Endoscopic Endonasal Reconstruction of Anterior

Original Article

Endoscopic Endonasal Reconstruction of Anterior Skull Base Defects: What Factors Really Affect the Outcomes? Mario Turri-Zanoni1,4, Jacopo Zocchi1, Alessia Lambertoni1, Marta Giovannardi3, Apostolos Karligkiotis1, Paolo Battaglia1,4, Davide Locatelli2,4, Paolo Castelnuovo1,4

OBJECTIVE: Endoscopic endonasal surgery has evolved in recent decades, requiring comparable advances in reconstructive techniques. This study aimed to retrospectively review outcomes of endoscopic anterior skull base reconstruction and to analyze factors associated with failures.

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METHODS: Data from patients who underwent endoscopic endonasal anterior skull base reconstruction in a single institution between 1998 and 2017 were collected. Patients were stratified according to selected risk factors: sex; age; previous surgery; disease treated (cerebrospinal fluid leaks, benign tumors, malignant tumors); single or multiple defects; defect dimension (6 cm2) and site (olfactory cleft, ethmoidal roof, planum sphenoidalis, posterior wall of frontal sinus); reconstruction technique (overlay graft, multilayer grafts, pedicled flap) and materials used; postoperative radiotherapy; and year of surgery. Statistical significance was assessed using Fisher exact test. Univariate logistic regression was implemented to analyze the association between risk factors and failures.

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RESULTS: Inclusion criteria were met by 513 cases with median follow-up of 96 months (range, 12e257 months). Success rate for initial repair was 95% (487/513), with 100% success rate for secondary closure after revision surgery. Failures were not significantly related to sex (P [ 0.54), reconstruction technique (P [ 0.28), location of defect (P [ 0.65), dimension

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Key words - Anterior skull base - Cerebrospinal fluid leak - Endoscopic surgery - Expanded endonasal approaches - Nasoseptal flap - Sinonasal tumor Abbreviations and Acronyms ASB: Anterior skull base CI: Confidence interval CSF: Cerebrospinal fluid CT: Computed tomography EEA: Endoscopic endonasal approach OR: Odds ratio

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(P [ 0.69), disease (P [ 0.83), or postoperative radiotherapy (P [ 0.83). Year of surgery, considered as a continuous variable, was associated with a statistically significant reduction of failures (odds ratio [ 0.89, P [ 0.005). CONCLUSIONS: Endoscopic surgery is safe and effective for anterior skull base reconstruction. Refinements in surgical technique and increasing experience have contributed to improved success rates.

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INTRODUCTION

T

he indications for endoscopic endonasal approaches (EEAs) have been expanded in recent decades to include treatment of meningoencephaloceles, benign and malignant sinonasal tumors, and intracranial pathologies. This evolution required comparable advances in reconstruction techniques to separate the sinonasal cavities from the intracranial space and to avoid potentially life-threatening complications, such as cerebrospinal fluid (CSF) leak, pneumocephalus, ascending meningitis, and brain abscess.1 In endoscopic skull base repair, the incidence of postoperative CSF leak is generally considered to be the most relevant primary outcome measure reflecting the success of skull base reconstruction.2 Concurrent advancements in endoscopic instrumentation, image-based navigation systems, and refinements in surgical techniques (e.g., the introduction of vascularized flaps) all have contributed to reducing skull base reconstruction failures from

From the Divisions of 1Otorhinolaryngology, and 2Neurosurgery, Department of Biotechnology and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, Varese; 3 Unit of Biostatistics, Department of Statistics, Monzino Hospital, Milan; and 4Head and Neck Surgery & Forensic Dissection Research Center, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy To whom correspondence should be addressed: Mario Turri-Zanoni, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.04.225 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.

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ORIGINAL ARTICLE MARIO TURRI-ZANONI ET AL.

