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Management of Achalasia: A Practical Guide
Abstract
Achalasia is a rare disorder of the esophagus caused by inflammation and subsequent degeneration of the ganglion cells of the myenteric plexus of the esophageal wall. This results in failure of the lower esophageal sphincter to relax with a loss of functional peristalsis in the lower esophagus. Achalasia is diagnosed by clinical symptoms, imaging, endoscopy, and manometric findings. For good surgical candidates, laparoscopic esophageal myotomy is the preferred therapeutic intervention. Patients can also be given the option of pneumatic dilation. Pharmacologic therapies are reserved for high-risk surgical candidates, in the form of endoscopic injections of botulinum toxin or oral medications, including calcium channel blockers, long-acting nitrates, or the phosphodiesterase-5 inhibitor, sildenafil.
Diseases affecting the esophagus are common. However, targeted drug delivery to the esophagus is challenging due to the anatomy and physiology of this organ. Current pharmacological treatment for esophageal diseases predominantly relies on the off-label use of drugs in various dosage forms, including those for systemic drug delivery (e.g. oral tablets, sublingual tablets, and injections) and topical drug delivery (e.g. metered dose inhaler, viscous solution or suspension, and endoscopic injection into the esophagus). In general, systemic therapy has shown the most efficacy but requires the use of high drug doses to achieve effective concentrations in the esophagus, which increases the risk of adverse effects and toxicity. Topical drug delivery has enormous potential in improving the way we treat patients with acute and chronic esophageal diseases, especially those requiring drugs that have low therapeutic index and/or significant adverse effects to non-targeted organs and tissues. This review will address the physiological, pathophysiological, and pharmaceutical considerations influencing topical drug delivery in the esophagus. The main conventional (e.g. liquid formulations, orodispersible tablets, lozenges, pastilles, troches, chewing gum) and innovative (e.g. stent-based, film-based, nanoparticulate-based) drug delivery approaches will be comprehensively discussed, along with the developments to improve their effectiveness for topical esophageal drug delivery. The translational challenges and future clinical advances of this research will also be discussed.
Achalasia significantly affects patients' quality of life and can be difficult to diagnose and treat.
To review the diagnosis and management of achalasia, with a focus on phenotypic classification pertinent to therapeutic outcomes.
Literature review and MEDLINE search of articles from January 2004 to February 2015. A total of 93 articles were included in the final literature review addressing facets of achalasia epidemiology, pathophysiology, diagnosis, treatment, and outcomes. Nine randomized controlled trials focusing on endoscopic or surgical therapy for achalasia were included (734 total patients).
A diagnosis of achalasia should be considered when patients present with dysphagia, chest pain, and refractory reflux symptoms after an endoscopy does not reveal a mechanical obstruction or an inflammatory cause of esophageal symptoms. Manometry should be performed if achalasia is suspected. Randomized controlled trials support treatments focused on disrupting the lower esophageal sphincter with pneumatic dilation (70%-90% effective) or laparoscopic myotomy (88%-95% effective). Patients with achalasia have a variable prognosis after endoscopic or surgical myotomy based on subtypes, with type II (absent peristalsis with abnormal pan-esophageal high-pressure patterns) having a very favorable outcome (96%) and type I (absent peristalsis without abnormal pressure) having an intermediate prognosis (81%) that is inversely associated with the degree of esophageal dilatation. In contrast, type III (absent peristalsis with distal esophageal spastic contractions) is a spastic variant with less favorable outcomes (66%) after treatment of the lower esophageal sphincter.
Achalasia should be considered when dysphagia is present and not explained by an obstruction or inflammatory process. Responses to treatment vary based on which achalasia subtype is present.
With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.
Peroral endoscopic myotomy (POEM) is an evolving therapeutic modality for achalasia. We aim to determine efficacy of POEM for the treatment of achalasia and compare it with laparoscopic Heller's myotomy (LHM).
Systematic review and meta-analyses was conducted on 19 studies using POEM for achalasia. Pubmed, Medline, Cochrane, and Ovid databases, were searched using the terms 'achalasia', 'POEM', 'peroral endoscopic myotomy', 'per oral endoscopic myotomy', and 'per-oral endoscopic myotomy'. Reduction in Eckhart's score and lower esophageal sphincter (LES) pressure were the main outcome measures.
A total of 1,045 patients underwent POEM in 29 studies. Ninety patients undergoing POEM was compared with 160 undergoing LHM in five studies. Nineteen and 14 studies, respectively, evaluated for Eckhart's score and LES pressure. There was significant reduction in Eckhart's score and LES pressure with effect sizes of -7.95 (p < 0.0001) and -7.28 (p < 0.0001), respectively. There was significant heterogeneity among the studies [(Q = 83.06; I (2) = 78.33 %; p < 0.0001) for Eckhart's score and (Q = 61.44; I (2) = 75.68 %; p < 0.0001) for LES pressure]. There were no differences between POEM and LHM in reduction in Eckhart's score, post-operative pain scores and analgesic requirements, length of hospital stay, adverse events, and symptomatic gastroesophageal reflux/reflux esophagitis. Operative time was significantly lower for POEM.
