Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders 9780323998659

Table of contents :
Half title
Half title
Copyright
Dedication
Contributors
Preface
CONTENTS
Chapter 1 Normal swallowing physiology
Introduction
Functional anatomy
Swallowing phases
Airway protection
Neurological control
Conclusions
References
Chapter 2 Dysphagia and other esophageal symptoms
Dysphagia and GERD
Dysphagia and PEH
Dysphagia and achalasia
Symptom evaluation
Upper endoscopy
Barium swallow
High-resolution manometry
Ambulatory 24-hour pH monitoring
Dysphagia and diverticula
Conflict of Interest
References
Chapter 3 Radiologic evaluation of dysphagia
Introduction
Oropharyngeal Abnormalities
Presbyesophagus
Achalasia
Scleroderma and other connective tissue diseases
References
Chapter 4 Endoscopic evaluation of dysphagia
Introduction
The importance of symptom assessment
Etiologies of esophageal dysphagia
Reliability of endoscopy in the assessment of dysphagia
Endoscopic dilation of esophageal strictures
Types of dilators
Dilation for specific indications
Anastomotic strictures following esophagectomy
Achalasia
Conclusions
References
Chapter 5 Manometric evaluation of dysphagia
Introduction
Equipment and performance
Parameters evaluated
Upper esophageal sphincter
Esophageal body
Lower esophageal sphincter
pHmonitoring
Classifications for esophageal motility disorders
Dysphagia and motility disorders
Achalasia
Esophagogastric junction outflow obstruction
Absent contractility
Distal esophageal spasm
Hypercontractile esophagus
Ineffective esophageal motility
Conclusions
References
Chapter 6 Achalasia
Introduction
Epidemiology and pathophysiology
Clinical presentation
Diagnostic evaluation
Barium swallow
Esophageal manometry
Ambulatory pH monitoring
Treatment
Pharmacologic treatment
Endoscopic treatment
Endoscopic botulinum toxin injection
Pneumatic dilatation
Surgical treatment
Laparoscopic Heller myotomy
LHM versus POEM
Esophagectomy
Conclusions
Conflict of Interest
Acknowledgments
References
Chapter 7 Primary esophageal motility disorders beyond achalasia
Disorders with impaired LES relaxation \(excluding Achalasia\)
Disorders of peristalsis with normal EGJ outflow
^^e2^^80^^9cSpastic^^e2^^80^^9d EMD
Treatment of ^^e2^^80^^9cSpastic^^e2^^80^^9d EMD
Hypomotility disorders
Treatment of hypomotile EMD
Conclusions
References
Chapter 8 Zenker's diverticulum from pathophysiology to novel therapeutic approaches
Introduction
Clinical features
Diagnosis
Treatment
Open transcervical approach
Endoscopic approach
Rigid endoscopic technique
Flexible endoscopic technique
Endoscopic septum division
Conclusions
Chapter 9 Gastroesophageal reflux disease and dysphagia
Introduction
Pathophysiology of GERD
Clinical presentation of GERD
Diagnostic work-up of patients with GERD and dysphagia
Upper endoscopy
Barium esophagram
High-resolution manometry
Ambulatory pH monitoring
Gastric emptying study
Management of patients with GERD and dysphagia
Lifestyle modifications and medical therapy
Endoscopic dilatation of GERD-related strictures
Antireflux surgery
Conclusions
Conflict of Interest
Acknowledgments
References
Chapter 10 Eosinophilic esophagitis focusing on dysphagia
Introduction
Epidemiology
Pathogenesis
Risk factors for EoE
Diagnosis guidelines
Clinical diagnosis of EoE
EoE-like disease
Endoscopic diagnosis
Histopathological diagnosis
Treatments
Drugs
Maintenance treatment
Future perspectives
Conclusion
References
Chapter 11 Pharmacologic causes of dysphagia
Introduction
Systemic effects of medications
Smooth and striated muscle
Blockade of afferent nerve conduction
Xerostomia
Extrapyramidal motor disturbances
Alcohol
Dysphagia due to therapeutic effects
Antineoplastics and immunosuppressants
Treatment toxicity
Secondary infection
Mucosal lesions due to allergic reactions
Direct esophageal mucosal injury
Antibiotics
Clindamycin
Rifampin
Penicillins
Antivirals
Bisphosphonates
Chemotherapeutics
Aspirin and NSAIDs \(ibuprofen, naproxen, and indomethacin\)
Quinidine
Ascorbic acid
Iron
Potassium chloride
Opioid-induced esophageal dysfunction \(OIED\)
Epidemiology
Pathophysiology of OIED
Diagnosis
Types of esophageal dysfunction
Acute versus chronic opioid use
Relationship between potency of opioid and OIED
Management/treatment
References
Chapter 12 Once an achalasia patient always an achalasia patient: evaluation and treatment of recurrent symptoms
Introduction
Diagnostic evaluation
Persistent dysphagia
Recurrent dysphagia
Treatment
Conclusions
Conflict of Interest
References
Chapter 13 Esophagectomy for recurrent dysphagia in esophageal motility disorders
Introduction
Indications
Clinical presentation
Diagnosis
Decision making
Preoperative optimization
Operative approach
Outcomes
Functional long-term outcomes
Conclusions
References
Index

Citation preview

DYSPHAGIA Diagnosis and Treatment of Esophageal Motility Disorders

Edited by

MARCO G. PATTI Department of Surgery, University of Virginia, Charlottesville, VA, United States

FRANCISCO SCHLOTTMANN Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina; Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States

FERNANDO AUGUSTO MARDIROS HERBELLA Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil

DYSPHAGIA

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright © 2023 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-323-99865-9 For Information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals Publisher: Stacy Masucci Editorial Project Manager: Pat Gonzalez Production Project Manager: Omer Mukthar Cover Designer: Miles Hitchen Typeset by Aptara, New Delhi, India

Dedication To our mentors who guided us in our journey.

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Contributors Marco E. Allaix Department of Surgical Sciences, University of Torino, Torino, Italy Vera Lucia Angelo Andrade Brazilian Federation of Gastroenterology, Brazilian Society Digestive Motility and Neuroendocrine, Federal University of Minas Gerais, Brazil Renata Azevedo Department of Speech Therapy, Federal University of São Paulo, São Paulo, Brazil Lavinia Barbieri Gastrointestinal Surgery Unit, IRCCS San Raffaele Hospital, Milan, Italy Andrea Costantini Department of Surgical, Oncological and Gastroenterological Sciences, Unit of Chirurgia Generale 1, University of Padua, Padua, Italy Mario Costantini Department of Surgical, Oncological and Gastroenterological Sciences, Unit of Chirurgia Generale 1, University of Padua, Padua, Italy Nirmal Desai Department of Medicine, University of Chicago, Chicago, IL, United States Mohamad El Moheb Department of Surgery, University of Virginia, Charlottesville, VA, United States Fernando Augusto Mardiros Herbella Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil Lauren Hermann Ideal Speech Solutions, Lewisburg, PA, United States Julie Huffman Department of Rehabilitation and Therapy, Speech-Language Pathology, UNC REX Hospital, Raleigh, NC, United States Thomas Hunold Department of Medicine, University of Chicago, Chicago, IL, United States Christopher Kaperak Department of Medicine, University of Chicago, Chicago, IL, United States Linda W. Martin Department of Surgery, University of Virginia, Charlottesville, VA, United States Benjamin M. Mervak Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States xi

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Contributors

Rafael Melillo Laurino Neto Department of Surgery, Nove de Julho University, Mandaqui Hospital, São Paulo, Brazil; Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil Kristen Olinger Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States Marco G. Patti Department of Surgery, University of Virginia, Charlottesville, VA, United States Francesco Puccetti Gastrointestinal Surgery Unit, IRCCS San Raffaele Hospital, Milan, Italy Fabrizio Rebecchi Department of Surgical Sciences, University of Torino, Torino, Italy Kavitt Robert Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, United States Riccardo Rosati Gastrointestinal Surgery Unit, IRCCS San Raffaele Hospital, Milan, Italy Renato Salvador Department of Surgical, Oncological and Gastroenterological Sciences, Unit of Chirurgia Generale 1, University of Padua, Padua, Italy Francisco Schlottmann Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina; Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States Elettra Ugliono Department of Surgical Sciences, University of Torino, Torino, Italy Júlio César de Soares Veloso Gastroenterologist and Digestive Endoscopist, President of the Brasilia/Brazil Gastroenterology Association, Brazil Sindri A. Viktorsson Department of Surgery, University of Virginia, Charlottesville, VA, United States Wenfei Wang Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, United States Thomas J. Watson Beaumont Health, Detroit, MI, United States Andrew M. Young Department of Surgery, University of Virginia, Charlottesville, VA, United States Chris Young Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States

Preface Benign esophageal diseases are a heterogenous group of disorders that may cause diverse symptoms, such as heartburn, regurgitation, and dysphagia. A motility disorder is often present, either primary such as in achalasia or secondary such as in gastroesophageal reflux disease. The treatment of these disorders is based on a thorough work-up that includes a barium swallow, upper endoscopy, esophageal manometry, and pH monitoring. The goal is to characterize each disorder precisely, with the aim of tailoring treatment. The best results are obtained in centers where a multidisciplinary team composed of radiologists, gastroenterologists, and surgeons is present and able to offer different treatment options. The authors of the 13 chapters have been carefully selected as they are experts in the treatment of these disorders, with many years of experience. Their recommendations for diagnosis and treatment are both based on evidence and personal experience. We do hope that our effort will be useful for both physicians in training as well as practicing gastroenterologists and surgeons. Marco G. Patti Francisco Schlottmann Fernando Augusto Mardiros Herbella

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CONTENTS Contributors Preface

1. Normal swallowing physiology

xi xiii

1

Fernando Augusto Mardiros Herbella, Rafael Melillo Laurino Neto, Renata Azevedo and Marco G. Patti Introduction Functional anatomy Swallowing phases Airway protection Neurological control Conclusions References

2. Dysphagia and other esophageal symptoms

1 1 5 7 7 10 10

13

Marco E. Allaix, Elettra Ugliono and Fabrizio Rebecchi Dysphagia and GERD Dysphagia and PEH Dysphagia and achalasia Dysphagia and diverticula Conflict of Interest References

3. Radiologic evaluation of dysphagia

13 16 16 20 22 22

25

Kristen Olinger, Chris Young, Lauren Hermann, Julie Huffman and Benjamin M. Mervak Introduction References

4. Endoscopic evaluation of dysphagia

25 34

37

Thomas J. Watson Introduction Conclusions References

37 49 50 vii

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Contents

5. Manometric evaluation of dysphagia

53

Fernando Augusto Mardiros Herbella, Rafael Melillo Laurino Neto, Francisco Schlottmann and Marco G. Patti Introduction Equipment and performance Parameters evaluated Classifications for esophageal motility disorders Conclusions References

6. Achalasia

53 53 55 56 64 64

67

Francisco Schlottmann, Fernando Augusto Mardiros Herbella and Marco G. Patti Introduction Endoscopic treatment Surgical treatment Conclusions Conflict of Interest Acknowledgments References

7. Primary esophageal motility disorders beyond achalasia

67 72 73 78 78 78 78

83

Mario Costantini, Renato Salvador and Andrea Costantini Disorders with impaired LES relaxation (excluding Achalasia): Esophago-gastric junction outflow obstruction (EGJOO) Disorders of peristalsis with normal EGJ outflow Conclusions References

84 87 101 103

8. Zenker’s diverticulum from pathophysiology to novel therapeutic approaches

105

Lavinia Barbieri, Francesco Puccetti and Riccardo Rosati Introduction Clinical features Diagnosis Treatment Open transcervical approach Endoscopic approach Conclusions

105 105 106 108 109 111 116

Contents

9. Gastroesophageal reflux disease and dysphagia

ix

119

Francisco Schlottmann, Fernando Augusto Mardiros Herbella and Marco G. Patti Introduction Management of patients with GERD and dysphagia Conclusions Conflict of Interest Acknowledgments References

10. Eosinophilic esophagitis focusing on dysphagia

119 124 127 127 127 127

129

Vera Lucia Angelo Andrade and Júlio César de Soares Veloso Introduction Epidemiology Pathogenesis Risk factors for EoE Diagnosis guidelines Endoscopic diagnosis Histopathological diagnosis Conclusion References

11. Pharmacologic causes of dysphagia

129 130 130 131 132 133 134 139 139

141

Nirmal Desai, Thomas Hunold, Christopher Kaperak, Wenfei Wang and Robert Kavitt Introduction Dysphagia due to therapeutic effects Aspirin and NSAIDs (ibuprofen, naproxen, and indomethacin) Opioid-induced esophageal dysfunction (OIED) Types of esophageal dysfunction References

141 144 149 151 153 157

12. Once an achalasia patient always an achalasia patient: evaluation and treatment of recurrent symptoms

161

Marco G. Patti, Francisco Schlottmann and Fernando Augusto Mardiros Herbella Introduction Conclusions

161 170

x

Contents

Conflict of Interest References

13. Esophagectomy for recurrent dysphagia in esophageal motility disorders

171 171

173

Andrew M. Young, Mohamad El Moheb, Sindri A. Viktorsson and Linda W. Martin Introduction Indications Clinical presentation Diagnosis Decision making Preoperative optimization Operative approach Outcomes Functional long-term outcomes Conclusions References Index

173 173 174 174 176 177 177 178 178 179 180 183

CHAPTER 1

Normal swallowing physiology Fernando Augusto Mardiros Herbella a, Rafael Melillo Laurino Neto b, Renata Azevedo c and Marco G. Patti d a

Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil Department of Surgery, Nove de Julho University, Mandaqui Hospital, São Paulo, Brazil Department of Speech Therapy, Federal University of São Paulo, São Paulo, Brazil d Department of Surgery, University of Virginia, Charlottesville, VA, United States b c

Introduction Swallowing is defined as a process in which liquid or solid substances arrive from mouth to stomach, passing through the pharynx and esophagus. This process occurs approximately 600 times a day, especially while awake and during feeding, but in a much smaller number, approximately 50 times a day, it also happens during sleep.1 It is a very complex behavior learned early in the individual’s development. Evidence shows that already in intrauterine life, around the 15th week of pregnancy, this process already occurs, seeking to regulate the volume of amniotic fluid. The process of sucking, swallowing, and breathing already takes place in newborns and develops with the introduction of new foods, allowing for their conscious control in early childhood.2 Despite being an innate function of the body, it is a complex process involving the coordinated function of several muscles and nerves.

Functional anatomy Many anatomical structures participate in the swallowing process. Several bones (mandible, maxilla, hard palate, hyoid, and cervical vertebrae), cartilage (thyroid,cricoid,arytenoid,and epiglottis),teeth,salivary glands (parathyroid, sublingual,and submandibular),and muscles take part in this process (Fig.1.1). After passing through the oral cavity, which includes lips, oral mucosa, teeth, gums, anterior two-thirds of the tongue, floor of the mouth and hard palate, food enters the pharynx, which is an organ common to the digestive and respiratory tract, allowing communication between these two systems. Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00005-1

Copyright © 2023 Elsevier Inc. All rights reserved.

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Figure 1.1 Midsagittal view of head and neck. Public Domain (from https://commons. wikimedia.org/wiki/File:Sobo_1906_328.png).

The pharynx is located in the posterior region of the nose, mouth, and larynx, being thus divided into three parts: nasopharynx, oropharynx, and laryngopharynx. After leaving pharynx, food enters the esophagus, where it is transported to the stomach (Fig. 1.2). In particular, regarding the participation of muscles in this process, we must keep in mind that more than 30 pairs of these are activated during swallowing. In Table 1.1, we have individually described each one, and how they are didactically grouped.3,4 All muscles, involved in swallowing are

Normal swallowing physiology

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Figure 1.2 Posterior view of head and neck. Public Domain (from https://commons. wikimedia.org/wiki/File:Sobo_1906_365.png).

striated, with the exception of the medial and distal esophagus, which have segments that are partially or completely smooth muscle. Muscle movements are controlled by several cranial and peripheral nerves and are coordinated within the brain stem. Somatic afferent and efferent feedback are provided

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Table 1.1 Swallowing-related musculature. Category

Muscle name

Muscles of the face

Orbicularis oris Buccinator Temporalis Masseter Medial pterygoid Lateral pterygoid Superior longitudinal Inferior longitudinal Transverse Verticalis Genioglossus Hyoglossus Styloglossus Palatoglossus Levator veli palatini Musculus uvulae Tensor veli palatini Superior pharyngeal constrictor Middle pharyngeal constrictor Inferior pharyngeal constrictor Stylopharyngeus Salpingopharyngeus Palatopharyngeus Mylohyoid Geniohyoid Digastric (anterior) Digastric (posterior) Stylohyoid Lateral cricoarytenoid Transverse arytenoid Thyroarytenoid Sternothyroid Sternohyoid Thyrohyoid Omohyoid Inferior pharyngeal constrictor Cricopharyngeus Upper fibers of esophagus

Muscles of mastication

Intrinsic muscles of the tongue

Extrinsic muscles of the tongue

Muscles of the soft palate

Pharyngeal musculature

Suprahyoid muscle

Muscles of the larynx

Infrahyoid muscle

Muscles of the upper esophagus

primarily via cranial and peripheral nerves (for striated musculature) and an autonomic enteric system (for smooth muscle).

Normal swallowing physiology

5

Swallowing phases Swallowing process is divided into four distinct phases: oral preparatory phase, oral propulsive phase, pharyngeal phase, and esophageal phase. Although the two oral phases have voluntary control, the other two are characterized by being reflex actions. It should also be noted that both oral and pharyngeal phases of swallowing share anatomical structures with the respiratory tract, what it does the protection of the airway, being of great importance throughout the process.5 1) Oral preparatory phase In the first phase of swallowing, there is a fractionation of food with formation of a cohesive bolus through mastication.6,7 Facial muscles (orbicularis oris and buccinators) closing the lips, as well as soft palate approaching to base of the tongue, delimit the oral cavity and prevent the premature escape of food to oropharynx, protecting the airway. Mastication muscles (masseter, temporalis, and medial and lateral pterygoid muscles) are used when solid food is ingested,promoting active movement of the jaw. On the other hand, tongue movements place food particles between the teeth, which are also mixed with saliva. Once mastication is complete, the bolus is contained between the dorsal surface of the tongue and the hard palate.8,9 2) Oral propulsive phase This phase begins after a cohesive bolus formation, with its transport backwards to the oropharynx, through oral cavity. Facial muscles remain contracted and soft palate rises, promoting isolation of the nasal cavity from oropharynx, and creating a closed pressure loop that facilitates bolus transport. Through the action of intrinsic and extrinsic muscles of the tongue (genioglossus, hyoglossus, styloglossus, palatoglossus, superior longitudinal), a wave-shaped movement of alimentary bolus, which passes from oral cavity to oropharynx, takes place. The entrance of the bolus into oropharynx is also facilitated by the contraction of muscles at base of the tongue (via contraction of hyoglossus muscle) and elevation of soft palate by contraction of this region muscles (levator veli palatini and musculus uvulae) (Fig. 1.3A). Stabilization of jaw and tongue at this stage is achieved by activating masticatory (temporalis, masseter, and medial and lateral pterygoids) and suprahyoid muscles (mylohyoid, geniohyoid, anterior digastric, posterior digastric, and stylohyoid).10,11

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Figure 1.3 Fluoroscopy of swallowing phases (A—oral, B—pharyngeal, C—esophageal).

3) Pharyngeal phase Although this phase of swallowing lasts approximately just 1 second, it is considered the most complex of all, requiring coordinated action of practically all muscles involved in this whole process12 (Table 1.1). The involuntary “trigger” for beginning this phase is the passage of alimentary bolus through anterior faucial pillar area, being influenced by the way in which transport took place in oral phase, as well as by characteristics (texture, taste, volume) of swallowed food.13,14 After this trigger, pharynx rises, by contraction of pharyngeal muscles (lateral cricoarytenoid, transverse arytenoid, and thyroarytenoid) and tongue base retraction through contraction of its extrinsic muscles (hyoglossus and styloglossus) and pharyngeal constrictors. This coordinated action, which occurs at a rate of 9 to 25 cm/s, is known as pharyngeal peristalsis, and results in pushing the bolus through the pharynx and into the proximal esophagus.15 Simultaneously with elevation of pharynx, there is also an elevation of hyoid bone by contraction of suprahyoid muscles (mylohyoid, stylohyoid, geniohyoid, and anterior and posterior bellies of digastric). This anterior and superior movement of larynx and hyoid bone, in addition to protecting airway, by aligning larynx below base of the tongue and inverting epiglottis, creates a source of negative pressure below bolus, that generates a suction mechanism, as well as creates a biomechanical force, that forces opening of upper esophageal sphincter (UES) (Fig. 1.3B). Assuming that labial and nasopharyngeal seals have remained intact, opening of UES creates an additional source of negative pressure, or “suction force” in upper esophagus, that greatly enhances the efficiency of pharyngeal bolus transit.13 As in the two previous swallow phases, in order to keep tongue and jaw stabilized, mastication muscles must remain active throughout the entire pharyngeal phase.

Normal swallowing physiology

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4) Esophageal phase Esophageal phase of swallowing begins when bolus passes through UES (Fig. 1.3C). UES opening happens due to the sum of biomechanical forces and relaxation of cricopharyngeal muscle. This short-term relaxation (0.5–1.2 seconds) takes place just long enough for food to pass into esophagus through UES, after which cricopharynx returns to its contracted state, preventing retrograde flow of bolus into hypopharynx.16,17 Esophageal peristalsis begins after food passes through UES, promoting the transport of the bolus to stomach through lower esophageal sphincter. This esophageal peristaltic wave travels inferiorly at a rate of approximately 3–4 cm/s and serves to squeeze the bolus through esophagus. Esophageal transit lasts between 8 and 13 seconds. Several secondary peristaltic waves also occur up to an hour after swallow and help to clear any remaining esophageal residue.18–20

Airway protection Airway protection is a fundamental part of normal swallowing, since incorrectly directing food to the airway can lead to broncho aspiration, often causing aspiration pneumonia, which is often a serious clinical situation.21 Some airway protection mechanisms during swallowing are well known. The first one is coordination and temporal integration of 2 phenomena that take place in the same anatomical pathway. Thus, pharyngeal phase of swallowing must take place at the beginning of expiration. When this phase of swallowing begins, there should be a brief apnea until the bolus leaves hypopharynx and reaches esophagus, when breathing resumes.22,23 The second aspect of airway protection involves movements of hypopharynx structures, such as vocal cords closure and epiglottis deflecting, as they seal the airway, preventing its penetration by food at swallowing.24 Another mechanism is sensory innervation of vocal cord, which are innervated by internal branch of superior laryngeal nerve (ISLN) of vagus nerve (CN X). ISLN serves two main purposes: to ensure that airway is completely closed during swallowing and to trigger reflexes that help eject or clear any penetrated or aspirated bolus material from airway.25–27

Neurological control Swallowing process involves a complex neuronal network with both voluntary and reflex components. Involved in this network are supratentorial

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cortex

central program generator

afferent reception

Motor neurons

cranial nerves

Muscles of swallowing

Sensory receptors in pharynx and esophagus

Figure 1.4 Central regulation of sequential oral, pharyngeal, and esophageal contraction (Adapted from Diamant28 ).

(cortical and subcortical), infratentorial (brain stem) components as well as peripheral nervous system (sensory and motor)28–30 (Fig. 1.4). From here on, we will review the contribution of central nervous system in swallowing process. A) Supratentorium Several cortical and subcortical structures participate in swallowing process. Oral preparatory and propulsive phases, in which voluntary feeding behaviors, as well as tongue movements, for food transport prevail, are controlled by structures located in the cortical region (such as primary and secondary sensorimotor cortex).31 These same structures, together with other subcortical structures (insula, anterior and posterior cingulate cortices, basal ganglia, amygdala, hypothalamus, and substantia nigra) are involved in pharyngeal phase of swallowing.32 The involvement of these structures can be both excitatory and inhibitory in all phases mentioned so far. Cortical representation of swallowing is characterized by being bilateral and asymmetrical, especially in motor and premotor cortices, which has important therapeutic implications, especially in recovery of swallowing disorders due to hemispheric stroke.33 B) Infratentorium Infratentorium structures (mainly the medulla oblongata within brainstem) are especially active during involuntary pharyngeal and esophageal phase of swallowing. A central program generator (CPG) located in the medulla participates in these two phases coordination. CPGs are neuronal pools composed of sensory, motor, and interneuron structure, whose joint action controls rhythmic and sequential actions in the body, such as locomotion, breathing, and swallowing.34

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Swallowing CPG can be defined as a neuronal chain that fires sequentially during this process.It is also believed that CPG is represented bilaterally in medulla oblongata, but both parts work in a synchronized way.35 Motor neurons that are part of the swallowing CPG [trigeminal (CN V), facial (CN VII), and hypoglossal (CN XII) motor nuclei; the nucleus ambiguus (nA) and the dorsal motor nucleus of the vagus nerve (CN X)] are located in the brainstem and cervical spinal neurons (C1 and C3).34,35 Of these nuclei, the main ones are CN XII and nA, as they innervate intrinsic and extrinsic muscles of the tongue (genioglossus, geniohyoid, styloglossus, and hyoglossus), as well as pharynx, larynx, and upper esophagus (specifically its striated musculature).35,36 Motor output for the lower esophagus (smooth muscle) is provided by the dorsal motor nucleus. Sensory neurons that participate in pharyngeal and esophageal phases of swallowing are also located in the brain stem (nucleus of the solitary tract and reticular formation). The sensitivity of oral, pharyngeal, and esophageal mucosa is sent to these neurons via the vagus nerve (CN X), while sensory information from the tongue is sent by lingual (CN V) and glossopharyngeal (CN IX) nerves.37,38 Sensory and motor neurons of both parts (dorsal and ventral) of swallowing CPG are integrated into the medulla oblongata through two groups of interneurons: dorsal swallowing group (DSG), located within the nucleus tractus solitarii, and the adjacent reticular formation and a ventral swallowing group (VSG) located in the ventrolateral medulla adjacent to the nA.30 DSG contains the generator neurons involved in triggering, shaping, and timing the sequential or rhythmic swallowing pattern, while VSG contains switching neurons, which distribute the swallowing drive to various pools of motoneurons involved in swallowing. It should be noted that the pathway including the peripheral afferent fibers, neurons in the DSG and VSG, and motoneurons forms an oligosynaptic loop involved in swallowing and the elementary reflexes34 (Fig. 1.5). Also notable is the fact that swallowing neurons are located in same places, at medulla, as neurons that control respiration and heart function, which allows the coordination of swallowing with these other autonomic functions of the body.39 Even today, many aspects of neuropharyngeal control of swallowing are not well-known, or your hypotheses, have not yet been proven. The more traditional point of view, which admits that muscle response of oropharyngeal phase was reflexive, and its reversal after the initial trigger was not possible34 , has been questioned, since researches have shown that

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Figure 1.5 Diagram of the swallowing central program generator (CPG) (Adapted from Jean30 ).

in normal swallowing, strength, and duration of muscle contraction can be modulated, depending on sensory information regarding texture, size, temperature, and flavor of the bolus.40 Research in this area is ongoing and will likely lead to increased understanding and improved intervention for individuals with dysphagia.

