urgently to avoid thepossibility of full thickness mucosal injury. Illicit drugs inballoons or condoms should not be removed endoscopically,as rupture can lead to sudden death.

There are non-endoscopic techniques for the treatment offood impaction; however, they are rarely used today.Glucagon has been used to relax the musculature of theLES. Other agents that relax the LES include calciumchannel blockers, nitrates, benzodiazepines, and anti-cholinergics. Meat tenderizer, or papain, has been used,although severe complications preclude its usage. Gas-forming agents have also been shown to have complicationsthat outweigh the benefits of their usage.


4.88 A chest X-ray (A) showing foreign bodies in theesophagus. These objects turned out to be paper clips(B), and they were removed at endoscopy usingstandard foreign body extraction equipment (C).

A

B

C

4.89 An endoscopic view of a guitar pick stuck inthe esophagus of a young patient.

Endoscopic removal has been found to have high rates ofsuccess for treating food impaction. Surgical backup mustbe available, and intervention should not be delayed longerthan 24 hours, as complication rates will increase. Someimpactions may be pushed through to the stomach by theendoscope, which may be attempted if luminal patencydistal to the object can be confirmed. A number of snares,forceps, baskets, and nets are passed through the biopsychannel of the endoscope, and the food is removed whole orin pieces (4.90). Following disimpaction, the esophagusshould be assessed for underlying pathology, which ispresent in 90% of cases.


4.90 A–E: The equipment used for endoscopic removalof esophageal foreign bodies. Special tools includebaskets (A, B), Roth net (C), a rat-tooth forceps (D),overtube (E), and miniature scissors.

A

B

C

D

E

ComplicationsComplications are estimated to occur in <5% of cases. Themost common complications are associated with esophagealmucosal changes, and include tears, ulcers, bleeding,perforation, edema, and luminal obstruction. Respiratorycomplications can also be seen, including aspiration andairway obstruction. Complications in the thorax can occursecondary to migration of the body from the esophagus, andinclude arterioesophageal fistulae, aortoesophageal fistulae,mediastinitis, pericarditis, and pericardial effusions.

Further readingAmerican Society of Gastrointestinal Endoscopy (ASGE)

Guidelines (2002). Guideline for the management ofingested foreign bodies. Gastrointestinal Endoscopy55:802–806.

Pill-induced injury

EpidemiologySince first being described in 1970, approximately 1,100cases of pill-induced injury have been reported, although thisis likely to be a gross under-representation of actual incidence.A study in Sweden in the 1970s reported an incidence of4/100,000 per year, although this figure is probably highertoday. Pill-induced esophageal injury affects patient of all agegroups, with reports in patients from 3–98 years old.

In reported cases, women have been injured 71% of thetime, with more women being injured by antibiotics,NSAIDs, and alendronate. Other risk factors for pill-induced injury are advanced age, decreased peristalsis, andextrinsic compression of the esophagus.


UES

LES

10–25%

50–70%

20%

Aorta

4.91 Schenatic figure showing the most prevalent sitesof pill-induced injury to the esophagus. Injury occurs atareas of esophageal narrowing, where the transit ofthe pill can be arrested. The most common site is inthe mid-esophagus, where a narrowing exists at thelevel of the right atrium. The distal esophagus, at thelevel of the lower esophageal sphincter, is the site of20% of injuries. The most proximal site of pill-inducedinjury is at the level of the UES.

PathophysiologyPatients who experience pill-induced injury usually havenormal esophageal function and structure. Even in normalsubjects, there are three natural areas of esophagealnarrowing which provide a potential site for pills to becomelodged: the cricopharyngeus muscle, the aortic arch, and thecardia. An enlarged left atrium provides another area ofnarrowing that a pill may lodge in (4.91).

As can be seen in Table 4.21, a wide variety ofmedications can cause injury, including NSAIDs,antibiotics, anti-hypertensives, minerals, and steroids. Injuryoccurs due to the direct irritant effects of the medications onthe esophageal mucosa. Medication factors that predisposeto sticking include gelatin capsules, sustained releasemedications, and larger pill size. When a pill becomeslodged, it will dissolve and release the contents directly ontothe esophageal mucosa. These contents can be caustic,which will cause mucosal injury. In other cases, such asferrous sulfate and tetracycline, the contents may lead to anacid burn. Other mechanisms of injury may includestimulation of gastroesophageal reflux, production ofhyperosmolarity, and intracellular poisoning.

Clinical presentationThe most common presentation of pill-induced injury is theabrupt onset of odynophagia in a patient taking a potentiallyinjurious medication. There is usually sudden onset andprogression of retrosternal pain over a period of 1–4 days,and the pain is often worsened with swallowing. Patientsmay report that they had the sensation of the pill sticking intheir throat prior to the onset of the symptoms. The painmay remain mild, or may progress to the point that thepatient is unable to swallow adequately enough to maintaintheir nutrition and hydration. Symptoms typically last fordays to a few weeks.

Differential diagnosisThe main differential diagnosis for pill-induced esophagealinjury is infectious esophagitis. If the pain is more burningin nature, GERD may be suspected as a possible diagnosis.If the retrosternal pain becomes constant, myocardialinfarction may be considered. If the dysphagia is moreslowly progressive, esophageal cancer may be aconsideration.

DiagnosisIf history reveals pill-induced injury as an obvious etiology,diagnosis is aimed at assessing predisposing factors orcomplications, and finding alternative therapy. Whensymptoms are gradual, atypical, or persistent, or when therelation to use of a suspect pill is unclear, endoscopy isindicated. Endoscopy is also indicated in this setting forimmunocompromised patients, or for those withhemorrhage. Barium esophagrams are lower in cost, andmay show extrinsic compression, but initial endoscopy issuperior for its ability to biopsy and provide an alternativediagnosis. On endoscopy (4.92), the physician will seediscrete ulcers with normal surrounding mucosa. Biopsieswill show acute inflammation.

