Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study

Introduction: despite advances in imaging diagnosticmodalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation.Material and methods: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival.Results: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. Conclusion: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group. (AU)

Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study.

INTRODUCTION: despite advances in imaging diagnostic modalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation. MATERIAL AND METHODS: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival. RESULTS: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. CONCLUSION: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group.

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study.

BACKGROUND AND AIMS: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. MATERIAL AND METHODS: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. RESULTS: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. CONCLUSIONS: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.

Metástasis adrenal como presentación de un hepatocarcinoma / Adrenal metastasis as presentation of hepatocellular carcinoma

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High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

BACKGROUND AND AIMS: Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. METHODS: This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. RESULTS: Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. CONCLUSIONS: In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Hepatitis fulminante por herpes virus tipo 6 en adultos inmunocompetentes / Fulminant hepatitis caused by herpes virus 6 in immunocompetent adults

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Transarterial chemoembolisation in intermediate-stage hepatocellular carcinoma. Survey on clinical practice in hospitals in the Madrid Region.

BACKGROUND: Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application. MATERIAL AND METHODS: A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C). RESULTS: Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria. CONCLUSION: Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.

Safety and efficacy of large balloon sphincteroplasty in a third care hospital.

BACKGROUND AND AIMS: large balloon sphincteroplasty (LBS) associated with sphincterotomy (ES) has gained acceptance as a useful tool in extracting difficult bile duct stones. Our purpose was to evaluate the efficacy and safety of LBS with balloons > or = 10 mm in clinical practice setting. PATIENTS AND METHODS: unicentre prospective study in a tertiary care hospital. All patients who underwent LBS associated with ES between July 2007 and March 2011 were included prospectively in a database recording clinical aspects, procedure data, outcome and complications.Success is the main outcome defined as complete stone removal documented by absence of any filling defect during a final occlusion cholangiogram and absence of clinical or radiological findings after the ERCP consistent with remaining stones. Complications as pancreatitis, cholangitis, post-ERCP bleeding, perforation and others were also measured. RESULTS: one hundred twenty procedures were made in 109 patients with balloons ranging from 10 to 20 mm. Success rate was 91% in the first attempt and 96.7% after two procedures. Mechanical lithotripsy was only needed in one case (0.8%). Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk patients. CONCLUSION: large balloon sphincteroplasty associated to sphincterotomy in clinical practice is a very effective and safe technique.

Endoscopic management of esophageal varices.

The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary prophylaxis.

Dilatación con balón asociada a esfinterotomía, evaluación de eficacia y seguridad en un hospital terciario / Safety and efficacy of large balloon sphincteroplasty in a third care hospital

Introducción y objetivos: la dilatación con balón de gran tamaño asociada a esfinterotomía es un recurso cada vez más utilizado en la extracción de coledocolitiasis de gran tamaño. El objetivo de este estudio es evaluar la eficacia y seguridad de la dilatación con balones mayores de 10 mm en un entorno de práctica clínica habitual. Pacientes y métodos: estudio prospectivo en un hospital terciario. Todos los pacientes en los que se realizó dilatación con balón mayor de 10 mm asociado a esfinterotomía entre julio de 2007 y marzo de 2011 se incluyeron prospectivamente en una base de datos incluyendo aspectos clínicos, del procedimiento, resultados y complicaciones. El éxito del procedimiento se definió como la extracción de todos los cálculos presentes documentada como ausencia de defectos de repleción en la colangiografía final y la ausencia de signos clínicos y/o radiológicos tras la CPRE sugestivos de persistencia de litiasis. La presencia de pancreatitis, colangitis, perforación y hemorragia post-CPRE también se documentó. Resultados: se realizaron 120 procedimientos en 109 pacientes diferentes, con balones entre 10 y 20 mm de diámetro. La tasa de éxito fue del 91% en el primer intento y del 96,7% tras dos procedimientos. La litotricia mecánica solo se necesitó en un caso (0,8%). La tasa de complicaciones fue del 4,2% debido a cinco casos de hemorragia post-CPRE en pacientes de alto riesgo de sangrado. Conclusión: la dilatación con balón asociada a esfinterotomía en condiciones de práctica clínica habitual muestra una tasa de éxito excelente con un índice de complicaciones reducido(AU)

