R. Persad

Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel

Background:The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments.Aim:The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel.Methods:DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT–PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting.Results:The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel.Conclusion:The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.

Medium-term Outcomes after Whole-gland High-intensity Focused Ultrasound for the Treatment of Nonmetastatic Prostate Cancer from a Multicentre Registry Cohort

BACKGROUNDnHigh-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer.nnnOBJECTIVEnTo report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort.nnnDESIGN, SETTING, AND PARTICIPANTSnFive-hundred and sixty-nine patients at eight hospitals were entered into an academic registry.nnnINTERVENTIONnWhole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnOur primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function.nnnRESULTS AND LIMITATIONSnMean age was 65 yr (47-87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4-10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23-61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64-74). This was 87% (95% CI: 78-93), 63% (95% CI: 56-70), and 58% (95% CI: 32-77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data.nnnCONCLUSIONSnWhole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments.nnnPATIENT SUMMARYnIn this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy.

The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies

Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance-like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions.

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial

BackgroundA growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6xa0months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures.Methods/designThe trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6xa0months post-randomisation).DiscussionThe Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery.Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

A systematic review of PFE pre-prostatectomy

Male Stress Urinary Incontinence is a complication post robotic radical prostatectomy. This is a major problem that needs to be solved, since it has great impact on quality of life affecting the patient’s physical activity and social well-being. A systematic review relating to literature on impact of preoperative PFE on continence outcomes for patients undergoing prostatectomy was conducted. The search strategy aimed to identify all references related to pelvic floor exercises and post-prostatectomy. Search terms used were as follows: (Pelvic floor exercises) AND (incontinence) AND (prostatectomy). The following databases were screened from 2000 to September 2017: CINAHL, MEDLINE (NHS Evidence), Cochrane, AMed, EMBASE, PsychINFO, SCOPUS, Web of Science. In addition, searches using Medical Subject Headings (MeSH) and keywords were conducted using Cochrane databases. Two UK-based experts in prostate cancer and robotic surgery were consulted to identify any additional studies. In the 6xa0months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the PFE and biofeedback groups and control groups (PFE alone), respectively (Pu2009=u20090.596) (Bales et al. in Urology 56: 627–630, 2000). This demonstrates preoperative PFE may improve early continence after RP. Geraerts et al. (Eur Urol 64:766–772, 2013) demonstrated the “incontinence impact” was in favour of a group with PFE at 3 and 6xa0months after surgery. This demonstrates again the advantage of preoperative PFE. Cornel et al. [World J Urol 23:353–355, 2005] determined the benefit of starting pelvic floor muscle exercise (PFE) 30xa0days before RP and of continuing PFE postoperatively for early recovery of continence as part of a randomised, prospective study (Moher quality A). This demonstrated preoperative PFE may improve early continence and QoL outcomes after RP. Post-prostatectomy incontinence is a bothersome complication of radical prostatectomy [Chughtai et al. in Rev Urol 15:61–66, 2013]. Weak pelvic floor muscles compromised normal pelvic floor function and led to urinary incontinence and erectile dysfunction. Strengthening the pelvic floor muscles was shown to significantly improve post-prostatectomy urinary continence, post-micturition dribble and erectile function. It would be prudent for all men to exercise their pelvic floor muscles to maintain normal pelvic floor function and start prior to surgery.

Prostate Cancer Survivorship Experience:Patient Reported Outcome Measures andFocus Group Results

Introduction: There are an ever increasing number of prostate cancer survivors. These patients are currently followed up in secondary care. Focus of care is on recurrence and acute management, not holistic care. nMethod: Over a 3 year period, patients attending follow-up appointments having completed treatment for organ confined prostate cancer and satisfying entry criteria were offered to join the programme. This comprises a database for PSA tracking and holistic assessment of patient needs run by a specialist nurse. The programme is supplemented by a Survivorship conference once a year, where patients have access to healthcare professionals discussing a range of topics related to prostate cancer. We assess patient satisfaction with questionnaires both pre and post conference and with a focus group in order to develop recommendations for the programme. nResults: We currently have 178 on the database 55 patients and friends visited the conference, with the majority specifying they would re-attend. The majority also ranked the conference as worthwhile re-attending. After the conference, we demonstrate patient concern decreases, with disease control and understanding increasing. We also show patients prefer the community based follow-up scheme, as opposed to a hospital based follow up. nConclusion: Survivorship care has yet to be developed fully in clinical practice; this paper demonstrates how we can do this as part of a co-led approach with patients.

Robotic radical cystectomy – revision and resection: An evolution in operative technique and platforms

Indocyanine green (ICG) fluorescence technology has also been used to delineate bowel perfusion. The optimal point of transaction can be marked under white (visible) light followed by intravenous injection of 6-8 mg of ICG [7]. The bowel is then visualized via near infrared laparoscopy and the point of transaction of the proximal is revised based on optimal bowel perfusion. This demonstrates the feasibility and advantages of the use of fluorescence imaging during creation of anastomosis; the advantages of endoscopic imaging to delineate integrity of the anastomosis as well the technique with regards to creating the anastomosis [7]. This can be used as part of cystectomy, when forming the conduit. To take this one step further, it can also be used, to assess the vasculature of the ileal conduit segment.

