C. Pozzan

Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC).

The serpin squamous cell carcinoma antigen complexed with IgM (SCCA‐IgM) has been reported as a promising serological marker for hepatocellular carcinoma (HCC). We aimed to further evaluate SCCA‐IgM diagnostic accuracy and to determine its prognostic role.

BCLC stage B hepatocellular carcinoma and transcatheter arterial chemoembolization: a 20-year survey by the Italian Liver Cancer group

Significant proportion of Hepatocellular Carcinoma (HCC) cases are diagnosed in stage B of Barcelona Clinic Liver Cancer (BCLC) algorithm, in which the standard of care is Transcatheter Arterial ChemoEmbolization (TACE). We aimed to ascertain adherence to current guidelines, survival and prognostic factors in BCLC stage B patients.

Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma.

OBJECTIVES:The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group.METHODS:We assessed the prognosis of 269 untreated HCC patients observed in the period 1987–2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compared the survival of the various substages.RESULTS:Median survival progressively decreased from stage B1 (n=65, 24.2%: 25 months) through stages B2 (n=105, 39.0%: 16 months) and B3 (n=22, 8.2%: 9 months), to stage B4 (n=77, 28.6%: 5 months; P<0.0001). Moreover, we observed a significantly different survival between contiguous stages (B1 vs. B2, P=0.0002; B2 vs. B3, P<0.0001; B3 vs. B4, P=0.0219). In multivariate analysis, the BCLC B subclassification (P<0.0001), MELD score (P=0.0013), and platelet count (P=0.0252) were independent predictors of survival.CONCLUSIONS:The subclassification of the intermediate-stage HCC predicts the prognosis of patients with untreated HCC. The prognostic figures identified in this study may be used as a benchmark to assess the efficacy of therapeutic intervention in the various BCLC B substages, whereas it remains to be established whether incorporation of the MELD score might improve the prognosis of treated patients.

Years of life that could be saved from prevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved.

Rise and fall of HCV‐related hepatocellular carcinoma in Italy: a long‐term survey from the ITA.LI.CA centres

Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV‐related HCC (HCV‐HCC) in a wide time range in Italy.

Capecitabine in advanced hepatocellular carcinoma.

Since sorafenib was demonstrated to be active as a systemic reatment in hepatocellular carcinoma (HCC) [1,2], no new drug ith molecular target has shown any efficacy in patients proressing under sorafenib or intolerant to its administration. We herefore read with great interest the report by Granito in DLD 3] on metronomic capecitabine in HCC after sorafenib failure. tandard chemotherapy has never been proved effective in HCC [4], ince HCC cells actively express the MDR proteins [5], and since the umor is associated with cirrhosis, that limits the drug tolerability. etronomic chemotherapy, with drug administration at low-dose nd continuous schedule, may indeed change the scenario in HCC nd Granito’s data indicate the safety and the potential anti-tumor ctivity of metronomic capecitabine. It can be of interest to briefly report our data, in support of hose reported by Granito since we administered metronomic apecitabine (1000 mg/day) in 25 prospectively recruited patients 16 males, 9 females) with a mean age of 67.5 (range 45–90). nformed consent was obtained from each patient and the study rotocol conforms to the ethical guidelines of the 1975 Helsinki eclaration (6th revision, 2008) and was approved by the instituion’s human research committee. Twenty-three patients had HCC ver cirrhosis (92%) and the disease was HCV-correlated in 11 cases 44%), HBV-related in 2 (8%), HBV/HCV in 1 (4%), to HCV/HBV with lcohol abuse in 3 (12%), alcoholic liver cirrhosis in 3 (12%), dysetabolic, primitive biliary cholangitis and cryptogenic in 1 each 12%). Most frequent co-morbidities were type II diabetes (32%) and ypertension (36%). Previous tumors were recorded in 4 patients 16%): 1 lung, 1 breast and 1 papillary thyroid cancer (completely ured) and 1 multiple myeloma (under clinical observation). Clinially, the patients were subgrouped as reported in Table 1. Twenty-two (88%) had a multifocal disease, 11 of these had also ortal neoplastic thrombosis and 8 had extrahepatic disease. Of the emaining three patients, who all had 2 lesions, 1 had portal thromosis and metastases and 2 were ECOG 1 and had progressed under

