RESUMEN
INTRODUCTION: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. METHODS: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. RESULTS: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. CONCLUSION: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.
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Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/terapia , Adulto , Anciano , Diagnóstico Precoz , Femenino , Humanos , Incidencia , Trasplante de Hígado/mortalidad , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
INTRODUCTION: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. MATERIAL AND METHODS: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean +/- standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. RESULTS: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. CONCLUSION: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival.
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Arteria Hepática/anomalías , Arteria Mesentérica Superior/anomalías , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Malformaciones Vasculares/complicaciones , Adenocarcinoma/complicaciones , Adenocarcinoma/cirugía , Adulto , Anciano , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/complicaciones , Colangiocarcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/cirugía , Pancreatectomía , Neoplasias Pancreáticas/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The sinusoidal obstructive syndrome is a complication typically associated with hematopoietic stem cell transplantation. This syndrome, more commonly known as veno-occlusive disease, has also been described after liver transplantation. It can have a life-threatening course. Herein, we describe the hepatic graft loss secondary to the development of a sinusoidal obstructive syndrome after a severe acute cellular rejection and toxic levels of once daily modified released tacrolimus (TAC). We discuss the role of the endotheliitis of acute rejection and toxic metabolites of some immunosuppressants such as azathioprine and TAC. Based on the current scientific evidence, we contemplate the possibility that the etiology of sinusoidal obstruction syndrome post-liver transplantation is multifactorial.
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Enfermedad Veno-Oclusiva Hepática/etiología , Trasplante de Hígado , Complicaciones Posoperatorias/etiología , Adulto , Quimioterapia Combinada , Femenino , Rechazo de Injerto/prevención & control , Enfermedad Veno-Oclusiva Hepática/patología , Humanos , Inmunosupresores/uso terapéutico , Complicaciones Posoperatorias/patologíaAsunto(s)
Síndrome de Budd-Chiari/prevención & control , Trasplante de Hígado/métodos , Hígado/irrigación sanguínea , Recolección de Tejidos y Órganos/métodos , Injerto Vascular/métodos , Síndrome de Budd-Chiari/etiología , Venas Hepáticas/trasplante , Humanos , Vena Ilíaca/trasplante , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Donadores VivosRESUMEN
BACKGROUND: An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years. METHODS: We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed. RESULTS: Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P < .001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P = .57). CONCLUSIONS: Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival.
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Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Anciano , Preescolar , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Estudios de Casos y Controles , Supervivencia de Injerto , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Cirrosis Hepática Alcohólica , Factores de Edad , Receptores de Trasplantes , Resultado del TratamientoRESUMEN
BACKGROUND: Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. METHODS: A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. RESULTS: After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.
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Paro Cardíaco , Hipotermia Inducida , Hipotermia , Femenino , Humanos , Anciano , Persona de Mediana Edad , Preservación de Órganos , Hipotermia/etiología , España , Perfusión , Hígado , OxígenoRESUMEN
We evaluate the 5-year results of a single-centre prospective randomized trial that compared cyclosporine microemulsion (CyA-me) in triple therapy (plus steroids and azathioprine) and Tacrolimus (Tac) in double therapy (plus steroids) for primary immunosuppression. One hundred adult patients undergoing liver transplantation were randomized to receive Tac (n=51) or CyA-me (n=49). Ten patients in group A, and thirty-one patients in group B had their main immunosuppressive agent switched. The switch was much more frequent from CyA-me to Tac (n=31; 62.3%), mainly because of lack of efficacy (n=12; 38.7%). Six of 10 patients were shifted from Tac to CyA-me for side effects. The clinical course of the majority of patients converted from CyA-me to Tac improved clearly after conversion. Donor age and acute rejection (number, severity and rejection free days) had a significative association with lack of efficacy in group B. In these series, the conversion to Tac from CyA-me could be accomplished safely, with an excellent long-term outcome.
