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• Tumour type was the single most potent prognostic factor for survival in BP-NETs. • FDG-PET scans were mostly positive in all three subtypes of BP-NETs. • LCNEC presented with the lowest 1, 2 and 5 year survival rates. Bronchopulmonary neuroendocrine tumours are divided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). To thoroughly describe a cohort of 252 patients with TC, AC and LCNEC (SCLC excluded). Collection of data from 252 patients referred to and treated at Rigshospitalet 2008-2016. Data was collected from electronic patient files and our prospective NET database. Statistics were performed in SPSS. 162 (64%) had TC, 29 (12%) had AC and 61 (24%) had LCNEC. Median age at diagnosis was 69 years (range: 19–89) with no difference between genders. Thoraco-abdominal CT was performed in all patients at diagnosis. FDG-PET/CT was performed in 207 (82%) at diagnosis and was positive in 95% of the entire cohort, with no difference between tumour types. Synaptophysin was positive in 98%, chromogranin A in 92% and CD56 in 97%. Mean Ki67 index was 5% in TC, 16% in AC and 69% in LCNEC (p < 0.001). Metastatic disease was found in 4% of TC, 27% of AC and 58% of LCNEC at time of initial diagnosis (p < 0.001). In total 179 patients (71%) underwent surgical resection; TC: 87%, AC: 72% and LCNEC: 28% (p < 0.001). Of the resected patients, 11 (6%) had recurrence. Five-year survival rate was 88% for TC, 63% for AC and 20% for LCNEC. In this comprehensive study of a cohort of 252 patients, one of the largest until date, with TC, AC and LCNEC, the gender distribution showed female predominance with 68%. FDG-PET/CT was positive in 95% of the patients independent of tumour type, which confirms that FDG-PET/CT should be a part of the preoperative work-up for TC, AC and LCNEC. Tumour type was the single most potent independent prognostic factor. [ABSTRACT FROM AUTHOR]

Introduction: miRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression by binding to comple mentary sequences on target mRNAs and their expression is often dysregulated in cancer. Aim(s): Little is known about the carcinogenesis of the slow growing neuroendocrine tumors and we therefore wanted to characterize miRNA expression in these. Materials and methods: miRNA expression in carcinoids, metastasis and normal intestinal tissue was characterized using miRNA arrays. Changes in miRNA expression were validated by in-situ hybridization and qPCR. miR-129-Sp and let-7 was selected and further characterized by mRNA arrays on total RNA from cells transfected with either miRNA. Heatmaps identified let-7 target genes involved in metastasis, miR-129-5p and its two targets EGR1 and G3BP 1 were validated by western blot analysis and luciferase assay and further examined by growth assays with ceils transfected with miR-129-5p or siRNAs against EGR1 and G3BP1. Results: miR-129-5p is down-regulated in carcinoids and the let-7 family is reduced in metastasis. When transfected into carcinoid cells, both Let-7 and miR-129-5p inhibited their growth and miR-129-5p was shown to target EGR1 and G3BP1. Knock down of EGR1 and G3BP 1 also resulted in growth inhibition mimicking that of miR-129-5p. Conclusion: miRNA expression alters intestinal carcinoids, leading to down regulation of miR-129-5p, and the let-7 family is lost in metastasis. Both are important for growth inhibition. [ABSTRACT FROM AUTHOR]

Introduction: Liver metastases (LM) are frequent in patients with neuroendocrine tumors (NETs) and are associated with decreased overall survival (OS). Several treatment options are available depending on degree, localization, size and number of LM. For optimal choice of treatment and correct staging, accurate imaging modalities are crucial. Aim(s): To assess and compare several different imaging options available for patients with NETs and to evaluate if presence of LM was associated with decreased OS. Materials and methods: Ninety-two prospectively enrolled patients with histologically verified NETs underwent 111In-DTPAOctreotide scintigraphy (SRS), 123I-Metaiodobenzylguanidine(M IBG) scintigraphy, 18F-Fluorodeoxyglucose-PET(FDG-PET) and computer tomography(CT). OS based on presence of LM was estimated by the Kaplan-Meier method. Mean follow-up time from FDG-PET was 31 months. Results: Ninety-two patients were enrolled and imaged by SRS, MIBG, FDG and CT. SRS was positive in 52 patients (56%). MIBG was positive in 37 patients (39%). FDG was positive in 27 patients (29%). CT was positive in 61 patients (66%). Sixty-six patients (72%) had liver-positive loci on at least one scan. Patients with FDG-PET positive LM had significantly poorer OS than FDG-PET negative patients with a hazard ration of 3.7 (95% CI:1.9-7.2, p<0.001). Conclusion: The sensitivity of CT seems to be superior to the radionuclide-based methods for detection of LM. FDG-PET identified the least LM. However, the only prognostic imaging modality was FDG-PET where detection of LM was associated with decreased OS. [ABSTRACT FROM AUTHOR]

