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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 33  |  Issue : 2  |  Page : 49-55

Bladder neck contracture as a complication of prostate surgery: Alternative treatment methods and prospects (literature review)


1 Department of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Medical Scientific and Educational Center of Lomonosov Moscow State University, Moscow, Russia; Department of Urology, Tashkent Medical Academy, Tashkent, Uzbekistan
2 Department of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Medical Scientific and Educational Center of Lomonosov Moscow State University, Moscow, Russia
3 Department of Ultrasound, Diagnostics of the Medical Scientific and Educational Center of Lomonosov Moscow StateUniversity, Moscow, Russia
4 Department of Urology, Tashkent Medical Academy, Tashkent, Uzbekistan

Date of Submission02-Sep-2021
Date of Decision25-Nov-2021
Date of Acceptance03-Dec-2021
Date of Web Publication29-Mar-2022

Correspondence Address:
Shukhrat Anvarovich Abbosov
Department of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_127_21

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  Abstract 


Bladder neck contracture (BNC) is one of the most common complications of surgical treatment of prostate diseases. The rate of postoperative BNC varies depending on the type of surgical treatment used. The options for treatment techniques for BNC can vary from endoscopic interventions to complex (abdominal) surgical interventions. This review evaluates various alternative surgical methods of BNC treatment. The search and analysis of publications in the databases PubMed (MEDLINE), Scopus, Cochrane Library, according to the keywords, “bladder neck sclerosis,” “benign prostatic hyperplasia,” “BNC,” “bladder neck stenosis,” “balloon dilation,” “treatment.” As a result, 71 publications were selected and included in this review. In addition to the standard treatment methods in the form of transurethral resection and incision of the bladder neck using electricity and laser energy, the urologist also has alternative methods of treatment, such as balloon dilation, placement of urethral stents, instillation of the bladder or intraoperative injection of cytostatic drugs, hormones, hyaluronic acid derivatives, and biomedical cell products into the bladder neck area. Although transurethral resection is currently the main treatment option for BNC, the recurrence rate after this procedure can reach up to 38%. According to the literature, balloon dilation can be a promising and minimally invasive method of treatment for recurrent BNC. This method can be used as the first stage in the treatment of recurrent contracture deformity. Furthermore, intravesical instillation of various anti-inflammatory drugs and cytostatics can be promising directions in the treatment and prevention of BNC.

Keywords: Benign prostatic hyperplasia, bladder neck contracture, prostate cancer, transurethral resection


How to cite this article:
Abbosov SA, Sorokin NI, Shomarufov AB, Kadrev AV, Ugli Nuriddinov KZ, Mukhtarov ST, Akilov FA, Kamalov AA. Bladder neck contracture as a complication of prostate surgery: Alternative treatment methods and prospects (literature review). Urol Sci 2022;33:49-55

How to cite this URL:
Abbosov SA, Sorokin NI, Shomarufov AB, Kadrev AV, Ugli Nuriddinov KZ, Mukhtarov ST, Akilov FA, Kamalov AA. Bladder neck contracture as a complication of prostate surgery: Alternative treatment methods and prospects (literature review). Urol Sci [serial online] 2022 [cited 2022 Oct 1];33:49-55. Available from: https://www.e-urol-sci.com/text.asp?2022/33/2/49/341251




  Introduction Top


Bladder neck contracture (BNC) is a widespread complication of prostate surgery and one of the outcomes of inflammatory processes in the bladder neck. The local sclerotic deformity process depends on the primary treatment method in the bladder neck and posterior urethra area and can also occur after radiation therapy of the pelvic organs in cancer.[1]

Depending on the operative technique and type of energy employed the incidence of BNC after transurethral surgery ranges from 0% to 9.6% during the initial surgery and increases to 15% during the second operation.[1] According to various studies, the prevalence of BNC after transurethral resection of the prostate (TURP) reaches 5%.[2],[3] According to the results of a meta-analysis, no significant differences were found when comparing the incidence of BNC after monopolar and bipolar TURP; however, there was a tendency toward an increase in BNC incidence after TURP when using a monopolar electrode.[4] Holmium laser enucleation of the prostate (HoLEP) is associated with the development of BNC in 1%–5% of cases.[5],[6] Enucleation and vapoenucleation of the prostate using a thulium laser (ThuLEP and ThuVEP) are associated with BNC in fewer than 4% of cases.[7],[8] According to the results of Gilfrich et al.(2021), photoselective vaporization (PVP) has the highest rate of repeated interventions for sclerotic complications from endourological methods of benign prostatic hyperplasia (BPH) treatment.[9] According to various authors, the prevalence of BNC after PVP using green light laser reaches 10%, which is significantly higher than for similar indicators for other transurethral techniques.[9],[10],[11] Nevertheless, HoLEP, ThuLEP, and TURP have comparable BNC rates.[9]