TreatmentThe initial treatment of pill-induced injury is to discontinuethe offending agent.


Non-steroidal anti-inflammatory drugs

Aspirin

Ferrous sulfate (especially sustainedrelease form)

Potassium chloride

Quinidine

Verapamil

Captopril

Glucocorticoids

Oral contraceptives

Ascorbic acid (vitamin C)

Phenytoin

Alendronate

Tetracycline

Doxycycline

Clindamycin

Ciprofloxacin

Cloxacillin/dicloxacillin

Alprenolol

Cellulose/fiber tablets

Chloroquine

Cromolyn

Clozapine

Foscarnet

Mexiletine

Pancreatic enzyme capsules

Penicillamine

Percogesic

Phenobarbitone

Retinoic acid

Theophylline (sustained release)

Zidovudine (AZT)

Lincomycin

Minocycline

Spiramycin

Emepronium bromide

Table 4.21 Medications causing esophageal mucosal injury


4.92 An endoscopic view of pill-induced esophagitis.Injury is most often seen as a superficial ulcer, but canevolve to a deep ulcer with perforation. There can also beformation of a stricture. Patients should be counselled toremain upright after taking their medications, and to takeall medications with copious amounts of fluids.

Anti-reflux therapy may be initiated to prevent an exacer-bation of the injury by gastric refluxate. Severe pain may besymptomatically relieved by use of a topical anesthetic.

On rare occasions, for severe injury, patients may requireintravenous hydration or nutrition while the injury is healing.Patients who develop strictures may require repeat dilations.

Patients with complications of pill-induced injury, such asesophageal perforation, mediastinitis, hemorrhage, and fiber-optic stricture, require further treatment of their specificcondition.

PreventionPatients should drink 4 oz of fluid with all medications, andshould drink more if they are taking pills that commonlycause injury. Patients should remain upright for 10 minutesafter taking medications, and up to 30 minutes afterparticularly injurious medications. Those who arebedridden, or have structural esophageal problems shouldavoid pills that are likely to cause esophageal injury.

Further readingKikendall JW (1991). Pill-induced esophageal injury.

Gastroenterol Clin North Am 20(4):835–846.


IntroductionInfectious esophagitis is a common condition, especially incertain high-risk groups. Commonly affected individualsinclude immunocompromised patients, such as transplantpatients, chemotherapy patients, and patients infected withthe human immunodeficiency virus (HIV).

Clinical presentationThe most common symptom of infectious esophagitis dueto any of the possible organisms is odynophagia. Inimmunocompromised patients, other symptoms maypresent including heartburn, nausea, fever, and GI bleeding.

EtiologyThe three most common causes of infectious esophagitis arecytomegalovirus (CMV), herpes simplex virus (HSV), andCandida albicans. In addition to the above common causes,other infections may be implicated, including varicella-zoster virus, Epstein-Barr virus, human papilloma virus,diptheria, various bacterial causes, syphilis, and the humanimmunodeficiency virus (HIV).

Candida albicansThis yeast is a normal component of oral flora, and is themost common cause of clinically relevant infectiousesophagitis. In addition to the high risk groups listed above,other groups at increased risk of candida esophagitis includethose with diabetes mellitus, alcoholics, those onglucocorticoid therapy, those on antibiotics, the elderly,patients with motility disorders, malnutrition, radiationtherapy, and hypochlorhydrics.

If oral thrush is seen on exam it assists in the diagnosis ofcandida esophagitis, as 75% of those with thrush andesophageal symptoms will have esophagitis (4.93).

Although empiric therapy is often instituted, diagnosis ismade by endoscopy with biopsy and brushings (4.94).Microscopic examination of the brushings will revealbudding yeast and hyphae. There is a distinctiveendoscopic appearance of candida esophagitis, with theesophageal mucosa being covered by adherent white-paleyellow plaques. The most common radiographicappearance of candida esophagitis is diffuse plaque-likelesions in a linear configuration. The plaques may becomeconfluent with progression of disease, and resembleulcers (4.95).

Treatment of candida esophagitis is with antifungal


4.95 Esophagram of a patient with candidaesophagitis. The diffuse, adherent plaquesgive the appearance of multiple long, linearulcers in this study.

4.94 Endoscopic view of esophagitis caused byCandida albicans. This is the most common form ofinfectious esophagitis in immunocompromisedpatients. Endoscopy classically shows white-paleyellow plaques that are adherent to the esophagealepithelium. Brushings will show hyphae along withbudding yeast.

4.93 A patient with oral thrush secondaryto infection with Candida albicans. (Photocourtesy of the Department ofDermatology, Cleveland ClinicFoundation.)

agents, usually fluconazole for 10–14 days (Table 4.22). Ifonly mild immunocompromise is present, topical agentsmay be a reasonable alternative. Treatment in patients whoare granulocytopenic requires amphotericin B to preventprogression to systemic fungal infection.

Cytomegalovirus (CMV)CMV is the most common cause of esophageal ulcer inpatients with acquired immunodeficiency syndrome(AIDS), and causes >50% of ulcers in this group. In CMVesophagitis, the virus infects the submucosal fibroblasts andendothelial cells, as opposed to the squamous epithelium.Due to a greater tendency for systemic infection with CMV,patients may present with more widespread GI symptoms,such as abdominal pain, nausea, and vomiting, in additionto odynophagia.

Endoscopy is necessary in order to confirm a tissuediagnosis, and biopsy specimens should be taken from thebase of the CMV ulcers due to the subepithelial nature ofthe infection. The endoscopic appearance of CMV showsserpiginous erosions and ulcers, which often coalesce toform larger, deep ulcers (4.96). A barium study in CMVesophagitis will show well circumscribed ulcers, that can bevertical, linear, and deep, and are often serpiginous (4.97).