Introduction: Today, grading, and thereby choice of treatment strategy for patients with neuroendocrine (NE) tumors, is mainly based on the proliferation index, Ki-67. As a supplement to this pathological evaluation, a whole body image analysis could be of value. Aim(s): To investigate the prognostic value of FDG-PET in patients with WHO grade I and IINE tumors. Materials and methods: Eighty-one prospectively enrolled patients with NE tumors grade I and II underwent FDG-PET imaging. The prognostic value of the FDG-PET scan was evaluated. There were 47 grade I tumors (Ki-67 index2<20). Follow-up time after the FDG-PET scan was 31 ± 12.6 months (mean + SD). Results: FDG-PET identified pathological loci in 42 of 81 patients, giving an overall modest sensitivity of 52%. During the 3-year follow-up, 22 of the 81 patients died, and of these 22 events, 19 were FDG-PET positive and three were FDG-PET negative. Thus, in the FDG-positive group, 45% died, compared to 7.7% of the FDG-negative. A positive FDG-PET scan was associated with a significantly higher risk of death (p<0.001), with an HR of 7.3 (95% confidence interval: 2.1 - 24.6) in these low-grade NE tumors. Conclusion: FDG-PET predicts survival of grade I and IINE tumors. We therefore propose that FDG-PET can be a valuable prognostic tool even in NE tumors classified as low-grade. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer. Patients and methods A total of 103 consecutive patients with newly diagnosed operable breast cancer with tumors ≥2 cm were independently examined preoperatively with conventional assessment (mammography, breast/axillary ultrasound, chest X-ray and blood samples) and PET/CT with no prior knowledge of the other. Results PET/CT identified a primary tumor in all but three patients (97%). PET/CT solely detected distant metastases (ovary, bones and lung) in 6 patients and new primary cancers (ovary, lung) in another two patients, as well as 12 cases of extra-axillary lymph node involvement. In 15 patients (15%), extra-axillary malignancy was detected by PET/CT only, leading to an upgrade of initial staging in 14% (14/103) and ultimately a modification of planned treatment in 8% (8/103) of patients. Conclusions PET/CT is a valuable tool to provide information on extra-axillary lymph node involvement, distant metastases and other occult primary cancers. Preoperative 18F-fluorodeoxyglucose–PET/CT has a substantial impact on initial staging and on clinical management in patients with early-stage breast cancer with tumors ≥2 cm. [ABSTRACT FROM PUBLISHER]

Aim. To develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. Methods. We selected one of four tumour-specific antibodies against human breast cancer and investigated (1), in immunedeficient (nude) mice with xenograft human breast cancer expressing the antigen if specific binding of the intratumorally injected, radioactively labelled, monoclonal antibody could be scintigraphically visualized, and (2) transportation to and retention in regional lymph nodes of the radioactively labelled antibody after subcutaneous injection in healthy rabbits. Results and Conclusion. Our paper suggests the theoretical possibility of amodel of dual isotope immuno-lymphoscintigraphy for noninvasive, preoperative, malignant sentinel node imaging. [ABSTRACT FROM AUTHOR]

We describe a small-angle x-ray scattering-based imaging technique that reveals the distribution and orientation of nano-scale structures over extended areas. By combining two measurement and analysis schemes, complementary structural information is available which renders the technique suitable for a broad range of applications, e.g. in materials science and bioimaging. Through a combination of current techniques and on-line analysis schemes, measurements with a so far unprecedented combination of speed, dynamic range and point density became feasible. This is illustrated by data recorded for a section of a mouse soleus muscle visualizing fine muscle and Achilles tendon structures down to the 10 nm range over a 10mm² sample area. [ABSTRACT FROM AUTHOR]

High-energy gamma probes have recently become commercially available, developed for 18F-FDG probe-guided surgery. The radiation received by the staff in the operating room might limit the use of it, but has never been determined. We therefore wanted to measure the absorbed staff doses at operations where patients had received a preoperative injection of 18F-FDG. Thrity-four patients with different cancers (breast cancer, melanoma, gastrointestinal cancers, respectively) were operated. At every operation the surgeon was monitored with a TLD tablet on his finger of the operating hand and a TLD tablet on the abdomen. The surgeon and anaesthesiologist were also monitored using electronic dosimeters placed in the trousers lining at 25 operations. The dose rate to the surgeon’s abdominal wall varied between 7.5–13.2 μSv/h, depending on tumour location. The doses to the anaesthesiologists and the finger doses to the surgeon were much lower. About 350–400 MBq, i.e. ca. eight times higher activities than those used in the present study are supposed to be necessary for guiding surgery. It can be calculated from the body doses measured that a surgeon can perform between 150–260 h of surgery without exceeding permissible limits for professional workers. The radiation load to the operating staff will generally be so small that it does not present any limitation for FDG-guided surgery. However, it is recommended to monitor the surgical staff considering that the surgeon may be exposed to other radiation sources, and since the staff often includes women of child-bearing age. [ABSTRACT FROM AUTHOR]