International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

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.

Thermal Ablation for Intrahepatic Cholangiocarcinoma in Cirrhosis: Safety and Efficacy in Non-Surgical Patients.

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.

Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules.

BACKGROUND & AIMS: Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. METHODS: This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. RESULTS: A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. CONCLUSION: These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. LAY SUMMARY: In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.

Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events.

The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child-Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612-622).

Características clínicas del carcinoma hepatocelular en España. Comparación con el período 2008-2009 y análisis de las causas del diagnóstico fuera de cribado. Estudio de 686 casos en 73 centros / Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers

Antecedentes y objetivo: En 2010 publicamos que en España el 53% de los carcinomas hepatocelulares (CHC) se diagnostican fuera de programas de cribado, lo que conlleva una menor supervivencia. El objetivo del presente estudio es evaluar la situación actual y las causas del diagnóstico fuera de cribado. Material y métodos: Registro prospectivo entre el 1 de octubre de 2014 y el 31 de enero de 2015 en 73 centros asistenciales españoles de segundo/tercer nivel. Se registraron las características basales y el primer tratamiento de los tumores primarios hepáticos incidentales de ese período. Resultados: Se incluyeron 720 pacientes: CHC (n=686), colangiocarcinoma intrahepático (n=29), hepatocolangiocarcinoma (n=2), otros (n=3). Los pacientes con CHC fueron varones en el 82% de los casos; media de 67 años; cirrosis en el 87%; etiología: alcohol 35%, VHC 30%, alcohol y VHC 15%, enfermedad hepática por depósito de grasa 6%; estadio tumoral: BCLC-0 11%, A 43%, B 19%, C 16% y D 11%; tratamiento inicial: quimioembolización transarterial (23%), ablación percutánea (22%), tratamiento sintomático (20%), resección (11%), sorafenib (11%). Se diagnosticaron fuera de cribado 356 pacientes (53%). Los motivos principales fueron la ausencia de diagnóstico previo de hepatopatía (76%) y la mala adherencia al cribado (18%). Estos pacientes eran predominantemente varones (p<0,001), de etiología alcohólica (p<0,001), con consumo activo de alcohol (p<0,001) y se diagnosticaron en estadios más avanzados (p<0,001), recibiendo menos tratamientos radicales (p<0,001). Conclusiones: En España, la principal causa del diagnóstico de CHC fuera del cribado es la ausencia de diagnóstico previo de enfermedad hepática, principalmente en varones con consumo de alcohol. La detección de hepatopatía en población asintomática y la mejora de la adherencia al cribado son los principales aspectos para mejorar la detección precoz (AU)

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 (AU)

Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers. / Características clínicas del carcinoma hepatocelular en España. Comparación con el período 2008-2009 y análisis de las causas del diagnóstico fuera de cribado. Estudio de 686 casos en 73 centros.

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.

Nuevos retos en la investigación clínica del carcinoma hepatocelular / New challenges in clinical research on hepatocellular carcinoma

Esta es una revisión actualizada de los distintos aspectos de cribado, diagnóstico precoz y tratamiento del carcinoma hepatocelular destacando especialmente los cambios sucedidos en los últimos dos años y las áreas de mejora que requieren trabajos de investigación clínica. El carcinoma hepatocelular (CHC) constituye actualmente el sexto cáncer más frecuente, con más de 740.000 casos diagnosticados anualmente, y la tercera causa de muerte por neoplasia a nivel mundial (1). Esta neoplasia aparece frecuentemente asociada a la presencia de una enfermedad hepática, siendo una de las principales causas de muerte en los pacientes afectos de cirrosis hepática (2,3). En los últimos años han aparecido novedades importantes en el diagnóstico, estadiaje y tratamiento del CHC que han permitido una mejora en el manejo de esta enfermedad (4-7). A pesar de que estos avances han cambiado completamente la historia natural del CHC, existen aún muchas áreas en las que se precisan avances para poder mejorar. El objetivo de este documento es discutir algunos aspectos controvertidos que a nuestro juicio constituyen retos en la investigación clínica del CHC (AU)

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 (AU)

New challenges in clinical research on hepatocellular carcinoma.

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.

Approach of the patient with a liver mass.

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.

Tratamiento del carcinoma hepatocelular avanzado / Treatment of advanced hepatocellular carcinoma

ResumenEn los últimos años hemos presenciado grandes progresos en el diagnóstico y tratamiento del carcinoma hepatocelular (CHC). Esto ha permitido cambiar la visión nihilista que se tenía de esta enfermedad, convirtiendo el CHC en una de las áreas con investigación básica y clínica más activa en los últimos años. Posiblemente, el mayor avance ha sido la demostración de que sorafenib, un inhibidor multiquinasa con acción antiproliferativa y antiangiogénica, constituye un tratamiento eficaz capaz de aumentar la supervivencia de los pacientes afectos de CHC en estadio avanzado. Este hallazgo ha sido la demostración de que estos fármacos que actúan selectivamente sobre las vías moleculares involucradas en la progresión tumoral pueden ser eficaces en el tratamiento del CHC y abre la puerta a la evaluación de estos agentes moleculares, solos o en combinación, en el CHC.ResumenEl objetivo de este documento es realizar una revisión del tratamiento del CHC en estadio avanzado, con especial énfasis en los diferentes agentes que están actualmente en evaluación(AU)

AbstractIn 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.AbstractThe present article provides a review of the treatment of advanced-stage HCC, with special emphasis on the distinct agents that are currently under evaluation(AU)

[Treatment of advanced hepatocellular carcinoma]. / Tratamiento del carcinoma hepatocelular avanzado.

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.

Gestión de la calidad en el Servicio Cántabro de Salud / Healthcare quality management in the Cantabrian Health Service

Los sistemas de calidad asisten a la transición de un enfoque de calidad del servicio (garantía de calidad) a un enfoque, más estratégico, de calidad de la organización, donde paciente y profesional tienen un papel preeminente. Los modelos de gestión también han evolucionado hacia una corresponsabilidad de gestores y clínicos, para lograr unas organizaciones más eficaces y eficientes. Esta evolución lleva al Servicio Cántabro de Salud a implantar una estrategia corporativa de "calidad en la gestión", con 2 entidades sinérgicas: el Modelo EFQM, como herramienta que ofrece un observatorio para evaluar la organización, compararla con los criterios de excelencia y detectar puntos fuertes y áreas de mejora, y como estrategia que permite orientar la mejora y nutrir los contratos de gestión posteriores. Un reformado Contrato de Gestión, que define anualmente los procesos clave y procesos estratégicos e introduce la dinámica de autoevaluación EFQM. Desaparece el anexo de calidad (AU)