The risk factors for developing BNC include the presence of prostatitis and urinary infection during the preoperative stage and the early postoperative period, a small BPH volume, trauma to the mucous membrane of the urethra and bladder neck, and the use of large-caliber instruments.[12],[13],[14],[15] Additional risk factors for BNC after transurethral interventions are patient age, history of cardiovascular disease, type 2 diabetes, obesity, and a long history of smoking.[12],[16]

Despite the significant increase in the number of patients undergoing therapy for prostate cancer through radiation or surgery, only a relatively small proportion of patients develop BNC, which requires further correction.[17],[18],[19],[20] Before the widespread use of robotic-assisted radical prostatectomy (RARP), BNC occurred in up to 36% of cases.[21] The use of robotic surgery led to a decrease in the risk of developing BNC, most likely due to improved visualization during the creation of a vesicourethral anastomosis. A number of reports from specialized robotic centers have indicated that the incidence of complications such as BNC tends to 0%.[18],[19],[21],[22],[23] Factors such as reduced blood loss and the use of a continuous suture in the formation of an urethrovesical anastomosis potentially contribute to the decreased incidence of BNC.[24] For example, Parihar et al. studied a cohort of 930 patients who underwent RARP between 2006 and 2012 for localized prostate cancer. BNC was detected in 15 patients (1.6%).[25]

Currently, urologists are armed with such treatment methods for BNC as cold-knife transurethral incision and resection (electrical or laser energy). However, the results remain unsatisfactory, with relapse rates as high as 32%.[26]

In this review, we analyzed the current evidence concerning the safety and efficacy of alternative methods for preventing and treating recurrent BNC.


  Methods Top


We searched and analyzed publications in PubMed (MEDLINE), Scopus, and the Cochrane Library using the keywords “bladder neck sclerosis,” “BPH,” “BNC,” “balloon dilation,” “treatment.” Abstracts of conferences, dissertations, and their abstracts were excluded from the analysis. As a result, 71 publications of the period from 1990 to 2021 were selected and included in this review.


  Etiology and Pathophysiology Top


Surgical bladder neck stenosis and urethral stricture are the results of luminal constriction caused by tissue fibrosis. Wounds that heal by primary intention undergo wound contraction in the proliferative phase, driven by myofibroblasts, with further collagen remodeling during the maturation phase. All wounds are therefore prone to some degree of contraction, which is all the more important in the context of a luminal end-to-end anastomosis. Healing by secondary intention occurs when there is a loss of mucosal apposition, which might be the result of tissue ischemia secondary to tension, wound contraction secondary to a hematoma, and foreign materials such as clips and poor technical apposition with resultant urinoma. Healing by secondary intention is driven by fibroblast differentiation into myofibroblasts, with increased collagen deposition, which has a much greater risk of wound contracture and hypertrophic scarring, with resultant luminal narrowing.[27] Various studies have shown that sclerosis is associated with the development of collagen-rich connective tissue with few fibroblasts and smooth muscle fibers in the scar area. The increase in type 3 collagen compared with type 1 collagen is a tissue reaction, resulting in fibrosis and stenosis of the lumen.[28],[29]

Depending on the complexity, clinical variants of BNC range from simple short annular strictures to obliterating stenosis, which requires a significant expansion of the surgical scope, from dilatation to volumetric reconstruction.[24] However, the treatment for BNC in most cases (50%–80%) ends with its recurrence.[7] BNC is therefore one of the most common and difficult to treat complications of endourological prostate surgery.


  Standard Treatment Methods for Bladder Neck Contracture Top


Bach et al. proposed a technique for bladder neck incision with laser energy at the 5 and 7 o'clock positions using a 2-μ 70-W continuous-wave laser (RevoLix™, LISA® laser products, Katlenburg, Germany). However, this method presented a recurrence rate of 50% and a successful re-intervention rate of only 14.3%, which is relatively low.[30] Ramirez et al. performed a deep lateral incision with a transurethral incision at 3 and 9 o'clock through the muscle fibers at the bladder neck, with an efficiency of 86% after two treatments. However, complete success without stress urinary incontinence after the first procedure was achieved in only 12 (24%) patients.[31]

There is a technique that combines dilatation and incision of the BNC. The bladder neck region is initially dilated with a 4 cm × 24 cm Fr UroMax Ultra™, a high-pressure urethral balloon dilator. A 24 Fr resectoscope is then inserted into the bladder, and an incision is performed at 3 and 9 o'clock. According to observation data within 1 year, 72% of the patient's required only one repeat procedure, and success was achieved in 14% of cases after two procedures.[31] Superior results were achieved in a small series by using a more complex open-surgery technique, the so-called T-plasty, which is basically a modified YV-plasty for highly recurrent BNC, with a success rate of 100%.[32]

It is important to note that cold-knife incisions might require repeated operations, with reduced efficiency in each subsequent case. Thus, according to the results of the study by Borboroglu et al. of 52 patients with BNC who underwent endoscopic treatment, 42% required at least 1 repeat procedure, and 11.5% required more than 2 additional procedures.[21]


  Alternative Endoscopic Treatment Methods for Bladder Neck Contracture Top


Alternative endoscopic treatment options for BNC include cold-knife incision, electrocautery, balloon dilation, stent placement, and high-frequency laser resection [Table 1].[33]
Table 1: Bladder neck closure treatment options and their outcomes

Click here to view



  Combined Therapy of Recurrent Bladder Neck Contracture Top


Due to the increased frequency of recurrence when using classical endoscopic methods for treating BNC, a number of researchers have developed a method that combines transurethral incision followed by the introduction of antiproliferative agents (mitomycin C, triamcinolone, hyaluronidase). Combined injections of steroid drugs are also employed as agents to combat fibrosis, scarring, and to reduce the recurrence of BNC. Eltahawy et al. reported a technique for administering triamcinolone after holmium laser incision, with a long recurrence-free period in 83% of patients (n = 24). The proposed mechanism of action for this combination is an increase in the local activity of endogenous collagenase combined with the effects of steroid hormones.[45] The mechanism of action for mitomycin C involves the reduction of scar formation by inhibiting fibroblast proliferation.[55],[56] Vanni et al. reported the absence of BNC recurrence in 90% of cases after the use of mitomycin C, known as an inhibitor of fibroblast proliferation, which prevents scar formation.[56] Redshaw et al. showed that the introduction of mitomycin C into the bladder after cold-knife incision provided a persistent recurrence-free period in 75% of patients with BNC.[57] A study by Farrell et al. showed 80% efficacy for urethrotomy with a mitomycin C injection and subsequent periodic self-catheterization in patients with postradiation BNC.[58] Studies of mitomycin C injections for treating BNC have shown the success of restoring adequate urination after 1 procedure in 58%–75% of cases and in 85%–89% of cases after two courses of administration.[56],[57],[58] Although the findings are of scientific and clinical interest, there are certain concerns about the safety of the proposed technique. It should be noted that with the use of mitomycin C, there are a number of complications, such as anaphylaxis, extravasation, and necrosis of the bladder neck due to improper injection, as well as local disturbances in the healing processes of the urothelial wound, which seriously limits the use of this drug in the treatment of BNC.[34],[59],[60],[61]


  Placement of the Urethral Stent Top


The UroLume® urethral stent (American Medical Systems, USA) was first introduced in 1988 by E. Milroy as a new, minimally invasive method for treating urethral strictures. Although the initial studies on the use of UroLume® were promising, numerous complications have been reported as the clinical experience grew, including stent migration, obstruction, secondary stricture associated with tissue ingrowth, hematuria, stent encrustation, and the need for reoperation.[45] Chiou et al. reported the results of urethral stent placement in patients with recurrent BNC after radical prostatectomy. BNC stabilization with the insertion of one urethral stent was noted in 13 of 25 (52%) patients, with a median follow-up of 2.9 years from the last urethral stent insertion. All patients responded to the questionnaire, and improvements in quality of life were noted in 23 of the 25 patients (92%).[46] The main disadvantages of the urethral stents were the increased incidence of complications and the need for additional surgery. Ramirez et al., therefore, offer endoscopic balloon dilation instead of urethral stenting.[62]


