Lysophosphatidic acid promotes ESCC progression by increasing the level of CCL2 secreted by esophageal epithelial cells.

BACKGROUND: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA1-LPA6). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain. METHODS: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells. RESULTS: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA1/3, ultimately causing an increase in CCL2 expression and secretion in Het-1a. CONCLUSIONS: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator.

[Results of emergency management of esophageal lesions related to caustic ingestion in children in the emergency department of the General Reference Hospital of Niamey (Niger)]. / Résultats de la prise en charge médico-chirurgicale en urgence des lésions œsophagiennes liées aux ingestions de produits caustiques chez l'enfant dans le service des urgences de l'Hôpital général de référence de Niamey (Niger).

Introduction: Caustic ingestion in children is a public health problem; it is mainly due to domestic accidents due to improper packaging and storage of caustic products. It is a medical and surgical emergency whose management is multidisciplinary. The lesions caused by the accidental ingestion of caustics can affect the functional and vital prognosis in 10% of cases. Methodology: A retrospective, descriptive study from January 2020 to December 2022 (2 years), carried out in the emergency department of the General Reference Hospital of Niamey (Niger). The study included patients less than 15 years old admitted for ingesting a caustic product. Results: Our study included 17 patients. The average age was 5 years, with age extremes of 2 to 11 years. We noted a male predominance with a sex ratio (M/F) of 2.4. Ingestion of caustic products was accidental in all cases. The caustic product was caustic soda in 59%. The average quantity of product ingested was 5 ml (2 ml to 20 ml). The average consultation time was 3 days (3 hours to 15 days). Clinically, dysphagia was the most functional sign, represented by 13 cases, or 76%. Regarding general signs, 3 patients (18%) were admitted with fever; blood pressure was normal in 15 patients (88%); and 2 patients (18%) were admitted in a state of shock. The respiratory rate was normal in 14 patients (82%). Four patients (24%) were admitted in a state of deterioration in the general condition associated with severe malnutrition and dehydration. On physical examination, 2 patients (12%) presented with abdominal defense at the epigastric level. Examination of the ENT sphere revealed benign buccopharyngeal ulcerations in 2 patients (12%). Esogastroduodenal fibroscopy was performed in 4 patients (24%). The caustic lesions observed in the esophagus were: Zargar stage I at 25%, stage Ila at 50%, and stage Illb at 25%. In the stomach, the lesions were Zargar stage I in 75% of cases and stage III in 25% of cases. An injected thoracic-abdominopelvic computed tomography (CT) was performed in 3 patients (18%). It revealed a lack of enhancement of the esophageal wall compatible with esophageal necrosis in one patient. An esophagogastroduodenal transit was performed in 8 patients (47%) admitted more than 72 hours after ingestion of the caustic. They showed esophageal stenoses longer than 3 cm in 3 patients, multiple esophageal stenoses in 2 patients, a single esophageal stenosis in 2 patients, and a single antropyloric stenosis in 1 patient. Therapeutically, all patients benefited from antiemetics to avoid vomiting and proton pump inhibitors. Intravenous antibiotic prophylaxis with third-generation cephalosporin was administered to 12 patients (71%). Corticosteroid therapy based on IV prednisolone at a dose of 1 g/1.73 m2 per day was used to limit or prevent stenoses in 9 patients (53%). Parenteral nutrition was administered to 7 patients (41%). Endoscopic dilations were performed in 2 patients (12%). Emergency surgical treatment was performed in 7 patients (41%): 3 patients underwent transitional feeding gastrostomies; in 3 others, esophagoplasties by colon transplant were performed, and 1 patient was treated by stripping of the esophagus associated with total gastrectomy. The postoperative course was marked by a leak of esocolic anastomosis in one patient for whom conservative treatment was performed with good progress. The average length of hospital stay was 5 days (1-32 days). Conclusion: Accidental caustic ingestions can have serious consequences. Preventing these accidents relies on raising public awareness of the dangers associated with improper storage of these products.

Optimization of tracheoesophageal fistula model established with T-shaped magnet system based on magnetic compression technique.

