Esophageal Muscularis Research Articles

A multi-level investigation of the genetic relationship between gastroesophageal reflux disease and lung cancer.

Observational studies have revealed a potential association between gastroesophageal reflux disease (GERD) and lung cancer (LC), but the genetic role in their comorbidity have not been fully elucidated. This study aimed to comprehensively dissect the genetic link underlying GERD and LC. Using large-scale genome-wide association study (GWAS) data, we investigated shared genetic architecture between GERD and LC. Our analyses encompassed genetic correlation, cross-trait meta-analysis, transcriptome-wide association studies (TWASs), and the evaluation of the causality though a bidirectional Mendelian randomization (MR) analysis with sufficient sensitivities. We identified a significant genome-wide genetic correlation between GERD and overall LC (rg =0.33, P=1.58×10-14), as well as across other subtype-specific LC (rg ranging from 0.19 to 0.39). After separating the whole genome into approximately 2,353 independent regions, 5 specific regions demonstrated significant local genetic correlation, with most significant region located at 9q33.3. Cross-trait meta-analysis revealed 22 pleiotropic loci between GERD and LC, including 3 novel loci (rs537160, rs10156445, and rs17391694). TWASs discovered a total of 49 genes shared in multiple tissues, such as lung tissues, esophagus muscularis, esophagus mucosa, and esophagus gastroesophageal junction. MR analysis suggested a significantly causal relationship between GERD and overall LC [odds ratio (OR) =1.34, 95% confidence interval (CI): 1.19-1.51], as well as other subtype-specific LC (OR ranging from 1.25 to 1.76). No evidence supports a significant causal effect of LC on GERD. Our findings suggest intrinsic genetic correlation underlying GERD and LC, which provides valuable insights for screening and management of LC in individuals with GERD.

Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels

Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca2+ influx pathways responsible. PAF (10−9–10−6 M) contracted EMM in a concentration-dependent manner. PAF (10−6 M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10−5 M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10−6 M)-induced contractions were abolished by extracellular Ca2+ removal but were not affected by diltiazem [a voltage-dependent Ca2+ channel (VDCC) inhibitor, 10−5 M]. PAF (10−6 M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca2+ channel (ROCC) inhibitor, 3 × 10−5 M], SKF-96365 [an ROCC and store-operated Ca2+ channel (SOCC) inhibitor, 3 × 10−5 M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca2+ influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individualswith ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p= 4.58×10-8, odds ratio= 1.28, 95% confidence interval= 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p= 5.49×10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized withhighly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta= 9.36×10-10), chromosome 10 at PLCE1 (rs7099485, pmeta= 1.48×10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta= 1.47×10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Eosinophils Infiltration in Esophageal Muscularis Propria Induces Achalasia-like Esophageal Motility Disorder in Mice.

Eosinophil infiltration in esophageal muscularis propria is common in achalasia (AC). This study aims to evaluate the effect of eosinophil infiltration in muscularis propria of the esophagus on esophageal motility in mice. A mouse model with eosinophil infiltration in the esophageal muscle layer was established by long term Ovalbumin (OVA) exposure. The histopathology features of esophageal muscularis propria as well as parameters of esophageal motility, such as lower esophageal sphincter pressure (LESP) and esophageal emptying, were compared between model and control group. In addition, the histopathology and motility of esophagus at each time point in the model group were compared. The esophageal motor function severely deteriorated in the model group, mimicking the abnormal esophageal motility of AC, with more eosinophils and fewer SOX-10-IR cells in esophageal muscularis propria in the model group, compared with control. With the prolongation of OVA treatment, esophageal motility disorder was aggravated, accompanied by increased eosinophils in the the muscle layer of esophagus and decreased SOX-10-IR cells in the model group. In addition, the eosinophil count was negatively correlated with SOX-10-IR cells. Long-term exposure to OVA assisted by alum may induce eosinophil infiltration in esophageal muscularis propria, reduced SOX-10-IR cells and abnormal esophageal motility, which simulates the functional and histopathological features of some AC patients. This suggests that eosinophil infiltration in esophageal muscularis propria may play a role in the pathogenesis of a subgroup of AC.

