Lowering the setting value of the esophageal endoscopic submucosal dissection device enabled tissue damage control in vitro porcine model.

One of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm2, II: 1.00 mm2, III: 1.91 mm2, and IV: 1.54 mm2. The mean highest temperature and mean heat denaturation area were significantly correlated (P < 0.001). In conclusion, Low-current ESD can suppress the actual temperature and thermal damage in the ESD wound.

Daidzein ameliorates experimental acute reflux esophagitis in rats via regulation of cytokines.

Context: Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. Objective: The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Methods: Adult male Wistar rats were classified into six groups: normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Results: Daidzein as a flavonoid has antioxidant properties and shows in vitro antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H2O2), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. Conclusion: The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part via alteration of inflammatory cytokines.

Deletion of TRPV4 enhances in vitro wound healing of murine esophageal keratinocytes.

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that is widely expressed in different body tissues and plays several physiological roles. This channel is highly expressed in esophageal keratinocytes where its activation mediates ATP release. However, whether TRPV4 has a role in wound healing of esophageal keratinocytes is unclear. In this study, we demonstrated that both cell migration and proliferation were slower in wild-type esophageal keratinocytes compared to cells having TRPV4 knockout. Our results suggest that TRPV4-mediated release of ATP from esophageal keratinocytes contributes to a decrease in the rate of in vitro wound healing via the ATP degradation product adenosine, which acts on A2B adenosine receptors.

An Insight to the Role of Thermal Effects on the Onset of Atrioesophageal Fistula: A Computer Model of Open-Irrigated Radiofrequency Ablation.

PURPOSE: Atrial fibrillation (AF) is the most common heart rhythm disorder in the world. Radiofrequency catheter ablation (RFCA) has become the preferred method of treatment for drug-refractory AF. One of the rare (< 0.2%) but deadly (≈ 80%) complications of RFCA is Atrioesophageal fistula (AEF). Although the exact pathophysiological events in developing AEF are not fully understood, one hypothesis is that the underlying cause may be thermal damage to the mucosa (the esophagus lumen). METHOD: The present study reports on a computer model of RFCA in the posterior wall of the left atrium (LA) which is in close proximity to the esophagus. A novel systematic approach was taken by considering a range of anatomical variations (obtained from clinical data) to study the spatial and temporal temperature data when RF energy was applied to cause a threshold temperature of 50 °C in the mucosa. The model is also used to investigate the spatial and temporal changes in mucosal temperature that may affect the reliability of the readings from esophageal temperature monitoring devices if they are not positioned accurately. RESULTS: The results suggest evidence of transmural esophageal lesions in all the anatomies except one, if the 50 °C temperature threshold is the only criteria used for identification of thermal damage. However, by taking into consideration the effect of time (temperature-time integral), only some anatomies were identified as being partially damaged. Investigating the temperature and the temperature gradient data during the ablation revealed that the increases in both the temperature and the temperature gradient were time, location and anatomy dependent. This finding may have significance in the design and development of next-generation temperature monitoring devices that will provide a temperature map rather than single point measurements. CONCLUSION: Studies such as the present work may provide more convenient platforms for investigating the effect of the many factors involved in the RF procedure and how they may link to the development of AEF.

Acute chest pain and esophageal mucosal injury following an extreme yoga position Case report.

A young lady complained of the sudden onset of intense chest pain, in consequence of an extreme hyperextension of the back in a yoga position. At endoscopy a large lesion of the esophageal epithelium was detected, involving the middle third of the anterior wall of the esophagus. Other symptoms reported by the patient were dysphagia and odynophagia, depicting the typical features of intramural hematoma, also known as intramural dissection or intramural perforation of the oesophagus. The patient was managed conservatively and symptoms disappeared within a week. A barium swallow at six months reported normal findings. Different types of accidents occurring during yoga practice are reported in the literature, mainly involving musculoskeletal or nervous systems. Visceral lesions are exceptional and no similar cases have been reported in the literature. KEYWORDS: Acute chest pain, Esophageal lesion, Intramural hematoma, Management of esophageal lesion.

Cat scratch esophagus

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Immediate and long-term outcome of corrosive ingestion.

BACKGROUND: Corrosive ingestion (CI) has short- and long-term consequences. The aim of this study was to assess the outcome of mucosal injury grade ≥ 2A. METHODS: Consecutive patients between January 2008 and January 2015 who presented within 48 h of CI were included. Details of substance ingested, intent, symptoms, injury grade at endoscopy, and treatment were obtained by a review of medical records. Patients aged less than 15 years or injury grade less than 2A were excluded. Patients were followed up using a structured symptom-based questionnaire and barium swallow. RESULTS: A total of 112 patients were admitted with CI during the study period. Eighty-two patients were included in the study. There was no relationship between the presence of symptoms or oral mucosal injury and the grades of gastrointestinal mucosal injury. Grades 2B and 3A were the most common grades of mucosal injury. Five patients died at index hospitalization. Patients were followed up for a median period of 31 months (6-72) during which 11 patients were lost to follow up. During follow up, 2 patients with high-grade injury died as a consequence of CI and 4 died of unrelated causes. Sixteen (26.6%) patients remained symptomatic. Forty-three patients underwent barium swallow. Esophageal stricture was identified in 11 patients, gastric stricture in 8, and combined esophageal and gastric in 2. High-grade esophageal mucosal injury was associated with a high risk of stricture formation (p = 0.02). CONCLUSIONS: CI is associated with high immediate and long-term morbidity and mortality.

