Reconstructed Bone Chip Detachment Is a Risk Factor for Sinusitis After Transsphenoidal Surgery

Transcription

1 The Laryngoscope VC 2013 The American Laryngological, Rhinological and Otological Society, Inc. Reconstructed Bone Chip Detachment Is a Risk Factor for Sinusitis After Transsphenoidal Surgery Yao-Wen Hsu, MD; Ching-Yin Ho, MD, PhD; Yu-Shu Yen, MD Objectives/Hypothesis: Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. Study Design: Prospective cohort study. Methods: We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July All patients were followed up with nasal endoscopy for at least 6 weeks. Results: Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Conclusions: Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis. Key Words: Sphenoid sinusitis, pituitary surgery, sellar reconstruction. Level of Evidence: 2b. Laryngoscope, 124:57 61, 2014 INTRODUCTION Pituitary adenoma is a common intracranial tumor, with an overall estimated prevalence of 16.7%. 1 Methods of pituitary surgery have evolved from the traditional transcranial approach to a microscopic sublabial transseptal approach, to the current endoscopic transsphenoidal approach. 2 In 1992, Jankowski et al. were the first to apply the endoscopic technique to access the pituitary. 3 The pure endoscopic transsphenoidal approach was refined by Jho et al., initiating the modern era of endoscopic pituitary surgery. 4,5 The complications of this surgery have been well documented. They include diabetes insipidus, cerebrospinal fluid (CSF) leak, hemorrhage, and rhinologic complications (synechiae, septal perforation, olfactory dysfunction, and sinusitis). 2,6 Sinusitis is defined as an inflammatory response involving the mucous membranes of the nasal cavity and paranasal sinuses. Sphenoid sinusitis usually occurs From the Department of Otolaryngology (Y.-W.H., C.-Y.H.), National Yang-Ming University, Taipei, Taiwan, Department of Neurosurgery, Neurologic Institute (Y.-S.Y.), Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan. Editor s Note: This Manuscript was accepted for publication December 6, The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Ching-Yin Ho, MD, Department of Otolaryngology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei 11217, Taiwan. cyho@vghtpe.gov.tw DOI: /lary in association with infection of other paranasal sinuses. Although isolated sphenoid sinusitis is an uncommon disease occurring in fewer than 3% of all sinusitis cases, 7 it can manifest as a complication after endoscopic transsphenoidal pituitary surgery. Rates of postoperative sinusitis reported in the neurosurgical literature range from 1% to 6.2%. 8,9 However, risk factors and pathogens associated with sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery have not been clearly identified. After removal of pituitary tumor, the sellar defect should be repaired to prevent CSF leak. Numerous reconstruction methods have been described, including the use of fat, muscle or fascial graft, collagen sponge, with a variety of buttress materials (cartilage, bone, silicone plate, and titanium mesh), and tissue sealants. 10,11 Studies that address the relationship between reconstruction methods and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, possible risk factors, and causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. This information may be useful for patient counseling, managing postoperative sinusitis, and advancing surgical techniques. MATERIALS AND METHODS This study was designed as a prospective cohort study. From July 2008 through July 2011, patients with a diagnosis of benign pituitary gland tumor who underwent endoscopic transsphenoidal pituitary surgery performed by the same surgeon at 57

2 TABLE I. Patients Characteristics. Total number of patients 182 Gender ratio (male:female) 92:90 Mean age at operation, yr Tumor size, mm mm 22 >10 mm 160 Tumor type Gonadotroph adenoma 58 (31.9%) Null cell adenoma 24 (13.2%) Lactotroph adenoma 23 (12.6%) Plurihormonal adenoma 23 (12.6%) Corticotroph adenoma 12 (6.6%) Mammosomatotroph adenoma 12 (6.6%) Somatotroph adenoma 9 (4.9%) Rathke s cyst 6 (3.3%) Craniopharyngioma 5 (2.7%) Others 10 (5.5%) Complication Sinusitis 57 (31.3%) Synechia 28 (15.4%) Cerebrospinal fluid leak 2 (1.1%) Meningitis 1 (0.5%) Taipei Veterans General Hospital in Taiwan were enrolled. The protocol was reviewed and approved by the institutional review board of Taipei Veterans General Hospital ( AC). Exclusion criteria included previous pituitary surgery or radiotherapy, preexisting paranasal sinus disease, and malignant pathology. The