Conclusions The physiology of normal swallowing is a complex process that involves many phases and structures and is not fully understood even today. Anomalies in this process lead to life-threatening situations, with impairment of both the digestive and respiratory functions. Understanding the normal physiology of swallowing is fundamental to evaluating and treating its disorders.

References 1. Lear C, Flanagan J, Moores C. The frequency of deglutition in man. Arch Oral Biol. 1965;10:83–99. 2. Delaney AL, Arvedson JC. Development of swallowing and feeding: prenatal through first year of life. Dev Disabil Res Rev. 2008;14:105–117.

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3. Malone JC,R AN.Anatomy,Head and neck,swallowing.In:StatPearls [Internet].Treasure Island, FL: StatPearls Publishing. 4. Moore KL,Dalley AF,eds.Clinically Oriented Anatomy.5th ed.Philadelphia,PA:Lippincott Williams & Wilkin; 2006. 5. Matsuo K, Palmer JB. Anatomy and physiology of feeding and swallowing: normal and abnormal. Phys Med Rehabil Clin N Am. 2008;19:691–707 vii. 6. Palmer JB, Rudin NJ, Lara G, et al. Coordination of mastication and swallowing. Dysphagia. 1992;7:187–200. 7. Gay T, Rendell JK, Spiro J. Oral and laryngeal muscle coordination during swallowing. Laryngoscope. 1994;104:341–349. 8. Dutra EH, Caria P, Rafferty KL, et al. The buccinator during mastication: a functional and anatomical evaluation in minipigs. Arch Oral Biol. 2010;55:627–638. 9. Dodds W. The physiology of swallowing. Dysphagia. 1989;3:171–178. 10. Palmer JB, Rudin NJ, Lara G, et al. Coordination of mastication and swallowing. Dysphagia. 1992;7:187–200. 11. Ergun GA, Kahrilas PJ, Lin S, et al. Pattern and modulation of tongue surface movement during deglutition. Paper presented at the Dysphagia Research Society (DRS) Annual Meeting; November 6–8, 1992. 12. Sonies BC, Parent LJ, Morrish K, et al. Durational aspects of the oral-pharyngeal phase of swallow in normal adults. Dysphagia. 1988;3:1–10. 13. Robbins J, Gensler G, Hind J, et al. Can thickened liquids or chin-down posture prevent aspiration? Ann Intern Med. 2008;148:I39. 14. Logemann JA, Pauloski BR, Colangelo L, et al. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res. 1995;38:556–563. 15. McConnel FM. Analysis of pressure generation and bolus transit during pharyngeal swallowing. Laryngoscope. 1988;98:71–78. 16. Ertekin C, Aydogdu I. Electromyography of human cricopharyngeal muscle of the upper esophageal sphincter. Muscle Nerve. 2002;26:729–739. 17. Ingelfinger FJ. Esophageal motility. Physiol Rev. 1958;38:533–584. 18. Humphries TJ, Castell DO. Pressure profile of esophageal peristalsis in normal humans as measured by direct intraesophageal transducers. Am J Dig Dis. 1977;22:641–645. 19. Goyal RK, Cobb BW. Chapter 11: Motility of the pharynx, esophagus, and esophageal sphincters.In:Johnson LR,ed.Physiology of the Gastrointestinal Tract.New York,NY:Raven Press; 1981:359–391. 20. De Vincentis N, Lenti R, Pona C, et al. Scintigraphic evaluation of the esophageal ransit time for the noninvasive assessment of esophageal motor disorders. J Nucl Med Allied Sci. 1984;28:137–142. 21. Martino R, Foley N, Bhogal S, et al. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke. 2005;36:2756–2763. 22. Martin BJ, Logemann JA, Shaker R, et al. Coordination between respiration and swallowing: respiratory phase relationships and temporal integration. J Appl Physiol. 1994;76:714– 723. 23. Klahn MS, Perlman AL. Temporal and durational patterns associating respiration and swallowing. Dysphagia. 1999;14:131–138. 24. Ardran GM, Kemp FH. The protection of the laryngeal airway during swallowing. Br J Radiol. 1952;25:406–416. 25. Ludlow C, Van Pelt F, Koda J. Characteristics of late responses to superior laryngeal nerve stimulation in humans. Ann Otol Rhinol Laryngol. 1992;101:127. 26. Nishino T, Tagaito Y, Isono S. Cough and other reflexes on irritation of airway mucosa in man. Pulm Pharmacol. 1996;9:285–292.

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27. Yoshida Y, Tanaka Y, Hirano M, et al. Sensory innervation of the pharynx and larynx. Am J Med. 2000;108(4 Suppl 1):51–61. 28. Diamant NE. Firing up the swallowing mechanism. Nat Med. 1996;2:1190–1191. 29. Lang IM. Brain stem control of the phases of swallowing. Dysphagia. 2009;24:333–348. 30. Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev. 2001;81:929–969. 31. Hamdy S, Mikulis DJ, Crawley A, et al. Cortical activation during human volitional swallowing: an event-related fMRI study. Am J Physiol Gastrointest Liver Physiol. 1999;277:G219–G225. 32. Sörös P, Inamoto Y, Martin RE. Functional brain imaging of swallowing: an activation likelihood estimation meta-analysis. Hum Brain Mapp. 2009;30:2426–2439. 33. Hamdy S, et al. Chapter 20: The organisation and re-organisation of human swallowing motor cortex. In: Paulus W, Tergau F, Nitsche MA, et al., eds. Supplements to Clinical Neurophysiology. Amsterdam: Elsevier; 2003:204–210. 34. Jean A. Brain stem control of swallowing: localization and organization of the central pattern generator for swallowing. In: Taylor A, ed. Neurophysiology of the Jaws and Teeth. London: Macmillan; 1990:294–321. 35. Doty R. Neural organization of deglutition. In: Charles FC, Werner H, eds. Handbook of Physiology: Alimentary Canal. Washington, DC: American Physiological Society; 1968:1861–1902. 36. Miller AJ. Deglutition. Physiol Rev. 1982;62:129–184. 37. Lang IM. Brain stem control of the phases of swallowing. Dysphagia. 2009;24:333–348. 38. Miller AJ, Bowman JP. Precentral cortical modulation of mastication and swallowing. J Dent Res. 1977;56:1154. 39. Bianchi AL, Denavit-Saubie´ M, Champagnat J. Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters. Physiol Rev. 1995;75:1– 45. 40. Teismann I, Steinstraeter O, Stoeckigt K, et al. Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing. BMC Neurosci. 2007;8:62.

CHAPTER 2

Dysphagia and other esophageal symptoms Marco E. Allaix, Elettra Ugliono and Fabrizio Rebecchi Department of Surgical Sciences, University of Torino, Torino, Italy

Dysphagia is a common symptom of different benign and malignant diseases, with the origin being oropharyngeal or esophageal. The causes of oropharyngeal dysphagia are functional, mechanical, or neurological while esophageal dysphagia is most frequently secondary to mechanical obstruction or esophageal motility disorders. Esophageal dysphagia is usually considered an “alarm symptom,” since it is the most common symptom of presentation of cancer of the esophagus. However, dysphagia may be secondary to several benign esophageal disorders, including gastroesophageal reflux disease (GERD), large hiatal hernias, primary esophageal motility disorders (achalasia), and, less frequently, esophageal diverticula. Since the main goal of the evaluation of a patient complaining dysphagia is to rule out the presence of esophageal cancer, a thorough evaluation of characteristics (onset, duration, and progression) of dysphagia, along with the presence of associated symptoms is key. This chapter is focused on the evaluation of dysphagia secondary to the most common benign esophageal disorders: GERD, paraesophageal hernia (PEH), achalasia, and diverticula of the esophagus.

Dysphagia and GERD When GERD is suspected to be the cause of dysphagia,both occurrence and severity of typical (heartburn, regurgitation) and atypical (cough, hoarseness, chest pain, dental erosions) symptoms of GERD should be assessed, along with the effect of antisecretory medications in terms of symptom relief. However, the sensitivity and specificity of typical symptoms are low, and a wrong diagnosis of GERD occurs in about 30% of patients.1 In addition, heartburn is reported in about 40% of achalasia patients secondary to food stasis and fermentation in the distal esophagus. Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00002-6 All rights reserved.

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Therefore, further investigation is needed to better define the diagnosis. The complete diagnostic work-up includes: r upper endoscopy, r barium esophagram, r high-resolution manometry (HRM), and r ambulatory 24-hour pH monitoring. Upper endoscopy is usually the first test obtained to confirm a diagnosis of GERD based on symptoms. However, endoscopic findings consistent with esophagitis are present in only about 50% of patients with pathologic reflux.2 The major goals of upper endoscopy are the detection of Barrett’s esophagus which is usually present in up to 14% of GERD patients, erosive esophagitis, esophageal cancer, and exclusion of gastric and duodenal diseases. Barium esophagram provides information about: r the length and diameter of the esophagus, r the presence, type, and size of a hiatal hernia, and r the presence of a Schatzki ring or a stricture. Reflux of gastric content into the esophagus is seldom demonstrated during a barium esophagram, even in symptomatic patients with positive ambulatory 24-pH monitoring.3,4 On the other hand, even if reflux is radiologically observed, 24-hour pH monitoring will not necessarily detect pathologic acid esophageal exposure. In fact, while the radiologic test evaluates the presence of reflux during a very short period of time (usually about 10 minutes), the ambulatory pH-monitoring assesses the occurrence of reflux episodes during 24 hours, both in the postprandial and fasting state, and in the upright and supine position. Esophageal peristalsis plays a key role in the antireflux mechanism because it governs esophageal clearance of the gastric contents. As a consequence, impaired peristalsis is associated with symptoms and mucosal injury secondary to reflux. Two indirect measurements of esophageal clearance are included in the DeMeester score at 24 hour- pH monitoring: (1) number of reflux episodes longer than 5 minutes, and (2) length of the longest episode. In addition, the average esophageal clearance time can be calculated by dividing the total time spent with pH below 4 by the number of reflux episodes. Therefore, severe symptoms and a higher degree of esophagitis (including Barrett’s esophagus) are reported more likely in GERD patients with abnormal peristalsis and in systemic diseases that impair esophageal peristalsis, such as connective tissue disorders. Abnormal peristalsis is present in 40%–50% of patients with GERD, and in about 20% of them, it is particularly severe with very low amplitude and/or abnormal propagation of the peristaltic waves (Ineffective Esophageal Motility).

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mmHg 150.0

140

UES 120

100

80

Peristalsis

60

40 30 20 10 0

LES

–10.0

Figure 2.1 Ineffective esophageal motility at high-resolution manometry. UES, upper esophageal sphincter; LES, lower esophageal sphincter.

The most reliable tool to assess the function of the upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) is the HRM. The primary goals of HRM are: 1) to rule out primary esophageal motility disorders, which may be misdiagnosed as GERD, 2) to measure LES resting pressure, length, and relaxation, 3) to assess amplitude and propagation of esophageal peristalsis (Fig. 2.1), 4) to measure the precise location of the LES for proper placement of the pH probe, and 5) to evaluate the pressure and coordination of the hypopharynx and cricopharyngeal muscle. The 24-hour pH monitoring is the gold standard for the diagnosis of GERD. The following variables are calculated: 1. frequency of reflux episodes, 2. duration of the longest reflux episode, 3. number of episodes longer than 5 minutes,

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4. time pH less than 4.0 (total), 5. time pH less than 4.0 in the supine position, and 6. time pH less than 4.0 in the upright position. These variables are integrated into a composite score (DeMeester score), with a value greater than 14.7 considered abnormal.

Dysphagia and PEH Most small PEHs are asymptomatic. Large PEHs may cause a wide variety of symptoms. The most common symptom is dysphagia which can be associated with chest pain and postprandial bloating. In addition, GERD might be present in the case of associated defect in competence of the gastroesophageal junction.Anemia is secondary to bleeding from mechanical or ischemic gastric ulceration. Respiratory symptoms such as asthma, cough, or dyspnea are caused by chronic aspiration. A large PEH may be also the cause of atrial fibrillation. The diagnostic work-up should include, beside symptom evaluation, (1) barium esophagram, (2) upper endoscopy, (3) HRM, and (4) 24-hour ambulatory pH monitoring. The barium swallow is considered the gold standard, since it is inexpensive, and provides an accurate evaluation of the size of PEH; in addition, it allows to define the anatomy of the esophagus and stomach, and the location of the gastroesophageal junction in relationship with the diaphragm (Fig. 2.2). Upper endoscopy is performed to rule out erosions and ulcerations, and to exclude the presence of malignancies. HRM and 24-hour pH monitoring are obtained in selected patients. The manometric evaluation of the LES in large PEH is challenged by proximal position of the gastroesophageal junction and tortuosity of the esophagus. In patients with smaller hernias, manometry provide useful information about both LES function and quality of the esophageal peristalsis. In particular, the presence of esophageal dysmotility alters the decision to perform a total fundoplication in favor of a partial fundoplication. Lastly, 24-hour pH monitoring is performed even more selectively, since it provides less reliable information about reflux in patients with large PEH than sliding hernias.

Dysphagia and achalasia Achalasia is the most common primary esophageal motility disorder, while diffuse esophageal spasm, nutcracker esophagus, and the hypertensive LES are less frequent.

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17

Figure 2.2 Large parasophageal hiatal hernia (PEH).

The diagnosis of achalasia is challenged by the fact that it is a rare condition and symptoms are not specific: dysphagia, regurgitation of undigested food and aspiration, heartburn, and chest pain. As a consequence, there is often a long delay between the onset of symptoms and the diagnosis.5 The diagnostic work-up includes symptom evaluation, upper endoscopy, barium esophagram, HRM, and ambulatory 24-hour pH monitoring.6,7

Symptom evaluation Dysphagia is the most common symptom since it is reported in about 95% of patients. It is often for both solids and liquids, even though it is usually first only for liquids. It may lead to weight loss; however, a stable weight is kept by most patients who change their diet. Regurgitation of undigested food is the second most frequent symptom and is present in about 60% of patients. It occurs more often in the supine position and may lead to aspiration. Heartburn is complained by about 40% of patients: it is not due to gastroesophageal reflux,but rather to stasis and fermentation of undigested

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food in the distal esophagus. Chest pain also occurs in about 40% of cases, due to esophageal distention and it is usually experienced at the time of a meal.8–10 The Eckardt score is the most commonly used score system. It is the sum of the scores for dysphagia, regurgitation, and chest pain (a score of 0 indicates the absence of symptoms, 1 indicates occasional symptoms, 2 indicates daily symptoms,and 3 indicates symptoms at each meal) and weight loss (a score of 0 indicates no weight loss, 1 indicates a loss of less than 5 kg, 2 indicates a loss of 5 to 10 kg, and 3 indicates a loss of more than 10 kg). The maximum score on the Eckardt scale is 12.11

Upper endoscopy It is usually the first test that is performed in patients with dysphagia to rule out the presence of a mechanical obstruction secondary to a peptic stricture or cancer. An infiltrating tumor of the gastroesophageal junction can mimic the clinical, radiological, and manometric findings of achalasia, resulting in impaired LES relaxation, esophageal dilatation, and absence of peristalsis. This condition, defined as “secondary achalasia” or “pseudo-achalasia,” should be suspected and ruled out in patients older than 60 years of age, with rapidly progressing dysphagia and excessive weight loss. However, these symptoms are not sensitive or specific.12 When a malignancy of the cardias is suspected, a CT scan and/or endoscopic ultrasound should be obtained.13–16 The endoscopic findings in achalasia patients widely range from a normal exam (in about 40% of cases) to tortuous and dilated esophagus with food retention. Esophageal mucosa can be normal or present signs of esophagitis (secondary to food stasis or to Candida infection).

Barium swallow Barium swallow provides information regarding anatomy and emptying of the esophagus.A narrowing at the level of the gastroesophageal junction,(the so-called bird beak), slow esophageal emptying of contrast with an air-fluid level, and tertiary contractions of the esophageal wall are typical radiologic findings (Fig. 2.3). The diameter, the shape, and the axis of the esophagus, and associated conditions such as an epiphrenic diverticulum are also defined. However, the barium swallow may not show abnormal findings in about 30% of patients, particularly in the early stages of the disease.

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Figure 2.3 Achalasia at barium swallow.

High-resolution manometry HRM is the gold standard for the diagnosis of achalasia that is characterized by a lack of peristalsis and absent or incomplete LES relaxation in response to swallowing. The LES is hypertensive in about 50% of patients. Based on manometric patterns of esophageal body contractility, achalasia is classified as follows: type 1, classic, with minimal esophageal pressurization; type 2, achalasia with pan-esophageal pressurization; and type 3, achalasia with spasm.17–19 Type 2 achalasia is associated with better outcomes than types 1 and 3.20

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Ambulatory 24-hour pH monitoring This test is rarely requested; however, it is recommended in selected untreated patients when the diagnosis is unclear between GERD and achalasia. The examination of the pH monitoring tracing allows to distinguish between the two conditions. In GERD patients, intermittent drops of the pH below 3 with subsequent return of the pH values above 5 characterize the tracing; in achalasia patients, there is a slow and progressive drift of the pH below 4 with no return to higher values.

Dysphagia and diverticula Esophageal diverticula are rare. They are located above the UES (pharyngoesophageal or Zenker diverticulum) or the LES (epiphrenic diverticulum). They are the result of abnormalities of the sphincters’ function in terms of resting pressure, relaxation in response to swallowing, and coordination with the segment above the sphincter. As a consequence, mucosa and submucosa protrude through the muscular layers, forming the outpouching. The Zenker diverticulum is the most common esophageal diverticulum and is three times more frequent in elderly men than in women. It is a protrusion of pharyngeal mucosa through a weak zone in the posterior wall of the pharynx, the so-called Killian’s triangle. About 90% of patients complain of dysphagia. Regurgitation of undigested foods, halitosis, and hoarseness can also be associated. Cervical borborygmi is almost pathognomonic of Zenker diverticulum. As the pouch enlarges, symptoms become more severe with resultant weight loss and malnutrition. As many as 30%–40% of patients describe chronic cough and repeated episodes of aspiration, some with subsequent pneumonia. Symptoms may be present for weeks to several years. GERD occurs in about 30% of patients. A sudden worsening of dysphagia and regurgitation in terms of severity and/or development of alarm symptoms such as local pain, hemoptysis, or hematemesis may be the sign of the presence of squamous cell carcinoma within the diverticulum. The diagnosis is suspected based on clinical symptoms and confirmed by barium swallow which shows the position and size of the diverticulum (Fig. 2.4). HRM shows a lack of coordination between the pharynx and the cricopharingeus muscle and often a hypertensive UES. In addition, it can show a hypotensive LES and abnormal esophageal peristalsis. Ambulatory pH monitoring allows to define if pathologic gastroesophageal reflux occurs.

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Figure 2.4 ZenKer diverticulum.

Diverticulum can also be diagnosed incidentally in patients who undergo flexible upper endoscopy because of unrelated symptoms. Similarly, the diagnostic workup of patients with suspected epiphrenic diverticulum includes (1) symptom evaluation; (2) barium swallow; (3) upper endoscopy; and (4) HRM. The symptom evaluation allows to assess of presence and duration of dysphagia, regurgitation, heartburn, hoarseness, cough, and chest pain. Barium swallow is performed to assess the location, diverticular size, neck size, and distance of the diverticulum from the gastroesophageal junction (Fig. 2.5). Upper endoscopy is performed aiming at excluding the presence of a peptic stricture or cancer as a cause of the dysphagia. Lastly, HRM is useful to demonstrate the presence of an underlying primary esophageal motility disorder.

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Figure 2.5 Epiphrenic diverticulum.

Conflict of Interest The authors have no conflicts of interest to declare.

References 1. Patti MG, Diener U, Tamburini A, Molena D, Way LW. Role of esophageal function tests in the diagnosis of gastroesophageal reflux disease. Dig Dis Sci. 2001;46:597–602. 2. Richter JE. Typical and atypical presentation s of gastroesophageal reflux disease. The role of esophageal testing in diagnosis and management. Gastroenterol Clin North Am. 1996;25:75–102. 3. Chen MY, Ott DJ, Sinclair JW, Wu WC, Gelfand DW. Gastroesophageal reflux disease: correlation of esophageal pH testing and radiographic findings. Radiology. 1992;185:483– 486. 4. Bello B, Zoccali M, Gullo R, Allaix ME, Herbella FA, Gasparaitis A, Patti MG. Gastroesophageal reflux disease and antireflux surgery-What is the proper preoperative work-up? J Gastrointest Surg. 2013;17:14–20. 5. Eckardt VF, Kohne U, Junginger T, et al. Risk factors for diagnostic delay in achalasia. Dig Dis Sci. 1997;42:580–585. 6. Fisichella PM, Raz D, Palazzo F, Niponmick I, Patti MG. Clinical, radiological and manometric profile in 145 patients with untreated achalasia. World J Surg. 2008;32:1974– 1979.

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7. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol. 2013;108:1238–1249. 8. Goldenberg SP, Burrell M, Fette GG, Vos C, Traube M. Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Gastroenterology. 1991;101:743–748. 9. Eckardt VF, Stauf B, Bernhard G. Chest pain in achalasia: patient characteristics and clinical course. Gastroenterology. 1999;116:1300–1304. 10. Perretta S, Fisichella PM, Galvani C, Gorodner MV, Way LW, Patti MG. Achalasia and chest pain: effect of laparoscopic Heller myotomy. J Gastrointest Surg. 2003;7:595–598. 11. Eckardt VF. Clinical presentations and complications of achalasia. Gastrointest Endosc Clin N Am. 2001;11:281–292. 12. Sandler RS, Bozymski EM, Orlando RC. Failure of clinical criteria to distinguish between primary achalasia and achalasia secondary to tumor. Dig Dis Sci. 1982;27:209– 213. 13. Tucker HJ, Snape Jr WJ, Cohen S. Achalasia secondary to carcinoma: manometric and clinical features. Ann Intern Med. 1978;89:315–318. 14. Kahrilas PJ, Kishk SM, Helm JF, et al. Comparison of pseudoachalasia and achalasia. Am J Med. 1987;82:439–446. 15. Rozman RW Jr, Achkar E. Features distinguishing secondary achalasia from primary achalasia. Am J Gastroenterol. 1990;85:1327–30 16. Moonka R, Patti MG, Feo CV, Arcerito M, De Pinto M, Horgan S, Pellegrini CA. Clinical presentation and evaluation of malignant pseudoachalasia. J Gastrointest Surg. 1999;3:456–461. 17. Pandolfino JE, Ghosh SK, Rice J, Clarke JO, Kwiatek MA, Kahrilas PJ. Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol. 2008;103:27–37. 18. Pandolfino JE, Kwiatek MA, Nealis T, Bulsiewicz W, Post J, Kahrilas PJ. Achalasia: a new clinically relevant classification by high- resolution manometry. Gastroenterology. 2008;135:1526–1533. 19. Bredenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ. International High Resolution Manometry Working Group. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil. 2012;24:57–65. 20. Salvador R, Costantini M, Zaninotto G, et al. The preoperative manometric pattern predicts the outcome of surgical treatment for esophageal achalasia. J Gastrointest Surg. 2010;14:1635–1645.

