Analysis of Risk Factors for Formation of Bladder Neck Contracture After Holmium Enucleation of Prostate

doi:10.21203/rs.3.rs-4714282/v1

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Analysis of Risk Factors for Formation of Bladder Neck Contracture After Holmium Enucleation of Prostate

https://doi.org/10.21203/rs.3.rs-4714282/v1

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PURPOSE: Holmium laser enucleation of prostate (HoLEP) offers a size independent approach to the treatment of benign prostatic hyperplasia (BPH). Bladder neck contracture (BNC) is a known complication after HoLEP. This study evaluates the incidence and risk factors associated with the formation of BNC after HoLEP.

METHODS: A retrospective review was conducted from 2020 to 2022 of men undergoing HoLEP by a single surgeon. Pre- and perioperative factors were compared including catheter dependence, previous and concurrent procedures, laser type, enucleated gland weight, and energy usage.

RESULTS: A total of 185 men were identified for the study. An incidence of BNC occurred in 9.2% of patients (n = 17). On univariate analysis, enucleated gland weight was significantly associated with BNC (72.2 vs 34.5, p = 0.007).  Of men with enucleated weight less than 18gm, 8 (23.7%) had BNCs vs 8 men (5.7%) with enucleated weight > 18 gm (p = <0.001). The presence of bladder stones at time of HoLEP was significantly associated with formation of BNC, as 17.6% of men with BNCs had bladder stones (p = 0.039). Prior urethral dilation was significantly associated with BNC (11.8%, p = 0.023). Mean time to diagnosis of BNC was 6.5 months. Mean follow up was 17.9 months.

CONCLUSIONS: Our study identified smaller glands, as well as concurrent bladder stones and previous stricture disease, as significant risk factors for the development of BNC after HoLEP.  This study underscores the importance of preoperative anatomical evaluation in patient counseling and discussion of individual risk factors.

Holmium laser enucleation of prostate

benign prostatic hyperplasia

bladder neck contracture

transurethral surgery

Lower urinary tract symptoms (LUTS) have a notable impact on daily life and can lead to a sequelae of genitourinary complications.^1,2 LUTS and the accompanying decrease in quality of life (QoL) is a significant affliction in the male population, and the prevalence of this disease is increasing with longer life spans and an aging population. When surgically indicated, HoLEP is an effective, durable, and size independent modality for the treatment of medication-refractory LUTS attributed to BPH.^3,4

Although advancements in surgical techniques have resulted in decreased postoperative complications, bladder neck contracture (BNC) is a known complication of transurethral procedures for bladder outlet obstruction. Rates between 0.8-5% have been documented in the literature, and the underlying mechanism of BNC is not currently well understood.^5–8 Theories extrapolated from the literature include a disruption of the microvasculature of the bladder neck by various means such as pressure ischemia from large scopes, laser resection, and mechanical manipulation during the procedure.^9,10 This microvascular damage and resultant ischemia leads to scar formation and the development of a bladder neck contracture. Increased incidence of BNCs have previously been associated with small gland size, longer operative times, and sheath size.^11–15

BNCs are associated with significant morbidity, often leading to decreased quality of life (QoL), recurrence of bothersome LUTS, and the potential for subsequent operative procedures.^9,16 Current techniques aimed at reducing the risk of BNC formation include smaller scope size (24 and 26Fr scopes), lower energy when resecting or coagulating at the bladder neck, and incision of the bladder neck in glands < 30gm.^5,15,17

The aims of the current study were to identify the incidence of BNCs after HoLEP at our high volume, tertiary care center and study potential risk factors in the formation of BNCs after HoLEP.

Study Design and Patient Population

A retrospective study was conducted of men undergoing laser enucleation between October 2020 through June 2022. All surgeries were performed by a single fellowship trained surgeon with an enucleation experience of over 400 cases. All patients who underwent laser enucleation of the prostate with a minimum of one-month follow-up were eligible for inclusion in the study. Indications for surgery included bothersome lower urinary tract symptoms (LUTS) or urinary retention due to BPH. Patients with less than one month of follow up were excluded from the study. This study received approval from the institutional review board (IRB# 201304085).

