GDF11 alleviates neointimal hyperplasia in a rat model of artery injury by regulating endothelial NLRP3 inflammasome activation and rapid re-endothelialization

Background Neointimal hyperplasia induced by interventional surgery can lead to progressive obliteration of the vascular lumen, which has become a major factor affecting prognosis. The rate of re-endothelialization is known to be inversely related to neointima formation. Growth differentiation factor 11 (GDF11) is a secreted protein with anti-inflammatory, antioxidant, and antiaging properties. Recent reports have indicated that GDF11 can improve vascular remodeling by maintaining the differentiated phenotypes of vascular smooth muscle cells. However, it is not known whether and how GDF11 promotes re-endothelialization in vascular injury. The present study was performed to clarify the influence of GDF11 on re-endothelialization after vascular injury. Methods An adult Sprague–Dawley rat model of common carotid artery balloon dilatation injury was surgically established. A recombinant adenovirus carrying GDF11 was delivered into the common carotid artery to overexpress GDF11. Vascular re-endothelialization and neointima formation were assessed in harvested carotid arteries through histomolecular analysis. CCK-8 analysis, LDH release and Western blotting were performed to investigate the effects of GDF11 on endothelial NLRP3 inflammasome activation and relevant signaling pathways in vitro. Results GDF11 significantly enhanced re-endothelialization and reduced neointima formation in rats with balloon-dilatation injury by suppressing the activation of the NLRP3 inflammasome. Administration of an endoplasmic reticulum stress (ER stress) inhibitor, 4PBA, attenuated endothelial NLRP3 inflammasome activation induced by lysophosphatidylcholine. In addition, upregulation of LOX-1 expression involved elevated ER stress and could result in endothelial NLRP3 inflammasome activation. Moreover, GDF11 significantly inhibited NLRP3 inflammasome-mediated endothelial cell pyroptosis by negatively regulating LOX-1-dependent ER stress. Conclusions We conclude that GDF11 improves re-endothelialization and can attenuate vascular remodeling by reducing endothelial NLRP3 inflammasome activation. These findings shed light on new treatment strategies to promote re-endothelialization based on GDF11 as a future target.

Analysis of long-term effect of ureteral balloon dilatation combined with internal and external drainage tube in the treatment of benign ureteral stricture

Purpose There are few reports about balloon dilatation combined with internal and external drainage tube in the treatment of ureteral stricture under interventional therapy. The aim of the study is to explore the safety, effectiveness and long-term efficacy of this treatment strategy. Materials and methods It is a retrospective and observational study. From October 2013 to October 2016, 42 patients with benign lower ureteral stricture received interventional treatment. Balloon dilatation combined with internal and external drainage tube implantation were used. There were 25 male patients and 17 female patients. There were 7 cases (16.7%) with congenital ureteral stricture, 12 cases (28.6%) with inflammation, 15 cases (35.7%) with ureteral stricture after lithotomy or lithotripsy, and 8 cases (19.0%) with ureteral stricture after pelvic or abdominal surgery. After the drainage tube was removed, B ultrasound, enhanced CTU or IVP of urinary system were reexamined every six months. The follow-up time was 12–60 months. Results The age was 52.9 ± 11.6 years. The length of ureteral stricture was 1.1 ± 0.5 cm. 42 patients completed interventional treatment, the technical success rate was 100%, no ureteral perforation, rupture or other complications were identified. Preoperative urea nitrogen 9.2 ± 2.3 mmol/L and creatinine 175.8 ± 82.8umol/L. Urea nitrogen and creatinine were 3.8–9.1 mmol/L and 45.2–189.6 umol/L when removing the drainage tube. There were significant differences in the levels of urea nitrogen and creatinine before and after tube removal (P < 0.05). The ureteral patency rate was 100% at 6 months, 93% at 12 months, 83% at 18 months, 79% at 24 months, 76% at 30 months and 73% at 36–60 months. The overall success rate was 73%. Multivariate Cox regression analysis showed that stenosis length was a risk factor for postoperative patency (P < 0.05). Conclusion Balloon dilatation combined with internal and external drainage tube implantation in the treatment of benign lower ureteral stricture is safe and effective.

