STING Procedure for Reflux

Steve J. Hodges

Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston‐Salem, NC, USA

Introduction

The endoscopic treatment of vesicoureteral reflux (VUR) involves the injection of a bulking agent at the orifice of an incompetent ureter in order to create a suitable flap–valve mechanism to prevent the retrograde flow of urine during voiding. Many different types of bulking agents have been used in the history of endoscopic reflux therapy, although the perfect agent has been elusive. The ideal substance for endoscopic treatment of reflux should be easily injectable, nonimmunogenic, stable, and safe for human use [1].

Search for the ideal bulking agent

Matouschek was the first to describe the endoscopic treatment of VUR in 1981 when he described the injection of Teflon® polytetrafluoroethylene (PTFE) at the ureteral orifice to increase resistance to urine back flow [2]. Following the publication of excellent results using the subureteral PTFE (Teflon) injection (the STING technique) by O’Donnell and Pruri, the procedure received general acceptance in Europe, but was not widely used in the United States, where there was concern over implant migration [3]. The numerous reports of PTFE migration to remote areas such as the brain and lung following injection in the urethra and bladder neck sealed the fate of PTFE therapy [4, 5]. In addition to the risk of migration, there was concern over the development of granulomatous reaction around the PTFE, leading to possible calcification and making subsequent reimplant surgery difficult [6].

Once it was clear the future of the endoscopic treatment of reflux would not include PTFE, scientists searched for other agents to be used in the desirable technique. Silicone (Macroplastique; Urpoplasty Inc., Minneapolis, MN, USA) was a very effective agent when used with the STING procedure, correcting reflux in over 80% of ureters, with little morbidity. Unfortunately, silicone can cause a local foreign body reaction, and on the basis of the variable size of its particulates (35–540 µm), has a theoretical potential for migration risk. Also, the difficulty in injecting the viscous solution made the procedure less desirable. Finally, Macroplastique came to light at a time of great concern over systemic collagen disorders arising from silicone implants, and the material never achieved popular use [1, 7]. Recently, however, studies have demonstrated improved results with polydimethylsiloxane as compared to commonly used agents (specifically with high‐grade reflux), raising the question as to whether this material should be revisited as a viable alternative [8].

The next agent to be explored for the endoscopic therapy of reflux was glutaraldehyde crosslinked bovine collagen (Contigen; C.R. Bard Inc., Murray Hill, NJ, USA). This substance has several characteristics that limited its widespread use for the STING procedure. First, it has the possibility of an allergic reaction, and therefore demands requisite allergy testing preinjection. Also, as has been noted in other areas of collagen injection (in cosmetic surgery, or the urethra for intrinsic sphincter incontinence), the substance has a limited staying power, and can show significant volume loss over time from the site of injection. Finally, long‐term efficacy was not comparable to other, more durable agents [1, 7].

Calcium hydroxylapatite (Coaptite; Boston Scientific Inc., Natick, MA, USA) is a mixture of water and glycerin with 3% methylcellulose gel. It had commendable results in studies on patients with reflux requiring endoscopic correction, but had a higher single injection failure rate when compared to competing agents. The material is thought to be biocompatible and nonmutagenic, and currently is indicated only for female stress urinary incontinence secondary to intrinsic sphincter deficiency [1].

As research into tissue engineering expanded in the 1990s, one of the first areas investigated for human use involved the growth of chondrocytes for the treatment of VUR in children. Autologous chondrocytes were harvested from the auricular cartilage of patients and six weeks after their harvest and growth in culture, they were suspended in an alginate solution that included calcium chloride and calcium sulfate, which provided a scaffold for cartilage formation. The cells were then injected cystoscopically using the STING technique. The elastic cartilage tissue formed was able to correct VUR without any evidence of obstruction, and represented the first human application of cell‐based tissue engineering technology for urologic applications [9].

However, the costs of the technique, as well as the need for a second harvesting procedure, limited the widespread use of the technology. In addition, variable degrees of cell growth appeared to occur, leading to inconsistent success rates [10].

Another novel material for use in the STING procedure was introduced in the late 1990s. Crosslinked dextranomer and hyaluronic acid (Deflux) had been used safely in the body for other indications for years, with no migration and long‐term durability. Deflux was thought to have many of the characteristics of an ideal and effective bulking agent, as it is thin enough to allow needle injection, yet viscous enough to maintain its volume, is biocompatible, elicits minimal inflammation, and maintains its periureteral configuration over time [11].