Manejo endoscópico del síndrome de Boerhaave / Endoscopic management of Boerhaave's syndrome

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Clinical and endoscopic predictors for intraprocedural mucosal injury during per-oral endoscopic myotomy.

BACKGROUND AND AIMS: Mucosal injury (MI) is one of the most common perioperative adverse events of per-oral endoscopic myotomy (POEM). Severe undertreated MI may lead to contamination of the tunnel and even mediastinitis. This study explored the characteristics, predictors, and management approaches of intraoperative MI. METHODS: A retrospective review of the prospectively collected database at a large tertiary referral endoscopy unit was conducted for all patients undergoing POEM between August 2010 and March 2016. MI was graded according to the difficulty of repair (I, easy to repair; II, difficult to repair). The primary outcomes were the incidence and predictors of intraoperative MI. Secondary outcomes were MI details and the corresponding treatment. RESULTS: POEM was successfully performed in 1912 patients. A total of 338 patients experienced 387 MIs, for an overall frequency of 17.7% (338/1912). Type II MI was rare, with a frequency of 1.7% (39/1912). Major adverse events were more common in patients with MI than in those without MI (6.2% vs 2.5%, P < .001). On multivariable analysis, MI was independently associated with previous Heller myotomy (odds ratio [OR], 2.094; P = .026), previous POEM (OR, 2.441; P = .033), submucosal fibrosis (OR, 4.530; P < .001), mucosal edema (OR, 1.834; P = .001), and tunnel length ≥13 cm (OR, 2.699; P < .001). Previous POEM (OR, 5.005; P = .030) and submucosal fibrosis (OR, 12.074; P < .001) were significant predictors of type II MI. POEM experience >1 year was a protective factor for MI (OR, .614; P = .042) and type II MI (OR, .297; P = .042). CONCLUSIONS: MI during POEM is common, but type II injury is rare. Previous POEM and submucosal fibrosis were significant predictors of type II mucosal injury. POEM experience after the learning curve reduces the risk of MI.

Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Numerous studies have highlighted the activation of NF-κB in the esophageal mucosa during the early stages of gastroesophageal reflux disease (GERD). The present study aimed to investigate the role of the TLR4/NF-κB signaling pathway in GERD rat models. METHODS: Wistar rats (n = 60) were recruited to establish a GERD animal model. Distal esophageal pH was assessed, followed by determination of the contents of thiobarbituric acid-reactive species (TBARS) and reactive oxygen species (ROS) in esophageal mucosa homogenate. ELISA was employed to detect the levels of inflammatory factors (IL-6, IL-8, IL-10 and TNF-α) in esophageal mucosa. The expression of MMP-3, MPP-9, Cldn1 and Cldn4 was determined by immunohistochemistry. RT-qPCR and western blot analysis were applied to evaluate the protein expressions in TLR4/NF-κB signaling pathway, while TUNEL staining was utilized to examine the apoptosis rate in the esophageal mucosal tissues. RESULTS: Distal esophageal pH of the rats was higher in the GERD + PDTC group than in other groups. Levels of inflammatory factors in esophageal mucosal tissues were downregulated with the inhibition of NF-κB, which was determined to be associated with the decreased contents of TBARS and ROS. Moreover, decreased MMP-3 and MPP-9 in addition to elevated Cldn1 and Cldn4 were detected in the esophageal mucosa as a result of the inactivation of NF-κB. The TLR4/NF-κB signaling pathway-related proteins (TLR4, NF-κB and IκBα); the rate of apoptosis was demonstrated to be suppressed in the GERD + PDTC group, while inactivating NF-κB was found to alleviate the tissue damage observed in the esophageal mucosa. CONCLUSION: The key findings of the current study demonstrate that the inactivation of the TLR4/NF-κB signaling pathway alleviates oxidative stress injury and promotes the repair of esophageal mucosal injury among rats with GERD, highlighting a potential novel GERD mechanism.

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury.

The esophagus, a straight tube that connects the pharynx to the stomach, has the complex architecture common to the rest of the gastrointestinal tract with special differences that relate to its function as a conduit of ingested substances. For instance, it has submucosal glands that are unique and have a specific protective function. It has a squamous lining that exists nowhere else in the gut except the anus and it has a different submucosal nerve plexus when compared to the stomach and intestines. All of the layers of the esophageal wall and the specialized structures including blood and lymphatic vessels and nerves have specific responses to injury. The esophagus also has unique features such as patches of gastric mucosa called inlet patches at the very proximal part and it has a special sphincter mechanism at the most distal aspect. This review covers the normal microscopic anatomy of the esophagus and the patterns of reaction to stress and injury of each layer and each special structure.

Adverse events during and after per-oral endoscopic myotomy: prevention, diagnosis, and management.

