Achalasia

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Peter J. Kahrilas - One of the best experts on this subject based on the ideXlab platform.

  • expert consensus document advances in the management of oesophageal motility disorders in the era of high resolution manometry a focus on Achalasia syndromes
    Nature Reviews Gastroenterology & Hepatology, 2017
    Co-Authors: Peter J. Kahrilas, Albert J Bredenoord, Mark A Fox, Prakash C Gyawali, Sabine Roman, Andre J P M Smout, John E. Pandolfino
    Abstract:

    High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular Achalasia. It has become apparent that the cardinal feature of Achalasia - impaired lower oesophageal sphincter (LES) relaxation - can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for Achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting Achalasia criteria that also benefit from therapies formerly reserved for Achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic Achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of Achalasia and Achalasia-like syndromes.

  • the functional lumen imaging probe detects esophageal contractility not observed with manometry in patients with Achalasia
    Gastroenterology, 2015
    Co-Authors: Dustin A Carlson, Peter J. Kahrilas, Zhiyue Lin, Joel M Sternbach, Erica Donnan, Laurel Friesen, Zoe Listernick, Benjamin Mogni, John E. Pandolfino
    Abstract:

    Background & Aims The functional lumen imaging probe (FLIP) could improve the characterization of Achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with Achalasia using FLIP topography. Methods Fifty-one treatment-naive patients with Achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Results Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I Achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II Achalasia. Contractility was detected in all 10 patients with type III Achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with Achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II Achalasia. These findings could have implications for additional subclassification to supplement prediction of the Achalasia disease course.

  • the spectrum of Achalasia lessons from studies of pathophysiology and high resolution manometry
    Gastroenterology, 2013
    Co-Authors: Peter J. Kahrilas, G E Boeckxstaens
    Abstract:

    High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of Achalasia. It has become apparent that the cardinal feature of Achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate Achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific. Laboratory studies indicate that Achalasia is an autoimmune disease in which esophageal myenteric neurons are attacked in a cell-mediated and antibody-mediated immune response against an uncertain antigen. This autoimmune response could be related to infection of genetically predisposed subjects with herpes simplex virus 1, although there is substantial heterogeneity among patients. At one end of the spectrum is complete aganglionosis in patients with end-stage or fulminant disease. At the opposite extreme is type III (spastic) Achalasia, which has no demonstrated neuronal loss but only impaired inhibitory postganglionic neuron function; it is often associated with accentuated contractility and could be mediated by cytokine-induced alterations in gene expression. Distinct from these extremes is progressive plexopathy, which likely arises from Achalasia with preserved peristalsis and then develops into type II Achalasia and then type I Achalasia. Variations in its extent and rate of progression are likely related to the intensity of the cytotoxic T-cell assault on the myenteric plexus. Moving forward, we need to integrate the knowledge we have gained into treatment paradigms that are specific for individual phenotypes of Achalasia and away from the one-size-fits-all approach.

  • a comparison of symptom severity and bolus retention with chicago classification esophageal pressure topography metrics in patients with Achalasia
    Clinical Gastroenterology and Hepatology, 2013
    Co-Authors: Frederic Nicodeme, Annemijn De Ruigh, Yinglian Xiao, Shankar Rajeswaran, Ezra N Teitelbaum, Eric S Hungness, Peter J. Kahrilas
    Abstract:

