Idiopathic Achalasia Research Articles

Comprehensive analysis of nutritional parameters in patients with idiopathic achalasia: A prospective study in India.

Achalasia cardia, a primary motility disorder of the esophagus, poses significant malnutrition risks. This study aims at comprehensively assessing the nutritional status in untreated achalasia patients, contrasting it with functional gastrointestinal disorders (FGIDs) cases and impact of per-oral endoscopic myotomy (POEM) on nutrition at one-year. We conducted a prospective study, including consecutive achalasia cases, from December 2021 to April 2022 at a tertiary care centre. Biochemical parameters, anthropometry, subjective global assessment (SGA) and malnutrition universal screening tool were used for nutritional assessment. Cases diagnosed with FGIDs served as controls. As many as118 cases (41.2 ± 13.9years, 61% males) with achalasia and 200 controls (43.4 ± 11.9years, 69% males) were included in the study. Sub-types of achalasia included type I (16.9%), II (76.3%) and III (6.8%). Overall, 38.1% and 6.8% cases were moderately and severely malnourished, respectively. As compared to controls, cases with achalasia had lower pre-albumin (19.4 vs. 25.2; p = 0.001), serum calcium (p = 0.012), vitamin D (p = 0.001), serum iron (p = 0.001), triceps fold thickness (p = 0.002) and hand-grip strength (p = 0.001). On univariate analysis, type-I achalasia, body mass index, % weight loss, lower esophageal sphincter pressures and Eckardt scores were predictors of malnourishment (SGA). On multivariate analysis, type of achalasia, mid arm circumference and low body mass index were significant predictors of malnourishment in cases with achalasia. There was significant improvement in the nutritional status after POEM at one-year follow-up. Achalasia patients demonstrate a notably higher risk of malnutrition compared to individuals with FGIDs. Nutritional status significantly improves after POEM. (NCT05161923).

OGBN P46 Megaoesophagus in a patient with achalasia treated with laparoscopic Heller cardiomyotomy

Abstract Background Achalasia is an oesophageal motility disorder that is a rare but important differential diagnosis in patients with dysphagia. Surgical treatment with laparoscopic Heller myotomy (LHM) and fundoplication is the gold standard; other options include peroral endoscopic myotomy (POEM), dilatation in cases that are unsuitable for surgery, and esophagectomy as a last resort. Methods We describe a case reported at our institution and the relevant workup, findings and management. Results A 41-year-old woman presented with persistent cough and shortness of breath on exertion. Chest x-ray showed right basal consolidation and a dense structure along the right mediastinum. CT revealed megaoesophagus with an oesophageal diameter of 7cm. Detailed history revealed long-standing history of progressive dysphagia and acid reflux and more recent history of weight loss, retrosternal pain and shortness of breath when eating solid foods. Workup included gastroscopy, oesophageal manometry and Chagas disease testing due to potential exposure to T. cruzi. A diagnosis of idiopathic achalasia was made, and she underwent laparoscopic Heller’s cardiomyotomy and Dor fundoplication. Conclusions Achalasia is an important differential in patients presenting with symptoms of dysphagia. This case reveals an atypical presentation of the disorder, suggesting a need to consider it in a wider range of presentations. Successful treatment of achalasia depends on timely diagnosis prior to oesophageal failure when it is still possible to intervene effectively.

The Comparison of Deep Sedation and Moderate Sedation in Pneumatic Balloon Dilation of Achalasia Patients