  Balloon Dilation Top


Balloon dilation is a minimally invasive procedure performed on an outpatient basis, which can be used as the first stage in the treatment of BNC. The balloon dilation procedure widens the lumen of the bladder neck by radially stretching the scar tissue using a balloon catheter.[63] This method can be used as minimally invasive, first-line therapy for secondary sclerosis of the bladder neck without obliteration. In 90% of cases, however, a second procedure might be required within the first 2 years.[34] Fibrocystoscopy and coaxial dilation, followed by periodic self-catheterization and dilatation of the bladder neck, is most often used to treat stenosis in vesicourethral anastomosis (after prostatectomy) and to prevent the recurrence and further progression of BNC. Such schemes of self-catheterization with dilatation are often performed on an outpatient basis, if the area of the sclerotic deformity is not extended, soft, and has no obliteration.[24] There is evidence for the use of balloon dilation as an alternative treatment for urethral strictures. The overall efficacy rate for balloon dilation for urethral strictures was 84.4%. Patients with a stricture in the area of the vesicourethral anastomosis have required repeated treatment in 50% of cases. Thirty-two percent of patients with postoperative sclerotic deformity of the bladder neck required a second procedure.[26] Park et al.(2001) reported that in patients with vesicourethral stricture after prostatectomy (n = 32), balloon dilatation of the urethra (24 of 32, 93%) was successful in combination with intermittent self-catheterization and dilatation for 3 months.[38] Another study involving 48 patients demonstrated a successful recurrence-free postoperative period when using this method within 1 year of follow-up. However, this option is only feasible for motivated patients, as dilated self-catheterization requires exceptional diligence and discipline from patients. Ultimately, many patients reject this treatment, probably due to its negative impact on quality of life.[64] In 2013, Ramirez et al. developed an algorithm [Figure 1] for managing patients with BNC who undergo endoscopic balloon dilatation and/or incision.[62]
Figure 1: Algorithm of management of patients with bladder neck contracture, who underwent endoscopic balloon dilation and/or incision (Ramirez et al., 2013)

Click here to view


There is evidence for the successful use of balloon dilation as the primary treatment for BNC after orthotopic plastic surgery of the bladder with a segment of the ileum (Studer's operation).[65] When using balloon dilation, the following complications can be observed: urinary retention, gross hematuria, infection, false passage, and urethral stricture.


  Physiotherapeutic Treatment of Bladder Neck Contracture Top


A number of studies have indicated that physiotherapeutic manipulations on the area of the operated bladder neck (magnetic and electrostimulation therapy on the hardware-software complex “Andro-Gin”) significantly enhance microcirculation and tissue tropism. As a result of the physiotherapeutic treatment if 66 patients, not a single case of BNC recurrence after transurethral resection of the bladder neck was reported.[66],[67]


  Biomedical Cell Products in the Treatment of Bladder Neck Fibrosis Top


Mesenchymal stem cells (MSCs) can promote the repair of damaged tissues by regulating the response of immunocompetent cells and the activity of structure-forming cells such as fibroblasts, which leads to a pronounced regenerative and anti-inflammatory effect. Inflammatory mediators can attract MSCs and alter their secretory profile, a process that is believed to facilitate immune responses and skin wound healing.[68] The main theory is that MSCs secrete regulatory peptides that affect multiple fibrogenetic pathways, have immunosuppressive effects, inhibit the transforming growth factor β1 (TGFβ1) pathway, and reduce oxidative stress. TGFβ1, an autocrine and paracrine inducer of extracellular matrix protein synthesis by fibrogenic cells plays a major role in the formation of fibrosis.[69] Activated TGFβ1 can phosphorylate Smad3, which is associated with the receptor and activator of collagen synthesis, leading to tissue fibrosis. TGFβ1/Smad3 pathway activation is a key mediator not only of the induction of epithelial-mesenchymal transition but also the synthesis of extracellular matrix molecules such as collagen I, fibronectin, and collagen III, leading to tissue fibrosis.[70]

Sangkum et al. showed that local injections of TGFβ1 into the urethral wall in rats caused disorganization of collagen bundles in the submucosa and periurethral tissue, while at the same reporting on the development of urethral stricture and the formation of fibrotic tissue on histological sections.[71]

The injection of stem cells derived from human adipose tissue into the experimental stricture area counteracts urethral fibrosis and elastosis and prevents functional bladder complications, with partial outflow obstruction caused by urethral stricture.[68] A study by Luo et al. revealed that intra-arterial transplantation of a bolus dose of MSCs or their vesicles counteracts the formation of strictures by means of an antifibrotic effect in a rat model.[70]


  Conclusions Top


All of the studied methods have their positive and negative aspects and can be used as methods for preventing and treating BNC, based on an individual approach and indications for implementing a specific technique in each case. Although transurethral resection is currently the main treatment option for BNC, the recurrence rate after this procedure can reach 38%. According to the literature, balloon dilation can be a promising and minimally invasive method for treating recurrent BN and can be used as the first stage in treating recurrent contracture deformity. Intravesical instillation of various anti-inflammatory drugs and cytostatics is also a promising direction in the treatment and prevention of BNC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Abstract
Introduction
Methods
Etiology and Pat...
Standard Treatme...
Alternative Endo...
Combined Therapy...
Placement of the...
Balloon Dilation
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