Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan.
Tohoku J Exp Med. 2012 Jan;226(1):45-53. doi: 10.1620/tjem.226.45.
Although Helicobacter pylori (H. pylori) eradication has some inhibitory effects on the subsequent development of gastric cancer, there are sporadic cases of gastric cancer even after successful eradication. The pathogenesis of gastric cancer emerging after H. pylori eradication remains to be clarified. In this study, employing Congo-red chromoendoscopy, which is capable of visualizing the acid-secreting fundic mucosa, we investigated the topographic relationship of the acid secretion pattern to the occurrence site of gastric cancers emerging after eradication. Fourteen consecutive patients who suffered from new gastric cancer after eradication, defined as lesions that were discovered at least 2 years after the eradication, were prospectively enrolled. Whether the neoplasias arose from acid-secreting or non-acid-secreting areas was evaluated with Congo-red chromoendoscopy. Biopsy specimens taken from the two areas were subjected to histologic evaluation and immunohistochemistry for Ki-67 and p53. The mean period from the eradication to the subsequent occurrence of gastric cancer was 74 (44) months. There were two cancer lesions in 5 cases, and thus there was a total 19 lesions from 14 cases. Congo-red chromoendoscopy revealed that all 19 lesions arose exclusively from non-acid-secreting areas. Histological examination revealed sustained hyperproliferation and accumulation of p53 protein was frequently detectable in non-acid-secreting areas. Genetic alteration such as p53 mutation seems to be already present in the residual non-acid-secreting areas after eradication, areas that could be the origin of gastric carcinogenesis after eradication. Identification of such high-risk areas should be a promising approach for estimating the individual cancer risk after eradication.
尽管幽门螺杆菌(H. pylori)的根除对胃癌的后续发展有一定的抑制作用,但仍有少数胃癌病例在根除后发生。H. pylori 根除后新发胃癌的发病机制仍需阐明。在这项研究中,我们采用刚果红 chromoendoscopy,可以观察到胃酸分泌的胃底黏膜,研究了胃酸分泌模式与根除后新发胃癌发生部位的拓扑关系。连续前瞻性纳入 14 例根除后新发胃癌患者,定义为根除后至少 2 年发现的病变。采用刚果红 chromoendoscopy 评估肿瘤是否起源于胃酸分泌区或非胃酸分泌区。对来自两个区域的活检标本进行组织学评估和 Ki-67 和 p53 的免疫组化分析。从根除到随后发生胃癌的平均时间为 74(44)个月。5 例中有 2 个癌灶,因此 14 例共 19 个癌灶。刚果红 chromoendoscopy 显示,所有 19 个病变均仅起源于非胃酸分泌区。组织学检查显示,非胃酸分泌区持续过度增殖,p53 蛋白蓄积频繁。根除后残留的非胃酸分泌区可能已经存在 p53 基因突变等遗传改变,这可能是根除后胃癌发生的起源。识别这些高风险区域可能是评估根除后个体癌症风险的一种有前途的方法。