[Esophagitis dissecans superficialis: two cases of the same rare entity]. / Esofagitis disecante superficial: dos casos de una misma entidad poco frecuente.

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment.

A case report of esophageal cancer in a patient with pemphigus vulgaris: A coincidence or something beyond that?

BACKGROUND: Pemphigus is a group of rare but serious autoimmune blistering disorders, affecting skin and mucus membrane. Different reports have been published in respect to the coexistence of pemphigus with neoplasms, especially lympho-proliferative ones. CASE: Here, we have reported a patient previously diagnosed with pemphigus vulgaris (PV) who developed esophageal squamous cell carcinoma (SCC). CONCLUSION: Dyspepsia and dysphagia in patients with PV might not be merely due to pemphigus erosions or simply an adverse effect of systemic corticosteroid such as irritant or candidal esophagitis and should raise the suspicion of more serious conditions in case of resistant symptoms without appropriate response to treatment.

The Regulation of Exosome-Mediated miR-132-3p/miR-132-3p-UUU on Radiation-Induced Esophageal Injury.

Radiation-induced esophageal injury (RIEI) is a major dose-limiting complication of radiotherapy, mainly acute esophagitis. However, understanding of radiation injury and repair mechanisms in esophageal epithelial cells remains limited. MiR-132-3p and its uridylated isoform (miR-132-3p-UUU) are upregulated in radiation esophageal injury, yet their role in radiation-induced esophageal injury progression remains unexplored. We expressed miR-132-3p and its uridine form in irradiated human esophageal epithelial cells (HEEC) and secreted exosomes was examined by real-time polymerase chain reaction (RT-PCR). Cell proliferation, migration, apoptosis and colony formation were used to determine biological effects. Cell cycle assays and dual luciferase reporter assays were used to assess the relationship between miR-132-3p and its uridylated isoforms and MEF2A. The addition of miR-132-3p mimics or overexpression of miR-132-3p significantly inhibited the proliferation and migration of esophageal epithelial cells (HEEC cells as well as primary cells) and increased radiation damage. This was reversed by its uridylated isoform by reducing binding to MEF2A and regulating the cell cycle. Furthermore, miR-132-3p and its triuridylated isomer also regulate apoptosis after irradiation through pathways other than reactive oxygen species (ROS). In conclusion, our data reveal that radiation-induced miR-132-3p uridylation and exosome-mediated intercellular communication and tri-uridylated isoforms are protective against radiation-induced esophageal injury. Furthermore, miR-132-3p offers new opportunities as a promising biomarker widely present in human body fluids for the prediction of radiation esophagitis as a biomarker.

Analysis of the pathogenesis of acute necrotizing esophagitis (black esophagus): A report of three autopsy cases.

Acute necrotizing esophagitis (ANE) is a rare condition characterized by black discoloration of the esophageal mucosa. We describe three autopsy cases of ANE, also known as black esophagus. The black discoloration was confined to the esophageal mucosa rather than to the gastric mucosa. The histological findings of brown pigmentation and acute inflammation led to an ANE diagnosis. The immediate cause of death was certified as ANE in all cases. In the three cases, one had hypertension, diabetes, and multiple cerebral infarctions, another had alcoholism, whereas the pre-existing condition was unknown in the remaining patient. Petechial hemorrhages were found on the gastric mucosa of all three patients as a finding of terminal hypothermia. In one case, frequent vomiting was observed prior to death. Blood alcohol was detected (the patient had been drinking immediately prior to death), and the onset of ANE was considered to have occurred several hours before death. The findings indicate that ANE occurs shortly before death in combination with frequent vomiting and terminal hypothermia in the setting of cerebrovascular disease or alcoholism.

Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis.

AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.

Radiobiological modeling of acute esophagitis after radiation therapy of head, neck, and thorax tumors: The influence of chemo-radiation.

