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Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC. [ABSTRACT FROM AUTHOR]

Objectives The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (≥70 years) and younger patients (<70 years). Design Multicentre retrospective cohort study and nested caseecontrol study. Patients 614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score. Results Ageing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis. Conclusions The overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups. [ABSTRACT FROM AUTHOR]

Background & Aims: Patients with cryptogenic cirrhosis (CC) can develop hepatocellular carcinoma (HCC), although the clinical characteristics of HCC in these patients have not been completely defined. We aimed to characterize the clinical features of patients diagnosed with HCC after CC during a 15-year period (1992–2006). Methods: The clinical characteristics of 45 consecutive CC patients with HCC were analyzed, along with modality of diagnosis, tumor stage, treatment, survival, and causes of death. Data were compared with those of 426 consecutive patients with HCC and only hepatitis C virus (HCV) infection, diagnosed during the same period at the Italian Liver Cancer group centers. Results: HCC patients with CC had similar impairments in liver function as patients with HCV infection (Child–Pugh class A: 53% vs 65%; P = .141). However, the HCC patients with CC had lower aminotransferase levels (P < .001) and higher platelet counts (P < .001). HCC was significantly less likely to be diagnosed during surveillance in CC patients (29% vs 64%; P < .0001). Patients with CC had a significantly greater prevalence of advanced HCC stage, according to Milano criteria (69% vs 41%; P < .0005), larger HCC size (4.9 vs 3.0 cm; P = .0001), lower amenability to any treatment (27% vs 42%; P = .036), and shorter survival times (P = .009, log-rank test) compared with HCV patients. Causes of death were similar in the 2 groups. Conclusions: Compared with HCV patients, HCC in CC patients often is diagnosed at an advanced stage, probably owing to lack of surveillance; this leads to limited treatment options and shorter survival times. [Copyright &y& Elsevier]

OBJECTIVES: Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance. METHODS: We selected 468 Child-Pugh class B and 140 class C patients from the ITA.LI.CA database, including 1,834 HCC patients diagnosed from January 1987 to December 2004. HCC was detected in 252 patients during surveillance (semiannual 172, annual 80 patients; group 1) and in 356 patients outside surveillance ( group 2). Survival of surveyed patients was corrected for the estimated lead time. RESULTS: Child-Pugh class B: cancer stage ( P < 0.001) and treatment distribution ( P < 0.001) were better in group 1 than in group 2. The median (95% CI) survivals were 17.1 (13.5–20.6) versus 12.0 (9.4–14.6) months and the survival rates at 1, 3, and 5 yr were 60.4% versus 49.2%, 26.1% versus 16.1%, and 10.7% versus 4.3%, respectively ( P= 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage ( P= 0.001) and treatment distribution ( P= 0.021) were better in group 1 than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1–12.1) versus 6.0 (4.1–7.9) months ( P= 0.740). CONCLUSIONS: These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments. [ABSTRACT FROM AUTHOR]

Background & Aims Ultrasound surveillance does not detect early stage hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the reasons for this have not been well studied. We assessed the rate at which ultrasound fails to detect early stage HCCs and factors that affect its performance. Methods We collected information on 1170 consecutive patients included in the Italian Liver Cancer (ITA.LI.CA) database who had Child–Pugh A or B cirrhosis and were diagnosed with HCC during semiannual or annual ultrasound surveillance, from January 1987 through December 2008. Etiologies included hepatitis C virus infection (59.3%), alcohol abuse (11.3%), hepatitis B virus infection (9%), a combination of factors (15.6%), and other factors (4.7%). Surveillance was considered to be a failure when patients were diagnosed with HCC at a stage beyond the Milan criteria (1 nodule ≤5 cm or ≤3 nodules each ≤3 cm). Results HCC was found beyond Milan criteria in 34.3% of surveilled patients (32.2% during semi-annual surveillance and 41.3% during annual surveillance; P < .01). Nearly half of surveillance failures were associated with at least one indicator of aggressive HCC (levels of AFP >1000 ng/mL, infiltrating tumors, or vascular invasion and metastases). Semiannual surveillance, female sex, Child–Pugh class A, and α-fetoprotein levels of 200 ng/mL or less were associated independently with successful ultrasound screening for HCC. Conclusions Based on our analysis of surveillance for HCC in patients with cirrhosis, the efficacy of ultrasound-based screening is acceptable. Ultrasound was least effective in identifying aggressive HCC, and at surveillance intervals of more than 6 months. [ABSTRACT FROM AUTHOR]

Background & Aims: It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined. Methods: A Markov model was built to compare CE of these two strategies, considering literature results and treatment modalities of 918 cirrhotic patients from the Italian Liver Cancer (ITA.LI.CA) database. Results: Results from the Markov model suggest that, compared to annual surveillance, semi-annual surveillance leads to a gain in quality-adjusted life expectancy, in an unselected cirrhotic population, of 1.35 quality-adjusted life-months (QALMs) over 10years since surveillance start in compensated patients, and of 0.73 QALMs in decompensated patients. Semi-annual surveillance was more cost-effective in compensated than in decompensated cirrhosis, with an incremental CE ratio (ICER) of 1997 and 3814€/QALM, respectively. In compensated cirrhosis, semi-annual surveillance was more cost-effective than the annual program when the annual HCC incidence was ⩾3.2% and the relative survival gain after cancer diagnosis was ⩾20% with respect to the annual program. In decompensated cirrhosis, semi-annual surveillance was cost-effective in patients amenable to liver transplantation. In both groups, CE of semi-annual surveillance improved with the increase of annual incidence and the survival benefit obtainable with HCC treatment. Conclusions: Both surveillance strategies for HCC in cirrhotic patients can be recommended, according to the individual risk profile for HCC occurrence and the expected survival gain obtainable after tumor diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Background & aims: This study investigates whether the aetiologic changes in liver disease and the improved management of hepatocellular carcinoma (HCC) have modified the clinical scenario of this tumour over the last 20years in Italy. Methods: Retrospective study based on the analysis of the ITA.LI.CA (Italian Liver Cancer) database including 3027 HCC patients managed in 11 centres. Patients were divided into 3 groups according to the period of HCC diagnosis: 1987–1996 (year of the “Milano criteria” publication), 1997–2001 (year of release of the EASL guidelines for HCC), and 2002–2008. Results: The significant changes were: (1) progressive patient ageing; (2) increasing prevalence of HCV infection until 2001, with a subsequent decrease, when the alcoholic aetiology increased; (3) liver function improvement, until 2001; (4) increasing “incidental” at the expense of “symptomatic” diagnoses, until 2001; (5) unchanged prevalence of tumours diagnosed during surveillance (around 50%), with an increasing use of the 6-month schedule; (6) favourable HCC “stage migration”, until 2001; (7) increasing use of percutaneous ablation; (8) improving survival, until 2001. Conclusions: Over the last 20years, several aetiologic and clinical features regarding HCC have changed. The survival improvement observed until 2001 was due to an increasing number of tumours diagnosed in early stages and in a background of compensated cirrhosis, and a growing and better use of locoregional treatments. However, the prevalence of early cancers and survival did not increase further in the last years, a result inciting national policies aimed at implementing surveillance programmes for at risk patients. [ABSTRACT FROM AUTHOR]

Background & Aims: The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 or 12month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance. Methods: We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.LI.CA centers. HCC was detected in 510 patients submitted to semiannual surveillance (Group 1) and in 139 submitted to annual surveillance (Group 2). In Group 1 the survival was presented as observed and corrected for the lead time. Results: The cancer stage was less severe in Group 1 than in Group 2 (p <0.001), with more single tiny (⩽2cm) and less advanced tumors. Treatment applicability was improved by the semiannual program (p =0.020). The median observed survival was 45months (95% CI 40.0–50.0) in Group 1 and 30months (95% CI 24.0–36.0) in Group 2 (p =0.001). The median corrected survival of Group 1 was 40.3months (95% CI 34.9–45.7) (p =0.028 with respect to the observed survival of Group 2). Age, platelet count, α-fetoprotein, Child-Pugh class, cancer stage, and hepatocellular carcinoma treatment were independent prognostic factors. Conclusions: Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis. [Copyright &y& Elsevier]