Navigating the landscape of liver cancer management: Study designs in clinical trials and clinical practice.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide and its prognosis is highly heterogeneous, being related not only to tumour burden but also to the severity of underlying chronic liver disease. Moreover, advances in systemic therapies for HCC have increased the complexity of patient management. Randomised-controlled trials represent the gold standard for evidence generation across all areas of medicine and especially in the oncology field, as they allow for unbiased estimates of treatment effect without confounders. Observational studies have many problems that could reduce their internal and external validity. However, large prospective (well-conducted) observational real-world studies can detect rare adverse events or monitor the occurrence of long-term adverse events. How best to harness real world data, which refers to data generated from the routine care of patients, and real-world 'evidence', which is the evidence generated from real-world data, represents an open challenge. In this review article, we aim to provide an overview of the benefits and limitations of different study designs, particularly focusing on randomised-controlled trials and observational studies, to address important and not fully resolved questions in HCC research.

Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection.

BACKGROUND AND AIMS: Assessment of recurrence risk after liver resection (LR) is critical in hepatocellular carcinoma (HCC), particularly with the advent of effective adjuvant therapy. The aim of the study was to analyze the clinical and pathological factors associated with recurrence, aggressive recurrence, and survival after LR. METHOD: Retrospective study in which all single HCC (BCLC-0/A) patients treated with LR between February 2000 and November 2020 were included. The main clinical variables were recorded. Histological features were blindly evaluated by two independent pathologists. Aggressive recurrence was defined as those that exceeded the Milan criteria at 1st recurrence. RESULTS: A total of 218 patients were included (30% BCLC 0 and 70% BCLC A), median (IQR) tumor size of 28 (19-42mm). The prevalence of microvascular invasion and/or satellitosis (mVI/S) was 39%, with a kappa-index between both pathologists of 0.8. After a median follow-up of 49 (23-85) months, 61/218 (28%) patients died, 32/218 (15%) underwent LT, 127 (58%) developed HCC recurrence. The prevalence of aggressive recurrence was 35% (44/127 Milan-out, with 20 cases at advanced stage), and the 5-year survival was 81%. The presence of mVI/S was the only independent predictor of recurrence [HR:1.83 (1.28-2.61), p<0.001], aggressive recurrence [HR:3.31(1.74-6.29), p<0.001] and mortality [HR:2.23(1.27- 3.91), p:0.005]. The presence of MTM was significantly associated with a higher prevalence of mVI/S, Edmonson Steiner grade III-IV, AFP values and vessels that encapsulate tumor clusters, but MTM was not significantly associated with recurrence, aggressive recurrence, or OS. CONCLUSION: The presence of mVI/S was the only independent risk factor for aggressive recurrence and mortality. This has important implications for early-stage patient management, especially in the setting of adjuvant immunotherapy or ab initio LT.

Incidence of Liver and Non-liver Cancers After Hepatitis C Virus Eradication: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. METHODS: This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. RESULTS: The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44). CONCLUSIONS: Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.

Direct-acting antivirals (DAAs) are effective drugs for eradicating hepatitis C virus (HCV). However, concerns about the risk of cancer after HCV eradication remain. Therefore, this study aimed to compare the incidence of cancer between patients treated with anti-HCV therapies in Catalonia (Spain) and properly matched, non-HCV-infected individuals (controls).This study was based on real-world data from the public healthcare system of Catalonia, specifically from patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), or DAA only (DAA). We calculated the incidence and rate ratios of overall cancer and hepatocellular carcinoma of HCV-treated patients.We observed that the rate of overall cancer increased in patients receiving DAA or IFN+DAA, whereas the rate of hepatocellular carcinoma increased in all groups of HCV-treated patients. Of note, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis. Thus, a close monitoring for detection of cancer in patients after HCV eradication seems reasonable, especially in those with cirrhosis.

MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up.

Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.

Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.

BACKGROUND & AIMS: Metallothionein-3 (hMT3) is a structurally unique member of the metallothioneins family of low-mass cysteine-rich proteins. hMT3 has poorly characterized functions, and its importance for hepatocellular carcinoma (HCC) cells has not yet been elucidated. Therefore, we investigated the molecular mechanisms driven by hMT3 with a special emphasis on susceptibility to sorafenib. METHODS: Intrinsically sorafenib-resistant (BCLC-3) and sensitive (Huh7) cells with or without up-regulated hMT3 were examined using cDNA microarray and methods aimed at mitochondrial flux, oxidative status, cell death, and cell cycle. In addition, in ovo/ex ovo chick chorioallantoic membrane (CAM) assays were conducted to determine a role of hMT3 in resistance to sorafenib and associated cancer hallmarks, such as angiogenesis and metastastic spread. Molecular aspects of hMT3-mediated induction of sorafenib-resistant phenotype were delineated using mass-spectrometry-based proteomics. RESULTS: The phenotype of sensitive HCC cells can be remodeled into sorafenib-resistant one via up-regulation of hMT3. hMT3 has a profound effect on mitochondrial respiration, glycolysis, and redox homeostasis. Proteomic analyses revealed a number of hMT3-affected biological pathways, including exocytosis, glycolysis, apoptosis, angiogenesis, and cellular stress, which drive resistance to sorafenib. CONCLUSIONS: hMT3 acts as a multifunctional driver capable of inducing sorafenib-resistant phenotype of HCC cells. Our data suggest that hMT3 and related pathways could serve as possible druggable targets to improve therapeutic outcomes in patients with sorafenib-resistant HCC.

