Thyroid surgery in children and adolescents: results from a multi-institutional German and Austrian database.

BACKGROUND: Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria. METHODS: Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied. RESULTS: In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection. CONCLUSION: Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.

Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors-A Retrospective Multi-Center Registry Analysis.

BACKGROUND: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. METHODS: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. RESULTS: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32-NR (not reached); n = 36), and the median PFS was 21 months (12-39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13-79; n = 22), and the median PFS was 3.5 months (2-14; n = 22) in RET-positive cases. CONCLUSIONS: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts.

[Local recurrence of iodine refractory thyroid cancers. Surgical therapy options for larynx and trachea infiltration]. / Lokalrezidive von jodrefraktären Schilddrüsenkarzinomen ­ chirurgische Therapieoption bei Infiltration des Kehlkopfs.

AIM: Local recurrence of thyroid carcinomas can result in tumor infiltration in the lower region of the larynx. Since these tumors typically no longer store iodine, treatment options are greatly limited. The present study describes our experience with laryngo-tracheal resection of such cases of local recurrence. MATERIALS AND METHODS: From July 2019 to November 2020, we treated five patients with malignant infiltration of the trachea and larynx due to local recurrence of a thyroid carcinoma. We performed laryngo-tracheal resection with end-to-end anastomosis in four patients and frontolateral partial laryngectomy in one patient. RESULTS: The median length of hospital stay was 6 days (5-14). An R0 resection was performed in two patients. Problems with the anastomosis or bilateral recurrent laryngeal nerve paralysis was not seen in any of the patients. One patient had to be reintubated on the second postoperative day due to lung failure. He was able to be extubated after five days. CONCLUSION: High tracheal resection with partial resection of the larynx was able to be performed with minimal risk. Although radical resections are rare, they expand oncological treatment options in the case of local recurrence of thyroid carcinomas that are iodine-refractory. High tracheal resection could be part of the oncological treatment spectrum in the case of local recurrence of thyroid carcinomas that no longer store iodine.

Increased numbers of bone marrow-derived cells in parathyroid adenoma.

BACKGROUND: In primary hyperparathyroidism (PHPT), the increased levels of parathyroid hormone (PTH) result in mobilisation of bone-marrow-derived cells (BMCs) into peripheral blood. However, the fate of these cells is still unknown. MATERIALS AND METHODS: In this study, we sought to investigate cells with typical surface markers of BMCs within parathyroid adenomas (PA) of patients with primary hyperparathyroidism. We therefore investigated PA and normal parathyroid glands (NPG) of 15 patients with PHPT by immunohistochemistry and PCR. RESULTS: mRNA levels for CD31, CD34 and CD45 were significantly increased in PA compared to NPG. Immunohistochemical staining for CD31 and CD34 revealed a significantly higher vessel density in PA. Furthermore, scattered single cells expressing CD31, CD34 or CD45 were significantly augmented compared to normal parathyroid glands and directly correlated with vessel density. mRNA levels of SDF-1 was increased whereas its major inhibitor dipeptidylpeptidase IV (DPP IV) is decreased in PA, suggesting that the SDF-1 axis plays a role in the migration of BMCs into PA. CONCLUSION: These data indicate a possible role of BMCs in the pathophysiology of PA of patients with PHPT.

Familial nonmedullary thyroid carcinoma-clinical relevance and prognosis. A European multicenter study. ESES Vienna presentation.

PURPOSE: Approximately 5% of differentiated thyroid carcinomas are of familial origin. These familial nonmedullary thyroid carcinomas (FNMTC) have an increased risk of multifocal disease and lymph node involvement. Consequently, higher recurrence rates and decreased disease-specific survival rates are described. The best surgical approach is discussed controversially. PATIENTS AND METHODS: A survey among the international members of the German Society of Endocrine Surgeons revealed 20 families with two or more first-degree relatives with FNMTC. The mean age of the 41 patients (30 female, 11 male) with FNMTC was 40.6 years (18-73 years). RESULTS: Total thyroidectomy was performed in 31 of 41 patients (76%). Ninety-five percent of the tumors were papillary carcinomas. Two of 41 patients had follicular carcinomas. Ten patients (24%) with papillary carcinomas were diagnosed with Hashimoto's thyroiditis. The mean tumor size was 1.45 cm. FNMTC was multifocal in 12 patients (29%). A systematic lymph node dissection was performed in 21 of 41 patients (51%). Lymph nodes metastases were found in seven of these 21 patients. Twenty-eight of the patients (68%) underwent postoperative radioiodine ablation. After a mean follow-up of 7.2 years, 39 patients (95%) were disease free. One patient developed local recurrence and lung metastases, 10 and 25 years, respectively, after initial diagnosis. Another patient died 2 years postoperatively from advanced metastatic disease. CONCLUSIONS: FNMTC is associated with an early onset of small, mostly papillary thyroid carcinomas and an increased risk of multifocality and lymph node involvement. Total thyroidectomy and systematic neck dissection are recommended together with radioiodine ablation. Screening for first-degree relatives should start at age 18 years.

