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Biomedical subjects

H Egawa

Publications and source records attributed to H Egawa.

At least 73 records · Page 4Linked to original sources

One-way donor-recipient HLA-matching as a risk factor for graft-versus-host disease in living-related liver transplantation.

Although one-way matching between an HLA-homozygous donor and a haploidentical recipient is a recognized risk factor in transfusion-associated graft-versus-host disease (GVHD), its impact in living-related liver transplantation (LRLT) has so far not been investigated. We present a case of fatal acute GVHD in our LRLT program that was attributed to one-way HLA matching between donor and recipient. Although the disappearance of donor cells in peripheral blood was suggested by genetic analysis, severe septicemia led to a fatal outcome. We further reviewed 280 LRLT cases and correlated one-way HLA matching with outcome. A total of 8 out of 280 donors (2.9%) and 11 out of 278 recipients (4.0%) were completely HLA homozygous in our LRLT program. Complete one-way HLA matching linked to GVHD was observed in four cases, including the present case. Although other contributing factors also need to be clarified, one-way HLA matching is a definite risk factor for GVHD in LRLT. We advocate caution before proceeding with one-way HLA donor-recipient combinations.

Fatal Outcome↗

Treatment of ornithine transcarbamylase deficiency in girls by auxiliary liver transplantation: conceptual changes in a living-donor program.

BACKGROUND/PURPOSE: Ornithine transcarbamylase (OTC) deficiency is an X-chromosome-linked genetic disorder resulting in hyperammonemia hepatic dysfunction, coma, and serious neurological sequelae. This report describes an experience in treating this condition with living-related liver transplantation. METHODS: Three children with OTC were treated with a living-related liver transplantation. Potential donors were evaluated with the allopurinol loading test to exclude heterozygotes. FK506 and low-dose steroids were used for immunosuppression. Auxiliary partial orthotopic transplantation (APOLT) was used in two of the cases. RESULTS: All three children survived and are doing well without protein restriction. CONCLUSIONS: These observations suggest that in OTC removal of the native liver is not necessary because (1) a partial liver segment with normal enzyme activity corrects the hyperammonemia, (2) in case of graft failure the native liver is an available backup, and (3) the native liver has the ability to recover function. As long as living-related donors serve as the main source of donor organs, APOLT is a safer approach to liver transplantation in OTC.

Amino Acid Metabolism, Inborn Errors↗

Affinity of four lectins for endocervical and endometrial non-neoplastic and neoplastic glandular epithelium.

AIMS: Endocervical and endometrial tissues were stained with four lectins to determine the difference in staining pattern between non-neoplastic and neoplastic conditions of these tissues. METHODS AND RESULTS: The lectins used were Ulex europaeus agglutinin (UEA), Dolicho biflorus agglutinin (DBA). Concanavalin A (Con A), and Phaseolus vulgaris agglutinin (PHA). Endocervical tissues included normal endocervical glands, microglandular hyperplasia, minimal deviation adenocarcinoma and endocervical adenocarcinoma, well to poorly differentiated types. Endometrial tissues were collected from normal endometrium, simple glandular hyperplasia, complex hyperplasia, atypical hyperplasia and adenocarcinoma grades 1-3. Non-neoplastic and neoplastic endocervical and endometrial glandular epithelium showed positive reaction for UEA, Con A and PHA. Non-neoplastic glands showed mild to moderate intensity and apical and/polar type of staining pattern for all lectins. Endocervical adenocarcinoma including minimal deviation adenocarcinoma (MDC) and adenocarcinoma well to moderately differentiated type showed diffuse cytoplasmic type of staining pattern for all lectins, but poorly differentiated adenocarcinoma of endocervix showed only a stromal pattern for all lectins. Endometrial hyperplasia and adenocarcinoma grades 1-3 showed positive reaction for all lectins except for DBA. The staining pattern of endometrial hyperplasia was variable, but adenocarcinoma grades 1-3 showed diffuse type. CONCLUSION: Intensity and staining patterns of lectins are helpful in distinguishing between endocervical and endometrial non-neoplastic and neoplastic lesions. Intense positive reaction of MDC, especially for Con A and PHA, can differentiate this lesion from normal endocervical glands. The stromal type of staining pattern of poorly differentiated endocervical adenocarcinoma can also have diagnostic significance. Negative reactions of DBA lectin for endometrial adenocarcinoma can be used for differentiating it from endocervical adenocarcinoma.

