Determination of causes of post-operative dysphagia after anti-reflux surgery based on intra-operative planimetry.

INTRODUCTION: Dysphagia after anti-reflux surgery (ARS) is one of the most common indications for re-operative anti-reflux surgery and a leading cause of patient dissatisfaction. Unfortunately, the factors affecting its development are poorly understood. We investigated the correlation between pre-operative manometric and the intra-operative impedance planimetry (EndoFLIP™) measurements and development of post-operative dysphagia. METHODS: A review of patients who underwent index robotic ARS in our institution. Patients who underwent pre-operative manometry and intra-operative EndoFLIP™ were included in our study. Dysphagia was assessed pre-operatively and at 3-month after surgery. RESULTS: Fifty-five patients (26.9%) reported post-operative dysphagia, and 34 (16.6%) reported new or worsening dysphagia. On pre-operative manometry, patients with post-operative dysphagia had a lower distal contractile integral [868.7 (IQR 402.2-1447) mmHg s cm vs 1207 (IQR 612.1-2111) mmHg s cm, p = 0.006) and lower esophageal sphincter (LES) pressure [14.7 IQR (8.9-23.6) mmHg vs 20.7 IQR (10.2-32.6) mmHg, p = 0.01] compared to those without post-operative dysphagia. They were also found to have higher pre-operative cross-sectional surface area (CSA) [83 IQR (44.5-112) mm2 vs 66 IQR (42-93) mm2, p = 0.02], and distensibility index (DI) [4.2 IQR (2.2-5.5) mm2/mmHg vs 2.9 IQR (1.6-4.6) mm2/mmHg, p = 0.003] compared to patients without post-operative dysphagia. Additionally, the decrease in CSA [- 34 (- 18.5, - 74.5) mm2 vs - 26.5 (- 10.5, - 53.7) mm2, p = 0.03] and DI [- 2.3 (- 1.2, - 3.7) mm2/mmHg vs - 1.6 (- 0.7, - 3.3) mm2/mmHg, p = 0.03] measurements were greater in patients with post-operative dysphagia. CONCLUSION: Patients who developed dysphagia post-operatively had poorer pre-operative motility and a greater change in LES characteristics intra-operatively. This finding suggests the utility of pre-operative manometry and intra-operative EndoFLIP in identifying patients at risk of developing dysphagia post-operatively.

Medium-term outcomes after magnetic sphincter augmentation vs. fundoplication for reflux disease due to hiatal hernia: a propensity-score matched comparison in 282 patients.

BACKGROUND: An increasing number of reflux patients opt for magnetic sphincter augmentation (MSA) instead of fundoplication. However, few studies compare the medium-term efficacy and safety of the procedures. METHODS: We conducted a retrospective single-center analysis of consecutive MSA and Nissen fundoplication cases between 01/2015 and 06/2020. Patients underwent surgery, including hiatoplasty, for medical treatment-resistant reflux due to hiatal hernia. Surgical revision and proton pump inhibitor (PPI) reuptake rates were the primary outcomes. We also compared adverse event rates. Patients with severe preoperative dysphagia/motility disorders were assigned different treatment pathways and excluded from the analysis. We used propensity-score matching to reduce confounding between treatments. RESULTS: Out of 411 eligible patients, 141 patients who underwent MSA and 141 with fundoplication had similar propensity scores and were analyzed. On average, patients were 55 ± 12 years old and overweight (BMI: 28 ± 5). At 3.9 years of mean follow-up, MSA was associated with lower surgical revision risk as compared to fundoplication (1.2% vs 3.0% per year, respectively; HR: 0.38; 95% CI 0.15-0.96; p = 0.04), and similar PPI-reuptake risk (2.6% vs 4.2% per year; HR: 0.59; 95% CI 0.30-1.16; p = 0.12). Adverse event rates during primary stay were similar (MSA vs. fundoplication: 1% vs. 3%, p = 0.68). Fewer patients experienced adverse events in the MSA group after discharge (24% vs. 33%, p = 0.11), driven by higher rates of self-limiting dysphagia (1% vs. 9%, p < 0.01) and gas/bloating (10% vs. 18%, p = 0.06) after fundoplication. Differences between MSA and fundoplication in dysphagia requiring diagnostic endoscopy (11% vs. 8%, p = 0.54) or surgical revision (2% vs. 1%, p = 1.0) were non-significant. The device explantation rate was 4% (5/141). CONCLUSION: MSA reduces the re-operation risk compared to fundoplication and may decrease adverse event rates after discharge. Randomized head-to-head studies between available surgical options are needed.

