Cochrane Corner
Cochrane Corner: Extracts from The Cochrane Library: Interventions for Chronic Rhinosinusitis with Polyps
Otolaryngology– Head and Neck Surgery 1–5 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815594375 http://otojournal.org
Neil Bhattacharyya, MD1, Richard J. Harvey, MD2, and Richard M. Rosenfeld, MD, MPH3
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract The ‘‘Cochrane Corner’’ is a section in the Journal that highlights systematic reviews relevant to otolaryngology–head and neck surgery, with invited commentary to aid clinical decision making. This installment features a pair of related Cochrane Reviews on surgical interventions for chronic rhinosinusitis, which identify only low-quality evidence that is insufficient for definitive conclusions. The related expert commentary, however, should help clinicians make the best treatment decisions based on the studies and outcomes identified in these Cochrane Reviews. Keywords systematic review, evidence-based medicine, chronic rhinosinusitis, nasal polyps, sinus surgery Received May 24, 2015; revised June 8, 2015; accepted June 12, 2015.
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hronic rhinosinusitis (CRS) is responsible for $8.3 billion in annual health care expenses, 18.3 million annual physician office visits, and about 1 in every 14 primary care visits with antibiotic prescriptions. The large health care burden attributed to CRS and the need for evidence-based recommendations to improve the quality of care are discussed fully in a recently updated clinical practice guideline from the American Academy of Otolaryngology— Head and Neck Surgery Foundation (AAO-HNSF).1 Although the guideline makes some recommendations regarding medical management of CRS (in favor of saline irrigation and topical nasal steroids; against antifungal therapy), there are no statements regarding surgical management. This Cochrane Corner complements the AAO-HNSF guideline by summarizing 2 reviews on CRS surgery, which, despite their rigorous methodology, are unable to reach any definitive conclusions.
Review Abstract 1: Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps, by Rimmer J, Fokkens W, Chong LY, Hopkins C2 Disclaimer. This is an abstract of a Cochrane Review published in the Cochrane Library 2014, Issue 12 (see
www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Library should be consulted for the most recent version of the review.
Background. Nasal polyps cause nasal obstruction, discharge, and reduction in or loss of sense of smell, but their etiology is unknown. The management of CRS with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol. Objectives. To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in CRS with nasal polyps. Search methods. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished trials. The date of the search was 20 February 2014. Selection criteria. Randomized controlled trials of any surgical intervention (eg, polypectomy, endoscopic sinus surgery) versus any medical treatment (eg, intranasal and/or systemic steroids), including placebo, in adult patients with CRS with nasal polyps. Data collection and analysis. We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies. 1 Department of Otology & Laryngology, Harvard Medical School, Boston, Massachusetts, USA 2 Department of Otolaryngology, Concord General Hospital, Sydney, Australia 3 Department of Otolaryngology, State University of New York Downstate Medical Center, Brooklyn, New York, USA
Corresponding Author: Richard M. Rosenfeld, MD, MPH, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 126, Brooklyn, NY 11203, USA. Email: [email protected]
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Main results. Four studies (231 participants randomized) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87), (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. Primary outcomes: symptom scores and quality of life scores. There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores. Two studies (one comparing ESS plus topical steroid versus antibiotics plus high-dose topical steroid, the other ESS versus systemic steroids) failed to find a difference in generic health-related quality of life scores. The quality of this evidence is low or very low. Endoscopic scores and other secondary outcomes. Two studies reported endoscopic scores. One study (ESS versus systemic steroids) reported a large, significant effect size in the surgical group, with a mean difference (MD) in score of 21.5 (95% confidence interval (CI) –1.78 to 21.22, n = 95) on a scale of 0 to 3 (0 = no polyposis, 3 = severe polyposis). In the other study (ESS plus topical steroid versus antibiotics plus high-dose topical steroid) no difference was found between the groups (MD 2.3%, 95% CI 217.4% to 12.8%, n = 34). None of the included studies reported recurrence rates. No differences were found for any objective measurements or olfactory tests in those studies in which they were measured. Complications. Complication rates were not reported in all studies, but rates of up to 21% for medical treatment and 14.3% for surgical treatment are described. Epistaxis was the most commonly reported complication with both medical and surgical treatments, with severe complications reported rarely. Authors’ conclusions. The evidence relating to the effectiveness of different types of surgery versus medical treatment for adults with CRS with nasal polyps is of very low quality. The evidence does not show that one treatment is better than another in terms of patient reported symptom scores and quality of life measurements. The one positive finding from amongst the several studies examining a number of different comparisons must be treated with appropriate caution, in particular when the clinical significance of the measure is uncertain. As the overall evidence is of very low quality (serious methodological limitations, reporting bias, indirectness and
imprecision) and insufficient to draw firm conclusions, further research to investigate this problem, which has significant implications for quality of life and healthcare service usage, is justified.