Adenocarcinoma↗

Portal vein reconstruction in pediatric liver transplantation from living donors.

OBJECTIVE: The authors analyze the surgical pattern and the underlying rationale for the use of different types of portal vein reconstruction in 110 pediatric patients who underwent partial liver transplantation from living parental donors. SUMMARY BACKGROUND DATA: In partial liver transplantation, standard end-to-end portal vein anastomosis is often difficult because of either size mismatch between the graft and the recipient portal vein or impaired vein quality of the recipient. Alternative surgical anastomosis techniques are necessary. METHODS: In 110 patients age 3 months to 17 years, four different types of portal vein reconstruction were performed. The portal vein of the liver graft was anastomosed end to end (type I); to the branch patch of the left and right portal vein of the recipient (type II); to the confluence of the recipient superior mesenteric vein and the splenic vein (type III); and to a vein graft interposed between the confluence and the liver graft (type IV). Reconstruction patterns were evaluated by their frequency of use among different age groups of recipients, postoperative portal vein blood flow, and postoperative complication rate. RESULTS: The portal vein of the liver graft was anastomosed by reconstruction type I in 32%, II in 24%, III in 14%, and IV 29% of the cases. In children <1 year of age, type I could be performed in only 17% of the cases, whereas 37% received type IV reconstruction. Postoperative Doppler ultrasound (mL/min/100 g liver) showed significantly (p < 0.05) lower portal blood flow after type II (76.6 +/- 8.4) versus type I (110 +/- 14.3), type III (88 +/- 18), and type IV (105 +/- 19.5). Portal vein thrombosis occurred in two cases after type II and in one case after type IV anastomosis. Portal stenosis was encountered in one case after type I reconstruction. Pathologic changes of the recipient native portal vein were found in 27 of 35 investigated cases. CONCLUSION: In living related partial liver transplantation, portal vein anastomosis to the confluence with or without the use of vein grafts is the optimal alternative to end-to-end reconstruction, especially in small children.

Adolescent↗

Living-related small bowel transplantation: the first case in Japan.

Intestinal failure has been managed with total parenteral nutrition (TPN), but occasionally complications such as obliteration of venous access or liver dysfunction occur. To overcome such complications, small bowel transplantation (SBT) was introduced. Since the introduction of tacrolimus in 1990, successful SBT cases have been reported. We performed SBT by using a living donor for a child with short bowel syndrome. The recipient (2.5 years old, male) was born with intestinal necrosis secondary to midgut volvulus. The length of the remaining small bowel was 30 cm. While being managed with TPN, his venous access gradually obliterated. Long-term survival could not be expected because of the difficulty in securing TPN access. The donor was his mother, whose distal ileum (100 cm) was used as a graft. The immunosuppression regimen consisted of tacrolimus, steroids and azathioprine. Three episodes of severe rejection and subsequent episodes of viral (EBV, CMV) infection were managed with steroid pulse therapy and antiviral drugs, respectively. The recipient suffered from anastomotic stenosis, and an operation was performed 13 months after transplantation to resect the stenotic segment. However, the patient died of Pneumocystis carinii pneumonia 16 months after transplantation. We conclude that organ retrieval from a living donor can be performed safely for SBT, but further study of the management of rejection as well as of viral infection is necessary, as it is for non-living-related SBT.

Adult↗

Growth and quality of life after living-related liver transplantation in children.

