Pierre Gaucher

Comparison of resection, liver transplantation and transcatheter oily chemoembolization in treatment of hepatocellular carcinoma

BACKGROUND/AIMS Resection and liver transplantation are currently considered as the most useful treatments for hepatocellular carcinoma. However, transcatheter oily chemoembolization may be favourably compared with these two surgical treatments in patients with anatomically operable tumors. METHODS Between 1985 and 1991, 122 patients with an Okuda stage I tumor were hospitalized in two French hospitals. Among these patients, 33 remained untreated, 42 were treated by transcatheter oily chemoembolization, 30 by resection and 17 by liver transplantation. The four groups were closely comparable except for age, the patients in the two surgical groups being significantly younger. Moreover, the frequency of pTNM II tumor was significantly higher in the resection group. RESULTS The 5-year probability of survival was close to 45% in each of the three treated groups and was significantly higher than in the untreated group (0% at 4 years, p < 0.0001). The probability of cancer recurrence and/or metastatic dissemination was lower after transcatheter oily chemoembolization than after surgery. CONCLUSION Thus, transcatheter oily chemoembolization seems comparable at 5 years with resection or transplantation for the treatment of resectable hepatocellular carcinoma.

Alcoholic Cirrhosis and Cobalamin Metabolism

The cobalamin status of 27 patients suffering from alcoholic cirrhosis and 20 control subjects was analyzed. Plasma cobalamin (p < 0.005), total corrinoids (p < 0.005) and their analogs (p < 0.05) were all significantly elevated in the cirrhosis patients. These differences were due to increased haptocorrin (HC)-bound corrinoid (p < 0.02), which could be explained by a deficient hepatic clearance of cobalamin bound to HC. The increase in the concentration of true cobalamin was greater than that of its analogs. There were positive correlations between cholestasis (serum alkaline phosphatase) and plasma analog concentrations (p < 0.05), HC-bound cobalamin (p < 0.005) and total corrinoids bound to HC (p < 0.005). The plasma concentrations of the indicators of cobalamin deficiency, homocysteine (p < 0.05) and methylmalonic acid (p < 0.001), were increased, which could indicate poor cellular penetration of vitamin B12 or a defect in the activation of the two vitamin-B12-dependent enzymes.

Crohn's disease and vitamin B12 metabolism

The concentrations of vitamin B12, its analogs, and the haptocorrin and transcobalamin carriers in 21 patients suffering from Crohns disease and a group of controls (20 adults) were measured. There were no significant differences in the mean values for vitamin B12, total corrinoids (vitamin B12 + analogs), or vitamin B12 or total corrinoids bound to haptocorrin or transcobalamin of the Crohns and control patients. There was a significant increase in the binding capacity of transcobalamin in the Crohns patients compared to the controls (P<0.001), but there was no difference in the binding capacities of haptocorrin. The serum concentrations of the markers of vitamin B12 status, homocysteine and methylmalonic acid, showed an increase (P<0.01) in homocysteine in the Crohns disease patients, but no change in methylmalonic acid. As the hyperhomocysteinemia was associated with normal folate concentrations, there may have been a defect in the activation of the enzyme due to altered intracellular vitamin B12 status.

Malabsorption of Vitamin B12 in Pancreatic Insufficiency of the Adult and of the Child

Vitamin B12 can bind two carrier proteins in the digestive tract, haptocorrin (R binder) and intrinsic factor, but only its binding to intrinsic factor allows its absorption. A malabsorption of vitamin B12 is observed in about 30% of adult patients with exocrine pancreatic insufficiency, using the Schilling test. None of the hypotheses that have tried to explain this malabsorption are entirely satisfactory. A failure to degrade haptocorrin can prevent the binding of vitamin B., to intrinsic factor. It has also been suggested that pancreatic secretion could modify the structure of intrinsic factor, enabling the uptake of the vitamin B12 intrinsic factor complex by the ileum. Other factors can also affect the binding of vitamin B., to intrinsic factor, such as the gastric pH and bile. The Schilling test is abnormal in nearly all cases of cystic fibrosis. One explanation could be the gastric hyperacidity observed in this disease. Despite the frequency of abnormal Schilling tests, vitamin B., deficiency is very rare in cases of exocrine pancreatic dysfunction, in adults as well as in children with cystic fibrosis. The assimilation of this vitamin with a tracer included in food instead of the crystalline labeled cobalamin used in the Schilling test remains to be investigated.

Biliary Excretion of Cobalamin and Cobalamin Analogues in Man

Using dialysis, gel filtration, isoelectrofocusing and radioaffinity assay, we studied the unsaturated and saturated binders of bile and the biliary concentration of cobalamin (Cbl) and Cbl analogues compared to the corresponding serum concentrations in 7 choledochodomized patients. Bile contained a single saturated or unsaturated R binder with a molecular mass of about 120,000. Differences in the isoelectrofocusing pattern were observed between unsaturated and saturated R binders and could correspond to two secretion origins, mucosal secretion and hepatocyte clearance, respectively. The concentration of total corrinoids is about 4 times higher in bile than in serum, and this could be explained by a hepatic clearance of serum Cbl analogue-R binder complexes, as previously described in the rabbit. Moreover, the enterohepatic circulation of Cbl seems likely in healthy individuals since the saturated biliary R binder is degraded by pancreatic juice.