Revision Sinus Surgery

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3. Aspirin intolerance (AI).

4. Immunodeficiency.

5. An immunologic reaction to fungi.

6. Presence of bacteria that are resistant to the applied antibiotic treatment.

Testing for inhalant allergies includes prick, intracutaneous, and running anaerobic sprint testing followed by nasal provocation testing, if clinically indicated [11]. The relevant sensitization-specific immunotherapy or the increasingly accepted sublingual immunotherapy should be performed for 3 years continuously. Although this is not a causative treatment option for CRS, it may reduce one relevant concomitant inflammatory stimulus rendering the mucosa prone to recurrent disease, and in some patients may help to prevent the development of allergic bronchial asthma.

Dysfunction of mucociliary clearance can be detected using the clinical test for saccharin transit time (STT),

Jan Gosepath

where a piece of saccharin is placed on the head of the inferior turbinate and the time taken until a sweet sensation is clearly felt in the pharynx is measured. Physiologically, a sweet sensation will be noticed after between 8 and 20 min. The functional integrity of the ciliary cells as motor units can be further evaluated with the help of video-interference contrast microscopy. In the case of a prolonged STT, this is a very valuable method to rule out syndromes of primary ciliary dyskinesia.

■Any impairment of mucociliary transport can be clinically relevant, as persistent stasis of the mucus blanket will trigger recurrent rhinosinusitis.

In a study published in 1997 we showed that patients suffering from recurrent CRS often do have a prolonged STT, but rarely a significant decrease in ciliary activity [14]. These observations could be explained either by poor coordination of ciliary activity in these patients and/or alterations of the nasal mucus in terms of viscosity and its content of enzymes, inflammatory mediators, and toxic proteins released from eosinophilic granulocytes. However, this study was able to show that endonasal sinus surgery may improve mucociliary transport time, as measured by STT, in patients with severe CRS.

One critical group in the range of patients suffering from CRS, and especially in the subgroup with nasal polyposis, are individuals with AI. It was understood early on that this particular entity is associated with a very high risk of recurrence of sinonasal polyposis independent of the number and kind of previous surgical interventions [7]. The diagnosis of AI is not always associated with the full clinical picture of the aspirin triad, which consists of:

(1) nasal polyposis, (2) intrinsic bronchial asthma, and

(3) aspirin-induced worsening of asthmatic symptoms,

often along with naso-ocular symptoms [23]. However, in sensitive individuals even very small single doses of aspirin may cause rhinorrhea, bronchiolar constriction, and pseudoanaphylactic shock symptoms related to a non- IgE-mediated pharmacological hypersensitivity reaction [24]. Not only aspirin, but most other nonsteroidal antiinflammatory drugs interact with the eicosanoid pathway (Fig. 5.1). All patients diagnosed with AI have a considerable chance of clinical improvement or decreased risk of recurrence if adaptive desensitization therapy is performed.

■A low-dose, low-risk, aspirin-desensitizing protocol using a maintenance dose of only 100 mg of oral aspirin per day is effective in the management of patients with Samter’s (aspirin) triad [8].

This low dosage, along with its minimal risk of adverse side effects, offers the option of a long-term and, if possible, life-long treatment, which is ultimately mandatory as a lasting effect of the desensitization.

In 143 patients characterized in a retrospective investigation we diagnosed AI in 55 (38.5%) [15]. Patients diagnosed with AI revealed to be the subgroup with (1) the highest rate of revision surgeries performed over time and (2) the shortest interval between the respective operations. According to the definition of AI it is obvious, that the subgroup of CRS patients with nasal polyps is likely to have the highest incidence of AI.