Background: Pneumatic Balloon Dilation (PBD) as an achalasia treatment is painful procedure because of tearing the lower esophageal sphincter (LES) muscle fibres. Recently, two sedation methods including the moderate sedation and deep sedation are used for increasing the convenience of the patients and gastroenterologist.
 Methods: To compare the efficacy of moderate and deep sedation in PBD in treatment of Idiopathic Achalasia (IA).
 Results: We prospectively assessed 200 IA patients. The first 100 patients (group A) underwent PBD by the moderate sedation using diazepam or midazolam and meperidine injections. The patients in the group B (100 patients) received midazolam, fentanyl and propofol as a deep sedation. The pulse rate (PR), systolic and diastolic blood pressure (SBP, DBP), respiratory rate (RR), and oxygen saturation were monitored before, during and after PBD and achalasia symptom scores (ASS) were collected before and 1.5 months after treatment. The mean PR during and after procedures in the group B were significantly lower compared to the group A (p 0.001, 0.028). The patients in group B revealed less SBP and DBP after PBD versus group A (p 0.004, 0.002). The mean psi for 30 mm and 35 mm balloon dilators were significantly increased in group B compared to group (p 0.0001, 0.002).
 Conclusion: We concluded that the deep sedation of achalasia patients in the PBD process can improved the efficacy of PBD and decreased the complications (transient chest pain) of the procedures. The patients with the deep sedation revealed less tachycardia and blood pressure rising and tolerated more pressure in balloon dilators.

The correlation between helicobacter pylori and idiopathic achalasia: A case control study.

Idiopathic achalasia is a common and well-recognized primary esophageal motility disorder with unknown etiology and is characterized by the abnormality of esophageal body peristalsis associated with an impaired relaxation of the lower esophageal sphincter (LES). The aim of this study is to explore the correlation between Helicobacter pylori and idiopathic achalasia. This study was conducted on 700 patients, with dysphagia, regurgitation, and non-cardiac chest pain (NCCP), who met our inclusion criteria. The mean ± SD age was 39.8 ± 11 (13-80 years), and 60% (420) of the participants were female. Of the participants, 108 had idiopathic achalasia and 105 were normal participants who were placed in the case and control groups, respectively. They were enrolled in the study based on high-resolution manometry. H. pylori was confirmed by a histological study. In the biopsy, specimens were taken by esophagogastroduodenoscopy. Our results revealed that 71.3% and 45% of the participants were H. Pylori positive in the case and control groups, respectively. The odds ratio (OR) was 3.3 (95% CI: 1.80-5.99, P < 0.05), indicating a statistically significant association between H. Pylori infection and the group classification. The dominant presenting symptoms in achalasia were dysphagia (97.2%) and NCCP (80.5%), but regurgitation (65.7%) was a dominant symptom in the normal participants. Diverse autoimmune and apoptotic phenomena induced by H. Pylori influence the pathogenesis of idiopathic achalasia, suggesting an underlying link between H. Pylori infection and idiopathic achalasia. This correlation should be confirmed by other clinical and experimental studies.

Peroral Endoscopic Myotomy (POEM) in a 19-Month-Old Girl with Primary Achalasia

Abstract Introduction Primary achalasia is an idiopathic motility disorder of the esophagus characterized by esophageal aperistalsis and incomplete relaxation of the lower esophageal sphincter (LES) in response to swallowing. The gold standard diagnostic method in adults is high-resolution manometry (HRM). Diagnostic criteria in adults are also used in children, but some HRM normal values may change depending on age. Case Report A 15-month-old girl was admitted to the hospital for evaluation due to persistent vomiting since birth. Vomiting included what she ate regardless of the amount of food she consumed. Barium esophagography revealed barium retention, esophageal dilatation, and a “bird's beak appearance” in the distal esophagus. Esophagogastroduodenoscopy revealed stenosis in the lower esophagus and bubbles at the esophagogastric junction.In HRM, the resting LES pressure was 43.4 mm Hg, there was pan-esophageal pressurization with 60% of swallows and no normal peristalsis. The patient was diagnosed with type II achalasia based on the Chicago 3.0 classification.First, the tube was inserted to ensure adequate nutrition of the patient, and approximately 4 months later, when the patient was 10 kg, the peroral endoscopic myotomy (POEM) procedure was performed.No complications developed during and after the procedure. At the 6th month after treatment, the patient was completely asymptomatic and her weight was within normal limits for her age. Conclusion POEM is an effective and safe method in the treatment of pediatric patients with idiopathic achalasia.

