[Cholelithiasis and primary hyperparathyroidism].
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Biomedical subjects
Publications and source records attributed to M Rothmund.
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Allotransplantation of parathyroid tissue in humans is desirable for treating long-term hypoparathyroidism (e.g., after inadvertent removal of parathyroid glands during thyroid surgery). Until now, parathyroid allotransplantation was not used clinically because its advantages were outweighted by the need of immunosuppression. To overcome the immunogenicity of the tissue to be transplanted, we employed the method of microencapsulation; first tried in islet cell transplantation for experimental allotransplantation of parathyroid tissue. We have been able to achieve long-term success in a rat model. After isolation and tissue culture, tissue pieces from parathyroid glands of 280 Lewis rats were encapsulated in barium alginate and grafted into hypocalcemic DA rats. From the 7th to the 90th day after transplantation the recipient rats (DA rats) showed a normal serum calcium concentration. This is the first report of successful long-term survival and function of microencapsulated allotransplanted parathyroid tissue.
In a multiinstitutional review, data on 396 patients with benign solitary or multiple insulinomas operated on in 15 centers were collected. In these 396 patients, 419 laparotomies (375 primary procedures and 44 reoperations) were performed. The rate of unnecessary laparotomies was 1.7%. Complications occurred after 132 operations (31.5%), requiring 27 reinterventions (6.4%). Ten (2%) patients died within 30 days of surgery. The success rate of first procedures in the centers was 94.9%. After reoperation, all but 2 (99.5%) of these patients were cured. The overall cure rate including those patients who had their primary operations elsewhere was 97.5%.
Theoretical surgery is defined as a nonoperative decision analysis and clinical and basic research supporting system for surgery. It developed to meet the needs of academic surgeons to coordinate communication with basic science disciplines. This article summarizes the development of this idea at the University of Marburg where theoretical surgery has reached departmental and institutional proportions. Its objectives and methods are described. Central to its operation are permanent working teams of 2 clinical surgeons, 1 basic scientist (theoretical surgeon), 1-2 technicians, and 1-2 students focusing on one problem in a joint interdisciplinary manner. Decision analysis with classification methods and the creation of decision trees and algorithms are central to the operation of this experiment. Lessons learned from this academic experiment and the accomplishments during the past 20 years are summarized on 3 levels of efficacy: performance, changing strategies, and outcome.
The clinical value of high-resolution real-time sonography for the diagnosis of acute and complicated appendicitis was prospectively investigated in 857 patients admitted with suspected appendicitis. The ultrasound findings were correlated with history and physical examination on admission. Sonography was able to make the diagnosis of appendicitis with a sensitivity of 89.7%, a specificity of 98.2%, an overall accuracy of 96.3%, and a positive and negative predictive value of 93.6% and 97%, respectively. Routine use of ultrasound before making therapeutic decisions has reduced the rate of unnecessary laparotomies from 20.3% to 11.3%. In 48 (24.7%) of 194 patients with proven appendicitis, the disease had progressed to perforation at laparotomy. History and clinical findings on admission classified 30 (62.5%) of these patients as "highly suspect;" however, 9 (18.8%) were classified as "equivocal" and 9 (18.8%) as "very unlikely." Only half (48%) of the patients with appendiceal rupture had white blood cell counts higher than 13,000/mm3 or fever above 38 degrees C (50%). Sonography enabled the visualization of the inflamed appendix and/or appendicular abscess in 44 (91.7%) patients with perforation. In 47 of 48 patients with appendiceal rupture, the ultrasound-aided diagnosis was made on hospital admission. Thus, the incidence of complicated appendicitis (24.7%) in our study population must be attributed to disease progression before admission and preclinical diagnostic delay.
In a randomized study subtotal parathyroidectomy (sPTX) was compared with total parathyroidectomy and autotransplantation of fresh tissue (PTX + AT) in 40 patients with severe secondary hyperparathyroidism (HPT). After surgery both groups were followed at 19 +/- 6 months (PTX + AT) and 19 +/- 7 months (sPTX) and at 43 +/- 9 months (PTX + AT) and 40 +/- 7 months (sPTX). There were 17 patients alive in each group at the time of the second follow-up. After sPTX, 2 patients required re-operation because of recurrent disease originating from the remaining parathyroid gland in the neck and another 2 patients were hypercalcemic at follow-up. After PTX + AT both serum calcium and alkaline phosphatase normalized significantly more often (p less than 0.03) than after sPTX. Re-operations were not required in this group. Radiological signs also improved significantly more after PTX + AT, as did clinical signs like pruritus (p less than 0.005) and muscle weakness (p less than 0.04). These results and the fact that in recurrent disease a re-operation at the autograft in the forearm is simpler than a re-operation in the neck, lead to the recommendation that PTX + AT should be considered as the method of choice in the surgical treatment of secondary HPT.
Twenty-five patients with permanent postoperative hypoparathyroidism received cryopreserved parathyroid autografts. Twelve patients had undergone cervical re-operations due to persistent or recurrent hyperparathyroidism and 10 patients had malfunction of a fresh autograft after total parathyroidectomy. Hypoparathyroidism occurred in 2 patients after subtotal parathyroidectomy and in 1 after the resection of a solitary adenoma following previous thyroid resection. The viability of the tissue was examined histologically prior to replantation in 22 patients and the amount of tissue needed for transplantation was determined by the ratio of necrotic cells vs. viable cells in the material. The patients were examined between 6 months and 125 months (median: 40 months) after replantation. Pre-operatively each patient required high doses of calcium and vitamin D metabolites to establish normocalcemia. This medication was reduced postoperatively, with 16 patients requiring no supplemental treatment. Nine patients still needed low doses of calcium and/or vitamin D. At follow-up all patients were free of hypocalcemic symptoms. Our results demonstrate that replantation of autologous cryopreserved parathyroid tissue is safe and effective therapy for permanent postoperative hypoparathyroidism. Thus, we regard it as an essential part of today's parathyroid surgery.
Owing to the complexity of the parathyroid hormone's metabolic interactions, clinical hypoparathyroidism is one of the most difficult of all endocrine disorders to treat. Therefore, causative treatment of this disorder by transplantation of parathyroid glands is highly desirable. We have recently documented the long-term in vivo function of iso- and allotransplanted rat parathyroid tissue without systemic immunosuppression in an animal model. In view of the potential clinical use of this method, human parathyroid tissue has been microencapsulated and transplanted over the highest immunological barrier. In a controlled, long-term animal study in the parathyroidectomized rat, the effect of microencapsulation on xenotransplanted human parathyroid tissue was evaluated over 30 weeks (native and microencapsulated parathyroid tissue = 40 rats respectively). Functionally, human parathyroid tissue was able to replace that of the rat. All animals that had received microencapsulated parathyroid tissue were normocalcemic for 16 weeks; 27/40 at the end of the study. In contrast, serum calcium concentrations dropped to post-parathyroidectomy levels within 4 weeks in those animals that had received native tissue only. Histologic evaluation of the explanted, functionally successful xenografts showed vital parathyroid tissue inside intact microcapsules surrounded by a small rim of fibroblasts. Avital fibrotic remnants were demonstrated in animals with non-encapsulated parathyroid tissue. Thus, we have established the feasibility of microencapsulation of human parathyroid tissue, preserving its viability over long periods in vivo even if xenotransplanted. In combination with an improved tissue culture method, transplantation of human parathyroid tissue and maintenance of its physiological function is reproducibly achieved without postoperative systemic immunosuppression over the highest transplantation barrier. This may be a crucial step towards the first clinical application of this method.
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