In vitro analysis of eicosanoid release from mixed leukocyte cultures using a functional enzyme immunoassay offers a new tool not only to help establish the diagnosis of AI, but also to individually monitor the effect and verify the success of a desensitization therapy over time. Long-term follow up over at least 3 years in a group of

Table 5.1  Clinical parameters after a 2-year course of low-dose aspirin desensitization with a daily maintenance dose of 100 mg (n = 18 patients). FEV1 forced expiratory volume in 1s

patients undergoing desensitization using a daily maintenance dose of as little as 100 mg of aspirin revealed the treatment to be effective both clinically as well as in vitro (Table 5.1, Fig. 5.2) [10]. Eicosanoid levels shifted back to a normal release pattern during therapy, with an increase of prostaglandin in relation to leukotriene release. This underlines a prominent role of cyclo-oxygenase (COX)-dependant mediators, which is in keeping with findings in recurrent nasal polyposis of aspirin-tolerant patients. Immunohistochemical staining of polypoid tissue revealed a downregulation of COX-2 in these tissues as compared to normal nasal mucosa [13]. This unveils a possible mechanism of increased proinflammatory leukotriene release in nasal polyps, since COX-mediated prostaglandin E2 (PGE2) release inhibits leukotriene release in the nasal mucosa of normal controls.

The exact etiologic mechanisms underlying the formation of nasal polyps remain obscure. However, this entity of chronic inflammatory disease of the nasal respiratory mucosa is associated with remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/ VEGF) plays an important role in inducing angiogenesis

40

and/or modulating capillary permeability. We investigated the expression and localization of VPF/VEGF in nasal polyps as compared to healthy controls in order to evaluate its significance in the pathophysiology of nasal polyps. The expression of VPF/VEGF in specimens of nasal polyps was markedly stronger than in specimens of healthy nasal mucosa of controls [12]. VPF/VEGF labeling in polypous tissue was located in vascular endothelial

5 cells as well as in basilar membranes and epithelial cells. The observed expression pattern in nasal polyps as opposed to controls of healthy nasal mucosa suggests that VPF/VEGF might play a significant role in the etiology of nasal polyposis. These findings need to be discussed with respect to the differential expression of COX isoenzymes -1 and -2 (COX-1 and COX-2, respectively) in nasal polyps, where COX-1 is upregulated and COX-2 is downregulated, following immunohistochemical analysis. Studies involving intestinal hyperplastic polyps suggest that COX-1 in particular can upregulate VPF/VEGF [25]. This mechanism might play a key role in polyp growth and edema formation in nasal polyposis.

Preoperative Medical Treatment

When patients present with moderate symptoms and limited mucosal changes after primary surgery, a combination of nasal irrigations, culture-guided antibiotics if purulent secretions, as well as topical and/or short-term oral steroids can reduce or even resolve symptoms and endoscopic findings. There is evidence that in some patients a long-term course of low-dose macrolides can help to reduce the presence of biofilm and inflammatory mediators [27]. In the majority of patients with recurrent nasal polyps, however, medical preoperative treatment can only serve to control the inflammatory reaction as much as possible and to optimize conditions until the necessary surgical revision is performed.

Postoperative Care and Long-Term Medical Management to Prevent Recurrence

Certain applications of medical therapy should have a prominent role in the treatment of CRS and can be valuable in reducing the risk of recurrent nasal polyposis, especially in patients who have previously undergone one or multiple surgical interventions. In an untreated course of CRS, patients may show improvement of subjective symptoms to an extent of approximately 25% in so-called “stable episodes” over a 4-week period, whereas objective clinical parameters vary insignificantly. In such episodes, mRNA of interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 and tumor necrosis factor-al-

Jan Gosepath

pha as well as peptidoleukotriene (pLT) and PGE2 levels are still detectable and appear to play a role in the persistence of inflammation in CRS [16].

■Initial postoperative medical management should focus on the support of immediate wound healing and the prevention of scarring, synechiae formation, and wound infections.

The preferred protocol to achieve these goals varies to a certain extent between surgeons and is mostly based on topical applications of irrigations and solutions including creams, decongestants, and steroids. Patients are usually seen in the office at weekly intervals for endoscopic follow up and crust removal from the surgical cavity, as necessary.

