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Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. Patients and methods Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early. Results A total of 240 transplants were performed in 236 patients (191♂/45♀) over 74 months, mean age 56.3±9.6 years, raw MELD score 15.5±7.7. Predominant etiologies were alcohol (n = 136) and HCV (n = 82), with hepatocellular carcinoma present in 129 (54.7%). Nine patients received combined liver and kidney transplants. The mean operating time was 315±64 min with cold ischemia times of 279±88 min. Thirty-one patients (13.1%) were transfused in the OR (2.4±1.2 units of PRBC). Extubation was immediate (p=0.015) in the fast-track group. Patient survival was 86.8% at 1 year and 78.6% at five years. Conclusion Fast-Tracking of Liver Transplant patients is feasible and can be applied as the standard of care

Introduction: Currently, kidney transplantation is the treatment of choice for patients with kidney disease who require replacement therapy. Dialysis is a necessary step, but not mandatory prior to transplantation. There is the possibility of pre-emptive transplantation or transplantation in pre-dialysis, that is, without previous dialysis. The aim of the present study is to evaluate the result of our experience with a pre-emptive kidney transplant from a deceased donor. Materials and methods: Retrospective, observational, matched cohort study. We compared 66 pre-emptive with 66 non pre-emptive recipients, who received a first renal graft performed at our centre, matched by age and gender of donors and recipients, time of transplant, immunological risk, immunosuppression and cold ischaemia time.Early graft loss, incidence of acute rejection, delayed graft function, renal function at 12 and 36 months and graft and recipient survival were assessed in this period. Results: The percentage of recipients who presented early graft loss, delayed graft function and acute rejection was similar in both groups. No differences were observed in their renal function at 12 and 36 months after transplantation, as well as the actuarial survival of patients (p = 0.801) and grafts (p = 0.693) in the studied period. The total calculated cost of the period on dialysis for the control group was 8,033,893.16 euros. Conclusions: Pre-emptive transplantation can yield comparable outcomes to those for post-dialysis kidney transplantation, and results in better quality of life for patients with end-stage kidney disease, as well as a reduced cost. Resumen: Introducción: Actualmente, el trasplante renal es el tratamiento de elección para pacientes con enfermedad renal que requieren terapia de sustitución. La diálisis es un paso necesario, pero no obligatorio, previo al trasplante. Existe la posibilidad del trasplante renal anticipado o en pre-diálisis, es decir, sin diálisis previa. El objetivo del presente estudio es evaluar el resultado de nuestra experiencia en el trasplante renal anticipado con donante cadáver. Materiales y métodos: Estudio observacional retrospectivo de tipo cohortes emparejadas. Seincluyó a 66 receptores de trasplante renal en situación pre-diálisis, frente a un grupo control de 66 pacientes ya en diálisis que recibieron un primer injerto renal, emparejados por edad y sexo de donante y receptor, momento del trasplante, riesgo inmunológico, inmunosupresión y tiempo de isquemia fría. Se evaluó la pérdida precoz del injerto, incidencia de rechazo agudo, función retrasada del injerto, función renal a los 12 y 36 meses y supervivencia de injerto y receptor en ese periodo. Resultados: El porcentaje de receptores que presentaron pérdida precoz del injerto, función retrasada del injerto y rechazo agudo fue similar en ambos grupos. Tampoco se observaron diferencias en la función renal a los 12 ni a los 36 meses después del trasplante, ni en lasupervivencia actuarial de pacientes (p = 0,801) e injertos (p = 0,693).El coste total del tratamiento renal sustitutivo en el grupo control fue: 8033893.16 euros. Conclusiones: El trasplante renal de donante cadáver ofrece a los pacientes en situación de prediálisis resultados superponibles a los de receptores en diálisis, además de ser económicamente rentable. Keywords: Pre-emptive renal transplant, Deceased donor, Patient and graft survival, Dialysis, Psychological aspects, Palabras clave: Trasplante renal anticipado, Donante cadáver, Supervivencia injerto y receptor, Diálisis, Impacto psicológico