CHAPTER 3

Radiologic evaluation of dysphagia Kristen Olinger a, Chris Young a, Lauren Hermann b, Julie Huffman c and Benjamin M. Mervak a

a Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States b Ideal Speech Solutions, Lewisburg, PA, United States c Department of Rehabilitation and Therapy, Speech-Language Pathology, UNC REX Hospital, Raleigh, NC, United States

Introduction Radiologic imaging provides a useful complement to endoscopy and manometry in patients presenting with signs and symptoms of dysphagia. The American College of Radiology Expert Panel on Gastrointestinal Imaging has published appropriateness criteria for the radiologic evaluation of dysphagia with or without an attributable cause. These appropriateness criteria provide evidence-based guidelines when making decisions on imaging and help to define whether a particular examination is “Usually Appropriate,” “May Be Appropriate,” or is “Usually Not Appropriate.”1 Generally, when imaging is indicated for dysphagia, fluoroscopy is the initial imaging modality of choice. The specific fluoroscopic examination may depend on the nature and location of dysphagia symptoms, and the patient’s medical and surgical history.2 During a fluoroscopic examination of the esophagus, the patient will ingest contrast material to allow the radiologist to visualize normal structures and esophageal abnormalities in real-time. A full evaluation of the esophagus is commonly referred to as a “barium swallow,” although providers should be aware that this term may be misleading, as examinations of the esophagus can be performed using either barium-based or iodinated (water-soluble) contrast material. The term “esophagram” is more generic, encompasses the use of both types of contrast material, and may be preferred in some practices. For patients who are able, an esophagram is generally performed in multiple obliquities in the upright, recumbent, and prone positions using static radiofluoroscopic images and/or cinefluoroscopy. Gas-forming crystals may also be ingested prior to contrast material for improved evaluation Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00012-9 All rights reserved.

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of mucosal abnormalities (a “double-contrast” esophagram). To test for dysphagia to pills, a half-inch diameter barium tablet may be ingested under fluoroscopic surveillance. A modified barium swallow (MBS) study, also called a videofluoroscopic swallow study,is a focused real-time examination of an ingested bolus passing through the oropharynx and proximal esophagus. Key observations during an MBS exam include the presence and timing of aspiration, reason for aspiration, and the effect of compensatory strategies.2–6 Barium contrast of standardized consistencies is used to evaluate swallowing different textures and volumes (e.g., thin liquid, slightly thick, mildly thick, moderately thick, puree, or solid). Traditionally, swallowing has been evaluated in three distinct phases, including oral, pharyngeal, and esophageal, and the field of view for an MBS ideally includes at least the lips, nasal cavity, larynx, pharynx, pharyngoesophageal segment, and cervical vertebrae using a lateral projection.3 However, up to 26% of patients may experience primary esophageal dysphagia with erroneous localization of symptoms to the oropharynx,7 with others experiencing pathophysiologic pharyngeal changes secondary to a primary esophageal etiology, or a multiphase dysphagia. Recent research supports approaching the oropharynx and esophagus as an interrelated system to accurately provide a differential diagnosis and suggest treatment.7,8 Thus, when possible, MBS should include an anteroposterior view to improve the assessment of bolus flow symmetry, pharyngeal contraction and residue, and may also benefit from the inclusion of an esophageal sweep to evaluate the entire swallowing chain.3,6 An alternative approach is to perform an esophagram and MBS at the same visit, if permitted by the patient’s insurance, which may be beneficial in the diagnosis of primary esophageal or multiphase motility disorders. A Radiologist and Speech-Language Pathologist (SLP) collaborate during the performance and interpretation of the MBS. This interdisciplinary approach is invaluable to determining the presence and degree of swallowing impairment, make judgments on sensory and motor function, and measure coordination and timing of swallowing events while taking into account patient variables like fatigue, medications, and mental status.8 At the conclusion of the MBS exam, the Radiologist and SLP can provide the patient and medical team recommendations on oral intake,compensations,rehabilitation targets, and referrals as indicated.3 Although there are many potential causes for dysphagia,this chapter is focused on findings that are commonly seen with oropharyngeal dysphagia, as well as esophageal motility disorders. Specifically, typical radiologic findings

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(A)

(B)

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(C)

Figure 3.1 Oropharyngeal abnormalities seen during a fluoroscopic modified barium swallow. (A) Moderate vallecular residue (thin arrow) and trace aspiration (thick arrow) seen in a patient with Parkinson’s disease with multiphase symptoms. (B) Large volume premature spillage before the swallow resulting in laryngeal penetration. (C) Frank aspiration posteriorly over the arytenoid cartilage (thin arrow) in a patient s/p ACDF.

for the most common entities including presbyesophagus, gastroesophageal reflux (GER), diffuse esophageal spasm, achalasia, and connective-tissue disease related esophageal dysmotility will be explored.

Oropharyngeal Abnormalities Common abnormalities in the oropharynx seen during an MBS may include reduced tongue control with spillage of the bolus into the pharynx during the oral phase, delayed initiation of the swallow, and reduced hyolaryngeal movement, or reduced pharyngeal contraction. Acquired abnormalities including degenerative changes of the cervical spine or postoperative distortion may also impact the swallow. These physiologic impairments—in isolation or combined with anatomic changes—may lead to laryngeal penetration or aspiration before, during, or after the swallow, or residue following a swallow (Fig. 3.1). While outside the scope of this chapter, these findings often result from underlying neuromuscular abnormalities resulting in impaired sensation, strength, or coordination of the swallow mechanism including lips, tongue, palate, laryngeal, or pharyngeal musculature. When abnormalities in oropharyngeal swallow are seen, patients may benefit from consultation of an SLP for recommendations on modifications or exercises that may improve swallow function.

Presbyesophagus The term presbyesophagus was proposed to explain radiologic changes that occur during and immediately after swallowing in older patients. Some controversy exists surrounding this diagnosis, and authors have suggested

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Figure 3.2 Presbyesophagus. Single contrast cinefluoroscopy performed during and following a swallow demonstrating a cessation of the primary stripping wave with incomplete emptying of ingested contrast material and tertiary contractions (arrow).

that radiologic findings may instead be due to another underlying type of esophageal dysmotility.9 Nonetheless, it is presented here as the features are commonplace and the term is frequently used in radiology reports. While there are no strict radiologic criteria for identification of presbyesophagus,features seen during an esophagram include decreased peristalsis or cessation of the primary peristaltic wave, tertiary contractions, and decreased relaxation of the lower esophageal sphincter (LES). A dilated esophagus may also be present. Although some features would require cinefluoroscopy to demonstrate, a static example of presbyesophagus evidenced by tertiary contractions is shown in Fig. 3.2. Gastroesophageal reflux disease (GERD) GER is a condition that occurs when gastric contents flow retrograde from the stomach back into the esophagus. This is thought to occur due to incompetence of the LES, which is related to an abnormally decreased

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pressure of the LES. As intra-abdominal pressure increases and exceeds the pressure of the LES, gastric material is able to flow retrograde into the esophagus. Gastroesophageal reflux disease (GERD) occurs when chronic GER causes symptoms over time. These symptoms may include such things as a burning sensation in the chest (often referred to as “heartburn”), regurgitation when laying down, and difficulty or painful swallowing (dysphagia or odynophagia). GERD can also lead to structural complications such as esophageal stricture or Barret esophagus. GERD impacts 10%–20% of the adult population in the United States and Western Countries.10 A biphasic esophagram is typically ordered for radiographic evaluation of GERD.2 However, it is important to note that patients with symptomatic GERD may not present with active GER during imaging, even with provocative maneuvers.Therefore,24-hour esophageal pH monitoring is often considered the most sensitive method for diagnosing GERD. In addition to active GER, there are several associated radiographic findings that may indicate the presence of GERD. These include esophageal dysmotility, hiatal hernia, shortening of the esophagus, esophageal stricture, and esophagitis (Fig. 3.3).10 Diffuse esophageal spasm (DES) Diffuse esophageal spasm, also known as corkscrew esophagus, is considered an unusual cause of dysphagia and noncardiac chest pain. Disagreements in how spastic activity presents manometrically as well as a lack of universally accepted diagnostic criteria and a gold standard diagnostic test have led to a limited understanding of this disease process.11 Radiographic findings of DES are often nonspecific but supportive, with esophagram findings of uncoordinated, spastic contractions of the esophagus leading to the corkscrew appearance and impaired clearance of esophageal contents (Fig. 3.4).12 These simultaneous contractions can present in several diseases, including diabetes, alcoholism, scleroderma to name a few. There is also significant overlap in the radiographic appearance of DES and vigorous achalasia (type 3), with some case reports suggesting that DES may progress to achalasia.13,14 One distinguishing feature on esophagram that favors DES over atypical achalasia is that intermittent lower esophageal relaxation will be maintained.

Achalasia Achalasia is an uncommon primary esophageal dysmotility disorder characterized by the absence of peristalsis with impaired relaxation of the LES. The etiology of achalasia is often unknown and potentially multifactorial. Most

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Figure 3.3 Findings associated with GERD. Biphasic esophagram demonstrating irregularity of the distal esophagus including a stricture at the level of the esophageal vestibule. A sliding type hiatal hernia is also seen. Barrett esophagus was found following endoscopy and biopsy.

cases are considered primary or idiopathic, which is thought to result from degeneration of the inhibitory ganglion cells at the esophageal myenteric plexus which leads to loss of smooth muscle motility and paradoxical loss of the LES’s ability to relax in response to peristalsis.15 In contrast, secondary achalasia presents as a fixed obstruction at the gastroesophageal junction secondary to malignancy (pseudoachalasia) or another extrinsic compression such as prior surgical intervention. Achalasia is defined traditionally by manometric criteria in a patient with a clinical history of dysphagia. Barium esophagram is considered a complementary test and alone is not sensitive enough to make the diagnosis, as reportedly up to one-third of patients will demonstrate normal findings.16 Radiographic features include the absence of peristalsis, esophageal dilatation with abrupt, and persistent narrowing in the region of the LES,

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Figure 3.4 Diffuse esophageal spasm. Double contrast esophagram demonstrates uncoordinated, spastic contractions throughout the esophagus resulting in a corkscrew appearance.

also known as the “bird-beak” appearance, and poor esophageal emptying (Fig. 3.5A).15 Differences in histopathologic changes depending upon the stage of achalasia may result in different radiographic manifestations. For example, studies have suggested that myenteric inflammatory changes early in the disease process may lead to vigorous (or spastic) achalasia which has a characteristic appearance on esophagram which can mimic diffuse esophageal spasm (Fig. 3.5B). As the disease progresses into classic achalasia (types I and II), the previously described traditional radiographic features predominate. Esophagram can also be of utility to assess end-stage changes which may have implications for treatment. For example, the esophagus may massively dilate to greater than 10 cm and develop a tortuous course through the chest in late-stage achalasia, known as the “sigmoid-shaped esophagus.”17

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(A)

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(B)

10 minutes delay

Figure 3.5 Imaging spectrum of achalasia. (A) Traditional appearance includes esophageal dilation with abrupt narrowing at the LES (“bird-beak” appearance). (B) Ten-minute postprocedural radiograph following a double contrast esophagram shows numerous uncoordinated spastic contractions throughout the mid to distal esophagus with impaired clearance of contrast concerning for DES however no significant relaxation of the lower esophageal sphincter was noted. Manometry confirmed the diagnosis of vigorous achalasia (Type 3).

Barium esophagram has a notoriously poor performance in differentiating obstructing lesions in the setting of pseudoachalasia from primary achalasia.18,19 A fixed rigid stricture at the gastroesophageal junction favors psuedoachalasia, whereas the gastroesophageal junction in achalasia may open transiently when the hydrostatic barium column in the esophagus exceeds the LES muscle tone. In equivocal cases, CT may be of use to evaluate the presence of a mass lesion or other source of extrinsic compression. Esophagography also plays a vital role in monitoring of patients following intervention, including detection of early postprocedural complications such as esophageal perforation, chronic complications such as GER, and early detection of patients likely to fail treatment. Reported clinical symptom improvement may not be a reliable predictor of improved esophageal

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Figure 3.6 Scleroderma. Double-contrast esophagram shows a patulous esophagus with persistent wide opening of the lower esophageal sphincter (arrow).

emptying in all cases. Timed barium esophagram is useful for identifying a subset of post-treatment patients that demonstrate persistently elevated barium columns indicating poor esophageal emptying despite clinical symptom improvement that may benefit from early repeat pneumatic dilation.20,21

Scleroderma and other connective tissue diseases Scleroderma and mixed connective tissue disease are rare but important causes of esophageal dysmotility resulting from replacement of smooth muscle by fibrotic tissue.22 The esophagus may be involved in up to 90% of scleroderma patients,23 although the stomach, small bowel, and colon can also be affected. Typical radiologic findings in scleroderma include a dilated, poorly peristaltic esophagus with wide-open LES (Fig. 3.6); mixed connective tissue disorder may appear similarly, although with additional involvement of the upper esophageal sphincter more commonly.23,24 Ancillary findings in both processes may include a hiatal hernia due to fibrosis and

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shortening of the esophagus.22 This, along with the poor function of the LES, predisposes to chronic GER and distal esophageal ulcers or Barrett’s esophagus.23 Other connective tissue diseases including Sjögren’s syndrome, lupus, inflammatory myopathies, and rheumatoid arthritis can also variably affect the esophagus.25 There is significant overlap in the pattern of involvement for these other connective tissue diseases, with the primary nonspecific finding of esophageal dysmotility and diminished peristalsis. Notably, the LES is less commonly involved than with scleroderma and mixed connective tissue disease.

References 1. ACR Appropriateness Criteria® . https://www.acr.org/Clinical-Resources/ACRAppropriateness-Criteria (Accessed August 2, 2021). 2. Levy AD, Carucci LR, Bartel TB, et al. ACR Appropriateness Criteria® Dysphagia. J Am College Radiol. 2019;16:S104–S115. doi:10.1016/j.jacr.2019.02.007. 3. Martin-Harris B, Jones B. The videofluorographic swallowing study. Phys Med Rehabil Clin N Am. 2008;19:769–785 viii. doi:10.1016/j.pmr.2008.06.004. 4. Jaffer NM, Ng E, Au FWF, Steele CM. Fluoroscopic evaluation of oropharyngeal dysphagia: anatomic, technical, and common etiologic factors. Am J Roentgenol. 2015;204:49–58. doi:10.2214/AJR.13.12374. 5. Logemann JA. Role of the modified barium swallow in management of patients with dysphagia. Otolaryngol Head Neck Surg. 1997;116:335–338. doi:10.1016/s01945998(97)70269-9. 6. Fynes MM, Smith C, Brodsky MB. The modified barium swallow study: when, how, and why? Appl Radiol. 2019 Sep 1;48(5):3–8. 7. Watts S, Gaziano J, Jacobs J, Richter J. Improving the diagnostic capability of the modified barium swallow study through standardization of an esophageal sweep protocol. Dysphagia. 2019;34:34–42. doi:10.1007/s00455-018-09966-5. 8. Martin-Harris B, Canon CL, Bonilha HS, Murray J, Davidson K, Lefton-Greif MA. Best practices in modified barium swallow studies. Am J Speech Lang Pathol. 2020;29:1078– 1093. doi:10.1044/2020_AJSLP-19-00189. 9. DeVault KR. Presbyesophagus: a reappraisal. Curr Gastroenterol Rep. 2002;4:193–199. doi:10.1007/s11894-002-0062-7. 10. editors JSK. Brant and Helms’ Fundamentals of Diagnostic Radiology. 5th ed. Philadelphia, PA: Wolters Kluwer; 2019. 11. Spechler S, Castell D. Classification of oesophageal motility abnormalities. Gut. 2001;49:145–151. doi:10.1136/gut.49.1.145. 12. Gorti H, Samo S, Shahnavaz N, Qayed E. Distal esophageal spasm: Update on diagnosis and management in the era of high-resolution manometry. World J Clin Cases. 2020;8:1026–1032. doi:10.12998/wjcc.v8.i6.1026. 13. Samo S, Carlson DA, Kahrilas PJ, Pandolfino JE. Ineffective esophageal motility progressing into distal esophageal spasm and then type III achalasia. ACG Case Rep J. 2016;3:e183. doi:10.14309/crj.2016.156. 14. De Schepper HU, Smout AJPM, Bredenoord AJ. Distal Esophageal spasm evolving to achalasia in high resolution. Clinical Gastroenterol Hepatol. 2014;12:A25–A26. doi:10.1016/j.cgh.2013.08.035.

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15. Ates F, Vaezi MF. The pathogenesis and management of achalasia: current status and future directions. Gut Liver. 2015;9:449–463. doi:10.5009/gnl14446. 16. Howard PJ, Maher L, Pryde A, Cameron EW, Heading RC. Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh.Gut. 1992;33:1011– 1015. doi:10.1136/gut.33.8.1011. 17. Hammad A, Lu VF, Dahiya DS, Kichloo A, Tuma F. Treatment challenges of sigmoidshaped esophagus and severe achalasia. Ann Med Surg. 2021;61:30–34. doi:10.1016/j.amsu. 2020.11.077. 18. Rozman RW, Achkar E. Features distinguishing secondary achalasia from primary achalasia. Am J Gastroenterol. 1990;85:1327–1330. 19. Tracey JP, Traube M. Difficulties in the diagnosis of pseudoachalasia. Am J Gastroenterol. 1994;89:2014–2018. 20. Vaezi MF, Baker ME, Richter JE. Assessment of esophageal emptying post-pneumatic dilation: use of the timed barium esophagram. Am J Gastroenterol. 1999;94:1802–1807. doi:10.1111/j.1572-0241.1999.01209.x. 21. Andersson M, Lundell L, Kostic S, et al. Evaluation of the response to treatment in patients with idiopathic achalasia by the timed barium esophagogram: results from a randomized clinical trial. Dis Esophagus. 2009;22:264–273. doi:10.1111/j.1442-2050.2008.00914.x. 22. Garrett JM, Winkelmann RK, Schlegel JF, Code CF. Esophageal deterioration in scleroderma. Mayo Clin Proc. 1971;46:92–96. 23. Rose S, Young MA, Reynolds JC. Gastrointestinal manifestations of scleroderma. Gastroenterol Clin N Am. 1998;27:563–594. doi:10.1016/S0889-8553(05)70021-2. 24. Marshall JB, Kretschmar JM, Gerhardt DC, et al. Gastrointestinal manifestations of mixed connective tissue disease. Gastroenterology. 1990;98:1232–1238. doi:10.1016/ S0016-5085(12)90338-8. 25. Sheehan NJ. Dysphagia and other manifestations of oesophageal involvement in the musculoskeletal diseases. Rheumatology (Oxford). 2008;47:746–752. doi:10.1093/rheumatology/ken029.

CHAPTER 4

Endoscopic evaluation of dysphagia Thomas J. Watson Beaumont Health, Detroit, MI, United States

Introduction Dysphagia is a common complaint driving patients to seek evaluation by medical professionals. An analysis of the 2012 National Health Interview Survey found that an estimated 9.44 million adults in the United States, or 1 in 25 (4%) of the adult population, reported swallowing difficulty.1 Of these, 2.14 million (22.7%) sought medical attention. Dysphagia, therefore, is a frequent problem facing the esophagologist. While several diagnostic modalities may be utilized in the work-up of dysphagia, the flexible upper endoscope has evolved into an important and ubiquitous tool. Because it allows an extension of the physical exam to include the lining of the pharynx, esophagus, stomach, and small intestine, flexible upper endoscopy facilitates the detection of structural and functional pathology of the foregut. In addition, with advancements in endoscopic therapeutics, the use of flexible upper endoscopy has expanded to the treatment of a variety of foregut disorders previously reserved for surgical therapy or less efficacious intraluminal interventions. Accordingly, the flexible endoscope holds a key position in both the evaluation and management of dysphagia.

The importance of symptom assessment As the clinician embarks on a diagnostic evaluation of foregut complaints,the importance of obtaining a detailed history of symptoms cannot be overemphasized. The symptomatology of patients with esophageal disease is quite variable, may not be easily linked to a foregut etiology, and can be difficult to elicit, requiring patience, persistence, and insight on the part of the clinician. An accurate symptom assessment not only determines the initial diagnostic workup but also is used for correlation with objective findings. Symptoms should be categorized as either primary or secondary, and the probability of relief of each following a proposed procedure estimated. The decision to Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00007-5 All rights reserved.

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operate or offer other invasive therapies weighs the severity of symptoms and the likelihood of their improvement with treatment against the risks of intervention. Relative to the complaint of dysphagia, an important determination is whether symptoms have their origins in an oropharyngeal or esophageal source. A carefully elicited history can distinguish the location of dysphagia in approximately 85% of cases.2 Stroke and other neurologic conditions are the most common causes of oropharyngeal dysphagia as they can lead to discoordinated swallowing.1 When an oropharyngeal source is suspected, barium esophagography is generally recommended as the initial diagnostic study to assess for swallowing impairment. For cases when an esophageal disorder other than achalasia is suspected, the American Gastroenterological Association recommends flexible esophagogastroduodenoscopy (EGD) as the first diagnostic test.3 Upper endoscopy, unlike radiography, offers the potential for both diagnosis and therapy, in the form of esophageal dilation, in a single session. When achalasia is suspected based on symptomatology, barium radiography, and high-resolution manometry (HRM) are warranted. When endoscopy is pursued and is normal, the clinician can choose between radiography, HRM, or an empiric trial of medical therapy for gastroesophageal reflux disease (GERD) as the next diagnostic step.

Etiologies of esophageal dysphagia Dysphagia can result from structural or neuromuscular (motility) disorders of the esophagus (Table 4.1). Structural disorders include both benign and malignant etiologies. Patients with a structural cause of dysphagia commonly report difficulty swallowing solids, whereas patients with an underlying neuromuscular cause typically report problems with both solids and liquids.4 When dysphagia is rapidly progressive over the course of weeks or a few months, a malignant cause should be considered. Stable, episodic dysphagia occurring over the course of years suggests a benign etiology. Benign strictures of the esophagus are the result of severe, chronic inflammation leading to collagen deposition and fibrosis. Peptic strictures resulting from GERD (Fig. 4.1) are responsible for up to 80% of benign esophageal strictures, though their incidence is decreasing with the increased use of proton pump inhibitors (PPIs).5 A prolonged history of heartburn prior to the onset of dysphagia suggests a GERD-induced stricture or, less commonly, esophageal adenocarcinoma (EAC). Eosinophilic esophagitis (EoE) is an increasingly recognized cause of structural dysphagia

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Table 4.1 Etiologies of esophageal dysphagia.

A. Structural 1. Benign a. Peptic stricture b. Eosinophilic esophagitis c. Schatzki ring d. Pill-induced stricture e. Radiation fibrosis f. Anastomotic stricture following foregut reconstruction g. Postfundoplication h. Esophageal web i. Cricopharyngeal bar j. Caustic injury k. Congenital stricture l. Extrinsic compression i. Vascular anomaly (i.e., dysphagia lusorium) ii. Benign mediastinal lymphadenopathy 2. Malignant a. Esophageal or esophagogastric junction carcinoma b. Extrinsic compression i. Lung cancer ii. Malignant mediastinal lymphadenopathy B. Neuromuscular Achalasia (Types 1–3) Esophagogastric junction outflow obstruction Distal esophageal spasm Hypercontractile esophagus Ineffective esophageal motility Absent contractility C. Functional Dysphagia

(Fig. 4.2). In patients undergoing EGD for any indication, the incidence of EoE has been found to be 6.5%.6 When EGD is performed for the complaint of dysphagia, EoE has been found in 10%–15% of cases. Any history of head or neck surgery or irradiation, prior antireflux surgery, ingestion of caustic substances, or the use of medications potentially injurious to the esophagus should be noted as they may suggest an etiology of dysphagia. Malignancy may lead to esophageal obstruction by either intraluminal tumor growth (Fig. 4.3), as can occur with EAC or esophageal squamous cell carcinoma, or extrinsic compression, as can occur with primary lung carcinoma or other cancers that result in mediastinal lymphadenopathy.

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Figure 4.1 Benign, concentric esophagal stricture resulting from gastroesophageal reflux.

Figure 4.2 Eosinophilic esophagitis with concentric mucosal rings.

Neuromuscular disorders causing esophageal dysphagia have been categorized using the Chicago Classification (CC) of esophageal motility disorders, currently in its fourth version (v4.0), based on the findings of HRM.7 As per the CC v4.0, defined motility disorders include achalasia (with its three subtypes), esophagogastric junction outflow obstruction, distal esophageal spasm, hypercontractile esophagus, ineffective esophageal

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Figure 4.3 Esophageal adenocarcinoma with intraluminal polypoid tumor growth.

motility, and absent contractility.7 The diagnosis of achalasia can be suspected based on endoscopic findings including a lower esophageal sphincter (LES) that is difficult to traverse with an adult endoscope, esophageal body dilation, and esophageal retention of food, ingested fluids, or saliva. A definitive diagnosis of achalasia, including categorization into one of its subtypes, requires HRM.