The goal of long-term medical treatment in the postoperative phase is to achieve a steady decrease of relevant inflammatory mediators and thus to prevent the formation of recurrent disease. Common regimens to accomplish this include:

1.Topical and systemic steroids.

2.Topical antifungal, antiseptic, or antibiotic treatment.

3.Systemic antibiotics and antihistamines.

4.Aspirin desensitization.

Topical and Systemic Steroids

Steroids, used topically or systemically or both generally have a strong anti-inflammatory effect and can reduce eosinophilia as they directly interact with several chemokines and cytokines involved in the inflammatory process. In particular, the suppressive effect on the T-cell production of IL-5 is an important aspect in this regard [1]. A large number of symptomatic clinical reports as well as prospective studies involving objective measurement of nasal function have established the role of topical steroids in polypoid CRS [6]. The main indication seems to be in the postoperative period, where they seem to have beneficial effects on the rate and frequency of relapsing polyps. Systemic corticosteroids were evaluated in nasal polyposis and seem to result in temporary symptomatic relief and can help to delay or facilitate surgical interventions [3].

Topical Antifungal, Antiseptic, or Antibiotic Treatment

Initial reports using nasal washed with amphotericin B showed promising results and so controlled clinical trials were initiated to further define the role of intranasal antifungal treatment in patients with CRS [21].

Heterogeneous experiences on the effectiveness of this treatment option have been published [5, 27]. Practical clinical experience suggests that the individual response to antifungal agents appears to be unpredictable, but the chance of a positive effect on the course of CRS seems to increase with the duration of treatment. Some of the existing studies reporting ineffectiveness were unblinded after only short-term applications of 8–12 weeks and suffered from a preselection of patients with massive polyposis. The latter certainly should be a criterion to take caution with any topical intranasal treatment as solutions and/or nebulized substances will not even penetrate into the paranasal cavities. However, further evaluation of this treatment modality in prospective, placebo-controlled trials will help to shed more light on its place in our armamentarium and on patient selection criteria.

■Whenever applying topical solutions intranasally, potential side effects on mucociliary clearance should not be overlooked.

In an in vitro study on primary human nasal respiratory cell cultures we evaluated the effects of different concentrations of several topical solutions on mucociliary clearance, as measured by ciliary beat frequency (CBF) over time [9]. In controls, perfused with cell culture medium (RPMI) only, CBF was measured at an average of 9.5±1.7 Hz, which remained constant over more than 12 h. Perfusion with a 5% solution of ofloxacin as an antibiotic solution led to an average CBF of 8 Hz, but ciliary activity ceased after 7 h. With a 50% ofloxacin solution, the average CBF was only 7.5 Hz and stopped after 6 h 30 min. Using antiseptic solutions, perfusion with 5% of Betadine revealed an average CBF of 7 Hz, which was kept up for 1 h 30 min; however, with 10% it was down to 4.5 Hz and lasted for only 30 min. Hydrogen peroxide was used in a 1% and in a 3% solution and seemed less ciliotoxic than Betadine, as 1% led to an average CBF of 7 Hz, which was kept up for over 8 h, and 3% to 6 Hz for 5 h 30 min. Using antifungal solutions, amphotericin B revealed only little ciliotoxicity in low concentrations, as CBF was measured at 9 Hz for 8 h at a concentration of 2.5% and at 8 Hz for 7 h at 5%. After increasing the concentration to a 10% solution, CBF dropped to 3.5 Hz and lasted only 2 h. Interestingly, no dose-dependent effect was observed after perfusion with clotrimazole at all three chosen concentrations of 10%, 20%, and 50%. CBF remained at a constant average frequency of 9 Hz, but stopped after no more than 30 min in all experiments. The strongest dose dependence was seen for itraconazole: at a concentration of 0.25%, a CBF of 6 Hz lasted for 7 h 45 min; at 0.5%, ciliary activity lasted only 1 h 15 min at 6 Hz and at 1% it was only 3 Hz for 30 min.