Regional lymph node involvement in T1 papillary thyroid carcinoma: a bicentric prospective SPECT/CT study.

PURPOSE: Hybrid imaging combining single photon emission computed tomography (SPECT) with (131)I and X-ray computed tomography (CT) performed at radioablation (RA) for thyroid carcinoma more accurately detects regional lymph node metastases (LNM) than does planar imaging. In this bicentric prospective study we used hybrid imaging in conjunction with histopathological examination to measure LNM frequency in a consecutive group of patients referred for RA due to stage T1 papillary thyroid carcinoma (PTC). METHODS: At the Departments of Nuclear Medicine of the Ludwig Maximilian University of Munich and the Friedrich Alexander University of Erlangen-Nuremberg SPECT/spiral CT is routinely performed in all PTC subjects at the time of RA. Screening of our SPECT/CT databases for PTC patients with T1 histology produced 98 patients from Munich and 53 patients from Erlangen, including 96 of 151 patients with microcarcinoma. In 69 patients of the entire group, cervical lymph node dissection had been performed, whereas nodal staging in the remaining 82 subjects was based on SPECT/CT. RESULTS: LNM incidence in the whole group was 26% [95% confidence interval (CI): 20-33%] versus 22% (95% CI: 15-31%) in the microcarcinoma subgroup. SPECT/CT was more accurate in 24.5% of our patients than planar imaging with regard to nodal staging. CONCLUSION: LNM occurs in one quarter of all patients with T1 PTC, and also in the subset with microcarcinoma. Performing (131)I SPECT/CT, either with therapeutic or diagnostic radioactivities, directly after thyroidectomy should provide more accurate staging of T1 PTC, thus facilitating optimal therapeutic management.

Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells.

Recently, parathyroid hormone (PTH) was shown to support survival of progenitor cells in bone marrow. The release of progenitor cells occurs in physiological and pathological conditions and was shown to contribute to neovascularization in tumors and ischemic tissues. In the present study we sought to investigate prospectively the effect of primary hyperparathyroidism (PHPT) on mobilization of bone marrow-derived progenitor cells. In 22 patients with PHPT and 10 controls, defined subpopulations of circulating bone marrow-derived progenitor cells (BMCs) were analyzed by flow cytometry (CD45(+)/CD34(+)/CD31(+) cells indicating endothelial progenitor cells, CD45(+)/CD34(+)/c-kit(+) cells indicating hematopoietic stem cells, and CD45(+)/CD34(+)/CXCR4(+) cells indicating progenitor cells with the homing receptor CXCR4). Cytokine serum levels (SCF, SDF-1, VEGF, EPO, and G-CSF) were assessed using ELISA. Levels of PTH and thyroid hormone as well as serum electrolytes, renal and liver parameters, and blood count were analyzed. Our data show for the first time a significant increase of circulating BMCs and an upregulation of SDF-1 and VEGF serum levels in patients with PHPT. The number of circulating BMCs returned to control levels measured 16.7 +/- 2.3 mo after surgery. There was a positive correlation of PTH levels with the number of CD45(+)/CD34(+)/CD31(+), CD45(+)/CD34(+)/c-kit(+), and CD45(+)/CD34(+)/CXCR4(+) cells. However, there was no correlation between cytokine serum concentrations (SDF-1, VEGF) and circulating BMCs. Serum levels of G-CSF, EPO, and SCF known to mobilize BMCs were even decreased or remained unchanged, suggesting a direct effect of PTH on stem cell mobilization. Our data suggest a new function of PTH mobilizing BMCs into peripheral blood.