BACKGROUND: The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula (TEF), but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control. We designed a T-shaped magnet system to overcome these problems and verified its effectiveness via animal experiments. AIM: To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs. METHODS: Twelve beagles were randomly assigned to groups in which magnets of the T-shaped scheme (study group, n = 6) or normal magnets (control group, n = 6) were implanted into the trachea and esophagus separately under gastroscopy. Operation time, operation success rate, and accidental injury were recorded. After operation, the presence and timing of cough and the time of magnet shedding were observed. Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing, and gross specimens of TEFs were obtained. Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery, and gross specimens were obtained. Fistula size was measured in all animals, and then harvested fistula specimens were examined by hematoxylin and eosin (HE) and Masson trichrome staining. RESULTS: The operation success rate was 100% for both groups. Operation time did not differ between the study group (5.25 min ± 1.29 min) and the control group (4.75 min ± 1.70 min; P = 0.331). No bleeding, perforation, or unplanned magnet attraction occurred in any animal during the operation. In the early postoperative period, all dogs ate freely and were generally in good condition. Dogs in the control group had severe cough after drinking water at 6-9 d after surgery. X-ray indicated that the magnets had entered the stomach, and gastroscopy showed TEF formation. Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm ± 1.29 mm (range, 3.52-6.56 mm). HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas. Dogs in the study group did not exhibit obvious coughing after surgery. X-ray examination 2 wk after surgery indicated fixed magnet positioning, and gastroscopy showed no change in magnet positioning. The magnets were removed using a snare under endoscopy, and TEF was observed. Gross specimens showed well-formed fistulas with a diameter of 6.11 mm ± 0.16 mm (range, 5.92-6.36 mm), which exceeded that in the control group (P < 0.001). Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining, and the structure was more regular than that in the control group. CONCLUSION: Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets. Most importantly, this model offers better controllability, which improves the flexibility of follow-up studies.

Evaluation of the effectiveness of mother milk exosomes in the experimental corrosive esophagitis model.

PURPOSE: We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS: 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS: A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION: It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.

Three-Dimensional Cell Culture Models to Investigate the Epithelial Barrier in Eosinophilic Esophagitis.

The squamous epithelium of the esophagus is directly exposed to the environment, continuously facing foreign antigens, including food antigens and microbes. Maintaining the integrity of the epithelial barrier is critical for preventing infections and avoiding inflammation caused by harmless food-derived antigens. This article provides simplified protocols for generating human esophageal organoids and air-liquid interface cultures from patient biopsies to study the epithelial compartment of the esophagus in the context of tissue homeostasis and disease. These protocols have been significant scientific milestones in the last decade, describing three-dimensional organ-like structures from patient-derived primary cells, organoids, and air-liquid interface cultures. They offer the possibility to investigate the function of specific cytokines, growth factors, and signaling pathways in the esophageal epithelium within a three-dimensional framework while maintaining the phenotypic and genetic properties of the donor. Organoids provide information on tissue microarchitecture by assessing the transcriptome and proteome after cytokine stimulation. In contrast, air-liquid interface cultures allow the assessment of the epithelial barrier integrity through transepithelial resistance (TEER) or macromolecule flux measurements. Combining these organoids and air-liquid interface cultures is a powerful tool to advance research in impaired esophageal epithelial barrier conditions.

Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool.

Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.

Modeling Radiation-Induced Epithelial Cell Injury in Murine Three-Dimensional Esophageal Organoids.

Esophageal squamous cell carcinoma (ESCC) is a deadly consequence of radiation exposure to the esophagus. ESCC arises from esophageal epithelial cells that undergo malignant transformation and features a perturbed squamous cell differentiation program. Understanding the dose- and radiation quality-dependence of the esophageal epithelium response to radiation may provide insights into the ability of radiation to promote ESCC. We have explored factors that may play a role in esophageal epithelial radiosensitivity and their potential relationship to ESCC risk. We have utilized a murine three-dimensional (3D) organoid model that recapitulates the morphology and functions of the stratified squamous epithelium of the esophagus to study persistent dose- and radiation quality-dependent changes. Interestingly, although high-linear energy transfer (LET) Fe ion exposure induced a more intense and persistent alteration of squamous differentiation and 53BP1 DNA damage foci levels as compared to Cs, the MAPK/SAPK stress pathway signaling showed similar altered levels for most phospho-proteins with both radiation qualities. In addition, the lower dose of high-LET exposure also revealed nearly the same degree of morphological changes, even though only ~36% of the cells were predicted to be hit at the lower 0.1 Gy dose, suggesting that a bystander effect may be induced. Although p38 and ERK/MAPK revealed the highest levels following high-LET exposure, the findings reveal that even a low dose (0.1 Gy) of both radiation qualities can elicit a persistent stress signaling response that may critically impact the differentiation gradient of the esophageal epithelium, providing novel insights into the pathogenesis of radiation-induced esophageal injury and early stage esophageal carcinogenesis.

Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation.

BACKGROUND: Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. METHODS: All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. RESULTS: 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. CONCLUSION: OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.

Predictors of anastomotic leak and conduit necrosis after oesophagectomy: Results from the oesophago-gastric anastomosis audit (OGAA).

BACKGROUND: Both anastomotic leak (AL) and conduit necrosis (CN) after oesophagectomy are associated with high morbidity and mortality. Therefore, the identification of preoperative, modifiable risk factors is desirable. The aim of this study was to generate a risk scoring model for AL and CN after oesophagectomy. METHODS: Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018-December 2018. Definitions for AL and CN were those set out by the Oesophageal Complications Consensus Group. Univariate and multivariate analyses were performed to identify risk factors for both AL and CN. A risk score was then produced for both AL and CN using the derivation set, then internally validated using the validation set. RESULTS: This study included 2247 oesophagectomies across 137 hospitals in 41 countries. The AL rate was 14.2% and CN rate was 2.7%. Preoperative factors that were independent predictors of AL were cardiovascular comorbidity and chronic obstructive pulmonary disease. The risk scoring model showed insufficient predictive ability in internal validation (area under the receiver-operating-characteristic curve [AUROC] = 0.618). Preoperative factors that were independent predictors of CN were: body mass index, Eastern Cooperative Oncology Group performance status, previous myocardial infarction and smoking history. These were converted into a risk-scoring model and internally validated using the validation set with an AUROC of 0.775. CONCLUSION: Despite a large dataset, AL proves difficult to predict using preoperative factors. The risk-scoring model for CN provides an internally validated tool to estimate a patient's risk preoperatively.

Esophageal remodeling in eosinophilic esophagitis.

PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a Th2 immune/antigen-mediated disorder characterized by esophageal dysfunction and eosinophilic inflammation. Worsening dysphagia and food impactions are significant complications associated with esophageal remodeling and fibrostenotic disease. This review highlights the most recent research findings pertaining to mechanisms of sub-epithelial fibrosis in EoE, current diagnostic tools, and therapeutic approaches. RECENT FINDINGS: Recent studies leveraging publicly available single cell sequencing databases and comparative proteomics have furthered our understanding of the mechanisms mediating fibrosis. Fibroblast crosstalk with the extracellular matrix and with epithelial, endothelial, and T cells have been implicated, with the likely existence of multiple fibroblast sub-types. Accurate diagnosis of remodeling with biopsies remains a challenge due to inadequate depth of sampling. Web-based tools incorporating epithelial findings show promise in predicting subepithelial fibrosis. Impedance planimetry with esophageal distensibility measurements are increasingly utilized tools to assess fibrostenotic severity. Immunostaining and luminal captured proteins associated with remodeling show promise as potential molecular markers of fibrosis. Anti-inflammatory therapy may improve esophageal fibrosis and distensibility, although specific fibrosis-targeted therapy is lacking. SUMMARY: Recent studies highlight novel mechanisms of fibrosis in EoE. Improved understanding of these mechanisms may lead to novel diagnostic strategies and therapies, and thereby inform treatment decisions.

Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis.

