OBJECTIVE:To convert suction pressure settings into practical, size-specific operating limits for suction ureteric access sheaths (sUAS). MATERIALS AND METHODS:Using an 8.7-F flexible ureteroscope with a standard 3.9-F working channel, we measured irrigation inflow at various pressures with no instrument, 270-μm laser fibre, and 1.9-F basket. Outflow was measured using 10/12-, 11/13-, and 12/14-F sUAS with suction applied via Neptune 3™ (Stryker, Kalamazoo, MI, USA) at 30-s intervals and pressures ranging from 50 to 300 mmHg. Inflow and outflow were matched by linear interpolation deriving conservative size- and instrument-specific suction pressure limits for all evaluated sUAS configurations. RESULTS:Ureteroscope irrigation inflow ranged from 30 to 130 mL/min as irrigation pressure irrigation increased from 50 cmH20 (gravity) to 300 mmHg. Working channel instruments reduced inflow: mean (± 2 × the standard error of the mean) change of -57.1% (1.6%) for the 1.9-F basket and -42.1% (2.1%) for the 270-μm laser fibre vs no instrument. Negative pressure via sUAS generated outflow as slow as 5 mL/min (10/12-F sUAS, 50 mmHg suction) and as fast as 700 mL/min (12/14-F sUAS, 300 mmHg suction). Outflow and negative pressure were linearly related (R2 0.94-0.99). Increased scope-to-sheath ratio (SSR) reduced irrigation outflow. Fully opening the valve significantly reduced outflow by 70.8% on average. The 40-cm sUAS modestly increased outflow by 13.3% on average compared to 50-cm sUAS of same diameter. Suction of 50-80 mmHg was ideal for maintaining flow equilibrium with 11/13- and 12/14-F sUAS. The small diameter and high SSR (0.87) of the 10/12-F sUAS required greater negative pressures (150-300 mmHg) to maintain flow equilibrium. CONCLUSIONS:Suction pressures as low as 50-80 mmHg are sufficient for majority of sUAS cases. Increasing irrigation inflow with pressure bag systems may counter excessive sUAS outflow; however, introducing instruments can negate this effect.
OBJECTIVES:To summarise the impact of the coronavirus disease 2019 (COVID-19) pandemic on urological practice globally with a focus on Australian initiatives, as the pandemic resulted in radical changes in healthcare infrastructure and policies. METHODS:We conducted a literature review of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE) and Web of Science medical databases. The key terms used to conduct our search algorithm comprised of 'COVID', 'wait list or wait time or delay', 'urology', 'surgery' and 'outcomes', and generated 231 articles. Abstracts were reviewed for relevance and 40 studies selected for full-text review. Society position statements and government level press release statements were identified through citation tracking and additionally included. RESULTS/DISCUSSION:The halt on elective surgical services during the pandemic was deemed necessary to curb infection rates and conserve healthcare resources. However, it resulted in extended wait times and large surgical backlogs with major downstream effects. Australia fared favourably with regards to infection rates compared to international populations consequent upon strict border control, vaccine mandates, and stringent lockdowns. However, similar trends were noted in both oncological and non-oncological urology service reduction, resulting in significant concerns regarding the long-term sequelae of delayed surgery and missed appointments upon patient clinical outcome. Initiatives including collaborative partnerships between public and private hospital sectors, government-funded programmes and adoption of telehealth were successfully established as part of Australia's efforts to stabilise our healthcare system in response to the pandemic. CONCLUSION:Australia's pandemic efforts have highlighted the escalating imbalance between increasing demand from a growing and ageing population on an already over-burdened system with finite resources. The additional strain of managing post-COVID-19 pandemic fallout in this context provides further challenges for clinicians and healthcare administrators alike. Collaboration by all stakeholders must continue in order to seek innovative solutions to maximise efficiency of healthcare service utilisation, so that quality universal healthcare provision may continue in the future.
