Nicola Nicoli

Severe impairment of antioxidant system in human hepatoma

Catalase (CAT), glutathione‐peroxidase (GSH‐Px) activity and reduced glutathione content (GSH) were measured in patients who had hepatocellular carcinoma, and values compared with those of normal liver and liver adjacent to neoplastic tissue. The results showed a remarkable reduction of CAT in tumor and corresponding tumor‐free tissue (P < 0.001 and P < 0.02, respectively). All neoplastic samples had a significant lower activity of CAT than the corresponding adjacent tumor‐free tissue (P < 0.05). The GSH‐Px activity of tumor tissue also was lower than normal (P < 0.001) but similar to that of adjacent tissue. No correlation was noted between the two enzyme activities. Glutathione content was extremely low in tumor (P < 0.001) and even in tumor‐free tissue (P < 0.05) when compared with normal liver. In all cases the content of GSH in neoplastic tissue was lower than that of the corresponding tumor‐free tissue (P < 0.05). Whereas in normal liver the activity of GSH‐Px was positively correlated with the content of GSH, in the neoplastic tissue such a relationship disappeared. All these findings suggest that the antioxidant system of hepatocellular carcinoma cell is severely impaired.

Asymptomatic hepatocellular carcinoma in Child's A cirrhosis

The present study deals with the natural history of 37 asymptomatic patients with cirrhosis and hepatocellular carcinoma, 25 with 2-9-cm tumors who were not surgically treated (first group) and 12 with tumors smaller than 4 cm who underwent resection (second group). All patients were in Childs A class. Two-year survival (according to life-table analysis by the Kaplan-Meier method) was 50% in the first group and 39% in the second group. This difference was not significant. In the first group no relation was found between survival and initial tumor size or alpha-fetoprotein levels. Ultrasound examinations at 3-mo intervals revealed the following patterns of tumor growth: (a) no significant growth during the follow-up (9 patients); (b) significant growth (tumor size at least doubling) only in the final stage of the disease (11 patients); (c) initial significant growth followed by a period of no increase in size (5 patients). These findings show that in our geographical area (a) 2-yr survival of untreated asymptomatic patients with hepatocellular carcinoma associated with cirrhosis does not differ from that of similar patients undergoing resection and (b) the tumor can exhibit long periods of no growth alternating with periods of exponential growth.

Lactobacillus plantarum Reduces Infection of Pancreatic Necrosis in Experimental Acute Pancreatitis

Background: Infection is the commonest cause of death in acute pancreatitis. Early reduction of commensal flora (particularly Lactobacillus species) and, at the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli, have recently been described during acute pancreatitis. Lactobacillus plantarum has been shown to be effective in reducing the egress of endotoxin and microbial translocation in several experimental models such as chemically induced hepatitis and ulcerative colitis. Aim: The aim of the study was to determine whether L. plantarum 299v (Lp 299v) is capable of effectively reducing microbial translocation in experimental pancreatitis. Methods: Acute pancreatitis was induced by isolation and ligation of the biliopancreatic duct in Lewis rats weighing 250–350 g. The animals were divided into 3 groups: group A, sham operation; group B, induction of pancreatitis and no further treatment, and group C, induction of pancreatitis + daily administration by gavage of a 5-ml/day suspension of Lp 299v at 0.5–1.0 × 109 bacteria/ml for 8 days, 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 h. Histological studies and microbiological analyses were performed. Results: At sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute pancreatitis was the specific disease investigated, only these animals were subjected to further study. In group B, we found pathogenic micro-organisms in the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in 10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus faecalis, Pseudomonas and Proteus species. In contrast, when the animals were kept under an ’umbrella’ of Lp 299v, growth of E. faecalis or E. coli were detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic tissue cultures. Conclusions:Lp 299v is effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative to antibiotic therapy.

