Pera M, Trastek V F, Carpenter H A, Fernandez P L, Cardesa A, Mohr U, Pairolero P C
Section of General Thoracic Surgery, Mayo Clinic, Rochester, Minnesota 55905.
Ann Thorac Surg. 1993 Jun;55(6):1386-92; discussion 1392-3. doi: 10.1016/0003-4975(93)91077-z.
We previously presented an experimental model of Barrett's adenocarcinoma of the esophagus by demonstrating that esophagojejunostomy combined with subcutaneous injection of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats resulted in development of adenocarcinoma in the distal esophagus. The present study was devised to investigate the influence of pancreatic and biliary duodenal-content reflux on the induction of esophageal carcinoma. Three groups of 8-week-old Sprague-Dawley rats were controls: the first was exposed to pancreatic reflux, the second to biliary reflux, and the third to both. The other three experimental groups were similar except that a 1/100 LD50 dose of 2,6-dimethylnitrosomorpholine was injected subcutaneously weekly, starting on day 15. Carcinoma of the esophagus was induced only in animals receiving the carcinogen after exposure to either pancreatic reflux (3/22, 13%) or pancreatic and biliary reflux (9/27, 33%). Half of the carcinomas were adenocarcinoma and half were squamous cell carcinoma. These findings suggest that under these experimental conditions, in which the carcinogen is used in a low dose, esophageal carcinoma is induced only when pancreatic secretions are present in the duodenal-content reflux. Biliary reflux, however, appears to exert a cocarcinogenic effect when combined with pancreatic secretions. The clinical relevance of these findings needs further evaluation. Conceivably, the elimination of pancreatic and biliary duodenal-content reflux in patients with documented Barrett's mucosa may inhibit the progression from metaplasia to adenocarcinoma.
我们之前通过证明在斯普拉格-道利大鼠中进行食管空肠吻合术并皮下注射2,6-二甲基亚硝基吗啉会导致远端食管腺癌的发生，提出了一种食管巴雷特腺癌的实验模型。本研究旨在调查胰液和胆汁十二指肠内容物反流对食管癌诱导的影响。将三组8周龄的斯普拉格-道利大鼠作为对照组：第一组暴露于胰液反流，第二组暴露于胆汁反流，第三组暴露于两者。其他三个实验组与之相似，只是从第15天开始每周皮下注射1/100 LD50剂量的2,6-二甲基亚硝基吗啉。仅在暴露于胰液反流（3/22，13%）或胰液和胆汁反流（9/27，33%）后接受致癌物的动物中诱发了食管癌。一半的癌为腺癌，一半为鳞状细胞癌。这些发现表明，在这些低剂量使用致癌物的实验条件下，仅当十二指肠内容物反流中有胰液时才会诱发食管癌。然而，胆汁反流与胰液结合时似乎具有促癌作用。这些发现的临床相关性需要进一步评估。可以想象，在有巴雷特黏膜记录的患者中消除胰液和胆汁十二指肠内容物反流可能会抑制从化生到腺癌的进展。