Reliability of endoscopy in the assessment of dysphagia Several studies have assessed the sensitivity of EGD in determining the etiology of dysphagia from an esophageal source. A report from 2005 found a diagnostic yield of 54% when EGD was used as the first test for the evaluation of dysphagia in patients over the age 40 years who presented with dysphagia and associated heartburn, odynophagia, and weight loss.8 A separate study performed a cost analysis comparing initial EGD with concomitant therapeutic intervention,as indicated,to initial barium radiography in patients with symptoms suggesting benign esophageal obstruction; the former was the more cost-effective strategy.9 When findings suspicious of esophageal malignancy are detected at the time of endoscopy, directed biopsies are indicated to confirm the diagnosis. When EoE is suspected based on the presence of dysphagia in the appropriate clinical setting,biopsies should be taken of both the proximal and distal esophagus even when the endoscopic findings are not typical for this condition.10,11 A systematic review of endoscopic findings in patients with EoE found linear furrows in 48%, esophageal mucosal rings in 44%, white

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plaques or exudates in 27%, strictures in 21%, erosive esophagitis in 17%, and a decreased esophageal caliber in 9%.12 The gross endoscopic findings were normal in 17%, a fact that highlights the importance of obtaining mucosal biopsies whenever the disease is suspected based on clinical grounds. Mucosal biopsies can also be of value in establishing the diagnosis of GERD as a cause of dysphagia. The histologic findings of basal cell hyperplasia,elongation of papillae,dilated intracellular spaces,and infiltration of neutrophils and eosinophils are evidence of GERD, and can be used to distinguish it from functional heartburn and dysphagia.13 The utility of random biopsies obtained during an EGD with normal visual findings is supported by these recognized changes resulting from GERD, in that a therapeutic trial may be initiated in cases where they are detected.

Endoscopic dilation of esophageal strictures As strictures, both benign and malignant, constitute the most frequent causes of mechanical obstruction of the esophagus, dilation is the centerpiece of therapy for associated dysphagia. Most adults can tolerate a regular oral diet when the esophageal luminal diameter is at least 18 mm (54 Fr), and a modified soft diet when the lumen is at least 15 mm (45 Fr).14 A luminal diameter of ≤13 mm leads to dysphagia for soft solids in most individuals. A larger luminal diameter still may lead to dysphagia when associated with an esophageal motility disorder. Strictures are categorized as either simple or complex based on their length, diameter, and associated findings. Simple strictures are short (≤2 cm), have a luminal diameter of at least 12 mm, and are symmetrical; they can be traversed easily with a standard adult flexible upper endoscope with an outer diameter of 9 mm. Complex strictures are long (>2 cm), have a luminal diameter 3 mm may be safe and appropriate.22,23 Given the high recurrence rates following dilation of fibrotic strictures, several adjuncts to dilation, including local injection of steroids, needle-knife electrocautery, and temporary placement of fully covered, self-expanding metal stents, have been proposed, though none has proven efficacious or been considered standard of care.

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Schatzki rings are mucosal webs that occur at the esophagogastric junction and denote the proximal extent of a hiatal hernia. They are best observed on barium esophagography as they may not be appreciated at the time of EGD when air is insufflated. While morphologically distinct from peptic strictures, which typically are concentric, fixed, fibrotic narrowings of the esophagus, Schatzki rings also may cause dysphagia and are treated in a similar fashion. Eosinophilic esophagitis Both bougie and balloon dilation have been used successfully to treat dysphagia associated with EoE. As stricturing can be multifocal across a long length of esophageal mucosa, bougie dilators have the advantage of dilating the entirety of the esophageal body when passed to an adequate depth. Two meta-analyses have shown that the risk of perforation from dilation in the setting of EoE is low, occurring in fewer than 1% of cases.24,25 Risk factors for adverse events resulting from esophageal dilation in the setting of EoE include a history of multiple dilations, younger age, proximal esophageal stricturing, and the inability to pass an endoscope beyond the level of stricturing.26 While full-thickness perforations are rare, mucosal lacerations and pain after dilation for EoE are common. The efficacy of dilation for EoE has been assessed in several reports. A review of 12 studies found improved dysphagia in 92% of patients with EoE after dilation.24 Another large retrospective study of dilation with or without the use of topical steroids found near-complete or complete resolution of dysphagia in up to 50% of patients with EoE.27 A consensus statement on the management of EoE recommended that dilation be reserved for patients with a dominant esophageal stricture or ring as well as for those who remain symptomatic despite optimal medical therapy. In such patients, dilation should be performed cautiously to a diameter not exceeding 18 mm.28

Anastomotic strictures following esophagectomy The reported incidence of anastomotic strictures following esophagectomy with foregut reconstruction varies greatly in the literature, ranging between 5% and 66%.29,30 Such wide variability reflects not only the different conduits used for esophageal replacement (stomach,colon,or small intestine) and the options for location of the anastomoses (neck or chest), but also is the result of nonuniformity in the definition of a stricture and of how thoroughly the diagnosis is sought. As the organ used most often for

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esophageal replacement is the stomach, the esophagogastric anastomosis is the most extensively studied. Anastomotic strictures result from ischemia of the esophageal replacement conduit, tension, or technical mishaps. Gastric conduits are associated with higher anastomotic stricture rates than other organs used for esophageal replacement, and cervical anastomoses lead to more strictures than those performed in the chest. Comorbid conditions, such as diabetes mellitus, cardiovascular disease, or a history of smoking, may be additional risk factors for stricture formation.31 The onset of postesophagectomy dysphagia can be a troubling complaint, particularly for the patient whose main preoperative symptom was difficulty swallowing. The report of dysphagia alone does not equate to the presence a stricture, as difficulty swallowing following esophagectomy can be attributable to several different causes, such as injury to a recurrent laryngeal nerve. An anastomotic stricture is commonly confirmed in the setting of postoperative dysphagia when a flexible adult upper endoscope cannot be passed beyond the esophagogastric anastomosis. Given the multiple diameters of currently available flexible endoscopes, this definition is subject to variability. Benign anastomotic strictures typically occur 2– 3 months (median 2.4 months) after esophagectomy due to collagen deposition and resultant fibrosis.29 Maloney-type bougies, over-the-wire rigid dilators, and balloon dilators all have been used with high initial success rates.30 Recurrence of dysphagia is a common problem, however, necessitating repeat sessions (a median of 2–9 per patient) at intervals as often as every 2–3 weeks.32,33 Some centers routinely treat any complaint of postesophagectomy dysphagia with blind, trans-oral bougie passage. While such an approach may be effective and facilitates serial self-dilation by the patient at home, the rate of stricture formation reported at those centers may be overestimated.

Achalasia Dilation for achalasia requires forceful disruption of the LES. Large diameter (30–40 mm) pneumatic balloons are used for this purpose (Fig. 4.5). Dilation is typically performed by passing the balloon over a guidewire under fluoroscopic guidance. A 30 mm balloon is used for the initial dilation. If dysphagia is not adequately palliated, repeat dilation may be undertaken within weeks to a few months using a 35 mm balloon. If this larger diameter also does not bring about adequate symptomatic relief, a third dilation may be performed with a 40 mm balloon. Using this strategy of progressively larger dilating

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Figure 4.5 Plain upper abdominal radiograph of a pneumatic balloon used for treatment of achalasia (Reprinted with permission from: Wehrmann T, Jacobi V, Jung M, et al. Pneumatic dilation in achalasia with a low-compliance balloon: results of a 5-year prospective evaluation. Gastrointest Endosc 1995;42(1):31-36.).

balloons, the reported symptomatic success rate has been as high as 88% at 3 years.34 The overall risk of perforation with PD is 3%–5%.35 A prospective, randomized trial compared PD to laparoscopic Heller myotomy (LHM) for relief of dysphagia.36 Symptom relief at 2 years was equivalent in both groups (86% with PD, 90% with LHM; P = 0.46) provided that serial dilations to progressively larger diameters were performed when needed. Esophageal perforation occurred in 4% of patients during PD. Endoscopic injection of botulinum toxin into the LES also has been used for the treatment of achalasia. While simple, low-risk, and initially effective in most cases, the symptomatic benefits generally are short-lived, lasting 6 months or less in >50% of cases.37 Tachyphylaxis is known to develop with repeated sessions, making serial injections an ineffective long-term strategy.

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More recently, per-oral endoscopic myotomy (POEM) has been popularized as an effective endoscopic treatment for achalasia.38 While a complete discussion of the procedure is beyond the scope of this manuscript, POEM allows a complete endoscopic myotomy of the LES and distal esophageal smooth muscle. The available data show that symptom scores and LES pressures are improved at follow-up of greater than 3 years with acceptable complication rates. The main side effect has been postprocedural GERD. A recent systematic review with meta-analysis found reflux symptoms in 19% of patients following POEM (compared to 8.8% following LHM with fundoplication), and abnormal esophageal acid exposure in 39% following POEM (compared to 16.8% following LHM with fundoplication).39

Conclusions The flexible endoscope is an essential and indispensable tool in the diagnostic and therapeutic armamentarium of the esophagologist. Despite its widespread use, the choice of EGD as the initial study in the evaluation of dysphagia has been controversial, given its invasiveness, cost, the need for sedation, and the availability of an inexpensive, noninvasive alternative in the form of contrast esophagography. With the introduction and popularization of endoscopic therapies for the treatment of dysphagia, however, the advantages of EGD as the principal diagnostic examination and treatment modality have made it the study of choice. For cases of esophageal dysphagia, when achalasia or an oropharyngeal source is not suspected, this approach is more effective and less costly than a strategy of radiography or HRM followed by endoscopic intervention. Benign strictures of various etiologies are the most common causes of dysphagia found at the time of endoscopy and can be treated with concomitant dilation. Barium esophagography remains an important secondary tool in the evaluation of esophageal dysphagia when an EGD does not reveal a diagnosis, either based on visual inspection or on the results of histopathology obtained from biopsies. The response to swallows of varying textures of barium allows assessment of bolus transit and correlation with both anatomic or physiologic abnormalities and symptoms. Esophageal motility disorders, which may be suspected based on clinical, endoscopic, or radiographic findings, are best categorized using HRM. Endoscopic biopsies are critical to the diagnosis of esophageal malignancy and EoE, both of which may be suspected from visual inspection of the esophagus. In addition, histologic findings can suggest GERD as an

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etiology of dysphagia in the absence of another obvious cause. A therapeutic trial of acid-suppressive medications may be initiated in cases where these abnormalities are detected. New endoscopic technologies and techniques, such as POEM, undoubtedly will continue to emerge, adding to the therapeutic armamentarium of the endoscopist in the ongoing pursuit of treatments for both structural and neuromuscular causes of dysphagia. The many unanswered questions in endoscopic assessment and treatment of esophageal dysphagia leave fertile grounds for further research.

References 1. Bhattacharyya N. The prevalence of dysphagia among adults in the United States. Otolaryngol Head Neck Surg. 2014;151:765–769. 2. Spieker MR. Evaluating dysphagia. Am Fam Physician. 2000;61:3639–3648. 3. Spechler SJ. American Gastroenterological Association medical position statement on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology. 1999;117:229–232. 4. Lew RJ, Kochman ML. A review of endoscopic methods of esophageal dilation. J Clin Gastroenterol. 2002;35:117–126. 5. Richter JE. Peptic strictures of the esophagus. Gastroenterol Clin North Am. 1999;28:875– 891. 6. Peery AF,Cao H,Dominik R,et al.Variable reliability of endoscopic findings with whitelight and narrow-band imaging for patients with suspected eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2011;9:475–480. 7. Yadlapati R, Kahrilas PJ, Fox MR, et al. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©. Neurogastroenterol Motil. 2021;33:e14058. 8. Varadarajulu S, Eloubeidi MA, Patel RS, et al. The yield and the predictors of esophageal pathology when upper endoscopy is used for the initial evaluation of dysphagia. Gastrointest Endosc. 2005;61:804–808. 9. Esfandyari T, Potter JW, Vaezi MF. Dysphagia: a cost analysis of the diagnostic approach. Am J Gastroenterol. 2002;97:2733–2737. 10. Arora AS. Management strategies for dysphagia with a normal-appearing esophagus. Clin Gastroenterol Hepatol. 2005;3:299–302. 11. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–1363. 12. Kim HP, Vance RB, Shaheen NJ, et al. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:988–996. 13. Savarino E, Zentilin P, Mastracci L, et al. Microscopic esophagitis distinguished patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48:473–482. 14. Dryden GW, McClave SA. Methods of treating dysphagia caused by benign esophageal strictures. Tech Gastrointest Endosc. 2001;3:135–143. 15. de Wijkerslooth LR, Vleggaar FP, Siersema PD. Endoscopic management of difficult or recurrent esophageal strictures. Am J Gastroenterol. 2011;106:2080–2091.

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16. Scolapio JS, Pasha TM, Gostout CJ, et al. A randomized prospective study comparing rigid to balloon dilators for benign esophageal strictures and rings. Gastrointest Endosc. 1999;50:13–17. 17. Saeed ZA, Winchester CB, Ferro PS, et al. Prospective randomized comparison of polyvinyl bougies and through-the-scope balloons for dilation of peptic strictures of the esophagus. Gastrointest Endosc. 1995;41:189–195. 18. Silvis SE, Farahmand M, Johnson JA, et al. A randomized blinded comparison of omeprazole and ranitidine in the treatment of chronic esophageal stricture secondary to acid peptic esophagitis. Gastrointest Endosc. 1996;43:216–221. 19. Swarbick ET, Gough AL, Foster CS, et al. Prevention of recurrence of oesophageal stricture, a comparison of lansoprazole and high-dose ranitidine. Eur J Gastroenterol Hepatol. 1996;8:431–438. 20. Tulman AB, Boyce Jr HW. Complications of esophageal dilation and guidelines for their prevention. Gastrointest Endosc. 1981;27:229–234. 21. Langdon DF. The rule of three in esophageal dilation. Gastrointest Endosc. 1997;45:111. 22. Kozarek RA, Patterson DJ, Ball TJ, et al. Esophageal dilation can be done safely using selective fluoroscopy and single dilating sessions. J Clin Gastroenterol. 1995;20:184–188. 23. Siersema PD, de Wijkerslooth LR. Dilation of refractory benign esophageal strictures. Gastrointest Endosc. 2009;70:1000–1012. 24. Bohm ME, Richter JE. Review article: oesophageal dilation in adults with eosinophilic oesophagitis. Aliment Pharmacol Ther. 2011;33:748–757. 25. Jacobs Jr JW, Spechler SJ. A systematic review of the risk of perforation during esophageal dilation for patients with eosinophilic esophagitis. Dig Dis Sci. 2010;55:1512–1515. 26. Dellon ES, Gibbs WB, Rubinas TC, et al. Esophageal dilation in eosinophilic esophagitis: safety and predictors of clinical response and complications. Gastrointest Endosc. 2010;71:706–712. 27. Schoepfer AM, Gschossmann J, Scheurer U, et al. Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids. Endoscopy. 2008;40:161–164. 28. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3–20. 29. Williams VA, Watson TJ, Zhovtis S, et al. Endoscopic and symptomatic assessment of anastomotic strictures following esophagectomy and cervical esophagogastrostomy. Surg Endosc. 2008;22:1470–1476. 30. Briel JW, Tamhankar AP, Hagen JA, et al. Prevalence and risk factors for ischemia, leak, and stricture of esophageal anastomosis: gastric pull-up versus colon interposition. J Am Coll Surg. 2004;198:536–541. 31. Van Heijl M,Gooszen JA,Fockens P,et al.Risk factors for development of benign cervical strictures after esophagectomy. Ann Surg. 2010;251:1064–1069. 32. Marjanovic G, Schrag HJ, Fischer E, et al. Endoscopic bougienage of benign anastomotic strictures in patients after esophageal resection: the effect of the extent of stricture on bougienage results. Dis Esophagus. 2008;21:551–557. 33. Honkoop P, Siersema PD, Tilanus HW, et al. Benign anastomotic strictures after transhiatal esophagectomy and cervical esophagogastrostomy: risk factors and management. J Thorac Cardiovasc Surg. 1996;111:1141–1146. 34. Farhoomand K,Connor JT,Richter JE,et al.Predictors of outcome of pneumatic dilation in achalasia. Clin Gastroenterol Hepatol. 2004;2:389–394. 35. Metman EH, Lagasse JP, d’Alteroche L, et al. Risk factors for immediate complications after progressive pneumatic dilation for achalasia. Am J Gastroenterol. 1999;94:1179–1185. 36. Boeckxstaens GE, Annese V, des Varannes SB, et al. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011;364:1807–1816. 37. Vaezi MF, Richter JE, Wilcox CM, et al. Botulinum toxin versus pneumatic dilation in the treatment of achalasia: a randomised trial. Gut. 1999;44:231–239.

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38. Inoue H, Sato H, Ikeda H, et al. Per-oral endoscopic myotomy: a series of 500 patients. J Am Coll Surg. 2015;221:256–264. 39. Repici A, Fuccio L, Maselli R, et al. GERD after per-oral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: a systematic review with metaanalysis. Gastrointest Endosc. 2018;87:934–943.

CHAPTER 5

Manometric evaluation of dysphagia Fernando Augusto Mardiros Herbella a, Rafael Melillo Laurino Neto a, Francisco Schlottmann b and Marco G. Patti c a

b c

Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina Department of Surgery, University of Virginia, Charlottesville, VA, United States

Introduction Esophageal manometry is a valuable tool for the evaluation of dysphagia as most esophageal motility disorders may cause this symptom. While in the past—early years of esophagology—esophageal manometry was not available and esophageal motility was studied mostly by radiologists, currently, the definition and classification of named esophageal motility disorders are based on manometric patterns. The development of new technology has expanded the application of esophageal manometry, allowing the evaluation not only of the esophagus but also of the proximal pharyngoesophageal segment.1 Thus, esophageal manometry is an invaluable tool in the work up of patients with dysphagia. Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice, a disease that may cause dysmotility and dysphagia. Thus, ambulatory prolonged esophageal pHmonitoring is also part of the work-up of patients with dysphagia.

Equipment and performance Esophageal manometry measures contraction or relaxation of esophageal muscles indirectly, interpretating pressures or resistance to flux as motility. It is performed inserting a nasogastric probe connected to a polygraph that will collect and present understandable data. There are 2 fundamental types of manometry: conventional and high-resolution. Conventional manometry (Fig. 5.1) consists of equipment that pumps water through a flow sensor and a catheter with multiple channels that open in different levels of the probe. The number of channels is usually between 4 and 8. Some channels are located at the same level to average pressures Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00008-7 All rights reserved.

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Figure 5.1 Equipment, probe, and graphics for both esophageal manometry systems.

to compensate for asymmetry of the force vectors of the sphincters. Thus, in order to evaluate different segments of the esophagus the probe must be pulled and relocated several times. The disadvantages associated with this system are (1) longer test time due to the necessity of probe relocation; (2) more discomfort due to longer time with the probe, and constant water dripping in the esophagus and pharynx; (3) loss of information in areas between sensors leading to motion artifacts when the esophagus moves during swallows moving the interest area away from sensors, with no evaluation of segmental defects of peristalsis; and (4) slow response of flow sensors making difficult the evaluation of the striated muscles of the proximal segment that relaxes and contracts faster than the smooth muscle of the middle and distal esophagus. Even though there are disadvantages of this system, it is still widely available and used due to the higher costs of high-resolution manometry. High-resolution manometry differs from conventional manometry because of the high number and density of sensors along the catheter. There are from 24 to 36 circumferential sensors spaced 1 cm apart. Usually, the technology employs solid-state pressure sensors located in the catheter, although there are water-perfused systems available as well.2 These characteristics compensate the disadvantages of the conventional manometry and allow the construction of intuitive color plots. The procedure starts with the evaluation of the basal pressure and length of the sphincters (upper and lower esophageal sphincters) during rest (landmark period when the patient is instructed not to swallow), followed by 10 swallows of water with about 30 seconds in between swallows to allow muscle repolarization when sphincters relaxation and peristalsis are

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measured. The current classification for motility disorders3 includes some special maneuvers, such as change in body position and provocative tests, in specific situations. pHmonitoring consists in the placement of a transnasal catheter inside the esophagus accoupled to a portable device for continuous monitoring of the intraluminal pH. Some catheters monitor only distal esophageal pH with a sensor placed 5 cm above the lower esophageal sphincter (determined by previous esophageal manometry) while it is possible to also monitor proximal pH with an additional sensor frequently located 15 cm above the lower esophageal sphincter, but there are variations in this placement. Intraluminal impedance may also be determined in combination with pHmonitoring to detect nonacid reflux.

Parameters evaluated Manometric parameters for the evaluation of esophageal motility have varied over time. Some metrics were created but did not gain acceptance due to uncertain clinical value. Basically, esophageal manometry must evaluate sphincters (upper and lower) basal pressure and relaxation and force and coordination of peristalsis. We will briefly describe the current parameters according to the Chicago classification in its more recent version.4

Upper esophageal sphincter Metrics for the upper esophageal sphincter were not incorporated in the Chicago classification. Disorders of the motility of the pharynx and upper sphincter can cause dysphagia and must be evaluated by esophageal manometry.5

Esophageal body Metrics for the esophageal body must evaluate coordination and force. Coordination is measured by the distal latency, a parameter that computes the time interval (in seconds) between the beginning of the upper esophageal sphincter relaxation and the contractile deceleration point, that is, measures the peristalsis velocity from the beginning of the swallow to the epiphrenic ampulla. This parameter will classify waves as peristaltic or premature and it is important for the diagnosis of the distal esophageal spasm. Force (or contraction vigor as called by the classification) is measured by the distal contractile integral (DCI) that is the product of the mean amplitude of contraction in the distal esophagus (mmHg) times the duration of contraction (s) times the length of the distal esophageal segment (cm), exceeding 20 mmHg for the region spanning from the transition zone to

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the proximal aspect of the lower esophageal sphincter. DCI classifies waves as ineffective (failed or weak), normal or hypercontractile.

Lower esophageal sphincter Previous Chicago classifications contemplated only the relaxation of the lower esophageal sphincter as a metric used to classify the motility disorders. Relaxation is measured by the integrated relaxation pressure (IRP) parameter that corresponds to the mean pressure of 4 seconds of greatest postdeglutitive relaxation in a 10 seconds gap after the beginning of a swallow. It is certainly the metric more valuable in the evaluation of patients with dysphagia. The new classification suggests the inclusion of parameters that measure the valve capacity of the sphincter but without further details.

pHmonitoring There are essentially two methods to define pathologic reflux by pHmonitoring with comparable accuracy. First, the time of acid exposure of the esophagus that is pathologic if greater than 6% of the period of monitoring. Second, the DeMeester score, a composite grading system that encompasses six different parameters: (1) total number of episodes of reflux, (2) % total time esophageal pH < 4, (3) % upright time esophageal pH < 4, (4) supine time esophageal pH < 4, (5) number of reflux episodes ≥ 5 minutes, and (6) longest reflux episode (minutes), that is pathologic if greater than 14.7. It must be mentioned that pHmonitoring can additionally correlate temporally episodes of reflux and symptoms. This is, however, not significant in the case of dysphagia since this symptom is not provoked immediately by an episode of reflux as is the case for heartburn, for example.

Classifications for esophageal motility disorders Different classifications for esophageal motility disorders based on manometric patterns have been created. Two, however, have gained acceptance, the one by Dr. Joel Richter for conventional manometry6 and the Chicago classification for high-resolution manometry. Richter’s classification is shown in Table 5.1. It was compiled in 2001 just before high-resolution manometry became available in clinical practice.This shows that a consensus was not achieved for a long time. The classification is based on the reference values, metrics, and parameters available at the time

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Table 5.1 Classification for motility disorders according to conventional manometry. Motility disorder

Manometric pattern

Achalasia

Absent distal peristalsis Abnormal lower esophageal sphincter relaxation Simultaneous contractions ≥20% waves Contraction amplitude >30 mm Hg – Increased mean distal amplitude (>180 mm Hg) and normal peristalsis – Resting lower esophageal sphincter pressure >45 mm Hg – ≥30% or more low distal amplitude or failed contractions – Resting lower esophageal sphincter pressure

Diffuse esophageal spasm

Hypercontracting esophagus – Hypertensive esophagus (nutcracker) – Hypertensive lower esophageal sphincter Hypocontracting esophagus – Ineffective oesophageal motility – Hypotensive lower esophageal sphincter

of conventional manometry and this must be remembered to interpret data from old studies at the light of current technology. The Chicago classification is named after the team of gastroenterologists at the Northwestern University in Chicago that were pioneers of high-resolution manometry. The first version of the classification was released in 2009. It has been periodically updated and the participant group eventually evolved to a panel of experts around the globe. The 4.0 version has just been released in 2021.3 The description of the motility disorders will be based on this new version (Table 5.2).

Dysphagia and motility disorders Achalasia Achalasia is defined manometrically by abnormal relaxation of the lower esophageal sphincter and aperistalsis (Fig. 5.2). Both conditions determine a slow or absent passage of the food bolus from the esophagus into the stomach, therefore causing dysphagia. The Chicago classification defined three subtypes of achalasia based on esophageal pressurization: Type I: incomplete lower esophageal sphincter relaxation, aperistalsis, and absence of esophageal pressurization. Type II: incomplete lower esophageal sphincter relaxation, aperistalsis, and pan-esophageal pressurization in at least 20% of swallows.

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Table 5.2 Classification for motility disorders according to high resolution manometry. Motility disorder

Disorders of the esophagogastric junction outflow

Manometric pattern

Achalasia

Abnormal relaxation of the lower esophageal sphincter and 100% failed peristalsis Esophagogastric junction Abnormal relaxation of the outflow obstruction lower esophageal sphincter and ≥20% elevated intrabolus pressure Disorders of peristalsis Absent contractility Normal relaxation of the lower esophageal sphincter and 100% failed peristalsis Distal esophageal spasm ≥20% swallows with premature/spastic contraction Hypercontractile ≥20% hypercontractile esophagus swallows Ineffective esophageal >70% ineffective swallows or motility ≥50% failed peristalsis

Figure 5.2 Manometric tracings for achalasia subtypes. Note the absence of relaxation of the lower esophageal sphincter during swallows in all cases (arrow).