Systemic Antibiotics and Antihistamines

Antibiotic treatment has not been established as an effective treatment in patients with CRS. A prominent pathogenic role of bacteria seems to be limited to acute forms of rhinosinusitis and is doubtful in CRS [18, 19]. Thus antibiotic treatment has mostly been proven effective in acute sinusitis [4]. There are only limited data from controlled studies on antibiotic treatment in CRS, and in most of these, a long-term effect on the course of CRS could not be shown [17]. Long-term applications of macrolides for at least 3 months may, however, have beneficial effects on clinical and in vitro parameters of CRS [26]. In addition to the antimicrobial mode of action, these drugs are known to have direct anti-inflammatory effects and may improve the viscoelasticity of the mucous blanket [20]. An inhibitory effect on biofilm production of Pseudomonas aeruginosa has also been described [2].

Antihistamines are known to play a role in the adjuvant treatment of sinusitis, but no efficacy has been established for antihistamines in CRS without allergic rhinitis being present as an underlying condition [22].

Aspirin Desensitization

The best timing to initiate a scheduled aspirin desensitization after sinus surgery is following the initial wound healing, at around the 3rd or 4th, but no later than the 6th postoperative week, before edematous or polypoid changes recur. To start desensitization therapy, patients need to be hospitalized for 2 days for close monitoring for potential pseudoanaphylactic reactions. Oral aspirin is given in increasing dosages over these 2 days (day 1: increase up to 100 mg, day 2: increase up to 500 mg). Doses are slowly increased only after a repeated check of airway resistance and forced expiratory volume in 1 s (FEV1), excluding a decrease in FEV1 of 25% or greater after the respective preceding dose. Should that occur, the previous dose is repeated without further increase at the time of the next application until lung function has recovered. On the 3rd day aspirin is reduced to 100 mg/day for long-term maintenance. In prospective trials, clinical reassessments as well as the functional in vitro assay were repeated at each follow-up visit of every patient, in an attempt to identify changes in the release of eicosanoids over time and to correlate these with the clinical course [10]. Since there is a relative overproduction of pLT in aspirin-sensitive individuals, it is desirable to achieve an increase in the “PGE2/pLT index” over time. We observed a significant improvement of in vitro findings, which was positively correlated to the individual clinical course and the recurrence rate of nasal polyps observed in this group of patients [8].

42

The data underline the role of the in vitro assay and indicate the effectiveness of a desensitization protocol that can be maintained as a long-term treatment without adverse side effects. The excellent compliance and low rate of adverse effects associated with a dose of 100 mg of aspirin per day was sufficiently validated in large cohorts of cardiovascular and neurological patients, using equivalent dosages for prevention protocols. Results sug-

5 gest that the recurrence rate of nasal polyps after surgical therapy can be reduced; however, only long-term treatment can secure a beneficial outcome over time.

Future Directions

As our understanding of pathophysiological mechanisms evolve, we will be able to develop more sophisticated and more effective medical treatment modalities for inflammatory diseases such as CRS. It will be crucial to define antigens and endogenous causative factors triggering the underlying immune response, especially at a genetic level. A therapeutic concept of the future will individually tailor a therapeutic strategy to a respective risk profile of a patient. Research will be dominated by identifying missing links between in vitro and in vivo parameters and between chronic inflammation of the upper and lower airway as their systemic parameters are most likely identical to a large extent. A next step, which will be of utmost relevance for any healthcare system confronted with disorders as prevalent as CRS, will be screening strategies characterizing patient profiles, ultimately leading to individualized prevention protocols.

Tips and Pearls

1.An individual workup including all relevant etiological factors is mandatory to tailor a medical management protocol to the needs of a patient suffering from recurrent CRS after previous surgery.