Clinical impact of esophageal muscle thickness on peroral endoscopic myotomy patients.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a standard procedure for achalasia, an esophageal motility disorder, characterized by a thickened lower esophageal sphincter muscularis propria (LEMP). Visualization of this anatomical stratification has been made possible by the advent of endoscopic ultrasound (EUS). However, the effect of LEMP thickness on treatment outcomes remains unclear. The objective of this study was to investigate whether LEMP thickness affects treatment response post-POEM. METHODS: This was a single-center, prospective cohort study of patients who underwent POEM between 2014 and 2021. Patients who underwent EUS to evaluate the LEMP before POEM were included in the study. We divided the patients into two groups according to muscle thickness measured by EUS (≥ 2.80 mm; group 1, < 2.80 mm; group 2). The pre- and post-procedural clinical parameters were compared between the two groups. RESULTS: Among 278 patients, 189 were enrolled. There were no significant differences in the pre- and post-Eckardt scores, integrated relaxation pressure, and distensibility index between the two groups divided by muscle thickness. Furthermore, there was no statistically significant difference in symptom recurrence, as measured by an Eckardt score > 3, post-procedural complications, or post-POEM GERD symptoms. However, patients with thicker lower esophageal sphincter muscle showed a greater decrease in Eckardt scores (ΔES ≥ 3) which was statistically significant (P = 0.002). CONCLUSION: POEM is an effective and safe treatment method for achalasia, regardless of LES muscle thickness. There was a statistically significant difference in the decrease of Eckardt scores of 3 or greater (ΔES ≥ 3) after POEM in the thicker LEMP group suggesting greater alleviation of symptoms in POEM patients with thicker lower esophageal muscle.

Efficacy and Safety of "Vacuum Swallowing" Based on a Strong Negative Esophageal Pressure in Healthy Individuals.

Vacuum swallowing is a unique method for improving the pharyngeal passage of a bolus by creating subatmospheric negative pressure in the esophagus. However, whether healthy individuals and other patients with dysphagia can reproduce vacuum swallowing remains unclear. Therefore, this study aimed to assess whether healthy individuals verified using high-resolution manometry (HRM) could reproduce vacuum swallowing and evaluate its safety using a swallowing and breathing monitoring system (SBMS). Two healthy individuals who mastered vacuum swallowing taught this method to 12 healthy individuals, who performed normal and vacuum swallowing with 5 mL of water five times each. The minimum esophageal pressure and the maximum pressure of the lower esophageal sphincter (LES) were evaluated during each swallow using the HRM. Additionally, respiratory-swallowing coordination was evaluated using the SBMS. Ten individuals reproduced vacuum swallowing, and a total of 50 vacuum swallows were analyzed. The minimum esophageal pressure (-15.0 ± 4.9 vs. -46.6 ± 16.7 mmHg; P < 0.001) was significantly lower, and the maximum pressure of the LES (25.4 ± 37.7 vs. 159.5 ± 83.6 mmHg; P < 0.001) was significantly higher during vacuum swallowing. The frequencies of the I-SW and SW-I patterns in vacuum swallowing were 38.9% and 0%, respectively, using the SBMS. Vacuum swallowing could be reproduced safely in healthy participants with instruction. Therefore, instructing exhalation before and after vacuum swallowing is recommended to prevent aspiration.

Exploratory study on the impact of intraesophageal pressure on quality of life in patients following total gastrectomy: a retrospective cohort study.