Review Abstract 2: Surgical interventions for chronic rhinosinusitis with nasal polyps, by Sharma R, Lakhani R, Rimmer J, Hopkins C3 Disclaimer. This is an abstract of a Cochrane Review published in the Cochrane Library 2014, Issue 11 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Library should be consulted for the most recent version of the review. Background. Surgical treatment of CRS with nasal polyps is an established treatment for medically resistant nasal polyp disease. Whether a nasal polypectomy with additional sinus dissection offers any advantage over an isolated nasal polypectomy has not been systematically reviewed. Objectives. To assess the effectiveness of simple polyp surgery versus more extensive surgical clearance in CRS with nasal polyps. Search methods. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished trials. The date of the search was 20 February 2014. Selection criteria. Randomized and quasi-randomized controlled trials in patients over 16 with CRS with nasal polyps, who have failed a course of medical management and who have not previously undergone any previous surgical intervention for their nasal disease. Studies compared nasal polypectomy with more extensive sinus clearance in this patient cohort. Data collection and analysis. We used the standard methodological procedures expected by The Cochrane Collaboration. Main results. We identified no trials which met our inclusion criteria. Six controlled trials (five randomized) met some but not all of the inclusion criteria and were therefore excluded from the review. Authors’ conclusions. We are unable to reach any conclusions as to whether isolated nasal polypectomy or more extensive sinus surgery is a superior surgical treatment modality for CRS with nasal polyps. There is a need for high-quality randomized controlled trials to assess whether additional sinus surgery confers any benefit when compared to nasal polypectomy performed in isolation.
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Comments on the Cochrane Reviews Comments by Bhattacharyya Endoscopic sinus surgery (ESS) for CRS is one of the most common currently performed outpatient otolaryngologic procedures, with greater than 257,000 ambulatory sinus surgeries performed annually in the United States.4 Although common, surgery for CRS is not without potential complications, including revisits for bleeding, pain, and fever/dehydration in up to 5% of patients, and carries with it rarer complications of cerebrospinal fluid leak and orbital injury.5 Therefore, there is a relative trade-off between the benefits of surgery for CRS and the potential harms. In this circumstance, a high level of evidence (ie, randomized controlled trials) would be extremely helpful in determining evidencebased guidelines for the role of surgery in the treatment of CRS with polyposis. The 2 currently featured Cochrane Reviews2,3 point out prominent evidence gaps in our understanding of surgery for CRS with polyposis. Each review highlights problems with our current evidence base. Sharma and colleagues3 sought to assess the effectiveness of simple polyp surgery vs more extensive surgical clearance. Unfortunately, even 2 decades after the initial adoption of ESS, the authors encountered an empty review. At first glance, sinus surgeons may not see the value in comparing simple nasal polypectomy with formal ESS for polyps. Intuitively, ESS is more ‘‘thorough’’ and may get to the ‘‘root’’ of the problem. This intuition may naturally lull surgeons into a false sense of superiority for ESS. However, some historical background is relevant. Upon its introduction, ESS was a dramatically less morbid way of tackling CRS with polyposis, especially compared with transnasal snare polypectomy and other invasive techniques. It demonstrated good outcomes in several cohort series with relative safety, and because it was a significant improvement relative to traditional techniques, it gained widespread adoption. Somewhat contemporaneously, topical nasal steroid sprays, which have been now shown to be effective in polyp reduction,6 were just beginning to attain more widespread adoption. Why revisit the question of the extent of surgery for CRS with polyps? First, given that nasal steroid sprays and other topical regimens, such as budesonide irrigations, have demonstrated effectiveness in polypoid rhinosinusitis, there is a distinct possibility that a subgroup of patients may benefit from intranasal polypectomy alone with subsequent topical regimens. Second, the now widespread availability of nasal endoscopy may allow for a more controlled office-based polypectomy than previously performed. This may save patients a general anesthetic, while decreasing the risk of operative complications and health care costs. Conversely, intranasal polypectomy may in fact be less effective than ESS, even with the advent of topical steroid regimens, leading to undertreatment. One of the main functions of an empty review is to point out evidence gaps, and this empty review3 should rekindle this important question.
Rimmer and coworkers2 explored surgical vs medical interventions for CRS with nasal polyps. After sifting the search results, 4 studies were included in a qualitative analysis with varied results. The authors concluded that the level of evidence was of very low quality, and the evidence did not show that one treatment was better than the other in terms of patient-reported quality of life. This review again highlights a significant evidence gap regarding the effectiveness of surgical intervention for CRS. At first glance, sinus surgeons might be tempted to ignore the findings: don’t we all know that ESS is effective for CRS, more effective than medical management? This thinking is unwise for several reasons, as detailed below. The characteristics of the studies qualifying for analysis in this review are of interest. First of all, each of the 4 studies each took place in otolaryngology departments in European countries; no studies from the United States qualified. Although CRS with polyposis may in fact behave similarly in Europe vs in the United States, one would prefer to apply more ‘‘local’’ data to construct evidence-based decisions. Second, the included studies are relatively old—from 1988 through 2004—with the older studies dating back to the relative infancy of ESS. These studies were also conducted when the demand for evidence-based decision making and its influence on health care policy were not as emphasized as currently. Should one be concerned about a Cochrane Review that fails to show the advantages of surgical intervention over medical therapy for CRS with polyposis? The answer is very likely yes. Although investigators continue to present results of case series of ESS for CRS, such studies will likely never appear in a Cochrane Review because they are neither controlled nor randomized. For example, a recent, prospective, multi-institutional clinical trial of medical vs surgical management of CRS, conducted with considerable rigor, was not included because the treatment allocation was not randomized.7 The lack of randomized trials regarding surgery for CRS may also affect decisions by third-party payers and perceptions by consumers and patients. Third-party payers will preferentially cite best evidence when determining coverage and may deny coverage based on a perceived lack of evidence. Consumers and patients, who also seek the best evidence with which to make health care decisions, would likely find the empty conclusions of the plain-language summary from this Cochrane Review less than motivating when considering ESS for CRS with polyps. These factors should strongly motivate us to undertake prospective, randomized clinical trials of ESS of sufficient quality to be included in a Cochrane Review, both with respect to the extent of surgical intervention and in comparison to medical management to close these important evidence gaps.
Comments by Harvey CRS has an enormous health and quality-of-life implication, on par with significant chronic disease such as heart failure.8 Our understanding of CRS, however, is poor, and enormous heterogeneity exists in the pathophysiological
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mechanisms that lead to chronic sinus dysfunction. This poor understanding, especially during prior decades, has produced scientifically unsound approaches with subsequent comparisons of simple interventions (ie, medical vs surgical) rather than treatment strategies to the disease process. This misdirected approach would be akin to a heart failure population, consisting of patients with multiple causes for their failing heart (arrhythmia, valvular disease, cardiomyopathy, or coronary artery disease), being assessed on the effectiveness of aortic valve replacement vs slow-release nitrates for improvement in cardiac function. An evolution in our understanding of nasal polyposis, as well as the association with asthma and lower airway disease, has occurred in the past 10 years. Our profession now widely accepts that simple ostial obstruction and infection may perpetuate some nonpolypoid CRS, but it is not the etiology of the condition under review: nasal polyposis.9,10 Nonetheless, half the studies in the Rimmer et al2 review on medical vs surgical therapy are nearly 2 decades old, and the remaining are more than a decade since publication. While well intended, these authors of studies published decades ago were working with simplistic models of CRS with nasal polyps and subsequent management strategies, which are likely to be considered flawed by our current understanding. Why would a chronic inflammatory condition, often affecting the entire airway, be effectively managed by surgery alone? Surely in the postsurgery period, when the perioperative medications resolve, we would have the same chronic inflammatory condition continue, but this time with an open sinus cavity. Unfortunately, this was to the surprise of some early researchers in the field—in the months after well-performed sinus surgery, the disease would only continue with the unfortunate ability to endoscopically visualize the inflammation rather than being hidden behind an intact lateral nasal wall. Our better understanding of the etiology of CRS with nasal polyps is accompanied by an improved understanding of the effectiveness of treatment modalities. While systemic medication reaches the sinus cavity via the circulation, simple topical nasal sprays neither reach the sinus cavity nor are currently indicated for the management of sinus disease.11,12 Surely, in retrospect, the 12-month end point of one of the higher quality included studies represents a patient population with nasal polyps who were essentially untreated in both arms: the surgical group having neither an intervention that addressed the pathophysiologic process nor a maintenance therapy that provided sinus therapy.13 And the comparison group, who received medical therapy, had a brief period of anti-inflammatory control 351 days prior. Why would a difference be expected between groups? The anticipated outcome of little benefit imparted to either intervention arm at 12 months was seen and expected. Future trials in CRS with nasal polyps need to have management strategies in line with our understanding of the disease. Surgery needs to be performed in a way that either modifies the pathophysiology or changes the ability to treat the condition, such as offering a route for local or topical
therapies. Surgery in CRS with nasal polyps is not an isolated intervention; it offers a change in approach to maintenance therapy of these patients with novel topical agents or corticosteroid irrigations as part of an overall treatment.14 The Sharma et al3 review on the extent of surgery potentially highlights similar misconceptions about the pathogenesis of CRS with nasal polyps. Dr Bhattacharya’s note that ‘‘ESS is more ‘thorough’ and may get to the ‘root’ of the problem’’ is most appropriate, because it still reflects many physicians’ opinion but is not in line with our scientific understanding of the condition. Such divergence between the basic science and clinical practice of the disease is a reflection of a problem that plagues many surgical disciplines. Why would more surgical modification of the sinuses alter an inflammatory condition unless it was coupled with an ongoing therapy that takes advantage of that change? Despite the lack of randomized trials of surgery, there are data to support such an approach, with lower revision rates reported from the UK national audit for patients undergoing ethmoidectomy vs polypectomy.15,16 Similarly, more extensive surgery to the frontal or maxillary sinus is also associated with longer times to recurrence or lower revision procedures.17,18 Unfortunately, all these studies are directed at surgical technique rather than CRS with nasal polyps management and fail to account or incorporate the local therapies used in disease maintenance. The efficacy of these ongoing local therapies is most likely to be affected by surgery.12,14 Dr Bhattacharyya’s critique of the knee-jerk response to discard these current data is most appropriate. As a representation of the highest level of observational research (interventional), these Cochrane reviews unfortunately represent what our profession has managed to compile for our patients, payers, independent review bodies, and health care resource managers. It is not possible to discuss different CRS endotypes with an insurance payer or government body, nor is it possible to discuss the appropriateness of more complete and time-consuming surgery for certain poorly defined subgroups. These distinctions arise from clinical and scientific insight. Those independent bodies rely on our specialty to provide the framework in which CRS interventions are interpreted. Surely, then, it is our responsibility to tackle these issues so that future studies offer comprehensive treatment strategies in well-defined patient populations rather than single intervention comparisons within a heterogeneous group.
