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Background and objective: Prostate cancer, the most common cancer among men worldwide, has significant impact on quality of life. Supportive care needs for those affected by prostate cancer are not well understood. This study aims to describe patient-reported unmet needs and explore supportive care priorities of men treated for prostate cancer. Methods: A cross-sectional survey was distributed to all men who had accessed prostate cancer services (including surgical, radiation, and medical oncology treatment modalities) at a tertiary hospital. The survey included qualitative questions exploring patient experience and a validated patient-reported outcome measure (Supportive Care Needs Survey Short Form 34). Clinical information was collected. Analyses included, descriptive statistics, multivariate logistic regression models and qualitative analyses using a framework method. Key findings and limitations: A total of 162 participants provided survey data. Domains about information, self-management, and sexual function were the highest ranked items with unmet needs. A qualitative analysis also identified “relationships”, “information”, and “the value of hindsight” constructs. Participants who identified three or more unmet needs expressed treatment regret (odds ratio 5.92, 1.98–22.23, p = 0.01). Conclusions and clinical implications: Understanding the unmet needs of patients may better inform supportive care interventions that address what is important to patients. Importantly, participants valued relationships. There may be opportunities to better meet the needs of patients by improving access to information and self-management resources, particularly around sexuality. Further research is warranted. Patient summary: Prostate cancer and its treatment impacts are not well understood. Prioritisation of relationships and improving access to information and self-management resources are important. Further attention to prostate cancer supportive care in clinical practice is needed.

Abstract Precision radiotherapy, such as targeted radioligand therapy, accentuates the precise delivery of radiation to tumor cells while limiting radiation damage to surrounding normal cells. Although recent clinical trial data has shown targeted radioligand therapy to have significant patient survival benefit, it is still unavoidable that the cancer cells will eventually adapt and develop radioresistance. Thus, the study of radiotherapy‐induced changes in the tumor microenvironment (TME) is crucial for developing strategies to best overcome radioresistance. To this end, organ‐on‐chip (OOC) systems with integrative sensors represent cutting‐edge pre‐clinical models for miniaturized 3D modelling and profiling of the TME. This Review features OOC systems which have demonstrated feasibility for radiation‐associated studies, as well as showcased the progress of different OOC systems for profiling core components of the TME. Furthermore, this Review discusses the knowledge gap in cancer‐on‐chip systems with integrative TME sensors for precision radiotherapy applications. It is anticipated that this Review can kickstart the propagation of new concepts and approaches to drive a new era of miniaturized sensors on OOC systems for precision radiotherapy.

Objective: To conduct a systematic literature review on urethral calculi in a contemporary cohort describing etiology, investigation, and management patterns. Methods: A systematic search of MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Articles, including case reports and case series on urethral calculi published between January 2000 and December 2019, were included. Full-text manuscripts were reviewed for clinical parameters including symptomatology, etiology, medical history, investigations, treatment, and outcomes. Data were collated and analyzed with univariate methods. Results: Seventy-four publications met inclusion criteria, reporting on 95 cases. Voiding symptoms (41.1%), pain (40.0%), and acute urinary retention (32.6%) were common presenting features. Urethral calculi were most often initially investigated using plain X-ray (63.2%), with almost all radio-opaque (98.3%). Urethral calculi were frequently associated with coexistent bladder or upper urinary tract calculi (16.8%) and underlying urethral pathology (53.7%) including diverticulum (33.7%) or stricture (13.7%). Urethral calculi were most commonly managed with external urethrolithotomy (31.6%), retrograde manipulation (22.1%), and endoscopic in situ lithotripsy (17.9%). Conclusion: This unique systematic review of urethral calculi provided a summary of clinical features and treatment trends with a suggested treatment algorithm. Management in contemporary urological practice should be according to calculus size, shape, anatomical location, and presence of urethral pathology.

