Understanding Achalasia Overview, Workup, & Treatment

JASON K. LEE B.S. BIO & RAD, RT (R) CT RRA(ARRT), RPA(CBRPA) RADIOLOGY JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE BALTIMORE, MD Understanding Achalasia Understanding Achalasia

1) Overview 2) Cause of Achalasia 3) Symptoms of Achalasia 4) Steps in Diagnosis 5) Risks of Untreated Achalasia 6) Types of Treatment 7) Surgical Outcomes Understanding Achalasia Understanding Achalasia

Overview: Achalasia is an uncommon swallowing disorder that affects about 1 in every 100,000 people. The major symptom of Achalasia is the difficulty swallowing (dysphagia). Most people are diagnosed between the ages of 25 and 60 years of age. Achalasia can not be cured, but symptoms can be controlled with treatment including drug therapy, pneumatic dilation, and surgery. Understanding Achalasia

Cause of Achalasia: Exact cause of Achalasia is unknown. Etiology of the denervation is unknown, but viral and autoimmune causes are suspected. Motor innervation of the esophagus is predominantly by the Vagus nerve. Smooth muscle of the distal esophagus and the lower esophageal sphincter is innervated by preganglionic, cholinergic fibers that originate in the dorsal motor nucleus in the brainstem and terminate in the myenteric (Auerbach’s) plexus. Researchers believe it is secondary to degeneration or a decrease in the neurons of the myenteric plexuses (Auerbach’s plexus). Understanding Achalasia

Cause of Achalasia: Overall, Achalasia is known as a neurogenic esophageal motility disorder characterized by impaired esophageal peristalsis and the lack of lower esophageal sphincter relaxation during swallowing. Achalasia is defined as the “failure to relax”. Treatments for Achalasia are aiming at decreasing the pressure gradient of the lower esophageal sphincter thus enhancing esophageal emptying while the patient is in the upright position. Understanding Achalasia

Cause of Achalasia:

Degeneration of the dorsal motor nucleus

Loss of ganglion cells in the distal esophagus

Degeneration of vagal fibers Understanding Achalasia

Achalasia can be broken down into two types: Primary versus Secondary.

Primary achalasia (idiopathic): Unknown cause of inflammatory neuron degeneration

Secondary achalasia (pseudoachalasia): Recognized pathologic causes of esophageal motility disorders often indistinguishable from primary achalasia such as Chagas disease, Sjogren’s disease, Sarcoidosis, Scleroderma. Understanding Achalasia

According to the American College of Gastroenterology:

“Achalasia must be suspected in those with dysphagia to solids and liquids and in those with regurgitation unresponsive to an adequate trial of proton pump inhibitor (PPI) therapy (strong recommendation, low- quality evidence).” Understanding Achalasia

According to the American College of Gastroenterology Recommendations:  All patients with suspected achalasia who do not have evidence of a mechanical obstruction on endoscopy or esophagram should undergo esophageal motility testing before a diagnosis of achalasia can be confirmed (strong recommendation, low-quality evidence).  The diagnosis of achalasia is supported by esophagram findings including dilation of the esophagus, a narrow esophagogastric junction with “ bird-beak ” appearance, aperistalsis, and poor emptying of barium (strong recommendation, moderate- quality evidence).  Barium esophagram is recommended to assess esophageal emptying and esophagogastric junction morphology in those with equivocal motility testing (strong recommendation, low-quality evidence).  Endoscopic assessment of the gastroesophageal junction and gastric cardia is recommended in all patients with achalasia to rule out pseudoachalasia (strong recommendation, moderate-quality evidence). Understanding Achalasia

Normal esophageal anatomy is shown on the left with abnormal lower esophageal anatomy On the right secondary to loss of innervation in the distal esophagus which leads to dysphagia With both solids and liquids as well as esophageal distention and obstruction. Understanding Achalasia

History: 1) Sir Thomas Willis first described cardiospasm in a patient with severe swallow difficulties. In 1672, he treated a patient by dilating the LES with a curved cork-tipped whalebone with a sponge at the distal end. This was utilized to push food in the stomach at the end of each meal. He noted the problem of lower esophageal narrowing led to massive dilatation of the esophagus. 2) Not until 1929 did Hurt and Rake first realize that the primary pathophysiology resulted from a failure in LES relaxation. 3) In 1937, F.C. Lendrum proposed that failure of the lower esophageal sphincter to relax causes functional esophageal obstruction, and the name changed from cardiospasm to achalasia. Understanding Achalasia