2.Analysis of mucociliary transport by the STT, and if abnormal, measurement of the CBF, assesses

a crucial functional parameter in a timeand cost-efficient manner, and should be performed routinely.

3.Although inhalant allergies have no causative role in CRS, they represent a relevant stimulus for eosinophilic mucosal inflammation and should be addressed appropriately.

4.The use of topical and/or systemic steroids, as well as the use of antibiotics or antifungal medications, should be tailored to the individual pathology.

5.Adaptive desensitization therapy can be performed successfully in patients with AI; however, only long-term treatment can secure a beneficial outcome over time. Using a novel low-dose aspi-

Jan Gosepath

rin-desensitizing protocol, this treatment can be maintained long term without adverse side effects.

6.Pathologic eicosanoid release patterns similar to those of patients suffering from AI have been demonstrated in patients with recurrent nasal polyposis and are currently being evaluated as therapeutic targets in these patients.

References

1.Bachert C, Geveart P (1999) Effect of intranasal corticosteroids on release of cytokines and inflammatory mediators. Allergy 54:116–123

2.Baumann U, King M, App EM, Tai S, Konig A, Fischer JJ, Zimmermann T, Sextro W, von der Hardt H (2004) Long term azithromycin therapy in cystic fibrosis patients: a study on drug levels and sputum properties. Can Respir J 11:151–155

3.Bonfils P (1998) Medical treatment of paranasal sinus polyposis: a prospective study in 181 patients. Ann Otolaryngol Chir Cervicofac 115:202–214

4.Buchem FL van, Knottnerus JA, Schrijnemaekers VJ, Peeters MF (1997) Primary-care-based randomised pla- cebo-controlled trial of antibiotic treatment in acute maxillary sinusitis. Lancet 349:683–687

5.Ebbens FA, Scadding GK, Badia L, Hellings PW, Jorissen M, Mullol J, Cardesin A, Bachert C, van Zele TP, Dijkgraaf MG, Lund V, Fokkens WJ (2006) Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. J Allergy Clin Immunol 118:1149–1156

6.Filiaci F, Passali D, Puxeddu R, Schrewelius C (2000) A randomized controlled trial showing efficacy of once daily intranasal budesonide in nasal polyposis. Rhinology 38:185–190

7.Gosepath J, Hoffmann F, Schafer D, Amedee RG, Mann WJ (1999) Aspirin intolerance in patients with chronic sinusitis. ORL J Otorhinolaryngol Relat Spec 61:146–150

8.Gosepath J, Schaefer D, Amedee RG, Mann WJ (2001) Individual monitoring of aspirin desensitization. Arch Otolaryngol Head Neck Surg 127:316–321

9.Gosepath J, Grebneva N, Mossikhin S, Mann WJ (2002) Topical antibiotic, antifungal, and antiseptic solutions decrease ciliary activity in nasal respiratory cells. Am J Rhinol 16:25–31

10.Gosepath J, Schaefer D, Mann WJ (2002) Aspirin sensitivity: long term follow up after up to 3 years of adaptive desensitization using a maintenance dose of 100 mg of aspirin a day. Laryngorhinootologie 81:732–738

11.Gosepath J, Amedee RG, Mann WJ (2005) Nasal provocation testing as an international standard for evaluation of allergic and non-allergic rhinitis. Laryngoscope 115:512–516

12.Gosepath J, Brieger J, Lehr HA, Mann WJ (2005) Expression, localization and significance of vascular permeability/ vascular endothelial growth factor (VPF/VEGF) in nasal polyps. Am J Rhinol 19:7–13

13.Gosepath J, Brieger J, Mann WJ (2005) New immunohistologic findings on the differential role of cyclooxygen- ase-1 (Cox-1) and Cox-2 in nasal polyps. Am J Rhinol 19:111–116

14.Hafner B, Davris S, Riechelmann H, Mann WJ, Amedee RG (1997) Endonasal sinus surgery improves mucociliary transport in severe chronic sinusitis. Am J Rhinol 11:271–274

