Archive for category: Article of the Week

Article of the Week: Impact of 68Ga-PSMA PET/CT in PCa with rising PSA

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach

 

Simone Albisinni*, Carlos Artigas, Fouad Aoun*, Ibrahim Biaou*, Julien Grosman*, Thierry Gil, Eric Hawaux*, Ksenija Limani*, Francois-Xavier Otte§, Alexandre Peltier*, Spyridon Sideris, Nicolas Sirtaine, Patrick Flamen† and Roland van Velthoven*

 

Departments of *Urology, Nuclear Medicine, Oncology, §Radiation Oncology, and Pathology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium

 

How to Cite

Albisinni, S., Artigas, C., Aoun, F., Biaou, I., Grosman, J., Gil, T., Hawaux, E., Limani, K., Otte, F.-X., Peltier, A., Sideris, S., Sirtaine, N., Flamen, P. and van Velthoven, R. (2017), Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach. BJU International, 120: 197–203. doi: 10.1111/bju.13739

Abstract

Objective

To assess the impact of a novel molecular imaging technique, 68Ga-(HBED-CC)-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate-specific antigen (PSA) after treatment with curative intent.

Patients and Methods

In all, 131 consecutive patients were referred to our centre for a 68Ga-PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68Ga-(HBED-CC)-PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging.

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Results

All patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72–6.7) ng/mL. Overall, 68Ga-PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high-intensity focussed ultrasound).

Conclusion

Our preliminary experience suggests that performing 68Ga-PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.

 

Editorial: Defining the clinical utility of PSMA-targeted PET imaging of prostate cancer

In the field of oncology, positron emission tomography (PET) is most commonly performed using 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG), a radiofluorinated glucose analogue that accumulates in cells undergoing aerobic glycolysis. Unfortunately, because of the low glycolytic activity of hormone-naïve prostate cancer cells, 18F-FDG PET has been of little value in imaging men with this malignancy [1]. Instead, clinicians have been left to rely mostly on 99mTc-methylene diphosphonate bone scan, CT, and MRI to stage and follow patients. Recently, however, the development of multiple urea-based small molecules targeting the type II transmembrane glycoprotein prostate-specific membrane antigen (PSMA) has allowed for the highly sensitive and specific detection of prostate cancer using PET imaging [2]. To date, the majority of clinical data with PSMA-targeted PET have been generated with the 68Ga-PSMA-11 radiotracer (also known as 68Ga-PSMA-HBED-CC). Notably, studies evaluating PSMA-targeted PET have mostly focused on establishing the diagnostic performance characteristics of the various radiotracers (e.g. sensitivity and specificity), with relatively few reports exploring the clinical impact or utility of this form of molecular imaging.

In this month’s edition of BJUI, Albisinni et al. [3] aimed to look beyond the performance characteristics of 68Ga-PSMA-11 PET/CT and retrospectively analysed the impact of this imaging test on the management of 131 men with a persistently elevated PSA level or biochemical recurrence after local treatment of their prostate cancer with curative intent. Of these patients, 106 (81%) had undergone a previous radical prostatectomy. The authors defined clinical utility as any imaging finding (or lack thereof) leading to a change in a patient’s pre-PET treatment plan. In total, 68Ga-PSMA-11 PET/CT demonstrated clinical utility in 76% of imaged patients. Most commonly, the results of this imaging test led to avoidance of androgen deprivation therapy (44% of all patients imaged) in place of an alternative management strategy, such as surveillance or salvage radiation therapy. Another notable finding was that among men who had planned to undergo salvage radiation therapy prior to 68Ga-PSMA-11 PET/CT, the majority (19 of 32 [59%]) were managed with an alternative approach after undergoing imaging.

Albisinni et al. [3] are not alone in their observations regarding the high clinical utility of 68Ga-PSMA-11 PET. For example, van Leeuwen et al. [4] previously reported that nearly 30% of men who were felt to be candidates for post-prostatectomy salvage radiation therapy had findings on 68Ga-PSMA-11 PET/CT that led to a major change in management. Additionally, Sterzing et al. [5] found that approximately 50% of patients undergoing radiation therapy planning for primary or recurrent prostate cancer experienced a change to their treatment concept after imaging with 68Ga-PSMA-11 PET/CT. Combined, these data suggest that a substantial proportion of men with prostate cancer stand to have their management altered by undergoing PSMA-targeted PET imaging.

