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The aim of this study is to investigate the cyclooxygenase (COX)-2 expression in esophageal epithelium of rat duodenoesophageal reflux model and the effect of a selective COX-2 inhibitor on esophageal adenocarcinogenesis in rats. A series of rats underwent a duodenoesophageal reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other group was given experimental chow containing nimesulide, a selective COX-2 inhibitor (nimesulide group). The animals were sacrificed sequentially after surgery and esophageal examinations were performed. In the control group, esophagitis, Barrett's esophagus (BE) and adenocarcinoma (EAC) were observed, and the frequency of these conditions increased with time. COX-2 expression, PGE(2) level and proliferative activity were up-regulated, predominantly in the inflamed esophageal epithelia, from the 10(th) week. In the nimesulide group, the esophagitis was mild and the frequency of BE was significantly lower than the control group, while EAC was not observed throughout the experiment. PGE(2) level and proliferative activity were lower in the nimesulide group than in the control group. COX-2 may play an important role in esophageal carcinogenesis through the activation of the inflammation-metaplasia-adenocarcinoma sequence. Nimesulide is effective in preventing BE and EAC by suppressing COX-2 activity.

Using the PCNA staining method, we examined the histopathological changes and cytokinetics on the gastric mucosa of the gastric remnant at the anastomosis 10, 20 and 50 weeks after gastrectomy. We conducted the distal gastrectomy in rats and divided them into three groups: Group 1, in which "a sham" operation was performed; Group 2, in which reflux of duodenum fluids was prevented by Roux-en Y anastomosis; and Group 3, in which reflux of duodenum fluids was allowed by gastro-jejunal anastomosis. Adenocarcinoma developed only at the anastomosis of the afferent loops in animals of Group 3 directly exposed to duodenum fluid. The PCNA labeling index at the anastomosis of the afferent loop was high from the early stages. In addition, labeling index tended to increase gradually, and PCNA positive cells were diffusely scattered, which indicated acceleration of cytosis. From these results, we concluded that the reflux of duodenum fluid was essential for the development of cancer in the remnant stomach. Moreover, cytosis was closely related to the development of epithelial cancer of the gastric mucosa at the anastomosis of the remnant stomach.

We reviewed 29 patients who developed carcinomas of the gastric remnant more than 10 years after the initial gastrectomy. The median age was 59 years (29-75), with a male-to-female ratio of 3.8:1. The reason for previous operation was stomach ulcer in 16 patients, chronic gastritis in 2, stomach polyp in 2, duodenal ulcer in 5 and stomach cancer in 4 patients. Regarding the type of the original operations, Billroth's operation I (B-I) was performed for 10 patients, Billroth's II (B-II) for 18 and Roux-en Y operation for one. The site of tumor was classified into three groups, stoma (gastroenterostomy), stump (gastric cut-end except stoma) and others (the site except stoma and stump). The patients reconstructed with B-II developed significantly more carcinomas in the stoma than those reconstructed with B-I, with the incidence of 10/18 and 0/10, respectively (p less than 0.05). The interval between the initial operation and the second one was significantly longer in patients with stomal cancer than in those with stump cancer (p less than 0.05). There were no significant difference in the frequency and degree of histologic change, such as intestinal metaplasia or glandular cystification in noncancerous areas, between the B-I and B-II patients. This study suggested that cancers of the gastric remnant, especially those developed in the stoma after B-II were different from the other remnant cancers in terms of carcinogenesis or cancer promotion, and that they were probably induced by duodenogastric reflux to the gastrojejunostomized area.

There has not come to any definite conclusion on morphological changes in post-vagotomy gastric mucosa. And, it was reported that duodenogastric reflux in consequence of pyloroplasty or gastroenterostomy could aggravate these gastric mucosal changes. To elucidate this problem, 34 Wistar male rats were subjected to either truncal vagotomy, duodenogastric reflux procedure (transection of the lower part of the duodenum and gastrojejunostomy), or truncal vagotomy with duodenogastric reflux procedure. After 12 weeks, rats were killed for histologic studies of gastric mucosa. Rats subjected to vagotomy with duodenogastric reflux procedure showed marked atrophy of gastric glands, reduction in number of parietal cells and gastrin cells, formation of small ulcer, and generation of heterotopic glands. Rats subjected to duodenogastric reflux also showed chronic ulceration in the prepyloric region on the lesser curvature and hyperplasia of gastric glands. However, no remarkable changes were observed in the stomach of rats with vagotomy. These results indicate that chronic influence of postvagotomy duodenogastric reflux can lead to severe gastritis as well as altered structure of gastric mucosa.