Resumen: Introducción: Actualmente, el trasplante renal es el tratamiento de elección para pacientes con enfermedad renal que requieren terapia de sustitución. La diálisis es un paso necesario, pero no obligatorio, previo al trasplante. Existe la posibilidad del trasplante renal anticipado o en prediálisis, es decir, sin diálisis previa. El objetivo del presente estudio es evaluar el resultado de nuestra experiencia en el trasplante renal anticipado con donante cadáver. Materiales y métodos: Estudio observacional retrospectivo de tipo cohortes emparejadas. Se incluyó a 66 receptores de trasplante renal en situación de prediálisis, frente a un grupo control de 66 pacientes ya en diálisis que recibieron un primer injerto renal, emparejados por edad y sexo de donante y receptor, momento del trasplante, riesgo inmunológico, inmunosupresión y tiempo de isquemia fría. Se evaluó la pérdida precoz del injerto, incidencia de rechazo agudo, función retrasada del injerto, función renal a los 12 y 36 meses y supervivencia de injerto y receptor en ese período. Resultados: El porcentaje de receptores que presentaron pérdida precoz del injerto, función retrasada del injerto y rechazo agudo fue similar en ambos grupos. Tampoco se observaron diferencias en la función renal a los 12 ni a los 36 meses después del trasplante, ni en la supervivencia actuarial de pacientes (p = 0,801) e injertos (p = 0,693).El coste total del tratamiento renal sustitutivo en el grupo control fue de 8.033.893,16 euros. Conclusiones: El trasplante renal de donante cadáver ofrece a los pacientes en situación de prediálisis resultados superponibles a los de receptores en diálisis, además de ser económicamente rentable. Abstract: Introduction: Currently, kidney transplantation is the treatment of choice for patients with kidney disease who require replacement therapy. Dialysis is a necessary step, but not mandatory prior to transplantation. There is the possibility of pre-emptive transplantation or transplantation in pre-dialysis, that is, without previous dialysis. The aim of the present study is to evaluate the result of our experience with a pre-emptive kidney transplant from a deceased donor. Materials and methods: Retrospective, observational, matched cohort study. We compared 66 pre-emptive with 66 non pre-emptive recipients, who received a first renal graft performed at our centre, matched by age and gender of donors and recipients, time of transplant, immunological risk, immunosuppression and cold ischaemia time.Early graft loss, incidence of acute rejection, delayed graft function, renal function at 12 and 36 months and graft and recipient survival were assessed in this period. Results: The percentage of recipients who presented early graft loss, delayed graft function and acute rejection was similar in both groups. No differences were observed in their renal function at 12 and 36 months after transplantation, as well as the actuarial survival of patients (P = 0.801) and grafts (P = 0.693) in the studied period. The total calculated cost of the period on dialysis for the control group was 8,033,893.16 euros. Conclusions: Pre-emptive transplantation can yield comparable outcomes to those for post-dialysis kidney transplantation, and results in better quality of life for patients with end-stage kidney disease, as well as a reduced cost. Palabras clave: Trasplante renal anticipado, Donante cadáver, Supervivencia injerto y receptor, Diálisis, Impacto psicológico, Keywords: Pre-emptive renal transplant, Deceased donor, Patient and graft survival, Dialysis, Psychological aspects

Resumen: El objetivo del presente estudio fue evaluar las concentraciones valle (Cpvalle) y la pauta posológica de tacrolimus tras la conversión de Prograf o Advagraf a Envarsus (nueva forma farmacéutica con tecnología Meltdose que mejora la absorción de fármacos liposolubles) en pacientes con trasplante renal estable, y su función renal.Se seleccionaron los pacientes trasplantados renales estables que fueron convertidos a Envarsus. Se definieron dos periodos: basal y conversión (Envarsus), y se estratificaron en función de la forma farmacéutica utilizada en el periodo basal. Se incluyeron 61 pacientes (24 con Advagraf y 37 con Prograf), con una edad media de 52 años. El tiempo medio postrasplante en el momento de la conversión a Envarsus fue de 76,3 meses y el seguimiento medio en el periodo basal y conversión fue de 10,1 y 11,6 meses, respectivamente.En el grupo Prograf y Envarsus las medianas Cpvalle fueron 6,6 vs 6,4 ng/ml (p = 0,636), con una dosis diaria media que disminuyó significativamente de 3 a 2 mg (p

The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function.We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52 years. The mean post-transplant time at the time of conversion to Envarsus was 76.3 months and the mean follow-up in the Baseline and Conversion period was 10.1 months and 11.6 months, respectively.In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/ml (p = .636), with a mean daily dose that decreased significantly from 3 mg to 2 mg (p

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.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups. An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5 mg iv oxaliplatin alone or 1.5 mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model. Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve. Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.