Efficacy of transarterial targeted treatments on survival of patients with hepatocellular carcinoma. An Italian experience.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) are not suitable for surgical therapy. Systemic chemotherapy, immunotherapy, and hormonotherapy have not had convincingly acceptable results. Therefore, transarterial catheter-targeted therapies such as intraarterial chemotherapy (IAC), possibly followed by transcatheter arterial chemoembolization (TACE), have been proposed. METHODS: A survival analysis curve was drawn using the Kaplan-Meier method for 164 patients, 100 with HCC who underwent TACE (69) or IAC (31), and a matched historic group of 64 who did not receive specific antineoplastic treatment. RESULTS: A significantly more favorable survival was observed for TACE-treated patients compared with IAC-treated patients (P < 0.001); TACE- and IAC-treated patients had a statistically superior survival than that of untreated patients (P < 0.001 and P < 0.025, respectively). This difference was still significant (P < 0.001) when the patients were subdivided into Classes A and B and Stages I and II following Child's and Okuda's criteria. The TACE- and IAC-treated groups had a good relationship between technical efficacy of therapy and survival. Stratifying the patients according to the degree of iodized oil (Lipiodol Ultrafluid, Guerbet, Aulnay-Sous-Bois, France) uptake in the three groups with Group 1 having an uptake greater than 75% of tumor mass, Group 2 having an uptake of 50%-75%, and Group 3 having an uptake less than 50%, survival at 6, 12, 24, 36, and 48 months was calculated as 94%, 88%, 67%, 53%, and 30%, respectively, for Group 1; 86%, 68%, 13%, 13%, and 0% for Group 2, and 43%, 23%, 6%, 6%, and 0% for Group 3 (Group 1 vs. Group 2: P < 0.001; Group 1 vs. Group 3: P < 0.001; Group 2 vs. Group 3: P < 0.001, respectively). The most important side effects after the intraarterial procedure were fever (46.2%), abdominal pain (36.6%), chemical cholecystitis (8%), and pancreatitis (1.7%). Death strictly related to treatment occurred in two patients; one had massive bleeding due to ruptured esophageal varices, and the other had a subphrenic abscess of a superficial HCC of the VIII segment. CONCLUSIONS: Transcatheter arterial chemoembolization and IAC were effective and relatively safe, and the authors believe that they have a primary role in treating patients with unresectable HCC larger than 5 cm; iodized oil uptake can be considered a suitable prognostic marker.

Gross pathologic types of hepatocellular carcinoma in Italian patients. Relationship with demographic, environmental, and clinical factors.

BACKGROUND: The prevalence of the different hepatocellular carcinoma (HCC) macroscopic types, and the association between these types and age, gender, blood group, alcohol and coffee intake, smoking habit, hepatitis virus markers, underlying cirrhosis, and cancer histologic type were retrospectively assessed in 416 unselected patients (321 with cirrhosis). METHODS: The gross pathologic types of HCC were assessed by ultrasonography combined, in most cases, with computed tomography and angiography. RESULTS: Solitary HCC was the most common cancer type (54.8%), followed by the multinodular (31%), diffuse (7.7%), and massive (6.5%) types. Cirrhosis and blood group other than O were independent risk factors for multinodular HCC (relative risk [RR] 1.6, P < 0.05; and RR 1.7, P < 0.005, respectively); the absence of cirrhosis and a heavy smoking habit were risk factors for the massive type (RR 4.9, P < 0.001; and RR 3.3, P < 0.01, respectively); and blood group O for the solitary type (RR 1.4, P < 0.001). The prevalence of highly undifferentiated cells increased as the tumor size did, so that grade IV cell atypia was associated with massive size of the carcinoma (P < 0.05). In cirrhotic patients, advanced liver dysfunction was associated with diffuse HCC (P < 0.05). As far as solitary HCC is concerned, the tumor size was greater in noncirrhotic than in cirrhotic patients (7 +/- 0.4 cm versus 4.8 +/- 0.15, P < 0.001). CONCLUSIONS: In Italian patients, HCC presents most frequently as a solitary nodule. The presence or absence of cirrhosis, blood group, and smoking habit can influence the likelihood of developing certain HCC shapes. The probability of harboring highly undifferentiated cells increases as the cancer increases in size. In cirrhosis, advanced liver dysfunction may predispose to diffuse HCC.

[Effects of polyunsaturated phosphatidylcholine in alcoholic liver diseases]. / Effetti della fosfatidilcolina polinsatura nelle epatopatie alcoliche.

The aim of this study is to assess "in vitro" the influence of polyunsaturated phosphatidylcholine on the erythrocyte membrane fluidity in alcoholics (greater than 180 g/die) and control subjects (less than 50 g/die), investigated by the evaluation of fluorescent polarization of DPH. In both groups a significant increase of membrane microviscosity was observed after incubation with 0.04 microM and 0.08 microM of PC compared to baseline values.

In vivo effect of chronic ethanol abuse on membrane alpha 1-glycoprotein of lymphocytes and immune response to various stimulating agents.

Data on the immune status of chronic alcoholic patients are rather conflicting probably due to the interference of liver disease and/or malnutrition on immune function. In order to avoid this kind of interference, peripheral lymphocytes from 12 chronic alcoholic patients in good nutritional status and without heavy liver damage and 15 healthy controls were examined in this study. Lymphocyte functional activity was evaluated by means of response to phytohemagglutinin, calcium ionophore A 23187, and autologous non-T-cells [autologous mixed lymphocyte reaction (AMLR)]. Phenotypical analysis was carried out by the indirect immunofluorescence technique using monoclonal antibodies specific to CD5 (mature T-lymphocytes), CD4 (helper/inducer T-lymphocytes), CD8 (suppressor/cytotoxic T-lymphocytes), glycoproteins, and an immunoglobulin fraction from rabbit directed to membrane alpha 1 acid glycoprotein (AGP) that is involved in T-cell activation process. Our results show significant impairment in AMLR while response to phytohemagglutinin, heterologous non-T-cells and carcinoma ionophore did not differ from controls. No differences were present in circulating T-lymphocytes expressing CD5, CD4, and CD8 on their membrane, whereas AGP-bearing lymphocytes were significantly lower in chronic alcoholics (14.4 +/- 8.6) than in controls (31.9 +/- 8.1; p less than 0.001). These results support the hypothesis of a direct action of alcohol on one of the pathways of lymphocyte activation and the role of the lymphocyte membrane AGP on the AMLR.

Survey of keratinophilic fungi in Alpine marmot (Marmota marmota) burrow soil and in adjoining soils.

Soil samples from 127 marmot (Marmota marmota) burrows were examined for keratinophilic fungi along with 48 soil samples from adjoining areas. The occurrence of keratinophilic fungi (especially Microsporum gypseum) was significantly higher in burrow soil. A review of the literature and our results support the hypothesis that the "animalization" (i.e. the enrichment of soil with hairs, crusts and other organic matters) of the environment may create conditions suitable for the growth of keratinophilic fungi. The presence of keratinophilic fungi in alpine mountain soil was noted for the first time.