Showing papers in "Clinical Transplantation in 2004"

Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies.

Abstract: We examined the rates of malignancy at 2 yr after transplantation in renal allograft patients receiving sirolimus (SRL) in continuous combination with cyclosporine (CsA), SRL as base therapy or SRL maintenance therapy after early withdrawal of CsA. A total of 1295 patients were enrolled in two double-blind studies comparing SRL with azathioprine (AZA) or placebo administered in continuous regimens with CsA. In two other trials (n = 161), SRL given as base therapy was compared with CsA. In the fifth trial, patients were randomly assigned at 3 months to either remain on CsA + SRL therapy (n = 215) or to have CsA eliminated with SRL being continued in concentration-controlled doses (n = 215). At 2 yr after transplantation, patients receiving SRL in continuous combination with CsA had a significantly lower incidence of skin cancer compared with patients receiving placebo. Patients receiving SRL as base therapy had no malignancies compared with a 5% incidence in those receiving CsA. The incidence of malignancy was significantly lower in patients receiving concentration-controlled SRL with elimination of CsA compared with those who remained on CsA + SRL. Based on the currently available data, patients receiving SRL-based therapy without CsA or SRL maintenance therapy after early CsA withdrawal have lower rates of malignancy in the first 2 yr after renal transplantation. SRL immunotherapy may be beneficial in protecting renal transplant patients from skin cancer even when given in combination with CsA.

Management of biliary tract complications after orthotopic liver transplantation.

Abstract: Introduction: Despite improved survival, biliary complications remain a significant cause of morbidity following orthotopic liver transplantation The aim of this study was to review the incidence, treatment and optimum management pathway of biliary complications at the Scottish Liver Transplant Unit Materials and methods: All patient data were collected prospectively onto a database at the Scottish Liver Transplant Unit with review of hospital records for validation Results: A total of 379 consecutive orthotopic liver transplants were performed in 333 adult patients between November 1992 and September 2001 Biliary complications occurred in 55 grafts (51 patients) (146%) and their incidence decreased with time Biliary complications occurred in 29 (109%) of the 265 choledocho-choledochostomies compared with 14 (25%) of the 56 with T-tubes Twenty-eight biliary leaks occurred, 22 of which were anastomotic Seventeen anastomotic leaks were successfully treated non-operatively Eight patients with biliary leaks subsequently developed an anastomotic stricture Of the 30 anastomotic strictures, stent insertion was successful in resolving six of 14 (42%) early anastomotic strictures compared with one of 12 (8%) late anastomotic strictures (p = 00479) Six (38%) of the 16 early anastomotic strictures required surgery for complete resolution, compared with 12 (86%) of the 14 late anastomotic strictures (p = 00106) Conclusion: The incidence of biliary complications has decreased with time The abandonment of choledocho-choledochostomy over a T-tube has been justified A combination of conservative, endoscopic, and radiological management has been effective in treating biliary leaks and early anastomotic stricture However endoscopic or radiological stenting was ineffective in the management of late anastomotic strictures, which were best treated by surgical intervention

Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease.

Abstract: Background: Acute renal failure (ARF) occurs in 5–50% ofpatients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT. Methods: We studied all OLT recipients between 9/1/1988 through 12/31/2000. Results: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1–12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1–8 yr). Multivariate logistic regression analysis revealed creatinine levels >1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005). Conclusions: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher10-yr survival rates when compared with patients maintained on dialysis.

Long-term outcome of liver transplantation for autoimmune hepatitis

Abstract: Autoimmune hepatitis (AIH) is a chronic inflam- matory disease of unknown etiology characterized by a loss of tolerance toward the hepatocellular epithelium.AIH is associated with hypergamma- globulinemia and circulating autoantibodies, and the majority of patients respond to immunosup- pressive treatment.The disease is most prevalent among women, displays an immunogenetic association with the human leukocyte antigen (HLA) A1-B8-DR3 or DR4 haplotypes (1), and the presence of extrahepatic syndromes (2).Auto- Abstract: Background: Liver transplantation is the final therapeutic option for about 10% of patients with autoimmune hepatitis (AIH) who do not respond to medical therapy.The aim of this study was to evaluate the long- term outcome in serologically defined subgroups of AIH after transplantation. Methods: Pre- and post-transplantation data of 28 patients with AIH transplanted between 1987 and 1999 were retrospectively analyzed and compared with 24 patients, who underwent liver transplantation because of Wilson's disease and glycogen storage disease type 1. Results: Serological analyses identified patients with AIH type 1 (n ¼ 13), type 2 (n ¼ 5), and type 3 (n ¼ 10).The 5-yr patient survival rate after liver transplantation was 78.2%, which was not significantly different from the control group.Six AIH patients and four control patients required re-transplantation because of initial non-function, chronic rejection or AIH recurrence.Patients transplanted for AIH (88%) had more episodes of acute rejection when compared with patients transplanted for genetic liver diseases (50%).Clinical and histological features of chronic rejection were present in four patients, which did not differ significantly from the controls. Recurrence of AIH was diagnosed in nine patients (32%) based upon the presence of autoantibodies, increased c-globulins, steroid dependency, and histological evidence of chronic hepatitis.These combined features were not found in any of the controls. Conclusions: Our data do not suggest that AIH subtypes influence prog- nosis after liver transplantation.Despite a high frequency of acute cellular rejection episodes and disease recurrence, transplantation for AIH has a 5-yr survival rate, which does not differ from that observed in patients transplanted for genetic liver diseases.

