Setting a direction for continuing professional development in anesthesiology: A synthesis of the outcome from an Utstein style meeting.

BACKGROUND: An Utstein style meeting of key stakeholders from the existing collaboration surrounding post-graduate training was arranged to set a direction for continuing professional development (CPD) of anesthesiologists in Denmark. A 2-day meeting was planned to guide discussions about competencies in anesthesiology, facilitate the development of a blueprint for a portfolio-based CPD program and provide examples of how a portfolio can be used in practice. METHODS: The meeting agenda was based on an adaptation of Kern's six-step approach to curriculum development. Twenty-four participants from the university hospitals in Denmark were invited. Prior to the meeting participants were informed of the objectives and the Utstein style process. RESULTS: Participants acknowledged a need for a more structured approach to CPD, preferably within the current organizational set up at the departmental level, and with a portfolio-based, individualized curriculum. It was recognized that CPD should contain an array of possibilities to accommodate needs and wants of both the individual and the department. It was emphasized that, while anesthesiologists are used to give feedback to trainees, many are less familiar in providing the same to peers, and psychological safety was identified as a prerequisite to support a culture where specialists can reflect openly on each other's performance. CONCLUSION: The results provide an insight into the attitudes, opportunities, and challenges of anesthesiologists in relation to continuing professional development in Denmark. Generally, participant suggestions are in line with the shift in medical education toward workplace-based learning, feedback and lifelong learning.

Machine learning predictive performance evaluation of conventional and fuzzy radiomics in clinical cancer imaging cohorts.

BACKGROUND: Hybrid imaging became an instrumental part of medical imaging, particularly cancer imaging processes in clinical routine. To date, several radiomic and machine learning studies investigated the feasibility of in vivo tumor characterization with variable outcomes. This study aims to investigate the effect of recently proposed fuzzy radiomics and compare its predictive performance to conventional radiomics in cancer imaging cohorts. In addition, lesion vs. lesion+surrounding fuzzy and conventional radiomic analysis was conducted. METHODS: Previously published 11C Methionine (MET) positron emission tomography (PET) glioma, 18F-FDG PET/computed tomography (CT) lung, and 68GA-PSMA-11 PET/magneto-resonance imaging (MRI) prostate cancer retrospective cohorts were included in the analysis to predict their respective clinical endpoints. Four delineation methods including manually defined reference binary (Ref-B), its smoothed, fuzzified version (Ref-F), as well as extended binary (Ext-B) and its fuzzified version (Ext-F) were incorporated to extract imaging biomarker standardization initiative (IBSI)-conform radiomic features from each cohort. Machine learning for the four delineation approaches was performed utilizing a Monte Carlo cross-validation scheme to estimate the predictive performance of the four delineation methods. RESULTS: Reference fuzzy (Ref-F) delineation outperformed its binary delineation (Ref-B) counterpart in all cohorts within a volume range of 938-354987 mm3 with relative cross-validation area under the receiver operator characteristics curve (AUC) of +4.7-10.4. Compared to Ref-B, the highest AUC performance difference was observed by the Ref-F delineation in the glioma cohort (Ref-F: 0.74 vs. Ref-B: 0.70) and in the prostate cohort by Ref-F and Ext-F (Ref-F: 0.84, Ext-F: 0.86 vs. Ref-B: 0.80). In addition, fuzzy radiomics decreased feature redundancy by approx. 20%. CONCLUSIONS: Fuzzy radiomics has the potential to increase predictive performance particularly in small lesion sizes compared to conventional binary radiomics in PET. We hypothesize that this effect is due to the ability of fuzzy radiomics to model partial volume effects and delineation uncertainties at small lesion boundaries. In addition, we consider that the lower redundancy of fuzzy radiomic features supports the identification of imaging biomarkers in future studies. Future studies shall consider systematically analyzing lesions and their surroundings with fuzzy and binary radiomics.

Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy - diagnostic performance and impact on therapeutic decision-making.

