MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC-Exo) for the prevention of esophageal stenosis after ESD in a porcine model. RESULTS: Pigs were randomly assigned into (1) ChGelMSC-Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGelMSC-Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFß1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. CONCLUSIONS: Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.

Analysis of gap length as a predictor of surgical outcomes in esophageal atresia with distal fistula: a single center experience.

PURPOSE: Long-gap esophageal atresia (LGEA) is still a challenge for pediatric surgery. No consensus exists as to what constitutes a long gap, and few studies have investigated the maximum gap length safely repairable by primary anastomosis. Based on surgical outcomes at a single institution, we aimed to determine the gap length in LGEA with a high risk of complications. METHODS: The medical records of 51, consecutive patients with esophageal atresia (EA) with primary repair in the early neonatal period between 2001 and 2021 were retrospectively reviewed. Three, major complications were found in the surgical outcomes: (1) anastomotic leakage, (2) esophageal stricture requiring dilatation, and (3) GERD requiring fundoplication. The predictive power of the postsurgical complications was assessed using receiver operating characteristic analysis, and the area under the curve (AUC) and the cutoff value with a specificity of > 90% were calculated. RESULTS: Sixteen patients (31.4%) experienced a complication. The AUC of gap length was0.90 (p < 0.001), and the gap length cutoff value was ≥ 2.0 cm for predicting any complication (sensitivity: 62.5%, specificity: 91.4%). CONCLUSION: A gap length ≥ 2.0 cm was considered as defining LGEA and was associated with an extremely high complication rate after primary repair.

[Endoscopic ultrasonography features of benign esophageal stenosis in children]. / å„¿ç«¥é£Ÿç®¡è‰¯æ€§ç‹­çª„çš„è¶ å£°å† é•œç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.

Self-expandable metallic stents may be more efficient than balloon dilatation alone for esophageal stricture after circumferential endoscopic submucosal dissection: a retrospective cohort study in China.

INTRODUCTION: Self-expandable metallic stents (SEMSs) can be used to treat esophageal stricture after circumferential endoscopic submucosal dissection (ESD), but its efficacy and placement timing remain to be determined. In this study, the treatment time and number of dilatations were compared between the SEMS placement group and the balloon dilatation (BD) group to clarify the efficacy and placement time of SEMSs in the treatment of esophageal stricture after circumferential esophageal ESD. METHODS: This was a retrospective cohort study. Patients with esophageal stricture after circumferential ESD between January 2015 and January 2020 were included. Data on the patients' demographic characteristics, esophageal lesion-related factors, esophageal stricture occurrence, and measures taken to treat the stricture were collected. The primary outcome was the treatment time, and the secondary outcome was the number of dilatations. RESULTS: The total number of dilatations was 30 in the SEMS group and 106 in the BD group. The average number of dilatations in the SEMS group (1.76 ± 1.64) was significantly lower than that in the BD group (4.42 ± 5.32) (P = 0.016). Among the patients who underwent SEMS placement first had a shorter treatment time (average 119 days) than those who underwent BD first (average 245 days) (P = 0.041), and the average number of dilatations inpatients who underwent SEMS placement first (0.71 ± 1.07) was significantly lower than that in the patients who underwent BD first (2.5 ± 1.54). CONCLUSION: SEMSs were more efficient in the treatment of esophageal stricture in a cohort of patients after circumferential esophageal ESD.

Oesophageal stricture in a cat with true pleuroperitoneal hernia.

A 2-year-old neutered male Bengal cat presented with solid food dysphagia and chronic regurgitation for >5 months. There were no clinical abnormalities on haematological or radiographic examinations. Thoracic radiography revealed a soft tissue opacity mass adjacent to the diaphragm in the caudoventral thorax. Ultrasonography revealed a protruding liver lobe surrounded by a hyperechoic lining from the diaphragm towards the thorax, and a pleuroperitoneal hernia was diagnosed. An endoscopy was performed to examine the cause of regurgitation, and an oesophageal stricture was observed. Endoscopic balloon dilation of the oesophageal stricture was performed, and the regurgitation was resolved immediately. However, regurgitation relapsed 2 months later, and computed tomography was performed to ascertain the cause. Computed tomography revealed oesophageal mural thickening and true pleuroperitoneal hernia with partial liver lobe herniation. A second endoscopy with balloon dilation was performed to treat the relapsing oesophageal stricture, and the clinical signs resolved without the need for herniorrhaphy. Nevertheless, oesophageal stricture could occur due to gastroesophageal reflux related to a pleuroperitoneal hernia; however, a definite link could not be elucidated in this case. This report describes a case of oesophageal stricture and concurrent true pleuroperitoneal hernia in a cat.