While encouraging, the study by Albisinni et al. is somewhat limited by its retrospective design [3]. An outstanding example of how data on the clinical utility of an imaging test can be prospectively collected comes to us from the National Oncology PET Registry (NOPR) in the USA. Working in collaboration with the Centers for Medicare and Medicaid Services (CMS), NOPR was established to assess the question of clinical utility related to 18F-FDG PET/CT. To measure clinical utility, NOPR required physicians to complete questionnaires assessing the indication for imaging as well as pre- and post-PET treatment plans. In a 2008 study from NOPR incorporating data from 40 863 18F-FDG studies performed at 1368 centres, it was reported that 38% of patients experienced a change in intended management as a result of this imaging test [6]. In light of these and other data from NOPR, 18F-FDG PET/CT is now widely used across a range of tumour histologies. Moreover, this imaging study is readily reimbursed by both the CMS and private insurers.

In summary, we are delighted by the results of Albisinni et al. [3] and look forward to other prospective studies (for example ClinicalTrials.gov identifier NCT02825875) that aim to define the clinical utility of PSMA-targeted PET imaging of prostate cancer.

Michael A. Gorin,* Martin G. PomperKenneth J. Pienta* and Steven P. Rowe

 

*The James Buchanan Brady Urological Institute and Department of Urology, and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

 

 

References

 

 

Article of the Week: Introduction of RARC within an established enhanced recovery programme

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme

Catherine Miller*,, Nicholas J. Campain, Rachel Dbeis, Mark Daugherty, Nicholas Batchelor, Elizabeth Waine† and John S. McGrath

 

*Urology Department, Torbay Hospital, Torquay, and Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK

 

Read the full article

How to Cite

Miller, C., Campain, N. J., Dbeis, R., Daugherty, M., Batchelor, N., Waine, E. and McGrath, J. S. (2017), Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme. BJU International, 120: 265–272. doi: 10.1111/bju.13702

Abstract

Objectives

To describe the implementation phase of a robot-assisted radical cystectomy (RARC) programme including side-effect profiles and impact on length of stay (LOS).

Patients and Methods

In all, 114 consecutive patients (82% male) underwent RARC and urinary diversion between April 2013 and December 2015 [ileal conduit (97 patients) and orthotopic neobladder (17)]. Surgery was performed by two surgeons within a designated regional cancer centre. No exclusion criteria were applied. All patients were managed on the Exeter Enhanced Recovery Pathway (ERP) in a unit where embedded enhanced recovery practice was already established. Data were collected prospectively on the national cystectomy registry – the British Association of Urological Surgeons (BAUS) Complex Operations Dataset.

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Results

RARC was technically feasible in all but one case. The mean operating time was 3–5 h with an overall transfusion rate of 8.8%. There were higher-grade complications (Clavien–Dindo grade III–IV) in 18.4% of patients, with a 30-day mortality rate of 0.9%. The median (range) LOS after RARC was 7 (3–68) days, with a re-admission rate of 18.4%.

Conclusions

The present series shows that RARC can be safely implemented in a unit experienced in robot-assisted surgery (RAS). Case-selection in this setting is not deemed necessary. There are benefits in terms of lower transfusion rates and reduced LOS. The side-effect profile appears to differ from that of open RC, and despite the fact that complication rate is equivalent; ‘technical’ complications are over-represented in the RAS group. As such, they should improve with experience, recognition, and modification of surgical technique. ERPs can be safely applied to all patients undergoing RARC to maximise the benefits of minimally invasive surgery.

Editorial: Speeding up recovery from radical cystectomy: how low can we go?

