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The clinical usefulness of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable. To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype. A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor-nodes-metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity. Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21-400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1-4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001). The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.

Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefit. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefit. A large cohort of consecutive patients with hepatocellular carcinoma (n=1328) from the ITA.LI.CA database (n=2951) were judged as potentially eligible for liver transplantation according to the following criteria: absence of macroscopic vascular invasion or metastases, age 70 years or younger, and absence of relevant extra-hepatic comorbidities. To assess the correlation between BCLC staging and non-liver transplantation survival, we did Cox univariate and multivariate analyses including the following covariates: BCLC stage, year of diagnosis, age, sex, cause of cirrhosis, model for end-stage liver disease score, α-fetoprotein concentrations, and treatment. Liver-transplantation survival benefit for patients was calculated, using Monte Carlo simulation analysis, as the patient's 5-year life expectancy with liver transplantation (estimated by the Metroticket model) minus the 5-year life expectancy without liver transplantation according to BCLC stage. 83 (6%) of 1328 patients had BCLC 0 stage disease, 614 (46%) had BCLC A, 500 (38%) had BCLC B–C, and 131 (10%) had BCLC D. In the Cox non-liver transplantation survival multivariate model, hazard ratios associated with increasing BCLC stages were 1·530 (95% CI 1·107–2·116) for BCLC A versus BCLC 0, 1·572 (1·350–1·830) for BCLC B–C versus BCLC A, and 1·470 (1·164–1·856) for BCLC D versus BCLC B–C. Results of the Monte Carlo simulation analysis confirmed the significant effect of BCLC classification on transplant benefit; in the adjusted model, a median 5-year transplant benefit of 11·19 months (IQR 10·73–11·67) for BCLC 0, 13·49 months (11·51–15·57) for BCLC A, 17·36 months (15·06–19·28) for BCLC B–C, and 28·46 months (26·38–30·34) for BCLC D. Liver transplantation could result in survival benefit for patients with hepatocellular carcinoma and advanced liver cirrhosis (BCLC stage D) and in those with intermediate tumours (BCLC stages B–C), regardless of the nodule number–size criteria (ie, Milan criteria), provided that macroscopic vascular invasion and extra-hepatic disease are absent. None.

Background A consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in \"very early\" and \"early\" stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment. Methods Data were collected in 530 \"very early\" and \"early\" HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P -value < 0.05 was considered statistically significant. Results \"Very early\" HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In \"early\" HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival. Conclusion patients with very early\" HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The \"early\" stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.

Surveillance of cirrhotic patients for early detection of hepatocellular carcinoma, based on ultrasonography and α1-fetoprotein determination, is a recommended practice. However, it has not been proved that this procedure can improve patient survival. We conducted a multicenter retrospective study on 1051 consecutive patients with hepatocellular carcinoma. The criteria for eligibility were presence of underlying cirrhosis, and description of cancer stage and modalities of its diagnosis. Among 821 patients fulfilling these criteria, the tumor was detected during semiannual surveillance in 215 individuals (group 1), during annual surveillance in 155 (group 2), and as a result of symptoms or incidentally in 451 (group 3). Survival of patients under surveillance was corrected for lead time. Cancer stage was similar in groups 1 and 2 and was less advanced than in group 3 (p < 0.001). The frequency of ablative treatments or chemoembolization was similar in groups 1 and 2 and was greater than in group 3 (p < 0.001). Both surveillance programs doubled the prevalence of potential candidates for liver transplantation (68.5% and 62.5%) with respect to group 3 (32.3%, p < 0.001). However, only 15 patients underwent transplantation. In groups 1 and 2, the 5-yr survival was equivalent and was greater than in group 3 (p < 0.001). By segregating patients according to severity of cirrhosis, the benefit was confined to compensated cirrhosis (adjusted relative risk of death for patients under surveillance0.59 [95% CI = 0.45–0.78]). Semiannual and annual surveillance equally improve the survival of cirrhotic patients with hepatocellular carcinoma and greatly increase the amenability rate to liver transplantation. When access to liver transplantation is limited, this benefit is restricted to patients with a good cirrhosis-related prognosis.

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.MethodsWe analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.ResultsMAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).ConclusionsThe prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

ObjectivesThe 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).DesignMulticentre retrospective cohort study and nested case–control study.Patients614 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.ResultsAgeing 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.ConclusionsThe 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.