History: 4) Dor reported his anterior partial fundoplication in 1962. 5) Toupet reported his posterior partial fundoplication in 1963. 6) Shimi and colleagues from the United Kingdom did the first Heller myotomy laparoscopically in 1991. Understanding Achalasia

History: Achalasia/Early Whale Bone Understanding Achalasia

Symptoms: Although most common symptoms is dysphagia, 1) Patients also experience the sensation of food sticking (solids or liquids) in their chest. It begins slowly and gradually worsens. 2) Atypical chest pain 3) Regurgitation of food and liquid 4) Constant heartburn 5) Inability to burp 6) Globus sensation in throat Understanding Achalasia

7) Hiccups 8) Weight loss 9) Frequent Nausea 10) Patients may also have pulmonary symptoms of cough and aspiration which can be secondary to aspiration. Understanding Achalasia

Prevalence of Symptoms in Patients With Achalasia

Presenting Symptom Patients Reporting the Symptom

Dysphagia 82%-100% Regurgitation 76%-91% Weight loss 35%-91% Chest pain 25%-64% Heartburn 27%-42% Nocturnal cough 37% Aspiration 8% Understanding Achalasia

Findings that may help in Diagnosis:

1. Chest X-ray 2. “Incidental Finding” on CT 3. Barium Swallow or Upper GI examination 4. Esophageal Manometry 5. Endoscopy Understanding Achalasia

Steps in Diagnosis: Chest X-ray

*A Chest radiograph may generally demonstrates a widen mediastinum with an air fluid level midline in the esophagus. *Anterior tracheal bowing may be present. *There may be a small or absent gastric air bubble. Understanding Achalasia

Steps in Diagnosis: Chest X-ray

Steps in Diagnosis: “Incidental Finding” on CT

*CT of the Chest may demonstrate a significantly enlarged esophagus containing residual food contents and/or fluid level. Understanding Achalasia

Steps in Diagnosis: “Incidental Finding” on CT

*CT of the Chest may demonstrate a significantly enlarged esophagus containing residual food contents and/or fluid level. Understanding Achalasia

Steps in Diagnosis: Barium Swallow/Upper GI Examination

*Examination generally reveal classic findings such as a distended esophagus with the “birds beak” appearance, as well as aperistalsis.

*Extensive dilation of the distal esophagus greater than 10cm in diameter which is tortuous in course is classified as a “Sigmoid Esophagus”. Understanding Achalasia

Known as the “Rat Tail” sign, this frontal view of a barium swallow/esophagram shows a distended distal esophagus with Tapering at the distal esophageal sphincter with only a small amount of contrast passing into the stomach. Understanding Achalasia

Steps in Diagnosis: Barium Swallow/Upper GI Examination “Timed Barium Esophagram” Patient ingests 100–250 mL of low-density barium over 30 to 45 seconds in the upright position. Three-on-1 spot radiographs are obtained at 1, 2, and 5 minutes. Healthy subjects empty this barium challenge completely over 1– 2 minutes, while most achalasia patients have residual barium in the esophagus at the end of 5 minutes. Among achalasia patients, the height of the residual barium column correlates with the severity of regurgitation and the slope of esophageal emptying from 1 to 5 minutes with the degree of dysphagia. Understanding Achalasia

Steps in Diagnosis: Classifying Achalasia Subtypes in relation to the Chicago classification system, in reference to findings based on Barium Swallow/Upper GI Examination

*More than several research papers have concluded similar findings.

Overall: *Maximal esophageal distention is demonstrated in Subtype 1 when compared to Subtype 2 and then when compared to Subtype 3. *The classic “birds beak” appearance is demonstrated in Subtype 1 and Subtype 2. *The esophagus has a corkscrew appearance and may have pulsion diverticulum in Subtype 3. Understanding Achalasia

Steps in Diagnosing: High-Resolution Esophageal Manometry (HREM) *Esophageal Manometry is the “Gold” standard for the diagnosis of esophageal motility disorders. *Involves placement of a transnasal catheter, placed with recording sites along its length (20-36 pressure sensors, placed 1 cm apart) into the stomach to measure pressure events in the esophagus after test swallows. *Color plots, referred to as pressure topography, are utilized for interpretation. *Interpretation based on Chicago classification system, Subtypes 1-3. Understanding Achalasia

