Esophageal manometry and 24-hour pH monitoring in esophagus surgery:28-year Chinese experience in a single center

Objective To retrospectively review the experience of esophageal manometry and 24-hour pH monitoring in e-sophagus surgery. Methods From 1982 to 2010,patients with unspecific chest pain and undergone esophageal surgery were received esophageal manometry and 24-hour pH monitoring. Results Among the patients with

Clinical outcomes and safety of high-resolution manometry guided superficial partial circular muscle myotomy in per-oral endoscopic myotomy for Jackhammer esophagus: Two cases report

BACKGROUND Jack hammer esophagus is a relatively rare disease and to date,there is no dramatic treatment option.Recently,conventional per-oral endoscopic myotomy (POEM) have expanded their area into Jackhammer esophagus.However,several complications such as post procedure motility disorders (e.g.,passage disturbance) are issues after POEM.To overcome these issues,we here introduced high-resolution manometry (HRM)-guided superficial partial circular muscle myotomy,which involves cutting only the superficial layer of the esophageal circular muscle.CASE SUMMARY We report two cases of patients with Jackhammer esophagus who were treated with HRM-guided extremely superficial partial circular muscle myotomy during POEM.Case 1 was a 53-year-old female with medication-refractory odynophagia and case 2 was a 47-year-old man who presented with chest pain.They were diagnosed with Jackhammer esophagus using HRM,and the hypercontractile segments of the esophagus were identified.HRM-guided extremely superficial partial circular muscle myotomy was performed while preserving the lower esophageal sphincter.Therefore,the circular and longitudinal muscle layers are preserved but hypercontractile movements are reduced,even after POEM.Patients’ clinical symptoms dramatically improved right after POEM,and 6-mo follow-up HRM revealed completely resolved status.During a 1-year follow-up period,patients were still in good health and remained symptom free.CONCLUSION HRM-guided superficial partial circular muscle myotomy may be a promising alternative to conventional POEM for treating Jackhammer esophagus with improved efficacy.

Transcutaneous cervical esophagus ultrasound in adults: Relation with ambulatory 24-h pH-monitoring and esophageal manometry

AIM: To determine the gastroesophageal refl uxate in the cervical esophagus (CE) and measure transcutaneous cervical esophageal ultrasound (TCEUS) f indings [anterior wall thickness (WT) of CE, esophageal luminal diameter (ELD), esophageal diameter (ED)]; to compare TCEUS findings in the patient subgroups divided according to 24-h esophageal pH monitoring and manometry; and to investigate possible cut-off values according to the TCEUS f indings as a predictor of gastroesophageal refl ux (GER). METHODS: In 45/500 patients, refl uxate was visualized in TCEUS. 38/45 patients underwent esophagogastroduo denoscopy (EGD), 24-h pH monitoring and manometry. RESULTS: The 38 patients were grouped according to 24-h pH monitoring as follows: Group A: GER-positive (n = 20) [Includes Group B: isolated proximal refl ux (PR) (n = 6), Group C: isolated distal reflux (DR) (n = 6), and Group D: both PR/DR (n = 8)]; Group E: no refl ux (n = 13); and Group F: hypersensitive esophagus (HSE) (n = 5). Groups B + D indicated total PR patients (n = 14), Groups E + F refl ux-negatives with HSE (n = 18), and Groups A + F refl ux-positives with HSE (n = 25). When the 38 patients were grouped according to manometry fi ndings, 24 had normal esophageal manometry; 7 had hypotensive and 2 had hypertensive lower esophageal sphincter (LES); and 5 had ineffective esophageal motility disorder (IEM). The ELD measurement was greater in group A + F than group E (P = 0.023, 5.0 ± 1.3 vs 3.9 ± 1.4 mm). In 27/38 patients, there was at least one pathologic acid refl ux and/or pathologic manometry fi nding. The cut-off value for ELD of 4.83 mm had 79% sensitivity and 61% specificity in predicting the PRbetween Groups B + D and E (AUC = 0.775, P = 0.015). CONCLUSION: Visualizing refluxate in TCEUS was useful as a pre-diagnostic tool for estimating GER or manometric pathology in 71.1% of adults in our study, but it was not diagnostic for CE WT.

