Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study.

BACKGROUND & AIMS: Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. METHODS: The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21-30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. RESULTS: The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. CONCLUSIONS: This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.

Surveillance and diagnosis of hepatocellular carcinoma: A systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) appears in most of cases in patients with advanced liver disease and is currently the primary cause of death in this population. Surveillance of HCC has been proposed and recommended in clinical guidelines to obtain earlier diagnosis, but it is still controversial and is not accepted worldwide. AIM: To review the actual evidence to support the surveillance programs in patients with cirrhosis as well as the diagnosis procedure. METHODS: Systematic review of recent literature of surveillance (tools, interval, cost-benefit, target population) and the role of imaging diagnosis (radiological non-invasive diagnosis, optimal modality and agents) of HCC. RESULTS: The benefits of surveillance of HCC, mainly with ultrasonography, have been assessed in several prospective and retrospective analysis, although the percentage of patients diagnosed in surveillance programs is still low. Surveillance of HCC permits diagnosis in early stages allows better access to curative treatment and increases life expectancy in patients with cirrhosis. HCC is a tumor with special radiological characteristics in computed tomography and magnetic resonance imaging, which allows highly accurate diagnosis without routine biopsy confirmation. The actual recommendation is to perform biopsy only in indeterminate nodules. CONCLUSION: The evidence supports the recommendation of performing surveillance of HCC in patients with cirrhosis susceptible of treatment, using ultrasonography every 6 mo. The diagnosis evaluation of HCC can be established based on noninvasive imaging criteria in patients with cirrhosis.

The ART-SCORE is not an effective tool for optimizing patient selection for DEB-TACE retreatment. A multicentre Spanish study / El ART-SCORE no es una herramienta eficaz para optimizar la selección de pacientes para el tratamiento con DEB-TACE. Estudio multicéntrico español

Introduction: The appropriate selection of hepatocellular carcinoma (HCC) patients who are eligible for transarterial chemoembolization (TACE) remains a challenge. The ART score has recently been proposed as a method of identifying patients who are eligible or not for a second TACE procedure. Objective: To assess the validity of the Assessment for Retreatment with TACE (ART) score in a cohort of patients treated with drug-eluting bead TACE (DEB-TACE). Secondary objective: to identify clinical determinants associated with overall survival (OS). Method: A retrospective, multicentre study conducted in Spain in patients with HCC having undergone two or more DEB-TACE procedures between January 2009 and December 2014. The clinical characteristics and OS from the day before the second DEB-TACE of patients with a high ART score (ART≥2.5) and a low ART score (ART 0-1) were compared. Risk factors for mortality were identified using Cox's proportional hazards model. Results: Of the 102 patients included, 51 scored 0-1.5 and 51 scored ≥2.5. Hepatitis C was more frequent in patients scoring ≥2.5. Median OS from the day before the second DEB-TACE was 21 months (95% CI, 15-28) in the group scoring 0-1.5, and 17 months (95% CI, 10-25) in the group scoring ≥2.5 (P=0.3562). Platelet count and tumour size, but not the ART score, were independent baseline predictors of OS. Conclusions: The ART score is not suitable for guiding DEB-TACE retreatment according to Spanish clinical practice standards (AU)

