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Article of the Week: 68Ga-PSMA has high detection rate of PCa recurrence after RP

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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.

68Ga-PSMA has high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment

 

Pim J. van Leeuwen*†, Phillip Stricker*†, George Hruby‡§, Andrew Kneebone‡§, Francis Ting*†, Ben Thompson†, Quoc Nguyen†, Bao Ho** and Louise Emmett**,††

 

*St Vincent’s Prostate Cancer Centre, St Vincent’s Clinic, Sydney, NSW, †Australian Prostate Cancer Research Centre – New South Wales, Garvan Institute of Medical Research/Kinghorn Cancer Centre, Sydney, NSW, ‡Radiation Oncology Department, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, §University of Sydney, Sydney, NSW, Northern Clinical School, University of Sydney, St Leonards, NSW, **Department of Diagnostic Imaging, St Vincent’s Public Hospital, Sydney, NSW, and ††University of New South Wales, Sydney, NSW, Australia

 

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Objectives

To examine the detection rates of 68Ga-PSMA-positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.

Materials and Methods

A total of 300 consecutive patients with prostate cancer (PCa) who underwent 68Ga-PSMA-PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan-I) database. For the present analysis, we included patients with BCR (prostate-specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito-Urinary Group (FROGG) guidelines. Two readers assessed each 68Ga-PSMA-PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological 68Ga-PSMA uptake was investigated, and detection rates were determined according to PSA level.

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Results

A total of 70 patients were included, and 53 positive 68Ga-PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05–0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1–0.19 ng/mL, 23%; PSA 0.2–0.29 ng/mL, 58%; PSA 0.3–0.49 ng/mL, 36%; and PSA 0.5–0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological 68Ga-PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the 68Ga-PSMA findings there was a major management change in 20 (28.6%) patients.

Conclusions

68Ga-PSMA appears to be useful for re-staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to 68Ga-PSMA findings.

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Editorial: PSMA-targeted imaging of PCa – the best is yet to come

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In recent years there has been increasing interest in imaging recurrent or metastatic prostate cancer with positron-emission tomography (PET) radiotracers targeting prostate-specific membrane antigen (PSMA [1]). The majority of this work has been performed using urea-based small molecules labelled with gallium-68 (68Ga). Within this class of radiotracers, 68Ga-PSMA-11 (also known as 68Ga-PSMA-HBED-CC) has been the most widely studied. In this month’s edition of BJUI, van Leeuwen et al. [2] report on the clinical utility of 68Ga-PSMA-11 PET/CT in men with rising PSA levels after radical prostatectomy being considered for salvage radiation therapy. In their study, 70 patients with negative conventional imaging findings and a median PSA of 0.2 ng/mL (all <1 ng/mL) were imaged with 68Ga-PSMA-11 PET/CT prior to initiating treatment. On PSMA-targeted PET/CT, 53 lesions were detected in 38 (54%) patients. Perhaps most significant among their findings was that 28.6% of men had radiotracer uptake outside of the prostatic fossa leading to a major change in clinical management. In total, these data demonstrate the great potential of PSMA-targeted imaging, particularly in men with biochemically recurrent prostate cancer.

