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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.

Background. Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity. Method. A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n = 152) was designed. PCT determination was tested on admission (first 72 hours). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, need for urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications. Results. PCT > 0.68mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT > 0.68mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis. Discussion. PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p

Recurrent pyogenic cholangitis is a chronic infection characterized by intrahepatic biliary stones and strictures. Escherichia coli is the commonest infecting organism. This disease is very common in East Asia but infrequent in Western countries, and few reports have been published in European series. The therapeutic approach for hepatolithiasis is highly individual and includes antibiotic therapy, endoscopic and percutaneous biliary drainage with stone removal and dilation of strictures, surgical resection of affected liver segments and liver transplantation. We report two cases of RCP in Chinese patients treated with liver transplantation at our center out of the 34 published in the literature.

Objective Our main purpose was to compare the modified computed tomography severity index (MCTSI), computed tomography severity index (CTSI), and acute physiological and chronic health evaluation (APACHE)-II predictions regarding severity according to the revised Atlanta classification 2012 and local complications in acute pancreatitis in a consecutive prospective cohort. Methods One hundred and forty-nine patients diagnosed with acute pancreatitis were prospectively enrolled. APACHE-II, MCTSI, and CTSI were calculated for all cases. Severity parameters included persistent organ or multiorgan failure, length of hospitalization, the need for intensive care, death, and local complications (intervention against necrosis and infected necrosis). Area under the receiver operating characteristic curve (AUROC) was calculated and the value of scoring systems was compared. Results Both CTSI and MCTSI were associated significantly with all the evaluated severity parameters and showed a correlation between imaging severity and the worst clinical outcomes. Persistent organ failure, persistent multiorgan failure, and death were found in 30 (20.1%), 20 (13.4%), and 13 (8.7%) patients, respectively. The most common extrapancreatic finding was pleural effusion in 76 (51.0%) patients. The AUROC for CTSI was higher for predicting persistent organ failure (0.749, 95% confidence interval [CI] 0.640-0.857), death (AUROC 0.793, 95% CI 0.650-0.936), intervention against necrosis (AUROC 0.862, 95% CI 0.779-0.945), and infected necrosis (AUROC 0.883, 95% CI 0.882-0.930). Conclusions CT indexes outperformed the classic APACHE-II score for evaluating severity parameters in acute pancreatitis, with a slight advantage of CTSI over MCTSI. CTSI accurately predicted pancreatic infections and the need for intervention.

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.

Resumen Introduccion El objetivo del presente estudio es analizar el impacto de la afectacion del ganglio de la arteria hepatica (GAH) en la supervivencia de los pacientes intervenidos de duodenopancreatectomia cefalica (DPC) por adenocarcinoma (ADK) de cabeza de pancreas. Metodos Estudio retrospectivo unicentrico de pacientes intervenidos de DPC por ADK de cabeza de pancreas, con estudio anatomopatologico independiente del GAH. Los pacientes se agruparon en: 1) pacientes sin afectacion del GAH ni ganglios peripancreaticos (GGP) (GPP−/GAH−); 2) pacientes con afectacion ganglionar peripancreatica (GPP+/GAH−), y 3) pacientes con afectacion ganglionar peripancreatica y de la arteria hepatica (GGP+/GAH+). Para el analisis de supervivencia se utilizaron las curvas Kaplan-Meier. Los factores pronosticos de supervivencia global (SG) y libre de enfermedad (SLE) fueron identificados mediante el analisis de regresion 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 distribucion 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 5 anos fue estadisticamente 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 anos fue estadisticamente 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 analisis multivariante el principal factor de riesgo tanto de SG como de SLE fue la invasion linfatica independientemente del estado del GAH. Conclusiones Nuestros resultados sugieren que la afectacion adenopatica impacta en la supervivencia del ADK de pancreas sin poder identificar la afectacion del GAH como marcador pronostico.

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 20 months (r: 1–159 months). 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.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels =?5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n?=?105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73?m2 to 86.1 [27.9] mL/min/1.73?m2) whereas it decreased in the MMF + TAC (n?=?106) group (88.4?[34.3]?mL/min/1.73 m2 to 83.2?[25.2]?mL/min/1.73 m2), with significant (p?0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

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

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.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.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.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).Advanced age alone should not exclude patients from LT.

Background The aim of our study was to determine the risk factors for extrapancreatic infection (EPI) occurrence and its predictive power for assessing severity and local complications in acute pancreatitis including infected pancreatic necrosis (IPN). Methods Clinical data of 176 AP patients prospectively enrolled were analysed. EPI analysed were bacteraemia, lung infection, urinary tract infection and catheter line infection. Risk factors analysed were: Leukocyte count, C-reactive protein, liver function test, serum calcium, serum glucose, Blood urea nitrogen, mean arterial pressure at admission, total parenteral nutrition (TPN), enteral nutrition, hypotension, respiratory, cardiovascular and renal failure at admission, persistent systemic inflammatory response (SIRS) and intrapancreatic necrosis. Severity outcomes assessed were defined according to the Atlanta Criteria definition for acute pancreatitis. The predictive accuracy of EPI for morbidity and mortality was measured using area-under-the-curve (AUC) receiver-operating characteristics. Results Forty-four cases of EPI were found (25%). TPN (OR:9.2 CI95%: 3.3–25.7), APACHE-II>8 (OR:6.2 CI95%:2.48–15.54) and persistent SIRS (OR:2.9 CI95%: 1.1–7.8), were risk factors related with EPI. Bacteraemia, when compared with others EPI, showed the best accuracy in predicting significantly persistent organ failure (AUC:0.76, IC95%:0.64–0.88), ICU admission (AUC:0.80 IC95%:0.65–0.94), and death (AUC:0.73 CI95%:0.54–0.91); and for local complications including IPN (AUC:0.72 CI95%:0.53–0.92) as well. Besides, it was also needed for an interventional procedure against necrosis (AUC:0.74 IC95%: 0.57–0.91). When bacteraemia and IPN occurs, bacteraemia preceded infected necrosis in all cases. On multivariate analysis, risk factor for IPN were lung infection (OR:6.25 CI95%1.1-35.7 p = 0.039) and TPN (OR:22.0CI95%:2.4–205.8, p = 0.007), and for mortality were persistent SIRS at first week (OR: 22.9 CI95%: 2.6–203.7, p = 0.005) and Lung infection (OR: 9.7 CI95%: 1.7–53.8). Conclusion In our study, EPI, played a role in predicting the severity and local complications in acute pancreatitis.

This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%).

BACKGROUND The characteristics of liver donors have changed over the last decade owing to the shortage of organs and high mortality on the waiting list, leading to wider use of extended-criteria donors, including older donors. The aim of this study was to evaluate the effect of matching donor-recipient age on morbidity at 1 year post-transplant and on long-term patient and graft survival. MATERIAL AND METHODS Retrospective study from a prospectively-obtained database including adult patients who had received a primary liver transplant (LT) from whole graft of brain-dead donors. Recipients were divided into 2 age groups

Reactivation of Chagas disease in the chronic phase may occur after solid organ transplantation, which may result in high parasitemia and severe clinical manifestations such as myocarditis and meningoencephalitis. The aim of the present study is to describe the prevalence of Chagas disease among solid organ–transplanted patients in a tertiary hospital from a nonendemic country. A cross-sectional study was performed at Vall d’Hebron University Hospital (Barcelona, Spain) from April to September 2016. Chagas disease screening was performed through serological tests in adult patients coming from endemic areas that had received solid organ transplantation and were being controlled in our hospital during the study period. Overall, 42 patients were included, 20 (47.6%) were male and median age was 50.5 (23–73) years. Transplanted organs were as follows: 18 kidneys, 17 lungs, and 7 livers. Three patients had Chagas disease, corresponding to a prevalence among this group of solid organ–transplanted patients of 7.1%. All three patients were born in Bolivia, had been diagnosed with Chagas disease and received specific treatment before the organ transplantation. We highly recommend providing screening tests for Chagas disease in patients with or candidates for solid organ transplantation coming from endemic areas, early treatment with benznidazole, and close follow-up to prevent clinical reactivations.

The number of organs retrieved from donation after circulatory death (DCD) donors has continued to rise in recent years. The functional superiority of DCD organs is achieved when the lungs are perfused with cold perfusion and livers with normothermic regional perfusion (NRP). Thus, a precise surgical technique is required to combine thoracic and abdominal organ procurement. The technique used at our center consists of a rapid laparotomy and middle sternotomy, then the abdominal aorta (Ao) and abdominal inferior vena cava (VC) are cannulated and the descending thoracic Ao is cross-clamped. NRP is started at that point. As a variation of previously described techniques, the thoracic vena cava is not initially clamped in order to improve the return of blood volume to the NRP circuit. The pulmonary artery is cannulated to flush the lungs and the left atrial appendage is opened for drainage. After 120 minutes, NRP perfusion is stopped and the organs are flushed with cold preservation solution. In 2016, 3 livers and 6 lungs were harvested at our center using the technique described. After a minimum follow-up of 1 year, no evidence of biliary complications was observed. The combined procurement of lungs after room temperature perfusion and liver after NRP without initial clamping of the thoracic VC is feasible, with excellent function post-transplantation.

