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1.
Hepatol Res ; 54(3): 300-314, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37850337

RESUMEN

AIM: To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors. METHODS: A total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd-cfDNA levels after LTx. Fifty-five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy-proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd-cfDNA were quantified using a next-generation sequencer based on single nucleotide polymorphisms. RESULTS: The dd-cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post-LTx. The dd-cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] ≥3) versus PB and versus non-AR (ADWR + PB). The dd-cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd-cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor-specific antibodies in PB samples. CONCLUSIONS: Donor-derived cell-free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large-scale cohort studies are warranted to optimize its use in differentiating various post-LTx etiologies.

2.
J Infect Chemother ; 25(7): 537-542, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30905632

RESUMEN

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and developing active tuberculosis. QuantiFERON®-TB Gold Plus (QFT-Plus) has two TB-specific antigens tubes (TB1 and TB2). TB1 elicits CD4 T-cell response, and TB2 elicits both CD4 and CD8 T-cells responses, with expected increased sensitivity. The aim of this study was to estimate the prevalence of LTBI in renal transplant recipients in Japan. We conducted a cross-sectional study by using two interferon-γ release assays (IGRAs), QFT-Plus and T-SPOT®.TB (TSPOT). One hundred thirty-five recipients were prospectively enrolled. The median age was 49 years (range: 20 to 79). The positivity rates of QFT-Plus and TSPOT were 5.9% (95%CI 3.0-11.3) and 3.7% (95%CI 1.6-8.4), respectively, with no significant difference. The concordance rate was 95.5% (κ coefficient, 0.76). Age of 60 years and higher was related to the higher positivity rate in both QFT-Plus and TSPOT. The positivity rates of TB1 and TB2 were 5.1% (95%CI 2.5-10.2) and 5.9% (95%CI 3.0-11.2), respectively, with no significant difference. The concordance rate was 99.3% (κ coefficient, 0.93). TB2 did not show a higher positivity rate compared with TB1. The estimated prevalence of LTBI by using the both IGRAs was 3.7-5.9% in renal transplant recipients. These results were equivalent to the IGRAs positivity rate in the general Japanese population, even under the condition of immunosuppressive therapy. In consideration of the higher risk of developing active TB from LTBI, we can use both IGRAs as acceptable tools for LTBI diagnosis in renal transplant recipients.


Asunto(s)
Ensayos de Liberación de Interferón gamma/estadística & datos numéricos , Trasplante de Riñón/efectos adversos , Tuberculosis Latente/epidemiología , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Antígenos Bacterianos/inmunología , Estudios Transversales , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Huésped Inmunocomprometido , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Japón/epidemiología , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Adulto Joven
3.
Circ J ; 82(8): 2165-2174, 2018 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-29877199

RESUMEN

BACKGROUND: The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. CONCLUSIONS: In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.


Asunto(s)
Leucocitos Mononucleares/trasplante , Enfermedad Arterial Periférica/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Anciano , Arteriosclerosis Obliterante/complicaciones , Progresión de la Enfermedad , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/etiología , Supervivencia sin Progresión , Tromboangitis Obliterante/complicaciones , Trasplante Autólogo
4.
Nephrology (Carlton) ; 23 Suppl 2: 70-75, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29968417

RESUMEN

AIM: Arteriolar hyalinosis (AH) is a common lesion in allograft biopsies taken following kidney transplantation. Recent studies have shown that severe AH may predict transplant outcomes and provide information about previous exposure to certain drugs, such as calcineurin inhibitors (CNI). However, the incidence of AH as a direct result of diabetic nephropathy (DN) after kidney transplantation has not been fully evaluated. This study aimed to assess the impact of primary DN on the development of AH lesions in patients who underwent kidney transplantation. METHODS: Eighty-three patients who underwent living-donor kidney transplantation between April 2005 and June 2015 were enrolled in this study. A total of 33 patients had DN prior to transplantation. Allograft biopsies were scored according to the Banff classification, and the relationship between the individual histological lesions and clinical baseline data was assessed. RESULTS: At early biopsy (3-12 months), there were no differences in the rates of AH lesions between the DN group and the non-DN group (ah ≥ 1: 37% vs. 41.3%, P = 0.719; aah ≥ 1: 14.8% vs. 6.5%; P = 0.453). However, there were significant differences between the groups in biopsies taken more than 3 years after the transplant (ah ≥ 2: 83.3% vs. 36.8%, P = 0.013; aah ≥ 2: 66.7% vs. 21.1%, P = 0.011). Multivariable analysis showed that both the length of time after transplantation and the presence of DN were independent risk factors for ah ≥ 2 (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.47-19.54, P = 0.011) and aah ≥ 2 (OR: 7.55, 95% CI: 1.49-38.33, P = 0.015). CONCLUSION: This is the first report showing that the presence of primary DN disease contributes to the development of severe AH late in the course after kidney allografts.


Asunto(s)
Arteriolas/química , Nefropatías Diabéticas/epidemiología , Hialina , Trasplante de Riñón/efectos adversos , Riñón/irrigación sanguínea , Enfermedades Vasculares/metabolismo , Adulto , Anciano , Aloinjertos , Arteriolas/patología , Biopsia , Distribución de Chi-Cuadrado , Nefropatías Diabéticas/patología , Femenino , Humanos , Incidencia , Japón/epidemiología , Trasplante de Riñón/métodos , Donadores Vivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/patología
5.
J Infect Chemother ; 23(7): 468-473, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28438462

RESUMEN

Renal transplant recipients are at increased risk of reactivating latent tuberculosis infection (LTBI) and progressing to active tuberculosis (TB). This study was conducted in National hospital for tuberculosis and renal transplantation (RT) in Japan. The purpose is to compare two interferon-γ release assays (IGRAs), QuantiFERON®-TB Gold in Tube (QFT) and T-SPOT®.TB (TSPOT), in patients after renal transplantation for detecting latent TB infection (LTBI). Total 92 renal transplant recipients (median age 46 years, range 17-75) were prospectively enrolled, and QFT and TSPOT were concurrently examined. Total subjects were 92 patients (median age 46 years, range 17-75). The positive rate in QFT and TSPOT were 6.5% (95% confidence interval (CI) 3.0-13.5) and 2.2% (95% CI 1.0-7.6), respectively. There was a significant difference in IGRAs positivity (P < 0.05). The negative rate in QFT and TSPOT were 91.3% (95% CI 83.8-95.5) and 95.7% (95% CI 89.3-98.3), respectively. There was no significant difference in IGRAs negativity. No patients among either IGRAs negative patients developed active TB during median follow-up of 994 days. Neither QFT nor TSPOT reaches estimated TB infection rate in Japan, especially elderly recipients aged 60 year-old or more. Therefore, both IGRAs might underestimate LTBI owing to immune suppressive therapy and aging. Physicians for renal transplantation need to understand the characteristics of both IGRAs and pay attention to the possibility of developing active TB even in patients of negative IGRAs results.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/normas , Trasplante de Riñón , Tuberculosis Latente/diagnóstico , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Huésped Inmunocomprometido , Interferón gamma/inmunología , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Adulto Joven
6.
Nephrology (Carlton) ; 20 Suppl 2: 93-5, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26031597

RESUMEN

Here, we report a case of focal segmental glomerular sclerosis (FSGS) recurrence immediately (47 minutes) after transplantation. A 1-hour biopsy specimen showed large periodic acid-Schiff-positive granules within the cells of the swollen proximal tubule, while electron microscopy revealed podocyte swelling and partial foot process effacement. These findings were worse on day 2 biopsy. Massive proteinuria and anuria were then observed. Two courses (2 × 2 times) of plasmapheresis and rituximab were administered, and the graft function gradually recovered. A day 22 biopsy specimen showed improvement in findings compared to those observed on day 2. One year after transplantation, no signs of FSGS recurrence are evident, and graft function remains good.


Asunto(s)
Anuria/etiología , Glomeruloesclerosis Focal y Segmentaria/cirugía , Trasplante de Riñón/efectos adversos , Riñón/patología , Proteinuria/etiología , Anuria/diagnóstico , Anuria/fisiopatología , Anuria/terapia , Biopsia , Femenino , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Riñón/ultraestructura , Túbulos Renales Proximales/patología , Microscopía Electrónica , Persona de Mediana Edad , Plasmaféresis , Podocitos/ultraestructura , Proteinuria/diagnóstico , Proteinuria/fisiopatología , Proteinuria/terapia , Recuperación de la Función , Recurrencia , Rituximab/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
7.
Int Surg ; 96(2): 111-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22026300

RESUMEN

This single-institution experience retrospectively reviewed the outcomes in 21 patients with primary duodenal adenocarcinoma. Twelve patients underwent curative surgery, and 9 patients underwent palliative surgery at the Chiba University Hospital. The maximum follow-up period was 8650 days. All pathologic specimens from endoscopic biopsy and surgical specimens were reviewed and categorized. Twelve (57.1%) patients underwent curative surgery (R0): 4 pancreaticoduodenectomies (PD), 4 pylorus-preserving PDs (PpPD), 2 local resections of the duodenum and 2 endoscopic mucosal resections (EMR). Palliative surgery was performed for 9 patients (42.9%) following gastro-intestinal bypass. The median cause-specific survival times were 1784 days (range 160-8650 days) in the curative surgery group and 261 days (range 27-857 days) in the palliative surgery group (P = 0.0003, log-rank test). The resectability of primary duodenal adenocarcinoma was associated with a smaller tumor size, a lower degree of tumor depth invasiveness, and less spread to the lymph nodes and distant organs.


Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Neoplasias Duodenales/mortalidad , Neoplasias Duodenales/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/patología , Duodeno/cirugía , Femenino , Humanos , Mucosa Intestinal/cirugía , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Cuidados Paliativos , Pancreaticoduodenectomía/métodos
8.
Nihon Rinsho ; 68(12): 2291-5, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21174694

RESUMEN

Kidney transplantation has been established to be the therapy for an end-stage renal disease. In Japan, living donor kidney transplantation is frequently performed (> 80%) because of a shortage of the deceased donors. The graft survival has been improved to 93.4% (5-year graft survival in living donor kidney transplantation after 2001). ABO-incompatible cases are increasing and more than 20% are ABO-incompatible in Japan (30% in our institution). In our institution, 225 kidney transplantations (182: living donors, 43: deceased donors) have been performed from 2004.4 to 2010.6. Although the graft survival is excellent, posttransplant infections including cytomegalovirus, EB virus and BK virus are problems which should be solved. For the safety of the recipients, we should use kidney grafts from brain-dead donors.


Asunto(s)
Trasplante de Riñón/tendencias , Muerte Encefálica , Humanos , Japón , Donadores Vivos , Complicaciones Posoperatorias
9.
J Hepatobiliary Pancreat Surg ; 16(2): 124-30, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19165415

RESUMEN

INTRODUCTION: The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems. METHODS: Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan. RESULTS: Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness. CONCLUSIONS: Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos/métodos , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Anciano , Péptido C/sangre , Cadáver , Niño , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión/métodos , Japón , Masculino , Persona de Mediana Edad , Preservación de Órganos , Selección de Paciente , Donantes de Tejidos
10.
Clin Med Insights Case Rep ; 12: 1179547619867330, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31391783

RESUMEN

Epstein-Barr virus (EBV) infection might induce not only posttransplantation lymphoproliferative disorder (PTLD) but also leiomyosarcoma. We report a case of EBV-associated leiomyosarcoma concurrently with PTLD after renal transplantation. The patient was a 30-year-old woman who underwent living donor kidney transplantation at 27 years of age. Preoperative EBV viral capsid antibody immunoglobulin M, immunoglobulin G (IgG), and EBV nuclear antigen IgG were negative. Multiple lung and liver tumors were detected 1.5 years after transplantation. She was diagnosed with PTLD after tumor biopsy. Her EBV DNA was 110 copies/mL detected by real-time polymerase chain reaction when PTLD was diagnosed. She received dose reduction of immunosuppressive therapy and several chemotherapies. Because her hepatic lesion was still progressive while pulmonary lesion was reduced, a liver tumor biopsy was performed, but the biopsy specimens were necrotic. A left lateral segmentectomy was performed as a third biopsy for treatment-resistant hepatic lesion 2.5 years after her first PTLD diagnosis. Pathologically, she was diagnosed with EBV-associated leiomyosarcoma. She was treated with sirolimus, but died 7 months after the operation. This is the first case of the coincidence of leiomyosarcoma associated with EBV and PTLD. This case was exceedingly rare; however, we must consider the coincidence of leiomyosarcoma associated with EBV and PTLD when encountering treatment-resistant PTLD.

11.
Hum Mutat ; 29(5): 703-8, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18320596

RESUMEN

Integration of hepatitis B virus (HBV) DNA into host DNA is detected in about 90% of HBV-related hepatocellular carcinoma (HCC), but the preferential sites of the viral integration etiologically relevant to oncogenesis have been controversial. By using an adaptor-ligation/suppression-PCR, we identified four integrations into the myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4) gene from 10 HCC patients with positive HBV surface antigen (HBsAg). Determination of the cellular-virus DNA junction demonstrated that various lengths of the virus were integrated within 300 bp of intron 3 flanked by the Alu element of MLL4. Chimeric hepatitis B virus X gene (HBx)/MLL4 transcripts and the HBx fusion proteins were detected. DNA microarray revealed that HBx/MLL4 fusion proteins suppressed unique genes in HepG2 cells. Finally, chromosomal translocations of intron 3 of MLL4 to the specific region of chromosome 17p11.2 in 22 out of 32 HCC patients were observed, showing that the intron 3 region of MLL4 gene would be a target of translocation breakpoint. In conclusion, the present data suggest that the translocation breakpoint of MLL4 gene is one of the preferential targets for HBV DNA integration into the MLL4 gene and the HBV DNA integration may be involved in liver oncogenesis.


Asunto(s)
Carcinoma Hepatocelular/virología , ADN Viral/genética , Proteínas de Unión al ADN/genética , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/virología , Integración Viral , Secuencia de Bases , Carcinoma Hepatocelular/genética , Cromosomas Humanos Par 17 , N-Metiltransferasa de Histona-Lisina , Humanos , Neoplasias Hepáticas/genética , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Translocación Genética
12.
Cell Transplant ; 17(1-2): 61-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18468236

RESUMEN

Although widely used, DMSO is toxic for pancreatic islets. We combined hydroxyethyl starch (HES) with DMSO to simplify the procedure of freezing and thawing, and to decrease the toxicity of DMSO. A preclinical study was performed using islets from beagle dogs. After storage for 4 weeks, the islets were thawed and examined. The islet structure was well maintained after thawing. Although the number of the islets decreased to 71.2 +/- 20.1%, the function of the islets was evaluated by static incubation after thawing and showed a 1.80 +/- 0.78 stimulation index. We have introduced this technique for the cryopreservation of human islets from non-heart-beating donors. Twelve cases of human islet cryopreservation were performed. The sample tube of each human cryopreservation was thawed to evaluate the morphology, contamination, and endocrine function. Although fragmentation was observed in five samples (41.6%), the other seven (58.4%) showed a normal structure when evaluated by microscopic and electron microscopic study. The stimulation index (SI) of static incubation deteriorated from 3.37 +/- 3.02 to 1.34 +/- 0.28 after thawing. We divided the thawed islets into two groups: group 1 (n=8), SI > 1.2; group 2 (n=4), SI < 1.2. The group 1 islets showed a higher rate of normal structure (87%) than did group 2 (25%). Moreover, the SI before cryopreservation was 4.01 +/- 3.57 in group 1, which was higher than the SI of 2.11 +/- 0.72 in group 2. Based on the good results from the preclinical study using a large-animal model, this method was introduced for clinical application. Even from the pancreata of non-heart-beating donors, a successful islet cryopreservation was achieved. However, the isolated islets with poor function should not be cryopreserved for transplantation.


Asunto(s)
Criopreservación/métodos , Crioprotectores , Dimetilsulfóxido , Derivados de Hidroxietil Almidón , Islotes Pancreáticos , Animales , Cadáver , Perros , Humanos , Trasplante de Islotes Pancreáticos , Donantes de Tejidos
13.
Gan To Kagaku Ryoho ; 35(8): 1387-90, 2008 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-18701855

RESUMEN

The patient was a 53-year-old male with Stage IV gastric cancer with Virchow's lymph node and para-aorta lymph node metastasis. The chemotherapy regimen was given S-1 orally at 80 mg/m(2) day on day 1 to 21 and CDDP intravenously at 60 mg/m(2) day on day 8, repeated for 35 days. After two courses and a reduced regimen with S-1 64 mg/m(2) day plus CDDP 35 mg/m(2) day, the tumor lesion became CR and the serum CEA 575 ng/mL level before therapy decreased to the normal level. The patient received six courses of oral S-1(64 mg/m(2) day)for 28 days followed by a 14- day rest as maintenance therapy. The serum CEA elevated 13 months after the treatment, and the patient received a reduced course and two-course S-1/CDDP therapy. The serum CEA decreased to normal level and the patient has now survived 1 year 5 months without recurrence.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aorta , Cisplatino/uso terapéutico , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tegafur/uso terapéutico , Biopsia , Antígeno Carcinoembrionario/sangre , Combinación de Medicamentos , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/sangre , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos X
14.
Oncogene ; 22(25): 3911-6, 2003 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-12813464

