The most important factors for predicting lymph node metastasis in early esophageal cancer are depth of tumor infiltration, angiolymphatic invasion, neural invasion and grade of lymphocytic infiltration. The best candidates for endoscopic therapy are tumors with high-grade lymphocytic infiltration, no angiolymphatic or neural invasion, mucosal infiltration or sm1 (only for ADK), and tumor <1 cm in size. For sm SCC and sm2/3 ADK the treatment of choice remains esophagectomy with standard lymphadenectomy.

In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its "incomplete" phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.

Background: The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. Patients and methods: A total of 118 consecutive cases (nine indefinite for non-invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non-invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12-206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. Results: Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p<0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. Conclusions: The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.

In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its "incomplete" phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.

Gastric carcinogenesis is a complex, multistep and multifactorial event, characterized by progressive cyto-histological dedifferentiation, in which the role of Helicobacter pylori infection has been established. Among the pathways relevant to gastric carcinogenesis and correlated with H. pylori infection, it has been demonstrated that the production of reactive oxygen species, with damage to the DNA, may be quite important. Oxidative damage, alone and/or in combination with exogenous and endogenous factors, induces several molecular changes. The assumption is that, in precancerous lesions, these molecular changes belong to the same biological spectrum as their invasive counterpart. The molecular profile of these preneoplastic lesions is heterogeneous, however, and there are still no molecular markers enabling the distinction between atypical hyperplastic lesions and low-grade noninvasive neoplasia (NiN) or between high-grade NiN and early invasive neoplasia. Indeed, within the spectrum of morphological changes characterizing this multistep evolution, dysplasia (NiN) is the lesion coming closest to the development of invasive adenocarcinoma. Several of the genetic and epigenetic alterations reported in gastric precancerous lesions affect DNA repair system genes, tumor suppressor genes, oncogenes, cell cycle regulators, growth factors, and adhesion molecules. Although we await reliable molecular markers, it is best to monitor patients harboring NiN closely with endoscopy and extensive bioptic sampling, and to eradicate any H. pylori to prevent the accumulation of oxidative DNA damage and its consequent progression. The growing body of evidence of the regression of precancerous changes and the high prevalence of superficial gastric carcinoma demonstrated in long-term follow-up studies on NiN make this approach mandatory.