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Early Gastric Cancer : prognostic factors.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.

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.
Medical doctors have to search for recurrent or metachronous lesions and for neoplasms in other organs (particularly lung and colorectal cancers: 34% of patients with an EGC die of another malignancy) (Namieno).

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.
Moreover he recommends a more accurate intraoperative and postoperative histologic examination of resection margins and the performing of a D2 lymphadenectomy . It's necessary for western surgeons to improve the quality of dissection of the lymph nodes at the hepatoduodenal ligament, around the common hepatic, splenic, and celiac arteries, and along the lesser gastric curvature in cases of subtotal gastrectomy (Guadagni).

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).
Pen A type gastric carcinoma (expansively penetrating growth invading the submucosa layer) tends to secrete VEGF, thus inducing tumor angiogenesis and resulting in venous invasion. Therefore intensive follow up is necessary for patients with Pen A type tumor, because this tumor type has a greater propensity for hematogenous metastasis (Tomoda).

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.
MSI analysis is rapid and inexpensive. MSI may be a useful screening marker to detect a high risk group for second primary cancer in some patients with sporadic single gastric and colorectal cancers (Yamashita).


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.

De Cosse J, MD.,Ph.D. Invited Commentary. World J Surg. 22, 873,1998.

Guadagni S et al. Causes of death and recurrence after surgery for early gastric cancer. World J Surg. 21, 434-439, 1997.

Csendes A MD. Invited Commentary. World J surg. 21, 439, 1997.

Bozzetti f et al. Early gastric cancer: unrecognized indicator of multiple malignancies. World J Surg. 24, 583-587, 2000.

Koseki K et al. Distinction of differentiated type early gastric carcinoma with gastric type mucin expression. Cancer 2000; 89: 724-32.

Adachi Y et al. Clinicopathologic study of early stage mucinous gastric carcinoma. Cancer 2000; 91: 698-703.

Maeda K et al. Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma. Cancer 1999;86: 566-71.

Tomoda M et al. Intramural neovascularization and growth pattern in early gastric carcinoma. Cancer 1999; 85: 2340-6.

Dohchin A et al. Immunostained cathepsins B and L correlate with depth of invasion and different metastatic pathways in early stage gastric carcinoma. Cancer 2000; 89:482-7.

Kawamura A et al. Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma. Cancer 2001; 91:339-45.

Yamashita K et al. Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract. Gut 2000;46:790-794.

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