Background/Aims Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters. Methods Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score. Results Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1. Conclusions The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.

中文翻译：

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贲门失弛缓症食管平滑肌表型改变。

背景/目的 贲门失弛缓症是一种以下食管括约肌松弛和食管蠕动受损为特征的疾病，主要由抑制性神经支配丧失引起。然而，人们对食管平滑肌的相关变化知之甚少。我们检查了圆形平滑肌的收缩表型和神经支配以及炎症状态，并将这些与患者特定参数相关联。方法对连续接受经口内镜肌切开术的贲门失弛缓症患者进行圆形平滑肌活检。通过免疫细胞化学测定轴突神经支配和神经递质亚型，并与定量聚合酶链反应 (qPCR) 一起使用来表征平滑肌增殖和细胞表型以及胶原蛋白表达。将这些组织与食管切除术中获得的对照组织进行比较，并与患者人口统计因素（包括年龄、症状发作和埃克哈特评分）相关。结果 25 名贲门失弛缓症患者获得平滑肌活组织检查。总体而言，与对照相比，肥大细胞数量和胶原蛋白沉积增加，但平滑肌细胞增殖增加。与对照组相比，轴突密度显着下降，贲门失弛缓症亚型之间没有差异。免疫细胞化学分析显示，收缩标记物 α-平滑肌肌动蛋白的表达增加，主要在 1 型贲门失弛缓症中，随着疾病持续时间的延长而增加，而 qPCR 发现平滑肌肌动蛋白 mRNA 增加，肌球蛋白重链和胶原蛋白 3a1 减少，但胶原蛋白 1a1 减少。结论 贲门失弛缓症中增厚的圆形平滑肌层大部分去神经支配，收缩表型改变且纤维化。经口内窥镜肌切开术期间获得的活组织检查为进一步研究贲门失弛缓症的病理生理学提供了一种手段。