Abstract Objectives This study aimed to compare long‐term (≥ 5 years) functional outcomes and reoperation rates following holmium laser enucleation of prostate (HoLEP) vs GreenLight photoselective vaporisation of prostate (GLPVP). Methods MEDLINE, Embase and Cochrane databases were searched from inception to December 2023. Included were randomised controlled trials (RCTs), cohort studies and case series studying HoLEP and/or GLPVP, where functional outcomes and reoperation rates were reported. Studies with <5‐year follow‐up were excluded. Evidence was synthesised as a comparison across all parameters. Quality of evidence was assessed with the Newcastle–Ottawa Scale. Results Of 3047 records identified, 25 were eligible, including two RCTs, two cohort studies, one cross‐sectional study and 20 case series. Twenty‐three studies focused on HoLEP or GLPVP, whilst two were comparative studies. HoLEP demonstrated long‐term durability of outcomes and low reoperation rates (mean 4.1%, range 2.0%–6.3%) at a mean follow‐up of 7.3 years. GLPVP also had durable outcomes at 5‐year follow‐up, but inconclusive evidence for improvements at 10 years. Reoperation rates were also higher (mean 12.6%, range 3.8%–33.3%). This is in keeping with findings of comparative studies, where HoLEP demonstrated greater improvements in all functional parameters except PVR, and lower reoperation rates. Findings are limited by patient attrition, lack of comparative studies and long‐term data beyond 10 years. Three studies examined the 180‐W GLPVP model at 5 years showed superior durability to earlier 80‐W/120‐W models. Conclusions Current evidence suggests that HoLEP provides significantly greater functional improvements and a lower reoperation rate when compared with the GLPVP 80‐W/120‐W model at 5‐year follow‐up. The 180‐W model is comparable with HoLEP based on limited data at 5 years, but there is a lack of data beyond 10 years for longer‐term functional outcomes.
Background/Objectives: Introducing new transformative surgical technology involves navigating a complex process from design to implementation, often hindered by various barriers that delay the transition into clinical practice. This review critically examines the barriers, proposes a unified guide for medical device implementation in the Australian healthcare system utilising the validated Medtech Innovation Guide, and compares regulatory frameworks in Australia, the United Kingdom, and the United States of America. Methods: We conducted a literature review using MEDLINE and EMBASE with MeSH terms or emtree terms and keywords “new OR novel” AND “surgical device OR medical device OR health technology OR surgical technology OR surgical instrument OR transformative technology OR technological innovation OR technological change” AND “implementation OR adoption OR innovation adoption” AND “surgery OR surgical” AND “Australia”. We also assessed governmental websites (gov.au) and documents as well as the Royal Australasian College of Surgeons (RACS) website, policies, and position statements. Furthermore, Australian medical technology start-up companies were asked for any published roadmaps. Results: Four key stakeholder groups were identified: medical professionals, government, hospitals, and patients/consumers. Barriers include surgeon scepticism, regulatory hurdles (e.g., Australian Register of Therapeutic Goods), hospital clearance processes, and meeting patient expectations. To address these challenges, we propose a five-phase system: surgical device development (phase one), compliance with regulatory processes (phase two), research and experimentation (phase three), finalisation for product launch (phase four), and product launch and assessment (phase five). Conclusions: By following our five-phase guide, innovators may better navigate the complexities of integrating transformative surgical technologies into Australian healthcare. Although there are limitations, this approach is based on the validated Medtech Innovation Guide and may help both experienced and inexperienced practitioners better implement innovative technology; however, real-world validation is required.
