First global forum on education on organ donation and transplantation for schools.

The Transplantation Society, in collaboration with the Canadian Society of Transplantation, organized a forum on education on ODT for schools. The forum included participants from around the world, school boards, and representatives from different religions. Participants presented on their countries' experience in the area of education on ODT. Working groups discussed about technologies for education, principles for sharing of resources globally, and relationships between education, and health authorities and non-governmental organizations. The forum concluded with a discussion about how to best help existing programs and those wishing to start educational programs on ODT.

Calcineurin inhibitor-free immunosuppressive strategy in elderly recipients of renal allografts from deceased donors: 1-year results from a prospective single center trial.

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Prospective age-matching in elderly kidney transplant recipients--a 5-year analysis of the Eurotransplant Senior Program.

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Impaired glucose tolerance in pancreas grafted diabetic patients is due to insulin secretory defects.

INTRODUCTION: Pancreas transplantation in diabetic patients can sustain insulin independence for years. The aim of the study was to measure the incidence of an impaired or diabetic glucose tolerance in patients after successful transplantation and analyse insulin resistance and insulin secretion. METHODS: 174 Type 1 diabetic recipients of simultaneous pancreas/kidney (SPK) transplants were investigated early (three months) and 95 patients late (five years) after transplantation using an oral glucose tolerance test combined with an iv arginine load. RESULTS: Although mean fasting blood glucose and HbA1c levels were within the normal range, only 65% of the patients displayed a normal glucose tolerance (NGT), whereas 25% had an impaired (IGT) and 10% showed a diabetic glucose tolerance (DGT). Fasting blood glucose and HbA1c values were significantly lower in patients with NGT compared to graft recipients with IGT or DGT, either three months or five years after SPK. Indicators of insulin resistance (fasting insulin, HOMA-IR, Matsuda/de Fronzo Index) were elevated in all graft recipients, but no differences were found between groups. In contrast insulin secretion was significantly reduced in patients with IGT and DGT early and late after transplantation. SUMMARY: Insulin resistance is a common feature after pancreas transplantation. However, either three months or five years after SPK abnormal glucose tolerance was mainly due to a reduced glucose- and arginine-induced secretory response of insulin.

The janus face of immunosuppression - de novo malignancy after renal transplantation: the experience of the Transplantation Center Munich.

After decades of successful organ transplantation clinicians continue to be troubled by the increasing incidence of cancers under maintenance immunosuppression. In this study, we examined rates of malignancies in 2419 renal transplant recipients transplanted in our institution between 1978 and 2005. In renal transplant recipients the cumulative incidence of cancer after 25 years was 49.3% for all tumors and 39.7% excluding non-melanoma skin cancers, compared with 21% for a normal sex- and age-matched population. The most frequent tumors observed were non-melanoma skin cancers (20.5%), kidney cancers (12.0%), and cancers of the pharynx, larynx, or oral cavity (8.2%). The general increase of cancer risk was 4.3-fold. Independent risk factors for the development of a tumor were male gender, older recipient age, the presence of preformed antibodies before transplantation, and the time on immunosuppression. Interestingly, the use of IL-2-receptor antagonists significantly reduced the tumor risk of transplant recipients. The tumor risk between immunosuppressive drugs typically used for maintenance immunosuppression was not significantly different. However, mammalian target of rapamycin (mTOR) inhibitor-based immunosuppressive protocols showed a clear tendency for lower malignancy rates. De novo malignancies following renal transplantation represent a serious problem endangering the prognosis of otherwise successfully transplanted patients. Future studies will have to address whether optimized immunosuppressive regimens including mTOR-inhibitors are capable of reducing the incidence or preventing the development of posttransplant malignancies.

Cholesterol atheroembolic disease in kidney allografts--case report and review of the literature.

Cholesterol atheroembolic renal disease is a rare cause of renal allograft dysfunction. Two recipients of cadaveric kidney transplantats from the same donor are discussed with presumed graft failure due to cholesterol emboli of donor origin. A review of the literature summarizes the reported cases in renal transplant recipients. While cholesterol embolization of presumed donor origin seems to have a poor renal outcome, cholesterol emboli originating in the recipient have a more favorable prognosis. As donors and recipients of increasing age or prominent atherosclerosis are accepted for transplantation, cholesterol atheroembolic renal disease may become more prevalent and should be considered in patients with renal allograft dysfunction.

Simultaneous pancreas-kidney transplantation: analysis of rejection.

UNLABELLED: The 3-year data concerning the occurrence of rejection episodes (RE) are reported herein. PATIENTS AND METHODS: Two hundred five simultaneous pancreas-kidney (SPK) transplantations were performed from May 1998 to September 2000, including 103 patients randomly assigned to tacrolimus (Tac) and 102 to cyclosporine microemulsion (CsA-ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil (MMF), and short-term corticosteroids. RESULTS: After a follow-up of 3 years, acute rejection episodes occurred in 41 patients receiving tacrolimus and in 51 patients receiving CsA ME. The majority of first rejection episodes in both groups occurred during the first 6 months (93% and 90%, respectively) and in most cases were treated with corticosteroids (88% and 90%). Actuarial rejection-free graft survival was not significantly different between the two groups (54% and 44% at 3 years posttransplant). In a multivariate analysis, HLA compatibility (P = .003) and graft vessel extension (P = .0005) had a significant influence on rejection-free survival. Rejection influenced pancreatic graft survival (P = .01) and pancreatic graft loss owing to rejection influenced patient survival (P = .02). In the intent-to-treat analysis of early rejection, first moderate-to-severe episodes (1 of 40 versus 12 of 47; P = .004) and refractory episodes (2 of 40 versus 10 of 47; P = .03) were significantly lower with tacrolimus than with CsA ME. Pancreatic graft survival was worse among late rejectors (53%) than nonrejectors (86%; P = .002). In addition, serum creatinine was highest in late rejectors. In conclusion, Tac-based immunosuppressive therapy shows advantages over CsA ME in terms of the severity of acute rejection episodes among patients undergoing SPK transplantation.

[Antithrombogenicity of human endothelial cells]. / Antithrombogenität humaner Endothelzellen.

UNLABELLED: In the preceeding decades, our understanding of the complexity in our haemostaseologic system has been evolutionized from a purely ex vivo standpoint to an increasingly in vivo oriented approach, by more and more respecting the immense metabolic interactions of our vascular endothelium, mainly thrombin, the central serine protease in our coagulatory system. So far, investigations concerning human endothelium only relied on experiments with embryonic human endothelial cells, derived from umbilical cord veins. The underlying investigation confronts the justified question about the transferability of such embryonic results to the adult vascular system. MATERIAL, METHODS: Micro- and macrovascular endothelial cells were isolated, purified and propagated in pure cultures. Integrated into an established filtration model, their potential to mediate antithrombogenicity was investigated. RESULTS, CONCLUSION: Surprisingly, immense differences in thrombin-induced antithrombogenicity were demonstrated. This justifies doubts concerning the transferability of HUVEC-based results to the whole human vascular system.

[Thrombin: antithrombotic properties and pharmacological consequences]. / Thrombin: thrombosehemmende Wirkungen und pharmakologische Konsequenzen.

During the last few years, the availability of endothelial cell cultures isolated from different vascular regions contributed to a significant increase in understanding the complex pro- and antithrombotic mechanisms in our circulatory system. The most important key enzyme is thrombin. Due to its haemostatic properties this serin protease catalyzes fibrin formation, activation of factors V, VIII and XIII as well as irreversible platelet aggregation. These processes may occur even within the circulatory system in case of endothelial stimulation (e. g. by inflammation mediators) for expression of binding sites for factors IX, IXa, X, Xa, von Willebrand protein and PAF. Thus not only catalytically activated coagulatory cascades, but also enhanced cooperation of platelets and granulocytes will occur. Paradoxically, in low intravascular concentration, thrombin, in combination with a healthy endothelial layer, may be the critical factor for the inhibition of thromboses. Respective antithrombogenic properties will mainly affect pre-venous microvascular circulation. In detail, they include thrombin-induced endothelial formation of antiaggregatory autacoids from platelet release products, anticoagulatory activation of protein C and absorption of active coagulation factors at endothelial heparan/ATIII complexes as well as release of profibrinolytic plasminogen activator of endothelial origin. The understanding of these complex regulatory functions enables not only a critical evaluation of actually discussed haemostasiologic risk factors (enhanced platelet reactivity, high concentrations of factor VII, VIII, fibrinogen, PAI, ATIII), but also the development of new pharmacologic strategies for prevention of thrombosis.

Cyclosporine: 20 years of experience at the University of Munich.

The history of solid organ transplantation is, from an immunotherapeutic standpoint, divided in the era before and after the introduction of cyclosporine to the clinic. The introduction of cyclosporine to the clinic in 1978 is looked upon as a turning point in transplantation. The immediate success of the new drug was based on the reduction of early graft rejection and the substantial improvement of 1-year graft survival. With growing experience in the use of this new compound, together with the ability to measure drug levels in serum, allograft rejection and organ survival could be improved even further. Because of the clinical results, cyclosporine became the gold standard in immunosuppressive therapy after organ transplantation. Even after 20 years, as more and more new immunosuppressants emerge, the clinical evaluation of a new drug is frequently compared versus a cyclosporine-based regimen. Today, cyclosporine is probably one of the best investigated drugs in the field of organ transplantation. Beside the undoubted benefits of cyclosporine, experimental and clinical studies have also revealed some unwanted effects, such as nephrotoxicity and an increased risk in development of malignant tumors. Here, we review the experience at our institution with transplant recipients receiving cyclosporine as the main immunosuppressant over the past 20 years.

[75-year-old patient with persistent abdominal complaints and vomiting during a cruise]. / 75-jährige Patientin mit persistierenden abdominellen Beschwerden und Erbrechen während einer Kreuzfahrt.

BACKGROUND: In elderly patients with gallstone disease, a gallstone ileus must be considered for unexplained abdominal pain. This is demonstrated in the following case report. CASE REPORT: A 75-year-old female patient presented with a 72-hour history of abdominal pain, nausea and vomiting. The patient's abdomen was mildly distended, although soft and nontender with bowel sounds present. Plain radiographs and ultrasound investigation of the abdomen were compatible with small bowel obstruction. To clarify the etiology, an abdominal computed tomography scan was obtained. These examinations disclosed air in the biliary tree, dilated small bowel and an impacted intraluminal abnormality in the terminal ileum compatible with a gallstone. Operative intervention confirmed the presence of a 3 cm obstructing calculus in the terminal ileum that was removed by an enterolithotomy. A two-step cholecystectomy and closure of the cholecystoduodenal fistula were performed 8 weeks later. The patient's recovery was uneventful. CONCLUSIONS: Although rare in a general population, gallstone ileus accounts for 25% of nonstrangulated small bowel obstructions in patients over the age of 65. The radiographic picture and ultrasound of small bowel obstruction and the presence of air in the biliary tree are suggestive for the diagnosis of a gallstone ileus. In our patient, the computed tomography and ultrasound findings confirmed the diagnosis and led to a prompt and directed surgical intervention. In patients with comorbid factors a two-step approach with enterolithotomy in a first and cholecystectomy in a second operation should be the therapeutic strategy of choice.

[Locoregional recurrence of colonic carcinoma: prognosis after surgical therapy]. / Das locoregionäre Rezidiv des Colon-Karzinoms: Prognose nach chirurgischer Therapie.

In a retrospective study, we analyzed prognostic factors in 143 patients with locally recurrent colonic cancer (excluding rectal cancer). We saw no influence of primary tumor state on long-term survival. In patients with curative resection the 5(3)-year probability of survival was significantly better than in patients with local palliative resection [45% (50%) vs. 5% (0%)]. In addition, we found striking differences in perioperative mortality which varied with therapeutic intention (37% for local palliative operations without resection, 16% in cases with palliative surgery with resection). No patient died after curative tumor resection.

[Locoregional recurrence of rectal carcinoma. Surgical therapy and prognosis]. / Das locoregionäre Rezidiv des Rectumcarcinoms. Chirurgische Therapie und Prognose.

In a retrospective analysis, 140 patients with locoregional recurrence of rectal carcinoma were investigated in respect of prognostic factors. Neither classification of the primary tumor nor adjuvant therapies showed any significant influence on long-term survival, calculated according to the Cutler-Ederer method. The 3-(5-) year probability of survival of 52 (18) % is significantly better in cases with local curative operations than the 3 (0) % in cases with local palliative operations. Therefore, early indication for a possible radical resection of the recurrent tumor is essential. In 37.1%, local curative operations could be performed. The probability of long-term survival is significantly influenced by the kind of recurrence. Patients with local recurrence (anastomosis) after primary resection have the best prognosis with a 84 (33) % 3-(5-) year probability of survival. Independent of the kind of primary operation, the survival data on the remainder of patients after local curative operation for recurrent tumors are comparable. They are, however, still better than for non-curative operations. The striking differences in perioperative mortality (3 months) with regards to therapeutic intention (25% for local palliative operations without resection, 7.1% in cases of palliative surgery with resection and 1.9% in cases with local curative operations) must result in criteria for resectability being determined preoperatively on the basis of intensive diagnostic measures. Thus, the rate of palliative operations without benefit for the patient may be minimized.

[Long-term results of unsuccessful thrombolysis and secondary thrombectomy of deep leg-pelvic vein thromboses: a critical analysis]. / Langzeitergebnisse nach erfolgloser Lyse und sekundärer Thrombektomie tiefer Bein-Beckenvenenthrombosen: eine kritische Analyse.

According to the literature, fibrinolytic therapy of acute thrombosis of the pelvic and deep lower leg fails in about 15%. As the primary patency rate correlates with the long term results, we intended to investigate whether the failures of 15% might be improved by a secondary thrombectomy. 87% of 31 thromboses treated by secondary thrombectomy were investigated by clinical, morphological and functional examinations. The data show that in case of the intervention taking place within 8 days (total age of the thrombus including the period of lysis treatment) the results were excellent, within 8-14 days they were still good. Patients below the age of 30 years benefited most by the therapy. However, the postulated "airtight effect" could not be demonstrated. Early diagnosis is of paramount importance. The period of lysis treatment should be limited and in case of failure a secondary thrombectomy should be offered to the patient.

[Thrombectomy after unsuccessful thrombolytic therapy of deep leg vein thromboses: an effective procedure?]. / Thrombektomie nach erfolgloser Lysetherapie tiefer Bein-Beckenvenenthrombosen: ein sinnvolles Verfahren?

Lysis of acute thromboses of the pelvic and deep lower leg veins is not always successful. According to the literature, 11-20% of the cases remain occluded. In such cases the majority of authors continue therapy with anticoagulants (heparin, dicumarol). 31 thromboses which had been unsuccessfully treated by lysis were subsequently thrombectomized after a few hours. All external iliac veins could be opened. The amount of occluded common iliac veins could be reduced from 94% to 16%. In 19% a stenosis due to a venous spur remained. The complete patency rate of the extremity veins could be improved by 55%. This shows that a marked improvement of the primary patency rate could be reached despite the failed lysis. This is a prerequisite of a favourable longtime result. An evaluation of the late results is planned and will be published at a later date.

Percutaneous cholecystostomy in acute acalculous cholecystitis.

Percutaneous cholecystostomy was performed in 8 poor-surgical-risk patients with acute acalculous cholecystitis. Seven patients had had previous laparotomy, 1 patient a coronary bypass operation. A transhepatic approach was used in all patients. Insertion of the drainage catheters was guided by ultrasound and fluoroscopy. Percutaneous drainage was successful in all patients, with no need for further surgical intervention. Two patients died, for reasons unrelated to the gallbladder disease. Percutaneous cholecystostomy may be definitive treatment for acute acalculous cholecystitis in the critically ill patient.

Studies on the role of central catecholaminergic mechanisms in the antidotal effect of the oxime HI 6 in soman poisoned mice.

The effects of atropine and the oxime HI 6 on running performance, brain and plasma cholinesterase activity and brain catecholamines were investigated in mice intoxicated with sublethal doses of soman (100 micrograms/kg s.c.). The running time on a rotating mash wire drum (total running time 60 min) after injection of soman was reduced to 17.2 min. Treatment with atropine (10 mg/kg i.p.) or HI 6 (55 mg/kg i.p.) improved the running performance to 48.2 and 44.8 min, respectively. Cholinesterase activity was decreased in soman poisoned mice to 47.3% in plasma and 43.5% in brain. Therapy with the oxime HI 6 resulted in a reactivation of soman-inhibited peripheral cholinesterase to 76.6%, but failed to reactivate central cholinesterase. Dopamine levels in mice brain were elevated in soman poisoning by 23.2%, whereas noradrenaline levels remained unchanged. The increase in brain dopamine levels was antagonized by atropine as well as by HI 6. The results of this study lead to the speculation that central dopaminergic mechanisms may be involved in soman toxicity as well as in the antidotal action of atropine and the mainly peripherally acting oxime HI 6.