Kidney transplant from the same donor without maintenance immunosuppression after previous hematopoietic stem cell transplant.

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.

Rejection of skin allografts by indirect allorecognition of donor class I major histocompatibility complex peptides.

LEW (RT1l) rats were immunized with peptides corresponding to the alpha helical region of the alpha 1 domain (peptide 1), the beta sheet of the alpha 2 domain (peptide 2), and the alpha helical region of the alpha 2 domain (peptide 3) of the RT1-Aav1 classical class I molecule of the DA (RT1av1) strain. The immunizations were without carriers, and the objective was to prime to indirect allorecognition without influencing direct recognition of the RT1-Aav1 molecule. The LEW rats mounted strong primary and secondary antibody responses to peptides 1 and 3, but only weak secondary responses to peptide 2. None of the antipeptide antibodies crossreacted with intact RT1-Aav1 class I molecules. The immunization also resulted in LEW antigen-presenting cell-dependent, CD4+ T cell proliferative responses, which were very strong against peptide 1 and weakest against peptide 2. LEW rats immunized with peptides 1 or 3, but most effectively with both peptides 1 and 3 together, showed accelerated rejection of DA skin allografts. This effect was not observed in LEW rats immunized with peptide 2. In response to the DA skin allograft, the peptide-immunized LEW rats showed markedly accelerated kinetics of antibody production to the intact RT1-Aav1 molecule. These data demonstrate that indirect allorecognition can play an important role in allograft rejection and have important implications for understanding allograft rejection and its regulation.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in adult liver transplantation.

BACKGROUND: A safe and effective preservation solution is a precondition for successful orthotopic liver transplantation (OLT). This study compared University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions in OLT. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 137 primary cadaveric. OLT performed between January 2003 and December 2006 at our institution. Sixty-eight grafts were harvested using UW and 69 using HTK. Recipients were managed similarly in regard to operative techniques and immunosuppression. We collected donor data including serum transaminases, serum sodium, ICU stay and assessed macroscopic liver quality. Recipient serum transaminases were collected on postoperative days 1, 7, 14, and 30. We compared biliary and vascular complications, as well as patient and graft survivals. RESULTS: Mean serum bilirubin levels were slightly higher in the HTK group at 1,7,14, and 30 days after transplantation, whereas transaminases were higher in the UW group. Primary nonfunction occurred in 1 patient in each group. Retransplantation was performed in 5 patients in the UW and in 9 patients in the HTK group. Biliary complication rates were similar in the UW and HTK groups (22% and 17%, respectively). Six arterial complications occurred in the HTK (8.7%) and 2 in the UW group (2.9%; P < .05). Mean follow-up was 25 months. Graft survival at 1, 12, and 36 months was 90%, 78%, and 75% versus 90%, 71%, and 71% in the UW versus HTK groups, respectively. One-, 12-, and 36-month patient survival rates were 93%, 78%, and 75% versus 93%, 78%, and 78% in the UW versus HTK groups, respectively. CONCLUSIONS: There were no significant differences in graft and patient survivals between the 2 groups. Whereas the biliary complication rates were comparable in both groups, the arterial complications were clearly higher in the UW group (8.7% vs 2.9%; P < .05%). UW and HTK solutions seemed to be equally safe and effective in the preservation of liver grafts. The high incidence of arterial complications in the UW group requires further prospective studies.

Results of resection and transplantation for hepatocellular carcinoma in cirrhosis and noncirrhosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Both liver resection (LR) and orthotopic liver transplantation (OLT) are surgical treatment options depending on the size of the tumor and the presence of cirrhosis. Liver cirrhosis is the main reason for the high early postoperative mortality after resection. Even in the Child A stage, extensive resections are not recommended. This study presented the results of surgical treatment (LR or OLT) for HCC in cirrhotic and noncirrhotic livers. We analyzed the data of 76 patients who underwent LR or OLT for HCC from January 2001 to December 2006. In noncirrhotic livers the following resections were performed: 30 right and extended right hemihepatectomies (54.5%); 11 left hemihepatectomies (20%); and 14 mono- or bisegmentectomies (25.5%). In cirrhotic livers the following procedures were performed: in Child A stage 1 right hemihepatectomy, 1 extended right hemihepatectomy, 1 extended left hemihepatectomy, and 4 mono- or bisegmentectomies; and in Child B stage, 3 mono- or bisegmentectomies. Among 11 patients who underwent transplantation, tumors in 2 patients exceeded the Milan criteria. Five patients in the LR group were treated with transarterial chemoembolization before transplantation. LR for HCC in cirrhosis should be performed with caution; there were no long-term survivors in our data. Our study confirmed that OLT shows good long-term survival in early HCC stages. However, this may also be true for stages above the Milan criteria. For HCC in noncirrhotic livers, LR remains the treatment of choice, justifying an extensive surgical approach. Such an approach achieved favorable long term survivals.

