Corrosive induced esophageal and gastric injury: Histopathological evaluation of surgically resected specimens over a decade in a tertiary care center.

BACKGROUND: Caustic ingestion is associated with long-term sequelae like esophageal stricture, gastric cicatrization, and long-term risk of dysplasia or even carcinoma. However, only a few small studies have explored histopathological aspects of caustic-induced esophageal/gastric injury. MATERIALS AND METHODS: We retrospectively evaluated specimens of patients undergoing surgery due to caustic ingestion-related complications from 2008 to 2020. Pathological examination was conducted by two independent gastro-pathologists to evaluate the extent and depth of the caustic injury, presence or absence of tissue necrosis, type and degree of inflammation, or presence of any dysplastic cells. RESULTS: A total of 54 patients underwent surgical exploration during the inclusion period and complete details of 39 specimens could be retrieved. The mean age of the included patients was 28.66 ± 9.31 years and 25 (64.1%) were male. The majority of patients (30; 76.9%) had a history of caustic ingestion more than three months before the surgery and the presence of long or refractory stricture was the most common indication for the surgery (20; 51.28%). In the resected specimen, a majority of patients had superficial esophageal or gastric ulcer (90.6%; 60.0%), transmural inflammation (68.8%; 65.6%), transmural fibrosis (62.5%; 34.4%), and hypertrophied muscularis mucosa (78.13%; 53.3%). However, none of the patients had dysplasia in the resected esophageal or gastric specimens. CONCLUSION: Caustic ingestion leads to mucosal ulceration, transmural inflammation, and transmural fibrosis which might be the reason for refractory stricture in such patients.

Prevention of Esophageal Stricture after Endoscopic Submucosal Dissection with an Autologous Esophageal Epithelial Cell Suspension: An Animal Study.

BACKGROUND: Severe esophageal stricture decreases patient's quality of life after circumferential endoscopic submucosal dissection (ESD). We aimed to evaluate the efficacy of autologous esophageal epithelial cell suspensions in preventing esophageal stricture after circumferential ESD. METHODS: Twelve male mini-pigs underwent circumferential ESD and were randomized into four groups: G1 (control), G2 (esophageal stent), G3 (autologous esophageal epithelial cell suspension), and G4 (autologous esophageal epithelial cell suspension combined with esophageal stent). Post-ESD status was observed in each group, and endoscopy was performed weekly. Esophageal stents were removed 3 weeks after ESD. The esophageal stricture rates and histologic characteristics were assessed 4 weeks after ESD. RESULTS: G1 showed the greatest weight loss (p < 0.05). Dysphagia scores were not significantly different among the groups. The esophageal mucosal stricture rates were 77.7 ± 2.9%, 74.2 ± 1.9%, 69.2 ± 3.8% and 65.9 ± 1.9% in G1-4, respectively; with the highest in G1 (G1 vs. G3, p = 0.005; G1 vs. G4, p = 0.001). The regenerated epithelium lengths were 4.408 ± 1.980 mm, 8.319 ± 0.857 mm, 11.801 ± 2.455 mm and 12.353 ± 1.111 mm in G1-4, respectively. The lowest degree of re-epithelialization was observed in G1, followed by G2, with the highest degrees in G3 and G4 (G1 vs. G3, p = 0.001; G1 vs. G4, p = 0.000). The maximum wound fibrosis thicknesses were 2.546 ± 0.389 mm, 2.136 ± 0.231 mm, 1.126 ± 0.211 mm and 1.131 ± 0.438 mm in G1-4, respectively, with higher degrees in G1 and G2 than in G3 and G4 (G1 vs. G3, p = 0.001; G1 vs. G4, p = 0.001). CONCLUSIONS: Autologous esophageal epithelial cell suspensions can promote re-epithelialization and reduce fibrosis, thus decreasing esophageal stricture severity after ESD.

A novel tetra-PEG based hydrogel for prevention of esophageal stricture after ESD in a porcine model.

Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer and precancerous lesions, but resection of a large mucosal area often leads to postoperative esophageal stricture. Biomaterials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a well-defined ammonolysis-based tetra-armed poly (ethylene glycol) (Tetra-PEG) hydrogel and investigated its efficacy and related mechanisms for preventing esophageal ESD-induced stricture in a porcine model. In terms of material properties, Tetra-PEG hydrogel present great biocompatibility，great capability to retain moisture, strong tissue adhesion and high mechanical strength. Then, six domestic female pigs were randomly divided into PEG (n = 3) and control groups (n = 3). A 3/4 of the esophageal circumference ESD was performed in all pigs. In PEG group, Tetra-PEG hydrogel was easily delivered via endoscopy and adhered to the ulcer bed tightly. Compared to control group, Tetra-PEG hydrogel accelerated esophageal ulcer healing at an early stage with enhanced epithelium regeneration, milder inflammation and lesser fibrosis by regulating TGF-ß/Smad2 signaling. Taken together, our findings reveal Tetra-PEG hydrogel is a promising and attractive candidate for preventing the formation of fibrotic stricture in the process of esophageal ESD-induced ulcer repair.

The Slender Esophagus: Unrecognized Esophageal Narrowing in Eosinophilic Esophagitis.

INTRODUCTION: Inflammation in eosinophilic esophagitis (EoE) often leads to esophageal strictures. Evaluating esophageal narrowing is clinically challenging. We evaluated esophageal distensibility as related to disease activity, fibrosis, and dysphagia. METHODS: Adult patients with and without EoE underwent endoscopy and distensibility measurements. Histology, distensibility, and symptoms were analyzed. RESULTS: Patients with EoE had significantly lower distensibilities than controls. We found a cohort with esophageal diameter under 15 mm despite lack of dysphagia. DISCUSSION: This study raises concern that current assessments of fibrostenosis are suboptimal. We describe a cohort with unrecognized slender esophagus that were identified through impedance planimetry measurements. This tool provides additional information beyond symptomatic, histologic, and endoscopic assessments.

The Impact of Pretreatment Esophageal Stenosis on Survival of Esophageal Cancer Patients.

BACKGROUND: Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC). METHODS: The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis. RESULTS: Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P < 0.001) and higher pStage (P < 0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P < 0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P < 0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis. CONCLUSIONS: Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

Worsened Fibrostenotic Outcomes in Eosinophilic Esophagitis Patients Due to COVID-19-Related Endoscopy Cancellations.

BACKGROUND: Indirect consequences of COVID-19 in eosinophilic esophagitis (EoE) are not known. AIM: To determine the impact of COVID-19-related endoscopy cancellations on outcomes in EoE patients. METHODS: In this retrospective cohort study, we assessed whether adult EoE patients who had routine endoscopy scheduled from mid-March 2020 to May 2020 (pandemic start) were canceled or proceeded, and if canceled, ultimately returned. We extracted clinical, endoscopic, and histologic data for their pre-COVID procedure as well as the next procedure performed, if a patient returned. Outcomes included histologic response (< 15 eos/hpf) and endoscopic severity. Those with delayed care were compared to those who returned as scheduled. RESULTS: Of 102 patients identified, 75 had procedures canceled, and 20 (27%) never returned. For the 55 who were canceled but returned, mean time between procedures was 1.1 ± 0.7 years with a delay of 0.5 ± 0.3 years. While treatment rates were similar between the pre- and delayed post-COVID EGD, more patients required a dilation after their return (71% vs 58%; p = 0.05) and their esophageal diameter had significantly decreased (16.8 mm to 15.0 mm; p < 0.001). Of 17 individuals who did not have stricture, narrowing, or dilation pre-pandemic, during their next endoscopy 5 (29%) had a stricture, 1 (6%) had a narrowing, and 7 (41%) required dilation. CONCLUSION: Of EoE patients with canceled endoscopies during the beginning of the COVID-19 pandemic, > 25% never returned for care, which is a previously unmeasured impact of the pandemic. Those who returned had > 1 year between procedures with progression of fibrotic features and need for esophageal dilation.

[Effect and mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection].

