Neoplastic disease after heart transplantation: single center experience.

OBJECTIVES: Mandatory use of prolonged immunosuppression in organ transplantation is complicated by an increased incidence of cancer. The current study represents a retrospective analysis of the incidence of neoplasms in our heart transplantation program. METHODS: Four-hundred and seventy-four patients (403 male and 71 female; mean age, 48.6+/-12.1 years), with at least 30 days of follow-up, were enrolled in this study. Patients received triple immunosuppression with cyclosporin A, azathioprine and steroids. Moreover, as a prophylactic anti-lymphocyte therapy, 388 patients (82%) were administered RATG, 67 patients (14%) received ALG and 19 patients (4%) OKT3. The mean follow-up time was 71.1+/-43.0 months. RESULTS: Fifty-five patients (11.6%) developed malignant neoplasms. The cancer frequencies were: solid tumors, 55%; non-Hodgkin lymphomas (NHL), 20%; Kaposi's sarcomas, 11%; skin cancers, 9%; undifferentiated sarcomas and myelomas, 5%. Solid tumors mainly affected the lung (39%), bowel (16%), stomach (6.5%), liver (6.5%), pancreas (6.5%) and oral cavity (6.5%). The times to the onset of cancer from transplantation were: Kaposi's sarcoma, 12.7+/-16.8 months; skin cancers, 34.5+/-23.8 months; solid tumors, 54.3+/-38.7 months; NHL, 60.1+/-36.4 months; undifferentiated sarcomas and myelomas, 90.0+/-15.6 months. As determined by univariate and multivariate analyses, sex, number of treated rejections, previous history of tumor, average dose of cyclosporine and prednisone and cyclosporine blood levels did not increase the incidence of malignancies. Univariate analysis suggests a significant correlation between the type of prophylactic immunoglobulins and the average dose of azathioprine with the incidence of neoplasms. Both univariate and multivariate analyses demonstrated a significant correlation between patient's age at the time of transplantation and risk of cancer occurrence (risk increased by 1.074/year; P=0.0056 with multivariate Cox regression). CONCLUSIONS: Cancer is a strong limitation for long-term survival after heart transplantation. The only risk factor recognized is the patient's age at the time of transplant. Furthermore, the type of prophylactic globulins used for induction therapy and some specific immunosuppressant agent (azathioprine) may play a significant role in the development of malignancies after transplantation.     

Sirolimus in heart transplantation: a single center initial experience

Sirolimus (SRL) is a potent non-nephrotoxic immunosuppressant. In our unit, SRL was administered to 17 heart transplant (HT) recipients at 1770+/-1234 days' posttransplant surgery, for the following reasons: (1) calcineurin inhibitor (CI) withdrawal due to renal insufficiency (RI; n=6); (2) neurotoxicity (n=1) and pancytopenia (n=1); (3) vascular graft disease (VGD) treatment (n=5); (4) immunosuppression optimization due to lung cancer (n=2); (5) CI use was delayed due to postsurgery RI (n=2). The mean follow-up was 190+/-165 days. Mean SRL doses (mg)/concentrations (ng/mL) at 7 (n=17), 30 (n=14), and 180 (n=8) days were: 1.2+/-0.6/5.9+/-6; 1.6+/-0.8/4.8+/-3.1; and 1.7+/-1.0/5.2+/-3.7. Among group 1, CI patients were discontinued without favorable functional impact. Neurotoxicity and pancytopenia improved, but there were no major clinical events in the VGD group. One "bridge" to CI was successfully performed (postsurgery RI). Total leukocyte count fell while hemoglobin, platelet, and cholesterol profiles were not affected. Ten of 15 patients (67%) were discontinued from CI without rejection and with a dose reduction of mycophenolate mofetil. There were 8 episodes (47%) of SRL-related toxicity, leading to 4 discontinuations (23%); 8 patients (47%) have died during follow-up.This retrospective analysis of outcomes in the context of severe complicated patients suggests that more premature introduction SRL is preferable, particularly in a large patient cohort.     

Cardiac transplantation in pediatric patients: fifteen-year experience of a single center

Background

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.

Methods

Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 ± 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.

Results

Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 ± 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.

Conclusions

Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.     

Osteoporosis after renal transplantation: single center experience

BACKGROUND: Osteoporosis is a major source of morbidity after renal transplantation. The aim of this retrospective study was to determine the independent influences of different parameters on bone mineral density (BMD) in various parts of the body after renal transplantation. METHODS: BMD was measured in 130 of 954 renal allograft recipients who underwent surgery between 1985 and 1999. RESULTS: Time since transplantation and cumulative prednisolone doses were significantly higher in patients who had osteoporosis of the lumbar vertebrae (P=0.06 and 0.034, respectively). Logistic regression analysis revealed that cumulative prednisolone dose was the only significant predictor of low vertebral BMD (P=0.02, r=0.33). For the neck of the femur, high blood urea nitrogen and low Mg levels were found to be the predictors of low bone density (P=0.002 and 0.04, respectively). Although parathyroid hormone levels were higher in femoral osteoporosis patients than in those not affected at this site, the difference was not statistically significant (P=0.294). Time since transplantation, cumulative prednisolone dose, and cyclosporine A dose were all found to have a major negative impact on BMD in the radius region (P=0.001, 0.000, 0.001, respectively). Regression analysis showed that cumulative prednisolone dose (P=0.0008, r=0.34), time since transplantation (P=0.005, r=0.27), body mass index (P=0.01, r=-0.21), male gender (P=0.02, r=-0.21), and age (P=0.04, r=0.16) all had major effects on radius BMD. In conclusion, the radius seems to be one of the major parts of the skeleton affected by factors introduced after renal transplantation.     

Tuberculosis after heart transplantation: twenty years of experience in a single center in Taiwan

The incidence of tuberculosis is slightly higher among heart transplantation cases than in the general population in Taiwan. Tuberculosis shows a high mortality rate ranging from 22% to 31% in transplant recipients. From October 1987 to October 2007, we performed 315 heart transplantations. Clinical records were reviewed for demographic data, clinical presentation, treatment, and outcome. Tuberculosis was diagnosed by cultures of any body sample in association with compatible symptoms and signs. Mortality was related to tuberculosis if there was evidence of active tuberculosis at the time of death and no other etiology accounted for death. Ten patients who had received heart transplants were diagnosed as tuberculosis. There were seven pulmonary lesions and seven extrapulmonary lesions. Treatment consisted of isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, ciprofloxacin, and levofloxacin. Seven patients completed the antituberculosis treatment: the median treatment duration was 1 year. Three patients developed hepatitis. There was no tuberculosis-related mortality. Ten out of a total of 315 patients (3.17%) represented a tuberculosis rate higher than that reported for the general Taiwan population (67/100,000). This high mortality of infection may be completely treated by a combination of at least three drugs except pyrzinamide because of side effects and tolerance.     

Long‐term outcome of pediatric renal transplantation: a single center experience

Abe T, Ichimaru N, Kakuta Y, Okumi M, Imamura R, Isaka Y, Takahara S, Kokado Y, Okuyama A. Long‐term outcome of pediatric renal transplantation: a single center experience.
Clin Transplant 2011: 25: 388–394. © 2010 John Wiley & Sons A/S. Abstract: Renal transplantation is the optimal treatment for pediatric end‐stage renal disease. We examined 51 children <20 yr old who underwent a total of 52 living‐donor renal transplantations at Osaka University Hospital between 1972 and 2004. The mean age at transplantation was 13.7 (3–19 yr). The mean duration of follow‐up was 16.5 yr. The five‐, 10‐, and 20‐yr patient survival rates following renal transplantation were 94%, 90%, and 87%, respectively. The five‐, 10‐, and 20‐yr graft survival rates were 76%, 65%, and 48%, respectively. A double‐drug regimen was used before 1987; this was replaced by a triple‐drug regimen including a calcineurin inhibitor in 1988. The five‐, 10‐, and 20‐yr graft survival rates after 1988 (89%, 80%, and 60%, respectively) were higher than those before 1987. Growth was examined among patients <15 yr old at the time of surgery, and height standard deviation (SD) scores (Z‐scores) were analyzed in 14 patients who displayed favorable renal function after transplantation. At the time of transplantation, mean SD score (SDS) was ?2.39, and mean final adult SDS was ?1.79. Rates of patient and graft survival after renal transplantation were mostly favorable. Future goals must include overcoming chronic rejection and establishing a steroid discontinuation protocol to improve growth.     

Urolithiasis after kidney transplantation in pediatric recipients: a single center report

BACKGROUND: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls. RESULTS: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS). CONCLUSIONS: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.     

Outcome of isolated small bowel transplantation in adults: experience from a single Italian center

AIM: Isolated small bowel transplantation is becoming the treatment of choice for adult patients with serious parenteral nutrition (PN) related complications: we report our three-year experience (December 2000-December 2003) from a single Italian center (Modena-Italy), with one of the larger European series. METHODS: We transplanted 14 patients, with a previous mean PN course of 27 months and a mean 21-month post-transplantation follow-up (range 3-36 months), obtaining a one-year actuarial survival rate of 92.3% with no intraoperative deaths. RESULTS: We lost 1 patient (7.2%), died for post-transplantation overwhelming sepsis following Cytomegalovirus (CMV) enteritis. Thirteen patients are alive, with one-year actuarial graft survival rate of 85.1%: 1 patient underwent graft removal (7.2%) for intractable severe acute rejection. Our immunosuppressive regimen was based on tacrolimus and 3 induction protocols: daclizumab (8 patients) with steroids, alemtuzumab (4 patients) and thymoglobulin (2 patients) without steroids. In 9 cases, we added sirolimus. Nine recipients experienced 22 episodes of acute cellular rejection (ACR), treated successfully in all cases but one. One patient (7.2%) was treated successfully for Post Transplant Lymphoproliferative Disease (PTLD) and is disease-free after 8 months. CONCLUSIONS: Small bowel transplantation can achieve optimal results depending on appropriate immunosuppressive management and candidate selection, added to shorter ischemia time and careful donor and graft selection.     

Urologic de novo malignancies after kidney transplantation: a single center experience

Introduction

Urologic cancers are the second or third most common malignancies in renal transplant (RT) recipients. This study sought to determine the incidence of and identify possible risk factors for urologic malignancies among patients who underwent transplantation at our center.

Methods

This retrospective, single-center cohort included 836 patients who underwent transplantation from 1994 to 2011 who remained under our care. A review of their medical records revealed 63 subjects with de novo cancer, including 21 with urologic malignancies (2.5%). We analyzed demographic and clinical data of cancer versus noncancer patients with differences considered to be significant at P < .05.

Results

The urologic malignancies included renal cell carcinoma (n = 13), prostate cancer (n = 5), and bladder transitional cell carcinoma (n = 3). The mean follow-up time was 10 ± 3.9 years. The mean age at diagnosis was 54 ± 7.4 years and the mean time from transplantation was 4 ± 3.3 years. The mortality rate among group was 19.0%. The analysis did not show significant differences in demographic or clinical characteristics between the groups, except for the prevalence of male gender and smoking status among the cancer cohort. No significant differences were observed for other suspected risk factors, including immunosuppressive protocols, time of pretransplantation dialysis, and age.

Conclusions

The development of urologic malignancies is an early event, frequently observed within 4-5 years after transplantation. Therefore, this period should be considered for routine urologic cancer screening.     

Liver transplantation from donation after cardiac death: a single center experience

BACKGROUND: Liver transplantation (LT) from controlled donation after cardiac death (DCD) donors has increased steadily during the past decade because of the donor shortage in the United States. Although early reports of LT from DCD donors provided evidence for acceptable outcomes, long-term graft and patient survival rates from these procedures have been reviewed only recently. METHODS: From February 1990 to June 2006, 1209 LTs were performed from donation after brain death (DBD) donors, and 24 were performed from DCD donors at our institution. Detailed review of donor and recipient characteristics, and survival rates were evaluated in the two groups. RESULTS: One- and 3-year patient survival was similar in both groups, (DCD 86.8%, 81.7% vs. DBD 84.0%, 76.0%, respectively; P=0.713). Graft survival appeared inferior in the DCD group compared with the DBD group at 1 year (69.1% vs. 78.7%) and 3 years (58.6% vs. 70.2%), but there was no statistical difference (P=0.082). There were no significant differences in hepatic artery thrombosis, portal vein thrombosis, primary nonfunction, and biliary stricture between the two groups. All cases with biliary stricture in DCD group finally led to graft loss, and all survived with retransplantation. CONCLUSION: The outcome of LT from DCD donors remains acceptable in our institution. Although biliary complication rate was similar in two groups, the consequence of this complication in DCD was more severe and often led to graft loss. Close observation of biliary complications after LT from DCD donors would be beneficial.     

Ten year survival after paediatric heart transplantation: a single centre experience.

OBJECTIVE: To report 10 years survival in children under the age of 16 years undergoing heart transplantation in a single institution. METHODS: One hundred and thirty nine/one hundred and ninety three patients (73%) survived more than 1 year after transplant. Seventy four (53%) of these survived more than 10 (10.0-20.1) years. Age at operation was 10 days-15.5 (mean 8.1) years. Patients were maintained on ciclosporin and azathiaprine alone. Routine steroids only given to 4 patients for either persistent rejection or deteriorating renal function. Rejection diagnosed on clinical or echocardiographic grounds. No routine biopsies were performed. Bi-annual coronary angiography was used to diagnose graft coronary disease. RESULTS: Graft coronary disease was found in 8 patients (11%), 2 were re-transplanted and have survived 4.3-7.2 years since. Two patients are alive without intervention 2.0-13.0 years from initial diagnosis. Two patients have undergone interventional procedures 11 and 16 years after transplantation and are alive 3 and 4 years, respectively, later. Seven patients have had post transplant lymphoproliferative disease (PTLD) and 6 have had no recurrence for 3-13 years after treatment. Impaired renal function with abnormal serum creatinine levels is increasingly common-11 patients have developed end stage renal failure, 7 requiring renal transplantation, hypertension occurred in only 3 patients other than those in renal failure. Late rejection episodes associated with probable non-adherence occurred in 7 patients. There were 10 late deaths; 2 from graft coronary disease; 1 from PTLD; 3 from renal failure; 3 from acute rejection and 1 from infection. Conditional actuarial survival from 1 year post transplant was 76 and 67% at 10 and 15 years, respectively. CONCLUSIONS: Survival for more than 10 years is increasingly realistic. In this age group adherence and deteriorating renal function are major challenges.     

Normal adult height after steroid-withdrawal within 6 months of pediatric kidney transplantation: a 20 years single center experience

Long-term corticosteroid treatment impairs growth in children after kidney transplantation (KTx). The impact of steroid withdrawal with respect to adult height remains to be elucidated. In this single-center retrospective analysis linear growth and graft function in 74 pediatric KTx patients transplanted between 1981 and 2001 was investigated. Mean follow up was 8.5years. Steroids were weaned off between months 4 and 6. Steroid withdrawal resulted in sustained catch-up growth after KTx. Absolute and standardized height velocity in prepubertal patients during the first year post-KTx was 8.9cm/year and +2.9 SD score (SDS), respectively (P<0.001 versus healthy children). Mean adult height amounted to -0.5±1.1 SDS and -1.0±1.3 SDS in prepubertal and pubertal patients and was within the normal range (>-2 SD) in 94% and 80% of them. Multiple regression analysis revealed age and standardized height at KTx as independent predictors of adult height (model r(2) =0.48). Overall graft survival at 5 and 10years was 92% and 71%, respectively. Steroid withdrawal during month 4-6 after KTx in prepubertal patients results in an adult height within the normal range, whereas catch-up growth is limited in pubertal patients.     

Orthotopic heart transplantation in elderly patients: a 10-year experience at a single center

INTRODUCTION: A consensus has not yet been reached regarding the indications for orthotopic heart transplantation (OHT) in elderly patients or the age limit contraindicating the procedure. The objective of this study was to assess OHT outcomes to determine whether elderly patients benefit from the procedure. METHODS: From February 1993 to February 2003, 178 OHTs were performed on recipients of mean age 47.4 +/- 15 years (range, 4 to 74) including 80.3% men. The population was divided into two groups: group A included patients >/= 60 years, and group B those younger than that age. Survival was analyzed for the overall population and for both age groups during a 10-year follow-up period. RESULTS: Group A included 36 patients (20.8%) and group B 142 patients (79.2%). Mean age was 63.7 +/- 2.9 years (60 to 74) in A, and 43 +/- 13.9 years (4 to 59) in B. In-hospital mortality was significantly higher among group A (n = 11, 31.4%) compared to B (n = 17, 12.1%, P =.008). Survival at 1, 5, and 10 years was 61.5% +/- 8%, 58.1% +/- 8.3%, and 49.8% +/- 10.5% group A; and 84.2% +/- 3%, 73.7% +/- 4.1%, and 69.9% +/- 4.7 for group B. Elderly patients showed a lower survival rate (49.8%) compared with the younger group (69.9%) at 10-year follow-up (P =.007). Conditional survival at 9 years failed to show significant differences (A 72.2% vs B 79.6%, P =.4). CONCLUSION: In our population, elderly recipients showed a higher in-hospital mortality. However, when the first post-OHT year was excluded, we found similar survival rates for both age groups.     

Outcome of simultaneous kidney pancreas transplantation: a single center analysis

The aim of this study was to evaluate the outcome of simultaneous kidney pancreas transplantation (SKPT) by various surgical techniques. The 161 patients submitted to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to 1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50 whole pancreas with enteric diversion (40 with systemic and 10 with portal drainage) (from 1999 to September 2002). A positive effect on patient survival was evident using enteric diversion versus the duct occlusion group (P = .005), and versus the bladder diversion group (.035), and on pancreas graft survival in the enteric diversion versus the duct occlusion group (P < .028). These improvements may be due to refined donor and patient selection criteria, surgical technique, and immunosuppression.     

Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin.

BACKGROUND: Coronary allograft vasculopathy (CAV) is a progressive complication after cardiac transplantation and limits survival. Hyperlipidemia is a known risk factor for CAV, and pravastatin is effective in decreasing cholesterol levels in adults after transplantation. However, few data exist regarding lipid profiles and statin use after pediatric heart transplantation. We evaluated the prevalence of hyperlipidemia in pediatric heart transplant recipients and assessed the efficacy and safety of pravastatin therapy. METHODS: We performed a retrospective chart review of lipid profiles > or =1 year after surgery in 50 pediatric cardiac transplant recipients to assess the incidence of hyperlipidemia. Twenty of these patients received pravastatin for hypercholesterolemia. Their primary immunosuppression therapy was cyclosporine/prednisone plus either azathioprine or mycophenolate mofetil. We reviewed serial lipid profiles, creatinine phosphokinase, and liver enzymes. RESULTS: Overall, 36% of the patients (n = 50) had total cholesterol (TC) concentrations > 200 mg/dl and 52% had low-density lipoprotein (LDL) >110 mg/dL beyond 1 year after transplantation. Of the 20 treated with pravastatin, TC (236 +/- 51 vs 174 +/- 33 mg/dl) and LDL levels (151 +/- 32 vs 99 +/- 21 mg/dl) decreased significantly with therapy (p <.0001). We found no symptoms; however, 1 patient had increased creatinine phosphokinase. Liver enzyme concentrations remained normal in all. CONCLUSIONS: Hypercholesterolemia is prevalent in pediatric cardiac transplant recipients. Pravastatin therapy is effective in decreasing TC and LDL levels, seems to be safe, and is tolerated well. Further studies are necessary to determine whether pravastatin treatment is beneficial in decreasing CAV.