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE). Alongside the traditional acquired and genetic risk factors for VTE, patients with IBD have pathogenic and clinical peculiarities that are responsible for the increased number of thromboembolic events occurring during their life. A relevant role in modifying this risk in a pro or antithrombotic manner is played by pharmacological therapies and surgery. The availability of several biological agents and small-molecule drugs with different mechanisms of action allows us to also tailor the treatment based on the individual prothrombotic risk to reduce the occurrence of VTE. Available review articles did not provide sufficient and updated knowledge on this topic. Therefore, we assessed the role of each single treatment, including surgery, in modifying the risk of VTE in patients with IBD to provide physicians with recommendations to minimize VTE occurrence. We found that the use of steroids, particularly if prolonged, increased VTE risk, whereas the use of infliximab seemed to reduce such risk. The data relating to the hypothesized prothrombotic risk of tofacitinib were insufficient to draw definitive conclusions. Moreover, surgery has an increased prothrombotic risk. Therefore, implementing measures to prevent VTE, not only with pharmacological prophylaxis but also by reducing patient- and surgery-specific risk factors, is necessary. Our findings confirm the importance of the knowledge of the effect of each single drug or surgery on the overall VTE risk in patients with IBD, even if further data, particularly regarding newer drugs, are needed.

OBJECTIVES: Surveillance of cirrhotic patients for early detection of hepatocellular carcinoma, based on ultrasonography and α 1-fetoprotein determination, is a recommended practice. However, it has not been proved that this procedure can improve patient survival. METHODS: We conducted a multicenter retrospective study on 1051 consecutive patients with hepatocellular carcinoma. The criteria for eligibility were presence of underlying cirrhosis, and description of cancer stage and modalities of its diagnosis. Among 821 patients fulfilling these criteria, the tumor was detected during semiannual surveillance in 215 individuals (group 1), during annual surveillance in 155 (group 2), and as a result of symptoms or incidentally in 451 (group 3). Survival of patients under surveillance was corrected for lead time. RESULTS: Cancer stage was similar in groups 1 and 2 and was less advanced than in group 3 ( p < 0.001). The frequency of ablative treatments or chemoembolization was similar in groups 1 and 2 and was greater than in group 3 ( p < 0.001). Both surveillance programs doubled the prevalence of potential candidates for liver transplantation (68.5% and 62.5%) with respect to group 3 (32.3%, p < 0.001). However, only 15 patients underwent transplantation. In groups 1 and 2, the 5-yr survival was equivalent and was greater than in group 3 ( p < 0.001). By segregating patients according to severity of cirrhosis, the benefit was confined to compensated cirrhosis (adjusted relative risk of death for patients under surveillance: 0.59 [95% CI = 0.45–0.78]). CONCLUSIONS: Semiannual and annual surveillance equally improve the survival of cirrhotic patients with hepatocellular carcinoma and greatly increase the amenability rate to liver transplantation. When access to liver transplantation is limited, this benefit is restricted to patients with a good cirrhosis-related prognosis.

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. 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. 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). 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.

The prevalence of acute diverticulitis (AD) has progressively increased in recent decades, with correspondingly greater morbidity and mortality. The aim of the study is to develop a predictive score to identify patients with the highest risk of complicated AD. The clinical records of 1089 patients referred to the emergency department (ED) over a five-year period were reviewed. In multivariate analysis, male sex (p < 0.001), constipation (p = 0.002), hemoglobin < 11.9 g/dL (p < 0.001), C reactive protein > 80 mg/L (p < 0.001), severe obesity (p = 0.049), and no proton pump inhibitor treatment (p = 0.003) were independently associated with complicated AD. The predictive assessment of complicated (PACO)-diverticulitis (D) score, including these six variables, was applied to the retrospective cohort and then validated prospectively in a cohort including 282 patients. It categorized patients into three risk classes for complicated AD. The PACO-D score showed fair discrimination for complicated AD with an area under the receiver operating characteristic curve of 0.674 and 0.648, in the retrospective and prospective cohorts, respectively. The PACO-D score could be a practical clinical tool to identify patients at highest risk for complicated AD referred to the ED so that appropriate diagnostic and therapeutic resources could be appropriately allocated. Further external validation is needed to confirm these results.