While a great deal of encouraging data with 68Ga-PSMA-11 has appeared in the medical literature, it is worth noting that several other small molecules that offer potential advantages over this agent have seen early clinical development. For example, PSMA-617 makes use of the DOTA chelation moiety in place of HBED-CC, allowing for a scaffold that can accommodate both diagnostic 68Ga and therapeutic lutetium-177 (177Lu) [3]. Additionally, our group has focused on fluorine-18 (18F)-labelled urea-based small molecules targeting PSMA, most recently 18F-DCFPyL [4]. 18F-labelled small molecules offer several potential advantages over those labelled with 68Ga. These include more favourable dosimetry allowing for higher injected radiotracer doses and lower-energy emitted positrons that have shorter path lengths to annihilation and therefore higher intrinsic spatial resolution [5]. Notably, a recent direct comparison of 68Ga-PSMA-11 and 18F-DCFPyL performed by Dietlein et al. [6] seems to confirm these advantages, having observed a higher rate of lesion detection as well as superior mean tumour-to-background ratios with the radiofluorinated compound. An additional advantage of 18F-labelled compounds is related to their longer half-life for radionuclide decay (109 vs 68 min for 68Ga). Given this difference, agents incorporating 68Ga typically require an on-site generator for radiotracer production, whereas 18F-based radiotracers can be produced en masse at a central site with a cyclotron and then delivered to remote locations via pre-existing distribution infrastructure (e.g. PETNET in the USA). Table 1 summarizes several relevant differences in the physical properties of 68Ga and 18F.

Table 1. Comparison of gallium-68 and fluorine-18
Radionuclide 68Ga 18F
Half-life, min 68 109
Method of production Generator Cyclotron
Average positron energy, keV 836.0 249.3
Average path length in soft tissue, mm 8.1 2.4
Positron yield per 100 disintegrations 89.14 96.86

 

In summary, these are exceptionally exciting times for the study of PSMA-targeted imaging of prostate cancer. With continued radiotracer development and accompanying well-designed clinical trials, there is no doubt we can drastically improve the care of men with prostate cancer.

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Michael A. Gorin*, Martin G. Pomper† 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

 

1 Lutje S, Heskamp S, Cornelissen AS et al. PSMA ligands for radionuclide imaging and therapy of prostate cancer: clinical status. Theranostics 2015; 5: 1388–401

 

2 van Leeuwen PJ, Stricker P, Hruby G et al. 68Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int 2016; 117: 732–9

 

3 Afshar-Oromieh A, Hetzheim H, Kratochwil C et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med 2015; 56: 1697–705

 

4 Szabo Z, Mena E, Rowe SP et al. Initial Evaluation of [(18)F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer. Mol Imaging Biol 2015; 17: 565–74
5 Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Appl Radiat Isot 2013; 76: 55–62

 

6 Dietlein M, Kobe C, Kuhnert G et al. Comparison of [18F]DCFPyL and [68Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol 2015; 17: 575–84

 

Article of the Week: URB937 reduces PGE2-induced bladder overactivity

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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.

URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats

Naoki Aizawa*, Giorgio Gandaglia†‡, Petter Hedlund§, Tetsuya Fujimura, Hiroshi Fukuhara, Francesco Montorsi†, Yukio Homma¶ and Yasuhiko Igawa*

 

Departments of *Continence Medicine, Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan, †Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy, ‡Department of Clinical and Experimental Pharmacology, Lund University, Lund, and §Division of Drug Research, Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden

 

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Objective

To determine if inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) can counteract the changes in urodynamic variables and bladder afferent activities induced by intravesical prostaglandin E2 (PGE2) instillation in rats.

Materials and methods

In female Sprague–Dawley rats we studied the effects of URB937, a peripherally restricted FAAH inhibitor, on single-unit afferent activity (SAA) during PGE2-induced bladder overactivity (BO). SAA measurements were made in urethane-anaesthetised rats and Aδ- and C-fibres were identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometry (CMG) in conscious animals and during SAA measurements was performed during intravesical instillation of PGE2 (50 or 100 μm) after intravenous administration of URB937 (0.1 and 1 mg/kg) or vehicle. In separate experiments, the comparative expressions of FAAH and cannabinoid receptors, CB1 and CB2, in microsurgically removed L6 dorsal root ganglion (DRG) were studied by immunofluorescence.

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Results

During CMG, 1 mg/kg URB937, but not vehicle or 0.1 mg/kg URB937, counteracted the PGE2-induced changes in urodynamic variables. PGE2 increased the SAAs of C-fibres, but not Aδ-fibres. URB937 (1 mg/kg) depressed Aδ-fibre SAA and abolished the facilitated C-fibre SAA induced by PGE2. The DRG nerve cells showed strong staining for FAAH, CB1 and CB2, with a mean (sem) of 77 (2)% and 87 (3)% of FAAH-positive nerve cell bodies co-expressing CB1 or CB2 immunofluorescence, respectively.

