When mutations of the RETproto-oncogene were found in 1993 to account for hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity to operate on patients prophylactically (i. e., at a clinically asymptomatic stage). Whether this approach is justified, and, if so, when and to which extent surgery should be performed remained to be clarified. A questionnaire was sent to all surgical departments in Germany and Austria. All of the patients who fulfilled the following criteria were enrolled: (1) preoperatively proved RET mutation; (2) age = 20 years, (3) clinically asymptomatic thyroid C cell disease; and (4) TNM classification pT0-1/pNX/pN0-1/M0. Seventy-five patients were identified, and fifteen mutations were detected in six codons. Two adolescents had unilateral pheochromocytomas as part of the multiple endocrine neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients underwent total thyroidectomy, and 57 patients went on to have lymph node dissection. Parathyroid glands were removed in 34 patients and autografted in 11. Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell hyperplasia (CCH) only was detected in the other 29 patients. Three patients had lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed. After surgery, five patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%) had a permanent unilateral recurrent nerve palsy. All but three patients (96%) were biochemically cured. In conclusion, prophylactic total thyroidectomy can be performed safely in experienced centers. We recommend prophylactic total thyroidectomy at age 6. Cervicocentral lymph node dissection should be included when calcitonin levels are elevated or if patients are older than 10 years. Bilateral lymph node dissection should be performed if LNMs are suspected or when patients with elevated calcitonin are older than 15 years.
Clinical outcome after surgery for primary hyperparathyroidism was evaluated in a prospective long-term, follow-up study. From August 1, 1987 to August 31, 1998 a total of 360 patients were prospectively investigated and included in a follow-up study. All patients underwent follow-up examinations at regular surveillance intervals. The postoperative course is known for 94.5% of all patients. Follow-up was 1 month to 10 years (median 24 months; mean 34.5 +/- 29.8 months). Asymptomatic primary hyperparathyroidism was rare (6%), and its true frequency could be confirmed only postoperatively because some of the patients were unaware of mild symptoms of hypercalcemic syndrome prior to surgery. Surgical cure was obtained in 97.7% of patients after initial cervical exploration; and successful parathyroidectomy provided long-term relief of symptoms. Within 2 years postoperatively, 84% of the patients recovered fully from hypercalcemic syndrome: in 58% of these patients recovery occurred within the first month after surgery. Skeletal symptoms persisted in 24% of patients 2 years postoperatively. To date no patient has developed recurrence of primary hyperparathyroidism. During follow-up in our study population mortality was significantly higher than the expected mortality risk for the German population as a whole (p = 0.00024). The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high cure rate and low morbidity, as well as the increased mortality, in our study population during follow-up after successful operative therapy for the disease emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.
Cultured mesothelial cells (HOMES) are very responsive to the proinflammatory cytokines, interleukin (IL)-l and tumor necrosis factor-α (TNF-α). E-selectin, ICAM-1 and VCAM-1 are known to play an important role, because they are presented by diverse cell types, for example endothelial cells (ECs), and interact with coresponding ligands on white blood cell membranes. In this study, the expression of ICAM-1, VCAM-1, E-selectin as well as PECAM-1 on cultured HOMES was studied over 5,24,48 and 72 h exposure to IL-1 β, interferon-γ and TNF-α. In previous studies we have shown that IL-l β and TNF-α increase the expression of ICAM-1, E-selectin and VCAM-1 on the cytoplasmatic membranes of HUVECs, HSVECs and HAFECs (ECs from human umbilical vein, saphenous vein and femoral artery, respectively). Using a comparative quantitative cell enzyme immunoassay, we found that expression of the adhesion molecules ICAM-1 and VCAM-1 was significantly increased on HOMES in a dose- and time-dependent manner, compared to nonstimulated cells. Thus, ICAM-1 increased dramatically after 5 h incubation with TNF-α. Values of about 450% of the control level were measured. VCAM-1 was similarly stimulated after 24 h incubation with the same cytokine, although its level of expression was significantly lower than that of ICAM-1. In contrast to findings in the literature, VCAM-1 was not found to be expressed constitutively. E-selectin was neither constitutively expressed nor markedly inducible on HOMES. Only weak expression was found after 24 h incubation with high-dose IL-lβ. PEC AM-1 was expressed constitutively, as became evident in antibody dilution studies. These data indicate that HOMES respond to inflammatory stimuli, in some ways in a similar fashion to vascular endothelial cells, but also show a specific pattern of antigen presentation. The results are important for a better understanding of inflammatory processes in serous cavities. The data are also relevant for the improvement of antithrombogenous surfaces of the lumina of vascular prostheses by cell seeding.
