Hypothesis / aims of study
Safe follow-up of patients with neurogenic lower urinary tract dysfunction (NLUTD) has multiple objectives: protection of the upper urinary tract to prevent renal failure; surveillance of the lower urinary tract to avoid infections, lithiasis, and tumours; adequate drainage and urinary continence; and, ultimately, improvement of quality of life.
Numerous treatments have been developed to achieve these goals. From the conservative medical treatment with anticholinergic drugs, B3 agonists, or botulinum toxin, to the use of surgery such as urinary diversion or augmentation cystoplasty (AC). When non-surgical therapies have failed, AC is indicated for an overactive and poorly compliant bladder, according to European Association of Urology (EAU) guidelines (1). Bladder augmentation has been found to be beneficial, especially in neurological conditions such as spinal cord injury (SCI), multiple sclerosis, and myelodysplasia (2).
This study aimed to review our long-term results on patients who previously underwent AC.
Study design, materials and methods
A retrospective study was conducted on patients who underwent AC from 1988 to 2018.
93 patients with refractory neurogenic detrusor overactivity who failed medical and endoscopic surgical treatments underwent AC. We had access to the clinical history of 70 of 93 patients. The remaining 23 patients were excluded from the study.
The following parameters were studied:
1) Epidemiology: patient's disease, age at the time of the surgery, years of follow-up.
2) Urodynamic: maximum cystometric capacity (MCC, mls) and maximum detrusor pressure (Pdet-max, cmH20). These parameters were obtained from the previous urodynamic (UD) study to the AC and the last UD that the patient had.
3) Pathological: symptoms (urgency, frequency, leakage, pain, autonomic dysreflexia or stress urinary incontinence); medication; the presence of vesicoureteral reflux (VUR); stone formation; complications after surgery; and carcinoma development.
The software used was the statistical package SPSS v.27. The McNemar test was carried out to contrast percentage differences between the pre and post-surgery. The Wilcoxon test was used for comparison of medians or average ranges of the pre and post measurements, in the event of non-compliance with the assumption of normality in the response variable. And the parametric Student's t-test for comparison of means, always under the non-violation of the normality assumption.
Results
Of the 70 patients, 47 were men and 23 were women. Patient follow-up for the study purpose ended in October 2023. AC was performed secondary to SCI (n=55), spina bifida (n=4), transverse myelitis (n=2), idiopathic detrusor overactivity (n=4), and others (n=5). The patient's median age at the time of AC was 37.4 (range: 10-75). At the time of the review of the patients, the median of follow-up was 19.35 years (range: 5-35).
Urodynamic parameters and the effect of Botox were analysed as follows:
a. MCC and Pdet-max pre and post-AC in all patients: MCC was increased from 158.25 to 480 (t=-10.61, p<0.001). Pdet-max was decreased from 67.07 to 18.43 (t=8.17, p<0.001).
b. MCC and Pdet-max without Botox: thirty-five patients (48%) did not receive Botox at any moment. MCC increased from 143 to 549 mls (Z=-3.82, p<0.001) and Pdet-max decreased from 69.5 to 19.4 (t=6.86, p<0.001).
c. MCC and Pdet-max pre and post-Botox: ten patients (14%) received Botox before and after the AC. MCC increased from 200 to 400 mls after surgery (Z=-1.71, p=0.08). Pdet-max decreased from 50.67 to 24.89 cmH20 after AC (t=2.3, p=0.05). Both results were a trend p-value (0.05<p<0.1).
d. MCC and Pdet-max in patients pre-Botox: eighteen patients (24.66%) received Botox injections pre-AC but not after. MCC increased from 125 to 490 mls (Z=-3.41, p<0.001). Pdet-max decreased from 72.64 to 19.50 (t=4.82, p<0.001).
e. MCC and Pdet-max post AC Botox: seven patients (10%) received Botox injections after AC. MCC increased from 100 to 400 mls after surgery (Z=-1.76, p=0.07). Pdet-max decreased from 68.75 to 26.25 cmH20 (t=2.54, p=0.08). Both results were a trend p-value (0.05<p<0.1).
Pathological results:
a) Symptoms: the most bothersome symptom to the patient was taken into account. Most of the patients suffered from leakage (45.3%) and urgency (21.1%). Both symptoms were reduced after the AC to 11.6% and 10.5%, respectively (p<0.05).
b) Medication: statistically significant differences were shown in pre and post medication (p<0.001). Of the 100% who took medication before, 46.4% continued to take it after, while 53.6% stopped taking it.
c) Vesicoureteral reflux: pre-existing VUR was identified in 9 patients (13%). One patient underwent a reimplantation at the same time as the AC. Another patient required a STING procedure before the AC. The other 7 patients did not require further surgery. After AC, 2 patients had ongoing VUR. One of them required reimplantation plus concomitant STING injection and the other patient underwent an STING injection alone. Despite these anti-reflux procedures, both patients had ongoing VUR but showed an improvement in grade (V to II and IV to II grade reflux, respectively).
d) Stones: the incidence of the stones was found in 12 patients (17.14%) after AC. Eight patients (66.7%) of these had bladder stones, and all of them were treated endoscopically. Four patients (73.3%) developed renal stones, 2 of which did not require treatment after specialist review.
e) Complications: one patient (1.4%) developed spontaneous bladder perforation sixteen years later of his AC, requiring an emergency laparotomy (Clavien-Dindo 3b).
f) Carcinoma development: three patients (4.3%), two men and one woman, developed carcinoma after AC. The first symptom in all cases was haematuria. The first male patient had invasive bladder carcinoma (BC) with lymph nodes and metastasis. The second male developed a small cell carcinoma. Lastly, the woman developed papillary carcinoma. All of them died because of the disease despite several treatments.
Interpretation of results
Probably the most important results to analyse were the urodynamic parameters of the surgery and their relation to Botox. We divided the patients into 4 different groups depending on the Botox effect to avoid confusion factors in the urodynamics results.
Overall, all patients significantly had an improvement in their urodynamic results (both bladder capacity and detrusor pressure).
However, when patients needed Botox to be added to their surgery, the improvement was smaller. This could be due to the sample size, but also could be interpreted as a failure of the surgery.
It was also remarkable that when patients who had Botox before surgery but not after or did not have Botox at any time, showed greater improvement than the groups of patients treated with Botox at some point.
Finally, we understand that one of the limitations of the study was the different sizes of the treatment groups, since most of the patients did not receive Botox because this treatment was accepted in 2011 and the series started in 1988.
Concluding message
1) AC is a treatment option in patients with neurogenic detrusor overactivity refractory, regardless of the use of Botox before and/or after.
2) Long follow-up is needed in these patients to assess urodynamic outcomes, symptoms conditions, and complications findings, like bladder perforation, or stone formation.
3) The overall incidence of carcinoma development is less than 5% and it is important to pay attention to the haematuria.
Finally, more studies with more long-term follow-up as well as more patients included are needed. We proposed further studies with a multicentre data collection.