Type III: incomplete lower esophageal sphincter relaxation and premature contractions (DL < 4.5 seconds) in at least 20% of swallows. Chicago Classification 4.0 also defined some scenarios that define an “inconclusive diagnosis of achalasia”: (1) absent contractility with no appreciable peristalsis in the setting of IRP values at the upper limit of normal; (2) evidence of appreciable peristalsis with changing position in the setting of a types I or II achalasia pattern; and (3) an abnormal IRP with evidence of spasm and evidence of peristalsis in the setting of a type III achalasia pattern. These patterns are indeed rare and open to criticism.7

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Dysphagia is the most common symptom of achalasia and almost all patients present with this symptom.8 Interestingly, there is no correlation between symptom severity and manometric findings or degree of esophageal dilatation.9 Achalasia evaluation and treatment will be detailed in Chapter 7.

Esophagogastric junction outflow obstruction Esophagogastric junction outflow obstruction was defined as functional obstruction in the early Chicago Classification versions.10 It is defined manometrically by normal peristalsis but abnormal relaxation of the lower esophageal sphincter (Fig. 5.3). Curiously, there was not a direct correlation with a similar diagnosis during the era of conventional manometry. Whether some of these cases represent patients included in the hypertensive lower esophageal sphincter diagnosis from the conventional classification is uncertain. If this is the case, this disease was extremely rare. As an example, in a series of 3471 conventional manometries, primary esophageal motility disorders were detected in 397 patients and only 2 had a hypertensive lower esophageal sphincter. After an extensive work-up, only one of the two patients underwent a myotomy with resolution of the symptoms.11 In fact, surgeons have been overly cautious about surgical treatment of primary motility disorders apart from achalasia, particularly for functional obstructions at the level of the lower sphincter.12 There was, however, a surge in the diagnosis of esophagogastric junction outflow obstruction with the Chicago classification. Some series show esophagogastric junction outflow obstruction in up to 11% of the performed manometries.13 This led to an unavoidable overtreatment when in most cases esophagogastric junction outflow obstruction is an isolated and irrelevant manometric finding in asymptomatic individuals14 or it is secondary to another problem such as a paraesophageal hernia. The Chicago Classification 4.0 tried to emphasize the need for clinical significance of cases diagnosed as esophagogastric junction outflow obstruction. It should be considered clinically relevant only in the presence of (1) an elevated IRP in supine and upright positions with evidence of peristalsis; (2) supportive investigations with other tests such as a barium swallow to document obstruction at the level of the gastroesophageal junction; (3) presence of chest pain and/or dysphagia. The Chicago classification is clear in stating that their metrics are not defined for operated patients. It must be remembered, however, that

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Figure 5.3 Manometric tracing for functional esophagogastric junction outflow obstruction. Note the lack of relaxation of the lower esophageal sphincter but normal peristalsis.

esophagogastric junction outflow obstruction is a common diagnosis in patients after operations on the esophagogastric junction with dysphagia, and probably the cause of the symptoms in several circumstances.15 Table 5.3 shows putative causes for a manometric diagnosis of esophagogastric junction outflow obstruction. Dysphagia is present from 25% to 70%.17,18 It is more common when there is a mechanical etiology for the obstruction.19 Esophagogastric junction outflow obstruction and other motility disorders evaluation and treatment will be detailed in Chapter 8.

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Table 5.3 Putative causes for a manometric diagnosis of esophagogastric junction outflow obstruction.

Early or incompletely expressed achalasia Mechanical process (postoperative, hiatal hernia, strictures, rings, tumors, etc.) Esophageal wall stiffness Central obesity Opioids usage False-positive finding Adapted from ref.16

Figure 5.4 Manometric tracings for a case of absent contractility is a patient with systemic sclerosis.

Absent contractility Absent contractility (or failure of peristalsis) is a term that was created to differentiate aperistalsis from achalasia and other disease processes that may lead to absent muscular contraction, such as connective tissue disorders.20 It is defined by 100% failed peristalsis with normal relaxation of the lower esophageal sphincter (Fig. 5.4). In other words, it differentiates itself from achalasia based solely on the relaxation of the lower esophageal sphincter. In half of the patients with connective tissue diseases, the rheumatic illness also affects the smooth muscle of the lower esophageal sphincter that may be almost undetectable by manometry.21 The Chicago classification technical review highlights that alternate complementary tests (including

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Figure 5.5 Manometric tracings for a case of distal esophageal spam.

timed upright barium esophagram and functional lumen imaging probe) are recommended to confirm or refute the presence of achalasia.22 Dysphagia is a common symptom in patients with absent contractility22 but even asymptomatic patients with collagen diseases often have esophageal body dysmotility.23 Esophageal dysmotility seems to positively correlate with the presence of interstitial lung disease.23 It must be remembered that gastroesophageal reflux diseases is frequently associated with this disease.24

Distal esophageal spasm Distal esophageal spasm is defined manometrically by the presence of by at least 20% of premature contractions with normal contractile vigor (Fig. 5.5). Inconclusive diagnosis occurs with premature contractions and low contractile vigor as measured by the DCI parameter. Following the same precepts mentioned for the esophagogastric junction outflow, the Chicago classification fixed some misconceptions that developed after the early versions of the Chicago classification and led to unnecessary treatment. First, symptoms (dysphagia or chest pain) are necessary to a clinically significant diagnosis. Second, it was acknowledged only in this last version that a primary esophageal motility only can have this name in the absence of gastroesophageal reflux disease that may cause the dysmotility.25 This usually resolves after appropriate reflux therapy26 and does not jeopardize the outcome.27 Dysphagia occurs in around 30% of the patients with distal esophageal spasm.28

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Figure 5.6 Manometric tracings for a case of hypercontractile esophagus.

Hypercontractile esophagus Hypercontractile esophagus is defined by excessive peristaltic vigor in at least 20 of the swallows (Fig. 5.6). Jackhammer esophagus was previously considered a synonym but currently jackhammer is a subset within the term hypercontractile esophagus (when repetitive prolonged contractions are present). In fact, three patterns were described in the last classification (single-peaked hypercontractile swallows, jackhammer, and hypercontractile swallows with a vigorous lower esophageal sphincter after-contraction). The clinical significance of these patterns is still elusive due to the rarity of the disease and recent definition. Similar to the other manometric disorders, the Chicago Classification 4.0 highlighted that clinical significance does not depend on manometric patterns only. Again, gastroesophageal reflux disease must be ruled out, symptoms (dysphagia/chest pain) must be present, and an obstruction at the esophagogastric junction must be ruled out before definitive diagnosis. Dysphagia is reported in around 60% of the patients with this disease.29

Ineffective esophageal motility Ineffective esophageal motility is defined by a disturbance in peristalsis with >70% ineffective swallows or ≥50% failed peristalsis (Fig. 5.7). This definition changed along time from more liberal definitions to more restricted, again, minimizing overdiagnosis, and overtreatment. Fragmented peristalsis

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Figure 5.7 Manometric tracings for a case of ineffective esophageal motility.

is not considered a disease per se any longer, but fragmented waves are now considered as ineffective swallows. Similar to absent contractility, ineffective esophageal motility is strongly associated with dysphagia and gastroesophageal reflux disease.

Conclusions Esophageal manometry is a valuable tool for the evaluation of dysphagia. Mostesophageal motility disorders may cause dysphagia. High-resolution manometry selected patterns that define motility disorders: achalasia, esophagogastric junction outflow obstruction, absent contractility, distal esophageal spasm, hypercontractile esophagus, and ineffective esophageal motility. Isolated manometric patterns are not enough to define clinically significant diseases. An evaluation of symptoms and a complete work-up are necessary as well. GERD may cause dysphagia and most manometric patterns must only be considered primary esophageal disorders in the absence of GERD. Thus, ambulatory prolonged esophageal pHmonitoring is essential to objectively diagnose GERD.

References 1. Silva LC, Herbella FA, Neves LR, Vicentine FP, Neto SP, Patti MG. Anatomophysiology of the pharyngo-upper esophageal area in light of high-resolution manometry. J Gastrointest Surg. 2013;17:2033–2038. doi:10.1007/s11605-013-2358-3. 2. Silva RMBD, Herbella FAM, Gualberto D. Normative values for a new water-perfused high resolution manometry system. Arq Gastroenterol. 2018;55(Suppl 1):30–34 Epub 2018 Aug 6. PMID: 30088532. doi:10.1590/S0004-2803.201800000-40.

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3. Yadlapati R, Kahrilas PJ, Fox MR, et al. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©. Neurogastroenterol Motil. 2021;33:e14058 PMID: 33373111; PMCID: PMC8034247. doi:10.1111/nmo.14058. 4. Lafraia FM, Herbella FAM, Kalluf JR, Patti MG. A pictorial presentation of esophageal high resolution manometry current parameters. Arq Bras Cir Dig. 2017;30:69–71 PMID: 28489175; PMCID: PMC5424693. doi:10.1590/0102-6720201700010019. 5. Pinna BR, Herbella FAM, de Biase N, Vaiano TCG, Patti MG. High-resolution manometry evaluation of pressures at the pharyngo-upper esophageal area in patients with oropharyngeal dysphagia due to vagal paralysis. Dysphagia. 2017;32:657–662 Epub 2017 May 20. PMID: 28528491. doi:10.1007/s00455-017-9811-5. 6. Richter JE. Oesophageal motility disorders. Lancet. 2001;358:823–828. 7. Herbella FAM, Del Grande LM, Schlottmann F, Patti MG. Changes in the treatment of primary esophageal motility disorders imposed by the new classification for esophageal motility disorders on high resolution manometry (Chicago Classification 4.0). Adv Ther. 2021 Epub ahead of print. PMID: 33772739. doi:10.1007/s12325-021-01714-w. 8. Herbella FA, Oliveira DR, Del Grande JC. Are idiopathic and Chagasic achalasia two different diseases? Dig Dis Sci. 2004;49:353–360 PMID: 15139481. doi:10.1023/ b:ddas.0000020486.71719.62. 9. Fisichella PM, Raz D, Palazzo F, Niponmick I, Patti MG. Clinical, radiological, and manometric profile in 145 patients with untreated achalasia. World J Surg. 2008;32:1974– 1979 PMID: 18575930. doi:10.1007/s00268-008-9656-z. 10. Carlson DA, Pandolfino JE. The Chicago criteria for esophageal motility disorders: what has changed in the past 5 years? Curr Opin Gastroenterol. 2012;28:395–402 PMID: 22476158; PMCID: PMC3790323. doi:10.1097/MOG.0b013e3283530f62. 11. Patti MG, Gorodner MV, Galvani C, et al. Spectrum of esophageal motility disorders. Implications for diagnosis and treatment. Arch Surg. 2005;140:442–449. 12. Herbella FA, Tineli AC, Wilson Jr JL, Del Grande JC. Surgical treatment of primary esopha-geal motility disorders. J Gastrointest Surg. 2008;12:604–608. 13. Csucska M, Masuda T, Bremner RM, Mittal SK. Esophagogastric junction outflow obstruction: are we missing anything? J Clin Gastroenterol. 2021;55:121–126 PMID: 32301830. doi:10.1097/MCG.0000000000001355. 14. Schupack D, Katzka DA, Geno DM, Ravi K. The clinical significance of esophagogastric junction outflow obstruction and hypercontractile esophagus in high resolution esophageal manometry. Neurogastroenterol Motil. 2017;29:1–9 Epub 2017 May 23. PMID: 28544670. doi:10.1111/nmo.13105. 15. Wilshire CL, Niebisch S, Watson TJ, et al. Dysphagia postfundoplication: more commonly hiatal outflow resistance than poor esophageal body motility. Surgery. 2012 Oct;152:584–592 discussion 592-4. Epub 2012 Aug 31. PMID: 22939748. doi:10.1016/ j.surg.2012.07.014. 16. Samo S, Qayed E. Esophagogastric junction outflow obstruction: Where are we now in diagnosis and management? World J Gastroenterol. 2019;25:411–417 PMID: 30700938; PMCID: PMC6350167. doi:10.3748/wjg.v25.i4.411. 17. Liu A, Woo M, Nasser Y, et al. Esophagogastric junction outflow obstruction on manometry: outcomes and lack of benefit from CT and EUS. Neurogastroenterol Motil. 2019;31:e13712 Epub 2019 Sep 15. PMID: 31523911. doi:10.1111/nmo.13712. 18. Song BG, Min YW, Lee H, et al. Combined multichannel intraluminal impedance and high-resolution manometry improves detection of clinically relevant esophagogastric junction outflow obstruction. J Neurogastroenterol Motil. 2019;25:75–81 PMID: 30646478; PMCID: PMC6326198. doi:10.5056/jnm18148.

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19. Blais P, Bennett MC, Gyawali CP. Upper esophageal sphincter metrics on highresolution manometry differentiate etiologies of esophagogastric junction outflow obstruction. Neurogastroenterol Motil. 2019;31:e13558 Epub 2019 Feb 27. PMID: 30815910. doi:10.1111/nmo.13558. 20. Menezes MA, Herbella FA, Patti MG. Laparoscopic antireflux surgery in patients with connective tissue diseases. J Laparoendosc Adv Surg Tech A. 2016;26:296–298 Epub 2016 Mar 30. PMID: 27027697. doi:10.1089/lap.2016.0097. 21. Abozaid HSM, Imam HMK, Abdelaziz MM, El-Hammady DH, Fathi NA, Furst DE. High-resolution manometry compared with the University of California, Los Angeles Scleroderma Clinical Trials Consortium GIT 2.0 in Systemic Sclerosis. Semin Arthritis Rheum. 2017;47:403–408 Epub 2017 May 19. PMID: 28624173. doi:10.1016/ j.semarthrit.2017.05.005. 22. Gyawali CP, Zerbib F, Bhatia S, et al. Chicago classification update (V4.0): technical review on diagnostic criteria for ineffective esophageal motility and absent contractility. Neurogastroenterol Motil. 2021:e14134 Epub ahead of print. PMID: 33768698. doi:10.1111/nmo.14134. 23. Schutyser W, Cruyt L, Vulsteke JB, Lenaerts JL, De Langhe E. The role of high-resolution manometry in the assessment of upper gastrointestinal involvement in systemic sclerosis: a systematic review. Clin Rheumatol. 2020;39:149–157 Epub 2019 Nov 11. PMID: 31709478. doi:10.1007/s10067-019-04794-w. 24. Tran S, Gray R, Kholmurodova F, et al. Laparoscopic fundoplication is effective treatment for patients with gastroesophageal reflux and absent esophageal contractility. J Gastrointest Surg. 2021 Epub ahead of print. PMID: 33904061. doi:10.1007/s11605-021-05006-0. 25. Herbella FA, Raz DJ, Nipomnick I, Patti MG. Primary versus secondary esophageal motility disorders: diagnosis and implications for treatment. J Laparoendosc Adv Surg Tech A. 2009;19:195–198 PMID: 19260789. doi:10.1089/lap.2008.0317. 26. Herbella FA, Tedesco P, Nipomnick I, Fisichella PM, Patti MG. Effect of partial and total laparoscopic fundoplication on esophageal body motility. Surg Endosc. 2007;21:285–288 Epub 2006 Nov 21. PMID: 17122978. doi:10.1007/s00464-006-0108-2. 27. Dell’Acqua-Cassão B, Herbella FA, Farah JF, Bonadiman A, Silva LC, Patti MG. Outcomes of laparoscopic Nissen fundoplication in patients with manometric patterns of esophageal motility disorders. Am Surg. 2013;79:361–365 PMID: 23574844. 28. Khalaf M, Chowdhary S, Elias PS, Castell D. Distal esophageal spasm: a review. Am J Med. 2018;131:1034–1040 Epub 2018 Mar 29. PMID: 29605413. doi:10.1016/ j.amjmed.2018.02.031. 29. Achem SR, Vazquez-Elizondo G, Fass R. Jackhammer esophagus: current concepts and dilemmas. J Clin Gastroenterol. 2021;55:369–379 PMID: 33337637. doi:10.1097/ MCG.0000000000001472.

CHAPTER 6

Achalasia Francisco Schlottmann a,b, Fernando Augusto Mardiros Herbella c and Marco G. Patti d a

Department of Surgery, Hospital Alemán of Buenos Aires, Buenos Aires, Argentina Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States c Department of Surgery, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil d Department of Surgery, University of Virginia, Charlottesville, VA, United States b

Introduction Achalasia is a rare primary esophageal motility disorder characterized by a lack of esophageal peristalsis and partial or absent relaxation of the lower esophageal sphincter (LES) in response to swallowing. Due to the impaired esophageal emptying, most patients experience dysphagia, regurgitation, and chest pain. Although there is no curative treatment for this disease, significant improvements in the ability to diagnose and treat achalasia have been achieved in the last two decades.

Epidemiology and pathophysiology Historically, the prevalence of achalasia has been reported as 1 in 100,000 individuals with equal frequency in men and women and with a bimodal distribution of incidence by age (peaks at around age 30 and 60 years). However, the number of patients diagnosed with achalasia has been increasing in the last decade due to a higher awareness of the disease and improved ability to establish the diagnosis [i.e., high-resolution manometry (HRM)].1 In physiologic conditions, the LES has a myogenic tone that prevents reflux of gastric contents, and it relaxes in response to swallowing and esophageal or gastric distension. The myenteric plexus regulates the LES through both excitatory (acetylcholine) and inhibitor (nitric oxide and vasoactive intestinal polypeptide) neurons. The esophageal body, on the other hand, does not have a resting tone. Primary peristalsis is initiated by central activation and propagated by peripheral mechanisms to produce deglutitive inhibition followed by excitation. The pathophysiology of achalasia involves the selective degeneration of inhibitory neurons of the esophageal myenteric plexus, which are needed for peristalsis of the smooth muscle of the esophageal body and relaxation of the tonic LES.2 Although inflammatory responses after viral infections (i.e., varicella-zoster, human Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00006-3 All rights reserved.

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papilloma, and herpes virus) and autoimmune reactions against myenteric neurons have been previously described, the etiology of this degenerative process is not fully understood yet.3–6 Besides idiopathic achalasia, there is a secondary form of the disorder caused by Chagas disease. In fact, in countries where Chagas disease is endemic (e.g., Brazil), the prevalence of achalasia is significantly higher.7 In these patients, the infection caused by the parasite Trypanosoma cruzi (inoculated through a bug bite) leads to an immunological reaction with destruction of the esophageal myenteric plexus, which ultimately causes a disease undistinguishable from idiopathic achalasia.8

Clinical presentation The clinical presentation of achalasia might mimic other disorders (e.g., gastroesophageal reflux disease). For this reason, there is often a long delay between symptoms onset and diagnosis. Most patients with achalasia suffer from the following symptoms9–11 : r Dysphagia (95%) for both solids and liquids is the most frequent symptom. While some patients are able to maintain a stable weight with dietary modifications, others experience progressive weight loss. r Regurgitation of undigested food (70%) is the second most common symptom. Regurgitation can eventually cause aspiration with cough, hoarseness, wheezing, and even episodes of pneumonia. r Heartburn (50%) due to stasis and fermentation of undigested food in the esophagus is also common. Unfortunately, this symptom is often attributed to gastroesophageal reflux, and patients are treated with proton pump inhibitors for a long time with a consequent delay in diagnosis. r Chest pain (40%) can also occur. Esophageal distension and noncoordinated esophageal contractions of abnormally high amplitude might be responsible. Eckardt score is a clinical grading system that can be used for the evaluation of symptoms and efficacy of treatment.12 Points are attributed to dysphagia, regurgitation, chest pain, and weight loss depending on their frequency (0–3 points) and the final score ranges from 0 to 12. Treatment is often considered effective if the score is equal to or less than 3 (Table 6.1).

Diagnostic evaluation A thorough diagnostic evaluation is needed to rule out malignancy or other gastrointestinal disorders, delineate the esophageal emptying and anatomy, and confirm the diagnosis of achalasia.13

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Table 6.1 Eckardt Score for esophageal achalasia. Score

Dysphagia

Retrosternal pain

Regurgitation

Weight loss

0 1 2 3

None Occasional Daily Each meal

None Occasional Daily Each meal

None Occasional Daily Each meal

None 10 kg

This clinical grading system is used for the evaluation of symptoms and efficacy of treatment. Points are attributed to each symptom and weight loss (final score ranges from 0 to 12). Treatment is often considered effective if the score is equal or less than 3.

Esophagogastroduodenoscopy (EGD) Typical endoscopic findings of achalasia include retained food in the esophagus, esophageal dilation/tortuosity, signs of esophagitis due to food stasis, and esophageal candidiasis. In 30%–40% of patients, however, the EGD might not show any abnormalities. Still, an EGD should always be done in patients with dysphagia to rule out mechanical causes such as malignancy or peptic stricture.

Barium swallow Classic radiologic findings of achalasia are narrowing at the level of the gastroesophageal junction (i.e., “bird beak” sign), slow emptying of the contrast into the stomach with an air-fluid level in the esophagus, and tertiary contractions of the esophageal wall (Fig. 6.1). An epiphrenic diverticulum can also be identified in some patients with achalasia. In advanced cases, severe esophageal dilatation with a sigmoid-shaped appearance can be found.

Esophageal manometry Esophageal manometry is the gold standard study to confirm the diagnosis of achalasia. Two main diagnostic criteria are needed: lack of esophageal peristalsis and partial or absent relaxation in response to swallowing. Interestingly, it was previously thought that the LES was hypertensive in all patients. It is currently known that only about 50% of patients have elevated LES pressure.14 HRM has improved the ability to diagnose and classify achalasia. In 2008, Pandolfino and colleagues proposed a new classification according to HRM manometric patterns (i.e., the Chicago classification).15 This classification, now in version 4.0, divides achalasia into three subtypes16,17 (Fig. 6.2): Type I: Abnormal median integrated relaxation pressure (IRP) and 100% failed peristalsis.

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Figure 6.1 Barium esophagram in a patient with achalasia. Esophageal dilatation and narrowing at the level of the gastroesophageal junction (“bird beak” sign).

Type II: Abnormal median IRP, 100% failed peristalsis, and ≥20% of swallows with panesophageal pressurization. Type III: Abnormal median IRP and ≥20% of swallows with premature/spastic contraction and no evidence of peristalsis (“spastic achalasia”). A previous study has shown that this classification might depict different stages in the evolution of the disease: type III the earliest stage, type II an intermediate stage II, and type I the final stage.18 In addition, the Chicago

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Figure 6.2 Chicago classification of esophageal achalasia. Type I: absence of esophageal pressurization; Type II: panesophageal pressurization; Type III: spastic achalasia with premature contractions.

classification has a prognostic value:patients with type II achalasia have better outcomes after endoscopic or surgical treatment, as compared to those with type I or III (type III with the highest failure rates).19–21

Ambulatory pH monitoring This test is recommended only in selected patients when the diagnosis is uncertain, in order to distinguish between gastroesophageal reflux disease (real reflux) and achalasia (false reflux). As dysphagia, regurgitation, and heartburn are common in both disorders, some patients can indeed be misdiagnosed. In both gastroesophageal reflux disease and achalasia, the reflux score and the percentage of time the pH is below 4 can be abnormal. The pH monitoring tracings, however, are significantly different: while real reflux is characterized by intermittent drops of the pH below 3 with subsequent return of the values above 5, in achalasia there is a slow and progressive drift of the pH below 4 with no or very slow return to higher values.

Treatment No curative treatment currently exists for this disorder. The main goal of therapy is palliation of symptoms by decreasing the LES pressure and improving the emptying of the esophagus into the stomach. Pharmacologic, endoscopic, and surgical treatment modalities are available.

Pharmacologic treatment Pharmacologic agents include smooth muscle relaxants, such as longlasting nitrates (e.g., isosorbide dinitrate) and calcium channel blockers (e.g., nifedipine), and 5 -phosphodiesterase inhibitors (e.g., sildenafil).

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Unfortunately, the duration of action is short, symptom improvement is very limited,and efficacy decreases over time. In addition,troublesome side effects (hypotension, headache, dizziness, and peripheral edema) are common with these medications. Therefore, pharmacologic agents are mostly reserved for frail patients who are unfit for more effective and durable treatments.22

Endoscopic treatment Endoscopic botulinum toxin injection Botulinum toxin decreases LES pressure by inhibiting acetylcholine release at the level of the cholinergic synapses. The standard protocol for endoscopic botulinum toxin injection (EBTI) into the LES consists of the injection of 100 units of botulinum toxin in four quadrants about 1 cm above the esophagogastric junction. Although symptom relief is obtained in the majority of patients after EBTI, the effect of botulinum toxin progressively diminishes over time,with more than 60% of patients experiencing recurrent symptoms after 1 year.23,24 EBTI can be safely repeated, but the efficacy is lower than in the initial treatment. For these reasons, EBTI should be used in patients who are unfit for surgery or endoscopic myotomy.

