Rubén Ciria

Comparative Short-term Benefits of Laparoscopic Liver Resection: 9000 Cases and Climbing.

Objective:To perform a systematic review of worldwide literature on laparoscopic liver resections (LLR) and compare short-term outcomes against open liver resections (OLR) by meta-analyses. Summary Background Data:There are no updated pooled data since 2009 about the current status and short-term outcomes of LLR worldwide. Patients and Methods:All English language publications on LLR were screened. Descriptive worldwide data and short-term outcomes were obtained. Separate analyses were performed for minor-only and major-only resection series, and series in which minor/major resections were not differentiated. Apparent case duplications were excluded. Results:A set of 463 published manuscripts were reviewed. One hundred seventy-nine single-center series were identified that accounted for 9527 LLR cases worldwide. Minor-only, major-only, and combined major–minor series were 61, 18, and 100, respectively, including 32, 8, and 43 comparative series, respectively. Of the total 9527 LLR cases reported, 6190 (65%) were for malignancy and 3337 (35%) were for benign indications. There were 37 deaths reported (mortality rate = 0.4%). From the meta-analysis comparing case-matched LLR to OLR (N = 2900 cases), there was no increased mortality and significantly less complications, transfusions, blood loss, and hospital stay observed in LLR vs OLR. Conclusions:This is the largest review of LLR available to date with over 9000 cases published. It confirms growing safety when performed in selected patients and by trained surgeons, and suggests that LLR may offer improved patient short-term outcomes compared with OLR. Improved levels of evidence, standardized reporting of outcomes, and assuring proper training are the next challenges of laparoscopic liver surgery.

A Prospective Study of the Efficacy of Clinical Application of a New Carrier-Bound Fibrin Sealant After Liver Resection

OBJECTIVE To examine the effectiveness of fibrin sealants as supportive treatment to improve hemostasis and decrease the incidence of bile leakage and intra-abdominal collections. DESIGN Prospective, controlled, quasiexperimental study. SETTING Tertiary referral center, University Hospital Reina Sofía. PATIENTS A total of 115 patients (58 in the control group and 57 in the collagen sponge group) scheduled for conventional hepatectomies. INTERVENTIONS Patients were distributed into groups for major and minor hepatectomies with or without application of a carrier-bound collagen sponge on the raw surface of the liver. MAIN OUTCOME MEASURES The main outcome measures were postoperative mortality, incidence and severity of postoperative surgical complications, and length of hospital stay. The secondary outcome measures were postoperative drainage output volume, transfusion requirements, and changes in biochemical parameters (hemoglobin, bilirubin, alanine aminotransferase, and platelet levels). RESULTS The fibrin sealant after major liver resection was effective for decreasing drainage volume (mean [SD] volume, 1124.7 [842.8] mL in the control group and 691.2 [499.5] mL in the collagen sponge group; P = .007) with a higher volume of output by drain each postoperative day in the control patients (P = .003); postoperative blood transfusion requirements (18.9% vs 7.0%, respectively; P = .04); moderate to severe postoperative complications (21% vs 8%, respectively; P = .03); and mean (SD) hospital stay (12.6 [6.7] vs 9.6 [5.1] days, respectively; P = .03). CONCLUSION The use of a new carrier-bound collagen sponge after major liver resection may be recommended because of its clinical and cost-savings effectiveness.

Prediction of graft dysfunction based on extended criteria donors in the model for end-stage liver disease score era.

Background. To explain the influence of recipient status combined with the accumulation of extended criteria donor (ECD) variables on the appearance of severe ischemia-reperfusion injury and graft survival in a model for end-stage liver disease (MELD)-based system, we analyzed our most recent consecutive liver transplantations (LTs), dividing them into two periods: 400 LTs (1992–2002; pre-MELD era) and 275 LTs (2002–2007; post-MELD era). Methods. Primary dysfunction (PD) was defined as primary graft failure that required emergency retransplantation or as initial poor function. Donor variables were included in a regression model to assess the probability of PD. Results. Donor age, macrovesicular steatosis more than 30%, and cold ischemia time were associated with allograft dysfunction. Mean probability of PD was 14.8%, 19.2%, 27.5%, and 37.4% for ECD 0, 1, 2, and more than or equal to 3, respectively (P=0.003). Distribution of no-mild, moderate, and severe ischemia-reperfusion injuries among MELD categories was 72.53%, 24.17%, and 3.30% (MELD group=12–19); 56.52%, 36.96%, and 6.5% (MELD group=20–28); and 23.91%, 54.35%, and 21.74% (MELD group ≥29), respectively (P=0.043). The development of PD according to ECD variables was 18.8%, 18.1%, 28.0%, and 35.3% for ECD 0, 1, 2, and more than or equal to 3, respectively (P=0.047). These variables were independent predictors of PD (Cox proportional regression model): ECD 2 (relative risk [RR]=1.59; 95% confidence interval [CI]=1.25–1.62), ECD 3 (RR=2.74; 95% CI=2.38–3.13), MELD 21 to 30 (RR=1.89; 95% CI=1.32–2.06), and MELD more than or equal to 30 (RR=3.38; 95% CI=2.43–3.86). Graft survival decreased, whereas MELD and the number of ECD variables increased. Conclusion. The combination of three or more ECD variables and an MELD more than or equal to 29 is the worst scenario for graft success after LT.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