ENDOSCOPIC ANTERIOR SKULL BASE RECONSTRUCTION

30%e40% postoperative CSF leak rates to 6.7%e11.5%, as evidenced by recent systematic reviews and meta-analyses.2,3 To further improve outcomes, it is paramount that we learn from the failures. Therefore, several studies have analyzed the most important risk factors associated with skull base reconstruction failure, identifying as possible factors involved the size of the defect,4,5 the anatomic site of the defect, the presence and flow rate of intraoperative CSF leak,1,2 the surgical technique used (free grafts vs. vascularized flaps),3 and the impact of previous or subsequent radiotherapy.5-7 However, data available in the current literature are conflicting, and case series have usually been heterogeneous, reporting different defects located in the anterior, middle, and posterior skull base together, precluding meaningful conclusions. It is consequently difficult to make evidence-based decisions to optimize reconstructive options for each specific type of skull base defect. The present study analyzed a large single-institution cohort of patients who had undergone endoscopic endonasal reconstruction of anterior skull base (ASB) defects either to manage CSF leak associated with meningoencephalocele or to repair defects resulting from expanded endonasal craniectomy for benign and malignant tumor resection. The study was designed to investigate factors that may impact surgical outcomes related both to the patient and to the pathology treated. MATERIALS AND METHODS A retrospective review was performed of patients who underwent endoscopic endonasal ASB reconstruction in a single tertiary-care referral center between June 1995 and February 2017. Exclusion criteria were as follows: 1) transcranial surgery or combined external and endoscopic approaches; 2) middle and posterior cranial fossa defects; 3) missing relevant data (e.g., preoperative imaging, surgical report, follow-up information); 4) 6 cm

1.19

0.30e4.61

0.64

0.90

0.34e2.36

0.62

Size of defect

2

2

Site of defect Olfactory cleft vs. ERTC Ethmoid roof vs. ERTC Year of surgery (continuous variable)

0.57

0.22e1.49

0.62

0.89

0.82e0.96

0.005*

Technique Single-layer vs. pedicled flap

1.04

0.21e5.12

0.55

Multilayer vs. pedicled flap

0.59

0.13e2.70

0.25

Material, autologous vs. synthetic

0.49

0.20e1.12

0.11

Postoperative RT, yes vs. no

1.11

0.47e2.61

0.31

OR, odds ratio; CI, confidence interval; CSFL, cerebrospinal fluid leak associated with meningoencephalocele; ASB-t, anterior skull base defect resulting after tumor resection (benign and malignant); ERTC, endoscopic resection with transnasal craniectomy (unilateral and bilateral); RT, radiotherapy. *Statistically significant.

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(Figure 2). This statistical trend was also validated graphically by distributing the surgical procedures in 3 homogeneous time groups with a declining path of failure rates (Figure 3). We further examined the interplay between the year of surgery and the reconstruction failure rates by stratifying the study population according to the defect size to confirm that defect size was not confounding the association we found between year of surgery and failures. In this regard, defects of 1e2 cm2 and 2e6 cm2 did not show statistically significant differences in failure rates with regard to the year of surgery. Conversely, when analyzing defects 6 cm2, the risk of failure gradually decreased as the year of surgery progressed, with statistically significant ORs of 0.80 and 0.72, respectively, and P values of 0.006 (95% CI, 0.68e0.94) and 0.04 (95% CI, 0.53e0.99), respectively (Table 3). According to these findings, it seems that the surgical outcomes of ASB reconstruction progressively improved over the years, especially when repairing smaller and larger ASB defects rather than intermediate-sized ones. DISCUSSION Over the past 20 years, EEAs have revolutionized the surgical management of sinonasal and skull base diseases.14 As increasingly complex extradural and intradural disease has been treated via EEAs, the difficulty of associated skull base and dural reconstruction has also significantly increased. Many articles and meta-analyses have found that high-flow leaks2 and larger defects4,15 are associated with increased risk of reconstruction failure, and therefore the use of pedicled vascularized flaps has been recommended to improve success rates.16 After a systematic review of the literature, Harvey et al.3 concluded that reconstruction with a vascularized flap for skull base defects >3 cm had a significant advantage over free grafting in preventing postoperative CSF leak.3 Moreover, Gruss et al.4 found a correlation between dural defect size 2 cm2, location of the defect in the central skull base, and nasoseptal flap failure and proposed these factors as significant predictors for reconstruction failure. However, current evidence is based on small case series of patients and pooled data analysis that considers outcomes from anterior, middle, and posterior skull base reconstruction together, precluding appropriate definition of factors specific to skull base reconstruction failures for each subsite. To limit selection bias and to reduce potential confounders that may affect the analysis, our study was designed to include only ASB defects. Anterior cranial fossa is peculiar in the ventral skull base given the low flow of CSF, the possibility for a safe epidural dissection, and the presence of bony structures able to buttress the reconstruction. Moreover, gravity pulls the frontal lobes on the inlay graft and helps to hold the material in position securely and prevent migration.17-19 Additionally, the nasoseptal flap generally struggles to reach the most anterior portion of the ASB toward the posterior wall of the frontal sinus, requiring alternative solutions.9,10 By reviewing a single-institution case series, the largest so far reported in the literature specifically analyzing endoscopic endonasal ASB repair, this study aims to offer a comprehensive analysis of factors that may correlate with reconstruction failure. Our data revealed that outcomes improved gradually over the years, hand in hand with the advances in surgical skills and expertise, technologic evolutions, and refinements in surgical