Conclusion

The present results show that URB937, a peripherally restricted FAAH inhibitor, reduces BO and C-fibre hyperactivity in the rat bladder provoked by PGE2, suggesting an important role of the peripheral endocannabinoid system in BO and hypersensitivity.

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Editorial: Unmasking roles of the peripheral endocannabinoid system associated with bladder overactivity

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Identifying regulatory roles of peripheral endocannabinoid systems for bladder function is a highly intricate task; nonetheless, in this issue of BJUI, a research report by Aizawa et al. [1] shows functional evidence for a role of fatty acid amide hydrolase (FAAH) in improving bladder overactivity induced by prostaglandin E2 (PGE2) in rats. By systemically blocking FAAH with URB937, an inhibitor of FAAH that does not penetrate the CNS, the authors found that afferent nerve activity and bladder cystometric parameters decreased in a rat overactive bladder model induced by intravesical perfusion of PGE2. Confirmation that ≈80% of dorsal root neurones at the Lumbar-6 dorsal root ganglia co-express FAAH and cannabinoid receptors 1 and 2 (CB1, CB2), emphasises the role of the peripheral endocannabinoid system during bladder overactivity induced by increased activity of C-fibres during PGE2 application.

Because FAAH catabolises CB ligands rapidly, a key regulatory role for pain perception was initially proposed [2]. Now, we recognise that the peripheral endocannabinoid system participates in both normal physiology and pathological conditions of the heart, liver, immune system, bone, skin, skeletal muscle, reproduction, and gastrointestinal tract [3]. The participation of the endocannabinoid system in regulating lower urinary tract function has been less studied; however, research evidence suggest an important regulatory role at different levels of the micturition reflex [4]. The study of Aizawa et al. [1] is important because it shows that the rat urinary bladder can be affected by the catabolism of endogenous ligands for CB1 and CB2 during systemic FAAH inhibition in conditions of bladder overactivity induced by PGE2. However, the experiments were performed in conditions where the urothelial cell layer was disturbed with the intravesical application of protamine sulphate. Although this seems to be the best approach to induce bladder overactivity with PGE2, it disturbs the sensory role of the urothelium for monitoring the urinary bladder filling status [5]. Thus, an alternative model for bladder overactivity requires an evaluation of an FAAH inhibitor. Supporting this suggestion, a recent report by Wang et al. [6] shows that intravesical application of a CB1agonist decreases bladder overactivity induced by intravesical nerve growth factor (NGF) in mice with an intact urothelial layer. Additionally, NGF did not induce bladder overactivity in knockout mice for the FAAH enzyme, reinforcing the suggestion for Aizawa et al. [1] about testing the peripherally-restricted inhibition of FAAH with URB937 in urothelium-intact rats.

The above comments and references recommend the performance of a pre-clinical evaluation of the endocannabinoid system using FAAH inhibitors to treat, for instance, neurogenic bladder overactivity in rats with spinal cord injury. Naturally, this overactive bladder model will prove to be more complicated and challenging to evaluate, but the results may provide overwhelming support for a rigorous assessment of the use of cannabinoids to treat urinary bladder dysfunction in humans [3]. At the mechanistic level it would be interesting to know at what part(s) of the micturition reflex is FAAH regulating bladder function. How significant is the catabolism of endogenous CB1/CB2 receptors during the storage and contraction phases of either normal or altered micturition? While the current study of Aizawa et al. [1] contributes to a deeper knowledge of the cannabinoid system in bladder dysfunction, additional studies are required to determine whether systemic inhibition of FAAH improves C-fibre mediated bladder sensory pathways in other animal models of detrusor and bladder overactivity.