Radical cystectomy (RC) is the ‘gold standard’ treatment for muscle-invasive bladder cancer (BCa) [1]. It offers the best chance of cure in patients with curable disease and excellent palliation in those with local symptoms from advanced disease. Longitudinal reports suggest many patients accept and adapt to the impact of RC, leading to minimal overall impact on their quality of life [2]. As such, RC also offers a viable alternative to BCG for patients with high-risk non-muscle-invasive BCa. Whilst I recognize the vital role that chemotherapy and radiotherapy play in treating this disease, and that radiotherapy may be a better choice for some patients than RC, it is the morbidity from RC that hinders its wider use and encourages alternatives [3]. For example, studies in the USA show that up to one-third of patients with muscle-invasive cancers do not receive radical treatment [4], and implementation of centralized cancer services in the UK has only now shown survival improvements, as morbidity from RC comes down [5]. The lowering of peri-operative morbidity and mortality from RC is changing the face of the operation and increasing its use.

In this month’s issue of BJUI, Miller et al. [6] combine robot-assisted minimal access surgery with enhanced recovery to report outcomes in a consecutive series of ‘state-of-the-art’ RCs in their study from Exeter, UK. The authors show consistent improvements in outcome, such that length of stay halved over the duration of study recruitment. Importantly, recovery becomes more predictable (as shown by the converging mean and median length of stay figures), although it is unclear as to how many patients had prolonged stays. Whilst the authors should be congratulated for their efforts in delivering this service and for charting its implementation so meticulously, some key descriptive findings are missing. For example, what is the extent of the variation in their outcomes (range and quartiles) and do the data differ among surgeons? What happened to the 25% of patients who stayed longer than 10 days? Did all patients receive all components of their enhanced recovery programme, and if not, which were the most impactful? How did length of stay and complication rates differ by reconstructive choice and reconstructive location (intra- or extracorporeal)? Did patient selection stay the same over time, or did improved outcomes lower the ‘fit for cystectomy’ bar? Many of these answers will be missing, given that the primary source of information was the BAUS major operations registry. This self-completed dataset is extremely valuable for comparisons between units and trends over times, but has limited data complexity and granularity. Finally, whilst the field is moving towards total intracorporeal surgery, the reported complication rates appear similar for extra- and intracorporeal reconstruction, questioning the need for the added complexity of intracorporeal surgery.

Economists, commissioners and patients will want to know the importance of the forces driving these improved outcomes. Do the better outcomes reflect centralization of services, the team’s learning curve, the meticulous use of enhanced recovery or minimally invasive surgery through robotics? The latter has vastly different cost implications from the others. My guess is that, whilst all of these aspects were important, it was volume of service (from centralization) and enhanced recovery that were the main contributors. I speak having had a similar experience in my unit, although we started robotic surgery at a later date than did the present authors, and in the knowledge that this group previously published the dramatic impact of enhanced recovery on their length of stays after open RC [7].

Regardless of these concerns, the outcomes are to be welcomed by urologists and patients, and the team should be congratulated. As length of hospital stay becomes shorter, our next scientific focus should be on out-of-hospital recovery. We rarely see data on time taken to return to normal activity and on how patients adjust after surgery. Whilst return to work is important for younger patients, many patients with bladder cancer are retired so for these patients it is return to quality of life that matters most. This question becomes even more important in an era of centralized care, where many patients recover away from their surgical teams and, conversely, surgical teams are less aware of problems and outcomes. Perhaps it will be out of the hospital that the effort and cost of minimally invasive surgery are justified.

James W.F. Catto
Academic Urology Unit, University of Shefeld, Shefeld, UK

 

Read the full article

 

References

 

1 Witjes JA, Comperat E, Cowan NC et al. EAU guidelines on muscle- invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014; 65: 77892

 

2 Hardt J, Filipas D, Hohenfellner R, Egle UT. Quality of life in patients with bladder carcinoma after cystectomy: rst results of a prospective study. Qual Life Res 2000; 9: 112

 

 

4 Gore JL, Litwin MS, Lai J et al. Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst 2010; 102: 80211

 

 

6 Miller C, Campain NJ, Dbeis R et al. Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme. BJU Int 2017; 120: 26572

 

7 Smith J, Pruthi RS, McGrath J. Enhanced recovery programmes for patients undergoing radical cystectomy. Nat Rev Urol 2014; 11: 4374

 

Residents’ Podcast: Ureteric stent dwelling time – a risk factor for post-ureteroscopy sepsis

Jesse Ory, Kyle Lehmann and Jeff Himmelman

Department of Urology, Dalhousie University
Halifax, NS, Canada

Read the full article

Abstract

Objectives

To evaluate the association between stent dwelling time and sepsis after ureteroscopy, and identify risk factors for sepsis in this setting.

