stricture

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  • 文章类型: Journal Article
    背景:自膨式金属支架(SEMS)可用于治疗环状内窥镜粘膜下剥离术(ESD)后的食管狭窄,但其疗效和放置时机尚待确定。在这项研究中,比较SEMS放置组和球囊扩张(BD)组的治疗时间和扩张次数,以阐明SEMS在环行食管ESD术后治疗食管狭窄中的疗效和放置时间.
    方法:这是一项回顾性队列研究。纳入2015年1月至2020年1月环行ESD后食管狭窄患者。关于患者人口统计学特征的数据,食管病变相关因素,食管狭窄的发生,并收集了治疗狭窄的措施。主要结果是治疗时间,次要结局是扩张次数.
    结果:SEMS组扩张总数为30,BD组为106。SEMS组平均扩张次数(1.76±1.64)明显低于BD组(4.42±5.32)(P=0.016)。首先接受SEMS放置的患者的治疗时间(平均119天)比首先接受BD(平均245天)短(P=0.041)。首次接受SEMS放置的患者平均扩张次数(0.71±1.07)明显低于首次接受BD放置的患者(2.5±1.54)。
    结论:在一组环食管ESD术后患者中,SEMS在治疗食管狭窄方面更有效。
    BACKGROUND: 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).
    CONCLUSIONS: SEMSs were more efficient in the treatment of esophageal stricture in a cohort of patients after circumferential esophageal ESD.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    背景:食管狭窄严重损害患者的生活质量,并提出了治疗挑战,特别是由于ESD/EMR后的高复发。目前的治疗管理症状,而不是解决疾病的病因。本文对食管狭窄的形成和复发机制进行综述。寻求突出潜在治疗干预的领域。
    方法:通过PUBMED使用搜索词进行文献检索:食管狭窄,粘膜切除术,粘膜下剥离术.通过人工审查确定了相关文章,并审查了其他文章的参考清单。
    结果:临床前研究和动物研究数据表明,可能导致食管狭窄的机制包括成纤维细胞过度分化,没有及时愈合的炎症反应,上皮屏障功能受损,以及导致它的多种方法因素。上皮屏障功能障碍可能是食管狭窄的起始机制。通过组织工程制造的细胞补片实现完美的上皮内化已被证明在治疗和预防食管狭窄方面是有效的。
    结论:食管狭窄的发展包括三个阶段:对食管上皮屏障(EEB)的结构损害,慢性炎症,和严重的纤维化,其中EEB的功能障碍或损伤是导致食管狭窄的起始机制。再上皮化对食管狭窄的治疗和预防至关重要。这些信息将帮助临床医生或科学家开发未来治疗食管狭窄的有效技术。
    Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease\'s etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention.
    A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles.
    Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures.
    The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:成纤维细胞在克罗恩病(CD)的狭窄形成中起关键作用,但了解其发病机制需要系统水平的研究以发现新的治疗目标。我们研究了全厚度CD组织,通过生成第一个单细胞RNA测序(scRNAseq)狭窄肠图谱来表征成纤维细胞的异质性和功能,并为治疗靶标验证提供原理证据。
    方法:我们进行了13例新鲜全厚度CD切除的scRNAseq,发炎不狭窄,和狭窄的节段以及7个正常的非CD肠段。将每个节段分成粘膜/粘膜下层或固有肌层,并分别分析总共99个组织样品和409,001个细胞。我们通过使用整个组织验证了cadherin-11(CDH11)作为潜在的治疗靶点,分离的肠细胞,NanoStringnCounter,下一代测序,蛋白质组学和动物模型。
    结果:我们的综合数据集揭示了狭窄CD中的成纤维细胞异质性,在粘膜/粘膜下层检测到大多数狭窄选择性变化,但不是肌肉层。细胞-细胞相互作用建模显示CXCL14+以及MMP/WNT5A+成纤维细胞在CD狭窄中显示出中枢信号传导作用。CDH11,一种成纤维细胞-细胞粘附分子,被广泛表达和上调,NanoStringnCounter验证了其促纤维化功能,RNA测序,组织靶表达,体外功能增益和丧失实验,蛋白质组学,以及敲除和抗体介导的CDH11阻断在实验性结肠炎中的作用。
    结论:全厚肠scRNAseq图谱揭示了以前未认识到的CD狭窄中的成纤维细胞异质性和相互作用,CDH11被验证为潜在的治疗靶标。这些结果为更好地理解CD狭窄的形成提供了新的资源,并开辟了潜在的治疗发展。
    Fibroblasts play a key role in stricture formation in Crohn\'s disease (CD) but understanding its pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full-thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single-cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation.