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Alvaro Munoz, Assistant Research Professor of Urology
Departments of Regenerative Medicine and Urology, Houston Methodist Research Institut e and Houston Methodist Hospital, Houston, TX, USA

 

References

 

1 Aizawa N, Gandaglia G, Hedlund P et al. URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats. BJU Int 2016; 117: 821–8

 

2 Cravatt BF, Demarest K, Patricelli MP et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 2001; 98: 9371–6

 

3 Maccarrone M, Bab I, Bıro T et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci 2015; 36: 277–96

 

4 Hedlund P. Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Neurourol Urodyn 2014; 33: 46–53

 

5 Birder L, Andersson KE. Urothelial signaling. Physiol Rev 2013; 93: 653–80

 

6 Wang ZY, Wang P, Bjorling DE. Activation of cannabinoid receptor 1 inhibits increased bladder activity induced by nerve growth factor. Neurosci Lett 2015; 589: 19–24

 

Article of the Month: IFES to manage non-neuropathic UAB in children

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Every Month the Editor-in-Chief selects an Article of the Month 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Sanam Ladi Seyedian, discussing her paper.

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

Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial

 

Abdol-Mohammad Kajbafzadeh, Lida Sharifi-Rad*, Seyedeh-Sanam Ladi-Seyedian and Sarah Mozafarpour

 

Department of Pediatric Urology, Pediatric Urology Research Center, and *Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

 

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Objectives

To assess the efficacy of transcutaneous interferential electrical stimulation (IFES) and urotherapy in the management of non-neuropathic underactive bladder (UAB) in children with voiding dysfunction.

Patients and Methods

In all, 36 children with UAB without neuropathic disease [15 boys, 21 girls; mean (sd) age 8.9 (2.6) years] were enrolled and then randomly allocated to two equal treatment groups comprising IFES and control groups. The control group underwent only standard urotherapy comprising diet, hydration, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation. Children in the IFES group likewise underwent standard urotherapy and also received IFES. Children in both groups underwent a 15-session treatment programme twice a week. A complete voiding and bowel habit diary was completed by parents before, after treatment, and 1 year later. Bladder ultrasound and uroflowmetry/electromyography were performed before, at the end of treatment course, and at the 1-year follow-up.

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Results

The mean (sd) number of voiding episodes before treatment was 2.6 (1) and 2.7 (0.76) times/day in the IFES and control groups, respectively, which significantly increased after IFES therapy in IFES group, compared with only standard urotherapy in the control group [6.3 (1.4) vs 4.7 (1.3) times/day, P < 0.002). The mean (sd) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively, which decreased significantly at 1 year after treatment in the IFES group compared with the controls, at 227 (86) vs 344 (127) mL (P < 0.01). Maximum urine flow increased and voiding time decreased significantly in the IFES group compared with controls at the end of treatment sessions and 1 year later (P < 0.05). All the children had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of 18 (33%) in the control group by the end of follow-up (P < 0.007). At the end of the treatment course, night-time wetting was improved in all children who had this symptom before the treatment in the IFES group (P < 0.01).

Conclusion

Combining IFES and urotherapy is a safe and effective therapy in the management of children with UAB.

Read more articles of the week

Editorial: The vexing problem of UAB in children – a viable alternative

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Underactive bladder, as defined by the International Children’s Continence Society (ICCS; impaired detrusor contractility that leads to low voiding frequency (<3 voids/day), hesitancy, incomplete bladder emptying, and high post-void residual urine volumes (PVRs) that may produce UTI and urinary incontinence) has been a vexing problem for many paediatric providers to manage.

