Urinary shedding of common DNA viruses and their possible association with bladder cancer: a qPCR-based study.

After a decade of human urinary microbiota research, little is known about the composition of the urinary virome and its association with health and disease. This study aimed to investigate the presence of 10 common DNA viruses in human urine and their putative association with bladder cancer (BC). Catheterized urine samples were collected from patients undergoing endoscopic urological procedures under anesthesia. After DNA extraction from the samples, viral DNA sequences were detected using real-time PCR. Viruria rates were compared between BC patients and controls. A total of 106 patients (89 males and 17 females) were included in the study. Fifty-seven (53.8%) were BC patients and 49 (46.2%) had upper urinary tract stones or bladder outlet obstruction. The viruses detected in the urine were human cytomegalovirus (2.0%), Epstein-Barr virus (6.0%), human herpesvirus-6 (12.5%), human papillomavirus (15.2%), BK polyomavirus (15.5%), torque teno virus (44.2%), and JC polyomavirus (47.6%), while no adenoviruses, herpes simplex virus 1 and 2, or parvoviruses were found. There were statistically significant differences in HPV viruria rates between cancer patients and controls (24.5% vs. 4.3%, p=0.032 after adjustment for age and gender). Viruria rates increased from benign to non-muscle-invasive and muscle-invasive tumors. Patients with a history of BC have higher HPV viruria rates than controls. Whether this relationship is a causal one remains to be established by further research.

Current antibiotic resistance patterns of rare uropathogens: survey from Central European Urology Department 2011-2019.

BACKGROUND: While the resistance rates of commonly detected uropathogens are well described, those of less frequent Gram-negative uropathogenic bacteria have seldom been reported. The aim of this study was to examine the resistance rates of less frequent uropathogenic Gram-negatives in a population of patients treated in a Department of Urology of a tertiary referral centre in Central Europe over a period of 9 years. METHODS: Data on all positive urine samples from urological in- and out-patients were extracted form the Department of Clinical Microbiology database from 2011 to 2019. Numbers of susceptible and resistant isolates per year were calculated for these uropathogens: Acinetobacter spp. (n = 74), Citrobacter spp. (n = 60), Enterobacter spp. (n = 250), Morganella morganii (n = 194), Providencia spp. (n = 53), Serratia spp. (n = 82) and Stenotrophomonas maltophilia (n = 27). Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin and colistin. RESULTS: Penicillin derivatives have generally poor effect except piperacillin/tazobactam. Cefuroxime is not efficient unlike cefotaxime (except against Acinetobacter spp. and S. maltophilia). Susceptibility to fluoroquinolones is limited. Amikacin is somewhat more efficient than gentamicine but susceptibilities for both safely exceed 80%. Nitrofurantoin shows virtually no efficiency. Cotrimoxazole acts well against Citrobacter spp., Serratia spp. and it is the treatment of choice for S. maltophilia UTIs. Among carbapenems, ertapenem was less efficient than meropenem and imipenem except for S. maltophilia whose isolates were mostly not suceptible to any carbapenems. CONCLUSIONS: Uropathogenic microorganisms covered in this report are noteworthy for their frequently multi-drug resistant phenotypes. Knowledge of resistance patterns helps clinicians choose the right empirical antibiotic treatment when the taxonomical assignment of the isolate is known but sensitivity results are pending.

Good long-term visual outcomes of parapapillary choroidal melanoma patients treated with proton therapy: a comparative study.

PURPOSE: To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years. METHODS: This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years. RESULTS: Mean follow-up was 120.8 ± 48.8 months (54.0-295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the "good visual outcome" (GVO) group, while the remaining 246 (79%) constituted the "poor visual outcome" (PVO) group, subdivided into 70 (22%) with a VA of 0.3-1.0 logMAR (0.1-0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (< 0.1 decimal). On multivariate analysis, older age (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P < 0.03), volume of the optic disc and macula receiving 50% of dose (30 CGE) (P = 0.02 and P < 0.001, respectively) were independent negative predictors of GVO. CONCLUSIONS: Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.

Outcomes of adolescents and young adults treated for brain and skull base tumors with pencil beam scanning proton therapy.

BACKGROUND: The use of proton therapy (PT) in adolescents and young adults (AYAs) is becoming increasingly popular. This study aims to assess the outcomes and late toxicity consequences in AYAs (15-39 years) with brain/skull base tumors treated with pencil beam scanning proton therapy. METHODS: One hundred seventy six AYAs treated curatively at the Paul Scherrer Institute (PSI) were identified. Median age was 30 years (range 15-39) and median prescribed dose was 70.0 Gy (relative biological effectiveness [RBE]) (range 50.4-76.0). The most common tumors treated were chordomas/chondrosarcomas (61.4%), followed by gliomas (15.3%), and meningiomas (14.2%). RESULTS: After a median follow up of 66 months (range 12-236), 24 (13.6%) local only failures and one (0.6%) central nervous system (CNS) distant only failure were observed. The 6-year local control, distant progression-free survival, and overall survival were 83.2%, 97.4%, and 90.2%, respectively. The 6-year high-grade (≥grade [G] 3) PT-related late toxicity-free survival was 88.5%. Crude late toxicity rates were 26.2% G1, 37.8% G2, 12.2% G3, 0.6% G4, and 0.6% G5. The one G4 toxicity was a retinopathy and one G5 toxicity was a brainstem hemorrhage. The 6-year cumulative incidences for any late PT-related pituitary, ototoxicity, and neurotoxicity were 36.3%, 18.3%, and 25.6%; whilst high-grade (≥G3) ototoxicity and neurotoxicity were 3.4% and 2.9%, respectively. No secondary malignancies were observed. The rate of unemployment was 9.5% pre-PT, increasing to 23.8% post-PT. Sixty-two percent of survivors were working whilst 12.7% were in education post-PT. CONCLUSIONS: PT is an effective treatment for brain/skull base tumors in the AYA population with a reasonable late toxicity profile. Despite good clinical outcomes, around one in four AYA survivors are unemployed after treatment.

Use of Prostate Specific Antigen Density Combined with Multiparametric Magnetic Resonance Imaging Improves Triage for Prostate Biopsy.

BACKGROUND: Multi-parametric magnetic resonance imaging (mpMRI)-directed biopsy for prostate cancer (PC) diagnosis improves the detection of clinically significant prostate cancer (CSPC) and decreases the rate of over-diagnosis of insignificant disease. The aim of this study was to investigate the value of mpMRI combined with prostate specific antigen density (PSAD) in the decision making related to the biopsy. METHODS: mpMRI and mpMRI/transrectal ultrasound fusion targeted biopsies with subsequent systematic biopsies were performed in 397 patients (223 biopsy-naïve and 174 with a previous biopsy). Detection rates of (CSPC) and insignificant PC were stratified using the PIRADS score, and the number of avoidable biopsies and missed (CSPC) were plotted against PSAD values of 0.1-0.5 ng/mL2. RESULTS: PIRADS <3 and PSAD <0.2 ng/mL2 were the safest criteria for not performing a biopsy. When applied to the biopsy-naïve group, 21.5% (48/223) of the biopsies could have been avoided and 3.7% (3/82) of CSPC would have been missed. In the repeat biopsy group, 12.6% (22/174) of biopsies could have been avoided and 6.9% (4/58) of (CSPC) would have been missed. CONCLUSIONS: A combination of mpMRI and PSAD might reduce the number of biopsies performed with the cost of missing <4% of CSPC.

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

PURPOSE: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS: Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS: These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

Comparison of MicroRNA Content in Plasma and Urine Indicates the Existence of a Transrenal Passage of Selected MicroRNAs.

MicroRNAs (miRNAs) in urine are examined as potential biomarkers. We examined the urine samples from 70 individuals (45 males, 25 females, mean age 65 years, range 20-84 years). Of the urine donors, 15 were healthy volunteers, 5 were patients with non-cancer diseases, 50 were patients with different stages of bladder cancer. To examine the spectrum of miRNAs in the cell-free fraction of urine, TaqMan Human miRNA Array Card A v.2.1 was used. A set of 30 miRNAs were found that are constantly present in urine supernatants independently of sex, age and health status of the subjects. We compared this set with miRNAs found in plasma, expressed in kidney and genito-urinary tract. Our results indicate that some miRNA could be transferred from the circulation into urine.

Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer.

