[Hyposplenism, an underrecognised immune diffeciency: Is sonography helpful?] / "Hyposplenie", eine weitgehend unerkannte Immunschwäche: Ist die Sonografie hilfreich?

The immunodeficiency syndrome of functional hyposplenia/asplenia is frequently unrecognized. The gold standard procedure for the diagnosis of this disease is technetium-99m scintigraphy of heat-denatured erythrocytes and the detection of pitted erythrocytes or Howell-Jolly bodies. Initial work suggests that this clinical presentation is associated with a small spleen. The aim of this review is to describe the value of B-mode and contrast-enhanced ultrasound in the identification of immunodeficiency caused by functional hyposplenism.

B-Mode Ultrasound and Contrast-Enhanced Ultrasound for the Detection of Splenic Involvement in Hodgkin Lymphoma: A Retrospective Analysis of 112 Patients.

PURPOSE: To assess splenic involvement using B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) compared with standard imaging with contrast-enhanced computerized tomography (CT) / 18-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients with Hodgkin lymphoma. MATERIALS AND METHODS: Imaging data from 112 patients from 12/2003 to 10/2022 with histologically confirmed Hodgkin lymphoma during staging or relapse were analyzed for splenic lymphoma involvement. In all patients, standard imaging (CT/PET-CT), along with B-mode US and CEUS examinations, was performed. Evidence of focal splenic lesions (FSLs) found by imaging procedures was suggestive of splenic involvement. Follow-up imaging was performed in each patient after treatment, and treatment response indicated definitive splenic involvement. RESULTS: 40 patients (35.7%) were identified by imaging modalities as having splenic involvement, which was confirmed by response during follow-up. Standard CT/PET-CT imaging detected splenic involvement in 36/112 patients (32.1%). FSLs were detected with B-mode US in 38 patients (33.9%) and CEUS in 36 patients (32.1%). The sensitivity of standard imaging, B-mode US, and CEUS was 90%, 95%, and 90%, respectively. CONCLUSION: B-mode US examination is a diagnostic method used in addition to standard imaging for the detection of splenic involvement in Hodgkin lymphoma. CEUS does not provide additional benefit compared to B-mode US and the standard reference procedure.

[Therapy concepts for thyroid carcinoma]. / Therapiekonzepte beim Schilddrüsenkarzinom.

Theranostics via the sodium iodide symporter (NIS) offer a unique option in differentiated thyroid carcinoma. The diagnostic and therapeutic nuclides have similar uptake and kinetics, making the NIS the most important theranostic target in this disease. Radioiodine refractory thyroid carcinomas (RRTC) are characterised by reduced/absent NIS expression, thus eliminating this structure as a theranostic target. Also due to limited therapeutic options, there are approaches to generate new theranostic targets in RRTC, via the expression of somatostatin receptors (SSTR) or the prostate-specific membrane antigen (PSMA), but the current evidence does not yet allow a final evaluation of the prospects of success.

Second primary malignancies induced by radioactive iodine treatment of differentiated thyroid carcinoma - a critical review and evaluation of the existing evidence.

PURPOSE: Concern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy. METHODS: An extensive literature search was performed in Ovid MEDLINE, Ovid MEDLINE and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Studies regarding RAI-induced SPMs or a dose-response relationship between RAI therapy and SPMs were identified, 10 of which were eligible for the analysis. We evaluated risk of bias in each study and judged quality of evidence (QOE) across all studies using the Grading of Recommendations, Assessment, Development and Evaluations approach. RESULTS: For the outcome "SPM", the relative effect (relative risk, hazard ratio, or odds ratio) of RAI vs. no RAI ranged from 1.14 to 1.84 across studies, but most results were not statistically significant. For the outcome "SHM", reported relative effects ranged from 1.30 to 2.50, with 2/3 of the studies presenting statistically significant results. In 7/8 of the studies, increased risk for SPM was shown with increasing cumulative RAI activity. QOE was "very low" regarding SPM after RAI and regarding a dose-response relationship, and "low" for SHM after RAI. CONCLUSION: Based on low quality evidence, an excess risk for the development of SPM cannot be excluded but is expected to be small.

