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1.
ESMO Open ; 8(5): 101636, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37703596

RESUMO

BACKGROUND: Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC. PATIENTS AND METHODS: This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30. RESULTS: Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P = 0.036). CONCLUSIONS: Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Receptores ErbB , Ramucirumab
2.
Transplant Proc ; 50(9): 2779-2782, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401397

RESUMO

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable.


Assuntos
Enteropatias/mortalidade , Intestinos/transplante , Falência Hepática/mortalidade , Seleção de Pacientes , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Enteropatias/complicações , Enteropatias/cirurgia , Intestinos/fisiopatologia , Japão , Falência Hepática/etiologia , Masculino , Nutrição Parenteral Total/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Encaminhamento e Consulta , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/mortalidade , Síndrome do Intestino Curto/cirurgia , Taxa de Sobrevida
3.
Transplant Proc ; 50(9): 2872-2876, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30318104

RESUMO

Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT.


Assuntos
Everolimo/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Fígado/métodos , Criança , Feminino , Humanos , Doadores Vivos , Resultado do Tratamento
4.
Mucosal Immunol ; 11(2): 437-448, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28766553

RESUMO

Foxp3+ Regulatory T cells (Tregs) play a critical role in the maintenance of colon homeostasis. Here we utilized photoconvertible KikGR mice to track immune cells from the caecum and ascending (proximal) colon in the steady state and DSS-induced colitis. We found that Tregs from the proximal colon (colonic migratory Tregs) migrated exclusively to the distal part of mesenteric lymph nodes (dMLN) in an S1PR1-dependent process. In the steady state, colonic migratory CD25+ Tregs expressed higher levels of CD103, ICOS, LAG3 and CTLA-4 in comparison with pre-existing LN Tregs. Intestinal inflammation led to accelerated Treg replacement in the colon, bidirectional Treg migration from the colon to dMLN and vice versa, as well as increases in Treg number, proliferation and expression of immunosuppressive molecules. This was especially apparent for CD25 very high Tregs induced in colitis. Furthermore, colonic migratory Tregs from the inflamed colon included more interleukin (IL)-10 producing cells, and demonstrated greater inhibition of T-cell proliferation in comparison with pre-existing LN Tregs. Thus, our results suggest that Tregs with superior immunosuppressive capacity are increased both in the colon and dMLN upon inflammation. These Tregs recirculate between the colon and dMLN, and are likely to contribute to the downregulation of intestinal inflammation.


Assuntos
Colite/imunologia , Colo/imunologia , Inflamação/imunologia , Linfonodos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Movimento Celular , Células Cultivadas , Colite/induzido quimicamente , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Lisoesfingolipídeo/metabolismo , Dodecilsulfato de Sódio , Receptores de Esfingosina-1-Fosfato , Proteínas Supressoras de Tumor/genética
5.
Orthop Traumatol Surg Res ; 103(8): 1193-1196, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28928048

RESUMO

INTRODUCTION: The purpose of this study was twofold: to investigate whether edoxaban significantly decreases the rate of venous thromboembolism (VTE) following closed-wedge high tibial osteotomy (CWHTO), in terms of phlebographic event, and to determine whether edoxaban is safe or increases the rate of hemorrhagic complications. We hypothesized that edoxaban would decrease the incidence of VTE and would not increase the rate of hemorrhagic complications. MATERIALS AND METHODS: We randomly enrolled 60 patients undergoing CWHTO. The patients were divided into two groups: one group receiving edoxaban (15mg in 5 patients, 30mg in 23 patients) and a non-edoxaban group. All patients underwent computed tomography venography on day 7to diagnose postoperative VTE. Blood samples were obtained on the day before CWHTO and on postoperative days 1, 3, 7 and 14. The incidence of VTE and hemorrhagic events in both groups was compared using unpaired Student t-test or chi-square test. RESULTS: The incidence of VTE was significantly greater in the non-edoxaban group (31.3% versus 7.1%; P=0.02). The incidence of deep vein thrombosis (DVT) was also significantly greater in the non-edoxaban group (28.1% versus 3.6%; P=0.01). A single patient from the edoxaban group experienced major bleeding. On days 3 and 7, D-dimer levels were significantly lower in the edoxaban group (P=0.03 and 0.003, respectively). On days 3, 7 and 14, activated partial thromboplastin time was significantly greater in the edoxaban group (P=0.02, 0.01 and 0.006, respectively). CONCLUSION: Patients undergoing CWHTO are at risk of postoperative VTE. Edoxaban helps prevent asymptomatic phlebographic VTE and DVT following CWHTO; however, the risk of major bleeding must be considered. LEVEL OF EVIDENCE: II.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Osteotomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Inibidores do Fator Xa/efeitos adversos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/métodos , Tempo de Tromboplastina Parcial , Flebografia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Prospectivos , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Tíbia/cirurgia , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
6.
Pediatr Transplant ; 21(6)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28556594

RESUMO

Breast FA is the most common breast tumor diagnosed in young women. Female renal transplant recipients on CsA have an increased risk of developing FA. However, reports of FA after LDLT have not been described. Our objectives were to determine the incidence of FA, analyze risk factors for FA, and evaluate treatment strategies in adolescent females after LDLT. A total of 18 female patients aged 10-19 years who underwent LDLT and survived at least one year after transplantation were enrolled in our study. The incidence of FA was 11.1%. To determine pre- or post-transplant conditions that are associated with FA after transplantation, the patients were divided into two groups according to the presence or absence of FA: FA group (n=2) and non-FA group (n=16). There were no differences in mean age at LDLT, mean age at breast evaluation, and mean duration between transplantation and breast evaluation between the two groups. However, there was a difference in the immunosuppressive regimen between the two groups. The FA group was maintained on CsA, whereas the non-FA group was maintained on tacrolimus. CsA might be implicated in FA development in adolescent females after LDLT.


Assuntos
Neoplasias da Mama , Fibroadenoma , Transplante de Fígado , Doadores Vivos , Complicações Pós-Operatórias , Adolescente , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/terapia , Criança , Feminino , Fibroadenoma/diagnóstico , Fibroadenoma/epidemiologia , Fibroadenoma/etiologia , Fibroadenoma/terapia , Humanos , Incidência , Transplante de Fígado/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Oncogene ; 36(20): 2824-2834, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-27893711

RESUMO

The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained. Dormant lung cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor (TKI) treatment. In terms of mechanism, we found that a negative regulator of ERBB signaling, MIG6/ERRFI1/RALT/Gene33, was induced by hypoxia both in vitro and in vivo. MIG6 expression prevented heterodimer formation of ERBB family RTKs, and suppressed their downstream signaling. Knockdown of MIG6 enhanced tumor cell growth under hypoxic conditions, and promoted the phosphorylation of ERK and AKT via increased EGFR-HER3 binding. Critically, sensitivity to an EGFR-TKI, as well as to irradiation under hypoxic conditions, was increased in MIG6 knockdown cells. The expression of MIG6 was partly correlated with a pS6 negative zone in patient tumors. Analyses of tumor sections from 68 patients with activating EGFR mutations showed that patients with high MIG6 expression showed significantly shorter survival after EGFR-TKI treatment than other groups. Collectively, our data suggest that dormant cancer cells with a high MIG6 expression level might be one of the causes of EGFR-TKI resistance in EGFR mutant lung cancer cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Receptores ErbB/genética , Hipóxia/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Ciclo Celular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/química , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/genética , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Fosforilação , Prognóstico , Ligação Proteica , Multimerização Proteica , Transdução de Sinais , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética
8.
Transplant Proc ; 48(4): 1095-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320565

RESUMO

BACKGROUND: Pediatric living donor liver transplant (LDLT) patients sometimes develop graft fibrosis after non-recurrent diseases such as biliary atresia (BA). Donor-specific antibodies (DSA) have recently been shown to play a possible role in graft damage after liver transplantation. We report the impact of DSA on pediatric LDLT for BA patients. METHODS: Patients under age 18 years who received LDLT for BA at our institution and who had at least 5 years' follow-up were identified, and 23 were eventually enrolled in this study. Pathological findings were assessed with the use of the last available biopsy. Patients were divided into 2 groups, DSA-positive and DSA-negative. Graft fibrosis after LDLT was assessed according to DSA groups. RESULTS: The mean patient age at transplant was 2.6 years. The mean time to the last available biopsy after LDLT was 8.2 years (4.8-15.6 years); 6 patients (26%) showed no fibrosis, whereas fibrosis was graded as F1, F2, or F3 in 8 patients (35%), 8 patients (35%), and 1 patient, respectively. DSA were observed in 12 patients (52%). Moderate graft fibrosis (F2 and F3) was found in 7 (58%) of the DSA-positive group, but only 2 (18%) of the DSA-negative group, showing a statistically significant difference (P < .05). Pre-transplant cross-matching was performed in 17 patients. The 2 patients with a positive cross-match were DSA-positive. Six cross-match-negative patients developed de novo DSA after LDLT. CONCLUSIONS: Graft fibrosis was observed after LDLT for BA during long-term follow-up, more commonly in DSA-positive patients. DSA may play a role in fibrosis formation.


Assuntos
Anticorpos/metabolismo , Atresia Biliar/cirurgia , Antígenos HLA/imunologia , Cirrose Hepática/etiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adolescente , Atresia Biliar/metabolismo , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Cirrose Hepática/metabolismo , Doadores Vivos , Masculino , Complicações Pós-Operatórias/metabolismo , Fatores de Tempo , Resultado do Tratamento
9.
Transplant Proc ; 48(4): 1282-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320604

RESUMO

BACKGROUND: On the basis of a comparison of the hemolytic complement titer in pigs with that in humans, the complement system of pigs was investigated. The response of innate immunity, such as the natural antibodies, against humans was also examined. METHODS: Hemolytic complement activity of pig serum was measured with the use of a microtitration technique. CH50 was determined according to the method of Mayer. ACH50 was assayed according to the methods of Platts-Milles and Ishizaka. Hemolytic activities of C1, C4, C2, C3, C5, C8, and C9 were estimated through the use of intermediate cells and reagents, as described previously. In addition, the pig natural anti-human antibody was studied with the use of human peripheral blood mononuclear cells (PBMCs). Human PBMCs were stained with 5% pig serum, followed by staining with fluorescein isothiocyanate-labeled goat anti-pig IgG and IgM. The resulting stained cells were quantified by use of a FACScalibur system. The alternative pathway of pig complement was also measured with the use of human erythrocytes and normal pooled pig serum with or without Mg(++)EGTA. RESULTS: Both the CH50 and ACH50 titers were lower than those of humans. Concerning the components, except for C3, each component, that is, C1, C4, C2, C5, C8, and C9, was also lower than that of humans, based on measured values for human complement components. Pig serum clearly contains natural antibodies, IgG and IgM, to human PBMCs. The alternative pathway of pig complement reacted with human erythrocytes. CONCLUSIONS: As a whole, pig innate immunity, the complement system and natural antibody, recognizes the surfaces of human cells.


Assuntos
Proteínas do Sistema Complemento/imunologia , Hemólise/imunologia , Imunidade Inata/imunologia , Animais , Anticorpos Anti-Idiotípicos/metabolismo , Ativação do Complemento/imunologia , Ensaio de Atividade Hemolítica de Complemento , Proteínas do Sistema Complemento/metabolismo , Eritrócitos/imunologia , Fibronectinas/metabolismo , Humanos , Leucócitos Mononucleares/imunologia , Proteínas Recombinantes/metabolismo , Sus scrofa , Suínos
10.
Transplant Proc ; 48(4): 1285-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320605

RESUMO

The inhibitory function of HLA-G1, a class Ib molecule, on monocyte/macrophage-mediated cytotoxicity was examined. The expression of inhibitory receptors that interact with HLA-G, immunoglobulin-like transcript 2 (ILT2), ILT4, and KIR2DL4 (CD158d) on in vitro-generated macrophages obtained from peripheral blood mononuclear cells and the phorbol 12-myristate 13-acetate (PMA)-activated THP-1 cells were examined by flow cytometry. cDNAs of HLA-G1, HLA-G3, HLA-E, and human ß2-microglobulin were prepared, transfected into pig endothelial cells (PECs), and macrophage- and the THP-1 cell-mediated PEC cytolysis was then assessed. In vitro-generated macrophages expressed not only ILT2 and ILT4 but CD158d as well. The transgenic HLA-G1 on PEC indicated a significant suppression in macrophage-mediated cytotoxicity, which was equivalent to that of transgenic HLA-E. HLA-G1 was clearly expressed on the cell surface of PEC, whereas the levels of HLA-G3 were much lower and remained in the intracellular space. On the other hand, the PMA-activated THP-1 cell was less expressed these inhibitory molecules than in vitro-generated macrophages. Therefore, the HLA-G1 on PECs showed a significant but relatively smaller suppression to THP-1 cell-mediated cytotoxicity compared to in vitro-generated macrophages. These results indicate that by generating HLA-G1, but not HLA-G3, transgenic pigs can protect porcine grafts from monocyte/macrophage-mediated cytotoxicity.


Assuntos
Antígenos HLA-G/fisiologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Animais , Animais Geneticamente Modificados , Antígenos CD/metabolismo , Citocinas/metabolismo , Citotoxicidade Imunológica/fisiologia , Células Endoteliais/imunologia , Endotélio/imunologia , Citometria de Fluxo , Antígenos HLA-G/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Receptores KIR2DL4/metabolismo , Suínos , Transfecção/métodos
11.
Transplant Proc ; 48(4): 1323-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320614

RESUMO

BACKGROUND: In our previous study, we reported on the development of substituting S147C for HLA-E as a useful gene tool for xenotransplantation. In this study we exchanged the codon of HLA-Ev (147), checked its function, and established a line of transgenic mice. METHODS: A new construct, a codon exchanging human HLA-Ev (147) + IRES + human beta 2-microgloblin, was established. The construct was subcloned into pCXN2 (the chick beta-actin promoter and cytomegalovirus enhancer) vector. Natural killer cell- and macrophage-mediated cytotoxicities were performed using the established the pig endothelial cell (PEC) line with the new gene. Transgenic mice with it were next produced using a micro-injection method. RESULTS: The expression of the molecule on PECs was confirmed by the transfection of the plasmid. The established molecules on PECs functioned well in regulating natural killer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity. We have also successfully generated several lines of transgenic mice with this plasmid. The expression of HLA-Ev (147) in each mouse organ was confirmed by assessing the mRNA. The chick beta-actin promoter and cytomegalovirus enhancer resulted in a relatively broad expression of the gene in each organ, and a strong expression in the cases of the heart and lung. CONCLUSION: A synthetic HLA-Ev (147) gene with a codon usage optimized to a mammalian system represents a critical factor in the development of transgenic animals for xenotransplantation.


Assuntos
Animais Geneticamente Modificados/genética , Códon/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Actinas/genética , Animais , Animais Geneticamente Modificados/imunologia , Linhagem Celular , Citomegalovirus , Células Endoteliais/metabolismo , Elementos Facilitadores Genéticos/genética , Genes Sintéticos , Humanos , Células Matadoras Naturais/fisiologia , Macrófagos/fisiologia , Camundongos , Regiões Promotoras Genéticas/genética , Suínos , Transfecção , Transplante Heterólogo , Antígenos HLA-E
12.
Transplant Proc ; 48(1): 251-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26915877

RESUMO

BACKGROUND: Hypercalcemia has been observed in patients after liver transplantation. However, it is rare that the hypercalcemia induced disseminated tissue calcification and heart failure. CASE REPORT: We report a rare case of heart failure caused by disseminated metastatic tissue calcification that involved extensive progressive myocardial calcification after liver transplantation. A 20-year-old man with end-stage liver disease due to biliary atresia underwent ABO-incompatible living donor liver transplantation. After successful transplantation, he suffered from antibody-mediated rejection. Subsequently, ABO-matched cadaveric liver retransplantation was successfully performed. Hypercalcemia developed gradually following the second transplantation. His serum calcium level increased to 18.3 mg/dL with sudden onset of ventricular tachycardia. Although he was resuscitated with a cardiopulmonary support device, he died of heart and liver failure. Histopathologic examination revealed systemic disseminated metastatic tissue calcification, including massive myocardial calcification. CONCLUSION: Progressive worsening of hypercalcemia resulted in disseminated metastatic tissue calcification and massive metastatic myocardial calcification, which led to heart failure after liver transplantation. Because hypercalcemia after liver transplantation can cause fatal tissue calcification, early intervention for hypercalcemia should be considered.


Assuntos
Calcinose/etiologia , Cardiomiopatias/etiologia , Hipercalcemia/etiologia , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Adulto , Atresia Biliar/complicações , Incompatibilidade de Grupos Sanguíneos/complicações , Cálcio/sangue , Evolução Fatal , Rejeição de Enxerto/complicações , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/cirurgia , Insuficiência Cardíaca/etiologia , Humanos , Fígado/patologia , Falência Hepática/etiologia , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Reoperação/efeitos adversos , Reoperação/métodos , Taquicardia Ventricular/sangue , Taquicardia Ventricular/etiologia
13.
Ultrasound Obstet Gynecol ; 37(3): 277-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21337653

RESUMO

OBJECTIVES: To document outcome and to explore prognostic factors in fetal left congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study of 109 patients with prenatally diagnosed isolated left CDH born between 2002 and 2007. The primary outcome was intact discharge, defined as discharge from hospital without major morbidities, such as a need for respiratory support including oxygen supplementation, tube feeding, parenteral nutrition or vasodilators. All patients were managed at perinatal centers with immediate resuscitation, gentle ventilation (mostly with high-frequency oscillatory ventilation) and surgery after stabilization. Prenatal data collected included liver and stomach position, lung-to-head ratio, gestational age at diagnosis and presence or absence of polyhydramnios. Stomach position was classified into four grades: Grade 0, abdominal; Grade 1, left thoracic; Grade 2, less than half of the stomach herniated into the right chest; and Grade 3, more than half of the stomach herniated into the right chest. RESULTS: Overall intact discharge and 90-day survival rates were 65.1% and 79.8%, respectively. Stomach herniation was classified as Grade 0 in 19.3% of cases, Grade 1 in 45.9%, Grade 2 in 13.8% and Grade 3 in 21.1%. Multivariate analysis revealed that liver position was the strongest prognostic variable for intact discharge, followed by stomach position. Based on our results, we divided patients into three groups according to liver (up vs. down) and stomach (Grade 0-2 vs. Grade 3) position. Intact discharge rates declined significantly from liver-down (Group I), to liver-up with stomach Grade 0-2 (Group II), to liver-up with stomach Grade 3 (Group III) (87.0%, 47.4% and 9.5% of cases, respectively). CONCLUSION: Current status and outcomes of prenatally diagnosed left CDH in Japan were surveyed. Stomach herniation into the right chest was not uncommon and its grade correlated with outcome. The combination of liver and stomach positions was useful to stratify patients into three groups (Group I-III) with different prognoses.


Assuntos
Estômago/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Feminino , Idade Gestacional , Hérnia Diafragmática/diagnóstico por imagem , Hérnia Diafragmática/embriologia , Hérnia Diafragmática/mortalidade , Hérnias Diafragmáticas Congênitas , Humanos , Recém-Nascido , Japão/epidemiologia , Masculino , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Prognóstico , Respiração Artificial , Estudos Retrospectivos , Estômago/anatomia & histologia , Estômago/embriologia , Taxa de Sobrevida
14.
Eur J Pediatr Surg ; 20(1): 45-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19347806

RESUMO

A boy aged 2 years and 7 months who had undergone duodeno-duodenostomy for duodenal atresia and annular pancreas in the neonatal period presented with recurrent pancreatitis. ERCP showed an incomplete pancreas divisum associated with pancreaticobiliary maljunction. At 3 years and 8 months of age, we performed a Frey procedure in combination with total excision of the extrahepatic bile duct. The main pancreatic duct was opened in the body and the head was cored out anteriorly. The pancreaticobiliary system was reconstructed with a Roux-en-Y anastomosis. The patient has been free from symptoms with excellent weight gain in the follow-up period of 20 months. The Frey procedure can be a safe and effective operation in children with chronic pancreatitis caused by complex pancreatobiliary disorders associated with duodenal atresia.


Assuntos
Ductos Biliares Extra-Hepáticos/anormalidades , Duodeno/anormalidades , Atresia Intestinal/complicações , Pâncreas/anormalidades , Pancreatite Crônica/cirurgia , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Atresia Intestinal/diagnóstico por imagem , Masculino , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/etiologia
15.
Kyobu Geka ; 61(7): 530-2, 2008 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-18616094

RESUMO

We evaluated a new portable device (CoaguCheck XS) for measuring the prothrombin time-international normalized ratio (PT-INR) in 63 patients after cardiac surgery, and compared the results with those of the conventional method. There was a good correlation between the PT-INR values measured conventionally and those obtained with the CoaguCheck XS. This new device was easy to use, data were obtained rapidly, and the results were reliable. The CoaguCheck XS will be particularly useful for outpatients. PT-INR self-management is expected to be introduced as soon as health insurance coverage is obtained.


Assuntos
Tempo de Protrombina/instrumentação , Procedimentos Cirúrgicos Cardiovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório
16.
Kyobu Geka ; 59(2): 141-3, 2006 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-16482909

RESUMO

A 63-year-old man was diagnosed as having grade IV mitral regurgitation (MR). Intraoperative examination revealed perforation (13x7 mm) of the anterior mitral leaflet (AML) and prolapse of the posterior mitral leaflet (PML). The prolapsing part of the PML was resected as a rectangle and the AML perforation was covered with this resected PML patch. A Carpentier-Edwards rigid ring (30 mm) was used to secure the mitral valve annulus after suturing the PML. The patient had an uneventful course after surgery and postoperative echocardiography showed no regurgitation.


Assuntos
Endocardite Bacteriana/complicações , Insuficiência da Valva Mitral/cirurgia , Prolapso da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Procedimentos Cirúrgicos Cardíacos , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/etiologia , Transplante Autólogo , Resultado do Tratamento
17.
Kyobu Geka ; 58(12): 1057-62, 2005 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-16281856

RESUMO

Introduction of off-pump coronary artery bypass grafting (off-pump CABG : OPCAB) makes it possible to shorten the bypass time and cardiac arrest time in patients with both ischemic heart disease and valvular disease. This may be beneficial in patients with poor cardiac function and renal dysfunction. However, it is unclear whether such patients can tolerate the changes of hemodynamics during vertical displacement of the heart. In 3 patients who had ischemic heart disease with non-ischemic mitral regurgitation, we performed OPCAB prior to mitral valve plasty. The changes of mitral regurgitation observed by transesophageal echocardiography and several hemodynamic parameters were monitored as the heart was moved to various positions during OPCAB. When a heart positioner (Starfish) was used, hemodynamic deterioration was not observed, and there was also no aggravation of mitral regurgitation. Based on these results, we conclude that it may be possible to carry out OPCAB safely in patients with associated mitral regurgitation.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/cirurgia , Adulto , Idoso , Ecocardiografia Transesofagiana , Hemodinâmica , Humanos , Masculino , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia
18.
Pediatr Surg Int ; 21(12): 964-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16235058

RESUMO

We recently introduced the laparoscopic percutaneous extraperitoneal closure (LPEC) method for the treatment of girls with inguinal hernia. Using the LPEC method, 129 girls underwent laparoscopic herniorrhaphy. A 5 mm laparoscope was inserted via the umbilicus. A 3 mm "snake retractor" was advanced through the lateral abdominal wall to measure the length of the hernia sac and contralateral patent processus vaginalis (PPV), respectively. The hernia sac and PPV were closed at the level of the internal inguinal ring with a 2-0 non-absorbable purse-string suture using Lapaherclosure, a special 19G needle that can hold a suture at the tip. The length of the hernial sac was significantly longer than that of contralateral PPV (mean 41 mm; range 18-70 mm; P < 0.05). There were no serious complications associated with the procedure. No recurrence of hernia or metachronous contralateral hernia has been identified so far. This approach enables us to perform contralateral exploration without any additional techniques, followed by immediate and accurate closure of the hernia sac and PPV. We conclude that the LPEC method is a safe and efficacious procedure with a low recurrence rate that should be viewed as an acceptable alternative to the traditional open approach.


Assuntos
Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Laparoscopia/economia , Tempo de Internação , Recidiva , Técnicas de Sutura , Fatores de Tempo
19.
Kyobu Geka ; 58(4): 289-93, 2005 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-15828248

RESUMO

The infarct exclusion technique with a xeno-pericardial patch which Komeda and associates firstly reported in 1990 is one of the best procedure to close ventricular septal perforation. A large patch can protect the perforation and the surrounding weak tissue from the internal left ventricular pressure. However, suturing this large patch to the left ventricular wall through the small incision is not technically easy because of the patch design in the ventricle. We modified the design of the patch. This round shaped bovine pericardial patch was sutured continuously to the left ventricular wall. Then, excessive part of the patch was trimmed to make a corn shape. Finally, the corn shaped patch fit the left ventricular wall naturally.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Ruptura do Septo Ventricular/cirurgia , Idoso , Humanos , Masculino , Técnicas de Sutura
20.
J Pediatr Surg ; 39(12): 1835-7, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15616944

RESUMO

BACKGROUND/PURPOSE: Laparoscopically assisted endorectal pull-through (EPT) via a perineal approach using a prolapsing technique (PA) for Hirschsprung's disease (HD) has been reported. However, the clinical outcome after this approach has not been reported. The purpose of this study was to compare the clinical outcome of PA and the conventional transabdominal approach (TA). METHODS: In the period between 1990 and 2001, 20 cases of HD underwent EPT with TA (group O), and 21 underwent EPT with PA (group L). There was no difference in age and weight distribution between the 2 groups. Clinical outcome was assessed 3 years after surgery. RESULTS: The operation time was comparable in the 2 groups (4.9 +/- 0.8 v 5.2 +/- 0.8 hr), whereas blood loss (98 +/- 52 v 36 +/- 30 mL) and postoperative complications requiring surgical intervention (26% v 0%) were significantly lower in group L. The incidence of postoperative enteritis (27% v 28%) and voluntary defecation (more than once every/2 days) were compatible in the 2 groups (70% v 87%). Soiling (small amount of involuntary stooling; >1 per month) was significantly less frequent in group L (45% v 14%). CONCLUSIONS: Laparoscopically assisted ETP with PA is less invasive and can provide a better clinical outcome compared with TA in terms of postoperative soiling.


Assuntos
Doença de Hirschsprung/cirurgia , Laparoscopia/métodos , Abdome , Humanos , Lactente , Períneo , Reto
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