When examined under the microscope, biopsy specimensof CMV infected cells will show intranuclear andcytoplasmic inclusions, and a halo surrounding the nucleus(4.98). In addition to histologic examination, biopsyspecimens should be sent for viral culture, which is moresensitive for the diagnosis.

Treatment options include both foscarnet andganciclovir, and patients with CMV esophagitis often


Organism Patient immune status Treatment

Cytomegalovirus Ganciclovir 5 mg/kg iv q12h for 14–21 days. Follow with maintenance therapy 90–120 mg/kg/day

Or foscarnet 90 mg/kg iv q12h for 12–21 days. Follow with maintenance therapy 90–120 mg/kg/day

Herpes simplex virus Acyclovir 250 mg/m2 iv q8h for 7–10 daysOr foscarnet 90 mg/kg iv q12h for 14–21 daysOr famciclovir 500 mg po bid for 14 days

Varicella-zoster virus Acyclovir 250 mg/m2 iv q8h for 7–10 daysOr foscarnet 90 mg/kg iv q12h for 14–21 daysOr famciclovir 500 mg po bid for 14 days

Candida albicans Immunocompetent Nystatin suspension 1–3 x 106 units po qid for 7 daysOr clotrimazole troche 10 mg dissolved in mouth 5 times

daily for 7 days

Immunosuppressed Fluconazole 100 mg po qd for 14 daysOr ketoconazole 200 mg po qd for 14 daysOr clotrimazole troche 100 mg dissolved in mouth tid for

14 daysOr fluconazole 100–200 mg iv qd

Immunosuppressed Amphotericin B 0.5 mg/kg/day iv to a cumulative dose of and granulocytopenic 1.5–2.0g over 6–12 weeks

bid: twice daily; iv: intravenous; po: by mouth; qd: once daily; qid: three times daily

Table 4.22 Treatment of infectious esophagitis


require a maintenance dose after an initial period of therapyof 2–3 weeks. Most patients who are immunocompromisedwill require a period of maintenance therapy after theinitial 2-week treatment course (Table 4.22). In patientswith AIDS, an ophthalmic exam should be pursued inpatients with CMV esophagitis to rule out a concomitantCMV retinitis.

4.97 CMV esophagitis on a bariumswallow esophagram can bedifferentiated from other infectiousetiologies by the presence of large,deep, serpiginous ulcers (arrow).

4.96 Endoscopic view of CMV esophagitis.Patients present with odynophagia, but mayalso complain of more systemic GI symptoms.Findings include erosions and ulcers that areclassically serpiginous in nature. These ulcerscan coalesce, forming larger, deep ulcers.

4.98 Histology from an esophageal biopsy in apatient with CMV esophagitis. Diagnosis ismade by demonstration of cytoplasmic andintranuclear inclusions (arrowhead), as well asthe nucleus of CMV infected cells beingsurrounded by a halo (arrow).


Herpes simplex virus (HSV)HSV is the most common viral cause of esophagitis. HSVesophagitis most often occurs secondary to reactivation of alatent infection, and it can occur in both immuno-compromised and competent hosts. As with other causes ofinfectious esophagitis, diagnosis is made by endoscopy.Endoscopic findings will show characteristic esophagealvesicles, which eventually rupture to form ulcers with raisededges. Barium esophagram findings include focal small

4.99 Histology in HSV esophagitis. Typical findingsare multinucleated giant cells (arrows), along withground glass intranuclear inclusion bodies. Viralculture can also be obtained in order to increase thesensitivity of the diagnosis.

ulcerations with a normal mucosa. HSV infects the epithelial cells, therefore biopsy

specimens must be taken from the margins of the ulcers,where there is squamous epithelium present (4.99).Histologic examination of biopsy specimens showsmultinucleated giant cells, ground glass nuclei, andCowdry’s type A intranuclear inclusion bodies. As withCMV, viral culture is more sensitive and should also beperformed (4.100).

Treatment of HSV esophagitis is with intravenousacyclovir until the patient can tolerate oral therapy (Table4.22). The total duration of therapy is 7–10 days.Immunocompetent patients will experience spontaneousresolution of the esophagitis in 2 weeks without any therapy.

Further readingBaehr PH, McDonald GB (1994). Esophageal infections:

risk factors, presentation, diagnosis, and treatment.Gastroenterol 106(2):509–532.

Castell DO, Richter JE (eds) (2003) The Esophagus, 4th edn.Lippincott, Williams, and Wilkins, Philadelphia.

Sutton FM, Graham DY, Goodgame RW (1994). Infectiousesophagitis. Gastrointest Endosc Clin N Am 4(4):713–729.

4.100 Schematic diagram to show biopsy sites. Differentorganisms that cause infectious esophagitis infectdifferent regions of the esophageal wall. For this reason,biopsy specimens must be taken from different areas ofthe lesions in order to increase the likelihood of isolatingthe organism. Candida albicans can be recovered fromthe surface of ulcers and plaques, and either brushings orbiopsies may be used. CMV infection is subepithelial, andthe ulcer base should be sampled. HSV is an infection ofepithelial cells, and biopsy of the ulcer margins will yieldoptimal results.

SummarySymptoms: odynophagia +/- heartburn, nausea, fever, GI

bleeding (especially in immunocompromised patients).Etiology: CMV is most common cause of ulcers.HSV: reactivation of latent infection can occur.Candida albicans: yeast, often with oral infection.Diagnosis: endoscopy and histology of biopsy specimens.Treatment: CMV – foscarnet and ganciclovir.

HSV – acyclovir.C. albicans – fluconazole.