Per-oral endoscopic myotomy (POEM) has surfaced as an effective endoscopic treatment modality for achalasia cardia (AC). Promising results in short- and mid-term follow-up studies have increased the use of POEM for the management of AC. POEM can be safely performed in an endoscopy suit, and major adverse events (AEs) are uncommon. AEs encountered during POEM or during the perioperative period principally include insufflation-related AEs, mucosal injuries, bleeding, pain, and aspiration pneumonia. Most insufflation-related AEs do not require an active intervention and therefore should not be considered as AEs in the true sense. When management of AEs is required, most intraoperative AEs can be managed at the same time without untoward consequences. Occurrences of AEs lessen after completion of the learning curve. However, experience alone does not ensure "zero" incidence of AEs, and early recognition remains essential. Postoperative AEs, like leaks, delayed bleeding, and delayed mucosal perforations, may pose special challenges for diagnosis and management. There is no standardized classification system for grading the severity of AEs associated with POEM, resulting in wide variation in their reported occurrences. Uniform reporting of AEs is not only crucial to comprehensively analyze the safety of POEM but also for comparison with other established treatment modalities like Heller's myotomy. GERD is an important long-term AE after POEM. Unlike the perioperative AEs, little is known regarding the intraoperative or patient-related factors that influence the occurrence of post-POEM GERD. Large prospective studies with long-term follow-up are required to determine the procedural factors associated with GERD after POEM.

Risk factors for symptomatic esophageal stricture after caustic ingestion-a retrospective cohort study.

Esophageal stricture is a major secondary complication of ingesting caustic agents. We examined our experiences with caustic injuries with a view to finding clinical and biological risk factors of esophageal strictures secondary to caustic ingestion. Records were retrieved for 58 adults admitted consecutively to our intensive care unit for caustic ingestion. Fifty cases were managed conservatively and therefore retained for analyses. Patients were grouped according to whether they developed strictures or not during the follow-up period. Mucosal damage was assessed by emergency endoscopy. Eleven patients (22%) developed a stricture. At referral, dysphagia, epigastric pain, and hematemesis were associated with secondary stricture (respectively P = 0.047, P = 0.008, P = 0.02). A high Zargar endoscopic grade (above IIa; P = 0.02), the ingestion of strong acids or alkalis (P = 0.006), hyperleukocytosis (P = 0.02), and a low prothrombin ratio (P = 0.002) were associated with a higher risk of developing a stricture. The median delay of stricture diagnosis was 12 (8;16) days after ingestion, with extreme values from 4 to 26 days. Initial symptoms such as dysphagia or hematemesis, early endoscopy showing >IIa grade esophagitis, and certain laboratory results should draw the physician's attention to a high risk of esophageal stricture.

Oesophageal ischaemia: an uncommon cause of chest pain.

A 79-year-old woman with a history of ischaemic heart disease and atrial fibrillation presented to hospital with severe chest pain. Blood tests showed an elevated D-dimer and a rise in troponin I. ECG showed right bundle branch block pattern and T wave inversion in leads V1 to V3, although these changes were present in old ECGs. A chest X-ray was done which was normal. Due to the nature and severity of her pain a CT aortic angiogram was done. This did not show any evidence of aortic dissection or a pulmonary embolism. The patient then had several episodes of haematemesis. An urgent oesophagogastroduodenoscopy was done which showed a circumferential, well demarcated area of blackened oesophageal mucosa. The patient was diagnosed with ischaemic damage to her oesophagus.

Relook endoscopy predicts the development of esophageal and antropyloric stenosis better than immediate endoscopy in patients with caustic ingestion.

Background and aims Early ( < 24 hours) esophagogastroduodenoscopy (EGD) is used to prognosticate mucosal injury after caustic ingestion. We aimed to compare differences in endoscopic grading on EGDs performed on day 5 and day 1 and to assess the impact of relook endoscopy findings on the development of esophageal and/or antropyloric cicatrization. Patients and methods Consecutive patients admitted within 24 hours of caustic ingestion between 2009 and 2014 underwent EGD and had their mucosal changes graded. Injuries of grade ≤ 2a were classified as mild and ≥ 2b were classified as severe. Patients were followed up for the development of cicatrization and managed per protocol. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were calculated to compare day 1 and day 5 EGD findings. Results A total of 62 patients (35 men; mean age 33 ±â€Š15) underwent both day 1 and day 5 EGDs. Antropyloric stenosis developed in 16 patients, esophageal strictures in nine, and four had both esophageal and antropyloric strictures. Compared with day 1 EGD, endoscopic grading of severe injury on day 5 had higher specificity (83 % vs. 65 %), higher PPV (60 % vs. 41 %), and higher positive LR (5.65 vs. 2.66) for predicting the development of esophageal stricture. Similarly, day 5 endoscopic grading had higher specificity (95 % vs. 61 %), higher PPV (88 % vs. 54 %), and higher positive LR (16 vs. 2.5) for predicting the development of antropyloric stenosis. Conclusion Endoscopic assessment on day 5 is a better predictor of esophageal and gastric cicatrization than day 1 EGD, which significantly overestimates the grade of injury.