OBJECTIVE:To quantify the amount of irrigation and bacteria that are absorbed into the venous system at various intrarenal pressures (IRPs) during ureterorenoscopy (URS). METHODS:We performed in vivo and ex vivo experiments to quantify fluid and bacteria reabsorption during raised IRP. The in vivo models used porcine kidneys of six adult living female pigs under general anaesthesia to simulate URS at serially increased IRPs. For the ex vivo models, porcine kidneys were procured on ice using renal transplant protocols. The renal artery was flushed and perfused with 0.9% normal saline and the renal vein left open to collect continuous venous flow. The ureter was cannulated with a retrograde catheter and the renal pelvis was distended at incrementally greater IRPs using irrigation containing either: (i) 8% acetic acid or (ii) Escherichia coli (E. coli) solution. Venous effluent was sampled every 3 min and tested for: (i) H+ ion concentration or (ii) E. coli colony-forming units per mL. RESULTS:Pyelovenous backflow of electrolyte solution and E. coli bacteria was exponentially proportional to IRP. E. coli bacteraemia was present in the venous blood at 30 mmHg IRP in one of six living animals. By 60 mmHg, two animals had bacteraemia, three animals by 75 mmHg, five animals by 90 mmHg IRP, and all six animals by 120 mmHg. The in vitro laboratory studies verified these results and quantified the degree of pyelovenous backflow at each of these pressures. In vitro, increasing IRP from 30 mmHg to 60 mmHg demonstrated a threefold increase in CFU/ml of E. coli. However, increasing IRP by the same magnitude from 60 mmHg to 90 mmHg demonstrated a 60-fold increase in CFU/ml of E. coli bacteraemia, and this continued exponentially up to 200 mmHg. CONCLUSION:Pyelovenous backflow increases exponentially after 60 mmHg IRP. Bacteraemia can occur at IRPs between 30 and 120 mmHg in living animals; bacteraemia occurred at an average IRP of 77 mmHg in our study.
OBJECTIVE:To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS:A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS:A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS:This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.
Introduction: Urological cancers account for a significant portion of cancer diagnoses and mortality rates worldwide. The traditional treatment options of surgery and chemoradiation can have significant morbidity and become ineffective in refractory disease. The discovery of the CRISPR system has opened up new avenues for cancer research by targeting specific genes or mutations that play a role in cancer development and progression. In this review, we summarise the current state of research on CRISPR in urology and discuss its potential for improving the diagnosis and treatment of urological cancers. Methods: A comprehensive literature search was conducted on databases including PubMed, Embase, and Cochrane Library. The keywords included CRISPR and urology OR prostate OR renal OR bladder OR testicular cancer. Results: CRISPR has been used extensively in a preclinical setting to identify and target genes in prostate cancer, including AR, NANOG, ERβ, TP53, PTEN, and PD-1. Targeting PRRX2 and PTEN has also been shown to overcome enzalutamide and docetaxel resistance in vitro. In bladder cancer, CBP, p300, hTERT, lncRNA SNGH3, SMAD7e, and FOXA1 have been targeted, with HNRNPU knockout demonstrating tumour inhibition, increased apoptosis and enhanced cisplatin sensitivity both in vitro and in vivo. Renal cancer has seen CRISPR target VHL, TWIST1, PTEN, and CD70, with the first in-human clinical trial of Anti-CD70 CAR T cell therapy showing an excellent safety profile and durable oncological results. Lastly, testicular cancer modelling has utilised CRISPR to knockout FLNA, ASH2L, HMGB4, CD24, and VIRMA, with NAE1 found to be over-expressed in cisplatin-resistant germ cell colonies. Conclusions: CRISPR is a cutting-edge technology that has been used extensively in the pre-clinical setting to identify new genetic targets, enhance drug sensitivity, and inhibit cancer progression in animal models. Although CAR T cell therapy has shown promising results in RCC, CRISPR-based therapeutics are far from mainstream, with further studies needed across all urological malignancies.
IntroductionVibrational spectroscopy (VS) is a new and rapidly evolving technology in cancer diagnostics. Originating from analytical chemistry, VS evaluates vibrations of nuclei to produce a unique “biological fingerprint.” While multiple studies have been published on this technology and physician awareness has increased, no systematic review has evaluated the role of VS in bladder cancer (BCa) tissue diagnosis. MethodsTo conduct this systematic review, we searched the MEDLINE, Embase, and Cochrane databases for studies that used Raman spectroscopy (RS), surface-enhanced RS (SERS), infrared spectroscopy (IR) or near-infrared spectroscopy (NIRS) to analyze human BCa specimens. Studies using animal tissue or liquid biopsies were excluded. We synthesized the evidence by comparing modalities, study design, data analysis techniques, and diagnostic accuracy. The quality of evidence was evaluated by the QUADAS-2 tool. ResultsOut of 362 results, 20 studies met our inclusion criteria. There has been growing interest in VS use in BCa, with 50% of the studies published in the past 5 years. RS was the most commonly used modality (65%), followed by IR (20%) and SERS (10%). Only one study compared RS to IR (5%). The mean sample size was 44 patients (range, 6–214). To date, there have been only 2 in vivo studies, with the remaining ex vivo studies performed with large variation in tissue preparation, data analysis, and reporting. Advancements in fiber optic probes and machine-learning data analysis techniques, and increased computational power have improved diagnostic accuracy up to 98% sensitivity and 100% specificity. ConclusionsVS shows high potential for BCa diagnosis, but there is a need for uniform reporting methods and studies with adequate sample sizes to validate the models. RS has shown promising results, with ongoing improvements in fiber optic probes allowing its integration into conventional cystoscopes. While no single VS modality has proven to be perfect, a multimodal approach is likely required to establish its value in clinical practice.
