Abstract
Background
The composite sinus stent was developed to support the nasal walls, stabilize the middle turbinate, and prevent adhesions following endoscopic sinus surgery (ESS).
Objective
This study sought to assess its safety and effectiveness.
Methods
A prospective clinical trial was conducted in a single medical center in 2016–2018. The study included 30 patients (64% males) with a mean age of 41.9 years, who were scheduled for bilateral ESS, were randomized to undergo composite sinus stent implantation for 14 to 28 days or middle meatus placement of a Telfa tampon for 2 to 3 days. Telfa is a nonadherent absorbent dressing that has been compared favorably with other packs for use following ESS. Both groups received the same postoperative treatment. Outcomes were evaluated endoscopically by the principal investigator and also by an independent investigator blinded to the intervention the patient had and by self-report questionnaires at 3 and 12 weeks postoperatively.
Results
The stent was successfully implanted and removed in all 29 treated sinuses, without complications. None of the stents showed granulation tissue or crusting. Compared to the tampon group, the stent group had significantly less inflammation (mean visual analog scale scores 0.2 vs 4.2 at 12 weeks, P = .01). The probability of having adhesion was 9.3 times greater in the control group compared to the study group (P = .026), and middle turbinate lateralization rate at 12 weeks was 3.8% versus 44% in the study group and the control group, respectively, at 12 weeks (P = .006). Patients who underwent stent implantation experienced higher symptomatic improvement (Sino-Nasal Outcome Test 22 of −37.13 vs −28.07, P = .01, in study and control groups, respectively). During stent implantation (2–4 weeks), patients did not suffer from any discomfort.
Conclusions
The composite sinus stent is safer and more effective than the Telfa tampon in maintaining sinus cavity patency and promoting healing following ESS.
Keywords
Introduction
Chronic rhinosinusitis (CRS) is a common health condition in the United States affecting as many as 11.1 million adult patients in 2007 and is the principal diagnosis in 4.9%±0.2% of the U.S. population who sought medical care, resulting in more than 257 000 sinus procedures performed in the United States annually. 1
According to the European Position Paper on Rhinosinusitis guidelines, CRS is considered uncontrolled, when the patient needs long-term antibiotics or systemic corticosteroids (in the last month), or if 3 or more features of partly controlled CRS (nasal blockage on most days of the week, mucopurulent rhinorrhea/postnasal drip on most days of the week, facial pain/headache, impaired olfaction, sleep disturbance/fatigue, and diseased mucosa on endoscopy) exist. 2
When medical treatment, including topical steroids, oral steroids, and antibiotics, prove ineffective, the option of surgery is recommended. The efficacy of endoscopic sinus surgery (ESS) in treating sinus disease is well established.3,4
However, approximately 10% to 15% of patients who have sinus surgery will undergo revision surgery.5–7 Revision rates due to surgical failure are a significant problem despite advances in operative and postoperative management. 8
The most common reasons for surgical failure are recurrent inflammation and polyposis, adhesion/synechiae formation, middle turbinate lateralization, and stenosis of the surgically enlarged sinus ostia. 9 Bassiouni et al. recently found that middle turbinate lateralization is associated with a more rapid need for future revision surgery. 10 In addition, middle turbinate lateralization has been implicated as playing a role in revision surgery, because of the potential for adhesion formation and obstruction of the ostiomeatal complex (OMC), and has been reported in up to 27% of revision cases.11–13 A number of techniques have been described to address this complication, including prophylactic middle turbinate resection “controlled synechiae” formation14,15 and middle turbinate suturing.
On the basis of several studies, it appears that inflammation is also an important factor in determining treatment outcomes.16,17
The incidence of adhesion formation following ESS has been reported in up to 27% of cases and may be a significant factor predisposing to recurrent disease and revision surgery. Postoperative adhesion rates have been reported in up to 27% of patients despite sinus irrigation and postoperative debridement being performed.4,18 Adhesions, which form between the middle turbinate and the lateral nasal wall, can lead to lateralization of the middle turbinate, obstruction of the sinuses, and inability for topical medications to reach the sinuses effectively.
