Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

BACKGROUND: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. METHODS: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. FINDINGS: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). INTERPRETATION: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. FUNDING: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.

The pregnant urologist.

Female urologists represent an ever-increasing percentage of the work force; more and more of our colleagues will be working through pregnancy. There is a lack of clear and concise advice for pregnant urologists about occupational risks during pregnancy. Urology exposes expectant mothers to potential risks from radiation, teratogenic and cytotoxic drugs, iodine hand scrub, infections, and long working hours. We aim to provide a review of the current evidence and guidance to aid expectant mothers in their decision making. Relevant research articles and up-to-date guidance were reviewed. The millisevert (the average accumulated background radiation dose to an individual for 1 year, exclusive of radon) was used as the main unit of radiation dose. There is no published evidence to date in pregnant clinicians that shows a received radiation dose of more than the recommended dose for a pregnant lady, and no data showing an increased risk of foetal abnormalities in clinicians who continue to screen during pregnancy; however, the data are from small studies. There is strong advice suggesting avoidance of contact with crushed or broken 5α-reductase inhibitor tablets (finasteride and dutasteride), mitomycin and other cytotoxic drugs during pregnancy. Pregnant surgeons should avoid frequent use of iodine hand wash. Good hygiene precautions will protect from many infections along with up-to-date immunisations and use of personal protective equipment for certain cases.

Perioperative outcomes of cytoreductive nephrectomy in the UK in 2012.

OBJECTIVES: To define the perioperative morbidity and 30-day mortality of cytoreductive nephrectomy (CN) using the British Association of Urological Surgeons (BAUS) nephrectomy dataset for 2012, the first year of public reporting of individual surgeon outcomes in the UK. PATIENTS AND METHODS: All nephrectomies recorded in the database in 2012 were analysed, and cytoreductive cases identified. Outcome measures were: blood loss of >1000 mL, transfusion requirement, intra- and postoperative complications assessed by Clavien-Dindo score, and 30-day mortality (including failure-to-rescue rate). Univariate and multivariate logistic regression analysis was used to assess predictors of adverse outcomes. RESULTS: In all, 279 cases were undertaken by 141 surgeons in 90 centres. World Health Organization (WHO) Performance Status (PS) was 0 or 1 in 72.4% (202 cases). Open nephrectomy was performed in 59% (163 cases), with the remainder laparoscopic. The conversion rate for laparoscopy was 14% (16 cases). In all, 40 patients underwent preoperative tyrosine-kinase inhibitor treatment. No significant differences in outcome were observed for this group. The 30-day mortality was 1.79%. Intraoperative complications occurred in 11.9% and postoperative complications in 20.8%. Complications of Clavien-Dindo grade ≥ III occurred in 8%. Blood loss of >1000 mL occurred in 15.4% of cases and 24.1% of patients required a perioperative transfusion. Tumour of >10 cm was an independent risk factor for blood loss of >1000 mL (P = 0.021) and intraoperative complications (P = 0.021). The number of metastatic sites was an independent predictor of blood loss of >1000 mL (P = 0.001) and transfusion requirement (P = 0.026) WHO PS of ≥2 was also independently associated with intraoperative complication risk (P = 0.021). CONCLUSIONS: CN in contemporary UK practice appears to have excellent perioperative outcomes overall. Risk factors for adverse perioperative outcomes include tumours of >10 cm, number of metastatic sites and WHO PS of ≥2. The balance of risk and benefit for CN should be carefully considered for patients with poor PS or extensive metastases.

Retroperitoneal Gastrointestinal Type Schwannoma Presenting as a Renal Mass.

Retroperitoneal schwannomas are extremely rare, and unreported in Urology. Often thought to be malignant from imaging the diagnosis is often delayed until Histology. We report a case of retroperitoneal schwanoma thought to be a malignant renal mass. Seventy three year old lady presented with abdominal pain. Imaging showed a mass attached to the renal pelvis thus she underwent a radical nephrectomy. Histology reported retroperitoneal schwannoma. Malignant forms are rare however treatment for these is surgical excision. Awareness of the existence of these tumors may help in avoiding unnecessary radical surgeries by opting for biopsy preoperatively.