Stapling peroral endoscopic myotomy over Heller?

Peroral endoscopic myotomy (POEM) has been considered a safe and effective endoscopic therapeutic option for idiopathic achalasia. However, loosening the lower esophageal sphincter inevitably increases the risk of reflux, and the benefits of POEM may be compromised compared with laparoscopic Heller myotomy (LHM), which can be accompanied by simultaneous partial fundoplication. Owing to limitations in the methodological quality of most studies, and the inconsistent assessment used, the rate of reflux varies significantly among different studies [1]. In a multicenter, randomized trial of 221 patients, POEM demonstrated noninferiority to LHM plus Dor fundoplication in controlling symptoms of achalasia at 2 years, but the incidence of reflux was significantly higher [2]. At 3 months, 57 % of patients in the POEM group and 20 % of patients in the LHM group had reflux esophagitis, as assessed by endoscopy; at 24 months, the corresponding percentages were 44 % and 29 % [2].

Influence of Anxiety and Depression on the Symptoms of Achalasia Patients: A Retrospective Cohort Study in China during COVID-19

Background: Idiopathic achalasia (AC) may be affected by anxiety and/or depression; however, reliable evidence is still lacking. The present retrospective cohort study aimed to explore the influence of psycho-mental factors on the severity of AC. Methods: All patients in the AC database of the Tianjin Medical University General Hospital from 2012 to 2020 were divided into two subgroups, intervention (n = 202) and medication (n = 84), according to previous treatments. Healthy people (n = 300) who underwent gastrointestinal endoscopy comprised the control group. The severity of symptoms and the anxiety and depression score of AC patients and controls were monitored by telephone and compared before and during COVID-19. In addition, the factors of AC symptoms during the COVID-19 were discussed by multiple linear regression. Results: During COVID-19, the anxiety and depression levels of AC patients and healthy individuals were deteriorated. For AC patients, before and after COVID-19, symptoms, anxiety, and depression scores in the medication group were more serious than those in the intervention group. Furthermore, previous therapy, depression, and gender were found to be significantly related to the severity of AC symptoms during COVID-19. Conclusions: The outbreak of COVID-19 made AC patients and healthy people anxious and depressed. Depression rather than anxiety might worsen the AC symptoms. Interventional therapy might protect AC patients against psychological abnormalities during COVID-19.

A Review of Peroral Endoscopic Myotomy for Achalasia

Peroral endoscopic myotomy (POEM) is a form of transluminal endoscopic natural orifice surgery (NOTES) that uses the beginnings of submucosal endoscopy to make the endoscopic equivalent of a surgical myotomy. POEM can be done in most patients who have primary idiopathic achalasia demonstrated manometrically symptomatic. Previous therapies for achalasia, such as pneumatic balloon dilation, botulinum toxin injection, or surgical myotomy, are not contraindications to POEM. Generally, POEM is done in 4 continuous steps: incision in the mucosa, construction of a submucosal tunnel, myotomy and closure of the incision in the mucosa. Endoscopic management has been revolutionary for the treatment of achalasia and other pathological entities, however, it must be performed in specialized centres and by endoscopist surgeons with extensive experience in the subject, to reduce the associated morbidity and mortality.

Over-the-scope clip and self-expandable metal stent: a comprehensive treatment for failed peroral endoscopic myotomy and fibrosis complications in idiopathic achalasia.

Over-the-scope clip and self-expandable metal stent: a comprehensive treatment for failed peroral endoscopic myotomy and fibrosis complications in idiopathic achalasia.