Pneumatic dilatation Pneumatic dilatation (PD) is a very effective endoscopic treatment modality for esophageal achalasia. The goal of this procedure is to weaken the LES by tearing its muscle fibers with the use of radial force. A graded approach is recommended starting with a 30-mm balloon and advancing to larger balloons (e.g., 35–40 mm) if symptoms persist after 2–4 weeks. Patients should be advised, however, that if symptoms recur rapidly after PD with a 40-mm balloon, the effectiveness of further PDs decreases significantly.25 Esophageal perforation is a potential serious complication of PD and should be suspected in patients who experience thoracic pain, subcutaneous emphysema, shortness of breath, and/or fever after PD. It is recommended to observe patients for at least 4 hours after the procedure; and a water-soluble iodine contrast (gastrografin) esophagogram or CT scan with oral contrast should be performed if any symptoms suggest perforation.22 As compared to EBTI, short- and mid-term outcomes are significantly better after PD. A previous Cochrane systematic review of seven randomized controlled trials showed that at 6 and 12 months, symptom remission rates were lower after EBTI than PD (52% vs 81%, P = 0.0015 and 37.5% vs 73%, P = 0.0002, respectively).26

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Long-term symptomatic remission rates after PD are variable in the literature (5-year success 40%–82%). Repeated PD sessions are needed in up to one-third of patients to achieve durable symptomatic relief.27–29 Peroral endoscopic myotomy In 2010, a new endoscopic treatment modality called peroral endoscopic myotomy (POEM) was described. The procedure consists in an endoscopic creation of a submucosal tunnel, which allows the myotomy of the circular fibers of the distal esophagus (the myotomy is usually started 10–12 cm above the gastroesophageal junction and extended down for 2–3 cm onto the stomach). In the initial report, POEM improved the Eckardt score (from mean 10 to 1.3) and reduced the resting LES pressure (from a mean of 52.4–19.9 mmHg) in 17 patients with esophageal achalasia, without serious complications related to the procedure.30 Following this study, many gastroenterologists and surgeons adopted POEM as the primary treatment for achalasia. Several studies have proven that POEM is a very effective treatment modality. For instance, Familiari and colleagues reported that clinical success was achieved in 94.5% of patients at a mean follow-up of 11 months.31 A meta-analysis including 36 studies with 2373 patients showed that clinical success (Eckardt score ≤3) was achieved in 98% of patients after POEM.32 Recent studies also confirmed optimal long-term success rates (5-year clinical success 78%–92%).33–35 The main concern with POEM is the onset of postprocedural gastroesophageal reflux related to the ablation of the LES without adding any antireflux procedure. In fact, objective assessments by pH monitoring have shown reflux rates of 38%–70% after POEM.36–39 Therefore, current guidelines suggest that pretreatment information on the risk of gastroesophageal reflux should be provided to patients and follow-up acid suppression therapy considered after POEM.22

Surgical treatment Laparoscopic Heller myotomy In 1914, Ernst Heller described the first surgical esophageal myotomy which was a transabdominal extra-mucosal myotomy performed on both the anterior and posterior walls of the distal esophagus and cardia.40 The original double myotomy (i.e.,anterior and posterior) was rapidly replaced by a single anterior myotomy as proposed by De Bruine Groeneveldt (1918) and Zaaijer

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Figure 6.3 Heller myotomy. The myotomy is extended proximally for about 6 cm above the esophagogastric junction, and distally for 2 or 3 cm onto the gastric wall.

(1923), and the surgical community embraced this operation as the treatment of choice for achalasia.41,42 In 1962, Dor described the “technique de Heller– Nissen modifiee,”which consisted in adding a partial anterior fundoplication to the myotomy in order to prevent postoperative reflux.43 In 1963, Toupet proposed a posterior fundoplication by fixing the gastric fundus to both edges of the myotomy (partial posterior fundoplication).44 At the beginning of the 1990s, the first laparoscopic Heller myotomy (LHM) was described and soon became the operation of choice worldwide.45 The LHM is usually started about 3 cm above the gastroesophageal junction at the 11 o’clock position. Once the proper submucosal plane is reached the myotomy is extended proximally for about 6 cm above the esophagogastric junction, and distally for 2 or 3 cm onto the gastric wall. Therefore, the total length of the myotomy is usually about 8–9 cm46 (Fig. 6.3). Two types of partial fundoplication can be added to the myotomy: Dor (180° anterior) or Toupet (240° posterior). Both fundoplications are

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Figure 6.4 Dor (partial anterior) fundoplication (the myotomy is covered by the fundoplication).

associated with similar rates of symptom relief and comparable incidence of postoperative reflux, and thereby the choice between Dor or Toupet fundoplication is often based on surgeon’s experience and preference47,48 (Figs. 6.4 and 6.5). Several studies have proven excellent outcomes after LHM. Boecxstaens and colleagues49 reported a therapeutic success (reduction of Eckardt score to 3 or less) of 90% at 2 years follow up. Zaninotto et al.50 studied 407 consecutive patients who underwent LHM and Dor fundoplication and reported a 90% success rate at a median follow-up of 30 months.

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Figure 6.5 Heller myotomy and Toupet (partial posterior) fundoplication.

Schlottmann and colleagues51 analyzed a consecutive series of 147 patients undergoing LHM and Dor fundoplication, and at a median follow-up of 22 months, 87% of patients had symptomatic resolution and required no additional treatment. The long-term results of the European achalasia trial confirmed the durable results of the operation: success rate of 84% after 5 years.28 Similarly, another randomized trial showed that only 8% of patients had symptom recurrence after a minimum follow-up of 5 years.29 LHM has also shown favorable outcomes in terms of incidence of postoperative reflux. A meta-analysis showed that the incidence of reflux after LHM plus fundoplication was 8.8%.23 Similarly, Salvador and colleagues52 objectively assessed reflux with pH monitoring in 463 patients after LHM and Dor fundoplication and found that the incidence of pathologic reflux was only 8.6%.

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LHM versus POEM Both LHM and POEM are now considered effective primary treatment modalities for achalasia. Main potential advantages of POEM over LHM include: less invasive, lack of abdominal incisions and intra-abdominal adhesions, faster recovery, avoidance of vagal nerve injury, and possibility of performing a longer myotomy. A previous systematic review and meta-analysis compared both procedures including 53 LHM studies (5834 patients) and 21 POEM studies (1958 patients). At 24 months, improvement of dysphagia after LHM and POEM was 90.0% and 92.7%, respectively (P = 0.01). Patients undergoing POEM were significantly more likely to develop GERD symptoms (OR 1.69), GERD evidenced by erosive esophagitis (OR 9.31), and GERD evidenced by pH monitoring (OR 4.30). The incidence of postoperative reflux assessed by pH monitoring after LHM and POEM was 11.1% and 47.5%, respectively.53 A multicenter trial randomized 221 patients to undergo either POEM (n = 112) or LHM plus Dor fundoplication (n = 109); clinical success at 2 years was observed in 83% and 81.7% after POEM and LHM, respectively. Improvement in esophageal function from baseline to 2 years assessed by measurement of the IRP of the LES did not differ significantly between groups. At 2 years, 44% of patients in the POEM group and 29% of patients in the LHM group had reflux esophagitis (OR 2.00, 95% CI 1.03–3.85). This randomized trial confirmed that a less invasive POEM approach was noninferior to LHM in controlling symptoms but resulted in more cases of gastroesophageal reflux.54 In patients with type III achalasia (“spastic achalasia”), POEM might be able to achieve better outcomes.For instance,a previous study showed that in patients with type III achalasia, the success rates were 98.0% and 80.8% after POEM and LHM, respectively (P = 0.01).55 Other studies also confirmed excellent outcomes after POEM in patients with type III achalasia.56,57 The better outcomes associated with POEM in this population might be related to the possibility of performing a longer myotomy in the esophageal body, as compared to LHM. Overall, LHM and POEM seem to achieve comparable success rates and should be considered primary treatment modalities for esophageal achalasia. However, patients undergoing POEM have a high risk of postprocedural gastroesophageal reflux. In patients with type III achalasia, POEM achieves higher rates of symptom improvement.

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Esophagectomy Patients with end-stage achalasia (i.e., dilated “sigmoid-shape” esophagus) might eventually require an esophagectomy. Esophageal resection is indeed challenging in these patients because the dilated esophagus occupies most of the posterior mediastinum, there is an altered anatomy with axial deviation, and vessels feeding the esophagus are often significantly enlarged. Therefore, even in patients with end-stage achalasia surgical or endoscopic myotomy should be attempted first.58–60 Esophagectomy should be a last resort reserved for patients with persistent or recurrent achalasia after the failure of previous less invasive treatments (PD, POEM, LHM) and radiologic progression of the disease.22

Conclusions Achalasia is a rare primary esophageal motility disorder characterized by a lack of esophageal peristalsis and partial or absent relaxation of the LES in response to swallowing. The quality of life of patients is affected by the presence of dysphagia, regurgitation, chest pain, and/or weight loss. Although there is no curative treatment for the disease, effective endoscopic and surgical treatment modalities are available to help patients achieving durable symptom relief.

Conflict of Interest Francisco Schlottmann, Fernando Augusto Mardiros Herbella, and Marco G. Patti declare that they have no conflicts of interest.

Acknowledgments Dr. Agustín Valinoti for his work in the illustrations of Heller myotomy and fundoplications.

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28. Moonen A, Annese V, Belmans A, et al. Long-term results of the European achalasia trial: a multicentre randomized controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016;65:732–739. 29. Persson J, Johnsson E, Kostic S, et al. Treatment of achalasia with laparoscopic myotomy or pneumatic dilatation: long-term results of a prospective, randomized study. World J Surg. 2015;39:713–720. 30. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42:265–271. 31. Familiari P, Gigante G, Marchese M, Boskoski I, Tringali A, Perri V, et al. Peroral endoscopic myotomy for esophageal achalasia: outcomes of the first 100 patients with short-term follow-up. Ann Surg. 2016;263:82–87. 32. Akintoye E, Kumar N, Obaitan I, Alayo QA, Thompson CC. Peroral endoscopic myotomy: a meta-analysis. Endoscopy. 2016;48:1059–1068. 33. Campagna RAJ, Cirera A, Holmstrom AL, et al. Outcomes of 100 patients more than 4 years after POEM for achalasia. Ann Surg. 2021;273:1135–1140. 34. Abdelfatah MM, Calderon LF, Koldhekar A, et al. Long-term outcome of per-oral endoscopic myotomy performed in the endoscopy unit with trainees. Surg Laparosc Endosc Percutan Tech. 2021;32(1):114–118. 35. Modayil RJ, Zhang X, Rothberg B, et al. Peroral endoscopic myotomy: 10-year outcomes from a large, single-center U.S. series with high follow-up completion and comprehensive analysis of long-term efficacy, safety, objective GERD, and endoscopic functional luminal assessment. Gastrointest Endosc. 2021;94(5):930–942. 36. Kumbhari V, Familiari P, Bjerregaard NC, et al. Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study. Endoscopy. 2017;49:634–642. 37. Sharata AM, Dunst CM, Pescarus R, Shlomovitz E, Wille AJ, Reavis KM, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg. 2015;19:161–170. 38. Worrell SG, Alicuben ET, Boys J, DeMeester SR. Peroral endoscopic myotomy for achalasia in a thoracic surgical practice. Ann Thorac Surg. 2016;101:218–224. 39. Teh JL, Tham HY, Soh AYS, et al. Gastro-esophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM). Surg Endosc. 2022;36(5):3308–3316. 40. Heller E. Extramukose cardioplastik beim chronischen kardiospasmus mit dilatation des oesophagus. Mitt Grenzgeb Med Chir. 1914;27:141–149. 41. De Bruine Groeneveldt JR. Over cardiospasmus. Ned T Geneesk. 1918;62:1281–1282. 42. Zaaijer JH. Cardiospasm in the aged. Ann Surg. 1923;77:615–617. 43. Dor J, Humbert P, Dor V, Figarella J. L’interet de la technique de Nissen modifiee dans la prevention du reflux apres cardiomyotomie extramuqueuse de Heller. Mem Acad Chir (Paris). 1962;88:877–883. 44. Toupet A. Technique d’oesophago-gastroplastie avec phréno-gastropexie appliquée dans la cure radicale des hernies hiatales et comme complément de l’opération de Heller dans les cardiospasmes. Mem Acad Chir (Paris). 1963;89:394–399. 45. Shimi S, Nathanson LK, Cuschieri A. Laparoscopic cardiomyotomy for achalasia. J R Coll Surg Edinb. 1991;36:152–154. 46. Schlottmann F, Nurczyk K, Patti MG. Laparoscopic Heller myotomy and Dor fundoplication: How I do it? J Laparoendosc Adv Surg Tech A. 2020;30:627–629. 47. Rawlings A, Soper NJ, Oelschlager B, et al. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial. Surg Endosc;. 2012;26:18–26. 48. Kumagai K, Kjellin A, Tsai JA, et al. Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for achalasia: results of a randomized clinical trial. Int J Surg;. 2014;12:673–680. 49. Boeckxstaens GE, Annese V, des Varannes SB, et al. Pneumatic dilation versus laparoscopic Heller myotomy for idiopathic achalasia. N Engl J Med. 2011;364:1807–1816.

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50. Zaninotto G, Costantini M, Rizzetto C, et al. Four hundred laparoscopic myotomies for esophageal achalasia: a single centre experience. Ann Surg. 2008;248:986–993. 51. Schlottmann F, Andolfi C, Kavitt RT, et al. Multidisciplinary approach to esophageal achalasia: a single center experience. J Laparoendosc Adv Surg Tech A. 2017;27:358–362. 52. Salvador R, Pesenti E, Gobbi L, et al. Postoperative Gastroesophageal reflux after laparoscopic Heller-Dor for achalasia: true incidence with an objective evaluation. J Gastrointest Surg. 2017;21:17–22. 53. Schlottmann F, Luckett DJ, Fine J, et al. Laparoscopic Heller myotomy versus peroral endoscopic myotomy (POEM) for achalasia: a systematic review and meta-analysis. Ann Surg. 2018;267:451–460. 54. Werner YB, Hakanson B, Martinek J, et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381:2219–2229. 55. Kumbhari V, Tieu AH, Onimaru M, et al. Peroral endoscopic myotomy (POEM) vs laparoscopic Heller myotomy (LHM) for the treatment of type III achalasia in 75 patients: a multicenter comparative study. Endosc Int Open. 2015;3:E195–E201. 56. Khashab MA, Messallam AA, Onimaru M, et al. International multicenter experience with peroral endoscopic myotomy for the treatment of spastic esophageal disorders refractory to medical therapy (with video). Gastrointest Endosc. 2015;81:1170–1177. 57. Zhang W, Linghu EQ. Peroral endoscopic myotomy for Type III achalasia of Chicago classification: outcomes with a minimum follow-up of 24 months. J Gastrointest Surg. 2017;21:785–791. 58. Mineo TC, Pompeo E. Long-term outcome of Heller myotomy in achalasic sigmoid esophagus. J Thorac Cardiovasc Surg. 2004;128:402–407. 59. Panchanatheeswaran K, Parshad R, Rohila J, et al. Laparoscopic Heller’s cardiomyotomy: a viable treatment option for sigmoid oesophagus. Interact Cardiovasc Thorac Surg. 2013;16:49–54. 60. Qiu S, Chai N, Zhai Y, et al. Advanced achalasia: good candidate for peroral endoscopic myotomy. Dis Esophagus. 2021;34:doaa097.

CHAPTER 7

Primary esophageal motility disorders beyond achalasia Mario Costantini, Renato Salvador and Andrea Costantini Department of Surgical, Oncological and Gastroenterological Sciences, Unit of Chirurgia Generale 1, University of Padua, Padua, Italy

“If we want everything to stay as it is, everything has to change” Tancredi in The Leopard, by G. Tomasi Lanza di Lampedusa, 1958 The existence of esophageal motility disorders (EMD) other than achalasia was known more than a century ago. With the advent of adequate technology (i.e., low-compliance perfused manometry), a better understanding and definition of primary EMD was possible and a classification that has been in use for some 40 years was developed. Based on the lower esophageal sphincter (LES) function and the strength and coordination of esophageal peristalsis, achalasia, diffuse esophageal spasm (DES), nutcracker esophagus (NE), nonspecific esophageal motor disorders (NEMD), and ineffective esophageal motility (IEM) were identified (Table 7.1).1 Then, at the beginning of the new millennium, following the inspired intuition of the late Ray Clouse and thanks to the rapid development of hardware and software, high-resolution manometry (HRM) of the esophagus was developed.In just a few years,it swept the field of esophageal motility, making the traditional perfused systems obsolete and, possibly, inaccurate. This revolution prompted the development of a new classification of EMD, named Chicago Classification (CC), first introduced in 2009 (CCv1.0)2, followed by an updated version in 2012 (CCv2.0)3. The aim of this new classification was to standardize the interpretation of HRM, but a widely accepted consensus was only obtained for a further version in 2015 (CCv3.0) when significant simplification was adopted4. As it is well known, CCv3.0 was recently updated to a further version (CCv4.0) in January 2021.5 This introduced some changes, especially as far as EMD other than achalasia was concerned: the use of both manometric and nonmanometric testing to confirm the diagnosis and the necessity of the correlation with symptoms for the clinical treatment.Moreover,a strong recommendation for a standardized Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00010-5 All rights reserved.

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Table 7.1 Classification of EMD following the traditional classification (Mod from Spechler and Castell1 ).

Inadequate LES relaxation Classic achalasia Atypical disorders of LES relaxation Uncoordinated contraction Diffuse esophageal spasm Hypercontraction Nutcracker esophagus Isolated hypertensive LES Hypocontraction Ineffective esophageal motility

manometric protocol including both supine and upright positions and provocative manometric maneuvers was emphasized. These caution changes were probably necessary for the large use of invasive treatments (i.e., POEM) in these disorders, easily leading to some overtreatment. The CC, in any of its releases, clearly separates EMD with or without impaired LES relaxation (i.e., Integrated 4s Relaxation Pressure, or 4sIRP, >15 mmHg) as the first step in its hierarchical algorithm, whereas the presence of normal or impaired esophageal peristalsis only comes second. The first EMD to be classified is therefore those with impaired LES relaxation, with absent or deranged (Achalasia) or with normal peristalsis (Esophago-Gastric Junction Outflow Obstruction, EGJOO). Achalasia is the most frequent and better known EMD and is discussed in detail in another chapter of this book. Then, if the LES relaxation is normal, EMD involving only the peristaltic activity of the gullet is classified (Table 7.2).5 For didactical purposes, in this chapter, these disorders are further grouped as spastic (disorders with some degree of deranged peristalsis—DES—or with hypercontractility— hypercontractile esophagus, HE) and hypomotile disorders (disorders with loss of contractility power, with increased % of ineffective swallows—IEM—or with complete loss of contractility, as in Absent Contractility—AC). It must be underlined, however, that this further distinction does not belong to the original CCv4.0.

Disorders with impaired LES relaxation (excluding Achalasia): Esophago-gastric junction outflow obstruction (EGJOO) Once vaguely classified as “Atypical disorders of LES relaxation” in patients with one or more manometric features precluding a diagnosis of true

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Table 7.2 Classification of EMD following the Chicago Classification 4.0 (Mod from Yadlapati et al.5 ).

1. Disorders of EGJ outflow with/without disorders of peristalsis Type I Achalasia Abnormal median IRP with 100% failed Peristalsis Type II Achalasia Abnormal median IRP, 100% failed peristalsis, with ≥20% swallows with pan-esophageal pressurization Type III Achalasia Abnormal median IRP with ≥20% swallows with premature/spastic contraction and no evidence of peristalsis EGJ outflow obstruction Abnormal median IRP (supine and upright), ≥20% elevated intrabolus pressure (supine), and not meeting criteria for achalasia 2. Disorders of peristalsis with normal EGJ Outflow a. “Spastic” disorders: Distal Esophageal Spasm Normal median IRP with ≥20% swallows with premature/spastic contractions Hypercontractile Normal median IRP with ≥20% hypercontractile Esophagus swallows (DCI > 8000 mmHg s cm) b. “Hypomotile” disorders Ineffective Esophageal Normal median IRP, with >70% ineffective Motility swallows or ≥50% failed peristalsis Absent Contractility Normal median IRP (supine and upright) with 100% failed peristalsis

achalasia,1 EGJOO is a relatively new defined clinical entity, whose characterization was possible only with HRM. CCv1.0 identified this condition as a major motor disorder of impaired LES relaxation and called it “functional obstruction.”2 Subsequent versions renamed the condition as EGJOO, requiring for the diagnosis an elevated IRP associated with weak/intact peristalsis (v2.0)3 or elevated IRP and simply “not types I–III achalasia” (v3.0).4 However, in the following years, nearly 10% of patients undergoing HRM were identified to have EGJOO,5 therefore, introducing some doubts about the clinical relevance of this finding. In CCv4.0, it was clearly stated that “a manometric diagnosis of EGJOO is always considered inconclusive” and further testing is now recommended to differentiate patients who would benefit from invasive intervention from patients in whom EGJOO is inconsequential and/or a possible distraction.5 The diagnosis of EJGOO now requires that the elevated median IRP in the supine position is persistent despite a change in the position, and intrabolus pressure must exceed 20 mmHg during at least 20% or more supine wet swallows (Fig. 7.1). When these alterations are found in a symptomatic patient, further tests including

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Figure 7.1 High-resolution manometry picture (15 mmHg isobaric contour) showing EGJ-OO in a patient complaining of dysphagia, with a 4-s IRP exceeding 25 mmHg in all wet swallows. Esophageal motility was normal. These findings were confirmed in the sitting position, and the diagnosis was confirmed with TBE. The patient underwent LHD, with good results.

timed barium swallow (TBE) with tablets and/or evaluation of distensibility of the EGJ with EndoFLIP are also suggested.5 All these changes highlight how a cautious approach is now recommended before diagnose EGJOO. EGJOO can be idiopathic or secondary. The latter may be caused by any mechanical obstruction of the esophagus, such as esophageal strictures, eosinophilic esophagitis, giant hiatal hernia, prior fundoplication or bariatric surgery, or malignancy.6 Abuse of opioid drugs must also be ruled out. Idiopathic EGJOO represents only 30%–40% of the patients with this manometric feature.7 The pathophysiology of “idiopathic” EGJOO is unclear but most authors see it as a precursor or a variant of achalasia. The main clinical manifestations of idiopathic EGJOO are dysphagia, chest pain, and regurgitation and treatments that aim to relieve the functional obstruction are the most effective. Symptoms in patients with EGJOO do not always require treatment, however. Some authors suggest that 44%–52% of the patients diagnosed with EGJOO improve without any pharmacological or surgical therapy.6 For the time being, there are no published guidelines on the management and treatment EGJOO, being so far simply the same as for achalasia. Medical treatments such as Ca2+ channel blockers and long-acting nitrates have been used, but with low response rates (only 50% of patients).7 Botox injections have also been used, showing that persistent symptom relief

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from a single session at 2 years was just 16.8%.7 On the assumption that idiopathic EGJOO is an achalasia’s precursor, some patients were also treated with pneumatic dilations (PD), with a positive outcome in two-thirds of the patients with a single 30-mm dilation, and in 79% of the patients retreated with a 35-mm balloon, after a median follow-up of 2 years.8 POEM was also used in this context. In an international multicenter study, POEM was performed in patients with disorders other than achalasia, including EGJOO, in which a positive outcome was reported in 93% of the cases.9 Reflux symptoms developed in 36% of this group, however. The main limitation of this study was the short follow-up (6.5 months). The same is true also for another recent multicentric study10 where 55 patients with EGJOO were treated with POEM, with a clinical success rate of 94% at 4 months. It is worth mentioning, however, that postprocedural 24-h pH proven reflux was recorded in 66% of patients (and esophagitis in 40%). Finally, a recent study from our group7 showed that laparoscopic Heller myotomy (with Dor fundoplication, LHD) showed symptom relief in 96% of patients with EGJOO, a figure comparable with the results achieved in patients with early-stage achalasia, both in the clinical outcome and the onset of postoperative reflux. Table 7.3 summarizes the reported success rates of treatment for EGJOO.

Disorders of peristalsis with normal EGJ outflow “Spastic” EMD Distal esophageal spasm (DES) Once labeled “Diffuse” esophageal spasm,3 this motility disorder occurring primarily in the smooth muscle portion of the distal esophagus, was more appropriately named as “Distal” esophageal spasm (DES)11 and as such incorporated in the CC. It has been recognized as a rare motility disorder with an unknown cause for a long-time. It is generally suspected in patients with chest pain and dysphagia in whom careful cardiac tests have excluded an ischemic heart disease, and endoscopy (with biopsy) has ruled out any esophageal mucosa anomalies. Barium swallow may be useful in the diagnosis of DES because the characteristic corkscrew appearance is suggestive (Fig.7.2),but these findings are inconstant,being observed only in a minority of patients with DES,12 and the sensitivity and specificity of radiology for the diagnosis is not known. In the past, the most used manometric definition was the presence of simultaneous contractions in the distal esophagus, with a minimum amplitude of 30 mm Hg,in 20%–80% of esophageal contractions,alternating

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Table 7.3 Success rate of different treatments for esophago-gastric junction outflow obstruction as reported in literature. Author, year

Number of Pts No treatment Medical treatment Botox

PD

Scherer, 2009 Porter, 2011 Van Hoeij, 2015 Clayton, 2016 Perez-Fernandez, 2016 Okeke, 2016 Lynch, 2017 Clayton & Richter 2018 Kashab, 2018 Jacobs, 2020 Salvador, 2021

9 36 47 15 25 22 43 33 15 55 25

0/3 (0%)

– – 26 (46%) – 13 (52%) – 19 (44%) – – – –

PD, pneumatic dilation; POEM, peroral endoscopic myotomy.

