[Ultrasound-guided ablation techniques for thyroid lesions]. / Ultraschallgeführte lokalablative Verfahren zur Behandlung von Schilddrüsenläsionen.

Ultrasound-guided ablation techniques have been increasingly introduced into routine treatment of thyroid lesions as a complement to existing surgical therapies and radioiodine treatment. In cystic or predominantly cystic lesions instillation therapy (ethanol/polidocanol ablation) has yielded good results. Novel thermal ablation techniques, including radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA) and high intensity focused ultrasound (HIFU), induce irreversible cellular effects by locally applying temperatures ≥ 60 °C to the targeted thyroid region. Lesions causing local symptoms or focal hyperfunctionality can thus be selectively treated under continuous sonographic monitoring. While a considerable body of evidence supports the efficacy and safety of various local ablative techniques, future challenges lie in initiating comparative prospective trials and in standardizing clinical practice, training and continuous quality assessment on a regional and superregional level. In the future, it shall be indicated to include local ablative techniques - so far not known to all patients in Germany - into the informed decision-making process as a suitable alternative or supplement to existing therapies.

Evaluation of activity kinetics in breast milk and calculation of the resulting effective radiation dose after 99mTc-MIBI scintigraphy of a breastfeeding women.

INTRODUCTION: In breastfeeding women, the indication for scintigraphic imaging is strongly restricted due to potential transition of the radiopharmaceutical to the child via breast milk. The potential activity uptake of the breastfed child depends on the chemical compound of the radio pharmaceutical as well as biokinetics and metabolism in the maternal body. METHODS: In the presented case 99mTc-MIBI scintigraphy was performed in a breastfeeding woman with sonographically suspicious thyroid nodules. Breastfeeding was interrupted for 30 hours and the breast milk during this period was collected and analysed to determine the excreted activity and the potentially resulting dose to the breastfed child. RESULTS: Activity concentration in the first breast milk sample (1.83 hours after administration of 500 MBq 99mTc-MIBI) was 380 Bq/mL, resulting in an absolute activity of 50 kBq for a sample size of 132 mL. Subsequently activity concentration decreased to 6 Bq/mL (29.8 hours p.i.). The calculated effective half-life of the secretion of 99mTc-MIBI via breast milk was 4.7 hours. The potentially resulting effective dose for the breastfed child was 13.4 µSv (ICRP80: dose coefficient: 0.13 mSv/MBq for 99mTc). CONCLUSION: Time activity curve showed a rapid decrease of the 99mTc-MIBI activity secreted to the breast milk. More than 90 % of the total secreted activity is attributable to the first 12 hours after administration. Therefore, an interruption of breastfeeding of 24 hours seems to be adequate.

[Radiofrequency ablation of benign thyroid nodules]. / Radiofrequenzablation benigner Schilddrüsenknoten.

Radiofrequency ablation is an effective tool to treat benign thyroid nodules up to about 100 ml. It is well tolerated and is - together with echopulse therapy - currently the most frequently used technique in Germany for the local therapy of benign thyroid nodules. Overall, a volume reduction of about 50 % to 70 % can be expected. Cystic nodules and mixed-pattern lesions respond slightly better than solid nodules. Initial volume, structure and echogenicity are important parameters influencing the therapeutic efficacy. Bipolar as well as monopolar methods are used - the choice of the method depends mainly on the personal experience. For bigger nodules, the bipolar technique is preferred. Cooled systems should be favored, especially when using larger probes. Serious side effects are rare (< 1 %) and transient in most cases.

[Anticipating Criteria for Discharge after Lu-177-PSMA Treatment - Discussion of Several Scenarios]. / Vorausschauende Entlassungskriterien nach Lu-177-PSMA-Therapie ­ Diskussion unterschiedlicher Szenarien.

