Surgical innovation revisited: A historical narrative of the minimally invasive "Agarwal sliding-clip renorrhaphy" technique for partial nephrectomy and its application to an Australian cohort.

Objective: To evaluate local clinical outcomes of sliding clip renorrhaphy, from inception to current utilization for open, laparoscopic, and robotically assisted partial nephrectomy. Methods: We reviewed prospectively maintained databases of three surgeons performing partial nephrectomies with the sliding-clip technique at teaching hospitals between 2005 and 2019. Baseline characteristics, operative parameters, including surgical approach, RENAL Nephrometry Score, and post-operative outcomes, including Clavien-Dindo classification of complications, were recorded for 76 consecutive cases. We compared perioperative and 90-day events with patient and tumor characteristics, stratified by operative approach and case complexity, using Wilcoxon rank-sum test for continuous variables and the Chi-squared or Fisher's exact test, for binary and categorical variables, respectively. Results: Open surgery (n = 15) reduced ischemia time and operative time, but increased hospital admission time. Pre- and post-operative estimated glomerular filtration rates did not change significantly by operative approach. Older patients (P = .007) and open surgery (P = .003) were associated with a higher rate of complications (any-grade). Six grade ≥3 complications occurred: these were associated with higher RENAL Nephrometry Score (P = .016) and higher pathological tumor stage (P = .045). Limits include smaller case volumes which incorporate the learning curve cases; therefore, these data are most applicable to lower volume teaching hospitals. Conclusion: The sliding-clip technique for partial nephrectomy was first described by Agarwal et al and has low complication rates, acceptable operative time, and preserves renal function across open and minimally invasive surgeries. This series encompasses the initial learning curve with developing the technique through to present-day emergence as a routine standard of practice.

Robot-assisted abdominal wall excision of a PSMA-detected prostate cancer metastasis.

Recent advances in novel functional imaging techniques such as PSMA PET may now offer the ability to identify small volume metastases which may otherwise go undetected. The treatment of these lesions is controversial, particularly in the oligometastatic state. We report the case of an abdominal wall metastasis detected with PSMA imaging which we treated with surgical excision. This resulted in an undetectable PSA 6 weeks post excision.

Fournier's gangrene in a man on empagliflozin for treatment of Type 2 diabetes.

BACKGROUND: Sodium-glucose cotransporter 2 (SLGT2) inhibitors has been associated with an increased risk of genital infections secondary to increased glycosuria. CASE REPORT: We report a case of a 41-year-old man with type 2 diabetes treated with empagliflozin and metformin who presented with scrotal swelling. He described multiple preceding episodes of genital thrush for which he self-administered over-the-counter anti-fungal treatment. On examination, he was afebrile and hemodynamically stable. Perineal examination revealed grossly swollen and indurated scrotum with bilateral inguinal lymphadenopathy. Investigations showed elevated inflammatory markers and HbA1c of 99 mmol/mol (11.2%). Computed tomography revealed features consistent with Fournier's gangrene. He underwent emergency exploration and debridement under anaesthetic with a later return to theatre for further exploration, washout and application of a vacuum dressing. He then received a split skin graft to his perineum. He required a 2-week course of intravenous antibiotics and was discharged home on oral antibiotics. Empagliflozin was ceased on admission and he was commenced on a basal bolus insulin regimen for glycaemic optimisation. CONCLUSION: There is a wide clinical spectrum of genital infections associated with SGLT2 inhibitors with most being generally mild and easily treated. However, risk factors such as diabetes, obesity, immunosuppressed states, smoking, alcohol abuse and end-stage renal or liver failure may increase the risk of potentially more severe infections such as Fournier's gangrene. Timely cessation of SGLT2 inhibitors in individuals with multiple risk factors may help prevent progression to more severe genital infections.

Evaluation of models predicting insignificant prostate cancer to select men for active surveillance of prostate cancer.