POEM is effective for achalasia and has similar outcomes as LHM. Multicenter randomized trials need to be conducted to further compare the efficacy and safety of POEM between treatment naïve achalasia patients and those who failed treatment.
The Chicago Classification (CC) of esophageal motility disorders, utilizing an algorithmic scheme to analyze clinical high-resolution manometry (HRM) studies, has gained acceptance worldwide.
This 2014 update, CC v3.0, developed by the International HRM Working Group, incorporated the extensive clinical experience and interval publications since the prior (2011) version.
Chicago Classification v3.0 utilizes a hierarchical approach, sequentially prioritizing: (i) disorders of esophagogastric junction (EGJ) outflow (achalasia subtypes I-III and EGJ outflow obstruction), (ii) major disorders of peristalsis (absent contractility, distal esophageal spasm, hypercontractile esophagus), and (iii) minor disorders of peristalsis characterized by impaired bolus transit. EGJ morphology, characterized by the degree of overlap between the lower esophageal sphincter and the crural diaphragm and baseline EGJ contractility are also part of CC v3.0. Compared to the previous CC version, the key metrics of interpretation, the integrated relaxation pressure (IRP), the distal contractile integral (DCI), and the distal latency (DL) remain unchanged, albeit with much more emphasis on DCI for defining both hypo- and hypercontractility. New in CC v3.0 are: (i) the evaluation of the EGJ at rest defined in terms of morphology and contractility, (ii) 'fragmented' contractions (large breaks in the 20-mmHg isobaric contour), (iii) ineffective esophageal motility (IEM), and (iv) several minor adjustments in nomenclature and defining criteria. Absent in CC v3.0 are contractile front velocity and small breaks in the 20-mmHg isobaric contour as defining characteristics.
Chicago Classification v3.0 is an updated analysis scheme for clinical esophageal HRM recordings developed by the International HRM Working Group.
© 2014 John Wiley & Sons Ltd.
Achalasia is a primary motor disorder of the esophagus characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. This results in patients' complaints of dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. Endoscopic finding of retained saliva with puckered gastroesophageal junction or barium swallow showing dilated esophagus with birds beaking in a symptomatic patient should prompt appropriate diagnostic and therapeutic strategies. In this ACG guideline the authors present an evidence-based approach in patients with achalasia based on a comprehensive review of the pertinent evidence and examination of relevant published data.Am J Gastroenterol advance online publication, 23 July 2013; doi:10.1038/ajg.2013.196.
Achalasia (Ach), diffuse esophageal spasm (DES), nutcracker esophagus (NE), and nonspecific motility disorder (NSMD) are described primary esophageal body motility disorders; however, their clinical symptom correlation is poorly understood. The aim of this study is to examine the association between a patient's presenting symptoms and their manometric diagnosis.
Manometric findings and reported symptoms of all patients undergoing esophageal manometry at the Creighton University Medical Center were prospectively entered in a database. Twenty-four-year data from 1984 through 2008 were accessed and analyzed.
Of the 4,215 patients, 130 (3.1%) had Ach, 192 (4.6%) had DES, 290 (6.9%) had NE, 508 (12.1%) had NSMD, and 3,095 (73.4%) had normal esophageal body motility. There was significant symptom overlap between the groups. Ach and DES had a similar symptom distribution, with dysphagia being the predominant symptom. Patients with NE, normal body motility, and NSMD presented predominantly with reflux symptoms. There was an increasing prevalence of esophageal dysmotility (DES and NSMD) with age, and women were found to be more likely to have NE than men.
In an individual, reported symptoms do not correlate with their manometric diagnosis in a predictable fashion, and a thorough physiological assessment should be obtained to understand and diagnose the disease process. Esophageal motility deteriorates with age.
Although the diagnosis of achalasia hinges on demonstrating impaired esophagogastric junction (EGJ) relaxation and aperistalsis, 3 distinct patterns of aperistalsis are discernable with high-resolution manometry (HRM). This study aimed to compare the clinical characteristics and treatment response of these 3 subtypes.
One thousand clinical HRM studies were reviewed, and 213 patients with impaired EGJ relaxation were identified. These were categorized into 4 groups: achalasia with minimal esophageal pressurization (type I, classic), achalasia with esophageal compression (type II), achalasia with spasm (type III), and functional obstruction with some preserved peristalsis. Clinical and manometric variables including treatment response were compared among the 3 achalasia subtypes. Logistic regression analysis was performed using treatment success as the dichotomous dependent variable controlling for independent manometric and clinical variables.
Ninety-nine patients were newly diagnosed with achalasia (21 type I, 49 type II, 29 type III), and 83 of these had sufficient follow-up to analyze treatment response. Type II patients were significantly more likely to respond to any therapy (BoTox [71%], pneumatic dilation [91%], or Heller myotomy [100%]) than type I (56% overall) or type III (29% overall) patients. Logistic regression analysis found type II to be a predictor of positive treatment response, whereas type III and pretreatment esophageal dilatation were predictive of negative treatment response.
Achalasia can be categorized into 3 subtypes that are distinct in terms of their responsiveness to medical or surgical therapies. Utilizing these subclassifications would likely strengthen future prospective studies of treatment efficacy in achalasia.