Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

INTRODUCTION: Esophageal epidermoid metaplasia (EEM) is a rare disease. METHODS: Patients with EEM diagnosed between 2014 and 2020 were reviewed. RESULTS: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. DISCUSSION: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

Microbiome of the Aerodigestive Tract in Health and Esophageal Disease.

The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.

The use of impedance planimetry (Endoscopic Functional Lumen Imaging Probe, EndoFLIP® ) in the gastrointestinal tract: A systematic review.

BACKGROUND AND PURPOSE: The EndoFLIP® system is a method of delineating impedance and was first designed to investigate the characteristics of the esophago-gastric junction. In the last decade, its use was widened to investigate other sphincteric and non-sphincteric systems of the gastrointestinal tract. The objective of the present systematic review was to summarize the available data in literature on the use of the EndoFLIP® system in the gastrointestinal tract, including sphincteric and non-sphincteric regions. We performed a systematic review in accordance with recommendations for systematic review using PRISMA guidelines without date restriction, until June 2020, using MEDLINE-PubMed, Cochrane Library, and Google Scholar databases. Only articles written in English were included in the present review. Five hundred and six unique citations were identified from all database combined. Of those, 95 met the inclusion criteria. There was a lack of standardization among studies in terms of anesthetic drugs use, probe placement, and inflation protocol. In most cases, only small cohorts of patients were included. Most studies investigated the EGJ, with a potential use of the EndoFLIP® to identify a subgroup of patients with achalasia and for intraoperative assessment of treatment efficacy in achalasia. However, the use of EndoFLIP® in the esophageal body (esophageal panometry), other esophageal diseases (gastro-esophageal reflux disease, eosinophilic esophagitis), and other sphincter regions (anal canal, pylorus) will need further confirmatory studies. The EndoFLIP® system provides detailed geometric data of the gastrointestinal lumen but further works are needed to determine its use in clinical practice.

Flip Technology for Assessing Esophageal Structural and Motor Disorders: a Skeptic's View.

PURPOSE OF REVIEW: Functional lumen impedance (FLIP) technology has become commercially available to assess structural and motor abnormalities of the esophagus. Increasing numbers of papers have described novel findings with this technology. This review examines the validity of the FLIP technique, how it compares with existing diagnostic modalities, and evidence to date on diagnostic accuracy. RECENT FINDINGS: FLIP studies require deep sedation at the time of endoscopy to complete. They assess a simulated state of esophageal obstruction in only a distal part of the esophagus rather than deglutitive motor function of the entire esophagus. The available normative dataset is small and not matched to the older age of patients typically being evaluated. The test-retest agreement in health and disease is unknown, as is the operator dependence on performing and interpreting findings. Studies to date have largely excluded patients with structural disorders, which FLIP cannot reliably distinguish from motor disorders. FLIP is an expensive technology that has been made clinically available without its true utility being established. For FLIP to be deemed a device ready for widespread clinical use, additional studies on validity, diagnostic accuracy, and outcomes need to be performed. Prospective clinical studies need to include all patients and assess the incremental cost-effectiveness of FLIP over more innovative use of existing technology, such as high-resolution manometry with provocative challenges.

Esophageal physiology-an overview of esophageal disorders from a pathophysiological point of view.

The esophagus serves the principal purpose of transporting food from the pharynx into the stomach. A complex interplay between nerves and muscle fibers ensures that swallowing takes place as a finely coordinated event. Esophageal function can be tested by a variety of methods, endoscopy, manometry, and reflux monitoring being some of the most important. Regarding pathophysiology, motor disorders, such as achalasia, often cause dysphagia and/or chest pain. Functional esophageal disorders are a heterogeneous group with hypersensitivity as a dominant pathophysiological factor. Gastroesophageal reflux disease often causes symptoms, such as heartburn and regurgitation, and a spectrum of disease, ranging from minimal mucosal damage visible only in the microscope to esophageal ulcers and strictures in the most severe cases. Eosinophilic esophagitis is an immune-mediated condition that can result in significant dysphagia and associated luminal narrowing. In the following, we will provide an overview of the most common esophageal disorders from a combined pathophysiological and clinical view.

Esophageal Functional Lumen Imaging Probe (FLIP): How Can FLIP Enhance Your Clinical Practice?

