Gian Ludovico Rapaccini

Percutaneous etharrol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients

In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Childs Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male‐female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow‐up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1‐year, 2‐year, and 3‐year survival percentages (by the Kaplan‐Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Childs class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1‐year, 2‐year, and 3‐year survival rates for patients with more than one HCC were 90%, 67%, and 31%, respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy‐to‐do, and low‐cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful. Cancer 1992; 69: 925–929.

Relationship between disease activity indices and colonoscopic findings in patients with colonic inflammatory bowel disease.

The Crohns disease activity index, a similar index devised for patients with ulcerative colitis, and other commonly used laboratory indicators of disease activity have been studied in 50 patients with colonic inflammatory bowel disease undergoing routine colonoscopic assessment and compared with the histological extent and activity of disease. There was only poor correlation between the colonoscopic or histological findings and the indices of disease activity studied, showing that these are not reliable measures of disease activity or extent at the tissue level.

Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

BACKGROUND/AIMS Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients. METHODS One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression. RESULTS The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development. CONCLUSIONS Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre.

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups Methods: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. Results: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, α fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. Conclusions: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence

Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child‐Turcotte‐Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions (P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases. (Liver Transpl 2005;11:1117–1126.)

Characteristics of hepatocellular carcinoma in Italy

BACKGROUND/AIMS This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.

Ultrasound-guided fine-needle biopsy of focal liver lesions: techniques, diagnostic accuracy and complications: A retrospective study on 2091 biopsies

Two thousand and ninety-one ultrasound-guided fine-needle biopsies were performed in 1946 patients to diagnose focal liver lesions. The diagnostic accuracy of fine-needle biopsies is very high (only one false positive was observed), both for aspiration biopsy (93.4%) and for cutting biopsy (95.1%). The difference is not statistically significant. In cases of hepatocellular carcinoma (but not in cases of metastasis or hepatic lymphoma), double biopsy (aspiration and cutting) showed higher diagnostic sensitivity than single methods. A certain number of benign focal liver lesions were also diagnosed. In the present series, no case of death following liver puncture was observed. Intraperitoneal hemorrhage was the most common complication. The risk with a cutting needle being higher than with an aspirative needle.

Long term effectiveness of resection and radiofrequency ablation for single hepatocellular carcinoma <= 3 cm. Results of a multicenter Italian survey.

BACKGROUND & AIMS The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma ≤3 cm and compensated cirrhosis. METHODS The study involved 544 Child-Pugh A cirrhotic patients (246 in the resection group and 298 in the radiofrequency group) observed in 15 Italian centers. Overall survival and tumor recurrence rates were analyzed using the Kaplan Meier method before and after propensity score matching. Cox regression models were used to identify factors associated with overall survival and tumor recurrence. RESULTS Two cases of perioperative mortality were observed in the resection group and the rate of major complications was 4.5% in the resection group and 2.0% in the radiofrequency group (p=0.101). Four-year overall survival rates were 74.4% in the resection group and 66.2% in the radiofrequency group (p=0.353). Four-year cumulative HCC recurrence rates were 56% in the resection group and 57.1% in the radiofrequency group (p=0.765). Local tumor progression was detected in 20.5% of ablated patients and in one resected patient (p<0.001). After propensity score matching, both survival and tumor recurrence were still not significantly different although a trend towards lower recurrence was observed in resected patients. Older age and higher alpha-fetoprotein levels were independent predictors of poor overall survival while older age and higher alanine-aminotransferase levels resulted to be independent factors associated with higher recurrence rate. CONCLUSIONS In spite of a higher rate of local tumor progression, radiofrequency ablation can provide results comparable to liver resection in the treatment of single hepatocellular carcinoma ≤3 cm occurring in compensated cirrhosis.

Contrast‐enhanced power Doppler of the intestinal wall in the evaluation of patients with Crohn disease

Background: Crohn disease (CD) manifests with highly variable signs and symptoms, and assessment of the status of the disease in the single patient can be difficult. This study was conducted to evaluate the efficacy of power colour Doppler ultrasonography, with and without echo‐enhancement, in distinguishing active from quiescent CD. Methods: Resistance Index (RI) of the superior mesenteric artery (SMA), bowel thickness of the affected loops and the presence of colour signals at power Doppler analysis prior to and after ultrasonography contrast agent injection (Levovist®) were evaluated in 48 patients with CD. Results: In our series, 26/48 patients had active and 22/48 had quiescent CD. A CDAI score ≥150 and a pathological (>5 mg/dL) C reactive protein were significantly correlated with active disease (P < 0.001 and P = 0.004, respectively). Intestinal wall thickness showed no significant correlation with disease status (7.5 ± 1.3 mm in active disease versus 6.8 ± 1.3 mm in quiescent disease; P = 0.11). Vascular signals in the affected loops were revealed in 11/22 patients (50%) with active disease and in 5/26 (20%) with quiescent disease (P = 0.052). After Levovist injection, colour signals were found in 22/22 with active and in 8/26 with quiescent CD (P < 0.001). SMA RI was significantly lower in active CD patients (0.81 ± 0.01 versus 0.83 ± 0.02; P = 0.001). Conclusions: Our data suggest that in patients with CD a finding of a SMA RI ≤ 0.81, or the presence of a colour signal in the wall of the affected loops, at power Doppler sonography, is indicative of active disease. Utilization of echo‐enhancer media can greatly improve the diagnostic sensitivity of intestinal wall power Doppler scan. A finding of intestinal wall thickening is not associated with active disease in our series.

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis†

Alpha‐fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha‐fetoprotein in patients with well‐compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child‐Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha‐fetoprotein serum levels (i.e., normal ≤20 ng/mL; mildly elevated 21‐200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan‐Meier method, was not significantly different among the three alpha‐fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤2 cm (P = 0.714). An alpha‐fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465‐0.606) to discriminate between survivors and deceased patients. Conclusion: Alpha‐fetoprotein serum levels have no prognostic meaning in well‐compensated cirrhosis patients with single, small HCC treated with curative intent. (HEPATOLOGY 2012)