Resumen Introduccion El beneficio de la duodenopancreatectomia cefalica (DPC) con reseccion de la vena mesenterica superior/vena porta (RVP) para el adenocarcinoma de pancreas (ADCP) es controvertido en cuanto a la morbilidad, mortalidad y supervivencia. Se analizan los resultados de la DPC con RVP en un centro terciario espanol. Metodos Entre 2002 y 2012, 10 pacientes fueron tratados mediante RVP (RVP+) y 68 con DPC estandar (RVP−). La morbilidad, mortalidad, supervivencia global (SG) y supervivencia libre de enfermedad (SLE) se compararon entre pacientes RVP+/RVP−. Los factores pronosticos fueron identificados con regresion de Cox. Resultados La mortalidad postoperatoria fue del 5% (4/78), todos los pacientes en el grupo RVP−. La morbilidad fue mayor en el grupo RVP− comparado con RVP+ (63 vs. 30%; p = 0,04). La SG a 3 y 5 anos fue 43 y 43% en el grupo RVP+, 35 y 29% en RVP− (p = 0,7). La SLE a 3 y 5 anos fue 28 y 15% en RVP+, 25 y 20% en RVP− (p = 0,84). La mediana de supervivencia fue de 23,1 meses en el grupo RVP− y de 22,8 meses en el grupo RVP+ (p = 0,73). Los factores relacionados con la SG fueron ausencia de tratamiento adyuvante (OR 2,9; IC95%: 1,39-6,14; p = 0,003), reseccion R1 (OR 2,3; IC95%: 1,2-4,43; p = 0,006), CA 19.9 ≥ 170 UI/mL (OR 2,3; IC95%: 1,22-4,32; p = 0,01). Los factores de riesgo para SLE fueron reseccion R1 (OR 2,6; IC95%: 1,41-4,95; p = 0,002); tumores pobremente diferenciados (OR 2,7; IC95%: 1,23-6,17; p = 0,01); tumores N1 (OR 1,8; IC95%: 1,02-3,19; p = 0,04); CA 19.9 ≥ 170 UI/mL (OR 2,4; IC95%: 1,30-4,54; p = 0,005). Conclusiones La RVP para ADCP puede realizarse con seguridad. Pacientes con RVP tienen una supervivencia comparable a los pacientes tratados mediante DPC estandar si se obtienen margenes libres.

Introduction The benefit of pancreaticoduodenectomy (PD) with superior mesenteric-portal vein resection (PVR) for pancreatic adenocarcinoma (PA) is still controversial in terms of morbidity, mortality and survival. We conducted a retrospective study to analyse outcomes of PD with PVR in a Spanish tertiary centre. Methods Between 2002 and 2012, 10 patients underwent PVR (PVR+ group) and 68 standard PD (PVR− group). Morbidity, mortality, overall survival (OS) and disease-free survival (DFS) were compared between PVR+ and PVR− group. Prognostic factors were identified by a Cox regression model. Results Postoperative mortality was 5% (4/78), all patients in PVR− group. Morbidity was higher in the PVR− group compared to PVR+ (63% vs 30%, P=.004). OS at 3 and 5 years was 43% and 43% in PVR+ group, 35% and 29% in PVR− group (P=.07). DFS at 3 and 5 years DFS were 28% and 15% in PVR+ group, 25% and 20% in PVR− group (P=.84). Median survival was 23.1 months in PVR− group, and 22.8 months in PVR+ group (P=.73). Factors related with OS were absence of adjuvant treatment (OR 2.9, 95%IC: 1.39–6.14, P=.003), R1 resection (OR 2.3, 95%IC: 1.2–4.43, P=.006), preoperative CA 19.9 level ≥ 170 UI/mL (OR 2.3, 95%IC: 1.22–4.32, P=.01). DFS risk factors were R1 resection (OR 2.6, 95%IC: 1.41–4.95, P=.002); moderate or poor tumour differentiation grade (OR 2.7, 95%IC: 1.23–6.17, P=.01); N1 lymph node status (OR 1.8, 95%IC: 1.02–3.19, P=.04); CA 19.9 level ≥ 170 UI/mL (OR 2.4, 95%IC: 1.30–4.54, P=.005). Conclusions PVR for PA can be performed safely. Patients with PVR have a comparable survival to patients undergoing standard PD if disease-free margins can be obtained.