AIM: The aim is to add a pragmatic contribution to the discussion of an algorithm to discharge patients treated with Lu-177-PSMA under the aspect of radiation protection. This also may be applied to therapies with other radioactive tracers in the future. MATERIAL AND METHODS: 478 cycles of Lu-177-PSMA-617 (140 patients) were analyzed. The remaining activity in the patient and the dose rate were correlated. From frequent intratherapeutic measurements (biexponential fit) scenarios for discharging patients are deduced. RESULTS: Thirty-four per cent of all patients treated with Lu-177-PSMA received 3 to 5 cycles per calendar year. The dose limit of 1 mSv per calendar year (German Law) at a distance of 2 m from the patient would be exceeded in 10 % and 15 % of the treated patients if discharged 72 hours after treatment given 3 and 4 cycles per calendar year, respectively. Mean specific dose rate was 0.00462µSv/(h MBq) at a distance of 1 m. A universal correlation between dose rate and the remaining activity in the patient could not be found. CONCLUSION: The multi cycle concept of the therapies with Lu-177 PSMA has to be taken into account prospectively when discharging the patients. Given the physical half-life of Lu-177 an anticipation of 4 treatment cycles per calendar year leads to a clearly arranged, conservative rule.

[Prenatal Radiation Exposure in Nuclear Medicine]. / Pränatale Strahlenexposition aus nuklearmedizinischer Indikation.

Radiation exposure from nuclear medicine procedures during pregnancy may cause uncertainty among patients and medical professionals. In 2019, the German Society of Medical Physics (DGMP) and the German Society of Radiology (DRG) published a fully revised version of the report "Prenatal Radiation Exposure Arising from Medical Indication, Dose Calculation, Conclusions for Physicians and Pregnant Women". This report offers a basis for dose calculation and determination of radiation exposure to the unborn. This review summarizes the most notable general adaptions made in the report's newest version and specifically points out the changes relevant to the field of nuclear medicine.The DGMP report provides physicians and medical physicists with means to estimate prenatal radiation exposure to the unborn conservatively, in a prompt and comprehensible approach. The rapidly evolving field of indications in nuclear medicine and radiology gave rise to the initiative of profoundly revising the previous version of the report from 2002. It now accounts for the extended range of devices, nuclear medicine hybrid imaging and radiotracers recently introduced. The most extensive change is a shift from the former 3-step-concept for the dose calculation to a 2-step-concept. In diagnostic nuclear medicine the first step comprises a conservative approximation of radiation exposure on the basis of current diagnostic reference levels (DRL). If exposure is assessed to be below 20 mSv, risk to the unborn child is sufficiently low, no further approaches are considered necessary. If calculated doses exceed 20 mSv, for diagnostic studies without existing DRL or in case of radionuclide therapies step 2 requires dose calculation based on administered activity and the stage of pregnancy.The DGMP report on prenatal radiation exposure offers valuable guidance for physicians and medical physicists in the field of nuclear medicine. The calculation concept provides an important basis to estimate radiation exposure to the unborn. Its extensive revision in 2019 accounts for recent scientific and technical developments and a reform of the stepwise approach to dose estimation.

[Evaluation of intratherapeutic 177Lu-HA-DOTATATE treatment in neuroendocrine tumors: dosimetry with SPECT, whole-body imaging and gamma probe]. / Evaluation der intratherapeutischen Dosimetrie bei der 177Lu-HA-DOTATATE Therapie neuroendokriner Tumoren mittels SPECT, Ganzkörperszintigraphie und Gammasonde.

AIM: Peptide receptor radionuclide therapy (PRRT) with 177Lu-HA-DOTATATE has evolved as a new path in the treatment of somatostatin-receptor-expressing neuroendocrine tumors. The kidneys are proven as organs at risk and should be evaluated dosimetrically. Overlap with other organs will make dosimetry based on planar scintigraphy inaccurate. Aim of this study was to approximate the contribution of the kidneys to conjugated planar views without the use of a SPECT/CT. MATERIAL AND METHOD: An algorithm was developed to determine the kidney dose using an EXCEL (Microsoft) based program. Dosimetric data were drawn and merged from three modalities: an individually calibrated gamma probe, a whole-body scintigraphy (WBS) and SPECT-acquisitions. The method was evaluated for 85 kidneys. Kidney masses were obtained via CT volumetry. RESULTS: The developed algorithm combines data from the three modalities. The ratio of the events within a kidney-VOI and the events from the summed coronary SPECT views (kidney ROI) represents the contribution of the kidney to the whole-body kidney ROI. This fraction was calculated to 49 % (17 % - 78 %) and 45 % (18 % - 75 %) for the left and the right kidney, respectively. Quantification of activity was deduced from equalizing the WBS count with the concurrent gamma probe measurement. Monoexponential curves were fitted to the obtained kidney activities, with resulting doses of 0,13 to 0,77 Gy/GBq (average 0,36 and 0,39 Gy/GBq for the left and the right kidney). CONCLUSION: The presented method is suitable to perform kidney dosimetry by using a gamma probe and a gamma camera, without using SPECT/CT.