Efficacy and Safety Analysis of Submucosal Tunnel Endoscopic Resection for Submucosal Masses in Esophageal Muscularis Propria.

Objective To analyze the efficacy and safety of submucosal tunnel endoscopic resection (STER) for the treatment of submucosal masses in esophageal muscularis propria. Method A total of 272 patients with submucosal masses in esophageal muscularis propria diagnosed and treated in our hospital from February 2019 to January 2022 were randomly selected for the study and then were randomly divided into the STER group (n = 136) and the endoscopic mucosal dissection (ESD) group (n = 136) according to the random number table method. Patients in the STER and ESD groups were treated with STER and ESD, respectively. The clinical data of patients from the two groups were collected and compared. The clinical effects and the changes of surgery-related indexes of patients after ESD and STER treatment were observed. The safety of ESD and STER was compared. The factors influencing the efficacy of STER treatment for submucosal masses in esophageal muscularis propria were analyzed. Result There were significant differences between the STER group and the ESD group in terms of tumor size, lesion level, adhesion and surgical approaches (P < 0.05). The effective rates of ESD treatment and STER treatment were 98.53% and 88.97%, respectively. Meanwhile, the effective rates of STER treatment were significantly higher than those in the control group (P < 0.05). In addition, the patients in the STER group had longer operation time, less blood loss, and shorter hospital stay compared with those in the ESD group (P < 0.05). Adverse reactions occurred during ESD treatment and STER treatment included delayed bleeding, adhesion, perforation, and pleural effusion with the total incidence of adverse reactions of 4.41% and 13.97%, respectively. The adverse reactions in STER group were prominently less than these in the ESD group (P < 0.05). Logistic multivariate regression analysis showed that independent risk factors, including tumor size, lesion level, adhesion, and surgical approaches, affected the efficacy of STER in the treatment of submucosal masses in esophageal muscularis propria (P < 0.05). Conclusion STER is an effective method for the treatment of submucosal masses in esophageal muscularis propria, which can exhibit a good effect with faster postoperative recovery and higher safety, thereby being worthy of clinical application and promotion. Tumor size, lesion level, adhesion, and surgical approaches are all related factors affecting the effect of STER treatment.

Microscopic anatomy of the upper aerodigestive tract in harbor seals (Phoca vitulina): Functional adaptations to swallowing.

Abandoned harbor seal pups (Phoca vitulina) are frequently recovered by rehabilitation centers and often require intensive nursing, gavage feeding and swallowing rehabilitation prior to anticipated release. Seal upper aerodigestive tract (UAT) histology descriptions relevant to deglutition are limited, impacting advances in rehabilitation practice. Therefore, we examined the histological characteristics of the harbor seal UAT to understand species-specific functional anatomy and characterize adaptations. To this end, we conducted gross dissections, compiled measurements and reviewed histologic features of the UAT structures of 14 preweaned harbor seal pups that died due to natural causes or were humanely euthanized. Representative samples for histologic evaluation included the tongue, salivary glands, epiglottis, and varying levels of the trachea and esophagus. Histologically, there was a prominent muscularis in the tongue with fewer lingual papillae types compared to humans. Abundant submucosal glands were observed in lateral and pharyngeal parts of the tongue and rostral parts of the esophagus. When compared to other mammalian species, there was a disproportionate increase in the amount of striated muscle throughout the length of the esophageal muscularis externa. This may indicate a lesser degree of autonomic control over the esophageal phase of swallowing in harbor seals. Our study represents the first detailed UAT histological descriptions for neonatal harbor seals. Collectively, these findings support specific anatomic and biomechanical adaptations relevant to suckling, prehension, and deglutition. This work will inform rehabilitation practices and guide future studies on swallowing physiology in harbor seals with potential applications to other pinniped and otariid species in rehabilitation settings.

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.

Endoscopic ultrasound-measured muscular thickness of the lower esophageal sphincter and long-term prognosis after peroral endoscopic myotomy for achalasia.

BACKGROUNDPeople with achalasia typically have a thick lower esophageal muscularis propria (LEMP), and peroral endoscopic myotomy (POEM) has been effective in treating most patients. LEMP thickness may be associated with the outcomes and prognosis after POEM. However, more evidence is needed regarding the relationship between LEMP thickness and patient prognosis after POEM.AIMTo assess the association between LEMP thickness, measured using endoscopic ultrasound (EUS), and long-term prognosis, especially relapse, after POEM for achalasia.METHODSAll medical records, including EUS data, of patients who underwent POEM to treat achalasia at Shengjing Hospital of China Medical University from January 2012 to September 2018 were retrospectively reviewed. LEMP thickness was measured by EUS, and a thickness of ≥ 3 mm was defined as thickened. The severity of patient symptoms was evaluated using the Eckardt score. Relapse was defined as a 3-point rise in the Eckardt score after a period of clinical remission. The relationship between patient characteristics, muscle thickness, and recurrence was analyzed.RESULTSEighty-two patients (32 males and 50 females, aged 17-78 years) and 85 POEM procedures were included. In total, 76.8% (63/82 patients) of patients had a thickened muscularis propria. Older age and longer disease course were associated with muscularis propria thickening (P < 0.05). The mean postoperative follow-up time was 35.4 ± 17.2 mo (range, 8-87.5 mo) in 60 patients. Five patients with Eckardt scores > 3 refused further management after their symptoms were relieved. The relapse rate was 12.73% (7/55 cases). Five patients, four of whom had muscularis propria thickening, had disease recurrence within 12 mo after the procedure. Achalasia relapsed in one patient who had a thickened muscularis propria after 24 mo and in another patient who did not have a thickened muscularis propria after 30 mo. Patients with recurrence were typically younger and had a shorter disease course (P < 0.05). The relapse rate in patients with a non-thickened muscularis propria tended to be higher (18.2%, 2/11 patients) than that in patients with a thickened muscularis propria (11.4%, 5/44 patients), although no significant difference was found. Age (hazard ratio = 0.92; 95% confidence interval: 0.865-0.979; P < 0.05) and being male (hazard ratio = 7.173; 95% confidence interval: 1.277-40.286; P < 0.05) were identified as risk factors for symptomatic recurrence by multivariable analysis using the Cox model.CONCLUSIONPatients with a thickened muscularis are typically older and have a longer disease course. Younger age and the male sex are associated with increased recurrence. Patients with a thin muscularis propria may be prone to relapse, although further validation is needed.

Oesophageal muscular hypertrophy and pulsion diverticulum in a Friesian horse

A 13-year-old Friesian stallion was referred for evaluation of acute coughing and bilateral nasal discharge. Thoracic radiographs revealed dilation of the terminal portion of the oesophagus, forming a thin-walled outpouching...

Genetic variants in GHR and PLCE1 genes are associated with susceptibility to esophageal cancer.

BackgroundEsophageal cancer (EC) is the leading cause of cancer‐related mortality worldwide. The underlying genetic risk factors remain unclear. The association between gene growth hormone receptor (GHR) and phospholipase C epsilon 1 (PLCE1) polymorphisms and the EC risk were identified in this study.MethodsA total of 506 EC cases and 507 controls were included in this research. Two SNPs (rs6898743 of GHR and rs2274223 of PLCE1) were selected and genotyped. The associations between gene polymorphisms and the EC risk were assessed by logistic regression analysis. The databases RegulomeDB, GTEx, and UALCAN were used for functional annotations.ResultsIn the allelic frequencies analysis, the rs6898743 of GHR was associated with decreased susceptibility of EC (OR = 0.83, 95% CI: 0.70–1.00, p = 0.049), while rs2274223 of PLCE1 was associated with increased 0.25‐fold EC risk (OR = 1.25, 95% CI: 1.02–1.53, p = 0.037). The “GC” genotype of rs6898743 was associated with a 0.24‐fold decreased risk of EC under co‐dominant model (OR = 0.76, 95% CI: 0.58–0.99, p = 0.046), and the “GA” genotype of rs2274223 was associated with increased EC risk under co‐dominant model (OR = 1.36, 95% CI: 1.04–1.77, p = 0.023). Using GTEx database, rs2274223 was found to be significant associated with increased PLCE1 expression (p = 4.1 × 10−7) in esophagus muscularis. The UALCAN database demonstrated that the GHR gene was under‐expressed in esophageal cancer tissues (p = 0.017).ConclusionThe gene GHR and PLCE1 polymorphisms are associated with EC in the general population and the results need to be verified in future.