Introducción: La selección de los candidatos ideales con carcinoma hepatocelular (CHC) que más se benefician de realizar quimioembolización transarterial (TACE) sigue siendo un reto. Recientemente se ha propuesto el índice ART para seleccionar a aquellos pacientes tributarios o no de realizar un segundo procedimiento de TACE. Objetivo: Evaluar la validez del índice ART en una cohorte tratada con TACE con partículas cargadas (DEB-TACE). Objetivo secundario: identificar los factores clínicos asociados con la supervivencia global. Método: Estudio retrospectivo multicéntrico español en pacientes con CHC tratados con≥2 DEB-TACE entre enero del 2009 y diciembre del 2014. Se compararon las características clínicas y la supervivencia global desde el día previo a la segunda DEB-TACE entre los pacientes con ART alto (ART≥2,5) y bajo (ART 0-1). Los factores de riesgo de mortalidad se identificaron usando el modelo de riesgos proporcionales de Cox. Resultados: De los 102 pacientes incluidos, 51 obtuvieron puntuación de 0-1,5 y 51 ≥ 2,5. La hepatitis C fue más frecuente en pacientes con puntuación ≥ 2,5. La supervivencia global mediana desde el día previo a DEB-TACE-2 fue de 21 meses (IC del 95%, 15-28) y de 17 meses (IC del 95%, 10-25) en los pacientes con ART 0-1,5 y ≥ 2,5, respectivamente (p=0,3562). Los factores basales predictores independientes de supervivencia fueron el recuento de plaquetas y el tamaño del tumor, pero no el índice ART. Conclusiones: El índice ART no es adecuado para guiar el retratamiento con DEB-TACE según los estándares de práctica clínica español (AU)

The ART-SCORE is not an effective tool for optimizing patient selection for DEB-TACE retreatment. A multicentre Spanish study.

INTRODUCTION: The appropriate selection of hepatocellular carcinoma (HCC) patients who are eligible for transarterial chemoembolization (TACE) remains a challenge. The ART score has recently been proposed as a method of identifying patients who are eligible or not for a second TACE procedure. OBJECTIVE: To assess the validity of the Assessment for Retreatment with TACE (ART) score in a cohort of patients treated with drug-eluting bead TACE (DEB-TACE). SECONDARY OBJECTIVE: to identify clinical determinants associated with overall survival (OS). METHOD: A retrospective, multicentre study conducted in Spain in patients with HCC having undergone two or more DEB-TACE procedures between January 2009 and December 2014. The clinical characteristics and OS from the day before the second DEB-TACE of patients with a high ART score (ART≥2.5) and a low ART score (ART 0-1) were compared. Risk factors for mortality were identified using Cox's proportional hazards model. RESULTS: Of the 102 patients included, 51 scored 0-1.5 and 51 scored ≥2.5. Hepatitis C was more frequent in patients scoring ≥2.5. Median OS from the day before the second DEB-TACE was 21 months (95% CI, 15-28) in the group scoring 0-1.5, and 17 months (95% CI, 10-25) in the group scoring ≥2.5 (P=0.3562). Platelet count and tumour size, but not the ART score, were independent baseline predictors of OS. CONCLUSIONS: The ART score is not suitable for guiding DEB-TACE retreatment according to Spanish clinical practice standards.

New advances in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients.

Optimal technique and response of doxorubicin beads in hepatocellular cancer: bead size and dose.

BACKGROUND/AIMS: It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC. METHODS: Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 µm), number of vials, doxorubicin dose, and degree of stasis. RESULTS: In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 µm in patients with portal vein thrombosis (P=0.05). Significant differences were seen for the number of median treatments, median doxorubicin dose, lobar infusion), and degree of complete stasis. The rate of adverse events was higher for larger beads than for smaller beads (28% vs. 16%; P=0.02). CONCLUSIONS: Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.

Acute and chronic hemodynamic changes after propranolol in patients with cirrhosis under primary and secondary prophylaxis of variceal bleeding: a pilot study.

BACKGROUND AND AIM: Prophylactic treatment of variceal bleeding in cirrhotic patients with beta-blockers is effective in only some patients. Our aim was to determine whether the response of the hepatic venous pressure gradient (HVPG) to the intravenous administration of propranolol predicts the response after chronic oral propranolol treatment. PATIENTS AND METHODS: We included prospectively cirrhotic patients with esophageal varices under primary prophylaxis (PP) and secondary prophylaxis (SP). The HVPG was measured at baseline and after a propranolol bolus (0.15 mg/kg intravenous). A patient was considered a good-responder if HVPG decreased to 12 mmHg or 20% from baseline. Patients then received oral propranolol (heart rate titrated). Poor-responders under SP were also included in a variceal band ligation program. After at least 3 months, a second hemodynamic study was conducted. RESULTS: Fifty-six patients were included (36 SP and 20 PP). Response rate was similar (32.1 and 41.9%, P=0.7) and the Pearson's correlation coefficient was 0.61 (P=0.001). In 81.4% patients, the first study predicted the response status of the second. Six patients rebled on follow-up between the studies, all of them were poor responders to intravenous propranolol. CONCLUSION: A single hemodynamic study using intravenous propranolol seems to predict chronic response to propranolol.