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Inmunosupresores/administración & dosificación , Trasplante de Hígado , Hígado/fisiopatología , Adulto , Anciano , Azatioprina/administración & dosificación , Ciclosporina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tacrolimus/administración & dosificaciónRESUMEN
INTRODUCTION: Among the strategies designed to optimize the number of existing liver grafts for transplantation, the implementation of the graft assessment process is one of the least explored. The main objective is to identify the risk factors presented by liver donors for «NO validity¼. Secondly, we analyzed the coincidence between the surgeon's assessment and that of the anatomo-pathologist in the invalid donors. MATERIAL AND METHOD: Retrospective study conducted from a prospective database that analyzes 190 liver donors, 95 valid and 95 NOT valid. The variables of each of them corresponding to the donation protocol of the National Transplant Organization are studied. Through a multivariate study we determine the independent risk factors of NO validity. We checked the causes of NO validity argued with the histopathological findings of these grafts. RESULTS: The independent risk factors of non-validity in the multivariate study (P < .05) were: dyslipidemia, personal medical history other than cardiovascular and abdominal surgical risk factors, GGT, BrT, and the result of previous liver ultrasound. The 3 most frequent causes of NO validity were: steatosis, fibrosis and macroscopic appearance of the organ. 78% of the biopsies confirmed the NO validity of the graft (in 57.9% of the cases the histological findings coincided with those described by the surgeon). The 22.1% of the biopsies hadnt pathological findings. CONCLUSIONS: The determination of the risk factors of NO validity will contribute to the design of future assessment scores that are useful tools in the process of liver graft assessment.).
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Trasplante de Hígado/normas , Hígado/patología , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/normas , Adulto , Anciano , Biopsia/métodos , Selección de Donante/métodos , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Femenino , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos/provisión & distribución , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricosRESUMEN
BACKGROUND: The presence of collateral circulation in liver cirrhosis patients with portal hypertension is quite frequent due to re-permeabilization of closed embryonic channels. In some cases, these shunts could measure over 1 cm wide, therefore, containing a significative blood flow. Its management during liver transplantation could be challenging due to possible complications resulting from either ligation of the shunts or from ignoring them. We present the case of a patient with recurrent hepatic encephalopathy (HE) and a large spontaneous portosystemic shunt (SPSS) who submitted to liver transplant and review the literature identifying options, complications, and outcomes with the aim of facilitating decision making. MATERIAL AND METHODS: A 68-year-old, Spanish man diagnosed with liver cirrhosis with portal hypertension and recurrent episodes of HE is proposed for LT. The patient's Child-Pugh score was A6-B7, and the Model for End-stage Liver Disease score was 12. Preoperatively, a computed tomography scan showed a large SPSS running to the inferior cava vein. During the surgery, a small-sized portal vein and a large shunt measuring almost 3 cm wide were identified. After reperfusion, portal vein flow was 1000 to 1100 mL/min. Owing to the previous HE and the risk of low portal flow, the shunt was closed increasing the portal flow to 1800 mL/min. The patient was discharged without any complications. CONCLUSIONS: The presence of large SPSSs are frequent during LT. Decision making intraoperatively can be challenging due to possible complications derived from ligation of the SPSS or from ignoring it. Either preoperative assessment of a further HE risk or portal vein flow measurement after reperfusion are essential to achieve a correct resolution.
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Encefalopatía Hepática/cirugía , Complicaciones Intraoperatorias/cirugía , Trasplante de Hígado/métodos , Vena Porta/anomalías , Malformaciones Vasculares/cirugía , Anciano , Circulación Colateral , Encefalopatía Hepática/complicaciones , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/cirugía , Complicaciones Intraoperatorias/etiología , Ligadura/efectos adversos , Ligadura/métodos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Trasplante de Hígado/efectos adversos , Masculino , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Recurrencia , Tomografía Computarizada por Rayos X , Malformaciones Vasculares/complicaciones , Vena Cava Inferior/diagnóstico por imagenAsunto(s)
Neoplasias de los Conductos Biliares/patología , Carcinoma Neuroendocrino/patología , Adulto , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares/patología , Conductos Biliares/cirugía , Carcinoma Neuroendocrino/cirugía , Conducto Colédoco/patología , Femenino , Humanos , Páncreas/patologíaRESUMEN
Between 1991 and 2013, 1,000 liver transplantations were performed at Virgen del Rocio Hospital (Seville, Spain). A retrospective study was conducted, analyzing the characteristics of recipients and donors, indications, surgical technique, complications and survival in 2 different stages (1991-2002 vs. 2003-2013) coinciding with the implementation of the MELD scale as a prioritization model. The most frequent indication were of hepatopathy of hepatocellular origin in 48.8%. There was a significant increase in the indications for hepatocarcinoma (8.6% and 24.1% P=0.03), and the rate of retransplantation (5.9% vs 9.6%, P=0.04). There was a change in the age of donation, going from 27.7 years in 1990 to 62.9 years in 2012 (P=0.001). The percentage of patients who did not require blood transfusion doubled (6.16 vs. 14.31%, P=.001). Survival of all patients after one, 5 and 10 years was 77, 63.5 and 51.3%, respectively.
