Gastroesophageal Reflux after Stapler-assisted Mucosectomy in inverse-NOTES technique for Barretts Esophagus

胃食管反流病（GERD）导致食管远端肠黏膜取代鳞状上皮（Barretts上皮，BE）。BE是一种兼性癌前病变，可导致浸润性腺癌。目前，密切的内镜监测被推荐用于早期发现不典型增生或浸润性癌症。目前治疗发育不良BE的方法是内镜下粘膜切除术（EMR）或射频消融术。EMR由于是切片切除的标本，使得组织学分析变得困难，但对于高度不典型增生或浸润性癌症的切除边缘进行评估是至关重要的。更大的切除范围，甚至是圆形切除，对介入手术后狭窄有很大的风险。晚期BE伴高度不典型增生，不适合EMR，目前采用食管切除术治疗，这被认为是一种侵入性高风险手术。在那里，我们开发了一种微创手术技术，用于BE的局部粘膜切除术，提供适合进一步分析的圆周整体标本。通过经胃入路，腹腔镜通过腹壁和胃壁插入胃，建立气腹。在吻合器辅助粘膜切除术（SAM）中，获得一个完整的、周向的整体标本，并通过避免开放性伤口愈合来防止狭窄的形成。我们已经证明了这种新方法在非存活猪模型和存活猪模型中的可行性。已证实手术是安全的，6周内无狭窄发生。然而，由于BE患者几乎完全患有GERD，因此SAM手术应伴有抗反流手术，如底折叠手术。在SAM中，进行环周粘膜切除术并使用环形订书钉重新连接粘膜。这种环状钉线理论上可能损害食管小括约肌的功能。因此，本提案的实验将评估SAM是否对胃反流有影响，SAM是否可以与nissen -底扩术联合使用，以及底扩术与SAM联合使用是否是有效的抗反流手术。SAM的成功实施可以改变BE和GERD的治疗方式。与目前的治疗方案不同，SAM和抗反流手术的结合可以使GERD和BE患者在一次治疗中得到长期有效的治疗。

Gastroesophageal reflux disease (GERD) leads to the replacement of squamous epithelium by intestinal mucosa in the distal esophagus (Barretts epithelium, BE). BE is a facultative precancerosis that can result in an invasive adenocarcinoma. Currently, close endoscopic surveillance is recommended for early detection of dysplasia or invasive cancer. The current treatment for dysplastic BE is endoscopic mucosal resection (EMR) or, alternatively, radiofrequency ablation. EMR makes histological analysis difficult due to resection of the specimen in pieces (piecemeal), but it is critical to assess the resection margins in cases with high-grade dysplasia or invasive cancer. A larger resection field, or even circular resection, presents a substantial risk for post- intervention strictures. Advanced BE with high-grade dysplasia that is not amenable to EMR is currently treated by esophagectomy, which is considered an invasive high-risk surgical procedure. There we devoloped a minimally invasive surgical technique for local mucosectomy for BE providing a circumferential en-bloc specimen suitable for further analysis. By a transgastric approach, a laparoscope is inserted into the stomach through the abdominal and gastric walls, and a pneumogastrium is established. In stapler-assisted mucosectomy (SAM) an intact, circumferential en-bloc specimen is obtained and stricture formation is prevented by avoiding open wound healing. We have demonstrated the feasibility of this novel method in a non-survival as well as in a survival porcine model. It has been demonstrate that the procedure is safe and that no strictures occur within 6 weeks. However, as patients with BE almost exclusively suffer from GERD the SAM procedure should be accompanied by antireflux surgery such as fundoplication. In SAM a circumferential mucosal resection with reconnection of the mucosa using circular staples is performed. This circumferential staple line could theoretically impair the function of the lesser esophageal sphincter. The experiment of this proposal will therefore evaluate the questions if SAM has an influence on GERD, if SAM could be combined with Nissen-fundoplication and if fundoplication is an effective antireflux procedure in combination with SAM. The successful implementation of SAM could change the way BE and GERD are treated. The combination of SAM and an antireflux procedure could allow patients with GERD and BE to be effectively treated long-term in a single-session, unlike current therapeutic options.