neurosurgeons at our institute use the endoscopic endonasal unilateral approach to the sella via an anterior sphenoidotomy. After removal of the pituitary tumor, the sellar floor defect is reconstructed with bone chips harvested from the nasal septum. The pituitary fossa and sphenoid sinus are also packed with a fat pad, harvested from the abdomen in most patients. Tissue sealants or fibrin glues are also used. Before the operation, all patients underwent routine magnetic resonance imaging (MRI) and nasal endoscopy. After the endoscopic transsphenoidal pituitary surgery, they were followed up at the rhinologic outpatient clinic for postoperative wound care. The follow-up assessments were conducted once every week or every 2 weeks, depending on the wound condition. The diagnosis of sinusitis was based on the clinical practice guidelines for adult sinusitis that was developed by the American Academy of Otolaryngology Head and Neck Surgery Foundation. 12 We used nasal endoscopy to confirm the diagnosis (i.e., to see inflammation of the sphenoid sinus mucosa with purulent discharge) in every patient and performed an endoscopy-directed pus culture. All patients were followed up for at least 6 weeks and until complete wound healing or cure of sinusitis. The following data were collected: patient age and sex, tumor size on MRI, skull base reconstruction method, operation time, postoperative nasal endoscopic findings (e.g., pus from sphenoid sinus, bone chip detachment, and synechia), and culture results. The patients were divided into two groups, based on the presence or absence of sphenoid sinusitis. SPSS 19.0 (IBM SPSS, Armonk, NY) software was used to analyze possible risk factors by the v 2 test and logistic regression. RESULTS We enrolled 182 patients who met the inclusion and exclusion criteria. There were 92 (50.5%) male and 90 (49.5%) female patients. Their mean age was 46.3 years (range, years). The mean follow-up time was 2.9 months (range, months). The majority (161, 88.5%) had pituitary adenomas. Postoperative nasal endoscopy showed sphenoid sinusitis in 57 (31.3%) patients and synechia in 28 (15.4%) patients. There were only two (1.1%) patients with postoperative CSF leak. Patient demographics, tumor characteristics, and surgical complications are summarized in Table I. The patients were divided into two groups: the sinusitis group (n 5 57) and the nonsinusitis group (n 5 125). There was no significant difference in age, sex, tumor size, operation time, use of fat pad, postoperative synechia. However, the rate of bone chip detachment (i.e., bone chip dropping out to the sphenoid sinus or superior meatus) in the sinusitis group (Fig. 1) was significantly greater than that in the nonsinusitis group (43.9% vs. 11.2%, P < 0.05). Multivariate analysis also revealed that bone chip detachment was the only significant risk factor for postoperative sinusitis (Table II). The sinusitis rate was 64.1% (n 5 25) in the 39 patients with bone chip detachment and 22.4% (n 5 32) in the 143 patients without bone chip detachment (P < 0.05). There was no significant difference regarding other characteristics (Table III). Among the 57 patients with sinusitis, the rate of positive culture was 94.7% (n 5 54). Thirty-one patients (54.4%) had a single pathogen, and 23 patients (40.4%) had multiple pathogens. The most common pathogen was methicillin-sensitive Staphylococcus aureus (23 Fig. 1. Postoperative sphenoid sinusitis. Bone chip in right sphenoid sinus with mucopus. B 5 bone chip, MT 5 middle turbinate, S 5 septum. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] 58

3 TABLE II. Risk Factors Analysis Between Sinusitis and Nonsinusitis Group. Sinusitis Group, n 5 57 Nonsinusitis Group, n X2/ANOVA, P Logistic Regression, P Gender, male 28 (49.1%) 64 (51.2%) Use of fat pad 38 (66.7%) 85 (68.0%) Bone chip detachment 25 (43.9%) 14 (11.2%) * * Synechia 10 (17.5%) 18 (14.4%) Mean age, yr Tumor size, mm Operation time, min ANOVA 5 analysis of variance. *Significantly different when P < patients, 40.4%), followed by Pseudomonas aeruginosa (14 patients, 24.6%), and methicillin-resistant Staphylococcus aureus (seven patients, 12.3%) (Table IV). DISCUSSION To our knowledge, this is the first prospective study of sphenoid sinusitis in patients who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction by bone chip for benign pituitary tumor. The overall postoperative sinusitis rate was 31.3%. Detachment of the reconstructed bone chip was the only statistically significant risk factor for postoperative sinusitis. Finally, the most common pathogens in postoperative sinusitis were found to be methicillin-sensitive S. aureus (40.4%), P. aeruginosa (24.6%), and methicillin-resistant S. aureus (12.3%). In contrast to previous reports, our study revealed a higher postoperative sphenoid sinusitis rate of 31.3%. A retrospective study by Cappabianca et al. found a rate of approximately 2.05% for sphenoid sinusitis after endoscopic endonasal transsphenoidal pituitary surgery; this rate is lower than that reported in most studies of microscopic transsphenoidal surgery (1% 4%). 8 A retrospective study by Lu et al. found that 6.2% of patients developed sphenoid sinusitis, shown on MRI, after endoscopic endonasal transsphenoidal surgery for pituitary adenoma. 9 A retrospective study by Gondim et al. found that 1.66% of TABLE III. Patients Characteristics in Bone Chip Detachment and No Detachment Group. Bone Chip Detachment, n 5 39 No Detachment, n v 2 /ANOVA, P Gender: male 22 (56.4%) 70 (49.0%) Use of fat pad 30 (76.9%) 93 (65.0%) Synechia 7 (17.9%) 21 (14.7%) Mean age, yr Tumor size, mm Operation time, min Sinusitis 25 (64.1%) 32 (22.4%) * ANOVA 5 analysis of variance. *Significantly different when P < patients developed sphenoid sinusitis after the same surgery. 5 The incidence of postoperative sphenoid sinusitis reported in the neurosurgical literature is generally 1% to 6.2%. However, from the standpoint of otorhinolaryngologists, Batra et al. reported a 7.5% rate of sphenoid sinusitis after transsphenoidal hypophysectomy (also a retrospective study). 13 Kennedy et al. reported that sinusitis was the most common complication after transsphenoidal hypophysectomy, with an incidence of 15%. 14 It is possible that the latter, higher, postoperative sinusitis rate is a more accurate estimate, because ear, nose, and throat (ENT) specialists are more alert to sinusitis. 13 However, these studies did not focus on pure endoscopic transsphenoidal pituitary surgery. Furthermore, the postoperative sinusitis rate in the previous reports may have been underestimated, owing to patient or doctor ignorance of sinusitis symptoms, diagnosis by follow-up MRI rather than serial nasal endoscopy, or relatively more potential for bias in retrospective studies. The current prospective study has the advantages of detailed postoperative nasal endoscopy by an ENT specialist and correct diagnosis of sinusitis according to the clinical practice guideline for adult sinusitis developed by the American Academy of Otolaryngology Head and Neck Surgery Foundation. 12 Moreover, follow-ups were performed weekly or every 2 weeks for at least 6 weeks and until the wound stabilized, with normal mucosa appearance and resolution of granulation or TABLE IV. Culture Results From 57 Sinusitis Patients. No. % Methicillin-sensitive Staphylococcus aureus Pseudomonas aeruginosa Methicillin-resistant Staphylococcus aureus Pseudomonas putida Klebsiella pneumonia Escherichia coli Enterobacter aerogenes Serratia marcescens Coagulase-negative Staphylococcus Haemophilus influenzae Other Gram-negative bacilli

4 sinusitis. Because of this study design, the higher postoperative sinusitis rate we found may be a more accurate assessment of incidence. The second reason for this higher postoperative sinusitis rate is also a point of interest. All of the sellar defects were repaired with bone chips harvested from the nasal septum. To investigate the possible risk factors of postoperative sinusitis, we divided patients into the sinusitis group and the nonsinusitis group. After analyzing multiple factors, including age, sex, tumor size, operation time, reconstruction methods, and postoperative nasal endoscopic findings such as synechia or bone chip detachment, we found that the only significant risk factor was bone chip detachment. Bone chip detachment occurred in 43.9% of the sinusitis patients and 11.2% of the nonsinusitis patients. On the other hand, the sinusitis rate was 64.1% (n 5 25) in the 39 patients with bone chip detachment, compared to 22.4% (n 5 32) in the 143 patients without bone chip detachment. The etiology of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery is not fully understood. Batra et al. suspected that bone or fat grafts used for sellar defect reconstruction may be devitalized after radiation therapy, consequently becoming a nidus for infection. 13 Lu et al. explained that the formation of sphenoid sinusitis is related to sphenoidotomy size, frequency of postoperative nasal care, and reaction to foreign bodies. 