Steps in Diagnosis: Esophageal Manometry: *Look for Elevated resting LES pressure, Incomplete LES relaxation, aperistalsis *Based on the Chicago Classification System: Manometry can be broken down into 3 subtypes. Understanding Achalasia

Steps in Diagnosing: Esophageal Manometry “Manometric subtypes based on Chicago Classification” 1. Type 1 Achalasia: Absence of peristalsis, no pressurization within the esophageal body, high integrated relaxation pressure 2. Type 2 Achalasia: Absence of peristalsis, and contractile activity, panesophageal pressurization > 30 mmHg, and high integrated relaxation pressure 3. Type 3 Achalasia: Absence of peristalsis, and two or more spastic contractions with or without periods of compartmentalized pressurization and a high integrated relaxation pressure Understanding Achalasia

Steps in Diagnosing: Esophageal Manometry Understanding Achalasia

Steps in Diagnosing: Barium Swallow and HREM Correlation Understanding Achalasia

Steps in Diagnosing: High-Resolution Esophageal Manometry (HREM) Understanding Achalasia

Steps of Diagnosis: High-Resolution Esophageal Manometry “Normal” after a wet swallow: Understanding Achalasia

Steps of Diagnosis: Esophageal Manometry

Type 1 “Classic” Achalasia is where there is absent peristalsis and absent contractile activity Understanding Achalasia

Steps of Diagnosis: Esophageal Manometry

Type 2 Achalasia is where there is absent peristalsis, absent contractile activity, panesophageal pressurization >30mmHg, and a high Integrated relaxation pressure Understanding Achalasia

Steps of Diagnosis: Esophageal Manometry

Type 3 Achalasia is where there is absent peristalsis, 2 or more spastic contractions with or without periods of compartmentalized pressurization, and a high Integrated relaxation pressure Understanding Achalasia

Steps of Diagnosis: Endoscopy *Primary role of Endoscopy in the workup of Achalasia is focused on ruling out a mechanical obstruction or pseudoachalasia both clinically and manometrically. *Endoscopic evaluation can also be useful in raising suspicion for the diagnosis of achalasia erroneously diagnosed with GERD. Endoscopic findings may include a dilated esophagus with retained food or saliva and a “puckered” gastroesophageal junction. *Endoscopic mucosa in achalasia may be normal; however as it becomes dilated, it is not uncommon to find inflammatory changes or ulcerations secondary to stasis, pill esophagitis, or candida infection. *Endoscopic findings at EGJ may also be associated with mild resistance. Understanding Achalasia

The Champagne Glass sign often seen in patients with history of Achalasia, is defined when the distal end of the lower esophageal sphincter relaxation Failure (LESRF) was proximal to the squamocolumnar junction (SCJ) and the SCJ was dilated in the retroflex view during endoscopy. Specifically CG-1 was defined as a distance from the SCJ to the lower end of LESRF of <1cm, and CG-2 was defined as a distance > 1 cm. The absence of the CG-0 during endoscopy cannot rule out Achalasia. Understanding Achalasia

According to the American College of Gastroenterology Recommendations:  Either graded pneumatic dilation (PD) or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy for the treatment of achalasia in those fit and willing to undergo surgery (strong recommendation, moderate-quality evidence).

 PD and surgical myotomy should be performed in high-volume centers of excellence (strong recommendation, low-quality evidence).

 The choice of initial therapy should be guided by patients’ age, gender, preference, and local institutional expertise (weak recommendation, low-quality evidence).

 Botulinum toxin therapy is recommended in patients who are not good candidates for more defi nitive therapy with PD or surgical myotomy (strong recommendation, moderate-quality evidence).

 Pharmacologic therapy for achalasia is recommended for patients who are unwilling or cannot undergo definitive treatment with either PD or surgical myotomy and have failed botulinum toxin therapy (strong recommendation, low-quality evidence). Understanding Achalasia Understanding Achalasia Understanding Achalasia

Types of Treatment: Drug Therapy *Oral pharmacologic therapies are the least effective treatment options in Achalasia. *Calcium channel blockers and long-acting nitrates are the two most common medications used to treat Achalasia. *They transiently reduce lower esophageal sphincter pressure by smooth muscle relaxation, facilitating esophageal emptying. *Overall, calcium channel blockers decrease lower esophageal sphincter pressure by 13-49% and improve patient symptoms by 0-75%. *The clinical response with pharmacologic agents is short acting and the side effects, such as headache, hypotension, and pedal edema, are common limiting factors. *Furthermore, they do not provide complete relief of symptoms. Understanding Achalasia