Cardiovascular disease in stable renal transplant patients in Norway: morbidity and mortality during a 5-yr follow-up.

Abstract: Background: Although cardiovascular disease is a major cause of death after renal transplantation (Tx), predictors for cardiovascular events have not been well defined. Aims of this cross-sectional study were first to assess cardiovascular morbidity and mortality in stable renal Tx patients, and to identify predictors for cardiovascular events during long-term follow-up. Methods: In all, 406 renal Tx patients (mean age: 47 yr, 60.1% males, 70.9% using cyclosporine A) commenced a baseline registration (median) 48 months after Tx, and 405 was thereafter followed in 5 yr. Kaplan–Meier plots and multivariate regression analysis (Cox proportional hazards model) were used to identify and characterize predictors for cardiovascular events. Results: There were 88 deaths (average annual mortality: 4.4%), and 74% of these were cardiovascular. In age groups 40–49, 50–59, and 60–69 yr, odds ratio for cardiovascular mortality in patients vs. general population was 46.2, 20.1, and 8.0, respectively. Death from ischemic heart disease (IHD) was independently predicted by baseline congestive heart failure (relative risk: RR 5.33), diabetes (RR 2.28), systolic blood pressure (mmHg, RR 1.02), age (yr, RR 1.06), and high-density lipoprotein cholesterol (mmol/L, RR 0.36). Predictors for a major ischemic heart event (death from or onset of IHD) were in addition baseline total cholesterol (mmol/L, RR 1.18) and cerebrovascular disease (RR 2.98). Conclusions: Thus, IHD was the major cause of death late after renal Tx, and a major ischemic heart event was predicted by baseline congestive heart failure, diabetes, age, hypertension, and hypercholesterolemia.

Pegylated interferon alpha-2b plus ribavirin in the treatment of post-liver transplant recurrent hepatitis C.

Abstract: Background: Histological recurrence of the hepatitis C virus (HCV) occurs in the majority of persons transplanted for cirrhosis as a result of HCV. Herein we analyze our experience with the use of both conventional and pegylated (PEG) interferon (IFN) in combination with ribavirin (RBV) in liver transplant recipients with recurrent HCV. Methods: Patients transplanted between 1992 and 2001 with post-orthotopic liver transplantation (OLT) histological recurrence of HCV, and who were treated with at least 6 months of IFN or PEG-IFN in combination with RBV were included in this analysis. A retrospective chart review was performed. Results: A total of 31 patients were included. Fifteen were treated with IFN/RBV and 16 with PEG-IFN/RBV. Of these 16, 11 had been begun on IFN/RBV and were changed to PEG-IFN/RBV because of persistent viremia. Three patients (20%) in the IFN/RBV group and six patients (37.5%) in the PEG-IFN/RBV group experienced a virologic response (VR) on therapy. Of the six patients experiencing VR in the PEG-IFN/RBV group, three (50%) were IFN/RBV non-responders. There were two sustained VRs (SVR). The 65.6% of all patients experienced a biochemical response (BR) on therapy. Seven deaths were observed. Dose modifications of IFN or PEG-IFN (87.1%) and RBV (80.6%) and the requirement for hematopoietic growth factors were frequent. Conclusions: Treatment of recurrent HCV infection with combination of IFN or PEG-IFN and RBV produced an on-therapy VR in 29% and BR in 65% of patients. Hematologic toxicity and dose modifications were frequent. Our experience with antiviral therapy for HCV post-OLT remains disappointing but PEG-IFN + RBV appears to produce VR in a sizable portion of IFN + RBV non-responders.

Mycophenolates in transplantation.

Abstract: The discovery of mycophenolic acid (MPA) as a potent immunosuppressant, able to inhibit B- and T-cell proliferation by blocking production of guanosine nucleotides required for DNA synthesis, allowed its potential in the field of transplantation to be realized. Mycophenolate mofetil (MMF), an MPA prodrug, has been shown to be an effective immunosuppressant in transplant therapy. Clinical trials in renal, heart, and liver transplant recipients have demonstrated that, in combination with cyclosporine and steroids, MMF therapy can reduce the incidence and severity of acute rejection episodes and improve graft and patient survival as well as graft function. Although MMF is generally well tolerated, optimal therapy may be limited by associated side effects, in particular gastrointestinal (GI) toxicity, which may occur in over 40% of patients. Dose changes resulting from GI side effects may potentially lead to sub-therapeutic dosing and impaired clinical outcomes. An enteric-coated formulation delivering MPA - enteric-coated mycophenolate sodium (EC-MPS) has been developed to improve MPA-related upper GI adverse events. EC-MPS delays the release of MPA, consistent with a functional enteric-coating. Recent clinical trials have demonstrated that EC-MPS is as effective and safe as MMF in both de novo and maintenance renal transplant patients.

Non-resective ablation therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list.

Abstract: Background: Orthotopic liver transplantation (OLT) for patients with small hepatocellular carcinoma (HCC) is widely accepted, and the usefulness of local ablation techniques as a bridge for liver transplantation is still under investigation. Methods: From December 1997 to February 2003, patients with cirrhosis and T0-T1-T2-T3 stage HCC received multi-modality ablative therapy (MMT) for the treatment of their HCC and were evaluated for OLT; listed, and transplanted when an allograft became available. MMT included radiofrequency ablation (RFA), and/or Trans-Arterial Chemo-Embolization (TACE), and alcohol (EtOH) ablation, followed by Trans-Arterial Chemo-Infusion (TACI), with repeated treatments based on follow up hepatic magnetic resonance imaging (MRI) during the waiting period for OLT. Results: A total of 135 HCC patients were seen at our center within this time frame. The intention-to-treat group included 33 (24.4%) patients with T0, T1, T2, T3 HCC and cirrhosis. There were 31 men and two women. The mean age was 53.6 ± 7.2 yr. All patients received MMT with a mean of 2.90 ± 1.5 procedures per patient. Tumor-node-metastasis (TNM) stages at time of listing were: T0 in one patient, T1 in nine patients, T2 in 17 patients, and T3 in six patients. Twenty-eight (85%) patients have received OLT. Five (12.19%) patients were listed and removed (dropout) from the transplant waiting list after waiting 5, 5, 5, 8, and 14 months respectively. The waiting time of the HCC listed group was 9.1 ± 14.8 months with a mean follow up of 32 months. OLT patient survival and cancer-free survival are 92.9% and 95.24%, respectively; the overall survival of intention-to-treat group was 79% at 32 months follow up. Predictors of dropout included an α-fetoprotein (AFP, >400 ng/mL) and T3 HCC stage. Conclusion: Aggressive ablation therapy with a short transplant waiting time optimizes the use of OLT for curative intent in selective cirrhotic HCC patients.

Post transplant lymphocele: a single centre experience.

Abstract: The occurrence of post renal transplant lymphocele is variable and the best approach to treatment is not well defined. The purpose of this study was to find out the incidence of post transplant lymphocele at our centre, identify demographic or surgical factors that may have influenced lymphocele formation, and distinguish the best approach to treatment. The charts of 138 consecutive renal transplant recipients from 1996 to 2001 were retrospectively reviewed. The demographic characteristics, comorbid illnesses, occurrence of lymphocele and its treatment modality were recorded. A total of 36 (26%) patients developed lymphoceles. There was a significant relationship between an increased body mass index (BMI) and lymphocele occurrence (P > 0.01). The recurrence rate with drainage alone was 33%, which decreased to 25% with sclerotherapy. In comparison, both laparoscopic and open surgical marsupialization had a much lower but similar recurrence rate of 12%. The laparoscopic method had less morbidity, a shortened hospital stay, and less infection than open surgery.

Factors associated with (un)willingness to be an organ donor: importance of public exposure and knowledge.

Abstract: Background: Transplantation is increasingly limited by the supply of donor organs. Identifying subgroups that do not support organ donation will allow targeted efforts to increase organ donation. Methods: A total of 185 non-acutely ill outpatients visiting a community physician's office voluntarily completed a survey designed to capture views and general knowledge/misconceptions about cadaveric organ donation/transplantation. Results: Of 185 patients, 86 were willing to donate, 42 were unwilling, and 57 were unsure. Willingness to donate was significantly associated with: having discussed the topic with family; having known a cadaveric organ donor; age 55 yr; having graduated high school; recognizing the organ shortage as the primary problem in transplantation; having received a post-high school degree; having seen public information within 30 d; and having a family member in health care (all p≤0.05). Not significant were: gender; race; religious affiliation or regular church attendance; knowing a transplant recipient or wait-listed patient; and having easy internet access. Those unwilling/unsure more often thought: organ allocation is based on race/income; organ donation is expensive for the donor family; designated donors may not receive full emergency room care; a brain-dead person can recover. Conclusions: Intense efforts to improve public awareness and knowledge about organ donation/transplantation are necessary to maximize donation and the overall success of transplantation.

Development of an unbiased method for the estimation of liver steatosis.

Abstract: Background: Steatosis significantly contributes to an organ's transplantability. Livers with >30% fat content have a 25% chance of developing primary non-function (PNF). The current practice of evaluating a hematoxylin and eosin (H&E) stained donor biopsy by visual interpretation is subjective. We hypothesized that H&E staining of frozen sections fails to accurately estimate the degree of steatosis present within a given liver biopsy. To address this problem of evaluating steatosis in prospective donor organs, we developed a fast, user friendly computer methodology to objectively assess fat content based on the differential quantification of color pixels in Oil Red O (ORO) stained liver biopsies. Methods: The accuracy of human visual estimation of fat content by H&E and ORO stains was compared with computer-based measurements of the same slides from 25 frozen sections of donor biopsies. Results: Samples with a fat content >20% showed marked variation between human interpretation and computer analysis. There was also a significant difference in the human interpretation of fat based on the method of staining. This difference ranged from 3 to 37% with H&E. Discussion: Use of ORO resulted in a more consistent estimation of liver steatosis compared with H&E, but human interpretations failed to correlate with computer measurements. Such differences in fat content estimations might result in the rejection of a potentially transplantable organ or the acceptance of a marginal one. Ideally, our protocol can rapidly be applied to clinical practice for accurate and consistent measurement of fat in liver sections for the ultimate purpose of increasing the number of successful transplantable organs.

An analysis of the OPTN/UNOS Liver Transplant Registry.

Abstract: Based on data reported to the OPTN/UNOS Liver Transplant Registry between 1988-2004: 1. There was a very small difference in 5-year graft survival rates comparing living and deceased donors in adult (4.3%) and pediatric patients (2.4%). 2. Although graft survival rates of split liver transplants were lower than whole liver grafts before 1998, 5-year graft survival results of more recent split grafts (65.8%) have become comparable to those of whole liver grafts (66.5%). Among recipients in good condition, split (67.7%) and whole grafts (70.0%) yielded equivalent survival rates. 3. Lower graft survival rates were noted in ABO incompatible grafts, non-heartbeating donors, regrafted patients, and recipients who were in the ICU before transplantation. 4. There was no recipient gender effect on liver transplant outcome. 5. Primary disease distributions were different for different races. Among adult patients, the largest fraction of white patients had alcoholic cirrhosis. Among Asians, Type B cirrhosis was most frequent. Among pediatric patients, biliary atresia constituted the majority of patients. Most of the patients with alpha-1 antitrypsin deficiency were white. Autoimmune hepatitis was most frequently found among black patients. 6. Although 5-year graft survival of black patients (60.2%) was lower than whites (68.1%), Hispanics (67.6%), and Asians (68.0%), black recipients with PBC (73.3%) and PSC (69.9%) had graft survival rates similar to those of whites (78.1%) (73.6%) and Hispanics (75.3%) (77.1%). 7. Zero HLA-A,-B,-DR mismatched livers had very rapid early failures. HLA matching correlated with graft survival in autoimmune hepatitis patients, but not in cirrhosis patients. 8. Short-term graft survival for liver transplants has improved steadily since 1990. However, long-term graft survival after the first year actually declined over time. 9. In adult transplants, 5-year graft survival of autoimmune-related diseases, PBC (77.3%), PSC (73.3%), AIH (74.2%) yielded higher graft survival rates than those of hepatitis B (71.5%) and C (63.2%). 10. In pediatric patients, 5-year survival of biliary atresia (75.4%), autoimmune cirrhosis (70.8%), and alpha-1-antitrypsin deficiency (85.0%) had high graft survival rates, except for acute liver failure (61.6%). 11. Hepatitis C recurrence is now one of the major causes of graft failure in adults. Thrombosis is a major factor in graft failure for pediatric transplants.

Pre-transplant treatment of hepatocellular carcinoma: assessment of tumor necrosis in explanted livers.

Abstract: Although liver transplantation (LT) is likely the most effective therapy for localized hepatocellular cancer (HCC), limited donor livers have resulted in prolonged waiting times for transplant. Pre-transplant therapy such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) may be needed to sustain patients who are waiting. Records, imaging studies, and pathology to identify tumor necrosis on 15 explanted livers with HCC were reviewed. Forty-nine nodules were removed from 15 explanted livers. Five nodules in three livers that received no pre-transplant therapy were excluded from the study. Of the remaining 44 nodules in 12 patients, 29 (66%) had 75% or more tumor necrosis. Fifteen nodules in five patients had <75% necrosis and these were due to local/non-local recurrences or perhaps suboptimal treatment with RFA, TACE or cisplatin gel injection. Mean waiting time for LT was 162.5 d. Nine of 13 patients had a different number of nodules when listed as were seen at explant, although stage changed in only three patients. One patient died 48 months post-LT (recurrent HCC), while the remaining patients are alive 2-55 months post-LT. We conclude that pre-transplant treatments for HCC are generally effective in achieving tumor necrosis. Factors involved in eventual extent of HCC seen at LT may include adequacy of treatment, accuracy of imaging techniques, local/non-local recurrences, and time waiting for transplant. We now need to determine if tumor necrosis can allow patients to wait longer for transplant and eventually affect long-term outcome.

Hypercoagulable state associated with kidney–pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy

Abstract: Background: The clinical consequences of type 1 diabetes mellitus (IDDM) include diabetic triopathy: retinopathy, nephropathy, and neuropathy, as well as microangiopathy, accelerated atherosclerotic disease, and hypercoagulability. The etiology of the hypercoagulability is multifactorial, involving various clotting factors or pathways (for example platelets, fibrinogen, individual components of the clotting system and/or fibrinolysis in different studies). The development of end-stage renal disease (ESRD), with the uremia-related platelet effect has the potential to protect from the existing hypercoagulable state. This has important implications for surgery, particularly simultaneous pancreas–kidney (SPK) transplantation, where the pancreas has historically been prone to thrombosis. This has led us to perform intra-operative thromboelastograms (TEG's) to evaluate the patient's current coagulation status. Methods: A TEG was performed in 85 SPK recipients along with a control group of 54 non-diabetic kidney transplant (KT) recipients. Results: For each of the 4 TEG coagulation parameters, the SPK recipients were significantly more hypercoagulable than the non-diabetic KT recipients. The use of intra-operative heparin is based on the degree of hypercoagulability by TEG and degree of operative hemostasis. There has been one PT lost to thrombosis (1%) in the first week following transplantation during this time. Conclusion: The use of TEG is a helpful adjunct to SPK surgery, demonstrating the patient's current coagulation status. Nearly all SPK recipients (type 1 IDDM with ESRD) have been demonstrated to be hypercoagulable. The TEG allows the judicious use of anti-coagulation at the time of surgery, and beyond.

Twenty years of clinical islet transplantation at the Diabetes Research Institute--University of Miami.

Abstract: Transplantation of allogeneic pancreatic islets for the treatment of patients with Type 1 diabetes mellitus (T1DM) is now a reality. The steady progress that has allowed for the recent successful clinical trials world-wide follows a steep learning curve and the perseverance of the international islet transplantation community. The Clinical Islet Transplant Program at the Diabetes Research Institute - University of Miami has contributed to the progress in the field with a 20-year track record. It has been a long journey and despite the intermediate success, more work is needed in order to achieve the ultimate goal of a safe and long-lasting treatment for patients with T1DM.

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults

Abstract: The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics A consecutive series (1994-2000) of 167 adult primary OLT were analysed Ninety-six patients had CON-OLT and 71 patients had PB-ES In PB-ES group two revascularization protocols were used In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq) In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim) One-, 3- and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns) Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns) Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups The total operation time was not different between both groups (94 h in PB-ES vs 100 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (89 h vs 107 h, 54 min vs 63 min, 82 min vs 114 min, 118 min vs 160 min and 87 min vs 114 min, respectively, p <005) RBC use in the PB-ES group was lower compared to the CON-OLT group (40 min vs 100 units, p <005) Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs 50 min, p <005); however REVT was significantly shorter in PB-Sim group (64 min vs 97 min, p <005) Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use In the PB-ES group there seems to be no adavantage for any of the revascularization protocols

Preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy and DFPP-enabled non-responders to undergo ABO-incompatible kidney transplantation.

Abstract: Patients undergoing ABO-incompatible kidney transplantation must have their anti-donor blood-type antibody titer (ADBT) reduced to below 1:16 by using either plasma-exchange (PEX) or double filtration plasma exchange (DFPP) before they can safely undergo a transplantation. The ADBT can be reduced to under 1:16 in most cases; however, some cases (non-responders) do not respond to PEX or DFPP treatment. To enable kidney transplantations to be performed in non-responders, we developed a new preconditioning regimen consisting of anti-CD20 monoclonal antibody (rituximab) infusions, a splenectomy, and DFPP. Four non-responders were infused with rituximab at a dose of 375 mg/m(2) weekly for 3-4 wk and splenectomized 1 or 2 wk before transplantation. Four to five DFPP-sessions were then performed after the splenectomy. Using this preconditioning regimen, the ADBT was reduced to below 1:16, enabling kidney transplantations to be successfully performed in all patients. After the kidney transplantation, no episodes of humoral rejection were observed, and only one episode of cellular rejection was encountered. The cellular rejection was associated with a reduction in immunosuppressant administration because of CMV infection that occurred 80 d after the kidney transplantation. The renal allografts were functioning well in all patients after a mean follow-up period of 390 d. No serious complications or side effects were encountered. We have developed a new preconditioning regimen that enables PEX and DFPP non-responders to undergo ABO-incompatible kidney transplantations.

Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation.

Abstract: Background: The colloid-based University of Wisconsin (UW) preservation solution has been used extensively in clinical pancreas transplantation. Experimental studies support the use of the crystalloid-based histidine-tryptophan-ketoglutarate (HTK) preservation solution for this purpose. Aim: We report our initial experience with HTK for pancreas allograft preservation and compare this to a contemporary experience with UW solution in conventional multiorgan deceased donors (<50 yr). Materials and methods: Retrospectively collected information on 33 pancreas transplants between September 2001 and October 2002 were analyzed for early graft function and complications up to 30 d after procurement and storage in either HTK or UW solutions. During multi-organ recovery, either UW solution (4–5 L) or HTK solution (8–10 L) was used for aortic perfusion and subsequent back-table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric, while the bladder was used for drainage in two cases. Patient outcomes were analyzed according to the preservation solution used. Sixteen pancreata were used in combination with a kidney allograft (SPK), seven were used in patients after prior kidney transplantation (PAK), while 10 were used in patients who were not in renal failure (PTA). Results: The UW group consisted of 17 patients (10 SPK, three PAK, four PTA) with a mean donor age of 29.5 ± 10.7, and a mean cold ischemia time of 15.1 ± 2.1 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346 IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient and graft survival was 100% at 1-month post transplant. In the HTK group there were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 ± 5.7 and a mean cold ischemia time 14.0 ± 1.3 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42 mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post-transplant. Conclusions: Early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.

Eversion thromboendovenectomy in organized portal vein thrombosis during liver transplantation.

Abstract: Portal thrombosis is no longer considered a contraindication for transplantation because of the technical experience acquired in the field of liver transplantation and the development of various surgical techniques. All the same, the results obtained in portal thrombosis patients are at times suboptimal, and the surgical technique used (thromboendovenectomy or veno-venous bypass) is also controversial. Between May 1988 and December 2001, 455 liver transplants were performed, of which 32 (7%) presented portal vein thrombosis. Of these, eight belonged to the first 227 transplants (group I), and 24 to the other 228 (group II). Of the 32 cases with portal thrombosis, 20 (62%) were type Ib, seven (22%) type II/III and five (16%) type IV. Twenty-two were males (69%), with a mean age of 50 yr (range: 30-70 yr); the thrombosis in all cases developed over a cirrhotic liver: 15 cases of an ethanolic origin, 11 because of hepatitis C virus, two cases of autoimmune aetiology, one case of primary biliary cirrhosis, one case because of hepatitis B virus and two cases of a cryptogenic origin. Five cases had a history of surgical treatment for portal hypertension. The surgical method in all cases consisted of an eversion thromboendovenectomy (ETEV) under direct visual guidance, with occlusion of the portal flow using a Fogarty balloon. Once re-canalization was achieved, we performed local heparinization and end-to-end portal anastomosis. In no case was systemic post-operative heparinization performed. In the 32 cases in which thrombectomy was attempted it was achieved in 31 of them (96%), failing only in a case of type IV thrombosis, which was resolved by portal arterialization. Of the 31 successful cases, only one with type IV thrombosis re-thrombosed. The 5-yr survival rate of the patients in the series was 69%, with 10 patients dying, of whom only two from causes related to the thrombosis and the thrombosis treatment, both with type IV thrombosis. The ideal treatment for portal thrombosis during liver transplantation is controversial and depends on its extension and the experience of the surgeon. In our experience, ETEV resolves most thromboses (types I, II and III), but management of type IV, which occasionally can be treated with this technique, may require more complex procedures such as bypass, portal arterialization or cavoportal haemitransposition.

Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantation.

Abstract: Background: This is a 4-yr follow-up of a trial using mycophenolate mofetil (MMF) induction in orthotopic liver transplantation (OLT). The goal of this study was to evaluate a multidrug approach that would reduce both early and long-term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection. Methods: This was a prospective, randomized, intent to treat study designed to compare the primary endpoints of rejection and infection, and secondary endpoints of liver function, renal function, bone marrow function, cardiovascular risk factors, and the recurrence of hepatitis C. Ninety-nine consecutive patients with end stage liver disease who underwent OLT were randomized to receive either cyclosporine microemulsion (N) (50 patients) or tacrolimus (FK) (49 patients) starting on postoperative day 2, with MMF and an identical steroid taper begun preoperatively. Results: Ninety of 99 patients (N 46, FK 44) completed the 4-yr follow-up. The overall 4-yr patient and graft survivals were 93 and 89%, respectively. There was no significant difference in 4-yr patient (N 96% vs. FK 90%, p = ns) or graft (N, 90% vs. FK, 88%, p = ns) survival between groups. The 4-yr rejection rate was not significantly different in either arm (N = 34%, FK = 24%; p = 0.28). There were no differences in infection rates in either arm. The patients with hepatitis C had no differences in the viral titers or Knodell biopsy scores between groups. However, in the hepatitis C subgroup (37 patients), the FK patients had a significantly lower rejection rate (p = 0.0097) and a significantly lower clinically recurrent hepatitis C rate (p = 0.05) than the N patients. No difference was seen in the percent of patients weaned off of steroids after 4 yr (N 51%, FK 49%). There were no differences in the incidences of diabetes mellitus and hypertension. When renal dysfunction was analyzed, a significant difference in the number of patients whose creatinine had increased twofold since transplant was seen (N 63%, FK 38%, p = 0.04). Conclusions: Use of MMF induction and maintenance following OLT in conjunction with either N or FK and an identical steroid taper, resulted in an acceptable long-term incidence of rejection and infection, without an increase in long-term graft or patient morbidity.

Renal transplantation offers a better survival in HCV-infected ESRD patients.

Abstract: Sezer S, Ozdemir FN, Akcay A, Arat Z, Boyacioglu S, Haberal M. Renal transplantation offers a better survival in HCV-infected ESRD patients. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00252. Abstract: The presence of hepatitis C virus (HCV) infection has been found to adversely affect the morbidity and mortality rates in the dialysis population. Renal transplantation is a treatment option after a careful pre-transplant evaluation. We designed this study to find the impact of HCV infection on patient survival, co-morbidity and allograft survival in a selected group of hemodialysis (HD) and transplant population. We retrospectively analyzed 116 renal transplant patients (94 HCV-negative, 22 HCV-positive) and 136 HD patients (106 HCV-negative, 30 HCV-positive) who had renal transplantation or underwent dialysis before 1996. The HCV-infected patients were evaluated by liver biopsy for the absence of advanced liver disease before transplantation. There was no clinical or laboratory decompensation of liver disease in transplant and dialysis patient groups. The overall 5-yr survival rates were 85.2% for renal transplant recipients and 74.5% for those on HD. The comparison results revealed a significant difference between HCV-infected patients with and without transplantation. The 3-yr renal allograft survival rates were comparable in HCV-positive and -negative patients, but the risk of chronic allograft nephropathy (CAN) and graft failure were higher at the fifth year in HCV-positive patients. In conclusion, renal transplantation should the preferred therapy in HCV-infected dialysis patients as it improves the survival rates. The presence of HCV infection increases the CAN rate and the influence on allograft survival is evident at the fifth year of assessment.

Morbid obesity does not preclude successful renal transplantation.

Abstract: Many renal transplantation centers arbitrarily deny transplantation to patients with morbid obesity usually defined as body mass index > 35. We present a series of 173 primary renal transplant patients in a new transplant program that accepted all recipients with 3 yrs or greater life expectancy and no active malignancy or infection. When the patient outcomes are divided into groups by body mass index, it can be seen as expected that patients with body mass index > 30 have an increased prevalence of wound infections (p < 0.05). However, aside from this complication there are no statistically significant outcome differences between the three groups realizing the possibility of type II statistical error because of small numbers. Graft survival, patient survival and other surgical complications are the same in all groups regardless of body mass index. At the end of the 3-yr interval with a minimum transplant follow-up of 3 months, 169 of 173 patients were alive and 163 of 173 transplants were functioning. Based on our experience, morbid obesity should not be used to exclude patients arbitrarily from transplantation anymore than advanced age or diabetes should.

Serum Cholestasis Markers as Predictors of Early Outcome After Liver Transplantation

Abstract: BACKGROUND: Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function. METHODS: The charts of 92 patients who underwent 95 liver transplantations at Rabin Medical Center between 1991 and 2000 were reviewed. Findings on liver function tests and levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) on days 2, 10, 30, and 90 after transplantation were measured in order to predict early (6 months) patient outcome (mortality and sepsis) and initial poor functioning graft. Pearson correlation, chi(2) test, and Student's t-test were performed for univariate analysis, and logistic regression for multivariate analysis. RESULTS: Univariate analysis. Serum bilirubin >/=10 mg/dL and international normalized ratio (INR) >1.6 on days 10, 30, and 90, and high serum ALP and low albumin levels on days 30 and 90 were risk factors for 6-month mortality; serum bilirubin >/=10 mg/dL on days 10, 30, and 90, high serum ALP, high GGT, and low serum albumin, on days 30 and 90, and INR >/=1.6 on day 10 were risk factors for sepsis; high serum alanine aminotransferase, INR >1.6, and bilirubin >/=10 mg/dL on days 2 and 10 were risk factors for poor graft function. The 6-month mortality rate was significantly higher in patients with serum bilirubin >/=10 mg/dL on day 10 than in patients with values of /=10 mg/dL [odds ratio (OR) 9.05, 95% confidence intervals (CI) 1.6-49.6] and INR >1.6 (OR 9.11, CI 1.5-54.8) on day 10; significant predictors were high serum ALP level on day 30 (OR 1.005, 1.001-1.01) and high GGT level on day 90 (OR 1.005, CI 1.001-1.01). None of the variables were able to predict initial poor graft functioning. CONCLUSIONS: Several serum cholestasis markers may serve as predictors of early outcome of liver transplantation. The strongest correlation was found between serum bilirubin >/=10 mg/dL on day 10 and early death, sepsis, and poor graft function. Early intervention in patients found to be at high risk may ameliorate the high morbidity and mortality associated with early cholestasis.

Sensitivity of expanded-criteria donor kidneys to cold ischaemia time.

Abstract: The United Network for Organ Sharing (UNOS), working in conjunction with organ procurement organizations and transplant programmes, has recently defined a class of cadaver kidney grafts for special allocation procedures to enhance utilization of those organs. The criteria defining these expanded-criteria donor (ECD) kidneys are donor age ≥ 60 yr or donor age between 50 and 59 yr plus two of the following characteristics: donor history of cerebrovascular accident (CVA), donor history of hypertension (htn), and elevated creatinine (> 1.5) at any time during donor management. Kidney grafts from ECD donors carry an increased relative risk of non-function compared to other cadaver kidney grafts. The goal of the special allocation procedure is to reduce the time associated with placement by matching ECD grafts with patients previously designated as being willing to accept them. In assessing the potential impact of these allocation procedures, the sensitivity of ECD grafts to cold ischaemia time (CIT) became of great significance. Specifically, we questioned whether minimization of CIT might reduce the relative risk of poor graft function, justifying reduction of the geographical range of placement and thereby reducing the time the grafts would spend in-transit. Methods: To assess this, we queried the SEOPF database for cadaveric kidney transplants between 1/1/1997 and 15/8/2002. There were 1312 transplants from ECD donors during this period and 8451 from non-ECD donors. Between these groups, there were no significant differences in recipient gender, ethnicity, peak and most recent panel reactive antibody (PRA). Recipients of ECD kidneys were significantly older: 50.9 ′ 13.0 yr vs. 44.9 ′ 13.9 (mean age ′ SD, P < 0.0001). There were statistically significant but very small differences in the degree of AB and DR mismatch between the groups. Results: Defining delayed graft function (DGF) as dialysis within the first week post-transplant and primary non-function (PNF) as dialysis within the first week and failure in the first year, we found an association with CIT as illustrated in Table 1. Overall, ECD kidneys had a significantly increased (P < 0.0001) incidence of PNF and DGF. Notably, PNF in ECD appeared to be uniformly distributed across CIT and while DGF was CIT-dependent, the DGF differences between ECD and non-ECD were fairly consistent across CIT. Conclusion: While CIT minimization is potentially beneficial, ECD kidneys do not appear to be more sensitive to it than non-ECD kidneys.

Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system

Abstract: Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.

Detection of cardiac allograft rejection by real‐time PCR analysis of circulating mononuclear cells

Abstract: Background: Detection of cardiac allograft rejection is based on the histological examination of endomyocardial biopsies (EMB). We have explored the possibility of whether graft rejection could be detected by characteristic gene expression patterns in peripheral blood mononuclear cells (PBMC) of heart-transplant recipients. Methods: The study included 58 blood samples of 44 patients. On the day of EMB, mononuclear cells were isolated from peripheral blood, and gene expression was measured by quantitative real-time PCR. Thirty-nine parameters, including cytokine and chemokine genes were analyzed. Gene expression results were correlated with histological assessment of concomitant evaluated EMB according to International Society for Heart and Lung Transplantation (ISHLT) nomenclature. Results: Gene expression of perforin, CD95 ligand, granzyme B, RANTES, CXCR3, COX2, ENA 78 and TGF-β1 was significantly different in PBMC of patients with mild to moderate degrees of allograft rejection (≥grade 2) compared with patients exhibiting no or minor forms of rejection (

The effect of bronchiolitis obliterans syndrome on health related quality of life

Abstract: Bronchiolitis obliterans syndrome (BOS) is the most important factor limiting long-term survival after lung transplantation, and has a substantial impact on patients' daily life in terms of disability and morbidity. Aim of our study was to examine the effects of BOS on health related quality of life (HRQL) in lung transplantation patients. Data on HRQL from 29 patients who developed BOS at least 18 months earlier were studied longitudinally. HRQL measures were: the Nottingham Health Profile (NHP), the State Trait Anxiety Inventory (STAI), the Self-rating Depression Scale (ZUNG), and the Index of Well Being (IWB). Furthermore questions concerning activities of daily life and dyspnea were asked. The majority of the patients were male, and the most common diagnosis was emphysema. After the onset of BOS, significantly more restrictions were reported on the dimensions energy and mobility of the NHP. These restrictions appeared to increase over time. After the onset of BOS, STAI scores remained more or less stable and close to the value of the general population. ZUNG scores were significantly higher after the onset of BOS, and patients experienced a lower level of well being than the general population. The percentage of patients that reported to be able to perform activities of daily life without effort declined dramatically after the onset of BOS. Furthermore, the percentage of patients complaining of dyspnea increased after the onset of BOS. In conclusion, our study showed that HRQL was negatively affected by the onset of BOS. However, in spite of these less favorable long-term results, even patients who develop BOS may at least temporarily benefit from a lung transplantation.

Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients

Abstract: Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean C(max) and C(min) (trough) values of micafungin in plasma were 6.31 +/- 1.08 and 1.65 +/- 0.54 microg/mL, respectively. The mean elimination half-life (t(1/2)) and mean area under the curve up to 12 h post-dosing (AUC 0-12 h) were 13.63 +/- 2.77 h and 50.04 +/- 6.48 microg.h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (+/-SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 +/- 0.04 and 0.054 +/- 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40-50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH.

Endoscopic diagnosis of cytomegalovirus infection of upper gastrointestinal tract in solid organ transplant recipients: Hungarian single-center experience

Abstract: Background: Cytomegalovirus (CMV) is considered to be the major cause of upper gastrointestinal (GI) symptoms in organ transplant recipients. In the diagnosis of GI CMV infection the detection of the virus in the mucosa is essential. The aim of the study was to evaluate the significance of CMV, detected in biopsy specimens from stomach and duodenum of solid organ transplant recipients. Methods: Data of 227 elective upper endoscopies on symptomatic organ transplant recipients were evaluated for clinical symptoms, endoscopic changes and conventional histologic alterations of mucosal biopsy samples. Qualitative PCR was performed for detection of the presence of CMV-DNA in each biopsy materials. Results: CMV-DNA was detected in biopsy samples of 91 patients (40.1%) while only in 20 cases (8.8%) the signs of CMV infections were found by conventional histology (p < 0.00001). No considerable differences could be observed in symptomatic, histologic alterations between CMV-PCR positive and negative groups. There were no endoscopic changes in 25.3% of CMV-PCR positive and 5.1% of negative patients. Conclusions: Qualitative PCR is an accurate method for the detection of CMV in the mucosa of the GI tract. Further investigations are needed for determination of the exact pathological role of detected CMV.

Knowledge and opinions about organ donation and transplantation among Vietnamese Americans in Seattle, Washington: a pilot study.

Abstract: Background: Racial/ethnic minorities comprise almost 50% of registrants on national waiting lists for organ transplantation in the USA. As the list continues to expand, organ shortage becomes a bigger problem. Increasing donation rates especially among racial minority groups would lower the waiting times for these groups. Purpose: Asian Americans are among the fastest growing and most diverse ethnic group in the USA, but research on their knowledge or opinions about organ donation is rare. Population: A non-random sample of 350 Vietnamese American church attendees and students attending a major university in Seattle (Washington), was drawn. Methods: A self-administered 39-item knowledge/opinion-based survey was conducted during June to August 2003. Results: Of 278 respondents (a 79.7% response rate), 69.1% knew blood-type made a difference in donation (p = 0.000), 61.6% knew transplant survival rates were high (p = 0.000), and 75.9% knew transplants could come from living donors (p = 0.000). But 53.4% also thought organs could be sold for money in the USA (p = 0.000), and 49.8% thought more people died of auto accidents and gunshot wounds than from heart disease (p = 0.000). Those who answered correctly to more than 50% of the knowledge questions were also more likely to favor donation (p = 0.007). Conclusion: We found among this study population that having correct knowledge about organ donation related to a willingness to donate.