9 Our study provides stronger evidence that bone chip detachment may increase the postoperative sphenoid sinusitis rate, with a relative risk of 2.86 (64.1% vs. 22.4%). A possible mechanism is the bone chip dropping out to the sphenoid sinus or superior meatus, causing obstruction of the sphenoid sinus opening and leading to secondary sinusitis. A bone chip that has become devitalized may also serve as a source of infection. Our culture results revealed that the pathogens associated with sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery are different from those of community-acquired acute bacterial rhinosinusitis. This information is important for initial choice of antibiotics. The three major pathogens were methicillinsensitive S. aureus (40.4%), P. aeruginosa (24.6%), and methicillin-resistant S. aureus (12.3%). In contrast, the most common bacteria isolated from the maxillary sinuses in acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 12 When treating postoperative sphenoid sinusitis, appropriate antibiotics directed against the causative pathogens are necessary. Clearing the source of infection is also important. The infected bone chip or necrotic fat pad that caused obstruction of sphenoid sinus drainage should be removed carefully under nasal endoscopy. Symptomatic and endoscopic resolution of sphenoid sinusitis was achieved in all 57 patients after culturedirected antibiotics with aggressive endoscopic debridement and local care. The CSF leak rate after transsphenoidal surgery is typically less than 5%. 11,15 A successful strategy of sellar defect reconstruction is necessary to prevent postoperative CSF leak and further meningitis or tension pneumocephalus. However, the indications and methods for sellar defect reconstruction differ among neurosurgeons. Cappabianca et al. reported that reconstruction was considered necessary in only one-third of patients undergoing endoscopic transsphenoidal procedures, mainly because of intraoperative CSF leaks. Their postoperative CSF leak rate was 2.3%. 16 Esposito et al. reported a graded-repair protocol for intraoperative CSF leaks. Their postoperative CSF leak rate was 2.5%, and more than 60% of patients can avoid autologous tissue grafts by this approach. 11 Senior et al. suggested that the only indication for reconstruction is intraoperative suspicion of a CSF leak. Their postoperative CSF leak rate was slightly higher (10.3%) than that of other series (0.4% 6.0%). 2 The CSF leak rate was 1.1% in our study, which was acceptable and even lower than the average rate reported in the literature. It may have been because we performed sellar defect reconstruction with bone chips in every case. Nevertheless, bone chip detachment was observed in 39 (21.4%) patients. Our results also reveal that bone chip detachment is a significant risk factor for postoperative sphenoid sinusitis. Sphenoid sinusitis can cause rare but serious complications, such as orbital cellulitis, cavernous sinus thrombosis, meningitis, epidural abscess, and intracerebral abscess. 7,17 Charalampaki et al. suggested widening the sphenoid ostium and avoiding packing the sphenoid sinus to prevent sphenoid sinus outlet obstruction. 18 Gondim et al. advocated less use of artificial material, which may serve as an environment for bacterial development. 5 According to our findings, reconstruction techniques should be modified to reduce the rate of bone chip detachment and subsequent sinusitis or potentially ascending infection. Indications of sellar defect reconstruction should also be reevaluated to achieve balance between CSF leak rate and postoperative sinusitis rate. The limitation of this study was the lack of control patients not receiving reconstruction with bone chip. Further studies comparing different reconstruction indications, materials, and techniques are necessary to build an ideal strategy for reconstruction. CONCLUSION The rate of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery is not as low as that reported in previous retrospective neurosurgical studies. Regular postoperative follow-up with nasal endoscopy and cooperation of a multidisciplinary team can prevent delayed diagnosis. Culture-directed antibiotics with careful endoscopic debridement can be effectively used to treat these patients. The bone chip used for sellar defect reconstruction may, however, drop out and become a risk factor for sinusitis. Reconstruction strategies should be further refined to avoid this complication. BIBLIOGRAPHY 1. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: a systematic review. Cancer 2004;101: Senior BA, Ebert CS, Bednarski KK, et al. Minimally invasive pituitary surgery. 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