15.Kaldenbach T, Schafer D, Gosepath J, Bittinger F, Klimek L, Mann WJ (1999) Significance of eosinophilic granulocytes in relation to allergy and aspirin intolerance in patients with sinusitis polyposa Laryngorhinootologie 78:429–434

16.Kühnemund M, Ismail C, Brieger J, Schaefer D, Mann WJ (2004) Untreated chronic sinusitis, a comparison of symptoms and mediator profiles. Laryngoscope 114:561–565

17.Legent F, Bordure P, Beauvillain C, Berche P (1994) A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of chronic sinusitis. Chemotherapy 40:8–15

18.Nadel DM, Lanza DC, Kennedy DW (1998) Endoscopically guided cultures in chronic sinusitis. Am J Rhinol 12:233–241

19.Nadel DM, Lanza DC, Kennedy DW (1999) Endoscopically guided sinus cultures in normal subjects. Am J Rhinol 13:87–90

20.Nagata T, Mukae H, Kadota J, Hayashi T, Fujii T, Kuroki M, Shirai R, Yanagihara K, Tomono K, Koji T, Kohno S (2004) Effect of erythromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model. Antimicrob Agents Chemother 48:2251–2259

21.Ponikau JU, Sherris DA, Kita H, Kern EB (2002) Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis. J Allergy Clin Immunol 110:862–866

22.Renvall U, Lindquist N (1974) A double blind clinical study with Monydrin tablet in patients with non allergic chronic rhinitis. J Int Med Res 7:235–292

23.Samter M, Zeitz HJ (1978) The aspirin triad and the prostaglandins. In: Samter M (ed) Immunological Diseases, 3rd edn. Little and Brown, Boston, pp 900–927

24.Schäfer D, Schmid M, Göde UC, Baenkler HW (1999) Dynamics of eicosanoids in peripheral blood cells during bronchial provocation in aspirin intolerant asthmatics. Eur Respir J 13:638–646

25.Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1996) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 87:803–809

26.Wallwork B, Coman W, MacKay-Sim A, Greiff L, Cervin A (2006) A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Laryngoscope 116:189–193

27.Weschta M, Rimek D, Formanek M, Polzehl D, Podbielski A, Riechelmann H (2004) Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial. J Allergy Clin Immunol 113:1122–1128

 Core Messages

■Technological advances continue to enhance endoscopic sinus surgical procedures. The development and utility of these techniques and devices continues to evolve and at this time the final chapter cannot yet be written. New technologies should enhance preoperative, intraoperative, and postoperative surgical treatment and care. Our ability to treat inflammatory as well as neoplastic disease will benefit from the availability of such devices.

■Intraoperative computed tomography as well as magnetic resonance imaging are presently available. There are several devices that have the capability of demonstrating surgical anatomic change, and such data can be transferred to update image guidance. This exciting development should enhance surgical procedures for both inflammatory and neoplastic disease.

■Endoscopic sinus surgery simulation facilitates educational opportunities for resident training and education as well as increasing skill set development for practitioners. These computerized systems provide a novel interactive scenario during which a specific surgical procedure can be programmed for simulation prior to a definitive procedure.

■The development of balloon sinus ostial dilation provides an alternative method for the treatment of localized anatomic and mucosal obstruction of sinus outflow tracts. Initial experience confirms the feasibility and safety of the technique, and early results suggest improved sinus function.

Introduction

The advent of endoscopic sinus surgery has revolutionized the surgical management of sinus disease. This minimally invasive approach was initially based on the development of illuminated endoscopes and video systems, which occurred simultaneously with enhancements in computed tomography (CT) scanning techniques. Refinement in surgical equipment, such as powered shavers and cutting instrumentation, permitted careful and meticulous removal of diseased mucosa and anatomic structures with minimal surgical trauma. The advent of image guidance enabled rhinologic surgeons to accurately localize surgical instruments while performing paranasal sinus and skull-base surgery for chronic inflammatory processes as well as neoplastic disease. Further development of these image-guidance systems and the related instrumentation has extended the indications for endoscopic procedures involving the base of skull. However, despite the accuracy of current image-guided systems, they are limited by the utilization of preoperative scan data, which do not reflect the surgical changes that occur as bone and soft tissue are removed. Several exciting and revolutionary intraoperative imaging systems have been developed that can provide intraoperative images, which can be used to update the image-guided system.

Surgical simulation training is currently being used in several surgical specialties.

■The endoscopic sinus surgery simulator (ES3) is an interactive computer-based platform, adapted from military flight simulation, which provides a virtual surgery experience for surgical education.

Several different modes, reflecting various skill sets and levels of difficulty, are available for training purposes. The ES3 has been validated by a multi-institutional study, and with the increasing focus on outcomes and assessment tools, may become an integral part of resident training

6 and physician credentialing.

Balloon sinus catheterization has been introduced for the treatment of frontal, sphenoid, and maxillary sinus outflow obstruction. Initial published results are promising in the setting of mucosal and anatomic obstruction. Additional studies including long-term outcome results are needed to define the role of this technology in the treatment of rhinosinusitis.

Intraoperative Imaging

Intraoperative imaging may prove to be one of the most important advances in image-guided revision endoscopic sinus surgery, particularly in the setting of neoplastic disease, and surgery at the skull base.

■Intraoperative imaging allows the surgeon to identify the limits of the skull base and orbit with greater accuracy, and to determine the extent of surgical resection and its potential effect on the anatomic relationship between the surrounding vital structures.

Stereotactic image-guided surgery was first introduced in conjunction with neurosurgical procedures to guide ablation of discrete areas; these initial cases were calibrated using plain films, anatomic landmarks, and anatomic atlases [2]. From that point, a series of framed stereotactic systems was developed. In 1986, Roberts and associates published reports of a frameless navigation system that utilized radiopaque glass beads as fiducial markers [11]. Since then, computer-aided surgery has undergone dramatic advances and become increasingly more available and user-friendly.

■Stereotactic image-guidance systems are still limited by their reliance on images obtained preoperatively. As surgery progresses and anatomy is altered, the images remain static and do not reflect the surgical changes.

Recent innovations have allowed for intraoperative updating of the images used in stereotactic surgery. Fluoroscopy has been used extensively in the operating room for neurosurgical, orthopedic, and vascular procedures.

More recently, the C-arm has been used to create reconstructed images for three-dimensional navigation by neurosurgeons and orthopedists [7, 10]; recently, Brown and colleagues investigated utilizing this technology during endoscopic sinus surgery [4]. In their initial experience with 14 patients, image quality was poor, but adjustments were made and for the final 6 patients they were able to produce images that allowed for evaluation of disease and anatomical structures with navigation accuracy similar to that found with CT images (within 2 mm). Limitations included image distortion and artifact caused by nasal packing and blood in the sinuses, as well as reduced image quality in patients with extensive nasal polyposis (Figs. 6.1 and 6.2).

One concern about intraoperative imaging is that of radiation exposure for the patient, the physician, and the operating room personnel. Traditional stereotactic surgical techniques utilize the preoperative CT scan data and therefore do not require intraoperative imaging with the associated radiation exposure. Manarey’s group investigated the amount of radiation exposure during FluoroCAT fluoroscopy to reconstruct triplanar images for stereotactic surgery [9]. Cumulative radiation exposures were measured for two separate scans in all three modes. The maximum surface and central radiation exposure (range 1.89–10.7 mG, depending on fluoroscopic mode) was significantly less than that of a sinus CT with imageguidance protocol (85.4 mG).