S2405 Pseudoachalasia in Lung Cancer

Introduction: Although not common, lung tumor-induced achalasia will occasionally be encountered by gastroenterologists in patients with dysphagia and/or achalasia. Clinical features suggesting the possibility of malignancy as a cause of achalasia include: abrupt development of the dysphagia, significant unintentional weight loss in a short period of time ( >15 pounds), age > 55 years; and extensive smoking history ( >20 years). Case Description/Methods: A 67-year-old male with extensive smoking history presented to the hospital with complaints of difficulty tolerating foods and liquids with intermittent nausea and vomiting. Patient has to cut food into pieces to be able to go down. At presentation he had lost 25lbs in 2 weeks. CT abdomen showed abnormality at the gastroesophageal junction. EGD which showed a severely ulcerated esophagus with a stenotic mass effect in the distal third of the esophagus preventing the scope from advancing into the stomach (Figure). Discussion: Differentiating between idiopathic achalasia and pseudoachalasia is difficult and is often only possible when there is a diagnosis of other illnesses observed to have caused patients to experience achalasia symptoms with malignancy accounting for about 5% of these cases (Campo, 2013). Esophageal and gastric cancers tend to be the most common malignancies that cause pseudoachalasia, accounting for up to 70% of cases (Gockel et al., 2005). It is quite rare to come across a case of lung cancer causing pseudoachalasia and for that reason very little literature exists about the association between the 2 and its clinical expressions. In this particular case the ability for food to go down albeit in extreme difficulty indicated that there was some peristalsis which is seen often in pseudoachalasia but not in idiopathic achalasia (Kim et al., 2015). Another factor which helped in our diagnosis was the inability of the scope to advance past the mass unless moderate pressure was applied. In achalasia patients, the scope should be able to advance past the gastroesophageal junction with no more than light pressure applied (Eckardt & Eckardt, 2009). Existing literature indicates that in many cases, the presentation of achalasia symptoms precedes the diagnosis of cancer in pseudoachalasia sufferers. Therefore, testing and retesting may need to be done to rule out malignancy in patients who present with achalasia symptoms who are over the age of 60 years, have a history of smoking, and have experienced rapid weight loss in a short period of time (Tucker, 1978).Figure 1.: EUS showing the periesophageal mass.

The comparisons of different therapeutic modalities for idiopathic achalasia: A systematic review and network meta-analysis.

Background: Current guidelines recommend per-oral endoscopic myotomy (POEM) and laparoscopic Heller's myotomy (LHM) as first-line treatment of idiopathic achalasia, but the optimum choice between different endoscopic and surgical modalities remains inconclusive. We conducted a network meta-analysis to compare the efficacy of 8 treatments for idiopathic achalasia.Materials and methods: Three major bibliographic databases were reviewed for enrollment of randomized controlled trials between January 2000 and June 2021. We included adults with idiopathic achalasia and compared two or more of eight interventions including botulinum toxin injection (BTI), pneumatic dilation (PD), BTI + PD, LHM without fundoplication, LHM followed with Dor or Toupet fundoplication, and POEM using either the anterior or posterior approach. Our focus was on clinical success rate, postsurgical acid reflux, and moderate-to-severe adverse events.Results: Twenty-four studies involved a total of 1987 participants for analysis. When compared with PD, POEM with anterior approach, POEM with posterior approach, LHM + Toupet, and LHM + Dor were all significantly superior to the other regimens in short-term efficacy, with POEM with anterior approach and LHM + Dor showing better improvement in mid-term efficacy. BTI showed a significantly lower efficacy than PD in both periods. Regarding safety, only LHM without fundoplication was significantly associated with higher acid reflux than PD, while LHM + Toupet, LHM without fundoplication, and LHM + Dor showed a non-significant increase in moderate-to-severe adverse events.Conclusions: For idiopathic achalasia, we suggest that POEM with an anterior or posterior approach and LHM with Dor or Toupet fundoplication be initially recommended. On the contrary, both LHM without fundoplication and BTI are not recommended as definitive therapy.