BACKGROUND: The usefulness of high-resolution impedance manometry (HRIM) in patients who underwent total gastrectomy with Roux-en-Y (R-Y) anastomosis has never been well validated. This study aimed to investigate whether intraesophageal pressure affects quality of life in patients who underwent total gastrectomy with R-Y anastomosis. METHODS: The participants comprised 12 patients who underwent total gastrectomy for gastric cancer between October 2014 and July 2022 and underwent a postsurgical HRIM examination. The association between the HRIM data and Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaires was analyzed. RESULTS: Esophageal body motility was normal in almost all patients. The anastomosis shape (circular stapler and overlap method with linear stapler) did not influence intraesophageal pressure. The integrated relaxation pressure and lower esophageal sphincter (LES) residual pressure during swallowing-induced relaxation were involved in "diarrhea subscale" scores (p = 0.0244 and p = 0.0244, respectively). The average maximum intrabolus pressure was not involved in postgastrectomy symptom. The contractile front velocity correlated with the "indigestion subscale," "diarrhea subscale," and "constipation subscale" (p = 0.0408, p = 0.0143, and p = 0.0060, respectively). The distal latency, i.e., the time from upper esophageal sphincter relaxation to contractile deceleration, was also associated with the "abdominal pain subscale" (p = 0.0399). LES pressure and esophageal body motility affected patients' quality of life after total gastrectomy. CONCLUSIONS: HRIM for the evaluation of intraesophageal pressure is useful for the functional assessment of esophagojejunostomy with the R-Y reconstruction after total gastrectomy.

Comparative clinical feasibility of antireflux mucosectomy and antireflux mucosal ablation in the management of gastroesophageal reflux disease: Retrospective cohort study.

OBJECTIVES: No definitive treatment has been established for refractory gastroesophageal reflux disease (GERD). Antireflux mucosectomy (ARMS) and antireflux mucosal ablation (ARMA) using argon plasma coagulation are promising methods. However, no study has compared these two. This study compared the efficacy and safety of the two procedures. METHODS: This multicenter, retrospective, observational study included 274 patients; 96 and 178 patients underwent ARMA and ARMS, respectively. The primary outcome was subjective symptom improvement based on GERD questionnaire (GERDQ) scores. The secondary outcomes included changes in the presence of Barrett's esophagus, Los Angeles grade for reflux esophagitis, flap valve grade, and proton pump inhibitor withdrawal rates. RESULTS: The ARMS group had higher baseline GERDQ scores (10.0 vs. 8.0, P < 0.001) and a greater median postprocedure improvement than the ARMA group (4.0 vs. 2.0, P = 0.002), and even after propensity score matching adjustment, these findings remained. ARMS significantly improved reflux esophagitis compared with ARMA, with notable changes in Los Angeles grade (P < 0.001) and flap valve grade scores (P < 0.001). Improvement in Barrett's esophagus was comparable between the groups (P = 0.337), with resolution rates of 94.7% and 77.8% in the ARMS and ARMA groups, respectively. Compared with the ARMA group, the ARMS group experienced higher bleeding rates (P = 0.034), comparable stricture rates (P = 0.957), and more proton pump inhibitor withdrawals (P = 0.008). CONCLUSIONS: Both ARMS and ARMA showed improvements in GERDQ scores, endoscopic esophagitis, flap valve grade, and the presence of Barrett's esophagus after the procedures. However, ARMS demonstrated better outcomes than ARMA in terms of both subjective and objective indicators.

Endoscopic pressure study integrated system using an ultrathin gastroscope for the functional assessment of the lower esophageal sphincter.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) represents an innovative approach for evaluating lower esophageal sphincter function by monitoring intragastric pressure using diagnostic gastroscopes. This study aimed to assess the feasibility and validity of employing ultrathin gastroscopes for EPSIS. METHODS: A retrospective analysis was conducted on a database of consecutive patients who underwent EPSIS using both ultrathin and regular gastroscopes between September 2021 and October 2023. The study compared EPSIS parameters between the two gastroscope types to evaluate the correlation of key metrics. RESULTS: Thirty patients underwent EPSIS with both ultrathin and regular gastroscopes. Significant positive correlations were observed in the pressure waveform: maximum intragastric pressure (mmHg) (ρ = 0.82, P < 0.001) and intragastric pressure gradient (mmHg/s) (ρ = 0.80, P < 0.001) when comparing the two gastroscopes. Maximum intragastric pressure (15.5 [5.3-20.3] vs. 18.5 [3.4-21.6], P < 0.001) and pressure gradient (0.16 [0.013-0.41] vs. 0.24 [0.0039-1.13], P < 0.001), (median [range]) were significantly lower with ultrathin gastroscopes. CONCLUSIONS: This study establishes that EPSIS parameters obtained with an ultrathin gastroscope exhibit a significant correlation with those obtained using a regular gastroscope, with each EPSIS parameter consistently lower. These findings support the viability of EPSIS for ultrathin gastroscopy and highlight its potential as a diagnostic tool for assessing lower esophageal sphincter function.

