Microbiome composition recovery after liver transplantation correlates with initial liver disease severity and antibiotics treatment.

Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications posttransplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pretranplantation and posttransplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative polymerase chain reaction was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity posttransplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared with low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases posttransplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus, and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.

Long-term outcomes (beyond 5 years) of liver transplant recipients-A transatlantic multicenter study.

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.

Effectiveness and safety of once-daily tacrolimus formulations in de novo liver transplant recipients: The PRETHI study.

Data comparing long-term effectiveness and safety of once-daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR-Tac (Advagraf) for up to 12 months post-transplant. Adult de novo liver transplant recipients who started IR-Tac (Prograf) and were converted to LCPT or PR-Tac 3-5 days post-transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR-Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR-Tac group (p = .291). Biopsy-proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR-Tac group (p = .166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p = .346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR-Tac group (p > .999). Patients in the LCPT group showed 45.7% higher relative bioavailability (Cmin /total daily dose [TDD]; p < .01) with similar Cmin and 33.3% lower TDD versus PR-Tac (p < .01). The evolution of renal function, safety profile, and the incidence of post-transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR-Tac. In de novo liver transplant patients, LCPT and PR-Tac showed comparable effectiveness with higher relative bioavailability, similar Cmin and lower TDD in the LCPT group. Renal function, safety, and post-transplant complications were comparable in LCPT and PR-Tac groups.

mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels).

BACKGROUND: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Left Lateral Sector In Situ Split Liver Transplantation Technique: Step-by-Step Video Demonstration.

The split liver technique enables transplanting 2 recipients with one single graft (typically an adult-child pair). It facilitates small recipients' access to liver transplantation and reduces mortality on the waiting list. However, splitting is technically demanding and may increase peri- and postoperative complications. To be able to obtain comparable outcomes to a full graft liver transplantation, careful donor-recipients selection, experienced surgeons, and logistic planning are paramount. The video shows an in situ split liver procedure from a 32-year-old brain stem death donor to generate a left lateral sector for a child and a right extended graft for an adult recipient.

Ultra Deep Sequencing of Circulating Cell-Free DNA as a Potential Tool for Hepatocellular Carcinoma Management.

BACKGROUND: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient's outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC. METHODS: Tumoral tissue, paired nontumor adjacent tissue and blood samples were collected from 30 HCC patients undergoing curative therapies. Deep sequencing targeting HCC driver genes was performed. RESULTS: Patients with more than 2 ng/µL of cfDNA at diagnosis had higher mortality (mean OS 24.6 vs. 31.87 months, p = 0.01) (AUC = 0.782). Subjects who died during follow-up, had a significantly higher number of mutated genes (p = 0.015) and number of mutations (p = 0.015) on cfDNA. Number of mutated genes (p = 0.001), detected mutations (p = 0.001) in cfDNA and ratio (number of mutations/cfDNA) (p = 0.003) were significantly associated with recurrence. However, patients with a ratio (number of mutations/cfDNA) above 6 (long-rank p = 0.0003) presented a higher risk of recurrence than those with a ratio under 6. Detection of more than four mutations in cfDNA correlated with higher risk of death (long-rank p = 0.042). CONCLUSIONS: In summary, cfDNA and detection of prevalent HCC mutations could have prognostic implications in early-stage HCC patients.

High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation.

Tacrolimus (TAC) is a dose-dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single-center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient's probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow-up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose-corrected concentration (C0 /D) between the third and sixth months post-LT. Of the 140 patients who underwent LT included in the study, the low-variability group (C0 /D CV < 27%) comprised 105 patients and the high-variability group (C0 /D CV ≥ 27%) 35 patients. One-, 3-, and 5-year patient survival rates were 100%, 82%, and 72% in the high-variability group versus 100%, 97%, and 93% in the low-variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high-variability group at 1 year (69 ± 16 ml/min/1.73 m2 vs. 78 ± 16 ml/min/1.73 m2 , p = 0.004) and at 2 years post-LT (69 ± 17 ml/min/1.73 m2 vs. 77 ± 15 ml/min/1.73 m2 , p = 0.03). High C0 /D CV 3-6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32-9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30-9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.

A multi-center post-market clinical study to confirm safety and performance of PuraStat® in the management of bleeding during open liver resection.