    Background & Aims We compared findings from timed barium esophagrams (TBEs) and esophageal pressure topography studies among Achalasia subtypes and in relation to symptom severity. Methods We analyzed data from 50 patients with Achalasia (31 men; age, 20–79 y) who underwent high-resolution manometry (HRM), had TBE after a 200-mL barium swallow, and completed questionnaires that determined Eckardt Scores. Twenty-five patients were not treated, and 25 patients were treated (11 by pneumatic dilation, 14 by myotomy). Nonparametric testing was used to assess differences among groups of treated patients (10 had type 1 Achalasia and 15 had type 2 Achalasia), and the Pearson correlation was used to assess their relationship. Results There were no significant differences in TBE measurements between patient groups. Of the 25 patients who received treatment, 10 had a manometric pattern consistent with persistent Achalasia after treatment (6 patients with type 1 and 4 patients with type 2 Achalasia), whereas 15 appeared to have resolved the Achalasia pattern (peristalsis was absent in 8 patients and weak in 7 patients). The height of the barium column at 5 minutes and Eckardt Scores were reduced significantly in patients who had resolved their Achalasia pattern, based on HRM. The integrated relaxation pressure and the TBE column height correlated at 5 minutes (r = 0.422; P Conclusions Patients who resolved their Achalasia pattern, based on HRM, showed improved emptying based on TBE measurements and improved symptom scores. There was no significant difference between patients with type 1 or type 2 Achalasia in TBEs. These findings indicate that normalization of the integrated relaxation pressure on HRM is a clinically relevant objective of treatment for Achalasia.

  • Achalasia a new clinically relevant classification by high resolution manometry
    Gastroenterology, 2008
    Co-Authors: John E. Pandolfino, Thomas B. Nealis, Jennifer Post, Monika A Kwiatek, William J Bulsiewicz, Peter J. Kahrilas
    Abstract:

    Background & Aims: 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. Methods: 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. Results: Ninetynine 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. Conclusions: 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.

John E. Pandolfino - One of the best experts on this subject based on the ideXlab platform.

  • expert consensus document advances in the management of oesophageal motility disorders in the era of high resolution manometry a focus on Achalasia syndromes
    Nature Reviews Gastroenterology & Hepatology, 2017
    Co-Authors: Peter J. Kahrilas, Albert J Bredenoord, Mark A Fox, Prakash C Gyawali, Sabine Roman, Andre J P M Smout, John E. Pandolfino
    Abstract:

    High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular Achalasia. It has become apparent that the cardinal feature of Achalasia - impaired lower oesophageal sphincter (LES) relaxation - can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for Achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting Achalasia criteria that also benefit from therapies formerly reserved for Achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic Achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of Achalasia and Achalasia-like syndromes.

  • the functional lumen imaging probe detects esophageal contractility not observed with manometry in patients with Achalasia
    Gastroenterology, 2015
    Co-Authors: Dustin A Carlson, Peter J. Kahrilas, Zhiyue Lin, Joel M Sternbach, Erica Donnan, Laurel Friesen, Zoe Listernick, Benjamin Mogni, John E. Pandolfino
    Abstract:

    Background & Aims The functional lumen imaging probe (FLIP) could improve the characterization of Achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with Achalasia using FLIP topography. Methods Fifty-one treatment-naive patients with Achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Results Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I Achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II Achalasia. Contractility was detected in all 10 patients with type III Achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with Achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II Achalasia. These findings could have implications for additional subclassification to supplement prediction of the Achalasia disease course.

  • Achalasia a new clinically relevant classification by high resolution manometry
    Gastroenterology, 2008
    Co-Authors: John E. Pandolfino, Thomas B. Nealis, Jennifer Post, Monika A Kwiatek, William J Bulsiewicz, Peter J. Kahrilas
    Abstract:

    Background & Aims: 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. Methods: 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. Results: Ninetynine 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. Conclusions: 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.

Marinello, Franco Guillermo - One of the best experts on this subject based on the ideXlab platform.

  • Abordaje Laparoscópico de la Acalasia. Análisis clínico, de calidad de vida y funcional
    'Universitat Autonoma de Barcelona', 2013
    Co-Authors: Marinello, Franco Guillermo
    Abstract:

    INTRODUCCIÓN La Acalasia es un trastorno esofágico primario con etiología desconocida. Por posibles causas genéticas, virales o autoinmunes, existe una inflamación mioentérica que conlleva a una destrucción neuronal inhibitoria. Esta destrucción tiene como resultado final la falla de relajación del EEI y la aperistalsis esofágica. Existen diversos tratamientos para tratar la Acalasia, ninguno de ellos curativo. La miotomía de Heller demostró ser el tratamiento con mejores resultados a largo plazo. PACIENTES Y METODOS Se realizó un estudio retrospectivo observacional de los pacientes con Acalasia esofágica primaria intervenidos por laparoscopia desde Octubre de 1998 a Diciembre de 2010. Todos los pacientes fueron diagnosticados por sospecha clínica y manometría confirmatoria. Los pacientes valoraron su sintomatología y calidad de vida preoperatoriamente. Se realizaron 2 controles postoperatorios: uno en el año 2003 que incluyó a los primeros pacientes intervenidos hasta esa fecha y otro durante los años 2010-11 que incluyó a todos los pacientes de la serie. Las variables del estudio fueron: a) Tiempo de seguimiento desde la intervención hasta el control realizado en el año 2010-11. Se realizaron 2 subanálisis: Por un lado, los pacientes fueron separados en 3 grupos (seguimiento entre 6 y 47 meses, 48 y 119 meses y más de 120 meses). Por otro lado, se separaron a todos los pacientes que habían tenido un control en el año 2003. A ellos se los comparó prospectivamente con los datos obtenidos en el control realizado en el año 2010-11. b) Edad del paciente al momento de la cirugía. c) Tiempo de evolución de la enfermedad al momento de la cirugía. d) Diámetro esofágico preoperatorio. e) Existencia de tratamiento endoscópico previo a la cirugía. En los controles postoperatorios se realizó una nueva evaluación clínica y de calidad de vida de los pacientes. Además se indicó una nueva manometría y pHmetría postoperatoria. RESULTADOS Se intervinieron a 95 pacientes, de los cuales 76 estuvieron disponibles para el control. El 55% fueron hombres y el 45% mujeres con una edad promedio de 45 años. La evolución de los síntomas fue de 52 meses hasta la cirugía y un 26% de pacientes habían recibido tratamiento endoscópico previo. Se apreció un 3% de perforación esofágica, un 2% de conversión y un 3% de morbilidad con mortalidad nula. Según el tiempo de seguimiento, se apreció una franca mejoría de los síntomas clínicos analizados en todos los grupos de menor, mediano y mayor plazo de seguimiento. La calidad de vida alcanzó niveles óptimos con respecto a los valores preoperatorios. Las presiones esfinterianas bajaron a niveles normales en los 3 grupos y se detectó un 10% de incidencia de reflujo gastro-esofágico (RGE). En el grupo de pacientes controlado prospectivamente, se evidenció que la sintomatología mejora a corto plazo pero que en el seguimiento a más de 10 años se deteriora progresivamente. La calidad de vida y las presiones esfinterianas se mantienen en niveles normales en ambos controles sin mayor incidencia de RGE a largo plazo. No se apreciaron diferencias en los resultados según las variables edad, tiempo de evolución de la enfermedad, diámetro esofágico preoperatorio y presencia de tratamiento endoscópico previo a la cirugía. Se detectaron un 10% de fracasos terapéuticos sin encontrar ninguna causa predisponente en el estudio estadístico inferencial. CONCLUSIONES El abordaje laparoscópico de la Acalasia ofrece mejoría sintomatológica y de calidad de vida con descenso de las presiones esfinterianas con una incidencia de RGE aceptable. Existe un empeoramiento de la sintomatología a largo plazo. Es un abordaje que puede ofrecerse a pacientes a cualquier edad, tiempo de evolución de la enfermedad, diámetro esofágico, e incluso con la presencia de tratamientos endoscópicos previos.INTRODUCTION Achalasia is a benign primary esophageal disorder. There is inflammation of the myoenteric plexus due to genetic, viral or autoimmune regulations, leading to destruction of the inhibitory neuronal circuits in the esophagus. The outcome of this inflammatory response is the lack of relaxation of the lower esophageal sphincter (LES) and esophageal aperistalsis. There are many treatment options for Achalasia, none curative. Heller myotomy has provided excellent long-term results and is the most suitable option. PATIENTS AND METHODS A retrospective observational study was performed with all the patients with primary esophageal Achalasia operated of laparoscopic Heller myotomy between October 1998 and December 2012. All patients were diagnosed of Achalasia due to clinical suspicion and confirmatory manometry, assessing their clinical status and quality of life preoperatively. Two postoperative controls were performed. The first control was in 2003 and included the first patients operated up to that year. The second control was done in 2010-11 and included all the patients of the series. The variables of the study were: a) Follow-up time from the surgery to the control performed in the years 2010-11. The patients were separated into 3 groups (follow up from 6 to 47 months, 48 to 119 months and more than 120 months). A prospective subanalysis was performed with the patients who had a control in 2003 and 2010-11. b) Patient's age at the moment of surgery. c) Evolution time from the onset of symptoms to surgery. d) Preoperative esophageal diameter e) Indication of endoscopic treatment prior to surgery. A new clinical and quality of life evaluation was performed postoperatively. Moreover, a postoperative manometry and esophageal pH monitoring were indicated. RESULTS Ninety-five patients underwent laparoscopic Heller myotomy. Seventy-six (80%) were available for follow-up. Evolution time of symptoms to surgery was 52 months and 26% of patients had had previous endoscopic treatment. There were a 3% of esophageal perforations, 2% of conversion to open surgery and 3% of morbidity with no mortality. According to the follow-up time, all groups improved the clinical symptoms analyzed. Quality of life scores improved after surgery. Manometric determinations showed normal LES pressures after myotomy in the 3 groups. Ten percent of overall 24-hour pH monitoring was abnormal. The group of patients followed up in 2003 and in 2011 showed a slight symptomatic deterioration with no impairment in quality of life and functional studies in the long term. There were no differences in the results when the other variables were analyzed (patient's age, evolution time of disease, esophageal diameter and previous endoscopic treatments). A 10% rate of therapeutic failures was detected. There was no preoperative predisponent cause of treatment failure in the statistical analysis. CONCLUSIONS The laparoscopic approach to Achalasia provides improvement in the clinical status and quality of life with reduction of lower esophageal sphincteric pressures and an acceptable rate of gastroesophageal reflux at short, medium and long-term follow-up. There is a slight deterioration of the symptoms in the long-term. It is a procedure that can be performed at any patient's age, evolution time of disease, esophageal diameter or even with previous endoscopic treatments