In the first few years after the introduction of Deflux and its acceptance into widespread use, it demonstrated excellent results and durability, and had become the agent of choice. As the experience with the use of Deflux grew, the techniques, methods, and circumstances of use evolved.

As the years have passed, complications have arisen from the use of Deflux as well, with overall success rates only in the 70% range, and reports of the implant causing long‐lasting inflammation and the formation of granulomas, and pseudocysts around the Deflux injection site. In many cases the implant has become calcified, mimicking a ureteral calcification on imaging studies, and the incidence of early and obstruction as a result of Deflux injection is increasing [12, 13].

In instances where Deflux is being considered as a treatment option, another dextranomer/hyaluronic acid‐based bulking agent (Vurdex; BioScience GmbH, Germany) has been developed, with similar results to Deflux but a significantly lower price [14].

Technique

The traditional STING procedure involved the injection of bulking material just outside the ureteral orifice at the 6 o’clock position, elevating a mound with the compressed ureteral orifice located at the top of the hillock. Using the traditional STING technique, the success rates with Deflux injection, while variable, were acceptable, but certainly lagged behind those of surgical reimplantation. The Atlanta group pioneered a novel method, termed “HIT” and now “double HIT,” which has raised the success levels of Deflux injection above 90% [15, 16]. In this method, the ureter is hydrodistended so that the needle may be placed inside the ureteral tunnel, a few millimeters within the orifice (see Video 155.1). This allows the first injection of the HIT technique to track bulking agent along the ureteral sheath, and more efficiently coapt the ureter (especially larger, dilated ureters). The second hit is similar to the traditional STING injection, but is slightly more cephalad, and coapts the ureteral orifice and elevates a mound of bulking material at the terminal ureter (see Video 155.2 for the complete double HIT technique). This technique creates a “mountain range” of bulking material along the course of the ureter, in contrast to the original simple hillock (Figures 155.1 and 155.2) [17].

Image described by caption. — **Figure 155.1** Locations of needle placement for the 1, intraureteric proximal technique (HIT); 2, intraureteric distal technique (double HIT); 3, traditional STING technique; and 4, superior tunnel. *Source:* Kuipers S, van der Horst EH, Verbeke JI, et al. Prevesical calcification and hydronephrosis in a girl treated for vesicoureteral re‐flux. *Glob Pediatr Health* 2016;3:2333794X16652272.

Reproduced with permission of Elsevier.

The double HIT method has not only been employed for primary VUR (90% cure), but also for repeat endoscopic injections (90%), VUR associated with paraureteral diverticula (81%), complex cases such as post reimplantation (88%), neurogenic bladders (78%), duplication anomalies (80%), and in adults (88%). Several other studies have supported the use of Deflux in the setting of anatomic variants such as duplex systems as well [17–20].

The experience with the double HIT technique was also important in identifying the need for sometimes large volumes of injectable material for cure. There is considered to be a 20% volume loss over time when using Deflux, so as a matter of technique it is important to use an adequate amount of material so that cure is ensured. Limiting the amount injected in an effort to limit costs often results in increased expenses later as failure rates are higher [21]. Also, failure is usually due to caudal migration of the bleb, so more proximal injection using the double HIT method, as well as the larger volumes, has improved results [17].

The use of hydrodistention in these procedures also led to studies correlating the degree of ureteral distention with reflux. A grading system has been developed for ureteral dilation, which correlates well with grade of reflux. The hydrodistention grading system defines grades of reflux as: H0, no hydrodistention; H1, ureteral orifice open but tunnel not evident; H2, tunnel seen only, and H3, extravesical ureter visualized (Figure 155.3). In studies, VUR and dynamic hydrodistention classification grades correlate significantly (P < 0.001), and provide a reliable method of evaluating the presence or absence of VUR. These findings, combined with the studies demonstrating a lack of correlation of intraoperative cystogram and late cure, have allowed surgeons to do away with the postoperative cystogram (at the time of the injection), as lack of hydrodistention can confirm cure [15, 22].

Only gold members can continue reading. Log In or Register to continue