Editorial article
Achalasia. New concepts
Acalasia. Nuevos conceptos
Antonio Ruiz de León San Juan
, Julio Pérez de la Serna y Bueno
Corresponding author
Servicio de Aparato Digestivo, Hospital Clínico San Carlos, Madrid, Spain
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New concepts" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "453" "paginaFinal" => "455" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Antonio Ruiz de León San Juan, Julio Pérez de la Serna y Bueno" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Antonio" "apellidos" => "Ruiz de León San Juan" "email" => array:1 [ 0 => "aruizdeleon@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Julio" "apellidos" => "Pérez de la Serna y Bueno" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Clínico San Carlos, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Acalasia. Nuevos conceptos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Esophageal achalasia is a common motility disorder related to different diseases. It is characterized by the absence of esophageal peristalsis and incomplete or absent relaxation of the lower esophageal sphincter (LES) after swallowing. These alterations cause retention of ingested food in the esophageal lumen and cause symptoms of dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory complications (aspiration pneumonia). According to its etiological mechanism, achalasia is classified as primary or idiopathic, unrelated to any known agent, and secondary (pseudoachalasia), associated with a systemic, neuromuscular, metabolic or tumoral disease. Recently, eosinophilic esophagitis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> has been added to the many known causes of pseudoachalasia, a process that should be included in the differential diagnosis of patients with suspected achalasia and atopic history. Similarly, some reports warn about the occurrence, during chronic opioid use, of esophageal motility disorders that mimic some forms of achalasia and obstruction to the flow of the esophagogastric junction (EGJ).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Primary achalasia, in the sporadic form of the disease, is the most common, with an estimated incidence of 1/100,000 population/year and a prevalence of 10/100,000. It affects both sexes equally and can occur at any age, although it is usually diagnosed between the ages of 25 and 60.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Different hypotheses on the etiology of achalasia include infectious, genetic, autoimmune and neurodegenerative causes; also, environmental agents. The importance of the latter has been questioned in some studies,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> while the hypothesis of a chronic ganglionitis of the myenteric plexus secondary to an aberrant immune response to antigens, unknown up to now, has been gaining favor. This mainly affects neurons that are responsible for coordinating peristalsis and LES relaxation.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Different studies, usually with a small number of patients, indicate a immunogenetic predisposition for the development of idiopathic achalasia. The association of achalasia with the presence of anti-myenteric plexus antibodies and certain HLA class II<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> alleles has been described. Genes potentially involved are related to certain polymorphisms of HLA, vasoactive intestinal peptide receptor and the interleukin 10 promoter.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding the diagnosis, the most important innovation has resulted from high-resolution manometry. The availability of up to 36 recording channels–which allow greater esophageal motility behavior information–its topographical representation and a new analysis methodology developed by <span class="elsevierStyleItalic">The International High Resolution Manometry Working Group</span> have led, through different versions known as Chicago I-III-III, to a new classification of esophageal motility disorders. New parameters such as integrated relaxation pressure (IRP) and panesophageal pressurization are essential to the new assessment of achalasia. IRP is a LES relaxation index that has been defined as the average relaxation pressure of EGJ during 4 contiguous seconds or noncontiguous in the 10 seconds following swallowing. Panesophageal pressurization is defined as a uniform pressure increase which extends from the upper esophageal sphincter to the GEJ. In achalasia, the average IRP is above normal limits and the normal peristaltic activity is replaced by a uniform and simultaneous pressure increase throughout the esophageal body (panesophageal pressurization), with or without spastic contractions. Based on these criteria, three different types of achalasia with therapeutic implications have been described.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> In type I (classic achalasia), very mild pressure increases are identified in the body of the esophagus in response to swallowing; in type II, swallowing triggers pressure increases affecting the entire body of the esophagus simultaneously and in type III, there are also large-amplitude spastic contractions in ≥20% of swallowing. Identifying the phenotypes described is important because it relates to histopathology<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8,9</span></a> and therapeutic response.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In normal subjects, performing multiple rapid swallows during high resolution manometry allows to determine the inhibition of esophageal peristalsis and LES tone, followed by a powerful peristaltic contraction. This motor response requires an intact neural function, both excitatory and inhibitory. Multiple rapid swallows test in achalasia shows, little or no LES relaxation, more evident in subtypes I and II.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The samples for pathological diagnosis in achalasia are generally obtained from autopsies, esophagostomy specimens or biopsies from surgical myotomy. The degeneration of the myenteric plexus is the characteristic histopathology, mainly in LES, and with varying degrees of inflammation. Recent studies with muscle layer biopsies obtained during peroral endoscopic myotomy show atrophy and fibrosis in the muscle layer, more important in type I than in types II and III, and a significant reduction in the interstitial cells of Cajal, which seem to be preserved in type III. This subtype has virtually no muscle atrophy and a lesser degree of fibrosis.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> Nodal destruction is greater in type I compared to type II.