Surgical Technique

Our practice is to perform urethral dilation with Van Buren sounds to 30 or 32 Fr prior to insertion of the scope elements. For laser resection and morcellation we use either a 26 Fr (Richard Wolf; Vernon Hills, IL) or a 28Fr (Karl Storz; Tuttlingen, Germany) laser resection scope depending on availability. We use the Lumenis Pulse 120H holmium laser with Moses 2.0 pulse modulation (Boston Scientific, Marlborough, MA) with settings of 2.0 J x 60 hz when available, but if this is not available then we use 2.0 j x 50 hz on long pulse width for enucleation. For hemostasis after enucleation, we use settings of 1.0 J x 40 hz on either Moses 2.0 pulse modulation (if available) or long pulse width for hemostasis. We use an en-bloc enucleation technique with early apical release for all cases. We use a Piranha morcellator (Richard Wolf Medical Instruments Corp, Vernon Hills, IL) for all cases. Patients standardly have a Foley catheter for 1 night and then the catheter is removed the day after surgery.

Evaluation of Outcome Measures

The primary outcome was the development of BNC as diagnosed on cystoscopy. Descriptive data were also collected. Operative time was discerned from anesthesia and nursing records. Preoperative measurements of prostatic enlargement were not routinely performed prior to intervention, given the prostate size-independent indication for use of this treatment modality, though often many of these imaging modalities had already been performed as a component of the workup.⁴ Variables collected included scope size, type of laser used, total energy, enucleated specimen weight, concurrent procedures, history of catheter dependence, prior procedures, or radiation. Wilcoxon rank-sum test and Fisher’s exact test were used to determine statistical association BNC and quantitative and qualitative variables of interest respectively. Multivariable logistic regression model were fit to determine odds ratios and test for statistical association between variables of interest controlling for other potential confounding variables. A receiver operator characteristic (ROC) curves was used to show the relationship between prostate size and BNC. All analysis was performed using R v4.1.0 with statistical significance set to p < 0.05.

A total of 188 men were identified for the study, and three men were excluded due to short term follow up. An incidence of BNC occurred in 9.2% of patients (n = 17). On univariate analysis, enucleated gland weight was significantly associated with BNC. The mean enucleated weight for patients without BNC was 72.5 g enucleated gland vs a mean of 34.5 g enucleated weight for patients with BNC, (p = 0.007). Amongst men with enucleated gland weight less than 18gm, 9 (23.7%) had BNCs vs 8 men (5.7%) with enucleated gram weight > 18 gm (p = < 0.001). The presence of bladder stones at time of HoLEP was a significant risk factor associated with the development of BNC, as 17.6% of men with BNCs had bladder stones (p = 0.039). Prior urethral dilation was significantly associated with BNC (11.8%, p = 0.023). Prior history of radiation was also noted to be statistically significant at 11.8% (p value = 0.023)We additionally found that having hypertension (HTN) as a comorbidity was significantly associated with the formation of a BNC (35.3%, p = .084). (Table 1)

Table 1

Patient pre and periprocedural characteristics
Variable	N	BNC = No	BNC = Yes	p-value
N	185	16	17
Total Energy Use				0.260
Mean		171.4	145.7
St. Dev.		78.5	66.2
Missing		26	2
Retention				0.438
No	86	47.3%	41.2%
Yes	98	52.7%	58.8%
Missing	1	1	0
Prior History of Radiation				0.023
No	180	99.4%	88.2%
Yes	3	0.6%	11.8%
Unknown	2	2	0
Prior TURP				0.094
No	165	90.5%	76.5%
Yes	20	9.5%	23.5%
Prior Urethral Dilation				0.023
No	182	99.4%	88.2%
Yes	3	0.6%	11.8%
Scope Size				0.698
26 Fr	21	11.9%	5.9%
28 Fr	164	88.1%	94.1%
Concurrent Bladder Stone				0.039
No	176	96.4%	82.4%
Yes	9	3.6%	17.6%
HTN				0.046
No	141	83.1%	70.6%
Yes	44	16.9%	29.4%
Row Percentage
Enucleated Prostate Weight				< 0.001
>=18gm	140	94.3%	5.7%
< 18 gm	38	76.3%	23.7%
Enucleated Prostate Weight				0.013
>=32 gm	117	94.9%	5.1%
< 32 gm	61	82%	18%
Enucleated Prostate Weight				0.078
>=110 gm	31	100.0%	0.0%
< 110 gm	147	89.1%	10.9%