Controlling for these issues has been shown to lead to better long-term outcomes. 19 Devices designed to enhance surgical success and counteract the tendency for scarring and synechiae formation are ubiquitous and include stents, packing, sponges, and gels. Space-filling devices frequently impair sinus aeration and drainage and can cause increased patient discomfort. Removal of these devices is frequently painful leading to prolonged recovery. 20
Silastic stent placed into the middle meatus after ESS has been effective in reducing postsurgical adhesions and middle turbinate lateralization.21,22
An ideal solution should act as a spacer to prevent adhesions and middle turbinate lateralization while allowing good drainage from the sinuses preventing edema and inflammation. Recently, the PROPEL stent (Intersect ENT) is in use. Three recently published clinical trials have demonstrated that the mometasone-eluting stent produced statistically significant reductions in inflammation, polyp formation, and postoperative adhesions. This absorbable stent, however, has some disadvantages including allergic reaction, granulation tissue formation, and stent migration. 23
The composite sinus stent (STS Medical Ltd., Israel) is a novel, Food and Drug Administration -approved, composite removable sinus stent system. We present our clinical results with this stent in a randomized controlled study.
Materials and Methods
Study Design and Procedure
A prospective 1:1 randomized design was used. The study was conducted in a single medical center. The protocol was approved by the local Helsinki Committee, approval number HMC-0001-16, and the Israel Ministry of Health, and all participants provided written informed consent prior to enrollment. The study was registered on the ClinicalTrials.gov website under identifier NCT02812199.
The study population included adult patients who were diagnosed with CRS in accordance with the guidelines of the American Academy of Otolaryngology —Head and Neck Surgery and showed evidence of sinus disease on computed tomography scans (Lund–Mackay score ≥2 bilaterally). All patients included in the study also had a deviated nasal septum. All were scheduled for primary or revision ESS and septal deviation repair. Exclusion criteria were known medical history of immunodeficiency, cystic fibrosis, allergy to nickel, polyurethane-induced dermatitis, sinonasal tumors, ciliary dysfunction, coagulation disorders, clinical evidence of invasive fungal sinusitis, and any oral steroid-dependent condition.
At entry to the study, all eligible patients completed the self-report Sino-Nasal Outcome Test (SNOT)-22 and were randomly divided into 2 groups by the envelope method. At study entry, eligible patients were asked to choose an envelope, with study group allocation enclosed inside. By the end of ESS, the envelope was opened and patient allocation was disclosed to the study principal investigator: post-ESS implantation of the composite sinus stent into the middle meatus (stent group) or post-ESS placement of a Telfa tampon into the middle meatus (control group). In both groups, the nasal cavity was additionally packed with Telfa to prevent postoperative bleeding. Telfa, a pack shown by several trials to cause less discomfort and other complications than many packs, is commonly used following nasal surgery. 24
Bilateral ESS, septoplasty (Killian incision and submucous resection of nasal septum), and bilateral inferior turbinate reduction were performed using traditional instrumentation in all cases but one. In one study group patient, only unilateral ESS and partial turbinectomy were performed. All patients received standardized postoperative care. In both groups, Telfa tampons were removed 2 days post-ESS. The stent was removed between 14 and 28 days after the surgery.
Throughout the study, patients in both groups were maintained on a standard medical regimen. At the day of the operation, patients were started on a 10-day course of antibiotics and a 4-day course of antifibrinolytic agents, and saline sprays were prescribed for 3 weeks. All medications taken at all points during the study were documented.
Outcome Measures
Device performance and efficacy were assessed by direct endoscopic examination performed by the principal investigator at the participating investigational center. The evaluations were instantaneous on the day of the study visit, and all endoscopic examinations were recorded and stored. Additional evaluation of the endoscopic photographs was performed by an independent U.S.-based ENT surgeon who was blinded to the patient group allocation. The examiner only evaluated endoscopic photographs without any patient information.
The primary outcome measures of this study were the rate of postoperative complications and the level of symptom relief associated with the use of the composite removable sinus stent compared to the control group.
Postoperative inflammation, adhesions of the middle turbinate to the lateral nasal wall, and middle turbinate lateralization were evaluated endoscopically by a clinical investigator, with photographic recording, at 3, 6, and 12 weeks after functional endoscopic sinus surgery (FESS). Inflammation was graded on a 10-point visual analog scale (VAS) of 1 (none) to 10 (severe erythema and edema and/or hypertrophy, and/or polypoid change). Adhesions of the middle turbinate were graded on a 5-point scale as follows: 1—none, 2—small but not obstructing, 3—obstructing but easily separated, 4—dense and separated with difficulty, and 5—severe with complete adhesion. The adhesions were characterized as either partial (scored 2–3) (Figure 1) or complete (scored 4–5) (Figure 2). The middle turbinate position was graded at 4-point scale as 1—medialized, 2—normal, 3—partially lateralized, and 4—lateralized. All scales used were validated by Smith et al. 25
An example of partial adhesion post-ESS.