Robotic radical cystectomy: intracorporeal versus extracorporeal versus orthotopic neobladder—Which is better?

ports is replaced with a robotic arm leaving the remaining 2 assistant ports for the surgical assistant [5]. Some series of RARC use an extracorporeal approach to ileal conduit creation [6]. The perioperative and 90-day postoperative outcomes of the first 71 consecutive patients who underwent RARC demonstrated overall 90-day complication rate were 65 % [6]. However, a large proportion of tumors were of low grade. This demonstrated robotassisted intracorporeal ileal conduit is safe, feasible and reproducible. Of the 18 IRCC institutions involved in a multi-institutional study, 167 patients underwent intracorporeal diversion (ileal conduit/106; neobladder/61) and 768 patients underwent extracorporeal diversion (ileal conduit/570; neobladder/198) [7]. This demonstrated that there was no difference in re-operation rate at 30 days between groups [7]. Patients who underwent IC diversion were less likely to experience a complication at 90 days (40 vs 50 %, p > 0.019) [7]. Patients were 32 % less likely to have complication if the urinary diversion was performed as an intracorporeal procedure [OR 0.68 (95 % CI 0.50–0.94, p > 0.02]. This clearly highlights that intracorporeal is better, especially with the advances in robotics. This has been re-enforced [8]. Robot-assisted intracorporeal ileal conduit can be accomplished safely with comparable operative, postoperative parameters and complications to open ileal conduit [8]. However, patients undergoing intracorporeal ileal conduit had improved body image. With intracorporeal stoma formation, no patients returned to the OR within 48 h, and only 7 % returned to the OR within 30 days [3]. The 90-day mortality rate was 2 %, and the 90-day complication rate was 42 % with the majority of complications being low grade [9]. Neobladder diversion had a lower risk of 90-day complications and Dear Editor,

Robotic radical cystectomy and enhanced recovery: a new pathway.

hospital stay. This is beneficial to the older patient, who may already be under the influence of polypharmacy. In today’s’ world, the focus seems to be on robotic surgery as the driving force behind shorter recovery periods and daycase surgery [4]. This highlights the importance of appropriate patient selection and post-operative care. With a far wider resectional area and greater stress response, than prostate surgery, a good enhanced recovery pathway is key to good patient outcomes. The key to successful post-operative recovery with robotic cystectomy is pre-operative, intraoperative, and post-operative care advances with implementation of cystectomy enhanced recovery pathways if possible [5]. This is a novel way to reduce length of stay and overall complications within 90 days of cystectomy without increasing readmissions or complications [6]. A well-designed pathway that accommodates all categories of patient in combination with robotic surgery can dramatically improve complications and length of stay compared to the national standards [7]. However, it must also be highlighted that many enhanced recovery programmes are standardised, and not tailored to an individual’s needs. When taking into account an older cohort of patients, a specifically tailored individual enhanced recovery programme is required [8]. This often requires a balance between a standardised protocol and an individually tailored plan. The enhanced recovery pathway implements a series of evidence-based interventions that decreases length of stay and complications without compromising patient outcomes [5]. A standard pathway incorporates pre-operative education, expectation setting, prehabilitation, nutrition evaluation, carbohydrate loading, venous thrombosis prophylaxis, normothermia maintenance, local anaesthesia, no nasogastric tubes or bowel prep, early feeding, and opioid avoidance [5]. Dear Editor, It was informative to read the article by Vanderwalde et al. [1]. This highlig hts that radical cystectomy is an option for elderly patients, with functional age determinants [1]. Minimally invasive surgery clearly allows a wider cohort to be treated. Enhanced recovery pathways are helpful towards this, but can robotic surgery and enhanced recovery alone improve outcomes for an older cohort of patients? The pathway should start pre-operatively, with assessment of the patient using cardiopulmonary exercise testing. The use of cardiopulmonary exercise testing is gaining popularity as a pre-operative functional assessment tool and is a useful adjunct to risk stratification before radical cystectomy [2]. It will also enable the performance status of the patient to be determined accurately. If performance status were not assessed, complications would be more likely. Enhanced recovery studies have shown objective parameters that can improve peri-op outcomes [3]. However, significant individual differences in peri-operative management of cystectomy exist, which may not necessarily result in good patients outcomes [3]. One of the points with enhanced recovery includes significantly less opioid analgesics. This contributes to decreased post-operative ileus and shorter length of

Erectile function post robotic radical prostatectomy: technical tips to improve outcomes?

Robotic surgery is becoming more and more commonplace. At the same time, so are complications, especially related to erectile function. The population being diagnosed with cancer is younger, with more aggressive cancers and higher expectations for good erectile function postoperatively. We conduct a retrospective analysis of literature over 20 years for Embase and Medline. Search terms used include (Robotic) AND (prostatectomy) AND (erectile function). There are a variety of multifactorial causes, resulting in worsening ED post-robotic radical prostatectomy; however, there are a number of treatments that can support this. There is much we can do to help prevent patients getting postoperative erectile dysfunction post-radical surgery. However, part of this is management of realistic patient expectations.