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Figure 2. Univariate logistic regression. Year of surgery reaches statistical significance. s-layer, single-layer reconstruction in an overlay fashion; m-layer, multilayer reconstruction; flap, pedicled flap used for

technique, emphasizing the importance of experience in this field. The overall success rate of 95% reported in this series of 513 patients who underwent endoscopic ASB reconstruction has been further improved to 96.5% in recent years, as shown in Figure 3. This is due mostly to standardization of the technique and to the refinement of the surgical details as well as to the learning curve of the surgeons. The sex and age of the patient, previous skull base surgery, disease treated, and presence of multiple defects were not associated with an increased risk of reconstruction failure. Similarly, the site and size of the defect do not seem to significantly influence the successful closure of the ASB, although they should be taken into account preoperatively to plan the most appropriate reconstruction strategy. Data emerging from this study outline that it is not the defect size per se that makes the reconstruction complex. Much more important is whether the borders of the defects can be identified and exposed, as this is what determines the ease, complexity, or even impossibility of the procedure. Thus, a huge ASB defect extending from orbit to orbit and from the planum sphenoidalis to the frontal sinuses may be easier to repair than a much smaller defect in which the precise borders are hardly identifiable. We consider every case of ASB defect a potential candidate for an avascular reconstruction, unless bony edges are not present. The absence of these borders precludes the positioning of the inlay grafts—the first intracranial intradural and the

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reconstruction; CSFL, cerebrospinal fluid leaks associated with meningoencephalocele; ASBt, anterior skull base defect resulting after benign and malignant tumor resection.

second intracranial extradural (in a sort of epidural pocket)—and so significantly increases the risk of postoperative leakage. For this reason, surgeons need to determine if the roof of the orbit and other bony structures capable of buttressing the reconstruction are still present, especially in complex malformative syndromes and in difficult cases of revision surgery.20 When analyzing the impact of the year of surgery adjusted for the defect size, we found that the major improvements in success rates over the years have been obtained for smaller and bigger defects, whereas intermediate-sized defects showed no statistically significant improvements in outcomes over time. This might be due to the limited statistical power for the smaller subgroups of intermediate-sized ASB defects or, alternatively, the fact that no significant progress has really been observed in this subset of patients. However, these findings support the concept that in endoscopic ASB reconstruction there is no directly proportional relationship between increased size of the defect and increased risk of failure. Concerning the available materials, as a general rule, we prefer to repair the skull base using autologous tissues, such as fascia lata or iliotibial tract, harvested from the patient’s thigh with minimal morbidity.21 This is based on the scientific demonstration of good integration of the connective tissue, as evinced by otologic experience in myringoplasty and previous experiences with skull base surgery.22 The process of wound healing after dura mater

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Figure 3. Distribution of the surgical procedure in 3 homogeneous time groups with a declining path of failure rates.

repair occurs by endogenous tissue (fibroblast migration from dura borders) replacing the graft, resulting ultimately in a thick scar. However, nondegradable materials cannot be replaced by endogenous tissue owing to their resistance to enzymatic and cellular processes; when they are biocompatible, they become enveloped in a thin layer of connective tissue during the healing process.23 In this respect, in the first years of our experience we observed 1 case of infection and extrusion of the heterologous material (synthetic dural substitute) some years after surgery followed by radiotherapy. This never occurred with autologous materials. Vascularized flaps are extremely useful in ASB reconstruction and are usually reserved for complex malformation cases, in revision surgery, and whenever exposure of the bony borders of the defect is not feasible or epidural dissection is demanding. Since inception of the nasoseptal flap in 2006,9 its ever-increasing use has probably contributed to improve reconstruction techniques as well as to reduce failure rates over the years. However, in this case series, it has been used only in 18 of 513 cases (3.5%), and therefore its impact as a confounder of the analysis is limited. In addition, the potential of the so-called septal flip flap,10 which is pedicled on septal branches of the ethmoidal arteries, has recently emerged, especially for repairing anteriorly placed ASB defects extending toward the region of the frontal recess. Advantages of vascularized reconstruction include excellent success rates and rapid healing of

Table 3. Univariate Logistic Regression Showing Impact of Year of Surgery on Anterior Skull Base Reconstruction Failure, Stratifying Patients’ Cohort According to Defect Size Risk Factors

Number

Size >6 cm2

156

Size 2e6 cm2

44

Size 1e2 cm2

70

Size