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S Uemoto

Publications and source records attributed to S Uemoto.

At least 37 records · Page 2Linked to original sources

Living-donor liver transplantation for Caroli's disease with intrahepatic adenocarcinoma.

A 36-year-old woman who had Caroli's disease with refractory cholangitis and complicated intrahepatic cholangiocarcinoma was successfully treated with living-donor liver transplantation. Preoperative computed tomography and ultrasonography showed a small nodule in the dilated intrahepatic bile duct. In the resected liver specimen, a small papillary tumor was located in the dilated intrahepatic bile duct of the right lobe. The pathological finding revealed a well differentiated papillary adenocarcinoma without invasion to the parenchyma. The patient is currently doing well 2.5 years after transplantation, with no signs of recurrence of the disease. For Caroli's disease, we believe we can achieve good results with liver transplantation, not only for cholangitis but also for the carcinoma when it is localized in the liver and the patient is carefully followed up.

Adult↗

Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance.

Although some previous studies have indicated the possibility of immunosuppression withdrawal in clinical liver transplantation, the mechanism of graft acceptance is not clear. The aim of this study is to elucidate the alloreactivity against the donor and intragraft cytokine profiles in living donor liver transplant (LDLT) recipients with graft acceptance. In October 1999, we had 23 patients who survived without immunosuppression after LDLT with a median drug-free period of 25 months (range: 3-69 months). They consisted of six patients who were electively weaned by an elective weaning protocol and 17 either forcibly or accidentally weaned patients due to various causes but mainly due to infection. We evaluated the alloreactivity against the donor in these patients by a mixed lymphocyte reaction and intragraft cytokine profiles by real-time reverse transcriptase-polymerase chain reaction. The development of donor-specific hyporeactivity was observed in the patients with graft acceptance. The cytokine pattern in the supernatant of the culture medium revealed a down regulation of T helper (Th) 1 cytokine INF gamma against the donor while no significant difference was seen in Th2 cytokine IL-10. Regarding the intragraft cytokine profiles, we could find no amplification of Thl cytokines (IL-2, INF y) and IL-4 while some of the patients revealed a gene expression of IL-10 with no significant difference from that of the normal, untransplanted liver specimen. In addition, no difference was observed in any other cytokines (IL-1beta, IL-8, IL-15, TNFalpha) compared with those of the normal controls. We propose that the down regulation of Th1 cytokine is one possible mechanism of graft acceptance in LDLT recipients.

Administration, Oral↗

Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation.

BACKGROUND: Acute allograft rejection (AR) in solid organ transplantation is generally regarded to develop through cell-mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, humoral immunity may play some roles in AR. Although flow cytometry crossmatch (FCXM) is reported as a useful method for the detection of antibodies against donor antigen, specific role of T- or B-cell FCXM and its sensitivity for AR is controversial. METHODS: T- and B-cell FCXM using fresh donor peripheral lymphocytes were performed before and after blood-type compatible living donor liver transplantation in 47 patients. IgM and IgG anti-donor antibodies were analyzed in relation to clinical AR. RESULTS: Positive pre-transplant T-cell FCXM was associated with a high incidence of positive post-transplant T-cell FCXM (p=0.017). Four of five cases (80%) with positive pre-transplant T-cell FCXM experienced earlier AR (day 8.0+/-4.4, mean+/-SD) than 16 of 42 cases (31%) with negative pre-transplant T-cell FCXM (17.3+/-6.8; p=0.016). In addition, higher dose of steroids was given to treat AR episodes in cases with positive pre-transplant T-cell FCXM (79.9+/-10.3 mg/kg/month) than in those with negative pre-transplant T-cell FCXM (47.1+/-26.6; p=0.039). In the first month after transplantation, 13 episodes of positive post-transplant T-cell FCXM were all concomitant with or preceded clinical AR compared with seven ARs in T-cell FCXM-negative cases (p<0.0001). T-cell FCXM between positive sera and third parties revealed some crossreactions. In contrast, detection of antibodies by B-cell FCXM in pre- and post-transplant phases was scarcely associated with AR, and no correlation was found between T- and B-cell FCXM before and after transplantation. CONCLUSIONS: Positive T-cell FCXM is closely related with AR and that before transplantation is a predictor of early and refractory AR as well as post-transplant FCXM. In contrast, not a few detections of antibodies irrelevant to AR are observed in B-cell FCXM, suggesting its low specificity.

