Hirofumi Tazawa

Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates

Previously, we detected B cells expressing receptors for blood group A carbohydrates in the CD11b(+)CD5(+) B-1a subpopulation in mice, similar to that in blood group O or B in humans. In the present study, we demonstrate that CD1d-restricted natural killer T (NKT) cells are required to produce anti-A antibodies (Abs), probably through collaboration with B-1a cells. After immunization of wild-type (WT) mice with human blood group A red blood cells (A-RBCs), interleukin (IL)-5 exclusively and transiently increased and the anti-A Abs were elevated in sera. However, these reactions were not observed in CD1d(-/-) mice, which lack NKT cells. Administration of anti-mouse CD1d blocking monoclonal Abs (mAb) prior to immunization abolished IL-5 production by NKT cells and anti-A Ab production in WT mice. Administration of anti-IL-5 neutralizing mAb also diminished anti-A Ab production in WT mice, suggesting that IL-5 secreted from NKT cells critically regulates anti-A Ab production by B-1a cells. In nonobese diabetic/severe combined immunodeficient (NOD/SCID/γc(null)) mice, into which peripheral blood mononuclear cells from type O human volunteers were engrafted, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production. Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients.

Treatment strategy for early hepatocellular carcinomas: Comparison of radiofrequency ablation with or without transcatheter arterial chemoembolization and surgical resection

The preferred choice between surgical treatment and radiofrequency ablation (RFA) for the treatment of small resectable hepatocelluar carcinoma (HCC) has become a subject for debate.

Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria.

BackgroundThe appropriate treatment strategy for advanced hepatocellular carcinoma (HCC) that does not meet the Milan criteria (MC) is unclear. The aim of this study was to determine the significance of surgical treatment for such patients.Study designFrom January 1990 to December 2007, 151 patients with HCC exceeding MC who underwent curative surgical treatment were enrolled. Survival and recurrence data and clinicopathological factors were examined. Prognostic factors were analyzed to identify those that contributed to improved surgical outcomes retrospectively.ResultsAfter the initial hepatectomy, the overall 3-, 5-, and 10-year survival rates were 73%, 55%, and 33%, respectively, for the 151 patients in this study; the corresponding disease-free survival rates were 36%, 30%, and 17%, respectively. A platelet count under 105/mm3, multiple tumors, and liver cirrhosis of noncancerous tissue were adverse survival and disease-free survival factors by univariate analysis. Platelet count was an independent prognostic factor by multivariate analysis. The 3-, 5-, and 10-year overall survival rates of HCC exceeding MC in patients whose platelet count was 105/mm3 or greater reached 76%, 65%, and 44%, respectively, and were comparable with those that met MC (86%, 68%, and 37%, respectively).ConclusionsHepatectomy for patients with advanced HCC exceeding MC improves survival, especially for patients with a sufficiently high platelet count, although recurrence rates after initial hepatectomy are high.

Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after liver transplantation (LT). The single‐nucleotide polymorphisms (SNPs) of C1QA [276A/G], FCGR2A [131H/R], and FCGR3A [158F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 89 living donor LT recipients in relation to the occurrences of postoperative infectious complications within 30 days after LT. Consistent with a lower affinity of the isoform encoded by FCGR3A [158F] to both IgG1 and IgG3, a significantly higher incidence of bloodstream infections (BSI) was observed in the FCGR3A [158F/V or F/F] than in the FCGR3A [158V/V] individuals. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of BSI, regardless of C1QA SNP. The predominant causative pathogen of BSI in the FCGR3A [158F/F or F/V] patients was gram‐positive cocci (73.3%), of which one third was methicillin‐resistant Staphylococcus aureus. No differences were observed in the incidence of fungal infections or in cytomegalovirus infections with respect to the three gene polymorphisms. Our findings indicate that FcγR SNPs are predisposing factors for BSI and can predict mortality after LT. This study provides a foundation for further prospective studies on a larger scale.

A huge metastatic liver tumor from leiomyosarcoma of the inferior vena cava: report of a case

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumor, and only a few cases of the resection of IVC leiomyosarcomas with synchronous liver metastases have been reported. This report describes a female patient who initially presented with a solitary, huge liver tumor and a retroperitoneal tumor. Following our preoperative diagnosis of primary liver cancer with a retroperitoneal lymph node metastasis, the patient underwent combined resection of both tumors. The surgical findings revealed that the retroperitoneal tumor originated from the IVC wall. The pathological and immunohistochemical findings revealed that both tumors were leiomyosarcomas. Although the liver tumor was much larger than the IVC tumor, we considered that the metastatic liver tumor arose from the IVC leiomyosarcoma. This was an instructive case because the metastatic liver tumor from the IVC leiomyosarcoma was so large as to be mistaken for a primary liver tumor.

Surgical treatment for portosystemic encephalopathy in patients with liver cirrhosis: Occlusion of portosystemic shunt in combination with splenectomy

Aim:  Operative ligation of the portosystemic shunt may control hepatic encephalopathy effectively, but the subsequent increase in portal vein pressure (PVP) leads to high mortality. Splenectomy can decrease inflow into the portal system, resulting in decreased portal pressure.

Renal vein extension using an autologous renal vein in a living donor with double inferior vena cava: a case report.

BACKGROUND When the kidney from a living donor with a double inferior vena cava (IVC) is harvested for renal transplantation, the short length of the renal vein may eventually create a technical problem for graft implantation. Herein, we have reported a rare case of renal vein extension using an autologous renal vein in a living donor with a double IVC. CASE REPORT A 70-year-old man with end-stage renal disease owing to autosomal-dominant polycystic kidney disease underwent a living donor kidney graft from his wife who had a double IVC. Because of the enlarged kidneys, the patient underwent a bilateral native nephrectomy with concomitant renal transplantation to create space in the pelvis. At nephrectomy, the recipients renal vein was used to extend the donor renal vein. On the back table, the vein graft was sutured to the donor renal vein, permitting a 3.0-cm extension. RESULTS The transplantation was performed safely without any complications; the recipients renal function and blood flow were excellent after the operation. CONCLUSION This case illustrated that an autologous renal vein graft is a preferable option to extend of short donor renal vein for recipients who require a simultaneous native nephrectomy.

Kinetics of Cellular and Humoral Immunity in a Successful Case of Positive Crossmatch Kidney Transplantation: A Case Report

A positive crossmatch remains one of the major barriers to successful kidney transplantation. Highly sensitized patients are at greater risk of hyperacute rejection and subsequent graft loss after transplantation. Although recent advances in desensitization therapy allow kidney transplantation in these patients, the success rate is quite low. Herein, we have reported a successful case of positive crossmatch living donor kidney transplantation using a desensitization protocol with an immune monitoring assay. A 42-year-old woman with end-stage renal disease due to IgA nephropathy had been on hemodialysis for 36 months. She showed positive T-cell and B-cell cytotoxic crossmatches with her husband owing to pretransplantation blood transfusions. We performed a preconditioning regimen comprising a single dose of rituximab (375 mg/m(2)) combined with double-filtration plasmapheresis (DFPP) followed by low doses of intravenous immunoglobulin (DFPP/IVIG treatment). Tacrolimus (target trough level, 5-10 ng/mL) and mycophenolate mofetil (1500 mg/body) were started 2 weeks before the DFPP/IVIG treatment. After 6 DFPP/IVIG sessions, the crossmatch became negative. An induction quadruple immunosuppression protocol included tacrolimus, mycophenolate mofetil, basiliximab, and methylprednisolone. After the transplantation, the patients immune status was evaluated regularly by mixed lymphocyte reactions (MLR) using an intracellular carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique (CFSE-MLR assay) and immunosuppressant therapy was adjusted accordingly. During the observation period, neither antibody-mediated rejection nor acute cellular rejection was encountered in this patient.

Incidental renal cell carcinoma presenting in a renal transplant recipient with autosomal dominant polycystic kidney disease: a case report

IntroductionWe report an instructive case of incidental renal cell carcinoma in a patient with autosomal dominant polycystic kidney disease who underwent simultaneous bilateral native nephrectomy and living donor renal transplantation.Case presentationA 57-year-old Asian man with end-stage kidney disease due to autosomal dominant polycystic kidney disease received a living kidney graft from his brother. Because of recurrent infection, chronic pain and enlarged kidneys, he underwent a bilateral nephrectomy with concomitant renal transplantation. The total weight of the removed kidneys was 6kg; the maximal diameter of the larger kidney was 28cm. His left kidney had a 1cm diameter tumor. Pathology indicated papillary renal cell carcinoma. At the time of this report, the transplant kidney function was normal with no evidence of local recurrence or distant metastasis.ConclusionThis case shows and reinforces the importance of considering the possibility of an occult malignancy in the native kidneys of patients with autosomal dominant polycystic kidney disease. Simultaneous bilateral native nephrectomy should be considered in these renal transplant recipients not only for preventing the development of adverse symptoms but also for detecting an occult malignancy.

Evidence for the Immunosuppressive Potential of Calcineurin Inhibitor-Sparing Regimens in Liver Transplant Recipients with Impaired Renal Function

Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state.