Thyroid stunning in radioiodine-131 therapy of benign thyroid diseases.

PURPOSE: Existence and cause of thyroid stunning was controversially discussed for decades but the underlying mechanism remains unclear. Numerous studies describe thyroid stunning in radioiodine-131 therapy (RIT) of differentiated thyroid carcinoma. However, there are no studies evaluating thyroid stunning in benign thyroid diseases caused by the radioiodine uptake test (RIUT). Therefore, the influence of pre-therapeutic tracer radiation dose on therapeutic iodine-131 uptake was evaluated retrospectively. METHODS: A total of 914 RIT patients were included. Exclusion criteria were anti-thyroid drugs, pre- and/or intra-therapeutic effective half-lives (EHL) beyond 8.04 days and externally performed RIUT or 24 h RIUT. All patients received RIUT 1 week before RIT. Thyroid volume was estimated via ultrasound. Tracer radiation dose to the thyroid was calculated retrospectively. The dependence of changes in the pre-therapeutic to the therapeutic extrapolated-maximum-131I-uptake (EMU) from the dose in RIUT was evaluated statistically. RESULTS: EMU in RIUT ranged from 0.10 to 0.82 (median: 0.35) and EMU in RIT ranged from 0.10 to 0.74 (median: 0.33). Averaged over the whole cohort the therapeutic EMU decreased significantly (2.3% per Gray intra-thyroidal tracer radiation dose). A disease-specific evaluation showed dose-dependent thyroid stunning from 1.2% per Gray in solitary toxic nodules (n = 327) to 21% per Gray in goiters (n = 135) which was significant for the subgroups of disseminated autonomies (n = 114), multifocal autonomies (n = 178) and goiters (p < 0.05) but not for Graves' diseases (n = 160) and solitary toxic nodules (p > 0.05). CONCLUSIONS: The presented data indicate for the first time a significant dependence of pre-therapeutic radiation dose on thyroid stunning in goiter and disseminated and multifocal autonomy. To achieve the desired intra-thyroidal radiation dose, RIT activity should be adapted depending on the dose in RIUT.

Further Investigation on High-intensity Focused Ultrasound (HIFU) Treatment for Thyroid Nodules: Effectiveness Related to Baseline Volumes.

RATIONALE AND OBJECTIVES: Several minimally invasive thermal techniques have been developed for the treatment of benign thyroid nodules. A new technique for this indication is high-intensity focused ultrasound (HIFU). The aim of this study was to assess effectiveness in varying preablative nodule volumes and whether outcome patterns that were reported during studies with other thermal ablative procedures for thyroid nodule ablation would also apply to HIFU. MATERIALS AND METHODS: Over the last 2 years, 19 nodules in 15 patients (12 women) whose average age was 58.7 years (36-80) were treated with HIFU in an ambulatory setting. Patients with more than one nodule were treated in multiple sessions on the same day. The mean nodule volume was 2.56 mL (range 0.13-7.67 mL). The therapeutic ultrasound probe (Echopulse THC900888-H) used in this series functions with a frequency of 3 MHz, reaching temperatures of approximately 80°C-90°C and delivering an energy ranging from 87.6 to 320.3 J per sonication. To assess the effectiveness of thermal ablation, nodular volume was measured at baseline and at 3-month follow-up. The end point of the study was the volume reduction assessment after 3 months' follow-up. Therapeutic success was defined as volume reduction of more than 50% compared to baseline. This study was retrospectively analyzed using the Wilcoxon signed rank test and Kendall tau. RESULTS: The median percentage volume reduction of all 19 nodules after 3 months was 58%. An inverse correlation between preablative nodular volume and percentage volume shrinking was found (tau = -0.46, P < .05). Therapeutic success was achieved in 10 out of 19 patients (53%). CONCLUSIONS: HIFU of benign thyroid nodules can be carried out as an alternative therapy for nodules ≤3 mL if patients are refusing surgery or radioiodine therapy.