Intraoperative monitoring is not useful in first cervical exploration for renal hyperparathyroidism because it cannot predict complete resection of parathyroid tissue. The parathormone level on the first postoperative day allows precise evaluation of the efficacy of the surgical procedure.
The diagnosis of ‘early inflamed’, ‘recurrent’ or ‘sub‐acute’ appendicitis is often difficult and accompanied by controversies between clinical data, histological findings, and their interpretation. The expression of the intercellular cell adhesion molecule‐1 (ICAM‐1), the vascular cell adhesion molecule‐1 (VCAM‐1), and E‐selectin has been studied in 61 appendicectomy specimens for possible use as a diagnostic tool. This study demonstrates a different expression of CAM by endothelial (EC) and mesothelial cells (MC) in the various stages of appendicitis, with early E‐selectin and ICAM‐1 expression in EC, followed by VCAM‐1 in EC and MC. Appendices from patients with prolonged clinical symptoms defined by clinicians as ‘chronic’ appendicitis showed VCAM‐1 expression and occasionally weak expression of E‐selectin in EC. In several cases, discrepancies were found between the pre‐operative ‘clinical’ diagnosis, the histomorphological findings, and the immunohistological results. In this context, the expression of E‐selectin and VCAM‐1 in comparison with the histological features has potential significance in the diagnosis of ‘early acute’, ‘sub‐acute’ or ‘recurrent’ appendicitis. In addition, a correlation was demonstrated between the histological stages of appendicitis and the kinetics of CAM expression. The study also indicates that the time course of E‐selectin expression in vivo is longer than is suggested from in vitro data. Copyright © 1998 John Wiley & Sons, Ltd.
The value of gradients for intact parathyroid hormone (PTH) in the assessment of graft function after total parathyroidectomy/autotransplantation for renal hyperparathyroidism was evaluated in a prospective follow-up study. Altogether 99 patients who underwent operation from August 1, 1987 to December 31, 1996 were prospectively investigated and reexamined postoperatively, including analyses of serum calcium, alkaline phosphatase, and intact PTH in the antecubital venous blood of both arms. The postoperative course is known for all patients. Of the 99 patients included in the study, 95 underwent one to nine reexaminations (median three) over follow-up periods of 1 month to 5 years (median 24 months). Reproducible PTH gradients were established during follow-up. Ninety percent of the calculated gradients were < or = 20. Intermittent postoperative hypocalcemia, due to calcium deficiency of the skeleton in renal osteopathy, led to an increase in PTH secretion and gradients. Increasing gradients > 20 during follow-up make graft-dependent recurrence probable. The presence of a gradient of approximately 1 in bilaterally elevated PTH levels may be an indication of hyperfunctioning parathyroid tissue in the neck or mediastinum. The combined assessment of the course of gradients for intact PTH, hormone levels in both arms, and serum calcium permits an objective evaluation of parathyroid graft function.
The purpose of this study was to evaluate whether the timing of completion thyroidectomy for differentiated thyroid carcinoma had an influence on the risk of the operation and patient's survival. From January 1, 1985 to March 31, 2001, 230 consecutive patients underwent surgery for differentiated thyroid carcinoma (178 papillary and 52 follicular carcinomas). In this article completion thyroidectomy was defined as the removal of the remaining thyroid tissue after any initial surgical procedure less than total thyroidectomy within an interval ranging from 3 days to 4 months after the initial surgical procedure. Of 99.1 % (n = 228) of the 230 patients the postoperative course is known for 1 month to 36 years with a median follow-up of 5 years. Among 81 patients undergoing thyroidectomy as the initial operation, recurrent laryngeal nerve palsy occurred in 13.5 % (n = 11). In 2 of these patients (2.5 %) recurrent laryngeal nerve palsy was permanent. Transient recurrent laryngeal nerve palsy occurred more frequent in patients who underwent completion thyroidectomy within 8 days to 3 months of the initial surgical procedure (20.5 %) than in patients, in whom completion thyroidectomy was performed either within 7 days of the primary operation or after a minimum of 3 months (5.2 % in each group). Disease-free survival as well as long-term survival was not different after thyroidectomy or completion thyroidectomy for all differentiated thyroid carcinomas and in patients with papillary carcinomas. In order to reduce surgical morbidity we suggest that completion thyroidectomy should be performed either within 7 days of the primary operation or after a minimum of 3 months.
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