Comments by Rosenfeld Perhaps one of the greatest challenges in medicine is acting with wisdom and confidence when high-level evidence is sparse. Such is the case with surgery for CRS with polyps, as pointed out in an ‘‘empty’’ Cochrane review, another with biased trials, and commentary from 2 international CRS experts who highlight uncertainty regarding efficacy and pathogenesis. So where does this leave the clinician faced with deciding among medical therapy, polypectomy, or ESS? The
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uncertainty noted above sounds a clarion call for honesty and shared decision making with patients. We may not know the true efficacy of ESS, but we do know from observational studies that some patients do well afterward, at least for a period of time, and that complications are minimal with experienced surgeons.7,15-18 Conversely, not all surgeons are experienced, and complications can be serious. Risk-averse patients with acceptable quality of life may opt for medical therapy, some may prefer an office-based polypectomy, and others will sleep best after a ‘‘thorough’’ cleaning with ESS. These are all valid choices that warrant respect. Two key issues limit our confidence in ESS efficacy: the risk of bias in existing studies and the confounding impact of concurrent medical therapy on an inflammatory airway disorder. Until more evidence is forthcoming, clinicians would be best served by humility and a sincere desire to understand patient preferences and respect them fully in shared decisions. Author Contributions Neil Bhattacharyya, interpretation, drafting, final approval; Richard J. Harvey, interpretation, drafting, final approval; Richard M. Rosenfeld, concept, drafting, final approval.
Disclosures Competing interests: Neil Bhattacharyya is a consultant for Intersect ENT, Entellus, and Sanofi Aventis. Richard J. Harvey is on the advisory board for Schering Plough, NeilMed, and GlaxoSmith-Kline; was a consultant with Medtronic, Olympus, and Stallergenes; is on the speakers bureau for Merek Sharp Dolme, Meda Pharma, and Arthrocare; and has received grant support from NeilMed. Sponsorships: None. Funding source: None.
References 1. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(suppl):S1-S39. 2. Rimmer J, Fokkens W, Chong LY, Hopkins C. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. 2014;12:CD006991. 3. Sharma R, Lakhani R, Rimmer J, Hopkins C. Surgical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. 2014;11:CD006990. 4. Bhattacharyya N. Ambulatory sinus and nasal surgery in the United States: demographics and perioperative outcomes. Laryngoscope. 2010;120:635-638.
5. Bhattacharyya N. Unplanned revisits and readmissions after ambulatory sinonasal surgery. Laryngoscope. 2014;124:19831987. 6. Kalish L, Snidvongs K, Sivasubramaniam R, Cope D, Harvey RJ. Topical steroids for nasal polyps. Cochrane Database Syst Rev. 2012;12:CD006549. 7. Smith TL, Kern RC, Palmer JN, et al. Medical therapy vs surgery for chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 2011;1:235-241. 8. Rudmik L, Mace J, Soler ZM, Smith TL. Long-term utility outcomes in patients undergoing endoscopic sinus surgery. Laryngoscope. 2014;124:19-23. 9. Snidvongs K, Chin D, Sacks R, Earls P, Harvey RJ. Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion. Laryngoscope. 2013;123:1070-1074. 10. Leung RM, Kern RC, Conley DB, Tan BK, Chandra RK. Osteomeatal complex obstruction is not associated with adjacent sinus disease in chronic rhinosinusitis with polyps. Am J Rhinol Allergy. 2011;25:401-403. 11. Harvey RJ, Goddard JC, Wise SK, Schlosser RJ. Effects of endoscopic sinus surgery and delivery device on cadaver sinus irrigation. Otolaryngol Head Neck Surg. 2008;139:137-142. 12. Grobler A, Weitzel EK, Buele A, et al. Pre- and postoperative sinus penetration of nasal irrigation. Laryngoscope. 2008;118: 2078-2081. 13. Alobid I, Benı´tez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy. 2005;60:452-458. 14. Snidvongs K, Pratt E, Chin D, Sacks R, Earls P, Harvey RJ. Corticosteroid nasal irrigations after endoscopic sinus surgery in the management of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2012;2:415-421. 15. Hopkins C, Slack R, Lund V, Brown P, Copley L, Browne J. Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Laryngoscope. 2009;119:2459-2465. 16. Masterson L, Tanweer F, Bueser T, Leong P. Extensive endoscopic sinus surgery: does this reduce the revision rate for nasal polyposis?Eur Arch Otorhinolaryngol. 2010;267:15571561. 17. Naidoo Y, Bassiouni A, Keen M, Wormald PJ. Risk factors and outcomes for primary, revision, and modified Lothrop (Draf III) frontal sinus surgery. Int Forum Allergy Rhinol. 2013;3:412-417. 18. Seiberling KA, Church CA, Tewfik M, et al. Canine fossa trephine is a beneficial procedure in patients with Samter’s triad. Rhinology. 2012;50:104-108.
