Biomedical subjects

Yuichi Matsui

Publications and source records attributed to Yuichi Matsui.

At least 19 recordsLinked to original sources

PubMed2006

Late-onset acute rejection after living donor liver transplantation.

AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids. METHODS: Adult living donor liver transplantation recipients (n=204) who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 mo. RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR. CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

Adolescent↗

PubMed2006

Efficacy of mycofenolate mofetil for steroid-resistant acute rejection after living donor liver transplantation.

AIM: To discuss the use of mycophenolate mofetil (MMF) as an immunosuppressant in steroid resistant rejection after liver transplantation. METHODS: The clinical records of 260 adult patients who underwent living donor liver transplantation (LDLT) were reviewed. Tacrolimus and methylprednisolone were used for primary immunosuppression. Acute rejection was first treated with steroids. When steroid resistance occurred, the patient was treated with a combination of steroids and MMF. Anti-T-cell monoclonal antibody was administered to patients who were not responsive to steroids in combination with MMF. RESULTS: A total of 90 (35%) patients developed acute rejection. The median interval time from transplantation to the first episode was 15 d. Fifty-four patients were steroid resistant. Forty-four patients were treated with MMF and the remaining 10 required anti-T-cell monoclonal antibody treatment. Progression to chronic rejection was observed in one patient. Bone marrow suppression and gastrointestinal symptoms were the most common side effects associated with MMF use. There was no significant increase in opportunistic infections. CONCLUSION: Our results demonstrate that MMF is a potent and safe immunosuppressive agent for rescue therapy in patients with acute rejection after LDLT.

Adolescent↗

PubMed2006

Aspergillus thyroiditis in a living donor liver transplant recipient.

Aspergillosis is increasingly recognized as an important nosocomial pathogen in immunocompromised patients. Infection is difficult to diagnose and typically has a fatal outcome. We describe a liver transplant patient with fulminant hepatic failure, who had persistent fever of undetected origin postoperatively and an increased (1-3)-beta-d glucan level. Gallium-67 citrate scanning showed abnormal uptake in the thyroid bilaterally. Fine needle biopsy of the thyroid revealed thyroidal invasion of Aspergillosis. Total thyroidectomy was performed and the C reactive protein level decreased to 1.01 mg/dl. The patient died of liver sepsis due to Pseudomonas aeruginosa. (1-3)-beta-d Glucan monitoring and systematic radionuclide images are useful modalities for early diagnosis of Aspergillosis.

Aspergillosis↗

PubMed2006

T-tube drainage for biliary stenosis after living donor liver transplantation.

The optimal strategies for bile duct stenosis after living donor liver transplantation with duct-to-duct biliary reconstruction remain unclear. Patients who underwent liver transplantation with duct-to-duct bile duct reconstruction (n=182) and were complicated with biliary stenosis (n=34) were analyzed. Treatment of biliary stenosis was attempted using an endoscopic approach or transhepatic biliary drainage. When this failed, the T-tube drainage technique was indicated. T-tube placement was performed in 14 patients. Intraoperative ultrasonography was performed to identify the bile duct. The common bile duct was cut open, a Kelly clamp was inserted and the stenotic portion was dilated, and a T-tube was inserted. The patients were scheduled to have the tube removed 1 year after insertion. Complications following T-tube placement or T-tube removal were negligible. The present technique can be an effective therapeutic option when endoscopic treatment is unsuccessful.

Bile Ducts↗

PubMed2006

Portal vein reconstruction in adult living donor liver transplantation using cryopreserved vein grafts.

No data are available for the management of venous jump or interposition conduits for portal vein (PV) reconstruction in adult living donor liver transplantation (LDLT). The feasibility of using cryopreserved vein grafts as PV conduits was examined. Cryopreserved vein (n = 23) was used as a patch, interposition, or jump graft. The patency results were compared with those of anastomosis without vein patch (n = 217) or those with vein autografts (n = 10). The 5-yr primary and secondary patency rates of the cryopreserved vein grafts were 58% and 79%, respectively. In conclusion, our data indicate that the use of cryopreserved vein grafts should be limited as conduits in PV reconstruction in adult LDLT.

Adult↗

PubMed2006

Systematic grading of surgical complications in live liver donors according to Clavien's system.

The lack of consensus on how to evaluate surgical complications of donors in live donor liver transplantation (LDLT) and incoherence of cumulative data hampers efficient comparison of the outcome worldwide. We considered that the application of the internationally validated classification system introduced by Clavien in 2004 might be beneficial. Operative complications of 243 patients who underwent live donor hepatectomy for adult LDLT between January 1996 and October 2005 at the University of Tokyo were analyzed according to the system. Definitions for each grade in the system are: grade I, deviation from the normal postoperative course but without the need for therapy; grade II, complication requiring pharmacologic treatment; grade III, complication with the need for surgical, endoscopic or radiological intervention (IIIa/b: without/with the need for general anesthesia); grade IV, life-threatening complication requiring intensive care; grade V, death. Surgical morbidity was recognized in 67 donors (28%). No deaths occurred. The numbers of patients with complications were: grade I, 36 (15%); II, 10 (4%); IIIa, 12 (5%); IIIb, 9 (4%); IV, 0; V, 0. Six in IIIb underwent surgical repair for bile leakage. Clavien's system is simple and informative. It may serve as a common tool for the quality assessment in live liver donor surgery worldwide, and we propose its application whenever surgical complication of live donor is discussed.

Adult↗

PubMed2005

Thrombotic microangiopathy in living-donor liver transplantation.

BACKGROUND: Thrombotic microangiopathy (TMA) is a fatal complication characterized by microvascular occlusive disorder resulting in systemic or intrarenal platelet aggregation, severe thrombocytopenia, and microangiopathic hemolytic anemia. Only sporadic case reports of TMA after cadaveric or living-donor liver transplantation (LDLT) have been described. METHODS: The authors report 10 (5% of the total series) TMA patients after LDLT and review the previously reported cases. TMA was diagnosed on the basis of progressive thrombocytopenia of unknown cause and microangiopathic hemolytic anemia, suggested by sharp elevation of serum lactate dehydrogenase levels and the presence of fractionated erythrocytes in blood smear. RESULTS: Of the 10 patients with TMA, 7 presented with viral hepatitis (2 with hepatitis B and 5 with hepatitis C virus infection) as the cause of end-stage liver disease. Clinical diagnosis of TMA was made at a median interval of 18 days (range, 3-356 days) from the time of transplantation. Conversion of calcineurin inhibitors (CNI) was conducted in nine patients. One patient recovered after CNI conversion alone. Plasma exchange was performed in eight patients. Three patients died. CONCLUSIONS: Immediate treatment of TMA should be initiated by reduction or conversion of CNI followed by plasma exchange. Hepatitis C virus infection might contribute to the high incidence of TMA in LDLT patients.

Adult↗

PubMed2005

NFAT and Osterix cooperatively regulate bone formation.

Immunosuppressants are crucial in the prevention of detrimental immune reactions associated with allogenic organ transplantation, but they often cause adverse effects in a number of biological systems, including the skeletal system. Calcineurin inhibitors FK506 and cyclosporin A inhibit nuclear factor of activated T cells (NFAT) activity and induce strong immunosuppression. Among NFAT proteins, NFATc1 is crucial for the differentiation of bone-resorbing osteoclasts. Here we show FK506 administration induces the reduction of bone mass despite a blockade of osteoclast differentiation. This reduction is caused by severe impairment of bone formation, suggesting that NFAT transcription factors also have an important role in the transcriptional program of osteoblasts. In fact, bone formation is inhibited in Nfatc1- and Nfatc2-deficient cells as well as in FK506-treated osteoblasts. Overexpression of NFATc1 stimulates Osterix-dependent activation of the Col1a1 (encoding type I collagen) promoter, but not Runx2-dependent activation of the Bglap1 (encoding osteocalcin) promoter. NFAT and Osterix form a complex that binds to DNA, and this interaction is important for the transcriptional activity of Osterix. Thus, NFAT and Osterix cooperatively control osteoblastic bone formation. These results may provide important insight into the management of post-transplantation osteoporosis as well as a new strategy for promoting bone regeneration in osteopenic disease.

Animals↗

PubMed2005

Superior vena cava graft for right liver and right lateral sector transplantation.

BACKGROUND: The usefulness of cryopreserved superior vena cava (SVC) grafts for venous reconstruction remains to be evaluated in right liver and right lateral sector transplantation. METHODS: Reconstruction of the hepatic vein was performed when the congested area in the liver graft was significant. A vein graft with a suitable shape and length meeting the demands for the venoplasty was selected, and SVC grafts were used in 20 recipients. Surgical techniques were classified into five types according to the necessity of middle or short hepatic vein reconstruction in the liver graft. Surgical outcomes and vein graft patency were evaluated. RESULTS: All 20 recipients survived the operation without any complications caused by congestion. Liver functions were well recovered in the early postoperative period. The 1-year primary patency rates of cryopreserved vein grafts used for reconstructed right hepatic veins, inferior right hepatic veins, and middle hepatic vein tributaries were 100%, 94%, and 42%, respectively. CONCLUSIONS: SVC grafts were feasible for outflow tract reconstruction in right liver and right lateral sector transplantation, although the long-term patency of the grafts for middle hepatic vein reconstruction remains to be evaluated.