  • Abordaje laparoscópico de la acalasia análisis clínico, de calidad de vida y funcional /
    Bellaterra : Universitat Autònoma de Barcelona, 2013
    Co-Authors: Marinello, Franco Guillermo, Universitat Autònoma De Barcelona. Departament De Cirurgia
    Abstract:

    INTRODUCCIÓN La Acalasia es un trastorno esofágico primario con etiología desconocida. Por posibles causas genéticas, virales o autoinmunes, existe una inflamación mioentérica que conlleva a una destrucción neuronal inhibitoria. Esta destrucción tiene como resultado final la falla de relajación del EEI y la aperistalsis esofágica. Existen diversos tratamientos para tratar la Acalasia, ninguno de ellos curativo. La miotomía de Heller demostró ser el tratamiento con mejores resultados a largo plazo. PACIENTES Y METODOS Se realizó un estudio retrospectivo observacional de los pacientes con Acalasia esofágica primaria intervenidos por laparoscopia desde Octubre de 1998 a Diciembre de 2010. Todos los pacientes fueron diagnosticados por sospecha clínica y manometría confirmatoria. Los pacientes valoraron su sintomatología y calidad de vida preoperatoriamente. Se realizaron 2 controles postoperatorios: uno en el año 2003 que incluyó a los primeros pacientes intervenidos hasta esa fecha y otro durante los años 2010-11 que incluyó a todos los pacientes de la serie. Las variables del estudio fueron: a) Tiempo de seguimiento desde la intervención hasta el control realizado en el año 2010-11. Se realizaron 2 subanálisis: Por un lado, los pacientes fueron separados en 3 grupos (seguimiento entre 6 y 47 meses, 48 y 119 meses y más de 120 meses). Por otro lado, se separaron a todos los pacientes que habían tenido un control en el año 2003. A ellos se los comparó prospectivamente con los datos obtenidos en el control realizado en el año 2010-11. b) Edad del paciente al momento de la cirugía. c) Tiempo de evolución de la enfermedad al momento de la cirugía. d) Diámetro esofágico preoperatorio. e) Existencia de tratamiento endoscópico previo a la cirugía. En los controles postoperatorios se realizó una nueva evaluación clínica y de calidad de vida de los pacientes. Además se indicó una nueva manometría y pHmetría postoperatoria. RESULTADOS Se intervinieron a 95 pacientes, de los cuales 76 estuvieron disponibles para el control. El 55% fueron hombres y el 45% mujeres con una edad promedio de 45 años. La evolución de los síntomas fue de 52 meses hasta la cirugía y un 26% de pacientes habían recibido tratamiento endoscópico previo. Se apreció un 3% de perforación esofágica, un 2% de conversión y un 3% de morbilidad con mortalidad nula. Según el tiempo de seguimiento, se apreció una franca mejoría de los síntomas clínicos analizados en todos los grupos de menor, mediano y mayor plazo de seguimiento. La calidad de vida alcanzó niveles óptimos con respecto a los valores preoperatorios. Las presiones esfinterianas bajaron a niveles normales en los 3 grupos y se detectó un 10% de incidencia de reflujo gastro-esofágico (RGE). En el grupo de pacientes controlado prospectivamente, se evidenció que la sintomatología mejora a corto plazo pero que en el seguimiento a más de 10 años se deteriora progresivamente. La calidad de vida y las presiones esfinterianas se mantienen en niveles normales en ambos controles sin mayor incidencia de RGE a largo plazo. No se apreciaron diferencias en los resultados según las variables edad, tiempo de evolución de la enfermedad, diámetro esofágico preoperatorio y presencia de tratamiento endoscópico previo a la cirugía. Se detectaron un 10% de fracasos terapéuticos sin encontrar ninguna causa predisponente en el estudio estadístico inferencial. CONCLUSIONES El abordaje laparoscópico de la Acalasia ofrece mejoría