Antimuscarinic and α-agonist drugs have not proven effective to warrant their recommendation, and urotherapy, which demystifies the condition and tries to teach children to void often, take the time to urinate, use correct posture, and promote dietary habits that seem to adjudicate fluid intake, resulting in appropriate urine production and regular bowel movements, have not fully solved the problems in all patients. More invasive therapies, i.e., percutaneous tibial nerve stimulation, intravesical electrical stimulation, and sacral neuromodulation provide some improvement in mollifying symptoms but long-term responses do not seem to be sustainable. Intermittent catheterisation, which immediately achieves bladder emptying on a timely schedule, is often a therapy that children and their parents prefer to avoid. All these management options with their varying responses have left patients resigned as their symptoms persist and their parents frustrated.

Kajbafzadeh et al. [1], in a study reported in this issue of the Journal, have clearly shown the value and potential promise of interferential electrical stimulation (IFES) for non-neuropathic underactive bladder in children. IFES changes bladder dynamics so that urinary frequency, bladder contractility, and PVRs improve to the extent that incontinence, both daytime and night-time, as well as UTIs, resolve. Although it is time consuming, as one would expect all therapies that reverse pathological processes might be, the promise that long-term responses remain salient is a testament to its worthiness. As a reference, Kajbafzadeh et al. [2] recently published similar responses in a randomised clinical trial of children with primary monosymptomatic enuresis, using standard urotherapy (as used in this current study [1]) with and without IFES, which revealed statistically significant improvement in enuretic episodes, both initially and after 1 year in those children treated with IFES. In a previous randomly allocated report of 30 children with myelomeningocele and detrusor overactivity, IFES was substantially effective in 20 vs 10 who were ‘sham controlled’ [3].

The authors [1] do indicate deficiencies in their study, the most glaring of which is the absence of a ‘sham’ group of children who should have ‘received’ IFES treatment without any actual ES. In clinical practice this is almost impossible to achieve. Long-term urodynamic data would also have been helpful in solidifying these responses when compared to pre-treatment investigations but again having families assent to a study that involves catheterising their child for this purpose is nearly impossible.

The authors did not comment on the improvement in bowel function these children may experience in the immediate period after treatment or in the long-term, but given the emphasis on better toileting it is presumed lower gastrointestinal function would have been helped as well. In addition, the authors [1] have left us wondering if these improved toileting habits changed the propensity towards UTIs over time. Nor have they expressed any improvement in behavioural issues as a result of this programme, or what effect, if any, has occurred regarding school performance and social interaction. It is now up to these pioneers, as well as future investigators, to lead the way to engage a child’s entire milieu and his family responses, to the acceptability of this treatment programme. Looking beyond just the immediacy of an IFES regimen and its effects on the urinary and gastrointestinal systems will surely tell us if this management schema truly has large scale merit for a wider cohort. That kind of communication would surely be an impetus for scientifically minded clinicians to delve into the ‘whys’ of its positive pathophysiological effects.

I commend the authors for their exceptional work and desire to find an effective, minimally invasive treatment that has long-term sustainability. The gauntlet has been dropped, only to be picked up by others (or these same providers) to address and answer the additional concerns and questions posed by this editorial.

Read the full article
Stuart B. Bauer
Department of Urology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA, 02115, USA

 

References

 

1 Kajbafzadeh AM, Sharifi-Rad L, Ladi-Seyedian SS, Mozafarpour S. Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial. BJU Int 2016; 117: 793–800

 

2 Kajbafzadeh AM, Sharifi-Rad L, Mozafarpour S, Ladi-Seyedian SS. Efficacy of transcutaneous interferential electrical stimulation in treatment of children with primary nocturnal enuresis: a randomized clinical trial. Pediatr Nephrol 2015; 30: 1139–45

 

3 Kajbafzadeh AM, Sharifi-Rad L, Baradaran N, Nejat F. Effect of pelvic floor interferential electrostimulation on urodynamic parameters and incontinency of children with myelomeningocele and detrusor overactivity. Urology 2009; 74: 324–9

 

Video: IFES to manage non-neuropathic UAB in children

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Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial

Abdol-Mohammad Kajbafzadeh, Lida Sharifi-Rad*, Seyedeh-Sanam Ladi-Seyedian and Sarah Mozafarpour

 

Department of Pediatric Urology, Pediatric Urology Research Center, and *Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

 

Read the full article

Objectives

To assess the efficacy of transcutaneous interferential electrical stimulation (IFES) and urotherapy in the management of non-neuropathic underactive bladder (UAB) in children with voiding dysfunction.