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Cochrane Corner: Extracts from The Cochrane Library: Interventions for Chronic Rhinosinusitis with Polyps
Otolaryngology– Head and Neck Surgery 1–5 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815594375 http://otojournal.org
Neil Bhattacharyya, MD1, Richard J. Harvey, MD2, and Richard M. Rosenfeld, MD, MPH3
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract The ‘‘Cochrane Corner’’ is a section in the Journal that highlights systematic reviews relevant to otolaryngology–head and neck surgery, with invited commentary to aid clinical decision making. This installment features a pair of related Cochrane Reviews on surgical interventions for chronic rhinosinusitis, which identify only low-quality evidence that is insufficient for definitive conclusions. The related expert commentary, however, should help clinicians make the best treatment decisions based on the studies and outcomes identified in these Cochrane Reviews. Keywords systematic review, evidence-based medicine, chronic rhinosinusitis, nasal polyps, sinus surgery Received May 24, 2015; revised June 8, 2015; accepted June 12, 2015.
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hronic rhinosinusitis (CRS) is responsible for $8.3 billion in annual health care expenses, 18.3 million annual physician office visits, and about 1 in every 14 primary care visits with antibiotic prescriptions. The large health care burden attributed to CRS and the need for evidence-based recommendations to improve the quality of care are discussed fully in a recently updated clinical practice guideline from the American Academy of Otolaryngology— Head and Neck Surgery Foundation (AAO-HNSF).1 Although the guideline makes some recommendations regarding medical management of CRS (in favor of saline irrigation and topical nasal steroids; against antifungal therapy), there are no statements regarding surgical management. This Cochrane Corner complements the AAO-HNSF guideline by summarizing 2 reviews on CRS surgery, which, despite their rigorous methodology, are unable to reach any definitive conclusions.
Review Abstract 1: Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps, by Rimmer J, Fokkens W, Chong LY, Hopkins C2 Disclaimer. This is an abstract of a Cochrane Review published in the Cochrane Library 2014, Issue 12 (see
www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Library should be consulted for the most recent version of the review.
Background. Nasal polyps cause nasal obstruction, discharge, and reduction in or loss of sense of smell, but their etiology is unknown. The management of CRS with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol. Objectives. To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in CRS with nasal polyps. Search methods. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished trials. The date of the search was 20 February 2014. Selection criteria. Randomized controlled trials of any surgical intervention (eg, polypectomy, endoscopic sinus surgery) versus any medical treatment (eg, intranasal and/or systemic steroids), including placebo, in adult patients with CRS with nasal polyps. Data collection and analysis. We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies. 1 Department of Otology & Laryngology, Harvard Medical School, Boston, Massachusetts, USA 2 Department of Otolaryngology, Concord General Hospital, Sydney, Australia 3 Department of Otolaryngology, State University of New York Downstate Medical Center, Brooklyn, New York, USA
Corresponding Author: Richard M. Rosenfeld, MD, MPH, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 126, Brooklyn, NY 11203, USA. Email: [email protected]
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Main results. Four studies (231 participants randomized) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87), (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. Primary outcomes: symptom scores and quality of life scores. There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores. Two studies (one comparing ESS plus topical steroid versus antibiotics plus high-dose topical steroid, the other ESS versus systemic steroids) failed to find a difference in generic health-related quality of life scores. The quality of this evidence is low or very low. Endoscopic scores and other secondary outcomes. Two studies reported endoscopic scores. One study (ESS versus systemic steroids) reported a large, significant effect size in the surgical group, with a mean difference (MD) in score of 21.5 (95% confidence interval (CI) –1.78 to 21.22, n = 95) on a scale of 0 to 3 (0 = no polyposis, 3 = severe polyposis). In the other study (ESS plus topical steroid versus antibiotics plus high-dose topical steroid) no difference was found between the groups (MD 2.3%, 95% CI 217.4% to 12.8%, n = 34). None of the included studies reported recurrence rates. No differences were found for any objective measurements or olfactory tests in those studies in which they were measured. Complications. Complication rates were not reported in all studies, but rates of up to 21% for medical treatment and 14.3% for surgical treatment are described. Epistaxis was the most commonly reported complication with both medical and surgical treatments, with severe complications reported rarely. Authors’ conclusions. The evidence relating to the effectiveness of different types of surgery versus medical treatment for adults with CRS with nasal polyps is of very low quality. The evidence does not show that one treatment is better than another in terms of patient reported symptom scores and quality of life measurements. The one positive finding from amongst the several studies examining a number of different comparisons must be treated with appropriate caution, in particular when the clinical significance of the measure is uncertain. As the overall evidence is of very low quality (serious methodological limitations, reporting bias, indirectness and
imprecision) and insufficient to draw firm conclusions, further research to investigate this problem, which has significant implications for quality of life and healthcare service usage, is justified.
