1 INTRODUCTION

Overactive bladder (OAB) is defined as urinary urgency, usually with daytime frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathologies.1 Pelvic organ prolapse (POP) is a major health-care problem that impairs the quality of life in women, and many urologists support the opinion that patients with POP often experience OAB symptoms.2-4 Several reports revealed that transvaginal POP repairs, such as transvaginal mesh (TVM) surgery, are effective treatment tools, and they lead to the disappearance or improvement in OAB symptoms.2, 3, 5, 6

However, only approximately 75% to 79% of patients experience such clinical effects of TVM surgery for OAB symptoms; conversely, >20% of patients experience worsening or no changes in symptoms after TVM surgery.3, 4 Therefore, many investigators attempted to define predictive markers for the improvement in urinary conditions, including OAB symptoms, after surgery.2-4, 7 Previous studies used the severities of preoperative subjective symptoms, including International Prostate Symptom Score, overactive bladder symptom score (OABSS), and urodynamic examination data, as useful preoperative predictors.2-4, 7 However, since the examination exclusively based on subjective symptoms cannot evaluate objective findings, such as detrusor overactivity and bladder outlet obstruction, and urodynamic tests are invasive and carry the risk of urinary tract infections, noninvasive and effective predictors of surgery outcomes are needed.2, 8

The measurement of bladder wall thickness (BWT) is supposedly a useful noninvasive parameter to evaluate the lower urinary tract function.9, 10 In fact, BWT was significantly correlated with clinical parameters, symptom scores, and uroflowmetry results under obstructive bladder conditions.11, 12 In addition to bladder outlet obstruction, BWT in women with OAB was greater than that in women with stress incontinence or normal urinary function.13-17 Thus, BWT has been hypothesized to reflect the bladder activity and urinary symptoms in various urinary disorders. Additionally, in recent years, sonographic parameters, including BWT, were reported to be useful predictors of outcomes in patients with lower urinary tract symptoms treated with an alpha-1 adrenoceptor antagonist.18 Similarly, BWT is considered a potentially useful parameter for monitoring the response to antimuscarinic treatment in patients with OAB.19, 20 However, the predictive value of BWT for OAB symptoms in POP patients treated with TVM has not been studied. Therefore, this study mainly aimed to determine the usefulness of BWT as a predictive marker for the improvement in OAB symptoms after TVM surgery in POP patients.

2 METHODS 2.1 Patients

The study group consisted of 41 women who underwent TVM surgery for POP and who met the diagnostic criteria for OAB using OABSS (urgency ≥2, total score ≥3)21 at Nagasaki University Hospital. Patients who underwent a sling procedure for stress incontinence at the time of the TVM surgery were excluded from the study. In addition, bladder or rectal cancers, urinary tract infection, additional perioperative treatment, including antimuscarinic drugs, or uncontrollable systemic disorder were the major exclusion criteria (Figure 1). We used a soft polypropylene mesh (Gynemesh PS; Ethicon, Somerville, New Jersey, or Polyform; Boston Scientific, Tokyo, Japan), and the surgical technique was similar to that of the French TVM group.22 Patients with anterior vaginal wall prolapse underwent the anterior TVM (A-TVM) procedure. The A-TVM procedure starts with anterior colpotomy after local infiltration. Repair of a cystocele required two arms of the transobturator mesh to be passed on both sides to suspend the cystocele. On either side, both arms of the mesh were passed into the paravesical region using a modified Emmet needle. The anterior subvesical strap was inserted into the tendinous arch of the pelvic fascia. Patients with both anterior and posterior vaginal wall prolapse underwent an anterior-posterior TVM (AP-TVM) procedure. The posterior subvesical strap was inserted into the tendinous arch 1 cm from the ischial spine using a gently curved needle. In the posterior TVM (P-TVM) procedure, posterior colpotomy was performed longitudinally, and the mesh was placed under the vaginal wall. On each side, one strap of the mesh was passed into the pararectal space through the sacrospinous ligament and exteriorized via incisions located outside and below the anus. Furthermore, patients without a uterus underwent total TVM (T-TVM), wherein one piece of a prosthetic mesh, consisting of two connected parts, is inserted into the anterior and posterior walls.22-24 All patients underwent the same surgical procedure using TVM by an expert surgeon (T.M.). Finally, 41 patients treated with TVM (anterior 24, posterior 0, anterior and posterior 12, and total 5) were enrolled in this study. Table 1 shows the baseline characteristics of the patients and the surgical procedures this study. This study was approved by the Nagasaki University Hospital Ethical Committee and was performed in accordance with the principles of the Declaration of Helsinki. All patients provided written informed consent.

