Intestinal perforation after pediatric liver transplantation: risk factors and management. / Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo.

BACKGROUND: Intestinal perforation (IP) after pediatric liver transplant (PLT) is an uncommon complication with high mortality reported. The aim of this study is to identify the risk factors and management of this complication. MATERIALS AND METHODS: Retrospective study of IP after PLT from January 2014 to October 2020. RESULTS: Four intestinal perforations were indentificated in 102 PLT (3,9%). Three patients with BA and one neonate with hemochromatosis (HC) presented this complication. The mean weight of patients with IP was 6.3± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0.05). All IP with BA had a previous laparotomy. Two living donors and two left lateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspected with clinical and biological signs of perforation, CT scan confirmed the diagnosis in patiens with BA and by direct visualization through the mesh for temporary closure in the patient with hemocromatosis. Urgent laparotomy was performed. We identified three colonic perforations, all of them in BA patients and all repaired with direct suture. The patient with HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure. CONCLUSION: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factors for IP in PLT. Urgent laparotomy after diagnosis should be performed in order to reduce mortality. Isolated IP with adequate treatment might not affect long term outcomes after pediatric liver transplantation.

INTRODUCCION: La perforación intestinal (PI) tras trasplante hepático pediátrico (THP) es una complicación poco frecuente, pero con una elevada mortalidad. El objetivo de este estudio es identificar los factores de riesgo y el manejo de esta complicación. MATERIAL Y METODOS: Estudio retrospectivo de la PI tras THP entre enero de 2014 y octubre de 2020. RESULTADOS: Se hallaron 4 perforaciones intestinales en 102 THP (3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB) y un neonato con hemocromatosis (HC). El peso medio de los pacientes con PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso del resto (p<0,05). Todos los pacientes con PI y AB habían sido sometidos previamente a laparotomía. Se implantaron 2 hígados de donantes vivos y 2 hígados laterales reducidos izquierdos. El diagnóstico de perforación intestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose con signos clínicos y biológicos de perforación, y confirmándose mediante escáner en los pacientes con AB y mediante visualización directa a través de la malla para el cierre temporal en el paciente con hemocromatosis. Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforaciones de colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias a enterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico. CONCLUSIONES: La perforación intestinal tras THP es una complicación poco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad, es conveniente practicar una laparotomía de urgencia tras el diagnóstico. Una PI aislada con un adecuado tratamiento puede no influir en los resultados a largo plazo tras un trasplante hepático pediátrico.

Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo / Intestinal perforation after pediatric liver transplantation: risk factors and management

Introducción: La perforación intestinal (PI) tras trasplante hepáticopediátrico (THP) es una complicación poco frecuente, pero con unaelevada mortalidad. El objetivo de este estudio es identificar los factoresde riesgo y el manejo de esta complicación. Material y métodos: Estudio retrospectivo de la PI tras THP entreenero de 2014 y octubre de 2020. Resultados: Se hallaron 4 perforaciones intestinales en 102 THP(3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB)y un neonato con hemocromatosis (HC). El peso medio de los pacientescon PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso delresto (p<0,05). Todos los pacientes con PI y AB habían sido sometidospreviamente a laparotomía. Se implantaron 2 hígados de donantes vivosy 2 hígados laterales reducidos izquierdos. El diagnóstico de perforaciónintestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose consignos clínicos y biológicos de perforación, y confirmándose medianteescáner en los pacientes con AB y mediante visualización directa a travésde la malla para el cierre temporal en el paciente con hemocromatosis.Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforacionesde colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias aenterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico.Conclusión: La perforación intestinal tras THP es una complicaciónpoco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad,es conveniente practicar una laparotomía de urgencia tras el diagnóstico.Una PI aislada con un adecuado tratamiento puede no influir en losresultados a largo plazo tras un trasplante hepático pediátrico.(AU)

Background: Intestinal perforation (IP) after pediatric liver trans-plant (PLT) is an uncommon complication with high mortality reported.The aim of this study is to identify the risk factors and management ofthis complication. Material and methods: Retrospective study of IP after PLT fromJanuary 2014 to October 2020. Results: Four intestinal perforations were indentificated in 102 PLT(3,9%). Three patients with BA and one neonate with hemochromatosis(HC) presented this complication. The mean weight of patients with IPwas 6.3 ± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0,05). AllIP with BA had a previous laparotomy. Two living donors and two leftlateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspectedwith clinical and biological signs of perforation, CT scan confirmed thediagnosis in patiens with BA and by direct visualization through themesh for temporary closure in the patient with hemocromatosis. Urgentlaparotomy was performed. We identified three colonic perforations, allof them in BA patients and all repaired with direct suture. The patientwith HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure.Conclusion: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factorsfor IP in PLT. Urgent laparotomy after diagnosis should be performed inorder to reduce mortality. Isolated IP with adequate treatment might notaffect long term outcomes after pediatric liver transplantation.(AU)

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

"Non-Touch" Vena Cava Technique as an Improvement in Combined Lung and Liver Procurement in Controlled Donation After Circulatory Death.

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.

Safety and Efficacy of Early Everolimus When Calcineurin Inhibitors Are Not Recommended in Orthotopic Liver Transplantation.

Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2. In 23 patients, immunosuppression was EVL + mycophenolate mofetil/mycophenolate sodium + steroids, and EVL + tacrolimus + steroids/mycophenolate sodium was used in 4 cases. Neurotoxicity disappeared in all patients. Renal function in patients with renal impairment improved from a median of 32 mL/min/1.73 m2 at the moment of implementation of EVL to 62 mL/min/1.73 m2 at 1 year. Four patients (14.3%) developed acute cellular rejection. We observed incisional hernia in 4 patients (14.3%), hematologic complications in 6 (21.4%), proteinuria in 2 (7.1%), edema and/or effusions in 8 (28.6%), and dyslipidemia in 12 (42.8%). No arterial complications were observed. EVL was withdrawn in 5 patients during the 1st year after LT. One-year patient survival was 92.7%. In conclusion, use of EVL within the 1st month after LT when calcineurin inhibitors are not recommended seems to be an effective therapeutic option with an acceptable safety profile.

Initial experience in sentinel lymph node detection in pancreatic cancer / Experiencia inicial en la detección del ganglio centinela en cáncer de páncreas

Background. The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. Materials and methods. Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc99m-labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. Results. Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. Conclusions. This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation (AU)

Objetivo. Tras una resección quirúrgica completa, la recidiva local del cancer de páncreas es de aproximadamente el 30%. La linfadenectomía extendida podría mejorar la supervivencia pero implica una morbilidad grave, por lo que una adecuada selección de los pacientes seria fundamental. Presentamos una nueva técnica de determinación del ganglio centinela (GC) en el cáncer de páncreas mediante el uso de SPECT/TC y sonda gamma. Materiales y Métodos. Siete pacientes con cáncer de páncreas estadío cT2N0M0 fueron incluidos entre 2009 y 2012 en este estudio prospectivo. El día antes de la cirugía se realizó una ecoendoscopia con inyección intratumoral de un nanocoloide marcado con Tc99m y dos horas más tarde se obtuvieron imágenes planares y de SPECT-TC. Intraoperatoriamente se realizó asimismo un rastreo con sonda gamma para detectar el GC. Resultados. La administración del radiotrazador fue posible en todos los pacientes. La linfogammagrafía detectó ganglios interaortocavos en 2 pacientes, ganglios en el ligamento hepatoduodenal en 1 paciente, inyección intravascular en 3 pacientes, tránsito intestinal en 5 pacientes y visualizó el conducto pancreático principal en 1 paciente. Debido a la progresión local, la resección quirúrgica pudo ser completada únicamente en 4 pacientes. La detección intraoperatoria del GC se completo en 2 pacientes, ambos con resultado negativo. Sólo en uno de estos pacientes el resultado pudo confirmarse con el estudio anatomopatológico definitivo. Conclusiones. Este nuevo método de detección del GC en cáncer de páncreas es viable pero complejo. Nuestros resultados preliminares con 7 pacientes no permiten una validación clínica (AU)

Initial experience in sentinel lymph node detection in pancreatic cancer.

BACKGROUND: The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. MATERIALS AND METHODS: Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc(99m)-labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. RESULTS: Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. CONCLUSIONS: This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation.

Acute Antibody-Mediated Rejection as Cause of Late Liver Allograft Failure: A Case Report.

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.

Analysis of adult 20-year survivors after liver transplantation.

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 m(2) (6-144 mL/min/1.73 m(2)). 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).

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: 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. RESULTS: 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 < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Immunosuppression based on everolimus in liver transplant recipients with severe early post-transplantation neurotoxicity.

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.

Early predictors of antiviral treatment response in liver transplant recipients with recurrent hepatitis C genotype 1.

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.

"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.

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.

Immunogenicity of pandemic influenza A H1N1/2009 adjuvanted vaccine in pediatric solid organ transplant recipients.

The aim of this study was to assess the immunogenicity of a vaccine against this virus in a prospective cohort of transplanted pediatric patients without previous influenza infection who received one dose of MF59®-adjuvanted pandemic H1N1/2009 vaccine. Seventeen patients who were being regularly followed up at the Outpatient Clinic of the Children's Transplant Unit (liver and kidney transplantation) in Hospital Universitari Vall d'Hebron (Barcelona) were included. Seroconversion was demonstrated in 15 of 17 (88.2%) vaccinated children. There were no rejection episodes or major adverse events. The MF59(®) -adjuvanted pandemic H1N1/2009 vaccine was safe and elicited an adequate response.

Liver resection and transplantation offer similar 5-year survival for Child-Pugh-Turcotte A HCC-patients with a single nodule up to 5 cm: a multicenter, exploratory analysis.

BACKGROUND AND AIM: The current guideline of the American Association for the Study of Liver Diseases recommends liver resection for Child-Pugh-Turcotte A patients with a single hepatocellular carcinoma, total serum bilirubin ≤ 1 mg/dL and absence of significant portal hypertension. This subset of patients would have a long-term survival comparable to transplantation. The main aim of this study is to evaluate the survival rates in patients with a single nodule ≤ 5 cm following resection. METHODS: Medical records of 105 Child-Pugh-Turcotte A patients who underwent liver resection between 1997 and 2009 were analyzed in 3 countries. RESULTS: One, 3-, and 5-year survival rate was 97%, 83%, and 66%, respectively, and no variable that can be assessed prior to liver resection predicted survival probabilities. CONCLUSIONS: Liver resection offers 5-year survival similar to transplantation for Child-Pugh-Turcotte A patients with hepatocellular carcinoma and a single nodule up to 5 cm, independently of any patient baseline characteristics.