Patients and Methods

In all, 36 children with UAB without neuropathic disease [15 boys, 21 girls; mean (sd) age 8.9 (2.6) years] were enrolled and then randomly allocated to two equal treatment groups comprising IFES and control groups. The control group underwent only standard urotherapy comprising diet, hydration, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation. Children in the IFES group likewise underwent standard urotherapy and also received IFES. Children in both groups underwent a 15-session treatment programme twice a week. A complete voiding and bowel habit diary was completed by parents before, after treatment, and 1 year later. Bladder ultrasound and uroflowmetry/electromyography were performed before, at the end of treatment course, and at the 1-year follow-up.

AOTMMayImg

Results

The mean (sd) number of voiding episodes before treatment was 2.6 (1) and 2.7 (0.76) times/day in the IFES and control groups, respectively, which significantly increased after IFES therapy in IFES group, compared with only standard urotherapy in the control group [6.3 (1.4) vs 4.7 (1.3) times/day, P < 0.002). The mean (sd) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively, which decreased significantly at 1 year after treatment in the IFES group compared with the controls, at 227 (86) vs 344 (127) mL (P < 0.01). Maximum urine flow increased and voiding time decreased significantly in the IFES group compared with controls at the end of treatment sessions and 1 year later (P < 0.05). All the children had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of 18 (33%) in the control group by the end of follow-up (P < 0.007). At the end of the treatment course, night-time wetting was improved in all children who had this symptom before the treatment in the IFES group (P < 0.01).

Conclusion

Combining IFES and urotherapy is a safe and effective therapy in the management of children with UAB.

Read more articles of the week

Article of the Week: Preoperative JJ stent placement to treat ureteric and renal stones

/1 Comment/by

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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Marianne Schmid and Dr. Atiqullah Aziz, discussing their Editorial.

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

Preoperative JJ stent placement in ureteric and renal stone treatment: results from the Clinical Research Office of Endourological Society (CROES) ureteroscopy (URS) Global Study

Dean Assimos, Alfonso Crisci*, Daniel Culkin†, Wei Xue‡, Anita Roelofs§, Mordechai Duvdevani, Mahesh Desai** and Jean de la Rosette†† on behalf of the CROES URS Global Study Group

 

Department of Urology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA, *Department of Urology, Careggi Hospital, Florence, Italy, †Department of Urology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, ‡Department of Urology, Renji Hospital, Shanghai, China, §Department of Urology, Rijnstate Hospital, Arnhem, The Netherlands, ††Department of Urology, AMC University Medical Centre, Amsterdam, The Netherlands, Department of Urology, Hadassah Ein-Kerem University Hospital, Jerusalem, Israel, and **Department of Urology, Muljibhai Patel Urological Hospital, Nadiad, India

 

Read the full article

Objective

To compare outcomes of ureteric and renal stone treatment with ureteroscopy (URS) in patients with or without the placement of a preoperative JJ stent.

Patients and Methods

The Clinical Research Office of the Endourological Society (CROES) URS Global Study collected prospective data for 1 year on consecutive patients with ureteric or renal stones treated with URS at 114 centres around the world. Patients that had had preoperative JJ stent placement were compared with those that did not. Inverse-probability-weighted regression adjustment (IPWRA) was used to examine the effect of preoperative JJ stent placement on the stone-free rate (SFR), length of hospital stay (LOHS), operative duration, and complications (rate and severity).