Predictors of Long-Term Outcomes, Recurrent Dysphagia, and Gastroesophageal Reflux After Per-oral Endoscopic Myotomy in Esophageal Motility Disorders

BackgroundThere is limited data on long-term outcomes of per-oral endoscopic myotomy (POEM). In this study, we aim to evaluate the efficacy of POEM in patients who completed a minimum follow-up of 5 years. MethodsData of patients who underwent POEM and completed ≥ 5-year follow-up were analyzed, retrospectively. Primary outcome of study was clinical success (Eckardt ≤ 3) at ≥ 5 years after POEM. Secondary outcomes included predictors of dysphagia and symptomatic gastroesophageal reflux disease (GERD) on long-term follow-up. ResultsThree hundred nineteen patients (males 182, mean age 40.5±14.2 years) completed a median of 73-(60–89) month follow-up. Esophageal motility disorders included idiopathic achalasia (type I 26.6%, type II 60.8%, type III 5.6%) and Jackhammer esophagus or distal esophageal spasm (2.8%). POEM was technically successful in 307 (96.2%) patients. Long-term success was 92.6% (overall), 92.1% (type I), 94.7% (type II), 87.5% (type III), and 75% (Jackhammer esophagus/distal esophageal spasm). Symptomatic GERD and reflux esophagitis were detected in 28.9% and 35.3% patients, respectively. On multivariate analysis, young age and female gender were independent risk factors for recurrent dysphagia (p = 0.037) and symptomatic GERD after POEM (p = 0.025), respectively. Lower post-POEM lower esophageal sphincter pressure was an independent predictor for reflux esophagitis (p = 0.016). ConclusionPOEM is an effective and durable treatment for achalasia and non-achalasia spastic motility disorders. Young patients and females may be at higher risk for recurrent dysphagia and symptomatic GERD, respectively.

LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis.

Idiopathic achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES). However, the pathogenesis of idiopathic achalasia remains unclear. To further understand the pathogenesis, we conducted lncRNA and mRNA microarray analyses. LES specimens from 5 patients and 4 controls were used for microarray. Potential target genes with significantly changed lncRNA and mRNA were predicted using cis/trans-regulatory algorithms, followed by the Gene Ontology and KEGG pathway enrichment analysis to understand the biophysical effect. Finally, 7,133 significantly dysregulated mRNAs (3,136 increased and 3,997 decreased), along with 6,892 significantly dysregulated lncRNAs (4,900 increased and 1,992 decreased). Biophysical function analysis revealed that the cell adhesion molecule (CAM) pathway was a common pathway. The predicted lncRNA targets of NRXN1 (Down FC: 9.07), NTNG2 (UP FC: 2.75), CADM1 (Down FC: 2.26), NLGN1 (Down FC: 4.60), NEGR1 (Down FC: 2.335), CD22 (Down FC: 5.62), HLA-DQB1 (Down FC: 5.06), and HLA-DOA (Down FC: 2.31) were inputted in this pathway, which was mainly located in the synapse part of the neural system and immune system. Our study demonstrates the lncRNAs and corresponding mRNAs that may play important roles in idiopathic achalasia.

Different Clinical Features of Idiopathic Achalasia in Various Countries

Idiopathic achalasia is a motility disorder affecting the lower esophageal sphincter. Dysphagia is a hallmark symptom, but patients may exhibit other symptoms. The aim of this review is to compare achalasia symptoms globally. PubMed and Google Scholar were filtered from 1952–2021 with the search terms achalasia, epidemiology, diet, countries, and genetics. A total of 14 articles addressed demographics, symptom profiles, genetics, and diagnosis criteria amongst 2463 patients. Data on countries’ climate and diet were obtained through Arc Geographic Information System (GIS) and Our World in Data. Countries were grouped by similar climate zones and diets. Achalasia symptoms varied by region. In West Africa, patients exhibit parotid swelling, anemia, and dehydration; diminished appetite in East Asia; dysphagia and weight loss in West Asia and Europe; respiratory symptoms, reflux, and retrosternal pain in North America; and vomiting in Southern Asia. Weighted percentages of dietary oils/fats were (24.3%) in North America, Western Asia (17.8%); Europe (17.7%); East Asia (17.6%); West Africa (14.7%); Southern Asia (13.8%); North Africa (12.4%); Northeast Africa (10.1%). Conditions such as Down Syndrome and Triple A syndrome are associated with achalasia. There was no correlation for achalasia presentation and climate zones. Achalasia symptoms are likely multifactorial. Diet, genetics, and environmental factors may play significant roles.

