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One feature of papillary thyroid cancer (PTC) is the frequently present somatic BRAFV600E mutation. PTCs are also characterized by a lymphocytic infiltration, which may correlate with an improved clinical outcome. The objective of the study was the characterization of BRAFV600E specific anti-immunity in PTC patients and correlation analyses with the clinical outcome. Fourteen HLA A2 positive PTC patients were included into the study of whom tumor tissue samples were also available. Of those, 8 PTC patients revealed a somatic BRAFV600E mutation. All PTC patients were also MHC class II typed. Tetramer analyses for detection of MHC class I and MHC class II-restricted, BRAFV600E epitope-specific T cells using unstimulated and peptide-stimulated T cells were performed; correlation analyses between MHC phenotypes, T cell immunity, and the clinical course were performed. In regard to unstimulated T cells, a significantly higher amount of BRAFV600E epitope specific T cells was detected compared to a control tetramer. Importantly, after overnight peptide stimulation a significantly higher number of BRAFV600E positive and BRAF WT epitope-specific T cells could be seen. In regard to the clinical course, however, no significant differences were seen, neither in the context of the initial tumor size, nor in the context of lymph node metastases or peripheral metastastic spread. In conclusion, we clearly demonstrated a BRAF-specific tumor immunity in PTC-patients which is, however, independent of a BRAFV600E status of the PTC patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was the quantification of circulating tumour cells (CTCs) in differentiated thyroid cancer (DTC) patients before and 6 weeks after radioiodine therapy (RIT). Context: Circulating tumour cells (CTCs) were described more recently in cancer patients, mostly correlating with poor outcome and advanced metastases. Design: Peripheral blood for identification and quantification of CTC before RIT or/and 6 weeks after RIT was provided by 55 DTC patients that received RIT for remnant tissue ablation. Patients: 13 follicular thyroid cancer (FTC) patients, 31 papillary thyroid cancer (PTC) patients and 11 patients having the follicular variant PTC (FV‐PTC) were included. Measurements: Peripheral blood mononuclear cells (PBMCs) were isolated and EpCAM‐positive CTCs were counted by immune fluorescent staining. Results: A CTC positivity of 31.8% before RIT could be observed. Six weeks after RIT, the CTC positivity was reduced to 13.6%. Paired data at both time points of blood sampling could be gathered for n = 33 DTC patients. These patients had significantly higher CTC numbers before RIT than 6 weeks afterwards (0.27 ± 0.47 vs 0.05 ± 0.15, P =.0215). Additionally, significantly reduced CTC numbers were also demonstrated in pre‐RIT CTC‐positive patients (0.88 ± 0.43 vs 0.05 ± 0.16, P =.0039). Conclusion: Our results indicate a reducing effect on the number of CTCs by RIT. Therefore, CTC enumeration should be considered as efficient tool for treatment monitoring during RIT. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3 × 105 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels < 0.3 ng/ml (no evidence of tumor recurrence) revealed a significantly higher amount of CTCs, also associated to their former tumor stage. Regarding the tumor-free papillary TC (PTC) patients the number of CTCs additionally correlated to the time point of radioiodine (RI) therapy: PTC patients with RI therapies > 8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy < 8 years ago. We found a clear correlation between the number of CTCs and the tumor stage. Importantly, PTC patients who are in remission may still have increased numbers of CTCs. Follow- up analyses in these patients will reveal whether these data will have a clinical impact. [ABSTRACT FROM AUTHOR]

Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin, basal CT measurement is frequently used for the preoperative diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT) cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114 patients (51 males) were included fulfilling the criteria of an increased preoperative bCT level (> 10 pg/ml) and the criteria of an available postoperative histology analysis. Based on a ROC plot analysis, the cut-off values for the diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were identified. The most precise bCT thresholds for the identification of MTC were = 46 pg/ml for males (sensitivity: 93.6 %, specificity: 95.0 %, PPV: 97 %, NPV: 90 %) and = 35 pg/ml for females (sensitivity: 87.3 %, specificity: 87.5 %, PPV: 98 %, NPV: 50 %). Using these cut-offs, only 6 % of male patients were not identified of having MTC, whereas 5 % were false positive (having instead C cell hyperplasia). In females, the discrepancy was higher since 13 % of female MTC patients were false negative by using the cut-off of = 35 pg/ml, and 13 % had false positive results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the identification of MTC vs. C cell hyperplasia and non-malignancy were defined, which can be used in clinical routine. In female patients, however, the accuracy is much lower compared to males. [ABSTRACT FROM AUTHOR]

To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA). Consecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists. In total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52–0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01). Contrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy. • Adrenal vein sampling without contrast medium is a safe and reliable procedure in the diagnostic pathway of primary aldosteronism. • Patients with aldosterone producing adenomas diagnosed by adrenal vein sampling had excellent clinical outcome after surgery. • The concordance between cross-sectional imaging and results from venous cannulation was only moderate. [ABSTRACT FROM AUTHOR]