Fifty-six consecutive pediatric recipients surviving more than 3 yr after living-related liver transplantation (LRLT) were evaluated in terms of growth, quality of life (QOL) and need for maintenance immunosuppression. Significant improvement in Z-score for height and weight were observed at last follow-up, ranging from 3 to 6 yr after transplantation, although catchup height gain lagged behind recovery in weight (height: -1.77 pre-transplant to -0.77 post-transplant, p<0.001; weight: -1.12 pre-transplant to -0.18 post-transplant, p<0.0001). 82% (46) recipients have remained in good health and have an excellent QOL as assessed in the most recent 6 months; these children lead similar daily lives to normal healthy children, with daily school attendance and full participation in activities including gymnastics and hiking. 3.6% (2) recipients attended school regularly but were unable to participate in sporting activities. 14% (8) recipients remain home or hospital-bound due to persistent complications in the past 6 months, with only minimal school attendance. Less than 10% of recipients were taking steroids by 2 yr post-transplantation, although approximately half of the children were receiving low-dose maintenance steroids at 1 yr. The mainstay immunosuppressant was tacrolimus, with 68% (38) recipients receiving daily therapy, 8.9% (5) alternate-day, 8.9% (5) twice a week, and 5.4% (3) a single dose weekly or alternate weeks. 7.1% (4) recipients were withdrawn completely from all immunosuppressants, including tacrolimus, for various reasons. 8.9% (5) patients have needed multiple immunosuppressive agents over the last 6 months. In conclusion, LRLT restores growth and offers excellent quality of life in pediatric recipients. The majority of recipients require minimal, steroid-free, immunosuppression by 2 yr post-transplant, but the occasional recipient still needs intensive longterm immunosuppression.

Adolescent↗

Application of in situ hybridization technique for quantitative assessment of ongoing symptomatic Epstein-Barr virus infection after living related liver transplantation.

For quantitative assessment of ongoing symptomatic Epstein-Barr virus (EBV) infection in pediatric recipients of liver transplantation, we determined the number of peripheral blood mononuclear cells (PBMC) infected by EBV by in situ hybridization (ISH) and related the results with clinical courses of those patients. Twenty-four patients had symptomatic EBV infection between February 1995 and March 1996. Blood samples were obtained from these 24 patients at the time of acute phase, from 13 of them during convalescence, and 37 pediatric patients before transplantation. ISH was performed on the PBMC and polymerase chain reaction (PCR) on DNA from whole blood. Oligonucleotide probes for ISH were chosen from coding sequences of EBV-encoded small nuclear RNA 1 (EBER1). Results of ISH were reported in a number of cells expressing EBER1/5 x 104 PBMC (#EBER1). Fever, diarrhea, upper respiratory symptoms, pleural effusion, ascites, lymphadenopathy, and lymphoproliferative disease (LPD) accompanied with EBV infection proven by serology, viral-specific stain or PCR were regarded as EBV related diseases (EBVD). All samples with positive #EBER1 were accompanied by positive EBV PCR. #EBERI was 68.2 +/- 144.9 (mean +/- SD) ranging from 0 to 621 in the acute phase, 0.20 +/- 0.41 ranging from 0 to 2 in the convalescence phase, 0.27 +/- 0.77 in 23 preoperative patients with positive serology, and 0 in all 14 preoperative patients with negative serology. The #EBER1 in ongoing EBVD was significantly greater than that of patients in convalescence or before transplantation. Patients with #EBERI greater than 10 had a significantly lower chance of convalescence and a higher mortality than patients with #EBER 1 less than 10. We conclude that #EBER1 could be a specific and quantitative marker of EBVD and might predict progression to LPD.

Child↗

Biliary complications in pediatric living related liver transplantation.

BACKGROUND: The goal of this study was to evaluate cause and outcome of biliary complications occurring after pediatric living related liver transplantation (LRLT). METHODS: A database of 205 pediatric patients (71 male and 134 female) undergoing 208 LRLT from June 1990 to April 1996 was reviewed. RESULTS: The overall incidence of bile duct complications was 13.9% (29 patients). There were 19 bile leaks, 7 anastomotic strictures, 8 intrahepatic biliary complications, and the bile duct was ligated inadvertently in 2 cases. Logistic regression analysis revealed hepatic artery thrombosis, ABO incompatible transplantation, intrapulmonary shunting in recipients, mode of artery reconstruction, and cytomegalovirus infection were all significant risk factors for biliary complications. CONCLUSIONS: Avoidance of ABO incompatible transplantation where possible, routine use of microvascular techniques for hepatic artery reconstruction to minimize the risk of artery thrombosis, earlier transplantation for patients with intrapulmonary shunt, and prophylaxis against cytomegalovirus infection should all reduce the rate of biliary complications after LRLT in pediatric recipients.