Types of Treatment: Pneumatic Dilatation *Pneumatic dilation is considered the most effective nonsurgical option for patients with Achalasia. *Pneumatic dilation uses air pressures to intraluminaly dilate and disrupt the circular muscle fibers of the lower esophageal sphincter. *Balloon distention to the maximum diameter endoscopically or by obliteration of the balloon waist during fluoroscopy is important in clinical effectiveness of the procedure rather than the balloon distention time. *The pressure required is usually 8-15 psi of air held for 15-60 sec. Understanding Achalasia

Types of Treatment: Pneumatic Dilatation *Studies suggest that by using the graded dilator approach, good to excellent relief of symptoms is possible in 50-93% of patients. *Cumulatively, dilation with 3.0, 3.5, and 4.0 cm balloon diameters results in good to excellent symptomatic relief in 74, 86, and 90% of patients with an average follow up of 1.6 years. *Initial dilation using a 3-cm balloon is recommended for most patients followed by symptomatic and objective assessment in 4-6 weeks. *If patients continue to be symptomatic, the next size dilator may be employed. Understanding Achalasia

Types of Treatment: Pneumatic Dilatation *In 1898, the first “pneumatic” dilation was performed by Russel. *Overall, a third of patients will experience symptom relapse over 4-6 years of follow-up. *The serial approach in pneumatic dilation may not be effective in younger males (age<45 years), possibly because of thicker LES musculature. *The most serious complication associated with pneumatic dilation is esophageal perforation. *After dilation, all patients must undergo radiographic testing by “gastrograffin” study by barium esophagram to exclude esophageal perforation. (Water Soluble Contrast Media). Understanding Achalasia

Types of Treatment: Pneumatic Dilatation Understanding Achalasia

Types of Treatment: Botox Injection *Botulinum toxin (Botox) is a potent presynaptic inhibitor of acteylcholine release from nerve endings. The toxin cleaves the protein (SNAP-25) involved in fusing presynaptic vesicles containing acetylcholine with the neuronal plasma membrane of targeted muscles. *This effect interrupts the neurogenic component of the sphincter; however , it has no effect on the myogenic influence maintaining basal LES tone. *Thus, the treatment is limited and most treatment effects are associated with an ~50% reduction in the basal LES pressure. *This reduction may be sufficient to allow esophageal emptying when esophageal pressure rises to a level where it can overwhelm the partially paralyzed LES. Understanding Achalasia

Types of Treatment: Botox Injection *This reduction may be sufficient to allow esophageal emptying when esophageal pressure rises to a level where it can overwhelm the partially paralyzed LES. *Via endoscopy, the standard approach is to place 100 units of the toxin using a sclero-needle just above the squamocolumnar junction in at least 4 quadrants. *The toxin is usually diluted in preservative-free saline and injected in 0.5-1 ml alliquots. *Doses higher than 100 units have not been shown to be more effective and the 12 month success rate ranges from 35 to 41%. Understanding Achalasia

Types of Treatment: Botox Injection *Although the initial (one-month) response rate is high (>75%), the therapeutic effect eventually wears off and repeat injection is often required in a significant portion of the patients. *Approximately 50% of patients relapse and require repeat treatments at 6-24 month intervals. *Serious side effects are uncommon and the main treatment specific issues are related to a 16-25% rate of developing chest pain and rare complications, such as mediastinitis and allergic reactions relate to egg protein. *Some evidence that injection of botulinum toxin into the LES may increase the difficulty in subsequent surgical myotomy. Understanding Achalasia

Types of Treatment: Botox Injection Understanding Achalasia

Types of Treatment: Myotomy *Historically, the treatment of achalasia by cardiomyotomy was first designed in 1901. In 1913, Heller won acclaim for the procedure by performing it abdominally on the anterior and posterior esophageal walls. *The Heller myotomy is the universally accepted surgical treatment for achalasia. * The muscle fibers of the lower esophageal sphincter are incised without disrupting the mucosal lining of the esophagus. *Patients may also develop gastroesophageal reflux after myotomy, so a Nissen fundoplication may be performed at the same time of myotomy to prevent GERD. Understanding Achalasia