BACKGROUND: In an era of personalized medicine, individualized risk assessment using easily available tools on the internet and the literature are appealing. However, uninformed use by clinicians and the public raises potential problems. Herein, we assess the performance of published models to predict insignificant prostate cancer (PCa), using a multi-national low-risk population that may be considered for active surveillance (AS) based on contemporary practice. METHODS: Data on men suitable for AS but undergoing upfront radical prostatectomy were pooled from three international academic institutions in Cambridge (UK), Toronto (Canada) and Melbourne (Australia). Four predictive models identified from literature review were assessed for their ability to predict the presence of four definitions of insignificant PCa. Evaluation was performed using area under the curve (AUC) of receiver operating characteristic curves and Brier scores for discrimination, calibration curves and decision curve analysis. RESULTS: A cohort of 460 men meeting the inclusion criteria of all four nomograms was identified. The highest AUCs calculated for any of the four models ranged from 0.618 to 0.664, suggesting weak positive discrimination at best. Models had best discriminative ability for a definition of insignificant disease characterized by organ-confined Gleason score ⩽6 with a total volume ⩽0.5 ml or 1.3 ml. Calibration plots showed moderate range of predictive ability for the Kattan model though this model did not perform well at decision curve analysis. CONCLUSIONS: External assessment of models predicting insignificant PCa showed moderate performance at best. Uninformed interpretation may cause undue anxiety or false reassurance and they should be used with caution.

The impact of prostate cancer on partners: a qualitative exploration.

OBJECTIVE: Prostate cancer and its treatment can result in numerous physical and psychological morbidities for the patient as well as his partner. This qualitative study aimed to explore the experiences of intimate spouses or partners of men diagnosed and/or treated for prostate cancer to better understand the personal impact of prostate cancer on the partner. METHODS: Twenty-seven partners participated in this study. Six focus groups were convened, and one in-depth interview was undertaken to explore the practical impact of prostate cancer on the intimate spouse/partner. All discussions were audio-recorded and transcribed and then coded using a thematic approach. RESULTS: Six themes emerged: (a) The influence of the man's response to prostate cancer on the partner, (b) The need to be involved in treatment and medical decision making, (c) Supporting a man who is experiencing a loss of masculinity, (d) Degree of congruence between each partner's coping responses, (e) Constrained communication, and (f) Changed roles and increased practical management. CONCLUSIONS: It is clear that prostate cancer impacts substantially on many areas of partner well-being. An effective intervention provided to this population seems warranted and may lead to improvements in partner well-being, assist the couple in lessening the impact of prostate cancer and its treatment on their relationship, and assist in the man's recovery.

Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy.

BACKGROUND: Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. METHODS: We examined the levels of CD31(+)CD45(-) cells (CECs) and CD31(+)CD45(-)CD117(+) (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31(+)CD45(-), CD31(+)CD45(-)CD146(+) (CECs) and CD31(+)CD45(intermediate)CD133(+) (CEPs) populations were quantified and subsequently enriched for further characterisation. RESULTS: In preclinical models, levels of CD31(+)CD45(-) cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31(+)CD45(-) cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31(+)CD45(-) cell population revealed an essentially homogenous population of large, immature platelets representing <0.1% of circulating platelets. CONCLUSION: Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy.

International multicentre study examining selection criteria for active surveillance in men undergoing radical prostatectomy.

BACKGROUND: The controversies concerning possible overtreatment of prostate cancer, highlighted by debate over PSA screening, have highlighted active surveillance (AS) as an alternative management option for appropriate men. Regional differences in the underlying prevalence of PSA testing may alter the pre-test probability for high-risk disease, which can potentially interfere with the performance of selection criteria for AS. In a multicentre study from three different countries, we examine men who were initially suitable for AS according to the Toronto and Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, that underwent radical prostatectomy (RP) in regards to:1.the proportion of pathological reclassification(Gleason score ≥7, ≥pT3 disease),2.predictors of high-risk disease,3.create a predictive model to assist with selection of men suitable for AS. METHODS: From three centres in the United Kingdom, Canada and Australia, data on men who underwent RP were retrospectively reviewed (n=2329). Multivariable logistic regression was performed to identify predictors of high-risk disease. A nomogram was generated by logistic regression analysis, and performance characterised by receiver operating characteristic curves. RESULTS: For men suitable for AS according to the Toronto (n=800) and PRIAS (410) criteria, the rates for upgrading were 50.6, 42.7%, and upstaging 17.6, 12.4%, respectively. Significant predictors of high-risk disease were:•Toronto criteria: increasing age, cT2 disease, centre of diagnosis and number of positive cores.•PRIAS criteria: increasing PSA and cT2 disease.Cambridge had a high pT3a rate (26 vs 12%). To assist selection of men in the United Kingdom for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Toronto criteria (AUC of 0.72). CONCLUSION: The proportion of pathological reclassification in our cohort was higher than previously reported. Care must be used when applying the AS criteria generated from one population to another. With more stringent selection criteria, there is less reclassification but also fewer men who may benefit from AS.

Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostate cancer.

BACKGROUND: Angiogenesis is fundamental to the progression of many solid tumours including prostate cancer. Sodium selenate is a small, water-soluble, orally bioavailable activator of PP2A phosphatase with anti-angiogenic properties. METHODS: This was a dose-escalation phase I study in men with asymptomatic, chemotherapy-naïve, castration-resistant prostate cancer. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included establishing the safety, tolerability and pharmacokinetic profile. RESULTS: A total of 19 patients were enrolled. The MTD was 60 mg per day. Dose-limiting toxicity (fatigue and diarrhoea) was observed at 90 mg per day. The most frequently reported treatment-related adverse events across all treatment cohorts were nausea, diarrhoea, fatigue, muscle spasms, alopecia and nail disorders. No grade 4 toxicities were observed and there were no deaths on study. Linear pharmacokinetics was observed. One patient had a PSA response >50%. Median time to PSA progression (for non-responders) was 14.2 weeks. Mean PSA doubling time increased during the main treatment phase from 2.18 months before trial to 3.85 months. CONCLUSION: Sodium selenate is well tolerated at a dose of 60 mg per day with modest single-agent efficacy similar to other anti-angiogenic agents. Further trials in combination with conventional cytotoxic regimens are warranted.

Patient outcomes in the acute recovery phase following robotic-assisted prostate surgery: a prospective study.

BACKGROUND: Robotic-assisted minimally invasive urologic surgery was developed to minimise surgical trauma resulting in quicker recovery. It has many potential benefits for patients with localised prostate cancer over traditional surgical techniques without taking a risk with the oncological result. OBJECTIVES: To report the specific surgical outcomes for the first Australian cohort of patients with localised prostate cancer that had undergone robotic-assisted radical prostatectomy (RARP) surgery. The outcomes represent the acute (in-hospital) recovery phase and include pain, length of stay (LOS), urinary catheter management and wound management. METHODS: Prospective descriptive survey of 214 consecutive patients admitted to a large metropolitan private hospital in Melbourne, Australia between December 2003 and June 2005. Patients had undergone RARP surgery for localised prostate cancer. Data were collected from the medical records and through interview at the time of discharge. Descriptive statistics were used to describe the frequency and proportion of outcomes. Patient characteristics were tabulated using cross tabulation frequency distribution and measures of central tendency. RESULTS: The findings from this study are highly encouraging when compared to outcomes associated with traditional surgical techniques. Transurethral catheter duration (median 7 days (IQ range 2)) and LOS (median 3 days (IQ range 2)) were considerably reduced. While operation time (median 3.30 h (IQ range 1.07)) was marginally reduced we would expect a further reduction as the surgical team becomes more skilled. CONCLUSION: The findings from this study contribute to building a comprehensive picture of patient outcomes in the acute (in-hospital) recovery phase for a cohort of Australian patients who have undergone RARP surgery for localised prostate cancer. As such, these findings will provide valuable information with which to plan care for patients' who undergo robotic-assisted surgery.

Robotic radical prostatectomy in Australia: initial experience.

The purpose of this study is to describe the initial experience of robotic-assisted radical prostatectomy (RARP) in Australia. Since the installation of the daVinci system at the Australian Institute for Robotic Surgery, Epworth Hospital, Melbourne in December 2003, 275 robotic-assisted radical prostatectomies have been performed by two surgeons. A prospective database is compiled for each procedure including patient, operative and outcome details. We report on the initial learning curve, surgical technique and modifications, anaesthetic considerations and surgical results comparative to open radical prostatectomy in a single surgeons experience along with margin positivity rates for the first 200 cases of RARP. RARP is the single most frequent adaptation of robotic-assisted surgery with promising initial results. Increasing availability of this modality will inevitably give rise to further adaptations. We present the initial Australian experience.