Infection with SARS-CoV-2 as a potential achalasia trigger.

Idiopathic achalasia is a chronic oesophageal motility disorder caused by loss of inhibitory neurons at the esophageal myenteric plexus resulting in incomplete relaxation of the lower oesophageal sphincter and abnormal peristaltism.Among the possible causes of this, an immune response secondary to infection by some viruses has been implicated. SARS-CoV-2 could be considered among them. The therapy option should be aimed at achieving the greatest clinical effectiveness according to each patient's health status.

Safety and Efficacy of Graded Gradual Pneumatic Balloon Dilation in Idiopathic Achalasia Patients: A 24-Year Single-Center Experience.

Pneumatic balloon dilation (PBD) is a first line treatment for idiopathic achalasia. Here we report the safety and efficacy of graded gradual PBD on short and long-term follow-up. We evaluated 1370 idiopathic achalasia patients over a period of 24 years (1994-2018), prospectively. 216 patients did not undergo PBD due to comorbid diseases. Ultimately, 1092 achalasia patients were enrolled. All patients underwent graded gradual PBD, with repeat dilation if symptoms relapsed. Response to treatment was evaluated by Vantrappen scoring system. Of 1092 achalasia patients, 937 patients were treated by PBD and 155 patients were treated by combined therapy (PBD 1 month after Botulinum toxin injection). In short-term follow-up, 728 of 1092 patients underwent one PBD and 77.3% of them had excellent or good response (responders), 163 patients (58.6%) who underwent two PBDs were responders, and 44 (51.2%) patients who underwent three PBDs were responders. Overall, 2193 balloon dilations were performed on 1092 patients (mean 2 PBDs/patient). Of 786 patients with long-term follow-up, 259 patients had excellent or good response with one PBD. The responders with two, three, and four or more dilations were 149, 67, and 67, respectively. The overall response rate was 69%. No any serious complications were noted by using the graded gradual method. Our results show that graded gradual PBD is a safe and effective method for treatment of achalasia patients, and achieves sufficient short and long-term symptomatic remission with high cumulative success rate.

Hepatitis in Idiopathic Hypereosinophilic Syndrome: Report of an Unusual Case

World Health Organization defines a rare diagnosis Idiopathic hypereosinophilic syndrome (HES) as a persistent eosinophilia for 6 months and resulting in end-organ dysfunction. Most of the patients present with nonspecific symptoms, while others will present with symptoms of the affected organs, commonly those involving the heart, skin, or nervous system. Gastrointestinal or liver involvement is estimated to affect up to one-third of patients with HES, although patients with clinically significant disease are limited to case reports. This is the first report of a patient presenting with idiopathic HES related hepatitis and achalasia. Hypereosinophilic syndrome has been reported to be associated with hepatic dysfunction; liver histology is mainly characterized by a diffuse eosinophilic inflammatory infiltrate. A 49-yr-old woman, diagnosed as a case of idiopathic hypereosinophilic syndrome with bone marrow and pulmonary eosinophilic infiltrates associated with peripheral eosinophilia,high IgE level developed features of chronic gatrornteritis, hepatitis, with a significant eosinophil component. She responded well to systemic glucocorticoid and Imatinib therapy with normalization of liver function tests within a few weeks.