Adolescent↗

Domino split-liver transplantation from a living donor: case reports of in situ and ex situ splitting.

The liver from a patient with familial amyloid polyneuropathy (FAP) scheduled for living donor liver transplantation can be split and transplanted into 2 adult patients with end-stage liver disease. We have performed this procedure, called domino split transplantation, twice. The native liver was split in situ in 1 patient with FAP and ex situ in the other patient with FAP. The recipients of the livers from the patients with FAP and their living donors are doing well without serious complications. Of the 4 secondary recipients, 3 patients survived. Domino split-liver transplantation from a living donor thus appears to be a promising procedure for expansion of the donor pool.

Adolescent↗

Liver transplantation for biliary atresia associated with malignant hepatic tumors.

The authors report 3 cases of liver transplantations in children between 4 and 10 years of age, complicated with malignant hepatic tumors after biliary atresia. The preoperative abdominal computed tomography (CT) scans of all 3 cases showed hepatic masses. The serum alpha-fetoprotein levels were elevated highly in 2 cases. After living-related liver transplantation (LRLT), the pathologic findings of the masses in the resected livers showed hepatocellular carcinoma in 2 cases and hepatoblastoma in the other. All cases were associated with biliary cirrhosis. The stage of the liver tumor in the 3 cases using the TNM system was IVA (T4, N0, M0), II (T2, N0, M0) and IVA (T4, N0, M0). Chemotherapy was used in all cases after liver transplantation, and all patients survived with no recurrence. The results suggest that even though malignant liver tumors rarely are complicated with biliary atresia in childhood, one should be alert to the occurrence of hepatic malignancy and perform routine screening of alpha-fetoprotein levels, abdominal CT scans, and magnetic resonance imagings.

Biliary Atresia↗

Pharmacokinetic and prognostic significance of intestinal MDR1 expression in recipients of living-donor liver transplantation.

BACKGROUND: Living-donor liver transplantation (LDLT) and subsequent immunosuppressive therapy with tacrolimus have been cornerstones in the recovery of patients from end-stage liver failure, but there has been no critical dosage regimen for tacrolimus therapy, especially the initial dosage. In this study, we examined whether the absorptive barriers, multidrug resistance protein (MDR1), or cytochrome P450 IIIA4 (CYP3A4) are important pharmacokinetic factors for tacrolimus and are prognostic indicators for LDLT outcome. METHODS: We used competitive polymerase chain reaction to evaluate the messenger ribonucleic acid (mRNA) expression levels of MDRL And Cyp3A4 in mucosal cells of the upper jejunum from a part of the Rroux-en- Y limb for biliary reconstruction during LDLT of recipients (n = 48). The tacrolimus dosage was started at an oral dose of 0.075 mg/kg every 12 hours and adjusted on the basis of its whole-blood trough level by use of a semiautomated microparticle enzyme immunoassay. RESULTS: The mRNA expression level of MDR1 (r = -0.776), but not CYP3A4 (r = -0.094), was inversely related to the concentration/dose ratio of tacrolimus. High levels of MDR1, but not CYP3A4, were strongly associated with reductions in survival rates after LDLT with the Kaplan-Meier method and log-rank statistics (P =.020 and P =.135, respectively). With use of a Cox regression procedure, high levels of MDR1 (relative risk, 12.99; 95% confidence interval, 1.64-103.23), but not CYP3A4 (relative risk, 0.93; 95% confidence interval, 0.87-1.00) appeared to be a significant prognostic indicator for poor survival. CONCLUSIONS: Intestinal MDR1 is not only a good probe with which to predict the interindividual variation in tacrolimus pharmacokinetics after LDLT but also a powerful prognostic indicator for the outcome of LDLT.

Adolescent↗

Living donor liver transplantation in Kyoto, 2001.