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4–5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

ObjectivesTo determine the impact of a criteria-led discharge initiative (CLD) on the hospital length of stay of patients undergoing a robotic-assisted laparoscopic prostatectomy (RALP). MethodsThis is a cohort study of prospectively collected data completed at a major tertiary hospital from December 2017 to August 2020. The CLD initiative consists of 4 criteria: clinical haemodynamic stability (heart rate < 100 beats/minute, systolic blood pressure > 100mmHg), a drain output of less than 50 mL, flatulence or bowel movement, and the ability to tolerate an oral diet. The primary outcome was hospital length of stay for patients before and after the introduction of CLD. ResultsOne hundred men undergoing RALP before the implementation of the CLD initiative were compared to 118 men undergoing RALP following the implementation of CLD. The patients had similar baseline demographic features. There was a significant difference found in hospital LOS with the pre-CLD group LOS (mean = 1.8 days, SE = 0.12) being longer than the LOS in the post-CLD group (mean = 1.4 days, SE = 0.09, P = 0.015). There were no significant between-group differences in the proportion of patients discharged on the first postoperative day and the 30-day readmission rate. ConclusionWithin our study population, we have demonstrated that the introduction of CLD was associated with reduced hospital LOS with no increase in adverse events. These findings support the need for the development of CLD in other conditions.

Abstract Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect multiparametric magnetic resonance imaging (mpMRI)-invisible prostate tumours and improve the sensitivity of detection of prostate cancer (PCa) in comparison to mpMRI alone. Numerous risk calculators have been validated as tools for stratification of men at risk of being diagnosed with clinically significant (cs)PCa. Objective: To develop a novel risk calculator using clinical parameters and imaging parameters from mpMRI and PSMA PET/CT in a cohort of patients undergoing mpMRI and PSMA PET/CT before biopsy. Design, setting, and participants: A total of 291 men from the PRIMARY prospective trial underwent mpMRI and PSMA PET/CT before transperineal prostate biopsy with sampling of systematic and targeted cores. Outcome measurements and statistical analysis: Novel risk calculators were developed using multivariable logistic regression analysis to predict detection of overall PCa (International Society of Urological Pathology grade group [GG] ≥1) and csPCa (GG ≥2). The risk calculators were then compared with the European Randomised Study of Screening for Prostate Cancer risk calculator incorporating mpMRI (ERSPC-MRI). Resampling methods were used to evaluate the discrimination and calibration of the risk calculators and to perform decision curve analysis. Results and limitations: Age, prostate-specific antigen, prostate volume, and mpMRI Prostate Imaging-Reporting and Data System scores were included in the MRI risk calculator, resulting in area under the receiver operating characteristic curve (AUC) values of 0.791 for overall PCa (GG ≥1) and 0.812 for csPCa (GG ≥2). Addition of the maximum standardised uptake value (SUVmax) on PSMA PET/CT for the prostate lesion, and of SUVmax for the mpMRI lesions for the MRI-PSMA risk calculator resulted in AUCs of 0.831 for overall PCa and 0.876 for csPCa (≥ISUP2).The ERSPC-MRI risk calculator had AUCs of 0.758 (p = 0.02) for overall PCa and 0.805 (p = 0.001) for csPCa. Both the MRI and MRI-PSMA risk calculators were superior to the ERSPC-MRI for both overall PCa and csPCa. Conclusions: These novel risk calculators incorporate clinical and radiological parameters for stratification of men at risk of csPCa. The risk calculator including PSMA PET/CT data is superior to a calculator incorporating mpMRI data alone. Patient summary: We evaluated a new risk calculator that uses clinical information and results from two types of scan to predict the risk of clinically significant prostate cancer on prostate biopsy. This risk model can guide patients and clinicians in shared decision-making and may help in avoiding unnecessary prostate biopsies.