Objective: To explore the role and specific mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection (ESD). Methods: Data of 81 patients [51 cases were male and 30 cases were female, aged (62.09±7.95) years] undergoing early esophageal cancer or precancerous lesions with a stripping range ≥3/4 circle hospitalized from January 2019 to February 2021 in Department of Gastroenterology, Zhongda Hospital, Southeast University. They were randomly divided into the control group (n=23), oral prednisone acetate group (n=28) and/or combined with local injection Triamcinolone acetonide group (n=30). Analysis the stenosis rates, endoscopic stent dilatation times, the scores of the Atkinson classification and QLQ-OES18 after 12 weeks. Also the expression of carbohydrate sulfotransferase15 (CHST15) mRNA, TGF-ß1 and Collagen-Ⅰ protein were compared by real-time PCR or immunohistochemistry. Results: The stenosis rates of the control group, oral prednisone acetate group and/or combined with local injection Triamcinolone acetonide group were 82.6% (19/23), 46.4% (13/28) and 20.0% (6/30) (P<0.001); endoscopic stent dilatation times [M (Q1,Q3)] in these three groups were 2 (1, 3), 0 (0, 0) and 0 (0, 0) (P<0.001). After ESD, the scores of the Atkinson classification and QLQ-OES18 in the three groups were lower than before (P<0.001); and the expression of CHST15 mRNA in the three groups were 4.31±0.13, 3.44±0.07 and 2.84±0.21 respectively (P<0.001). Compared with the control group, the expression of CHST15 mRNA in oral prednisone acetate group was down-regulated (P<0.001), and was the lowest in oral prednisone acetate combined with local injection Triamcinolone acetonide group (P<0.001). As CHST15 mRNA was down-regulated, the expression of TGF-ß1 and Collagen-I protein was also down-regulated (P<0.05). Conclusions: Oral prednisone alone or combined with local injection of triamcinolone acetonide both can prevent esophageal stenosis effectively. Oral combined with local injection of glucocorticoid is particularly more effective. Glucocorticoid can reduce the expression of CHST15 mRNA, thereby inhibiting the expression of TGF-ß1 and Collagen-I protein.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. METHODS: Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro. RESULTS: TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling. CONCLUSIONS: Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

Mediastinal Lymph Node Metastasis of Esophageal Cancer with Esophageal Stenosis Diagnosed via Transesophageal Endoscopic Ultrasound with Bronchoscope-guided Fine-needle Aspiration.

An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.

Dilation-predominant approach versus routine care in patients with difficult-to-treat eosinophilic esophagitis: a retrospective comparison.

BACKGROUND: Little is known about esophageal dilation as a long-term treatment approach for eosinophilic esophagitis (EoE). We examined the impact of a "dilate and wait" strategy on symptom management and safety of patients with EoE. METHODS: This retrospective cohort study included two patient groups: those who underwent a dilation-predominant approach (≥ 3 dilations as sole therapy or for histologically refractory disease [> 15 eos/hpf]); and those who had routine care (< 3 dilations or histologic response). Group characteristics were compared and outcomes for the dilation-only group assessed. RESULTS: 53/205 patients (26 %) received the dilation-predominant strategy (total 408 dilations), predominantly for histologic treatment nonresponse (75 %). These patients were younger (33 vs. 41 years; P = 0.003), had a narrower baseline esophageal diameter (9.8 vs. 11.5 mm; P = 0.005), underwent more dilations (7.7 vs. 3.4; P < 0.001), but achieved a smaller final diameter (15.7 vs. 16.7 mm; P = 0.01) vs. routine care. With this strategy, 30 patients (57 %) had ongoing symptom improvement, with esophageal caliber change independently associated with symptom response (adjusted odds ratio 1.79, 95 % confidence interval 1.16-2.78); 26 (49 %) used the strategy as a bridge to clinical trials. Over a median follow-up of 1001 days (interquartile range 581-1710), no deaths or dilation-related perforations occurred, but there were nine emergency room visits, including one for post-dilation bleeding and four for food impaction. CONCLUSIONS: A dilation-predominant long-term treatment strategy allowed for symptom control or bridge to clinical trials for patients with difficult-to-treat EoE. Close follow-up and monitoring for complications are required.

Histological changes in the human esophagus following triamcinolone injection to prevent esophageal stricture after endoscopic submucosal dissection.