Caustic injury

EpidemiologyMost caustic ingestion injuries occur in children youngerthan 3 years of age, and there have even been reports ofcaustic injuries to neonates. In the US, there areapproximately 5,000 accidental caustic injuries each year,with an increasing trend. Data from Denmark have found anincidence of pediatric ingestion of 34/100,000, withesophageal burns in 16/100,000. The most commonoffending agents are lye and drain cleaners, dishwasherdetergent, denture cleanser, and batteries. In adults, mostinjuries are associated with suicide attempts. In adults inDenmark, an incidence of ingestion of 1/100,000 wasreported, with 61% being suicide attempts.

PathophysiologyAlkali injury (or lye injury) follows a specific sequence ofinjury. There is initial submucosal edema and congestion,followed by inflammation with vessel thrombosis. Thesuperficial layers then slough, followed by necrosis of themuscularis, and organizing and fibrosis of the deep layers,with delayed re-epithelialization. Superficial burns oftenheal normally, burns involving the muscularis show delayedhealing with fibrosis, and circumferential burns may lead tostrictures. Stricture formation may take up to 4 weeksfollowing the initial insult. If there is transmural liquefactivenecrosis, esophageal perforation may occur.

Injury is worse with a more alkaline solution, with themost severe injury being cause by substances with pH of 14.Acid-induced injuries are less common than alkaline, andthe mechanism involves coagulation necrosis, and theformation of a protective eschar.

Clinical presentationInjuries can result in a range of findings, from mild oralburns or sore throat, to rapidly progressive life-threateningcomplications. Establishing the timing and nature ofingestion is an important part of the history, and it is oftennecessary to obtain history from surrogates. There is a poorcorrelation between the severity of symptoms and the extentof the esophageal injury. Oropharyngeal symptoms includepain, odynophagia, ulceration, drooling, and tongue edema.Stridor, aphonia, and hoarseness may be signs of laryngealinjury. Esophageal insult leads to dysphagia, odynophagia,chest pain, and back pain. Physicians must be alert for signsof serious injury (airway obstruction, aspiration, and


Grade Endoscopic findings

0 Normal

1 Edema and erythema of esophageal mucosa

2A Superficial ulcers, exudates, and bleeding

2B Deep focal or circumferential ulcers

3A Focal necrosis; deep ulcers with gray, black, or brown discoloration

3B Extensive necrosis

4 Perforation

Table 4.23 Classification of caustic injury

perforation), including agitation, cyanosis, hypoxia, fever,leukocytosis, tachycardia, and shock. Following initialstabilization, injuries may continue to progress toesophageal stricture.

DiagnosisFiberoptic laryngoscopy is an easy and safe way to examinethe larynx and pharynx in most settings. Endoscopy is themost valuable tool in evaluating caustic injury, but thephysician must be careful to avoid perforation (Table 4.23,4.101). In this setting, endoscopy should be used only fordiagnostic purposes, and it should be stopped before passingthe scope through any area of severe or circumferentialburn. The endoscopy should be performed within 48 hoursof the ingestion, while the wall retains its strength.

A chest radiograph is the most important radiological study,as it can reveal pulmonary infiltrates and signs of perforation,such as subcutaneous emphysema, pneumothorax, andpneumomediastinum. Contrast swallowing studies can beused to rule out perforation, but are more important inplanning future evaluation and treatment after the initial insulthas resolved (approximately 3 weeks after the injury).

Treatment Figure 4.102 presents treatment algorithm for caustic injury.Initial treatment of caustic injury involves basic resuscitationwith intravenous fluids, obtaining intravenous access, givingprophylactic antibiotics, and providing airway support aswarranted. Endoscopy should take place within 24–48 hoursafter the patient is stabilized. Patients who can swallow canstart a liquid diet 48 hours after being stabilized, but those whocannot swallow may require total parenteral nutrition (TPN)or nasogastric tube feeding (with endoscopic guidance).

Steroids have been studied to prevent the development ofesophageal stricture, especially in second and third degreeburns. If used, steroids should always be given withantibiotics, and they should be given early and in high doses(2 mg/kg/day). Stenting may also be used in order to avoidstricture formation. Dilation is currently used for thetreatment of secondary esophageal strictures (4.103), usingthe technique of antegrade dilation. If there are multiple orextensive segments, retrograde dilation may be considered.


4.101 Schematic diagram showing the findings thatcan be expected with the different grades of causticesophageal injury (grade 2A left, grade 2B right).

4.102 Treatment algorithmfor caustic injury. Due to thepossibility of airwaycompromise and esophagealperforation, caustic injuriesmust be aggressivelytreated. Initial treatmentincludes resuscitation,including intravenous fluidsand intubation if there isairway involvement.Endoscopy should be donein the first 24–48 hours, tohelp establish prognosis andguide therapy. Those withgrade 1 or 2A usually dowell, but strictures develop in70–100% of those with 2B or3A injuries. Patients withgrade 3B have a 65% earlymortality rate, and oftenrequire esophagealresection. (EGD:esophagogastro-duodenoscopy.)

Acute caustic injury

Resuscitation

Abdominal and chest radiographs

Perforation

Surgery

4

EGD

2B or 31 or 2A

Nasoenteric tube

Observe for perforation

No therapy

Injurygrade

Perforation is a concern with dilation, and treatmentsshould be gentle with an aim of slow improvement.

Surgery is indicated for the emergency treatment ofesophageal necrosis and perforation. This type of injury islife-threatening, as it leads to mediastinitis, sepsis, andshock. Surgery may also be used for delayed reconstruction,following an emergency resection or following failedconservative therapy.

PrognosisPatients with grade 1 and 2A injury have an excellentprognosis, without acute morbidity or chronic strictureformation. Grade 2B/3A injuries develop strictures in70–100% of cases. Grade 3B is associated with an earlymortality rate of 65%, and a high rate of esophagealresection. There is an association with the development ofSCC of the esophagus following caustic injury, with areported 1,000-fold increase in risk.