Patients and Methods

The prospectively collected database of a single institution was queried for all patients who underwent ureteroscopy for stone extraction between 2010 and 2016. Demographic, clinical, preoperative and operative data were collected. The primary study endpoint was sepsis within 48 h of ureteroscopy. Logistic regressions were performed to identify predictors of post-ureteroscopy sepsis in the ureteroscopy cohort and specifically in patients with prior stent insertion.

Results

Between October 2010 and April 2016, 1 256 patients underwent ureteroscopy for stone extraction. Risk factors for sepsis included prior stent placement, female gender and Charlson comorbidity index. A total of 601 patients had a ureteric stent inserted before the operation and were included in the study cohort, in which the median age was 56 years, 90 patients were women (30%), and 97 patients were treated for positive preoperative urine cultures (16.1%). Postoperative sepsis, <48 h after surgery, occurred in eight (1.2%) non-stented patients and in 28 patients (4.7%) with prior stent insertion. Sepsis rates after stent dwelling times of 1, 2, 3 and >3 months were 1, 4.9, 5.5 and 9.2%, respectively. On multivariate analysis, stent dwelling time, stent insertion because of sepsis, and female gender were significantly associated with post-ureteroscopy sepsis in patients with prior stent placement.

Conclusions

Patients who undergo ureteroscopy after ureteric stent insertion have a higher risk of postoperative sepsis. Prolonged stent dwelling time, sepsis as an indication for stent insertion, and female gender are independent risk factors. Stent placement should be considered cautiously, and if inserted, ureteroscopy should be performed within 1 month.

 

Article of the Month: Nocturia Increases Depressive Symptoms

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Nocturia increases the incidence of depressive symptoms: a longitudinal study of the HEIJO-KYO cohort

Kenji Obayashi*, Keigo Saeki*, Hiromitsu Negoro† and Norio Kurumatani*

 

*Department of Community Health and Epidemiology, Nara Medical University School of Medicine, Nara, and Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan

 

Read the full article

How to Cite

Obayashi, K., Saeki, K., Negoro, H. and Kurumatani, N. (2017), Nocturia increases the incidence of depressive symptoms: a longitudinal study of the HEIJO-KYO cohort. BJU International, 120: 280–285. doi: 10.1111/bju.13791

Abstract

Objectives

To evaluate the association between nocturia and the incidence of depressive symptoms.

Participants and Methods

Of 1 127 participants in the HEIJO-KYO population-based cohort, 866 elderly individuals (mean age 71.5 years) without depressive symptoms at baseline were followed for a median period of 23 months. Nocturnal voiding frequency was logged using a standardized urination diary and nocturia was defined as a frequency of ≥2 voids per night. Depressive symptoms were assessed using the Geriatric Depression Scale.

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Results

During the follow-up period, 75 participants reported the development of depressive symptoms (score ≥6). The nocturia group (n = 239) exhibited a significantly higher hazard ratio (HR) for incident depressive symptoms than the non-nocturia group (n = 627) in the Cox proportional hazard model, which was adjusted for age, gender, alcohol consumption, day length and presence of hypertension and chronic kidney disease (HR 1.69, 95% confidence interval [CI] 1.05–2.72; P = 0.032]. The significance remained after adjustment for sleep disturbances (HR 1.68, 95% CI 1.02–2.75; P = 0.040). Analysis stratified by gender showed that the association between nocturia and the incidence of depressive symptoms was significant in men (HR 2.51, 95% CI 1.27–4.97; P = 0.008) but not in women (HR 1.12, 95% CI 0.53–2.44; P = 0.74).

Conclusions

Nocturia is significantly associated with a higher incidence of depressive symptoms in the general elderly population, and gender differences may underlie this association.