The contribution of lysophosphatidic acid receptors in the response of human lower esophageal sphincter under the electrical field stimulation.

BACKGROUND: This study aims to identify the impact on the reaction while the clasp and sling fibers of the human lower esophageal sphincter are under the electrical field stimulation, by adding lysophosphatidic acid receptor subtypes antagonist. METHODS: Between March 2018 to December 2018, muscle strips were isolated from 28 patients who underwent esophagectomy for mid-third esophageal carcinomas. Muscle tension measurement technique in vitro and electrical field stimulation were used to examine the effects of selective lysophosphatidic acid receptor antagonist on the clasp and sling fibers of human lower esophageal sphincter. RESULTS: The optimal frequency of frequency-dependent relaxation in clasp fibers and contraction in sling fibers induced by electrical field stimulation is 64 Hz and 128 Hz respectively. The selective lysophosphatidic acid 1 and 3 receptor antagonist produced no significant difference in the frequency-dependent relaxation in clasp fibers and contraction in sling fibers induced by the electrical field stimulation (P > 0.05). CONCLUSION: The electrical field stimulation induced a frequency-dependent relaxation in clasp fibers and contraction in sling fibers. The lysophosphatidic acid 1 and 3 receptors are not involved in the response of clasp and sling fibers of the human lower esophageal sphincter induced by the electrical field stimulation.

Magnetic sphincter augmentation and high-resolution manometry: impact of biomechanical properties on esophageal motility and clinical significance for selection and outcomes.

Magnetic sphincter augmentation (MSA)was introduced as an alternative to laparoscopic Nissen fundoplication (LNF). This reproducible, outpatient procedure addresses the etiology of gastroesophageal reflux disease by implanting a ring of magnetic beads across the esophagogastric junction (EGJ). MSA is designed to resist effacement of the lower esophageal sphincter (LES) and, similar to LNF, results in restoration of anti-reflux barrier competency by increasing overall length, intraabdominal length and resting pressure of the sphincter. However, the novel use of magnets to augment the physiology of the LES poses unique challenges to the physiology of the EGJ and esophagus. These impacts are best revealed through manometry. The degree of restrictive forces at the EGJ, as measured by intrabolus pressure and integrated relaxation pressure, is higher after MSA compared with LNF. In addition, contrary to the LNF, which retains neurohormonal relaxation capability during deglutition, the magnetic forces remain constant until forcibly opened. Therefore, the burden of overcoming EJG resistance is placed solely on the esophageal body contractile force, as measured by distal contractile integral and distal esophageal amplitude. The main utility of preoperative manometry is in determining whether a patient's esophagus has sufficient contractility or peristaltic reserve to adapt to the challenge of an MSA. Manometric thresholds predictive of MSA outcomes deviate from those used to define named Chicago Classification motility disorders. Therefore, individual preoperative manometric characteristics should be analyzed to aid in risk stratification and patient selection prior to MSA.

Evolution in the treatment of gastroesophageal reflux disease over the last century: from a crural-centered to a lower esophageal sphincter-centered approach and back.

The surgical management of gastroesophageal reflux disease (GERD) has evolved significantly over the past century, driven by increased understanding of the physiology of the reflux barrier, its anatomic components, and surgical innovation. Initially, emphasis was on reduction of hiatal hernias and crural closure as the etiology behind GERD was felt to be solely related to the anatomic alterations caused by hiatal hernias. With persistence of reflux-related changes in some patients despite crural closure, along with the development of what is now modern manometry and the discovery of a high-pressure zone at the distal esophagus, focus evolved to surgical augmentation of the lower esophageal sphincter (LES). With this transition to an LES-centric approach, attention shifted to reconstruction of the angle of His, ensuring sufficient intra-abdominal esophageal length, development of the now commonly employed Nissen fundoplication, and creation of devices that directly augment the LES such as magnetic sphincter augmentation. More recently, the role of crural closure in antireflux and hiatal hernia surgery has again received renewed attention due to the persistence of postoperative complications including wrap herniation and high rates of recurrences. Rather than simply preventing transthoracic herniation of the fundoplication as was originally thought, diaphragmatic crural closure has been documented to have a key role in re-establishing intra-abdominal esophageal length and contributing to the restoration of normal LES pressures. This progression from a crural-centric to a LES-centric approach and back has evolved along with our understanding of the reflux barrier and will continue to do so as more advances are made in the field. In this review, we will discuss the evolution of surgical techniques over the past century, highlighting key historical contributions that have shaped our management of GERD today.