BACKGROUND: Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. METHODS: From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. RESULTS: The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P < 0.05). There was no significant difference in the thickness of the regenerated epithelium and muscularis propria layer of the ESD ulcer scar. CONCLUSIONS: Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

Woody hardness classification impact on salvage laryngectomy functional outcomes.

PURPOSE: Post-radiation therapy salvage surgeries are challenging for surgeons due to tissue fibrosis. The woody hardness classification is valuable in differentiating the degree of neck stiffness, but its clinical utility has not been evaluated. We applied it to patients undergoing salvage laryngectomy to study the impact of woody hardness on postoperative outcomes. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing salvage laryngectomy between 2014 and 2019. Patients were assigned into the A (extremely woody hard), B (moderately woody hard), or C (mildly woody hard) woody hardness class. The primary outcome was pharyngoesophageal stricture development. Secondary outcomes included time to pharyngoesophageal stricture, pharyngocutaneous fistula development, time to pharyngocutaneous fistula, development of post-operative complications, and tracheoesophageal puncture complications. RESULTS: Fifty-one patients were included in the study: Class A 1 patient, Class B 30 patients, and Class C 20 patients. The single Class A patient was grouped with the Class B patients. The development of a pharyngoesophageal stricture shows consistent negative association with woody hardness despite most analyses not reaching statistical significance. These associations are robust to a number of confounding variables in multivariate logistic and time to event analyses. Furthermore, the time to event analysis controlling for squamous cell carcinoma diagnosis led to a statistically significant association between woody hardness (i.e., A/B higher risk) and time to stricture (HR=5, p=0.02). CONCLUSIONS: This study suggests that this classification may be useful in predicting pharyngoesophageal stricture formation in salvage laryngectomy patients and could be used to implement stricture preventive measures.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions.

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.

Use of the Functional Lumen Imaging Probe in Clinical Esophagology.

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

Penfigoide de mucosas: cuando la mucosa oral puede ser la clave para el diagnóstico de una estenosis esofágica de origen desconocido / Mucous Membrane Pemphigoid: When the Mouth Can Give a Clue to the Diagnosis of an Esophageal Stenosis of Unknown Origin

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30-Day Outcomes Following Esophageal Replacement in Children: A National Surgical Quality Improvement Project Pediatric Analysis.

INTRODUCTION: The optimal method of esophageal replacement remains controversial. The aim of this study was to evaluate 30-d outcomes of children in the National Surgical Quality Improvement Project Pediatric (NSQIP-P) database who underwent esophageal replacement from 2012 to 2018. METHODS: Demographics, comorbidities, and procedural technique was identified in NSQIP-P and reviewed. Thirty-day outcomes were assessed and stratified by gastric pull-up or tube interposition versus small bowel or colonic interposition. Categorical and continuous variables were assessed by Pearson's chi-square, Fisher's exact, and Wilcoxon rank-sum tests, respectively. Multivariate logistic regression was performed to estimate the effects of procedure technique and clinical risk factors on patient outcomes. RESULTS: Of the 99 cases of esophageal replacement included, 52 (52.5%) utilized a gastric conduit, whereas 47 (47.5%) involved small bowel/colonic esophageal interposition. Overall risk of complications was 52.5%, the most common of which were perioperative transfusion (30.3%), surgical site infection (11.1%), and sepsis (9.1%). Risk of unplanned reoperation was 17.2%, and risk of mortality was 3.0%. Risk for complications, reoperation, and readmission did not differ significantly between those who underwent gastric esophageal replacement and those who underwent small bowel or colonic interposition. Median operative time was shorter in the gastric esophageal replacement group (5.2 versus 8.1 h, P = 0.009). CONCLUSIONS: Among children in NSQIP-P who underwent esophageal replacement from 2012 to 2018, the risk of 30-d complications, unplanned reoperation, and mortality was relatively frequent and was similar across operative techniques. Opportunities exist to improve preoperative optimization, utilization of blood transfusion services, and infectious complications in the perioperative period irrespective of operative technique. LEVEL OF EVIDENCE: Level III, retrospective comparative study.