[Systemic treatment of patients with metastatic neuroendocrine Neoplasia]. / Systemtherapie von neuroendokrinen Neoplasien.

Due to the complexity and heterogeneity of metastatic NEN an interdisciplinary expert team should be involved in an individualized treatment strategy. SSA is the mainstay of antisecretory treatment in most functioning tumors. In antiproliferative intention SSA are first line treatment in receptor positive low proliferative NET. In intestinal metastatic disease PRRT is best established second line treatment. Further options are Everolimus (labeled) and tyrosine kinase inhibitors (off-label). Everolimus is the only approved drug for antiproliferative treatment in patients with metastatic lung NET, whereas in pancreatic NET more therapeutic options are available (SSA, chemotherapy, PRRT, Sunitinib, Everolimus) without a standard of best sequence. In patients with metastatic NEC standard first line treatment (platinum + etoposide) has not changed for decades and new treatment options for this fatal disease are urgently needed. Benefit of immunotherapy is limited to a small subset of patients - new combinations are under investigation. This review summarizes the standard of care, criteria of treatment selection and new developments for systemic therapy in patients with metastatic NEN.

Diagnostic Impact of Dual-Time PET/CT with 68Gallium-PSMA in Prostate Cancer and 68Gallium-DOTATOC in Neuroendocrine Tumors.

BACKGROUND: The timing of imaging for 68gallium (68Ga)-PSMA and 68Ga-DOTATOC are stated to be around 60 min post-injection (p.i.). In some lesions, late imaging (3-4 h p.i.) showed advantages. The aim of our evaluation was to demonstrate the relevance of an "early" late acquisition. METHODS: We retrospectively evaluated 112 patients who underwent 68Ga-DOTATOC-PET/CT and 82 patients who underwent 68Ga-PSMA-PET/CT. The first scan was acquired 60 min (±15 min) after application. In cases of diagnostic ambiguity, a second scan was performed 30-60 min later. Pathological lesions were analyzed. RESULTS: Almost half of all 68Ga-DOTATOC cases and about one-third of all 68Ga-PSMA examinations showed a change in findings due to the second acquisition. In total, 45.5% of neuroendocrine tumor (NET) patients and 66.7% of prostate cancer (PCa) patients showed relevant TNM classification changes. For 68Ga-PSMA, there were significant increases in sensitivity and specificity from 81.8% to 95.7% and from 66.7% to 100%, respectively. Statistically significant improvements in sensitivity (from 53.3% to 93.3%) and specificity (from 54.6% to 86.4%) were demonstrated for NET patients. CONCLUSION: Early second images can improve diagnostics with 68Ga-DOTATOC and 68Ga-PSMA PET/CT.

Application of the American Thyroid Association Risk Assessment in Patients with Differentiated Thyroid Carcinoma in a German Population.

BACKGROUND: The American Thyroid Association (ATA) uses criteria to assess the risk for persistent disease in differentiated thyroid carcinoma (DTC) after radioiodine therapy (RAI). There are no data available showing that this classification can be adopted unadjusted by Germany. AIM: The aim of our study is to investigate whether the ATA classification can be applied to a German population for short-term prognosis. Furthermore, we investigated the influence of an age cutoff value. METHODS: We retrospectively analyzed 121 patients who were referred to our tertiary referral center. Patients were classified into risk categories, and the therapy response was determined according to ATA. RESULTS: A total of 73/83 (88%) ATA low-risk patients and 12/19 (63%) intermediate-risk patients showed an excellent response; 2/19 (11%) high-risk patients had a biochemical, and 6 (31%) had a structural incomplete response. Of all 39 patients ≥55 years, 84% had an excellent response. Using a cut off of 50 years, 50/62 (81%) of the older patients showed an excellent response. CONCLUSION: The ATA risk classification is able to estimate the response to RAI therapy in a German population. A shift from 55 to 50 years as an age cutoff value does not result in any relevant change in the treatment response.