On multivariable analysis, men with concurrent bladder stones (OR 10.3, p = 0.010), and men with an enucleated prostate weight of < 18gm had a significantly higher association with formation of bladder neck contracture (OR 4.71, p = 0.006) (Table 2). History of prior urethral dilation was not significant. Mean time to diagnosis of BNC was 6.5 months. Mean follow up was 17.9 months. Factors such as total energy use, use of Moses laser, size of scope (26 vs 28Fr), and history of previous outlet procedure (TURP, PVP, Urolift), or retention were not statistically significant.

Table 2

Multivariable Logistic Regression Model - Estimating Odds of BNC
Multivariable Logistic Regression Model - Estimating Odds of BNC
Variable	Odd's Ratio	95% Lower	95% Upper	p-value
Prostate Size < 18mL	4.71	1.57	14.10	0.006
Prior TURP/Prostatic Urethral Lift/Laser Vaporization/Urethral Dilation	2.16	0.70	6.71	0.182
Concurrent Bladder Stone	8.03	1.41	45.61	0.019

Since its introduction into clinical practice, HoLEP has been shown to provide a safe and effective approach for the treatment of BPH.¹¹ Unfortunately, bladder neck contractures are an infrequent, but significant, complication of transurethral surgery for bladder outlet obstruction.¹² Despite knowledge of this complication, rates of stricture formation after HoLEP do not seem to have decreased over time, despite advancement in surgical technique.^7,16

In a large prospective study of over 1,216 HoLEP procedures, history of chronic prostatitis, worse preoperative QOL, use of 28Fr sheath, and longer postoperative catheterization were associated with an increased risk of BNCs.¹² Our study did not find a statistically significant difference between the use of a 26 Fr versus a 28 Fr scope. This is consistent with a study from Thai et. al. who found that while the 28 Fr sheath had a higher incidence of blood loss requiring blood transfusions, there was no overall difference in the rate of BNCs.¹⁵ Interestingly, in a study of 100 patients at a single center, a 22 Fr sheath was associated with better QoL and IPSS by reducing the rate of urethral injury when compared with a 26Fr sheath.¹⁸ Further study is needed to determine the ideal size scope in order to reduce urethra trauma, while still maintaining adequate flow, vision, and adenoma manipulation during the procedure.

In our results, prostate size was inversely correlated with the risk of BNC formation, with enucleated gland weight < 18gm showing a significantly higher risk for the formation of BNC. (Table 1) This finding can be corroborated in the literature and also across other modalities of transurethral surgery for BPH.^5,6,11 However, Elsaqa et. al. found the opposite to be true, and that larger prostate glands were positively correlated with BCN formation.⁷ Shah et. al. found a higher incidence of urethral and meatal stenosis in patients with prostate > 100g, but no incidence of bladder neck contracture.¹⁹ Differences in data could potentially be explained by duration of resection in larger glands, with prolonged resection times increasing risk of ischemia due to pressure on the tissues and risk of hemorrhage, in addition to urethral mucosal impairment in the setting of prostatitis or continuous catheterization.⁶ Conversely, it may be that a large gland is protective against the formation of a BNC, as the bladder neck diameter in large glands is greater and therefore any stenosis or decrease in BN diameter may not become clinically significant.

