Comparative Study between Microscopic and Endoscopic Endonasal Trans-Sphenoidal Surgeries for Nonfunctioning Pituitary Macro-Adenomas

Background: The transsphenoidal surgery has emerged as the standard treatment of pituitary adenomas. The endonasal transsphenoidal approach either microscopic or endoscopic affords a rhinological recovery with fewer sinonasal complaints. Aim of the work: Comparison between microscopic and endoscopic endonasal trans-sphenoidal approaches in nonfunctioning pituitary adenomas. Patients and Methods: Thirty patients with nonfunctioning pituitary adenomas were included from March 2015 to October 2020. The patients were subdivided into two groups, Group [A]: 15 patients for an endoscopic endonasal transsphenoidal approach, and Group [B]: 15 patients for microscopic endonasal transsphenoidal approach. All patients were subjected to history taking, general and neurological examination, visual, rhinological, endocrine and radiological assessment. All patients were followed up and examined by an attending neurosurgeon, otolaryngologist and endocrinologist one and three months and then yearly thereafter. The data were obtained and recorded. Complete tumor resection was the primary outcome. Other secondary outcomes included operative data and postoperative complications. Results: Operative time ranged from 60.0 150.0 minutes [mean 108.0 and 88.0 minutes in groups A and B respectively]. Complete tumor resection achieved in 13 patients [86.7%] of group A compared to 10 patients [66.7%] in group B. Subtotal tumor resection achieved for 2 patients [13.3%] and 3 patients [20%] of groups A and B, respectively. Partial resection and insufficient removal was reported in one patient [6.7%] for each in group B. Conclusion: The endoscopic endonasal approach provides more favorable tumor removal, and hence was associated improved visual field and acuity, less postoperative pain and shorter hospitalization.


INTRODUCTION
Nonfunctioning pituitary adenomas account for approximately 30% of all pituitary adenomas and due to their lack of clinically detectable hormonal activity they tend to present with mass effects such as headache, visual field deficits, cranial nerve defects, or rarely cavernous sinus syndrome. If there is extensive tissue destruction, hypopituitarism results and expresses clinically. The nonfunctional pituitary tumors are not associated with clinical or biochemical evidence of hormone hypersecretion. Apoplexy is rare in nonfunctional pituitary adenomas; it can occur in all adenoma subtypes but is more common in nonfunctioning pituitary adenomas, with intra-tumor hemorrhage, which represents a medical emergency [1] .
The diagnosis of non-functioning pituitary tumors is achieved by both clinical and radiological tools. Computerized tomography [CT] scan and Magnetic Resonance Imaging [MRI] play an important role in the established of a final diagnosis. MRI with contrast is useful to define the precise size and extension of the tumors, evaluate vascular relationships, and detect any invasion of the surrounding structures. Also, it is important to detect the post-operative residual or recurrent tumor. CT scan of the paranasal sinuses is a very important tool before surgery [2] The development of transsphenoidal approaches to the sella, was a major progress in the pituitary surgery. It permits resection of more than 95% of tumors using variations of this technique. The endonasal transsphenoidal approach either microscopic or endoscopic has many advantages over sublabial or transseptal techniques. It avoids the risks associated with other approaches [e.g., nasoseptal perforations, synechiae, upper lib numbness, anosmia and septal abscess [3] . However, the superiority of one approach over the other [endoscopic versus microscopic] is not well-established yet, especially in our institution due to recent introduction of endoscopic surgery.

AIM OF THE WORK
The aim of this work is to compare the clinical and radiological outcome between microscopic and endoscopic endonasal trans-sphenoidal approaches in nonfunctioning pituitary tumors.

PATIENTS AND METHODS
A prospective study was conducted on 30 patients with nonfunctioning pituitary tumors from March 2015 to October 2020, at neurosurgery department in Damietta University Hospital and Damanhur national institute The patients were subdivided randomly into two equal groups [closed envelope method], unless specific intervention is indicated for specific patient. Here, a shift to the indicated approach was made, and the patient was excluded from the study.
The groups were Group [A] for an endoscopic endonasal transsphenoidal approach and Group [B] for microscopic transsphenoidal approach.

Preoperative evaluation
All patients were subjected to preoperative assessment which includes: history taking, systemic and neurological examination, visual, rhinological, endocrine and radiological assessment. The pituitary tumors were classified according to their invasiveness using Hardy classification system into grades and stages.

Operative approaches
The approaches were achieved through the nasal, sphenoid, sellar, and sellar reconstruction phases. The used endoscope is [1D Karl Storz, Tuttlingen, Germany] a rigid scope 4 mm diameter, 30 cm in length, and with 0degree and 30-degree, according to the different steps of the surgical operation. The used microscope was [MOLLER Hi-R 1000]

Postoperative assessment
All patients were assessed immediately for neurological condition, vital signs and all data were recorded. The patients were monitored for nasal or post nasal CSF leak after removal of the packs. Postoperative ophthalmologic conditions including, visual acuity, fundus examination and visual field were assessed. Cases with intra-operative CSF leak, insertion of temporary lumbar drain was done. A protocol for monitoring fluid balance, electrolytes imbalance, and blood sugar were checked every 24 hours and managed. CT in a case of severe headache, sudden deterioration of vision, or deterioration of the conscious level.

Fellow up
All patients were followed up and examined by an attending neurosurgeon, otolaryngologist and endocrinologist one month after surgery, 3 months, and then yearly thereafter. Hormonal outcome was the lowest post-operative values documented after long term follow up. Radiological outcome was MRI done three months post-operatively in uncomplicated cases, and it was classified into, total [no radiological evidence of residual tumor], subtotal [less than 20% tumor residual], partial [tumor residual 20%-50%], and insufficient removal [more than 50% residual]. Visual and clinical outcome was categorized into improved, stationary, and worse. The outcome was verified through a summation of clinical, hormonal, and radiological finding. Complementary treatment; Gama Knife and radiation therapy had been used for cases with cavernous sinus residual.

Ethical considerations
The research was approved by the Institution Research Board [IRB] of Damietta faculty of medicine, Al-Azhar University. Informed verbal consent was obtained from each participant in the study.

Statistical analysis
Data was fed to the computer and analysed using IBM, SPSS software package version 20.0. [Armonk, NY: IBM Corp]. Qualitative data were described using number and percentage. The Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range [minimum and maximum], mean, and standard deviation, median and interquartile range [IQR]. Significance of the obtained results was judged at the 5% level. Case presentations are shown in figures [1][2][3][4].

DISCUSSION
The goals of endonasal transsphenoidal surgery in nonfunctioning pituitary adenomas include decompression of the optic apparatus, regain normal pituitary gland and stalk. Therefore outcomes can be measured using a combination of imaging, and clinical parameters.
In our study, we observed that the male patients were predominant [60%] than females, and the mean age was [36.4] year old, approximating what reported by Al-Shami et al. [4] while C esa k et al. [5] reported a higher mean age [59.6 years] for microscopic group and [58.7 year] for endoscopic group with predominant male patients.
In our study, we reported [60%] of the pituitary macroadenomas is stage B in both groups, which were coincident with Dallapiazza et al. [6] .
In our study, we reported a better recovery as regard visual field and visual acuity in endoscopic group [90%] than microscopic group [72.7%]. However, we didn`t observe any postoperative visual deterioration in contrast to Dallapiazza et al. [6] , as they achieved [39%] recovery of visual defects in endoscopic cases; however, C esa k et al. [5] reported better results in the form of [96%] improvement in patients with preoperative visual deficits. This might be explained by residual tumors, longstanding preoperative optic apparatus compression in our study.
We reported a higher percentage of gross total removal [GTR] in the endoscopic group [86.7%] than in microscopic group [66.7%]. These results were in agreement with Little et al. [7] who reported 83.7% gross total removal rates in endoscopic group. Our results were also in line with Kassis et al. [8] who reported GTR rates as 86.1% in endoscopic group versus 65.5% in microscopic group, respectively. Messerer et al. [9] reported GTR in 50% of microscopic group and 74% in endoscopic group, while Karppinen et al. [10] reported 56% and 45% GTR in endoscopic and microscopic groups respectively. However, C esa k et al. [5] observed 72% GTR in endoscopic group and 80% in microscopic group. The improved results with endoscopic group are best explained by the increased parasellar and suprasellar tumor propagation. Sabry et al. [11] reported that volume reduction in the microscopic group had a mean of 82.4% which was not significantly different from the endoscopic group volume reduction [89.1%].
We reported 20% intraoperative bleeding in endoscopic versus 6.7% in microscopic procedure. However, postoperative anosmia reported equally in both groups and postoperative sinusitis with abscess formation reported in one patient of the microscopic group. C esa k et al. [5] reported that rhino-logical complications [bleeding, inflammation] were noted in fewer than 8% in both groups. Agam et al. [12] reported 1.1 % of postoperative epistaxis of patients with both endoscopic and microscopic approaches.
The intra-operative CSF leak was slightly higher in the microscopic [13.3%] than endoscopic procedure [6.7%]. Jane Jr. et al. [13] reported that 30% of their patients had intraoperative CSF leak. One of them [5.5%] experienced require surgical repair of the sellar floor.
Our results showed a trend over time toward a reduced percentage of total complications for patients undergoing endoscopic resection due to improvement of learning curve. However, Agam et al. [12] reported that CSF leak was slightly higher for the endoscopic group [3.5%] versus [2.4%] in microscopic group with decreasing CSF leak as learning curve becomes better. Sabry et al. [11] reported higher incidence of CSF leak up to 40% in microscopic group and 15.2% in endoscopic group. C esa k et al. [5] reported higher incidence in the endoscopic cases [10.67%] versus [3%] in the microscopic ones.
In our study, we did not report any case of meningitis. However, Pablo et al. [14] reported meningitis in 2.7% of patients in microscopic group and 2.1% in endoscopic group. Dallapiazza et al. [6] reported meningitis in 1% of patients in whom CSF leak was persistent. Skulsampaopol and Hansasuta [15] reported meningitis in [3%], one of the three ensued from postoperative CSF leakage, whereas the other two patients did not have postoperative leakage.
In our study, we reported postoperative diabetes insipidus [DI] in 6.7% equally in both groups. C esa k et al. [5] experienced a higher percentage of DI in both groups [14%], which is not consistent with our data, may be due to different numbers of cases.
In the current study, the microscopic group had longer mean duration of hospital stay [7 days], compared to 6 days for the endoscopic group. This matches the significantly shorter hospital stay for endoscopic resection of non-functioning pituitary adenoma [NFPA] in multiple studies including Sabry et al. [11] and Higgins et al. [16] CONCLUSION We conclude that, the direct endonasal transsphenoidal approach with either endoscopic or microscopic is a safe and effective method to remove nonfunctioning pituitary adenomas associated with a rapid rhinological recovery and a low occurrence of serious long term sinonasal complaints. The endoscopic endonasal approach provides more complete tumor removal, less postoperative pain, shorter hospitalization, fewer postoperative complications. Improvement of the learning curve of endoscopic endonasal approach allows it to become the gold standard for pituitary adenomas in the future.

Financial and Non-financial Relationships and Activities of Interest
None