Investigation of factors potentially influencing calcitonin levels in the screening and follow-up for medullary thyroid carcinoma: a cautionary note.

BACKGROUND: The malignant transformation of thyroid C cells is associated with an increase in human calcitonin (hCT), which can thus be helpful in the early diagnosis of medullary thyroid carcinoma (MTC). For this reason, hCT levels should be determined in all patients with nodular goitre. Hashimoto's thyroiditis, nodular goitre and proton pump inhibitor (PPI) therapy are factors reported to influence basal serum hCT concentrations. The diagnostic role of mildly to moderately increased hCT levels is thus a matter of debate. In this study, we attempt to clarify the role of the aforementioned factors. METHODS: From 2008 to 2009, we collected data from 493 patients who were divided into five groups. We assessed whether there were significant differences in hCT levels between patients with Hashimoto's thyroiditis, patients with nodular goitre, patients with PPI therapy, and healthy control subjects. In addition, we investigated whether a delayed analysis of blood samples has an effect on serum hCT concentrations. RESULTS: Immunoradiometric assays (Calcitonin IRMA magnum, MEDIPAN) revealed that the time of analysis did not play a role when low levels were measured. Delayed analysis, however, carried the risk of false low results when serum hCT concentrations were elevated. Men had significantly higher serum hCT levels than women. The serum hCT concentrations of patients with Hashimoto's thyroiditis and nodular goitre were not significantly different from those of control subjects. Likewise, PPI therapy did not lead to a significant increase in serum hCT concentrations regardless of the presence or absence of nodular goitre. CONCLUSIONS: Increases in serum hCT levels are not necessarily attributable to Hashimoto's thyroiditis, nodular goitre or the regular use of PPIs and always require further diagnostic attention.

Correlation between sonography and antibody activity in patients with Hashimoto thyroiditis.

OBJECTIVES: Patients with Hashimoto thyroiditis show structural changes of the thyroid that can be identified by a variety of sonographic criteria. We conducted this study to investigate whether there is a correlation between sonography and antibody activity and to assess the role of sonography in the diagnosis and follow-up of Hashimoto thyroiditis. In addition, we present a new classification system (termed the VESINC system [volume, echogenicity, sonographic texture, pseudonodular hypoechoic infiltration, nodules, and cysts]), which helps improve the clarity of sonographic findings. METHODS: The study included 223 consecutive patients with previously diagnosed Hashimoto autoimmune thyroiditis who attended the thyroid clinic of the German Armed Forces Central Hospital in Koblenz for follow-up examinations between 2006 and 2008. Laboratory tests were performed to measure the levels of free triiodothyronine, free thyroxine, thyrotropin, anti-thyroglobulin antibodies (TgAbs), and antithyroid peroxidase antibodies (TPOAbs). Sonography was performed according to a strict protocol. We then assessed whether a correlation existed between antibody activity and the 6 sonographic variables of the VESINC system. RESULTS: Hypoechogenicity, heterogeneity, and pseudonodular hypoechoic infiltration were associated with significantly higher TPOAb activity (P < .001). There were no significant correlations between the other sonographic variables examined (cysts, nodules, and volume) or the biometric data with the TPOAb and TgAb levels. In addition, an assessment of TgAb levels did not show significant differences in correlations with any of the sonographic variables. CONCLUSIONS: Sonography is a noninvasive diagnostic imaging modality that provides information about the level of inflammatory activity. Markedly decreased echogenicity, heterogeneity, and multifocal pseudoinodular hypoechoic infiltration are indicative of a high level of inflammatory activity. The sonographic classification system presented here (VESINC system) can be a useful tool for comparing sonographic findings in a rapid and objective manner during follow-up of Hashimoto thyroiditis.

Primary Staging of Prostate Cancer Patients with [18F]PSMA-1007 PET/CT Compared with [68Ga]Ga-PSMA-11 PET/CT.

