Recent Submissions

  • Thulium laser vapo-enucleation treatment for prostates >100 cc following urinary retention

    Patel, Sheena; Khan, Masood (2022-08)
    Introduction: Practical advantages of Thulium in the endoscopic treatment of BPH include its technical versatility, precision and safety, offering reduced need for haemostasis and risk of injury. Evidence has shown Holmium laser to be effective in the treatment of chronic retention, however no studies address the use of Thulium laser for larger prostates after urinary retention. Objectives: We have selected this group in our retrospective analysis on the efficacy of Thulium laser vapo-enucleation for men with both urinary retention and large prostate volumes greater than 100 cc. Methods: We analysed a 10-year single centre operation database of 740 Thulium vapo-enucleation of prostates. An inclusion of 47 living patients with prostates over 100 cc who have undergone the procedure following urinary retention secondary to bladder outflow obstruction (BOO) from benign prostatic hyperplasia (BPH). Patients were sub grouped into Group 1: 100-149 cc and Group 2: >150 cc. Results: Number of patients in sub groups 1 (n = 27) and 2 (n = 20) had mean prostate volumes of 116 and 173 cc respectively, with the largest measuring 234 cc. Mean resected volumes were 26 g (range 15-50.5 g) and 28 g (range 2-57 g). The overall trial without catheter (TWOC) pass rate for all patients in our series was 96% with comparable results between the two groups. Overall known early and late complication rates for all patients was 17% (UTI 13%, urosepsis 2%, AUR 2%) and 12.5% (failure 5%, OAB symptoms 5%, significant haematuria requiring surgical intervention 2.5%) respectively. Success of surgery was 96%, with an average follow-up of 5 months and no re-referrals for lower urinary tract symptoms following discharge. Conclusion: We show the use of Thulium laser vapo-enucleation to be safe and effective in the treatment of retention for large prostates. Results have demonstrated signs of long-term efficacy with a low failure rate.
  • A BURST-BAUS consensus document for best practice in the conduct of scrotal exploration for suspected testicular torsion: the Finding consensus for orchIdopeXy In Torsion (FIX-IT) study

    Asif, Aqua; Summerton, Duncan (2022-06)
    Objectives: To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology. Materials and methods: A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines. Results: Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred. Conclusions: We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.
  • A mutated prostatic acid phosphatase (PAP) peptide-based vaccine induces PAP-specific CD8 + T cells with ex vivo cytotoxic capacities in HHDII/DR1 transgenic mice

    Khan, Masood (2022-04)
    Background: Current treatments for castrate (hormone)-resistant prostate cancer (CRPC) remain limited and are not curative, with a median survival from diagnosis of 23 months. The PAP-specific Sipuleucel-T vaccine, which was approved by the FDA in 2010, increases the Overall Survival (OS) by 4 months, but is extremely expensive. We have previously shown that a 15 amino accid (AA) PAP sequence-derived peptide could induce strong immune responses and delay the growth of murine TRAMP-C1 prostate tumors. We have now substituted one amino acid and elongated the sequence to include epitopes predicted to bind to several additional HLA haplotypes. Herein, we present the immunological properties of this 42mer-mutated PAP-derived sequence (MutPAP42mer). Methods: The presence of PAP-135-143 epitope-specific CD8+ T cells in the blood of patients with prostate cancer (PCa) was assessed by flow cytometry using Dextramer™ technology. HHDII/DR1 transgenic mice were immunized with mutated and non-mutated PAP-derived 42mer peptides in the presence of CAF®09 or CpG ODN1826 (TLR-9 agonist) adjuvants. Vaccine-induced immune responses were measured by assessing the proportion and functionality of splenic PAP-specific T cells in vitro. Results: PAP-135-143 epitope-specific CD8+ T cells were detected in the blood of patients with PCa and stimulation of PBMCs from patients with PCa with mutPAP42mer enhanced their capacity to kill human LNCaP PCa target cells expressing PAP. The MutPAP42mer peptide was significantly more immunogenic in HHDII/DR1 mice than the wild type sequence, and immunogenicity was further enhanced when combined with the CAF®09 adjuvant. The vaccine induced secretory (IFNγ and TNFα) and cytotoxic CD8+ T cells and effector memory splenic T cells. Conclusions: The periphery of patients with PCa exhibits immune responsiveness to the MutPAP42mer peptide and immunization of mice induces/expands T cell-driven, wild-type PAP immunity, and therefore, has the potential to drive protective anti-tumor immunity in patients with PCa.
  • Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study)

    Kockelbergh, Roger (2022-09)
    Objective: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and methods: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results: Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion: Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes.
  • Timing of elective surgery and risk assessment after SARS-CoV-2 infection: an update: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, Centre for Perioperative Care, Federation of Surgical Specialty Associations, Royal College of Anaesthetists, Royal College of Surgeons of England

    Summerton, Duncan (2022-05)
    The impact of vaccination and new SARS-CoV-2 variants on peri-operative outcomes is unclear. We aimed to update previously published consensus recommendations on timing of elective surgery after SARS-CoV-2 infection to assist policymakers, administrative staff, clinicians and patients. The guidance remains that patients should avoid elective surgery within 7 weeks of infection, unless the benefits of doing so exceed the risk of waiting. We recommend individualised multidisciplinary risk assessment for patients requiring elective surgery within 7 weeks of SARS-CoV-2 infection. This should include baseline mortality risk calculation and assessment of risk modifiers (patient factors; SARS-CoV-2 infection; surgical factors). Asymptomatic SARS-CoV-2 infection with previous variants increased peri-operative mortality risk three-fold throughout the 6 weeks after infection, and assumptions that asymptomatic or mildly symptomatic omicron SARS-CoV-2 infection does not add risk are currently unfounded. Patients with persistent symptoms and those with moderate-to-severe COVID-19 may require a longer delay than 7 weeks. Elective surgery should not take place within 10 days of diagnosis of SARS-CoV-2 infection, predominantly because the patient may be infectious, which is a risk to surgical pathways, staff and other patients. We now emphasise that timing of surgery should include the assessment of baseline and increased risk, optimising vaccination and functional status, and shared decision-making. While these recommendations focus on the omicron variant and current evidence, the principles may also be of relevance to future variants. As further data emerge, these recommendations may be revised.
  • VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis

    Morgan, Bruno (2022)
    Background: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit. Methods: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable. Results: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression. Conclusions: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease. Trial registration: NCT02057913.
  • Prostate cancer: early detection and assessing clinical risk using deep machine learning of high dimensional peripheral blood flow cytometric phenotyping data

    Khan, Masood (2021)
    Detecting the presence of prostate cancer (PCa) and distinguishing low- or intermediate-risk disease from high-risk disease early, and without the need for potentially unnecessary invasive biopsies remains a significant clinical challenge. The aim of this study is to determine whether the T and B cell phenotypic features which we have previously identified as being able to distinguish between benign prostate disease and PCa in asymptomatic men having Prostate-Specific Antigen (PSA) levels < 20 ng/ml can also be used to detect the presence and clinical risk of PCa in a larger cohort of patients whose PSA levels ranged between 3 and 2617 ng/ml. The peripheral blood of 130 asymptomatic men having elevated Prostate-Specific Antigen (PSA) levels was immune profiled using multiparametric whole blood flow cytometry. Of these men, 42 were subsequently diagnosed as having benign prostate disease and 88 as having PCa on biopsy-based evidence. We built a bidirectional Long Short-Term Memory Deep Neural Network (biLSTM) model for detecting the presence of PCa in men which combined the previously-identified phenotypic features (CD8+CD45RA-CD27-CD28- (CD8+ Effector Memory cells), CD4+CD45RA-CD27-CD28- (CD4+ Effector Memory cells), CD4+CD45RA+CD27-CD28- (CD4+ Terminally Differentiated Effector Memory Cells re-expressing CD45RA), CD3-CD19+ (B cells), CD3+CD56+CD8+CD4+ (NKT cells) with Age. The performance of the PCa presence 'detection' model was: Acc: 86.79 ( ± 0.10), Sensitivity: 82.78% (± 0.15); Specificity: 95.83% (± 0.11) on the test set (test set that was not used during training and validation); AUC: 89.31% (± 0.07), ORP-FPR: 7.50% (± 0.20), ORP-TPR: 84.44% (± 0.14). A second biLSTM 'risk' model combined the immunophenotypic features with PSA to predict whether a patient with PCa has high-risk disease (defined by the D'Amico Risk Classification) achieved the following: Acc: 94.90% (± 6.29), Sensitivity: 92% (± 21.39); Specificity: 96.11 (± 0.00); AUC: 94.06% (± 10.69), ORP-FPR: 3.89% (± 0.00), ORP-TPR: 92% (± 21.39). The ORP-FPR for predicting the presence of PCa when combining FC+PSA was lower than that of PSA alone. This study demonstrates that AI approaches based on peripheral blood phenotyping profiles can distinguish between benign prostate disease and PCa and predict clinical risk in asymptomatic men having
  • Endoscopic surgical simulation using low-fidelity and virtual reality transurethral resection simulators in urology simulation boot camp course: trainees feedback assessment study

    Berridge, Christopher; Kailavasan, Mithun (2021-08)
    Objectives: The objective of our study was to study trainees' feedback and rating of models for training transurethral resection of bladder lesions (TURBT) and prostate (TURP) during simulation. Methods: The study was performed during the ''Transurethral resection (TUR) module" at the boot camp held in 2019. Prior to the course, all trainees were required to evaluate their experience in performing TURBT and TURP procedures. Trainees simulated resection on two different models; low-fidelity tissue model (Samed, GmBH, Dresden, Germany) and virtual reality simulator (TURPMentor, 3D Systems, Littleton, US). Following the completion of the module, trainees completed a questionnaire using a 5-point Likert scale to evaluate their assessment of the models for surgical training. Results: In total, 174 simulation assessments were performed by 56 trainees (Samed Bladder-40, Prostate-45, TURPMentor Bladder-51, Prostate-37). All trainees reported that they had performed < 50 TUR procedures. The Samed model median scores were for appearance (4/5), texture (5/5), feel (5/5) and conductibility (5/5). The TURPMentor median score was for appearance (4/5), texture and feel (4/5) and conductibility (4/5). The most common criticism of the Samed model was that it failed to mimic bleeding. In contrast, trainees felt that the TURPMentor haptic feedback was inadequate to allow for close resection and did not calibrate movements accurately. Conclusions: Our results demonstrate that both forms of simulators (low-fidelity and virtual reality) were rated highly by urology trainees and improve their confidence in performing transurethral resection and in fact complement each other in providing lower tract endoscopic resection simulation.