BACKGROUND: PuraStat® is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat® in liver resections performed for metastatic tumors. METHODS: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were ≥18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat® for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use. RESULTS: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat® application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified. CONCLUSION: This study confirms the safety, efficacy and ease of use of PuraStat® in the management of bleeding in liver surgery.

Delayed sequential abdominal wall closure in pediatric liver transplantation to overcome "large for size" scenarios.

BACKGROUND: Primary abdominal wall closure after pediatric liver transplantation (PLT) is neither always possible nor advisable, given the graft-recipient size discrepancy and its potential large-for-size scenario. Our objective was to report the experience accumulated with delayed sequential closure (DSC) guided by Doppler ultrasound control. METHODS: Retrospective analysis of DSC performed from 2013 to March 2020. RESULTS: Twenty-seven DSC (26.5%) were identified out of 102 PLT. Transplant indications and type of grafts were similar among both groups. In patients with DSC, mean weight and GRWR were 9.4 ± 5.5 kg (3.1-26 kg) and 4.7 ± 2.4 (1.9-9.7), significantly lower and higher than the primary closure cohort, respectively. The median time to achieve definitive closure was 6 days (range 3-23 days), and the median number of procedures was 4 (range 2-9). Patients with DSC had longer overall PICU (22.5 ± 16.9 vs. 9.1 ± 9.7 days, p < .05) and hospital stay (33.4 ± 19.1 vs 23, 9 ± 19.8 days (p < .05). These differences are less remarkable if the analysis is performed in a subgroup of patients weighing less than 10 kg. Two patients presented vascular complications (7.4%) within DSC group. No differences were seen when comparing overall, 3-year graft and patient survival (96% and 96% in the DSC group). CONCLUSIONS: DSC is a simple and safe technique to ensure satisfactory clinical outcomes to overcome "large for size" scenarios in PLT. In addition, we were able to avoid using a permanent biological material for closing the abdomen.

Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference.

The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.

Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients.

Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.

Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, AEC, SEOM, SERAM, SERVEI y SETH / Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH

El carcinoma hepatocelular (CHC) es la neoplasia primaria de hígado más frecuente y una de las causas de muerte más común en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, evaluación pronóstica y, especialmente, en el tratamiento del CHC. Por tal motivo, desde la Asociación Española para el Estudio del Hígado (AEEH) se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento: Sociedad Española de Trasplante Hepático (SETH), Sociedad Española de Radiología Médica (SERAM), Sociedad Española de Radiología Vascular e Intervencionista (SERVEI), Asociación Española de Cirujanos (AEC) y Sociedad Española de Oncología Médica (SEOM). Se han tomado como documentos de referencia las guías de práctica clínica publicadas en 2016, aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica y la fuerza de la recomendación se basa en el sistema GRADE. (AU)

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system. (AU)

Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, AEC, SEOM, SERAM, SERVEI y SETH.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.

Expanding Indications of Liver Transplantation in Spain: Consensus Statement and Recommendations by the Spanish Society of Liver Transplantation.

BACKGROUND: The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain. METHODS: A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the "Grading of Recommendations Assessment, Development, and Evaluation" system. RESULTS: The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient's age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer. CONCLUSIONS: We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario.

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.

Recipient Age for Liver Transplantation: Should It Be Limited? A Propensity Score Matching Analysis of a Large European Series.

BACKGROUND AND AIMS: The demand for older patients not to be denied access to liver transplantation (LT) has intensified as the European population continues to live longer and maintains better health. AIM: This study aims to ascertain the impact of recipient age on the post-LT survival in 2 well-balanced populations at Vall d'Hebron University Hospital. METHODS: From January 1990 to December 2016, LT recipients (young group: 50-65 years of age; elderly group: >65 years of age) were compared by means of a propensity score matching (PSM) method. RESULTS: Prior to PSM, graft survival and patient survival were worse for the elderly group (P < .001). In 1126 LT recipients, a caliper width of 0.01 was used based on the donor (age, sex, cause of donor death, and donor intensive care unit stay) and recipient covariates (sex, body mass index, indication for LT, intraoperative blood transfusion, cardiovascular risk factors, and Model for End-Stage Liver Disease [MELD]-Era). After PSM, 206 patients were matched; 1-, 5-, and 10-year patient survival rates were 77%, 63%, and 52% vs 80%, 64%, and 45% (P = .50) for young vs elderly recipients, respectively. Similar graft survival rates were observed in both groups (P = .42). CONCLUSIONS: Advanced age alone should not exclude patients from LT.