Current technology also allows for intraoperative magnetic resonance imaging (MRI). This modality provides superior soft-tissue imaging without radiation exposure. The soft-tissue detail is particularly beneficial in cases of endoscopic resection of tumors of the anterior skull base. Disadvantages of MRI include expense, longer scanning time, and the necessity of specialized, nonfer-

Fig. 6.1  Xoran X-cat intraoperative computed tomography (CT) scanner in use

romagnetic operating room equipment and instruments. Early experience utilizing intraoperative MRI was been reported, and demonstrated the feasibility and accuracy of this modality [8]. More recently, Anand et al. published their experience with intraoperative MRI during endoscopic transsphenoidal resections of pituitary tumors. Residual tumor was identified in three out of ten patients using intraoperative MRI. Additional endoscopic resection was performed and there were no intraoperative complications [1].

Ultimately, the utility of intraoperative imaging will be judged based on its benefits, technical difficulties and limitations, and potential risks.

Endoscopic Sinus Surgery Simulator

Endoscopic sinus surgery requires the ability to work with both hands in a small space around delicate structures. Varied anatomy and the close proximity of vital structures such as the orbit and skull base contribute to the difficulty in gaining proficiency in these procedures. Residents typically acquire these skills through a process that begins with observation and progresses to operative experience under the supervision of attending surgeons. Practice on cadaver models is available, but is limited by the cost and availability of cadaveric specimens. In response to the need for repeated practice to develop these

skills, the idea of a surgical simulator was explored. The field of aviation has used simulators for years to train and improve the skills of both commercial and military pilots. As a Department of Defense contractor, Lockheed Martin has been responsible for the development and implementation of many of these flight simulators and assembled a team to engineer a surgical training device.

The result of these efforts is the endoscopic sinus surgery simulator (ES3), which utilizes both visual and haptic (force) feedback in a virtual reality environment.

6 There are four principle components of this system: (1) a Silicon Graphics Inc. Octane workstation, which serves as the simulation host platform, (2) a personal computer (PC)-based haptic controller, which provides control and coordination between an instrument handle and a set of virtual surgical instruments, (3) a PC-based voice recog- nition-enabled instructor, which operates the simulator based on spoken commands, and (4) an electromechanical platform, which includes a replica of an endoscope, a surgical tool handle, and a mannequin head (Figs. 6.3 and 6.4).

■The endoscopic sinus surgery simulator collects and analyzes performance data in real time to provide immediate feedback to the participant regarding performance errors.

The system also archives data for end-results analysis. It provides an opportunity for residents to practice maneuvers repeatedly to gain proficiency without the risk of patient harm. It also allows for residents to repeat a specific scenario as needed, and since the perioperative aspects of patient care have been eliminated, the simulator allows for more procedures to be completed within a

set period of time. All of these factors will help to accelerate the learning curve for students and residents, while enhancing patient safety. The simulator also provides an objective assessment of surgical skill and would help to standardize residency training programs with regard to endoscopic sinus procedures.

In a prospective, multi-institutional study by Fried and associates, 10 expert otolaryngologists, 14 residents, and 10 medical students were evaluated using the ES3 [6]. They each performed 23 trials with the simulator, beginning at novice mode and ending at advanced mode. Their findings show that in the novice mode, there is a significant difference in the starting point between all three groups, but as the number of repetitions increases, the scores improve and the gap between attending physicians, residents and medical students closes, with all three groups achieving the same endpoint after ten repetitions. After completing the novice trials, exercises performed in the intermediate and advanced modes did not show any statistically significant differences between the three groups’ total scores. The results in the novice mode clearly demonstrate three different skill levels at the beginning, with all three levels ultimately ending at a level of high performance. Moreover, the variations seen at the outset in all three groups were significantly narrowed, indicating that the performance was comparable between the members of each group. Thus, simulator training can bring individuals to a higher level of proficiency as well as decrease the variability within each group. These findings support prior data published by Weghorst and her group, which validates the ability of the simulator to distinguish among varying levels of initial expertise, as well as the ability of the simulator to increase the level of proficiency with repeated trials [12].