Cristina De Fazio

Hepatocellular carcinoma in Italian patients with cirrhosis.

BACKGROUND AND METHODS Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months. RESULTS Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery. CONCLUSIONS In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.

Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: A comparison with ursodeoxycholic acid alone

Chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) have distinct physicochemical and metabolic properties which, being complementary, should favor more rapid removal of cholesterol from gallstones when both bile acids are administered together. To see if the combination is more effective and well tolerated, we have compared 5 mg/kg of CDC plus 5 mg/kg of UDC with a 10-mg/kg dose of UDC alone in 120 patients with radiolucent, sonographically confirmed gallstones and characteristics favoring complete dissolution. Ursodeoxycholic acid was chosen as the reference because it dissolves stones faster and is better tolerated than CDC. To minimize the influence of stone size, the major determinant of dissolution, patients were divided, on admission, into two groups according to the maximum stone diameter: 50 had stones less than or equal to 5 mm, 70 had stones greater than 5 mm but less than 15 mm. The effects of treatment on stone dissolution evaluated by cholecystography and ultrasonography at 6, 12, and 24 mo, were analyzed by the actuarial life-table method. In the group with smaller stones, significantly more patients had obtained complete dissolution after treatment with the combination (52%) than after treatment with UDC alone (24%) at 6 mo. After longer periods, results were still better with the combination, although the differences from UDC alone became smaller. In the patients with larger stones, rates of complete and partial dissolutions were higher after treatment with the combination (51% vs. 24% with UDC) at 6 mo and again the differences had become smaller after longer treatment. Although not statistically significant, stone calcification occurred more often with UDC (7 cases) than with the combination (1 case). We conclude that CDC plus UDC is preferable to UDC alone because it dissolves stones more quickly, with a lower incidence of stone calcification, and may result in reduced cost of treatment.

Ultrasound-assisted percutaneous liver biopsy: Superiority of the Tru-Cut over the Menghini needle for diagnosis of cirrhosis

A total of 1192 consecutive patients with diffuse liver disease were randomized to have percutaneous liver biopsy specimens taken with the Menghini or the Tru-Cut needle, to compare tissue yield, safety, and accuracy of the two needles for diagnosing cirrhosis. The sites of puncture were determined by prebiopsy ultrasound scans. Adequate samples were obtained from 94% with the Tru-Cut needle and from 79.2% with the Menghini needle (p less than 0.001). Accuracy in diagnosing cirrhosis was 89.5% for the Tru-Cut needle and 65.5% for the Menghini needle (p less than 0.05). Complication rates were very low and similar for both needles. Under these conditions, the Tru-Cut needle is superior to the Menghini needle for diagnosing cirrhosis.

Effect of Loxiglumide on Gallbladder Contractile Response to Cerulein and Food in Humans

The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose-dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying.

Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas

PURPOSE To establish whether segmental transcatheter arterial chemoembolization (TACE) treatment may improve the rates of survival in patients with compensated cirrhosis and inoperable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Fifty-six patients with compensated cirrhosis and inoperable HCC were treated with segmental TACE. One hundred forty treatments (mean, 2.5 per patient; 30-60 mg Epirubicin, 4-10 mL Lipiodol, and Gelfoam particles) were administered. RESULTS During the 69-month study, 25 patients (45%) died of tumor progression, 12 (21%) of liver failure, nine (16%) of gastrointestinal hemorrhage, and three (5%) of other causes; seven patients (13%) are still alive. The 3-year rate of survival was 32%. Intention-to-treat analysis determined that patients with Child-Pugh class A disease (n = 44; 79%) or a single <5-cm HCC (n = 21; 37%) had a higher rate of survival than those with Child-Pugh class B disease (n = 12; 21%; P <.002) or a larger HCC (n = 35; 63%; P <.02) and patients (n = 41) who were treated with more than one course of TACE had a higher rate of survival than those who were treated with a single TACE procedure (n = 15; P <.0003). Multivariate analysis was used to predict rates of survival by number of treatments (hazard ratio, 0.6; CI, 0.48-0.86; P <.004), Child-Pugh class (hazard ratio, 2.8; CI, 1.41-5.74; P <.003), and tumor size (hazard ratio, 3.8; CI, 1.81-8.01; P <.001). The 3-year rate of survival in patients with Child-Pugh class A disease and a < or =5-cm-HCC (n = 16) was 56%. This result was similar to the 50% 3-year rate of survival in untreated historic controls with similar characteristics. CONCLUSION The rate of survival in patients with compensated cirrhosis and inoperable HCC did not appear to improve with use of TACE therapy.

Detection of liver involvement in inflammatory bowel disease by abdominal ultrasound scan

SummaryFifty patients with ulcerative colitis, 24 with Crohns disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twentytwo percent of ulcerative colitis patients, 29% of Crohns disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohns disease patients and 6% of controls (P<0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients.