Background & Aims: The pituitary gland is located near the center of the cranium base, caudally surrounded by a bony basket structure of the sphenoid bone named “Sella Turcica." The adjacent structures, such as optic chiasma stated superiorly, are of clinical and surgical importance(1, 2). Surgery is the first-line treatment for the large nonfunctional pituitary adenomas with clinical signs and symptoms (e.g., optic chiasma compression) and most functional adenomas (4). The very primary surgical access to pituitary adenomas was provided via trans-facial or trans-cranial approaches. The trans-sphenoidal approach was introduced later in the early 1900. However, this approach was abandoned due to serious complications and a higher mortality rate (5-8). With the advent of the microscope and later the endoscope and its application in the trans-sphenoidal approach, the endoscopic endonasal trans-sphenoidal approach (EETSA) has been rapidly accepted and well established for its advantages such as a better visualization, more complete tumor resection, and lower complications (8-10). However, as the access to a pituitary adenoma is provided through a bony defect in the sella turcica floor, postoperative cerebrospinal fluid (CSF) leak is a risk with the recently reported prevalence of 0/5-12% in endoscopic approach (11-16). To avoid it, various reconstruction strategies and materials have been introduced. In nonrigid reconstructions, materials such as fat, fascia, dural replacements, mucosal or muscular grafts, and pedicled mucosal flap of the nasal septum, middle or inferior turbinate are used. In rigid reconstructions, bone, cartilage, titanium mesh, ceramic implants, and bone cement are adopted (8,21). None of them being known superior to the other, heterogenous algorithms have been designed principally based on the grade or risk of CSF leak (22, 23).
Rigid reconstruction is supposed to strengthen and protect the reconstructed area well. However, donors cite morbidities in autografts (e.g., nasal bone or cartilage) (24), infection transmission in allografts (e.g., cadaveric iliac crest) (25), high costs, low biocompatibility, infection, and radiologic artifacts in synthetic grafts (e.g., Medpor) (26) are among the challenges both the patients and the surgeons encounter (19).
Moreover, minimal data exist on the spontaneous sella turcica re-ossification following EETSA, which can debate the necessity of rigid reconstruction. This pilot study consequently aims to consider the possible self-repair of sella turcica without any rigid reconstruction in eight patients with pituitary adenoma.
Methods: In this retrospective pilot study, the pituitary adenoma data bank of Rasoul Akram hospital's skull base research center was reviewed for the patients who had undergone EETSA between March 2014 to February 2018.
Those with available pre-operation paranasal sinuses CT scan, data bank documented measures of the intra-operation bony defect, evidence of the complete tumor resection according to the MRI three months after the surgery, and no evidence of tumor recurrence based on the last MRI ( 2018 or 2019) were included if no revision surgery or radiotherapy before or/and after the operation was conducted. They were accidentally called, and the first ten patients accessible by the documented phone number were invited to take a paranasal sinuses CT scan to evaluate sella turcica spontaneous re-ossification after informed consent.
The CT scans were evaluated, and measurements, including the maximum diameters of bone defect in the coronal and sagittal planes on the CT scans - using the Picture Archiving and Communication Systems (PACS) - Osirix system-, were compared with the defect size created intraoperatively. The area of the defect was calculated using the equation for the area of an Ellipse (major radius multiplying by minor radius Multiplying by pi.)
All procedures performed in this study were in accordance with the ethical standards of the Iran University of Medical Sciences research ethics committee (IR.IUMS.REC.1395.29082) and with the 1964 Helsinki Declaration and its later amendments.
Median and interquartile ranges (IQ) were used for the descriptive analysis of quantitative variables. Mann-Whitney test was used to compare independent quantitative variables, and Wilcoxon Signed Ranked test was used for quantitative dependent variables. The Spearman test evaluated the correlations. The statistical software IBM SPSS Statistics for Windows version 22.0 (IBM Corp. Released 2013, Armonk, New York) was used for the statistical analysis. P values <0.05 were considered statistically significant.
Results: Eight patients with no rigid reconstruction were included in the final analysis, with a median age of 40/5 years old (IQ=17), of whom six were female. After a median of 46 months (IQ=20.5, range 12-60), length, width, and the area of the bony defect were significantly reduced (21.5 to 9.3 mm, 15.6 to 9.4, and 297.90 to 77.5 mm2, respectively p values=0.01) leading to the median of 74.1% (IQ=11.2%, range 67.8-99.2%) self-repair of the primary bony defect.
The area of the intraoperative bony defect was significantly correlated with the final bony regenerated area and with the area of defect remaining after follow-up. (r=0.929, p value=0.001, and r=0.976, p value≤0.001, respectively). A negative correlation between age and the bony regeneration speed (the monthly percentage of the repaired area) was also detected. (r=-0.762, p value= 0.02)
Conclusion: In this study, spontaneous bony regeneration was shown to occur in all eight studied individuals (median of 74.1%, range of 67.8-99.2%) with various types of pituitary adenomas and primary defect areas (median of 297.9, range of 78.5 to 575.52 mm2) after a median of 46 months. The results align with the only previous study that reported spontaneous ossification in 94% of the 17 patients with pituitary adenomas in the median of 36 months (27). There are no more available data on sella turcica spontaneous bony regeneration. However, there is evidence of potential spontaneous re-ossification of the mandible, which is of the same bone type (irregular), showing even better healing without reconstruction strategies (29, 32-35). CSF leak risk, which is the most salient concern in EETSA, determines the reconstruction strategy in the skull base surgeries. Nonrigid reconstruction, whether intraoperative CSF leak is present or not, has led to permissible postoperative CSF leak (38,42,43). Moreover, the postoperative CSF leak rate was not significantly different with or without the use of Buttress in a recent meta-analysis (38). Putting all these findings together and considering the natural sphenoid spontaneous bony regeneration capability, the authors suggest that rigid reconstruction of sella turcica following EETSA may not be necessary.