Search

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 65.5years, 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 2.4months (interquartile ranges [IQR], 0.8-3.8), 10.8months (IQR, 4.5-16.9), and 17.5months (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.

[Background & Aims] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic., [Methods] An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave., [Results] Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37)., [Conclusions] The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making., [Lay summary] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Background/aim Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib. Materials and methods SL were prospectively collected in 311 HCC patients who started sorafenib. SL from sorafenib cohort were compared to those from a control patient group selected to match SL type and demographics. HRAS, KRAS and BRAF mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining. Results Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas (n = 4), squamous-cell carcinomas (SCC)(n = 5), basal-cell carcinomas (BCC)(n = 3) and seborrheic keratosis (n = 5). HRAS and KRAS mutations were detected in 4 SL, while no mutations showed in control SL. Nuclear pERK immunostaining was identified in 33.3% of cases versus 5.3% of controls. Most SL (90%) from patients with DAE were proliferative with intense immune infiltration (73%). Conclusions The onset of SL and their molecular profile did not impact negatively on patient's prognosis, but intense proliferation of SL may reflect compensatory activation of MAPK pathway and warrants their close monitoring.

Sorafenib has been widely used to treat unresectable hepatocellular carcinoma (HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well-preserved liver function. We evaluated the overall survival (OS) and tolerance to sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP-A HCC patients. We prospectively studied 130 patients with advanced HCC who started sorafenib between January 2011 and December 2015. Patients were classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients was 10 months. CP-A patients had a median survival rate significantly longer than CP-B patients: 12 months vs. 6 months. The OS found in our group of CP-B patients was 6.5 months, which is higher than that found in most studies done so far. When stratified, our CP-B patients had better OS than ever reported. The dose of the drug was interrupted due to adverse events (AEs) in 38 (29%) of the patients, of whom 20 (30%) were CP-A patients and 18 (28%) were CP-B patients. This real-life cohort of CP-B HCC patients treated with sorafenib had a higher survival than that described in the literature, with a satisfactory safety profile. Despite the high prevalence of severe AEs in CP-B patients, there were fewer treatment interruptions in this group, indicating that Child-Pugh B patients can tolerate treatment and may benefit from sorafenib.

A 50-year-old male underwent liver transplantation due to cryptogenic cirrhosis and was admitted with severe pain in the left leg as well as phlogosis. Amoxicillin/clavulanic acid was prescribed, assuming bullous erysipelas. Among the tests performed, the latex agglutination test for the Cryptococcus sp. antigen was positive, and in both the blood culture and blister culture Cryptococcus sp. was isolated. Daily fluconazole was started. Even though liposomal amphotericin B has been started on the fifth day of hospitalization, the patient progressed to death.

Estudos com sujeitos não humanos mostraram que o estabelecimento de controle inadvertido pela localização pode prejudicar a aquisição de relações condicionais em procedimentos de matching-to-sample (MTS). O objetivo do Experimento 1 foi verificar se esse fenômeno ocorreria com indivíduos com Transtorno do Espectro Autista (TEA) em sessões de treino com MTS sem procedimentos adicionais que pudessem favorecer a aquisição, tais como procedimentos de esvanecimento, dicas e correção. Todos os três participantes mostraram controle pela localização mesmo depois de completar um mínimo de 50 sessões de treino com MTS arbitrário com dois estímulos de comparação. Um segundo estudo foi realizado para verificar se o controle pela localização ocorreria durante o procedimento MTS usando três estímulos comparação. Dezesseis participantes completaram duas sessões de treino. Os resultados deste estudo indicam que 13 desses participantes exibiram controle pela localização no início do treino. Em conjunto, os resultados de ambos os experimentos indicam que o controle pela localização pode prejudicar a aquisição de relações condicionais em indivíduos com TEA, utilizando procedimentos MTS, sem procedimentos adicionais de aprendizagem sem erro, como apresentação ou esvanecimento de dicas.Palavras-chave: controle por localização, matching-to-sample, discriminação condicional, Transtorno do Espectro Autista.