Phenome-wide analyses establish a specific association between aortic valve PALMD expression and calcific aortic valve stenosis

Calcific aortic valve stenosis (CAVS) is a frequent heart disease with significant morbidity and mortality. Recent genomic studies have identified a locus near the gene PALMD (palmdelphin) strongly associated with CAVS. Here, we show that genetically-determined expression of PALMD in the aortic valve is inversely associated with CAVS, with a stronger effect in women, in a meta-analysis of two large cohorts totaling 2359 cases and 350,060 controls. We further demonstrate the specificity of this relationship by showing the absence of other significant association between the genetically-determined expression of PALMD in 9 tissues and 852 phenotypes. Using genome-wide association studies meta-analyses of cardiovascular traits, we identify a significant colocalized positive association between genetically-determined expression of PALMD in four non-cardiac tissues (brain anterior cingulate cortex, esophagus muscularis, tibial nerve and subcutaneous adipose tissue) and atrial fibrillation. The present work further establishes PALMD as a promising molecular target for CAVS.

Endoscopic treatment of Zenker's diverticulum by complete septotomy: initial experience in 19 patients.

Background and study aims Endoscopic treatment of Zenker’s Diverticulum (ZD) using a flexible endoscope and a diverticuloscope consists of myotomy of the cricopharyngeus muscle, sparing the lower part of the diverticular septum. However, recurrence occurs in up to 54 % of patients at 4 years. We assessed the feasibility and safety of a complete septotomy in endoscopic treatment of ZD. Patients and methods We conducted a retrospective analysis of a prospectively collected database at a single referral center. All consecutive patients treated by complete resection of the diverticular wall were included. The endoscopic technique used a distal attachment cap and division of the ZD septum using a Dual Knife or a Triangle Tip knife in endocut mode, until the esophageal muscularis propria was seen and no residual diverticulum remained. Symptoms were evaluated using the Augsburger questionnaire. Results Nineteen patients, 10 of whom were men with mean age 79 ± 12 years, were treated by complete septotomy for a symptomatic ZD with a median size of 2.5 cm (range 1–5 cm). The clinical success rate was 100 % and the complication rate was 10 % (one pneumonia and one atrial fibrillation). Median hospital stay was 2 days (range 1–3 days). On Day 1 esophagogram, no extraesophageal contrast leakage was seen, periesophageal CO 2 was still visible in two patients, and complete ZD regression was seen in 63 % of patients. The 6-month clinical success rate was 100 %, with two patients lost to follow-up, and a median symptom score of 0 (range 0–4). After a mean ± SD follow-up of 9 ± 5 months, the clinical success rate was 94 % (16/17). Conclusion Complete endoscopic septotomy is a feasible and safe therapeutic modality in patients with symptomatic ZD that does not require use of a diverticuloscope, and with good short-term efficacy. The complete regression of the diverticulum observed on Day 1 in 63 % of patients could be a marker of long-term clinical success.

Thoracoscopic surgery combined with endoscopic creation of a submucosal tunnel for a large complicated esophageal leiomyoma

