Miwa Koichi, Miyashita Tomoharu, Hattori Takanori
Surgical Oncology, Division of Cancer Medicine, Graduate School of Medicine, Kanazawa University.
Nihon Rinsho. 2004 Aug;62(8):1433-8.
We observed the sequential development of columnar lined epithelium associated with adenocarcinoma, squamous dysplasia related with squamous cell carcinoma and adenosquamous carcinoma which were induced by duodeno-esophageal or gastro-duodeno-esophageal reflux in rats. Wistar male rats, weighing approximately 250 g were employed. Animals received total gastrectomy and were reconstructed with esophago-jejunostomy, which causes unavoidable duodeno-esophageal reflux. The animals were sacrificed every 10 weeks after surgery until 50 weeks. Erosions and basal cell hyperplasia were observed in the lower esophageal squamous epithelium at 10 weeks after surgery. At 20 weeks, glandular structures featured with galactose oxidase-Schiff-positive staining (foveolar metaplasia) appeared in the basal layer of esophageal squamous epithelium. At 30 weeks, the glands developed and formed cysts which were stained with concanavalin A (pyloric glandular metaplasia) or/and high iron diamine and alcian blue (intestinal metaplasia). Since 40 weeks after surgery, esophageal carcinomas were found. As adenocarcinomas were surrounded by the columnar-lined epithelium, squamous cell carcinoma and adenosquamous carcinoma were accompanied by squamous dysplasia. Persistent duodeno-esophageal reflux can change the stem cells of squamous epithelium to make columnar-lined cells. As part of the sequence of events leading to the development of columnar-lined epithelium, foveolar metaplasia was observed followed by the appearance of pyloric glandular metaplasia and intestinal metaplasia. Chronic duodenal reflux induces the development of esophageal carcinoma not only adenocarcinoma also squamous cell carcinoma and adenosquamous carcinoma. These pathways of carcinogenesis were different dual patterns.
我们观察了大鼠十二指肠-食管或胃-十二指肠-食管反流诱导的与腺癌相关的柱状上皮化生、与鳞状细胞癌相关的鳞状发育异常以及腺鳞癌的序贯发展过程。选用体重约250g的雄性Wistar大鼠。动物接受全胃切除并进行食管空肠吻合术重建,这会导致不可避免的十二指肠-食管反流。术后每10周处死一批动物,直至50周。术后10周,在食管下段鳞状上皮中观察到糜烂和基底细胞增生。20周时,食管鳞状上皮基底层出现经半乳糖氧化酶-席夫染色呈阳性的腺管结构(小凹上皮化生)。30周时,腺管进一步发育并形成囊肿,经刀豆球蛋白A染色呈阳性(幽门腺化生)或/和高铁二胺及阿尔辛蓝染色呈阳性(肠化生)。术后40周起发现食管癌。腺癌被柱状上皮化生所包绕,鳞状细胞癌和腺鳞癌伴有鳞状发育异常。持续的十二指肠-食管反流可使鳞状上皮干细胞转变为柱状上皮细胞。作为导致柱状上皮化生发展的一系列事件的一部分,先观察到小凹上皮化生,随后出现幽门腺化生和肠化生。慢性十二指肠反流不仅可诱导腺癌,还可诱导鳞状细胞癌和腺鳞癌的发生。这些致癌途径呈现不同的双重模式。