It has been theorized that other factors in addition to the size of the gland alone can lead to the progression to clinical BPH requiring intervention such as prostatitis, vascular infarction, and the tensile strength of the capsule.²⁰ In the smaller gland, the presence of chronic inflammation or prostatitis leading to LUTS may predispose patients to form BNCs after HoLEP due to poor wound healing. Therefore, in these patients with small glands presenting with clinical LUTS as the result of chronic inflammation, surgeons may consider addressing the underlying prostatitis in an effort to reduce the risk of the resultant formation of fibrosis that may result in a BNC after HoLEP.²¹.

In addition to gland size, we identified a significant positive correlation between the presence of bladder stones at the time of surgery, and the formation of BNCs. This correlation has not been identified elsewhere in the literature to our knowledge. It is suspected that the incidence of bladder calculi is mainly associated with urinary stasis and recurrent urinary tract infections due to bladder outlet obstruction as seen in BPH and other genitourinary abnormalities.²² Therefore, the mechanism of BNC formation in patients with bladder stones may be that the stones may induce chronic inflammation and destruction of the microvasculature of the bladder neck tissue, leading to poor healing of the inflamed tissue postoperatively.^9,10

Our study also found that a history of urethral dilation was a statistically significant risk factor in the development of BNCs. Interestingly, a study found that pre-calibrating the urethra before HoLEP with Van Buren urethral sounds to 28 Fr had a protective effect on the risk of urethral stricture formation.²³ The finding of statistical significance of BNCs in patients with a history of urethral dilation likely demonstrates that the tissue is already devitalized due to prior instrumentation. In a similar pathogenesis to the formation of BNCs, the presence of a prior urethral stricture may signify that damage to the mucosal microvasculature is already present. This theory could also be applied to the statistical significance of prior radiation in formation of BNC.

One of our limitations is that this is a retrospective analysis with single sample data, limited sample size, and overall small number of events. It would be of benefit to do a multi-center prospective study with a larger sample size in order to accurately characterize preoperative, intraoperative, and postoperative measures associated with risk of BNCs.

Future studies should be aimed at carefully stratifying patients based on preoperative characteristics. Additionally, careful anatomical evaluation prior to surgery, such as cross-sectional imaging, ultrasound, or cystoscopy can aid in a patient centered discussion of the individual risks and benefits of HoLEP based on the size and configuration of anatomy. It would also be interesting to further explore the relationship between the presence of bladder stones preoperatively and the formation of BNCs.

Our study identified smaller gland size, as well as concurrent bladder stones, prior radiation treatment, and previous stricture disease as significant risk factors for the development of BNC after HoLEP. Given these findings, we believe this underscores the importance of preoperative anatomical evaluation such as transrectal or abdominal ultrasound, cross-sectional imaging and cystoscopy prior to surgical intervention, as is recommended in the guidelines.²⁴ This interrogation will enable the physician to engage in meaningful risk and benefit discussions with patients and improve the quality of shared decision making when deciding on the optimal treatment modality for BPH.

Funding:

None

Author Contribution

Susan Talamini: Conceptualization, Methodology, Investigation, Writing – Review/EditingRebekah Keller: Investigation, Writing- Review/editingBriana Kaplunov: Writing – Review and EditingAdam Ostergar: Writing – Review and EditingDaniel Wong: Writing – Review and EditingHayden Hill: Writing – Review and EditingJoel Vetter: Conceptualization, Methodology, InvestigationAlethea Paradis: Conceptualization, MethodologyCharles Nottingham: Conceptualization, Methodology, Investigation, Writing – Review/Editing

Acknowledgments:

Washington University School of Medicine in St. Louis, Barnes-Jewish Hospital

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No competing interests reported.

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Analysis of Risk Factors for Formation of Bladder Neck Contracture After Holmium Enucleation of Prostate

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Abstract

Introduction

Methods

Study Design and Patient Population

Surgical Technique

Evaluation of Outcome Measures

Results

Discussion

Conclusions

Declarations

Funding:

Author Contribution

Acknowledgments:

References

Additional Declarations

Status:

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