BackgroundThe standard surgical method for symptomatic submucosal tumors (SMTs) or tumors with unclear biological behavior is enucleation. Minimally invasive approaches are usually considered appropriate for surgical enucleation; thus, thoracoscopic and laparoscopic enucleation is performed widely and safely. However, it is sometimes difficult to enucleate large and complicated esophageal tumors using thoracoscopic surgery, and even if rare, there is the risk of requiring thoracotomy or esophagectomy. In the present case, we enucleated a large and complicated leiomyoma safely using a new combined method with endoscopic and thoracoscopic procedures.Case presentationA 42-year-old woman presented to our hospital for a detailed examination of an abnormal finding in her health check-up chest X-ray images. She complained of upper abdominal pain after eating, and computed tomography revealed an esophageal tumor measuring 60 mm in length surrounding her lower thoracic esophagus. Esophagogastroduodenoscopy revealed a huge complicated SMT at the esophagogastric junction. Cytological examination with endoscopic ultrasound-guided fine-needle aspiration showed that the tumor was a leiomyoma. To enucleate this large and complicated esophageal SMT safely and without damaging the esophageal mucosa, we performed endoscopic and thoracoscopic procedures. We created a submucosal tunnel, endoscopically, and then performed thoracoscopic surgery to enucleate the tumor completely from the esophageal muscularis. Using these combined procedures, we were able to easily mobilize even a complicated tumor of this size from the mucosa and completed the surgery thoracoscopically without difficulty. As a result, the tumor was dissected safely with a minimal defect in the muscularis and without damaging the mucosa. Finally, we closed the defect in the esophageal muscularis with continuous sutures, thoracoscopically, and closed the entry of the submucosal tunnel using clips, endoscopically.ConclusionsUsing these combined procedures, we safely enucleated a huge complicated esophageal SMT. The increased mobility of the tumor after creating the submucosal tunnel contributed to the minimal defect in the muscular layer and prevented injury to the esophageal mucosa, possibly leading to fewer postoperative complications such as esophageal stenosis and local infection.

Experimental Study of the Tissue Repair of Neo-Esophagus After Esophageal Muscularis Resection.

Attempts have been made to observe the tissue repair of neo-esophagus after esophageal muscularis resection and to investigate possibility of the regeneration repair of esophageal muscularis resection in neo-esophagus. Sixteen pigs were divided into two groups: group A and group B. Pigs in group A were performed with the partial resection of mere esophageal muscularis propria reserved mucosa muscle layer in a segment of thoracic esophagus. Pigs in group B were performed with nitinol composite artificial esophagus with polyester sewing rings replacement a segment of thoracic esophagus resection. Pigs in the two groups were performed with euthanasia at the following times: 2, 4, 6, and 12 months for postmortem analysis, which demonstrated the absence of esophageal muscularis regeneration in the specimens that were sampled from different time points. Reserved mucosa muscle layer did not show hyperplasia to repair coloboma of esophageal muscularis propria deletion in group A. These results suggest that after esophageal muscularis resection, including mucosa muscle layer or esophageal muscularis propria, the coloboma of esophageal muscularis was repaired with connective tissue filling quickly. It would be very difficult for the regeneration repair of esophageal muscularis in neo-esophageal tissue structure after esophageal muscularis resection.

Value and limitation of endoscopic ultrasonography on the diagnosis of gastrointestinal submucosal tumor prior to endoscopic resection

Objective To investigate the efficacy and limitation of endoscopic ultrasonography(EUS) on the diagnosis of gastrointestinal submucosal tumor (SMT) prior to endoscopic resection. Methods Data of 211 patients, who were confirmed as gastrointestinal SMT before operation and received endoscopic resection for gastrointestinal submucosal tumor at Department of Gastroenterology, Shanghai Ruijin Hospital from January 2016 to December 2018 were analyzed. The value and limitation of EUS for SMT were investigated according to the final pathology. Results For the lesion distribution, 66 were in esophagus, 108 in stomach, 2 in duodenum and 35 in rectum. The accuracy of tumor origin by EUS was 99.5% (210/211). The accuracy of tumor nature by EUS was 75.8% (160/211). For the lesions originated from different locations, the diagnostic accuracy for lesion originated from esophageal mucosa/submucosa, esophageal muscularis propria, gastric mucosa/submucosa, gastric muscularis propria, duodenal submucosa, rectal mucosa/submucosa by EUS were 90.0%(54/60), 83.3%(5/6), 31.0%(13/42), 89.4%(59/66), 50.0%(1/2), 82.9%(29/35), respectively. With respect to hypoechoic lesions, leiomyoma, leiomyoma/gastrointestinal stromal tumor, and neuroendocrine tumor were the predominant type of tumor originated from esophageal mucosa, gastrointestinal muscularis propria and rectal mucosa/submucosal, respectively. Conclusion Although EUS is indispensible for the diagnosis of gastrointestinal submucosal tumor, it plays a limited role in the differential diagnosis of various lesions originated from gastric mucosa and submucosa. Since part of the submucosal tumors may be potential for malignant development, an diagnosis made by EUS should be more careful. Key words: Endoscopy; Endoscopic ultrasonography; Submucosal tumor

Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders?

