Faculty Bibliography

OBJECTIVE:While single sugar tests are controversially discussed, combination tests with meals are gaining more attention. The aim of this study was to analyze the impact of adding a test meal to lactulose hydrogen breath tests (LHBT) on hydrogen values and abdominal symptoms in patients with functional gastrointestinal disorders (FGIDs). METHODS:Data of 81 FGID patients between 2014-2018 were analyzed. Patients underwent LHBT with 30 g lactulose + 300 mL water and a nutrient challenge test (NCT) including 400 mL liquid test meal + 30 g lactulose. To statistically assess the effect of a test meal on abdominal symptoms and H2, mixed-effect models were used. RESULTS:Adding a test meal to LHBT showed a significant increase in nausea [odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7], decrease in abdominal pain (OR 0.7; 95% CI, 0.6-0.9), borborygmi (OR 0.5; 95% CI, 0.4-0.6), diarrhea (OR 0.4; 95% CI, 0.3-0.6), and H2 production (estimate -5.3, SE 0.7, P < 0.001). The effect on bloating was only significant in functional dyspepsia, irritable bowel syndrome-functional dyspepsia mixed type and functional abdominal pain/bloating (OR 0.1; 95% CI, 0.0-0.2; OR 1.7; 95% CI, 1.2-2.3 resp OR 4.4; 95% CI, 1.8-10.6). CONCLUSIONS:Significant effects on abdominal symptoms and H2 production by adding a test meal to LHBT in FGID patients are shown. Increased occurrence of nausea may be caused by gastric/duodenal hypersensitivity; decreased H2, diarrhea and borborygmi by slower and more physiologic gastric emptying resulting in later arrival of the test substance in the bowel. We recommend NCTs instead of LHBT to more physiologically represent FGID patients' meal-induced burden.

BACKGROUND:F-fluorodeoxyglucose (FDG) PET or PET/CT has shown the capacity to better identify the primary tumour site and detect additional sites of metastasis. However, its clinical impact is not well established. We performed a systematic review and meta-analysis of prior studies to assess the impact of FDG-PET or PET/CT on the management of patients with CUP. MATERIALS AND METHODS:Pubmed and EMBASE databases were searched up to 4th February 2021. Studies that reported the proportion of patients with CUP who experienced a management change after FDG-PET or PET/ computed tomography (CT) were included and the proportions were pooled using the random-effects model. Study quality was assessed using QUADAS-2. Subgroup analysis was conducted to explore heterogeneity. RESULTS: = 82%). The specific reason for management change was more commonly detection of the primary site (22% [95% CI 18-28%]) than detection of additional metastatic sites (14% [95% CI 10-19%]). The pooled proportions of patients with management changes were similar among numerous subgroups (range, 32.8%-38.2%). CONCLUSION:FDG-PET or PET/CT had a meaningful impact on the management of patients with CUP. Approximately, a third of patients had their management changed because of FDG-PET or PET/CT results, and this finding was consistent across numerous subgroups.

RATIONALE AND OBJECTIVES:Prostate gland volume (PGV) should be routinely included in MRI reports of the prostate. The recently updated Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 includes a change in the recommended measurement method for PGV compared to version 2.0. The purpose of this study was to evaluate the agreement of MRI-based PGV calculations with the volumetric manual slice-by-slice prostate segmentation as a reference standard using the linear measurements per PI-RADS versions 2.0 and 2.1. Furthermore, to assess inter-reader agreement for the different measurement approaches, determine the influence of an enlarged transition zone on measurement accuracy and to assess the value of the bullet formula for PGV calculation. MATERIALS AND METHODS:Ninety-five consecutive treatment-naive patients undergoing prostate MRI were retrospectively analyzed. Prostates were manually contoured and segmented on axial T2-weighted images. Four different radiologists independently measured the prostate in three dimensions according to PI-RADS v2.0 and v2.1, respectively. MRI-based PGV was calculated using the ellipsoid and bullet formulas. Calculated volumes were compared to the reference manual segmentations using Wilcoxon signed-rank test. Inter-reader agreement was calculated using intraclass correlation coefficient (ICC). RESULTS:Inter-reader agreement was excellent for the ellipsoid and bullet formulas using PI-RADS v2.0 (ICC 0.985 and 0.987) and v2.1 (ICC 0.990 and 0.994), respectively. The median difference from the reference standard using the ellipsoid formula derived PGV was 0.4 mL (interquartile range, -3.9 to 5.1 mL) for PI-RADS v2.0 (p = 0.393) and 2.6 mL (interquartile range, -1.6 to 7.3 mL) for v2.1 (p < 0.001) with a median difference of 2.2 mL. The bullet formula overestimated PGV by a median of 13.3 mL using PI-RADS v2.0 (p < 0.001) and 16.0 mL using v2.1 (p < 0.001). In the presence of an enlarged transition zone the PGV tended to be higher than the reference standard for PI-RADS v2.0 (median difference of 4.7 mL; p = 0.018) and for v2.1 (median difference of 5.7 mL, p < 0.001) using the ellipsoid formula. CONCLUSION:Inter-reader agreement was excellent for the calculated PGV for both methods. PI-RADS v2.0 measurements with the ellipsoid formula yielded the most accurate volume estimates. The differences between PI-RADS v2.0 and v2.1 were statistically significant although small in absolute numbers but may be of relevance in specific clinical scenarios like prostate-specific antigen density calculation. These findings validate the use of the ellipsoid formula and highlight that the bullet formula should not be used for prostate volume estimation due to systematic overestimation.

PURPOSE:Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. METHODS:Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. RESULTS:SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. CONCLUSION:PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy. TRIAL REGISTRATION:This trial was retrospectively registered under the name "Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA" (NCT03187990) on 06/15/2017 ( https://clinicaltrials.gov/ct2/show/NCT03187990 ).

INTRODUCTION/BACKGROUND:The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas. MATERIALS AND METHODS/METHODS:In this retrospective cohort study, we screened over 52'000 PET/CT scans to identify patients diagnosed with either soft tissue, bone or Ewing sarcoma and had a staging scan at our institution before initial therapy. We used a Wilcoxon signed-rank to assess which PET/CT metric was associated with survival in different patient subgroups. Receiver-Operating-Characteristic curve analysis was used to calculate cutoff values. RESULTS:= 0.03). DISCUSSION/CONCLUSIONS:Our analysis shows that the outcome of soft tissue, bone and Ewing sarcomas is associated with different PET/CT metrics. We could not confirm the previously suggested superiority of volume-based metrics in soft tissue sarcomas, for which we found SUVmax to remain the best prognostic factor. However, bone sarcomas should probably be evaluated with tumor volume rather than FDG PET activity.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.

BACKGROUND:Identification of pretherapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F-FDG-positron emission tomography (PET), computed tomography (CT) perfusion and dynamic contrast enhanced magnetic resonance imaging (MRI) in patients with gastro-esophageal cancer and investigated their histopathological correlation. METHODS:Thirty-one consecutive patients (28 males; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (N.=22) and esophageal squamous cell carcinoma (N.=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUV<inf>max</inf>, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum-slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. RESULTS:IVIM and PET parameters showed significant negative correlations: MTV and bval (r<inf>s</inf> =-0.643, P=0.002), TLG and bval (r<inf>s</inf>=-0.699, P<0.01) and TLG and fp (r<inf>s</inf>=-0.577, P=0.006). Positive correlation was found for TLG and D (r<inf>s</inf>=0.705, P=0.000). Negative correlation was found for bval and staging (r<inf>s</inf>=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (r<inf>s</inf>=0.547, P=0.007), BF and regression index (r<inf>s</inf>=0.753, P=0.005) and for time-to-peak and staging (r<inf>s</inf>=0.557, P=0.005). CONCLUSIONS:IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

BACKGROUND:Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa. METHODS:We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D'Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher's, and chi-square tests where used for statistical testing. RESULTS:One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p < 0.001) and D'Amico score (p < 0.05). The rate of free surgical margins and PSA persistence after RPE was 64% and 17% for the CI and 77% and 6% for the PSMA group (p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group. CONCLUSION:Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was associated with a significantly lower rate of postsurgical PSA persistence.

Bone regeneration is a complex process and the clinical translation of tissue engineered constructs (TECs) remains a challenge. The combination of biomaterials and mesenchymal stem cells (MSCs) may enhance the healing process through paracrine effects. Here, we investigated the influence of cell format in combination with a collagen scaffold on key factors in bone healing process, such as mineralization, cell infiltration, vascularization, and ECM production. MSCs as single cells (2D-SCs), assembled into microtissues (3D-MTs) or their corresponding secretomes were combined with a collagen scaffold and incubated on the chicken embryo chorioallantoic membrane (CAM) for 7 days. A comprehensive quantitative analysis was performed on a cellular level by histology and by microcomputed tomography (microCT). In all experimental groups, accumulation of collagen and glycosaminoglycan within the scaffold was observed over time. A pronounced cell infiltration and vascularization from the interface to the surface region of the CAM was detected. The 3D-MT secretome showed a significant mineralization of the biomaterial using microCT compared to all other conditions. Furthermore, it revealed a homogeneous distribution pattern of mineralization deposits in contrast to the cell-based scaffolds, where mineralization was only at the surface. Therefore, the secretome of MSCs assembled into 3D-MTs may represent an interesting therapeutic strategy for a next-generation bone healing concept.

PURPOSE/OBJECTIVE:Zr-immunoPET tracers. METHODS:for normal liver and sites of disease and liver signal-to-noise ratio were measured. RESULTS:Q.Clear reconstructions with β = 3600 provided the highest scores for image quality. Images reconstructed with β-values of 3600 or 5200 using only 50% or 25% of the original counts provided comparable or better image quality scores than standard OSEM reconstruction images using 100% of counts. CONCLUSION/CONCLUSIONS:Zr-immunoPET tracers.