Liu Xiuli, Kuo Enoch, Wang Kai, Perbtani Yassen B, Yang Dennis, Draganov Peter
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
Gastroenterology Res. 2021 Oct;14(5):281-289. doi: 10.14740/gr1454. Epub 2021 Aug 31.
Peroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in achalasia. Esophageal mucosal changes in achalasia have only been studied in esophagectomy specimens. Cardia mucosal changes in achalasia have not been reported previously. We aimed to further characterize the esophageal, gastric cardia, and muscularis propria changes in achalasia.
This was a pilot study. Patients with clinically and radiographically confirmed achalasia who underwent POEM were enrolled in the study. Mucosal biopsies were taken 1 cm proximal and 1 cm distal to the gastroesophageal junction, and muscularis propria biopsies were taken from the mid esophagus. Tissues were submitted for histological evaluation.
Eighteen patients (10 male and eight female, mean age: 60.7 (standard deviation (SD): 13) years) were enrolled in this pilot study. Nine patients had type II achalasia, two type III, one type I, five esophageal gastric outlet obstruction, and one unspecific type achalasia. The mean duration of symptoms prior to POEM was 79 (range 1 - 480) months. All patients had a dilated esophagus on examination, but no endoscopic evidence of Barrett's esophagus. Esophageal, gastric cardia, and muscular biopsies were performed in 17, 13, and 17 patients, respectively. Basal hyperplasia, spongiosis, ballooning, and parakeratosis were seen in 92.3%, 100%, 100%, and 76.5% of cases, respectively. Intraepithelial lymphocytosis was seen in 70.5% of cases, and active esophagitis was seen in 23.5% of case. Six (35.3%) cases had few intraepithelial eosinophils, but none of them had > 15 eosinophils per high power field. Histologic findings in gastric cardia mucosa included carditis (69.2%), gastritis (7.6%), and reactive gastropathy (15.4%). One case (7.6%) showed low-grade dysplasia arising from intestinal metaplasia in the cardia. Absence of ganglion cells in the muscular biopsies was noted in 88.2% of cases, and the remaining two showed rare residual ganglion cells with ganglionitis in one case (5.8%). Muscular atrophy and interstitial fibrosis were observed in 52.9% and 82.3% of the cases, respectively. Two cases (11.7%) had eosinophilic inflammation in the muscularis propria and one of them was accompanied by lymphocytic inflammation.
Muscular biopsies in our study revealed loss of ganglion cells, supporting the view that achalasia is a primary esophageal disease with ganglion cell depletion. Squamous mucosa in achalasia showed changes mimicking reflux and lymphocytic esophagitis. Cardia mucosa in achalasia patients often were inflamed and uncommonly showed intestinal metaplasia and glandular dysplasia.
经口内镜下肌切开术（POEM）已越来越多地用于治疗贲门失弛缓症。既往研究报道贲门失弛缓症患者肌肉嗜酸性粒细胞浸润频率较高。贲门失弛缓症的食管黏膜变化仅在食管切除标本中进行过研究。此前尚未报道过贲门失弛缓症患者贲门黏膜的变化。我们旨在进一步明确贲门失弛缓症患者食管、胃贲门及固有肌层的变化特征。
这是一项前瞻性研究。纳入经临床和影像学确诊为贲门失弛缓症且接受POEM治疗的患者。在胃食管交界处近端1 cm和远端1 cm处取黏膜活检组织，并在食管中段取固有肌层活检组织。将组织送检进行组织学评估。
本前瞻性研究共纳入18例患者（男性10例，女性8例，平均年龄：60.7（标准差（SD）：13）岁）。9例为Ⅱ型贲门失弛缓症，2例为Ⅲ型，1例为Ⅰ型，5例为食管胃出口梗阻，1例为非特异性贲门失弛缓症。POEM术前症状的平均持续时间为79（范围1 - 480）个月。所有患者检查时均有食管扩张，但内镜检查未发现巴雷特食管的证据。分别对17例、13例和17例患者进行了食管、胃贲门和肌肉活检。基底增生、海绵形成、气球样变和不全角化分别见于92.3%、100%、100%和76.5%的病例。70.5%的病例可见上皮内淋巴细胞增多，23.5%的病例可见活动性食管炎。6例（35.3%）病例上皮内有少量嗜酸性粒细胞，但均无每高倍视野超过15个嗜酸性粒细胞。胃贲门黏膜的组织学表现包括贲门炎（69.2%）、胃炎（7.6%）和反应性胃病（15.4%）。1例（7.6%）病例显示贲门肠化生伴低级别异型增生。肌肉活检中88.2%的病例未见神经节细胞，其余2例中有1例（5.8%）可见罕见的残留神经节细胞伴神经节炎。分别有52.9%和82.3%的病例观察到肌肉萎缩和间质纤维化。2例（11.7%）固有肌层有嗜酸性炎症，其中1例伴有淋巴细胞炎症。
我们的研究中肌肉活检显示神经节细胞缺失，支持贲门失弛缓症是一种原发性食管疾病伴神经节细胞减少的观点。贲门失弛缓症的鳞状黏膜表现出类似反流和淋巴细胞性食管炎的变化。贲门失弛缓症患者的贲门黏膜常发炎，罕见肠化生和腺体异型增生。