[Is there an unmet need to establish a young talent section "Young DGN" within the German Society of Nuclear Medicine (DGN)? - Results of a 2021/2022 web-based survey among German Nuclear Medicine professionals]. / Besteht der Bedarf zur Gründung einer Nachwuchsorganisation "Young DGN" innerhalb der Deutschen Gesellschaft für Nuklearmedizin (DGN)? Ergebnisse einer webbasierten Umfrage in der deutschen Nuklearmedizin 2021/2022.

AIM: In various medical societies, dedicated young talent sections provide an important basis for promoting young members. However, the German Society of Nuclear Medicine (DGN) had not yet implemented such a section. Therefore, the aim of this work was to assess the opinion of nuclear medicine professionals in Germany on establishing a young talent section within the DGN ("Young DGN"). METHODS: An initiative group of young DGN members developed a survey questionnaire comprising 18 questions. The questionnaire was initially sent as a PDF to the members of the DGN University Committee (Hochschulausschuss) by e-mail on 10/12/2021. As an online survey, the questionnaire was then emailed at four additional time points between 12/23/2021 and 3/18/2022 via the DGN eBrief and on 2/23/2022 to the members of the mailing list of the Berufsverband Deutscher Nuklearmediziner (BDN). RESULTS: The survey closed on 3/31/2022 with 111 responses (n=104 online surveys, n=7 PDFs). The median age of participants was 32.5 years (range, 20-80). 86% of participants indicated that they were interested in a Young DGN section, of which 67% were willing to participate. 79% indicated that nuclear medicine was an exciting field for them. 96% expressed interest in additional education offers and 60% in the establishment of a mentoring program. 75% believed that Young DGN would improve the visibility of the specialty. CONCLUSION: The survey results indicate strong support for the establishment of a young talent section within the DGN among nuclear medicine professionals in Germany. A large proportion of those who participated in the survey would envision active involvement. There was a particular consensus on the desire to expand the range of education and training activities.

[Therapy concepts for thyroid carcinoma]. / Therapiekonzepte beim Schilddrüsenkarzinom.

Theranostics via the sodium iodide symporter (NIS) offer a unique option in differentiated thyroid carcinoma. The diagnostic and therapeutic nuclides have similar uptake and kinetics, making the NIS the most important theranostic target in this disease. Radioiodine refractory thyroid carcinomas (RRTC) are characterised by reduced/absent NIS expression, thus eliminating this structure as a theranostic target. Also due to limited therapeutic options, there are approaches to generate new theranostic targets in RRTC, via the expression of somatostatin receptors (SSTR) or the prostate-specific membrane antigen (PSMA), but the current evidence does not yet allow a final evaluation of the prospects of success.

[High clinical value of bone scintigraphy as a staging method for breast cancer]. / Hohe klinische Wertigkeit der Skelettszintigrafie beim Staging des Mammakarzinoms.

BACKGROUND: Bone scintigraphy is a sensitive method for imaging bone metastases in patients with breast cancer. Despite its firm establishment in clinical routine, there are hardly any reliable data from larger homogeneous collectives on the value of bone scintigraphy in the context of staging of first diagnosed breast cancer patients. AIM: The aim of our work was to evaluate the real-life performance of bone scintigraphy as a staging examination in female patients with the initial diagnosis of breast cancer. PATIENTS AND METHODS: We retrospectively evaluated the data of the patients examined in the year 2015 with the first diagnosis of breast cancer at the University Hospital Marburg by bone scintigraphy. In addition a follow-up over a period of 30 months after the first bone scintigraphy was performed. For this purpose we evaluated whether the results of this initial diagnostic could be confirmed in following diagnostic. RESULTS: 207/258 patients showed no suspicious findings in the initial bone scintigraphy, 48 had an unclear finding, which is why 42 patients received further diagnostics. In follow-up, new bone metastases were found in 4 patients, all of these had scintigraphic findings in the primary diagnosis, which were considered "unclear". Depending on the evaluation of the event (suspicious for metastasis/suspicious for metastasis and unclear), the sensitivity was 37.5%/100%, the specificity 100%/80%, the positive predictive value 100%/15.7% and the negative predictive value 98%/100%. CONCLUSION: By using bone scintigraphy and, if necessary, subsequent further imaging or histological clarification, a clinically significant diagnosis was obtained in 99,2% of the examined patients and confirmed in the follow-up. This result shows the good real-life performance of bone scintigraphy as a staging examination in patients with first diagnosed breast carcinomas.

