Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy.

BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100%) and EUS-FNAB (97.1%) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

Improved esophagography screening for esophageal motility disorders using wave appearance and supra-junctional ballooning.

BACKGROUND: High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders (EMDs); however, it requires specialized equipment. The development of more accessible screening examinations is expected. We evaluated the utility of barium esophagography (BE) screening using two novel findings to diagnose EMDs. METHODS: Between January 2013 and October 2020, 244 patients with suspected EMDs who underwent both HRM and BE were analyzed. The EMD diagnosis was based on HRM findings using Chicago Classification version 3.0. BE was performed using sequential esophagography with barium sulfate. Three conventional BE findings (air-fluid level, rosary-bead/corkscrew appearance, and absent/weak peristalsis) and two novel BE findings (wave appearance and supra-junctional ballooning) were used for diagnosis. RESULTS: The sensitivity and specificity of BE screening using the two novel findings and conventional findings to diagnose EMDs were 79.4% and 88%, respectively [area under the receiver-operating characteristic curve (AUC) = 0.837]. Without these novel findings, they were 63.9% and 96%, respectively (AUC = 0.800), respectively. Achalasia was highly correlated with the air-fluid level (88.7%). Absent contractility was highly correlated with absent/weak peristalsis (85.7%). Relatively high correlations were observed between distal esophageal spasm and rosary-bead/corkscrew appearance (60%), and between achalasia and wave appearance (59.7%). The intra-observer reproducibility and inter-observer agreement for individual BE findings were 84.4% and 75%, respectively. Wave appearance was associated with higher integrated relaxation pressure (IRP) and shorter distal latency. Supra-junctional ballooning was associated with higher IRP. CONCLUSIONS: BE screening using two additional novel findings to diagnose EMDs could be useful in general practice.

Comparisons of outcomes between ProKnife injection endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large gastric lesions in ex vivo porcine model study: A randomized controlled trial.

Objective: To compare treatment outcomes between injection endoscopic submucosal dissection using ProKnife (P-ESD) and conventional ESD (C-ESD) for gastric lesions. Methods: In this randomized controlled trial, we compared treatment outcomes of P-ESD and C-ESD for simulated gastric lesions ≥3 cm in resected porcine stomachs. Predictive factors associated with ESD difficulties were investigated using logistic regression analysis. Results: Seventy lesions were screened; however, two lesions were excluded. A total of 12 endoscopists performed 68 ESDs: 34 P-ESDs and 34 C-ESDs. The ESD procedure time of P-ESD (36.3 [28.4-46.8] min) was significantly shorter than that of C-ESD (46 [36.4-64.6] min; p = 0.0014). The technical success rates did not differ between the P-ESD and C-ESD groups (en bloc resection rate, 100% in both groups; complete resection rate, 94.1% and 85.3%, respectively; p = 0.23). The number of injections during P-ESD (7.5 [6-10] times) was significantly higher than during C-ESD (4 [3-5] times; p < 0.001), but the total volume of injected solution during P-ESD (20 [16-26.3] ml) was significantly smaller than during C-ESD (27.5 [20-31.5] ml; p = 0.0019). In multivariate analysis, less ESD experience (odds ratio [OR], 3.9) and selection of C-ESD as the ESD method (OR, 3.8) were independent predictive factors associated with ESD difficulties. Conclusions: Compared with C-ESD, P-ESD had a shorter procedure time but also allowed for notable technical success and safety.

Rhythmic contraction but arrhythmic distension of esophageal peristaltic reflex in patients with dysphagia.

BACKGROUND: Reason for dysphagia in a significant number of patients remains unclear even after a thorough workup. Each swallow induces esophageal distension followed by contraction of the esophagus, both of which move sequentially along the esophagus. Manometry technique and current system of classifying esophageal motility disorders (Chicago Classification) is based on the analysis of the contraction phase of peristalsis. GOAL: Whether patients with unexplained dysphagia have abnormalities in the distension phase of esophageal peristalsis is not known. METHODS: Using Multiple Intraluminal esophageal impedance recordings, which allow determination of the luminal cross-sectional area during peristalsis, we studied patients with nutcracker esophagus (NC), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD). RESULTS: Distension contraction plots revealed that swallowed bolus travels significantly faster through the esophagus in all patient groups as compared to normals. The luminal cross-sectional area (amplitude of distension), and the area under the curve of distension were significantly smaller in patients with NC, EGJOO, and FD as compared to normals. Bolus traverses the esophagus in the shape of an "American Football" in normal subjects. On the other hand, in patients the bolus flow was fragmented. ROC curves revealed that bolus flow abnormalities during peristalsis are a sensitive and specific marker of dysphagia. CONCLUSION: Our findings reveal abnormality in the distension phase of peristalsis (a narrow lumen esophagus) in patients with dysphagia. We propose that the esophageal contraction forcing the swallowed bolus through a narrow lumen esophagus is the cause of dysphagia sensation in patients with normal contraction phase of peristalsis.