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> These findings indicate that type I would be the final condition of the spectrum of esophageal motility disorders, or that achalasia represents a family of disorders rather than a single disease with a well-defined pathophysiological profile.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The new possibilities to advance the diagnosis and treatment of achalasia have come from the hand of a new device (EndoFLIP<span class="elsevierStyleSup">®</span>), which uses impedance planimetry to measure EGJ distensibility, generating a functional intraluminal image. This system has shown that patients with achalasia have a decreased distensibility which does not increase with expanding volumes, as in the case of healthy subjects.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> In addition, patients with type II achalasia have less distensibility and increased LES resting pressure than patients with type I achalasia.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> The use of EndoFLIP<span class="elsevierStyleSup">®</span> can help the diagnosis in patients with high suspicion of achalasia and inconclusive manometric alterations.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">As for treatment, there is, for the moment, none able to restore the esophagus's motility function; treatment of achalasia is, therefore, palliative and aims to reduce the basal LES pressure to limits in which the opposition to esophagogastric transit is minimal and until the symptoms disappear, while avoiding the occurrence of gastroesophageal reflux.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The drug therapy has not experienced significant changes in recent years; 2<span class="elsevierStyleHsp" style=""></span> of the most used drugs are nitrates and calcium channel blockers, both with limited effectiveness and frequent side effects, so their use is reserved for exceptional cases of very high-risk patients, or as a bridge to another more effective treatment.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Surgical treatment of achalasia is based on myotomy of the muscle layer of the distal esophagus and the LES. The technique has been used since 1913, when it was first described by the German surgeon Ernst Heller, with slight modifications being introduced. At present, it is generally performed laparoscopically and supplemented with a partial fundoplication to prevent reflux. Surgical myotomy obtains good results in 89% of cases (76–100%), with a variable reduction of its efficacy after 5 years, depending on the series.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Forced EGJ dilatation is the oldest treatment of achalasia. The first description of the disease and the first dilatation was made by Willis in 1674, which used a whale bone with a sponge at the end as a dilator. Since then dilator models and methodology have undergone many profound changes. Currently, it is performed by inflating a balloon in the EGJ, which causes partial rupture of the circular muscle fibers of the LES. The most commonly used balloon is Rigiflex. The available sizes range between 30 and 40<span class="elsevierStyleHsp" style=""></span>mm in diameter. Satisfactory outcome rate is around 85%.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> The therapeutic response varies between the different types described through high resolution manometry. The best results are obtained in patients with achalasia type II and the worst in type III: laparoscopic myotomy is better suited for the latter type. Results are also better in women and in patients >40 years of age.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The recent addition of impedance planimetry to dilatation (EsoFLIP<span class="elsevierStyleSup">®</span>) allows to perform a hydraulic balloon dilatation, with diameter and distensibility control, avoiding the use of radiological control.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Self-expanding metal stents as treatment for achalasia have been used by very few groups and, therefore, the experience worldwide is very limited. 30<span class="elsevierStyleHsp" style=""></span>mm diameter nitinol self-expanding metal <span class="elsevierStyleItalic">stents</span> are used, which are placed endoscopically in the GEJ and then removed on the fourth or fifth day. It has been described as a safe method, with a success rate of about 83% over 10 years.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Endoscopy-guided intra-sphincter injections of 80–100<span class="elsevierStyleHsp" style=""></span>IU botulinum toxin distributed in the 4<span class="elsevierStyleHsp" style=""></span>EGJ quadrants produces a clear reduction in LES resting pressure. However, its effects are temporary, with symptomatic recurrence in the first 6–12 months in nearly 50% of patients, which considerably limits their use.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Peroral endoscopic myotomy is a relatively new endoscopic procedure based on an esophageal mucosa incision and the creation of a submucosal tunnel which allows dissection of the circular muscle layer of about 7–8<span class="elsevierStyleHsp" style=""></span>cm along the esophageal body and up to 3<span class="elsevierStyleHsp" style=""></span>cm in the gastric lesser curvature. Incision closure is performed with endoclips.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> It is a long learning curve technique which, in expert hands, reaches therapeutic response figures of 90%. The most common complications during surgery include: subcutaneous emphysema, pneumothorax, pneumomediastinum, hemorrhage, pleural effusion, segmental atelectasis and pneumoperitoneum.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> The incidence of gastroesophageal reflux and esophagitis is superior to that reported after pneumatic dilatation or surgery. There are no long-term studies.</p><p id="par0085" class="elsevierStylePara elsevierViewall">As for future prospects, the large multicenter studies on the genome, and improvement of new diagnostic techniques will contribute to a better detection of the genetic predisposition to the disease and a more precise identification of candidates for different types of treatment subgroups. The possibility of a stem-cell treatment for neurological injury recovery is undoubtedly one of the most attractive therapeutic hypotheses.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ruiz de León San Juan A, Pérez de la Serna y Bueno J. Acalasia. Nuevos conceptos. Med Clin (Barc). 2017;148:453–455.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of achalasia and eosinophilic esophagitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Mandaliya" 1 => "A.J. DiMarino" 2 => "S. 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