Is the Toxicity of Salvage Prostatectomy Related to the Primary Prostate Cancer Therapy Received?

PURPOSE: To compare the toxicity profile and oncological outcome of salvage radical prostatectomy following focal therapy versus salvage radical prostatectomy after radiation therapies (external beam radiation therapy or brachytherapy). MATERIALS AND METHODS: Data concerning all men undergoing salvage radical prostatectomy for recurrent prostate cancer after either focal therapy, external beam radiation therapy or brachytherapy were retrospectively collected from 4 high volume surgical centers. The primary outcome measure of the study was toxicity of salvage radical prostatectomy characterized by any 30-day postoperative Clavien-Dindo complication rate, 12-month continence rate and 12-month potency rate. The secondary outcome was oncological outcome after salvage radical prostatectomy including positive margin rate and 12-month biochemical recurrence rate. Biochemical recurrence was estimated using Kaplan-Meier methods and significant differences were calculated using a log rank test. Median followup was 29.5 months. RESULTS: Between April 2007 and September 2018, 185 patients underwent salvage radical prostatectomy of whom 95 had salvage radical prostatectomy after focal therapy and 90 had salvage radical prostatectomy after radiation therapy (external beam radiation therapy or brachytherapy). Salvage radical prostatectomy after radiation therapy was associated with a significantly higher 30-day Clavien-Dindo I-IV complication rate (34% vs 5%, p <0.001). At 12 months following surgery, patients undergoing salvage radical prostatectomy after focal therapy had significantly better continence (83% pad-free vs 49%) while potency outcomes were similar (14% vs 11%). Men undergoing salvage radical prostatectomy after radiation therapy had a significantly higher stage and grade of disease together with a higher positive surgical margin rate (37% vs 13%, p=0.001). The 3-year biochemical recurrence after focal therapy was 35% compared to 32% after radiation therapy (p=0.76). In multivariable analysis, men undergoing salvage radical prostatectomy after focal therapy experienced a higher risk of biochemical recurrence (HR 0.36, 95% CI 0.16-0.82, p=0.02). CONCLUSIONS: This multicenter study demonstrates the toxicity of salvage radical prostatectomy in terms of perioperative complications and long-term urinary continence recovery is dependent on initial primary prostate cancer therapy received with men undergoing salvage radical prostatectomy after focal therapy experiencing lower postoperative complication rates and better urinary continence outcomes.

Defining a national reference level for intraoperative radiation exposure in urological procedures: FLASH, a retrospective multicentre UK study.

OBJECTIVES: To define reference levels for intraoperative radiation during stent insertion, ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL); to identify variation in radiation exposure between individual hospitals across the UK, between low- and high-volume PCNL centres, and between grade of lead surgeon. PATIENTS/SUBJECTS AND METHODS: In all, 3651 patients were identified retrospectively across 12 UK hospitals over a 1-year period. Radiation exposure was defined in terms of total fluoroscopy time (FT) and dose area product (DAP). The 75th percentiles of median values for each hospital were used to define reference levels for each procedure. RESULTS: Reference levels: ureteric stent insertion/replacement (DAP, 2.3 Gy/cm2 ; FT, 49 s); URS (DAP, 2.8 Gy/cm2 ; FT, 57 s); PCNL (DAP, 24.1 Gy/cm2 ; FT, 431 s). Significant variations in the median DAP and FT were identified between individual centres for all procedures (P < 0.001). For PCNL, there was a statistically significant difference between DAP for low- (<50 cases/annum) and high-volume centres (>50 cases/annum), at a median DAP of 15.0 Gy/cm2 vs 4.2 Gy/cm2 (P < 0.001). For stent procedures, the median DAP and FT differed significantly between grade of lead surgeon: Consultant (DAP, 2.17 Gy/cm2 ; FT, 41 s) vs Registrar (DAP, 1.38 Gy/cm2 ; FT, 26 s; P < 0.001). CONCLUSION: This multicentre study is the largest of its kind. It provides the first national reference level to guide fluoroscopy use in urological procedures, thereby adding a quantitative and objective value to complement the principles of keeping radiation exposure 'as low as reasonably achievable'. This snapshot of real-time data shows significant variation around the country, as well as significant differences between low- and high-volume centres for PCNL, and grade of lead surgeon for stent procedures.

Carotid Access for Endovascular Repair of Aortic Pathology: A Systematic Review.

BACKGROUND: Endovascular repair is now preferred to open access for the management of aortic diseases. This is typically performed via the femoral artery; however, not all patients are eligible for this. This systematic review summarizes the current evidence for utilizing the carotid artery as an alternative access route. METHODS: A systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using 4 electronic databases. RESULTS: The search found 11 case reports representing 12 patients eligible for analysis (mean age 64.5 years). This included 3 thoracic aneurysms, 3 abdominal aneurysms, 4 penetrating ulcers, 1 endoleak, and 1 pseudoaneurysm. An open procedure was contraindicated in 83% (10/12) due to the poor physiological fitness of the patient. In 75% (9/12) of cases, traditional endovascular access was contraindicated by severe iliac disease. The remainder were contraindicated because of an existing ligated aortic stump (1/12, 8.3%) or technical difficulty with graft deployment via the femoral artery (2/12, 16.7%). There was 1 death, with the 30-day mortality 8.3%. The same patient suffered the only spinal ischemia before death (8.3%). There were no cases of stroke (0%), with one case of transient ischemic attack (8.3%). CONCLUSIONS: Although there is a relative paucity of literature, this study demonstrates when traditional endovascular access is impossible and an open procedure contraindicated, carotid artery access for endovascular repair of aortic pathology is a viable alternative with good 30-day survival and low rates of neurological sequelae.

Radiologically guided percutaneous aspiration and sclerotherapy of symptomatic simple renal cysts: a systematic review of outcomes.

Simple renal cysts are common benign lesions of the kidney with up to 4% of patients developing symptoms necessitating intervention including pain and haematuria. We conducted a systematic review of the literature to determine the efficacy and safety of aspiration-sclerotherapy of symptomatic simple renal cysts. A systematic review using Cochrane guidelines was conducted on published literature from 1990 to 2020. RCTs, cohort studies and case series meeting the inclusion criteria were reviewed and cumulative analysis of outcomes was performed. A total of 4071 patients from 57 studies underwent aspiration ± sclerotherapy for their simple renal cysts. 87.7% of patients who had aspiration with sclerotherapy demonstrated 'treatment success' with a >50% reduction in cyst size and complete resolution of symptoms. 453 minor, transient complications occurred (11.2%) whilst a major complication rate of less than 0.1% (4 patients) was reported. Pooled analysis of all available current literature demonstrates that aspiration-sclerotherapy is a safe and effective first-line therapy for symptomatic simple renal cysts. Although we are unable to compare those undergoing aspiration alone to aspiration-sclerotherapy, it is evident the use of a sclerosing agent is integral to treatment success; however, the optimum agent, volume, injection frequency, and dwelling time are yet to be defined. Cyst size should be considered when discussing treatment options; however, we conclude it reasonable for aspiration-sclerotherapy to be used in the first instance in all cases of symptomatic simple renal cysts. Furthermore, we propose definitions of treatment outcome measures in order to allow direct comparative analysis across future studies.

The "Is mpMRI Enough" or IMRIE Study: A Multicentre Evaluation of Prebiopsy Multiparametric Magnetic Resonance Imaging Compared with Biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. OBJECTIVE: To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naïve or have had previous negative biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. RESULTS AND LIMITATIONS: Across ten sites, 2642 men were included (January 2011-November 2018). Mean age and PSA were 65.3yr (standard deviation [SD] 7.8yr) and 7.5ng/ml (SD 3.3ng/ml), respectively. Of the patients, 35.9% had "negative MRI" (scores 1-2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG≥2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15ng/ml/ml was used in MRI scores 1-2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12ng/ml/ml. ISUP GG≥3 (Gleason ≥4+3) was found in 2.4% (15/617) of men with MRI scores 1-2. They key limitations of this study are the heterogeneity and retrospective nature of the data. CONCLUSIONS: Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. PATIENT SUMMARY: Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone.

Robot-assisted Radical Prostatectomy After Focal Therapy: Oncological, Functional Outcomes and Predictors of Recurrence.