– – – – 3/6 (50%) 0/7 (0%) 3/4 (75%) – – – –

0/2 (0%) 21/36 (59%) 5/5 (100%) 7/11 (64%) 3/3 (100%) 4/6 (60%) 2/6 (33%) – – – –

POEM

– – 1/3 (33%) – 4/4 (100%) – – – – – – – 22/33 (67%) – – 14/5 (93.3 %) – 47/55 (94%) – –

Myotomy

3/3 (100%) – – – – – 1/1 (100%) – – – 24/25 (96%)

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Figure 7.2 Barium swallow in a patient with DES showing corkscrew (or rosary beads) appearance of the esophagus, and delayed passage of contrast to the stomach. The corkscrew appearance results from premature, nonpropulsive contractions of the esophageal circular muscles, as seen with HRM. Unfortunately, this finding, albeit suggestive for a spastic EMD, is found in only a minority of patients. EMD, esophageal motility disorders.

with a normal peristalsis.1 The CC introduced some new parameters,2 such as the pressurization front velocity (PFV), allowing the definition of rapidly conducted contractions when PFV was ≥8 cm/s. Another new parameter was the distal contractile integral (DCI), that incorporated qualities of

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Figure 7.3 High-resolution manometry picture (15 mmHg isobaric contour) in a patient with DES. A peristaltic contraction (DL = 4.8 seconds) can be seen after the first swallow (left), whereas a premature contraction with a DL = 4.3 seconds is evident after the second swallow. This patient had 40% of premature contractions and 60% of normal peristaltic waves, with a normally functioning LES (median IRP = 12 mmHg s cm). DCI was in the normal range in all occasions.

esophageal pressurization—length and vigor—and was expressed as mmHg s cm. DCI was considered elevated when exceeding >5000 mmHg s cm and was incorporated in the definition of DES, just to be dropped in the second release of the classification. Moreover, CCv2.0 used distal latency (DL) rather than contraction velocity. DL measures the time from UES relaxation to the contractile deceleration point when the contraction slows down in the proximity of the LES.3 This was based on a study by Pandolfino et al. in 1070 patients who were thought of having DES, reporting that DL was better suited for the diagnosis of DES than CFV.3 A better understanding of these new manometric parameters introduced with HRM may be found in a different chapter of this book. Finally, CCv3.0 and the last CCv4.0 maintained the same criteria to define DES: normal LES function (Median IRP ≤15 mmHg) and ≥20% spastic or premature contractions in the distal esophagus, defined as contractions with a DL 180 mm Hg (i.e., the upper limit of pressure in normal).1 With the advent of HRM, the definition was updated by using DCI instead (mean DCI of >5000 mm Hg cm s) and the disorder was included in the CCv1.0 and CCv2.0,to be dropped in CCv3.0 and CCv4.0.2–5 In CCv3.0, the term NE was in fact replaced by Jackhammer Esophagus (JE), referring to patients with two or more peristaltic waves with DCI >8000 mmHg cm s,4 to be renamed again as HE in CCv4.0, defined with the same criteria but in presence of clinically relevant symptoms of dysphagia and noncardiac chest pain5 (Fig. 7.4). This newest version recommends

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Figure 7.4 Hypercontractile esophagus with Jackhammer Esophagus. The HRM picture (15 mmHg isobaric contour) shows two hypercontractile swallows with DCI of 9450 and 8390 mmHg s cm. The patient had a normal LES relaxation (4s IRP < 15 mmHg). The CCv4.0 identifies other two subgroups of hypercontractile esophagus: single peak hypercontractile swallow and hypercontractile esophagus with LES after-contraction.4 While the jackhammer phenotype depicted in the figure most likely reflects true pathology, these other patterns cannot be of prognostic value or tailor treatment yet, because of the lack of studies mostly due to the rarity of the disease.

great caution before diagnosing HE, to ensure mechanical obstruction at the EGJ has been ruled out and that criteria for achalasia or DES are not met. GERD may be also present in up 35% of the patients with esophageal hypercontractility.16 The HE is no longer synonymous with JE, as three phenotypes of HE can be observed: single-peaked hypercontractile swallows, JE, and hypercontractile swallows with a vigorous LES after-contraction .5 These different phenotypes patterns cannot be of prognostic value or indicate treatment yet, because the available data about the clinical presentation of HE are scarce and controversial, and several authors have failed to report any significant correlation of hypercontractile waves with clinical. Various studies have attempted to link higher contraction vigor to more frequent or more severe symptoms. In a recent cohort study,17 patients who complained of dysphagia had a slightly but significantly higher median DCI than those who did not. A significant correlation between DCI and the presence and/or severity of dysphagia has also been found in other studies. These findings are relatively weak however, thus an overall recommendation of a cautious approach to these patients is mandatory.18

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Table 7.4 Suggested hierarchy of treatment options for spastic esophageal motility disorders: the “Charleston approach” (modified from Khalaf M et al.19 ).

1. 2. 3. 4. 5. 6. 7.

Reassurance and good information Proton pump inhibitors (PPIs) and peppermint oil tablets Nitrates and calcium channel blockers Phosphodiesterase-5 inhibitors Tricyclic antidepressants Endoscopic botulinum toxin injection Myotomy (POEM or surgical myotomy)

Treatment of “Spastic” EMD More than one-third of the patients undergoing function studies for different reasons and recognized as having DES or HE report no symptoms at all, whereas another third may report mild symptoms only.14 These patients hardly need or request treatment. When symptoms of dysphagia and/or chest pain lead to the diagnosis, some sort of treatment may be required. Unfortunately, an effective treatment for spastic EMD has not been found yet, for the lack of good performed clinical trials and the different manifestations of these conditions. The first and most important therapeutic tool in these patients is good information and reassurance: when a patient realizes that his/her symptoms are related to a functional disease of the esophagus and not to other causes (heart ischemia, malignancy), he/she are content, and usually do not require further treatment. Only when the symptom burden is severe enough to impact the quality of life of the patients, are other forms of treatment (pharmacological, endoscopic, or surgical) necessary. Medical therapy for spastic EMD includes different drugs19 (Table 7.4). The use of PPIs is based on observations that esophageal spasms induced by GERD may cause chest pain and that manometry cannot distinguish between idiopathic and acid-induced EMD clearly. Nitrates, nifedipine, and diltiazem directly affect the smooth muscle by reducing the amplitude and duration of the esophageal contractions. Phosphodiesterase inhibitors (sildenafil) work by causing relaxation of the smooth muscle through the release of nitric oxide, leading to the reduction of esophageal contractile amplitude, and symptomatic relief in patients with spastic motility. Tricyclic antidepressants may influence esophageal perception. Finally, recent data show that sublingual dissolvable peppermint tablets in patients with dysphagia and noncardiac chest pain may be of help in these conditions,

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especially in DES.Because of its smooth muscle relaxing properties,its highly favorable safety profile,its widespread availability,and the discouraging results often obtained with other drugs, an initial trial of peppermint oil tablets may be the first step of an approach to symptomatic spastic EMD following the old well-known aphorism “start low, go slow.”19 In the past, PDs were used in DES as well as in achalasia. Patti et al.20 reported satisfactory results in 26% of DES or NE patients treated nonsurgically, one-third of them received PD. Because of the inconsistent reported results and the intrinsic complications of the procedure, PD is seldom used nowadays. Botulinum toxin (BT) injections were applied to spastic EMD, too. One study recently compared BT versus saline in 16 DES and 6 NE patients. One-month after treatment, the patients had significant decreases in their dysphagia score, but not in the chest pain score.18 Marioux et al. reported their experience with BT in hypercontractile or spastic EMD, trying to relate the results to the CC in use at that time (CCv2.0). They reported good results lasting more than 6 months in 71% of seven patients with JE, and in 60% of six patients with DES. They also reported a fatality due to a mediastinitis in a patient with DES, however.21 The same group recently reported a study comparing BT versus saline in 23 patients with spastic EMD (including type 3 Achalasia) and found a similar 30% clinical improvement in both the treated and sham groups.18 Surgical treatment for spastic EMD may be indicated when symptoms persist after adequate trials with medical therapy. Some studies in the 1960s reported success rates ranging from 69% to 100%, involving a total number of 63 patients.18 The introduction of minimally invasive surgery in the 1990s gave new impulse to the surgical treatment of spastic EMD: in 1994, Filipi and Hinder reported five cases of thoracoscopic myotomy, three of them were patients with DES.18 Patti et al.20 compared surgical and nonsurgical treatments in patients with EMD: myotomy performed through a left thoracoscopy proved superior (80% satisfactory results) to medical therapy (26%). In a later study, the same authors compared the thoracoscopic and laparoscopic approaches in 19 patients with DES: the results weighed slightly in favor of laparoscopy.22 A comparative analysis of thoracoscopic versus laparoscopic myotomy with fundoplication in 88 patients with EMD (13 DES) showed overall results favoring the abdominal approach.18 A summary of these results is reported in Table 7.5. Finally, there was only an old report of long-myotomy performed in four patients with NE,18 with good results in three out of four. Patti et al.22 also described their results in treating NE, claimed to be satisfactory in 60%–83% of patients for dysphagia, and in

Table 7.5 Outcomes of surgical treatment with myotomy in patients with spastic esophageal motility disorders (mod. from Costantini et al.18 ).

Author, year

Complained symptoms Improvement Dysphagia Chest pain Dysphagia Chest pain Median F/U (%) (%) (%) (%) (mos)

4 42b 19c 3 10 16d 13

NE DES DES DES DES DES DES

Th-ta Th-t Th-t Th-s Th-s Th-t Th-s vs Lap

100 – – 100 – 94 n.r.

100 100 – 100 – 75 n.r.

100 70 84 66 86 75 71.5

75 88 90 100 80 81 n.r.

24 68 24 – – 81 30

19

DES

80

58

12

NE

Th-s (n = 5) Lap (n = 14) Th-s (n = 5) Lap (n = 7) Th-t

47

80

100

70

80 86 60 83 88

65 80 40 50 100

125 52 88 32 36

Leconte et al., 2007 20

DES

a One urgent thoracotomy for perforation after b DES was diagnosed in 38/42 pats (90%). c Four patients had an esophagectomy. d DES was diagnosed in 12/16 pats (75%).

PD, with repair and myotomy.

DES, distal esophageal spasm; Lap, laparoscopy; NE, nutcracker esophagus; Th-t, thoracotomy; Th-s, thoracoscopy.

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Traube et al., 1987 Ellis et al., 1999 Eypasch et al., 1992 Filipi et al., 1994 Patti et al., 1995 Nastos et al., 2002 Champion et al., 2002 Patti et al., 2005

Number Type of esophageal Surgical of pats motility disorders approach

95

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40%–50% for chest pain.Some of these patients,however,had a poor relaxing LES, and therefore would have been classified differently with present manometric standards. Interestingly, for some 15 years, no more studies using surgical myotomy for spastic EMD appeared in the literature apart from a couple of case reports. This may reflect the somewhat unsatisfactory results obtained and the consequent decreasing enthusiasm for surgery in these patients. Another possible explanation is, of course, the recent application of POEM to spastic EMD. In fact, following the extraordinary success in treating achalasia, POEM was soon enthusiastically used in patients with spastic EMD as well. Table 7.6 reports the results of recently published papers, with a success rate ranging from 63% to 100%.18 The follow-up is, however, short (only two studies had a follow-up >2 years), and the adverse event rate is not negligible. Moreover, no comparative study with other treatments is available, being all retrospective series, with only a multicentric study. A recent meta-analysis23 confirmed an improvement in 25/26 patients with DES (96%) and in 20/28 patients with JE (71.4%). The appeal of this approach lies in the possibility of performing a very long myotomy, from the upper esophagus to a few centimeters below the cardia, as it was possible with the thoracotomic or thoracoscopic approach. Yet some reservations are necessary before recommending this treatment. In fact, the long-term effects of trading a previously hyper-peristaltic esophagus for a functionally aperistaltic one, as the result of a complete myotomy, are not known yet. This is not a trivial concern, especially in the light that POEM may induce postoperative reflux in up to 50% of cases. A careful selection of the patients is the key in these disorders, as in any foregut function diseases.

Hypomotility disorders Absent contractility The CC defines AC when median IRP is normal and 100% of swallows show failed peristalsis. Failed peristalsis was first defined in CCv1.0 as no continuous pressure domain above an isobaric contour of 30 mm Hg in the distal esophagus.2 In CCv2.0, a lower threshold was chosen, defining failed a contraction when minimal (5 mm long, none of which extends between the tops of two mucosal folds Grade C Mucosal breaks that extend between the tops of ≥ 2 mucosal folds, but which involve 90% at 1 hour, 60% at 2 hours, and 10% at 4 hours. Medical treatment of underlying gastroparesis might help improving GERD symptoms.

Management of patients with GERD and dysphagia Lifestyle modifications and medical therapy Once GERD is appropriately diagnosed and other causes of dysphagia have been ruled out, patients should follow lifestyle modifications and start medical therapy. Lifestyle modifications include elevation of the head of

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the bed, avoidance of meals before bedtime, dietary interventions (e.g., avoiding fatty meals, soft drinks, or chocolate), avoidance of toxic habits (alcohol and tobacco), and weight loss. Numerous pharmacologic agents for the treatment of GERD are available: nonabsorbable agents (antacids and alginate formulations), histamine-2 receptor antagonists, proton pump inhibitors (PPIs), potassium channel acid blockers, prokinetic agents, and inhibitors of transient LES relaxations. PPIs are currently the first line and dominant treatment for GERD.10 In patients with erosive esophagitis, PPIs are highly effective: 80% and 90% healing rates at 4 and 8 weeks, respectively.11 Once the esophagitis is healed, the majority of patients report symptom amelioration. Patients with nonerosive reflux, however, have a significantly lower symptom response rate to PPIs.12 In nonrespondent patients, underdosing and lack of adherence should always be investigated. Overall, if dysphagia is mostly related to the severity of esophagitis and the large amount of acidic reflux, medical therapy will likely be effective in most patients. However, if anatomical factors are involved (i.e., stricture, Schatzki ring, hiatal hernia) an endoscopic or surgical intervention might be needed.

Endoscopic dilatation of GERD-related strictures Patients with GERD-related strictures (“peptic strictures”) typically present with dysphagia and weight loss, along with other GERD symptoms (i.e., heartburn and regurgitation). Medical therapy must still be maximized to control esophageal inflammation. In addition, multiple biopsies of the stricture are recommended to exclude malignancy. Endoscopic dilatations with either a bougie or a through-the-scope (TTS) balloon should be performed by experienced operators. Patients should be informed about potential complications such as chest pain, bleeding,and/or perforation.It is recommended to start with small dilatation diameters (i.e., 10 mm) and increase gradually over further procedures to reduce the risk of complications. In patients with refractory or recurrent strictures, the intralesional injection of steroids (e.g., triamcinolone) following dilatation might also be beneficial.13,14 Schatzki rings are fibrous rings most commonly located in the lower esophagus which are strongly associated with pathologic acid exposure and hiatal hernia. Schatzki rings can also be present in patients with eosinophilic esophagitis. Although medical therapy alone is effective in some patients

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with symptomatic Schatzki rings,esophageal dilatation with a bougie dilator, or TTS balloon is often needed. In patients with several failed dilatation attempts, incisional therapy with a needle knife can also be considered.15

Antireflux surgery Patient selection is extremely important to obtain favorable postoperative outcomes after antireflux surgery. The presence of large hiatal hernia, for instance, is a very good indication for antireflux surgery. Symptomatic patients with large a hiatal hernia (>3–5 cm) have more severe reflux episodes and higher risk of GERD complications (severe esophagitis, strictures, Barrett´s esophagus). Medical therapy alone is less likely to be effective in patients with a severely altered gastroesophageal junction anatomy, and thereby these patients should be strongly considered for antireflux surgery.7 PPIs alter the pH of the gastric juice but do not eliminate the occurrence of gastroesophageal reflux episodes. For this reason, while patients on PPIs often present symptomatic relief of their heartburn (intrinsically related to the acidity of the reflux episodes), regurgitation and respiratory symptoms might persist. A fundoplication restores the LES function and abolishes reflux of all gastric content into the esophagus. Therefore, if patients suffer from severe regurgitation along with dysphagia, an antireflux operation is a very good alternative. Patients with poor adherence to medical therapy, refusal to long-term medication or presenting with side effects related to PPIs should also be considered for antireflux surgery.16 Hiatal hernia repair and wrap construction are the key technical steps of the operation. Closure of the diaphragmatic crura with interrupted nonabsorbable sutures is recommended.Although reinforcement of the hiatus with a mesh has been advocated to reduce recurrence rates,17 current evidence does not support the systematic use of prothesis.18 Mesh reinforcement of the hiatus might be useful in selected cases such as large hernias with poor quality of the crura (usually elderly patients) or redo operations.19 There are two main types of fundoplication during an antireflux operation: total 360° fundoplication (Nissen fundoplication) or partial posterior 240° fundoplication (Toupet fundoplication). In patients with dysphagia as predominant symptom or with severely impaired esophageal motility, a partial fundoplication is preferred (Fig. 9.5). Studies with long-term follow-up have shown excellent results after antireflux surgery.20–22

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Figure 9.5 Total “Nissen” fundoplication and partial “Toupet” fundoplication.

Conclusions Patients with GERD and dysphagia should undergo a thorough diagnostic evaluation. Lifestyle modifications and optimal medical therapy provide symptom relief in many patients. The presence of peptic strictures or Schatzki ring might require endoscopic dilatation. An antireflux surgery is recommended in selected patients with GERD and dysphagia.

Conflict of Interest The authors have no conflict of interest to declare.

Acknowledgments Dr. Agustín Valinoti for his work in the illustrations of total and partial fundoplication.

References 1. Vakil N, van Zanten SV, Kahrilas P, Dent K, Jones R. Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–1920. 2. El-Serag HN, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastroesophageal reflux disease: a systematic review. Gut. 2014;63:871–880. 3. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122:1500–1511.

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4. Shaheen NJ, Hansen RA, Morgan DR, et al. The burden of gastrointestinal and liver diseases. Am J Gastroenterol. 2006;101:2128–2138. 5. Fisichella PM, Schlottmann F, Patti MG. Evaluation of gastroesopheal reflux disease. Updates Surg. 2018;70:309–313. 6. Herbella FAM, Schlottmann F, Patti MG. Pathophysiology of gastroesophageal reflux disease:how an antireflux procedure works (or does not work).Updates Surg.2018;70:343– 347. 7. Schlottmann F, Andolfi C, Herbella FA, Rebecchi F, Allaix ME, Patti MG. GERD: Presence and size of hiatal hernia influence clinical presentation, esophageal function, reflux profile, and degree of mucosal injury. Am Surg. 2018;84:978–982. 8. Diener U, Patti MG, Molena D, Fisichella PM, Way LW. Esophageal dysmotility and gastroesophageal reflux disease. J Gastrointest Surg. 2001;5:260–265. 9. de Mello Del Grande L, Herbella FAM, Katayama RC, Lima WG, Patti MG. Transdiaphragmatic pressure gradient (TPG) has a central role in the pathophysiology of gastroesophageal reflux disease (GERD) in the obese and it correlates with abdominal circumference but not with body mass index (BMI). Obes Surg. 2020;30:1424–1428. 10. Scarpignato C, Hongo M, Wu JCY, et al. Pharmacologic treatment of GERD: where we are now, and where are we going? Ann N Y Acad Sci. 2020;1482:193–212. 11. Dekkers CP, Beker JA, Thjodleifsson B, Gabryelewicz A, Bell NE, Humphries TJ. Double-blind comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. The European Rabeprazole Study Group. Aliment Pharmacol Ther. 1999;13:49–57. 12. Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol. 2007;41:131– 137. 13. Burr NE, Everett SM. Management of benign oesophageal strictures. Frontline Gastroenterol. 2019;10:177–181. 14. Ramage Jr JI, Rumalla A, Baron TH, et al. A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures. Am J Gastroenterol. 2005;100:2419–2425. 15. Adler DG, Siddiqui AA. Endoscopic management of esophageal strictures. Gastrointest Endosc. 2017;86:35–43. 16. Schlottmann F, Herbella FA, Allaix ME, Rebecchi F, Patti MG. Surgical treatment of gastroesophageal reflux disease. World J Surg. 2017;41:1685–1690. 17. Oelschlager BK, Pellegrini CA, Hunter J, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg. 2006;244:481–490. 18. Angeramo CA, Schlottmann F. Laparoscopic paraesopheal hernia repair: to mesh or not to mesh. Systematic review and meta-analysis. Ann Surg. 2022;275(1):67–72. 19. Laxague F, Sadava EE, Herbella F, Schlottmann F. When should we use mesh in laparoscopic hiatal hernia repair? A systematic review. Dis Esophagus. 2021;34(6):doaa125. 20. Dallemagne B,Weerts J,Markiewicz S,et al.Clinical results of laparoscopic fundoplication at ten years after surgery. Surg Endosc. 2006;20:159–165. 21. Morgenthal CB, Shane MD, Stival A, et al. The durability of laparoscopic Nissen fundoplication: 11-year outcomes. J Gastrointest Surg. 2007;11:693–700. 22. Robinson B, Dunst CM, Cassera MA, Reavis KM, Sharata A, Swanstrom LL. 20 years later: laparoscopic fundoplication durability. Surg Endosc. 2015;29:2520–2524.

CHAPTER 10

Eosinophilic esophagitis focusing on dysphagia Vera Lucia Angelo Andrade a and Júlio César de Soares Veloso b

a Brazilian Federation of Gastroenterology, Brazilian Society Digestive Motility and Neuroendocrine, Federal University of Minas Gerais, Brazil b Gastroenterologist and Digestive Endoscopist, President of the Brasilia/Brazil Gastroenterology Association, Brazil

Introduction Eosinophilic esophagitis (EoE) is a chronic allergic disease of the esophagus of multifactorial etiology, antigen-immunomediated characterized by symptoms related to esophageal dysfunction and histopathologically characterized by the presence of high concentration of intraepithelial eosinophils (≥15 eosinophils per high power field -eos/hpf).1,2 EoE was described in the late 1970s by Landers et al. having been identified as a clinical-pathological entity since 1993 by Attwood et al. The incidence has grown in recent years, with an exponential increase in articles published. The first studies showed that it was epidemiologically more prevalent in male children and adolescents. A potential genetic component has been suggested as it is more common in Caucasians and has many familial cases.3,4 It is more frequent in males (3:1). It has a bimodal peak incidence: children/ adolescents and adults aged 30/50 years old. The diagnosis is based on the European Directive and the International Consensus which demonstrates that the diagnostic criteria for EoE include the presence of esophageal symptoms, suggestive endoscopic findings, and esophageal infiltration of eosinophils (eos).5 An abnormal chronic Th2-type immune response characterized by intense eosinophilic esophageal inflammation is already established in EoE. As a consequence of this chronic inflammatory process, connective tissue remodeling occurs, which can evolve with histopathological subepithelial fibrosis. These endoscopic changes can be seen as esophageal trachealization and clinically manifest as dysphagia. EoE is one of the main causes of dysphagia or food impaction in adults,showing the relevance of the approach in this chapter.6,7 Dysphagia: Diagnosis and Treatment of Esophageal Motility Disorders. Copyright © 2023 Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-323-99865-9.00001-4 All rights reserved.

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Epidemiology Early studies show that EoE was epidemiologically more prevalent in male children and adolescents.1,2 EoE has emerged over the past 3 decades as a major cause of upper gastrointestinal morbidity.3 Study published on the epidemiology and natural history of EoE concluded that its incidence is increasing and this increase would not only be an artifact of greater surveillance and detection. The incidence and prevalence of EoE have been investigated worldwide, but most population-based studies have been conducted in North America and Europe.Published epidemiological studies should be carefully evaluated, since it is essential to recognize the differences in results performed in different centers and during different periods of time. For example, proton pump inhibitor (PPI) responsive esophageal eosinophilia may or may not have been excluded in some studies.8 EoE has strong genetic and environmental components, with a risk of EoE for other siblings estimated at 2.4% and a sibling recurrence-risk ratio greater than 40.Families with more than one affected member are frequently observed. In general, patients with EoE tend to be younger, male, white and have associated atopic disorders.9

Pathogenesis The etiopathogenesis of EoE is not yet fully understood, but it is known that it is an immune response mediated by Th2 lymphocytes, which secrete the interleukins in response to food and environmental factors and related to genetic susceptibility. There is an alteration in the epithelial barrier and eosinophilic infiltration, which may present eosinophilic abscesses. According to the literature on EoE, there is hypersensitivity not mediated by IgE (delayed hypersensitivity), with partial participation of IgE-mediated hypersensitivity (immediate hypersensitivity). Acute EoE associated with an immediate food hypersensitivity is supposedly present, but it is an unusual condition.18 Briefly, when allergens are ingested and come into contact with the stratified squamous epithelium of the esophagus. Microbial antigens can also cause activation of the innate and acquired immune system. Subsequently,they cross this epithelium and activate dendritic cells through the induction of stromal lymphoprotein (TSLP). TSLP is a cytokine related to the induction of the Th2 immune reaction produced mainly by epithelial cells and basophils. Activated dendritic cells induce Th2 proliferation, leading to an increase in cytokines associated with eosinophilic inflammation, such as IL-5, IL13, and IL15.10 IL-5 recruits intramedullary eosinophils or those from

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the peripheral intravascular compartment and stimulates the proliferation and maturation of eosinophils in the bone marrow, which will be recruited into the esophagus, attracted by eotaxin-3, produced by squamous epithelial cells activated by IL-13. IL-13 and IL-15 induce epithelial secretion of eotaxin-3, one of the most specific chemotactic factors for eosinophils. IL-13 can also attenuate the barrier function of the squamous epithelium, decreasing the gene expression of the epidermal differentiation complex, such as filaggrin or involucrin. Activation and degranulation of eosinophils will be responsible for the inflammatory pattern of the disease.10,11 The mechanism and reason for progression to fibrosis are not established. However,some pathophysiological mechanisms have already been described. Activated eosinophils,together with mast cells,produce transforming growth factor-beta (TGF-b1). The action of fibroblasts is also reported and periostine, triggering fibrotic changes in the esophageal wall, leading to smooth muscle dysfunction. The proliferation of fibroblasts will determine esophageal collagen remodeling. The role of eosinophil degranulation is noteworthy. Eosinophils degranulate, release toxic proteins that serve as a defense system but can also cause tissue damage and ultimately fibrosis. It can be concluded that, as a consequence of this inflammation, there may be stenosis formation with upstream dilation and longitudinal shearing. Chemotaxin CCL26, TGF-b1, helper T cells (Th1 and Th2), and TSLP are fundamental in the fibrosis process that will clinically manifest as dysphagia. Improving our understanding of the pathogenesis of EoE and recognition of phenotypes of EoE, may also have implications for treatment decisions and outcome assessment.11,12

Risk factors for EoE Several risk factors have already been mentioned in the literature, including13,14 : r Aeroallergens. EoE is often associated with atopic/allergic disorders and can cross-react with food allergens. r Celiac disease (CD). The possible association between EoE and CD is controversial. A cross-sectional study concluded that there is a weak increase in EoE in patients with CD. r Connective tissue disease (CTDs). There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes, particularly those involved in hypermobility (Ehlers–Danlos, Marfan Syndrome).