An example of complete adhesion post-ESS.
The relief of symptoms of CRS was assessed with SNOT-22 at 12 weeks after FESS.
Secondary outcome measures of the study were pain associated with removal of the composite sinus stent, assessed by a pain questionnaire on a scale of 0—no pain to 10—very severe pain, and discomfort from the stent while in the nose, assessed by a discomfort questionnaire on a 10-point scale of 1 (none) to 5 (very severe). Study group patients filled the pain and discomfort questionnaires after the stent removal and the control group patients filled the questionnaires after the packing removal. The discomfort values were compared to the patients’ discomfort level prior to ESS.
Safety was assessed by stent conformation, stent migration, state of the stent on removal, and adverse events reported throughout the study.
Stent Description
Composite sinus stent systems (ArchSinus, STS Medical) were supplied for investigational use. The system consists of balloon expandable stent, made of an outer polyurethane and inner nitinol alloy bodies, and a balloon catheter-based delivery system (Figure 3).
The composite sinus stent on balloon catheter-based delivery system, before and after inflation. The stent is composed of an outer polyurethane and inner nitinol alloy bodies. Composite sinus stent insertion and deployment is mediated via balloon-based delivery system.
The stent is intended for use in adult patients, for insertion into the middle meatus following ESS to maintain ostiomeatal complex patency, prevent adhesion, and provide middle turbinate stabilization.
The stent function is based on a delicate force equilibrium between the nitinol and polyurethane stent bodies.
Composite sinus stent insertion and deployment is mediated via balloon-based delivery system. The balloon provides precise positioning, and it does not require any additional adjustments.
When deployed, the polyurethane stent body limits radial outward force of the nitinol body and thus does not promote any mucosal irritation or crusting. As a result, the patients do not feel the implanted stent.
It is important to note that nitinol crush resistance prevents stent diameter reduction and subsequent migration. This unique quality keeps the stent in place, without embedding into the mucosa, at body temperature.
Lowering the stent temperature with cold saline causes shrinkage, facilitating easy removal. Stent removal can be performed as an in-office procedure, without anesthesia.
Composite sinus stent is not drug eluting; however, due to its mechanical stability, it keeps the nasal passage open during the implantation period, thereby making it accessible for standard medication treatment.
Statistical Analysis
Statistical analysis was performed with SAS® Version 9.4 under Windows® 2008 Terminal. Dichotomous variables (restenosis and adhesion) were analyzed using logistic regression repeated measures model with subject random effect. SNOT-22 was analyzed using linear regression adjusted for the baseline value. Inflammation was analyzed using repeated measurements linear model with subject random effect. P value <.05 was considered significant.
Results
Baseline Clinical Characteristics
Clinical characteristics and demographic data are described in Table 1. The study population included 32 patients who met all the eligibility criteria of the study. One patient underwent one-sided ESS and turbinectomy and subsequent unilateral stent implantation, and 2 patients had to reschedule the ESS operation and withdrew from the study. The remaining patients (29 treated sinuses) completed the 12-week follow-up. Mean age of the patients was 41.9 (±15.0) years; 19 (63%) were men. Relevant comorbid factors included nasal polyps in 7 patients (23.3%), 3 in the stent group and 4 in the control group, asthma in 5 (16.7%), allergy in 9 (30%), and current smoking in 7 (23.3%). Four patients underwent previous ESS (13.3%). The mean total Lund–Mackay score at baseline was 8.4 in the stent group and 9.7 in the control group.
Demographic and Baseline Characteristics.
Abbreviations: CT, computed tomography; SNOT-22, Sino-Nasal Outcome Test 22.
aL–M scores are based on CT scan within 6 months prior to implant placement.
Stent Safety
The composite stent was successfully implanted in all 29 treated sinuses. There were no device-related adverse events or complications during implantation and no cases of stent migration. On stent removal, 14 to 28 days after placement (Figure 4), no granulation tissue was observed.