Background and aims: large balloon sphincteroplasty (LBS) associated with sphincterotomy (ES) has gained acceptance as a useful tool in extracting difficult bile duct stones. Our purpose was to evaluate the efficacy and safety of LBS with balloons >=10 mm in clinical practice setting. Patients and methods: unicentre prospective study in a tertiary care hospital. All patients who underwent LBS associated with ES between July 2007 and March 2011 were included prospectively in a database recording clinical aspects, procedure data, outcome and complications. Success is the main outcome defined as complete stone removal documented by absence of any filling defect during a final occlusion cholangiogram and absence of clinical or radiological findings after the ERCP consistent with remaining stones. Complications as pancreatitis, cholangitis, post-ERCP bleeding, perforation and others were also measured. Results: one hundred twenty procedures were made in 109 patients with balloons ranging from 10 to 20 mm. Success rate was 91% in the first attempt and 96.7% after two procedures. Mechanical lithotripsy was only needed in one case (0.8%). Complication rate was 4.2% due to five cases of post-ERCP bleeding in high risk patients. Conclusion: large balloon sphincteroplasty associated to sphincterotomy in clinical practice is a very effective and safe technique(AU)

Uso de gadolinio como contraste en CPRE en pacientes con reacciones adversas a contrastes yodados / Use of gadolinium as contrast agent in endoscopic retrograde cholangiopancreatography in patients with iodine allergy

Introducción Para la realización de colangiopancreatografía retrógrada endoscópica (CPRE) es necesario el uso de contrastes radiológicos, utilizándose habitualmente contrastes yodados. La pauta de actuación ante pacientes que han sufrido reacciones adversas a contrastes yodados y que van a recibir una CPRE es controvertida. Objetivo Evaluar la seguridad y eficacia de un contraste basado en gadolinio en pacientes con reacciones alérgicas previas a contrastes yodados durante la realización de CPRE. Material y métodos Se utilizó gadobutrol como agente de contraste, un compuesto basado en el gadolinio, sin utilizar profilaxis previa. Se realizaron 13 procedimientos en 11 pacientes con antecedentes de reacciones adversas previas a contrastes yodados. Resultados Las CPRE fueron completadas satisfactoriamente en todos los casos, obteniéndose 13 colangiogramas y un pancreatograma. La calidad de imagen obtenida fue buena, equiparable a la obtenida con los contrastes yodados utilizados habitualmente, y permitiendo realizar el diagnóstico y la terapéutica endoscópica sin suponer una limitación. No se encontraron efectos adversos relacionados con el contraste y tampoco complicaciones post-CPRE. Conclusiones El gadobutrol, un contraste basado en gadolinio, es una alternativa segura y eficaz en pacientes alérgicos a contrastes yodados(AU)

Introduction Radiologic contrasts are required during endoscopic retrograde cholangiopancreatography (ERCP). The most frequently used are iodine-based contrast media. Controversy still surrounds the optimal strategy in patients with previous adverse reactions to iodine contrasts that need to undergo an ERCP. Objective To evaluate the safety and efficacy of a gadolinium-derived contrast medium in patients with previous reactions to iodine-derived agents during ERCP. Material and methods Thirteen ERCP were performed in 11 patients with well-established adverse reactions to iodine compounds. ERCP was carried out with gadobutrol, a non-ionic gadolinium compound and without prophylaxis. Results In all patients, ERCP were satisfactorily completed. Thirteen cholangiograms and one pancreatogram were obtained. All procedures were technically successful, allowing diagnosis and endotherapy. The quality of the images was good, similar to those obtained with standard contrast media, and did not represent a limitation. No contrast-related adverse events were observed, and there were no post-ERCP complications. Conclusions Gadolinium-derived agents are a safe and effective alternative in iodine-allergic patients (AU)

[Use of gadolinium as contrast agent in endoscopic retrograde cholangiopancreatography in patients with iodine allergy]. / Uso de gadolinio como contraste en CPRE en pacientes con reacciones adversas a contrastes yodados.