Recent innovations in esophageal diagnostic testing have enhanced gastroenterology clinical practice by facilitating more nuanced and advanced evaluation of esophageal symptoms. Among these pivotal advances is the FDA-approved functional lumen imaging probe (FLIP), which utilizes impedance planimetry via volumetric distension of a catheter-mounted balloon at the time of sedated upper endoscopy, to acquire esophageal dimensions and pressures. In real time, FLIP can display cross-sectional areas (CSA) and distensibility indices (ratios of CSA to intra-balloon pressures) throughout the esophagus, most notably at the esophagogastric junction, as well as secondary peristaltic esophageal body contractile patterns. As the use of FLIP has progressively spread and permeated into the practice of clinical gastroenterology since its introduction, increasing data on and experiences with its applications have accumulated to guide its utility in clinical practice. In this current review developed for gastroenterologists and foregut surgeons across clinical practice, we provide an introduction to FLIP technology and metrics and discuss the clinical scenarios in which performance of or referral for FLIP may be helpful in the evaluation and management of patients with commonly encountered esophageal symptoms and disorders. Specifically, we discuss the potential applications and limitations of FLIP as a complementary diagnostic modality in patients with non-obstructive dysphagia, established or suspected achalasia spectrum disorders, eosinophilic esophagitis, gastroesophageal reflux disease and those undergoing esophageal surgery.

An Animal Study of Implantation of an Esophageal Pacemaker Based on Per-Oral Endoscopic Myotomy Approach for Alleviation of Esophageal Peristalsis Disorders.

BACKGROUND To restore esophageal peristalsis of achalasia patients by sequenced electric stimulation, an appropriate method must be established to implant the electrodes and pacemaker safely and effectively. We combined POEM (per-oral endoscopic myotomy) and abdominal wall puncture in pigs in order to explore a feasible procedure for the implantation. MATERIAL AND METHODS Five healthy male pigs were used in the present study with the permission of the Ethics Committee of Tianjin Medical University General Hospital. The electrodes were implanted in esophageal submucosal tunnel by POEM with the end of the electrode deposited in the abdominal cavity using NOTES technique. A pacemaker was then positioned under the skin of the abdomen. Finally, the electrodes were connected with the pacemaker with the help of endoscopy in the abdominal cavity. Esophageal peristalsis of these pigs after implantation was monitored for esophageal intraluminal pressure changes using electronic gastroscopy and a high-resolution manometry (HRM). The observation lasted for 6 h. RESULTS The procedure was effective to implant the electrode and the pacemaker using POEM and NOTES techniques. The connection of the 2 devices was also successful. Esophageal intraluminal pressure changes after electrical stimulation were recorded using HRM. Vital signs of the pigs were stable during the 6-h follow-up. CONCLUSIONS From this small-sample, short follow-up animal study, it was found that the implantation of esophageal electrodes and pacemaker based on POEM and NOTES is feasible, safe, and effective. Nevertheless, there is urgent need for long-term follow-up to confirm or disprove the safety of the procedure.

Applying the Functional Luminal Imaging Probe to Esophageal Disorders.

PURPOSE OF REVIEW: The functional luminal imaging probe (FLIP) uses high-resolution planimetry to provide a three-dimensional image of the esophageal lumen by measuring diameter, volume, and pressure changes. The goal of this review is to summarize the most recent advances in applying the (FLIP) to esophageal disorders. RECENT FINDINGS: The FLIP has been studied in esophageal disease states including gastroesophageal reflux disease (GERD), achalasia, and eosinophilic esophagitis. It has also been used in the investigation of dysphagia. The FLIP is a valuable tool for the diagnosis of esophageal diseases as well as guiding treatments and predicting treatment response. As further research is done, the FLIP may become the initial test for the patient with undifferentiated dysphagia at the time of their index endoscopy.

Esophageal motility patterns are altered in older adult patients. / Los patrones de motilidad esofágica están alterados en pacientes adultos mayores.