Objective:To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. Background:Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. Methods:Multicenter, retrospective, matched cohort 1:2 study. Study group: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3–142) months. Results:The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). Conclusions:Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

“Very Early” Intrahepatic Cholangiocarcinoma in Cirrhotic Patients: Should Liver Transplantation Be Reconsidered in These Patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm (“very early”) in which results after LT can be acceptable. Twenty‐nine patients comprised the study group, eight of whom had a “very early” iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the “very early” iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1‐, 3‐ and 5‐year actuarial survival of those in the “very early” iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5‐year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Donor-recipient matching: Myths and realities

Liver transplant outcomes keep improving, with refinements of surgical technique, immunosuppression and post-transplant care. However, these excellent results and the limited number of organs available have led to an increasing number of potential recipients with end-stage liver disease worldwide. Deaths on waiting lists have led liver transplant teams maximize every organ offered and used in terms of pre and post-transplant benefit. Donor-recipient (D-R) matching could be defined as the technique to check D-R pairs adequately associated by the presence of the constituents of some patterns from donor and patient variables. D-R matching has been strongly analysed and policies in donor allocation have tried to maximize organ utilization whilst still protecting individual interests. However, D-R matching has been written through trial and error and the development of each new score has been followed by strong discrepancies and controversies. Current allocation systems are based on isolated or combined donor or recipient characteristics. This review intends to analyze current knowledge about D-R matching methods, focusing on three main categories: patient-based policies, donor-based policies and combined donor-recipient systems. All of them lay on three mainstays that support three different concepts of D-R matching: prioritarianism (favouring the worst-off), utilitarianism (maximising total benefit) and social benefit (cost-effectiveness). All of them, with their pros and cons, offer an exciting controversial topic to be discussed. All of them together define D-R matching today, turning into myth what we considered a reality in the past.

Prediction models of donor arrest and graft utilization in liver transplantation from maastricht-3 donors after circulatory death.

Shortage of organs for transplantation has led to the renewed interest in donation after circulatory–determination of death (DCDD). We conducted a retrospective analysis (2001–2009) and a subsequent prospective validation (2010) of liver Maastricht‐Category‐3‐DCDD and donation‐after‐brain‐death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

Auxiliary liver transplantation in children.

Purpose of reviewAuxiliary liver transplantation (ALT) has developed as a technique for treating patients with acute liver failure. The surgical techniques of ALT have been refined and current patient survival appears to be similar to that observed with conventional liver replacement for acute liver failure. Recent findingsOur understanding of liver regeneration has improved with experience and it is possible to identify patient and disease groups that are more likely to regenerate and wean off immunosuppression after ALT. Withdrawal of immunosuppression is possible in at least two thirds of survivors up to 4 years post transplant. Young patients have most to gain in the long term from immunosuppression withdrawal. Documentation of liver regeneration should be performed by liver histology, nuclear medicine scanning and CT volumetry. Weaning should be gradual to allow for graft atrophy to avoid complications. ALT has also been utilised for the management of inborn errors of metabolism based in the liver and for other rare problems and these will be briefly addressed in the review. SummaryAuxiliary liver transplantation should be considered for the treatment of children with acute liver failure satisfying current criteria for liver transplantation.

An organ allocation system for liver transplantation based on ordinal regression

Liver transplantation is nowadays a widely-accepted treatment for patients who present a terminal liver disease. Nevertheless, transplantation is greatly hampered by the un-availability of suitable liver donors; several methods have been developed and applied to find a better system to prioritize recipients on the waiting list, although most of them only consider donor or recipient characteristics (but not both). This paper proposes a novel donor-recipient liver allocation system constructed to predict graft survival after transplantation by means of a dataset comprised of donor-recipient pairs from different centres (seven Spanish and one UK hospitals). The best model obtained is used in conjunction with the Model for End-stage Liver Disease score (MELD), one of the current assignation methodology most used globally. This problem is assessed using the ordinal regression learning paradigm due to the natural ordering in the classes of the problem, via a cascade binary decomposition methodology and the Support Vector Machine methodology. The methodology proposed has shown competitiveness in all the metrics selected, when compared to other machine learning techniques and efficiently complements the MELD score based on the principles of efficiency and equity. Finally, a simulation of the proposal is included, in order to visualize its performance in realistic situations. This simulation has shown that there are some determining factors in the characterization of the survival time after transplantation (concerning both donors and recipients) and that the joint use of these sets of information could be, in fact, more useful and beneficial for the survival principle. Nonetheless, the results obtained indicate the true complexity of the problem dealt within this study and the fact that other characteristics that have not been included in the dataset may be of importance for the characterization of the dependent variable (survival time after transplantation), thus starting a promising line of future work.

Impact of age on liver regeneration response to injury after partial hepatectomy in a rat model.

BACKGROUND Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration. OBJECTIVE To assess the effect of age on liver regeneration in an experimental in vivo animal model of 70%-partial hepatectomy. METHODS Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined. RESULTS Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- α) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-β were higher in young rats. CONCLUSION Liver regeneration is delayed and reduced in aged animals submitted to liver resection.