Jean-Pierre Etienne

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.

Survival after a first episode of spontaneous bacterial peritonitis. Prognosis of potential candidates for orthotopic liver transplantation

Abstract To determine the potential role of orthotopic liver transplantation (OLT) in cirrhotic patients surviving a first episode of spontaneous bacterial peritonitis (SBP), medical records of 79 patients presenting with a first episode of SBP were reviewed. Of these patients, 37 were selected as potential candidates for OLT using the following criteria: absence of hepatocellular carcinoma; no severe organ failure other than the liver; age ≤ 66 years; and survival after SBP > 60 days. Survival time was calculated from the day of SBP diagnosis. Prognostic value of clinical, biological and bacteriological data recorded at the time of SBP was determined using univariate and multivariate analysis (Coxs regression model).

Prospective study of clinical and biochemical features of symptomatic choledocholithiasis

One hundred consecutive patients were prospectively studied to assess the clinical and biochemical features of symptomatic choledocholithiasis. Biochemical tests were performed during the three days following the onset of symptoms. Pain was the most frequent symptom of choledocholithiasis, observed in 75% of the patients, but rarely occurred alone (12%). Clinical symptoms were not different according to age. High serum gamma glutamyl transpeptidase and alkaline phosphatase were the most frequent biochemical abnormalities in patients with symptomatic choledocholithiasis: they were increased in 94 and 91% of cases, respectively. Only one patient had no biochemical abnormality. Serum transaminases could reach very high levels just as in hepatitis. Biochemical data did not differ regardless of whether the common bile duct was enlarged or not. Biochemical abnormalities had been studied over the first 10 days of spontaneous evolution in 25 patients while choledocholithiasis persisted: serum bilirubin and transaminases significantly decreased while serum gamma glutamyl transpeptidase, alkaline phosphatase, and amylase remained unchanged. These results indicate that, in patients with suggestive symptoms, choledocholithiasis is unlikely in the absence of biochemical abnormalities in the first three days following the onset of symptoms.

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.

Interobserver agreement in the physical diagnosis of alcoholic liver disease

Agreement among six physicians for 18 clinical signs in 50 alcoholic patients was prospectively studied. Twenty patients had alcoholic cirrhosis, 14 noncirrhotic alcoholic liver disease, and 16 alcoholics had no clinical or biochemical abnormalities. Agreement was assessed by kappa index for categorical variables and by intraclass correlation coefficient for the others. A good agreement was observed for ascites (r=0.75) and splenomegaly (r=0.75). It was fair for jaundice (r=0.65), Dupuytrens contracture (r=0.65),and vascular spiders (r=0.64). However, it was poor for white nails (r=0.27) and hepatic consistency (r=0.11). Agreement was better among senior physicians than junior physicians. In order to assess which signs contributed to differentiate the three groups of patients, a stepwise discriminant analysis was realized; it identified three variables: vascular spiders (P<0.001), splenomegaly (P<0.001), and abdominal wall collateral veins (P<0.01). These results suggest that studies based on physical findings must be cautiously considered.

Impaired functions of normal peripheral polymorphonuclear leukocytes in cirrhotic ascitic fluid

The function of normal polymorphonuclear cells in the ascitic fluid of 32 patients with cirrhotic ascites and 17 patients with malignant ascites was studied independently of ascitic fluid heat-labile factors. Polymorphonuclear (PMN) function was assessed by a chemiluminescence method using preopsonized zymosan as stimuli. The chemiluminescence response was higher in malignant ascitic fluid than in cirrhotic ascitic fluid (0.84 and 0.15, respectively, p < 0.001). These results were confirmed by a microbiological assessment of phagocytosis. Suppressive factors were evidenced by making ascitic fluid dilutions and using cell-free chemiluminescence measurements. Addition of malignant ascitic fluid to cirrhotic ascitic fluid showed that there is also a deficiency in supportive factors other than C3. The impaired PMN production of oxidative metabolites we observed in cirrhotic ascitic fluid can partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis independently of C3 levels.

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.

Treatment of gallstones with piezoelectric lithotripsy and oral bile acids: A multicenter study

The efficacy of the combination of piezoelectric lithotripsy and oral bile acids in the treatment of gallbladder stones was assessed. Three hundred and sixty-three patients with symptomatic radiolucent gallstones in functioning gallbladder were treated in five medical centers using the same protocol with the EDAP LT 01 lithotripter. No anesthesia, analgesia or sedation was used. After one session of lithotripsy, fragmentation was observed in 89% of the patients, and satisfactory fragmentation (fragments less than or equal to 5 mm) in 29%. The satisfactory fragmentation rate was higher in patients with solitary stones less than or equal to 20 mm than in patients with solitary stones 21-35 mm or multiple stones (p less than 0.001). After multiple sessions (mean 1.6 session/patient, range 1-5) the overall rate of satisfactory fragmentation was 50%. After 12 months on oral bile acid therapy, complete clearance of the gallbladder was observed in 69% of patients with solitary stones less than or equal to 20 mm, 25% of patients with solitary stones 21-35 mm and 37% of patients with multiple stones. No complication was observed during the lithotripsy. During follow-up under bile acid therapy, there were five complications (1.4%): four patients had acute cholecystitis and one had mild, self-limited pancreatitis. We conclude that piezoelectric lithotripsy with the EDAP lithotripter is a safe and effective treatment which can be performed in outpatients. Satisfactory fragmentation and rapid disappearance of stones are obtained mainly in patients with solitary stones less than or equal to 20 mm.

Low early gallstone recurrence rate after successful extracorporeal lithotripsy in patients with solitary stones

Piezoelectric lithotripsy with the EDAP LT-01 machine combined with adjuvant bile acid therapy results in complete clearance of radiolucent gallstones in selected patients. We assessed stone recurrence rate in 84 patients with complete clearance of stone fragments and followed up at least 12 months after cessation of bile acid therapy (mean 17 months, range 12-33). Fifty-four patients had a solitary stone and 30 multiple stones. Bile acid therapy was continued for 3 months after complete fragment stones clearance which was ascertained by two consecutive ultrasound examinations. Stone recurrence was assessed by ultrasonography at 6 and 12 months, and then at least once a year. Gallstone recurrence occurred in 5 patients (6%) between 9 and 12 months with no further recurrence up to 33 months. The rate of recurrence at one year was 3.7% in patients with a solitary stone and 10% in patients with multiple stones. Only one patient with stone recurrence had recurrent biliary pain. We concluded that early gallstone recurrence rate after successful lithotripsy seems to be low in patients with solitary stones.