Thermal ablation of thyroid nodules: are radiofrequency ablation, microwave ablation and high intensity focused ultrasound equally safe and effective methods?

OBJECTIVES: This study compares volume reduction of benign thyroid nodules three months after Radiofrequency Ablation (RFA), Microwave Ablation (MWA) or High Intensity Focused Ultrasound (HIFU) to evaluate which of these methods is the most effective and safe alternative to thyroidectomy or radioiodine therapy. MATERIAL AND METHODS: Ninety-four patients (39 male, 55 female) with a total of 118 benign, symptomatic thyroid nodules were divided into three subgroups. HIFU was applied to 14 patients with small nodules. The other 80 patients were divided up into two groups of 40 patients each for RFA and MWA in the assumption that both methods are comparable effective. The pre-ablative and post-ablative volume was measured by ultrasound. RESULTS: RFA showed a significant volume reduction of nodules of 50 % (p<0.05), MWA of 44 % (p<0.05) and HIFU of 48 % (p<0.05) three months after ablation. None of the examined ablation techniques caused serious or permanent complications. CONCLUSION: RFA, MWA and HIFU showed comparable results considering volume reduction. All methods are safe and effective treatments of benign thyroid nodules. KEY POINTS: • Thermal Ablation can be used to treat benign thyroid nodules • Thermal Ablation can be an alternative to thyroidectomy or radioiodine therapy • Radiofrequency Ablation, Microwave Ablation, High Intensity Focused Ultrasound are safe and effective.

Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFß and JNK/AP-1.

Glucocorticoids such as dexamethasone are widely co-prescribed with cytotoxic therapy because of their proapoptotic effects in lymphoid cancer, reduction of inflammation and edema and additional benefits. Concerns about glucocorticoid-induced therapy resistance, enhanced metastasis and reduced survival of patients are largely not considered. We analyzed dexamethasone-induced tumor progression in three established and one primary human pancreatic ductal adenocarcinoma (PDA) cell lines and in PDA tissue from patients and xenografts by FACS and western blot analysis, immunohistochemistry, MTT and wound assay, colony and spheroid formation, EMSA and in vivo tumor growth and metastasis of tumor xenografts on chicken eggs and mice. Dexamethasone in concentrations observed in plasma of patients favored epithelial-mesenchymal transition, self-renewal potential and cancer progression. Ras/JNK signaling, enhanced expression of TGFß, vimentin, Notch-1 and SOX-2 and the inhibition of E-cadherin occurred. This was confirmed in patient and xenograft tissue, where dexamethasone induced tumor proliferation, gemcitabine resistance and metastasis. Inhibition of each TGFß receptor-I, glucocorticoid receptor or JNK signaling partially reversed the dexamethasone-mediated effects, suggesting a complex signaling network. These data reveal that dexamethasone mediates progression by membrane effects and binding to glucocorticoid receptor.

Comparison of Mono- and Bipolar Radiofrequency Ablation in Benign Thyroid Disease.