The living-donor liver transplant program at Kyoto University Hospital entered its 12th year in 2001. The rapid increase in adult patients that occurred with active use of right hemi-liver grafts is now reaching its plateau, limited by OR facilities and bed capacity. Graft selection is now being polarized to the left lateral section and right hemi-liver, and disease indications are becoming more similar to those for Western cadaveric programs, including a program for hepatocellular carcinoma. With the active introduction of right hemi-liver grafts, donor selection requires more multifactorial attention. Although most anatomical variants are managed surgically without significant risk, small-for-size grafts combined with high-risk patients are often a continuing problem even with the use of right hemi-liver grafts. Solutions for small-for-size syndrome with or without persistent portal hypertension and massive ascites are urgent targets of research. It will take some more time in Japan until the final establishment of a mutual compensatory system between cadaveric and living donor programs covering medical and socioeconomical aspects is achieved.

Adolescent↗

Living donor liver transplantation for fulminant hepatic failure.

BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated only for elective cases of pediatric patients with end-stage liver disease. In Japan, however, where liver transplantation from brain-dead donor is performed very rarely, this indication has been expanded to emergency cases such as fulminant hepatic failure (FHF). METHODS: Thirty-eight patients with FHF were treated between May 1992 and April 1999. Causes of acute liver failure were non-A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one each. RESULTS: Four patients did not undergo LDLT because of severe brain damage or combined multiple organ failure. The remaining 34 patients underwent a total of 36 LDLTs, including two retransplantations; 16 children received transplants of 17 lateral segments, three children and eight adults transplants of 11 left lobes, and seven adults transplants of eight right lobes. A total of 15 recipients died, four of primary graft dysfunction, three of refractory acute rejection, two of pneumonia, and one each of ductopenic rejection, sepsis, aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ failure by chrome poisoning, and unknown hepatic failure. Primary graft dysfunction developed in adult recipients with small-for-size graft transplants, whereas refractory acute rejection and ductopenic rejection occurred in six grafts each of children with non-A, non-B FHF. CONCLUSIONS: LDLT can be safely expanded to cases of FHF in adult patients. Primary graft dysfunction in adult recipients with small-for-size left lobe grafts can be overcome by using right lobes. However, refractory acute rejection and ductopenic rejection in children remain a major problem.

Adolescent↗

Tacrolimus and myocardial hypertrophy.

Tacrolimus has been used as an immunosuppressive agent in the transplantation of all solid organs. Tacrolimus-induced hypertrophic cardiomyopathy has been reported to be an unusual but serious complication. To elucidate the effects of tacrolimus on myocardial hypertrophy, we studied the relationship between the blood levels of tacrolimus and cardiac wall thickening. Our findings demonstrated that tacrolimus-induced myocardial hypertrophy correlated with tacrolimus blood levels, and that myocardial hypertrophy induced by tacrolimus was reversible. However, no patients developed clinically significant symptoms related to myocardial hypertrophy.

Adolescent↗

Right lobe graft in living donor liver transplantation.

BACKGROUND: For the sake of donor safety in living donor liver transplantation (LDLT), the left lobe is currently being used most often for the graft. However, size mismatch has been a major obstacle for an expansion of the indication for LDLT to larger-size recipients, because a left lobe graft is not safe enough for them. METHODS: In 1998, LDLT using a right lobe graft was introduced and performed on 26 recipients to overcome the small-for-size problem. The right lobe, which does not include the middle hepatic vein of the donor, was used. Initially, indication for right lobe LDLT was basically defined as an estimated left lobe graft volume/recipient body weight ratio (GRWR) of <0.8%, which was later raised to <1.0%. RESULTS: All the donors recovered from the operation without persistent complications. Two donors with transient bile leakage were successfully treated with a conservative approach. A right lobectomy resulted in more blood loss (337+/-175 ml), and a longer operative time (6.67+/-0.85 hr) than a lateral segmentectomy, but not a left lobectomy. Grafts with a GRWR >0.8% were implanted in all recipients, except for two, who received relatively smaller right lobes (GRWR of 0.68% and 0.66%). In one of these two, the right lobe from the donor was used as the orthotopic auxiliary graft. Postoperative transitory increases in total bilirubin and aspartate transaminoferase for right lobe donors were higher than those for the left lateral segmentectomy. Nineteen recipients (73.1%) were successfully treated with this procedure. The causes of death were not specific for right lobe LDLT, except for one patient with a graft that had multiple hepatic venous orifices. These multiple and separate anastomoses of the hepatic veins caused an outflow block as a result of a positional shift of the graft, which finally led to graft loss. CONCLUSION: Our experience suggests that right lobe grafting is a safe and effective procedure, resulting in the expansion of the indication for LDLT to large-size recipients. How to deal with the possible variation in the anatomy of the right lobe graft should be given attention throughout the procedure.

