Antonio Rafecas

Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy

BACKGROUND Surgical resection has been the treatment of choice for hepatocellular carcinoma (HCC), but the resection rate remains low in cirrhotic patients and recurrence is common. Unfavorable results compared with benign disease and the shortage of organ donors have led to a restricted indication for orthotopic liver transplantation (OLT) for HCC. STUDY DESIGN The aim of this study was to analyze the results of our surgical approach to HCC in patients with cirrhosis. The first treatment strategy indicated in these patients was OLT. From January 1990 to May 1999, 85 patients underwent OLT and the remaining 35 had surgical resection. RESULTS One-, 3-, and 5-year survival rates were 84%, 74%, and 60% versus 83%, 57%, and 51%, respectively, in the OLT and resection groups (p = 0.34). Hepatic tumor recurrence was much less frequent in the OLT group than in the resection group. The 1-, 3-, and 5-year disease-free survival rates were 83%, 72%, and 60% versus 70%, 44%, and 31%, respectively (p = 0.027). In the multivariate Cox regression analysis, macroscopic vascular invasion was the only factor independently associated with death or recurrence after OLT (p = 0.006). After partial liver resection, the tumors significantly associated with mortality and recurrence in the multivariate analysis were solitary or multiple tumors greater than 2cm with microscopic vascular invasion (pathologic pT3) (p = 0.01). CONCLUSIONS Our results confirm that in cirrhotic patients, OLT may provide better outcomes than liver resection in carefully selected HCC and that longterm survival is similar to the results of OLT in cirrhotic patients without tumors.

The impact of donor age on liver transplantation: influence of donor age on early liver function and on subsequent patient and graft survival.

BACKGROUND The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT). METHODS Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses. RESULTS Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001). CONCLUSIONS Advanced donor age is associated with lower graft and recipient survival.

Complete Versus Selective Portal Triad Clamping for Minor Liver Resections: A Prospective Randomized Trial

Objective:To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. Summary Background Data:Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia. Patients and Methods:Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded. Results:No differences were observed in the amount of hemorrhage (671 ± 533 mL versus 735 ± 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 ± 4.6 versus 4.5 ± 2.7 μkat/L, P = 0.01) and AST (10.2 ± 8.7 versus 4.9 ± 2.1μkat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity. Conclusions:Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.

Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)–infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)–coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV‐coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow‐up was 2.6 years (interquartile range = 1.25‐3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty‐eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty‐three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty‐six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3‐fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5‐5.8]. Independent factors for severe infections included a pretransplant Model for End‐Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70‐7.1), a history of AIDS‐defining events before transplantation (HR = 4.0, 95% CI = 1.9‐8.6), and non–tacrolimus‐based immunosuppression (HR = 2.5, 95% CI = 1.3‐4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV‐coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non–tacrolimus‐based immunosuppression. Liver Transpl 18:70–82, 2012.

Results Of Using The Recipient's Splenic Artery For Arterial Reconstruction In Liver Transplantation In 23 Patients

BACKGROUND Arterial reconstruction is essential in liver transplantation. In some patients there may be an inadequate flow as a result of stenosis, intimal dissection, or anomalies of the hepatic artery. METHODS This study analyzes our experience with 23 patients in whom arterial anastomosis was performed using the splenic artery due to the inadequacy of the hepatic artery. During the same period an aortoiliac conduit was used in 12 liver transplantations due to the same problem. RESULTS No splenic infarction, pancreatitis, or other related complications were found. Artery thrombosis developed in only two patients in the aortoiliac conduit group. One- and three-year patient actuarial survival were 78% vs. 80% and 72% vs. 80%, respectively, for the splenic artery group and the aortoiliac conduit group. CONCLUSIONS Anastomosis with the splenic artery is an alternative in liver transplantation and is particularly suitable when splenomegaly is present.

Extra‐anatomic venous graft for portal vein thrombosis in liver transplantation

Sir: We read with interest the article by J. P. Lerut et al. about liver transplantation (OLT) and portal vein anomalies [2]. This paper analyzes a very large (53 patients), but quite heterogeneous, group of patients. Preoperative portal vein thrombosis (PVT), phlebitis, and previous surgery for portal hypertension are difficult situations in OLT, and it is our opinion that the surgical management is not the same for all of them. With regard to PVT, it can be concluded from Lerut et al.’s study that blind or, more recently, eversion portal venous thrombectomy is the preferred surgical technique in 26 out of 32 cases (81 %). Mortality after this procedure was high (4/26; 15 %), and severe intraand postoperative bleeding were frequent complications (7/26; 27 %). Portal vein rethrombosis is another complication that has been frequently reported after this procedure [3,5]. Their experience with splenomesenteric confluence dissection is even worse, with 80 % mortality (4/5).

Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge

Fundamento Se presenta la experiencia del programa de trasplante hepatico del Hospital de Bellvitge en 500 trasplantes realizados durante 15 anos, con el objetivo de poner de manifiesto los cambios que se han producido y exponer los resultados a largo plazo de esta terapeutica. Pacientes y metodo Se consideraron y compararon 5 grupos de 100 trasplantes consecutivos (I-V). Resultados Las indicaciones mas frecuentes fueron el hepatocarcinoma (23%), la cirrosis alcoholica (22,8%) y la hepatopatia cronica por virus C (18,8%). En 59 pacientes se llevaron a cabo 65 retrasplantes (13%), cuyas indicaciones mas frecuentes fueron la trombosis arterial (13 pacientes) y el fallo primario del injerto (10 pacientes). En 19 enfermos se realizo un trasplante combinado hepatorrenal. La causa mas frecuente de muerte del donante en el grupo I fueron los traumatismos craneales (80%), mientras que en el grupo V fue la enfermedad vascular (52%). Otras diferencias significativas entre estos grupos se observan en la proporcion de pacientes en estadio 2 y 3 de la clasificacion UNOS (el 45 frente al 19%), en el consumo de hemoderivados (29,6 [26] frente a 4,6 [5,3] concentrados de hematies), en la frecuencia de reintervenciones por hemoperitoneo (el 22 frente al 5%), en la estancia en UCI (13 [13] frente a 7,4 [11] dias) y en el hospital 40 [52] frente a 23,7 [17] dias), y en la incidencia de rechazo (el 46 frente al 20%) y de fallo primario del injerto (el 9 frente al 3%). Sin embargo, la prevalencia de infeccion (el 48 frente al 54,5%) y la incidencia de complicaciones biliares (el 26 frente al 20%) no han presentado variaciones significativas. La supervivencia actuarial de los pacientes trasplantados desde 1990 es del 83 y del 70% al ano y a los 5 anos, respectivamente. Conclusiones Se observa una mejoria notable y progresiva de los resultados del trasplante hepatico. Sin embargo, los tumores de novo, la recidiva de la hepatitis por virus C y el rechazo cronico pueden limitar los resultados a largo plazo.

Liver transplantation without steroid induction in HIV-infected patients.

Until recently, human immunodeficiency virus (HIV) infection was considered an absolute contraindication for liver transplantation in Spain. We present the first 4 cases of liver transplantation (LT) carried out in our center in patients infected with HIV and coinfected by the hepatitis C virus (HCV), immunosuppressed with cyclosporine A (CyA) and basiliximab, but without steroids. The 4 patients were male, with a mean age of 38.25 ± 4.5 years. Mean time of HIV infection was 114 ± 62.3 months and all patients were receiving highly active antiretroviral therapy (HAART). HCV genotypes of the 4 patients were 4, 1b, 1b, and 1a. Two patients were classified as Child‐Turcotte‐Pugh C (10 and 11 points), 1 was B (8 points), and the patient with hepatocellular carcinoma was A (5 points). Immunosuppression consisted of basiliximab and monotherapy with CyA. There were no postoperative infections. With a follow‐up of 17 ± 8 months, all patients are alive. There was only 1 acute rejection episode, and this was solved with steroid pulses. Three patients showed HCV recurrence with enzymatic and histological changes and were treated with interferon and ribavirin. One patient had negative HCV–ribonucleic acid after 6 months of treatment. In conclusion, HIV infection should not be considered an absolute contraindication for liver transplantation. The evolution of this type of patients will probably depend on the HCV infection. Immunosuppression without steroids may reduce opportunistic infection. (Liver Transpl 2004;10:1320–1323.)

Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning.

Apoptosis, necrosis and neovascularization are three processes that occur during ischemic preconditioning in a range of organs. In the stomach, the effect of this preconditioning (the delay phenomenon) has helped to improve gastric vascularization prior to esophagogastric anastomosis after esophagectomy. Here we present a sequential study of the histological recovery of the gastric fundus and the phenomena of apoptosis, necrosis and neovascularization in an experimental model of partial gastric ischemia. Partial gastric devascularization was performed by ligature of the left gastric vessels in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 1, 3, 6, 10, 15 and 21 days. Histological analysis, caspase-3 activity, DNA fragmentation and vascular endothelial cell proliferation (Ki-67) were measured in tissue samples after sacrifice. After 24 h of partial gastric ischemia, rates of apoptosis and necrosis were higher in the experimental groups than in controls. Tissue injury was higher 3 and 6 days post-ischemia. From day 10 after partial gastric ischemia, apoptosis and necrosis started to decrease, and on days 15 and 21 showed no differences in relation to controls. Neovascularization began between days 1 and 3, reaching its peak at 15 days after ischemia and coinciding with complete histological recovery. Both necrosis and apoptosis play a role in tissue injury during the first days after partial gastric ischemia. After 15 days, the evolution of both the histology and the neovascularization suggested that this is the optimal time for performing gastric transposition.

Comparative Study of Celsior and Belzer Solutions for Hepatic Graft Preservation: Preliminary Results

HE SCARCITY OF donors and the increase in the number of transplant candidates have stimulated research to minimize the loss of donated organs. Preservation solutions are available to conserve the organs for a determinate period. In liver transplant (LT) Belzer and Brettschneider solutions give satisfactory results. However, graft malfunction remains a problem and other solutions are being examined. This randomized comparative study aims to examine the hepatic function of grafts perfused with Celsior solution (CS) and Belzer solution (BS) following liver transplant in adults.