BACKGROUND AND AIMS: Eosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined. METHODS: We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) and analysed the gene expression profile in these biopsies by total RNA-sequencing (RNA-seq). Moreover, we employed the publicly accessible RNA-seq dataset (series GSE148381) as reported by Greuter et al, encompassing a comprehensive genomic profile of patients presenting with EoE variants. RESULTS: A novel, diagnostic gene expression panel that can effectively distinguish patients with histologically active conventional EoE from patients with EoE in histological remission and control individuals, and from three newly discovered EoE variants was identified. Histologically Active EoE Diagnostic Panel (HAEDP) consists of 53 genes that were identified based on differential expression between histologically active EoE, histological remission and controls (p≤0.05). By combining the HAEDP with EDP, we expanded our knowledge about factors that may contribute to the inflammation in EoE and improved our understanding of the underlying mechanisms of the disease. Conversely, we suggested a compact group of genes common to both HAEDP and EDP to create a reliable diagnostic tool that might enhance the accuracy of EoE diagnosis. CONCLUSION: We identified a novel set of 53 dysregulated genes that are closely associated with the histological inflammatory activity of EoE. In combination with EDP, our new panel might be a valuable tool for the accurate diagnosis of patients with EoE as well as for monitoring their disease course.

Large-Caliber Empiric Esophageal Dilation Results in Sustained Improvement for Selected Patients With Nonobstructive Dysphagia.

INTRODUCTION: Empiric esophageal dilation (EED) remains a controversial practice for managing nonobstructive dysphagia (NOD) secondary to concerns about safety and efficacy. We examine symptom response, presence of tissue disruption, and adverse events (AEs) after EED. METHODS: We examined large-caliber bougie EED for NOD at 2 tertiary referral centers: retrospectively evaluating for AEs. Esophageal manometry diagnoses were also reviewed. We then prospectively assessed EED's efficacy using the NIH Patient-Reported Outcomes Measurement Information System disrupted swallowing questionnaire to assess dysphagia at baseline, 1, 3, and 6 months after EED. Treatment success was defined by improvement in patient-reported outcome scores. RESULTS: AE rate for large-caliber dilation in the retrospective cohort of 180 patients undergoing EED for NOD was low (0.5% perforations, managed conservatively). Visible tissue disruption occurred in 18% of patients, with 47% occurring in the proximal esophagus. Obstructive motility disorders were found more frequently in patients with tissue disruption compared with those without (44% vs 14%, P = 0.05). The primary outcome, the mean disrupted swallowing T -score was 60.1 ± 9.1 at baseline, 56.1 ± 9.5 at 1 month ( P = 0.03), 57 ± 9.6 at 3 months ( P = 0.10), and 56 ± 10 at 6 months ( P = 0.02) (higher scores note more symptoms). EED resulted in a significant and durable improvement in dysphagia and specifically solid food dysphagia among patients with tissue disruption. DISCUSSION: EED is safe in solid food NOD and particularly effective when tissue disruption occurs. EED tissue disruption in NOD does not preclude esophageal dysmotility.

Proactive esophageal cooling during laser cardiac ablation: A computer modeling study.

BACKGROUND AND OBJECTIVES: Laser ablation is increasingly used to treat atrial fibrillation (AF). However, atrioesophageal injury remains a potentially serious complication. While proactive esophageal cooling (PEC) reduces esophageal injury during radiofrequency ablation, the effects of PEC during laser ablation have not previously been determined. We aimed to evaluate the protective effects of PEC during laser ablation of AF by means of a theoretical study based on computer modeling. METHODS: Three-dimensional mathematical models were built for 20 different cases including a fragment of atrial wall (myocardium), epicardial fat (adipose tissue), connective tissue, and esophageal wall. The esophagus was considered with and without PEC. Laser-tissue interaction was modeled using Beer-Lambert's law, Pennes' Bioheat equation was used to compute the resultant heating, and the Arrhenius equation was used to estimate the fraction of tissue damage (FOD), assuming a threshold of 63% to assess induced necrosis. We modeled laser irradiation power of 8.5 W over 20 s. Thermal simulations extended up to 250 s to account for thermal latency. RESULTS: PEC significantly altered the temperature distribution around the cooling device, resulting in lower temperatures (around 22°C less in the esophagus and 9°C in the atrial wall) compared to the case without PEC. This thermal reduction translated into the absence of transmural lesions in the esophagus. The esophagus was thermally damaged only in the cases without PEC and with a distance equal to or shorter than 3.5 mm between the esophagus and endocardium (inner boundary of the atrial wall). Furthermore, PEC demonstrated minimal impact on the lesion created across the atrial wall, either in terms of maximum temperature or FOD. CONCLUSIONS: PEC reduces the potential for esophageal injury without degrading the intended cardiac lesions for a variety of different tissue thicknesses. Thermal latency may influence lesion formation during laser ablation and may play a part in any collateral damage.

