Olivier Ink

A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma

A randomized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma. These patients represented 41% of patients with hepatocellular carcinoma seen during the inclusion period. In the remaining 59%, 9% had resectable tumours and 50% had unresectable tumours with contraindication for chemoembolization. Patients received either repeated chemoembolization with gelfoam powder and doxorubicin (group 1) or symptomatic treatment (group 2). There was no difference in age, prevalence of cirrhosis or staging according to Okuda between the two groups of patients. A complete tumour response (assessed by arteriography, ultrasonography and serum alphafetoprotein) was observed in four patients, and a partial response in three other patients from group 1. Actuarial survival rates were 33 and 24% in group 1 and 52 and 31% in group 2 at 6 and 12 months, respectively (differences were not significant--logrank test). With the treatment used in our study, chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma. There were, however, some complete or partial responses. The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients. Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma.

Prognostic factors in patients with hepatocellular carcinoma attempts for the selection of patients with prolonged survival

A prognostic study based on 127 untreated patients with hepatocellular carcinoma was undertaken to evaluate their survival time and to find clinical and biologic criteria which allow the selection of patients with a survival time longer than 60 days who could enter a therapeutic trial. Twenty‐eight clinical and biologic variables were assessed using univariate and multivariate semiparametric regression (Coxs) models. Ten variables were isolated by univariate analysis. Multivariate analysis found a negative relationship between a survival time longer than 60 days and five of these variables; these variables were in decreasing order: encephalopathy, alcohol consumption, aspartate amino transferase (AST), blood urea nitrogen, and total bilirubin. Prevalence, positive, and negative predictive values of encephalopathy were 20%, 27.5%, and 97% respectively. When three other criteria: ASAT > four times the upper limit of the normal (N), blood urea nitrogen > N, and total bilirubin > 2N were added, their prevalence, positive, and negative predictive values were 72%, 89.7%, and 57.1% respectively. These results suggest that in countries where incidence of hepatocellular carcinoma is low and recruitment of patients difficult, absence of encephalopathy must be the only criterion for selection of patients with hepatocellular carcinoma in therapeutic trials; whereas, in countries with a high incidence of hepatocellular carcinoma the other criteria may be added.

Culture-negative neutrocytic ascites: a less severe variant of spontaneous bacterial peritonitis

The clinical signs and symptoms, the biological data and the prognosis of 38 cirrhotic patients with culture-positive spontaneous bacterial peritonitis and 15 cirrhotic patients with culture-negative neutrocytic ascites were compared. The diagnosis of culture-negative neutrocytic ascites was based on the following criteria: an ascitic fluid polymorphonuclear count greater than 250/mm3, a negative ascitic fluid culture and the absence of previous antibiotic therapy and intraabdominal source of infection. All patients were treated by antibiotic therapy. There were no differences in clinical signs and symptoms and Pugh grading between the two groups of patients. Serum creatinine and prevalence of positive-blood culture were higher in spontaneous bacterial peritonitis. Patients with culture-positive spontaneous bacterial peritonitis had a higher ascitic fluid polymorphonuclear count and a lower ascitic fluid pH. Mortality was higher in patients with culture-positive spontaneous bacterial peritonitis than in patients with culture-negative neutrocytic ascites (relative risk: 2.6, p less than 0.01): cumulative mortality was, respectively, 50% and 20% at 1 months, 61% and 33% at 6 months, 75% and 41% at 1 year. The higher mortality observed in patients with culture-positive spontaneous bacterial peritonitis persisted after hospitalization (relative risk: 3, p less than 0.03). Our results suggest that culture-negative neutrocytic ascites is a less severe variant of spontaneous bacterial peritonitis.

Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis.

Objective Large-volume paracentesis associated with plasma volume expansion with albumin is an effective, safe, but costly therapy for ascites in patients with cirrhosis. The aim of this study was to compare the use of a synthetic plasma expander, hydroxyethyl starch (HES), with that of albumin. Design Sixty cirrhotic patients with ascites were studied. Patients were randomly assigned to be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200 ml/I of ascites removed, n = 27). None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry. Clinical and laboratory data were obtained before and 1, 3 and 15 days after treatment Results There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study. None of the patients developed renal impairment during the trial. One patient (HES group) presented with hyponatremia. Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites removed did not differ between the albumin (7.9 ± 4.41) and HES (6.9 ± 5.3 I) groups. However, there was a significant difference in weight loss between the albumin and HES groups (7.9 ± 5.2 kg vs 4.7 ± 3.4 kg; p = 0.01). Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia. Conclusion HES is well tolerated in patients with cirrhosis. There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis. The lesser degree of weight loss observed with HES needs further study.

Nodular regenerative hyperplasia of the liver, peliosis hepatis, and perisinusoidal fibrosis. Association with angioimmunoblastic lymphadenopathy and severe hypoxemia.

Three different liver lesions were found in a 20-year-old woman with angioimmunoblastic lymphadenopathy. The lesions included nodular regenerative hyperplasia of the liver, perisinusoidal fibrosis, and peliosis hepatis. It is suggested that the association of angioimmunoblastic lymphadenopathy with this broad spectrum of liver lesions was not fortuitous.

Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial

BACKGROUND/AIMS Norfloxacin is useful to prevent infections in hospitalized cirrhotic patients with low ascitic fluid protein concentrations. It is also effective in preventing the recurrence of spontaneous bacterial peritonitis. The aim of our study was to determine the efficacy of norfloxacin in the primary prophylaxis of gram-negative bacilli infections in cirrhotic patients with low ascitic fluid protein levels (<15 g/l). METHODS One hundred and seven patients were randomized to receive norfloxacin (400 mg/day; n=53) or placebo (n=54) for 6 months. The patients had no history of infection since cirrhosis diagnosis and no active infection. RESULTS The probability of gram-negative infection was significantly lower among patients treated with norfloxacin than among those treated with placebo. Six gram-negative bacilli infections occurred in the placebo group and none in the treatment group. Severe infections (spontaneous bacterial peritonitis, neutrocytic ascites and bacteremia) developed in nine patients in the placebo group (17%) and in one patient in the norfloxacin group (2%; p<0.03). There was no between-group difference in the overall rate of infection or in survival. In ten patients from the norfloxacin group, gram-negative bacilli not present in baseline stool cultures were transiently isolated in follow-up cultures. CONCLUSIONS These data show that primary prophylaxis with norfloxacin for 6 months is effective in the prevention of infections caused by gram-negative bacilli in cirrhotic patients with low ascitic fluid total protein levels.