RESUMEN

Integration of Hepatitis B Virus (HBV) DNA into liver cell DNA has been well established, but its implication in liver carcinogenesis is still being debated. In particular, insertion of the viral genome into cellular genes has been viewed as a rare event. By using HBV-Alu PCR, we have now isolated, from nine hepatocellular carcinomas, nine HBV-DNA integration sites showing that the viral genome mutates key regulatory cellular genes: neurotropic tyrosin receptor kinase 2 (NTRK2) gene, IL-1R-associated kinase 2 (IRAK2) gene, p42 mitogen-activated protein kinase 1 (p42MAPK1) gene, inositol 1,4,5-triphosphate receptor type 2 (IP3R2) gene, inositol 1,4,5-triphosphate receptor (IP3R) type 1 (IP3R1) gene, alpha 2,3 sialyltransferase (ST3GAL VI or SITA) gene, thyroid hormone uncoupling protein (TRUP) gene, EMX2-like gene, and human telomerase reverse transcriptase (hTERT) gene. This result brings to 15 the total number of genes targeted by HBV in a study of 22 human liver cancers. Overall, we found that both the inositol 1,4,5-triphosphate receptor gene and the telomerase gene were targeted by HBV in two different tumors. Thus, HBV frequently targets cellular genes involved in cell signalling and some of them may be preferential targets of the viral integration.


Asunto(s)
Carcinoma Hepatocelular/virología , ADN de Neoplasias/análisis , ADN Viral/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Neoplasias Hepáticas/virología , Mutagénesis Insercional , Telomerasa/genética , Integración Viral , Canales de Calcio/genética , ATPasas Transportadoras de Calcio/genética , Carcinoma Hepatocelular/genética , Proteínas de Unión al ADN/genética , Hepatitis B/virología , Virus de la Hepatitis B/genética , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Quinasas Asociadas a Receptores de Interleucina-1 , Neoplasias Hepáticas/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Proteínas Quinasas/genética , Receptor trkB/genética , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Ribosómicas/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Sialiltransferasas/genética , Factores de Transcripción/genética , beta-Galactosida alfa-2,3-Sialiltransferasa
15.
Anticancer Res ; 23(3C): 2987-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12926150

RESUMEN

BACKGROUND: Radiofrequency ablation (RFA) is one of the standard percutaneous therapies for hepatocellular carcinoma (HCC), but RFA has not been applied to treat bone metastasis from HCC. CASE: A 65-year-old male patient, who underwent hepatectomy for HCC two and a half years previously, complained of pain in his right thigh. Imaging modalities and a needle biopsy revealed metastatic HCC in his right acetabulum. The first RFA therapy was attempted under computed tomography (CT) guidance with 42 Gy radiation therapy. The second RFA therapy was performed for tumor recurrence in his pelvis at 4 years after the first RFA. CONCLUSION: RFA is a safe, easy, repeatable and effective therapy and should be one of the most important therapeutic modalities for bone metastasis from HCC.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Óseas/radioterapia , Carcinoma Hepatocelular/radioterapia , Terapia Combinada , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Persona de Mediana Edad
16.
Cell Transplant ; 21(2-3): 559-63, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22793065

RESUMEN

Grafts from non-heart-beating donors (NHBDs) are used because of the limited availability of heart-beating brain-dead donors. These grafts sustain ischemic damage, and the severity of this damage varies among different areas of an organ. This study determined whether the results of islet isolation were correlated with the clinical outcomes of kidney transplantations in cases where both grafts were harvested from the same NHBD. Islets we isolated from the pancreata of 23 NHBDs between February 2004 and March 2007. Forty-six kidneys were also harvested from these NHBDs. The recipients of kidney transplants were divided into the successful isolation (n = 14) and failed isolation (n = 32) groups depending on the results of islet isolation. The clinical outcomes of kidney transplantation were compared between the recipients in these two groups. The immediate graft function rate and the 1-year graft survival rate after kidney transplantation in both groups were similar. Hemodialysis after transplantation was required for 6.0 days (SD, 5.2 days) in the successful isolation group and for 12.7 days (13.1 days) in the failed isolation group (p < 0.05). The serum creatinine concentrations at 1, 3, 6, and 12 months after transplantation were elevated in the failed isolation group (p < 0.05). The islet yield was inversely correlated with the requirement of hemodialysis (days) and the serum creatinine level at 1 month after transplantation. However, hemodialysis was required for only 7 days in the recipients of six kidneys that were obtained from NHBDs from whom <40,000 IEQ were obtained (extreme failure of islet isolation). The results of islet isolation were found to correlate with the kidney function after transplantation when both grafts are harvested from the same NHBD. However, the marginal conditions of NHBDs affect the results of islet isolation more than they do the posttransplantation kidney function.