Quantity of stents removed by time from sinus surgery. No granulation tissue or crusting was observed on stent removal, independently of the implantation time.
Primary Outcomes
Analysis of the endoscopically rated post-ESS outcomes revealed that the stent group was characterized by lower mean inflammation levels than the control group, with the mean VAS scores of 0.2 versus 4.2 at 12 weeks as well as faster postoperative healing (P = .01; Figure 5).
Level of inflammation in the stent and control groups over the study period. Inflammation levels are similar in study and control groups prior to surgery. Study group demonstrates lower inflammation level 6 and 12 weeks post-ESS and faster healing process. FESS, functional endoscopic sinus surgery.
Adhesion at 12 weeks was estimated by the principal investigator and the independent ENT surgeon. Each evaluator scored adhesion at 3 levels—none (1 on a 5-point scale), partial (2–3 on a 5-point scale), and complete (4–5 on a 5-point scale). The principal investigator estimated that 7.7% and 44% had adhesions in study and control groups, respectively, 12 weeks post-ESS (P = .026). Moreover, 0% and 16% of the patients from the study group and the control group, respectively, demonstrated complete adhesions at 12 weeks post-ESS. Independent evaluator estimated that 4.5% and 31.2% had adhesions in study and control groups, respectively, 12 weeks post-ESS. Thus, it can be concluded that there is a high agreement between the 2 evaluators (Table 2).
Primary and Secondary Outcomes for Stent vs. Control Group.
Abbreviations: MT, middle turbinate; NA, not applicable; PI, principal investigator; SNOT-20, Sino-Nasal Outcome Test 20.
aSNOT-20 mean difference.
Middle turbinate lateralization rate before ESS (lateralization before surgery was due to concha bullosa, deviated nasal septum, polypoid concha, and paradoxical concha) was similar in both groups (85.2% in the control group and 84.6% in the study group). According to Chan et al., middle turbinate lateralization was assessed as “present” if a rigid 4‐mm endoscope was unable to be passed into the middle meatus because of lateralization of the turbinate and “absent” if the scope was able to pass into the middle meatus. 21 In our study, we considered middle turbinate lateralization to be present if the middle meatus was narrower than 2 mm.
Middle turbinate lateralization at 12 weeks was estimated by the principal investigator and independent ENT surgeon. Each evaluator scored lateralization at 3 levels—none (1–2 on a 4-point scale), partial (3 on a 4-point scale), and complete (4 on a 4-point scale). The principal investigator estimated that 3.8% and 44.0% had middle turbinate lateralization in study and control groups, respectively. Only 3.8% and 16% from study and control group, respectively, suffered from complete middle turbinate lateralization 12 weeks post-ESS. Independent evaluator estimated that 3.8% and 19% had lateralization in study and control groups, respectively, 12 weeks post-ESS. In addition, 0% and 9.5% from study group and control group, respectively, suffered from complete middle turbinate lateralization 12 weeks post-ESS. In general, we can conclude that there is a high agreement between the 2 evaluators (Table 2). The probability of having middle turbinate lateralization was 18.8 times greater in the control group compared to the study group (P = .028).
Figure 6(A) to (D) demonstrates the images of a stent placement in a patient of the study group during all stages of the study (stent in place at time zero, stent in place at 3 weeks, after stent removal at 3 weeks, end result at 12 weeks). Figure 7 demonstrates a patient in the control group at 12 weeks, in which edema and mucoid discharge are evident, there is lateralization of the middle turbinate, and the OMC is obstructed.
A, Stent in place at time zero. B, Stent in place at 3 weeks post-ESS. C, After stent removal at 3 weeks. D, Study group patient at 12 weeks. Open sinus with no signs of inflammation.
Control group patient at 12 weeks. Middle turbinate lateralization and restenosis are evident.
The reduction in SNOT-22 scores obtained in the study group is strongly greater than that obtained in the control 37 versus 28 for raw difference. After adjusting for the baseline differences, the reduction in SNOT-22 scores obtained in the study group is significantly greater, with P = .01.
Secondary Outcomes
All patients were asked to fill a pain questionnaire to assess pain level associated with either stent or packing removal. The pain was assessed on a 10-point scale as follows: 0—no pain, 2.5—mild, 5—moderate, 7.5—severe, and 10—very severe.