Eosinophilic esophagitis (EoE), a disorder identified by its esophageal mucosal features, often is associated with esophageal motility abnormalities, which are manifestations of esophageal muscle dysfunction. Those motility abnormalities sometimes normalize with treatments that reduce esophageal eosinophilia, suggesting that eosinophils can cause reversible esophageal motility disturbances, perhaps by releasing myoactive and neuroactive eosinophil products. Although achalasia uncommonly is associated with EoE as currently defined, most achalasia patients have evidence of an abnormal accumulation of eosinophils and/or their degranulation products in the esophageal muscularis propria, a location inaccessible to routine endoscopic evaluation. Achalasia is an idiopathic condition resulting from destruction of neurons in the myenteric plexus of the esophagus, and degranulating eosinophils release toxic proteins capable of destroying those neurons, thereby causing the irreversible motility abnormalities of achalasia. This report reviews data on the association of esophageal eosinophilia with achalasia and other esophageal motility abnormalities. Based on this review, we propose that EoE, like eosinophilic gastroenteritis, might have mucosal-predominant and muscle-predominant forms with different clinical manifestations. A muscle-predominant form of EoE could underlie a variety of reversible and irreversible esophageal motility disorders, including achalasia. The concept that esophageal motility abnormalities might develop from a muscle-predominant form of EoE warrants serious consideration and further investigation.

PS01.109: A RARE TUMOR OF THE CERVICAL ESOPHAGUS: SCHWANNOMA

Abstract Background Schwannomas esophagus is very rarely seen. In this study, a schwannoma case with cervical esophagus was presented. Methods A 26-year-old female presented with dysphagia. In esophageal ultrasonography, a homogeneous, hypoechoic, and smooth-sided lesion originating from the proximal esophagus muscularis propria was detected. MRI revealed a well-defined mass lesion located in the cervical esophagus. Results The left cervical incision was performed and the lesion was enucleated. After the enucleation, saline was inserted into the enucleated area, and air was injected into the nasogastric tube to investigate the possibility of mucosal injuries. The esophageal muscle layers were then primarily closed with absorbable sutures. Frozen section examination was benign. Postoperative histopathological evaluation was assessed as accordance with schwannoma (Figure). Oral diet was started on the 3th postoperative day. There were no complications postoperatively. The patient was discharged on the 5th postoperative day. Conclusion The vast majority of esophageal tumors are cancer. Benign esophagial tumors constitute less than 1% of all esophageal tumors. Approximately 80% of benign esophagus tumors are leiomyomas. Esophageal schwannoma is very rare and difficult to diagnose by endoscopy and imaging methods. In these cases, surgery provides both definitive diagnosis and treatment. Disclosure All authors have declared no conflicts of interest.

Adjuvant External Beam Radiotherapy in Locally Advanced Differentiated Thyroid Cancer