    We performed scRNAseq of 13 fresh full-thickness CD resections containing noninvolved, inflamed nonstrictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next-generation sequencing, proteomics, and animal models.
    Our integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and up-regulated, and its profibrotic function was validated using NanoString nCounter, RNA sequencing, tissue target expression, in vitro gain- and loss-of-function experiments, proteomics, and knock-out and antibody-mediated CDH11 blockade in experimental colitis.
    A full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and open potential therapeutic developments. This work has been posted as a preprint on Biorxiv under doi: 10.1101/2023.04.03.534781.
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  • 文章类型: Multicenter Study
    背景:关于内镜下狭窄切开术(ES)在治疗小肠深部狭窄中的作用的数据很少。我们的目的是研究基于气囊辅助小肠镜检查的ES(基于BAE的ES)治疗克罗恩病(CD)相关的小肠深部狭窄的疗效和安全性。
    方法:这项多中心回顾性队列研究包括2017年至2023年期间接受基于BAE的ES治疗的CD相关小肠深部狭窄的连续患者。结果包括技术上的成功,临床改善,无手术率,无再干预率,和不良事件。
    结果:28例CD患者接受了58例基于BAE的ES手术治疗,治疗无法通过的小肠深部狭窄,中位随访时间为519.5天(四分位距,306-728天)。在26例(92.9%)患者中,有56例(96.0%)手术在技术上成功。20例患者(71.4%)在第8周表现出临床改善。1年的累计无手术率为74.8%(95%置信区间[CI],60.3-92.9%)。较高的体重指数与手术需求减少相关(风险比=0.084,95%CI,0.016-0.45,P=0.0036)。需要再次干预的术后不良事件(出血和穿孔)发生在3.4%的手术中。
    结论:基于BAE的新型ES提供了很高的技术成功,良好的疗效,与CD相关的小肠深部狭窄的安全性,这可能为内窥镜球囊扩张和手术提供替代方案。
    There is little data on the role of endoscopic stricturotomy (ES) in treating deep small bowel strictures. We aimed to investigate the efficacy and safety of balloon-assisted enteroscopy-based ES (BAE-based ES) for deep small bowel strictures associated with Crohn\'s disease (CD).
    This multicentre retrospective cohort study included consecutive patients with CD-associated deep small bowel strictures treated with BAE-based ES between 2017 and 2023. The outcomes included technical success, clinical improvement, surgery-free rate, reintervention-free rate, and adverse events.
    Twenty-eight patients with CD underwent 58 BAE-based ES procedures for non-passable deep small bowel strictures, with a median follow-up time of 519.5 days (interquartile range, 306-728 days). Fifty-six (96.0%) procedures were technically successful in 26 (92.9%) patients. Twenty patients (71.4%) showed clinical improvement at week 8. The cumulative surgery-free rate at 1 year was 74.8% (95% confidence interval [CI], 60.3-92.9%). A higher body mass index was associated with a decreased need for surgery (hazard ratio = 0.084, 95% CI, 0.016-0.45, P = 0.0036). Postprocedural adverse events (bleeding and perforation) requiring reintervention occurred in 3.4% of the procedures.
    The novel BAE-based ES provides high technical success, favorable efficacy, and safety in CD-associated deep small bowel strictures, which may provide an alternative for endoscopic balloon dilation and surgery.