Patient flow diagram

TABLE 1. Patients' characteristics at the presurgical stage Entire OABSS responder OABSS nonresponder P value Number of patients 41 30 11 - Age, y 68.0 ± 7.3 69.0 ± 4.7 69.3 ± 8.1 .539 POP-Q stage (%) .545 0 0 (0) 0 0 1 0 (0) 0 0 2 4 (9.8) 2 2 3 33 (80.5) 25 8 4 4 (9.8) 3 1 Postmenopausal status 39 (95.1) 29 10 .448 Hormone replacement therapy (%) 0 (0) 0 (0) 0 (0) Parity 2.1 ± 0.9 1.9 ± 0.8 2.2 ± 0.8 .889 Previous surgery (%) Hysterectomy 4 (9.8) 3 (10.0) 1 (9.1) .931 Reconstructive surgery 8 (19.5) 7 (23.3) 1 (9.1) .308 Others 0 (0) 0 (0) 0 (0) 1.000 Surgical procedure (%) .566 Anterior 24 (58.5) 19 (63.3) 5 (45.5) Posterior 0 (0) 0 (0) 0 (0) Anterior and posterior 12 (29.3) 8 (26.7) 4 (36.4) Total 5 (12.2) 3 (10.0) 2 (13.6) OABSS Q1 Daytime frequency 0.9 ± 0.7 1.1 ± 0.6 0.6 ± 0.7 .048 Q2 Nighttime frequency 1.3 ± 0.8 1.3 ± 0.8 1.3 ± 0.9 .915 Q3 Urgency 2.0 ± 1.6 2.8 ± 1.1 2.3 ± 0.9 .136 Q4 Urgency incontinence 1.0 ± 1.5 1.2 ± 1.7 0.4 ± 0.7 .243 Total score 5.1 ± 3.3 6.3 ± 3.1 4.6 ± 2.1 .071 Voided volume (mL) 199.6 ± 154.5 167.5 ± 118.5 289.3 ± 209.4 .097 Qmax (mL/s) 16.7 ± 11.4 14.8 ± 9.8 21.9 ± 14.3 .066 PVR (mL) 65.4 ± 78.0 68.5 ± 80.9 56.9 ± 72.6 .751 Note: Data are presented as mean ± SD. Abbreviations: OABSS, overactive bladder symptom score; POP-Q, Pelvic Organ Prolapse-Quantification; PVR, postvoid residual urine volume; Qmax, maximum urinary flow rate. 2.2 Evaluation of BWT and urinary conditions

BWT was evaluated by ultrasonographic examination before and 6 months after the surgery at three sites in the bladder: the anterior wall, trigone, and dome, as reported earlier.25, 26 All patients were examined by one urologist (T.M.). Ultrasonography was performed by a transvaginal approach using a conbex probe (HI VISION Avius, 7.5 MHz B mode; Hitachi-Aloka Medical, Ltd, Tokyo, Japan). When the examination was performed, <50 mL of urine pooled in the bladder (Figure 2). All patients simultaneously filled in the self-reporting questionnaire for evaluating the OABSS. The validated Japanese language questionnaire was completed by patients in a separate and secluded space. Patients with lower OABSS after surgery than before operation were considered responders, while those with worsening or unchanged OABSS after operation were considered nonresponders. Briefly, OABSS responders in this study were defined as individuals with a decrease in the total score of OABSS by 1 point or more. In addition, the maximum urinary flow rate (Qmax) and voided volume (VV) were determined using free uroflowmetry, and postvoid residual urine volume (PVR) was measured using suprapubic ultrasonography.

Transvaginal ultrasonography for the bladder wall showing measurements of the trigone and parts of the dome

2.3 Statistical analysis

Data are presented as the number of patients (percentage, %) or mean ± SD. All statistical analyses were performed using the JMP14 software (SAS Institute Inc, Cary, North Carolina). Differences in the changes in parameters from baseline to 6 months in patients were examined using the paired Student's t or Wilcoxon signed rank tests. Values of P < .05 were considered statistically significant.

3 RESULTS 3.1 Changes in urinary symptoms after surgery

Among the 41 patients evaluated, TVM surgery improved urinary condition in 30 patients,

as evaluated by the OABSS (73.2%). However, the score deteriorated in 6 patients (14.6%) and was unchanged in 5 patients (12.2%). There was no case of POP recurrence, especially during the follow-up period regarding surgery. Table 2 shows the changes observed in the OABSS and objective findings, including uroflowmetry, after TVM surgery. After the operation, the total OABSS of all patients decreased significantly (5.1 ± 3.3 to 2.9 ± 2.9; P < .001). In OABSS responders, the total score improved from 6.3 ± 3.1 to 2.0 ± 2.0 (P < .001). The individual questionnaires showed that the Q1 (Daytime frequency) and Q3 (Urgency) scores were significantly decreased by TVM surgery (0.9 ± 0.7 to 0.3 ± 0.5 and 2.0 ± 1.6 to 1.0 ± 1.6, respectively), whereas the changes in Q2 (Nighttime frequency) and Q4 (Urgency incontinence) were not significant (1.3 ± 0.8 to 1.1 ± 0.9 and 1.0 ± 1.5 to 0.5 ± 1.1, respectively) in patients overall. In OABSS nonresponders, total OABSS and all items in the OABSS did not improve after TVM operation. Finally, among the 41 patients, 30 and 11 were found to be OABSS responders and OABSS nonresponders, respectively (73.2% and 26.8%, respectively). In objective findings, the PVR of patients overall and OABSS responders improved after operation (overall, 65.4 ± 78.0 mL to 19.7 ± 33.7 mL, P < .001; OABSS responders, 68.5 ± 80.9 mL to 19.6 ± 35.8 mL, P < .001). However, not all objective findings significantly improved after operation in OABSS nonresponders (Table 2).