The treatment effects of acotiamide in esophagogastric outflow obstruction: a prospective longitudinal observational study.

OBJECTIVES: We have found that an altered lower esophageal sphincter (LES) accommodation response is an underlying cause of esophagogastric junction outflow obstruction (EGJOO). The objective of this study was to examine the treatment effect of acotiamide, a prokinetic agent which improves impaired gastric accommodation in functional dyspepsia, in patients with EGJOO. METHODS: A prospective observational longitudinal study was conducted between October 2014 and March 2020. Acotiamide (100 mg, 3 times a day) was administered to 25 patients with EGJOO for 4 weeks. High-resolution manometry (HRM) was performed just before and after 4 weeks of treatment. RESULTS: As the primary outcome, the extent of integrated relaxation pressure (IRP) after treatment (14.6, 12.1-22.0 mmHg) was significantly lower than that before treatment (19.4, 17.1-27.4 mmHg). The extent of LES accommodation index after treatment (32.7, 21.0-40.0 mmHg) was also significantly lower than that before treatment (39.3, 31.2-50.2 mmHg). Acotiamide normalized the IRP (< 15 mmHg) in 13 of 25 patients with EGJOO (52%), and the IRP was decreased in 20 of 25 patients with EGJOO (80%). As the secondary outcome, the total FSSG score in 25 patients with EGJOO before and after acotiamide treatment showed no significant difference. In a sub-analysis of 13 patients in whom EGJOO was normalized by acotiamide, however, dysphagia was reported to be significantly improved by acotiamide. CONCLUSIONS: Acotiamide has a treatment effect on patients with EGJOO via a reduction in the IRP level through the lowering of both the basal LES pressure and LES accommodation response. Dysphagia is a key symptom to be evaluated and treated in patients with EGJOO.

Onigiri esophagography as a screening test for esophageal motility disorders.

BACKGROUND/AIMS: No screening test for esophageal motility disorder (EMD) has been established, the objective of this study is to examine the potential usefulness of our newly developed "Onigiri esophagography" combined with an obstruction level (OL) classification system in screening for EMD. METHODS: A total of 102 patients with suspected EMDs who underwent both high-resolution manometry (HRM) and Onigiri esophagography between April 2017 and January 2019 were examined. The EMD diagnosis was performed based on the Chicago classification version 3.0 by HRM. Onigiri esophagography was performed using a liquid medium (barium sulfate) followed by a solid medium, which consisted of an Onigiri (a Japanese rice ball) with barium powder. The extent of medium obstruction was assessed by the OL classification, which was defined in a stepwise fashion from OL0 (no obstruction) to OL4 (severe obstruction). RESULTS: The patients with OL0 (32.3%), OL1 (50.0%), OL2 (88.0%), OL3 (100.0%), and OL4 (100.0%) were diagnosed EMDs by HRM. The area under the curve, as determined by a receiver operating characteristic analysis, for the OL classification was 0.86. Using the cutoff value of OL1, the sensitivity and specificity were 87.3% and 61.3%, respectively, while using a cutoff value of OL2, the sensitivity and specificity were 73.2% and 90.3%, respectively. CONCLUSION: In conclusion, Onigiri esophagography combined with the OL classification system can be used as a screening test for EMDs with a cutoff value of OL1.

Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows.

The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

Distension-contraction profile of peristalsis in patients with nutcracker esophagus.

INTRODUCTION: High amplitude peristaltic esophageal contractions, that is, nutcracker esophagus, were originally described in association with "angina-like pain" of esophageal origin. However, significant number of nutcracker patients also suffer from dysphagia. High-resolution esophageal manometry (HRM) assesses only the contraction phase of peristalsis. The degree of esophageal distension during peristalsis is a surrogate of relaxation and can be measured from the intraluminal esophageal impedance measurements. AIMS: Determine the amplitude of distension and temporal relationship between distension and contraction during swallow-induced peristalsis in nutcracker patients. METHODS: HRM impedance (HRMZ) studies were performed and analyzed in 24 nutcracker and 30 normal subjects in the Trendelenburg position. A custom-built software calculated the numerical data of the amplitudes of distension and contraction, the area under the curve (AUC) of distension and contraction, and the temporal relationship between distension and contraction. RESULTS: In normal subjects, the distension peaks similar to contraction traverse sequentially the esophagus. The amplitude of contraction is greater in the nutcracker esophagus but the amplitude of distension and area under the curve of distension are smaller in patients compared to controls. Distension peaks are aligned closely with contraction in normal subjects, but in patients, the bolus travels faster to the distal esophagus, resulting in a smaller time interval between the onset of swallow and distension peak. Receiver operative characteristics (ROC) curve reveals high sensitivity and specificity of the above parameters in patients. CONCLUSION: Abnormalities in the distension phase of peristalsis are a possible mechanism of dysphagia in patients with nutcracker esophagus.

