Initial treatment for most bladder cancers (BCs) involves transurethral resection (TUR) or tumours. Often more cancer is found after the initial treatment in around half of patients, requiring a ...second resection. Repeat transurethral resection (reTUR) is recommended for high-risk, non–muscle-invasive bladder cancer (NMIBC) to remove any residual disease and improve cancer outcomes.
To systematically review the practice and therapeutic benefit of an early reTUR for high-risk NMIBC.
A systematic review of original articles was performed using PubMed/Medline and Web of Science databases in December 2016 (initial) and October 2017 (final). We searched the references of included papers.
We screened 15 209 manuscripts and selected 31 detailing 8409 persons with high-grade Ta and T1BC for inclusion. Detrusor muscle was found at initial TUR histology in 30–100% of cases. Residual tumour at reTUR was found in 17–67% of patients following Ta and in 20–71% following T1 cancer. Most residual tumours (36–86%) were found at the original resection site. Upstaging occurred in 0–8% (Ta to ≥T1) and 0–32% (T1 to ≥T2) of cases. Conflicting data report the impact of reTUR on subsequent recurrence and cancer-specific mortality. Recurrence for Ta was 16% in the reTUR group versus 58% in the non-reTUR group. For T1, recurrence ranged from 18% to 56%, but no clear trend was identified between reTUR and control. No clear relationship between reTUR and progression was found for Ta, although for T1 rates were higher in the non-reTUR group in series with control populations (5/6 studies). Overall mortality was slightly reduced in the reTUR group in two studies with controls (22–30% vs 26–36% no reTUR).
Residual tumour is common after TUR for high-risk NMIBC. The reTUR helps in the diagnosis of this residual cancer and may improve outcomes for cancers initially staged as T1.
Some bladder cancers (BCs) are aggressive but confined to the bladder surface. Initial treatment includes endoscopic resection. More cancer is found after the initial treatment in approximately half of patients. In the aggressive but confined group of BC, a second resection, a few weeks after the first, may help find this residual cancer and improve outcomes, although the evidence quality for this is weak.
We present a large, contemporary systematic review on the role and potential benefits of early repeat transurethral resection for high-risk, non–muscle-invasive bladder cancer. In summary, more cancer is found after the initial treatment in around half of patients; it is therefore imperative to perform an oncologically sound initial resection. A second resection can help find residual cancer and may improve outcomes, although the evidence quality for this is weak, and a large, multicentred, prospective, intention-to-treat randomised controlled trial on re-resection for Ta and T1 tumours is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
AbobotulinumtoxinA injections reduced urinary incontinence episodes and improved urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity incontinence performing ...regular clean intermittent catheterization. AbobotulinumtoxinA was well tolerated with no increase in the risk of urinary tract infections in comparison with placebo.
For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory.
To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI.
Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported.
Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle.
The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo).
At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p < 0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses.
Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC.
In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adrenergic receptors of the β
3
-subtype (β
3
-ADRs) seem to represent a new target for a more effective pharmacological treatment of overactive bladder (OAB), a wide spread urinary disorder. A ...promising opportunity for OAB therapy might rely on the development of selective β
3
-ADR agonists, but an appropriate preclinical screening, as well as investigation of their pharmacological mechanism(s), is limited by poor availability of human bladder samples and of translational animal models. In this study, we used the porcine urinary bladder as experimental tool to ascertain the functions of β
3
-ADRs in the control the parasympathetic motor drive. Tritiated acetylcholine (
3
H-ACh), mainly originated from neural stores, was released by electrical field stimulation (EFS) in epithelium-deprived detrusor strips from pigs bred without estrogens. EFS produced simultaneously
3
H-ACh release and smooth muscle contraction allowing to asses neural (pre-junctional) and myogenic (postjunctional) effects in the same experiment. Isoprenaline and mirabegron produced on the EFS-evoked effects a concentration-dependent inhibition antagonized by L-748,337, a high selective β
3
-ADR antagonist. The analysis of the resultant pharmacodynamic parameters supports the notion that in pig detrusors, as well as in previously described human detrusors, the activation of inhibitory β
3
-ADRs can modulate neural parasympathetic pathways. In such inhibitory control, the involvement of membrane K
+
channels, mainly of the SK type, seems to play a pivotal role similarly to what previously described in humans. Therefore, the isolated porcine detrusor can provide a suitable experimental tool to study the mechanisms underlying the clinical efficacy of selective β
3
-ADR compounds for human use.