INTRODUCTION: Radiologic contrasts are required during endoscopic retrograde cholangiopancreatography (ERCP). The most frequently used are iodine-based contrast media. Controversy still surrounds the optimal strategy in patients with previous adverse reactions to iodine contrasts that need to undergo an ERCP. OBJECTIVE: To evaluate the safety and efficacy of a gadolinium-derived contrast medium in patients with previous reactions to iodine-derived agents during ERCP. MATERIAL AND METHODS: Thirteen ERCP were performed in 11 patients with well-established adverse reactions to iodine compounds. ERCP was carried out with gadobutrol, a non-ionic gadolinium compound and without prophylaxis. RESULTS: In all patients, ERCP were satisfactorily completed. Thirteen cholangiograms and one pancreatogram were obtained. All procedures were technically successful, allowing diagnosis and endotherapy. The quality of the images was good, similar to those obtained with standard contrast media, and did not represent a limitation. No contrast-related adverse events were observed, and there were no post-ERCP complications. CONCLUSIONS: Gadolinium-derived agents are a safe and effective alternative in iodine-allergic patients.

Creación de ascitis artificial para el tratamiento mediante radiofrecuencia percutánea del hepatocarcinoma cercano al diafragma / Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma adjacent to the diaphragm

La cirugía constituye la primera línea de tratamiento curativo en el hepatocarcinoma (CHC). Sin embargo, una gran mayoría no se puede beneficiar de la misma debido al avanzado estadio tumoral, disfunción hepática severa o mala condición clínica. Por ello, se han introducido varias técnicas de ablación guiadas por imagen. Entre ellas, la radiofrecuencia percutánea (RFp) constituye una alternativa eficaz como tratamiento curativo. Sin embargo, la localización de la lesión cerca de estructuras como el diafragma o el tracto gastrointestinal, limita esta técnica debido al riego de daño térmico colateral y a un tratamiento incompleto por mala visualización. La introducción de ascitis artificial previa puede separar el CHC de los órganos adyacentes y mejorar la ventana acústica. El objetivo de este estudio fue evaluar la viabilidad, seguridad y eficacia de la RFp con ascitis artificial para el tratamiento del CHC adyacente al diafragma (AU)

Surgical resection is the first-line curative treatment of hepatocellular carcinoma (HCC). However most patients are unable to undergo surgical resection because of advanced tumoral stage, severe liver dysfunction or poor clinical status. Therefore, image-guided tumor ablation techniques have been introduced for the treatment of unresectable HCC. Among them, radiofrequency ablation (RFA) has been demonstrated to be an effective alternative curative therapy. However, local ablative therapy for tumors located close to structures such as the diaphragm or gastrointestinal tract is technically challenging because of the risk of collateral thermal damage to nearby structures or incomplete treatment of the HCC resulting from poor visibility on sonography. The introduction of artificial ascites can separate adjacent organs from the tumor and improve the sonic window. The aim of this study was to evaluate the feasibility, safety and efficacy of RFA with artificial ascites for HCC adjacent to the diaphragm (AU)

[Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma adjacent to the diaphragm]. / Creación de ascitis artificial para el tratamiento mediante radiofrecuencia percutánea del hepatocarcinoma cercano al diafragma.

Surgical resection is the first-line curative treatment of hepatocellular carcinoma (HCC). However most patients are unable to undergo surgical resection because of advanced tumoral stage, severe liver dysfunction or poor clinical status. Therefore, image-guided tumor ablation techniques have been introduced for the treatment of unresectable HCC. Among them, radiofrequency ablation (RFA) has been demonstrated to be an effective alternative curative therapy. However, local ablative therapy for tumors located close to structures such as the diaphragm or gastrointestinal tract is technically challenging because of the risk of collateral thermal damage to nearby structures or incomplete treatment of the HCC resulting from poor visibility on sonography. The introduction of artificial ascites can separate adjacent organs from the tumor and improve the sonic window. The aim of this study was to evaluate the feasibility, safety and efficacy of RFA with artificial ascites for HCC adjacent to the diaphragm.