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease.

INTRODUCTION: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. METHODS: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. RESULTS: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0-0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1-3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7-34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4-74.3%], p < 0.01). CONCLUSIONS: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

Relationship between distension-contraction waveforms during esophageal peristalsis: effect of bolus volume, viscosity, and posture.

High-resolution esophageal manometry (HRM) in its current form assesses only the contraction phase of peristalsis. Degree of esophageal distension ahead of contraction is a surrogate of relaxation and can be measured from intraluminal esophageal impedance measurements. The characteristics of esophageal contractions, i.e., their amplitude, duration, velocity, and modulating factors, have been well studied. We studied the effect of bolus volume and viscosity and posture on swallow-induced distension and contraction and the temporal relationship between the two. HRM impedance recordings of 50 healthy subjects with no esophageal symptoms were analyzed. Eight to ten swallows of 5 and 10 mL of 0.5 N saline and a viscous bolus were recorded in the supine and Trendelenburg positions. Custom-built computer software generated the distension-contraction plots and numerical data of the amplitudes of distension (cross-sectional area) and contraction, and the temporal relationship between distension and peak contraction. The hallmarks of distension waveforms are that 1) distension peak, similarly to contraction, travels the esophagus in a peristaltic fashion, and the amplitude of distension increases from the proximal-to-distal direction; 2) the amplitude of distension is greater with 10 mL than with 5 mL and greater in Trendelenburg than in supine posture; and 3) bolus viscosity increases the amplitude of distension and alters the temporal relationship between distension and contraction waveforms. We describe the characteristics of esophageal distension during peristalsis and the relationship between distension and contraction in a relatively large cohort of normal subjects. These data can be used to compare differences between normal subjects and patients with various esophageal motility disorders in future studies.NEW & NOTEWORTHY We studied esophageal distension (surrogate of inhibition) ahead of contraction during peristalsis from intraluminal esophageal impedance measurements. Esophageal distension, similarly to contraction, travels the esophagus in a sequential manner, and the amplitude of esophageal distension increases from proximal to distal direction in the esophagus. Bolus volume, viscosity and posture have significant effects on the amplitude of distension and its temporal relationship with contraction.

[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.

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 patient's 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.

BACKGROUND AND AIM: 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. METHODS: From May 2013 to July 2014, 97 patients (54 women, 43 men; age, 16-89 years) with suspected EMDs were assessed by high-resolution manometry in Kyushu University Hospital. Esophageal motility was evaluated by measuring the distal contractile integral (DCI), basal lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). Data on age, gender, body mass index (BMI), Brinkman Index, and blood tests were retrospectively collected and analyzed. RESULTS: Fifty patients were diagnosed as normal, nine with achalasia, twelve with esophagogastric junction outflow obstruction, four with distal esophageal spasm, one with jackhammer esophagus, six with absent peristalsis, ten with frequent failed peristalsis, and five with weak peristalsis. The median DCI was 1229.0 mmHg-s-cm, the median basal lower esophageal sphincter pressure was 25.3 mmHg, and the median IRP was 9.6 mmHg. Patients with major motility disorders were excluded from analysis. By multivariate regression analysis, BMI (P = 0.029) and total cholesterol (P = 0.023) were negatively associated with DCI, while BMI (P = 0.007) was negatively associated with IRP and glucose (P = 0.044) was positively associated with IRP. CONCLUSIONS: Both BMI and total cholesterol could be highly predictive factors for esophageal body contractility, while BMI and glucose could be predictive factors for lower esophageal sphincter contractile function.

New Approach to Diagnosis and Treatment of Esophageal Motility Disorders by High-Resolution manometry.

Esophageal motility disorders (EMD) is characterized by impaired coordinated esophageal motility function with symptoms including dysphasia, heartburn or noncardiac chest pain. Since EMDs is functional disorders, it is usually difficult to make a diagnosis by conventional examinations including endoscopy and esophagography. Recently developed high-resolution manometry allows us to evaluate esophageal motility function precisely and to make a differential diagnosis of EMDs, together with Chicago Classification (CC) version 3.0 (CC ver3.0). In this article, we reviewed diagnosis of EMDs based on CC ver3.0 and current treatment strategy for EMDs.