The incidence of thyroid cancer has been increasing over the past 30 years. The follicular-cell-derived thyroid carcinomas (DTC) – papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) – are most common (79 and 13%, respectively). Initial treatment of DTC involves resection of the primary tumour. Post-operative therapy consists of radioactive iodine ablation for most patients, followed by thyroid-stimulating hormone (TSH) suppression with thyroxine. An ongoing controversy in the surgical treatment of DTC is the extent of thyroid gland resection. Consensus guidelines recommend total or near-total thyroidectomy in high-risk DTC (PTC tumour >1–2cm, any tumour, node, metastasis [TNM] stage III and IV [extrathyroidal spread], any N1 [regional metastasis] or M1 [distant metastasis], any patient 㹅 years and <16 years of age, aggressive histological subtypes) rather than thyroid lobectomy as the initial procedure of choice, given its advantages of treating potential multicentric disease, facilitating maximal uptake of adjuvant radioactive iodine and facilitating post-treatment follow-up by monitoring serum thyroglobulin levels and neck ultrasonography. Low-risk patients are currently treated by thyroid lobectomy or total (or near-total) thyroidectomy; in fact, conflicting views persist for low-risk patients who have differentiated thyroid cancer. The main arguments for lobectomy in low-risk PTC patients are that there is no clear evidence that total thyroidectomy may affect the survival of patients with low-risk PTC, and that total thyroidectomy increases the risk of recurrent laryngeal nerve injury and hypoparathyroidism even in the hands of an experienced endocrine surgeon.
Abstract Background The usefulness of rapid intraoperative monitoring of intact (1–84) parathyroid hormone (PTH) is not clearly defined in the surgical management of secondary HPT in the patients on haemodialysis. The aim of this study was to define the normal pattern of decay during surgery for secondary HPT using the rapid intact (1–84) PTH assay during operation. Methods Fifty patients on haemodialysis underwent neck exploration for secondary HPT. The therapeutic goal in all patients was the subtotal resection of four or more glands and bilateral transcervical thymectomy. PTH levels were monitored using a rapid immunochemiluminometric assay. Peripheral blood samples were assayed at induction of anaesthesia, after dissection but before resection, and 20 and 40 min after resection in all patients. All patients were followed up for at least 6 months. PTH levels were expressed as absolute values, as multiples of the upper limit of normal and as the percentage decline from pre-excision values. Results Forty-eight patients (96 per cent) were considered cured after surgery. Twenty patients (40 per cent) had a PTH level less than twice normal and 20 patients (40 per cent) had a PTH level between two and four times normal at 20 min. At late follow-up, all these patients were cured. Ten patients (20 per cent) had a PTH level greater than four times normal at 20 min. Eight of these patients were cured. Seven of these eight had a PTH level at 20 min, while not less than four times normal, less than 40 per cent of the original value. In contrast, the two failures had neither a decline to less than four times normal nor a decay to less than 40 per cent of the original value. One has been reoperated with resection of a fifth gland and one awaits reoperation. Conclusion The intraoperative decay of PTH during surgery for secondary HPT in patients on haemodialysis is slower than that in patients with normal renal function. However, 20 min after resection, a decline to less than four times the upper limit of normal is predictive of cure. Variability of decay slopes in individual patients may reflect molecular heterogeneity or biphasic metabolism of the hormone.
Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation.We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class.BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples.In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600-1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600-3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P < 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P < 0.00000006), and absence of tumor capsule (P < 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation.Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.
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