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Purpose Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. Methods We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. Results There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p  < 0.01), with 300 differently expressed probe sets ( p  < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes ( PPME1 , HDAC11 , SOCS7 , CIC , THRA , ERBB2 , PPP1R9A , HDGF , RAD51AP1 , and CDK1 ) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. Conclusion Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.

INTRODUCTION: Radioiodine-refractory differentiated thyroid cancer (RAIR DTC), although rare, constitutes a real clinical challenge due to its prognosis despite a growing number of available treatment modalities. This study aimed to analyze the real-world efficacy and toxicity of lenvatinib therapy in a group of Polish patients with advanced RAIR DTC. MATERIAL AND METHODS: A group of 27 patients was eligible for lenvatinib therapy due to measurable, progressive, RAIR DTC, of whom 21 ultimately received the treatment. Treatment outcomes were assessed in terms of Response Evaluation Criteria in Solid Tumors (RECIST) as well as Kaplan-Meier estimates of overall survival and progression-free survival (PFS) for the whole cohort and for subgroups receiving lenvatinib as the first or subsequent line of targeted therapy. PFS was reported using both intention-to-treat (ITT) and per-protocol (PP) definitions, depending on whether treatment discontinuation was treated as censoring. Treatment toxicity was evaluated according toCommon Terminology Criteria for Adverse Events (CTCAE). RESULTS: Median overall survival (OS) in the whole group was 38.9 months [95% confidence interval (CI): 23.8– not reached (NR)], while one-year and two-year survival rates were 0.85 (95% CI: 0.72–1.00) and 0.63 (95% CI 0.45–0.89), respectively. ITT-PFS was 21.3 months (95% CI: 12.2–NR). One-year ITT-PFS was 0.75 (95% CI: 0.57– .00), while 2-year ITT-PFS was 0.44 (95% CI: 0.22–0.76). Similar estimates were obtained using the PP-PFS definition. All patients reported treatment-related side effects, the most common being proteinuria, weight loss, hypertension, and mucositis. CONCLUSION: This retrospective analysis of a Polish RAIR thyroid cancer cohort demonstrated very good efficacy of lenvatinib in the first-line setting, while its activity in the second-line setting, although still present, was reduced. Based on these results, we suggest that lenvatinib should again be available for the treatment of RAIR thyroid cancer in Poland.

The purpose of the present guidelines on the 131 I therapy of benign thyroid disorders formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians on how to treat benign thyroid conditions employing optimal 131 I activities. The recommendations were formulated based on recent literature and expert opinion regarding rationale, indications and contraindications for the use of 131 I procedures, as well as the adequate 131 I activities in different thyroid disorders, and the administration and patient preparation techniques to be used. Recommendations are also provided on history and examinations before 131 I therapy, patient counselling and precautions associated with 131 I therapy. Furthermore, potential side effects and alternative treatment modalities are reviewed. Special attention is paid to these aspects in the treatment of children undergoing this procedure.

TERT promoter (TERTp) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of TERTp mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the BRAF V600E mutation. A total of 189 consecutive PTC specimens with known BRAF mutational status were evaluated. TERTp mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional TERTp alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the TERTp hotspot mutations were highly correlated with the presence of the BRAF V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of TERTp mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A—U133, set B—HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

At most centres, the standard treatment for differentiated thyroid cancer (DTC) comprises total thyroidectomy, radioiodine treatment and thyroid-stimulating hormone (TSH) suppressive therapy. There is, however, considerable disagreement over the appropriate treatment for DTC in children. Some dispute the use of total thyroidectomy and/or question the routine application of iodine-131 therapy in children. The aim of this study was to perform a retrospective analysis of treatment results and prognostic factors for DTC in children treated at our centre. The study included 109 children with DTC (aged 6-17 years). The primary treatment comprised total thyroidectomy in 81 cases, radioiodine therapy in 85 cases and TSH suppressive therapy with L-thyroxine in all patients. Uni- and multivariate analysis of prognostic factors for disease-free survival was performed using the Cox regression method. The actuarial survival rate was 100%, and the 5- and 10-year actuarial disease-free survival rates were 80% and 61% respectively. Univariate analysis revealed that older age, total thyroidectomy and radioiodine treatment had a positive impact on disease-free survival whereas there were no statistical differences with regard to the child's sex, histological type of cancer or lymph node status. On multivariate analysis, radical surgery was estimated to be the most significant factor (P=0.007) for disease-free survival, while less than total thyroidectomy increased the relative risk of relapse by a factor of 10. Radioiodine treatment decreased the relative risk of relapse by a factor of 5, but with borderline significance (P=0.07). Permanent postoperative complications were observed in 17% of children: in 11 laryngeal palsy occurred, in six there was hypoparathyroidism, and one suffered from both. It is concluded that total thyroidectomy and radioiodine treatment significantly improve recurrence-free survival in children and should be routinely applied even in young children as the primary treatment of DTC.