PURPOSE: Radiofrequency ablation (RFA) is an approved minimal invasive method for the treatment of benign thyroid nodules. Several experimental, mainly ex vivo animal studies have compared the effectiveness of different RFA procedures in liver tissue. The aim of this retrospective clinical study was to evaluate the difference between monopolar and bipolar RFA in thyroid tissue considering thyroid volume reduction, patient discomfort and ultrasound evaluation. METHODS: Eighteen patients with symptomatic complex benign thyroid nodules were treated in a single RFA session. Nine patients were treated with monopolar RFA, and nine other patients were treated with bipolar RFA. All patients underwent assessments before therapy and at 3-month follow-up (3MFU) including a complete hormone status (T3, T4, TSH, TG, TPOAb, TgAb, TRAb) and several ultrasound (US) evaluations using B-mode and color-coded Doppler imaging. The US evaluations contained measurement of volume, US Doppler, US echogenicity and US elastography. Additionally, applied energy (kJ), power output (W), number of shots (N) and total treatment time (s) were recorded in every case. RESULTS: Monopolar RFA resulted in a significant (p < 0.05) average thyroid volume reduction of Ø 18 ± 77 ml (25.1 ± 103%) and a nodule volume reduction of Ø 10.6 ± 22 ml (60.3 ± 62%). Bipolar RFA resulted in a significant (p < 0.05) average thyroid volume reduction of Ø 21.2 ± 54 ml (43.2 ± 84%) and a nodule volume reduction of Ø 13.8 ± 33 ml (70.8 ± 46%). Both groups showed equal results concerning volume reduction (p > 0.05). Monopolar RFA did not lead to any significant changes concerning the US scores, whereas bipolar RFA led to a significant (p < 0.05) reduction in US Doppler and nodular blood flow. No significant difference between both groups could be found concerning applied energy, treatment time, power output and number of shots (p > 0.05). CONCLUSION: Bipolar RFA did not show any disadvantages in comparison with monopolar RFA in the treatment of benign thyroid nodules. It shows better performance in terms of volume reduction and is superior when it comes to feasibility and patient discomfort. The recent study confirms the good ex vivo results for bipolar RFA.

Minimally invasive local ablative therapies in combination with radioiodine therapy in benign thyroid disease: preparation, feasibility and efficiency - preliminary results.

PURPOSE: Initial studies of combinations of radioiodine therapy (RIT) and local ablative procedures for the treatment of thyroid nodules have shown promising results. The goal of this study was to evaluate the effectiveness of RIT combined with radiofrequency ablation (RFA) in patients with goitres and to determine which ablative procedure is the most suitable for a combined therapy. METHODS: Thirty patients with goitres were divided into two subgroups. A test group of 15 patients received combined therapy (RIT + RFA) and a control group of 15 patients received RIT mono therapy. All patients underwent assessments including ultrasound, laboratory evaluation (T3, T4, TSH, TG, TPOAb, TgAbTRAb) and scintigraphic imaging with Tc-99m-Pertechnetate. The 3-month volume reduction was used to evaluate therapy effectiveness. RESULTS: Combined therapy (subgroup 1) resulted in a significant (p < 0.05) thyroid volume reduction (22.3 ± 54 ml/32.2 ± 58.2%) with better performance (p > 0.05) than the control group (20.2 ± 32.2 ml/29.6 ± 42.1%). All patients became euthyroid after treatment. No major discomfort or complications occurred. A review of the literature investigating combinations of other local ablative procedures with RIT was performed to determine the most promising combination. CONCLUSIONS: The present study confirms the positive experiences with the combined therapy of RIT and local ablative procedures shown in the current literature and approves this approach for the treatment of goitres with RFA + RIT. These findings, when confirmed by further studies, should expand the indication of combined therapy as a minimally invasive alternative to surgery.

Cooled microwave ablation of thyroid nodules: Initial experience.

OBJECTIVE: To evaluate if internally cooled microwave ablation (cMWA) is a safe and effective method for treatment of benign and malign thyroid nodules. METHODS: 9 patients with 11 symptomatic cold benign thyroid nodules and 1 recurrent thyroid carcinoma ranging in volume from 9.1 to 197ml (mean size 52±â€Š57ml) were treated with cMWA. The mean age of the patients was 59 years. Pain during the treatment was measured on a 10-point scale. Side effects revealed by ultrasound or patients' complaints were documented. Periablative efficacy was measured 24h after cMWA as change (Δ) in serum thyreoglobulin (Tg). Nodule elasticity was measured on a 4-point scale, blood circulation and echogenicity on a 3-point scale. RESULTS: All patients tolerated cMWA well. Median pain intensity averaged 2.1±0.8 (range: 1-3). Postablative hematoma was observed in all cases. In no cases ablation led to hoarseness, superficial burns, nodule ruptures, vagal reactions or dysphagia. cMWA lead to a significant decrease of blood circulation, nodule echogenicity and a significant increase of elasticity (Δ = 1.1 ±â€Š0.33; 0.8 ±â€Š0.4 and 1.1 ±â€Š0.6 points)(p<0.05). An average increase of 4495ng/ml Tg was measured (p<0.05). CONCLUSIONS: cMWA is an effective and secure method for treatment of thyroid nodules.