Decreased activity of scavenger enzymes in human hepatocellular carcinoma, but not in liver metastases

SummaryTo investigate the role of oxygen free radicals in hepatocellular carcinoma we assayed tissue scavenger enzymes (superoxide dismutase and selenium-dependent glutathione peroxidase) in liver homogenate, plasma concentrations of vitamins A and E and the serum selenium level from 19 control patients, 23 cases of hepatocellular carcinoma and 18 cases of metastases to liver from different carcinomas. In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver and in metastases-bearing liver; the enzyme activities of the latter tissues were not different from control liver. In contrast, normal liver adjacent to the hepatocellular carcinoma had decreased activity of superoxide dismutase. Serum selenium concentrations were significantly decreased in patients with hepatocellular carcinoma and those with liver metastases, while vitamin A was significantly decreased only in the former. These findings suggest that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.

Contribution of CT to characterization of focal nodular hyperplasia of the liver

Our personal series of 20 cases of focal nodular hyperplasia (FNH) of the liver is presented. All lesions were studied with computed tomography (CT), 16 of which with surgical control. Retrospective evaluation of the CT features of the identified FNH, along with those of five hepatocellular adenomas (HCA) and 30 hepatocellular carcinomas (HCC), allowed the definition of specific patterns leading to a correct characterization of FNH in 78% of cases. This greatly reduced the diagnostic errors, with the sole exception of patients with fatty liver in whom nuclear medicine may eventually provide a correct characterization. Fine-needle biopsy is thus only necessary in the dubious cases. A precise diagnostic workup of FNH is necessary, since it may avoid the surgical intervention.

Decreased activity of liver glutathione peroxidase in human hepatocellular carcinoma

Glutathione peroxidase (GSH-Px) activity, one of the scavenger enzymes of oxygen active radicals, has been measured in hepatocellular carcinoma (HCC) of 17 patients and the values compared with the activity of adjacent tumor-free tissue and with those of 30 histologically normal livers. The results demonstrate a reduced GSH-Px activity in neoplastic tissue (21.19 vs 33.74 U/g prot.; P less than 0.001). However, the adjacent tumor-free liver also had a reduced activity when compared with normal tissue (23.15 vs 33.74 U/g prot.; P less than 0.01), but this value did not differ from that of HCC tissue. These data suggest that HCC might develop in a GSH-Px-deficient condition.

Serum copper and ceruloplasmin in early and in advanced hepatocellular carcinoma: diagnostic and prognostic relevance.

To evaluate the prognostic value of serum copper (S-Cu) and ceruloplasmin and their pathophysiologic significance in human hepatocellular carcinoma (HCC), we studied 49 patients with HCC (20 of which were submitted to partial hepatectomy) compared with 110 patients with liver cirrhosis. In HCC both S-Cu and ceruloplasmin were higher than in cirrhosis; moreover, S-Cu was correlated with the extension of HCC, evaluated by instrumental data and by surgical inspection. In cirrhotic patients, mean S-Cu was 122.9 μg/dl (SD, 29.3), in early HCC, 153.0 μg/dl (SD, 34.5), and in advanced HCC, 193.1 μg/dl (SD, 37.7). Variance analysis gave F = 59.4. In HCC patients S-Cu was positively correlated with ceruloplasmin and with fibrinogen. Survival, evaluated by Mantels test stratified for surgical therapy, was longer in patients with S-Cu levels lower than 175 μg/dl and in those at an earlier stage. We therefore conclude that S-Cu has a relevant diagnostic value in detecting HCC also in early stage and allows prognostic evaluation as regards survival.

Reduction of liver glutathione peroxidase activity and deficiency of serum selenium in patients with hepatocellular carcinoma.

Twelve adults with hepatocellular carcinoma (HCC) and 8 individuals with hystologically normal liver, were measured for serum selenium concentration and glutathione peroxidase (GSH-Px) of liver tissue. It was found a reduced serum selenium and liver GSH-Px in patients with HCC. Serum selenium concentration and the enzyme activity were positively correlated (p < 0.01). The increased risk of carcinoma in selenium deficiency may be partially due to a reduced activity of GSH-Px, one of the most important scavenger enzymes of oxygen toxic radicals.