Successful endovascular treatment of a large idiopathic azygos arch aneurysm.

Idiopathic azygos vein aneurysms are rare and typically present as incidentally discovered mediastinal masses. Treatment is advisable when the aneurysm enlarges or is complicated by compression symptoms, rupture, or thromboembolic disease. The authors describe successful endovascular treatment of a symptomatic azygos vein aneurysm by means of embolization with coils at the azygos vein close to the dilated arch but respecting the bulb itself. The patient reported symptoms of cough, wheezing, and persistent hiccups, and the procedure resulted in thrombosis of the azygos vein and aneurysm retraction on imaging, accompanied by resolution of symptoms.

Usefulness of surveillance programmes for early diagnosis of hepatocellular carcinoma in clinical practice.

BACKGROUND/AIMS: Surveillance programmes (SPs) for hepatocellular carcinoma (HCC) in patients with cirrhosis intend to diagnose the tumour in its early stages when an effective therapy can be applied. The aims of this study have been to compare the survival of patients with HCC being diagnosed or not in SPs, and to establish a more accurate profile of the best target population. METHODS: From January 1996 to June 2005, 290 patients with HCC were included. The relationship between being diagnosed or not in an SP and survival has been analysed in a univariate analysis. Pretreatment variables found to be significant predictors of survival in univariate analysis were included in a multivariate analysis. RESULTS: The mean survival for patients diagnosed in SPs (27 months, 16.6-37.4) was significantly longer than in patients being diagnosed out of these programmes (6 months, 2.6-9.4) (P=0.001). Child-Pugh class A [beta 1.4, 95% confidence interval (CI) 1.14-1.78; P=0.0002] and being diagnosed in SPs (beta 0.4, 95% CI 0.3-0.6; P=0.0003) became the only independent predictive factors of longer survival. CONCLUSIONS: SPs for HCC allow the detection of small tumours and the application of intention-to-cure therapies, which improves survival. However, these programmes do not improve prognosis in patients with advanced cirrhosis.

Comparison of staging systems to predict survival in hepatocellular carcinoma.

PURPOSE: Some new staging systems in hepatocellular carcinoma (HCC) have been described in the last years. The aim of this study was to compare the survival-predicting capacity of some variables and the prognostic classifications. METHODS: Demographic, clinical, analytical variables and tumour characteristics were collected in a study including 115 patients with HCC. Predictors of survival were identified using the Kaplan-Meier test and the Cox model. Comparison between different staging systems was carried out. RESULTS: The 1-, 2- and 3-year estimated survival was 65%, 45% and 30%, respectively. Child-Pugh score and alpha-fetoprotein level greater than 400 UI/l were independent predictors of survival in the Cox model. Although all systems correctly differentiated between patients regarding survival (Kaplan-Meier, log rank < 0.05 for all), the Barcelona Clinic Liver Cancer (BCLC) showed a better discriminatory ability than the other evaluated scores. In addition, the independent homogenizing ability and stratification value of BCLC was better than that of other systems. On the contrary, model for end-stage liver disease (MELD) showed the worst results. CONCLUSIONS: Child-Pugh score and alpha-fetoprotein levels were the only independent predictors of survival in patients with HCC. Child-Pugh score showed a better prediction value for survival when compared with MELD. BCLC is more accurate than the other prognostic models evaluated in this investigation.