Upper gastrointestinal bleeding

EpidemiologyUpper GI bleeding is a common indication for endoscopicexamination, and this is often performed on an emergencybasis. Upper GI bleeding may be secondary to pathology inany area of the GI tract from the mouth to the ligament ofTreitz, and there are several conditions involving theesophagus and proximal stomach which are importantcauses. The common esophageal causes of bleeding areesophageal varices, reflux esophagitis (4.104), and ulcers(NSAID-induced or infectious), with less common causesbeing Mallory–Weiss tear, Cameron’s ulcer (4.105),Dieulafoy’s lesion, vascular malformations, aortoentericfistulae, and neoplasms. Patients with upper GI bleeding areat risk of cardiac, pulmonary, renal, and neurologicalcomplications.


4.103 Esophagram showing a stricture formed afteringestion of a caustic substance. Caustic strictures usuallyrequire esophageal dilation, and are often longer andnarrower than benign strictures. There is a high rate ofcomplications associated with dilation of esophagealstrictures, and up to 50% may require surgery.

4.104 Esophagitis and esophageal ulceration arepart of the spectrum of disease most often locatednear the SCJ, and most commonly secondary toacid reflux injury of the esophageal mucosa. Othercauses of esophagitis include infection,medications, and radiation. Classification systems,such as the LA Classification, help to assessprognosis and guide therapy, as esophagitis andulceration can be a cause of upper GI bleeding if severe.


4.105 The endoscopic appearance of a Cameron’slesion. This ulcer appears as a linear gastricerosion in a hiatal hernia. This is a diagnosis to beconsidered in the evaluation of occult GI blood loss.

Clinical presentationPatients may present with signs of hemodynamic instability,such as fatigue, palpitations, chest pain, syncope, anddyspnea. Other presenting symptoms may include nausea,pallor, and diaphoresis. Orthostatic hypotension occurs afterapproximately 20% blood loss, with pronouncedtachycardia and hypotension presenting after 25–40% lossof blood volume. Patients with upper GI bleeding usuallypresent with signs of hemorrhage, including melena andhematemesis, and may present with hematochezia if the rateof blood loss is brisk.

DiagnosisNasogastric aspiration should be performed, and may show‘coffee ground’ material if the bleeding is from an uppersource, or frank blood if the bleeding is continual. A salinelavage should be started if frank blood or coffee groundmaterial is found. Endoscopy is the diagnostic goldstandard, and offers therapeutic options as well. Ifnasogastric aspiration is clear, endoscopy can be performed

on an elective basis, but the presence of frank blood orcoffee ground material requires emergency endoscopicevaluation.

TreatmentThe goals of treating GI bleeding are hemodynamicsupport, minimization of complications, and providingeffective therapy to control the bleeding. Initial resuscitationshould be with intravenous fluids and blood products, andairway protection is essential. After hemodynamic stability isachieved, the patient with signs of continued bleedingshould undergo upper endoscopy to localize the site ofbleeding, and to identify possible therapeutic options(sclerotherapy, epinepherine injection, or electrocautery).

Further readingHuang CS, Lichtenstein DR (2003). Nonvariceal upper

gastrointestinal bleeding. Gastroenterol Clin North Am32(4):1053–1078.

Varices

EpidemiologyEsophageal varices (4.106, 4.107) are enlarged portal-systemic collateral veins that form as a consequence ofincreased portal pressure secondary to portal hypertension.

While varices develop in most patients with portalhypertension, bleeding occurs in only one-third of patientswith varices. An episode of variceal hemorrhage carries a30–50% risk of death. This is the most common cause ofbleeding in patients with cirrhosis or portal hypertension.Table 4.24 shows the grading system used to classifyesophageal varices, based on the endoscopic appearance ofthe veins. This classification is important as it givesinformation on prognosis and likelihood of imminentvariceal bleed. Classification also helps to guide therapy andhelps the physician decide when banding is appropriate.

Clinical presentationPatients may present with other stigmata of chronic liverdisease, such as spider angiomata, gynecomastia, testicularatrophy, palmar erythema, jaundice, ascites, orhepatosplenomegaly which may assist the physician in the


Grade Endoscopic appearance

I Dilated veins (<5 mm) still at the level of the surrounding tissue

II Dilated veins (>5 mm), straight, protruding into the esophageal lumen without obstruction

III Large, winding, and tense veins with considerable obstruction of the esophageal lumen

IV Obstruction of the esophageal lumen nearly complete, with signs of danger of impending hemorrhage (cherry red spots)

Table 4.24 Classification of esophageal varices

4.106 Endoscopy showing esophageal varices ofmoderate size.

4.107 Barium esophagram showingesophageal varices.

diagnosis. Variceal bleeding is usually painless and massive,and is associated with other signs of GI bleeding, such astachycardia and shock. Risk factors for bleeding inindividuals with varices include the degree of portalhypertension and the size of the varices. Varices areextremely unlikely to bleed if portal pressure is <12 mmHg.

DiagnosisOn upper endoscopy, varices may be oozing blood, or mayshow a ‘red wale’ sign or a cherry red spot, signifying arecent bleed.

TreatmentAn acute variceal bleed resolves spontaneously in 50% ofpatients. Patients with variceal bleeding often haveconcomitant coagulopathies, and clotting factors should bereplaced at the initial resuscitation. Variceal bleeding oftenrequires endoscopic intervention to control, althoughbleeding may also respond to intravenous octreotide orvasopressin as an initial adjunctive therapy.

Sclerotherapy (4.108) is effective for variceal bleeding,and is currently the first line treatment. Banding (4.109,4.110) is also now being used to control bleeding, and this


4.108 Tools used for endoscopic sclerotherapy. Thistreatment is used to achieve hemostasis in the setting of bleeding esophageal varices. The long, flexiblesclerotherapy needle is passed through one of the portsof the endoscope. The needle is unsheathed, advanced,and the sclerosing solution is injected into the vein and/orthe surrounding area. Sclerosants that are commonlyused to control hemorrhage include sodium tetradecylsulfate and ethanolamine.

