Internal radiation therapy for hepatocellular carcinoma. Results of a French multicenter phase II trial of transarterial injection of iodine 131-labeled Lipiodol.

Preliminary Phase I trials have shown iodine 131 (131I)-Lipiodol (ethiodized oil; Laboratoires Guerbet, Aulnaysous-Bois, France) to be well tolerated and most likely effective in the treatment of hepatocellular carcinoma (HCC). In this multicenter Phase II trial, the authors tested the feasibility and reproducibility of this treatment in other medical institutions and evaluated its efficacy in 50 patients with unresectable Stage I or II HCC, by the classification of Okuda et al. The authors studied 47 men and 3 women (63.9 +/- 7.1 years old) with Stage I (n = 18) or II (n = 32) HCC, by the classification of Okuda et al., which was verified by histologic findings (n = 25), cytologic findings (n = 11), or association of a tumor with alpha-fetoprotein serum values greater than 500 micrograms/l (n = 14). This multicenter trial (1) confirmed that the 131I-Lipiodol treatment is well tolerated; (2) showed that there is a high reproducibility of results with respect to other institutions and an objective tumor response in 40% of the cases; and (3) indicated the necessity of performing a randomized controlled study.

Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding.

Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy.

[Obstructive intramural hematoma of the esophagus. A rare complication of endoscopic sclerotherapy of esophageal varices]. / Hématome intramural obstructif de l'oesophage. Une complication rare de la sclérose endoscopique des varices oesophagiennes.

Obstructive intramural hematoma of the esophagus is an unusual complication of endoscopic sclerotherapy. We report three patients with liver cirrhosis who experienced such a complication. In our series, the frequency was 1.6 percent. A few hours after sclerotherapy, all three patients complained of low retrosternal pain, dysphagia and hypersialorrhea. Endoscopy was performed in two patients and showed a typical bluish submucosal mass occupying the esophageal lumen. Outcome was favorable in all patients within one week of conservative treatment. We hypothesized that hematoma could be ascribed to variceal puncture. The extension of the hematoma with dissection of the esophageal wall which had been fragilized by previous sclerotherapy sessions could have been facilitated by impaired coagulation.

Gastroesophageal endoscopic features in cirrhosis. Observer variability, interassociations, and relationship to hepatic dysfunction.

Nowadays, gastroesophageal endoscopic features of portal hypertension are the recognized predictive factors for bleeding and consequently allow the selection of patients for prophylactic therapies. The aim of this prospective study was to investigate the interobserver agreement, the interassociations between these features, and the relationship between these signs and the degree of hepatic dysfunction. In 100 consecutive cirrhotic patients (84% with alcoholism) without history of digestive bleeding, gastroesophageal endoscopic examination was performed and recorded using a videoendoscope. Four independent observers evaluated the following endoscopic features: the size, extent, color, and red signs of esophageal varices, the mosaic pattern, congestive gastropathy, fundic varices, and associated lesions of the stomach. Agreement was assessed using kappa statistics (kappa) and a quantitative score. The size of esophageal varices was significantly associated with their extent and the presence of red signs, whereas no relation was found either between gastropathy or mosaic pattern and fundic varices, or between esophageal and gastric features. Agreement between observers was good for the size of esophageal varices (kappa = 0.59), the presence of red signs (kappa = 0.60), and of gastric-associated lesions (kappa = 0.68) and gastropathy (kappa = 0.50), while it was poor for the extent (kappa = 0.37) and the color (kappa = 0.28) of esophageal varices as well as for the mosaic pattern (kappa = 0.38). The Child-Pugh score significantly increased along with the presence or the size of esophageal varices as well as with the presence of red signs; no relationship could be shown between this score and the presence of gastric features. We conclude that (1) interobserver agreement was good for the main endoscopic features, especially for the size and the red signs of esophageal varices; (2) esophageal patterns were significantly associated between themselves and related to hepatic dysfunction; and (3) gastric patterns were related neither to esophageal features nor to hepatic dysfunction and were not associated between themselves.

Atrial natriuretic peptide, plasma renin activity, plasma volume, systemic vascular resistance and cardiac output in patients with cirrhosis.

