[Imaging of neuroendocrine tumors of the gastrointestinal tract : Value of (hybrid) imaging diagnostics in radiology]. / Bildgebung von neuroendokrinen Tumoren des Gastrointestinaltrakts : Bedeutung der (hybriden) bildgebenden Diagnostik in der Radiologie.

CLINICAL/METHODICAL ISSUE: Neuroendocrine tumors (NET) represent a heterogeneous group of rare tumors that predominantly arise in the gastrointestinal tract. At the time of initial diagnosis, the NET has already spread locoregionally in about half of the patients, and 27% of patients have already developed distant metastases. Since this plays a crucial role in therapy planning, accurate diagnostic imaging is important. STANDARD RADIOLOGICAL METHODS: Due to its high temporal and spatial resolution (multiphasic including arterial phase), computed tomography (CT) plays a decisive role in primary staging and follow-up care, while magnetic resonance imaging (MRI) with its excellent soft tissue contrast offers advantages in the assessment of parenchymal organs in the upper abdomen. METHODICAL INNOVATIONS: Somatostatin receptor (SSR) positron emission tomography (PET) provides additional functional information that not only helps to detect the primary tumor and distant metastases, but also has a significant influence on therapeutic management in a theranostic approach. PERFORMANCE: Hybrid imaging using SSR-PET/CT has proven to be particularly effective in the detection of NET. Compared to conventional imaging, it provides additional information in 68% of patients, which has a significant impact on clinical management. ACHIEVEMENTS: Imaging of NET requires the combined use of various methods such as ultrasound, CT, MRI, and PET/CT to enable accurate diagnosis and effective treatment planning. PRACTICAL RECOMMENDATIONS: SSR-PET/CT is a valuable tool for the accurate staging of neuroendocrine tumors of the gastrointestinal tract, especially with small metastases, while MRI with hepatocyte-specific contrast agent and diffusion-weighted imaging is useful for the specific assessment of liver metastases.

Validation of the standardization framework SSTR-RADS 1.0 for neuroendocrine tumors using the novel SSTR­targeting peptide [18F]SiTATE.

OBJECTIVES: Somatostatin receptor positron emission tomography/computed tomography (SSTR-PET/CT) using [68Ga]-labeled tracers is a widely used imaging modality for neuroendocrine tumors (NET). Recently, [18F]SiTATE, a SiFAlin tagged [Tyr3]-octreotate (TATE) PET tracer, has shown great potential due to favorable clinical characteristics. We aimed to evaluate the reproducibility of Somatostatin Receptor-Reporting and Data System 1.0 (SSTR-RADS 1.0) for structured interpretation and treatment planning of NET using [18F]SiTATE. METHODS: Four readers assessed [18F]SiTATE-PET/CT of 95 patients according to the SSTR-RADS 1.0 criteria at two different time points. Each reader evaluated up to five target lesions per scan. The overall scan score and the decision on peptide receptor radionuclide therapy (PRRT) were considered. Inter- and intra-reader agreement was determined using the intraclass correlation coefficient (ICC). RESULTS: The ICC analysis on the inter-reader agreement using SSTR-RADS 1.0 for identical target lesions (ICC ≥ 85%), overall scan score (ICC ≥ 90%), and the decision to recommend PRRT (ICC ≥ 85%) showed excellent agreement. However, significant differences were observed in recommending PRRT among experienced readers (ER) (p = 0.020) and inexperienced readers (IR) (p = 0.004). Compartment-based analysis demonstrated good to excellent inter-reader agreement for most organs (ICC ≥ 74%), except for lymph nodes (ICC ≥ 53%). CONCLUSION: SSTR-RADS 1.0 represents a highly reproducible and consistent framework system for stratifying SSTR-targeted PET/CT scans, even using the novel SSTR-ligand [18F]SiTATE. Some inter-reader variability was observed regarding the evaluation of uptake intensity prior to PRRT as well as compartment scoring of lymph nodes, indicating that those categories require special attention during further clinical validation and might be refined in a future SSTR-RADS version 1.1. CLINICAL RELEVANCE STATEMENT: SSTR-RADS 1.0 is a consistent framework for categorizing somatostatin receptor-targeted PET/CT scans when using [18F]SiTATE. The framework serves as a valuable tool for facilitating and improving the management of patients with NET. KEY POINTS: SSTR-RADS 1.0 is a valuable tool for managing patients with NET. SSTR-RADS 1.0 categorizes patients with showing strong agreement across diverse reader expertise. As an alternative to [68Ga]-labeled PET/CT in neuroendocrine tumor imaging, SSTR-RADS 1.0 reliably classifies [18F]SiTATE-PET/CT.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