Various forms of low urinary tract symptoms (LUTS) seem dependant upon dysregulation of the purinergic pathway which produces sensory- or motor-activated incontinence. A body of evidence in human ...urinary bladders supports a link between up-regulation of purinergic activity and the pathogenesis of detrusor instability. This study investigated the potential role of adenosine 5′-triphosphate (ATP) in the control of detrusor motor drive in a model of porcine urinary bladder. The involvement of ATP on excitatory activity was assessed by measuring neurally-evoked
3H-acetylcholine (ACh) release and smooth muscle contraction in detrusor strips. Epithelium-deprived preparations were used to minimize the influence of non-neural sources of ACh and ATP on parasympathetic neurotransmission. ACh release and smooth muscle contractility were not significantly affected by neural ATP in normal detrusor, but markedly enhanced when ATP hydrolysis was reduced by ectoATPase inhibitors, as well as by α,β-methylene-ATP (ABMA), agonist resistant to ecto-enzymes degradation. Prejunctional P2X receptors located on cholinergic nerves are involved in such potentiating effect. These purinergic heteroreceptors were characterized as P2X
3 subunits by means of the putative antagonists: NF449 (P2X
1,3 selective), NF023 (P2X
1,3 selective), PPNDS (P2X
1 selective) and A-317491 (P2X
3 selective). In porcine detrusor, P2X
3 receptors are functionally expressed at neural site facilitating neurogenic ACh release. When purine breakdown is experimentally down-regulated to mimicking the impaired purinergic pathway observed in pathological human bladders, endogenous ATP can markedly enhance detrusor contractility through activation of these receptors. Since P2X
3 blockade represents a potential therapeutic approach for diseases of the urinary tract, isolated porcine detrusor represents a reliable model for development of novel selective P2X
3 antagonists beneficial in the treatment of detrusor hyperactivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
1. Detrusor underactivity (DU) is a urodynamic diagnosis and underactive bladder is a terminology that should be reserved for describing symptoms and clinical features related to DU.
2. Invasive ...urodynamics is the only widely accepted method for diagnosing DU.
3. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred over indwelling catheters.
4. Medical and surgical therapies are discussed, but the level of evidence is low.
The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS.
A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology.
Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered.
The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts).
The European Association of Urology guidelines on underactive bladder in non-neurogenic adult men are presented here. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural ...system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs.
► Suprasacral spinal cord injury (SCI) disrupts urine storage and voiding functions. ► SCI alters the morphology, chemistry and electrical properties of bladder afferent neurons ► Synaptic remodeling in the spinal micturition reflex pathway occurs after SCI. ► Nerve growth factor contributes to neuroplasticity of bladder and sphincter reflexes after SCI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes.
We conducted a ...retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery.
The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio OR, 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor.
In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.
We determined the effect of pelvic organ decentralization and reinnervation one year later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral ...transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. After exclusions, 8 were reinnervated 12 months post-decentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 months later; four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher, compared to decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots, compared to their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at one year after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.
Objectives
To analyze sequential changes of diabetic cystopathy based on urodynamic data in patients with diabetes mellitus.
Methods
Participants included male diabetes patients who underwent a ...pressure flow study at Nagoya University Graduate School of Medicine, Nagoya, Japan, from April 2005 to October 2016. Patients with a previous history of lower urinary tract dysfunction were excluded. Bladder dysfunction was categorized into four urodynamic patterns: (i) normal; (ii) detrusor overactivity with normal detrusor contractility; (iii) detrusor hyperreflexia/impaired contractility; and (iv) detrusor underactivity. The urodynamic patterns were evaluated according to the presence of diabetic retinopathy and nephropathy, which was correlated to diabetes mellitus duration. Furthermore, the association of clinical factors with voiding function, as well as sensory function, was investigated.
Results
A total of 57 patients were enrolled. Detrusor overactivity with normal detrusor contractility patterns was seen only in cases with neither diabetic retinopathy nor diabetic nephropathy, whereas the prevalence of detrusor hyperreflexia/impaired contractility pattern was highest in cases with diabetic retinopathy. Detrusor underactivity pattern was found with the highest frequency in cases with both diabetic retinopathy and diabetic nephropathy. On multivariate analysis, the existence of diabetic retinopathy was only significantly correlated with bladder contractility index. Furthermore, multivariate analysis showed that first desire volume and maximum cystometric capacity were significantly positively correlated with post‐void residual urine volume, and also negatively correlated with voiding efficiency independent of bladder contractility index.
Conclusions
Diabetes patients have diverse progressive bladder dysfunction according to the diabetes stage. An optimal screening program is necessary to detect and manage diabetic cystopathy at an early stage.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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