The present study aimed to assess relationships between plasma levels of atrial natriuretic peptide (ANP) and plasma volume, systemic vascular resistances, cardiac output and plasma renin activity in patients with cirrhosis. Thirty patients were included: eight with no history of liver disease were used as controls; 22 patients had biopsy-proven alcoholic cirrhosis without ascites (n = 11) and with ascites (n = 11). Mean ANP plasma level was significantly higher in both groups of cirrhotic patients than in controls (P less than 0.05). In the control group, ANP and plasma renin activity were inversely correlated (P less than 0.05) but no correlation was found in cirrhotic patients. In the group of patients with ascites, ANP plasma levels were inversely correlated to plasma volume (P less than 0.05) and to cardiac output (P less than 0.01) and directly correlated to systemic vascular resistances (P less than 0.01). Using multiple regression analysis, ANP remained correlated only with systemic vascular resistances (P less than 0.05). These results suggest that cirrhotic patients have high plasma levels of ANP whether or not they have ascites. In the light of current knowledge of ANP actions, the relationships between ANP plasma levels and plasma volume, cardiac output, and systemic vascular resistances are paradoxical in cirrhotic patients with ascites. ANP does not seem to play a critical role in the pathogenesis of sodium and water retention observed in these patients.

[Computerized tomographic diagnosis of hepatocarcinoma after injection of lipiodol into the hepatic artery]. / Diagnostic scanographique des hépatocarcinomes après injection de lipiodol dans l'artère hépatique.

Iodized oil (lipiodol) injected into the hepatic artery is selectively retained by hepatocarcinomas, as demonstrated by computerized tomography (CT) performed one week after the injection. The value of this technique for the diagnosis of hepatocarcinoma was assessed in a retrospective study of 45 patients. In 39 per cent of the cases intrahepatic tumoral extension was determined by the iodized oil which showed tumoral nodules that had not been detected by conventional methods, such as ultrasonography and CT alone. The lesions revealed by the iodized oil were small nodules around the main tumour. The combined iodized oil-CT technique plays an important role in the choice of treatment, especially when surgical excision is contemplated. It might also contribute to an early diagnosis of hepatocarcinoma in patients at risk, as illustrated by four of our cases where conventional morphological examinations had been negative.

Verapamil has no effect on porto-hepatic pressure gradient, hepatic blood flow and elimination function of the liver in patients with liver cirrhosis.

This study aimed to assess the effects of verapamil, a calcium-channel blocker, on porto-hepatic pressure gradient and on hepatic function as measured by the intrinsic hepatic clearance of indocyanine green (ICG) in patients with biopsy proven alcoholic cirrhosis. Hepatic venous pressures and hepatic extraction of ICG were measured before and 60 min after intravenous injection of 10 mg of verapamil in 19 consecutive patients. Hepatic blood flow and intrinsic hepatic clearance of ICG were calculated in the 10 patients whose hepatic extraction fraction was higher than 10%. No significant difference was observed when comparing porto-hepatic pressure gradient (17.72 +/- 4.79 vs. 17.77 +/- 4.43 mmHg), hepatic blood flow (13.47 +/- 4.75 vs. 16.13 +/- 7.88 ml.min-1.kg-1) and intrinsic hepatic clearance of ICG (1.99 +/- 0.54 vs. 1.97 +/- 0.45 ml.min-1.kg-1) before and after verapamil injection. We conclude that verapamil has no beneficial effect in patients with alcoholic cirrhosis.

Effect of propranolol on metabolic activity of the liver in patients with alcoholic cirrhosis.

Many studies have been performed to investigate the haemodynamic effects of propranolol. However, little is known of its actions on the metabolic activity of the liver. This study aimed to investigate the influence of propranolol on hepatic function as assessed by the galactose elimination capacity (GEC) and the intrinsic clearance of indocyanine green (ICG). 15 patients with biopsy-proven alcoholic cirrhosis and portal hypertension were studied. 10 had GEC and ICG clearance measured before and after the i.v. injection of 15 mg of propranolol (group P) and 5 had ICG clearance measurement before and after normal saline injection (group C). Propranolol significantly reduced heart rate (P less than 0.005) and the porto-hepatic pressure gradient (P less than 0.01). Hepatic blood flow was not changed. GEC was not altered by propranolol. Propranolol decreased the intrinsic hepatic clearance of ICG as determined by the 'sinusoidal' model by 12% (P less than 0.01). This suggests that propranolol may have an inhibitory action on the hepatic elimination of ICG that is independent of any effect on total liver blood flow or drug metabolism, since intrinsic clearance is not influenced by changes in blood flow and ICG is thought not to be metabolized.