BACKGROUND: Hybrid imaging with prostate-specific membrane antigen (PSMA) is gaining importance as an increasingly meaningful tool for prostate cancer (PC) diagnostics and as a guide for therapy decisions. This study aims to investigate and compare the performance of [18F]PSMA-1007 (18F-PSMA) and [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA) in the initial staging of PC patients. METHODS: The data of 88 biopsy-proven patients were retrospectively evaluated. PSMA-avid lesions were compared with the histopathologic Gleason Score (GS) for prostate biopsies, and the results were plotted by receiver operating characteristic (ROC)-curve. Optimal maximum standardized uptake value (SUVmax) cut-off values were rated using the Youden index. RESULTS: 18F-PSMA was able to distinguish GS ≤ 7a from ≥7b with a sensitivity of 62%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 67% for a SUVmax of 8.95, whereas sensitivity was 54%, specificity 91%, PPV 93%, and accuracy 66% for 68Ga-PSMA (SUVmax 8.7). CONCLUSIONS: Both methods demonstrated a high concordance of detected PSMA-avid lesions with histopathologically proven PC. 18F-PSMA and 68Ga-PSMA are both suitable for the characterization of primary PC with a comparable correlation of PSMA-avid lesions with GS. Neither method showed a superior advantage. Our calculated SUVmax thresholds may represent valuable parameters in clinical use to distinguish clinically significant PC (csPC) from non-csPC.

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse.

This study aimed to compare the diagnostic performance of [18F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (18F-PSMA) and [68Ga]Ga-PSMA-11 PET/CT (68Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of 18F-PSMA and 68Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. 18F-PSMA showed PC-lesions in 87.5% (112/128 patients), while 68Ga-PSMA identified them in 88.9% (121/136). For 18F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710−0.932), while for prostatectomized 68Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410−0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for 18F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to 68Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings.

Age- and Sex-Graded Data Evaluation of Vaccination Reactions after Initial Injection of the BNT162b2 mRNA Vaccine in a Local Vaccination Center in Germany.

A high vaccination rate of older and particularly chronically ill people against coronavirus disease-2019 (COVID-19) is likely one of the most important factors in containing the pandemic. When Germany's vaccination campaign started on December 2020, vaccination prioritization was initially carried out starting with older population groups. Side effect rates in 1065 individuals who had received the first dose of the messenger ribonucleic acid (mRNA) vaccine BNT162b2 Tozinameran from BioNTech/Pfizer three weeks earlier were examined retrospectively. An age- and gender-graded data analysis showed clear age and gender differences with regard to vaccine-related adverse effects. In 77% of all individuals over 80 years of age, no local or systemic side effects were reported after the first vaccination, whereas in the age group up to 80 years, only 37% showed no side effects. In the whole study population, 64% of females and 73% of males reported no adverse effects. The initial vaccination with mRNA vaccine BNT162b2 shows an overall low profile of side effects. Particularly in those over 80 years, an extraordinarily good tolerance with equally good effectiveness is evident. The sex comparison showed that women suffer more often from adverse vaccination reactions. In order to achieve sufficient herd immunity, both age- and gender-dependent vaccination reactions and any difference in the maintenance of immunity should be considered in future vaccination strategies.

Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma.

Gallium-68 (Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography showed a pathological prostate-specific-membrane-antigen uptake in 76% (500 of 660 patients). Positive scans were positively associated with prostate-specific-antigen (p<0.001). For patients with prostate-specific-antigen <0.2 ng mL, the PSMA-positive tumor lesions rate was 41%. Patients with prostate-specific-antigen of 0.2-<0.5 ng mL, 0.5-<1.0 ng mL, 1.0-<2.0 ng mL, and 2.0-<5.0 ng mL showed rates of 44.7%, 61.7%, 72.3%, 85.2%, respectively, and for prostate-specific-antigen of ≥5.0 ng mL it increased to 94%. Prostate-specific-antigen velocity was also correlated with PSMA-positive tumor lesions (p<0.001). In contrast, no association was found for prostate-specific-antigen doubling time (p=0.74). PSMA-positive tumor lesions were significantly increased in patients with primary intermediate- (Gleason Score7) and high-risk (Gleason Score>7) vs. low-risk prostate cancer (Gleason Score<7) (p<0.001). Our data confirm the high performance of Ga-prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography for the detection of recurrent prostate cancer. This may alter treatment planning and has been documented in other studies as well.