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Food allergens. EoE in adults is substantially triggered by foods. There was a substantial histologic improvement after elemental diet. r Helicobacter pylori. A study showed that the decrease in the prevalence of this bacteria was related to the increase in the prevalence of EoE. However, there is a lack of more consistent data to support this conclusion. r Herpes simplex virus Infections. The growing number of study reports shows that untreated EoE may increase the risk of herpes virus infection, although there is a lack of data explaining the associated mechanisms. r PPI. The use of PPI has already been reported to induce IgE antibodies to certain foods. Although the mere demonstration of a plausible association does not establish cause and effect, further studies on the role of acid suppression in the development of EoE are needed. An in vitro study using esophageal squamous cell culture showed that the use of PPI blocks the expression and production of eotaxin-3 induced by Th2 cytokines, suggesting its effect in reducing eosinophilic inflammation is independent of the reduction in gastric acidity.

Diagnosis guidelines Diagnostic guidelines on EoE were published in 2007 and updated in 201116 and 2018.1

Clinical diagnosis of EoE The clinical symptoms are considerably different between children and adults. In children, unspecific symptoms are presented (e.g., heartburn, nausea, vomiting, abdominal pain) in addition to dysphagia, while in adults, eating difficulties (e.g., repeated dysphagia or food impaction) are predominantly presented.13,16,18 A recent Japanese study describes symptoms in adults with EoE.6 This study gathered 886 cases, of which 469 (52.9%) had symptoms, such as dysphagia or food impaction. Heartburn or acid regurgitation was observed in 224 (25.3%),chest pain in 59 (6.7%),epigastric pain, or abdominal pain in 42 (4.7%), other symptoms in 38 (4.3%), and no symptoms in 167 (18.8%) cases. The symptoms were divided into three categories as follows: typical symptoms, such as dysphagia and food impaction, other symptoms of the gastrointestinal tract: heartburn, regurgitation, chest, and/or abdominal pain, epigastric pain, globe sensation, odynophagia, and anorexia and no symptoms found incidentally during screening or medical examinations. This same study illustrated the prevalence of EoE symptoms distributed by age groups. Chest pain or discomfort was significantly more common in the middle-aged group, anorexia was significantly more

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common in the elderly group, and the prevalence of other symptoms was similar among the age group. The most characteristic symptom of EEo was dysphagia/food impactation. Other symptoms that strongly suggested EEo were persistent heartburn and regurgitation in adults. Symptoms of gastroesophageal reflux disease (GERD) can also mimic EoE; however, both of these diseases are distinct in gene expression, response to therapy, association with allergies and histopathology.17

EoE-like disease A new EoE-like disease without tissue eosinophilia found in EoE families has been described. Study concludes that patients suffering from “EoE without eosinofilia” do not meet diagnostic criteria for EoE. However, its clinical manifestation, immunohistology, and gene expression pattern suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, appears to be just one phenotype of a broader spectrum of “inflammatory dysphagia syndrome.” As in conventional EoE, the leading symptom in all patients with EoE-like syndrome was dysphagia for solids without tissue eosinophilia found in EoE families impactions. The study evaluated the clinical characteristics of EoE phenotypes to determine predictors of these phenotypes in the natural history of EoE. Fibrostenotic, inflammatory, and mixed phenotypes were associated with clinically significant differences. Inflammatory phenotypes were more prevalent in young people and less likely to present dysphagia or food impaction. Every 10 years of increasing age, the chance of having a fibrostenotic phenotype, with risk of impaction and dysphagia more than doubles.18,19

Endoscopic diagnosis Although there is no pathognomonic endoscopic sign associated with EoE, upper endoscopy is the first step in evaluating a patient with solid food dysphagia. The role of endoscopic findings such as fixed and/or transient concentric rings, grooves or vertical streaks, edema with erasure of the vascular network, narrowing of the esophageal caliber, mucosal fragility like “crepe paper” stenoses and, as suggestive of EoE already –is well established.1,7 Fig. 10.1 showing rings and food impaction. A prospective study researched the accuracy of the EoE—Endoscopic Reference Score (EREFS) in diagnosis and determining response to treatment. A study concluded that the EREFS demonstrated good inter and intra-observer agreement, but new studies need to validate it. Table 10.1 summarizes the endoscopic aspects evaluated and grades classifications.20

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Figure 10.1 Endoscopic findings of rings (left) and food impaction (right) in eosinophilic esophagitis. Table 10.1 Endoscopic reference score (EREFS) in eosinophilic esophagitis.20 Endoscopic Grade 0 Grade 1 aspects

Exudate

Edema Furrows

Rings

Strictures a If

Grade 2

Absent Mild (covering Severe (involving 6 cm, or megaesophagus) with increased tortuosity is pathognomonic of end-stage achalasia (Fig. 13.1). In severe cases, the distal esophagus may have a sigmoid morphology that deviates from its normal axis11 (Fig. 13.2). Such anatomy imposes a significant challenge to surgeons,

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(A)

(B)

Figure 13.1 Imaging findings in late-stage achalasia. (A) Esophagram from a 62 years old with 15 years of dysphagia, no prior interventions. (B) Axial images from chest CT, same patient. On endoscopy, the esophagus was filled with liquid and mostly solid material.

especially when attempting a myotomy.12 Endoscopy should be performed to assess for neoplasia or stricture. Manometry should also be performed to confirm or rule out the diagnosis of achalasia since a prior diagnosis may not always be accurate. In fact, one of the most common causes of persistent

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(A)

(B)

(C)

Figure 13.2 Example of sigmoid esophagus. Esophagram from a 34-year-old patient s/p Heller myotomy and Dor fundoplication 8 years prior, with recurrent symptoms. Note angulation of distal esophagus. (A) AP projection. (B) Lateral projection. (C) Additional lateral projection.

dysphagia after Heller myotomy is the misdiagnosis of achalasia.6 Typical findings include aperistalsis of the esophageal body with low amplitude and partly repetitive contractions on manometry.13 This may be challenging or impossible if a massively dilated or tortuous esophagus is present.14 One case series found no particular manometric pattern in patients with end-stage achalasia and in half of the patients the tip of the catheter could not be advanced to the lower esophageal sphincter.

Decision making When other options have failed, the last resort is esophagectomy.15,16 Massive dilatation will often present with severe symptoms and predisposes patients to neoplasia, aspiration pneumonia, weight loss, respiratory symptoms, and a poor quality of life. Myotomy can be considered for mega-esophagus. Some case series have reported very high success rates in reducing dysphagia in this setting (up to 92% success) without increased complications.17 One group has reported success with myotomy with a diameter up to 12 cm.18 Data for success rates for myotomy with extremely dilated esophagus is limited, but suggests that the operation may be safe and effective at sizes > 6 cm, especially if the patient may not tolerate an esophagectomy. If other treatments fail then the progressive dilatation and tortuosity will lead to end-stage disease. Esophagectomy in appropriate patients can allow for

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alimentation to resume as well as reduce the risk of respiratory disease and neoplasia.

Preoperative optimization When reviewing diagnostic studies, prior interventions like Dor or Toupet or other types of fundoplication or endoscopic procedures should also be evaluated for effectiveness and to verify that the recurrent dysphagia is not related to a complication of the procedure, like an overly tight fundoplication. CT angiography should be obtained in the case of prior surgical interventions to assess for adequacy of gastric blood supply. If considering a colonic conduit, it is appropriate to perform preoperative CT angiography and colonoscopy to assess for adequacy of conduit and screen for neoplasia. A segment of the colon reliant on collateral blood flow via marginal arteries will be at risk of ischemia if used as a conduit. If esophageal malignancy is detected on preoperative workup then an appropriate multidisciplinary evaluation should be pursued with the consultation of radiation oncology, medical oncology, surgical oncology, pathology, radiology to determine the optimal approach to staging and management of the malignancy and endstage dysphagia. If the patient is presenting with severe weight loss surgery should be delayed to optimize nutrition, with the placement of a percutaneous or surgical jejunostomy tube. Wound healing and anastomotic integrity will both be compromised by a poor preoperative nutritional status. Even if enteral access is obtained intraoperatively or postoperatively, it is less than ideal to be correcting severe malnutrition while also recovering from esophageal surgery. A percutaneous gastrostomy may remove the option of a gastric conduit so should be avoided.

Operative approach The tortuous and distorted anatomy makes esophagectomy for dysmotility more challenging than for malignancy. Dilatation, adhesions, and robust collateral blood supply will make dissection more technically challenging when attempting to create a plane between the mediastinum and the esophagus. Prior interventions can also contribute to adhesions in the field, especially when it comes to mobilization of the esophagus near the hiatus. Both a transhiatal or transthoracic approach can be considered, but some experts favor the transthoracic approach as it is associated with less perioperative blood loss and intraoperative complications.

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The first choice of esophageal replacement is always the stomach. Gastric conduits require fewer anastomoses and tend to have a more robust and reliable blood supply. Colonic interposition can be an alternative if the gastric conduit is not feasible.A prior fundoplication or other more extensive gastric surgery may render the stomach unusable as a conduit. A colonic interposition will perhaps yield less regurgitation than a gastric conduit but may be challenged by a less reliable arterial supply, venous congestion, conduit distortion over time, intrinsic colonic pathology, such as polyps or malignancy and impaired peristalsis. Retrospective analysis has shown higher complications with nongastric conduits, higher leak rates (up to 36% for jejunal and 32% for colonic in a retrospective review19 ), increased rates of surgical site infections, pneumonia, and death. Jejunal conduits can be considered and are favored by some. In this circumstance, a long segment is needed, and augmenting the blood supply (supercharging) in the neck has led to better outcomes. The jejunum is a closer size match to a normal esophagus, is always used in an isoperistaltic fashion, does not undergo lengthening with age, and is very unlikely to have intrinsic pathology. A 10-year retrospective review of supercharged jejunal interpositions, where microvascular augmentation is performed to improve blood flow to the interposition, demonstrated intact jejunal peristalsis, and functional outcomes in many patients. However, complication rates and overall mortality were still high.20

Outcomes This is a benign disease process and yet operative mortality is up to 5.4%, comparable to that of surgery for carcinoma. This is likely multifactorial and reflects the complexity of esophagectomy, with known complication rates exceeding 50% in the best of hands.21 It is also related to the poor nutritional, functional, and respiratory status of patients who require surgery. Patients should be appropriately counseled about the risk of mortality as well as that of anastomotic leakage (up to 10% prevalence in one meta-analysis). Postoperative respiratory complications also present at a similar rate to that seen in patients who undergo esophagectomy for cancer.22

Functional long-term outcomes As has been demonstrated, esophagectomy for end-stage achalasia is by definition a last-resort treatment, making it a rare occurrence. As a result, few large volume studies exist focusing on esophagectomies for this

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specific disease process.23 They often also include patients that underwent esophagectomy for malignancy or perforation.24 However, by nature of the different disease processes, studying the long-term and functional outcomes after esophagectomy for benign disease is more applicable than in malignant disease, as most patients undergoing esophagectomy for achalasia have a much longer lifespan than those undergoing resection for esophageal cancer. The ability of an esophagectomy in relieving symptoms of the underlying disease has been shown to be high,16,25 with 75-100% of patients on an unrestricted diet one year after surgery.16 The most commonly observed longterm issues have been found to be gastroesophageal reflux symptoms (5.0%– 34.0%), dysphagia (13.5%–85.9%), anastomotic stricture requiring dilation (27.5%),16,26 dumping syndrome or delayed gastric emptying (34.0%)26 and in some cases, Barrett´s esophagus developing in the esophageal remnant.27 The wide incidence of persistent dysphagia stems from inconsistency in definition between the various studies. Most patients had significant improvement in their symptoms, with a large portion in some studies having mild symptoms that generally were shown to improve with time.26 It has been proposed that colonic interposition carries an advantage when performing an esophagectomy for end-stage achalasia where longterm results are of higher consideration, as they would have lower rates of anastomotic stricture, regurgitation, and dumping syndrome and would provide protection from chronic acid exposure to the proximal esophagus when compared to a gastric conduit.28 As has been pointed out before, colonic interposition is technically more challenging as it requires three anastomoses compared to only one when a gastric conduit is utilized. Patients with a colonic interposition have been shown to have good long-term outcomes, although 11.0% required reoperation for redundancy of the graft, whereas 89.0% had no symptoms of dysphagia.24 No study has directly compared the different options, but a meta-analysis on the long-term outcomes of the different conduits failed to identify any tangible difference.5

Conclusions Esophagectomy for end-stage achalasia is an effective and definitive treatment option but carries a high mortality rate, and functional and lifestyle changes, especially relevant when considering the benign nature of the disease. As such, it should only be performed at expert centers after careful consideration and after the exhaustion of other possible treatment options. The choice of the operative approach and reconstruction method is at the

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hand of the operating surgeon as no definitive evidence favors one over the other. Long-term outcomes are good overall and most patients ultimately have a resolution of their symptoms.

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19. Bakshi A, Sugarbaker DJ, Burt BM. Alternative conduits for esophageal replacement. Ann Cardiothorac Surg. 2017;6:137–143. 20. Blackmon SH, et al. Supercharged pedicled jejunal interposition for esophageal replacement: a 10-year experience. Ann Thorac Surg. 2012;94:1104–1111 discussion 1111–3. 21. Low DE, et al. Benchmarking complications associated with esophagectomy. Ann Surg. 2019;269:291–298. 22. Masabni K, Kandagatla P, Popoff AM, Rubinfeld I, Hammoud Z. Is esophagectomy for benign conditions benign? Ann Thorac Surg. 2018;106:368–374. 23. Torres-Landa S, Crafts TD, Jones AE, Dewey EN, Wood SG. Surgical outcomes after esophagectomy in patients with achalasia: a NSQIP matched analysis with non-achalasia esophagectomy patients. J Gastrointest Surg. 2021;25:2455–2462. 24. Greene CL, et al. Long-term quality of life and alimentary satisfaction after esophagectomy with colon interposition. Ann Thorac Surg. 2014;98:1713–1719 discussion 1719–20. 25. Felix VN. Esophagectomy for end-stage achalasia. Ann. N. Y. Acad. Sci. 2016;1381:92–97. 26. Irino T, et al. Long-term functional outcomes after replacement of the esophagus with gastric, colonic, or jejunal conduits: a systematic literature review. Dis Esophagus. 2017;30:1–11. 27. Rocha, M JR, Ribeiro U, Jr S, R AA, Szachnowicz S, Cecconello I. Barrett’s esophagus (BE) and carcinoma in the esophageal stump (ES) after esophagectomy with gastric pull-up in achalasia patients: a study based on 10 years follow-up. Ann Surg Oncol. 2008;15:2903–2909. 28. Peters JH, et al. Esophageal resection with colon interposition for end-stage achalasia. Arch Surg. 1995;130:632–636 discussion 636–7.

Index Page numbers followed by “f” and “t” indicate, figures and tables respectively.

A Achalasia, 16, 19f, 29, 30, 38, 47, 57, 67, 98 clinical presentation, 68 diagnostic evaluation, 68 dilation for, 47 endoscopic treatment, 49 epidemiology, 67 imaging spectrum of, 30 pathophysiology, 67 secondary, 30 Acquired abnormalities, 27 Acute alcohol consumption, 144 Aeroallergens, 131 Airway protection, 7 mechanisms, 7 movements of hypopharynx structures, 7 American College of Radiology Expert Panel on Gastrointestinal Imaging, 25 American Gastroenterological Association, 38 Anastomotic strictures, 46 Anemia, 16 Antineoplastics and immunosuppressants, 144 Antireflux mechanism, 14 surgery, 126 Ascorbic acid, 150 Aspirin, 149 Autonomic enteric system, 2

B Balloon dilators, 44 Barium esophagography, 38 Barium esophagram, 14, 30, 32, 70f, 122, 123f Barium swallow, 16, 18, 19f, 25, 69, 87, 89f, 106f, 162f, 162 Barrett´s esophagus, 14, 101, 122, 166, 179 Bisphosphonates, 148 Botulinum toxin, 72

Budesonide, 137

C Candida esophagitis, 145 Celiac disease, 131 Central program generator (CPG), 8 defined, 9 Chagas disease, 68 Chemotherapeutics, 149 Chest pain, 91 Clindamycin, 147 Cohesive bolus formation, 5 Connective tissue disease (CTDs), 131 Conventional manometry, 53 Corkscrew esophagus, 29 Cranial and peripheral nerves, 2 Cricopharyngeal myotomy, 111f

D DeMeester score, 14, 56, 124 Diffuse esophageal spasm (DES), 27, 29, 31f, 83, 141 Direct esophagealmucosal injury, 145 Distal contractile integral (DCI), 55, 91 Distal esophageal spasm, 62, 87 Diverticular pouch resection, 110 Diverticulectomy, 110 Dor fundoplication, 75f, 76 Dorsal swallowing group (DSG), 9 Double-contrast esophagram, 33f Doxycycline, 146 Drugs, 147t cause, 143t systemic effect of, 142t Dupilumab, 138 Dysphagia, 13, 16, 17, 26, 37, 38, 43, 57, 59, 60, 62, 68, 91, 121, 129, 141, 163 diagnosis, 17 endoscopic evaluation, 37 manometric evaluation, 53 pharmacologic causes of, 141 183

184

Index

radiologic evaluation, 25 smooth and striated muscle, 141 systemic effects of medications, 141

E Eckardt score, 18, 68 EGJ obstruction disorder, 98 Endoscopic botulinum toxin injection (EBTI), 72 Endoscopic dilatations, 125 Endoscopic diverticulostomy, 114 115f, 112 Endoscopic grading of esophagitis, 121t Endoscopic reference score (EREFS), 133, 134t Endoscopic septum division, 115 Endoscopic technique, 113 End-stage motility disorders, 173 Eosinophilic esophagitis, 38, 41, 46, 129 diagnosis of, 134 diagnostic guidelines, 132 etiopathogenesis, 130 like disease, 133 risk factors, 131 Eosinophils, 131 Epiphrenic diverticulum, 18, 22f Esophageal achalasia, 161, 170 Esophageal adenocarcinoma (EAC), 38 Esophageal cancer, 166 Esophageal dilators, 43 Esophageal diverticula, 20 Esophageal dysfunction, 153 Esophageal dysmotility, 27, 62 Esophageal dysphagia, 13 etiologies of, 39t Esophageal injury, 149 Esophageal manometry, 53, 69 Esophageal motility, 55 Esophageal motility disorders (EMD), 56, 83 Esophageal perforation, 72 Esophageal peristalsis, 7, 14 Esophageal phase, 5, 7 Esophageal pressure topography plots, 154f Esophageal strictures endoscopic dilation of, 42 Esophagectomy, 78, 169, 173, 176 Esophagogastric junction outflow obstruction, 59, 60, 84 Esophagogastroduodenoscopy (EGD), 69

Esophagography, 32 Esophagram, 25, 30, 174 Extrapyramidal motor disturbances, 144

F Facial muscles, 5 Flexible endoscope, 37, 113 Flexible esophagogastroduodenoscopy, 38 Fluticasone spray, 137 Food allergens, 131 Fragmented peristalsis, 63, 99

G Gas-forming crystals, 25 Gastric emptying study, 124 Gastroesophageal junction (GEJ), 18, 162 Gastroesophageal reflux disease (GERD), 13, 17, 28, 30f, 38, 53, 62, 71, 119, 166 clinical presentation, 121 pathophysiology of, 119 related strictures, 125 related symptoms, 121

H Head and neck midsagittal view, 2f posterior view, 3 Helicobacter pylori, 132 Heller myotomy, 76, 74f, 173 Hiatal hernia repair, 126 High-resolution manometry (HRM), 14, 19, 38, 54, 56, 83, 86f, 122, 123f Hypercontractile esophagus, 62, 91, 92f Hyper-peristaltic esophagus, 96 Hypertensive esophageal peristalsis, 91 Hypomotile disorders, 84 Hypomotility disorders, 96, 101

I Incomplete myotomy, 163 Indocyanine green (ICG) fluorescence imaging, 170 Ineffective esophageal motility (IEM), 15f, 63, 83, 98 Inflammatory myopathies, 34 Infrahyoid muscle, 4t Integrated relaxation pressure (IRP), 56, 69

Index

Invasive therapies, 37 Iron, 150

185

P

Laparoscopic hellermyotomy, 73 Lifestyle modifications, 124 Lower esophageal sphincter (LES), 15, 28, 40, 55, 67, 173

Paraesophageal hernia, 13 Penicillins, 148 Peroral endoscopic myotomy (POEM), 73 Persistent dysphagia, 163 Pharmacologic agents, 71 Pharyngeal peristalsis, 6 Pharyngeal phase, 5 Phosphodiesterase inhibitors, 93 Pneumatic dilations, 44, 72, 87, 167, 173 Polyvinyl dilators, 44 Potassium chloride, 150 Presbyesophagus, 27, 28f Pressurization front velocity (PFV), 91 Proton pump inhibitors (PPIs), 38, 130, 136 Pseudo-achalasia, 18

M

Q

Maloney-type bougie dilators, 43 Medical therapy, 93 Modified barium swallow (MBS), 26 Motility disorders, 54, 57, 57t Motor neurons, 9 Mucosal abnormalities, 25 Mucosal biopsies, 42 Mucosal defects, 145 Mucosal injury, 150 Multiphase dysphagia, 26 Multiple rapid swallows test (MRS), 99 Muscle movements, 2 Myotomy, 176

Quinidine, 150

J Jackhammer esophagus, 62, 91

K Killian–Jamieson diverticulum, 105 Killian’s triangle, 20, 107f

L

N National Health Interview Survey, 37 Neuromuscular disorders, 40 Neuromuscular (motility) disorders, 38 Nissen fundoplication, 127f, 165 Nonspecific esophageal motor disorders (NEMD), 83

O Opioid-induced esophageal dysfunction (OIED), 151, 153, 156 Oral cavity, 1 Oral propulsive phase, 5 Oropharyngeal abnormalities, 27f Oropharyngeal dysphagia, 13

R Radiologic imaging, 25 Recurrent dysphagia, 162 Redo myotomy, 168 Reflux-induced esophageal strictures, 45 Respiratory symptoms, 16 Rheumatoid arthritis, 34 Richter’s classification, 56 Rifampin, 148

S Salivary gland hypofunction, 143 Savary–Gilliard probes, 137 Schatzki rings, 46, 125 Scleroderma, 33f, 33 Secondary achalasia, 18 Sensory neurons, 9 Short myotomy, 163 “Sigmoid-shaped esophagus”, 30 Sjögren’s syndrome, 34 Smooth muscle relaxants, 71 Speech-Language Pathologist (SLP), 26 Structural disorders, 38 Super-squeezing esophagus, 91 Swallowing neurons, 9 Swallowing process, 1, 5 anatomical structures, 1

186

Index

central nervous system, 8 central program generator, 10f cortical representation, 8 distinct phases, 5 fluoroscopy, 6f neuronal network, 7 neuropharyngeal control, 9 pharyngeal phase, 7 physiology, 1 preparatory phases, 8 propulsive phases, 8 related musculature, 4t Systemic corticosteroids, 137

V

T

Z

Tachyphylaxis, 47 Tetracycline, 146 Topical corticosteroids, 136 Toupet fundoplication, 127f TTS technique, 44

Zenker’s diverticulum (ZD), 20, 21f, 105, 107f clinical features, 105 diagnosis, 105, 108 endoscopic procedures, 111 endoscopic view, 108f exposition of, 108 open transcervical approach, 109 treatment, 108 Z-POEM, 116

U Upper endoscopy, 14, 16, 18, 21, 38, 121, 162, 174 Upper esophageal sphincter, 6, 15, 55

Ventral swallowing group (VSG), 9 Videofluoroscopic swallow study, 26

W Water-perfused systems, 54 Wire-guided polyvinyl, 43 Wound healing and anastomotic integrity, 177

X Xerostomia, 143