Peroral Endoscopic Myotomy for Achalasia in Older Adults: A Retrospective Analysis of 39 Cases with a Minimum Follow-Up of 5 Years.

Peroral endoscopic myotomy (POEM) has demonstrated favorable short-term safety and efficacy in older adults, while a comprehensive understanding of the long-term outcomes were vague. We aimed to evaluate clinical outcomes in older adults' 5-year postop after undergoing POEM to treatment achalasia. Older adults from a single hospital who received POEM between January 2010 and January 2017 were analyzed. Older persons were reached to evaluate their symptoms at present and encouraged repeat examinations for objective follow-up. The clinical success, POEM-related indicators, POEM-related adverse events, and quality of life were assessed. Thirty-nine older adults with a mean age of 70.82 ± 4.72 who underwent POEM were studied at a mean 84.23 ± 25.06 month follow-up. The preoperative diagnosis was achalasia type I in 7 older adults, achalasia type II in 26 older adults, and achalasia type III in 2 older adults. Sixteen older adults had prior treatment and 21 older adults suffered from comorbidities. The median operative time was 50 (25-120) minutes, and perioperative adverse events were recorded in four older adults. The current Eckardt scores were significantly lower than that before POEM (2.08 ± 2.12 vs. 6.58 ± 1.78, P < 0.001). Besides, long-term clinical success was gained in 66.7% of older adults. Three older adults received postop treatment for symptom recurrence. Ultimately, 80.6% of old adults expressed satisfaction with POEM, while 27.8% of older adults suffered from symptomatic reflux. In conclusion, POEM can provide symptomatic improvement in a large proportion of older adults with achalasia at 5-year postop.

Endoscopic pressure study integrated system for the diagnosis of achalasia.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool used to evaluate lower esophageal sphincter (LES) function. EPSIS allows the measurement of intragastric pressure (IGP) during gastric insufflation through esophagogastroduodenoscopy (EGD) and records its pressure waveform. This study aimed to assess the usefulness and applicability of EPSIS as an adjunct diagnostic modality for achalasia. METHODS: This case-control study was conducted using a database of patients who underwent EGD, barium swallow (BS), high-resolution manometry (HRM), and EPSIS between January 2022 and December 2022. The achalasia (experimental) group (n = 35) consisted of patients with a definitive diagnosis of achalasia. The control group (n = 34) consisted of patients with no abnormalities in EGD, BS, or HRM and no abnormal acid reflux confirmed with 24-h pH-impedance monitoring. EPSIS findings were compared between the two groups and characterized by the waveform pattern (uphill or flat), maximum IGP (IGP-Max), pressure difference, and the gradient of the waveform. RESULTS: All patients in the achalasia group showed an uphill pattern, in contrast to 21 patients (61.8%) in the control group. IGP-Max demonstrated the best diagnostic accuracy for achalasia, with a cut-off value of 15.8 mmHg (100% sensitivity, 58.8% specificity, and area under the curve [AUC] 0.78). The pressure gradient also demonstrated good diagnostic accuracy, with a cut-off value of 0.40 mmHg/s (80% sensitivity, 61.8% specificity, and AUC 0.76). CONCLUSION: This study demonstrated that EPSIS can be applied as a diagnostic modality in patients with achalasia.

Anterior reconstruction of the esophageal hiatus: a novel approach for the repair of large diaphragmatic hernias.

Introduction: Paraesophageal hernias (PEH) often require surgical repair. The standard approach, primary posterior hiatal repair, has been associated with a high recurrence rate. Over the past few years, we have developed a new approach for repairing these hernias, which we believe restores the original anatomy and physiology of the esophageal hiatus. Our technique includes anterior crural reconstruction with routine anterior mesh reinforcement and fundoplication. Objective: To determine the safety and the clinical success of anterior crural reconstruction with routine mesh reinforcement. Material and methods: Data were collected retrospectively on 178 consecutive patients who had a laparoscopic repair of a symptomatic primary or recurrent PEH between 2011 and 2021 using the above technique. The primary outcome was clinical success, and the secondary outcome was 30 days of major complications and patient satisfaction. This was assessed by imaging tests, gastroscopies, and clinical follow-up. Results: Mean follow-up was 65 (SD 37.1) months. No intraoperative or 30 days postoperative mortality or major complications were recorded. Recurrence rate requiring a re-operation was 8.4% (15/178). Radiological and gastroenterological evidence of minor type 1 recurrence was 8.9%. Conclusion: This novel technique is safe with satisfactory long-term results. The outcome of our study will hopefully motivate future randomized control trials.

