Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study. Hepatology 53

In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (ChildPugh class B7) who underwent RFA for 859 HCC 35 mm in diameter (1-2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow-up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person-years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease-free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease-free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1-8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure-related deaths occurred in 1,921 RFA sessions. Estimated 3-and 5-year overall and disease-free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. Conclusion: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences. (HEPATOLOGY 2010;000:000-000.) H epatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide. 1 Most HCC patients have underlying cirrhosis, which complicates management of their cancer and is often the direct cause of death. 2 Internationally endorsed guidelines currently recommend surgical resection for early-stage HCCs in patients with well-preserved liver function. 3,4 When surgery is not possible

Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma

Background & aims: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. Methods: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. Results: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). Conclusions: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival

Wasting in gastrointestinal tract cancers: clinical and etiologic aspects

One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs

Background & aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006-2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006-2010; 2011-2015; 2016-2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions: In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and implications: Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients' eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics

Monofocal hepatocellular carcinoma: how much does size matter?

none88mixedPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐Baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, VeronicaPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, Veronic

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material depriva- tion (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treat- ments progressively decreased as the SMD worsened. Consequently, overall survival was bet- ter in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival