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Mads Hvid Poulsen,1,2 Jørn Skibsted Jakobsen,3 Mike Allan Mortensen,1,4 Poul Flemming Høilund-Carlsen,4,5 Lars Lund1,2,41Department of Urology, Odense University Hospital, Odense, Denmark; 2Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark; 3Department of Urology, Herlev and Gentofte University Hospital, Copenhagen, Denmark; 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Department of Nuclear Medicine, Odense University Hospital, Odense, DenmarkObjective: The effect of curative treatment for oligometastatic prostate cancer patients is unsolved, both with regard to morbidity and mortality. With this study, we provide some of the first long-term follow-up data on progression and mortality in oligometastatic prostate cancer patients after curative treatment of their primary tumor.Methods: A cohort of 210 patients with diagnosed prostate cancer was established between 2008 and 2010. All patients were scheduled for intended curative treatment, and all underwent blinded 18F-choline positron-emission tomography/computed tomography at inclusion prior to curative treatment. Upon unblinding, 12 patients (6%) were recategorized as being oligometastatic. They had a mean age of 64 years,median prostate-specific antigen of 18 ng/mL, and median Gleason score of 7. Six patients were staged as T3, one T2, and five T1. The patients had a medianof one bone metastasis (range 1–2). All underwent intended curative radiotherapy or prostatectomy. Mean follow-up was 10.1 (8.9–11.0) years.Results: During follow-up of the 12 patients, three (25%) had biochemical recurrence, two developed castration-resistant disease, and one died due to prostate cancer.Conclusion: Our results suggest that intended curative treatment of the primary tumor in oligometastatic prostate cancer may have a role in highly selected patients.Keywords: prostate cancer, oligometastases, treatment

Abstract Background Otitis media (OM) is a very common condition in children and occurs during years that are critical to the development of learning, literacy, and math skills. Therefore, among a large cohort of Danish conscripts, we aimed to examine the association between hospitalisation with OM in early childhood and cognitive function and educational level in early adulthood. Methods We conducted a population-based prevalence study using linked data from healthcare databases and conscription records of Danish men born between 1977 and 1983. We identified all hospitalisations with OM before 8 years of age. Cognitive function was measured by the Boerge Prien validated group intelligence test (Danish Børge Prien Prøve, BPP). We adjusted for potential confounders with and without stratification by hearing impairment. Furthermore, we examined the association between hospitalisation with OM and the prevalence of having achieved a General Certificate of Secondary Education (GCSE), stratified by quartiles of BPP scores. Results Of the 18 412 eligible conscripts aged 18–25 years, 1000 (5.5%) had been hospitalised with OM before age 8. Compared with conscripts without such a record, the adjusted prevalence ratio (PR) for a BPP score in the bottom quartile was 1.20 (95% confidence interval [CI]: 1.09–1.33). There was no major difference in the proportion of men with a GCSE and those without among those hospitalised with OM in early childhood. For men in the bottom and upper quartiles of BPP scores, the PRs for early childhood hospitalisation with OM were 0.89 (95% CI: 0.59–1.33) and 0.96 (95% CI, 0.88–1.05), respectively. Among men with severe hearing impairment, the proportion with a BPP score in the bottom quartile did not differ between those with and without an OM hospitalisation [PR = 1.01 (95% CI: 0.78–1.34)]. Conclusions Overall, we found that hospitalisation with OM in early childhood was associated with a slightly lower cognitive function in early adulthood. Hospitalisation for OM did not seem to influence the prevalence of GSCE when level of BPP was taken into account.

Introduction: Medical students have previously been shown to be just as effective for video rating as experts. We want to compare medical students to experienced surgeons as video assessors of simulated robot-assisted radical prostatectomy (RARP) performance., Materials and Methods: Video recordings of three RARP modules on the RobotiX (formerly Simbionix) simulator from a previous study were used. Five novice surgeons, five experienced robotic surgeons, and five experienced robotic surgeons in RARP performed a total of 45 video-recorded procedures. The videos were assessed with the modified Global Evaluative Assessment of Robotic Skills tool as both full-length and an edited edition that only included the first 5 minutes of the procedure., Results: Fifty medical students and two experienced RARP surgeons (ES) performed a total of 680 video ratings of full-length videos and 5-minute videos (2-9 ratings per video). Medical students and ES showed poor agreement for both full-length videos and 5-minute videos (0.29 and -0.13, respectively). Medical students could not discriminate between the skill level of the surgeons in either full-length videos or 5-minute videos ( P = 0.053-0.36 and P = 0.21-0.82), whereas ES could discriminate between novice surgeons and experienced surgeons (full-length, P < 0.001, and 5 minutes, P = 0.007) and intermediate and experienced surgeons (full-length, P = 0.001, and 5 minutes, P = 0.01) in both full-length videos and 5-minute videos., Conclusion: We found that medical students cannot be used to assess RARP because they showed poor agreement with the ES rating for both full-length videos and 5-minute videos. Medical students could not discriminate between surgical skill levels., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Society for Simulation in Healthcare.)

Background: Feedback is important for surgical trainees but it can be biased and time-consuming. We examined crowd-sourced assessment as an alternative to experienced surgeons' assessment of robot-assisted radical prostatectomy (RARP)., Methods: We used video recordings (n = 45) of three RARP modules on the RobotiX, Simbionix simulator from a previous study in a blinded comparative assessment study. A group of crowd workers (CWs) and two experienced RARP surgeons (ESs) evaluated all videos with the modified Global Evaluative Assessment of Robotic Surgery (mGEARS)., Results: One hundred forty-nine CWs performed 1490 video ratings. Internal consistency reliability was high (0.94). Inter-rater reliability and test-retest reliability were low for CWs (0.29 and 0.39) and moderate for ESs (0.61 and 0.68). In an Analysis of Variance (ANOVA) test, CWs could not discriminate between the skill level of the surgeons (p = 0.03-0.89), whereas ES could (p = 0.034)., Conclusion: We found very low agreement between the assessments of CWs and ESs when they assessed robot-assisted radical prostatectomies. As opposed to ESs, CWs could not discriminate between surgical experience using the mGEARS ratings or when asked if they wanted the surgeons to perform their robotic surgery., (© 2023. The Author(s).)

Objective: To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer., Results: Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (< 0.1 ng/ml) at follow-up 6 months after surgery. One patient with longer follow-up than 6 months experienced biochemical recurrence. At 3-months follow-up all patients reported considerable incontinence, at 6-month follow-up, pad usage decreased to 1 or 2 pads daily. Based on our initial results, the idea to introduce sRARP as a nationwide option remains and further patients will be included to establish the true role of sRARP in patients with recurrence after primary radiotherapy for PCa., (© 2022. The Author(s).)

Introduction: Lymph node metastases are a key prognostic factor in prostate cancer (PCa), but detecting lymph node lesions from PET/CT images is a subjective process resulting in inter-reader variability. Artificial intelligence (AI)-based methods can provide an objective image analysis. We aimed at developing and validating an AI-based tool for detection of lymph node lesions., Methods: A group of 399 patients with biopsy-proven PCa who had undergone 18 F-choline PET/CT for staging prior to treatment were used to train (n = 319) and test (n = 80) the AI-based tool. The tool consisted of convolutional neural networks using complete PET/CT scans as inputs. In the test set, the AI-based lymph node detections were compared to those of two independent readers. The association with PCa-specific survival was investigated., Results: The AI-based tool detected more lymph node lesions than Reader B (98 vs. 87/117; p = .045) using Reader A as reference. AI-based tool and Reader A showed similar performance (90 vs. 87/111; p = .63) using Reader B as reference. The number of lymph node lesions detected by the AI-based tool, PSA, and curative treatment was significantly associated with PCa-specific survival., Conclusion: This study shows the feasibility of using an AI-based tool for automated and objective interpretation of PET/CT images that can provide assessments of lymph node lesions comparable with that of experienced readers and prognostic information in PCa patients., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Purpose: Definitive diagnosis of prostate cancer is based on biopsies, a procedure associated with side-effects. The use of biomarkers in blood and urine could potentially help clinicians select patients for whom biopsies are needed. The aim of the study was to test a new urine and plasma biomarker test in detecting medium and high grade prostate cancer. Materials and methods: Blood and urine samples were prospectively collected from 41 patients prior to prostate biopsy or TUR-P and again after 3 months. The cohort included patients with suspicion of prostate cancer and patients with prior prostate cancer diagnosis. The mRNA expression of ten selected genes measured by PCR were used together with clinical data in multiple algorithms for prediction of medium-high grade prostate cancer in prostate biopsies. The testing was originally developed and validated in the USA. The method was transferred to a local Danish laboratory. Medium and high grade cancer was defined as Gleason score ≥ 3 + 4. Results: Using the biomarker test, prior to any prostate procedures, the sensitivity for detecting medium-high grade prostate cancer was 100% and the specificity was 56% and 63%, depending on the cut-off point used. When using the biomarker test, following biopsy or TUR-P, the sensitivity and specificity were reduced to 89% and 28-34% respectively. When comparing results, there was a significant difference ( p  < 0.05), favoring the test performed prior to the procedures. Conclusions: We were able to predict the presence of medium-high grade prostate cancer, thereby confirming earlier findings of the biomarker test.

Aim: To test the feasibility of a fully automated artificial intelligence-based method providing PET measures of prostate cancer (PCa)., Methods: A convolutional neural network (CNN) was trained for automated measurements in 18 F-choline (FCH) PET/CT scans obtained prior to radical prostatectomy (RP) in 45 patients with newly diagnosed PCa. Automated values were obtained for prostate volume, maximal standardized uptake value (SUV max ), mean standardized uptake value of voxels considered abnormal (SUV mean ) and volume of abnormal voxels (Vol abn ). The product SUV mean  × Vol abn was calculated to reflect total lesion uptake (TLU). Corresponding manual measurements were performed. CNN-estimated data were compared with the weighted surgically removed tissue specimens and manually derived data and related to clinical parameters assuming that 1 g ≈ 1 ml of tissue., Results: The mean (range) weight of the prostate specimens was 44 g (20-109), while CNN-estimated volume was 62 ml (31-108) with a mean difference of 13·5 g or ml (95% CI: 9·78-17·32). The two measures were significantly correlated (r = 0·77, P<0·001). Mean differences (95% CI) between CNN-based and manually derived PET measures of SUVmax, SUVmean, Vol abn (ml) and TLU were 0·37 (-0·01 to 0·75), -0·08 (-0·30 to 0·14), 1·40 (-2·26 to 5·06) and 9·61 (-3·95 to 23·17), respectively. PET findings Vol abn and TLU correlated with PSA (P<0·05), but not with Gleason score or stage., Conclusion: Automated CNN segmentation provided in seconds volume and simple PET measures similar to manually derived ones. Further studies on automated CNN segmentation with newer tracers such as radiolabelled prostate-specific membrane antigen are warranted., (© 2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: The use of molecular imaging in staging of prostate cancer (PC) is debated. In patients with newly diagnosed PC we investigated the diagnostic value of 18 F-flouromethylcholine positron emission tomography/computed tomography ( 18 F-FCH-PET/CT) for the detection of bone and lymph node metastases compared to whole-body bone scintigraphy (WBS) with technetium-99-methylene diphosphonate ( 99m Tc-MDP) and results of extended pelvic lymph node dissection, respectively., Materials and Methods: Between January 2013 and April 2016, 143 patients, aged 49-83, mean 69, years with newly diagnosed PC and disease characteristics necessitating WBS underwent both WBS and 18 F-FCH-PET/CT using magnetic resonance imaging as standard. Eighty of these patients underwent pelvic lymph node dissection as part of radical prostatectomy or prior to external beam radiation and in these results of 18 F-FCH-PET/CT were compared to histologic findings., Results: Bone metastases were detected in 8/143 patients and sensitivity and specificity of WBS were 37.5% and 85.2% versus 100.0% and 96.3% with 18 F-FCH-PET/CT, P=0.63 and 0.002, respectively. Histologically confirmed metastases to regional lymph nodes were found in 25/80 patients. Suspicious choline uptake on PET/CT in pelvic lymph nodes was found in 35 patients. Sensitivity, specificity, PPV, NPV and accuracy of 18 F-FCH-PET/CT in detection of lymph node metastases were 62.5%, 69.6%, 46.9%, 81.3% and 67.5%, respectively., Conclusions: Findings in this study suggested that 18 F-FCH-PET/CT is a more sensitive and specific method for detection of bone metastases from PC than WBS and could potentially reduce the need for confirmatory imaging if used instead of WBS. However, 18 F-FCH-PET/CT performs sub-optimally in pre-operative staging of lymph node metastases in patients undergoing extended pelvic lymph node dissection.

Objective: This proof of concept study investigated whether dual time point FDG-PET/CT with image acquisition after 1 and 3 h could be useful in preoperative staging of patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection for high-risk prostate cancer., Results: Twenty patients with high-risk prostate cancer underwent dual time point FDG-PET/CT before undergoing surgery. Histologically confirmed lymph node metastases were found in 9/20 (45%). A median of 19 (range 10-41; n = 434) lymph nodes were removed per patient. Pelvic lymph nodes with detectable FDG uptake were seen in two patients only, but the FDG-avid lesion on PET did not correspond with pathological findings in either patient. We found a significant increase in maximal standardized uptake value of the prostate of around 30% between early and late imaging. We found no correlation between clinical findings after radical prostatectomy and PET measurements.

A three component one-pot cascade reaction was developed for the synthesis of 1,4,5-trisubstituted γ-lactams. The resulting scaffold can be modified independently at three positions, two of which are conveniently accessed by changing the components of the one-pot reaction. The phases of building block generation, scaffold synthesis and subsequent appendage modification were adapted to library production, which resulted in a screening library of 500 compounds., (Copyright © 2015 Elsevier Ltd. All rights reserved.)