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Introduction Few available data indicate that a mutation-based “neoadjuvant” therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term “neoadjuvant” therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. Methods In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. Patients Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. Results In all three cases, the “neoadjuvant” therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term “neoadjuvant” treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term “neoadjuvant” therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. Conclusions A short-term mutation-based “neoadjuvant” therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Background Iodine-induced thyroid dysfunctions are, despite their rare occurrence, important clinical syndromes. Their immediate recognition can avoid serious consequences. Important triggers can be iodine-containing contrast agents, amiodarone or iodine-containing disinfectants. Iodine-induced hypothyroidism and hyperthyroidism need to be distinguished, whereby the former is usually self-limiting. Objectives The aim of this article is to present current knowledge on the pathogenesis, therapy, and prophylaxis of iodine-induced thyroid dysfunction. Materials and methods We performed a literature search of current publications and linked them to daily clinical experience. Results and conclusion In iodine-induced hyperthyroidism, antithyroid drugs and perchlorate are primarily used to decrease thyroid hormone synthesis and further iodine uptake into the thyroid. For the prophylaxis of x‑ray contrast agent-induced hyperthyroidism, perchlorate can be administered in high-risk settings in combination with antithyroid drugs, if possible starting one day before the iodine exposure.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

SummaryAim: In a screening study on people of working age the prevalence of morphological thyroid disorders was 33.1 %. It is not known precisely whether this further increases after retirement. The present study aimed to establish whether the increase in the prevalence of morphological and functional thyroid disorders continues beyond working age in elderly citizens. Methods: 223 participants were recruited in an institute for geriatric rehabilitative medicine. All patients were screened by thyroid ultrasound, measurement of serum levels of thyroid hormones and thyroid related autoantibodies as well as measurement of urinary iodine excretion. Results: The median thyroid volume was 17 ml (range 4-41 ml) in men and 16 ml (range 0.4-73 ml) in women. 27/59 (46 %) of the men (median age [range]: 77 [58-87] years) and 85/139 (61 %) of the women (median age [range]: 77 [52-97] years), or a total of 112/198 (57 %) residents, showed morphological thyroid abnormalities. There was no clear increase with age. 85 % of the participants without a history of thyroid treatment were euthyroid. 12 % showed a subclinical hyperthyroidism whereas 1 % showed a biochemically manifest hyperthyroidism. 2 % were biochemically hypothyroid. Tg-antibodies was elevated in 10 (5 %) and TPO-antibodies in 18 (9 %) of the patients. Median iodine excretion was 129 pg/l. 41.5 % of the patients showed iodine excretion values below 100 pg/l whereas only 7 % of the patients showed a severe iodine deficiency with an excretion below 50 pg/l. Conclusion: Compared to a previously described population of working age, the prevalence of morphological thyroid disorders does not further increase above the age of 65; thyroid function abnormalities in this iodine sufficient screening population were relatively rare.

Die praoperative Lokalisationsdiagnostik von Nebenschilddrusenadenomen beim primaren Hyperparathyreoidismus (pHPT) ermoglicht eine fokussierte unilaterale Operation. Zur Standarddiagnostik zahlen die Sonographie und Technetium-99m-Sestamibi-Szintigraphie. Das neueste Verfahren zur Darstellung hyperfunktioneller Nebenschilddrusen stellt die C-11-Methionin-Positronenemissionstomographie/Computertomographie (PET/CT) dar. Es wurde eine selektive Literaturrecherche in PubMed mit den Stichworten „primary hyperparathyroidism and methionine“, „primary hyperparathyroidism and PET“, „parathyroid adenomas and methionine“ und „parathyroid adenomas and PET“ durchgefuhrt. Mithilfe des Methionin PET/CT gelingt es in 79–91 % solitare Nebenschilddrusenadenome nachzuweisen. Vorteile des Verfahrens sind eine hohe Sensitivitat auch bei Rezidiveingriffen oder gleichzeitig bestehenden Knotenstrumen sowie eine exakte anatomische Zuordnung auch von atypisch gelegenen Adenomen. Eine vollstandige Darstellung einer Mehrdrusenerkrankung gelingt dagegen nur selten. Als ungunstig zu bewerten sind derzeit noch die eingeschrankte Verfugbarkeit der Methode und die vergleichsweise hohen Kosten. Durch das Methionin-PET/CT ist bei der Mehrzahl der untersuchten Patienten mit pHPT eine exakte Lokalisation solitarer Nebenschilddrusenadenome moglich. Eine Indikation zur Durchfuhrung besteht vor allem bei praoperativ negativer Standarddiagnostik und bei Rezidiveingriffen.

Die Neufassung bzw. Uberarbeitung bestehender Leitlinien zur Nachsorge des Schilddrusenkarzinoms ist aufgrund zahlreicher Publikationen in jungerer Vergangenheit und neu gewonnener Erkenntnisse unverzichtbar und tragt zu einer erwunschten Standardisierung des Patientenmanagements bei. Neuerungen auf diagnostischem Gebiet betreffen in erster Linie die Etablierung der Hybridbildgebung (z. B. 131 I-SPECT/CT), eine kontinuierliche Verbesserung der sonografischen Techniken und die Weiterentwicklung der Thyreoglobulin-Assays. Zunehmend gewinnt eine risikoorientiertes, individualisiertes Follow-up, z. B. mit einer „liberalisierten“ Einstellung des TSH, d. h. dem Verzicht auf eine lebenslange Suppression, an Bedeutung. Nachsorgeintervalle und insbesondere die Frequenz der Untersuchungen werden neu definiert und an das veranderte Patientenspektrum angepasst. Fragen der Lebensqualitat und psychosoziale Aspekte rucken mehr und mehr ins Blickfeld und sind Teil einer umfassenden Patientenbetreuung.

Ablative radioiodine therapy is the treatment of choice in patients with differentiated thyroid cancer, the only exception being the unifocal, very small papillary thyroid cancer. The TSH-stimulation can be achieved by a waiting period for 2-3 weeks after thyroidectomy without medication or by the use of recombinant human TSH (rhTSH). Both options lead to high success rates. “Single dose cure” using activities between 1.85 and 3.7 GBq 131 I is standard. Since 2010 rhTSH is approved by the EMA for the indications pT1-4, N0-1, cM0. Survey studies did not find any inferiority of ablation with rhTSH or iatrogenic hypothyroidism in the high-risk patient group. Renal clearance is not reduced after rhTSH administration, thus the 131 I blood dose and the whole body doses are lower in patients under rhTSH. Comparing identical 131 I activities after endogeneous or exogeneous stimulation, rhTSH will minimize the acute adverse effects of 131 I. A short-term withdrawal of levothyroxine some days before rhTSH-injection lowers the iodine plasma level, which may be advantageous for the ablation success if lower 131 I activities are used. A rhTSH-based diagnostic 131 I whole-body scintigraphy 3-6 months after ablation is standard for therapy control. At this time, the rhTSH-stimulated thyroglobulin-level is essential for a personalized risk stratification. Tg-measurements by a second generation assay should be used for follow-up care. Metaanalyses have shown that radioiodine ablation lowers the mortality rate, the risk of locoregional recurrences and the risk of late metastasizing. Therefore, ablation has shown a clear benefit.

High resolution sonography is the method of choice for the evaluation of thyroid volume and lesions. For the work-up of cervical nodules the main criteria concern size, echo pattern, micro calcifications, delineation and the differentiation solid / cystic. The combination or the absence of certain features as halo, delineation, micro calcification, “satellites”, hypoechogenicity, vascularisation is often indicative for a benign condition, whereas there is no specific indicator for malignancy. Duplex sonography as a new modality is helpful for the visualization of nodular perfusion, although no substitute for scintigraphy and fine needle aspiration cytology. The latter is high ranking in various international guide lines with demand for additional data.

Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra-tumourous thymopoiesis and export of inefficiently tolerized T-cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self-antigens in the thymic medulla and plays an essential role in ‘central’ tolerance in both humans and mice. However, while inactivating AIRE mutations result in the ‘autoimmune polyendocrinopathy syndrome type 1’ (APS-1), its major features are not well reproduced in AIRE-knock-out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable tools to test conclusions drawn from mouse models. Here we show, in a large series, that ∼95% of thymoma patients are ‘chimeric’; expression of AIRE and major AIRE-related autoantigens (eg insulin) were undetectable in their tumours but maintained in their remnant thymic tissue and lymph nodes. Notably, despite the AIRE-deficient thymopoiesis in thymomas, disorders and autoantibodies typical of APS-1 were distinctly uncommon in these patients. The one striking similarity was in the recently observed neutralizing anti-type I interferon (IFN) antibodies, which are found at diagnosis in 100% of patients with APS-1 and in ∼60% of patients with thymomas, as we show here. We conclude that APS-1 type autoantigens must be protected from autoimmunity by mechanisms that do not extend to the muscle autoantigens so frequently targeted in thymoma patients but so rarely recognized in APS-1. Thus our findings argue strongly for a tolerogenic function of AIRE beyond its role in negative T-cell selection in human thymopoiesis, and/or for specific autoimmunization against muscle in thymomas. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inhaled drugs can only be effective if they reach the middle and small airways. This study introduces a system that combines a trans-nasal application of aerosols with noninvasive pressure support ventilation.In a pilot study, 7 COPD patients with GOLD stages II and III inhaled a radiolabeled marker dissolved in water via a trans-nasal route. The mean aerosol particle size was 5.5 µm. Each patient took part in two inhalation sessions that included two application methods and were at least 70 hours apart. During the first session ("passive method"), the patient inhaled the aerosol through an open tube system. The second session ("active method") included pressure support ventilation during the inhalation process. A gamma camera and planar scintigraphy was used to determine the distribution of aerosol particles in the patient's body and lung.The pressure supported inhalation ("active method") results in an increased aerosol lung deposition compared to the passive method. Above all, we could demonstrate deposition in the lung periphery with relatively large aerosol particles (5.5 µm).The results prove that the combination of trans-nasal inhalation with noninvasive pressure support ventilation leads to significantly increased particle deposition in the lung.

INTRODUCTION Inhaled drugs can only be effective if they reach the middle and small airways. This study introduces a system that combines a trans-nasal application of aerosols with noninvasive pressure support ventilation. METHODS In a pilot study, 7 COPD patients with GOLD stages II and III inhaled a radiolabeled marker dissolved in water via a trans-nasal route. The mean aerosol particle size was 5.5 µm. Each patient took part in two inhalation sessions that included two application methods and were at least 70 hours apart. During the first session ("passive method"), the patient inhaled the aerosol through an open tube system. The second session ("active method") included pressure support ventilation during the inhalation process. A gamma camera and planar scintigraphy was used to determine the distribution of aerosol particles in the patient's body and lung. RESULTS The pressure supported inhalation ("active method") results in an increased aerosol lung deposition compared to the passive method. Above all, we could demonstrate deposition in the lung periphery with relatively large aerosol particles (5.5 µm). DISCUSSION The results prove that the combination of trans-nasal inhalation with noninvasive pressure support ventilation leads to significantly increased particle deposition in the lung., Einleitung: lnhalativ applizierte Medikamente können ihre Wirkung nur dann besonders effektiv entfalten, wenn sie bis in die mittleren und kleinen Atemwege gelangen. Das vorgestellte Verfahren kombiniert eine transnasale Aerosolapplikation mit einer pneumatischen Schienung der kleinen Atemwege. Methode: Bei 7 Patienten mit COPD im Stadium II und III nach GOLD erfolgte eine transnasale Inhalation eines in Wasser gelösten radiopharmakologischen Marker-Präparats bei einer mittleren Partikelgröße von 5,5 µm. Bei allen Patienten wurden in einem Abstand von mindestens 70 Stunden zwei unterschiedliche Applikationsmethoden angewandt. Bei der ersten („passiv“) inhalierte der Patient transnasal durch ein offenes Schlauchsystem, bei der zweiten („aktiv“) erfolgte eine Inhalation mit Atmungsunterstützung durch positiven Atemwegsdruck (pneumatische Schienung). Die planaren Szintigramme der Lunge sowie des Ganzkörpers wurden angefertigt, um die Verteilung der Aerosolteilchen zu detektieren. Ergebnisse: Bei der unter nichtinvasiver druckunterstützter Atmung („aktiv“) durchgeführten transnasalen Inhalation kommt es, im Vergleich zur „passiven“ Inhalation, zu einer erhöhten Deposition des Aerosols in der Lunge. Darüber hinaus konnte bei der „aktiven“ und „passiven“ Inhalation ein Nachweis von Aerosolpartikeln in der Lungenperipherie bei verhältnismäßig großen Aerosolteilchen (5,5 µm) beobachtet werden. Diskussion: Die Ergebnisse belegen, dass die Kombination aus transnasaler Inhalation und nichtinvasiver druckunterstützender Beatmung (pneumatische Schienung) zu einer deutlich verbesserten Partikeldeposition in der Lunge führt.

Purpose: To investigate and compare the quantitative accuracy of 90Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of 90Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct 90Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Minimally invasive operative procedures to cure primary hyperparathyroidism (pHPT) are challenging the conventional bilateral exploration in localized single-gland disease. However, concomitant thyroid nodules can hamper the limited approaches. It was the aim of this study to establish and evaluate a standardized diagnostic algorithm, applicable in an endemic goiter region, directing pHPT patients to an individually adapted surgical approach. METHODS: 40 consecutive patients with pHPT were enrolled in a prospective study. According to a standardized diagnostic protocol, patients were selected for either open minimally invasive parathyroid exploration (OMIP), unilateral parathyroid exploration (UP) followed by thyroid surgery or bilateral cervical exploration (BE). PTH was monitored intraoperatively, follow-up was 2 weeks and 6 months postoperatively. RESULTS: 21 patients (52.5%) were selected for OMIP. 2 out of 21 (9.5%) procedures had to be converted to the conventional bilateral approach. 12 patients (30%) were correctly scheduled for UP and additional thyroid resection, and in 7 patients (17.5%) primary BE was necessary. All patients were normocalcemic at 6 months follow-up. CONCLUSIONS: 95% of patients could be scheduled for the appropriate surgical approach by the applied pre-therapeutic algorithm. This makes parathyroidectomy a predictable operative procedure in the routine clinical setup even in an endemic goiter region.

In 56 postoperative patients with primary hyperparathyroidism we analysed retrospectively whether a single-sided or minimal invasive operative procedure could have been utilized. Additionally the sensitivity of 9 9 m TC-Sestamibiscintiscanning and ultrasound of the neck region was assessed. Single gland disease was found in 49 patients, 6 patients had primary multiglandular disease and one patient revealed a double adenoma. The overall sensitivity of 9 9 m TC-Sestamibiscintiscanning and ultrasound was found to be 78% and 53% respectively. In 46 patients the operation would have been started minimal invasive, in 7 of these patients a conversion to bilateral exploration would have been necessary because of four gland hyperplasia, double adenoma or misleading preoperative localisation. In 39 patients a successful minimal invasive procedure would have been possible. A primary bilateral exploration would have been necessary in 10 patients because of either coexisting goiter or questionable localisation of the pathological altered gland. Since sensitivity of localisation diagnostics is low with regard to multiglandular disease, parathyroid hormone should be monitored intraoperatively whenever minimal invasive operative procedures are performed.

In primary hyperparathyroidism (pHPT) preoperative localization of parathyroid adenomas enables focussed unilateral parathyroidectomy. Ultrasound and sestamibi scintigraphy are the recommended standard procedures for primary diagnostics of pHPT and C-11 methionine positron emission tomography computed tomography (Met-PET/CT) is the latest technique for localization of hyperfunctioning parathyroid glands.This review presents the results of Met-PET/CT on the basis of a selective literature search using the keywords "primary hyperparathyroidism and methionine", "primary hyperparathyroidism and PET", "parathyroid adenomas and methionine" and "parathyroid adenomas and PET".Localization of single gland adenomas can be achieved with Met-PET/CT in 79-91 % of cases. The advantages of this procedure are a high sensitivity even in operations for recurrencies or concomitant thyroid nodules and an accurate detection even with atypical localizations. In multiglandular disease a localization of more than one hyperfunctioning gland remains difficult. Potential limitations of the method include the restricted availability and the relatively high costs of Met-PET/CT.Using Met-PET/CT hyperfunctioning parathyroid glands can be exactly localized in most patients with pHPT. Indications for this procedure are mostly when preoperative standard tests are negative and in parathyroid surgery for recurrencies.

Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error.The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB.To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit parameters and their standard error estimated by using SAAM numerical and NUKFIT showed differences of1%. The differences for the time-integrated activity coefficients were also1% (standard error between 0.4% and 3%). In general, the application of the software is user-friendly and the results are mathematically correct and reproducible. An application of NUKFIT is presented for three different clinical examples.The software tool with its underlying methodology can be employed to objectively and reproducibly estimate the time integrated activity coefficient and its standard error for most time activity data in molecular radiotherapy.