BACKGROUND: Radioligand therapy (RLT) with [177Lu]Lu-DOTA-TATE has become a key treatment option for advanced gastroenteropancreatic neuroendocrine tumors (NETs). In Poland, RLT has been reimbursed since March 2023 within the national drug program B.139. In order to monitor real-world data and patient characteristics, the Polish RLT Registry was established under the auspices of the Polish Society of Endocrinology. MATERIAL AND METHODS: This first report summarizes two years of data collection in six major clinical centers. The Registry includes retrospective and prospective data on demographics, primary tumor site, hormonal activity, prior therapies, type of progression leading to qualification, as well as the safety of administered RLT. RESULTS: The analyzed cohort reflects the real-world population of Polish patients referred for RLT. Most patients presented with advanced, progressive NETs after multiple treatment lines. Registry data allowed characterization of referral patterns, disease progression leading to qualification, and the patient care pathway from initial diagnosis to RLT. Due to the short observation period, survival outcomes such as progression-free survival (PFS) and overall survival (OS) are not yet available. CONCLUSIONS: This is the first national real-world evidence report on RLT for NET in Poland. The Registry provides unique insight into patient characteristics and clinical practice in the early phase of therapy implementation. Collected data will serve as a basis for the development of national recommendations and optimization of NET management.

Introduction:The aim of this prospective study was to evaluate long-term outcomes in differentiated thyroid cancer (DTC) patients postoperatively treated with distinct RAI activities of 30 mCi, 60 mCi, and 100 mCi.Material and methods:The analysis involved 277 low-risk and 46 intermediate-risk patients, who underwent radioiodine (RAI) ablation with 30 mCi, 60 mCi or 100 mCi under prospective, randomized clinical trials. Seventy-eight patients from the low-risk group received 30 mCi, whereas 125 and 74 patients received 60 mCi and 100 mCi, respectively. Regarding the intermediate-risk group, 20 patients were given 60 mCi, and 26 subjects were given 100 mCi. The mean time of follow-up was 11 years.Results:An excellent treatment response was obtained in 88%, 89% and 90% of low-risk patients treated with 30 mCi, 60 mCi, and 100 mCi, respectively, and in 85% of intermediate-risk patients, who were administered 60 or 100 mCi. An indeterminate response was achieved in 9.4% and 6.5%, whereas an incomplete structural response was obtained in 1.4% and 6.5% of low-risk and intermediate-risk patients, respectively. An incomplete biochemical response was observed only in 2.2% of intermediate-risk patients. The differences in treatment response regarding RAI activity were not significant.Conclusions:RAI activity of 30 mCi demonstrates a comparable efficacy as 60 mCi and 100 mCi in low-risk DTC. RAI activity of 60 mCi seems to be effective in intermediate-risk DTC.

INTRODUCTION: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas. MATERIAL AND METHODS: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3–1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5–4 years). RESULTS: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved. CONCLUSIONS: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.

The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients. 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases. BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours <= 10 mm were over-represented among BRAF negative population (p=0.03). No association between BRAF mutation and other clinicopathological factors was observed. BRAF status was associated neither with relapse nor with disease-free survival (DFS) (p=0.76). Nodal status, extrathyroidal invasion and tumour size significantly influenced DFS. The risk of PTC recurrence is mainly related to the presence of lymph node metastases and extrathyroidal invasion, whereas no impact of BRAF V600E mutation has been demonstrated.