Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis.

INTRODUCTION: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. METHODS: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. RESULTS: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2-8.7) years and 5.7 (IQR 4.8-8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). CONCLUSIONS: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup.

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools.

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures.

Barriers to seeking post-abortion care in Paktika Province, Afghanistan: a qualitative study of clients and community members.

BACKGROUND: Unsafe abortion is a leading cause of maternal mortality. In Afghanistan, which has experienced decades of armed conflict and where abortion is highly restricted, maternal mortality is high at 638 maternal deaths per 100,000 live births. Post-abortion care (PAC) is a lifesaving package of interventions to reduce morbidity and mortality related to induced or spontaneous abortion, but is rarely provided and often of poor quality, particularly in humanitarian settings. In July 2018, we conducted a study to identify the factors that influence access to and use of PAC services at Sharana Provincial Hospital. METHODS: In-depth interviews (IDIs) were conducted with ten women who had received PAC services at Sharana Hospital, and eight focus group discussions (FGDs) were conducted with 40 married women and 40 married men aged 18-45 from four villages surrounding Sharana Hospital. RESULTS: PAC clients and community participants discussed similar barriers to seeking PAC, including cost, distance to the health facility, the need for male accompaniment to seek care, perceived and actual quality of care, stigma and shame. Despite the mentioned stigma around abortion, community members expressed willingness to help women to receive PAC. CONCLUSIONS: Our results suggest that while some barriers are not unique to PAC, others, especially those related to stigma around abortion, may be specific to PAC. It is important for the Ministry of Public Health and its partners to prioritize addressing these barriers to ensure that women have access to this critical life-saving care.

The management impact of 68gallium-tris(hydroxypyridinone) prostate-specific membrane antigen (68Ga-THP-PSMA) PET-CT imaging for high-risk and biochemically recurrent prostate cancer.

PURPOSE: To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). METHODS: One hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded. RESULTS: HR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 µg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 µg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 µg/L, 0%; PSA 0.5-1.0 µg/L, 35%; PSA 1.0-5.0 µg/L, 69%; PSA 5.0-10.0 µg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%). CONCLUSIONS: 68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 µg/L.

Initial outcomes of local anaesthetic freehand transperineal prostate biopsies in the outpatient setting.

OBJECTIVES: To evaluate the histopathological outcomes, morbidity and tolerability of freehand transperineal (TP) prostate biopsies using the PrecisionPoint™ access system (Perineologic, Cumberland, MD, USA) under local anaesthetic (LA) in the day surgery and outpatient environments, as systematic and targeted biopsies can be taken with the potential for reduced morbidity, particularly sepsis. PATIENTS AND METHODS: In all, 176 patients underwent freehand TP prostate biopsies from May 2016 to November 2017. The procedure was carried out either under LA alone or with the addition of sedation. Magnetic resonance imaging (MRI) scans were reported using the Prostate Imaging-Reporting and Data System (PI-RADS), version 2. Tolerability was assessed using a visual analogue scale pain score for each procedural stage. Histopathological outcomes and complications were recorded. RESULTS: The mean (range) age was 65 (36-83) years, median (range) prostate-specific antigen level was 7.9 (0.7-1374) ng/mL, and the mean (range) prostate volume 45 (15-157) mL. Biopsies were taken under LA alone (160 patients, 90%) or under LA with sedation (16, 9%). The main indication for biopsy was primary diagnosis (88.6%). In all, 91 (52%) patients underwent systematic TP biopsies (mean 24.2 cores). Cognitive MRI-targeted biopsies alone were performed in 45 patients (26%; mean 6.8 cores), and 40 (23%) had both systematic and target biopsies (mean 27.9 cores). Of the 75 patients who had primary systematic biopsies alone, 46 (61%) were positive, and 28/46 (60.9%) were diagnosed with clinically significant disease (Gleason ≥3+4). VAS pain scores were greatest during LA administration. There were five complications (2.8%, Clavien-Dindo Grade I/II). No patients developed urosepsis. CONCLUSIONS: Freehand TP biopsies using the PrecisionPoint access system is a safe, tolerable and effective method for systematic and targeted biopsies under LA in the outpatient setting. It has replaced transrectal biopsies in our centre and has potential to transform practice.

A cross-sectional survey of mental health clinicians' knowledge, attitudes, and practice relating to tobacco dependence among young people with mental disorders.

BACKGROUND: Mental health services in England are smoke-free by law and expected to provide comprehensive support to patients who smoke. Although clinicians' knowledge in this area is reported to be limited, research exploring the issue in Child and Adolescent Mental Health Services (CAMHS) is lacking. This study aimed to investigate the knowledge, attitudes, and practice of clinicians working within specialist and highly specialist Child and Adolescent Mental Health Services (CAMHS) relating to tobacco dependence, its treatment and its relation to mental disorder. METHODS: A cross-sectional survey of clinicians working across all CAMHS teams of a large UK National Health Service mental health Trust. RESULTS: Sixty clinicians (50% response rate) completed the survey. Less than half (48.3%) believed that addressing smoking was part of their responsibility, and half (50%) asserted confidence in supporting patients in a cessation attempt. Misconceptions relating to smoking were present across all staff groups: e.g. only 40% of respondents were aware of potential interactions between smoking and antipsychotic medications, although psychiatrists were more knowledgeable than non-medical clinicians (91.6% vs 27.1%; OR 3.4, p < .001). Self-reported attendance at smoking-related training was significantly associated with more proactive clinical practice. CONCLUSIONS: There is a need to improve clinicians' knowledge, capacity and confidence in effectively identifying, motivating, supporting and treating young smokers in the context of treatment for mental disorders.