[Well-being and psychosocial activities in nursing homes : Survey of residents]. / Befinden und psychosoziale Aktivitäten im Pflegeheim : Befragung von Bewohnern.

BACKGROUND: Assessment and self-assessment frequently differ, e. g. in psychosomatic disorders and complaints. At the same time the prevalence of corresponding disorders in old age is high. OBJECTIVE: This study investigated psychosocial factors from the perspective of nursing home residents and compared this self-assessment with data collected in other scientific studies with assessments by nursing home staff. The aim was to develop specific recommendations for the nursing home sector. MATERIAL AND METHODS: In this cross-sectional pilot study 256 nursing home residents (average age 81 ± 10.3 years, 69 % female, 31 % male) were questioned about their physical, psychological and social activities and well-being in semistructured anonymous interviews. Psychological screening tests were simultaneously implemented to assess symptoms of depression and dementia using the short form of the geriatric depression scale (GDS-K) and the mini mental status test (MMST). RESULTS: The results showed that 44.6 % of the residents had symptoms of depression and 76.1 % revealed signs of development of dementia. More than half assessed their physical health as good to very good. According to comparable studies nursing staff assessed persistent pain in 20.7 % of all nursing home residents while personal interviews with the residents showed that persistent pain (39.8 %) was almost twice as frequent. Life satisfaction showed a significant correlation with the following items from the self-assessment: participation in nursing home activities (r = 0.171, p = 0.008), mobility (r = -0.131; p = 0.045), emotional activity (r = 0.136, p = 0.038), subjectively experienced physical health (r = -0.420, p < 0.001) and persistent pain (r = -0.178, p = 0.006). Life satisfaction correlated highly significantly with symptoms of depression (r = -0.617, p < 0.001) and cognitive performance (r = 0.251, p = 0.001). CONCLUSION: The findings of this study encourage further research on the characteristic features of satisfied residents and (psycho)therapeutic support in order to promote factors for well-being and a positive quality of life in nursing homes.

Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy.

Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A(*)0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma.

A successful approach for the detection of Fabry patients in Argentina.

Fabry disease is an X-linked lysosomal disorder caused by the deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). In males, the laboratory diagnosis is based on the demonstration of decreased levels of alpha-Gal A activity, while in females, the disease is diagnosed by the identification of a mutation in alpha-Gal A gene. Fabry disease in Argentina is underdiagnosed. To date, no comprehensive screening study of Fabry disease in our country has been reported. The present study aimed at developing a targeted screening for the detection of Fabry patients from Argentina based on the set of typical signs and symptoms. We received 121 blood samples from probable Fabry patients for enzymatic and genetic assay. We diagnosed six Fabry patients from six unrelated families, representing a yield of detection of 4.96%. The mutations detected in five of the families analysed were missense mutations: p.Leu243Trp, p.Asp155His, p.Leu415Pro, p.Cys94Tyr and p.Leu191Pro. After the detection of a Fabry patient, his/her relatives were also screened. In the course of these family studies, other 64 Fabry patients, 29 males and 35 females, were detected. To our knowledge, this is the first comprehensive screening of Fabry disease in Argentina. We detected 70 patients in a period of 2.5 years. The development of targeted protocols and the constitution of interdisciplinary groups for the identification of patients with Fabry disease are recommended to obtain a higher yield in the process.