There are few data on the outcomes and toxicity of radical prostatectomy (RP) among men experiencing local recurrence of prostate cancer (PC) following focal therapy (FT). To characterise perioperative, oncological, and functional outcomes after salvage robot-assisted RP (S-RALP) and determine the risk factors for S-RALP failure, we conducted a multicentre cohort study of 82 patients undergoing S-RALP after FT. All had histological confirmation of PC recurrence, with metastatic disease excluded using pelvic magnetic resonance imaging, a bone scan, and/or positron emission tomography/computed tomography. Progression-free survival was 74%, 48%, and 36% at 12, 24, and 36mo after surgery, respectively. The 12-mo continence rate was 83%. There were no intraoperative complications and no major postoperative complications. On multivariable analysis, only infield recurrence (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.11-12.85; p=0.03) and pT3b stage (HR 5.0, 95% CI 1.53-16.39; p=0.008) were independent predictors of recurrence. This study represents the largest series of salvage surgery after FT and shows that this approach is safe with no increase in toxicity when compared to primary RALP. Men identified as having infield recurrence after FT appear to have phenotypically aggressive disease and should be counselled regarding the potential need for a multimodal therapeutic approach. PATIENT SUMMARY: Robotic surgery after focal therapy for prostate cancer is safe and achieves postoperative continence results similar to those for robotic radical prostatectomy in treatment-naïve patients. However, if the cancer recurrence is within the previously treated field, the oncological prognosis seems to be worse.

Transcarotid transcatheter aortic valve implantation: A systematic review.

BACKGROUND: The carotid artery is a novel access route for transcatheter aortic valve implantation (TAVI), especially useful in patients unsuitable for traditional access routes including transfemoral (TF), subclavian, transapical (TAp), and aortic (TAo). This systematic review summarizes the evidence on TAVI via the carotid artery for its efficacy and safety. METHODS: A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA) guidelines on three online databases: Medline (via Pubmed), SCOPUS, and Cochrane Database. RESULTS: There were 8 non-randomized controlled trials identified comprising 650 patients in four TAVI vascular access sites: transcarotid (TC) (N=364), TF (N=100), TAp (N=151), TAo (N=35). The 30-day rates of mortality and neurological complications for TC TAVI were 6.5% and 3.8%, respectively, with 1 incidence of myocardial infarction. Other complications included vascular complications (7.7%), insertion of new pacemaker (17.4%), atrial fibrillation (5.2%), and acute kidney injury (6.9%), bleeding episodes (14.3%), of which 13 (3.6%) cases were life-threatening; 5 (1.4%) were major; and 35 (9.3%) were minor cases. Follow-up to 1 year showed 19 further deaths. There were no significant differences in terms of mortality rates [risk ratio (RR)=0.31, 95%CI 0.05-1.79; p=0.19] and onset of dialysis treatment (RR=2.53, 95%CI 0.31-19.78; p=0.38) between the TC and TAp groups. CONCLUSION: The available data on TC TAVI show comparable technical feasibility with other traditional access routes, representing a viable alternative. However, the paucity of data warrants the need for larger randomized controlled trials to establish a firm conclusion.

Incisional Hernia in Renal Transplant Recipients: A Systematic Review.

Incisional hernia follows midline laparotomy in 8 to 20 per cent of cases, but the rate following lateral incision is not well documented. This systematic review summarizes incisional hernia rate after open renal transplant. We searched EMBASE, MEDLINE, and the Cochrane Library databases from January 2000 to November 2016 inclusive. The outcomes included in our analysis were the posttransplant incisional hernia rate, significant patient risk factors for incisional hernia, the definition of incisional hernia used, the method used to detect incisional hernia, and the incision used for transplantation. Eight retrospective case series were identified, three describing renal transplant recipients and five describing incisional hernia repairs postrenal transplant. All reported the incisional hernia rate postrenal transplant at the host institution. The hernia rate ranged from 1.1 to 7.0 per cent, with a mean of 3.2 per cent. Factors associated with incisional hernia were body mass index >30, age >50, cadaveric graft, and reoperation through the same incision. Despite the significant comorbidity of renal transplant recipients, the incisional hernia rate postrenal transplant is significantly lower than that of post-midline laparotomy. The reasons for this are discussed. This demonstrates the importance of operative technique, local tissue quality and biomechanical factors in the formation of incisional hernia.

A rare urological presentation of appendicitis.

A 17-year-old boy with no medical comorbidities, but a significant family history of malignancy, presented to Accident and Emergency following 3 days of increasing rectal pain, symptoms of bladder outflow obstruction (poor flow, intermittent stream and hesitancy) and dysuria. Notably he had no abdominal pain. Digital rectal examination revealed a tender, enlarged prostate. Inflammatory markers were significantly raised (white cell count 17.7, C reactive protein 191). He was diagnosed clinically as prostatitis and commenced on intravenous antibiotics. Despite this his pain and inflammatory markers deteriorated, necessitating a CT of his abdomen and pelvis. This demonstrated multiloculated large thick-walled abscesses in the pelvis closely related to the rectum, prostate and seminal vesicles with some bowel wall thickening. Laparoscopy demonstrated a large colonic mass adherent to surrounding structures. The procedure was converted to laparotomy to enable resection of the mass via a limited right haemicolectomy. He recovered well and was discharged. Histopathological analysis of the specimen revealed appendicitis.

Bowel perforation presenting three months after suprapubic catheter insertion.

An 82-year-old male with multiple comorbidities, including previous laparotomies, had a suprapubic catheter (SPC) inserted under guidance with ultrasound and a flexible cystoscope. Three months following the procedure, having returned for a flexible cystoscopy for ongoing bladder pain syndrome, he became peritonitic postoperatively.A CT scan and subsequent laparotomy confirmed the SPC to be passing through a section of terminal ileum. The bowel was resected and he recovered well after a long hospital admission. A literature search found this delayed presentation of bowel perforation following SPC insertion to be rare, with only a few other cases reported. In particular, previous abdominal surgery increases the risk of this complication. This case serves as a reminder of the rare but potentially significant risk of SPC insertion and unusually highlights that this may not present immediately.

Contemporary outcomes and prediction of adherent perinephric fat at partial nephrectomy: a systematic review.

OBJECTIVE: Current guidelines recommend partial nephrectomy for the management of T1a tumours. Adherent perinephric fat (APF) has been recognized as a complicating feature of such surgery. The objective of this article was to present a systematic review of the published literature investigating APF aetiology, risk factors and outcomes. MATERIALS AND METHODS: To identify relevant studies, the PubMed, MEDLINE, Web of Science and Google Scholar databases were searched from 1990 to 2017. RESULTS: Eight studies studying APF were identified. The aetiology of APF appears to be multifactorial, but is thought to be associated with a systemic, chronic inflammatory state secondary to metabolic syndrome. Several risk factors have been identified. Clinically, APF is more prevalent in ageing and male populations, particularly those with high body mass index and waist measurements. Radiological risk factors for APF include increased perinephric fat thickness and stranding, which can be combined to produce the Mayo Adhesive Probability (MAP) score, a predictive index that has been validated in small, external cohorts. The presence of APF at partial nephrectomy is associated with increased operative time and estimated blood loss. However, there is no documented increase in warm ischaemia time or perioperative complications in patients with APF. CONCLUSIONS: More studies are required to identify outcomes and risk factors for APF. Early identification of patients with APF can allow surgeons to guide preoperative planning and patient assessment.

Laparoscopic vs robotic nephroureterectomy: Is it time to re-establish the standard? Evidence from a systematic review.

OBJECTIVE: To conduct a systematic review of comparative studies of laparoscopic nephroureterectomy (LNU), the standard management for upper urothelial tumours, and robot-assisted NU (RANU) that has emerged as a viable alternative. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all studies reporting on both LNU and RANU for upper urothelial tract tumours. RESULTS: In all, 1630 patients were included, of which 838 underwent LNU and 792 RANU. Three studies reported on mean operative time and found it to be less in LNU, with two reporting this to be significant (RANU 298 vs LNU 251 min, P = 0.03; 306 vs 234 min, respectively, P < 0.001). Both studies reporting on median node count found this to be higher in the robotic groups: RANU 5.5 vs LNU 1.0 and RANU 21 vs LNU 11. Positive surgical margins (RANU 1.69% vs LNU 7.06%, P = 0.18), bladder recurrence (24.6% vs 36.89%, P = 0.09), and distant metastases (27.50% vs 17.50%, P = 0.29) were not significantly different between the two techniques. Disease-specific mortality did not differ between the two techniques (RANU 7.5% vs LNU 12.5%, P = 0.46), but postoperative mortality was reduced in RANU (0.14% vs 1.32%, P = 0.03). Overall complication rates were statistically lower in RANU, at 12.5% vs 18.8% (P < 0.001). CONCLUSIONS: This review suggests these techniques are equivalent in terms of perioperative and oncological performance. Furthermore, there may be a lower overall complication rate, as well as postoperative mortality in the robotic group. Further research in the form of a randomised controlled trial is warranted.