4.109 Equipment used for band ligation. The barrel isplaced at the end of the endoscope, and the scope isinserted. The varix is identified, and the barrel ispositioned with the varix entering the barrel. The rubberband is then released, and the scope is withdrawn.Current kits allow the deployment of multiple bandswithout changing equipment.

method carries a lower risk of stricture formation andsystemic toxicity. If local therapy does not control thebleeding, balloon tamponade with a Blakemore tube may beused. This tube provides temporary relief by directcompression of the bleeding vessel, but definitive therapymust still be performed. Other considerations includeavoidance of subsequent bleeding, which may be addressedwith beta-blocker therapy or with placement of atranshepatic intrajugular portosystemic shunt (TIPS).

Complications and further managementFollowing an acute bleed, patients are at risk of re-bleedingfor up to 6 weeks, with the greatest risk being during the first48 hours after their initial bleed. The risk of re-bleeding at1 year is approximately 70%, and prevention of subsequenthemorrhage is essential. Screening endoscopy should beroutinely performed, with a frequency determined by

bleeding history and number and size of varices.Prophylactic banding is often done on a scheduled basis.Early re-bleeding is more common in patients with renalfailure, over 60 years old, and those with a severehemorrhage. Late re-bleeding is common in patients withrenal failure, large varices, severe liver disease, alcoholabuse, and hepatocellular carcinoma.

Mallory–Weiss tear A Mallory–Weiss tear is an esophagogastric mucosal tear,which occurs in the region of the GEJ, with an incidence of4/100,000 (4.111). Patients often report a history ofretching, or non-bloody vomiting, which was followed byhematemesis, although this history is not necessary.Prolonged coughing may also lead to this type of tear. Theyusually stop bleeding spontaneously and recurrences areuncommon.


4.110 Endoscopic view of esophagealvarices after being banded using the bandligator instrument. The barrel can be seenat the end of the endoscope, and a varix,with a blue rubber band around it, is seenthrough the barrel. After banding, thevarices typically slough off in 2–3 daysfollowing treatment.

4.111 A Mallory-Weiss lesion is a tear in themucous membrane that occurs at the junctionof the esophagus and the stomach. It iscaused by prolonged vomiting or coughing,and can lead to massive hematemesis andhematochezia. A minor tear can heal on itsown, but a more severe tear may requireendoscopic intervention and bloodtransfusions.

Gastroenterology SocietyGuidelines

AchalasiaACG Guidelines: Vaezi MF, Richter JE (1999). Diagnosis

and management of achalasia. American Journal ofGastroenterology 94:3406–3412.

Ambulatory 24-Hour esophageal pH monitoringAGA (1996) American Gastroenterological Association

medical position statement: guidelines on the use ofesophageal pH recording. Gastroenterology110:1981–1996.

Barrett’s esophagusACG Guidelines: Sampliner RE (2002). Updated

guidelines for the diagnosis, surveillance, and therapyof Barrett’s esophagus. American Journal ofGastroenterology 97:1888–1895.

Esophageal manometryPandolfino JE, Kahrilas PJ (2005). American

Gastroenterological Association medical positionstatement: Clinical use of esophageal manometry.Gastroenterology 128: 207–208.

Pandolfino JE, Kahrilas PJ (2005). AGA Technical Reviewon the Clinical Use of Esophageal Manometry,Gastroenterology 128:209–224.

115

Foreign bodyASGE Guidelines: (2002). Guideline for the management

of ingested foreign bodies. Gastrointestinal Endoscopy55:802–806.

Gastroesophageal reflux disease ACG Guidelines: DeVault KR, Castell DO (2005). Updated

guidelines for the diagnosis and treatment ofgastroesophageal reflux disease. American Journal ofGastroenterology 100(1):190–200.

Oropharyngeal dysphagiaAGE (1999) AGA Technical Review on the Management

of Oropharyngeal Dysphagia. Gastroenterology116:455–478.

Index117

Note: Page numbers in bold refer tomajor references to the topics; those initalic refer to tables or boxed material

acetylcholine 2, 37achalasia 37–44

clinical presentation 38complications 46definition 37diagnosis 17, 38–41, 47differential diagnosis 42epidemiology 38etiology and pathophysiology 37–8,48guidelines 115treatment 42, 43–6

acid clearance, prolonged 70–1acid exposure, hypopharyngeal 20, 83acid hypersecretion 71acid regurgitation

defined 31presenting symptoms 69

acid suppressive therapy 54, 56, 75, 76acyclovir 105, 107adenocarcinoma 69

clinical presentation 62diagnosis 62–3epidemiology 62prognosis 68staging and treatment 64–8, 65surveillance in Barrett’s esophagus86, 86

adventitia 2, 66AIDS 105, 106alcohol consumption 62, 114alendronate 101allergic conditions 54, 55alprazolam 51ambulatory monitoring

bile reflux 21–3

pH 17–21, 73, 75

amphotericin B 105, 105anatomy, esophageal 1–2

anticholinergic drugs 98antifungal agents 103, 105, 105aorta, tumor invasion 66aortic arch 59aperistalsis 38, 40, 41, 47

causes 38argon plasma coagulation 88arytenoid medial wall, erythema/edema

80, 82aspiration 36, 46asthma 84, 85Auerbach’s (myenteric plexus) 2, 37–8

balloon dilation 43–4, 43, 60balloon tamponade 114band ligation 113–14Bard EndoCinch sewing capsule 77,

78barium esophagram 13–14

achalasia 39–40double contrast 13, 14, 97esophageal rings 56, 57esophageal web 53fluoroscopic observation 14full-column 13, 14GERD 73hiatal hernia 92indications 13infectious esophagitis 106, 107motility disorders 47oropharyngeal dysphagia 35stricture 58, 59timed swallow 39–40varices 112Zenker’s diverticulum 94, 95

