Kazumasa Muta

Diagnosis and Treatment Strategy of Achalasia Subtypes and Esophagogastric Junction Outflow Obstruction Based on High-Resolution Manometry.

Background: Based on Chicago Classification version 3.0, the disorders of esophagogastric junction outflow obstruction (EGJOO) include achalasia (types I, II and III) and EGJOO. Although no curative treatments are currently available for the treatment of the disorders of EGJOO, medical treatments, endoscopic pneumatic dilation (PD), laparoscopic Heller myotomy (LHM), and per-oral endoscopic myotomy (POEM) are usually the sought-after modes of treatment. Since the etiology and pathogenesis might vary depending on the types of EGJOO disorders, treatment strategies should be considered based on those subtypes. Summary: Based on the accumulated evidences, the treatment strategies of our institution are as follows: effects of medical treatments on achalasia are limited. Either PD or LHM/POEM can be considered a first-line in achalasia type I, according to the patients wish. PD and POEM can be considered first-line in achalasia types II and III, respectively. Conversely, In EGJOO, medical treatments including drugs like acotiamide and/or diltiazem can be tested as a first-line, and PD and POEM will be considered second and third-line treatments, respectively. Key Messages: The classification of subtypes based on high-resolution manometry will help us consider which treatment option can be selected as a first-line treatment depending upon the subtypes of disorders of EGJOO. Acotiamide has the potential to cure patients with EGJOO.

Effects of Acotiamide on the Esophageal Motility Function in Patients with Esophageal Motility Disorders: A Pilot Study.

Background and Aim: Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs). Methods: Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day. Results: Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO. Conclusions: Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO.

Clinical characteristics associated with esophageal motility function.

Esophageal motility disorders (EMDs) affect coordinated esophageal contractility. Recent developments in high‐resolution manometry have improved diagnosis of EMDs; however, the etiology of EMDs remains to be determined. This study aimed to determine which clinical characteristics are associated with esophageal motility.

A case of non-cardiac chest pain caused by esophageal motility disorder observed on esophageal high-resolution manometry

A 20-year-old man was referred to our hospital with dysphagia and chest pain. Heart disease was denied. No abnormality was observed in upper esophagogastroduodenoscopy and fluoroscopy;furthermore, no gastric acid-related symptoms were observed on combined esophageal multichannel intraluminal impedance and pH monitoring. Esophageal high-resolution manometry (HRM) performed by liquid swallow revealed normal peristalsis;however, HRM performed while the patient was taking solid meals showed abnormal contraction, and the patient simultaneously complained of chest pain. Therefore, we diagnosed this case as non-cardiac chest pain due to esophageal motility disorder.

Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function

Background and Aim: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans. Methods: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry. Results: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0–15.8, n = 10) than in normal esophageal motility (13.3, 12.8–14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0–14.1, n = 10) and normal esophageal motility (13.3, 12.8–14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure. Conclusions: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs.

Tu1147 Acotiamide Has the Potential to Become a Promising Treatment for Patients With Esophagogastric Junction Outflow Obstruction

detected by the high-throughput sequencer were confirmed by a direct sequencing procedure. Results: Seven variants were extracted by the high-throughput sequencer, and were analyzed using direct sequencing. Because the present study aimed to identify variants strongly associated with esophageal achalasia, variants were considered to indicate susceptibility to esophageal achalasia only when the variants were detected in all samples by both highthroughput and direct sequencing. Only the rs4898 T/C polymorphism was detected in all samples by both high-throughput and direct sequencing. Therefore, rs4898 was identified to indicate susceptibility to esophageal achalasia. This polymorphism is included in an intron of the synapsin 1 (SYN-1) gene and exon 5 of the tissue inhibitor of metalloproteinase-1 (TIMP-1). The polymorphism was detected in 16 of 21 patients with esophageal achalasia, including seven homozygous cases and nine heterozygous cases (76.2%), while seven of the 20 HVs, including five homozygous and two heterozygous cases (35.0%), were detected. The polymorphismwasmore frequently detected in female patients with esophageal achalasia. The age of onset and the need for surgical treatment were not associated with the frequency of the polymorphism. Conclusion: A genetic polymorphism, rs4898, in patients with esophageal achalasia was identified using a high-throughput sequencer with an original panel of target genes. The region of rs4898 is included in an intron of SYN-I, which is associated with the function of synapses, and in exon 5 of TIMP-I. The rs4898 polymorphism is considered to be a new risk marker for esophageal achalasia, and may be associated with the pathogenesis of esophageal achalasia through the altered expression of SYN-1 and/or TIMP-1.