Real-Life Performance of F-18-FDG PET/CT in Patients with Cervical Lymph Node Metastasis of Unknown Primary Tumor.

BACKGROUND: Neoplasms in the head and neck region possess higher glycolytic activity than normal tissue, showing increased glucose metabolism. F-18-Flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can identify an unknown primary tumor (CUP). AIM: The aim of this study was to assess the real-life performance of F-18-FDG-PET/CT in detecting primary sites in patients with cervical lymph node metastasis of CUP. METHODS: A retrospective data analysis of 31 patients who received FDG-PET/CT between June 2009 and March 2015 in a CUP context with histologically confirmed cervical lymph node metastasis was included. RESULTS: In 48% of the patients (15/31), PET/CT showed suspicious tracer accumulation. In 52% of the patients (16/31), there was no suspicious radiotracer uptake, which was confirmed by the lack of identification of any primary tumor in 10 cases until the end of follow-up. FDG-PET/CT had a sensitivity of 67%, specificity of 91%, PPV of 92%, and NPV of 63% in detecting the primary tumor. Additionally, PET/CT showed suspicious tracer accumulation according to further metastasis in 32% of the patients (10/31). CONCLUSION: FDG-PET/CT imaging is a useful technique for primary tumor detection in patients in a cervical CUP context. Furthermore, it provides information on the ulterior metastasis of the disease.

Theranostics in Thyroid Cancer.

The main targeting structure for theranostics in thyroid cancer is the sodium-iodine symporter (NIS), which has been used in clinical routine for the diagnosis and treatment of thyroid diseases for more than 70 years. Because the different iodine (I) nuclides (123I, 124I, 131I) have the same kinetics, uniquely congruent theranostics are possible in differentiated thyroid cancer. Besides the NIS, there are further possibilities by using expression of somatostatin receptors or the expression of the prostate-specific membrane antigen, for example, in radioiodine-refractory differentiated thyroid cancer, medullary thyroid cancer, or anaplastic thyroid cancer.

Perioperative diagnostics of patients referred for radioiodine therapy of differentiated thyroid carcinoma: referral center experience in an iodine-insufficient country.

PURPOSE: The interdisciplinary "Martinique-Principles" of four international professional societies concerned with the patient management of differentiated thyroid cancer (DTC) patients were agreed upon. Differences in perioperative diagnostics can lead to differences in clinical decision founding regarding the treatment of thyroid carcinoma. Our aim was to analyze the perioperative diagnostics of patients referred for postoperative I-131 therapy of DTC. METHODS: We retrospectively examined the data of 142 patients who were referred to our center for the first course of postsurgical I-131 therapy. We extracted data on perioperative diagnostics. RESULTS: Fine-needle biopsy (FNB) was performed in 27/142 patients. In 17 patients, FNB yielded findings suspicious of malignancy, in 3 patients a follicular lesion was reported. An intraoperative frozen section analysis was performed in 79/142 patients. 5/63 patients showed already a cytologically proven malignancy. In 10/79 patients, the frozen section had a nonmalignant result, although DTC was found on final assessment. In 2/79 patients, frozen section analysis was indecisive, although the final report confirmed DTC. In the remaining 67 patients, frozen section yielded DTC. CONCLUSIONS: There is room for improvement in perioperative diagnostics surrounding thyroid surgery, currently many procedures are performed without adequate information on potential presence of thyroid cancer. More frequent use of FNB might be able to decrease the number of unnecessary thyroid surgeries, increased use of frozen section might decrease the number of second operations and might contribute to less discordance between experts in the field of DTC treatment.

Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer-A New Diagnostic and Therapeutic Target?

Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients' tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients' eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

[Follow-up of differentiated thyroid cancer]. / Nachsorge beim differenzierten Schilddrüsenkarzinom.