Asunto(s)
Islotes Pancreáticos/citología , Adolescente , Adulto , Anciano , Muerte Encefálica , Cadáver , Separación Celular , Creatinina/sangre , Supervivencia de Injerto , Humanos , Trasplante de Islotes Pancreáticos , Trasplante de Riñón , Persona de Mediana Edad , Diálisis Renal , Donantes de Tejidos , Resultado del Tratamiento , Adulto Joven
17.
J Hepatobiliary Pancreat Sci ; 17(2): 101-7, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19618100

RESUMEN

BACKGROUND/PURPOSE: Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. METHODS: Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. RESULTS: No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). CONCLUSIONS: Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Donadores Vivos , Trasplante de Páncreas/métodos , Adulto , Anciano , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Japón/epidemiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento
18.
J Hepatobiliary Pancreat Sci ; 17(2): 193-6, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20454909

RESUMEN

BACKGROUND: The simultaneous transplantation of pancreas and kidney from live donors is performed in select countries. One of the reasons for this reduced applicability is the invasiveness of the donor operation. We propose the method of laparoscopic-assisted operation to be performed on live donors with minimal invasion. METHOD: The donor was placed in the right lateral decubitus position. A 7-cm upper midline incision was made, and a handport was installed in addition to two or three 12-mm ports. After the removal of the left kidney graft, the spleen and the distal part of the pancreas were completely mobilized. The splenic vein and artery were identified and mobilized. The donor was then rotated to a supine position. Dissection of the pancreatic parenchyma using ultrasound shears and ligation of the splenic vessels were performed through midline incision under direct vision. The distal part of the pancreas and the spleen were extracted. RESULTS: Since December 2007, 3 donors have undergone this operation. In all 3 cases, the postoperative course was uneventful, and both the renal and pancreatic grafts functioned well. CONCLUSION: This technique is minimally invasive and safe, and may become the standard method of live donor operation for simultaneous pancreas-kidney transplantation.


Asunto(s)
Laparoscopios , Laparoscopía/métodos , Nefrectomía/métodos , Pancreatectomía/métodos , Factores Socioeconómicos , Estudios de Seguimiento , Humanos , Trasplante de Riñón/métodos , Trasplante de Páncreas/métodos , Estudios Retrospectivos , Resultado del Tratamiento
19.
Clin Transplant ; 20 Suppl 15: 38-41, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16848874

RESUMEN

The patient was a 52-year-old man who received an ABO-compatible but non-identical living-related renal graft from his wife. The graft started to function immediately and the urine output rate was over 100 mL/h. However, this was gradually decreased within 12 h after transplantation. On day 2 post-transplant, the urine output almost stopped. A biopsy specimen revealed lymphocyte dominant cellular infiltration in the interstitium with mild tubulitis (according to Banff's schema grade Ia) and no C4d deposition in peritubular capillaries. Immunohistochemistry disclosed T-cell infiltration. The patient responded to a course of steroid pulse therapy (five days of 500 mg of methylprednisolone). The urine output gradually increased and the level of serum creatinine gradually decreased to 1.0 mg/dL. These clinical and histological findings strongly suggested acute cellular rejection. Acute cellular rejection occurring within 24 h post-transplant is extremely rare. In the present case acute cellular rejection occurred within the first day after living-related renal transplantation and was strongly suspected from histopathological findings in the allograft biopsy specimen.


Asunto(s)
Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Riñón/patología , Prednisolona/administración & dosificación , Sistema del Grupo Sanguíneo ABO/inmunología , Enfermedad Aguda , Biopsia , Donación Directa de Tejido , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/patología , Humanos , Trasplante de Riñón/patología , Donadores Vivos , Masculino , Persona de Mediana Edad , Quimioterapia por Pulso
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