Results

Of 8 189 patients with ureteric stones, there were 978 (11.9%) and 7 133 patients with and without a preoperative JJ stent, respectively. Of the 1 622 patients with renal stones, 590 (36.4%) had preoperative stenting and 1 002 did not. For renal stone treatment, preoperative stent placement increased the SFR and operative time, and there was a borderline significant decrease in intraoperative complications. For ureteric stone treatment, preoperative stent placement was associated with longer operative duration and decreased LOHS, but there was no difference in the SFR and complications. One major limitation of the study was that the reason for JJ stent placement was not identified preoperatively.

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Conclusions

The placement of a preoperative JJ stent increases SFRs and decreases complications in patients with renal stones but not in those with ureteric stones.

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Editorial: Some like it safe

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Since the implementation of ureteroscopy (URS) about 100 years ago, technological as well as peri-operative management improvements have made URS the treatment of choice for ureteric and renal stones. Depending on stone location and size, stone-free rates of up to 100% have been reported in combination with low peri-operative complications and short hospital stay. Endoscopic therapy of stone disease, e.g. (primary) URS, reflects the zeitgeist: minimally invasive, fast, efficient and economic. There is, however, still a lack of consensus on the question of preoperative stenting in stone management strategies. The underlying aim of preoperative stenting is to cause passive dilation of the ureter, allowing easier access to the upper urinary tract during a secondary URS.

In the current issue of the BJUI, Assimos et al. [1] report higher stone-free rates, as well as fewer complications, with the use of a JJ stent before URS in patients with renal stones, and their article, therefore, supports the previously reported findings of retrospective series with observational, multicentre evidence [2]. Their findings do not, however, corroborate improved outcomes for prestented patients with ureteric stones [1]. Notably, more stents overall were placed in the presence of renal stones compared with ureteric stones (36.4 vs 11.9%). Primary URS may not always be feasible because of anatomical abnormalities, a narrow ureteric lumen, complex ureteric path or previous instrumentation [3]. In such cases, further manipulation risking trauma and potentially long-term stricture formation should be avoided and ureteric stent placement is necessary before further therapy. Indeed, it is possible that renal stone treatment may be associated with increased ureteric manipulation; therefore, passive ureteric dilation might be helpful and facilitate endocopic access to the renal pelvis. A direct elective prestenting in these patients followed by a secondary URS, therefore, warrants discussion. Although prestenting is an additional procedure, it has the potential to lower healthcare costs by decreasing complications rates, operating time and re-operation rates, especially for large proximal stones [4].

Routine preoperative stenting is not necessarily recommended by current guidelines [5]; however, the management of pre-URS stent placement is left to institutional and international practice patterns. Indeed, as shown in Figs 1 and 2 of the present paper [1], the incidence of preoperative JJ stenting varied tremendously by country. Whereas the large majority of patients with ureteric (88.1%) as well as renal (63.6%) stones were treated without a stent, in Germany, for example, >50% of patients were stented before URS. Also in China, Chile, Egypt and Israel, a higher percentage of patients with ureteric stones primarily received a JJ stent.

The use of stents is known to cause discomfort, pain and urinary symptoms, and therefore can represent significant health problems for the patient. These negatively affect daily activities, work capacity and quality of life [6]. Other disadvantages of a stenting may be higher costs associated with the need for interval procedure(s) and additional hospital stay(s). In addition, as recently reported, preoperative ureteric stent placement was not an independent predictor of stone-free status after flexible URS for renal stone removal [7].

Although there is no consensus or definite recommendation for pre-URS stenting, it should be considered and discussed with the patient when obtaining preoperative consent, especially for purely elective, non-urgent cases and in the presence of renal stones.

Long-term outcomes will show whether or not pre-URS stenting makes a difference with regard to the formation of ureteric strictures. Finally, surgical strategies need to weigh carefully the benefits to the patients and improved outcomes against cost-effectiveness.