Day-case holmium laser enucleation of the prostate for gland volumes of < 60 mL: early experience.

OBJECTIVE: To examine the safety and effectiveness of holmium laser enucleation of the prostate (HoLEP), as a day-case procedure for selected patients. PATIENTS AND METHODS: Thirty-eight men underwent HoLEP as a day-case procedure; they were discharged with an indwelling catheter for 48 h with 'Hospital In The Home' nursing management. They were evaluated for symptomatic and flow rate improvements after 3 months. Morbidity, length of stay, the duration of catheterization and readmission rates were evaluated. RESULTS: The objective symptom score and flow-rate improvements were equivalent to those previously published for transurethral resection of the prostate (TURP). There were five minor complications, three of which required readmission to hospital and one repeat surgery. The mean stay after surgery was 302 min. CONCLUSIONS: Day-case HoLEP is a safe and effective treatment for symptomatic benign prostatic hyperplasia. The outcomes are equivalent to those from TURP. Whilst there were three re-admissions to hospital, two only required an overnight stay and no patient required a blood transfusion.

Case report: holmium laser resection and lasertripsy for intravesical ureterocele with calculus.

The holmium laser has established an important role in urology, particularly in the treatment of benign prostatic hyperplasia (BPH) and urolithiasis. Its light (wavelength 2140 nm) has a high coefficient of absorption in water, such that 95% of the laser energy is absorbed in 0.5 mm of water. Thus, the majority of the laser energy is contained superficially, imparting the holmium laser with excellent cutting and tissue ablation properties. It provides sharp incision with simultaneous hemostasis. Perhaps the most significant benefit of the holmium laser is its versatility when delivered through rigid or flexible endoscopes using quartz fibers of various sizes. We present the use of this laser in the ablation of an intravesical ureterocele with calculus.

A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: Rationale, recruitment, and design issues.

Deficiencies of selenium have been associated with an increased cancer risk, and several clinical and animal trials have suggested that improved selenium nutrition may reduce the incidence of several kinds of cancer, including lung, colorectal, and breast. Results from recent trials also show an anticarcinogenic effect of selenium in the prostate. There is converging evidence from epidemiologic, experimental animal, and molecular biology studies for an antitumor effect of selenium. Evidence suggests there are two modes of action of selenium affecting cancer risk: first, by functioning as an essential nutrient that provides the catalytic centers of a number of selenoenzymes, including some with antioxidant and redox functions; second, by serving as a source of selenium metabolytes that affect carcinogenesis in other ways. The first mechanism appears most relevant to protection against cancer initiation, the second against cancer progression. There is conclusive evidence of the increased risk of prostate cancer for a male with a family history of the disease. As a result of this evidence, and the evidence supporting the chemopreventive properties of selenium, this study proposed that a trial to test the effect of selenium on men at high risk for development of prostate cancer is appropriate. This article describes the Australian Prostate Cancer Prevention Trial Using Selenium (APPOSE) trial to test the hypothesis that daily dietary supplementation with selenium will reduce prostate cancer incidence in a population of men who are at increased risk because of a first-degree relative with prostate cancer.

Experience with the holmium laser as an endoscopic lithotrite.

INTRODUCTION: Holmium laser lithotripsy represents an additional option in the management of urinary tract calculi. We report the results of a cohort of patients with ureteric and bladder calculi treated with this modality. METHODS: Twenty-three patients underwent holmium laser lithotripsy to treat ureteric or bladder calculi. Power settings of 0.5 J to deliver 2.5-4.0 watts were used for the ureteric calculi, and up to 30 watts for the bladder calculi. RESULTS: The mean ureteric stone size was 7.3 mm (range 4-10 mm). One stone was upper ureteric, seven were mid-ureter and nine were lower-ureter. Eighteen of the 19 patients with ureteric calculi were free of stones 28 days postoperatively. The remaining patient was clear by 12 weeks. All patients with bladder calculi were completely cleared of stones. There were no intraoperative complications. DISCUSSION: Ureteric stone position can limit the use of extracorporeal shock wave lithotripsy due to imaging difficulties. Ureteric lithotripsy overcomes this problem. The holmium laser has proven to be safe and effective in clearing urinary stone burdens of a variety of sizes, sites and compositions in this cohort of patients.