Squamous Cellular Carcinoma Antigen Serum Determination as a Biomarker of Barrett Esophagus and Esophageal Cancer: A Phase III Study

Goal: To evaluate the potential role of the determination of the immunocomplexed form of squamous cell carcinoma antigen [SCCA-immunoglobulin (Ig)M] for the screening of Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). Background: The cost-effectiveness of surveillance in BE is still debated and the use of biomarkers in screening and surveillance still not recommended. No information is available regarding SCCA-IgM determination in BE. Study: SCCA-IgM levels were determined (enzyme-linked immunosorbent assay) in 231 patients prospectively recruited, 71 with BE, 53 with EAC, and 107 controls, including 42 blood donors and 65 patients with gastroesophageal reflux. SCCA-IgM cutoffs between BE/EAC and controls and for BE “at risk” versus short nondysplastic BE were calculated by receiver operating characteristic curves. Immunostaining for SCCA-IgM was obtained in a subgroup of patients. Results: Median SCCA-IgM values were significantly higher in BE and EAC than in controls (P=0.0001). Patients with SCCA-IgM levels above the cutoff had a 33 times higher relative risk of harboring BE or EAC (P=0.0001). Patients “at risk,” with long or dysplastic BE had SCCA-IgM levels significantly higher than those with short nondysplastic BE (P=0.035) and patients with SCCA-IgM above the cutoff had a 8 times higher relative risk of having BE “at risk.” SCCA was expressed in Barrett mucosa but not in cardiac metaplasia. Conclusions: Serum SCCA-IgM determination allows the identification of patients at risk for BE/EAC and the stratification of BE patients in subgroups with different cancer risk. Because of the still limited number of controls, large, prospective studies are required to confirm this evidence.

1071 CONVENTIONAL AND DC-Beads-MEDIATED TRANSARTERIAL CHEMOEMBOLIZATION: ANY DIFFERENCE IN NEOANGIOGENESIS?

this study was to define markers of cirrhosis and HCC using SR-FTIR microspectroscopy. Methods: The study has been focused on liver samples obtained from surgical specimens including normal livers (n = 7) and patients with HCC on cirrhosis from alcohol (n = 6) or HCV (n =6) aetiology. Frozen tissue sections stained with H&E were performed for histological examination. Adjacent tissue sections were investigated using SR-FTIR microspectroscopy experiments. The variance was addressed by multivariate statistical methods such as principal component analysis (PCA). Results: We strived firstly to discriminate the spectroscopic profile of healthy and pathological liver. The infrared spectral pattern of cirrhosis or HCC exhibited significant differences in the composition of lipids, proteins and sugars when compared with tissue from normal liver. Then, we investigated the spectral differences that discriminate tumor tissue from cirrhosis. Detailed analysis demonstrates a frequency shift in proteins suggesting changes in the proteome but the major discrimination was observed on sugars. Furthermore, SR-FTIR experiments followed by PCA analysis allowed the discrimination between hyperplastic and dysplastic cirrhotic nodules on sugars. Infrared signatures of dysplastic nodules superimposed with HCC suggesting that FTIR microspectroscopy allows diagnosing tissue changes associated with early stages of cancer. Finally, experiments were performed on a conventional IR microscope using an internal IR source. Despite the lower spatial resolution of such a device, it was possible to reproduce the results obtained in the exploratory phase using synchrotron radiations. Conclusions: Infrared microspectroscopy allows discriminating various grades of cirrhosis and HCC. This approach that can be easily implemented into hospitals may open new avenues for clinical applications and personalized medicine.

244 DIAGNOSTIC AND PROGNOSTIC ROLE OF SCCA-IGM IN HEPATOCELLULAR CARCINOMA (HCC)

generation of reactive oxygen species (ROS), phosphorylation/ inactivation of GSK-3b as well as phosphorylation of PI-3K, ERK1/2, JNK1/2, p38MAPK and STAT3. Invasiveness of cancer cells was prevented either by inhibiting ERK1/2, PI3K or JNK1/2 as well as by preventing ROS generation. Finally, OSM was expressed “in vivo” in tumor cells of HCC in areas also positive for hypoxia-related antigens. Conclusions: OSM, which is expressed in human HCC cells and peritumoral cirrhotic tissue, can induce EMT in human hepatic cancer cell lines and stimulate their increased invasiveness through the involvement of redox-dependent activation of EMT-related critical kinases and transcription factors.