Progress in the treatment and prevention of esophageal stenosis after endoscopic submucosal dissection.

The primary treatment for early esophageal cancer and precancerous lesions is endoscopic submucosal dissection (ESD). However, this approach leads to a high incidence of postoperative esophageal stenosis, which can significantly impact a patient's quality of life. While various methods are available to prevent post-ESD esophageal stenosis, their effectiveness varies. Therefore, this study aims to provide an overview of the currently employed methods for preventing post-ESD esophageal stenosis in clinical practice in view of assisting clinical practitioners.

A retrospective cohort study on oesophageal food bolus obstruction in the North Denmark region in 2021-two thirds were never diagnosed with a cause.

BACKGROUND: Food bolus obstruction (FBO) leading to hospital treatment is often associated with eosinophilic oesophagitis (EoE), stenosis, or oesophageal cancer (1). Danish national guidelines recommend that patients with FBO undergo a diagnostic upper endoscopy within two weeks of presentation to exclude possible malignancy, and histological evaluation of eight biopsies (2, 3). AIMS: The aims of this study were to (1) report the incidence and describe the causes and treatment of FBO in the North Denmark Region (NDR), (2) determine the proportion of patients who underwent upper endoscopy and biopsy according to regional and national guidelines, and (3) identify International Classification of Diseases 10th Revision (ICD-10) diagnosis and procedure codes applied to the hospital visits due to FBO in the NDR. METHODS: Among all acute hospital visits in the NDR in 2021, all visits with ICD-10 codes possibly reflecting FBO, as well as a random sample of 14,400 visits with unspecific ICD-10 codes (R and Z codes), were screened manually for possible FBO. Diagnosis, follow-up, and treatment of all patients with FBO were recorded. RESULTS: The median patient age was 66.0 (Q1-Q3: 49.8-81.0) years, and half of the patients had experienced FBO before. Two thirds of patients (66.0%) were never diagnosed with a cause of FBO, followed by 17.3% with EoE. 30% of patients did not undergo upper endoscopy within two weeks of the hospital visit, and 50.7% were never biopsied in the oesophagus. Of 1886 hospital visits with registry ICD-10 codes that possibly reflected FBO, 8.4% were due to FBO, while FBO was present in 0.028% of the random sample of unspecific ICD-10 codes. CONCLUSIONS: Most hospitalized FBO patients in the NDR in 2021 were never diagnosed with a cause. In these patients there is a high risk of overlooked EoE or upper gastrointestinal cancers. The area needs immediate focus and changed routines to improve treatment and prevent new FBO.

Predictive factors for esophageal stenosis in patients receiving prophylactic steroid therapy after endoscopic submucosal dissection for esophageal squamous cell carcinoma.

BACKGROUND: Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC. METHODS: Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. RESULTS: Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. CONCLUSIONS: Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Research on triamcinolone-loaded thermosensitive chitosan hydrogels for preventing esophageal stricture induced by endoscopic submucosal dissection.

Early-stage esophageal cancer is primarily treated by endoscopic submucosal dissection (ESD). However, extensive mucosal dissection creates a significant risk of postoperative esophageal stricture. Clinically, postoperative stricture can be prevented by glucocorticoids; however, there are drawbacks to both systemic and local administration of glucocorticoids, and improving drug administration methods is crucial. In this study, we developed a chitosan-based thermosensitive hydrogel for triamcinolone (TA) delivery. Our results indicated that the hydrogel remains liquid at low temperatures and can be injected into the esophageal wound site through an endoscopic biopsy channel. Upon reaching body temperature, the hydrogel undergoes spontaneous gelation and firmly adheres to the wound surface. The liquid phase enables convenient and precise delivery, while the gel phase achieves remarkable adhesion, tensile strength, and resistance to degradation. Moreover, the hydrogel exhibited an extended release duration of >10 days when loaded with a 10 mg dose. In vitro studies revealed that the hydrogel suppresses the proliferation and fibrogenesis of human scar fibroblasts (HKF). In a rat skin dermal defect model, the hydrogel attenuated keloid formation during the healing process. Consequently, the chitosan-based thermosensitive hydrogel developed in this study for triamcinolone delivery may be an effective tool for preventing post-ESD esophageal stricture.