Dual-Time Point [68Ga]Ga-PSMA-11 PET/CT Hybrid Imaging for Staging and Restaging of Prostate Cancer.

Routine [68Ga]Ga-PSMA-11 PET/CT (one hour post-injection) has been shown to accurately detect prostate cancer (PCa) lesions. The goal of this study is to evaluate the benefit of a dual-time point imaging modality for the staging and restaging of PCa patients. Biphasic [68Ga]Ga-PSMA-11 PET/CT of 233 patients, who underwent early and late scans (one/three hours post-injection), were retrospectively studied. Tumor uptake and biphasic lesion detection for 215 biochemically recurrent patients previously treated for localized PCa (prostatectomized patients (P-P)/irradiated patients (P-I) and 18 patients suspected of having primary PCa (P-T) were separately evaluated. Late [68Ga]Ga-PSMA-11 PET/CT imaging detected 554 PCa lesions in 114 P-P patients, 187 PCa lesions in 33 P-I patients, and 47 PCa lesions in 13 P-T patients. Most patients (106+32 P-P/P-I, 13 P-T) showed no additional PCa lesions. However, 11 PSMA-avid lesions were only detected in delayed images, and 33 lesions were confirmed as malignant by a SUVmax increase. The mean SUVmax of pelvic lymph node metastases was 25% higher (p < 0.001) comparing early and late PET/CT. High positivity rates from routine [68Ga]Ga-PSMA-11 PET/CT for the staging and restaging of PCa patients were demonstrated. There was no decisive influence of additional late imaging with PCa lesion detection on therapeutic decisions. However, in a few individual cases, additional delayed scans provided an information advantage in PCa lesion detection due to higher tracer uptake and improved contrast.

PSA and PSA Kinetics Thresholds for the Presence of 68Ga-PSMA-11 PET/CT-Detectable Lesions in Patients With Biochemical Recurrent Prostate Cancer.

68Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying the prostate-specific-antigen (PSA) and PSA kinetics thresholds for detecting and localizing recurrent PC. This retrospective analysis includes 581 patients with biochemical recurrence (BC) by definition. The performance of 68Ga-PSMA-11 PET/CT in relation to the PSA value at the scan time as well as PSA kinetics was assessed by the receiver-operating-characteristic-curve (ROC) generated by plotting sensitivity versus 1-specificity. Malignant prostatic lesions were identified in 77%. For patients that were treated with radical prostatectomy (RP) a PSA value of 1.24 ng/mL was found to be the optimal cutoff level for predicting positive and negative scans, while for patients previously treated with radiotherapy (RT) it was 5.75 ng/mL. In RP-patients with PSA value <1.24 ng/mL, 52% scans were positive, whereas patients with PSA ≥1.24 ng/mL had positive scan results in 87%. RT-patients with PSA <5.75 ng/mL had positive scans in 86% and and for those with PSA ≥5.75 ng/mL 94% had positive scans. This study identifies the PSA and PSA kinetics threshold levels for the presence of 68Ga-PSMA-11 PET/CT-detectable PC-lesions in BC patients.

The significance of FNAC in diagnosing differentiated thyroid cancer and the discrepancy between theory and practice - a multi-centre study.