Guía de Práctica Clínica sobre Diagnóstico y Tratamiento del Carcinoma Hepatocelular (actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI, SETH) / Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos anos ˜ han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Espanola ˜ para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Espanola ˜ de Trasplante Hepático, la Sociedad Espanola ˜ de Radiología Médica, la Sociedad Espanola ˜ de Radiología Vascular e Intervencionista y la Sociedad Espanola ˜ de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos anos. ˜ La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE.

Utilidad del perfil molecular en el diagnóstico, pronóstico y tratamiento del carcinoma hepatocelular / Usefulness of the molecular profile in the diagnosis, prognosis and treatment of hepatocellular carcinoma

El carcinoma hepatocelular es una de las causas más importantes de muerte por cáncer y actualmente es la principal causa de muerte en pacientes con cirrosis hepática. Diversas sociedades científicas han compilado guías de práctica clínica basadas en la evidencia y de este modo se dispone de criterios homogéneos para establecer y predecir el pronóstico y orientar la opción de tratamiento más favorable para cada estadio evolutivo. En todos estos aspectos la valoración de los pacientes se basa en instrumentos convencionales: evaluación clínica, determinaciones analíticas y exploración mediante técnicas de imagen. Por el momento, la investigación de perfiles moleculares no ha llevado a que esta información modifique la decisión clínica. Múltiples investigaciones han aportado información relevante de la posible clasificación del tumor en función de anomalías genéticas y de la posible identificación de dianas moleculares, y en el futuro este tipo de datos se incorporará a la práctica convencional de manera similar a lo que ha ocurrido en cáncer de mama, pulmón, colorrectal o melanoma (AU)

Hepatocellular carcinoma is one of the most significant causes of death from cancer and is currently the main cause of death in patients with hepatic cirrhosis. Various scientific societies have compiled evidence-based clinical practice guidelines. Homogeneous criteria are therefore available for establishing and predicting the prognosis and directing the most favorable treatment option for each evolutionary stage. In all of these aspects, patient assessment is based on conventional instruments: clinical assessment, laboratory tests and examinations using imaging techniques. For now, research into molecular profiles has not resulted in this information impacting the clinical decision. Numerous investigations have provided relevant information on the possible classification of tumors based on genetic abnormalities and on the possible identification of molecular targets. In the future, this type of data will be incorporated into conventional practice in a similar manner as has occurred with breast, lung, colorectal and melanoma (AU)

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)

Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH / Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Española para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Española de Trasplante Hepático, la Sociedad Española de Radiología Médica, la Sociedad Española de Radiología Vascular e Intervencionista y la Sociedad Española de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE (AU)

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system (AU)

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)

Tratamiento del carcinoma hepatocelular en España. Análisis de 705 casos en 62 centros / Treatment approach of hepatocellular carcinoma in Spain. Analysis of 705 patients from 62 centers

Fundamento y objetivo: El carcinoma hepatocelular (CHC) es la principal causa de muerte en pacientes con cirrosis, y su situación actual en España no es bien conocida. Por esto, se ha creado un registro nacional para evaluar las características de los pacientes con CHC de novo. Pacientes y método: Entre el 1 de octubre de 2008 y el 31 de enero de 2009, 62 centros de referencia registraron las características demográficas, clínicas y tumorales, la primera opción de tratamiento y la elegibilidad para el trasplante ortotópico hepático (TOH) de los CHC diagnosticados en este tiempo. Resultados: Se contabilizaron 705 casos nuevos de CHC, un 78% en varones; la edad media era de 65 años y un 89% eran cirróticos (el 58% con Child-Pugh clase A, el 42% estaban infectados por el virus de la hepatitis C, el 30% consumía alcohol). Solo 334 casos (47%) se diagnosticaron mediante cribado. El tamaño del nódulo principal y el estadio Barcelona Clinic Liver Cancer fueron significativamente menores en el grupo de cribado que en el resto (p<0,001). La aplicabilidad de los tratamientos radicales (resección y ablación percutánea) fue significativamente mayor (el 47,5 frente al 24,6%; p<0,001), así como la evaluación para el TOH (el 31 frente al 12%; p<0,001). El cribado no fue diferente en función del sexo (p=0,204) ni de la edad (≤50 años; <65; <75 y >75 años) (p=0,171). La quimioembolización fue el tratamiento más indicado: en tumores iniciales (46,4%), en tumores mayores de 5cm (15,7%), en multifocales (37,9%) y como puente al TOH (33%). Conclusión: La mayoría de los CHC en España se diagnostican fuera de los programas de detección precoz y esto limita la posibilidad de aplicación de tratamientos con intención curativa (AU)