Aim: The aim of this study was to evaluate the performance of various radiobiological models in predicting the occurrence of acute esophagitis (AE) during radiation therapy (RT) of head, neck, and thoracic tumors with concurrent and sequential chemotherapy. According to recent studies, the probability of AE following RT by normal tissue complication probability models is predictable. Materials and Methods: A total of 100 patients with nasopharynx, larynx, Hodgkin's lymphoma, spinal metastases, and oral cavity and lung tumors were included in the study. Half of these patients were treated by concurrent chemo-radiotherapy (Con. CRT) and the other half were treated by radiotherapy alone or sequential chemo-radiotherapy (RT + seq. CRT). Radiobiological models of several types were used as follows,: Lyman-generalized equivalent uniform dose (gEUD), Lyman-MED, log-logistic, logit, and logistic. Parameters were estimated using maximum likelihood estimation, and models were compared using Akaike information criteria. Results: Based on follow-up data, the behavior of dose-response curves differed markedly between the Con. CRT and RT + seq. CRT groups. The best fit with clinical results was offered by the Lyman-MED model for the Con. CRT group and the Lyman-gEUD model for the RT + seq. CRT group. Depending on the model used, the parameter of D50 was considerably lower (up to three times) in the Con. CRT group compared to the RT + seq. CRT group. Conclusions: The incidence of AE significantly differed between the two treatment groups in all the models. New parameter estimates could be used for predicting the probability of acute esophagitis after chemo-RT.

Infectious Esophagitis in Children.

Infectious esophagitis is the third most common cause of esophagitis after gastroesophageal reflux disease and eosinophilic esophagitis (EoE) and should always be considered in the differential of patients with dysphagia and odynophagia. The most common organisms causing disease are candida, Herpes simplex virus (HSV) and cytomegalovirus (CMV). It is well recognized that an impaired local or systemic immune system is a risk factor for disease; however, esophageal dysmotility and disruptions in esophageal homeostasis and the esophageal milieu are likely to represent additional risk factors in disease pathogenesis.

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial.

PURPOSE: Hypofractionated radiation therapy has been safely implemented in the treatment of early-stage non-small cell lung cancer (NSCLC) but not locally advanced NSCLC owing to prohibitive toxicities with photon therapy. Proton therapy, however, may allow for safe delivery of hypofractionated radiation therapy. We sought to determine whether hypofractionated proton therapy with concurrent chemotherapy improves overall survival. METHODS AND MATERIALS: The Proton Collaborative Group conducted a phase 1/2 single-arm nonrandomized prospective multicenter trial from 2013 through 2018. We received consent from 32 patients, of whom 28 were eligible for on-study treatment. Patients had stage II or III unresectable NSCLC (based on the 7th edition of the American Joint Committee on Cancer's staging manual) and received hypofractionated proton therapy at 2.5 to 4 Gy per fraction to a total 60 Gy with concurrent platin-based doublet chemotherapy. The primary outcome was 1-year overall survival comparable to the 62% reported for the Radiation Therapy Oncology Group (RTOG) 9410 trial. RESULTS: The trial closed early owing to slow accrual, in part, from a competing trial, RTOG 1308. Median patient age was 70 years (range, 50-86 years). Patients were predominantly male (n = 20), White (n = 23), and prior smokers (n = 27). Most had stage III NSCLC (n = 22), 50% of whom had adenocarcinoma. After a median follow-up of 31 months, the 1- and 3-year overall survival rates were 89% and 49%, respectively, and progression-free survival rates were 58% and 32%, respectively. No acute grade ≥3 esophagitis occurred. Only 14% developed a grade ≥3 radiation-related pulmonary toxic effect. CONCLUSIONS: Hypofractionated proton therapy delivered at 2.5 to 3.53 Gy per fraction to a total 60 Gy with concurrent chemotherapy provides promising survival, and additional examination through larger studies may be warranted.

Lymphocytic Esophagitis: Current Understanding and Controversy.

This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.

Clinical and Histopathologic Features Can Help Target Immunohistochemical Stain Use in the Diagnosis of Viral Esophagitis.