Pain level associated with stent removal was lower than the pain associated with packing removal with the mean level of 3.7 versus 6.0 in study and control groups, respectively.
All patients were examined for discomfort level experienced during packing or stent implantation time. The level of discomfort was assessed using discomfort questionnaire taken at packing removal day for control group patients and at stent removal day for study group patients. Discomfort was graded on a 10-point scale as 0—state prior to ESS, 1–5 (improvement), −1 to (−5)—worsening graded as none, very mild, mild, severe, and very severe.
Study patients experienced less discomfort compared to the standard of care patients with mean discomfort levels of +3.4 and −2.8, respectively.
Discussion
The primary objective of ESS is to restore paranasal sinus function by reestablishing the physiologic pattern of ventilation and mucociliary clearance. The goal is to remove irreversibly diseased mucosa and bone, preserve normal tissue, and judiciously widen the true natural ostia of the sinuses. The OMC is most often the primary target of ESS, because minimal inflammation in this area can lead to disease in the maxillary, anterior ethmoid, and frontal sinuses. In many patients with CRS, the middle turbinate is located too close to the lateral nasal wall and needs to be medialized during surgery to avoid narrowing of the middle meatus. However, in up to 24% of cases, the turbinate moves laterally during the healing process.10–12 This may be due to the original location of the middle turbinate, such that surgical medialization is not sufficient to change the “memory” of the turbinate structure. In addition, if septoplasty was also performed during surgery, the postoperative swelling of the septal mucosa might push the turbinate laterally. Although middle turbinate lateralization does not always cause recurrence of symptoms, Bassiouni et al. recently found that middle turbinate lateralization is associated with a more rapid need for future revision surgery. 10 Studies have suggested that turbinate lateralization may be prevented by inserting a stent into the middle meatus at the end of ESS. 22
Nasal packs are used to prevent postoperative bleeding and mucosal synechia. A large systemic review and meta-analysis (925 patients) showed that the use of middle meatal packing after ESS led to a decrease in synechiae formation. 23 However, in addition to severe discomfort they may cause, nasal packs pose a risk of infection and subsequent mucosal damage, edema, and stenosis and therefore need to be removed by postoperative day 2 or 3. Endonasal tissue damage may occur through pressure by nasal packs or during placement and removal. 24 Our previous animal trial showed that the composite sinus stent is safe with no adverse effects and easily removed. 26 In our present trial, we examined the stent safety and efficacy in human patients.
Hosemann et al. 27 assessed the normal wound healing process of the paranasal sinuses using both clinical and experimental (animal) investigations, describing the first phase (days 1–10) as being dominated by crusting with no change in the underlying residual mucosa and the second phase (up to 30 days) as being characterized by edematous swelling of the residual mucosa. Based on our experience, the optimal time for stent removal is 3 weeks after ESS, after blood clots have been eliminated and the middle turbinate has been stabilized in a new position.
The primary goals of early postoperative care are to reduce mucosal inflammation and infection, improve short-term patient symptoms, promote early return of ciliary function, and prevent complications. Optimizing these goals should incur the best chance to maintain long-term symptomatic improvement and minimize the need for revision ESS. Following a successful ESS procedure, an open and accessible sinus cavity will allow for continued topical medical therapy, which is critical for long-term success by minimizing mucosal inflammation. 28
We describe the first trial in humans with the composite sinus stent. The results support previous animal study showing that the stent was effective at reducing inflammation, mucosal adhesions, and middle turbinate lateralization after sinus surgery, thereby sustaining the operative results, without adverse effects. The present proof-of-concept study should be followed by a large multicenter case–control study to statistically establish its benefit.
Conclusions
This first clinical trial of a composite sinus stent placed during ESS shows that the stent is safe for use in humans, is effective in promoting healing, and avoids inflammation, adhesions, and middle turbinate lateralization.
Footnotes
Author Contributions
Dan Yaniv was involved in conception and design, interpretation of data, and drafting the manuscript. Lena Shlosberg contributed to acquisition, analysis, and interpretation of data. Eitan Yaniv, principal investigator and surgeon, was involved in conception and design, drafting, and final approval of the manuscript.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Lena Shlosberg, STS Medical, QA manager. Eitan Yaniv, STS Medical, Medical advisor.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.