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

Hematopoiesis is prognostic for toxicity and survival of 223Radium treatment in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival, hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin-levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis as well as adverse events during and after therapy were scored (grade 0-4) according to the CTCAE recommendations. The association of pre-therapeutic hematopoiesis, survival, HT and numbers of 223Ra cycles was analyzed. RESULTS: Median survival in all patients was 69.9 weeks; 77% of patients had pre-existing impaired Hb (1.7% grade 3, 12.5% grade 2, 62.5% grade 1). 8/56 (14.3%) had impaired Plt (grade 1) Maximum toxicity (Tox) grades of patients during treatment were grade 4 (Hb 1.7%; Plt 1.7%), grade 3 (Hb 14.3%; Plt 7.1%; Leu 7.1%), grade 2 (Hb 33.9%; Plt 7.1%; Leu 23.2%), grade 1 (Hb 46.4%; Plt 17.9%; Leu 23.2%) and grade 0 (Hb 5.4%; Plt 66.1%; Leu 44.6%). Interestingly, patients with thrombocytopenia had a significantly shorter survival compared to those with normal Plt levels (21 weeks vs not reached; P<0.003). As expected patients with pre-therapeutic low Hb-level (<10g/dL) had a significantly shorter survival compared to those with Hb-level >10g/dL (28 weeks vs not reached, P<0.004), whereas survival of patients with mildly impaired Hb (>10 but <13.5g/dL) did not differ from patients with normal levels of Hb (X vs. Y, P=...). Also patients with impaired Hb also developed significantly more grade 3 and 4 HT (Hb <10g/dL: 42.9 vs 14.3%, P<0.001; Plt <150G/mL: 25.0% vs 6.3%; P=0.002) and received significantly fewer treatment cycles (Hb<10g/dL: 5.1 vs 5.8, P<0.04; Plt <150G/mL: 3.4 vs 5.6; P<0.001). Neither extent of bone metastases nor previous chemotherapy were associated with survival, number of 223Ra cycles and HT. CONCLUSION: Patients with metastatic castration-resistant prostate cancer and impaired hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra therapy suffer from significantly more high-grade HT, shorter survival and receive significantly fewer 223Ra treatments. Therefore, Hb-levels and platelet counts are essential parameters for adequate patient selection for 223Ra therapy.

[Hemato-oncological imaging : Importance of hybrid procedures]. / Hämatoonkologische Bildgebung : Stellenwert der Hybridverfahren.

CLINICAL/METHODICAL ISSUE: Biomedical imaging procedures play a major role in hemato-oncological diseases with respect to pre-therapeutic staging and assessment of treatment response. STANDARD RADIOLOGICAL METHODS: Originally, the therapeutic management was the domain of computed tomography (CT) and whole-body magnetic resonance imaging (MRI). METHODICAL INNOVATIONS: Over the last decade these purely morphological techniques have gradually been replaced by hybrid imaging techniques, such as positron emission tomography-CT (PET/CT) and PET/MRI, which also provide metabolic and functional information. PERFORMANCE: For lymphomas, the PET tracer 18F-fluorodeoxyglucose (18 F-FDG) is meanwhile so well-established that its use is a cornerstone of the Lugano classification; however, for multiple myeloma the search for an optimal PET tracer that can also detect early disease stages is still ongoing. Functional MRI techniques, such as diffusion-weighted imaging (DWI), perfusion-weighted imaging and dynamic contrast-enhanced imaging have shown promising results for both lymphomas and multiple myelomas. ACHIEVEMENTS: The PET/MRI technique can combine the different types of information due to its truly multiparametric approach. PRACTICAL RECOMMENDATIONS: In the future PET/MRI could possibly become the hybrid imaging technique of choice for hemato-oncological diseases.

Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors.

OBJECTIVE: To analyze the clinical efficacy of (90)Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. METHODS: Data from 19 pancreatic cancer patients (9 females/10 males) who had received (90)Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. RESULTS: The median age at (90)Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after (90)Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at (90)Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. CONCLUSION: (90)Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities.

Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.

PURPOSE: Diabetes mellitus type 2 (2DM) is associated with altered bone quality. In order to analyze associated changes on a molecular level, we investigated the gene expression of key factors of osteoblast metabolism in type 2 diabetics. METHODS: Total mRNA and protein of bone samples from 2DM patients and non-diabetic patients were isolated, and subsequently, reverse transcription polymerase chain reaction (RT-PCR) or Western blot was performed. Furthermore, pro- and anti-inflammatory serum cytokine levels were determined using a cytokine array. RESULTS: Expression of runt-related transcription factor 2 (RUNX2) was increased by 53 %. Expression of the bone sialoproteins, secreted phosphoprotein 1 (SPP1; osteopontin), and integrin-binding sialoprotein (IBSP), was elevated by more than 50 %, and activating transcription factor 4 (ATF4) expression was 13 % lower in the investigated diabetes group compared to the control group. Similarly, the expression of versican (VCAN) and decorin (DCN) was upregulated twofold in the diabetic group. At the same time, 2DM patients and controls show alterations in pro- and anti-inflammatory cytokine levels in the serum. CONCLUSIONS: This study identifies considerable changes in the expression of transcription factors and extracellular matrix (ECM) components of bone in 2DM patients. Furthermore, the analysis of key differentiation factors of osteoblasts revealed significant alterations in gene expression of these factors, which may contribute to the dysregulation of energy metabolism in 2DM.

Short communication: Is consumption of a cheese rich in angiotensin-converting enzyme-inhibiting peptides, such as the Norwegian cheese Gamalost, associated with reduced blood pressure?

Epidemiological and clinical studies have shown that angiotensin-converting enzyme (ACE)-inhibiting peptides derived from dairy products may decrease blood pressure. These peptides have been identified in many cheeses, and Gamalost, a traditional Norwegian cheese, is particularly rich in these peptides. The aim of this cross-sectional study was to examine whether frequency of Gamalost intake was associated with blood pressure in a Norwegian population sample. Blood pressure and other clinical measurements, including the factors of metabolic syndrome, were obtained from 168 participants (56% female, mean age = 51 yr) who completed a questionnaire about dietary habits and other health-related factors. Mean Gamalost intake was 2 servings per week. The prevalence of hypertension was 23.8% in the population, with mean systolic and diastolic blood pressures of 128 and 78 mmHg, respectively. Intake of Gamalost was inversely associated with systolic blood pressure. Each increase in frequency unit of Gamalost intake corresponded to a reduction in systolic blood pressure of 0.72 mmHg, after controlling for sex, age, education, waist circumference, physical activity, smoking status, and dairy food intake. Results from this study indicate that consumption of Gamalost (or other foods rich in ACE-inhibiting peptides) may reduce blood pressure.

Turnover of Se in adequately fed chickens using Se-75 as a tracer.

Inorganic selenium (Se) in the form of selenite is applied to livestock to avoid Se deficiency. Selenite is, however, an artificial Se source in diets of unsupplemented chickens. It is therefore hypothesized that organic Se sources, such as Se-enriched yeast and wheat, could be a more suitable Se supply in animal nutrition, although information on the transition of Se from organic Se sources in fast-growing chickens is scarce. In this work, chickens were fed a low Se diet (0.27 ± 0.01 mg Se/kg, Se-enriched yeast) until 20 days of age, after which the Se concentration was increased to maximum concentration allowed by the poultry industry in Europe (0.5 p.p.m. Se). At the same time, a daily contribution of carrier-free (75)Se tracer from labelled wheat was administered from day 20 to 27. The chickens showed S and Se homeostasis, as the concentration of S and Se in liver, blood or kidney remained about constant, and steady state of S and Se in the other organs was reached 1 day after the diet shift. The uptake of (75)Se was readily seen in all organs. After 1 week, the depuration of the (75)Se tracer was followed, and biological half-lives and retention in individual organs were determined. The shortest biological half-lives were observed in major metabolic organs, the liver, kidney and pancreas with half-lives close to 4 days. There was a significant (p < 0.05) uptake in lung, brain and muscle that reached steady state when the administration of (75)Se was terminated. The half-life of (75)Se in heart was 9 days and 7 days in blood. The longest half-lives were observed in muscle (12 days), brain and lungs (13 days). All half-lives were shorter than in Se deplete animals.

[Guillain-Barré syndrome with dysphagia after frontal sinusitis]. / Guillain-Barré-Syndrom mit Dysphagie nach Sinusitis frontalis.

One week after an acute sinusitis, a male patient developed a hypernasal voice, dysphagia, diplopic images, ataxia and paresthesias. He had paresis of the glossopharyngeal and abducens nerves, weakness of the arms and legs, and reflex deficiency. The neurography showed a motor axonal demyelinating neuropathy, so that the diagnosis of Guillain-Barré syndrome was made. After five courses of plasmapheresis, the symptoms improved rapidly.

[Importance of PET/CT for imaging of colorectal cancer]. / Stellenwert der PET/CT zur Bildgebung des kolorektalen Karzinoms.