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Atiqullah Aziz, and Marianne Schmid
Department of Urology, University Medical Centre Hamburg- Eppendorf, Hamburg, Germany

 

References

 

1 Assimos D, Crisci A, Culkin D et al. Preoperative JJ stent placement in ureteric and renal stone treatment: results from the Clinical Research Office of Endourological Society (CROES) ureteroscopy (URS) Global Study. BJU Int 2016; 117: 648–54

 

2 Netsch C, Knipper S, Bach T, Herrmann TR, Gross AJ. Impact of preoperative ureteral stenting on stone-free rates of ureteroscopy for nephroureterolithiasis: a matched-paired analysis of 286 patients. Urology 2012; 80: 1214–9

 

3 Cetti RJ, Biers S, Keoghane SR. The difficult ureter: what is the incidence of pre-stenting? Ann R Coll Surg Engl 2011; 93: 31–3

 

4 Chu L, Farris CA, Corcoran AT, Averch TD. Preoperative stent placement decreases cost of ureteroscopy. Urology 2011; 78: 309–13 

 

5 Turk C, Petřík A, Sarica K et al. EAU guidelines on interventional treatment for urolithiasis. Eur Urol 2015; doi: 10.1016/j.eururo.2015. 07.041. [Epub ahead of print]

 

6 Joshi HB, Newns N, Stainthorpe A, MacDonagh RP, Keeley FX Jr, Timoney AG. Ureteral stent symptom questionnaire: development and validation of a multidimensional quality of life measure. J Urol 2003; 169: 1060–4

 

7 Ito H, Sakamaki K, Kawahara T et al. Development and internal validation of a nomogram for predicting stone-free status after flexible ureteroscopy for renal stones. BJU Int 2015; 115: 446–51

 

Video: Some like it safe

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Preoperative JJ stent placement in ureteric and renal stone treatment: results from the Clinical Research Office of Endourological Society (CROES) ureteroscopy (URS) Global Study

Dean Assimos, Alfonso Crisci*, Daniel Culkin†, Wei Xue‡, Anita Roelofs§, Mordechai Duvdevani, Mahesh Desai** and Jean de la Rosette†† on behalf of the CROES URS Global Study Group

 

Department of Urology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA, *Department of Urology, Careggi Hospital, Florence, Italy, †Department of Urology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, ‡Department of Urology, Renji Hospital, Shanghai, China, §Department of Urology, Rijnstate Hospital, Arnhem, The Netherlands, ††Department of Urology, AMC University Medical Centre, Amsterdam, The Netherlands, Department of Urology, Hadassah Ein-Kerem University Hospital, Jerusalem, Israel, and **Department of Urology, Muljibhai Patel Urological Hospital, Nadiad, India

 

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Objective

To compare outcomes of ureteric and renal stone treatment with ureteroscopy (URS) in patients with or without the placement of a preoperative JJ stent.

Patients and Methods

The Clinical Research Office of the Endourological Society (CROES) URS Global Study collected prospective data for 1 year on consecutive patients with ureteric or renal stones treated with URS at 114 centres around the world. Patients that had had preoperative JJ stent placement were compared with those that did not. Inverse-probability-weighted regression adjustment (IPWRA) was used to examine the effect of preoperative JJ stent placement on the stone-free rate (SFR), length of hospital stay (LOHS), operative duration, and complications (rate and severity).

Results

Of 8 189 patients with ureteric stones, there were 978 (11.9%) and 7 133 patients with and without a preoperative JJ stent, respectively. Of the 1 622 patients with renal stones, 590 (36.4%) had preoperative stenting and 1 002 did not. For renal stone treatment, preoperative stent placement increased the SFR and operative time, and there was a borderline significant decrease in intraoperative complications. For ureteric stone treatment, preoperative stent placement was associated with longer operative duration and decreased LOHS, but there was no difference in the SFR and complications. One major limitation of the study was that the reason for JJ stent placement was not identified preoperatively.

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Conclusions

The placement of a preoperative JJ stent increases SFRs and decreases complications in patients with renal stones but not in those with ureteric stones.

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