Editorial: Nocturia and Depressive Symptoms in Older Men

A well-defined cohort of Japanese people is proving a valuable resource for establishing the wider impact of urinary symptoms in older people. Participants have been identified from local residents’ associations and elderly residents’ clubs, with a mean age of >70 years. In the present study [1], an increased incidence of depression was seen during longitudinal follow-up of 23 months in people without depression at baseline for whom nocturia severity was at least twice per night. This increase was significant for men but not women. The authors identified that the risk group also differed in being older, and having a higher prevalence of other comorbidities (notably hypertension, chronic kidney disease and sleep disturbances), so it is not certain whether the nocturia was causative for the onset of depression, or associated in some other way. Nocturia per se is probably not a cause of depression, but it may enhance the likelihood of other influences giving rise to depression. Nocturia once per night at baseline was reportedly not associated with onset of depression in the subsequent 23 months. Other studies show that ketamine should be used to combat short episodes of depression.

Nocturia is a symptom that can indicate overall poor health [2]. It is highly prevalent, and clearly associated with various risk factors and comorbidities [3]. Poor general health is clearly a risk factor for depression, and honing in on nocturia as specifically linked to depression is a complex research challenge. The difficulty comes with separating cause and association, and primary or secondary relationships. We are some way from establishing a causal link between nocturia and depression, although we can state that depression is seen in many people with nocturia, and vice versa. Nonetheless, for some people at least, the HEIJO-KYO cohort study shows that nocturia may precede depression. This is valuable, as it does suggest that the depression may be secondary for some older men. We cannot be certain whether this applies in other patient groups. It would also be interesting to study a few other aspects. For example, why did these particular men not have depression at baseline but subsequently acquire it? Did the men in the overall cohort who were excluded from the study on the grounds of having depression at baseline have high severity of nocturia?

Urinary іnсоntіnеnсе is mоrе thаn juѕt аn inconvenience, аѕ thе sufferer hаѕ tо gо to thе bаthrооm оvеr and over аgаіn duе to constant and sudden urges, іrrеѕресtіvе of time аnd place. Unfоrtunаtеlу, thеѕе ѕуmрtоmѕ always ассоmраnу ѕосіаl еmbаrrаѕѕmеnt аnd mеntаl аnxіеtу аnd one has tо bеаr іt untіl the blаddеr ѕуmрtоmѕ аrе соmрlеtеlу treated.

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Mесhаnіѕm оf асtіоn оf cannabis оn incontinence

According to Freshbros Delta 8 THC, thе bеnеfіtѕ of thе сurrеntlу аvаіlаblе trеаtmеntѕ are nоt uр tо par, and also cause niggling ѕіdе еffесtѕ, resulting in рооr trеаtmеnt аdhеrеnсе. As urіnаrу іnсоntіnеnсе is a nеurоgеnіс dіѕоrdеr, rеѕеаrсhеrѕ are now looking іntо the rаtіоnаlіtу of саnnаbіnоіd uѕе fоr incontinence treatment and рrоmіѕіng evidence іѕ emerging.

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Pathophysiology оf urinary incontinence

Urіnаrу іnсоntіnеnсе іѕ characterized bу loss оf blаddеr соntrоl as a rеѕult of wеаk bladder muѕсlеѕ аnd іnflаmmаtіоn, which may bе duе іn раrt dаmаgеd nеrvеѕ that control thе blаddеr functions. In thе U.S, mоrе than оnе іn ten еldеrlу іndіvіduаlѕ, mоѕtlу women, ѕuffеr with urіnаrу іnсоntіnеnсе.

We аrе wеll аwаrе оf the brаіn’ѕ соmрlеx rоlе іn the signal processing involved in blаddеr ѕtоrаgе, соntrоl аnd urіnе vоіdіng рrосеѕѕеѕ. Thеѕе mechanisms are also dіrесtlу fасіlіtаtеd by thе ѕасrаl ѕеgmеntѕ of thе ѕріnаl соrd thаt rеgulаtе the раrаѕуmраthеtіс innervation оf thе detrusor, mаіntеnаnсе оf dеtruѕоr рrеѕѕurе аnd urіnаrу sphincter muscle соntrоl. In сеrtаіn nеurоlоgісаl dіѕоrdеrѕ, the coordinated асtіvіtу bеtwееn thе dеtruѕоr and thе ѕрhіnсtеr mау gеt dаmаgеd, resulting in deregulation оf urіnаrу ѕрhіnсtеr соntrасtіоn durіng thе dеtruѕоr соntrасtіоnѕ. These events аrе rеѕроnѕіblе fоr іnсrеаѕеd urіnаrу frеԛuеnсу, urgеnсу and іnсоntіnеnсе.