Barrett’s esophagus 8, 62, 63, 69, 70,86–8

definition 86, 87diagnosis 72, 86, 87

Barrett’s esophagus (continued)epidemiology 86guidelines 115treatment 76, 86, 88

benzodiazepines 98bile reflux, ambulatory monitoring

21–3

biopsy, infectious esophagitis 105, 106,107

‘bird’s beak’ narrowing 39Blakemore tube 114bleeding 72, 110–14

clinical presentation 111diagnosis 111epidemiology 110hiatal hernia 92treatment 111varices 112–14

botulinum toxin 36, 43, 44, 45, 51bougienage, mechanical 52, 54, 56Bravo wireless pH monitoring system

21

bronchiectasis 85bronchitis, chronic 85

calcium-channel blockers 43, 46, 48,51, 51, 98

Cameron’s lesion 92, 110, 111Candida albicans infection 103–5, 107caustic injury 62, 108–10

cervical dysphagia 35, 36chest pain 32, 38, 48, 49, 72, 84children 98, 108cimetidine 75cirrhosis 112cisapride 76clotrimazole 105coiling (‘corkscrew’) esophagus 48,

49computed tomography (CT) 98cough, chronic 84, 85

Index118

Cowdry’s type A intranuclear inclusionbodies 107

cranial nerve lesions 34cytomegalovirus (CMV) infection

105–6

deglutition, see swallowingdental erosions 84, 85diaphragmatic hiatus 8diet

modification in GERD 75see also foods

diffuse esophageal spasm (DES) 17,47, 48, 49

dilationcomplications 60motility disorders 51pneumatic/balloon 43–4, 43rings 52, 56, 57strictures 60, 61, 109–10webs 52, 53

dilators, types 61diltiazem 51, 51diverticula 52, 94–7

dorsal motor nucleus 3, 37drugs

affecting LES pressure 71causing mucosal injury 102see also pill-induced injury

duodenogastroesophageal reflux(DGER) 21–3

duplication cyst 52dysphagia 32–3

in achalasia 38cervical 35, 36definition 32diagnosis 33etiology 32, 33in GERD 69motility disorders 49oropharyngeal 33–6, 115solids 33, 56, 57, 97

echoendoscopes 10–11endoscopic mucosal resection (EMR)

86, 88endoscopic therapies

Barrett’s esophagus 86, 87GERD 75, 77–8

endoscopic ultrasound 10–13

endoscopy 5–10

achalasia 40, 41diverticula 96equipment 5–7esophageal landmarks 9foreign body 99–100

endoscopy (continued) GERD 72, 73, 75, 74hiatal hernia 93indications 5infectious esophagitis 105, 106, 107pseudodiverticula 97stricture 59technique 8–10varices 112webs and rings 53, 56

epithelial damage, GERD 71, 72esomeprazole 75esophageal wall

endosonography 11, 12normal anatomy 1–2

tumor invasion 65–6esophagitis

classification 73, 74eosinophilic 54, 55infectious 103–7

pill-induced 102, 103reflux 69, 72, 73, 74, 110

esophagogastroduodenoscopy (EGD)86

ethnicity 62, 69

famciclovir 105famotidine 75fine needle aspiration (FNA) 10, 64,

67fluconazole 105, 105folds, esophageal 14foods

affecting LES 71associated with heartburn 31impaction in esophagus 98see also diet

foreign body 98–100, 115foscarnet 105–6, 105fundoplication 44, 76–7

ganciclovir 105–6, 105gas reflux 26, 28gastric cardia, endoscopy 8, 10, 40,

41gastric emptying, delayed 70, 71Gastroenterology Society Guidelines

115gastroesophageal junction (GEJ)

achalasia 40, 41adenocarcinoma 63endoscopic treatments in GERD 77,78mucosal injury 114normal 9

gastroesophageal reflux disease(GERD) 62, 69–79

clinical presentation 31, 69–70, 70diagnosis and evaluation 24, 72–5differential diagnosis 73epidemiology 69etiology and pathophysiology 70–1extra-esophageal (atypical)

symptoms 32–3, 80–5guidelines 115histopathology 72risk of Barrett’s esophagus 86treatments 75–9

gatekeeper reflux repair 77, 79giant cells, multinucleated 107globus 32

glucagon 98graft-versus-host disease (GVHD) 52ground glass nuclei 107

heartburn 31, 69, 72, 33Heller myotomy 43, 44, 45hematemesis 111, 114hematochezia 111, 114hepatocellular carcinoma 114hepatosplenomegaly 112Herpes simplex infection 105, 107

hiatal hernia 8, 89–93

associated conditions 70, 71, 92–3etiology 89prevalence 89treatment 76, 92, 93types 89, 90–1

hiccup 32histamine receptor antagonists (H2RA)

75, 76hoarseness 8, 62, 70hormones, affecting LES pressure 71human papilloma virus (HPV) 62hydralazine 51hypercontractile esophagus 17, 47, 49hypocontractile esophagus 47, 50–1hypotension 111

imipramine 51immunocompromise 103, 104, 105–6impedance, esophageal 24–30, 73

combined with manometry 24,28–30combined with pH monitoring 24,26–8

ineffective esophageal motility (IEM)17, 47, 50–1

infectious esophagitis 103–7

inflammatory cells 72inlet patches 9

Index 119

innervation, esophageal 2, 3, 37–8interarytenoid bar 82isosorbide 51

ketoconazole 105Killian’s triangle 94, 95

lansoprazole 75laryngeal carcinoma 52laryngitis 80leiomyoma 68, 69lifestyle modification 75–6, 75liver disease 112, 114Los Angeles classification 73, 74lower esophageal sphincter (LES) 1,