The relationship between thromboembolic events (TEs) and immune-oncology (IO) agents in patients with metastatic renal cell carcinoma (mRCC) with inferior-vena-cava (IVC) thrombus has not been explored despite conferring significant morbidity. A late 30s female is diagnosed with mRCC with a level-II IVC thrombus after presenting with back pain. Two weeks post initiation of immunotherapy, she re-presented with bilateral sub-massive pulmonary emboli requiring IVC and pulmonary thrombectomy. This case exposes a potential relationship between mRCC and IVC thrombus with IO agents that creates a critically hypercoagulable state. This issue requires further investigation given the apparent under-reporting of TEs in these patients.
PURPOSE OF REVIEW:Recently, there has been emerging interest in the treatment of primary tumours in metastatic prostate cancer based on major trials that have provided evidence for radiation therapy and cytoreductive radical prostatectomy. Preclinical studies have further established the molecular features of metastatic disease that provide a rationale for primary treatment.RECENT FINDINGS:Several randomised controlled trials and other prospective studies have demonstrated a benefit in overall survival, predominantly in low-volume disease. Advancements in precision medicine also offer insight into improving selection, staging and monitoring.SUMMARY:In this review, the authors highlight and review recent data on emerging and established treatment options and shift towards personalised medicine for hormone-sensitive metastatic prostate cancer.
Prostate cancer is the second most frequent cancer in men, with increasing prevalence due to an ageing population. Advanced prostate cancer is diagnosed in up to 20% of patients, and, therefore, it is important to understand evolving mechanisms of progression. Significant morbidity and mortality can occur in advanced prostate cancer where treatment options are intrinsically related to lipid metabolism. Dysfunctional lipid metabolism has long been known to have a relationship to prostate cancer development; however, only recently have studies attempted to elucidate the exact mechanism relating genetic abnormalities and lipid metabolic pathways. Contemporary research has established the pathways leading to prostate cancer development, including dysregulated lipid metabolism-associated de novo lipogenesis through steroid hormone biogenesis and β-oxidation of fatty acids. These pathways, in relation to treatment, have formed potential novel targets for management of advanced prostate cancer via androgen deprivation. We review basic lipid metabolism pathways and their relation to hypogonadism, and further explore prostate cancer development with a cellular emphasis.
Oligometastatic prostate cancer (OMPC) has been proposed as an intermediary state between localised disease and widespread metastases, with varying definitions including 1, 3, or ≤5 visceral or bone metastasis. Traditional definitions of OMPC are based on staging with conventional imaging, such as computerised tomography (CT) and whole-body bone scan (WBBS). Novel imaging modalities such as prostate-specific membrane antigen positron emission tomography (PSMA PET) have improved diagnostic utility in detecting early metastatic prostate cancer (PC) metastases compared with conventional imaging. Specifically, meta-analytical data suggest that PSMA PET is sensitive in detecting oligometastatic disease in patients with biochemical recurrence (BCR) post-radical treatment of PC. Recent trials have evaluated PSMA PET-guided metastases-directed therapy (MDT) in oligometastatic recurrent disease, typically with salvage surgery or radiotherapy (RT). To date, these preliminary studies demonstrate promising results, potentially delaying the need for systemic therapy. We aim to report a comprehensive, multidisciplinary review of PSMA-guided MDT in OMPC. In this review, we highlight the utility of PMSA PET in biochemically recurrent disease and impact of PSMA PET on the definition of oligometastatic disease and outline data pertaining to PSMA-guided MDT.