Gender disparities and woman-specific trends in Barrett’s esophagus in the United States:An 11-year nationwide populationbased study

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the United States,but many patients who are at risk of EAC are not screened.Current practice guidelines include male gender as a predisposing factor for BE and EAC.The population-based clinical evidence regarding female gender remains limited.AIM To study comparative trends of gender disparities in patients with BE in the United States.METHODS A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)database.Patients with a primary or secondary diagnosis code of BE were identified.The major outcome of interest was determining the gender disparities in patients with BE.Trend analysis for respective outcomes for females was also reported to ascertain any time-based shifts.RESULTS We identified 1204190 patients with BE for the study period.Among the included patients,717439(59.6%)were men and 486751(40.4%)were women.The mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(H.pylori),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of H.pylori and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among women has steadily increased from 2009 to 2019.The existing knowledge concerning BE development has historically focused on men,but our findings show that the risk in women is not insignificant.

Exercise benefits meet the esophagus

Gastroesophageal reflux disease(GERD)is defined by recurrent and troublesome heartburn and effortless regurgitation or by the specific complications of this condition—that is,esophagitis,esophageal peptic strictures,and Barrett esophagus.1Although GERD is caused by gastric contents'reaching the esophagus,gastric juices can also reach other anatomical locations(pharynx,mouth,larynx,and airways),leading to(or worsening)extra-esophageal conditions(notably asthma)or symptoms(e.g.,wheezing,cough).1 Together with obesity,GERD is the main risk factor for gastroesophageal malignancies.

Robotic Surgery: An Effective Treatment Option for Epiphrenic Diverticulum Associated with Nutcracker Esophagus

Background: Epiphrenic Diverticulum is frequently associated with esophageal motility disorders, such as nutcrackers esophagus. The diagnosis is usually made using imaging studies such as a Barium esophagogram, and esophageal manometry. Surgical treatment options for epiphrenic diverticulum and EN include diverticulectomy and wide myotomy. Aim: The resection of three epiphrenic diverticula and extensive myotomy were performed by robotic thoracoscopy uneventfully. Case presentation: A 65-year-old female complaining of dysphagia for solid foods, Chest pain and regurgitation. Esophagogastroduodenoscopy (EDG) with difficulty in advancing the endoscope at 25 cm and demonstrating an ED, no hiatal hernia and normal stomach and duodenum. Barium Esophagogram showed multiple diverticula and tortuosity throughout the esophagus. Conclusion: With robotic surgery, surgeons can perform highly precise operations with enhanced 3D vision and control. Through this cutting-edge approach, the treatment of ED associated with EN can be drastically changed, promising better outcomes for patients.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Large isolated fibrous tumors in the upper esophagus: A case report

BACKGROUND Solitary fibrous tumors(SFT)are rare spindle cell tumors that are usually benign.A total of 10 cases of SFTs in the upper esophagus have ever been reported.Here,we report the anesthetic management of a patient with a large isolated fibrous tumor of the upper esophagus compressing the tracheal membrane.We also provide a literature review of the current research.CASE SUMMARY We report the case of a 49 year old male with“cough aggravation and wheezing after exercise”,who underwent esophagectomy for a large isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.We advise the use of a single-lumen tube with a blocker in patients with difficult airways to reduce the incidence of airway injury and fibrinoscopy at all stages of the perioperative period to guide airway management.This case study is the first report of the anesthetic management of a large,isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.CONCLUSION This rare case emphasizes the importance of perioperative management of anesthesia in patients with large isolated fibrous tumors of the upper esophagus that compress the tracheal membrane.The use of blocker reduce the incidence of airway injury and fibrinoscopy at the perioperative period to guide airway mana-gement.

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

Hybrid argon plasma coagulation for the treatment of Barrett’s esophagus:A prospective,multicenter study

BACKGROUND The incidence of Barrett’s esophagus(BE)in China is lower compared to the Western populations.Hence,studies conducted in the Chinese population has been limited.The current treatment options available for BE treatment includes argon plasma coagulation(APC),radiofrequency ablation and cryoablation,all with varying degrees of success.AIM To determine the efficacy and safety of HybridAPC in the treatment of BE.METHODS The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment.These procedures were performed by seven endoscopists from different tertiary hospitals.The duration of the procedure,curative rate,complications and recurrent rate by 1-year follow-up were recorded.RESULTS Eighty individuals were enrolled for treatment from July 2017 to June 2020,comprising of 39 males and 41 females with a median age of 54 years(range,30 to 83 years).The technical success rate of HybridAPC was 100%and the overall curative rate was 98.15%.No severe complications occurred during the operation.BE cases were classified as short-segment BE and long-segment BE.Patients with short-segment BE were all considered cured without complications.Thirty-six patients completed the one-year follow-up without recurrence.Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment.The mean duration of the procedure was 10.94±6.52 min.CONCLUSION Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up,especially in cases of short-segment BE.This technique could be considered as a feasible alternative ablation therapy for BE.

Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus

AIM To investigate the relationship between pathological oropharyngeal(OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes.METHODS In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease(GERD). We enrolled only patients with a reflux symptom index(RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal highresolution manometry(HRM). Patients were divided into two groups on the basis of a normal or pathological p H-metric finding(Ryan Score) and all manometric characteristics of the two groups were compared.RESULTS We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure(median 71 mmH g vs 126 mmH g, P = 0.004) and the median proximal contractile integral(median 215.5 cm·mmH g·s vs 313.5 cm·mmH g·s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mm Hg isobaric contour(38.7% vs 15.38%, P < 0.0001).CONCLUSION In patients with suspected GERD-related extraesophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility.

Gastroesophageal manometry and 24-hour double pH monitoring in neonates with birth asphyxia

INTRODUCTIONBirth asphyxia may lead to disturbances of gastroenteric motility of newborn infants[1.2] . The change of gut pressure and reflux are the major manifestations of the motor disturbance [3-9] . To evaluate the effects of perinatal asphyxia on the gastroenteric motility, gastric and esophageal pressure and double pH were measured in a group of asphyxiated newborns. And. their pathophysiological and anatomical effects on gastroenteric function were discussed.

Deanxit relieves symptoms in a patient with jackhammer esophagus:A case report

Jackhammer(hypercontractile) esophagus presents with dysphagia and chest pain. Current treatments are limited. We describe a 60-year-old man who presented with dysphagia, chest pain and heartburn for a period of 1 year. His workup showed Barrett's esophagus on endoscopy and high-resolution manometry demonstrated jackhammer esophagus with esophagogastric junction outflow obstruction. The patient was treated with proton pump inhibitor and nifedipine but without resolution of his symptoms. He was followed up to assess the efficacy of treatment with deanxit(flupentixol + melitracen). Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment without troublesome side effects.

Pathologic and Clinical Analysis of Carcinosarcoma of Esophagus (20 Cases)

Objective:Carcinosarcoma of esophagus is an infrequent disease. Here, the pathologic data of larger specimens of this disease are reviewed and analyzed for studying its clinical characteristics in order to provide support information for clinical diagnosis. Methods: To review and study the clinical data of 20 patients of esophageal carcinosarcoma. Results: Most of esophageal carcinosarcoma grew like pileus or polypus in esophagus, a few of them were infiltrating. Microscopic examination of the resected specimens indicated that the tumor is composed of sarcomatous element and carcinomatous element (the main element), and the surface of such tumor was covered mostly by carcinoma tissues. The result of biopsy showed that the tumor is squamous cell carcinoma. X-ray examination indicated that there was polypus-like smooth and tidy filling defect in the esophagus of such patient, and its mucous membrane showed “daubing-trace” like characteristics. Conclusion: Carcinosarcoma of esophagus is a tumor of low invasion, which grows mainly in the esophageal lumen. The clinical symptoms of this tumor are different from those of esophagus carcinoma in certain degree. The “daubing-trace” like characteristics is typical of X-ray picture. The results of most endoscopic biopsies demonstrate squamous cell carcinoma or lower differentiation carcinoma, which are difficult for confirmed diagnosis before operation.

Distal esophageal spasm:Update on diagnosis and management in the era of high-resolution manometry

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago dassification of esophageal motility disorders (CC).DES is diagnosed by finding of≥20%premature contractions,with normal lower esophageal sphincter (LES)relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0.This feature differentiates it from achalasia type 3,which has an elevated LES relaxation pressure.Like other spastic esophageal disorders,DES has been linked to conditions such as gastroesophageal reflux disease,psychiatric conditions,and narcotic use.In addition to HRM,ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions.Functional lumen imaging probe (FLIP),a new cutting-edge diagnostic tool,is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP.Medical treatment in DES mostly targets symptomatic relief and often fails.Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time.Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

Can high resolution manometry parameters for achalasia be obtained by conventional manometry?

