Investigating the Mechanisms Underlying U46619-Induced Contraction on Porcine Lower Esophageal Sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

Conventional versus oblique fiber-sparing endoscopic myotomy for achalasia cardia: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: GERD is common after peroral endoscopic myotomy (POEM). Selective sparing of oblique fibers may reduce the incidence of reflux esophagitis after POEM. In this study, we compared the incidence of GERD between conventional myotomy (CM) versus oblique fiber-sparing (OFS) myotomy in patients with achalasia. METHODS: Eligible patients with type I and II achalasia who underwent POEM from January 2020 to October 2020 were randomized into 2 groups (CM and OFS myotomy). Exclusion criteria were type III achalasia, sigmoid esophagus, and history of Heller's myotomy. The primary study outcome was incidence of reflux esophagitis (at least grade B) in the 2 groups. Secondary outcomes were reflux symptoms, esophageal acid exposure, clinical success, and adverse events. RESULTS: One hundred fifteen patients were randomized into CM (n = 58) and OFS myotomy (n = 57) groups. POEM was technically successful in all patients. Overall, reflux esophagitis was found in 56 patients (48.7%). The incidence of at least grade B esophagitis was similar in both groups (CM vs OFS myotomy: 25.9% vs 31.6%, P = .541). The mean number of reflux episodes (48.2 ± 36.6 vs 48.9 ± 40.3, P = .933), increased esophageal acid exposure >6% (45.5% vs 31.7%, P = .266), and high DeMeester scores (38.6% vs 41.5%, P = .827) were similar in both groups. There was no difference in the rate of symptomatic reflux (GERD questionnaire score >7) or use of proton pump inhibitors at 1 year. CONCLUSIONS: Sparing of sling fibers has no significant impact on the incidence of significant reflux esophagitis after POEM. Novel strategies need to be explored to prevent reflux after POEM. (Clinical trial registration number: NCT04229342.).

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

BACKGROUND: Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM. METHODS: This retrospective two-center observational study focused on patients undergoing LES-preserving POEM (LES-POEM) for NAEMD. Eckardt scores were assessed pre-POEM and at 6, 12, and 24 months post-POEM, with follow-up endoscopy at 6 months to evaluate for reflux esophagitis. Clinical success, defined as an Eckardt score ≤3, served as the primary outcome. RESULTS: 227 patients were recruited over 84 months until May 2021. Of these, 16 underwent LES-POEM for an NAEMD (9 with HCE and 7 with DES). The median pre-POEM Eckardt score was 6.0 (interquartile range [IQR] 5.0-7.0), which decreased to 1.0 (IQR 0.0-1.8; P<0.001) 6 months post-POEM. This was sustained at 24 months, with an Eckardt score of 1.0 (IQR 0.0-1.8; P<0.001). Two patients (12.5%) developed Los Angeles grade A or B esophagitis. CONCLUSIONS: LES-POEM for NAEMD demonstrates favorable clinical outcomes, with infrequent esophagitis and reintervention for LES dysfunction rarely required.

Esophagogastric Junction Outflow Obstruction (EGJOO): A Manometric Phenomenon or Clinically Impactful Problem.

PURPOSE OF REVIEW: Esophagogastric junction outflow obstruction (EGJOO), defined manometrically by impaired esophagogastric junction relaxation (EGJ) with preserved peristalsis, can be artifactual, due to secondary etiologies (mechanical, medication-induced), or a true motility disorder. The purpose of this review is to go over the evolving approach to diagnosing and treating clinically relevant EGJOO. RECENT FINDINGS: Timed barium esophagram (TBE) and the functional lumen imaging probe (FLIP) are useful to identify clinically relevant EGJOO that merits lower esophageal sphincter (LES) directed therapies. There are no randomized controlled trials evaluating EJGOO treatment. Uncontrolled trials show effectiveness for pneumatic dilation and peroral endoscopic myotomy to treat confirmed EGJOO; Botox and Heller myotomy may also be considered but data for confirmed EGJOO is more limited. Diagnosis of clinically relevant idiopathic EGJOO requires symptoms, exclusion of mechanical and medication-related etiologies, and confirmation of EGJ obstruction by TBE or FLIP. Botox LES injection has limited durability, it can be used in patients who are not candidates for other treatments. PD and POEM are effective in confirmed EGJOO, Heller myotomy may also be considered but data for confirmed EGJOO is limited. Randomized controlled trials are needed to clarify optimal management of EGJOO.