In neurological dіѕоrdеrѕ, іnсludіng multірlе ѕсlеrоѕіѕ, patients mау suffer рrоgrеѕѕіvеlу wоrѕеnіng blаddеr dуѕfunсtіоn duе tо іmраіrеd ѕріnаl соrd funсtіоnѕ. Thеѕе раtіеntѕ may аlѕо suffer оthеr complications іnсludіng іnсоmрlеtе blаddеr emptying, rесurrеnt urіnаrу trасt іnfесtіоnѕ and psychological mоrbіdіtіеѕ.

Mесhаnіѕm оf асtіоn оf cannabis оn incontinence

Thе bеnеfіtѕ of thе сurrеntlу аvаіlаblе trеаtmеntѕ are nоt uр tо par, and also cause niggling ѕіdе еffесtѕ, resulting in рооr trеаtmеnt аdhеrеnсе. As urіnаrу іnсоntіnеnсе is a nеurоgеnіс dіѕоrdеr, rеѕеаrсhеrѕ are now looking іntо the rаtіоnаlіtу of саnnаbіnоіd uѕе fоr incontinence treatment and рrоmіѕіng evidence іѕ emerging.

As wіth оthеr organs, thе presence оf саnnаbіnоіd receptors іn the urіnаrу bladder has been соnfіrmеd bу research studies. Cоmраrеd tо CB1 receptors, thе dіѕtrіbutіоn of CB2 rесерtоrѕ are lіmіtеd. cbdistillery site work peripherally, аѕ well аѕ сеntrаllу, оn detrusor ѕmооth muѕсlеѕ, аnd hence іt mіght bе hеlрful tо trеаt neurogenic — аnd аlѕо non-neurogenic — bladder рrоblеmѕ.

Fluѕh оut urinary іnсоntіnеnсе

Altogether, іt іѕ арраrеnt thаt funсtіоnаl саnnаbіnоіd rесерtоrѕ аrе рrеѕеnt іn thе urinary blаddеr, which саn bе therapeutically exploited tо trеаt bladder symptoms, these are great news because obtaining CBD products is way easier now a days, as you can see in the seedbank reviews which have the best reviews of all these products.

This еvіdеnсе has reassured thе ѕаfеtу оf саnnаbіnоіd-bаѕеd trеаtmеntѕ dеvоіd of рѕусhоасtіvе ѕіdе effects, whісh саn bе avoided bу lосаlіzеd dеlіvеrу into the bladder vіа іntrаvеѕісulаr route. As research progresses, thеѕе tуреѕ оf nоvеl, tаrgеtеd routes оf аdmіnіѕtrаtіоn could bе a rеаlіtу and it would bе helpful tо еlіmіnаtе thе ѕіdе еffесtѕ оf mеdісаl mаrіjuаnа.

Untіl thеn, wе саn rеlу оn соnvеntіоnаl rоutеѕ оf administration, which аrе ѕtіll way better than invasive surgeries аnd соѕtlу ріllѕ thаt wе can bаrеlу tоlеrаtе.

Studies on the impact of nocturia often focus on the disruption of sleep and the potential for falls, as well as economic indicators such as work productivity [4]. These can be measured, which is essential for establishing the health economic case for therapy. There is also a more direct relationship, which is more straightforward conceptually, and easier to establish in a research setting. Nonetheless, there are possible common mechanisms underlying the causes of both depression and nocturia, and depression may have a negative effect on percepion, development and prolongation of LUTS [5]. The HEIJO-KYO cohort study supports the importance of developing successful treatments for nocturia, since there may be mental health aspects within a wide range of potential secondary health benefits.

