RESUMEN
BACKGROUND: Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula. METHODS: The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor). RESULTS: Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. CONCLUSION: Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevance Clinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated. Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula. Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.
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Grasa Intraabdominal/fisiopatología , Lipólisis/fisiología , Pancreatectomía/efectos adversos , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Anciano , Animales , Modelos Animales de Enfermedad , Ácidos Grasos no Esterificados/análisis , Femenino , Humanos , Lipasa/antagonistas & inhibidores , Lipólisis/efectos de los fármacos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/fisiopatología , Fístula Pancreática/prevención & control , Jugo Pancreático/fisiología , Complicaciones Posoperatorias/fisiopatología , Ratas Sprague-Dawley , Factores de RiesgoRESUMEN
Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting the small vessels that mainly presents in children and young adults. It is characterized by tissue deposition of immunoglobulin A (IgA) immune complexes with the classic manifestations of purpura, arthritis, arthralgia, and gastrointestinal and renal involvements. We report a case of HSP nephritis that occurred 2 years after living-donor liver transplantation (LDLT). After pulse steroid administration, the patient's symptoms disappeared and blood markers normalized. To the best of our knowledge, this is the first HSP case to be reported in a liver transplant recipient.
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Vasculitis por IgA/etiología , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias , Glomerulonefritis por IGA/etiología , Glomerulonefritis por IGA/patología , Humanos , Vasculitis por IgA/patología , Donadores Vivos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/patologíaRESUMEN
BACKGROUND: There has been no public structured training program for transplant surgeons in Japan. However, such a program is crucial for optimizing liver transplant surgery and training young professionals in liver transplant surgery. A comprehensive training program was recently developed and the underlying concepts, structure and curriculum, and results of this program are described here. METHODS: We developed a 3-year training program in 2014 called the Six National University Consortium in Liver Transplant Professionals Training (SNUC-LT) program supported by the Ministry of Education, Culture, Sports, Science, and Technology. This program is based on strong cooperation among 6 national universities (Kumamoto, Okayama, Nagasaki, Kanazawa, Niigata, and Chiba Universities). The program includes various courses to help trainees learn transplant theory and practice as well as to teach surgical skills required to safely perform transplant surgery. RESULTS: Three trainees completed the specially designed 3-year curriculum. They attended lectures on transplant theory for an average of 59 hours and participated in an average of 44 liver transplant surgeries and 51 liver resections for transplant practice. Trainees from low-volume centers had sufficient opportunities to attend operations in high-volume centers because of the cooperative agreement among the universities. After finishing the program, the trainees were certified as talent-proven liver transplant surgeons. CONCLUSIONS: The SNUC-LT program is the first national program in Japan to have strong professional support. Our multicenter program enables young surgeons to have more abundant knowledge, more extensive experience, better surgical skills, and smoother communication skills in the field of liver transplantation.
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Educación de Postgrado en Medicina/métodos , Trasplante de Hígado/educación , Desarrollo de Programa , Cirujanos/educación , Curriculum , Humanos , Japón , UniversidadesRESUMEN
Arterial dissection is a rare complication after liver transplantation (LT). We report a case of extensive isolated spontaneous celiac trunk dissection (ISCTD) up to the proper hepatic artery, left gastric artery, and splenic artery after living donor liver transplantation. A 48-year-old woman with cryptogenic liver cirrhosis underwent living donor liver transplantation. Intraoperative and postoperative Doppler ultrasound revealed sufficient flow in the hepatic artery, portal vein, and hepatic vein. On postoperative day (POD) 10, Doppler ultrasound showed reduction of hepatic arterial flow. On POD 16, a contrast-enhanced computed tomography scan showed that the ISCTD extended to the proper hepatic artery, left gastric artery, and splenic artery with an entry tear on the proximal side of the celiac trunk. Although the computed tomography scan showed ischemia of a small part of the liver, blood flow to the liver was kept to some extent. Because all false lumens were occluded by thrombi and the liver enzyme levels normalized, we chose conservative therapy with antiplatelet agents. The patient was discharged on POD 53. She remains well without any liver dysfunction after 18 months with reduction in all false lumens and a patent hepatic artery. Several cases of ISCTD have been reported apart from LT, most of which were treated with conservative therapy. We conclude that conservative therapy could be the first choice in ISCTD even after LT.
