Development of the Organ Donation and Transplantation Knowledge Survey for use in Asian American adolescents.

The need for kidney transplantation among Asian Americans is increasing owing to hypertension, diabetes mellitus, and the shortage of available organs. This need is likely to increase as the relatively young Asian population ages. However, knowledge about organ donation and transplantation in this population has been little investigated. The objectives of this study was to develop an Organ Donation and Transplantation Knowledge Survey for use in Asian Americans and to examine its psychometric properties. Internal consistency (Cronbach alpha) and factor analyses were used to determine the reliability and validity of the survey in 121 Asian American adolescents residing on the Big Island of Hawaii. Our results indicate that the survey had adequate reliability and was psychometrically valid for evaluating knowledge about organ donation and transplantation. More studies are needed to validate the usefulness and psychometric properties of the Organ Donation and Transplantation Knowledge Survey in other groups.

HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes.

Improvements in human immunodeficiency virus (HIV)-associated mortality make it difficult to deny transplantation based upon futility. Outcomes in the current management era are unknown. This is a prospective series of liver or kidney transplant recipients with stable HIV disease. Eleven liver and 18 kidney transplant recipients were followed for a median of 3.4 years (IQR [interquartile range] 2.9-4.9). One- and 3-year liver recipients' survival was 91% and 64%, respectively; kidney recipients' survival was 94%. One- and 3-year liver graft survival was 82% and 64%, respectively; kidney graft survival was 83%. Kidney patient and graft survival were similar to the general transplant population, while liver survival was similar to the older population, based on 1999-2004 transplants in the national database. CD4+ T-cell counts and HIV RNA levels were stable; and there were two opportunistic infections (OI). The 1- and 3-year cumulative incidence (95% confidence intervals [CI]) of rejection episodes for kidney recipients was 52% (28-75%) and 70% (48-92%), respectively. Two-thirds of hepatitis C virus (HCV)-infected patients, but no patient with hepatitis B virus (HBV) infection, recurred. Good transplant and HIV-related outcomes among kidney transplant recipients, and reasonable outcomes among liver recipients suggest that transplantation is an option for selected HIV-infected patients cared for at centers with adequate expertise.

Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging.

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.

A randomized trial of exercise and dietary counseling after liver transplantation.

We report results of a randomized clinical trial of a combined intervention of exercise and dietary counseling (ExD) after orthotopic liver transplantation (OLT). Of the 151 patients randomized into ExD or usual care (UC), 119 completed testing 2, 6 and 12 months post-OLT. Testing included assessment of exercise capacity (VO(2peak)), quadricep muscle strength, body composition (DXA), nutritional intake (Block 95) and health-related quality of life (SF-36). The intervention consisted of individualized counseling and follow-up to home-based exercise and dietary modification. Repeated measure ANOVA was performed to determine differences over time between ExD and UC with a secondary analysis to determine differences over time between adherers (Adh), nonadherers (Nadh) to the intervention and UC. The ExD group showed greater increases in VO(2peak) (p = 0.036), and self-reported general health (p = 0.038) compared to UC. Both groups demonstrated increases in muscle strength, body weight, body fat and other SF-36 scale scores. Adherence to the intervention was 37% with positive trends in VO(2peak) and body composition observed in Adh compared to Nadh and UC. These data suggest improvements in exercise capacity and body composition are achieved with nutrition and exercise behavior modifications initiated early after OLT and with regular follow-up.

Report of a National Conference on Donation after cardiac death.

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.

Posttransplantation growth in pediatric liver recipients.

The aim of this retrospective analysis was to evaluate the growth of 96 pediatric liver transplant recipients from February 1988 to June 1999. Inclusion criteria were the following: age younger than 18 years, follow-up longer than 1 year, transplantation for a nontumor indication, and no retransplantation. Linear height and growth velocity SD scores were correlated to age, sex, indication for transplantation, immunosuppression, and graft type. Transplant recipients of all ages and indications and both sexes were growth retarded at transplantation. Recipients aged younger than 24 months showed growth within the first year to achieve a height distribution equal to that of an age-matched population. Posttransplantation growth inversely correlated with height standard score at transplantation. Children older than 2 years at transplantation established new growth curves, but remained growth retarded. As children approached the prepubertal growth acceleration, growth deficits frequently were erased. Transplant recipients with biliary atresia and alpha(1)-antitrypsin deficiency showed increased growth performance compared with those who underwent transplantation for chronic hepatitis or fulminant hepatic failure. Boys were less growth retarded at transplantation and showed improved posttransplantation growth performance versus girls. No correlation to immunosuppression or graft type was identified. We conclude that early transplantation of children who show growth retardation is optimal for restoration of growth potential, whereas delaying transplantation in older children impedes potential growth.

Mixed allogeneic chimerism as a reliable model for composite tissue allograft tolerance induction across major and minor histocompatibility barriers.

BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting may be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a major MHC mismatch without the need for long-term immunosuppression. METHODS: Mixed allogeneic chimeras were prepared by using rat strains with strong MHC incompatibility [WF (RT1Au), ACI (RT1Aa)] WF + ACI-->WF, n=23. The bone marrow (BM) of recipient animals was pretreated with low-dose irradiation (500-700 cGy), followed by reconstitution with a mixture of T cell-depleted syngeneic (WF) and allogeneic (ACI) cells. Additionally, the recipient animals received a single dose of anti-lymphocyte serum (10 mg) 5 days before bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day before BMT to 10 days post-BMT. Hindlimb transplants were performed 12 months after BMT. Five animals received a limb allograft irradiated (1000 cGy) just before transplantation. Rat chimeras were characterized (percentage of donor cells present within the bloodstream) by flow cytometry at 3 and 12 months after BM reconstitution and after hindlimb transplantation. RESULTS: Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 18/23 animals. Multi-lineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60% (n=18) no sign of limb rejection was present for the duration of the study. All animals with chimerism <20% (n=5) developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) developed at >60 days in 14/21 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n=10). Five out of five animals with irradiated limb transplants showed no sign of GVHD at >100 days. CONCLUSIONS: Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. Partial functional return should be expected. The BM transplanted as part of the hindlimb allograft plays a role in the etiology of GVHD. Manipulating that BM before transplantation may influence the incidence of GVHD. This represents the first reliable rat hindlimb model demonstrating rejection-free CTA survival in an adult animal across a major MHC mismatch without the long-term need for immunosuppressive agents.

Expression of intercellular adhesion molecule-1 in the cortex of preserved rat kidneys.

BACKGROUND: Prolonged cold ischemia has been shown to be an important factor in the development of posttransplant renal dysfunction. The exact mechanisms have not been completely defined. The expression of intercellular adhesion molecule-1 (ICAM-1) (CD 54) in rat kidneys stored in University of Wisconsin (UW) solution was studied in an attempt to correlate ischemia time with immunogenicity of the graft. METHODS: Kidneys from male Lewis rats were perfused with UW solution, removed, and bathed in UW solution at 4 degrees C for 4, 12, 24, and 48 h. For the evaluation of expression of ICAM-1, immunohistochemical staining, Western blotting, and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were performed. RESULTS: Immunohistochemical staining in normal, nonischemic kidneys revealed that glomerular capillaries expressed ICAM-1 but that tubular cells did not. The preserved kidneys were analyzed by immunohistochemistry, Western blotting, and semiquantitative RT-PCR and showed increased transcription and expression of ICAM-1 in the cortex of the kidney. Expression reached a maximum at 24 h and declined at 48 h. The ICAM-1 protein expression in the preserved kidney cortex relative to control kidneys was increased at 4 h (1.68 +/- 0.60-fold of control kidneys, P = 0.06), 12 h (2.38 +/- 0.90-fold, P = 0.02), 24 h (3.70 +/- 1.29-fold, P = 0.01), and 48 h (2.00 +/- 0.54-fold, P = 0.01). The messenger RNA expression (the ratio of ICAM-1 to glyceraldehyde-3-phosphate dehydrogenase) in preserved kidneys cortex relative to control kidneys was increased at 4 h (1.19 +/- 0.14-fold of control kidneys), 12 h (1.38 +/- 0.16-fold), 24 h (1.77 +/- 0.29-fold), and 48 h (1.19 +/- 0.12-fold) (P < 0.05 for all time points). CONCLUSIONS: We conclude that cold preservation of rat kidneys in UW solution induces increasing levels of ICAM-1 cell surface expression and gene transcription. Further study is necessary to determine if this increase in adhesion molecule expression increases the immunogenicity of the allograft and contributes to the development of posttransplant renal dysfunction.

Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.

The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P =.87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P =.0001). An alpha-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > or = 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < or = 6.5 cm, or < or = 3 nodules with the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P =.0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT.

Posttransplantation lymphoproliferative disorders in pediatric patients undergoing liver transplantation.

OBJECTIVES: To study the clinicopathologic and molecular genetic findings in posttransplantation lymphoproliferative disorders (PTLDs) following pediatric liver transplantation and to determine the applicability of a recently proposed consensus classification system. DESIGN: The clinical, pathologic, and molecular genetic findings of 11 PTLDs that occurred in 10 patients are presented. These 10 patients were derived from a group of 121 pediatric patients who underwent liver transplantation at the University of California, San Francisco. The PTLDs were classified using the proposed Society for Hematopathology scheme. Clonality was determined by immunohistochemical detection of monotypic immunoglobulin or by using polymerase chain reaction-based methods to detect monoclonal immunoglobulin heavy-chain gene rearrangements. Epstein-Barr virus (EBV) was detected by immunohistochemistry, in situ hybridization, or polymerase chain reaction. Epstein-Barr virus typing and the presence of LMP1 gene deletions were also analyzed by polymerase chain reaction. RESULTS: There were 3 early lesions, 4 polymorphic PTLDs, and 4 monomorphic PTLDs. Monoclonality was demonstrated in 8 of 9 cases assessed. Epstein-Barr virus was present in all cases; of 9 cases assessed by polymerase chain reaction, the virus was type A in 8 and type B in 1. No EBV LMP1 gene deletions were identified. The corresponding liver explants were negative for EBV in 8 cases and positive in 1 case. Greater than 3 foci of disease and monomorphic PTLD were associated with decreased actuarial survival (P <.05). CONCLUSIONS: The prognosis of pediatric patients with PTLD is favorable for early lesions and polymorphous PTLD, particularly in patients with localized disease. Multifocal disease and monomorphic PTLD are associated with an unfavorable prognosis.

Physical activity and health-related quality of life in liver transplant recipients.

The US Surgeon General's Report on Physical Activity and Health recommends that people of all ages engage in regular physical activity, and that significant health benefits can be obtained through a moderate amount of physical activity. Physical activity appears to improve health-related quality of life (HRQOL) by enhancing physical functioning in persons compromised by poor health. The Medical Outcomes Study Short Form-36 (SF-36) Health Status Questionnaire was sent to all patients who were 5 years or more post-liver transplantation at the University of California at San Francisco. Additional questions related to coexisting medical conditions and participation in regular physical activity were included. SF-36 scale scores were compared between active and inactive patients. Regression analysis was also performed to determine the contributions of coexisting medical conditions and physical activity to the physical scales of the SF-36 questionnaire. Patients who participated in regular physical activity had significantly higher scores on all physical scales and the physical component scale (PCS). The regression model, which included age, sex, time posttransplantation, retransplantation, recurrence of hepatitis C, number of comorbid conditions, and physical activity participation showed that both the number of comorbid conditions and participation in physical activity were significant independent contributors to the physical functioning scale and PCS. This study indicates that physical activity is related to HRQOL after liver transplantation independent of other coexisting medical conditions.

Surgical anatomy of the left lateral segment as applied to living-donor and split-liver transplantation: a clinicopathologic study.

OBJECTIVE: To evaluate intrahepatic vascular and biliary anatomy of the left lateral segment (LLS) as applied to living-donor and split-liver transplantation. SUMMARY BACKGROUND DATA: Living-donor and split-liver transplantation are innovative surgical techniques that have expanded the donor pool. Fundamental to the application of these techniques is an understanding of intrahepatic vascular and biliary anatomy. METHODS: Pathologic data obtained from cadaveric liver corrosion casts and liver dissections were clinically correlated with the anatomical findings obtained during split-liver, living-donor, and reduced-liver transplants. RESULTS: The anatomical relation of the left bile duct system with respect to the left portal venous system was constant, with the left bile duct superior to the extrahepatic transverse portion of the left portal vein. Four specific patterns of left biliary anatomy and three patterns of left hepatic venous drainage were identified and described. CONCLUSIONS: Although highly variable, the biliary and hepatic venous anatomy of the LLS can be broadly categorized into distinct patterns. The identification of the LLS duct origin lateral to the umbilical fissure in segment 4 in 50% of cast specimens is significant in the performance of split-liver and living-donor transplantation, because dissection of the graft pedicle at the level of the round ligament will result in separate ducts from segments 2 and 3 in most patients, with the further possibility of an anterior segment 4 duct. A connective tissue bile duct plate, which can be clinically identified, is described to guide dissection of the segment 2 and 3 biliary radicles.

Experience with the use of sirolimus in liver transplantation--use in patients for whom calcineurin inhibitors are contraindicated.

Sirolimus (SRL) provides effective immunosuppression for kidney transplantation and may be useful in patients with delayed allograft function after kidney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patients with renal insufficiency or acute mental status impairment were administered SRL after liver transplantation (5- to 10-mg load, 1 to 4 mg/d). Immunosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline mental status or serum creatinine level), tacrolimus (TAC) therapy was initiated. Twelve patients received primary transplants, 1 patient received a combined liver-kidney transplant, and 1 patient received a third transplant. Follow-up was 2 to 7 months. Calcineurin inhibitors were initially withheld in 9 patients, and therapy was aborted because of toxicity in the remaining 5 patients. Mean times to the initiation of SRL and TAC therapy were 5.4 +/- 4.6 and 26.8 +/- 24.4 days, respectively. Serum trough levels of SRL did not correlate with dose or other patient variables. Two patients died after prolonged pretransplantation hospital courses in the intensive care unit. Six patients experienced acute rejection, but only 1 patient required antilymphocyte therapy. Serum creatinine levels at the start of SRL therapy were 2.2 +/- 1.1 and 1.2 +/- 0.6 mg/dL at 3 months. All 3 patients with neurological indications for SRL had a return to their baseline mental status. All patients had improved liver function chemistry test results and prothrombin times. No patients developed leukopenia or thrombocytopenia. SRL is safe after liver transplantation in patients with acute neurological or renal impairment. SRL is an attractive alternative when calcineurin inhibitors are undesirable, but serum trough levels of SRL should be monitored. A prospective randomized study of an SRL-based calcineurin inhibitor-avoiding regimen compared with standard therapy in patients with renal insufficiency will further evaluate the role for SRL in liver transplantation.