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Hepatopatías/cirugía , Trasplante de Hígado , Adolescente , Adulto , Femenino , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: The greater survival of transplanted patients is accompanied by an increase in the rate of de novo malignancies (NM), which are the most frequent late-onset complication. We can distinguish between non-melanoma skin cancers (NMSC), post-transplant lymphoproliferative disorders (PTLD) and solid organ cancers (SOC). Our objective is to determine the incidence of the different types of NM, the time elapsed until diagnosis and survival rates in our setting. METHODS: We conducted a retrospective study of 1071 liver transplant patients from 1990 to 2015 at our center. We analyzed the demographic variables, incidence of NM and survival. RESULTS: 184 NM developed in 1071 transplant patients (17%), specifically 19% of the males and 13% of the females (P=.004). The most frequent NM were NMSC (29%), lung (18%), head and neck (16%), PTLD (10%) and gastrointestinal (8%). The median time of diagnosis was 7.9 years in NMSC, 3.9 years in PTLD and 9.8 years in SOC. Patients with NMSC had significantly better survival than those with PTLD or SOC. The incidence of de novo tumors (excluding NMSC) was 1889/100,000 transplants/year. By gender, lung cancer was the most common TOS in men and breast cancer in women. CONCLUSION: In our setting, excluding NMSC, the incidence is 8.8 times greater than estimations for the general population, with a high rate of lung cancer, so we should implement preventive and diagnostic strategies.
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Trasplante de Hígado , Neoplasias/epidemiología , Complicaciones Posoperatorias/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
AIM: To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. METHODS: This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic). Histological analysis (haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis (TUNEL), proliferation (Ki-67), angiogenesis (CD31) and fibrogenesis (α-SMA) were performed. When a tumour xenograft reached the target size, it was re-implanted in a new nude mouse. Three sequential tumour xenograft generations were generated (F1, F2 and F3). RESULTS: The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth (69.9%), followed by intraperitoneal (57.6%) and pancreatic (55%) models. Tumour development was faster in the subcutaneous model (17.7 ± 2.6 wk) compared with the pancreatic (23.1 ± 2.3 wk) and intraperitoneal (25.0 ± 2.7 wk) models (P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models (F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics. CONCLUSION: In our experience, the faster development and greatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.
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Adenocarcinoma/patología , Neoplasias Pancreáticas/patología , Investigación Biomédica Traslacional/métodos , Trasplante Heterólogo/métodos , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/cirugía , Estudios Prospectivos , Factores de Tiempo , Neoplasias PancreáticasAsunto(s)
Adenocarcinoma/parasitología , Ascariasis/complicaciones , Ascaris lumbricoides/aislamiento & purificación , Neoplasias Pancreáticas/parasitología , Adenocarcinoma/diagnóstico , Animales , Ascariasis/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnósticoRESUMEN
Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Dasatinib/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Compuestos Organoplatinos/farmacología , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Dasatinib/administración & dosificación , Sinergismo Farmacológico , Femenino , Humanos , Ratones , Ratones Desnudos , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Transfección , Familia-src Quinasas/metabolismoRESUMEN
We report five patients who underwent laparotomy for liver metastasis from breast cancer without extrahepatic spread, with the intention to perform liver resection. All these patients had been subjected to modified radical mastectomy following systemic chemotherapy and periodical consecutive investigations to detect distant spreading. After laparotomy, patients have been regularly followed. Case 1, right trisegmentectomy in a 53-year-old woman, 36.5 months after the mastectomy. In the 17th postoperative month she continues without relapse. Case 2, hepatic artery ligature in a 41-year-old woman, 15 months after the mastectomy. In the 17th postoperative month she died. Case 3, bisegmentectomy (VI-VII) in a 51-year-old woman, 24 months after the mastectomy. In the 17th postoperative month she died. Case 4, exploratory laparotomy in a 51-year-old woman, 91 months after the mastectomy. In the 31th postoperative month she remains alive. Case 5, segmentectomy (IV) in a 59-year-old woman, 112 months after the mastectomy. In the 33th postoperative month she continues without relapse. As a conclusion, the surgical resection of liver metastasis from breast tumors after chemotherapy must be used in selected cases.