Routine Bile Culture From Liver Donors as Screening of Donor-Transmitted Infections in Liver Transplantation.

Bacterial infections are an important threat in the early post-liver transplantation period. Donor-transmitted infections, although rare, can have high mortality. The utility of routine culture from the donor bile duct as screening of donor-transmitted infection has not been evaluated. We performed a retrospective study of 200 consecutive liver transplants between 2010 and 2015. Demographic, clinical, and microbiological data were collected from the recipients' medical records. Clinical data included pretransplantation, perioperative, and posttransplantation information (until 30 days after the procedure). The 3-month patient survival and/or retransplantation were recorded. A total of 157 samples from the donor bile duct were collected and cultured. Only 8 were positive. The microorganisms isolated were as follows: Klebsiella pneumoniae, n = 2; Escherichia coli, n = 1; Enterobacter cloacae, n = 1; Streptococcus anginosus, n = 1; Streptococcus sp., n = 1; multiple gram-negative bacilli, n = 1; and polymicrobial, n = 1. All of the microorganisms were susceptible to the antibiotic prophylaxis administered. During the first month after transplantation, 81 recipients developed 131 infections. Only 1 of these recipients had a donor with a positive bile culture, and none of the infections were due to the microorganism isolated in the donor's bile. The 3-month overall survival was 89.5%, and there were no differences between recipients with positive donor bile cultures and those with negative donor bile cultures (87.5% versus 89.26%; P > 0.99). Routine testing of donor bile cultures does not predict recipients' infection or survival after liver transplantation and should not be recommended.

¿Es realmente la afectación del ganglio de la arteria hepática un factor de mal pronóstico en el adenocarcinoma de páncreas? / Is the involvement of the hepatic artery lymph node a poor prognostic factor in pancreatic adenocarcinoma?

INTRODUCCIÓN: El objetivo del presente estudio es analizar el impacto de la afectación del ganglio de la arteria hepática (GAH) en la supervivencia de los pacientes intervenidos de duodenopancreatectomía cefálica (DPC) por adenocarcinoma (ADK) de cabeza de páncreas. MÉTODOS: Estudio retrospectivo unicéntrico de pacientes intervenidos de DPC por ADK de cabeza de páncreas, con estudio anatomopatológico independiente del GAH. Los pacientes se agruparon en: 1) pacientes sin afectación del GAH ni ganglios peripancreáticos (GGP) (GPP-/GAH-); 2) pacientes con afectación ganglionar peripancreática (GPP+/GAH-), y 3)pacientes con afectación ganglionar peripancreática y de la arteria hepática (GGP+/GAH+). Para el análisis de supervivencia se utilizaron las curvas Kaplan-Meier. Los factores pronósticos de supervivencia global (SG) y libre de enfermedad (SLE) fueron identificados mediante el análisis de regresión de Cox. RESULTADOS: Entre enero de 2005 y diciembre de 2014 se intervinieron 118 pacientes, y el GAH fue analizado en 64 de ellos. La mediana de seguimiento fue de 20 meses (r: 1-159 meses). La distribución por grupos fue la siguiente: GPP-/GAH- en 12 (19%), GPP+/GAH- en 40 (62%), GGP+/GAH+ en 12 (19%) y CGP-/CGH+ en 0 (0%), La SG a 1, 3 y 5años fue estadísticamente mejor en el grupo GPP-/GAH- (82, 72 y 54%) comparado con GPP+/GAH- (68, 29 y 21%) y GGP+/GAH+ (72, 9 y 9%) (p = 0,001 vs p = 0,007). La probabilidad acumulada de recidiva a 1, 3 y 5 años fue estadísticamente inferior en el grupo GPP-/GAH- (18, 46 y 55%) comparado con el grupo GPP+/GAH- (57, 80 y 89%) y grupo GGP+/GAH+ (46, 91 y 100%) (p = 0,006 vs p = 0,021). En el análisis multivariante el principal factor de riesgo tanto de SG como de SLE fue la invasión linfática independientemente del estado del GAH. CONCLUSIONES: Nuestros resultados sugieren que la afectación adenopática impacta en la supervivencia del ADK de páncreas sin poder identificar la afectación del GAH como marcador pronóstico

