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April 2001. Review Article. Namieno describes recurrent cases after curative resection for early gastric cancer even though the tumour had seemed to be completely resected by surgery. The author defines pathologic features of recurrence in findings that can be assessed preoperatively by endoscopy and by biopsy. The reported cumulative mortality rate due to recurrence of early gastric cancer ranges from 2% to 4% in the literature and 1% in his study. The submucosal cancers are significantly more prone to recurrence than the mucosal carcinomas. Moreover the macroscopically elevated type and the compound type cancers recur more often than depressed type carcinomas. Differentiated adenocarcinomas have a high potential for venous invasion, while undifferentiated adenocarcinomas are characterized by a lymphatic invasion. Therefore differentiated carcinomas recur in the form of blood-borne metastases and surgeons cannot control bloodstream-containig carcinoma cells, whereas involved lymph nodes can be dissected by surgery.
Postoperative thorough follow up is indicated in particular in the cases of macroscopically compound and elevated -type carcinomas, microscopically differentiated carcinomas and lymphatic involvement with depressed, undifferentiated EGCs. Although the preoperative staging and treatment selection, the patients should deserve protection from uncertainty by gastric resection (De Cosse).
Guadagni underlines the high recurrence risk for the intestinal histologic type, corresponding to the well differentiated type reported by Japanese authors. Bozzetti confirms that patients undergoing surgery for EGC (especially the intestinal type) may have a circa 50% higher risk of a second tumor and should be periodically checked for others tumors, mainly in the supramesocolic area (Bozzetti). With recent development of minimal treatment for early gastric cancer it's important to reaffirm that the identification of specific indicators of the metastatic potential of primary tumors has become more important. Differentiated type gastric carcinoma(DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. The G type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastases (Koseki). Mucinous gastric carcinoma is rare and whether MGC behaves more aggressively than nonmucinous gastric carcinoma is controversial. Adachi indicates that although the macroscopic features of early MGC differ from those of early NMGC, patient prognosis and the frequency of lymph node metastasis do not differ (Adachi).
Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. Multivariate analysis concludes that VEGF expression ( as well as submucosal invasion and lymph node metastases) is an indipendent predictor of disease recurrence (Maeda). Cathepsin B and cathepsin L, both lysosomal cysteine proteases, degrade the extracellular matrix during tumor progression. Tumors with overexpression of cathepsin have powerful potential for invasiveness in the early stage of gastric carcinoma. Moreover cathepsins may be one of the determinants of the metastatic route (Dohchin). Kawamura refers of a retrospective case-control study conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful EMR therapy for EGC and on 14 patients without recurrence. Thirty percent of patients with recurrent disease shows microsatellite instability (MSI-H) whereas none of the patients with nonrecurrent disease does so (Kawamura).
MSI is thought to play an important role in the development of multiple primary cancers of the gastrointestinal tract. References
Namieno T et al. Tumor recurrence following resection for early gastric carcinoma and its implications for a policy of limited resection. World J Surg. 22, 869-873,1998.
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