Acute kidney injury in urology patients: incidence, causes and outcomes.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and is associated with high mortality rates. However, the epidemiology of AKI in urology patients may differ due to a higher proportion of post-renal causes and surgical procedures that result in the intentional removal of renal parenchyma. OBJECTIVES: We performed a study to examine the incidence, aetiology and outcomes of AKI in a urological population. PATIENTS AND METHODS: We performed a single-centre observational study including all hospitalised patients who sustained AKI within the Urology Department over an 18 month period. Patients with AKI were prospectively identified by a hospital-wide, electronic AKI reporting system that also allows demographic, hospital admission and co-morbidity data collection. Data regarding aetiology of AKI and details of surgical procedures were added retrospectively by manual case-note search. RESULTS: 587 episodes of AKI occurred in 410 urology patients, giving an overall incidence of 6.7%. 137 (33.4%) were elective cases of whom 58 had undergone nephrectomy (radical and partial). Urinary obstruction and sepsis were the predominant causes of AKI in the 273 patients (66.6%) admitted as an emergency. Overall 30-day mortality was 7.8%; increasing severity of AKI was associated with mortality (4.8% in stage 1, 9.1% in stage 2, 14.9% in stage 3, P = 0.007). At time of discharge, only 57.7% of patients had recovered pre-morbid renal function. The observational nature of this study is a limitation, preventing determination of causality of associations. CONCLUSIONS: AKI is common in urology patients. The underlying aetiologies of AKI in this group may explain a lower overall mortality, although increasing AKI severity remains a marker of patients at higher risk of poor outcomes. The low rate of renal recovery suggests that urology patients who sustain AKI are exposed to a significant risk of CKD and its attendant consequences for long term health.

Update on the management of T1 renal cortical tumours.

There are a range of treatment strategies for the management of patients with small incidental renal cortical tumours including active surveillance, radiofrequency ablation, cryotherapy, radical nephrectomy and partial nephrectomy. A large number of such tumours are benign and might therefore be over-treated with radical nephrectomy. There are emergent short-term oncological and clinical outcomes for cryotherapy and radiofrequency ablation, and recent studies have illustrated the benefits of partial nephrectomy for minimizing the risk of progression to chronic kidney disease. The outcomes of these different treatment methods are discussed.

Chronic regional pain syndrome after subtalar arthrodesis is not prevented by early hyperbaric oxygen.

Subtalar arthrodesis was performed on a 48-year-old, non-insulin-dependent diabetic with a history of chronic ankle instability and lateral ankle pain. In the early post-operative period he presented as an emergency with an infection at the operative site. This was treated with 2 returns to the operating theatre for washout and debridement. His wounds were left open and at 3 weeks after emergency admission he was referred for adjunctive hyperbaric oxygen (HBO) therapy to aid healing by secondary intention. He received a total of 19 hyperbaric sessions, at a pressure of 2.2 ATA, one treatment per day for 5 days a week. Shortly after commencing HBO therapy his ankle became increasingly painful, despite the introduction of analgesia. By 7 weeks after emergency admission his wounds had virtually healed but hyperesthesia persisted over the dorsum of the foot. A computerized tomography scan at 5 1/2 months post-operatively showed satisfactory joint fusion and revealed no evidence of infection. Symptoms and signs at this time were compatible with a diagnosis of chronic regional pain syndrome (CRPS). There is published evidence to suggest that HBO therapy may be a useful modality in the treatment of established CRPS. Here, we seek to publicize a case in which early treatment with HBO for another indication did not prevent the simultaneous development of CRPS Type 1.

Hematocrit change in tropical scuba divers.

OBJECTIVE: Direct evidence that dehydration results from scuba diving is scanty. Increased hematocrit (Ht) is a commonly used proxy measure for dehydration. This study sought evidence that an increase in Ht occurs over the course of a scuba dive in tropical conditions. As a secondary outcome, evidence was sought that the degree of Ht increase is correlated to pressure exposure. METHODS: Twenty male and 21 female scuba divers were recruited at a remote tropical dive site. Water temperature was 30 degrees C (+/- 1 degrees C). Each diver gave venous blood relating to 1 dive only. Mean maximum dive depth was 13.6 m (+/- 3.7 m [SD]) and mean duration 39.5 minutes (+/- 4.5 minutes [SD]) using air as the breathing gas. Blood was taken at a mean of 12.4 minutes (+/- 3.5 minutes [SD]) before diving and a mean of 16.2 minutes (+/- 3.7 minutes [SD]) after diving. After centrifugation of microcapillaries, Ht was estimated on a visual plate reader. RESULTS: A paired Wilcoxon test showed evidence (P < .001) for a change in Ht. The mean difference between predive and postdive measurements was 0.0073 (95% confidence interval: 0.0104-0.0042), equating to a mean relative Ht increase of 1.78%. Similar results were found for the sexes individually. A correlation between maximum depth of dive and Ht increase was statistically significant, although the correlation itself was weak (P = .049, Spearman's r = .326). CONCLUSIONS: There is evidence of a statistically significant increase in Ht over the course of a single warm-water scuba dive. This increase is small and is within the range of error associated with the techniques of Ht estimation employed in this study. Depth exposure was found to correlate with Ht increase. In view of the small magnitude of change in the Ht, there is no reason to amend protocols for fluid resuscitation of recreational scuba divers suspected to have experienced decompression injury in tropical locations.