INTRODUCTION: After non-invasive diagnostic modalities high risk thyroid nodules are investigated with fine needle aspiration cytology in order to find the right surgical strategy for suspected malignancies. Despite the clear recommendation by the European and the American associations (ETA, ATA) its clinical value is doubted and its importance in clinical practice not fully clarified. METHODS: A multicentric study of 119 patients with differentiated thyroid cancer operated on in 24 surgical departments was conducted. The aim was not only to evaluate the use of FNAC as a diagnostic tool, but also to investigate its diagnostic validity and compare it with that of other, non-invasive diagnostic methods. RESULTS: FNAC was used only in 25 % of malignant thyroid nodules. In these patients sensitivity of FNAC was 60 %. In 40 % with preoperative FNAC, the result had an impact on the surgical approach. 17 % underwent surgery only because of the FNAC result, and 23 % underwent a planned surgical resection with total thyroidectomy and lymphadenectomy on account of the FNAC result. In comparison to non-invasive diagnostics (ultrasonography in conjunction with scintigraphy with Na99mTcO4) FNAC reached the same sensitivity. DISCUSSION: The results of our study reveal a limited application of preoperative FNAC in diagnosing thyroid nodules as well as a limited conclusiveness in our study population if not performed according to standards. In order to increase the benefits of this diagnostic modality, it seems to be important to perform FNAC according to the guidelines and in a standardized manner. FNAC should always be conducted in combination with ultrasonography. An experienced cytopathologist should be consulted and the Bethesda classification system should be established.

The Impact of 68Ga-PSMA PET/CT and PET/MRI on the Management of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein with significantly increased expression in the cells and metastases of prostate carcinoma (CaP). PSMA-expression correlates with higher serum levels of prostate-specific antigen (PSA) and a higher Gleason score (GS). This finding has led to the development of novel imaging modalities such as 68Ga-/18F-labeled PSMA positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). This article reviews the literature pertaining to various new imaging technologies for the management of CaP. PSMA positron emission tomography/computed tomography appears to be an excellent diagnostic tool, that may drastically impact the management of a large number of patients with primary and recurrent CaP.

The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-<0.5 ng/ml the PR was 45%, 62% for PSAV of 0.5-<1.0 and 72% for PSAV of 1.0-<2.0 ng/ml. The PR increased to 85% for PSAV of 2.0-<5.0 and reached 94% at PSAV of ≥5.0 ng/ml. At PSA of <1 ng/ml/y the PR of PSAvel was 50% and increased to 98% at PSA >5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (<0.2 ng/ml). Thus 68Ga-PSMA-11 PET/CT both identify and localize recurrent disease with implications for a more direct treatment approach (localized vs. systemic therapy).

[Diagnostic significance of multiparametric MRI combined with US-fusion guided biopsy of the prostate in patients with increased PSA levels and negative standard biopsy results to detect significant prostate cancer - Correlation with the Gleason score. Korrelation mit dem Gleason Score]. / Diagnostischer Stellenwert der multiparametrischen MRT mit gezielter Fusionsbiopsie der Prostata bei Patienten mit PSA-Anstieg und negativer Stanzbiopsie zur Detektion klinisch signifikanter Prostatakarzinome. Korrelation mit dem Gleason Score.