TABLE 2. Changes in OABSS and urological parameters by surgery Overall OABSS responder OABSS nonresponder Variables Presurgery Postsurgery P value Presurgery Postsurgery P value Presurgery Postsurgery P value OABSS Q1 Daytime frequency 0.9 (0.7) 0.3 (0.5) <.001 1.1 (0.6) 0.2 (0.4) <.001 0.6 (0.7) 0.5 (0.7) 1.000 Q2 Nighttime frequency 1.3 (0.8) 1.1 (0.9) .332 1.3 (0.8) 1.1 (0.9) .350 1.3 (0.9) 1.4 (1.0) 1.000 Q3 Urgency 2.0 (1.6) 1.0 (1.6) .001 2.8 (1.1) 0.6 (1.1) <.001 2.3 (0.9) 2.2 (2.0) .914 Q4 Urgency incontinence 1.0 (1.5) 0.5 (1.1) .070 1.2 (1.7) 0.2 (0.7) <.001 0.4 (0.7) 1.3 (1.7) .125 Total score 5.1 (3.3) 2.9 (2.9) <.001 6.3 (3.1) 2.0 (2.0) <.001 4.6 (2.1) 5.4 (3.7) .406 Voided volume (mL) 199.6 (154.5) 220.9 (157.0) .649 167.5 (118.5) 217.2 (145.0) .262 289.3 (209.0) 231.3 (195.3) .375 Qmax (mL/s) 16.7 (11.4) 20.1 (12.0) .080 14.8 (9.8) 18.8 (10.2) .139 21.9 (14.3) 23.8 (16.1) .426 PVR (mL) 65.4 (78.0) 19.7 (33.7) <.001 68.5 (80.9) 19.6 (35.8) .001 56.9 (72.6) 20.0 (28.5) .078 Note: Data are expressed as mean (SD). Abbreviations: OABSS, overactive bladder symptom score; PVR, postvoid residual urine volume; Qmax, maximum urinary flow rate. 3.2 Changes in BWT after surgery

Table 3 shows the measurements of BWT at three different sites and their mean values before and after TVM surgery. No significant differences in BWT were observed among the three sites before surgery. Postsurgical BWT levels at the anterior and dome regions were altered significantly, along with the mean levels at all three sites (P < .001). However, BWT at the trigone region was not altered significantly (P = .741).

TABLE 3. Changes in urinary bladder wall thickness in all patients Bladder wall thickness (mm) Transvaginal mesh surgery P value Before After Anterior 5.73 ± 1.25 4.75 ± 1.37 <.001 Trigone 6.09 ± 1.28 6.26 ± 2.18 .741 Dome 5.82 ± 1.09 4.98 ± 1.34 <.001 Mean of the three sites 5.88 ± 1.17 5.33 ± 1.53 <.001 3.3 Correlation between BWT and urinary symptoms after surgery

Figure 3 shows the correlation between the changes observed in BWT and OABSS after surgery. In OABSS responders, BWT at the anterior wall and dome was significantly decreased after TVM surgery (5.46 ± 1.32 mm to 4.47 ± 1.20 mm and 5.56 ± 1.06 mm to 4.65 ± 1.20 mm, respectively). In contrast, in OABSS nonresponders, these two parameters exhibited a decreasing trend but did not reach significance (6.56 ± 1.02 mm to 5.89 ± 1.53 mm and 6.62 ± 1.02 mm to 5.88 ± 1.55 mm, respectively; P = .126 and P = .093, respectively). BWT at the trigone region was unchanged after surgery in both responders and nonresponders (5.69 ± 1.27 mm to 5.69 ± 2.08 mm, P = .501, and 7.04 ± 0.89 mm to 7.53 ± 2.13 mm, P = .169, respectively). The mean BWT at all three sites before and after TVM surgery was significantly different among OABSS responders (5.57 ± 1.21 mm and 4.94 ± 1.63 mm, P < .001), unlike among nonresponders (6.74 ± 0.92 mm to 6.43 ± 1.84 mm, P = .254).

