Open and endovascular treatment by covered and multilayer stents in the therapy of renal artery aneurysms: mid and long term outcomes in a single center experience.

AIM: The purpose of this paper is to evaluate the mid and long terms outcomes of open and endovascular surgical treatment, as well as multilayer stent, in patients affected by Renal Artery Aneurysm (RAA). PATIENTS AND METHODS: Twenty five patients with RAA (24 monolateral and 1 bilateral aneurysm, 26 aneurysms) were observed between 2000 and 2015: 4 were not treated due to the small size of the aneurysm (< 2.5 cm); out of the remaining, 16 underwent endovascular treatment, 2 were treated by open surgery consisting in aneurysmectomy and graft reconstruction and 5 (in 1 patient bilateral) were treated by ex vivo repair and autotransplantation. RESULTS: Out of the 22 patients treated for RAA, one patient operated upon open surgery presented an early thrombosis of a PTFE graft, followed by nephrectomy (4.7%); one patient underwent autotransplantation showed an ureteral kinking without functional consequences. In a follow-up ranging from 1 and 11 years (mean 5 years), no deaths were observed; all the renal arteries repaired were patents and 16 out of 21 patients had a significative reduction of systemic blood pressure. DISCUSSION: The choice of the best treatment is based on aneurysm's morphology according to Rundback's classification. The type I, involving the main renal artery, is always treated by endovascular approach; type II, involving renal artery bifurcations may be treated by open surgery or multilayer stents; type III (hilar or intraparenchymal aneurysms) needs only an open surgical treatment as autotransplantation. CONCLUSION: Based on our experience it seems that most of RAAs may be treated by endovascular technique. The ex vivo autotransplantation represents the first-line treatment in hilar and intraparenchymal aneurysms. Multilayer stents seem to have good outcome in the treatment of aneurysms involving arterial bifurcations. Mid and long term results, related to kidney preservation and to normalization of blood pressure, seems satisfying.

Orofacial diseases in solid organ and hematopoietic stem cell transplant recipients.

OBJECTIVE: Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at risk of several diseases, principally attributable to immunosuppression. This global overview of SOT/HSCT-associated orofacial diseases is aimed at providing a practical instrument for the oral healthcare management of SOT/HSCT recipients. METHODS: Literature search was made through MEDLINE. The associations between orofacial diseases and SOT/HSCT were assessed using observational studies and case series and were classified into 'association', 'no association', and 'unclear association'. RESULTS: Lip/oral cancers, drug-induced gingival overgrowth (DIGO), infections, including hairy leukoplakia and, less frequently, post-transplantation lymphoproliferative disorders (PTLDs) and oral lichenoid lesions of graft-versus-host disease (GVHD), were associated with SOT. Lip/oral cancers, GVHD, mucositis, DIGO, infections and, less frequently, PTLDs were associated with HSCT. Associations of orofacial granulomatosis-like lesions and oral mucosa-associated lymphoid tissue-type lymphoma with SOT, and of pyogenic granuloma and hairy leukoplakia with HSCT were unclear. Periodontal disease and dental caries were not associated with SOT/HSCT. For none of the local treatments was there a strong evidence of effectiveness. CONCLUSIONS: Solid organ transplant/HSCT recipients are at risk of orofacial diseases. Adequate management of these patients alleviates local symptoms responsible for impaired eating, helps prevent systemic and lethal complications, and helps where dental healthcare has been neglected.

Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up.

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function.

Expanded criteria for hepatocellular carcinoma after liver transplantation: a 20-year evolution.

BACKGROUND/AIM: Milan Criteria (MC) consent excellent survivals for hepatocellular carcinoma (HCC) after liver transplantation (LT). However, several new expanded criteria were proposed, with the intent to increase the HCC patients eligible for LT, maintaining acceptable recurrence rates. The aim of the present study was to analyze a cohort of HCC patients, evaluating the evolutions in its management during the last 20 years and comparing the disease-free survivals among three different periods. METHODOLOGY: HCC patients (n = 122) were transplanted and stratified in three periods: 1st (1988-1998, liberal selection), 2nd (1999-2003, use of MC) and 3rd (2004-2008, use of UCSF criteria). The three periods were analyzed and their survivals were compared. RESULTS: Statistical differences were reported at univariate analysis regarding to both dimensional (total tumor diameter) and biological (alpha feto-protein, microvascular invasion) HCC features. Comparing the 5-year survival rates, a progressive increase was observed in the three periods (62.6%, 87.9% and 88.4%, respectively), with a significant difference between 1st and the second periods (p = 0.008). CONCLUSIONS: In our experience, use of UCSF criteria is safe, with a contemporaneous increased number of transplants and better survivals. Introduction of new selection criteria, also based on biological features, is on the way.

An unusual case of hepatic carcinosarcoma.

We report a rare case of a hepatic carcinosarcoma with rabdomyosarcomatous differentiation in its sarcomatous component. A 71-year old Caucasian female patient underwent a liver resection for a 4-cm lesion developed on an underlying HCV-related cirrhosis. Post-operative course was uneventful and the patient was discharged 5 days after surgery. At pathology, the tumor presented the features of hepatocellular carcinoma and rhabdomyosarcoma Three months later the patient experienced a liver recurrence, dying 2 months later for systemic disease. The reported case presents several peculiarities, i.e. the female gender, the HCV-related cirrhotic status, and the European origin of the patient. However, the outcome of our case confirms that this neoplasm pursues a highly aggressive course with poor prognosis.

Long-term Glomerular Filtration Rate and Kidney Disease: Improving Global Outcomes Stage Stability After Conversion to Once-Daily Tacrolimus in Kidney Transplant Recipients.

Close monitoring of estimated glomerular filtration rate (eGFR) is important for early recognition of worsening renal function to prevent further deterioration. Safe conversion from twice-daily tacrolimus (TD-Tac) to once-daily tacrolimus (OD-Tac) has been reported, but the effects on eGFR are contrasting. The aim of our study is to evaluate long-term stability of eGFR after 1:1 conversion from TD-Tac to OD-Tac and the effects on serum cytokine blood levels. Forty-six consecutive kidney transplant recipients treated with TD-Tac 3 to 5 years post-transplant, with stable renal function, were enrolled in the study (2009-2011). Clinical and biochemical parameters were evaluated for 12 months before conversion up to 6 years after conversion. The patients served as their own controls. A panel of cytokines was evaluated repeatedly during the first year after conversion. Mean values of eGFR were not different long-term after conversion (P = .11) compared with baseline, and the majority of patients remained stable on Kidney Disease: Improving Global Outcomes stage during the study period; eGFR was stable in 30.0% after 5 years, decreased > 1 mL/min/1.73 m2/y in 13.3%, and improved > 1 mL/min/1.73 m2/y in 56.7%. Cytokine levels and C-reactive protein did not show any significant deterioration. Metabolic parameters were stable during the 6 years of follow-up. OD-Tac therapy can preserve an effective immunosuppressive state together with a safe profile of eGFR.

Surgical Technique Notes of Arterial Vascular Reconstruction During Kidney Transplantation: Personal Experience and Literature Review.

BACKGROUND: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated. METHODS: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared. RESULTS: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups. CONCLUSIONS: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Minimization of immunosuppressive therapy and immunological monitoring of kidney transplant recipients with long-term allograft survival.

Incidence of cardiovascular complications, cancers and chronic allograft nephropathy (CAN) suggests reduction of immunosuppressive dosages. Some studies analyzed the effects of minimization of immunosuppression until the avoidance of immunosuppressive drugs. However minimization seems to be related to a higher incidence of acute rejection. Induction of tolerance after transplantation and use of immunological tests that could monitor the immune reactivity are required. The aim of this study is to evaluate immunological state in a group of recipients after deceased and living donor kidney transplantation and to minimize immunosuppressive therapy monitoring simultaneously clinical and immunological parameters. We analyzed 41 patients, 38 from deceased donors and 3 from living donor kidney transplantation. All patients were treated with triple immunosuppressive therapy: cyclosporine or sirolimus or tacrolimus, mycophenolate mofetil and steroids. In all recipients the presence of CD8+CD28- T suppressor cells (Ts) was analyzed. Patients were divided in 2 groups, according to the presence of Ts. In patients with Ts, (Group A, n=19), mycophenolate mofetil (MMF) was progressively reduced and then stopped. Steroids were subsequently reduced and then interrupted, maintaining an immunosuppressive therapy with low doses of calcineurin inhibitors (CNI) or sirolimus (SIR). 22 patients were without presence of Ts: we enrolled for the study only patient acute rejection free, without proteinuria and with creatinine levels stable (Group B, n=19). In these patients, MMF was reduced and then stopped, while steroids were decreased to 5 mg at alternate days, maintaining CNI or SIR at medium therapeutic dosages (minimized therapy). Patient and graft overall survival in Group A and in Group B were respectively at 100% and 94.7%. Incidence of acute rejection was respectively at 0% in group A and 15.7% in Group B. Presence of episodes of acute rejection in Group B confirms risk of later minimization of steroids and the relevance of the analysis of recipient immunological reactivity before modification of immunosuppressive therapy. A careful evaluation of recipient immune reactivity with the presence of T regulatory cells can allow adequate and personalized immunosuppressive regimens, without high risks of acute rejection.

Primary nonfunction: timing retransplantation versus hemodynamic parameters and kidney function.

BACKGROUND: Patients with acute liver failure (ALF) show an aggravated hyperdynamic circulation. We evaluated potential changes in systemic hemodynamics and improved kidney function induced by the molecular adsorbent recirculating system (MARS) in a group of patients with primary nonfunction (PNF). PATIENTS AND METHODS: In the intensive care unit we treated 18 patients with PNF (6 females and 12 males) after orthotopic liver transplantation (OLT) of overall mean age 47.8 years (range, 28-60 years). Continuous MARS treatment was performed on all patients with a kit change every 8 hours during a mean of 10 days (range, 1-20 days). Double-lumen catheter type veno-venous access was used for the blood supply. The blood flow rate was 150 to 250 mL/min, depending on the hemodynamic situation of the patient. Blood passed through an albumin nonpermeable, high flux dialysis membrane. During MARS treatment we monitored the hemodynamic condition, using a series of parameters: heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) before (baseline value) as well as after 1 hour (T1), 3 hours (T2), and the end of treatment (T3). RESULTS: There was a progressive decrease in positive inotropic support (dobutamine, norepinephrine) and significant improvement in hemodynamic parameters, such as MAP (P< .01), PVRI/SVRI/V(mean) (P< .002), and KARI (P< .01). The improved kidney functions were shown by significant improvements in serum creatinine (P< .03), urea (P< .02), and urine volume (P< .005). Eleven patients were alive: 6 with OLT and 5 without OLT. Seven patients died: 4 after OLT and 3 before OLT due to multiorgan failure. CONCLUSIONS: The MARS device significantly improved the hemodynamic parameters and kidney function that also determine patient survival in ALF (61.1%) with PNF while awaiting retransplantation presumably by removal of certain vasoactive substances.

Pediatric acute liver failure with molecular adsorbent recirculating system treatment.

BACKGROUND: The prognosis of pediatric acute liver failure (PALF) has been significantly improved by emergency orthotopic liver transplantation (OLT). Since 2004, the molecular adsorbent recirculating system (MARS) has been proposed as a bridging procedure. The aim of our study was to assess its efficacy in children with PALF. PATIENTS AND METHODS: Since 1999 we performed treatment of 39 fulminant hepatic failure (FHF) cases with MARS. Since September 2004 we treated 6 pediatric patients with FHF who were of mean age 10.6 years (range, 3-15 years) including 4 females and 2 males. In 3 cases the cause of FHF was unknown; in 2 cases, it was induced by paracetamol overdose; and in 1, by acute hepatitis B virus. Inclusion criteria were: bilirubin >15 mg/dL; creatinine >or=2 mg/dL; encephalopathy grade >II; and International normalized ratio (INR) >2.5. Other estimated parameters were: AST and ALT serum levels, lactate, and urine volume. Neurological status was monitored using the Glasgow Coma Scale (GCS). Continuous MARS treatment was performed in all patients with a kit change every 8 hours. Intensive care unit (ICU) treatment was applied to optimize regeneration and to prevent cardiovascular complications. RESULTS: We observed a significant improvement among levels of bilirubin (P< .009), ammonia (P< .005), creatinine (P< .02), GCS (P< .002), and predictive criteria and as Sequential Organ Failure Assessment (SOFA) and Pediatric End-Stage Liver Disease (PELD). Three children underwent OLT: 1 died after 5 days due to primary nonfunction and 2 children are alive after a median follow-up of 14 months. In 2 children the MARS treatment led to resolution of clinical status without liver transplantation. One child died before OLT due to sepsis and multiorgan failure. CONCLUSIONS: We concluded that application of the MARS liver support device in combination with experienced ICU management contributed to improve the clinical status in children with PALF awaiting liver transplantation.

Hemodynamic improvement as an additional parameter to evaluate the safety and tolerability of the molecular adsorbent recirculating system in liver failure patients.

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an extracorporeal acute liver failure (ALF) support system method using albumin-enriched dialysate to remove albumin-bound toxins. PATIENTS AND METHODS: Since 1999 we performed 2027 MARS treatments in 191 patients: 39 fulminant hepatic failure (FHF), 16 primary nonfunction (PNF), 21 delayed function (DF), 94 acute-on-chronic liver failure (AoCHF), 7 post-hepatic resection, and 14 intractable pruritus. RESULTS: We divided the complications by the AoCHF versus the ALF populations. Among 83 ALF patients, we observed worsening of hemodynamic parameters in 16 patients: 3 with PNF, 2 with DF without retransplantation, 9 with FHF, and 2 after hepatic resection. Among 94 AoCHF patients, 42 showed hemodynamic instability requiring intensive care unit support. Our study did not note significant adverse effects (1.8%), except for infections and hemorrhage from the central venous catheter not due to MARS treatment. The thrombocytopenia was controlled through administration of platelets before the start of treatment when a patient showed a level under 30,000 mm(3). CONCLUSION: Our results confirmed that nonbiological hepatic support by MARS was safe and tolerable.

Simultaneous pancreas-kidney transplantation: a single-center experience and prospective analysis.

In patients with end-stage chronic kidney disease (CKD) and type 1 diabetes mellitus (DM 1), simultaneous pancreas-kidney (SPK) transplantation is currently considered the gold standard therapy. The aim of this study was to analyze and report the long-term clinical outcomes of the 23 SPK transplantations performed at our institution over an 84-month period (January 1, 2000 to December 31, 2006). A prospective analysis of these patients included donor, recipient, and transplantation characteristics. The only requirements for transplantation were blood group compatibility and a negative cross-match. Bladder drainage via pancreaticoduodenocystostomy was performed in all of the patients. Due to a pulmonary embolus 1 patient (4.3%) died at 2 months. The actuarial patient survival rates at 3 months and 1, 3, and 5 years were 95.6%. Causes for the renal graft loss were chronic allograft nephropathy in 3 cases (13%) and death of the patient in 1 case (4.3%). The actuarial censored renal allograft survival rates at 3 months and at 1 year were 100%, and at 3 and 5 years were 91.3%. Causes for the renal graft loss were chronic rejection in 1 case (4.3%) and patient death in 1 case (4.3%). The actuarial censored pancreatic allograft survival rates at 3 months and at 1 and 3 years were 100%, and at 5 years was 95.6%. The results of this work add further evidence that SPK is the gold standard therapy for selected patients with end-stage CKD due to DM 1.

Combined liver-kidney transplantation in polycystic disease: case reports.

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.

Ethical aspects of renal transplantation from living donors.

Kidney transplantation from living donors is widely performed all over the world. Living nephrectomy for transplantation has no direct advantages for the donor other than increased self-esteem, but it at least remains an extremely safe procedure, with a worldwide overall mortality of 0.03%. This theoretical risk for the donor seems to be justified by the socioeconomic advantages and increased quality of life of the recipient, especially in selected cases, such as pediatric patients, when living donor kidney transplantation can be performed in a preuremic phase, avoiding the psychological and physical stress of dialysis, which in children is not well tolerated and cannot prevent retarded growth. According to the Ethical Council of the Transplantation Society, commercialism must be effectively prevented, not only for ethical but also medical reasons. The risks are too high, not only for the donors, but also for the recipients, as a consequence of poor donor screening and evaluation with consequent transmission of human immunodeficiency virus (HIV) or other infective agents, as well as of inappropriate medical and surgical management of donors and also recipients, who are often discharged too early. Most public or private insurance companies consider kidney donation a safe procedure without long-term impairment and therefore do not increase the premium, whereas recipient insurance of course should cover hospital fees for the donors. "Rewarded gifting" or other financial incentives to compensate for the inconvenience and loss of income related to the donation are not advisable, at least in our opinion. Our Center does not perform anonymous living organ donation or "cross-over" transplantation.

Preliminary evaluation of the new TACR flex method versus MEIA method in the therapeutic monitoring of tacrolimus in organ transplantation.

Tacrolimus (FK506) is an effective macrolide immunosuppressant widely used to prevent organ rejection following transplantation. Monitoring blood levels of tacrolimus is essential to assess organ rejection versus toxicity, because of the narrow therapeutic range and pharmacokinetic variability. The increased request for therapeutic drug monitoring is an interesting challenge for clinical laboratories. The automated immunoassay methods provide correct results and a turnaround time considerably reduced compared to HPLC and HPLC-MS which remain the gold standard for accuracy and economical advantages. A new immunoassay method, TACR Flex Dimension, is a commercially available, automated pretreatment test. The purpose of this study was to compare two analytical methods: the MEIA II tacrolimus immunoassay using the IMx analyzer and the new TACR Flex tacrolimus immunoassay on the Dimension system. Tacrolimus results obtained using the two methods were compared using European control and 93 whole blood samples from kidney and liver transplant patients. The tacrolimus concentrations measured by Flex Dimension for all samples were higher (0.7 to 16.1 ng/mL) than results obtained with MEIA (0.2 to 13.4 ng/mL), a mean difference expressed in percentage of 31.7%, and a correlation coefficient of 0.85. The data obtained by both methods using three European controls showed similar concentrations. The TACR Flex Dimension method provided a higher automation level and therefore a lower incidence of preanalytical errors and a lower turnaround time.

Is legalizing the organ market possible?

INTRODUCTION: Two opposing views of the human body have existed since time began. Can it be traded or does its value go beyond a monetary one? Today it is illegal to sell organs but the success of organ transplantation has give rise to an enormous controversy. The continued increase in the need for organs has lead to a major use of live donors. Consequently, clandestine selling of organs is becoming more widespread for two main reasons: scientific progress and market demand. Our aim was to consider the protection of ethical principles through legislation. MATERIALS AND METHODS: Based on the principle that it is morally unacceptable for people to die on a waiting list, we analysed various ways in which the National Health Service could give incentives to live donors, including reimbursement of health expenses, tax relief, pension or early retirement benefits, or education grants for the children. Possible incentives for cadaveric organ donation included reimbursal of health and funeral costs, or increase in widow/er's pension. CONCLUSION: The tendency may be toward reimbursement of costs rather than actual payments. A legal, ethical organ market could save thousands of human lives, but it must be correctly regulated.

Molecular adsorbents recirculating system treatment in acute-on-chronic hepatitis patients on the transplant waiting list improves model for end-stage liver disease scores.

BACKGROUND: The aim of our study was to show an improvement in Model for End-Stage Liver Disease (MELD) score after treatment with Molecular adsorbents recirculating system (MARS) in acute-on-chronic hepatitis (AoCHF) patients. MELD was adopted to determine the prognosis of patients with liver chronic desease. We evaluated the possibility to improve the MELD score of patients awaiting liver transplantation using a liver support device, namely, MARS. PATIENTS AND METHODS: From September 1999 to April 2006, we treated 80 patients whose diagnoses were hepatitis C, 41.25%; hepatitis B, 27.5%; alcholic, 17.5%; intoxication, 8.75%; primary biliary cirrhosis, 5%. The overall mean age was 45 years (23 to 62), the cohort included 56 men and 24 women. Inclusion criteria were bilirubin >15 mg/dL; MELD >20; encephalopathy >II; and International Normalized Ratio, >2.1. Other parameters evaluated included ammonia, creatinine, lactate, glutamic oxalic transminase, and guanosine 5'-triphosphate. All patients were treated with a mean of 6-hour cycles of MARS (range, 5 to 8 hours) for a minimum of three treatments and a maximum of 20 treatments over 3 months. Clinical conditions were evaluated by improved hemodynamic parameters, kidney function, liver function, coagulation, neurologic status using the SOFA score, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II Criteria. RESULTS: The MELD score for all categories of living patients showed significant improvements at the end of treatment and at 3-months follow-up, but the small number of patients was a limitation to determine prediction of mortality. CONCLUSION: Our study shows that MARS treatment improved multiple organ functions-liver, renal, neurologic, and hemodynamic. The improved MELD score gave patients on the transplant waiting list longer survival, allowing them a greater opportunity for liver transplantation.

Fertility following solid organ transplantation.

Fertility is usually restored in women after solid organ transplantation, and successful pregnancies have been reported in female recipients of kidney, liver, heart, pancreas-liver, and lung transplants. However, women with solid organ allografts have higher incidence of pregnancy complications like hypertension, preeclampsia, preterm delivery. Hypertension appears to be dependent on the type of immunosuppressive agents. The influence of pregnancy on the risk of rejection is poorly known on the basis of available data. Rejection rate appears to be at least similar to the nonpregnant population. In some cases, such as in liver transplant pregnant women, even higher as compared to the nonpregnant population. Maintaining appropriate blood levels of immunosuppressive drugs is currently recommended. Malformation rate in the offsprings of transplanted women appears to not be increased; long-term follow- up of children born to allograft recipients is necessary to investigate possible developmental, immunological, or oncological disorders. We followed 70 pregnancies after kidney transplantation and nine after liver transplantation. All recipients were maintained on immunosuppressive therapy during pregnancy, except one mother who refused immunosuppression and experienced transplant rejection. Hypertension was the most frequent complication during pregnancy: in 23% of kidney transplantated mothers and in one out of nine liver transplant recipients. The only malformation observed in the newborns was the dislocation of the hip in the child of a kidney transplant recipient.