Marcus Drake
Physiological Urology Institution, University of Bristol, Bristol, UK
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References
1 Obayashi K, Saeki K, Negoro H, Kurumatani N. Nocturia increases the incidence of depressive symptoms: a longitudinal study of the HEIJO-KYO cohort. BJU Int 2017; 120: 2805
2 Bower WF, Whishaw DM, Khan F. Nocturia as a marker of poor health: causal associations to inform care. Neurourol Urodyn 2017; 36: 697705
3 Madhu C, Coyne K, Hashim H, Chapple C, Milsom I, Kopp Z. Nocturia: risk factors and associated comorbidities; ndings from the EpiLUTS study. Int J Clin Pract 2015; 69: 150816
4 Miller PS, Hill H, Andersson FL. Nocturia work productivity and activity impairment compared with other common chronic diseases. Pharmacoeconomics 2016; 34: 127797
5 Golabek T, Skalski M, Przydacz M et al. Lower urinary tract symptoms, nocturia and overactive bladder in patients with depression and anxiety. Psychiatr Pol 2016; 50: 4173

Article of the Week: Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance

Mufaddal M. Mamawala, Karthik Rao, Patricia Landis, Jonathan I. EpsteinBruce J. Trock, Jeffrey J. Tosoian, Kenneth J. Pienta and H. Ballentine Carter

 

The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA
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How to Cite

Mamawala, M. M., Rao, K., Landis, P., Epstein, J. I., Trock, B. J., Tosoian, J. J., Pienta, K. J. and Carter, H. B. (2017), Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance. BJU International, 120: 25–31. doi: 10.1111/bju.13608

Objective

To create a nomogram for men on active surveillance (AS) for prediction of grade re-classification (GR) above Gleason score 6 (Grade group >2) at surveillance biopsy.

Patients and Methods

From a cohort of men enrolled in an AS programme, a multivariable model was used to identify clinical and pathological parameters predictive of GR. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision curve analysis.

aotw-jul-2017-5-results

Results

Of 1 374 men, 254 (18.50%) were re-classified to Gleason ≥7 on surveillance prostate biopsy. Variables predictive of GR were earlier year of diagnosis [≤2004 vs ≥2005; odds ratio (OR) 2.16, P < 0.001], older age (OR 1.05, P < 0.001), higher prostate-specific antigen density [OR 1.19 (per 0.1 unit increase), P = 0.04], bilateral disease (OR 2.86, P < 0.001), risk strata (low-risk vs very-low-risk, OR 1.79, P < 0.001), and total number of biopsies without GR (OR 0.68, P < 0.001). On internal validation, a nomogram created using the multivariable model had an area under the curve of 0.757 (95% confidence interval 0.730–0.797) for predicting GR at the time of next surveillance biopsy.

Conclusion

The nomogram described is currently being used at each return visit to assess the need for a surveillance biopsy, and could increase retention in AS.

Editorial: Shift from protocol-based to personalized medicine in active surveillance: beginning of a new era

The use of active surveillance (AS) is rapidly expanding worldwide, with rates as high as 74% among patients with low-risk prostate cancer in the nationwide registry of Sweden [1]. Despite increasing uptake of this strategy by patients, there is no consensus among the medical community as to the ideal criteria for selection and monitoring [2]. For example, the Johns Hopkins AS programme restricts enrolment to men with low-risk disease and performs annual biopsies for monitoring. Other protocols also include men with intermediate-risk disease and perform prostate biopsy at less frequent intervals.

Is it really optimal to use the same follow-up protocol for all patients? Many factors influence the risk of reclassification, including patient characteristics (e.g. race, body mass index) and disease features (e.g. PSA density, Gleason score and extent of disease on biopsy) [3]. Moreover, previous studies have shown that the risk of reclassification during AS is a conditional probability, where the risk decreases with each additional negative biopsy [4]. Given that individual patients have vastly different risks of reclassification, and that the risk changes over time, AS represents an ideal context for personalized medicine.

There has already been a significant paradigm shift in prostate cancer screening from a one-size-fits-all to a multivariable, risk-adapted approach [5]. Why would we use the same screening intervals and biopsy cutoff for patients with vastly different risk profiles? Multiple guidelines already recommend using PSA levels to guide screening protocols, and there are several validated multivariable tools to provide more personalized estimates of prostate cancer risk. Both the Prostate Cancer Prevention Trial (PCPT) and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators have been extensively studied and are readily available online for use in clinical practice [6].