13failure of relaxation 17, 37, 38, 39,41foreign body 98hypertensive 17, 40, 47, 50hypotensive 17, 47, 92normal function 2–3substances affecting pressure 71transient relaxation (TSLER) 70, 71

lymph nodes, tumor involvement 67

Mallory-Weiss tear 92, 110, 114, 114

Maloney dilator 52, 61manometry, esophageal 14–17

achalasia 40, 41combined with multi-channelintraluminal impedance 24, 28–30criteria for esophageal motilitydisorders 17diffuse esophageal spasm 17, 47, 48,49equipment 14, 15, 16GERD 73guidelines 115hypertensive LES 50indications 14–15, 15ineffective esophageal motility 17,47, 50normal values 16nutcracker esophagus 17, 47, 49oropharyngeal dysphagia 35technique 15–16

meat tenderizer 98Meissner’s plexus 2metoclopramide 75, 76motility, ineffective esophageal (IEM)

17, 47, 50–1motility disorders

non-achalasia 47–51, 17see also achalasia

motor innervation 2, 3, 37–8

mucosainjury 54, 92, 100, 102, 110, 114,114

normal 1–2

muscleskeletal 1smooth 1, 2

muscularis propria 1–2, 66myenteric (Auerbach’s) plexus 2, 37–8myotomy 43, 44, 45

necrosis 110neoplasms, benign 68, 69

neoplasms, malignant 62–8

causing pseudoachalasia 42clinical features 42, 62diagnosis 62–3epidemiology 62prognosis 68risk 33, 86, 86staging and treatment 64–8, 65

neuromuscular disorders 33, 34neurotransmitters 2, 37nifedipine 43, 51, 51nitrates 32, 43, 46, 48, 51, 51, 98nitric oxide 2nitric oxide-containing neurons 3, 38nitroglycerin 32, 51nizatidine 75non-erosive reflux disease (NERD) 69,

75non-steroidal anti-inflammatory drugs

(NSAIDs) 60, 92, 101nucleus ambiguus 3, 37nutcracker esophagus 17, 47, 49nystatin 105

obesity 70odynophagia 32, 69, 102, 103omeprazole 75oral symptoms 31, 33oropharyngeal dysphagia 33–6

guidelines 115

pantoprazole 75papain 98Patterson-Kelly (Plummer-Vinson)

syndrome 54percutaneous gastrostomy (PEG) 36perforation 44, 45, 110peristalsis

failure 38, 40, 41, 47normal 2–3, 16, 37–8

pH monitoring 17–21, 73, 75combined with bile monitoring 22,23

pH monitoring (continued)combined with multi-channel

intraluminal impedance (MII) 24, 26–8

equipment 18GERD 83, 20guidelines 115indications 17, 18normal values 18, 18technique and equipment 18, 19

pill-induced injury 101–3

Plummer-Vinson (Patterson-Kelly)syndrome 54

portal hypertension 112pregnancy 70promotility (prokinetic) agents 75, 76proton pump inhibitors (PPIs) 60, 92

GERD diagnosis 72, 73GERD therapy 75, 81, 84

pseudoachalasia 41, 42pseudodiverticula 96–7psoriasis 52pyrosis (heartburn) 31, 33, 69, 72

rabeprazole 75radiofrequency ablation 75, 77ranitidine 75reflux

gas 26, 28impedance tracing 24, 26see also gastroesophageal reflux

disease (GERD)regurgitation

in achalasia 38non-acid 31

renal failure 114respiratory symptoms 32, 84, 85rings

‘A’ 52, 55, 57‘B’ (Schatzki’s) 52, 54–6, 93

salivary function, impaired 71Savary dilation 53Savary-Gilliard dilator 61Savary-Miller classification 74Schatzki’s ring 52, 54–6, 93scleroderma 17, 47sclerotherapy 113sigmoid esophagus 39Sjögren’s syndrome 71skeletal muscle 1skeletal muscle disorders 34skin diseases, blistering 52smoking 62, 71smooth muscle 1, 2smooth muscle relaxants 51

Index120

spasm, diffuse esophageal (DES) 17,47, 48, 49

sphincter, see lower esophagealsphincter (LES); upper esophagealsphincter (UES)

squamocolumnar junction (SCJ) 8, 10,57, 86, 87

squamous cell carcinoma (SCC) 69clinical presentation 62diagnosis 62–3epidemiology 62etiology and risk factors 46, 110prognosis 68staging and treatment 64–8, 65

squamous hyperplasia 72squamous metaplasia 86, 87squamous mucosa 9stenosis, esophageal 35, 36stenting 60, 61, 68, 109steroids 60, 109Stevens–Johnson syndrome 52Stretta catheter 77strictures 58–60, 109, 110submucosa, tumor invasion 65

surgeryachalasia 43, 44, 45antireflux 44, 75, 76–7caustic injury 110hiatal hernia 92, 93

swallowingcontrast studies 108impedance-manometry classification29impedance tracing 25normal physiology 2–3, 37–8

swallow therapy 36

tachycardia 111T-cell lymphocytes 38thrush, oral 103, 104thyroid disease 52tissue resistance, breakdown 71TNM classification 65, 68tracheoesophageal fistula 68transhepatic intrajugular portosystemic

shunt (TIPS) 114trazodone 51, 51

ulcers, HSV 107upper esophageal sphincter (UES) 1

foreign body 98incomplete relaxation 94normal function 2–3

vagus nerve 2, 3, 37varicella-zoster virus 10varices 112–14

vasoactive intestinal polypeptide- (VIP)containing neurons 3, 38

videofluoroscopy 35vocal cords 8, 80, 82, 83, 83volvulus, gastric 92, 93

water brash 31webs 35, 52–4

weight loss 33, 38, 42, 72

X-ray, chest 98, 99, 108

Zenker’s diverticulum 52, 94, 95Zollinger–Ellison syndrome 71

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