Types of Treatment: Myotomy Understanding Achalasia

Types of Treatment: Peroral Endoscopy Myotomy (ePOEM) *First performed by Dr. H. Inoue at the Digestive Disease Center, Showa University, Northern Yokohama Hospital, in 2008. *POEM procedure is a relatively new less invasive procedure which can be performed by an endoscope. *An initial incision will be made in the internal lining of the esophagus which permits passage of the scope. The internal layer of the esophagus is exposed and the muscle in the lower esophagus is cut. Several endoscopic clips are then used to close the esophageal incision. Understanding Achalasia Understanding Achalasia

Type of Treatment: Achalasia Type 2 prior to ePOEM procedure Understanding Achalasia

Type of Treatment: Achalasia Type 2 Post ePOEM procedure Understanding Achalasia

Type of Treatment: Interesting Case: Esophagogastric Bypass Understanding Achalasia

Surgical Outcomes: *The Heller myotomy with a fundoplication is the optimal surgical treatment of achalasia, with effective symptom control in 90 to 97 percent of the patients. *The therapeutic endoscopic procedure POEM is safe and has a high clinical success rate at 91% at 2 years in patients. Researchers noted that the therapeutic success of POEM decreased over time as the clinical success rate of the procedure at 6 months follow-up had been 98%. Reflux is also common after POEM and can be treated with proton pump inhibitors. Understanding Achalasia

According to the American College of Gastroenterology Recommendations:

 Patient follow-up after therapy may include assessment of both symptom relief and esophageal emptying by barium esophagram (strong recommendation, low-quality evidence).

 Surveillance endoscopy for esophageal cancer is not recommended (strong recommendation, low-quality evidence). Understanding Achalasia

Risks of Untreated Achalasia: The prevalence of Esophageal Squamous Cell Carcinoma (ESSC) in subjects with esophageal achalasia is 26 in every 1000 cases, whereas the prevalence of Esophageal Adenocarcinoma (EA) is 4 in every 1000 cases. Patients with achalasia have a 50 times higher risk of presenting with ESCC than the general population, and the disease manifests 20-25 years after achalasia symptom onset. Multiple mechanisms are related to the development of ESCC in achalasia, and they include bacterial overgrowth, food stasis, genetic alterations, and chronic inflammation. Understanding Achalasia References:

 http://learningradiology.com/archives04/COW%20100- Achalasia/achalasiacorrect.htm  https://pdfs.semanticscholar.org/d3b2/251a01b6ff27ecdb9ed18643768dd10f c5af.pdf  http://www.baylorhealth.edu/Documents/BUMC%20Proceedings/1999%20V ol%2012/No.%204/12_%204_%20Vanderpool.pdf  An Overview of Achalasia and Its Subtypes. Gastroenterol Hepatol (NY). 2017 Jul; 13(7): 411–421.  https://www.vcuthoracicimaging.com/  The Diagnosis and Misdiagnosis of Achalasia: It Does Not Have to Be so Difficult. https://www.cghjournal.org/article/S1542-3565(11)00622-7/fulltext References:

 Clinical, Endoscopic, and Radiologic Features of Three Subtypes of Achalasia, Classified Using High-Resolution Manometry  Clinical Characteristics and Treatment Outcomes of 3 Subtypes of Achalasia According to the Chicago Classification in a Tertiary Institute in Korea  Chicago Classification of Esophageal Motility Disorders: Lessons Learned  http://www.annalsgastro.gr/index.php/annalsgastro/article/view/2019/1585  Presentation, Diagnosis, and Management of Achalasia  Moonen A, Boeckxstaens G. Current diagnosis and management of achalasia. J Clin Gastroenterol. 2014;48(6):484-490  Diagnosis and Management of Achalasia. https://gi.org/guideline/diagnosis- and-management-of-achalasia/  Achalasia Awareness, Dip Mukherjee, NHS Improvement and HETT Show References:

 https://www.uptodate.com/contents/surgical-myotomy-for- achalasia?source=related_link#H2199811729  https://www.mdedge.com/gihepnews/article/117437/gastroenterology/poem -procedure-effective-over-long-term-achalasia  Achalasia and esophageal cancer: risks and links. Clin Exp Gastroenterol. 2018; 11: 309–316  https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/esoph agus_stomach/swallowing_disorders.pdf Questions?