INTRODUCTION AND AIMS: Since the 1960s, several studies have shown the effect of aging on esophageal motility, with inconsistent results. The aim of the present study was to evaluate the manometric results in older adult patients (=60 years of age) with an esophageal disorder and compare them with adults under 60 years of age. MATERIALS AND METHODS: A cross-sectional, retrospective study was conducted that included a sample of 1,175 patients (936 older adults and 239 non-older adults). The patients were evaluated and compared with respect to (i) sex, (ii) main complaint for which esophageal manometry was indicated, (iii) comorbidities, (iv) current medications, (v) smoking, and (vi) manometry results. RESULTS: Patient age ranged from 19 to 92 years (women made up 76.5% of the older adults and 72.8% of the non-older adults). Normal lower esophageal sphincter relaxation and normal peristalsis were more frequent in the non-older patient group (91.1% vs. 84.8% and 87.4% vs. 76%, respectively). The manometry results for the non-older adults vs. the older adults, respectively, were: achalasia (2.9% vs. 5.9%); hypercontractile disorder (9.2% vs. 10.4%); hypocontractile disorder (38.5% vs. 47.6%); and normal values (49.4% vs. 36.1%). After excluding the variables that could change esophageal motility, the results revealed significant differences between the two study groups. CONCLUSIONS: Esophageal manometry demonstrated statistically significant differences between the older adult and non-older adult study population evaluated.

Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

GI Manifestations With a Focus on the Esophagus: Recent Progress in Understanding Pathogenesis.

PURPOSE OF REVIEW: Esophageal dysfunction is common in systemic sclerosis (SSc) patients. Limited treatment options are available for scleroderma esophageal disease. Here, we discuss recent updates on the diagnosis, treatment, and characterization that have been made in patients with scleroderma esophageal disease. RECENT FINDINGS: In the past few years, novel diagnostic tools have provided insight into esophageal dysmotility in SSc patients. New drugs are being tested and might improve symptoms and quality of life in SSc patients with esophageal dysfunction. Molecular stratification methods have facilitated the identification of molecular signatures in the esophagus of SSc patients. The Friend leukemia integration 1 (Fli1) conditional knockout mouse is the first animal model to report an esophageal phenotype with SSc features. The clinical presentation in SSc patients with esophageal dysfunction is heterogeneous, complicating diagnosis and management. The improvement of diagnostic tools for esophageal symptoms and dysfunction and the use of molecular approaches in SSc mouse models and patient biopsies offer an opportunity to improve the characterization of SSc esophageal disease, which should help improve management and treatment decisions.

Advancements in the use of manometry and impedance testing for esophageal functional disorders.

INTRODUCTION: The utilization of high-resolution manometry (HRM) has enhanced our understanding and assessment of esophageal motor disorders. Moreover, the combination of impedance technology with HRM (HRIM) has further improved our knowledge of esophageal physiology and the clinical evaluation of dysmotility, thanks to the addition of accurate measurement of bolus transit. Areas covered. This paper provides an overview of current knowledge in the use of HRIM for the study of esophageal functional disorders by reporting mainly the results of many publications and several systematic reviews in this field. Expert opinion. HRIM has represented a relevant improvement in the assessment of esophageal motility and has required the development of new metrics, such as the esophageal impedance integral ratio, the bolus flow time, the nadir impedance pressure and the impedance bolus height, which increase the evaluation of esophageal bolus transit. An extension of impedance is represented by functional lumen imaging probe (FLIP), which determines the biophysical properties and the distensibility of the esophagus and permits to detect contractility patterns not seen on HRM alone. We eagerly wait for a new and fruitful iteration of the Chicago Classification, now in version 3.0, which can cover the ongoing clinical experience of HRIM.

The dysphagia stress test for rapid assessment of swallowing difficulties in esophageal conditions.