Review Abstract 2: Surgical interventions for chronic rhinosinusitis with nasal polyps, by Sharma R, Lakhani R, Rimmer J, Hopkins C3 Disclaimer. This is an abstract of a Cochrane Review published in the Cochrane Library 2014, Issue 11 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Library should be consulted for the most recent version of the review. Background. Surgical treatment of CRS with nasal polyps is an established treatment for medically resistant nasal polyp disease. Whether a nasal polypectomy with additional sinus dissection offers any advantage over an isolated nasal polypectomy has not been systematically reviewed. Objectives. To assess the effectiveness of simple polyp surgery versus more extensive surgical clearance in CRS with nasal polyps. Search methods. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished trials. The date of the search was 20 February 2014. Selection criteria. Randomized and quasi-randomized controlled trials in patients over 16 with CRS with nasal polyps, who have failed a course of medical management and who have not previously undergone any previous surgical intervention for their nasal disease. Studies compared nasal polypectomy with more extensive sinus clearance in this patient cohort. Data collection and analysis. We used the standard methodological procedures expected by The Cochrane Collaboration. Main results. We identified no trials which met our inclusion criteria. Six controlled trials (five randomized) met some but not all of the inclusion criteria and were therefore excluded from the review. Authors’ conclusions. We are unable to reach any conclusions as to whether isolated nasal polypectomy or more extensive sinus surgery is a superior surgical treatment modality for CRS with nasal polyps. There is a need for high-quality randomized controlled trials to assess whether additional sinus surgery confers any benefit when compared to nasal polypectomy performed in isolation.
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Comments on the Cochrane Reviews Comments by Bhattacharyya Endoscopic sinus surgery (ESS) for CRS is one of the most common currently performed outpatient otolaryngologic procedures, with greater than 257,000 ambulatory sinus surgeries performed annually in the United States.4 Although common, surgery for CRS is not without potential complications, including revisits for bleeding, pain, and fever/dehydration in up to 5% of patients, and carries with it rarer complications of cerebrospinal fluid leak and orbital injury.5 Therefore, there is a relative trade-off between the benefits of surgery for CRS and the potential harms. In this circumstance, a high level of evidence (ie, randomized controlled trials) would be extremely helpful in determining evidencebased guidelines for the role of surgery in the treatment of CRS with polyposis. The 2 currently featured Cochrane Reviews2,3 point out prominent evidence gaps in our understanding of surgery for CRS with polyposis. Each review highlights problems with our current evidence base. Sharma and colleagues3 sought to assess the effectiveness of simple polyp surgery vs more extensive surgical clearance. Unfortunately, even 2 decades after the initial adoption of ESS, the authors encountered an empty review. At first glance, sinus surgeons may not see the value in comparing simple nasal polypectomy with formal ESS for polyps. Intuitively, ESS is more ‘‘thorough’’ and may get to the ‘‘root’’ of the problem. This intuition may naturally lull surgeons into a false sense of superiority for ESS. However, some historical background is relevant. Upon its introduction, ESS was a dramatically less morbid way of tackling CRS with polyposis, especially compared with transnasal snare polypectomy and other invasive techniques. It demonstrated good outcomes in several cohort series with relative safety, and because it was a significant improvement relative to traditional techniques, it gained widespread adoption. Somewhat contemporaneously, topical nasal steroid sprays, which have been now shown to be effective in polyp reduction,6 were just beginning to attain more widespread adoption. Why revisit the question of the extent of surgery for CRS with polyps? First, given that nasal steroid sprays and other topical regimens, such as budesonide irrigations, have demonstrated effectiveness in polypoid rhinosinusitis, there is a distinct possibility that a subgroup of patients may benefit from intranasal polypectomy alone with subsequent topical regimens. Second, the now widespread availability of nasal endoscopy may allow for a more controlled office-based polypectomy than previously performed. This may save patients a general anesthetic, while decreasing the risk of operative complications and health care costs. Conversely, intranasal polypectomy may in fact be less effective than ESS, even with the advent of topical steroid regimens, leading to undertreatment. One of the main functions of an empty review is to point out evidence gaps, and this empty review3 should rekindle this important question.
Rimmer and coworkers2 explored surgical vs medical interventions for CRS with nasal polyps. After sifting the search results, 4 studies were included in a qualitative analysis with varied results. The authors concluded that the level of evidence was of very low quality, and the evidence did not show that one treatment was better than the other in terms of patient-reported quality of life. This review again highlights a significant evidence gap regarding the effectiveness of surgical intervention for CRS. At first glance, sinus surgeons might be tempted to ignore the findings: don’t we all know that ESS is effective for CRS, more effective than medical management? This thinking is unwise for several reasons, as detailed below. The characteristics of the studies qualifying for analysis in this review are of interest. First of all, each of the 4 studies each took place in otolaryngology departments in European countries; no studies from the United States qualified. Although CRS with polyposis may in fact behave similarly in Europe vs in the United States, one would prefer to apply more ‘‘local’’ data to construct evidence-based decisions. Second, the included studies are relatively old—from 1988 through 2004—with the older studies dating back to the relative infancy of ESS. These studies were also conducted when the demand for evidence-based decision making and its influence on health care policy were not as emphasized as currently. Should one be concerned about a Cochrane Review that fails to show the advantages of surgical intervention over medical therapy for CRS with polyposis? The answer is very likely yes. Although investigators continue to present results of case series of ESS for CRS, such studies will likely never appear in a Cochrane Review because they are neither controlled nor randomized. For example, a recent, prospective, multi-institutional clinical trial of medical vs surgical management of CRS, conducted with considerable rigor, was not included because the treatment allocation was not randomized.7 The lack of randomized trials regarding surgery for CRS may also affect decisions by third-party payers and perceptions by consumers and patients. Third-party payers will preferentially cite best evidence when determining coverage and may deny coverage based on a perceived lack of evidence. Consumers and patients, who also seek the best evidence with which to make health care decisions, would likely find the empty conclusions of the plain-language summary from this Cochrane Review less than motivating when considering ESS for CRS with polyps. These factors should strongly motivate us to undertake prospective, randomized clinical trials of ESS of sufficient quality to be included in a Cochrane Review, both with respect to the extent of surgical intervention and in comparison to medical management to close these important evidence gaps.
