Different carcinogenesis in the gastric remnant after gastrectomy for gastric cancer.
BACKGROUND
The incidence of gastric remnant cancer after surgery for gastric malignancies has been increasing. The interval between previous operations and the diagnosis of gastric remnant cancer, location of cancer development, and histologic type were different from those after surgery for benign diseases. However, very little is known about the reasons for these differences. Patients with gastric cancer already have cancer-related gastric mucosal changes at gastrectomy, and they undergo a wide range of dissection of nerve distribution to the stomach due to lymph node dissection. Therefore, the effects of preliminary administration of a carcinogenic agent and denervation of the gastric mucosa on tumorigenesis in the gastric remnant were investigated.


METHODS
Using male Wistar rats, N-methyl-N'-nitro-N-nitroguanidine (MNNG; 50 mg/L) was given in drinking water for 10 weeks. The animals were then assigned into four groups of those undergoing Billroth I (B-I) gastrectomy or Billroth II (B-II) gastrectomy, with and without denervation. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after gastrectomy, the following investigations were performed: histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen (PCNA).


RESULTS
In macroscopic findings, the groups undergoing nitrosoguanide (NG) gastrectomy with denervation showed a significant increase in the development of whitish, nodular changes in the gastric body. These changes mainly consisted of intestinal metaplasia in microscopic findings. In the NG gastrectomy group, the cancer developed at a lower rate of incidence at the anastomotic site and in the gastric body (1 of 11 rats and 1 of 11 rats, respectively). Conversely, a higher incidence of cancer development (5 of 13 rats) in the gastric body was observed in the group that underwent NG gastrectomy with denervation. Furthermore, the denervation group showed a significant increase in the PCNA labeling index and a distinct increase in the staining of Alcian blue positive mucin in the mucosa of the gastric body. The cancers that developed in the gastric body showed horizontal growth and were accompanied by intestinal metaplasia. In contrast, the cancers that developed in the gastric stumps showed downward growth, and were always accompanied by adenocystic proliferation, but not intestinal metaplasia.


CONCLUSIONS
Different processes of carcinogenesis in the gastric remnant are postulated after the surgery for gastric malignancies. The developed cancer is defined by its location and the gastric mucosal changes that developed at the time of gastrectomy.
Kaminishi
M
M
Third Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
Shimizu
N
N
Yamaguchi
H
H
Hashimoto
M
M
Sakai
S
S
Oohara
T
T
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000502:physiology; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D018530:Gastric Stump; D006801:Humans; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009607:Nitrosourea Compounds / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology / Q000601:surgery*
D002273:Carcinogens; D009607:Nitrosourea Compounds; D008769:Methylnitronitrosoguanidine; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea