Faculty Bibliography

BACKGROUND:Statins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans. METHODS:A prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a β3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated. RESULTS:0.14, p=0.16, respectively). CONCLUSIONS:Treatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m^-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EE_warm) and after a mild cold stimulus of two hours (EE_cold). CIT was calculated as the difference between EE_cold and EE_warm. BAT activity was assessed by ¹⁸F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EE_cold and CIT were significantly related to levels of free T4 (R² = 0.11, p=0.0025 and R² = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R² = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R² = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.

For clinically significant, locally confined prostate cancer, whole-gland radical prostatectomy and radiotherapy are established effective treatment strategies that, however, come at a cost of significant morbidity related to urinary and sexual side effects. The concept of risk stratification paired with a better understanding of prognostic factors has led to the development of alternative management options including active surveillance and focal therapy for appropriately selected patients with localized disease. High-intensity focused ultrasound (HIFU) is one such minimally invasive, image-guided treatment option for prostate cancer. Due to the relative novelty of HIFU and the increased use of magnetic resonance imaging in prostate cancer, many radiologists are not yet familiar with imaging findings related to HIFU, their temporal evolution as well as imaging appearance of recurrent disease after this type of focal therapy. HIFU induces sharply demarcated, localized coagulative necrosis of a tumor through thermal energy delivered via an endorectal or transurethral ultrasound transducer. In this pictorial review, we aim at providing relevant background information that will guide the reader through the general principles of HIFU in the prostate, as well as demonstrate the imaging appearance of expected post-HIFU changes versus recurrent tumor.

PURPOSE/OBJECTIVE:Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. MATERIALS AND METHODS/METHODS:Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. RESULTS:Y-microspheres was 1.88 µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2 µSv/h. CONCLUSION/CONCLUSIONS:Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5 µSv/h).

BACKGROUND/AIMS:Small intestinal bacterial overgrowth (SIBO) is a common condition in disorders of gut-brain interaction (DGBI). Recently, a combined scintigraphy-lactulose hydrogen breath test (ScLHBT) was described as an accurate tool diagnosing SIBO. We aim to analyze whether a lactulose nutrient challenge test (NCT), previously shown to separate DGBI from healthy volunteers, is equivalent to ScLHBT in diagnosing SIBO. METHODS:We studied data of 81 DGBI patients undergoing ScLHBT with 30 g lactulose and 300 mL water as well as NCT with 30 g lactulose and a 400 mL liquid test meal. Differences in proportion of positive SIBO diagnoses according to specified cecal load and time criteria for NCT and ScLHBT, respectively, were tested in an equivalence trial. An odds ratio (OR) range of 0.80-1.25 was considered equivalent. RESULTS:Diagnosis of SIBO during NCT was not equivalent to SIBO diagnosis in ScLHBT, considering a hydrogen increase before cecal load of 5.0%, 7.5%, or 10.0%, respectively ([OR, 3.76; 90% CI, 1.99-7.09], [OR, 1.87; 90% CI, 1.06-3.27], and [OR, 1.11; 90% CI, 0.65- 1.89]). Considering only time to hydrogen increase as criterion, the odds of a positive SIBO diagnosis in the NCT (0.65) was lower than in ScLHBT (1.70) (OR, 0.38; 90% CI, 0.23-0.65). CONCLUSIONS:This study could not show an equivalence of NCT and ScLHBT in diagnosing SIBO. A possible explanation might be the different transit times owing to unequal testing substances. The effect of this deviation in relation to consecutive therapy regimens should be tested in further prospective studies.

PURPOSE/OBJECTIVE:Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown promise for detecting nodal and distant prostate cancer (PCa) metastases. However, its performance for local tumor staging is not as well established. The purpose of this study was to review the diagnostic performance of PSMA-PET for determining seminal vesical invasion (SVI) and extraprostatic extension (EPE). METHODS:Pubmed and Embase databases were searched until January 12, 2020. Studies assessing accuracy of PSMA-PET in determining SVI and EPE were included. Study quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity were calculated using hierarchical summary receiver operating characteristics modeling. Heterogeneity was explored using meta-regression analyses for anatomical imaging component (MRI vs CT) and by testing for a threshold effect. RESULTS:Twelve studies (615 patients) were included. Pooled sensitivity and specificity were 0.68 (95% CI 0.53-0.81) and 0.94 (95% CI 0.90-0.96) for SVI and 0.72 (95% CI 0.56-0.84) and 0.87 (95% CI 0.72-0.94) for EPE. Meta-regression analyses showed that for SVI, PET/MRI demonstrated greater sensitivity than PET/CT (0.87 [95% CI 0.75-0.98] vs 0.60 [95% CI 0.47-0.74]; p = 0.02 for joint model) while specificity was comparable (0.91 [95% CI 0.84-0.97] vs. 0.96 [95% CI 0.93-0.99]) but not for EPE (p = 0.08). A threshold effect was present for studies assessing EPE (correlation coefficient = 0.563 [95% CI, -0.234-0.908] between sensitivity and false-positive rate). CONCLUSION/CONCLUSIONS:PSMA-PET has moderate sensitivity and excellent specificity for assessing local tumor extent in patients with PCa. PET/MRI showed potential for greater sensitivity than PET/CT in assessing SVI.

OBJECTIVES/OBJECTIVE:To assess interreader agreement of manual prostate cancer lesion segmentation on multiparametric MR images (mpMRI). The secondary aim was to compare tumor volume estimates between MRI segmentation and transperineal template saturation core needle biopsy (TTSB). METHODS:We retrospectively reviewed patients who had undergone mpMRI of the prostate at our institution and who had received TTSB within 190 days of the examination. Seventy-eight cancer lesions with Gleason score of at least 3 + 4 = 7 were manually segmented in T2-weighted images by 3 radiologists and 1 medical student. Twenty lesions were also segmented in apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) series. First, 20 volumetric similarity scores were computed to quantify interreader agreement. Second, manually segmented cancer lesion volumes were compared with TTSB-derived estimates by Bland-Altman analysis and Wilcoxon testing. RESULTS:Interreader agreement across all readers was only moderate with mean T2 Dice score of 0.57 (95%CI 0.39-0.70), volumetric similarity coefficient of 0.74 (0.48-0.89), and Hausdorff distance of 5.23 mm (3.17-9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. CONCLUSIONS:We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors. KEY POINTS/CONCLUSIONS:• Manual prostate cancer segmentation in mpMRI shows moderate interreader agreement. • There are no significant differences between T2, ADC, and DCE segmentation agreements. • There is a systematic difference between volume estimates derived from biopsy and MRI.

BACKGROUND:F]FDG PET/CT. METHODS:in the corresponding tissue depot by simple linear regression. RESULTS: = 0.42, p = 0.009). CONCLUSION/CONCLUSIONS:F] FDG PET-based imaging for quantification of BAT activity. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

PURPOSE/OBJECTIVE:F-FDG PET/MR for the TNM classification. METHOD/METHODS:F-FDG PET/MR for the TNM classification were evaluated. RESULTS:F-FDG PET/MRI without statistical significance (p = 0.3827). CONCLUSION/CONCLUSIONS:F-FDG-PET/MR in this setting is necessary to assess the true value of this modality.

The aim of this study was to test an interactive up-to-date meta-analysis (iu-ma) of studies on MRI in the management of men with suspected prostate cancer. Based on the findings of recently published systematic reviews and meta-analyses, two freely accessible dynamic meta-analyses (https://iu-ma.org) were designed using the programming language R in combination with the package "shiny." The first iu-ma compares the performance of the MRI-stratified pathway and the systematic transrectal ultrasound-guided biopsy pathway for the detection of clinically significant prostate cancer, while the second iu-ma focuses on the use of biparametric versus multiparametric MRI for the diagnosis of prostate cancer. Our iu-mas allow for the effortless addition of new studies and data, thereby enabling physicians to keep track of the most recent scientific developments without having to resort to classical static meta-analyses that may become outdated in a short period of time. Furthermore, the iu-mas enable in-depth subgroup analyses by a wide variety of selectable parameters. Such an analysis is not only tailored to the needs of the reader but is also far more comprehensive than a classical meta-analysis. In that respect, following multiple subgroup analyses, we found that even for various subgroups, detection rates of prostate cancer are not different between biparametric and multiparametric MRI. Secondly, we could confirm the favorable influence of MRI biopsy stratification for multiple clinical scenarios. For the future, we envisage the use of this technology in addressing further clinical questions of other organ systems.