Serum nitric oxide levels in patients with benign and malignant biliary disease: a prospective single center study.

BACKGROUND

Despite advances in new diagnostic modalities, the differentiation of malignant from benign causes of biliary obstruction still remains difficult. The nitric oxide (NO) system is considered to be an important component in mediating cytokine activation of macrophages in inflammation. It also modulates tumorigenesis and regulates cell proliferation, angiogenesis, survival, and DNA repair. Although NO and its role in pancreatobiliary disorders has not been studied previously, the present study is designed to evaluate NO synthesis and metabolism in patients with biliary obstruction and to determine its usefulness in differentiating between benign and malignant causes of biliary obstruction.

MATERIALS AND

METHODS

Seventy-nine consecutive patients (60 malignant and 19 benign) with a history of biliary obstruction either with a benign or a malignant cause and 23 age-matched and sex-matched controls were included in this prospective study. NO metabolites, and conventional inflammation and tumor markers were determined.

RESULTS

In patients with malignant biliary obstruction (MBO), serum NO metabolites were found to be significantly elevated (P<0.001). The receiver operating characteristic analysis showed that an NO level of 1.095 was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 78.3% and a specificity of 84.2% (area under the curve=0.821). Correlation analysis suggested that carbohydrate antigen 19-9 and carcinoembryonic antigen levels were correlated with NO levels for differentiating benign from malignant cause of biliary obstruction.

CONCLUSIONS

Serum NO-associated tissue injury might be associated with the development of pancreatobiliary neoplasia by creating a local environment that is enriched with reactive oxygen species, cytokines, and other growth factors that may promote endothelial cell apoptosis. Moreover, serum NO levels may be used as an adjunctive marker to identify malignant causes of the obstructive jaundice.