Relationship Between Urinary 8-hydroxydeoxyguanine (8-OHdG) Levels and Clinicopathological Findings in Hepatobiliary Malignancies.

BACKGROUND/AIM: Oxidative stress is defined as an imbalance between the pro-oxidant and antioxidant potential of cells leading to intracellular DNA damage. To clarify the oxidative stress response as a tumor marker, we investigated measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in hepatobiliary diseases. MATERIALS AND METHODS: Relationships between urinary 8-OHdG levels and clinicopathological factors were analyzed in 101 patients, including 84 with hepatobiliary malignancies, and 18 healthy volunteers. Co-existing biliary inflammation was detected in 8 patients. RESULTS: Urinary 8-OHdG levels did not correlate with any clinical or liver functional parameters. The existence of inflammation and any tumor-related factor did not correlate with urinary 8-OHdG levels either. Urinary 8-OHdG levels were significantly higher in patients with benign and malignant diseases than in healthy volunteers (p<0.05), but not significantly different between benign and malignant diseases. Among patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma, urinary 8-OHdG levels tended to be higher in patients with lymph node metastasis-positive than in those with lymph node-negative disease (p=0.057). CONCLUSION: The clinical significance of oxidative DNA damage and increases in its urinary metabolites in patients with hepatobiliary malignancies or inflammatory diseases remain unknown. Further studies are necessary to clarify the relationship between node metastasis and oxidative stress as a prognostic marker.

Upregulated plasma and urinary levels of nucleosides as biological markers in the diagnosis of primary gallbladder cancer.

We first detected aberrant nucleoside levels in the plasma, urine, bile, and tissues from cases and controls to explore them as biomarkers in the diagnosis of gallbladder cancer. Reversed-phase high-performance liquid chromatography was used to assess the levels of ten nucleosides in these samples from gallbladder cancer patients, gallstone patients, and healthy controls. Plasma and urine samples were collected from patients with gallbladder cancer (n = 202), patients with gallstones (n = 203), and healthy controls (n = 205); bile and tissue samples were collected from 91 gallbladder cancer patients, 93 gallstone patients; and 90 were donated after cardiac death. Of the ten nucleosides analyzed, eight urinary nucleosides, five plasma nucleosides, three bile nucleosides, and one tissue nucleoside were significantly upregulated in the gallbladder cancer patients compared to control groups (p < 0.05). Among these upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and 95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%, respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively, and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These results suggest that nucleosides may be as useful as biological markers for gallbladder cancer.

Urinary gonadotropin peptide in patients with cancer of digestive organs.

Urinary gonadotropin peptide (UGP) has been measured in gynecological and urological cancers, but its usefulness in the diagnosis of cancers of digestive organs has not been investigated. In this report, UGP was measured by sandwich enzyme immunoassay in 311 patients, including 166 patients with cancers of digestive organs and 43 healthy controls. Positive rates of UGP in various cancers of digestive organs were as follows: biliary tract 61.5%, pancreas 61.5%, esophagus 50.0%, liver 38.7%, colon and rectum 24.2%, and stomach 23.9%. The positive rate of UGP in benign diseases was 8.1%, and most false-positive patients were postmenopausal females. Positive rates of UGP were increased at advanced stages of gastric cancers, and UGP was decreased after tumor resection. From these results, it is suggested that UGP can be used as a tumor marker for the cancers of digestive organs.

Severe renal hypouricemia secondary to hyperbilirubinemia.

A 64-year-old man with alcoholic liver cirrhosis had a progressive decrease in the serum uric acid (UA) until it became undetectable, an increase renal UA clearance, mild glycosuria with normal serum glucose and a decrease in the tubular reabsorption of phosphate in association with cholestasis secondary to a gallbladder carcinoma. All these abnormalities returned to normal when the serum bilirubin levels decreased following surgical treatment. This clinical observation suggests that the reversible renal tubular transport defect was secondary to high levels of serum bilirubin.