The etiology of delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PPPD) is unclear. This study aimed to ascertain the incidence of DGE in a transmesocolic anastomosis (TA) versus an antecolic anastomosis (AA) group of patients. Retrospective study including the last 40 consecutive patients with TA (2004–2006) and the first 40 consecutive patients with AA (2006–2010) performed at our centre. Preoperative, surgical and postoperative data were prospectively collected until patient discharge. No preoperative differences were found. Overall postoperative morbidity was higher in the TA group (75 vs 47 %; p = 0.012). No significant differences in DGE were found (TA: 35 % vs AA: 20 %; p = 0.1). Termino-terminal pancreatic anastomosis, gastrostomy, prophylactic somatostatin and the presence of intra-abdominal collections were associated with DGE. On multivariate analysis, only intra-abdominal collections (OR: 4.95 % CI: 1.36–11.8; p = 0.012) predicted DGE. Among patients without other surgical complications (n = 46), DGE rate was significantly higher in the TA group (TA: 38 % vs AA: 12 %, p = 0.04). Overall, no significant differences in DGE were found between groups. AA could be a protective factor for DGE when no other surgical complications appear.

The immunosuppressive management of liver transplant recipients suffering early calcineurin inhibitor-induced neurotoxicity is a challenge in daily clinical practice. We have assessed the use of everolimus as the main immunosuppressant in patients presenting severe neurotoxicity in the early post-transplantation period. From October 1988 to October 2012, 10 patients in our center received everolimus because of severe neurotoxicity in the 1st 3 months after transplantation. We analyzed several variables associated with this treatment, including patient characteristics, time from liver transplantation to conversion to everolimus, immunosuppression regimens before and after conversion, treatment efficacy, adverse events, and discontinuation after conversion. Median follow-up after conversion to everolimus was 27 months (range, 1-63 mo). Neurotoxic events were: akinetic mutism in 4 patients, repeated convulsions in 3, cerebrovascular accident in 1, Guillain-Barré syndrome in 1, and disabling tremor in 1. Treatment with calcineurin inhibitors was discontinued in all patients. Post-conversion regimens consisted of everolimus plus mycophenolate mofetil (MMF) plus steroids in 7 patients, everolimus plus MMF in 1, everolimus plus steroids in 1, and everolimus alone in 1. Liver function was maintained for ≥1 month in all patients except 1, who presented a severe rejection that was treated with steroid bolus and Neoral cyclosporine. Neurologic function was fully recovered in 8 patients. In 1 patient with akinetic mutism and another with convulsions, tacrolimus was reintroduced at 2 months and 1 month, respectively, after resolution of the neurotoxic event. Everolimus is feasible and effective as the main immunosuppressant in patients suffering severe neurotoxicity during the 1st 3 months after transplantation. It allows neurologic function to be recovered while maintaining adequate liver function.

The aim of this study was to analyze the outcome of patients undergoing hepatic resection for melanoma liver metastases.Patients undergoing liver resection for melanoma metastases at the Hospital Vall d'Hebron and Hospital Clinic, Barcelona, were reviewed. Selection criteria were: good performance status, feasibly complete and safe resection, and absence of visceral extrahepatic metastases.Between 1994 and 2007, 14 liver resections were performed for melanoma liver metastases. The primary tumor was cutaneous in 8 patients and ocular in 6. Two patients underwent urgent liver surgery due to tumor bleeding. In these patients, complete melanoma staging was not performed and extrahepatic metastases were found during surgery or during the postoperative course. Six of 13 patients (46.2%) developed liver recurrence during follow-up. One- and 3-year actuarial patient survivals were 77 and 49%, respectively. Excluding the patients who underwent urgent liver surgery, the 1- and 3-year actuarial patient survivals in those with primary ocular and cutaneous melanoma were 83 and 56% and 80 and 60%, respectively.Liver resection may be considered as part of oncosurgical treatment in patients with melanoma liver metastases, since prolonged survival was observed, albeit with a high recurrence rate. Nevertheless, it should be taken into account that our study included only a small number of patients.

Objective Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT). Materials and Methods Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival. Results The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 ± 33 months (range, 10 days–178 months). Mean follow-up after conversion was 10 ± 9 months (range, 1.5–25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug. Conclusions In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.

Background Despite now being an infrequent complication in liver transplantation (LT) recipients, acute liver failure is still associated with high mortality. Case Report Here we report a case of acute liver failure 11 months after AB0-compatible LT in a hepatitis C–positive 50-year-old male recipient caused by late antibody-mediated rejection (AMR). De novo donor-specific antibodies appeared later in a previously negative donor-recipient crossmatch, leading to a rapid deterioration of liver function. Conclusions We highlight the importance of an accurate diagnosis and an early therapeutic intervention. The analysis of this case brings novel and generalizable insights to the differential diagnosis of acute liver failure after LT.

To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d’Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2–129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1–112.5) months. At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p

Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization (1-3). Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc) (4). Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications.

The ability to generate patient-specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three-dimensional extracellular matrix (ECM) scaffolds as bioactive substrates for cell differentiation with the long-range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention--indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X-100, 1% Triton X-100/0.1% sodium dodecyl sulfate (SDS) and 0.02% Trypsin-0.05% EGTA/1% Triton X-100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix-bound basic fibroblast growth factor and vascular endothelial growth factor. Trypsin caused structural deterioration and growth factor loss. Triton/SDS-decellularized scaffolds maintained 3 h of leak-free blood flow in a rodent transplantation model and supported repopulation with human iPSC-derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS-based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering.

Background Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known. Aim To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality. Methods A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality. Results Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21 %) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13–135 IU/L), 27 (11–152 IU/L) and 0.6 mg/dL (0.3–1.1 mg/dL). Renal dysfunction was observed in 40 % of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m2 (6–144 mL/min/1.73 m2). Sixty-one percent of 20-year survivors had arterial hypertension, 43 % dyslipidemia, 25 % de novo tumors and 21 % diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32 %) and between the 1st and 5th year post-transplant (25 %). After 5th year from transplant, hepatitis C recurrence (22 %) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year. Conclusion Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).

Summary The success of current antiviral treatment for hepatitis C virus (HCV) recurrence in liver transplant (LT) recipients remains limited. We aimed at evaluating the value of IL28B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response (SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty-nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks (OR: 3.74, 95% CI: 1.64–9.39; P = 0.003) and treatment compliance (OR: 35.27, 95% CI: 3.35–365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28B genotype significantly correlates with virological response at week 4 (OR 3.23; 95% CI, 1.12–9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on-treatment and may facilitate therapeutic strategies incorporating new antiviral agents.

AIM To describe one case of bilateral Tapia’s syndrome in a liver transplanted patient and to review the literature. METHODS We report a case of bilateral Tapia’s syndrome in a 50-year-old man with a history of human immunodeficiency virus and hepatitis C virus child. A liver cirrhosis and a bi-nodular hepatocellular carcinoma, who underwent liver transplantation after general anesthesia under orotracheal intubation. Uneventful extubation was performed in the intensive care unit during the following hours. On postoperative day (POD) 3, he required urgent re-laparotomy due to perihepatic hematoma complicated with respiratory gram negative bacilli infection. On POD 13, patient was extubated, but required immediate re-intubation due to severe respiratory failure. At the following day a third weaning failure occurred, requiring the performance of a percutaneous tracheostomy. Five days later, the patient was taken off mechanical ventilation and severe dysphagia, sialorrea and aphonia revealed. A computerized tomography and a magnetic resonance imaging of the head and neck excluded central nervous injury. A stroboscopy showed bilateral paralysis of vocal cords and tongue and a diagnosis of bilateral Tapia’s syndrome was performed. With conservative management, including a prompt establishment of a speech and swallowing rehabilitation program, the patient achieved full recovery within four months after liver transplantation. We carried out MEDLINE search for the term Tapia’s syndrome. The inclusion criteria had no restriction by language or year but must provide sufficient available data to exclude duplicity. We described the clinical evolution of the patients, focusing on author, year of publication, age, sex, preceding problem, history of endotracheal intubation, unilateral or bilateral presentation, diagnostic procedures, type of treatment, follow-up, and outcome. RESULTS Several authors mentioned the existence of around 70 cases, however only 54 fulfilled our inclusion criteria. We found only five published studies of bilateral Tapia’s syndrome. However this is the first case reported in the literature in a liver transplanted patient. Most patients were male and young and the majority of cases appeared as a complication of airway manipulation after any type of surgery, closely related to the positioning of the head during the procedure. The diagnosis was founded on a rapid suspicion, a complete head and neck neurological examination and a computed tomography and or a magnetic resonance imaging of the brain and neck to establish the origin of central or peripheral type of Tapia’s syndrome and also the nature of the lesion, ischemia, abscess formation, tumor or hemorrhage. Apart from corticosteroids and anti- inflammatory therapy, the key of the treatment was an intensive and multidisciplinary speech and swallowing rehabilitation. Most studies have emphasized that the recovery is usually completed within four to six months. CONCLUSION Tapia’s syndrome is almost always a transient complication after airway manipulation. Although bilateral Tapia’s syndrome after general anesthesia is exceptionally rare, this complication should be recognized in patients reporting respiratory obstruction with complete dysphagia and dysarthria after prolonged intubation. Both anesthesiologists and surgeons should be aware of the importance of its preventing measurements, prompt diagnosis and intensive speech and swallowing rehabilitation program.

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis. A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years. Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p

Background Evaluate the safety of surgery in relation to bevacizumab in the first-line treatment of metastatic breast cancer (mBC) in two international trials. Patients and methods The incidence, type and timing of post-surgical bleeding events and wound-healing complications were assessed in surgical patients in the AVastin And DOcetaxel (AVADO) (NCT00333775) and Avastin THErapy for advaNced breAst cancer (ATHENA) (NCT00448591) trials. Both study protocols followed recommendations to withhold bevacizumab for at least 6 weeks before elective surgery and to wait 28 days (or until the wound was fully healed) after major surgery before recommencing bevacizumab therapy. Results In AVADO, 221 surgical procedures (55 major, 166 minor) were performed in 155 patients. In ATHENA, 1190 surgical procedures (435 major, 755 minor) were performed in 672 patients. One bevacizumab-treated AVADO patient (0.9%) who underwent surgery experienced a grade 3 bleeding event. In ATHENA, six patients (0.9%) who underwent surgery experienced grade 3 bleeding events and one patient (0.1%) experienced a grade 4 bleeding event. No grade 5 bleeding events in patients undergoing surgery were reported in either study. One grade 3 wound-healing complication was reported in each of the AVADO arms: placebo (n = 46, 2.2%), bevacizumab 7.5 mg/kg (n = 57, 1.8%) and bevacizumab 15 mg/kg (n = 52, 1.9%). Incidence of grade 3–4 wound-healing complications in ATHENA was 2.2% and 1.3% in patients undergoing minor or major surgery, respectively. Conclusions Surgery can be performed on patients with mBC undergoing bevacizumab therapy with a low risk of severe bleeding or wound-healing complications post surgery, if current labelling recommendations are adhered to.

Background The aim of this study was to analyze the evolution of biliary complications over 20 years among adult patients undergoing liver transplantation (OLT) at our institution. Patients and methods Between 1985 and 2007, we performed 1000 OLT in 789 adults and 211 children. To ascertain the evolution of biliary complications among adult OLT from October 1988 to September 2007, we compared the first 100 to with the last 200 adult OLT. Results Duct-to-duct was the most common biliary anastomosis performed in both periods (1st; 89% and 2nd; 94%; P = NS). However, a T-tube was used more frequently in the first period (1st; 46% vs 2nd; 6.6%; P < .001). The remaining cases underwent a hepaticojejunostomy (1st; 11% vs 2nd; 7.6%). Biliary complications were more frequent in the first period (1st; 20% vs 2nd; 9%; P < .01). In the first period, the use of a T-tube caused 32% of complications, all of them being bile leaks; but there were none in the second period. Arterial thrombosis or strictures were related to biliary complications in 10% and 33.3% among the first and second periods, respectively. The severity of complications according to the Clavien classification was similar in both periods: IIIa, 15% versus 33.3%; IIIb, 55% versus 55.5%; and IV, 15% versus 11.1%, respectively (P = NS). Conclusion The biliary complication rate among adult patients post-OLT decreased over 20 years at our institution, probably owing to the abandonment of the routine use of a T-tube as well as to advances in immunosuppressive protocols, organ preservation, and preoperative patient management.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.