Radical Prostatectomy for Nonmetastatic Prostate Cancer in Renal Transplant Recipients: Outcomes for a Large Contemporary Cohort and a Matched Comparison to Patients Without a Transplant.

BACKGROUND AND OBJECTIVE: It is unknown whether renal transplant receipt (RTR) status can affect perioperative and oncological outcomes of radical prostatectomy (RP). Our aim was to evaluate oncological and functional outcomes of RTR patients treated with RP for cN0M0 prostate cancer (PCa) via comparison with a no-RTR cohort. METHODS: RTR patients who had undergone RP at seven European institutions during 2001-2022 were identified. A multi-institutional cohort of no-RTR patients treated with RP during 2004-2022 served as the comparator group. Propensity score matching (PSM) at a ratio of 1:4 was used to match no-RTR patients to the RTR cohort according to age, prostate-specific antigen, and final pathology features. We used Kaplan-Meier plots and multivariable Cox, logistic, and Poisson log-linear regression models to test the outcomes of interest. KEY FINDINGS AND LIMITATIONS: After PSM, we analyzed data for 102 RTR and 408 no-RTR patients. RTR patients experienced higher estimated blood loss (EBL), longer length of hospital stay (LOS) and time to catheter removal, higher postoperative complication rates, and a lower continence recovery rate (all p < 0.001). On multivariable analyses, RTR independently predicted unfavorable operative time (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.18-1.25), LOS (OR 1.57, 95% CI 1.32-1.86), EBL (OR 2.24, 95% CI 2.18-2.30), and time to catheter removal (OR 1.93, 95% CI 1.68-2.21), but not complications or continence recovery. There were no significant differences for any oncological outcomes (biochemical recurrence, local or systemic progression) between the RTR and no-RTR groups. While no PCa deaths were recorded, the overall mortality rate was significantly higher in the RTR group (17% vs 0.5%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although RP is feasible for RTR patients, the procedure poses non-negligible surgical challenges, with longer operative time and LOS and higher EBL, but no major differences in terms of complications and continence recovery. The RTR group had similar oncological outcomes to the no-RTR group but significantly higher overall mortality related to causes other than PCa. Therefore, careful selection for RP is required among candidates with previous RTR. PATIENT SUMMARY: Removal of the prostate for prostate cancer is possible in patients who have had a kidney transplant, and cancer control outcomes are comparable to those for the general population. However, transplant patients have a higher risk of death from causes other than prostate cancer and the prostate surgery is likely to be more challenging.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer.

BACKGROUND: The IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual's cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1-<5%), intermediate-risk (5-<20%), and high-risk (≥20%) groups. OBJECTIVE: To externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. DESIGN, SETTING, AND PARTICIPANTS: Prospective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. RESULTS AND LIMITATIONS: There were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. CONCLUSIONS: The IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. PATIENT SUMMARY: We previously developed a calculator that predicts patients' risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

PPIRank - an advanced method for ranking protein-protein interations in TAP/MS data.

BACKGROUND: Tandem affinity purification coupled with mass-spectrometry (TAP/MS) analysis is a popular method for the identification of novel endogenous protein-protein interactions (PPIs) in large-scale. Computational analysis of TAP/MS data is a critical step, particularly for high-throughput datasets, yet it remains challenging due to the noisy nature of TAP/MS data. RESULTS: We investigated several major TAP/MS data analysis methods for identifying PPIs, and developed an advanced method, which incorporates an improved statistical method to filter out false positives from the negative controls. Our method is named PPIRank that stands for PPI ranking in TAP/MS data. We compared PPIRank with several other existing methods in analyzing two pathway-specific TAP/MS PPI datasets from Drosophila. CONCLUSION: Experimental results show that PPIRank is more capable than other approaches in terms of identifying known interactions collected in the BioGRID PPI database. Specifically, PPIRank is able to capture more true interactions and simultaneously less false positives in both Insulin and Hippo pathways of Drosophila Melanogaster.

Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments. There is evidence that the quality of the initial surgical procedure (transurethral resection of bladder tumor [TURBT]) and administration of postoperative bladder chemotherapy significantly reduce cancer recurrence rates and improve outcomes (cancer progression and mortality). There is surgeon-reported evidence that TURBT practice varies significantly across surgeons and sites. There is limited evidence from clinical trials of intravesical chemotherapy that NMIBC recurrence rate varies significantly between sites and that this cannot be accounted for by differences in patient, tumor, or adjuvant treatment factors, suggesting that how the surgery is performed may be a reason for the variation. OBJECTIVE: This study primarily aims to determine if feedback on and education about surgical quality indicators can improve performance and secondarily if this can reduce cancer recurrence rates. Planned secondary analyses aim to determine what surgeon, operative, perioperative, institutional, and patient factors are associated with better achievement of TURBT quality indicators and NMIBC recurrence rates. METHODS: This is an observational, international, multicenter study with an embedded cluster randomized trial of audit, feedback, and education. Sites will be included if they perform TURBT for NMIBC. The study has four phases: (1) site registration and usual practice survey; (2) retrospective audit; (3) randomization to audit, feedback, and education intervention or to no intervention; and (4) prospective audit. Local and national ethical and institutional approvals or exemptions will be obtained at each participating site. RESULTS: The study has 4 coprimary outcomes, which are 4 evidence-based TURBT quality indicators: a surgical performance factor (detrusor muscle resection); an adjuvant treatment factor (intravesical chemotherapy administration); and 2 documentation factors (resection completeness and tumor features). A key secondary outcome is the early cancer recurrence rate. The intervention is a web-based surgical performance feedback dashboard with educational and practical resources for TURBT quality improvement. It will include anonymous site and surgeon-level peer comparison, a performance summary, and targets. The coprimary outcomes will be analyzed at the site level while recurrence rate will be analyzed at the patient level. The study was funded in October 2020 and began data collection in April 2021. As of January 2023, there were 220 hospitals participating and over 15,000 patient records. Projected data collection end date is June 30, 2023. CONCLUSIONS: This study aims to use a distributed collaborative model to deliver a site-level web-based performance feedback intervention to improve the quality of endoscopic bladder cancer surgery. The study is funded and projects to complete data collection in June 2023. TRIAL REGISTRATION: ClinicalTrials.org NCT05154084; https://clinicaltrials.gov/ct2/show/NCT05154084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42254.

HoLEPs: A Comparative Study of Men With Massive Prostate Volumes ≥150 mL and <150 mL.

OBJECTIVE: To assess outcomes following Holmium Laser Enucleation of Prostate (HoLEP) in men with prostate volumes ≥150cc and compare this to men with prostate volumes ≤150 cc. PATIENTS & METHODS: We analyzed our prospective database of consecutive patients undergoing HoLEP in a single tertiary public hospital between October 2016 and January 2019. We excluded patients with clinically significant prostate cancer or neurogenic bladders. Preoperative prostate volume was measured on MRI or ultrasonography. Perioperative variables and functional outcomes were recorded. RESULTS: Of 304 HoLEPs performed, we included 97 patients with prostate volume of ≥150 cc and 186 patients with prostate volume <150 cc. Comparing both cohorts (≥150 cc vs <150 cc): mean age was 71.5 vs 68.3 years, prostate volume 195 cc vs 93 cc, preoperative Qmax 9.6mL/s vs 10mL/s, American Urology Association Symptom Score (IPSS) 21 points vs 20.5 points; mean PSA 13.2µg/L vs 8.8µg/L; laser duration 86 vs 59 minutes; morcellation duration 29 vs 14 minutes; enucleated weight was 124 g vs 60 g. One patient (1%) from the ≥150 cc cohort required a surgical procedure for stress urinary incontinence, and none from the <150 cc cohort, but this did not achieve statistical significance (P = .12). There were no statistically significant differences in postoperative Qmax (32.3 vs 26.4 mL/s; P = .12), IPSS (5.9 points vs 7.3points; P = .23), mean PSA (3.9 µg/L vs 2.2 µg/L; P = .60), stricture incidence (1% vs 2.7%; P = .63), or significant stress urinary incontinence (4.1% vs 0.5%; P = .08). CONCLUSION: Our large series demonstrates that HoLEP is safe and effective in patients with massive prostates (≥150 cc), with similar outcomes compared to patients with prostates <150 cc.

Community perceptions of the impact of war on unintended pregnancy and induced abortion in Protection of Civilian sites in Juba, South Sudan.

Conflict and mass displacement into Protection of Civilian (POCs) sites in South Sudan led to the breakdown of community and family structures, increasing women and girls' vulnerability to gender-based violence and exacerbating already poor sexual and reproductive health outcomes. As one component of a study on post-abortion care, this study explores community perceptions of unintended pregnancy and abortion in a POC in Juba. Four focus group discussions were conducted with 36 women and married men aged 18-45 living in the POC. Although initial reactions to induced abortion were generally negative, participants discussed that unintended pregnancy and induced abortion appeared to have increased during the current conflict. Their discussion of abortion became less condemnatory as they described changes in people's situation due to war, including instability and poverty, transactional sex, disruption of marital norms, rape, and low contraceptive use. This is one of the first studies to investigate community perceptions and practices related to unintended pregnancy and abortion in South Sudan. Despite the beliefs that these are taboo topics, the discussions provide an opening to reduce abortion stigma. To ensure lasting stigma reduction, investment in women and girls to improve gender equity is needed.