INTRODUCTION: Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker. MATERIAL AND METHODS: In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined. RESULTS: The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively. CONCLUSION: Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer.

Oncological Outcomes of Patients with Concomitant Bladder and Urethral Carcinoma.

INTRODUCTION: The study aimed to investigate oncological outcomes of patients with concomitant bladder cancer (BC) and urethral carcinoma. METHODS: This is a multicenter series of 110 patients (74 men, 36 women) diagnosed with urethral carcinoma at 10 referral centers between 1993 and 2012. Kaplan-Meier analysis was used to investigate the impact of BC on survival, and Cox regression multivariable analysis was performed to identify predictors of recurrence. RESULTS: Synchronous BC was diagnosed in 13 (12%) patients, and the median follow-up was 21 months (interquartile range 4-48). Urethral cancers were of higher grade in patients with synchronous BC compared to patients with non-synchronous BC (p = 0.020). Patients with synchronous BC exhibited significantly inferior 3-year recurrence-free survival (RFS) compared to patients with non-synchronous BC (63.2 vs. 34.4%; p = 0.026). In multivariable analysis, inferior RFS was associated with clinically advanced nodal stage (p < 0.001), proximal tumor location (p < 0.001) and synchronous BC (p = 0.020). CONCLUSION: The synchronous presence of BC in patients diagnosed with urethral carcinoma has a significant adverse impact on RFS and should be an impetus for a multimodal approach.

Treatment and outcomes of urethral recurrence of urinary bladder cancer in women after radical cystectomy and orthotopic neobladder: a series of 12 cases.

INTRODUCTION: The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature. PATIENTS AND METHODS: A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed. RESULTS: The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months. CONCLUSIONS: UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis.

PTCOG Ocular Statement: Expert Summary of Current Practices and Future Developments in Ocular Proton Therapy.

Although rare cancers, ocular tumors are a threat to vision, quality of life, and potentially life expectancy of a patient. Ocular proton therapy (OPT) is a powerful tool for successfully treating this disease. The Particle Therapy Co-Operative Ocular Group (PTCOG Ocular) formulated an Evidence and Expert-Based Executive Summary of Current Practices and Future Developments in OPT: Comparative dosimetric and clinical analysis with the different OPT systems is essential to set up planning guidelines, implement best practices, and establish benchmarks for eye preservation, vision, and quality of life measures. Contemporary prospective trials in select subsets of patients (e.g., tumors near the optic disc and/or macula) may allow for dosimetric and clinical analysis between different radiation modalities and beamline systems to evaluate differences in radiation delivery and penumbra, and resultant tumor control, normal tissue complication rates, and overall clinical cost-effectiveness. To date, the combination of multimodal imaging (fundus photography, ultrasound, etc.), ophthalmologist assessment, and clip surgery with radiation planning have been keys to successful treatment. Increased use of 3D imaging (CT/MRI) is anticipated although its spatial resolution might be a limiting factor (e.g., detection of flat diffuse tumor parts). Commercially produced ocular treatment planning systems are under development and their future use is expected to expand across OPT centers. Future continuity of OPT will depend on (i) maintaining and upgrading existing older dedicated low-energy facilities, (ii) maintaining shared, degraded beamlines at large proton therapy centers, and (iii) developing adapted gantry beams of sufficient quality to maintain the clinical benefits of sharp beam conformity. Option (i) potentially offers the sharpest beams, minimizing impact on healthy tissues, whilst (ii) and (iii) potentially offer the advantage of substantial long-term technical support and development as well as the introduction of new approaches. Significant patient throughputs and close cooperation between medical physics, ophthalmology, and radiotherapy, underpinned by mutual understanding, is crucial for a successful OPT service.

Bladder cancer is associated with decreased urinary microbiota diversity and alterations in microbial community composition.

INTRODUCTION: Human urine microbiota (UM) research has uncovered associations between composition of microbial communities of the lower urinary tract and various disease states including several reports on the putative link between UM and bladder cancer (BC). The aim of this study was to investigate male UM in patients with BC and controls using catheterised urine specimens unlike in previous studies. METHODS: Urine samples were obtained in theatre after surgical prepping and draping using aseptic catheterisation. DNA was extracted and hypervariable region V4 of the 16S rRNA gene was amplified using 515F and 806R primers. Sequencing was performed on Illumina MiSeq platform. Sequencing data were processed using appropriate software tools. Alpha diversity measures were calculated and compared between groups. Prevalence Interval for Microbiome Evaluation was used to test differences in beta diversity. RESULTS: A total of 63 samples were included in the analysis. Mean age of study subjects was 65.1 years (SD 12.5). Thirty-four men had bladder cancer and 29 participants were undergoing interventions for benign conditions (benign prostate hyperplasia or upper urinary tract stone disease). BC patients had lower UM richness and diversity than controls (83 vs. 139 operational taxonomic units, P = 0.015; Shannon index: 2.46 vs. 2.94, P = 0.049). There were specific taxa enriched in cancer (Veillonella, Varibaculum, Methylobacterium-Methylorubrum) and control groups (Pasteurella, Corynebacterium, Acinetobacter), respectively. CONCLUSION: BC patients had lower bladder microbiota richness and diversity than controls. Specific genera were enriched in cancer and control groups, respectively. These results corroborate some of previous reports while contradicting others. Future microbiota research would benefit from parallel transcriptomic/metabolomic analysis.

Multi-camera optical tracking and fringe pattern analysis for eye surface profilometry in ocular proton therapy.

Background and purpose: An optical tracking system for high-precision measurement of eye position and orientation during proton irradiation of intraocular tumors was designed. The system performed three-dimensional (3D) topography of the anterior eye segment using fringe pattern analysis based on Fourier Transform Method (FTM). Materials and methods: The system consisted of four optical cameras and two projectors. The design and modifications to the FTM pipeline were optimized for the realization of a reliable measurement system. Of note, phase-to-physical coordinate mapping was achieved through the combination of stereo triangulation and fringe pattern analysis. A comprehensive pre-clinical validation was carried out. Then, the system was set to acquire the eye surface of patients undergoing proton therapy. Topographies of the eye were compared to manual contouring on MRI. Results: Pre-clinical results demonstrated that 3D topography could achieve sub-millimetric accuracy (median:0.58 mm) and precision (RMSE:0.61 mm) in the clinical setup. The absolute median discrepancy between MRI and FTM-based anterior eye segment surface reconstruction was 0.43 mm (IQR:0.65 mm). Conclusions: The system complied with the requirement of precision and accuracy for image guidance in ocular proton therapy radiation and is expected to be clinically tested soon to evaluate its performance against the current standard.

HPV persistence and its oncogenic role in prostate tumors.

HPV has carcinogenic effects at several anatomical sites in women and men. Whether the presence of HPV in the genitourinary tract of men is associated with a higher prostate cancer risk has been a matter of research for a long-time and the results are still not fully conclusive. Similarly, the question of the reservoir of HPV infection in men is not clearly resolved. HPV DNA presence and types were evaluated by means of polymerase chain reaction in the tissue of 146 patients with benign prostate hyperplasia and prostate cancer. HPV-specific antibodies were analyzed by enzyme-linked immunosorbent assay in the sera of all patients and 172 controls. In addition, 256 biopsies taken from non-tumorous tissues were analyzed. No statistically significant differences were observed in HPV DNA prevalence between patients with benign prostate hyperplasia (2%) and patients with prostatic cancer (2%; P = 1.000). The seropositivity rates did not differ significantly between groups of subjects except for antibodies against HPV 6 VLPs which were found more often in prostate cancer patients (adjusted P = 0.018). Similarly, no difference in the seroprevalence rates for HPV 16 E6 and/or E7 oncoproteins between groups of patients and healthy controls was detected. The overall HPV prevalence in 256 healthy tissue samples was 4%. The results indicate that HPV infection is not associated with prostate oncogenesis in men. However, they imply that multiple tissues of the male genitourinary tract may be important reservoirs for the transmission of some HPV types.

Pretreatment quality assurance of flattening filter free beams on 224 patients for intensity modulated plans: a multicentric study.

PURPOSE: Pretreatment quality assurance data from four centers, members of the European TrueBeam council were analyzed with different verification devices to assess reliability of flattening filter free beam delivery for intensity modulated radiotherapy (IMRT) and RapidArc (RA) techniques. METHODS: TrueBeam(®) (Varian Medical System) is a new linear accelerator designed for delivering flattened, as well as flattening filter free beams. Pretreatment dosimetric validation of plan delivery was performed with different verification devices and responses to high dose rates were tested. Treatment planning was done in Eclipse planning system (PRO 8.9, AAA 8.9). γ evaluation was performed with (dose difference) = 3% and (distance to agreement) = 3 mm scoring the gamma agreement index (GAI, % of field area passing the test). Two hundred and twenty-four patients with 1-6 lesions in various anatomical regions and dose per fraction ranging from 1.8 Gy to 25 Gy were included in the study; 88 were treated with 6 MV flattening filter free (X6FFF) beam energy and 136 with 10 MV flattening filter free (X10FFF) beam. Gafchromic films in solid water, delta(4), arccheck, and matrixx phantom were used to verify the dose distributions. Additionally, point measurements were performed using a PinPoint chamber and a Farmer chamber. RESULTS: Dose calculation as well as dose delivery was equally accurate for IMRT and RA delivery (IMRT: GAI = 99.3% (±1.1); RA: GAI = 98.8% (±1.1) as well as for the two beams evaluated (X6FFF: GAI = 99.1% (±1.0); X10FFF: GAI = 98.8% (±1.2). Only small differences were found for the four verification devices. A point dose verification was performed on 52 cases, obtaining a dose deviation of 0.34%. The GAI variations with number of monitor units were statistically significant. CONCLUSIONS: The TrueBeam FFF modality, analyzed with a variety of verification devices and planned with Eclipse planning system is dosimetrically accurate (within the specified limits 3 mm/3%) for both X6FFF and X10FFF beam energy.

[HIV and male infertility disorders]. / HIV a poruchy muzske plodnosti.

This review article provides information on the impact of HIV-1 on male reproductive functions. HIV-positive patients of reproductive age with now a long-term prognosis may wish to have children. If only one partner is infected, natural conception brings the risk of virus transmission. The article reviews the reproduction possibilities for HIV-positive couples and explains the ways to reduce the risk of transmitting the virus to the healthy partner or a child. Assisted reproduction techniques, especially intrauterine insemination, in vitro fertilization and intracytoplasmic sperm injection in combination with sperm washing can successfully reduce the risk of HIV transmission. Current trends and dilemmas of infertility treatment in HIV-positive couples are discussed.

Bladder Microbiota Are Associated with Clinical Conditions That Extend beyond the Urinary Tract.

BACKGROUND: Since the discovery of the human urinary microbiota (UM), alterations in microbial community composition have been associated with various genitourinary conditions. The aim of this exploratory study was to examine possible associations of UM with clinical conditions beyond the urinary tract and to test some of the conclusions from previous studies on UM. METHODS: Catheterised urine samples from 87 men were collected prior to endoscopic urological interventions under anaesthesia. The composition of the bacterial community in urine was characterized using the hypervariable V4 region of the 16S rRNA gene. Samples from 58 patients yielded a sufficient amount of bacterial DNA for analysis. Alpha diversity measures (number of operational taxonomic units, ACE, iChao2, Shannon and Simpson indices) were compared with the Kruskal-Wallis test. Beta diversity (differences in microbial community composition) was assessed using non-metric dimensional scaling in combination with the Prevalence in Microbiome Analysis algorithm. RESULTS: Differences in bacterial richness and diversity were observed for the following variables: age, diabetes mellitus, dyslipidemia, smoking status and single-dose preoperative antibiotics. Differences in microbial community composition were observed in the presence of chronic kidney disease, lower urinary tract symptoms and antibiotic prophylaxis. CONCLUSIONS: UM appears to be associated with certain clinical conditions, including those unrelated to the urinary tract. Further investigation is needed before conclusions can be drawn for diagnostics and treatment.

MRI and FUNDUS image fusion for improved ocular biometry in Ocular Proton Therapy.

INTRODUCTION: Ocular biometry in Ocular Proton Therapy (OPT) currently relies on a generic geometrical eye model built by referencing surgically implanted markers. An alternative approach based on image fusion of volumetric Magnetic Resonance Imaging (MRI) and panoramic fundus photography was investigated. MATERIALS AND METHODS: Eighteen non-consecutive uveal melanoma (UM) patients, who consented for an MRI and had their tumour base visible on panoramic fundus photography, were included in this comparative analysis. Through generating digitally-reconstructed projections from MRI images using the Lambert azimuthal equal-area projection, 2D-3D image fusion between fundus photography and an eye model delineated on MRI scans was achieved and allowed for a novel definition of the target base (MRI + FCTV). MRI + FCTV was compared with MRI-only delineation (MRIGTV) and the conventional (EyePlan) target definition (EPCTV). RESULTS: The combined use of fundus photography and MRI to define tumour volumes reduced the average discrepancies by almost 65% with respect to the MRI only tumour definitions when comparing with the conventionally planned EPCTV. With the proposed method, shallow sub-retinal tumour infiltration, otherwise invisible on MRI, can be included in the target volume definition. Moreover, a novel definition of the fovea location improves the accuracy and personalisation of the 3D eye model. CONCLUSION: MRI and fundus image fusion overcomes some of the limitations of ophthalmological MRI for tumour volume definition in OPT. This novel eye tumour modelling method might improve treatment planning personalisation, allowing to better anticipate which patients could benefit from prophylactic treatment protocols for radiation induced maculopathy.

GPU accelerated Monte Carlo scoring of positron emitting isotopes produced during proton therapy for PET verification.

Objective.Verification of delivered proton therapy treatments is essential for reaping the many benefits of the modality, with the most widely proposedin vivoverification technique being the imaging of positron emitting isotopes generated in the patient during treatment using positron emission tomography (PET). The purpose of this work is to reduce the computational resources and time required for simulation of patient activation during proton therapy using the GPU accelerated Monte Carlo code FRED, and to validate the predicted activity against the widely used Monte Carlo code GATE.Approach.We implement a continuous scoring approach for the production of positron emitting isotopes within FRED version 5.59.9. We simulate treatment plans delivered to 95 head and neck patients at Centrum Cyklotronowe Bronowice using this GPU implementation, and verify the accuracy using the Monte Carlo toolkit GATE version 9.0.Main results.We report an average reduction in computational time by a factor of 50 when using a local system with 2 GPUs as opposed to a large compute cluster utilising between 200 to 700 CPU threads, enabling simulation of patient activity within an average of 2.9 min as opposed to 146 min. All simulated plans are in good agreement across the two Monte Carlo codes. The two codes agree within a maximum of 0.95σon a voxel-by-voxel basis for the prediction of 7 different isotopes across 472 simulated fields delivered to 95 patients, with the average deviation over all fields being 6.4 × 10-3σ.Significance.The implementation of activation calculations in the GPU accelerated Monte Carlo code FRED provides fast and reliable simulation of patient activation following proton therapy, allowing for research and development of clinical applications of range verification for this treatment modality using PET to proceed at a rapid pace.

Commissioning and quality assurance of a novel solution for respiratory-gated PBS proton therapy based on optical tracking of surface markers.

We present the commissioning and quality assurance of our clinical protocol for respiratory gating in pencil beam scanning proton therapy for cancer patients with moving targets. In a novel approach, optical tracking has been integrated in the therapy workflow and used to monitor respiratory motion from multiple surrogates, applied on the patients' chest. The gating system was tested under a variety of experimental conditions, specific to proton therapy, to evaluate reaction time and reproducibility of dose delivery control. The system proved to be precise in the application of beam gating and allowed the mitigation of dose distortions even for large (1.4cm) motion amplitudes, provided that adequate treatment windows were selected. The total delivered dose was not affected by the use of gating, with measured integral error within 0.15cGy. Analysing high-resolution images of proton transmission, we observed negligible discrepancies in the geometric location of the dose as a function of the treatment window, with gamma pass rate greater than 95% (2%/2mm) compared to stationary conditions. Similarly, pass rate for the latter metric at the 3%/3mm level was observed above 97% for clinical treatment fields, limiting residual movement to 3mm at end-exhale. These results were confirmed in realistic clinical conditions using an anthropomorphic breathing phantom, reporting a similarly high 3%/3mm pass rate, above 98% and 94%, for regular and irregular breathing, respectively. Finally, early results from periodic QA tests of the optical tracker have shown a reliable system, with small variance observed in static and dynamic measurements.