Effect of esophageal muscle fibrosis on prognosis of per-oral endoscopic myotomy (POEM) in achalasia patients.

BACKGROUND AND AIMS: Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM). METHODS: Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made. RESULTS: A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-ß1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-ß1, collagen I, and III were positively correlated with eosinophil count (all P < 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P < 0.05). CONCLUSION: Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-ß1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.

Outcome of sequential dilatation in achalasia cardia patients: a prospective cohort study.

BACKGROUND: Sequential increment of balloon diameter for endoscopic pneumatic dilatation is a protocol that is used for symptomatic relief in achalasia cardia. However, most of the studies evaluating its effectiveness are retrospective in nature. This study intended to look into the efficacy of the above protocol in a prospective fashion. METHODS: Consecutive patients of achalasia cardia (n = 72) attending gastroenterology department were subjected to graded dilatation with 30, 35, and 40 mm pneumatic balloon and followed up (median 48 weeks; range: 4-96 weeks) with Eckardt score. Efficacy was assessed by proportion of patients achieving and maintaining clinical remission (Eckardt score ≤ 3) without requiring surgery during follow-up. RESULT: Overall 91% of patients (60 out of 66 with follow-up data) remained symptom free without requirement of surgery. Proportion of type 3 achalasia patients was significantly higher in the group requiring surgery compared to those who did not (p = 0.005). Threshold of 12 mm Hg in 4-week post-dilatation integrated relaxation pressure noted to predict future requirement of surgery in type 3 achalasia patients with sensitivity and specificity of 75% and 85%, respectively. Major adverse events requiring in-patient management were 2.9% with perforation noted in 1.9%. CONCLUSION: A sequential increment of balloon diameter for pneumatic dilatation in achalasia is an effective mode of therapy to achieve and maintain clinical remission in achalasia. The incidents of adverse events are low in this approach. Type 3 achalasia patients are more likely to require surgery despite sequential dilatation.

Mast cell effects on esophageal smooth muscle and their potential role in eosinophilic esophagitis and achalasia.

Mast cells and eosinophils are the key effector cells of allergic disorders. Although most studies on eosinophilic esophagitis (EoE), an allergic disorder of the esophagus, have focused on the role of eosinophils, recent studies suggest a major role for mast cells in causing the clinical manifestations of this disease. Cellular and animal studies have demonstrated that mast cells can cause esophageal muscle cells to proliferate and differentiate into a more contractile phenotype, and that mediators released by degranulating mast cells such as tryptase and histamine can activate smooth muscle contraction pathways. Thus, activated mast cells in the esophageal muscularis propria might cause esophageal motility abnormalities, including the failure of lower esophageal sphincter relaxation typical of achalasia. In addition, mast cells have been implicated in the pathogenesis of a number of neurodegenerative disorders of the central nervous system such as Alzheimer's and Parkinson's diseases, because degranulating mast cells release proinflammatory and cytotoxic mediators capable of damaging neurons. Such mast cell degranulation in the myenteric plexus of the esophagus could cause the loss of enteric neurons that characterizes achalasia. In this report, we review the molecular mechanisms of esophageal smooth muscle contraction, and how mast cells products might affect that muscle and cause neurodegeneration in the esophagus. Based on these data, we present our novel, conceptual model for an allergy-induced form of achalasia mediated by mast cell activation in the esophageal muscularis propria.

Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video).