Aspartate Aminotransferases↗

PubMed2005

Alternatives to the double vena cava method in partial liver transplantation.

Minimizing graft congestion in partial liver transplantation is important, especially when the graft weight is marginal for the recipient metabolic demand. We prefer the double vena cava technique for reconstructing middle hepatic vein tributaries with thick, short hepatic veins because the technique can reduce the warm ischemic time of the graft and make a wide anastomosis. This technique requires a cryopreserved superior or inferior vena cava. We devised an alternative double vena cava method using iliac or femoral vein grafts and applied it to two right liver transplantation patients. There was no postoperative hepatic venous outflow block in either patient. In conclusion, application of this technique, even in the absence of a suitable vena cava, can help to minimize graft congestion.

Adult↗

PubMed2005

Reconstruction of the middle hepatic vein tributary in a right lateral sector graft.

A right lateral sector graft (RLSG) was devised to overcome graft-size disparity in living donor liver transplantation (LDLT). When the RLSG has a middle hepatic vein (MHV) tributary, which drains a significant part of segment VI, the MHV tributary (V6) should be reconstructed to avoid congestion of the RLSG. In the donor operation, congestive area of segment VI was identified by 5 minutes of simultaneous clamping of V6 and the hepatic artery to the right lateral sector. An RLSG was harvested, preserving the V6 orifice. After plastic surgery of outflow veins including V6 using venous grafts, the RLSG was implanted into the recipient. In 19 patients who received RLSG in our institution, 2 RLSGs required V6 reconstruction. The postoperative courses of these two recipients and donors were uneventful. In conclusion, the present technique might be useful to avoid complications due to congestion and poor function of the relevant graft area and might help to expand the indications for RLSG.

Adult↗

PubMed2005

Coagulation and fibrinolytic profiles and appropriate use of heparin after living-donor liver transplantation.

Heparin is widely used to reduce the incidence of vascular thrombosis after liver transplantation. Appropriate use of heparin based on changes in coagulation and fibrinolytic profiles, however, has not yet been discussed in detail. We performed living-donor liver transplantation for 128 adult patients. In this series, dalteparin (25 IU/kg/d) was administered until post-operative day (POD) 2. On POD 3, the anticoagulant drug was changed to heparin (unfractionated heparin sodium, 5000 U/d), the dose of which was changed according to the level of activated clotting time (ACT) targeted between 130 and 160 s. The plasma level of plasmin-alpha2 plasmin inhibitor complex, thrombin-antithrombin III complex (TAT), and fibrin degradation product D-dimer (FDP-DD) were monitored in the 21 patients. Predictors for heparin doses were analyzed among clinical parameters (n = 128). Four patients (3%) were complicated with thrombosis despite the above-mentioned anticoagulation protocol. Transfusion and/or relaparotomy for hemostasis were necessary for bleeding in 19 patients (15%). The TAT level markedly elevated until POD 3 and FDP-DD peaked later. The required heparin dose to maintain adequate ACT levels increased linearly until POD 8, and kept constant thereafter, which correlated with the weight of the liver graft (p = 0.01). Thus, frequent monitoring of the heparin dosage is necessary to keep the ACT level in the target range in the first post-operative week. High hemorrhage complications in our series indicate that the lower target ACT range may be preferable in the second post-operative week.

Adult↗

PubMed2005

[Appliance of microarray technology to clinical organ transplantation].

Although recent advances in immunosuppressive therapy have dramatically enhanced the early survival of solid organ transplant recipients, acute rejection still occurs in some recipients. Long-term immunosuppressive drug administration, furthermore, entails a number of potentially significant problems such as infection, spontaneous neoplasm and drug toxicity. Alloantigen specific tolerance induction is the ultimate goal in transplant immunology, and can be induced in a rodent model; however, the precise mechanism by which specific tolerance is affected are not clearly understood, and the current immunosuppression regimens have all failed to achieve this goal in a clinical setting. DNA microarray technology has made it possible to analyze the expression of a large number of genes and revolutionized many areas of biology and medicine. This new technology can provide non-biased, global expressions of tens of thousands of genes simultaneously. Recent studies on gene expression profiles in various diseases, including allograft rejection, have successfully provided important information and new insights into the biological mechanisms of these diseases. In this article, we reviewed these insights, especially with the viewpoint of appliance of microarray technology to clinical solid organ transplantation.