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  • 文章类型: Journal Article
    目的:ESD后食管狭窄,尤其是全圆周ESD后仍然是一个未解决的问题,没有理想的策略。我们的主动新颖的自我控制防狭窄水球可能是一种选择。
    方法:将2018年2月至2020年8月食管ESD后预期会导致整个环形粘膜缺损的食管肿瘤性病变患者纳入研究。我们使用了一种新型的自我控制的预防狭窄的水球结合口服泼尼松龙作为纳入患者的预防策略。
    结果:37例患者(女性9例,男性28例,年龄在52至82岁之间的患者)完成了为期12周的治疗,包括类固醇治疗和球囊置入。纵向直径的中值尺寸为7cm(范围从4到14cm)。所有病变均获得治愈性切除,中位手术时间为110分钟(范围为50至180分钟)。在4例患者中发现球囊迁移。因此,有3例患者(8.1%)出现狭窄。一般来说,病人可以忍受气球,只有轻微的不舒服,比如偶尔喉咙痛,咳嗽,和胸骨后疼痛.此外,在随访期间,未观察到与口服类固醇相关的显著不良事件,也未发现复发.
    结论:我们基于口服类固醇治疗的新型自我控制的预防狭窄的水球是有效和安全的。该策略很好地防止了完全环状ESD后的食管狭窄。
    Post-ESD esophageal stricture especially after wholly circumferential ESD remains an unresolved issue without ideal strategies. Our initiative novel self-control stricture-preventing water balloon may be an alternative.
    Patients with esophageal neoplastic lesions expected to result in a whole circular mucosa defect after esophageal ESD from February 2018 to August 2020 were included in the study. We used a novel self-control stricture-preventing water balloon combined with oral prednisolone as preventive strategy for the enrolled patients.
    Thirty-seven patients (9 females and 28 males, patients aged 52 to 82 years) finished the 12-week treatment including steroid treatment and balloon placement. The median size of longitudinal diameter was 7 cm (range from 4 to 14 cm). All the lesions achieved curative resection and the median procedure time was 110 min (range 50 to 180 min). Balloons were found migration in 4 patients. As a result, there were 3 patients (8.1%) experienced stricture. Generally, patients could tolerate to balloons, only with mild uncomfortableness, such as occasional sore throat, cough, and retrosternal pain. In addition, during the follow-up period, no significant adverse events associated to oral steroid administration were observed and no recurrence was found.
    Our novel self-control stricture-preventing water balloon based on the oral steroid therapy is effective and safe. This strategy well prevents esophageal stricture after complete circumferential ESD.
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  • 文章类型: Meta-Analysis
    目的:曲安奈德(TA)在预防食管狭窄中的作用尚不明确。本荟萃分析旨在评估其预防内镜黏膜下剥离术(ESD)后食管狭窄的安全性和有效性。
    方法:在包括PubMed在内的电子数据库中进行了全面搜索,Cochrane图书馆,Embase用于可能的对照研究。主要结果是狭窄率和所需的内镜下球囊扩张术(EBD),次要结局包括并发症。随机效应用于计算合并结果。进行敏感性分析和发表偏倚以验证结果的稳健性和可靠性。结果:共获得10项研究,共499例患者。在汇总分析中,发现曲安奈德注射液降低狭窄发生率有统计学意义(OR=0.29,95%CI[0.11,0.80],P<0.05)和内窥镜球囊扩张次数(MD=-3.33,95%CI[-4.15,-2.50],P<0.0001)与对照组相比。曲安奈德注射治疗不会增加并发症的风险(OR=-0.77%,CI[-1.62,0.09],P=0.08)。亚组分析表明,与不进行任何预防相比,内镜黏膜下剥离术后单次注射曲安奈德可显着降低狭窄的发生率。不同浓度和单次剂量的曲安奈德可降低狭窄的发生率。还表明,根据病变大小的剂量比固定剂量在预防食管狭窄方面更有效。结论:曲安奈德注射可减少狭窄形成的发生率以及对EBD的需要,而不会增加并发症。
    OBJECTIVE: The role of triamcinolone acetonide (TA) in the prevention of esophageal stricture is not well established. This meta-analysis aimed to evaluate its safety and efficacy for the prevention of esophageal stricture after endoscopic submucosal dissection (ESD).