BACKGROUND: Augmentation of the lower esophageal sphincter (LES) is the primary goal of both surgical and endoscopic therapies for gastroesophageal reflux disease (GERD). The feasibility, efficacy, safety, and reversibility of a newly developed endotherapy for GERD using intraluminal magnets referred to as a magnet closure device (MCD) were evaluated. METHODS: This study involved nine cadaveric and six survival pigs. The MCD consisted of a ring neodymium magnet attached to a 2-0 polypropylene suture and suture anchor. The MCD was deployed onto the esophageal wall at the region of the LES using an endoscopic suturing device. Two to three MCDs were placed on opposing walls to induce closure of the esophageal lumen. LES pressures were measured using high-resolution manometry at the index procedure (baseline and immediately post-MCD placement) and at survival endoscopy. Endoscopic removal of the devices was performed followed by necropsy at week 2. RESULTS: MCDs were successfully deployed in all cadaveric (n = 22) and survival animals (n = 12). In cadavers, 20/22 (91%) sutures were full-thickness with no adjacent organ injury. In survival animals, mean LES pressure increased from 8.4 mmHg (baseline) to 32.4 mmHg immediately post-procedure (p < 0.01). No clinically significant adverse events occurred. Repeat endoscopy at two weeks showed intact MCDs in 4/6 (67%) animals with significant increase in median LES pressure (n = 4, 24.0 mmHg versus 7.4 mmHg [baseline], p < 0.05). Endoscopic removal of MCDs was successfully achieved. CONCLUSIONS: Endoscopic augmentation of the LES using a new MCD was feasible, safe and reversible with significantly increased LES pressures recorded. Future studies are needed to enhance durability. These preliminary results on a reversible technique are promising and may represent an attractive alternative to endoluminal GERD therapy.

Effect of electrical stimulation therapy of the lower esophageal sphincter in GERD patients with ineffective esophageal motility.

BACKGROUND: Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) is a novel technique in antireflux surgery. Due to the minimal alteration at the LES during surgery, LES-EST is meant to be ideal for patients with gastroesophageal reflux disease (GERD) and ineffective esophageal motility (IEM). The aim of this prospective trial (NCT03476265) is to evaluate health-related quality of life and esophageal acid exposure after LES-EST in patients with GERD and IEM. METHODS: This is a prospective non-randomized open-label study. Patients with GERD and IEM undergoing LES-EST were included. Follow-up (FUP) at 12 months after surgery included health-related quality of life (HRQL) assessment with standardized questionnaires (GERD-HRQL) and esophageal functional testing. RESULTS: According to the study protocol, 17 patients fulfilled eligibility criteria. HRQL score for heartburn and regurgitation improved from 21 (interquartile range (IQR) 15-27) to 7.5 (1.25-19), p = 0.001 and from 17 (11-23.5) to 4 (0-12), p = 0.003, respectively. There was neither significant improvement of esophageal acid exposure nor reduction of number of reflux events in pH impedance measurement. Distal contractile integral improved from 64 (11.5-301) to 115 (IQR 10-363) mmHg s cm, p = 0.249. None of the patients showed any sign of dysphagia after LES-EST. One patient needed re-do surgery and re-implantation of the LES-EST due to breaking of the lead after one year. CONCLUSION: Although patient satisfaction improved significantly after surgery, this study fails to demonstrate normalization or significant improvement of acid exposure in the distal esophagus after LES-EST.

Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

Simplified endoscopic pressure study integrated system for the diagnosis of gastroesophageal reflux disease.

Endoscopic pressure study integrated system (EPSIS) is a novel tool for the diagnosis of gastroesophageal reflux disease. It enables the evaluation of the function of the lower esophageal sphincter by monitoring intragastric pressure (IGP) while insufflating the stomach during esophagogastroduodenoscopy. EPSIS can predict abnormal acid reflux with high accuracy based on previous studies. IGP was measured by inserting through the working channel of the scope an intragastric catheter connected to a pressure measuring device. Herein, we assess the feasibility of an updated EPSIS system, which can be performed just by connecting a flush tube to the working channel. This method does not require inserting foreign objects in the stomach and spares catheter insertion in order to simplify the procedure and reduce costs. A single-center pilot study was conducted to evaluate the association between catheter-based EPSIS and the updated EPSIS. The results of EPSIS in 20 patients who underwent both methods were assessed. In all cases, the waveform pattern of IGP measured by catheter-based EPSIS and updated EPSIS was consistent with 15 uphill pattern and five flat pattern. Intraobserver agreement of waveform pattern was perfect between two examiners with kappa value = 1. Intraclass correlation coefficient (ICC) for intraobserver reliability for maximum IGP was excellent with 0.91 (95% confidence interval [CI] of 0.77 < ICC < 0.96) and for pressure gradient was also good with 0.89 (95% CI of 0.71 < ICC < 0.95). In conclusion, our study suggests that the updated EPSIS can be performed without the use of a catheter.