Abstract. Objectives. This study aimed to describe patterns of presentation, etiology, risk factors, management, and treatment outcomes of periurethral abscesses using a systematic review framework. Materials and methods. After prospective registration on the PROSPERO database (CRD42020193063), a systematic review of Web of Science, Embase, PubMed, and Cochrane scientific databases was performed. Articles published between 1900 and 2021 were considered. Extracted data included symptoms, etiology, medical history, investigations, treatment, and outcomes. Collated data were analyzed using univariate methods. Results. Sixty articles met the inclusion criteria reporting on 270 patients (211 male, 59 female) with periurethral abscess. The most common clinical features were pain (41.5%), pyuria (41.5%), dysuria (38.5%), urinary frequency (32.3%), fever (25%), and a palpable mass (23%). Predisposing risk factors included the presence of a sexually transmitted infection or urinary tract infection (55.0%), urethral strictures (39.6%), and recent urethral instrumentation (18.7%). Management approaches included open incision and drainage (64.3%), conservative management with antibiotics (29.8%), and minimally invasive techniques (needle aspiration, endoscopic drainage). Time trend analysis of etiology revealed a decreased incidence of infection (sexually transmitted infection/urinary tract infection, human immunodeficiency virus) and higher incidence of diabetes mellitus and periurethral bulking injections in recent years. Conclusions. Periurethral abscesses may display a wide range of clinical features. Presentation, risk factors and underlying etiology vary with sex. The optimal management technique is guided by abscess size. Open incision and drainage combined with antibiotics continues to be the mainstay of management. However, minimally invasive techniques are gaining favor. To the authors' knowledge, this is the first systematic appraisal and management algorithm for periurethral abscess.

Abstract A South Asian (SA) cardiovascular phenomenon exists whereby SAs have excess burden of cardiovascular disease (CVD) despite having low prevalence of recognized CVD risk factors. The aim of the current study was to determine whether perturbations in monocyte biology contribute to this phenomenon via higher circulating cell numbers, a more pro‐inflammatory phenotype, and higher transmigration and adhesion. Adhesion is linked to vascular inflammation whereas transmigration is linked to tissue inflammation. SA men with (N = 10; SAs with central obesity [CO‐SA]) and without (N = 10; lean SA [LE‐SA]) central obesity, plus White European counterparts (N = 10; white Europeans with central obesity [CO‐WE], N = 10; lean white Europeans [LE‐WE]) participated. An ex vivo assay mimicking blood flow dynamics coupled to flow cytometry determined the adhesion and transmigration of monocyte subsets toward chemokine‐rich media cultured from pre‐adipocytes (absolute responses). Migration and adhesion were also standardized for differences in numbers of circulating monocytes between participants (relative responses). Metabolic and inflammatory markers were assessed. SAs had higher absolute (but not relative) adhesion and migration of monocytes than WEs. Central obesity was associated with higher absolute and relative adhesion and migration of monocytes. SAs had higher concentrations of all monocyte subsets compared with WEs coinciding with adverse cardiovascular‐inflammatory profiles. LE‐SAs had similar monocyte concentrations, transmigration, and adhesion compared with CO‐WEs, corresponding with similar cardiovascular‐inflammatory profiles. The study provides novel evidence for higher monocyte counts associated with higher transmigration and adhesion in SA compared with WE men. Importantly, similar monocyte biology and cardiovascular‐inflammatory profiles were seen in LE‐SAs compared with CO‐WEs, which may contribute to the higher risk of CVD at lower body mass index experienced by SAs.

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Urosymphyseal fistula (UF) is an uncommon complication in patients with prostate cancer who undergo radiation therapy. UF formation can lead to complications such as symphyseal septic arthritis or osteomyelitis with consequences of severe illness and pain. Often major surgical correction is required, however this case report demonstrates that a less invasive approach may be successful in select patients.

Testicular torsion (TT) is a urological emergency, which requires a time-sensitive approach to diagnosis and management. TT predominantly presents with severe, sudden onset, unilateral testicular pain in men under the age of 21. It is a clinical diagnosis with assistance from a scrotal ultrasound or confirmation via scrotal exploration. Here we present an interesting case of a 67-year-old man with TT. This case demonstrates that medical professionals should have a high degree of clinical suspicion for men of all ages with unilateral scrotal pain.

Abstract Background Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. Results The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78–91%) and 60% (95% CI 50–68%) and a sensitivity of 36% (95% CI 25–49%) and 62% (95% CI 49–74%), respectively, for detection of metastatic disease. Conclusion Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC.

Purpose: Testosterone replacement therapy (TRT) is commonly used for various causes of androgen deficiency and subsidized by the Pharmaceutical Benefits Scheme (PBS) in Australia when appropriate. In response to a sharp increase in the prescribing of subsidized TRT, the Australian government instituted new, stricter prescription criteria in April 2015. We aim to demonstrate longitudinal changes in the prescription patterns of subsidized TRT over time. Materials and Methods: The publicly available PBS database was accessed for TRT prescription data between 1992–2018. Population estimate data was collected from the Australian Bureau of Statistics for population-adjustment. Data analysis was performed according to class and specific formulation of TRT. Total and population-adjusted trends were considered, as was indexation to 2015 when restrictions were implemented. Results: Longitudinal trends in subsidized TRT prescription demonstrated a progressive overall increase since 2000, according to total prescriptions and population-adjusted estimates, with greater use of topical formulations (gel, patch, cream/spray) and injections. Since 2015, a 37% decline in total population-adjusted prescriptions was observed (1,399–883 per 100,000 persons). Since 2015, relatively increased use of injections (50%) and 1% gel (30%) comprise the majority of contemporary TRT. Annual financial burden due to TRT was $AU16,768 per 100,000 persons prior to 2000 (mean cost 1992–2000), increasing to $AU112,539 in 2018 (due to use of injections). The rate of change in costs slowed after the restrictions were introduced in 2015. Conclusions: The restrictions in subsidized TRT eligibility enforced by the PBS have reduced overall TRT prescriptions and slowed the cumulative financial burden.

In contemporary urological practice periurethral abscesses are rare. We report the case of a 61-year-old presenting with a painless penile mass and urinary retention. He underwent imaging with ultrasonography, targeted antibiotics and successful source control through open incision and drainage. He has been symptom, recurrence and complication free at 24 months post intervention. Risk factors for abscesses include obstruction, trauma, urethral diverticula and urethral carcinoma. Inadequate detection and treatment may lead to urethral fistulae, strictures and rarely, necrotizing fasciitis. To our knowledge, this is the first report of a periurethral abscess presenting as a painless penile mass causing urinary retention.

Abstract Background Spontaneous renal fornix rupture (SRFR) causing urinoma is an uncommon but serious condition in pregnancy. Limited information is available to describe the natural history and outcomes to guide appropriate treatment. The aim of this study was to determine the natural history and outcomes of SRFR to determine appropriate management recommendations. Methods A systematic review of literature databases was performed, using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) checklist from 1950 – April 2020. Inclusion criteria included any urinary extravasation from the kidney or ureter during pregnancy, or in the 8 weeks following delivery, confirmed via imaging or surgery. Haematomas and non-confirmed cases were excluded. Results A total of 1579 records were originally identified, of which 39 case reports were appropriate for inclusion. SRFR was most commonly reported during the first pregnancy (72%), 19/30 during the third trimester and 9 in the post-natal period. All patients presented with pain, with haematuria positive on urine dipstick in only 36% of 26 reported cases. Ultrasound was the most frequently used imaging modality, resulting in a diagnosis in 42% of cases. All cases reported on treatment procedures including ureteric stents (46%), percutaneous drain (15%), conservative management (15%), nephrostomy (13%) and ureteral catherization (10%). Long term urological outcomes were positive, however women suffering SRFR were significantly more likely to undergo pre-term labour. Conclusion While selected cases may be successfully managed conservatively, urinary diversion, through ureteric stents, should be considered the management of choice in these individuals. Clinicians should be mindful of an increased risk of premature delivery and its’ associated negative fetal outcomes.

Isolated prostate cancer metastasis to the adrenal gland is rare. We report a case of concordant high uptake in a solitary adrenal metastasis on both prostate-specific membrane antigen and fluorodeoxyglucose positron-emission tomography in a patient with castrate-resistant prostate cancer. Good initial biochemical response was achieved with laparoscopic adrenalectomy. The patient developed lymph node recurrence 12 months later, although remains asymptomatic on hormonal treatment 22 months post-operatively, in keeping with prior results for metastasis-directed therapy which can delay time to additional treatment. Application of dual tracer PET can be valuable for prostate cancer staging and guidance of metastasis-directed treatment.

PSMA PET is more accurate than conventional imaging (CT/bone scan) for staging of intermediate- or high-risk prostate cancer (PCa), but 5–10% of primary tumours have low PSMA ligand uptake. FDG PET has been used to further define disease extent in end-stage castrate-resistant PCa and may be beneficial earlier in the disease course for more accurate staging. The objective of this study was to review the available evidence for patients undergoing both FDG and PSMA PET for PCa staging at initial diagnosis and in recurrent disease. A systematic literature review was performed for studies with direct, intraindividual comparison of PSMA and FDG PET for staging of PCa. Assessment for radioligand therapy eligibility was not considered. Risk of bias was assessed. 543 citations were screened and assessed. 13 case reports, three retrospective studies, and one prospective study were included. FDG after PSMA PET improved the detection of metastases from 65% to 73% in high-risk early castration-resistant PCa with negative conventional imaging (M0). Positive FDG PET was found in 17% of men with negative PSMA PET for postprostatectomy biochemical recurrence. Gleason score ≥8 and higher PSA levels predicted FDG-avid metastases in BCR and primary staging. Variant histology (ductal and neuroendocrine) was common in case reports, resulting in PSMA-negative FDG-positive imaging for 3 patients. Dual-tracer PET for PCa may assist in characterising high-risk disease during primary staging and restaging. Further studies are required to determine the additive benefit of FDG PET and if the FDG-positive phenotype may indicate a poorer prognosis.

Background: Diagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort. Materials and methods: Seminal plasma samples of 151 men being investigated for prostate cancer were analyzed with 1H-NMR spectroscopy. After adjustment for buffer (add-to-subtract) and endogenous enzyme influence on metabolites, metabolite profiling was performed with multivariate statistical analysis (principal components analysis, partial least squares) and targeted quantitation. Results: Seminal plasma metabolites best predicted low- and intermediate-risk prostate cancer with differences observed between these groups and benign samples. Lipids/lipoproteins dominated spectra of high grade samples with less metabolite contributions. Overall prostate cancer prediction using previously described metabolites was not validated. Conclusion: Metabolomics of seminal plasma in vitro may assist urologists with diagnosis and monitoring of either low or intermediate grade prostate cancer. Less clinical benefit may be observed for high-risk patients. Further investigation in active surveillance cohorts, and/or in combination with in vivo magnetic resonance spectroscopic imaging may further optimize localized prostate cancer outcomes.

Background: Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers. Methods: Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D’Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis. Results: From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size. Conclusion: PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination–urine markers.

GPS campaigns on glaciers during jökulhlaups show how subglacial floods affect glacier motion and shed light on the dynamics of such floods. Three such campaigns have been carried out on southern and western Vatnajökull, southeast Iceland, over known jökulhlaup paths. Two slowly rising jökulhlaups from Grímsvötn and two rapidly rising jökulhlaups from the western and eastern Skaftá cauldrons were captured in these campaigns, with maximum discharge ranging from 240 to 3300 m3 s−1. Glacier surface movements measured in these campaigns are presented along with the corresponding discharge curves. The measurements are interpreted as indicating: (1) initiation of rapidly rising jökulhlaups with a propagating subglacial pressure wave, (2) decreased glacier basal friction during jökulhlaups, (3) subglacial accumulation of water in slowly rising jökulhlaups and (4) lifting of the glacier caused by subglacial water pressure exceeding overburden in both rapidly and slowly rising jökulhlaups. The latter two observations are inconsistent with assumptions that are typically made in theoretical and numerical modelling of jökulhlaups. Both viscous and elastic deformation of the glacier as well as turbulent hydraulic fracture at the ice/bedrock interface are important in the dynamics of the subglacial pressure wave at the front of rapidly rising jökulhlaups.