CLINICAL/METHODICAL ISSUE: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has emerged as a very useful imaging modality in the management of colorectal carcinoma. Data from the literature regarding the role of PET/CT in the initial diagnosis, staging, radiotherapy planning, response monitoring and surveillance of colorectal carcinoma is presented. Future directions and economic aspects are discussed. STANDARD RADIOLOGICAL METHODS: Computed tomography (CT), magnetic resonance imaging (MRI) and FDG-PET for colorectal cancer and endorectal ultrasound for rectal cancer. METHODICAL INNOVATIONS: Combined FDG-PET/CT. PERFORMANCE: While other imaging modalities allow superior visualization of the extent and invasion depth of the primary tumor, PET/CT is most sensitive for the detection of distant metastases of colorectal cancer. ACHIEVEMENTS: We recommend a targeted use of PET/CT in cases of unclear M staging, prior to metastasectomy and in suspected cases of residual or recurrent colorectal carcinoma with equivocal conventional imaging. The role of PET/CT in radiotherapy planning and response monitoring needs to be determined. Currently there is no evidence to support the routine use of PET/CT for colorectal screening, staging or surveillance. PRACTICAL RECOMMENDATIONS: To optimally exploit the synergy between morphologic and functional information, FDG-PET should generally be performed as an integrated FDG-PET/CT with a contrast-enhanced CT component in colorectal carcinoma.

[SPECT/CT for staging and treatment monitoring in oncology. Applications in differentiated thyroid cancer and liver tumors]. / SPECT/CT zum initialen Staging und Therapiemonitoring in der Onkologie. Indikationen beim differenzierten Schilddrüsenkarzinom und bei Lebertumoren.

CLINICAL/METHODICAL ISSUE: Hybrid imaging of function and morphology has gained significant importance for lesion detection and treatment monitoring in oncology. In patients with differentiated thyroid carcinoma (DTC) a planar whole body scan is carried out after radioiodine therapy (RIT) for staging. However, due to limited spatial resolution the diagnostic accuracy of this scintigraphy method is impaired. Radioembolization utilizing (90)Yttrium loaded micro-spheres by selective internal radiotherapy (SIRT) allows a minor invasive therapy of primary and secondary liver tumors. In order to avoid side effects of the micro-spheres caused by an outflow into intestines, stomach or lungs, imaging the arteries supplying the liver has to be performed by means of technetium-99m macroaggregated albumin ((99m)Tc-MAA) and scintigraphy. The limited morphological information supplied by scintigraphy is again a challenge in treatment monitoring. STANDARD RADIOLOGICAL/NUCLEAR MEDICAL METHODS: (131)Iodine whole body scanning is used for staging in patients with DTC 3-4 days after ablation. Monitoring of the tumor marker thyroglobulin and selective radioiodine whole body scans are available for patients with a high risk profile in the further follow-up with imaging of the arteries supplying the liver by means of (99m)Tc-MAA scintigraphy in preparation of SIRT. METHODICAL INNOVATIONS: Single photon emission computed tomography/computed tomography (SPECT/CT) of the neck and thorax with a therapeutic activity of radioiodine for staging after ablation. Techniques include imaging of arteries supplying the liver by means of (99m)Tc-MAA SPECT/CT before SIRT and evaluation and quantification of the uptake of liver tumors, especially in comparison to the uptake of liver parenchyma by means of SPECT/CT. PERFORMANCE: Due to the integration of combined functional and morphological information SPECT/CT can be used to characterize the morphology and iodine uptake of lesions more accurately, resulting in optimized staging in patients with DTC in comparison to whole body iodine scans and SPECT/CT provides more accurate imaging of the arterial supply of the liver and of potential outflows of micro-spheres into other organs. SPECT/CT allows evaluation and quantification of the uptake of liver tumors. ACHIEVEMENTS: Improved postablative staging in patients with differentiated thyroid cancer by SPECT/CT in comparison to radioiodine whole body scans can be achieved. Improved planning and monitoring of SIRT therapies utilizing SPECT/CT leads to optimized therapeutic doses within liver lesions. PRACTICAL RECOMMENDATIONS: Integration of SPECT/CT into the clinical standard for postablative staging in patients with DTC is recommended as well as utilization of SPECT/CT during the planning process, for dose calculation and treatment monitoring of SIRT therapies.

Sensorial quality and bone strength of female and male broiler chickens are influenced by weight and growth rate.

1. An experiment was conducted with 98 male and 98 female broiler chickens (Ross 308) to study the effect of growth rate, induced by different dietary means, sex and live weight (1500 g and 2000 g) at slaughter on production parameters, bone strength and sensorial characteristics of the breast meat. 2. The birds were divided into four groups and individually fed a standard commercial diet, a high energy diet or low energy diet from d 11 to slaughter at between d 28 and 39. Three groups were fed ad libitum and a further group was fed a restricted amount of the high energy feed. Half of the birds in each group were slaughtered at approximately 1500 g and the other half at 2000 g live weight. 3. The diets resulted in different growth rates. The chickens fed the high energy and the commercial diet had the highest growth rate at both live weights at slaughter. The restricted fed chickens had lower bone strength than the chickens fed the low energy diet. 4. Breast meat from male broilers was juicer, more tender and less hard than breast meat from females. Chickens slaughtered at 2000 g live weight were juicer than those slaughtered at 1500 g. Chickens given the high energy feed ad libitum and restricted had different growth rates, but the sensory parameter related to texture showed no difference. 5. It was concluded that an increased slaughter weight might improve meat quality due to improved juiciness.

[Gastroenteropancreatic neuroendocrine tumors: diagnosis and therapy in nuclear medicine]. / Neuroendokrine Tumoren des gastroenteropankreatischen Systems: Nuklearmedizinische Diagnostik und Therapie.

The over expression of somatostatin receptors (SSTR) in neuroendocrine tumors (NET) enables diagnosis and targeted therapy using radio-labelled somatostatin analogues. PET with (68)Ga-DOTATATE or (68)Ga-DOTATOC, both with a high affinity to the SSTR subtype 2, enables diagnosis of NET with a very high sensitivity and has a significant influence on the therapeutic management of patients with NET. In particular, therapy with (177)Lu-DOTATATE, which offers a considerably lower nephrotoxicity as compared to (90)Y-DOTATOC, has only few side effects and is usually well tolerated. Up to 46% of patients suffering from GEP-NET show a response to this therapy, which is able to mitigate tumour-related symptoms and significantly improve quality of life.

[Whole-body MRI and FDG-PET/CT imaging diagnostics in oncology]. / Ganzkörper-MRT und FDG-PET/CT in der bildgebenden onkologischen Diagnostik.

The advent of whole-body MRI (WB-MRI) has introduced a systemic approach to oncologic imaging compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as whole-body scanners at 1.5 Tesla and also recently 3 Tesla, combined with acquisition acceleration techniques, have made WB-MRI clinically feasible. With this method dedicated assessment of individual organs with various soft tissue contrast, high spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage.PET/CT has established itself as a powerful modality in the staging of patients suffering from malignant tumors. In addition to the morphologic information provided by the CT component of this hybrid modality, the PET component contributes invaluable metabolic information, which greatly enhances accuracy in the assessment of lymphatic spread and viability of tumor tissue. Whole-body MR diffusion imaging is a novel and promising technique which may contribute to superior sensitivity in the detection of tumor manifestations. In the assessment of distant metastatic spread WB-MRI is highly sensitive and has advantages over PET/CT, especially in those tumors frequently spreading to the liver, bone or brain. WB-MRI is also very attractive as a radiation-free alternative for imaging of pediatric tumor patients in whom multiple follow-up examinations may be required.WB-MRI allows for precise assessment of the bone marrow and has been proven to be highly accurate for the staging of hematologic diseases, such as multiple myeloma. In this article recent developments and applications of WB-MRI in oncologic imaging are addressed and compared to the results of PET/CT.

[Quantification of immunohistochemical expression of somatostatin receptors in neuroendocrine tumors using 68Ga-DOTATATE PET/CT]. / Quantifizierung der Somatostatinrezeptorexpression neuroendokriner Tumoren mit der (68)Ga-DOTATATE-PET/CT.

PURPOSE: The immunohistochemical expression of somatostatin receptor (SSTR) subtype 2 was compared to quantitative (68)Ga-DOTATATE PET in neuroendocrine tumors (NET). MATERIAL AND METHODS: In 27 patients suffering from metastatic NET the expression of somatostatin receptors (SSTR, score 0-3) and the Ki-67 index were assessed. The immunohistochemical findings were compared with the (68)Ga-DOTATATE PET uptake in these tumors using the SUV(max) (standardized uptake value). Both values were compared with the Ki-67 proliferation index. RESULTS: The SUV(max) in NET without SSTR expression was significantly lower compared to those with SSTR expression (p <0.05), even though 3 out of 5 NETs with a score of 0 showed a high uptake of (68)Ga-DOTATATE. The SUV(max) correlated significantly (r=0.40, p <0.05) with the score of immunohistochemical SSTR expression (negative, score 0, moderate, score 1 and high, scores 2 and 3). The Ki-67 index correlated inversely with the SSTR expression score (r=-0.42, p <0.05), but not significantly with the SUV(max) (r=-0.33, p=0.11). CONCLUSION: (68)Ga-DOTATATE uptake was moderately correlated with the results of immunohistochemical SSTR analyses. However, SSTR negative NET may show high uptake of (68)Ga-DOTATATE.