INTRODUCTION: The aim of this study is to analyze the impact of hepatic artery lymph node (HALN) involvement on the survival of patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). METHODS: A single-center retrospective study analyzing patients who underwent PD for PA. Patients were included if, during PD, the HALN was submitted for pathologic evaluation. Patients were stratified by node status: PPLN- (peripancreatic lymph node)/HALN-, PPLN+/HALN- and PPLN+/HALN+. Survival analysis was estimated by the Kaplan-Meier method, and Cox regression was used for risk factors analyses. RESULTS: Out of the 118 patients who underwent PD for PA, HALN status was analyzed in 64 patients. The median follow-up was 20months (r: 1-159months). HALN and PPLN were negative in 12 patients (PPLN-/HALN-, 19%), PPLN was positive and HALN negative in 40 patients (PPLN+/HALN-, 62%), PPLN and HALN were positive in 12 patients (PPLN+/HALN+, 19%) and PPLN was negative and HALN positive in 0 patients (PPLN-/HALN+, 0%). The overall 1, 3 and 5-year survival rates were statistically better in the PPLN-/HALN- group (82%, 72%, 54%) than in the PPLN+/HALN- group (68%, 29%, 21%) and the PPLN+/HALN+ group (72%, 9%, 9%, respectively) (P = .001 vs P = .007). The 1, 3 and 5-year probabilities of cumulative recurrence were also statistically better in the PPLN-/HALN- group (18%, 46%, 55%) than in the PPLN+/HALN- group (57%, 80%, 89%) and the PPLN+/HALN+ group (46%, 91%, 100%, respectively) (P = .006 vs P = .021). In the multivariate model, the main risk factor for overall survival and recurrence was lymphatic invasion, regardless of HALN status. CONCLUSIONS: In pancreatic adenocarcinoma patients with lymph node disease, survival after PD is comparable regardless of HALN status

Is the involvement of the hepatic artery lymph node a poor prognostic factor in pancreatic adenocarcinoma? / ¿Es realmente la afectación del ganglio de la arteria hepática un factor de mal pronóstico en el adenocarcinoma de páncreas?

INTRODUCTION: The aim of this study is to analyze the impact of hepatic artery lymph node (HALN) involvement on the survival of patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). METHODS: A single-center retrospective study analyzing patients who underwent PD for PA. Patients were included if, during PD, the HALN was submitted for pathologic evaluation. Patients were stratified by node status: PPLN- (peripancreatic lymph node)/HALN-, PPLN+/HALN- and PPLN+/HALN+. Survival analysis was estimated by the Kaplan-Meier method, and Cox regression was used for risk factors analyses. RESULTS: Out of the 118 patients who underwent PD for PA, HALN status was analyzed in 64 patients. The median follow-up was 20months (r: 1-159months). HALN and PPLN were negative in 12patients (PPLN-/HALN-, 19%), PPLN was positive and HALN negative in 40patients (PPLN+/HALN-, 62%), PPLN and HALN were positive in 12 patients (PPLN+/HALN+, 19%) and PPLN was negative and HALN positive in 0 patients (PPLN-/HALN+, 0%). The overall 1, 3 and 5-year survival rates were statistically better in the PPLN-/HALN- group (82%, 72%, 54%) than in the PPLN+/HALN- group (68%, 29%, 21%) and the PPLN+/HALN+ group (72%, 9%, 9%, respectively) (P=.001 vs P=.007). The 1, 3 and 5-year probabilities of cumulative recurrence were also statistically better in the PPLN-/HALN- group (18%, 46%, 55%) than in the PPLN+/HALN- group (57%, 80%, 89%) and the PPLN+/HALN+ group (46%, 91%, 100%, respectively) (P=.006 vs P=.021). In the multivariate model, the main risk factor for overall survival and recurrence was lymphatic invasion, regardless of HALN status. CONCLUSIONS: In pancreatic adenocarcinoma patients with lymph node disease, survival after PD is comparable regardless of HALN status.