Overview of the MELD score and the UNOS adult liver allocation system.

On February 27, 2002, the United Network for Organ Sharing (UNOS) introduced a new allocation policy for cadaveric liver transplants, based on the Model for End-Stage Liver Disease (MELD) score. This new policy stratifies the patients based on their risk of death while on the waiting list. We analyzed the background and main features of this new allocation policy to evaluate the effects on waiting list dynamics as well as the accuracy of MELD as a predictor of pretransplantation mortality and posttransplantation outcome. MELD has proved to be accurate as a predictor of waiting list mortality, but seems to be less accurate to predict posttransplantation outcome. Immediate effects of the new policy were a reduction in the waiting list, while organs were primarily directed to sicker patients with reduced waiting times. There was a statistically but not significantly reduced number of patients removed from the list due to death or severity of sickness. The balance between medical urgency and transplant benefit is still to be defined as is the relationship between pretransplantation criteria and posttransplantation outcomes, and the way this relationship should be included in the allocation policy.

Characterization of dendritic cell subsets in patients undergoing renal transplantation.

Dendritic cells (DCs) play a key role in transplantation tolerance and immune reactions to transplants. In order to ascertain whether DC levels are predictive for rejection, we examined the levels and expression patterns of DCs of renal transplant patients following immunosuppressive and/or surgical interventions. Myeloid (HLA-DR+/CD11c+) and plasmacytoid (HLA-DR+/CD123+) DCs were characterized by flow cytometry over 28 days. We demonstrated that myeloid DCs and plasmacytoid DCs in peripheral blood were discernable and dramatically decreased following renal transplantation and immunosuppression. Furthermore, the expression of CD62L was significantly up-regulated (P=.032), while CD86 was significantly down-regulated (P=.008) on myeloid but not plasmacytoid DCs. Although DC levels alone were not predictive for the occurrence of a rejection episode, in combination with other factors they may be indicative of rejection, thereby sparing the patient a biopsy.

Successful staged kidney and liver transplantation for glycogen storage disease type Ib: A case report.

Glycogen storage disease type Ib is a rare metabolic disease caused by a defect of the G6P transporter. Patients suffer from hypoglycemic episodes; growth and developmental delay; osteoporosis; neutropenia; and tendency to infections, ovarian cysts, and liver adenomas. Terminal kidney disease is a rare complication. Liver transplantation has been performed to prevent malignant transformation of hepatic adenomas. We present the case of a female patient with glycogenosis type Ib who had severe hypoglycemic episodes and recurrent infections since early childhood. She became dialysis dependent at the age of 24 years. Kidney transplantation was performed at age 30, and liver transplantation 2 years later. The main indication for liver transplantation were the persistent, therapy-refractory hypoglycemic episodes. The transplanted kidney function is stable. The liver transplantation resulted in the disappearance of hypoglycemic episodes, with the patient leading a normal life and eating a normal diet. The neutropenia did not recover, but there were no more significant infectious episodes after liver transplantation. This is, to the best of our knowledge, the first communication of a dual kidney and liver transplant performed in a patient with glycogenosis type Ib. It confirmed the beneficial effect of liver transplantation on the quality of life of patients with severe hypoglycemia. The transplantation should be attempted earlier in the course of the disease to reduce complications and allow catch-up growth. Hepatocyte transplantation may be considered; however, long-term results seem to be rather poor in the few documented cases.

Changes in quality of life after renal transplantation.

Quality of life is becoming an increasingly important concept in the evaluation of different therapeutic interventions. In this cross-sectional study, quality of life analyzed in 76 renal transplant patients was compared with 65 patients with end-stage renal disease (ESRD) awaiting transplantation. Both groups were asked to estimate their subjective quality of life by responding to a multidimensional questionnaire that sought information in the following areas: (1) sociodemographic data, (2) a personality test (Giessen-Test), (3) information about employment, (4) assessment of anxiety and depression (GHQ-28), (5) the SF-36 as an important measurement for quality of life, and (6) the ESRD symptom checklist-transplantation module. The sociodemographic profiles of both groups were similar. The SF-36 revealed significantly higher values for transplant recipients in terms of physical functioning (P < or = .001), general health perceptions (P < or = .01), social functioning (P < or = .01), and physical summary value (P < or = .001). The other tests (Giessen-Test and GHQ-28) and employment data showed no significant differences between the two samples. Collectively, the data demonstrate a considerable improvement in quality of life in renal transplant patients. Despite good physical recovery and higher quality of life after transplantation, the rate of vocational rehabilitation remained low, partially explained by the currently high levels of unemployment.

Computerized CT-based 3D visualization technique in living related liver transplantation.

INTRODUCTION: For living donor liver transplantation (LDLT) accurate diagnostic workup is essential. Multiple imaging approaches are currently used. Problems arise in the assessment of vascular and bile duct anatomy, liver graft volume, and vascular territories involved. A 3D visualization system that improves anatomic assessment, allows interactive surgery planning, and acts as an intraoperative guide with enhanced precision is required. Refinements in computed tomography (CT) technology with the introduction of multidetector-row CT scanners and implementation of mathematical methods on computerized digital data has enabled CT-based 3D visualizations. MATERIALS AND METHODS: Sixteen LDLT candidates and three LDLT recipients were assessed by multislice CT examination. Image processing of the digital raw data for 3D visualization included segmentation and calculation of center lines. A hierarchical mathematical model representing the vascular and biliary tree was created. This allowed calculation of individual vascular territories. RESULTS: 3D CT-based visualization in LDLT facilitates diagnostic workup with high accuracy for analyses of vascular and bile duct variants, volumetry, and assessment of the optimal surgical splitting line of the living donor liver. Resultant areas of either arterial devascularization or venous congestion can be displayed and quantified preoperatively. The diagnostic method is of major impact on patient selection and directly influences intraoperative surgical guidance. The currently practiced "multiple imaging approach" approach, especially with regard to invasive diagnostics, can be avoided in the future.

Expression of the ectoenzyme RT6 is not restricted to resting peripheral T cells and is differently regulated in normal peripheral T cells, intestinal IEL, and NK cells.

The RT6 alloantigenic system of the rat has originally been defined on T lymphocytes of the peripheral lymphatic organs and has been considered to be selectively expressed on mature peripheral T cells. Studying NK cells and intestinal intraepithelial lymphocytes (IEL), we have now found that both cell types also express RT6 and that the expression patterns found for IEL and NK cells were markedly different from each other and also from the expression pattern previously described for T cells of the peripheral lymphatic organs. In lymph nodes, spleen, and blood both RT6- and RT6+ T cells have been found and the density of RT6 expression on the positive cells has been shown to vary over a broad range. In contrast more than 98% of intestinal IEL stained for RT6 and the RT6 density was about tenfold higher than on strongly positive T cells of the peripheral lymphatic organs. Furthermore, the same high RT6 density was also found on IEL of athymic nude rats althogh these cells, to a large extent, lacked other T cell markers. This probably indicates that RT6 expression is an early event in the maturation of intestinal IEL which can occur already before the expression of T cell-specific membrane molecules. The conclusion that the expression of RT6 may be differently regulated in IEL and other T cell populations was further substantiated by the observation that RT6 was also present on IEL of diabetes-prone BB rats which are known to lack RT6 positive T cells in peripheral lymphatic organs. For NK cells still another pattern of RT6 expression was found. Unlike peripheral T cells and IEL, only a small subset of NK cells in blood and spleen expressed RT6. The percentage of RT6 positive cells was increased by in vitro stimulation of isolated NK cells with high concentrations of recombinant rat IL-2 indicating that RT6 expression may be associated with an activated state in NK cells. Taken together, these findings demonstrate that the expression of RT6 is not restricted to T cells and is differently regulated in normal peripheral T cells, intestinal IEL, and NK cells. Since it has recently been demonstrated that the RT6 gene contains two functional promoter regions with major structural disparity it is very likely that the distinct patterns of RT6 expression in different cell types reflect the differential use of the two promoters. The development of this complex control of RT6 expression in evolution may have been driven by a beneficial effect resulting from the use of the RT6 molecular function by several different lymphocyte populations.

Multivisceral resection and intraperitoneal chemotherapy in recurrent intra-and extrahepatic HCC.

Full text is available as a scanned copy of the original print version.