OBJECTIVES: Herpes simplex virus (HSV) and cytomegalovirus (CMV) immunohistochemical stains (IHC) are frequently applied on esophageal biopsies. Our aims were to identify IHC use patterns in viral esophagitis (VE), and clinicopathologic features of VE that could guide IHC use. METHODS: We included 58 VE cases and 60 controls, defined as patients with negative HSV/CMV IHC between January 2006 and July 2017. Biopsies were reviewed and histologic features and clinical data recorded. RESULTS: Thirteen cases required IHC for diagnosis. IHC was performed in 13 HSV and 5 CMV cases where diagnostic viral inclusions were present. VE patients were more likely to have endoscopic ulcer (P=0.002) and be immunocompromised (P<0.001). Pretest clinical concern for VE was common (P=0.006). Histologically, VE patients were more likely to have ulcer (P=0.004), ulcer exudate rich in neutrophils and histiocytes (P=0.001), neutrophils in squamous mucosa (P<0.001), histiocyte aggregates >15 (P<0.001) and spongiosis (P<0.001). Controls had frequent eosinophils, alone (P=0.008) or admixed with other inflammatory cells (P<0.0001). CONCLUSIONS: IHC is used in VE biopsies despite definite viral inclusions on hematoxylin and eosin and in patients without concerning histology or clinical concern for VE. History, endoscopic findings, and histology can be used to better target IHC use in VE.

Bidirectional crosstalk between eosinophils and esophageal epithelial cells regulates inflammatory and remodeling processes.

Eosinophils accumulate adjacent to epithelial cells in the mucosa of patients with eosinophilic esophagitis (EoE), yet the bidirectional communication between these cells is not well understood. Herein, we investigated the crosstalk between human eosinophils and esophageal epithelial cells. We report that blood-derived eosinophils have prolonged survival when cocultured with epithelial cells; 96 ± 1% and 30 ± 6% viability was observed after 7 and 14 days of coculture, respectively, compared with 1 ± 0% and 0 ± 0% of monoculture. In the presence of IL-13 and epithelial cells, eosinophils had greater survival (68 ± 1%) at 14 days compared with cocultures lacking IL-13. Prolonged eosinophil viability did not require cellular contact and was observed when eosinophils were cultured in conditioned media from esophageal epithelial cells; neutralizing GM-CSF attenuated eosinophil survival. The majority of eosinophil transcripts (58%) were dysregulated in cocultured eosinophils compared with freshly isolated cells. Analysis of epithelial cell transcripts indicated that exposure to eosinophils induced differential expression of a subset of genes that were part of the EoE esophageal transcriptome. Collectively, these results uncover a network of crosstalk between eosinophils and esophageal epithelial cells involving epithelial mediated eosinophil survival and reciprocal changes in cellular transcripts, events likely to occur in EoE.

Esophagitis dissecans superficialis associated with acute transoral paraquat poisoning: Clinical study of 15 cases.

To analyze the clinical characteristics and therapeutic effects of transoral paraquat poisoning combined with Esophagitis dissecans superficialis (EDS). A retrospective observational study was conducted on paraquat poisoning patients between January 1, 2011 and August 30, 2016 in Qilu hospital. Fifteen patients with EDS were enrolled in this study. The clinical characteristics, prognosis, and pathological features of esophageal necrosis mucosa of these patients were retrospectively analyzed and summarized. Esophageal mucosal dissection occurs mainly within 3-8 days after transoral paraquat poisoning in 15 patients. Dosage of paraquat is range from 50 to 100 ml. Most patients have physical problems with swallowing before the intramural esophageal dissection occurred. And there are other symptoms, including sore throat or dysphagia (100%), nausea and vomiting (86.7%), heartburn or upper abdominal pain (73.3%), hematemesis (60%), abdominal distension (20%) and cough frequently (6.7%). In death group, most patients demonstrate features of the multiple organ failure when the esophageal mucosal stripping happened, including lung injury, renal failure, and hepatic failure. The shape of esophageal dissection was tubular in 60%, irregular in 40%, and they vary in size. Pathological examination showed extensive injury, necrosis and hemorrhage of digestive tract epithelium, and obvious inflammatory reaction of epithelial tissue. Transoral paraquat poisoning has certain damage to the patient's esophageal mucosa, and some may be complicated with EDS, and the prognosis is poor, especially when combined with multiple organ dysfunction. Esophageal damage is mainly located in the esophageal mucosa and have different degrees. Special attention should be paid on such patients.

