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Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population., Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded., Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE., Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis., Materials and Methods: This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors' unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm., Results: Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6-46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7-20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7-not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication., Conclusions: Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Background and Objective: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs., Material and Methods: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded., Results: A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001)., Conclusions: In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

This is an updated review of screening, early diagnosis and treatment of hepatocellular carcinoma, focusing on the advancements occurred in the last years and highlighting the challenges in clinical research. Hepatocellular carcinoma (HCC) is nowadays the sixth most frequent cancer worldwide with up to 740,000 new cases diagnosed each year, and it is the third most prevalent cause of cancer-related-death worldwide (1). This neoplasm usually appears linked to an underlying liver disease, being one of the most relevant causes of death in patients diagnosed of liver cirrhosis (2,3). In the last years, important advancements in terms of diagnosis, staging and treatment of HCC, improving the management and outcome of the disease, have been made (4-7). Despite the fact that these improvements have absolutely changed natural history of HCC, there are several areas that still need further advancements. The aim of this document is to discuss some controversial aspects, which in our opinion constitute real challenges in clinical research of HCC.

The widespread use of imaging techniques has led to an increased diagnosis of incidental liver tumours. The differential diagnosis is extremely broad since it may range from benign asymptomatic lesions to malignant neoplasms. The correct characterisation of a liver mass has become a diagnostic challenge for most clinicians. They can be divided in two major categories; cystic lesions, usually benign with excellent long-term outcome, and solid lesions, in which malignancy should be excluded. A particular population is those patients with cirrhosis, who have high risk for hepatocellular carcinoma development. Dynamic imaging techniques have a pivotal role in the diagnostic work-up of liver tumours, allowing a confident diagnosis in most cases. If imaging is not conclusive, a biopsy should be requested to obtain a definitive diagnosis.

In the last few years, much progress has been made in the diagnosis and treatment of hepatocellular carcinoma (HCC). Due to these advances, HCC is no longer regarded as a disease with an extremely poor prognosis and has become the focus of some of the most active basic and clinical research in recent years. The most important advance is possibly the demonstration that sorafenib, a multikinase inhibitor with antiproliferative and antiangiogenic properties, is an effective treatment, able to increase survival in patients with advanced-stage HCC. This increased survival has demonstrated that these drugs, which act selectively on the molecular pathways involved in tumoral progression, can be effective in the treatment of HCC and has opened the door to the evaluation of these molecular agents, alone or in combination, in HCC. The present article provides a review of the treatment of advanced-stage HCC, with special emphasis on the distinct agents that are currently under evaluation., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

Early diagnosis of hepatocellular carcinoma (HCC) in nodules smaller than 2 cm detected by screening ultrasounds becomes essential given that, at that stage, no vascular invasion is usually detected and treatment is associated with a high rate of long-term survival. Improvements in imaging techniques in the last few years have allowed a conclusive diagnosis of HCC in these small nodules without invasive procedures. However, a conclusive diagnosis of HCC by imaging is not always possible and, in more than half of cases, biopsy is needed. On the other hand, histological confirmation of HCC in such tiny nodules is very complex, and in most cases impossible because of the limited sample obtained. In addition, serum tumor markers currently available show low accuracy and are useless for early diagnosis. Progress in the knowledge of molecular mechanisms associated with malignant transformation will allow the use of new techniques that will facilitate diagnosis for HCC in very early stages.

In the present work Concanavalin-A-induced T suppressor function has been studied in 28 patients with active alcoholic cirrhosis and 22 patients with inactive cirrhosis. Control subjects were 14 alcoholics without liver disease and 70 healthy individuals with normal liver function tests. Suppressor T cell function was decreased in active alcoholic cirrhosis whereas this change was not observed in inactive cirrhosis nor in alcoholics without liver disease. The suppressor T cell activity of normal individuals was inhibited by heat-inactivated serum pretreatment of patients with alcoholic cirrhosis. The data suggest that there is some kind of serum factor in alcoholic cirrhosis able to affect lymphocyte suppressor activity. No linear correlation could be established between serum level of circulating immune complexes (CIC), determined by solid-phase C1q-binding assay, and suppressor T cell function. There were no differences between sera of alcoholic cirrhosis patients with or without CIC regarding their inhibition of suppressor T cell activity of normal individuals. These results suggest that these serum factors are not related to the presence of CIC.

We analyzed the response to phytohemagglutinin (PHA) of peripheral blood (PBL), intraepithelial (IEL) and lamina propia (LPL) lymphocytes in eight patients with Crohn's disease (CD). We also studied the effect of indomethacin, a prostaglandin synthetase inhibitor, and monocyte depletion on mitogen-induced stimulation of these cells. The blastic stimulation index was significantly lower in PBL and intestinal mucosa lymphocytes of CD than in controls (p less than 0.001). This index increased after addition of indomethacin in PBL and LPL and after monocyte depletion in PBL. The suppressor index on blastic stimulation, obtained when indomethacin had been added to the cultures was higher in PBL and intestinal mucosa lymphocytes of patients with CD than in controls. After monocyte depletion, this suppressor index decreased significantly in PBL and did not change in controls. These data suggest that prostaglandins could be one of the responsible factors for hyporesponsiveness of lymphocytes in CD.

Cellular immunity has been implicated in the pathogenesis of Crohn's disease. In the present work, we have studied T-lymphocytes subsets in peripheral blood and intestinal mucosa of eight patients with active disease, using monoclonal antibodies. Intraepithelial and lamina propia OKT-3 +ve cells were significantly lower than in peripheral blood (p less than 0.001). We have found an increase of B cells and OKT-8 +ve cells in intestinal mucosa with a significant decrease in helper/suppressor ratio. These findings are in accordance with a high suppressor-cytotoxic function in patients with active diseases.

Many findings suggest that the alterations in immune response observed in intestinal inflammatory diseases may play a part in their pathogenesis. This observation led us to study 22 patients with chronic ulcerative colitis, of whom seven were in the acute stage and the other 15 were asymptomatic. The T and B lymphocyte populations were determined as well as the serum levels of immunoglobulins and acid alpha-1-glycoprotein as acute phase reactants. The results were compared with those obtained from a control group of 10 normal individuals. No statistically significant differences were observed in the percentages and absolute values of T and B lymphocytes as compared with the controls. nor in relation to the activity of the lesions. Neither were there any observable variations in the serum concentrations of immunoglobulins. On the other hand, analysis of the acid alpha-1-glycoprotein showed highly significant values as related to the degree of activity of the inflammatory lesion (p less than 0.005). Our results confirmed the value of determining serum acid alpha-1-glycoprotein levels as an index of inflammatory activity. The immunitary parameters under study did not vary in the different stages of the disease.