Early vs. standard unclamping technique in minimal access partial nephrectomy: a meta-analysis of observational cohort studies and the Lister cohort.

To evaluate if early unclamping (EUC) of the renal pedicle compromises perioperative outcomes in minimally invasive partial nephrectomy (PN). The cohort study includes all robot-assisted PN performed between September 2012 and September 2015 by a single surgeon at the Lister Hospital, Stevenage, UK. The systematic review and meta-analysis was performed according to the PRISMA guidelines identifying studies comparing EUC and standard unclamping (SUC) in either laparoscopic or robot-assisted PN. The Lister cohort prospectively reported 84 cases of robot-assisted PN (SUC = 22, EUC = 62) with a mean age of 58 years (SD = 11). The operative time (OT), estimated blood loss (EBL) and warm ischaemia time (WIT) were 186.5 min (SD = 33.8), 125.5 mls (SD = 188.91) and 16.7 min (SD = 5.6), respectively. The data from the Lister cohort were included in the meta-analysis. The systematic review identified four studies, encompassing 666 cases (313 SUC, 353 EUC), for inclusion in the final analysis. There was a statistically significant difference in WIT in favour of the EUC group [-10.59 min (95% CI -16.58, -4.60)]. Specifically, the reduction in WIT was more pronounced in laparoscopic PN (-15.43 min (95% CI -19.05, -11.81)), when compared with the robotic PN [-5.60 min (95% CI -5.70, -5.50)]. There was no statistical difference in OT [-3.97 min (95% CI -14.22, 6.28)]. EBL was found to be increased in the EUC group [71.39 ml (95% CI -0.78, 143.56)]. There was no statistically significant difference in transfusion rates or complications between the two groups. The EUC technique for robot-assisted PN appears to offer a safe limited period of WIT without compromising perioperative outcomes and morbidity.

A systematic review of transcatheter aortic valve implantation via carotid artery access.

BACKGROUND: The carotid artery is a novel access route for transcatheter aortic valve implantation (TAVI). This may represent a viable alternative in patients unsuitable for TAVI via traditional transfemoral access, up to 20%, as well as other access routes such as subclavian, transapical and aortic. This systematic review summarises the current evidence for its safety and feasibility. METHODS: A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA) guidelines using five electronic databases. RESULTS: 16 studies were identified, including three prospective cohort studies, one retrospective cohort study, three case series and eight case reports. Data on 74 patients (mean age 76.9years) was extracted including pre-operative work-up, technical procedure details and outcomes. This found 1 intraoperative death, 2 further deaths within 30days, two incidences of transient ischaemic attack, no incidences of stroke, myocardial infarction, carotid access site complications or infection, 1 patient required new dialysis and 1 patient had an intraoperative dissection which resolved. Follow-up from 30days to 1year showed symptomatic improvement and echocardiographic improvement in line with those seen in transfemoral TAVI. CONCLUSIONS: The available data on TAVI via carotid access demonstrate technical feasibility with comparable outcomes to other traditional access routes. A low number of patients, heterogeneous clinical endpoints and relatively short follow-up periods limit formal meta-analysis and firmer conclusions. For patients in which other access routes are impossible, TAVI via carotid access represents a viable and potentially crucial alternative in patients who might otherwise be untreatable.

Preventing the co-prescription of tamoxifen and fluoxetine in General Practice.

In 2010 a population-based cohort study showed that there was decreased efficacy of the breast cancer drug tamoxifen when used in combination with fluoxetine, a commonly used SSRI antidepressant. The aim of this project was to identify patients who may be affected by this co-prescription and suggest a change in medication. The project was conducted across two GP practices in Clevedon (The Riverside Practice & The Green Practice), Bristol. The patients were all from the active patients register at each surgery. A search was conducted to find all those on tamoxifen and fluoxetine, using the EMIS computer system. These patients would then be sent a letter to attend clinic. The new data would then be discussed with them before recommending a change of antidepressant (typically to sertraline). Three patients were found to be on both medications. They were all called into clinic and changed from fluoxetine to sertraline. Furthermore a presentation was given to all GPs at the two surgeries alerting them to the new guidelines. A message was also set up to flash on the computer system whenever an attempt was made to co-prescribe the two drugs. All the patients on tamoxifen in these two practices are now receiving the optimum treatment. Furthermore interventions have been put in place to ensure that this remains the case in future. Another data collection should be conducted in one year. This project provides a good example of how this problem could be resolved at other GP surgeries.