Acute esophageal stricture after bone marrow transplant.

Esophageal stricture after bone marrow transplantation (BMT) is exceptionally rare, with only a few cases reported in the literature. We present an interesting case of a 58-year-old male with refractory multiple myeloma who developed dysphagia five days following his second bone marrow transplantation. He was found to have a severe esophageal stricture. The patient was treated with multiple esophageal dilations and triamcinolone injections in the following weeks to months, resulting in an improvement in symptoms. Although the exact underlying mechanism remains unknown, high-dose chemotherapy conditioning with melphalan prior to BMT likely contributed to the stricture. Our case highlights the importance of heightened post-bone marrow transplantation management for rare complications, such as an esophageal stricture.

Short and Medium Term Outcomes of Open and Laparoscopic Assisted Oesophageal Replacement Procedures.

AIM OF THE STUDY: We describe the short- and medium-term outcomes following open and laparoscopic assisted oesophageal replacement surgery in a single tertiary paediatric surgical centre. METHODS: A retrospective review (institutional audit approval no. 3213) on patients who underwent open or laparoscopic-assisted oesophageal replacement (OAR vs. LAR) at our centre between 2002 and 2021 was completed. Data collected (demographics, early complications, stricture formation, need for oesophageal dilatations, and mortality) were analysed using GraphPad Prism v 9.50 and are presented as median (IQR). RESULTS: 71 children (37 male) had oesophageal replacement surgery at a median age of 2.3 years (IQR 4.7 years). 51 were LAR (6 conversions). Replacement conduit was stomach (n = 67), colon (n = 3), or jejunum (n = 1). Most gastric transpositions had a pyloroplasty (46/67) or pyloromyotomy (14/67). Most common pathology was oesophageal atresia (n = 50 including 2 failed transpositions), caustic injury (n = 19 including 3 due to button battery), stricture of unknown cause (n = 1), and megaoesophagus (n = 1). There were 2 (2.8 %) early postoperative deaths at 2 days (major vessel thrombosis), 1 month (systemic sepsis), and one death at 5 years in the community. The rate of postoperative complications were comparable across LAR and OAR including anastomotic leak, pleural effusions, or early strictures. More patients with caustic pathology needed dilatations (60 % vs 30 % in OA, p = 0.05). CONCLUSIONS: Outcomes of open and laparoscopic-assisted oesophageal replacement procedures are comparable in the short and medium term. Anastomotic stricture is higher in those with caustic injury. LEVEL OF EVIDENCE: IV.

Risk factors for total laryngectomy associated proximal esophageal stricture formation in head and neck cancer patients.

BACKGROUND: Development of esophageal strictures is common after the total laryngectomy of head and neck cancer patients. While endoscopic techniques like dilatation by balloon or Salvary bougies are well established, risk factors and pathophysiology for development of refractory strictures are less well understood. OBJECTIVE: To evaluate risk factors associated with occurrence and recurrence of total-laryngectomy-associated esophageal strictures in head and neck cancer patients. METHODS: We analyzed retrospectively a cohort of 170 head and neck squamous cell carcinoma patients, who underwent total laryngectomy between 2007 and 2017. The outcome measure was laryngectomy-associated proximal esophageal stricture needing an endoscopic dilatation by using a balloon or Savary dilators. RESULTS: Of the 170 patients in the cohort, 32 (18.8%) developed strictures. Mean time between surgery and first endoscopic intervention was 24.4 months. Significant predictive factors were age ≥ 65 (p=0.017), nodal status N> 1 (p=0.003), continued alcohol abuse after surgery (p=0.005) and diabetes mellitus (p=0.005). In a subgroup, 17 of 32 patients developed refractory strictures and needed more than three dilatations to relieve dysphagia. Postoperative mean (p=0.016) and maximum (p=0.015) C-reactive protein (CRP) were predictive for refractory strictures. CONCLUSION: Symptomatic strictures occurred in 18.8% of the cases. Age, nodal status N>1, continued alcohol abuse and diabetes mellitus were predictive factors. For refractory stenosis (>3 dilatations needed) mean and maximum postoperative CRP were predictive. This may indicate that systemic inflammatory response post-surgery is involved in the stricture formation process.

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.