Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism (sHPT) is common in patients with chronic renal failure. Despite the initiation of new therapeutic agents, several patients will require parathyroidectomy (PTX). Total PTX with autotransplantation of parathyroid tissue (TPTX+AT) and subtotal parathyroidectomy (SPTX) are currently considered as standard surgical procedures in the treatment of sHPT. Recurrencerates after TPTX+AT or SPTX are between 10% and 12% (median follow up: 36 months).</p> <p>Recent retrospective studies demonstrated a lower rate of recurrent sHPT of 0–4% after PTX without autotransplantation and thymectomy (TPTX) with no higher morbidity when compared to the standard procedures. The observed superiority of TPTX is flawed due to different definitions of outcomes, varying follow up periods and different surgical treatment strategies (with and without thymectomy).</p> <p>Methods/Design</p> <p>Patients with sHPT (intact parathyroid hormone > 10 times above the upper limit of normal) on long term dialysis (>12 months) will be randomized either to TPTX or TPTX+AT and followed for 36 months. Outcome parameters are recurrence rates of sHPT, frequencies of reoperations due to refractory hypoparathyroidism or recurrent/persistent hyperparathyroidism, postoperative morbidity and mortality and quality of life. 50 patients per group will be randomized in order to obtain relevant frequencies of outcome parameters that will form the basis for a large scale confirmatory multicentred randomized controlled trial.</p> <p>Discussion</p> <p>sHPT is a disease with a high incidence in patients with chronic renal failure. Even a small difference in outcomes will be of clinical relevance. To assess sufficient data about the rate of recurrent sHPT after both methods, a multicentred, randomized controlled trial (MRCT) under standardized conditions is mandatory.</p> <p>Due to the existing uncertainties the calculated number of patients necessary in each treatment arm (n > 4000) makes it impossible to perform this study as a confirmatory trial. Therefore estimates of different outcomes are performed using a pilot MRCT comparing 50 versus 50 randomized patients in order to establish a hypothesis that can be tested thereafter.</p> <p>If TPTX proves to have a lower rate of recurrent sHPT, no relevant disadvantages and no higher morbidity than TPTX+AT, current surgical practice may be changed.</p> <p>Trial registration</p> <p>International Standard Randomized Controlled Trial Number Registration (ISRCTN86202793)</p

Persistent ischemia impairs myofibroblast development in wound granulation tissue: a new model of delayed wound healing

We describe a new animal model designed to assess the impact of ischemia on wound healing. Eight patterns of arterial lesion in the limb were first tested in 24 Wistar rats. Resection of the external iliac artery down to the femoral artery at the level of the knee was chosen as the reference model and performed on the left limb of 45 rats; the right limb was used as the control. Skin wounds measuring 1.2 x 0.8 cm were created on both feet. Ischemia was assessed by blood flow measurement, which decreases dramatically in the ischemic limb. A significant delay in wound closure with a decrease in wound contraction was observed in the ischemic limb. Myofibroblast quantification showed a significant delay in appearance as well as a decrease in the number of these cells in the ischemic wound. Vascular endothelial growth factor-A appearance and evolution were qualitatively similar in both situations. However, collagen type I mRNA was markedly decreased in ischemic granulation tissue 10 days after wounding. These findings suggest that decreased wound contraction plays an important role in delayed ischemic wound healing, probably due to reduced myofibroblast development and activity