sintomatológica y de calidad de vida con descenso de las presiones esfinterianas con una incidencia de RGE aceptable. Existe un empeoramiento de la sintomatología a largo plazo. Es un abordaje que puede ofrecerse a pacientes a cualquier edad, tiempo de evolución de la enfermedad, diámetro esofágico, e incluso con la presencia de tratamientos endoscópicos previos.INTRODUCTION Achalasia is a benign primary esophageal disorder. There is inflammation of the myoenteric plexus due to genetic, viral or autoimmune regulations, leading to destruction of the inhibitory neuronal circuits in the esophagus. The outcome of this inflammatory response is the lack of relaxation of the lower esophageal sphincter (LES) and esophageal aperistalsis. There are many treatment options for Achalasia, none curative. Heller myotomy has provided excellent long-term results and is the most suitable option. PATIENTS AND METHODS A retrospective observational study was performed with all the patients with primary esophageal Achalasia operated of laparoscopic Heller myotomy between October 1998 and December 2012. All patients were diagnosed of Achalasia due to clinical suspicion and confirmatory manometry, assessing their clinical status and quality of life preoperatively. Two postoperative controls were performed. The first control was in 2003 and included the first patients operated up to that year. The second control was done in 2010-11 and included all the patients of the series. The variables of the study were: a) Follow-up time from the surgery to the control performed in the years 2010-11. The patients were separated into 3 groups (follow up from 6 to 47 months, 48 to 119 months and more than 120 months). A prospective subanalysis was performed with the patients who had a control in 2003 and 2010-11. b) Patient's age at the moment of surgery. c) Evolution time from the onset of symptoms to surgery. d) Preoperative esophageal diameter e) Indication of endoscopic treatment prior to surgery. A new clinical and quality of life evaluation was performed postoperatively. Moreover, a postoperative manometry and esophageal pH monitoring were indicated. RESULTS Ninety-five patients underwent laparoscopic Heller myotomy. Seventy-six (80%) were available for follow-up. Evolution time of symptoms to surgery was 52 months and 26% of patients had had previous endoscopic treatment. There were a 3% of esophageal perforations, 2% of conversion to open surgery and 3% of morbidity with no mortality. According to the follow-up time, all groups improved the clinical symptoms analyzed. Quality of life scores improved after surgery. Manometric determinations showed normal LES pressures after myotomy in the 3 groups. Ten percent of overall 24-hour pH monitoring was abnormal. The group of patients followed up in 2003 and in 2011 showed a slight symptomatic deterioration with no impairment in quality of life and functional studies in the long term. There were no differences in the results when the other variables were analyzed (patient's age, evolution time of disease, esophageal diameter and previous endoscopic treatments). A 10% rate of therapeutic failures was detected. There was no preoperative predisponent cause of treatment failure in the statistical analysis. CONCLUSIONS The laparoscopic approach to Achalasia provides improvement in the clinical status and quality of life with reduction of lower esophageal sphincteric pressures and an acceptable rate of gastroesophageal reflux at short, medium and long-term follow-up. There is a slight deterioration of the symptoms in the long-term. It is a procedure that can be performed at any patient's age, evolution time of disease, esophageal diameter or even with previous endoscopic treatments