High resolution manometry(HRM) is a new technology that made important contributions to the field of gastrointestinal physiology. HRM showed clear advan-tages over conventional manometry and it allowed the creation of different manometric parameters. On the other side, conventional manometry is still wild available. It must be better studied if the new technology made possible the creation and study of these parameters or if they were always there but the colorful intuitive panoramic view of the peristalsis from the pharynx to the stomach HRM allowed the human eyes to distinguish subtle parameters unknown or uncomprehend so far and if HRM parameters can be reliably obtained by conventional manometry and data from conventional manometry still can be accepted in achalasia studies. Conventional manometry relied solely on the residual pressure to evaluate lower esophageal sphincter(LES) relaxation while HRM can obtain the Integrated Relaxation Pressure. Esophageal body HRM parameters defines achalasia subtypes, the Chicago classification, based on esophageal pressurization after swallows. The characterization of each subtype is very intuitive by HRM but also easy by conventional manometry since only wave amplitudes need to be measured. In conclusion, conventional manometry is still valuable to classify achalasia according to the Chicago classification. HRM permits a better study of the LES.

Viscosity of food boluses affects the axial force in the esophagus

AIM: To study the effect of viscosity on axial force in the esophagus during primary peristalsis using a newly validated impedance-based axial force recording technique. METHODS: A probe able to simultaneously measure both axial force and manometry was positioned above the lower esophageal sphincter. Potable tap water and three thickened fluids were used to create boluses of different viscosities. Water has a viscosity of 1 mPa·s. The three thickened fluids were made with different concentrations of Clinutren Instant thickener. The viscous fluids were in appearance comparable to pudding (2 kPa·s), yogurt (6 kPa·s) and slush ice (10 kPa·s). Six healthy volunteers swallowed 5 and 10 mL of boluses multiple times. RESULTS: The pressure amplitude did not increase with the bolus viscosity nor with the bolus volume whereas the axial force increased marginally with bolus volume (0.1 > P > 0.05). Both techniques showed that contraction duration increased with bolus viscosity (P < 0.01). Association was found between axial force and pressure but the association became weaker withincreasing viscosity. The pressure amplitude did not increase with the viscosity or bolus volume whereas the axial force increased marginally with the bolus size. CONCLUSION: This indicates a discrepancy between the physiological functions that can be recorded with axial force measurements and pressure measurements.

CARCINOMA ARISING IN BARRETT'S ESOPHAGUS (A REPORT OF 51 CASES)

Fifty-one patients with carcinoma arising in Barrett's esophagus were treated surgically from 1971 to 1990. This represented 10.2% of all treated cases with esophageal carcinoma during the same period. The mean age was 63 years. The most common symptom was dysphagia. According to PTNM staging, 18 were stage II,3 stage III and 3 stage IV. All patients were treated bysurgery. The 30-day hospital mortality was 3.98%. Theone, two and five-year survival rates were 45.9%, 25.0%and 13.6%, respectively. The 5-year survival rate wassignificantly greater for patrents with stage II (25.0%)than for parients with stage III + IV (4.s%) (P<0.05) andfor tumor length less than 6 cm (21%) than for tumorlength greater than 6 cm (0). The results indicate that thesurvival rate following resection is closely related to theclinical stage and tumor size.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus

AIM:To assess the sampling quality of four different forceps(three large capacity and one jumbo) in patients with Barrett's esophagus.METHODS:This was a prospective,single-blind study.A total of 37 patients with Barrett's esophagus were enrolled.Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy.The following forceps were tested:A:FB-220 K disposable large capacity;B:BI01-D3-23 reusable large capacity;C:GBF-02-23-180 disposable large capacity;and jumbo:disposable Radial Jaw 4 jumbo.The primary outcome measurement was specimen adequacy,defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa.RESULTS:A total of 436 biopsy samples were analyzed.We found a significantly higher proportion of adequate biopsy samples with jumbo forceps(71%)(P < 0.001 vs forceps A:26%,forceps B:17%,and forceps C:18%).Biopsies with jumbo forceps had the largest diameter(median 2.4 mm)(P < 0.001 vs forceps A:2 mm,forceps B:1.6 mm,and forceps C:2mm).There was a trend for higher diagnostic yield per biopsy with jumbo forceps(forceps A:0.20,forceps B:0.22,forceps C:0.27,and jumbo:0.28).No complications related to specimen sampling were observed with any of the four tested forceps.CONCLUSION:Jumbo biopsy forceps,when used with a diagnostic endoscope,provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.