    METHODS: A comprehensive search was performed in electronic databases including PubMed, the Cochrane Library, Embase for possible controlled studies. The primary outcomes were stenosis rate and endoscopic balloon dilatation (EBD) sessions required, and secondary outcome included complications. Random effects were used to calculate the pooled outcome. Sensitivity analysis and publication bias were conducted to verify the robustness and reliability of the results. Results: Ten studies containing 499 patients were obtained. In the pooled analysis, statistical significance was found in triamcinolone acetonide injection reduced the incidence of stenosis (OR = 0.29, 95% CI [0.11, 0.80], P < 0.05) and the number of endoscopic balloon dilation (MD = -3.33, 95% CI [-4.15, -2.50], P < 0.0001) compared with control. Triamcinolone acetonide injection therapy did not increase the risk of complications (OR = -0.77%, CI [-1.62, 0.09], P = 0.08). Subgroup analysis indicated that the single injection of triamcinolone acetonide after endoscopic submucosal dissection significantly reduced the incidence of stenosis compared with without any prophylaxis. Different concentrations and single session volume of triamcinolone acetonide reduced the incidence of stenosis. It also showed that the dose according to the size of the lesion was more effective than the fixed dose in preventing esophageal stricture. Conclusion: Triamcinolone acetonide injection can reduce the incidence of stricture formation as well as the need for EBD sessions without increasing complications.
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  • 文章类型: Journal Article
    食管胃吻合口狭窄是食管癌术后最常见的并发症之一,其发病机制尚不完全清楚,由于缺乏合适的动物模型,吻合口狭窄的治疗和预防受到限制。胃管供血不足被认为是术后吻合口狭窄的危险因素。在这项研究中,我们使用热成像技术建立了稳定的啮齿动物模型,该模型具有由缺血引起的食管胃吻合口狭窄。简而言之,将30只雄性SD大鼠分为对照组和缺血组。在术中热成像的帮助下进行食管胃缺血吻合,以确定灌注不良区域。采用非配对t检验和Welch校正分析两组间的差异。术后第84天,对照组,未观察到吻合口狭窄,而在缺血组中,15只动物中有12只(80%)出现了明显的吻合口狭窄,无法让2.7毫米的内窥镜通过。对照组和缺血组吻合口直径分别为2.80±0.15mm和1.73±0.44mm(p<0.01),(分别通过内窥镜检查和钡射线照相进行评估)。H&amp;E染色和Masson三色染色显示,缺血组吻合口的结缔组织增生和胶原沉积较对照组多。因此,这种新的大鼠模型可以作为进一步研究预防食管胃吻合口狭窄的潜在干预措施的平台。
    Esophagogastric anastomosis stricture is one of the most common postoperative complications after esophagectomy; yet, its pathogenesis is still not fully understood, and the treatment and prevention of anastomotic stricture are limited due to the lack of a proper animal model. The insufficient blood supply in the gastric tube is considered a risk factor for postoperative anastomotic strictures. In this study, we used thermal imaging to develop a stable rodent model with esophagogastric anastomotic stricture caused by ischemia. Briefly, 30 male Sprague-Dawley rats have been divided into the control group and the ischemia group. The esophagogastric ischemia anastomosis was performed with the help of intraoperative thermal imaging to identify the poor perfusion area. An unpaired t test with Welch\'s correction was used to analyze the difference between the two groups. On postoperative day 84, in the control group, no anastomosis stricture was observed, while in the ischemia group, 12 out of 15 animals (80%) developed obvious anastomosis stricture which could not let a 2.7-mm endoscope pass through. The diameter of the anastomosis in the control group and the ischemia group were 2.80 ± 0.15 mm and 1.73 ± 0.44 mm (p < 0.01), respectively (evaluated by endoscopy examination and barium radiography). H&E stain and Masson\'s trichrome showed that the anastomosis in the ischemia group had more connective tissue hyperplasia and collagen deposition than control group. Thus, this new rat model can be used as a platform to further investigate the potential interventions for prevention of esophagogastric anastomotic stricture.
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