Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.
Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.
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DOI：
10.1007/s00464-013-3210-2
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Marks JM
中科院分区：
文献类型：
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作者：
Wu Y;Schomisch SJ;Cipriano C;Chak A;Lash RH;Ponsky JL;Marks JM
食管内镜黏膜下剥离术（ESD）是治疗早期食管癌和高度Barrett异型增生的有效微创治疗方法。然而，环周或大ESD后食管狭窄的形成限制了其广泛应用。丝裂霉素C（MMC）、常山酮（Hal）和转化生长因子β3（TGF-β3）具有抗瘢痕形成作用，可防止ESD后狭窄形成。使用内镜粘膜切除术（EEM）技术，在猪模型中切除8- 10 cm长的环形食管粘膜段。该部位未经治疗（对照，n = 6）或立即以及在第1周和第2周接受40次均匀分布的抗瘢痕形成剂注射。采用高、低剂量组：MMC 5 mg（n = 2）、0.5 mg（n = 2）; Hal 5 mg（n = 2）、1.5 mg（n = 2）、0.5 mg（n = 2）; TGF-β3 2 μg（n = 2）、0.5 μg（n = 2）。狭窄形成的程度由每周透视检查的食管管腔缩小百分比确定。当狭窄超过80%或动物无法维持体重时，对动物实施安乐死。对照组在2周时管腔直径减小78.2 ± 10.9%，并在第3周时人道处死。与2周时相比，Hal组显示平均狭窄形成减少（低剂量68.4%，高剂量57.7%），而两个TGF-β3剂量组均未显示显著变化（低剂量65.3%，高剂量76.2%）。MMC在预防狭窄方面最有效（低剂量53.6%，高剂量35%）。值得关注的是，用高剂量MMC治疗的食管壁似乎坏死并最终导致穿孔。而低剂量MMC、TGF-β3和Hal处理区则出现上皮再生和健康。MMC和Hal的初步数据表明，EEM后有希望减少食管狭窄的形成。需要更多的动物数据进行充分的统计分析，以确定抗瘢痕形成治疗的总体疗效。
Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.