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Disección Aórtica/terapia , Arteria Celíaca , Embolización Terapéutica , Trasplante de Hígado/efectos adversos , Adulto , Disección Aórtica/diagnóstico por imagen , Angiografía , Arteria Celíaca/diagnóstico por imagen , Femenino , Humanos , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Ultrasonografía DopplerRESUMEN
BACKGROUND: Colon cancer accompanying decompensated liver cirrhosis is a rare clinical condition. Usually, treatment of colon cancer is prioritized, with cirrhosis dealt with later. CASE REPORT: We present a case of end-stage liver disease due to nonalcoholic steatohepatitis evaluated for living donor liver transplant. During the pretransplant examination, an ascending colon cancer was detected. Liver function was too poor to perform colon resection first. Simultaneous living donor liver transplant and colonic resection were carried out. The patient developed left lung metastasis at 2 different times during the first postoperative year, and both of them were resected. The patient received the standard chemoradiotherapy. Now, the patient is alive at 42 months postprocedure and recurrence-free at 31 months postoperatively. CONCLUSION: Simultaneous liver transplantation and colon resection are possible with acceptable long-term outcomes. Immunosuppressive therapy after transplantation increases the risk for cancer recurrence. So the patient should undergo close surveillance.
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Colectomía/métodos , Neoplasias del Colon/cirugía , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Enfermedad del Hígado Graso no Alcohólico/cirugía , Neoplasias del Colon/complicaciones , Terapia Combinada , Enfermedad Hepática en Estado Terminal/etiología , Femenino , Humanos , Donadores Vivos , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Resultado del TratamientoRESUMEN
Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), an effective drug for disseminated intravascular coagulation, is also known to exhibit an anti-inflammatory effect through binding to the high-mobility group box 1 protein (HMGB-1) known as a proinflammatory mediator. We examined the effect of recombinant human TM (rTM) on a partial warm hepatic IRI model in wild-type (WT) and toll-like receptor 4 (TLR-4) KO mice focusing on the HMGB-1/TLR-4 axis. As in vitro experiments, peritoneal macrophages were stimulated with recombinant HMGB-1 protein. The rTM showed a protective effect on liver IRI. The rTM diminished the downstream signals of TLR-4 and also HMGB-1 expression in liver cells, as well as release of HMGB-1 from the liver. Interestingly, neither rTM treatment in vivo nor HMGB-1 treatment in vitro showed any effect on TLR-4 KO mice. Parallel in vitro studies have confirmed that rTM interfered with the interaction between HMGB-1 and TLR-4. Furthermore, the recombinant N-terminal lectin-like domain 1 (D1) subunit of TM (rTMD1) also ameliorated liver IRI to the same extent as whole rTM. Not only rTM but also rTMD1 might be a novel and useful medicine for liver transplantation. This is the first report clarifying that rTM ameliorates inflammation such as IRI in a TLR-4 pathway-dependent manner.
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Inflamación/prevención & control , Hígado/irrigación sanguínea , Daño por Reperfusión/complicaciones , Trombomodulina/uso terapéutico , Receptor Toll-Like 4/metabolismo , Animales , Inflamación/etiología , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de SeñalRESUMEN
The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.
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Hígado Graso/fisiopatología , Preservación de Órganos , Daño por Reperfusión , Índice de Severidad de la Enfermedad , Animales , Trasplante de Hígado , Masculino , Consumo de Oxígeno , Perfusión , Ratas , Ratas WistarRESUMEN
PURPOSE: This study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival in patients with initially unresectable colorectal liver metastases (CRLM). METHODS: We reviewed the literature of prospective, controlled trials of systemic chemotherapy for patients with unresectable liver-only CRLM, including resectable extrahepatic metastases. Pearson's correlation coefficients were calculated. RESULTS: A total of 26 patient groups from 18 studies were reviewed. The response rate was significantly correlated with the conversion rate (r = 0.66) and R0 resection rate (r = 0.43) in overall patients. In subgroup analysis, only the conversion rate in patients with chemotherapy only (r = 0.75) and anti-EGFR therapy (r = 0.78) were significantly strongly correlated with the response rate. A non-significant strong trend toward correlation between response and conversion rates was observed in patients with bevacizumab (r = 0.73, p = 0.10). The regression line in the scatter plot of patients using bevacizumab showed a less steep slope. This indicated that conversion rates were relatively less affected by response rates under anti-VEGF therapy compared with the other patient groups. The response rate in chemotherapy-only patients was significantly correlated with median progression-free survival (r = 0.61) and overall survival (r = 0.66). CONCLUSIONS: Chemotherapy without molecular target agents and with anti-EGFR agents shows similar results of correlation between response and conversion/R0 resection rates. Under anti-VEGF therapy, conversion would be expected, even with a relatively lower response rate.
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Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma/secundario , Cetuximab/uso terapéutico , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Hepatectomía , Humanos , Neoplasias Hepáticas/secundario , Metastasectomía , Terapia Molecular Dirigida , Panitumumab , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
The factors that influence long-term outcomes after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC) are not well known. Compared with deceased-donor transplantation, LDLT has an increased likelihood of a related donor and a decreased number of human leukocyte antigen (HLA) mismatches. To clarify the effects of donor relatedness and HLA mismatch on the outcomes after LDLT, we retrospectively analyzed 444 Japanese patients. Donors were blood relatives for 332 patients, spouses for 105, and "other" for 7. The number of HLA A-B-DR mismatches was none to two in 141, three in 123, and four to six in 106 patients. The 15-year survival rate was 52.6%, and PBC recurred in 65 patients. Recipient aged 61 years or older, HLA mismatches of four or more (maximum of six), graft:recipient weight ratio less than 0.8, and husband donor were adverse indicators of patient survival. IgM 554 mg/dL or greater, donor-recipient sex mismatch, and initial immunosuppression with cyclosporine were significant risks for PBC recurrence, which did not affect patient survival. In subgroup analysis, conversion to cyclosporine from tacrolimus within 1 year diminished recurrence. Prospective studies are needed to determine the influence of pregnancy-associated sensitization and to establish an optimal immunosuppressive regimen in LDLT patients.
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Rechazo de Injerto/prevención & control , Antígenos HLA/inmunología , Inmunosupresores/uso terapéutico , Cirrosis Hepática Biliar/cirugía , Trasplante de Hígado , Donadores Vivos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Japón , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
This nationwide survey investigated the actual practices for supporting and confirming the decision-making involved in related living-organ donations in Japan, focusing on organ type and program size differences. Answers to a questionnaire survey were collected from 89 of the 126 (71%) kidney and 30 of the 35 (86%) liver transplantation programs in Japan that were involved in living-donor transplantations in 2013. In 70% of the kidney and 90% of the liver transplantation programs, all donors underwent "third-party" interviews to confirm their voluntariness. The most common third parties were psychiatrists (90% and 83%, respectively). Many programs engaged in practices to support decision-making by donor candidates, including guaranteeing the right to withdraw consent to donate (70% and 100%, respectively) and prescribing a set "cooling-off period" (88% and 100%, respectively). Most donors were offered care by mental health specialists (86% and 93%, respectively). Third parties were designated by more of the larger kidney transplant programs compared with the smaller programs. In conclusion, the actual practices supporting and confirming the decision to donate a living organ varied depending on the organ concerned and the number of patients in the program.
Asunto(s)
Toma de Decisiones , Familia/psicología , Trasplante de Riñón/psicología , Trasplante de Hígado/psicología , Donadores Vivos/psicología , Obtención de Tejidos y Órganos/métodos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Adulto , Actitud Frente a la Salud , Femenino , Estudios de Seguimiento , Humanos , Japón , Masculino , Motivación , Pronóstico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Our previous work revealed that the recipients with the highest pre-existing numbers of CD8(+) effector T cells (TE ) [hyperparathyroidism (HPT)E recipients] occupied approximately 30% of adult transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre-existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty-one HPTE recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow-up until post-operative day 2000. Regarding the immunological mechanism, in type 1 TE perforin and interferon (IFN)-γ were generated through the self-renewal of CD8(+) central memory T cells (TCM ), but decreased in the early post-transplant period due to marked down-regulation of interleukin (IL)-12 receptor beta-1 of TCM. In type 2, the self-renewal TCM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL-12Rß1(+) TCM levels, and increased at the highest level around the pre-transplant levels of IL-12Rß1(+) TCM . However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.
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Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Metilprednisolona/efectos adversos , Ácido Micofenólico/análogos & derivados , Linfocitos T Citotóxicos/efectos de los fármacos , Tacrolimus/uso terapéutico , Anciano , Femenino , Expresión Génica , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Hiperparatiroidismo/inmunología , Hiperparatiroidismo/mortalidad , Hiperparatiroidismo/patología , Hiperparatiroidismo/cirugía , Memoria Inmunológica , Interferón gamma/genética , Interferón gamma/inmunología , Donadores Vivos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Perforina/genética , Perforina/inmunología , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Donante no EmparentadoRESUMEN
BACKGROUND: Herpes zoster (HZ) is the most common manifestation of latent varicella zoster virus reactivation, which occurs naturally as a result of aging or in immunocompromised patients. Solid organ transplant recipients are at increased risk for HZ owing to their chronic immunosuppression. Although several reports investigated risk factors for the development of HZ in heart or renal transplantation, data in liver transplantation (LT) are limited. METHODS: We evaluated clinical data retrospectively in 377 adult patients undergoing LT between January 2005 and December 2012 in our institution. We analyzed the incidence rate of HZ and the standardized incidence ratio (SIR) by comparing with the general Japanese population. We additionally investigated risk factors for HZ after LT. RESULTS: HZ developed in 27 (7.16%) of the 377 patients after LT. The incidence rate of HZ after LT was 17.83 per 1000 person-years, which was significantly higher than in the general Japanese population (SIR = 4.61; 95% confidence interval [CI], 4.13-5.14). Multivariate analysis showed that older age (hazard ratio [HR] = 3.95; P < 0.001) and exposure to mycophenolate mofetil (HR = 3.03; P = 0.007) were independent risk factors for HZ after LT. CONCLUSIONS: This is the first and largest study, to our knowledge, to investigate the incidence rate of HZ and risk factors for development of HZ after LT in the Japanese population. Further investigations to focus on immunosuppressive regimens to reduce the risk for HZ incidence in this high-risk population could establish a new protocol of immunosuppression after LT.
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Herpes Zóster/etiología , Huésped Inmunocomprometido , Trasplante de Hígado , Infecciones Oportunistas/etiología , Complicaciones Posoperatorias/etiología , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Herpes Zóster/epidemiología , Herpes Zóster/inmunología , Humanos , Terapia de Inmunosupresión/efectos adversos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Cuidados Posoperatorios/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/inmunología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.
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Carcinoma Hepatocelular/radioterapia , Fallo Hepático/cirugía , Neoplasias Hepáticas/radioterapia , Trasplante de Hígado , Donadores Vivos , Recurrencia Local de Neoplasia/radioterapia , Terapia Recuperativa , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Terapia Combinada , Humanos , Fallo Hepático/etiología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/cirugíaRESUMEN
This study aimed to investigate the role of initial priming of interleukin (IL)-12 receptor beta-1 in CD8(+) central memory T cells (initial IL-12RTCM priming) and CCR7-negative subsets (CNS) in effector cell expansion and clinical outcome after living donor liver transplantation (LDLT). One hundred and six patients who underwent LDLT were classified into the following three groups according to hierarchical clustering of CD8(+) CD45 isoforms before LDLT: I, naive-dominant; II, effector memory-dominant; and III, effector-dominant. The pre-existing CD8(+) effector cells (TE ) and activated immune status increased progressively from group I to group II to group III. Groups I, II and III received tacrolimus (Tac)/glucocorticoid (GC) regimens. Eighteen group III recipients received Tac/mycophenolate mofetil (MMF) and were defined as group IV. Initial IL-12RTCM priming was slightly, moderately and markedly decreased in droups I, II, and III, respectively. Initial priming of IL-12Rß1 in CNS was decreased markedly in the three groups with marked decreases of TE , perforin and interferon (IFN)-γ; all parameters were restored by up-regulation of IL-12Rß1(+) TCM through the self-renewal of TCM . The lag time required until coupled up-regulation of IL-12Rß1 of TCM and CNS to above baseline was 12, 20 and 32 days in groups I, II and III, respectively. Inferior clinical outcomes were associated with increasing lag time. In contrast, the initial priming of IL-12Rß1 in TCM and CNS remained above baseline in group IV due to MMF-mediated increase of IL-12Rß1. Early coupled up-regulation of TCM and CNS leads to efficient TE differentiation and optimal clinical outcomes.
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Antígenos CD8/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Receptores de Interleucina-12/inmunología , Linfocitos T Citotóxicos/inmunología , Tacrolimus/uso terapéutico , Adulto , Antígenos CD8/genética , Diferenciación Celular/efectos de los fármacos , Femenino , Expresión Génica , Glucocorticoides/uso terapéutico , Humanos , Memoria Inmunológica/efectos de los fármacos , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Antígenos Comunes de Leucocito/genética , Antígenos Comunes de Leucocito/inmunología , Hígado/inmunología , Hígado/patología , Hígado/cirugía , Donadores Vivos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Perforina/genética , Perforina/inmunología , Receptores CCR7/deficiencia , Receptores CCR7/genética , Receptores CCR7/inmunología , Receptores de Interleucina-12/agonistas , Receptores de Interleucina-12/genética , Linfocitos T Citotóxicos/efectos de los fármacos , Factores de Tiempo , Receptores de Trasplantes , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
BACKGROUND: Severe sepsis is a life-threatening complication after liver transplantation (LT) that can be difficult to diagnose and appropriately treat after LT because of patients being treated with immunosuppressants. The present study examines perioperative changes in serum procalcitonin (PCT), a specific marker of systemic bacterial infection, and determines the value of PCT as a diagnostic tool for bacteremia or rejection. METHODS: Perioperative serum PCT levels were prospectively assessed in 104 consecutive adult patients undergoing LT (living-donor LT, n = 90; deceased-donor LT, n = 14) between May 2010 and August 2012. RESULTS: Serum PCT levels remarkably increased soon after LT and gradually decreased thereafter, but were not increased in patients diagnosed with cytomegalovirus infection or acute cellular rejection. Serum PCT levels in patients who underwent deceased-donor LT were significantly higher than in those who underwent living-donor LT until postoperative day (POD) 7. Serum PCT levels were significantly higher in patients with bacteremia than in those without bacteremia after POD 14. In patients with post-transplant bacteremia, PCT levels increased again after POD 7 in patients who died within 3 months of LT, while levels remained low after POD 7 in patients who were alive. A positive predictive value of 83.3% for bacteremia and a negative predictive value of 97.4% were obtained at PCT cutoffs of 2.0 and 0.5 ng/mL, respectively. CONCLUSION: Serum PCT measurement, using appropriate cutoff values, could help diagnose severe infection, and might be able to differentiate bacteremia from acute cellular rejection.
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Bacteriemia/sangre , Calcitonina/sangre , Rechazo de Injerto/sangre , Trasplante de Hígado/efectos adversos , Precursores de Proteínas/sangre , Adulto , Anciano , Bacteriemia/diagnóstico , Biomarcadores/sangre , Péptido Relacionado con Gen de Calcitonina , Infecciones por Citomegalovirus/sangre , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Humanos , Inmunidad Celular , Hepatopatías/cirugía , Donadores Vivos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry. METHODS: Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months. RESULTS: Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level ≥0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function. CONCLUSIONS: Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos , Adulto , Anciano , Péptido C/sangre , Muerte Súbita Cardíaca , Diabetes Mellitus Tipo 1/sangre , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Supervivencia de Injerto , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: The prognosis of intestinal failure has improved dramatically in the past few decades with the development of parenteral nutrition (PN). However, PN-dependent patients still have numerous complications. Intestinal transplantation can significantly improve their prognosis and quality of life. We report on the impact of intestinal transplantation for intestinal failure in Japan. METHODS: Intestinal transplantations have been performed in Japan since 1996. Standardized forms were sent to all known intestinal transplantation programs, asking for information on intestinal transplantations performed between 1996 and June 31, 2012. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method and analyzed with the Wilcoxon statistic. RESULTS: Five institutions provided data on 24 grafts in 21 patients. There were 12 cadaveric and 12 living related donor transplants. Causes of intestinal failure included short gut syndrome (n = 9), intestinal motility function disorders (n = 11), retransplantation (n = 3), and other (n = 1). The overall 1- and 5-year patient survival rates were 86% and 68%, respectively. In cases (n = 15) after 2006, the 1-year patient survival rate was 92%, and the 5-year survival rate was 83%. One- and five-year graft survival rates were 87% and 78%, respectively. More than 80% of all current survivors discontinued PN. CONCLUSIONS: Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN. After 2006, patient and graft survival rates approached rates associated with standard treatment for end-stage intestinal failure. Further improvements are expected with early referral due to suitable donor organ and pretransplant management.
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Enfermedades Intestinales/cirugía , Intestinos/trasplante , Donadores Vivos , Femenino , Supervivencia de Injerto , Humanos , Enfermedades Intestinales/mortalidad , Japón/epidemiología , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
BACKGROUND: Hepatic arterial reconstruction during living donor liver transplantation (LDLT) is a very delicate and technically complicated procedure. Post-LDLT hepatic arterial complications are associated with significant morbidity and mortality. METHODS: We retrospectively analyzed the details of post-operative hepatic arterial complications in 673 consecutive adult LDLT recipients between January 1996 and September 2009. RESULTS: Hepatic arterial complications occurred in 43 of 673 adult recipients (6.4%) within a median of 13 post-transplant days (range, 1-63). These included hepatic artery thrombosis (including anastomotic stenosis) in 33 cases, anastomotic bleeding in seven cases, and rupture of anastomotic aneurysm in three cases. To treat these complications, surgical re-anastomosis was performed in 26 cases, while the other 17 cases underwent conservative therapies, including four angioplasties by interventional radiology. Biliary complications after hepatic arterial complications occurred in 17 cases. The overall survival rate after LDLT was significantly lower in the hepatic arterial complication group compared with that in the non-complication group (60.7% vs. 80.1% at one yr, 44.3% vs. 74.2% at five yr, respectively; p < 0.001). Multivariate analysis showed that the extra-anatomical anastomosis (p = 0.011) was the only independent risk factor for hepatic arterial complications. CONCLUSION: Because hepatic arterial complications after LDLT are associated with poor patient survival, early diagnosis and immediate treatment are crucial. The anatomical anastomosis may be the first choice for the hepatic arterial reconstruction to the extent possible.
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Arteriopatías Oclusivas/etiología , Arteria Hepática/cirugía , Trasplante de Hígado , Donadores Vivos , Complicaciones Posoperatorias , Adolescente , Adulto , Anciano , Anastomosis Quirúrgica/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes , Adulto JovenRESUMEN
INTRODUCTION: Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. MATERIALS AND METHODS: Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. RESULTS: The risk factors for early outcome of the recipients were cold ischemia time (≥ 10 hours), Model for End-stage Liver Disease score (≥ 20), and donor age (≥ 55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. CONCLUSION: The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.