Human plasma membrane-associated sialidase (Neu3) is unique in specifically hydrolyzing gangliosides, thought to participate in cell differentiation and transmembrane signaling, thereby playing crucial roles in the regulation of cell surface functions. We have discovered levels of mRNA for this sialidase to be increased in restricted cases of human colon cancer by 3-to 100-fold compared with adjacent nontumor mucosa (n ‫؍‬ 32), associated with significant elevation in sialidase activity in tumors (n ‫؍‬ 50). In situ hybridization showed the sialidase expression in epithelial elements of adenocarcinomas. In cultured human colon cancer cells, the sialidase level was downregulated in the process of differentiation and apoptosis induced by sodium butyrate, whereas lysosomal sialidase (Neu1) was upregulated. Transfection of the sialidase gene into colon cancer cells inhibited apoptosis and was accompanied by increased Bcl-2 and decreased caspase expression. Colon cancer exhibited a marked accumulation of lactosylceramide, a possible sialidase product, and addition of the glycolipid to the culture reduced apoptotic cells during sodium butyrate treatment. These results indicate that high expression of the sialidase in cancer cells leads to protection against programmed cell death, probably modulation of gangliosides. This finding provides a possible sialidase target for diagnosis and therapy of colon cancer.

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BACKGROUND.In colorectal carcinoma, venous invasion has been related to patient

LC is not likely to worsen the survival rate of patients with GBC compared with the survival rate of patients undergoing a standard open radical procedure, as long as additional excision is conducted for patients with laparoscopically removed pT2 or pT3 GBCs. Special attention should be paid to prevention of bile spillage during LC.

The records of 45 patients with carcinoma of the gallbladder who had undergone surgical resection at least 5 years previously were reviewed retrospectively to determine which factors influence long-term survival. Seventeen patients survived at least 5 years and 23 died from recurrence (five patients were excluded from analysis). Of the 17 long-term survivors 15 had tumours superficial to the subserosa that showed a non-infiltrative growth pattern. Those alive at 5 years were more likely than short-term survivors to have tumours that were papillary (P < 0.05) or well differentiated (P < 0.01) adenocarcinoma. Venous, lymphatic and perineural invasion was more common in short- than in long-term survivors (87 versus 29 per cent, P < 0.001). Patients with tumours limited to the muscularis and those with non-infiltrative subserosal involvement are likely to have better survival and may have a chance of cure after extended cholecystectomy.

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Computer-assisted three-dimensional (3D) reconstruction of the biliary tree including extrahepatic and intrahepatic parts was performed from surgical or autopsy materials from 12 patients with hepatohilar bile duct carcinoma in an effort to visualize three-dimensionally the distribution of carcinoma and dysplasia. In each case, material including a hepatic lobe was reduced to serial slices 1 mm thick using a ham slicer, then the tumors, ducts with carcinoma in situ, and those with dysplasia were submitted to reconstruction. In a 3D map of biliary tree reproduced on a display, a dysplastic zone was shown in most cases surrounding a focus of carcinoma, justifying the assumption of a dysplasia-carcinoma sequence. The carcinoma itself proved to form multiple foci along bile ducts in as many as 42% of the patients, in some of whom the foci were independent without any intervening dysplasia. These results suggest that as extensive a surgical measure as possible should be taken in designing a strategy against this tumor.

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