Bipolar radiofrequency ablation of benign thyroid nodules using a multiple overlapping shot technique in a 3-month follow-up.

Purpose The aim of this study was to evaluate the decrease of benign thyroid nodules after bipolar radiofrequency ablation (RFA) in a 3-month follow-up using a multiple overlapping shot technique ('MOST'). Methods A total of 18 patients with 20 symptomatic benign thyroid nodules (17 cold nodules, 3 hyperfunctioning nodules) were treated in one single session by bipolar RFA. Bipolar ablation was performed using MOST. The nodule volumes were measured prior to ablation and 3 months after the procedure using ultrasound. The population consisted of either solid (>80% solid tissue within the volume of interest), complex, or cystic nodules (<20% solid tissue within the volume of interest). Results Bipolar RFA resulted in a highly significant (p < 0.0001) decrease of nodule volume (ΔV), median 5.3 mL (range 0.13-43.1 mL), corresponding to a relative reduction in mean of 56 ± 17.9%. Median initial volume was 8 mL (range 0.48-62 mL); 3 months after ablation a median volume of 2.3 mL (range 0.3-32 mL) was measured. Nodule growth ≥50% occurred in 70% (14 nodules). At the follow-up no complications such as infections, persisting pain, nerve injuries or immunogen stimulation occurred. Patients with cold nodules (15) remained euthyroid, with hyperfunctioning nodules either euthyroid (2) or latent hypofunctional (1). Conclusion The use of bipolar RFA is an effective, safe and suitable thermoablative technique to treat benign thyroid nodules. Combined with the multiple overlapping shot technique it allows sufficient ablation.

Evaluation of fear of radiation and isolation before and after radioiodine therapy.

BACKGROUND: Prior to undergoing radioiodine therapy (RIT), patients regularly have concerns about isolation on the ward (mandatory for RIT for at least 48 hours in Germany due to radiation protection legislation) as well as fear of the presence of radioactive substances. In this study, these fears were investigated before and after RIT. METHODS: A questionnaire was developed for completion both before and after radioiodine therapy. Questions included: (i) "Are you afraid of a therapy with radioactive substances?" (ii) "Do you have reservations about contact with radioactive substances?" and (iii) "Are you anxious about isolation?" Possible answers were made in a qualitative representation using a scale of 1-4 (4=full agreement, 3=mostly agreement, 2=partial agreement, and 1=no agreement). Further questions included, for example, sources of information used prior to therapy. A total of 209 patients treated by single or preplanned multiple RIT were surveyed over a period of 8 months (return 109). Analysis was done in subgroups according to age, education, disease, and number of RITs. RESULTS: Question 1, "Are you afraid of a therapy with radioactive substances?" showed a similar statistically relevant decline in each subgroup (p<0.05), except for patients with multiple RIT (p=0.81). Asked about the handling of radioactive substances and their perception about the safety in this regard, the entire collective showed a highly statistically significant (p<0.01) decrease with little variability between the groups. The question concerning fear of isolation resulted in a significant decrease (p<0.05) in all subgroups, except for patients with multiple RIT (p=0.13). Analysis of sources of information before RIT showed that older patients preferred printed material and rarely used online resources, while younger patients used the internet more frequently, in addition to printed materials. Finally, most patients would undergo radioiodine therapy again (medical indication provided), with 54% fully agreeing and only 4% not agreeing. CONCLUSIONS: The survey demonstrates a reduction in concerns about nuclear radiation, use of unsealed radioactive materials, and isolation on the ward after RIT. Surprisingly, concerns rise again before a subsequent therapy.