Acute and extremely severe necrotic esophagitis accompanied by hyperglycemic hyperosmolar syndrome in a subject with type 2 diabetes mellitus.

Acute necrotic esophagitis is characterized by blacking in the esophageal mucosa and is rarely accompanied by diabetes mellitus, especially under severe hyperglycemic conditions. Here we show a very rare case of a patient who had acute and extremely severe necrotic esophagitis accompanied by hyperglycemic hyperosmolar syndrome.

The esophageal dose-volume parameters for predicting Grade I-II acute esophagitis correlated with weight loss and serum albumin decrease in lung cancer radiotherapy.

INTRODUCTION: Acute esophagitis (AE) is a commonly encountered side effect of curative thoracic radiotherapy (CTRT) for lung cancer patients. Nevertheless, its identification for widely used scoring systems depends on patients' statements. It is aimed to evaluate the correlation between the esophagus doses during CTRT and Grade 1-2 AE, weight change, and change in serum albumin (Alb) levels. SUBJECTS AND METHODS: The data collected from 124 lung cancer patients treated with ≥60 Gy CTRT were evaluated retrospectively. Weight and serum Alb level difference of each patient, throughout CTRT, were calculated. The percentage of the esophagus volume receiving ≥5 Gy (V5), V10, V35, V50, and V60; the absolute esophagus volume receiving ≥60 Gy (V60(cc)); the length of esophagus receiving ≥60 Gy (L60); the average esophagus dose (Dmean); and the maximum esophagus dose (Dmax) were the dose parameters calculated. The correlations were performed by Spearman's rank correlation coefficient. RESULTS: Grade 1 and Grade 2 AE were reported in 62 and 25 patients, respectively. All of the dose parameters were correlated with Grade 1-2 AE (P < 0.001) and weight loss (P < 0.001 for all, except Dmax P = 0.018). Decrease in serum Alb level was significantly correlated with all the parameters, but V5 and V10. Receiver operating characteristic curve analysis was performed for five parameters with the highest correlation coefficient (V35, V50, V60(%), V60(cc), and Dmean), and the cutoff values were 39.5%, 28.17%, 2.21%, 0.5cc, and 26.04 Gy, respectively. CONCLUSIONS: The correlation of the dose parameters that might be effective on Grade 1-2 AE with the weight loss and Alb loss was investigated, and the cutoff values corresponding to the best sensitivity and specificity were identified.

Lymphocytic Esophagitis With Predominance of CD4 T Cells and Expansion of Th1 Cells Is Associated With Achalasia.

OBJECTIVES: Although histologic features in biopsies suggesting a possibility of achalasia would be helpful diagnostically, such features remain unknown. The goal of this study was to explore the prevalence, histologic features, and immunophenotype of lymphocytic esophagitis (LyE) in achalasia biopsies. METHODS: The study group consisted of 57 patients with achalasia. Controls comprised 52 patients with severe gastroesophageal reflux disease (GERD) and normal esophageal motility. CD4/CD8 immunophenotype of lymphocytes was analyzed by immunohistochemistry. RESULTS: LyE was identified in 30% (17/57) of patients with achalasia and 6% (3/52) of patients with GERD, indicating a strong association with achalasia (odds ratio, 6.94; 95% confidence interval, 1.90-25.38). LyE was focal in 59% (10/17) of the cases and diffuse in 41% (7/17). CD4 T-cell predominance over CD8 T cells was observed in 88% of patients with achalasia and LyE. T helper 1 (Th1) cells, but not T helper 2 cells, were expanded in CD4 T cells; in the absence of evident infection, this was compatible with the role of Th1 cells in organ-specific autoimmunity. CONCLUSIONS: Achalasia should be considered in the differential diagnosis of clinical entities associated with CD4-predominant LyE. Additional studies to explore the significance of Th1 cells in achalasia-associated LyE are warranted.