Adolescent↗

Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen.

Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti-HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti-HBc-positive healthy individuals. HBV DNA was detectable in 13 of 14 healthy donors who were positive for both anti-HBc and antibodies to hepatitis B surface antigen (anti-HBs), but in none of 3 who were positive for anti-HBs alone. The detected HBV genomes from these subjects included covalently closed circular DNA and pregenomic RNA, the replication intermediate of HBV. Notably, 5 of 7 cases tested were predominantly infected with wild type HBV strains without any mutations in the precore and core promoter regions under the presence of circulating antibody to hepatitis B e antigen. Interestingly, a predominant clone detected in one donor showed a 63-nucleotide deletion in the precore region including an encapsidation signal sequence. Our findings indicate that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied by ongoing viral replication and few nucleotide mutations in the precore and core regions.

Adult↗

Small bowel transplantation using grafts from living-related donors. Two case reports.

A living-related small bowel transplantation (SBT) was performed in two pediatric patients with short bowel syndrome. In both cases, the donor was the patient's mother. The distal ileum (100 cm, 120 cm) was harvested and the ileocolic vessels, ileocecal valve, and terminal ileum were left intact. The two donors were discharged from the hospital on postoperative days 15 and 6, respectively. Recipient 1 was a 2 year 6 month-old boy with short bowel syndrome who underwent SBT due to loss of venous access. The graft vein was anastomosed to the recipient's infrarenal inferior vena cava. Despite triple immunosuppression (tacrolimus, steroid, and azathioprine), there were four episodes of rejection. The patient had been on total parenteral nutrition for almost his entire posttransplant course. He died from Pneumocystis carinii pneumonia 16 months after the transplantation. Recipient 2 was a 4 year 5 month-old girl with short bowel syndrome who underwent an isolated small bowel transplantation because of recurrent line sepsis. Her pretransplant bilirubin was 8.0 mg/dl and a biopsy showed severe fibrosis. The graft vein was anastomosed to the recipient's inferior mesenteric vein. After transplantation, her bilirubin level became normal within 10 days. Triple immunosuppression (tacrolimus, steroid, and cyclophosphamide) together with a 3-day course of OKT-3 made her post-transplant course feasible. After overcoming a single episode of rejection she left the hospital 4 months after SBT. The patient is currently (10 months after transplantation) hospitalized due to rejection, which is being successfully controlled, and she is off total parenteral nutrition. From our experience, harvesting of the distal ileum for use as a bowel graft can be safely performed. The advantages of living-related grafts, optimal graft length, and choice of vascular reconstruction in SBT are yet to be explored.

Adult↗

Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient.

We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/microg total RNA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly throughout this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. These results suggested that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Living related liver transplantation from donors with the left-sided gallbladder/portal vein anomaly.

The presence of a left-sided gallbladder poses a unique challenge for living related liver donation. Associated anomalies include segment IV atrophy, absence of portal vein bifurcation, and abnormal intrahepatic portal branches to segments II and III. The complex is rare, but is more frequent in Japan. Of 379 living related liver transplants from our institution, the complex has been encountered on four occasions (incidence: 1.1%), and we herein review our experience. Anomalies were identified preoperatively (by computed tomography and ultrasound) in all instances. One donor was turned down because there was no common portal trunk to segment II and III branches. Three donors underwent successful retrieval using a modified technique. There were no complications in the donors or recipients relating to the complex. Thus, living related liver retrieval can be achieved safely in the presence of the left-sided gallbladder/portal anomaly complex, but technical modifications are required.

Adolescent↗