AIMS: To increase diagnostic precision and to reduce overtreatment of low-risk malignant disease, multiparametric MRI (mpMRI) combined with ultrasound (US) fusion guided biopsy of the prostate were performed. METHODS: In 99 male patients with increased PSA plasma levels and previous negative standard biopsy procedures, mpMRI was carried out followed by US fusion guided perineal biopsy. PI-RADS-Data (PS) of mpMRI and histopathological Gleason score (GS) were categorized and statistically compared. RESULTS: Lesions in 72/99 (73 %) of patients were determined to be suspect of malignancy, based on a PS 4 or 5. In 33/99 (33 %) of patients, malignancy could not be confirmed by histopathology. With regard to the remaining 66 patients with previous negative biopsy results, 42 (64 %) were diagnosed with a low-grade carcinoma (GS 6, 7a) and 24 (36 %) with a high-grade carcinoma (GS ≥ 7b). The proportion of corresponding results in mpMRI (PS 4-5) when a high-grade carcinoma had been detected, was 21/24 (88 %), which related to a sensitivity of 88 % and a negative predictive value (NPV) of 85 % (p = 0,002). In addition, 35 of 42 patients (83%), graded PS 4-5 in mpMRI, were diagnosed with low-grade carcinoma-positive (p < 0,001). Sensitivity to differentiation between low- and high-grade carcinomas (GS ≤ 7a vs. ≥ 7b) by means of PS was 88 % with a NPV of 70 % (p = 0,74). CONCLUSION: Our results suggest that mpMRI combined with US-fusion guided biopsy is able to detect considerably higher rates of clinically relevant prostate malignancies compared to conventional diagnostic procedures. However, no statistical significance could be shown regarding the differentiation between high- and low-grade carcinomas. It is hoped that the hybrid methods PSMA-PET/CT or PSMA-PET/MRI will lead to the next optimization step in the differentiation between high- and low-grade carcinomas which so far has been unsatisfactory.

Diagnostic performance of 68Gallium-PSMA-11 PET/CT to detect significant prostate cancer and comparison with 18FEC PET/CT.

BACKGROUND: Radiolabeled prostate-specific membrane antigen (PSMA) has proven to be a highly accurate method to detect recurrence and metastases of prostate cancer, but only sparse data is available about its performance in the diagnosis of clinically significant primary prostate cancer. METHODS: We compared 68Ga-PSMA-11 PET/CT in 25 patients with 18FEC PET/CT in 40 patients with suspected prostate carcinoma based on an increased PSA level.The PET/CT results were compared with the histopathologic Gleason Score (GS) of biopsies. RESULTS: The 68Ga-PSMA-11 PET/CT revealed highly suspect prostatic lesions (maximum standardized uptake value/SUVmax >2.5) in 21/25 patients (84%), associated with GS≥6 (low-grade/high-grade carcinoma). Two histopathologic non-malignancy-relevant cases (GS<6) had PSMA-SUVmax ≤2.5; all histopathologic high-grade cases (GS≥7b) showed PSMA-SUVmax >12.0 which further increased with rising GS. There were 2 false positives and no false negative findings for high-grade prostate cancer using a cut off-level for SUVmax of 2.5.In contrast, the 18FEC PET/CT showed suspected malignant lesions in 38/40 patients (95%), which included 3 lesions with GS<6. The mean SUVmax values did not differ with different GS. There were 11 false positives and 1 false negative for detection of high-grade prostate cancer (cut off 2.5).By means of ROC analysis a SUVmax of 5.4 was found to be an optimal cut off-level to distinguish between low- and high-grade carcinoma in 68Ga-PSMA-11 PET/CT (AUC=0.9692; 95% CI 0.9086;1.0000;SD(AUC)=0.0309)). Choosing a cut off-level of SUVmax5.4, 68Ga-PSMA-11 PET/CT was able to distinguish between GS ≤7a/≥7b with a sensitivity of 84%, a specificity of 100%, a negative predictive value (NPV) of 67%, and an efficiency of 88% (p<0.001).The ROC analysis revealed a SUVmax 6.5 as an optimal cut off-level to distinguish between low- and high-grade carcinoma in 18FEC PET/CT (AUC=0.7470; 95% CI 0.5919;0.9020;SD(AUC)=0.0791) with a sensitivity of 61% and a specificity of 92%; but the efficiency was only 70% and the NPV 50% (p=0.01). CONCLUSION: 68Ga-PSMA-11 PET/CT guided biopsy of the prostate increases diagnostic precision and is likely to help to reduce overtreatment of low-grade malignant disease as well as detect the foci of the highest Gleason pattern. Both methods (68Ga-PSMA-11,18FEC) were suitable to detect primary prostate cancer, but the excellent image quality, the higher specificity and the good correlation of positive scans with GS are advantages of 68Ga-PSMA-11.