BACKGROUND: Esophageal dysphagia is a common symptom in gastroenterology practice. Current rapid assessment tools are limited to oropharyngeal dysphagia and do not translate well to esophageal conditions. We aim to create a novel tool, the dysphagia stress test (DST), to evaluate swallowing in patients with esophageal disease characterized by dysphagia. METHODS: Adults with eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), achalasia, and dysphagia not otherwise specified (NOS) participated. Patient controls with non-esophageal diagnoses and healthy controls were also recruited. Participants completed the DST with five bolus challenges: water, applesauce, rice, bread, barium tablet and rated their swallowing difficulty and pain. A study clinician observed and documented water use and refusal of any challenges. Participants also completed measures of esophageal symptoms, hypersensitivity, and symptom anxiety to evaluate the DST validity. Collinearity of bolus challenges guided item reduction. KEY RESULTS: A total of 132 subjects participated. Both control groups and GERD patients had the best swallowing ability, while achalasia, EOE, and dysphagia NOS scored poorer. About 90% of patients were able to attempt or pass each of the bolus challenges, suggesting high acceptability. Construct validity of the DST is evidenced by modest negative correlations with symptom severity, hypersensitivity, and anxiety. The DST does not appear to be influenced by brain-gut processes. Applesauce, rice, and bread demonstrated collinearity; thus, the DST was reduced to three challenges. CONCLUSIONS & INFERENCES: The DST is the first rapid assessment tool designed for gastroenterology clinics with direct observation of swallowing ability across several conditions to mitigate issues related to patient self-report of esophageal symptoms.

Diffuse Esophageal Leiomyomatosis in Pediatric Patients: A Systematic Review and Quality of Evidence Assessment.

BACKGROUND: Diffuse esophageal leiomyomatosis (DEL) is a rare disorder characterized by benign hypertrophy of esophageal smooth muscle cells. No rigorous summary of available evidence on how to best manage these patients exists. OBJECTIVE: To define the clinical features and outcomes of pediatric patients with DEL. MATERIALS AND METHODS: A systematic literature search of the PubMed and Cochrane databases was performed with respect to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (end-of-search date: October 6, 2018). The algorithm: "esophageal leiomyomatosis AND (children OR pediatric*)" was implemented. RESULTS: Thirty-five studies including a total of 58 patients were analyzed. The female:male ratio was 1.45:1. Mean patient age was 8.54 ± 4.67 years. The most common disease manifestations were dysphagia and gastrointestinal symptoms (90.0%, 95% confidence interval [CI]: 78.2-96.1), followed by failure to thrive (57.9%, 95% CI: 36.2-76.9) and pulmonary symptoms (56.4%, 95% CI: 41.0-70.7). Alport syndrome (AS) was seen in 57.7% (95% CI: 44.2-70.1) of the patients. The most commonly implemented procedure was esophagectomy (85.2%; n = 46/54; 95% CI: 73.1-92.6) with gastric transposition (37.8%; n = 17/45; 95% CI: 25.1-52.4). Postoperative complications developed in 33.3% (n = 15/45; 95% CI: 21.3-48) of the patients. All-cause mortality was 7.0% (95% CI: 2.3-17.2) and disease-specific mortality was 3.5% (95% CI: 0.3-12.6). CONCLUSION: DEL is an uncommon condition that typically occurs in the setting of AS. Esophagectomy with gastric transposition is the mainstay of treatment. Although complications develop in one-third of the patients, mortality rates are low.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

BACKGROUND: The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. METHODS: We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). RESULTS: We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. CONCLUSION: We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology.

The Role of Novel Functional Probes in the Evaluation and Treatment of Esophageal Disease.

The understanding of esophageal function and dysfunction in a variety of disease states has been driven largely by the introduction of a variety of measurement technologies. Included in these are contrast esophagram, computed tomography, high-resolution manometry, and 24-hour pH monitoring. Two novel measurement technologies, the functional lumen imaging probe (FLIP) and mucosal impedance (MI) catheter have recently introduced and studied. This review will discuss the technological basis of these tools and the evidence behind their application in the measurement of esophageal anatomy, physiology, and histology pertaining to a number of diseases, including gastroesophageal reflux disease, achalasia, and esosinophilic esophagitis.

Esophageal tissue engineering: from bench to bedside.

For various esophageal diseases, the search for alternative techniques for tissue repair has led to significant developments in basic and translational research in the field of tissue engineering. Applied to the esophagus, this concept is based on the in vitro combination of elements judged necessary for in vivo implantation to promote esophageal tissue remodeling. Different methods are currently being explored to develop substitutes using cells, scaffolds, or a combination of both, according to the severity of lesions to be treated. In this review, we discuss recent advances in (1) cell sheet technology for preventing stricture after extended esophageal mucosectomy and (2) full-thickness circumferential esophageal replacement using tissue-engineered substitutes.