Short term safety of magnetic sphincter augmentation vs minimally invasive fundoplication: an ACS-NSQIP analysis.

PURPOSE: Magnetic Sphincter Augmentation (MSA) is an FDA-approved anti-reflux procedure with comparable outcomes to fundoplication. However, most data regarding its use are limited to single or small multicenter studies which may limit the generalizability of its efficacy. The purpose of this study is to evaluate the outcomes of patients undergoing MSA vs fundoplication in a national database. MATERIALS AND METHODS: The 2017-2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Registry was utilized to evaluate patients undergoing MSA or fundoplication. Patients requiring Collis gastroplasty, paraesophageal hernia repair, and emergency cases, were excluded. Patient outcomes included overall complication rates, readmissions, reoperations, and mortality. RESULTS: A total of 7,882 patients underwent MSA (n = 597) or fundoplication (n = 7285). MSA patients were younger (51 vs 57, p < 0.001), and more often male (49.6 vs 34.3%, p < 0.001). While patients undergoing MSA experienced similar rates of reoperation (1.0 vs 2.0%, p = 0.095), they experienced fewer readmissions (2.2 vs 4.7%, p = 0.005), complications (0.6 vs 4.0%, p < 0.001), shorter mean (SD) hospital length of stay(days) (0.4 ± 4.3 vs 1.8 ± 4.6, p < 0.001) and operative time(min) (80.8 ± 36.1 vs 118.7 ± 63.7, p < 0.001). Mortality was similar between groups (0 vs 0.3%, p = 0.175). On multivariable analysis, MSA was independently associated with reduced postoperative complications (OR 0.23, CI 0.08 to 0.61, p = 0.002), readmissions (OR 0.53, CI 0.30 to 0.94, p = 0.02), operative time (RC - 36.56, CI - 41.62 to - 31.49. p < 0.001) and length of stay (RC - 1.22, CI - 1.61 to - 0.84 p < 0.001). CONCLUSION: In this national database study, compared to fundoplication MSA was associated with reduced postoperative complications, fewer readmissions, and shorter operative time and hospital length of stay. While randomized trials are lacking between MSA and fundoplication, both institutional and national database studies continue to support the use of MSA as a safe anti-reflux operation.

Modified peroral endoscopic myotomy technique with retrograde on-demand myotomy for achalasia: a retrospective cohort study (with video).

BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.

Peroral endoscopic myotomy and its use in non-achalasia disorders.

The aim of this review is to provide an overview of per-oral endoscopic myotomy (POEM) and its utilization in non-achalasia disorders of the esophagus. POEM, a relatively novel endoscopic technique, involves submucosal tunneling to access esophageal muscle layers, enabling selective myotomy and mitigating the consequences of motor disorders of the esophagus. POEM is an effective treatment modality for diffuse esophageal spasm providing resolution of chest pain and dysphagia in a majority of patients who have refractory symptoms despite medical therapy. The results of POEM are more equivocal compared to esophagogastric junction outflow obstruction (EGJOO). POEM in EGJOO has been shown to have a 93% clinical success rate in 6 months. POEM appears to be more effective in motor disorders that affect the lower esophageal sphincter, such as EGJOO and opioid-induced esophageal dysfunction. While the current data for POEM in other entities such as DES and HE are positive, more supportive data are required to make POEM a consistent recommendation for patients.

A Novel Therapeutic Method in Gastro-esophageal Reflux Disease.