Comments by Harvey CRS has an enormous health and quality-of-life implication, on par with significant chronic disease such as heart failure.8 Our understanding of CRS, however, is poor, and enormous heterogeneity exists in the pathophysiological
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mechanisms that lead to chronic sinus dysfunction. This poor understanding, especially during prior decades, has produced scientifically unsound approaches with subsequent comparisons of simple interventions (ie, medical vs surgical) rather than treatment strategies to the disease process. This misdirected approach would be akin to a heart failure population, consisting of patients with multiple causes for their failing heart (arrhythmia, valvular disease, cardiomyopathy, or coronary artery disease), being assessed on the effectiveness of aortic valve replacement vs slow-release nitrates for improvement in cardiac function. An evolution in our understanding of nasal polyposis, as well as the association with asthma and lower airway disease, has occurred in the past 10 years. Our profession now widely accepts that simple ostial obstruction and infection may perpetuate some nonpolypoid CRS, but it is not the etiology of the condition under review: nasal polyposis.9,10 Nonetheless, half the studies in the Rimmer et al2 review on medical vs surgical therapy are nearly 2 decades old, and the remaining are more than a decade since publication. While well intended, these authors of studies published decades ago were working with simplistic models of CRS with nasal polyps and subsequent management strategies, which are likely to be considered flawed by our current understanding. Why would a chronic inflammatory condition, often affecting the entire airway, be effectively managed by surgery alone? Surely in the postsurgery period, when the perioperative medications resolve, we would have the same chronic inflammatory condition continue, but this time with an open sinus cavity. Unfortunately, this was to the surprise of some early researchers in the field—in the months after well-performed sinus surgery, the disease would only continue with the unfortunate ability to endoscopically visualize the inflammation rather than being hidden behind an intact lateral nasal wall. Our better understanding of the etiology of CRS with nasal polyps is accompanied by an improved understanding of the effectiveness of treatment modalities. While systemic medication reaches the sinus cavity via the circulation, simple topical nasal sprays neither reach the sinus cavity nor are currently indicated for the management of sinus disease.11,12 Surely, in retrospect, the 12-month end point of one of the higher quality included studies represents a patient population with nasal polyps who were essentially untreated in both arms: the surgical group having neither an intervention that addressed the pathophysiologic process nor a maintenance therapy that provided sinus therapy.13 And the comparison group, who received medical therapy, had a brief period of anti-inflammatory control 351 days prior. Why would a difference be expected between groups? The anticipated outcome of little benefit imparted to either intervention arm at 12 months was seen and expected. Future trials in CRS with nasal polyps need to have management strategies in line with our understanding of the disease. Surgery needs to be performed in a way that either modifies the pathophysiology or changes the ability to treat the condition, such as offering a route for local or topical
therapies. Surgery in CRS with nasal polyps is not an isolated intervention; it offers a change in approach to maintenance therapy of these patients with novel topical agents or corticosteroid irrigations as part of an overall treatment.14 The Sharma et al3 review on the extent of surgery potentially highlights similar misconceptions about the pathogenesis of CRS with nasal polyps. Dr Bhattacharya’s note that ‘‘ESS is more ‘thorough’ and may get to the ‘root’ of the problem’’ is most appropriate, because it still reflects many physicians’ opinion but is not in line with our scientific understanding of the condition. Such divergence between the basic science and clinical practice of the disease is a reflection of a problem that plagues many surgical disciplines. Why would more surgical modification of the sinuses alter an inflammatory condition unless it was coupled with an ongoing therapy that takes advantage of that change? Despite the lack of randomized trials of surgery, there are data to support such an approach, with lower revision rates reported from the UK national audit for patients undergoing ethmoidectomy vs polypectomy.15,16 Similarly, more extensive surgery to the frontal or maxillary sinus is also associated with longer times to recurrence or lower revision procedures.17,18 Unfortunately, all these studies are directed at surgical technique rather than CRS with nasal polyps management and fail to account or incorporate the local therapies used in disease maintenance. The efficacy of these ongoing local therapies is most likely to be affected by surgery.12,14 Dr Bhattacharyya’s critique of the knee-jerk response to discard these current data is most appropriate. As a representation of the highest level of observational research (interventional), these Cochrane reviews unfortunately represent what our profession has managed to compile for our patients, payers, independent review bodies, and health care resource managers. It is not possible to discuss different CRS endotypes with an insurance payer or government body, nor is it possible to discuss the appropriateness of more complete and time-consuming surgery for certain poorly defined subgroups. These distinctions arise from clinical and scientific insight. Those independent bodies rely on our specialty to provide the framework in which CRS interventions are interpreted. Surely, then, it is our responsibility to tackle these issues so that future studies offer comprehensive treatment strategies in well-defined patient populations rather than single intervention comparisons within a heterogeneous group.