P-OGC51 A Review of Post-Oesophagectomy Benign Anastomotic Strictures

Background Benign anastomotic strictures (BAS) are a known risk of oesophageal resection, leading to significant post-operative morbidity and a reported incidence of BAS varies widely from 8.83% to 42.38%. This review aims to assess incidence, risk factors for development as well as treatment. Methods An electronic search using specific search terms using Medline, Embase and the Cochrane Library to identify all articles studying the development of BAS in adults post oesophagectomy was carried out. Inclusion criteria were patients who underwent any form of oesophagectomy for malignant disease (Ivor Lewis, McKeown, thoracoabdominal, transhiatal,minimally invasive); patients in study &gt;18-year-old; study reported only benign anastomotic strictures and any study design with a minimum of 6 patients. Only articles published in the English language were included. Review articles, case reports and conference abstracts were all excluded Results Seven studies reported on the incidence of BAS and an average of 34.1% was found. Cervical anastomosis, anastomotic leak development. Cardiovascular disease, diabetes and gastric conduit and smaller gun size in a stapled anastomosis were also found to be associated with BAS. Hypertension, neoadjuvant chemotherapy, transhiatal oesophagectomy or transthoracic were not found to be associated with BAS. The mainstay of management appears to be endoscopic balloon dilatation with adverse reported outcomes related to stent management. Conclusions BAS after oesophagectomy is common. Several risk factors have been identified and balloon dilatation appears to be the mainstay of treatment.

P-OGC73 Effect of pyloroplasty on the need for endoscopic intervention for delayed gastric emptying post oesophagectomy

Background Delayed gastric emptying (DGE) is a common complication following oesophagectomy, affecting 15-39% of patients. Controversy remains regarding the role of pyloric drainage procedures during oesophagectomy with gastric conduit reconstruction in reducing DGE. This study investigated the effect of pyloroplasty at the time of oesophagectomy on the need for endoscopic pyloric intervention post-operatively. Methods We performed a retrospective analysis of all oesophagectomies performed in a single tertiary centre over a 10-year study period between 1 January 2010 and 31 December 2019. Electronic records were reviewed to analyse patient demographics, operative details and post-operative outcomes, as well as the need for endoscopic procedures after surgery. Patients were dichotomized into two groups, with those who had pyloroplasty performed at oesophagectomy compared to those who did not. Patients who died ≤30 days after oesophagectomy were excluded from analysis. Patients were followed up for a median of 32 months (IQR 19-60). Results 298 patients were eligible for the study, of whom 80/298 (26.8%) had a pyloroplasty performed. Demographics were evenly matched between the two groups. Patients undergoing Ivor-Lewis oesophagectomy were significantly more likely to have had pyloroplasty performed (90.0% vs. 24.3%; p &lt; 0.001). Pyloroplasty had no significant effect on post-operative complication rates, ICU admission, need for re-operation or length of hospital stay. Patients without a pyloroplasty were significantly more likely to require endoscopic pyloric balloon dilatation (43.1% vs. 12.4%, p &lt; 0.001) or pyloric botox injection (12.4% vs. 3.8%, p = 0.029) after oesophagectomy. Conclusions In this study, patients who had a pyloroplasty at the time of oesophagectomy were significantly less likely to require endoscopic pyloric balloon dilatation and/or pyloric botox injection post-operatively. This has significant long-term implications for both patients’ quality of life post-operatively and demands on over-stretched endoscopic services.

Comparison studies of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in the treatment of neurogenic cricopharyngeal muscle dysfunction

BACKGROUND: Cricopharyngeal muscle dysfunction (CPD) management has been challenging in clinical practice. OBJECTIVE: To compare the efficacy and safety of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in treating CPD. METHODS: Forty patients with CPD were randomly divided into two groups, namely the botulinum toxin injection group (BTX group) and balloon dilatation group (BD group). Patients in the BTX group received a single ultrasound-guided injection of 50 units of botulinum toxin type A, while the BD group received dilatation therapy five times per week, consecutively for two weeks. Relative opening percentage of the upper esophageal sphincter (UES), the penetration-aspiration scale (PAS), and the Dysphagia Outcome Severity Scale (DOSS) were evaluated by a videofluoroscopic swallowing study (VFSS) at baseline, 1-month, and 3-months posttreatment. The Functional Oral Intake Scale (FOIS) and Standardized Swallowing Assessment (SSA) were also used to evaluate participants’ swallowing function at baseline and the 1-week, 2-week, 1-month, and 3-month follow-ups. RESULTS: A generalized estimating equation (GEE) model revealed the significant main effect for time in UES, PAS, DOSS, FOIS, and SSA compared to baseline (P <0.05), while no group-by-time interactions (except for the PAS assessment) or main effect for treatment was detected among the above multiple variances. No systematic complications or severe adverse effects were noted. CONCLUSION: Both ultrasound-guided botulinum toxin type A injections and balloon dilatation therapy have been proven as safe and effective treatments for CPD patients. Future clinical trials with longer follow-up periods and more participants are warranted.