BACKGROUND: Gastro-esophageal reflux disease (GERD/GORD) is a chronic condition in which gastric acid flows backwards up into the esophagus, causing heart burn and a higher disposition to esophageal cancer. The reflux is caused by impairment of the lower esophageal sphincter (LES). Over the past century gastro-esophageal reflux has become the principal gastrointestinal condition of our time. The proton pump inhibitor class of drugs is effective in ameliorating the symptoms of reflux. The cost of investigation of patients in Europe is €100 billion per annum. The cost in days lost from work is €100 billion per annum in Europe. The global cost is 3 times this amount. METHODOLOGY: The proposed device for treating gastro-esophageal reflux is a biodegradable valve that is placed non surgically in the esophago-gastric junction to prevent reflux from the stomach to the esophagus. EXPERIMENT RESULTS: 50 simulator studies were performed with the patented device to elucidate the most consistent method of insertion and fixation in a human like simulator. The simulator was designed to replicate the normal human gastro-esophageal anatomy and characteristics. Four animal insertions were performed under ethical regulation at Amsterdam Medical Centre, Netherlands. Three cadaveric experiments were performed at Hackensack University Hospital, New Jersey, USA, to verify the positive outcomes of the simulator studies. CONCLUSION: Successful outcomes of simulator studies and cadaveric experiments allowed the design freeze of a NoReflux device for treating gastro-esophageal reflux disease.

[SURGICAL TREATMENT VERSUS ENDOSCOPIC TREATMENT FOR ACHALASIA IN THE MODERN ERA].

INTRODUCTION: Achalasia is a disorder of esophageal motility characterized by absent relaxation of the lower esophageal sphincter and abnormal peristalsis of the esophagus during swallowing. The etiology is divided into primary idiopathic achalasia and secondary achalasia and classified into 3 subtypes based on manometric evaluation, according to the Chicago 4.0 classification. The goal of the therapy is symptomatic improvement and prevention of late complications. While there are several endoscopic therapies, the gold standard therapy is laparoscopic Heller myotomy. Since its debut in 2008, per-oral-endoscopic-myotomy (POEM) became an accepted treatment for achalasia with non-inferior short term outcomes compared to Heller myotomy. In the following review, we will explore the indications, guidelines, and controversies in the modern treatment of achalsia, focusing on the Heller myotomy versus POEM.

[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

The Clinical Efficacy, and Long-Term Outcomes Between Pneumatic Dilation and Laparoscopic Heller Myotomy in Achalasia.

Introduction: Achalasia is the most well-known motility disorder, characterized by the lack of optimal relaxation of the lower esophageal sphincter during swallowing and the absence of peristalsis of the esophageal body. Laparoscopic Heller esocardiomyotomy (LHM) and pneumatic dilation (PD) were the main treatment options for achalasia. Currently, the therapeutic methods are complemented by per-oral endoscopic myotomy (POEM). Materials and Methods: we performed a retrospective study, analyzing the data and evolution of 98 patients with achalasia, admited and treated in the General and Esophageal Surgery Clinic of the St. Mary Clinical Hospital-Bucharest between January 2016 and June 2023. The treatment was performed by PD in 25 cases and the majority LHM. The average duration of symptoms in the case of PD was 48 months, and 24 months in LHM. The patients were evaluated before and after the treatment procedures by the Eckardt clinical score and investigations such as timed barium esophagogram (TBO) and esophageal manometry. Results: Although patients had the same Eckardt score before treatment, a statistically significant decrease of the Eckardt score was obtained at the post-therapeutic evaluation after undergoing LHM compared to PD. Recurrence of symptoms was more frequent in the case of PD, requiring another therapeutic intervention. The cost of treatment, as well as the number of hospitalization days were reduced in the case of PD. Conclusions: The treatment of achalasia with LHM is more effective regarding recurrence of symptoms, even if it involves higher costs and a longer hospital stay compared to DP.