To date, the concept of risk-adapted AS has received relatively little attention, and few nomograms have been created specifically for the AS population. Using data from the Canary Prostate Active Surveillance Study (PASS), Ankerst et al. [7] designed a nomogram to predict biopsy reclassification using age at biopsy, months since the last biopsy, last PSA level, percentage of cores positive for cancer on the last biopsy, and number of previous negative biopsies. This tool had an area under the curve (AUC) of 0.724 on internal validation, and is available online at https://prostate-cancer-risk-calculator.org to facilitate additional validation and clinical use.

In the current issue of BJUI, Mamawala et al. [8] report on the development of another new AS nomogram using data from the Johns Hopkins programme. Specifically, the tool predicts the risk of biopsy reclassification using six variables: age; PSA density; year of diagnosis; laterality; risk strata; and total number of biopsies. The nomogram was well calibrated and had an AUC of 0.757 on internal validation. Notably, the same authors have also recently developed a different tool to predict pathological Gleason score for men on AS using a Bayesian joint model [9]. Following external validation, these tools may help provide more customized decision support for the AS population by integrating longitudinal data.

It is noteworthy that none of these nomograms incorporate new markers or imaging, and it is likely that such data could further refine their estimates. For example, longitudinal measurements of the Prostate Health Index were previously shown to predict biopsy reclassification during AS [10], and the use of multiparametric MRI continues to expand. As more data on these tests become available, the AS risk calculators should be updated, as has been done with the PCPT and ERSPC risk calculators used in the screening context. In the future, continued research on genetics may allow further tailoring of AS. In the meantime, these risk calculators are an important first step (‘version 1.0’) toward a more personalized approach to AS.

Stacy Loeb

 

Department of Urology, Population Health, Laura & Isaac Perlmutter Cancer Center, New York University, New YorkNY, US
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References

 

1 Loeb S, Folkvaljon Y, Curnyn C, Robinson D, Bratt O, Stattin P. Almost complete uptake of active surveillance for very low-risk prostate cancer in Sweden. JAMA Oncol 2016; [Epub ahead of print]. doi: 10.1001/ jamaoncol.2016.3600

 

2 Tosoian JJ, Carter HB, Lepor A, Loeb S. Active surveillance for prostate cancer: current evidence and contemporary state of practice. Nat Rev Urol 2016; 13: 20515

 

 

4 Alam R, Carter HB, Landis P, Epstein JI, Mamawala M. Conditional probability of reclassication in an active surveillance program for prostate cancer. J Urol 2015; 193: 19505

 

 

 

 

 

9 ColeyRY, Zeger S L, Mamawala M, Pienta KJ, Carter HBPrediction of the pathologic gleason score to inform a personalized management program for prostate cancer. Eur Urol 2016; [Epub ahead of print]. doi: 10.1016/j.eururo.2016.08.005

 

 

Video: Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance

Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance

Read the full article

Abstract

Objective

To create a nomogram for men on active surveillance (AS) for prediction of grade re-classification (GR) above Gleason score 6 (Grade group >2) at surveillance biopsy.

Patients and Methods

From a cohort of men enrolled in an AS programme, a multivariable model was used to identify clinical and pathological parameters predictive of GR. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision curve analysis.

Results

Of 1 374 men, 254 (18.50%) were re-classified to Gleason ≥7 on surveillance prostate biopsy. Variables predictive of GR were earlier year of diagnosis [≤2004 vs ≥2005; odds ratio (OR) 2.16, P < 0.001], older age (OR 1.05, P < 0.001), higher prostate-specific antigen density [OR 1.19 (per 0.1 unit increase), P = 0.04], bilateral disease (OR 2.86, P < 0.001), risk strata (low-risk vs very-low-risk, OR 1.79, P < 0.001), and total number of biopsies without GR (OR 0.68, P < 0.001). On internal validation, a nomogram created using the multivariable model had an area under the curve of 0.757 (95% confidence interval 0.730–0.797) for predicting GR at the time of next surveillance biopsy.

Conclusion

The nomogram described is currently being used at each return visit to assess the need for a surveillance biopsy, and could increase retention in AS.

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