Whole-body MRI at 1.5 T and 3 T compared with FDG-PET-CT for the detection of tumour recurrence in patients with colorectal cancer.

The purpose of this study was to assess the diagnostic accuracy of whole-body MRI (WB-MRI) at 1.5 T or 3 T compared with FDG-PET-CT in the follow-up of patients suffering from colorectal cancer. In a retrospective study, 24 patients with a history of colorectal cancer and suspected tumour recurrence underwent FDG-PET-CT and WB-MRI with the use of parallel imaging (PAT) for follow-up. High resolution coronal T1w-TSE and STIR sequences at four body levels, HASTE imaging of the lungs, contrast-enhanced T1w- and T2w-TSE sequences of the liver, brain, abdomen and pelvis were performed, using WB-MRI at either 1.5 T (n = 14) or 3 T (n = 10). Presence of local recurrent tumour, lymph node involvement and distant metastatic disease was confirmed using radiological follow-up within at least 5 months as a standard of reference. Seventy seven malignant foci in 17 of 24 patients (71%) were detected with both WB-MRI and PET-CT. Both investigations concordantly revealed two local recurrent tumours. PET-CT detected significantly more lymph node metastases (sensitivity 93%, n = 27/29) than WB-MRI (sensitivity 63%, n = 18/29). PET-CT and WB-MRI achieved a similar sensitivity for the detection of organ metastases with 80% and 78%, respectively (37/46 and 36/46). WB-MRI detected brain metastases in one patient. One false-positive local tumour recurrence was indicated by PET-CT. Overall diagnostic accuracy for PET-CT was 91% (sensitivity 86%, specificity 96%) and 83% for WB-MRI (sensitivity 72%, specificity 93%), respectively. Examination time for WB-MRI at 1.5 T and 3 T was 52 min and 43 min, respectively; examination time for PET-CT was 103 min. Initial results suggest that differences in accuracy for local and distant metastases detection using FDG-PET-CT and WB-MRI for integrated screening of tumour recurrence in colorectal cancer depend on the location of the malignant focus. Our results show that nodal disease is better detected using PET-CT, whereas organ disease is depicted equally well by both investigations.

Characterization of the morphology and composition of commercial negative resists used for lithographic processes.

We present a spectroscopic and microscopic characterization of the chemical composition, structure, and morphology of two commercial negative resists using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). For this purpose, films of a novolak-based resist (ma-N 2400) and hydrogen silsesquioxane (HSQ) are treated under different conditions (temperature, deep ultraviolet (DUV) exposure, CHF(3) plasma). Topographic AFM images show that both heating and DUV exposure strongly affect the surface morphology of as-prepared ma-N 2400 resist films. These different treatment conditions also lead to decreasing roughnesses, which indicates structural reorganization. Furthermore, the decrease of the photoactive compound (bisazide) in the ma-N 2400 resist films, observed in FTIR spectra, suggests cross-linking of the resist after CHF(3) plasma treatment, heating, or DUV exposure. XPS measurements on different CHF(3) plasma-treated surfaces reveal that a structurally homogeneous fluorine-containing polymer is generated that is responsible for an enhanced etch resistance. FTIR measurements of HSQ films show a correlation between the degree of HSQ cross-linking and baking time.

Unusual energy shifts in resonant photoemission spectra of organic model molecules.

We study the electronic structure of zinc phthalocyanine (ZnPc) and 1,4-octa-decyl substituted zinc phthalocyanine [(Dec)(8)PcZn] thin films (approximately 6-15 nm) using resonant photoemission spectroscopy and X-ray absorption spectroscopy (XAS) at room temperature and at liquid He temperature. From XAS we conclude that the probability amplitude of the lowest unoccupied molecular orbital is located predominantly at the inner C and N atoms of the molecules. Nonlinear energy shifts in resonant photoemission were observed; large shifts are explained by reduced electrical conductivity of inhomogeneously oriented molecules.