Michel Neunlist - One of the best experts on this subject based on the ideXlab platform.

  • serum from Achalasia patients alters neurochemical coding in the myenteric plexus and nitric oxide mediated motor response in normal human fundus
    Gut, 2006
    Co-Authors: Bruley Des S Varannes, J Chevalier, S Pimont, Jc Le Neel, Markus Klotz, Kh Schafer, J P Galmiche, Michel Neunlist
    Abstract:

    Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of Achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with Achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of Achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from Achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from Achalasia patients showed a decrease in the proportion of NOS (−26% of NSE positive neurones; p = 0.016) and VIP (−54%; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+16%; p v −14.5 (5.0); p = 0.036). Conclusions: Serum from Achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in Achalasia.

M A Valdovinos - One of the best experts on this subject based on the ideXlab platform.

  • gelatinase b matrix metalloproteinase 9 as innate immune effector molecule in Achalasia
    Clinical and translational gastroenterology, 2018
    Co-Authors: Janette Furuzawacarballeda, Gonzalo Torresvillalobos, Lise Boon, Fernanda Romerohernandez, Estefania Ugarteberzal, Erik Martens, Jennifer Vandooren, Vasily Rybakin, Enrique Cossadame, M A Valdovinos
    Abstract:

    Objectives Achalasia is a primary esophageal motility disorder resulting from selective loss of inhibitory neurons in the esophageal myenteric plexus, likely due to an autoimmune response with involvement of the adaptive immune system. Innate immune processes of the host constitute the bridge between environmental etiological factors and the adaptive immune system. Although these remain poorly investigated, they might be of diagnostic and therapeutic relevance. In view of the role of extracellular proteolysis in organ-specific autoimmunity, we studied gelatinases of the matrix metalloproteinase (MMP) family in Achalasia patients. Methods The presence of MMP-2 and MMP-9 proteoforms was analyzed in sera of two cohorts of Achalasia patients. Additionally, with the use of immunohistopathological analysis, in situ MMP-2 and MMP-9 expression was investigated. Finally, we tested the paradigm of remnant epitopes generating autoimmunity (REGA) for Achalasia-associated autoantigens by evaluating whether autoantigenic proteins are cleaved by MMP-9 into remnant epitopes. Results We showed significantly increased ratios of MMP-9/MMP-2 and activated MMP-9/proMMP-9 in sera of Achalasia patients (n = 88) versus controls (n = 60). MMP-9-positive and MMP-2-positive cells were more abundant in Achalasia (n = 49) versus control biopsies from transplant donors (n = 10). Furthermore, extensive damage within the plexus was found in the tissues with more MMP-9-positive cells. Additionally, we documented Achalasia-associated autoantigens PNMA2, Ri, GAD65, and VIP as novel MMP-9 substrates. Conclusions We provide new biomarkers and insights into innate immune mechanisms in the autoimmune pathology of Achalasia. Our results imply that extracellular protease inhibition is worthwhile to test as therapeutic intervention in Achalasia.