The present study demonstrates that endoscopic injection therapy is an effective and safe treatment for VUR in adult patients. Conducted via modified HIT techniques adopted for dilated ureteral orifice, we achieved successful results in 75% of patients and over 90% of patients were cured after the first operation.
A previous meta-analysis has shown that refinement of injection materials and methods has led to the present success rate over 70% in children [14]. Recently, by a single experienced pediatric urologist, HIT has been reported to have a high success rate in adult [15], although this was among patients with mainly low-grade VUR. The present study demonstrates high success rates even in grade IV filling VUR applying modified HIT techniques adopted for adult ureters.
Reported predictors for success include a volcano-like mound appearance [16], mound height (as assessed by ultrasound) [17] and injection volume [18]. Moreover VUR grade [19] and timing of VUR are suspected predictors [20]. And also, HD grade could be another predictor, seeing the fact HD grade is reported to have high correlation with VUR grade [21], in accordance with our present results. In adult ureter, additional risks are exist seeing the present study, like that the deformity (‘dropped’ or ‘kinked’) and the pathological stiffness owing to historical change more evident in adult ureters.
To manage these requirements, the injection must be conducted carefully with the needle align with the ureter puncturing at the adequate location where good tissue-softness guaranteed, so as to ensure enough mound appearance and height. We used two kinds of methods, I-HIT or G-HIT, with technique-selection according to HD grade adopted for large-caliber adult ureter. As a result, we found high success rate even in grade IV VUR. The flow chart that we developed and is presented here may provide a guide for the selection of injection technique.
In the present study, we found ureteral deformities or a history of anti-reflux surgery were associated with reduced success of outcomes. Anatomical anomalies like complete duplicated ureter pose a challenge to injection [22]; therefore, ureterocele and Hutch diverticulum are considered contraindications for endoscopic injection therapy [23]. In these complicated ureters, care must be taken to inject with an adequate volume to create sufficient mound height. These risks may be ameliorated using meticulous methods like I-HIT or G-HIT.
In the present study, we have experienced one case of acute pyelonephritis requiring antibiotic infusion before discharge. In this case, single sided VUR confirmed by intraoperative cystography may lead to subsequent f-UTI. Maintaining bladder volume and considering the intraoperative VUR could result in better outcomes. In this meaning, intraoperative cystography has some benefit.
This study showed the prevalence of occult VUR to be considerable postoperatively (6%). Although intraoperative cystography is not recommended for detection of occult VUR owing to its low sensitivity [24], other methods to predict occult VUR are needed. Alternatively, protective injection according to HD grade could be recommended [25], so that VUR grade is reported to have high correlation with HD grade [21] as mentioned in the former section.
We recommend 6 months of follow-up including ultrasound examination after surgery, based on our finding that temporary postoperative HN until 3 months occurred in nearly 20% of patients. One of the risks of obstruction, the beak sign of ureterovesical junction [16], may have contributed to any case of persistent HN.
The present study had some limitations which should be acknowledged. First, this was a retrospective study with a small sample size. However, we included all consecutive patients, and all operations were performed by a single urologist at a single institution, thereby reducing bias relating to the cohort. Secondly, not all patients underwent repeated VCUG after successful treatment. Although late recurrence was reported in 20% of cases over the 2 years [26–28]. Three month postoperative VCUG examinations are widely performed while late VCUG is not routinely performed due to the radiation exposure involved [29]. We performed regular urinalysis and ultrasound postoperatively and would recommend that repeated VCUG is performed in cases where at least one episode of f-UTI or repeated afebrile UTI are experienced. Long-term follow-up including ultrasound or dimercaptosuccinic acid examination of growth and blood pressure is important for patients with renal scarring [30]. Further randomized clinical trials with larger cohorts evaluating long-term clinical outcomes, prevention of f-UTI, and renal function are required to fully confirm the efficacy and safety of injection therapy in adult patients.