ImportanceAs incidence of differentiated thyroid cancer rises, treatment paradigms have become increasingly defined. Despite this, locally advanced disease continues to be challenging to manage. Postoperative therapy in the form of radioactive iodine (RAI) is generally recommended, but the role of external beam radiation therapy (EBRT) is less well defined.ObjectiveTo investigate the role of EBRT in locally advanced differentiated thyroid cancer.Design, Setting, and ParticipantsFor this retrospective cohort study, patients treated surgically for T4a differentiated thyroid cancer at the University of Texas MD Anderson Cancer Center from January 2000 through December 2015 were recruited, and 88 patients were included for analysis.ExposuresAdjuvant treatment with RAI alone or both RAI and EBRT.Main Outcomes and MeasuresDisease-free survival (DFS), defined as the time from primary surgery to locoregional or distant recurrence or death due to any cause. Kaplan-Meier survival analysis was completed. Univariate and multivariate analysis was completed with Cox proportional hazards model to determine predictors of DFS.ResultsA total of 88 patients (44 women [50%]; mean [SD] age, 58.2 [15.3] years) were included in the analysis. Median (range) follow-up was 117 (12-164) months. Forty-four patients (50%) underwent RAI alone and 44 patients (50%) underwent RAI with adjuvant EBRT. Patients undergoing RAI alone did not receive EBRT owing to invasion into the recurrent laryngeal nerve only (n = 14 [32%]) or invasion into the tracheal perichondrium and/or esophageal muscularis only (n = 18 [41%]). Five-year DFS was 43% in those undergoing RAI alone, compared with 57% in those undergoing RAI and EBRT (effect size = 14%; 95% CI, −7% to 33%). Patients undergoing RAI alone had an increased rate of locoregional failure (effect size = −32%; 95% CI, −47% to −16%), with those undergoing RAI treatment alone, for minimal tracheal perichondrium and/or esophageal muscularis invasion having worse locoregional control than those with recurrent laryngeal nerve invasion only (effect size = 49%; 95% CI, 20% to 71%). Age (adjusted hazard ratio [adjusted HR], 1.02/y; 95% CI, 1.00 to 1.05) and esophageal invasion (adjusted HR, 2.30; 95% CI, 1.16 to 4.60) were independent predictors of worse DFS.Conclusions and RelevanceThe addition of EBRT to RAI results in good disease control in locally advanced differentiated thyroid cancer, particularly in patients with tracheal or esophageal invasion treated with aggressive surgical resection. Increased age and presence of esophageal invasion were independent predictors of poor disease control.

Catheter‐based high‐frequency intraluminal ultrasound imaging is a powerful tool to study esophageal dysmotility patients

High-resolution manometry (HRM) is currently the most important diagnostic test for esophageal motility disorders, providing information on the contraction pattern of the circular muscle layer, which helps classify these esophageal motor diseases. However, with the increasing development of ultrasound, other techniques, such as high-frequency intraluminal ultrasound (HFIUS), have gained importance. This technique uses a flexible shaft with a central wire integrated into a standard endoscope, which facilitates real-time sonography. Its main utility is to provide anatomical information on the structure of the esophageal wall, including both the circular and longitudinal layers that constitute the esophageal muscularis propria. Increasing knowledge about these motility disorders has led to the hypothesis that, in addition to an abnormal contraction pattern of the circular muscle, an overall increased muscle thickness and an abnormal longitudinal muscle contraction could be added as pathophysiological factors. The increase in muscle thickness could be an important indicator of the severity of diseases, such as achalasia, distal esophageal spasm, or hypercontractile esophagus. More studies are required before definitive conclusions can be reached, but HFIUS employed simultaneously with HRM could provide a more complete and precise evaluation of these esophageal motor disorders.

New orthotopic implantation model of human esophageal squamous cell carcinoma in athymic nude mice.

Subcutaneous xenograft is a common method to establish animal models of human esophageal squamous cell carcinoma (ESCC). However, the growth microenvironment of transplanted tumors is different from primary tumors. Orthotopic implantation models can provide more biologically relevant context in which to study the disease. So far, an orthotopic implantation model of ESCC has rarely been reported. The human ESCC cell line KYSE30 was transfected with pLVX-Luciferase plasmids. KYSE30-Luciferase cells were isolated and injected into the flanks of nude mice to develop a subcutaneous tumor. An orthotopic implantation model was established using the fragments derived from the subcutaneous tumor. Fluorescence imaging was used to observe the development of the orthotopic implanted tumor. Hematoxylin and eosin staining was performed to evaluate the invasion and metastasis of the tumor. KYSE30 cells were successfully transfected with pLVX-Luciferase plasmids. A primary tumor was developed in all mice. The mice experienced body weight loss. The implanted tumor infiltrated into the esophageal muscularis propria. However, neither distant organ nor lymph node metastasis was found. The progression of the primary tumor was monitored by in vivo fluorescence imaging. The orthotopic implantation model can be established by sewing the fragments of human ESCC to the abdominal esophagus of a nude mouse. The progression of an orthotopic implantation tumor can be monitored in real time by in vivo fluorescence imaging.