Luigi Bolondi

Characterization of small nodules in cirrhosis by assessment of vascularity : The problem of hypovascular hepatocellular carcinoma

In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver (EASL) recommendations, as a criterion for characterizing small (1‐3 cm) nodules in cirrhosis. A total of 72 nodules (1‐2 cm, n = 41; 2.1‐3 cm, n = 31) detected by ultrasonography in 59 patients with cirrhosis were included in the study. When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography, the lesion was considered to be hepatocellular carcinoma (HCC) according to EASL criteria. When one or both techniques showed negative results, ultrasound‐guided biopsy was performed. In cases with negative results for malignancy or high‐grade dysplasia, biopsy was repeated when an increase in size was detected at the 3‐month follow‐up examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%; 44% of 1‐2‐cm nodules and 84% of 2‐3‐cm nodules). Fourteen nodules (19.4%) had negative results with both techniques (hypovascular nodules). Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion, the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of small nodules in cirrhosis; thus, biopsy frequently is required in this setting. Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as highly suspicious for HCC. (HEPATOLOGY 2005.)

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: Key role of immunosuppression

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)–based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 ± 86.4 ng/mL in recurrent vs. 169.9 ± 33.3 in tumor‐free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral‐ vs. non–viral‐related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha‐fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence‐free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered. (Liver Transpl 2005;11:497–503.)

Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors

Background/Aims: The hepatocyte receptor for asialoglycoproteins (ASGP‐R) internalizes macromolecules exposing galactosyl residues (MEGRs) which can be used as liver‐addressed drug carriers. This receptor was also found on the cells of the large majority of well differentiated hepatocarcinomas (HCCs). The aim of the present experiments was to ascertain whether ASGP‐R of HCCs is functionally active and these tumors can internalize higher quantities of MEGRs than extra‐hepatic tissues.

Caution in the use of boldo in herbal laxatives: A case of hepatotoxicity

A case is reported in which a several-fold increase in transaminases and γ-GT was detected in an elderly male patient with fatty liver. The patient was regularly taking a mixture of herbal products, used as a laxative, for a number of years, with no alteration of blood chemistry until 6 months before the present observation. However, the composition of the mixture had been modified by the manufacturer in the past 5 months, with addition of boldo leaf extracts. Transaminases promptly returned to normal after withdrawal of the laxative. It is concluded that boldo leaf extracts might be hepatotoxic, at least in elderly patients with fatty liver.