The management of differentiated thyroid carcinoma has shown considerable changes in recent years, moving away from a fixed therapy regimen towards individual treatment strategies. The aim of our work (literature research) is to present current developments in the follow-up of differentiated thyroid cancer.For the management of individual follow-up, an initial evaluation and, at later time points, the re-evaluation of the risk of recurrence is crucial. The performance of I-131-diagnostics after radioiodine therapy can provide essential information and can be seen as a survey of a new baseline situation, in order to be able to draw a comparison in case of a rising Thyreoglobulin (Tg).The measurement of Tg with a highly sensitive assays shows a high negative predictive value. Negative Tg measurements with these assays seem to indicate complete remission even with Tg antibodies being present. An increasing Tg value in follow-up implies further diagnostic work-up, primarily neck ultrasonography. Sonographically suspicious findings should be subjected to fine needle biopsy, whereby in addition to cytological processing, determination of Tg from the sample can be recommended. If the suspicious lesion cannot be displayed sonographically and Tg values keep rising, computed tomography (CT) and magnetic resonance imaging (MRI) of the neck region can provide further information. FDG-PET/CT has also shown an excellent performance in this setting.The previously fixed therapy regimen has been realigned towards an individual treatment management. Current studies and guidelines lead to a repetitive recurrence risk evaluation and the adjustment of the aftercare planning to the individual risks with appropriately selected examination methods and personalized intervals of assessment.

Reference values for quantitative parameters in renal scintigraphy with Tc-99m-MAG3.

BACKGROUND: Reference values are the basis for an increase of standardisation and examiner independence, and thus an improvement in the inter-institutional comparability. However for renal Mercaptoacetyltriglycin (MAG3)-scintigraphy the establishment of such values however did not find its way into clinical routine despite the convincing advantages. AIM: The aim was to establish reference values for the decisive quantitative parameters of MAG3 renal scintigraphy. The reference values should help to significantly improve and facilitate the interpretation of the examination results in everyday clinical practice. METHODS: We retrospectively evaluated all MAG3 renal scintigraphies performed in the Department of Nuclear Medicine, University Hospital Marburg between 01/2014 and 08/2017. The total sample of non-pathological renal scintigrafies included 247 patients aged between 25 days and 88 years. All investigtions were performed according to the present guidelines of the German Association for Nuclear Medicine. We analysed the ratio from pulse count rate after 20 minutes/Time (T) max and the Tmax separately. RESULTS: Reference values for the Tmax and 20 min/T(max) count ratio of the MAG3 renal scintigraphy were defined for all adults over 18 years and divided by age catogories. For children aged 0-0.5 years and 0.5-2 years reference values for Tmax were defined. CONCLUSION: The results show a high degree of consistency with the reference values screened out in previous studies. This underlines the reliability of the reference values as a diagnostic tool in clinical application. The defined values are clinically feasible and promise a simplified and improved interpretation of the MAG3 renal scintigraphy.

Score-based improvement of the indication for surgical treatment of thyroid lesions.

BACKGROUND: The prevalence of focal lesions in the thyroid is high in Germany. In 2018 about 70 000 thyroid surgeries were performed, although the malignancy rate of such findings is low. For this reason it is important to conduct an adequate selection of patients for whom surgery is indicated. AIM: The aim of our work was to validate the preoperative indication for surgery of thyroid lesions based on an independent, self-developed clinical score. PATIENTS AND METHODS: The patient data were evaluated retrospectively over the period 2013 to 2014. A prerequisite for inclusion was that the patients had carried out their complete treatment in domo. The multiparametic score was determined retrospectively and ranges from 3 to 15. The subjective improvement of symptoms (self-disclosure > 6 months postoperatively) and the presence of malignant histology were evaluated as positive outcome parameters. RESULTS: From a collective of 180 patients, 36 patients could be included, in whom all score-relevant parameters had been surveyed. The score distribution was 10 % score 3, 12.5 % score 4, 25 % score 5, 25 % score 6, 12.5 % score 7, 7.5 % score 8, 5 % score 9 and 2.5 % score 10. Using ROC analysis shows an AUC of 0.903, which is a very good differentiation. With a CUT-off score of 7 or higher, 86 % of patients have benefited from surgery. CONCLUSION: Our score with the parameters clinical complaints, sonographically defined size of the thyroid and the cytological result of a fine needle biopsy can lead to an improvement of the indication for surgical treatment of thyroid nodules.