Cronkhite-Canada syndrome with esophagus involvement and six-year follow-up: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare, noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities. CCS polyps are distributed through the whole digestive tract, and they are common in the stomach and colon but very uncommon in the esophagus. CASE SUMMARY: Here, we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea, alopecia, and loss of his fingernails. Laboratory data indicated anemia, hypoalbuminemia, hypocalcemia, hypokalemia, and positive fecal occult blood. Endoscopy showed numerous polyps scattered throughout the digestive tract, including the esophagus. He was treated with nutritional support and glucocorticoids with remission of his symptoms. CONCLUSION: Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms. Treatment should be individualized for each patient according to their therapy response. Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

Expression of CD25, mast cell markers and T-cell markers in eosinophilic esophagitis.

While eosinophilic esophagitis (EOE) is defined by histologic presence of eosinophils, a few studies have established the presence of mast cells in EOE and even shown their correlation with symptom persistence despite resolution of eosinophils. Expression of aberrant mast cell markers CD25 and CD2 have not been studied in EOE. This study quantifies the number of hotspot cells per high power field expressing CKIT/CD117, tryptase, CD25, CD2 and CD3 by immunohistochemical stains in endoscopic esophageal biopsies of the following three cohorts: (1) established and histologically confirmed EOE, (2) suspected EOE with biopsies negative for eosinophils, and (3) no history of or suspicion for EOE with histologically unremarkable biopsies. In this study, mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry, and that invite further study into the role that these cells may play in EOE.

Endoscopic and histologic utility of transnasal endoscopy in pediatric eosinophilic esophagitis.

Unsedated transnasal endoscopy (TNE) is an alternative method of examining the esophageal mucosa in pediatric patients with eosinophilic esophagitis (EoE), reducing cost, time, and risk associated with frequent surveillance esophagogastroduodenoscopies (EGD). Adequacy of transnasal esophageal biopsies for the evaluation of eosinophilic esophagitis histologic scoring system (EoEHSS) has not yet been evaluated. We compared procedure times, endoscopic findings, and EoEHSS scoring for EoE patients undergoing TNE versus standard EGD. Sixty-six TNE patients and 132 EGD controls matched for age (mean age 14.0 years) and disease status (29.3% active) were included. Compared to patients undergoing standard EGD, patients undergoing TNE spent 1.94 h less in the GI suite (p < 0.0001), with comparable occurrence rates of all visual endoscopic findings and most EoEHSS components. TNE serves as a useful tool for long-term disease surveillance, and consideration should be given to its use in clinical trials for EoE.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

[Transoral robotic surgery in the management of solitary fibrous tumor at the entrance of the hypolaryngeal esophagus: a case report and literature review].

To explore the clinical diagnosis and treatment experience of isolated fibrotic tumor （SFT） occurring in the larynx, hypopharynx and esophageal inlet with a wide range.The patient, admitted to the Department of Otolaryngology-Head and Neck Surgery of Tangdu Hospital of Air Force Medical University was a female aged at 78 years, who was diagnosed with SFT primarily occured at laryngeal, hypopharynx and esophageal entrance. The clinical data, surgical methods, histopathology characteristics of the patient were analyzed respectively. It's proved that a tumor sized about 3.8 cm×2.8 cm×2.0 cm with slippy surface was found at the entrance of the laryngeal, hypopharynx and esophageal entrance, covering the laryngeal vestibule, glottis and right piriform fossa, which was completely resected by transoral robotic surgery. The postoperative pathological diagnosis was SFT. The patient recovered well after surgery and showed no recurrence within 16-month follow-up. SFT occurring in the larynx, hypopharynx, and esophageal inlet is very rare, and transoral da Vinci robotic surgical resection of the tumor in this area is feasible, and has the advantages of clear field of vision, less bleeding, less trauma, fewer complications, and quicker postoperative recovery.