ABO Blood-Group System↗

Hepatic artery thrombosis in living related liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss in pediatric patients. We previously reported that the microsurgical techniques for arterial anastomosis can reduce the incidence of HAT in living related liver transplantation (LRLT). The purpose of this study is to analyze the risk factors for HAT after LRLT. A total of 245 patients received 250 liver transplants. METHODS: Eight arteries in eight patients, reconstructed with the use of loupe magnification (HAT; 1/8, 12.5%), were excluded from this study. We observed HAT in 4 patients of the 242 transplants (1.7%, HAT group). Seventeen factors were compared between the HAT and the control group (those without HAT). RESULTS: HAT occurred in 3 of 33 grafts (9%) from ABO-incompatible donors, whereas it occurred in 1 of 209 grafts (0.5%) from identical or compatible donors (P=0.008). The corrected volume of fresh-frozen plasma intraoperatively transfused in the HAT group (46.9+/-30.3 ml/kg) was significantly (P=0.015) different from that in the control group (10.2+/-1.9 ml/mg). In all four patients with HAT, emergent revisions of the anastomosis were performed. Two patients with ABO-incompatible grafts died of hepatic failure and sepsis. CONCLUSIONS: Although microsurgical techniques can minimize the surgical risk factors for HAT, overtransfusion of fresh-frozen plasma in high-risk patients (ABO incompatible) may be a critical factor in the development of HAT in LRLT.

Arterial Occlusive Diseases↗

Presence of anti-FKBP12 autoantibodies in patients with liver allografts: its association with allograft rejection.

BACKGROUND: It was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts. METHODS: We investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting. RESULTS: The autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1) (P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects. CONCLUSIONS: These results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.

Absorption↗

Serotonin as a useful parameter for cold and warm ischemic injury in small bowel transplantation.

We investigated serotonin as a parameter of cold and warm ischemic injury prior to transplantation. Lewis rats were used as both donors and recipients, and the proximal 20 cm of jejunum served as the graft. The grafts were preserved in 4 degrees C lactated Ringer's solution for 0, 6, 12, 18, and 24 hr after harvest for cold ischemia (n=7/group). The superior mesenteric artery was clamped for 0, 15, 30, 60, and 120 min before harvest for warm ischemia (n=7/group). The serotonin concentration was measured in the luminal effluent and the preservation solution before transplantation, and total serotonin was calculated as the sum of these amounts. Finally, transplantation was performed heterotopically. Total serotonin increased significantly with both cold and warm ischemic time (P<0.01 by analysis of variance, Fisher's PLSD); however, between 18 hr and 24 hr of cold ischemic time only, there were no significant changes. Total serotonin levels correlated well with cold and warm ischemic time, as shown by linear regression analysis (cold ischemia: R2=80.2%, P<0.01; warm ischemia: R2=92.8%, P<0.01). We established the cutoff level of total serotonin to predict the graft survival at 2200 ng, and using this critical level, graft survival was predicted by total serotonin with a sensitivity of 71.4% and a specificity of 89.8%. Immunohistochemical staining with the serotonin antibody revealed that the number of serotonin-positive cells decreased with both cold and warm ischemic time. In conclusion, serotonin is a useful parameter of cold and warm ischemic injury before transplantation and can assist in predicting graft survival.

Animals↗

Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has recently been performed in patients with noncirrhotic metabolic liver diseases. However, long-term outcomes for the preserved native liver and the transplanted liver graft have not been clearly established yet. METHODS: The recipient was a 36-month-old girl with ornithine transcarbamylase deficiency. She underwent APOLT, using her father's left lateral segment. RESULTS: Liver function was normalized soon after APOLT and the patient was able to ingest a normal diet without medication. Coexistence of the well-functioning native liver and graft was demonstrated in a computed tomography scan, Doppler ultrasonography, scintigraphy, and histological examination, during a relatively long-term follow-up period. CONCLUSIONS: APOLT seems to be most useful for the treatment of noncirrhotic metabolic liver diseases.

Biopsy↗

A hepatic graft tuberculosis transmitted from a living-related donor.

Exclusion of occult diseases in the donor organ and prevention of infectious disease transmission are minimal requirements in organ transplantation. We report here a case of hepatic graft tuberculosis, which was most likely transmitted by the graft from the living-related donor. The course of the recipient included tuberculosis, rejection, and other infections, which led to vanishing bile duct syndrome. Due to various infections and tuberculosis, as well as a strong interaction between rifampicin and tacrolimus, the patient died of pneumonia on day 273 after transplantation. This case emphasizes the importance of care in the selection of a living-related donor for liver transplantation.

Adult↗