O procedimento matching-to-sample (MTS) tem sido amplamente utilizado para o estabelecimento de relações condicionais emergentes. Nesse procedimento, respostas de escolha são emitidas em diferentes localizações. Tal característica pode favorecer o estabelecimento de um controle inadvertido pela localização. No procedimento go/no-go com estímulos compostos, respostas são emitidas em uma única localização. Com o objetivo de avaliar se relações condicionais emergentes poderiam ser produzidas em crianças com autismo a partir do procedimento go/no-go com estímulos compostos, sem o estabelecimento de controle inadvertido pela localização, foram realizados dois estudos. No Estudo 1, quatro crianças autistas, que apresentaram controle pela localização no procedimento MTS, foram submetidas ao treino das relações AB e BC com o procedimento go/no-go com estímulos compostos no qual, respostas emitidas na presença dos estímulos compostos A1B1, A2B2, B1C1 e B2C2 eram seguidas de reforço e respostas na presença de compostos A1B2, A2B1, B1C2 e B2C1 não eram. Em seguida, os participantes realizaram testes para verificar a emergência de relações que não foram diretamente treinadas (BA, CB, AC e CA). Os resultados mostraram que apenas um dos quatro participantes atingiu critério de aprendizado no treino das relações condicionais e exibiu desempenhos consistentes com a emergência de relações de simetria, transitividade e equivalência após a reapresentação de sessões de treino e testes. Todos os participantes apresentaram o padrão de responder em todos os compostos apresentados. Como decorrência do Estudo 1, foi realizado um segundo estudo que pretendeu verificar se relações condicionais emergentes podem ser estabelecidas em indivíduos com diagnóstico de autismo a partir de um treino com o procedimento go/no-go com estímulos compostos em que a duração dos estímulos compostos aos quais o participante não deveria responder foi gradualmente aumentada com o objetivo de evitar respostas diante deles. Para tanto, outras três crianças diagnosticadas com autismo foram submetidas às mesmas fases experimentais do Estudo 1 dentre as quais algumas diferiam pela manipulação na duração dos compostos. Os resultados mostraram que apenas um dos participantes atingiu critério para realização dos testes de Simetria, mas não exibiu desempenho consistente com a emergência de tais relações. Os outros dois participantes não atingiram critério de aprendizagem na fase de Pré-treino ou de Treino, devido ao estabelecimento do padrão de responder em todos os compostos. Os resultados indicam ainda que o procedimento de aumento gradual na duração dos estímulos favoreceu o aprendizado das relações condicionais para um dos participantes, mas pode gerar o estabelecimento do controle inadvertido pela duração dos estímulos. Os participantes que realizaram o treino com o procedimento MTS não atingiram critério de aprendizagem e exibiram desempenhos indicativos do estabelecimento de controle inadvertido pela localização. Concluiu-se que o procedimento go/no-go com estímulos compostos, embora tenha permitido o estabelecimento de desempenhos emergentes para um dos participantes, pode gerar um padrão de responder em todos os compostos mesmo com o procedimento de aumento gradual na duração dos compostos diante dos quais o participante não deve responder. Matching-to-sample procedure is widely used for establishing emergent conditional relations. However, adventitious control by location, rather than the conditional control, can be established with this procedure in individuals with autism. With the go/no-go procedure with compound stimuli, participants responses are emitted in a single location. Aiming to assess whether emergent conditional relations could be established in autistic children with a go/no-go procedure with compound stimuli, without the establishment adventitious control by location, two studies were conducted. Study 1 sought to verify if the go/no-go procedure with compound stimuli would establish emergent conditional relations in children diagnosed with autism who had control by the location in training with Matching-to-sample procedure. Four autistic children, who showed adventitious control by location in a matching-to-sample task, were submitted to AB and BC training with the go/no-go procedure with compound stimuli. Responses emitted in the presence of A1B1, A2B2, B1C1 and B2C2 compounds were followed by reinforcers and responses emitted in the presence of A1B2, A2B1, B1C2 and B2C1 were not. After that, participants were submitted to tests to verify emergence of conditional relations (BA, CB, AC and CA) that were not directly trained. The results showed that only one of the four participants met the learning criterion in training and exhibited emergent performances in tests only after retraining the baseline relations. In most of the training sessions, all participants responded to all compounds stimuli. These results show that refrain from responding is difficult to be established with the go/no-go procedure in children with autism. Study 2 was conducted to verify if refrain from responding would be established in children with autism if the duration of compounds that should not control responding in training was gradually increased. Other three children diagnosed with autism were submitted to the same procedure as conducted in Study 1, except that during pre-training and training duration of some compounds were gradually increased in some sessions. Results showed that only one participant met the learning criteria in training, but did not showed emergent performances in tests. The other two participants responded to all compounds in most of the sessions. The results indicate that the gradual increase of stimuli duration did not established refrain from responding for some participants and produced adventitious control by stimuli duration for most of them. Although one participant showed emergent performances with the go/no-go procedure with compound stimuli, this procedure can produce responses to all compounds stimuli even when some compounds duration is gradually increased.