Animals↗

PubMed2004

Preemptive therapy for hepatitis C virus after living-donor liver transplantation.

BACKGROUND: Living-donor liver transplantation (LDLT) is important for patients with end-stage viral hepatitis because of the cadaveric organ shortage. Preliminary results, however, indicate that LDLT might be disadvantageous for patients positive for hepatitis C virus (HCV). METHODS: The subjects were 23 patients who underwent LDLT for HCV cirrhosis. All the patients preemptively received antiviral therapy consisting of interferon-alfa2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months (group 1). The therapy was continued for at least 12 months even when the HCV RNA test remained positive (group 2). The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death. RESULTS: Eight patients were removed from the protocol. Nine patients were assigned to group 1 and the other six to group 2. The sustained virologic response ratio was 39% (9 of 23). There was a significant difference between the groups in the histologic activity score 1 year after the therapy. The cumulated 3-year survival of the HCV-positive patients was 85%, which was comparable with that of patients negative for HCV (n=93 [90%]). CONCLUSIONS: The present preemptive antiviral protocol after LDLT is safe and might warrant a controlled study for confirming its benefit on graft survival.

Adult↗

PubMed2004

Sharing the middle hepatic vein between donor and recipient: left liver graft procurement preserving a large segment VIII branch in donor.

There are few reported techniques to minimize the congestion in the donor after left liver graft procuring. If a large tributary of the middle hepatic vein (MHV) draining segment VIII (V8) converges into the root of the MHV in a donor of left liver, this branch should be preserved on the donor side. The volume of congested area when the V8 was ligated was predicted preoperatively by computed tomography (CT) and examined intraoperatively by the clamp test. Postoperative regeneration of the donor liver was evaluated by CT volumetry. This technique was used in 3 cases. The regeneration rate after 3 months of the right paramedian sector was 27, 38, and 8%, and that of the right lateral sector was 31, 63, and 39% in each donor, respectively. No severe complications occurred in the donors. In conclusion, V8 preservation in donors who underwent left liver resection led to satisfactory regeneration both of the right paramedian and lateral sectors and can minimize congestion in remnant liver.

Adolescent↗

PubMed2003

Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade.

The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunologic tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs). Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for pro-inflammatory factors, including interferon-gamma-inducible cytokines and chemokines, as well as apoptosis-related genes, which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days posttransplant. These results provide evidence that immunologic tolerance can be induced and maintained in the presence of prominent pro-inflammatory gene expression in vivo.

Animals↗

PubMed2003

Living-donor liver transplantation in adults: Tokyo University experience.

The objective of this study was to analyze the experience of a single center with living-donor liver transplantation (LDLT) for adult patients. Ninety consecutive LDLT procedures were analyzed. Preoperative status, morbidity, hospital stay duration, and postoperative graft function and survival rates were examined. Donors showed only minimal morbidity and were discharged 15 +/- 6 days after LDLT. Morbidity in the patients included acute rejection (32%), vascular complications (8%), and biliary complications (20%). The mortality rate was 6% and three additional patients experienced late death. The 2-year cumulative survival rate was 92%. The present results suggest that LDLT can be performed with an acceptable outcome in adult patients.

Cholestasis, Intrahepatic↗

PubMed2003

Vein reconstruction in modified right liver graft for living donor liver transplantation.

OBJECTIVE: To report the authors' experience with hepatic vein reconstruction and plasty in living donor liver transplantation for adult patients. SUMMARY BACKGROUND DATA: A right liver graft without the middle hepatic vein (MHV) trunk (modified right liver graft) can cause severe congestion of the right paramedian sector. However, the need for MHV reconstruction has not been fully recognized. METHODS: From June 2000 to December 2001, 30 adult patients received a modified right liver graft. Major MHV tributaries were preserved and reconstructed under the authors' criteria. Plasty of recipient hepatic veins for a wide outflow orifice was performed when necessitated. The regeneration of paramedian and lateral sectors of the grafts was examined by computed tomography 1 and 3 months after the operation. RESULTS: MHV tributaries were reconstructed in 18 grafts. Plasty of recipient hepatic veins was performed in 15 patients. All patients survived the operation. The regeneration of paramedian and lateral sectors was equivalent. CONCLUSIONS: A modified right liver graft can provide satisfactory surgical results if hepatic vein reconstruction and plasty are performed using the present techniques.

Adolescent↗