http://repub.eur.nl/res/aut/33018/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/24957/ 2009-04-13T00:00:00Z Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group. Discussion. The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas. Trial registration number. (trialregister.nl) NTR1422. http://repub.eur.nl/res/pub/25955/ 1978-06-14T00:00:00Z The prime cause of failure of a transplanted kidney is immunological rejection of the graft. Graft rejection will not occur, when the transplanted organ is obtained from a donor which is genetically identical to the recipient (isogenic transplant). Graft rejection can always occur, when donor and recipient are genetically different (allogenic transplant). Unrelated people are always genetically different. Only when donor and recipient are monozygotic twins, complete genetic identity exists. Thus a transplanted organ will be antigenic, when donor and recipient are not monozygotic twins. The immune reaction, evoked by the antigens of such an allograft, consists of two components. In the first place, antibodies will be produced, which are specifically directed against the transplanted antigens (the so called humoral immune response). Secondly, immune reactive cells are generated, which specifically can attack the transplanted organ (the cellular immune response). The mechanism of the destruction of the allograft is complicated and only partly known. Both different types of antibodies and different types of cells are involved. Microscopically, arteritis and a cellular infiltrate can be seen (Busch et al., 1977). Progressive damaging of the glomeruli and tubuli results in a increasing loss of function of the transplanted kidney. Two factors determine the strength of the immune reaction of the recipient against the allograft. These factors are the immune response potential of the recipient and the strength of the antigenic stimulus (Lengerova, 1969). The strength of the antigenic stimulus is dependent on the immunogenetic difference between donor and recipient. Consequently, two methods are available to prevent allograft rejection, namely modification of the immune response and selection of compatible donor-recipient pairs.