Changes in bladder wall thickness (BWT) before and after transvaginal mesh surgery in overactive bladder symptom score (OABSS) responders and OABSS nonresponders. In OABSS responders, BWT at the anterior wall and dome and mean BWT at all three sites after surgery was significantly lower than before surgery

3.4 Prognostic roles of BWT for the efficacy of the surgery

Table 4 shows the relationship between lower OABSS and BWT before surgery. All measurements of BWT at the three sites in OABSS responders were significantly lower than those in OABSS nonresponders. In addition, the mean BWT at all three sites was also significantly different among the responders, and it showed the most significant difference among the parameters evaluated. In addition, when the postoperative BWT change between OAB responders and OAB nonresponders was examined, BWT decreased postoperatively in the OAB responder group at all sites. However, no statistically significant difference was observed (Table 5). Furthermore, we examined the correlation between the changes in bladder capacity (VV + PVR) and BWT before and after operation. Consequently, the increase in postoperative bladder capacity was statistically significantly inversely correlated with BWT (r = −0.4541, P = .005). In contrast, improvement in OAB symptoms and BWT with receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.858 (95% CI, 0.713-1.003) and 0.868 (95% CI, 0.743-0.993) for anterior wall and dome, respectively. When the cutoff values for BWT were defined as 6.72 mm and 6.41 mm for the anterior wall and dome, the sensitivities were 77.8% and 77.8%, and the specificities were 79.3% and 75.9%, respectively, for the predicted improvement in OAB symptoms after TVM surgery (Figure 4A,B).

TABLE 4. Bladder wall thickness before surgery and improvement in overactive bladder symptoms by surgery Bladder wall thickness, presurgery (mm) OABSS responder OABSS nonresponder P value Anterior; mm, mean ± SD 5.46 ± 1.32 6.56 ± 1.02 .017 Trigone 5.69 ± 1.27 7.04 ± 0.89 .003 Dome 5.56 ± 1.06 6.62 ± 1.02 .008 Mean of the three sites 5.57 ± 1.12 6.77 ± 0.92 <.001 Abbreviation: OABSS, overactive bladder symptom score. TABLE 5. Changes in bladder wall thickness by operation between improvements in overactive bladder symptom scores Changes in BWT by operation (mm) OABSS responder OABSS nonresponder P value Anterior; mm, mean ± SD −1.03 ± 1.22 −0.82 ± 1.54 .676 Trigone −0.01 ± 1.86 0.61 ± 1.60 .207 Dome −0.91 ± 1.32 −0.82 ± 1.31 .765 Mean of the three sites −0.62 ± 1.18 −0.32 ± 1.37 .507 Abbreviations: BWT, bladder wall thickness; OABSS, overactive bladder symptom score.

Receiver operating characteristic (ROC) curves for the relationship between preoperative bladder wall thickness (BWT) and improvement in overactive bladder (OAB) symptoms. The black line shows the ROC curve in JMP software. The yellow line in the plot is a straight line at a 45-degree angle tangent to the ROC curve, and the contact point with the ROC curve shows the optimal cutoff value

In addition, the unfit rate for the diagnosis of OAB was 61.0% (25/41). Furthermore, the deviation from diagnostic criteria for OAB and BWT with ROC showed an AUC of 0.698 (95% CI, 0.531-0.864) and 0.703 (95% CI, 0.510-0.895) for the anterior wall and dome, respectively. When the cutoff values for BWT were defined as 6.43 mm and 6.74 mm for the anterior wall and dome, the sensitivities were 80.0% and 84.0%, and the specificities were 56.3% and 50.0%, respectively, for predicting the deviation of the diagnosis for OAB after TVM surgery (Figure 5A,B).

Receiver operator characteristic (ROC) curves for the relationship between preoperative bladder wall thickness (BWT) and deviation for diagnosis of overactive bladder (OAB) using OAB symptom score (OABSS). The black line shows the ROC curve. The yellow line in the plot is a straight line at a 45-degree angle tangent to the ROC curve, and the contact point with the ROC curve shows the optimal cutoff value

4 DISCUSSION

This study shows that presurgical measurement of BWT using ultrasound may be a useful predictor of lower OABSS after TVM surgery in patients with POP. In general, the most useful method to evaluate bladder activity is supposedly a conventional urodynamic test. In fact, in previous studies, urodynamic tests revealed useful predictive factors for improving OAB symptoms in POP after TVM surgery.3, 4 However, this test is invasive, time-consuming, and presents various types of risks.8 Clinical parameters, such as age, body mass index, postmenopausal status, and smoking, have similarly been investigated as potential predictive factors for improved OAB symptoms after TVM repair, and some of them were identified as useful predictors.3 In this study, we focused on the measurement of BWT due to its noninvasive nature.

One of our interesting results is that all BWT parameters were significantly thinner in OABSS r