655 EVALUATION OF THE MODIFIED DOR TECHNIQUE FOR SURGICAL TREATMENT OF ACALASIA

Abstract Achalasia is the main esophageal motility disorder and has a significant negative impact on the patient's quality of life. Achalasia patients have dysphagia and vomiting, often associated with chest pain, leading to significant weight loss. The treatment of achalasia should be primarily to decrease the pressure of the lower esophageal sphincter. There are different therapeutic options for the treatment, and laparoscopic myotomy is the standard treatment, despite the improvement of new techniques such as POEM. Methods Prospective and retrospective study carried out in a university hospital with 33 patients with achalasia, operated with the wide myotomy technique associated with modified Dor fundoplication, from January 2017 to November 2020. The diagnosis was made by clinical, endoscopic, radiological and manometric studies. Symptomatic assessment and therapeutic success were performed using the Eckardt score before and after the operation. Rezende's classification was used to classify the degree of megaesophagus. The degree of megaesophagus was correlated with the result of the technique. The results were analyzed using the IBM SPSS Statistics Version 26 software. Results Patients with idiopathic achalasia 28 (84.8%). Preoperative Eckardt score average 5.93 points, preoperative clinical stage I = 7 (21.2%), clinical stage II = 12 (36.4%) and clinical stage III = 14 (42.4%). 48-hour postoperative hospital stay. Average postoperative Eckardt score 0.30 points, with 32 (97%) clinical stage 0, and 1 (3%) in clinical stage I in the postoperative period. Remission rate of the disease after treatment 100%. There was no correlation between the degree of the megaesophagus with the preoperative symptoms or with the therapeutic result. There were no complications or need for reintervention. There were no reports of symptoms of GERD. Conclusion According to clinical, radiological and endoscopic data, the technique was considered safe and effective for the treatment and regression of achalasia symptoms in all degrees of megaesophagus in the present study. In addition, the technique was also effective as an anti-reflux mechanism, preventing the onset of symptoms of iatrogenic GERD.

Circulating levels of cytokines, chemokines and growth factors in patients with achalasia.

Idiopathic achalasia is a disease that is characterized by the absence of peristalsis and incomplete relaxation of the lower esophageal sphincter, which is accompanied by dysphagia, regurgitation, chest pain and weight loss. The role of inflammatory infiltrates in the pathogenesis of achalasia remains controversial, although the infiltrating cell profile in the tissue has been previously characterized histologically and immunohistochemically. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with achalasia and the clinical disease characteristics. The cytokine, chemokine and growth factor serum profiles of 68 patients with achalasia and 39 healthy individuals were explored using the 27-Bio-Plex Pro Human Cytokine assay. Reductions in the levels of inflammatory mediators IL-1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 (MIP-1)α and MIP-1β, regulated upon activation normal T cell expressed and presumably secreted, TNF-α and VEGF were detected in the serum samples of patients with achalasia compared with those in the control group (P<0.05). However, significant associations between the expression in the levels of inflammatory factors and clinical characteristics of the patients were not found (P>0.05). These results suggest that achalasia is a disease that has a local but not a systemic inflammatory pattern. Further studies are required to improve the current understanding of the mechanism underlying this disease.

Third space endoscopy: the future of treating gastrointestinal dysmotility.

Third space endoscopy (TSE) or submucosal endoscopy provides with the opportunity for minimally invasive management of various gastrointestinal disorders. TSE is a relatively new field and the knowledge on its utility continues to advance. The purpose of this review is to provide with updated evidence on the efficacy and utility of TSE in gastrointestinal motility disorders including achalasia and refractory gastroparesis. Peroral endoscopic myotomy (POEM) is a safe procedure with emerging evidence on its durability as well. Major technical variations do not appear to impact the outcomes of POEM. Recent randomized trials suggest superiority of POEM over pneumatic dilatation and noninferiority over Heller's myotomy in idiopathic achalasia. With regard to gastric POEM (G-POEM), recent evidence confirms its efficacy in refractory gastroparesis. Although effective, the long-term outcomes of G-POEM are not well known. In addition, the criteria for patient selection remain elusive. TSE has emerged as a new frontier in the endoscopic management of gastrointestinal motility disorders. While short-term outcomes are encouraging, the durability of TSE remains to be seen in achalasia as well as refractory gastroparesis. Insights regarding patient selection and predictors of outcomes may help optimizing the results of gastric POEM in refractory gastroparesis.