Background and objective: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis and its current situation in Spain is not well known. Therefore, a national registry was created to assess the characteristics of patients with de novo HCC. Patients and method: Between 1/10/2008 and 31/1/2009, 62 centers reported the baseline demographic, clinical and tumor characteristics, the first choice of treatment and eligibility for transplantation (OLT) of HCC diagnosed during this time. Results: There were 705 new cases of HCC, 78% men, mean age 65 years, 89% cirrhosis (58% Child-Pugh class A, 42% HCV, 30% alcohol). Only 334 cases (47%) were diagnosed by screening. The size of the main nodule and BCLC stage were significantly lower in the screening group than in the rest (p<0.001). The applicability of radical therapies (resection and percutaneous ablation) was significantly higher (47.5% versus 24.6%, p<0.001) as well as the evaluation for OLT (31% versus 12%, p<0.001). The screening did not differ according to gender (p=0.204) or age (<50 years, <65, <75, >75 years) (p=0.171). Chemoembolization was the most common treatment: initial tumors (46.4%), tumors >5cm (15.7%), multifocal HCC (37.9%) and as a bridge to OLT (33%). Conclusion: The majority of HCC patients are diagnosed in Spain out of early detection programs, and this limits the chance for early diagnosis and effective therapy (AU)

Diagnóstico y tratamiento del carcinoma hepatocelular / Diagnosis and treatment of hepatocellular carcinoma

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Ecografía con contraste de segunda generación (SonoVue) en la valoración del tratamiento percutáneo del carcinoma hepatocelular. Comparación con la TC multifásica / Second-generation ultrasound contrast agents (SonoVue) in the evaluation of percutaneous treatment of hepatocellular carcinoma: comparison with multiphase CT

Objetivo: Determinar la eficacia de la ecografía con contraste (EC) de segunda generación en la valoración del tratamiento percutáneo del carcinoma hepatocelular (CHC), tanto de una forma precoz (< 24 h), como al mes después del tratamiento. Asimismo, se analiza la utilidad de la tomografía computarizada (TC) en la valoración inmediata después del tratamiento, hecho cuestionado hasta el momento. Material y métodos: Se han incluido en el estudio 30 pacientes afectados de CHC de pequeño tamaño, no tributarios de resección quirúrgica, tratados mediante alcoholización o radiofrecuencia. Antes del tratamiento, pasadas menos de 24 h de tratamiento, y 1 mes postratamiento efectuaron una EC (con software especial de contrastes y bajo índice mecánico) y una TC multifásica. Se compararon los hallazgos de las exploraciones a las 24 h (EC y TC) y los de la EC 1 mes postratamiento con los de la TC al mes (gold standar).Resultados: Valorado con TC al mes, el tratamiento percutáneo obtuvo una respuesta completa en 22 de los 30 pacientes. La EC y la TC realizadas antes de las 24 h postratamiento obtuvieron, respectivamente, los siguientes resultados: sensibilidad (S), 12,5 (28,5%); especificidad (E), 95,4 (95,4%); rentabilidad diagnóstica (RD), 73,3 (79,3%); valor predictivo positivo (VPP), 50 (66%); valor predictivo negativo (VPN), 75 (80,6%). Los resultados de la EC realizada al mes postratamiento fueron: S, 87,5%; E, 95,4%; RD, 93,3%; VPP, 87,5%, y VPN, 95,4%.Conclusión: La EC y la TC realizadas antes de las 24 h postratamiento tienen escasa utilidad para detectar la persistencia tumoral valorada de forma inmediata postratamiento. Dados los buenos resultados de la EC realizada al mes postratamiento, esta exploración podría sustituir a la TC para valorar la necesidad de nuevos tratamientos

Objective: to determine the efficacy of ultrasonography using second-generation contrast agents (CUS) in the evaluation of percutaneous treatment of hepatocellular carcinoma (HCC), both for early evaluation (< 24 hours) and for evaluation one month after treatment. Likewise, the usefulness of computerized tomography (CT) for evaluation immediately after treatment, to date controversial, is assessed. Material and methods: A total of 30 patients with small-sized HCC without indications for surgery treated by radiofrequency ablation or alcohol injection were included in the study. All patients underwent CUS (using special contrast software and low mechanical index) and multiphase CT prior to treatment, within 24 hours of treatment, and one month after treatment. CT findings one month after treatment were taken as the gold standard. Findings at CUS and CT examination within 24 hours of treatment and CUS findings at one month were compared with the gold standard. Results: CT performed one month after percutaneous treatment found a complete response in 22 of the 30 patients. Comparison of CUS and CT findings within 24 hours of treatment with the gold standard yielded the following results: (CUS/CT) Sensitivity (S) = 12.5/28.5%, specificity (SP) = 95.4/95.4%, diagnostic yield (DY) = 73.3/79.3%, positive predictive value (PPV) = 50/66%, negative predictive value (NPV) = 75/80.6%. The results of CUS performed one month after treatment were : S = 87.5%, SP = 95.4%, DY = 93.3%, PPV = 87.5% and NPV = 95.4%.Conclusion: CUS and CT performed within 24 hours of treatment are of little use in detecting tumor persistence immediately after treatment. Given the good results obtained using CUS one month after treatment, this technique could substitute CT to assess the need for retreatment