Comments by Rosenfeld Perhaps one of the greatest challenges in medicine is acting with wisdom and confidence when high-level evidence is sparse. Such is the case with surgery for CRS with polyps, as pointed out in an ‘‘empty’’ Cochrane review, another with biased trials, and commentary from 2 international CRS experts who highlight uncertainty regarding efficacy and pathogenesis. So where does this leave the clinician faced with deciding among medical therapy, polypectomy, or ESS? The
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uncertainty noted above sounds a clarion call for honesty and shared decision making with patients. We may not know the true efficacy of ESS, but we do know from observational studies that some patients do well afterward, at least for a period of time, and that complications are minimal with experienced surgeons.7,15-18 Conversely, not all surgeons are experienced, and complications can be serious. Risk-averse patients with acceptable quality of life may opt for medical therapy, some may prefer an office-based polypectomy, and others will sleep best after a ‘‘thorough’’ cleaning with ESS. These are all valid choices that warrant respect. Two key issues limit our confidence in ESS efficacy: the risk of bias in existing studies and the confounding impact of concurrent medical therapy on an inflammatory airway disorder. Until more evidence is forthcoming, clinicians would be best served by humility and a sincere desire to understand patient preferences and respect them fully in shared decisions. Author Contributions Neil Bhattacharyya, interpretation, drafting, final approval; Richard J. Harvey, interpretation, drafting, final approval; Richard M. Rosenfeld, concept, drafting, final approval.
Disclosures Competing interests: Neil Bhattacharyya is a consultant for Intersect ENT, Entellus, and Sanofi Aventis. Richard J. Harvey is on the advisory board for Schering Plough, NeilMed, and GlaxoSmith-Kline; was a consultant with Medtronic, Olympus, and Stallergenes; is on the speakers bureau for Merek Sharp Dolme, Meda Pharma, and Arthrocare; and has received grant support from NeilMed. Sponsorships: None. Funding source: None.
References 1. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(suppl):S1-S39. 2. Rimmer J, Fokkens W, Chong LY, Hopkins C. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. 2014;12:CD006991. 3. Sharma R, Lakhani R, Rimmer J, Hopkins C. Surgical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. 2014;11:CD006990. 4. Bhattacharyya N. Ambulatory sinus and nasal surgery in the United States: demographics and perioperative outcomes. Laryngoscope. 2010;120:635-638.
5. Bhattacharyya N. Unplanned revisits and readmissions after ambulatory sinonasal surgery. Laryngoscope. 2014;124:19831987. 6. Kalish L, Snidvongs K, Sivasubramaniam R, Cope D, Harvey RJ. Topical steroids for nasal polyps. Cochrane Database Syst Rev. 2012;12:CD006549. 7. Smith TL, Kern RC, Palmer JN, et al. Medical therapy vs surgery for chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 2011;1:235-241. 8. Rudmik L, Mace J, Soler ZM, Smith TL. Long-term utility outcomes in patients undergoing endoscopic sinus surgery. Laryngoscope. 2014;124:19-23. 9. Snidvongs K, Chin D, Sacks R, Earls P, Harvey RJ. Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion. Laryngoscope. 2013;123:1070-1074. 10. Leung RM, Kern RC, Conley DB, Tan BK, Chandra RK. Osteomeatal complex obstruction is not associated with adjacent sinus disease in chronic rhinosinusitis with polyps. Am J Rhinol Allergy. 2011;25:401-403. 11. Harvey RJ, Goddard JC, Wise SK, Schlosser RJ. Effects of endoscopic sinus surgery and delivery device on cadaver sinus irrigation. Otolaryngol Head Neck Surg. 2008;139:137-142. 12. Grobler A, Weitzel EK, Buele A, et al. Pre- and postoperative sinus penetration of nasal irrigation. Laryngoscope. 2008;118: 2078-2081. 13. Alobid I, Benı´tez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy. 2005;60:452-458. 14. Snidvongs K, Pratt E, Chin D, Sacks R, Earls P, Harvey RJ. Corticosteroid nasal irrigations after endoscopic sinus surgery in the management of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2012;2:415-421. 15. Hopkins C, Slack R, Lund V, Brown P, Copley L, Browne J. Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Laryngoscope. 2009;119:2459-2465. 16. Masterson L, Tanweer F, Bueser T, Leong P. Extensive endoscopic sinus surgery: does this reduce the revision rate for nasal polyposis?Eur Arch Otorhinolaryngol. 2010;267:15571561. 17. Naidoo Y, Bassiouni A, Keen M, Wormald PJ. Risk factors and outcomes for primary, revision, and modified Lothrop (Draf III) frontal sinus surgery. Int Forum Allergy Rhinol. 2013;3:412-417. 18. Seiberling KA, Church CA, Tewfik M, et al. Canine fossa trephine is a beneficial procedure in patients with Samter’s triad. Rhinology. 2012;50:104-108.
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