Endoscopic Transsphenoidal Surgery for Cushing’s Disease: A Review

Ever since the 1960s, transsphenoidal surgery has been the modality of choice for treating Cushing’s disease. Subsequent visualization of the pituitary fossa and sphenoid sinus may be done either with the operating microscope or with the relatively new endoscope. The endoscope due to its panoramic view allows greater visualization as compared to the operating microscope. It confers greater access to the cavernous sinus, sella, suprasellar, and parasellar regions and accommodates higher magnifications. It is bi-dimensional, however as opposed to the operating microscope that provides a three-dimensional view and allows greater depth perception. This article provides a comprehensive review of the advantages and disadvantages of the endoscope and compares it to the operating microscope. We hope this article will prove useful to both clinicians and academicians alike in their approach and management of Cushing’s disease.

This article aims to compare the two techniques by summarizing the findings of recent clinical series published in literature with a special focus on the advantages of the endoscope along with any shortcomings when compared to the operating microscope. We hope this article will prove useful to clinicians and academicians alike in their approach and management of Cushing's disease.

Review
Traditionally the transseptal/translabial approach with the use of the operating microscope is the gold standard transsphenoidal approach [8,15,17,20,24]. It is associated with minimal morbidity and mortality [15]. However, with recent advances, the endoscope has come forward as an effective tool -one with the potential to perhaps surpassing the use of the microscope to become the modality of choice in Cushing's disease [15,[20][21][28][29][30][31][32]. Many studies throughout the literature comment on the endoscope's ability to achieve better resection rates, lesser invasiveness, and fewer complications [7,17,[20][21][22]. Advocates of the microscope, however, criticize its panoramic view for its lack of three-dimensional vision and depth perception, and the inability to conduct meticulous microsurgical procedures that comes with it [7,19,21]. Others, meanwhile favor the panoramic view as it leads to better visualization of the bony structures covering the carotid arteries and the optic nerve [6-7, 17-22,24,26,29-30,33-36].
Remission rates, reported in the literature for transsphenoidal surgery for Cushing's disease vary between 42% and 95% [21]. The majority of remission rates lie between 70% and 85% with no significant improvement in the past years [21]. According to Qiao et al, there is no difference in remission rates between the endoscope and the microscope for Cushing's disease [30]. There may be fewer recurrences with the endoscope but this advantage disappears when follow up time is taken into account [30].
Being a relatively newer innovation, there are only a few reports that look at the efficiency and prognostics of a purely endoscopic technique for Cushing's disease. The effectiveness of pituitary surgery is evaluated by normalization of hormone levels and degree of tumor removal [15]. At the moment, data suggests that the endoscope is at least equivalent or in some cases even superior to the operating microscope [15,22]. Please refer to Table 1 for the salient features including remission rates, recurrences, complications, etc. of clinical series published in the literature on the use of the endoscope for Cushing's disease [2,[7][8][9][17][18]21,26,29,32,34].

Operative technique
The procedure is done under general anesthesia. It is conducted in collaboration with an otolaryngologist. The patient is kept supine with the head maintained in a fixed position using a three-pin Mayfield clamp. The head of the bed is elevated. Frameless stereotaxy is used for neuronavigation ( Figure 1). Using the binostril, bimanual technique, the endoscope is inserted and the Hadad flap is raised. The sphenoid ostium is identified. The posterior septum is removed to expose the vomer. The sphenoid sinus is identified and the intersinus septum is removed. The anterior part of the sella is then opened using a drill and Kerrison rongeur.
After identifying the bony landmarks of the optic nerve, carotid artery, and opticocarotid recess, a disc dissector is used to remove dura from the bone of sella floor. The dura is opened and separated from the gland underneath using a micro dissector. Care should be taken not to coagulate dura as this may lead to white discoloration that may hinder tumor identification [19]. Once the bone has been removed, neuronavigation is used to locate the tumor. Resection is then carried out using a micro dissector, suction device, and ring curettes of varying diameters and orientations. The tumor is identified as a discolored gray region upon the orange-pink coloration of the gland.
The sellar defect is repaired using the Hadad flap followed by fibrin adhesive, Surgicell, and Gellfoam.
Video 1 reviews the operative technique for endoscopic transsphenoidal surgery.

Advantages of the endoscope
The hallmark feature of endoscopic transsphenoidal surgery is the superior view one has of the sphenoid sinus and the pituitary fossa [7][8]13,15,17,20,22,30,34,36]. It gives greater lighting hence contributing to the better visualization and -depending on the scope used -an ability to operate at an angle [7][8]13,15,21,30]. Its panoramic vision allows greater exploration of the sella, suprasellar, and parasellar regions including the cavernous sinus area -as opposed to the traditional microscope that allows visualization only in a straight line between the scope and the pathology being observed [7][8]13,15,[20][21][22]30,34]. This means that the surgeon can now visualize tumors superiorly at the base of the third ventricle, inferiorly to the lower clivus, and laterally to the carotids and the cavernous [15]. The endoscope also allows higher magnifications, which make it an excellent choice for patients with Cushing's disease which are typically small tumors.
Another significant advantage of the endoscope is that it allows the surgeon greater access to the cavernous sinus [30,35]. Previously tumor invasion of the cavernous sinus was considered a negative prognosticator and an absolute contradiction to surgery [35]. It has been rightfully called the anatomic jewel box by Parkinson due to the density of neurovascular structures within its dural walls [25]. With the development of the endoscope, however, this is no longer the case and tumors reaching into the cavernous sinus can be successfully operated on and removed using a 30-degree scope [35].
Since the endoscopic approach does not utilize transseptal dissection, there is less postoperative pain and discomfort [7][8]17]. Hospital stays are shorter with fewer complications [7][8]17,22]. In particular, there are decreased incidences of septal perforation, epistaxis, and transient Diabetes Insipidus (DI) with the endoscopic technique [8,13,22]. This leads to greater patient satisfaction scores. It is because of these reasons and the fact that it causes minimal skull base trauma that Storr et al [17] emphasize the use of endonasal endoscopic transsphenoidal surgery in pediatric age groups. In their case series, Storr et al. also report fewer PICU admissions and blood transfusions. Also, being minimally invasive, reoperation, when needed, is much simpler as compared to the microscope which unfortunately brings about a greater distortion of normal anatomy [8,22]. Additionally, the wider field of vision of the endoscope serves helpful during reoperation when normal anatomical landmarks have been disrupted [17,19,22].

Disadvantages of the endoscope
The operating microscope resorts to its three-dimensional vision and depth perception, giving the surgeon the ability to operate in three-dimensional space -a feature that is, unfortunately, missing in the endoscope [7][8]20,30]. The endoscope is bidimensional and hence does now provide any depth perception [7,[20][21]30]. This is by far the biggest disadvantage of the endoscope as the lack of stereoscopic vision makes it difficult to discriminate adenomas from surrounding hypophyseal tissue [13]. Although 3D endoscopes have been developed and are available in the market to address this issue, their widespread adaptation and the subsequent results remain to be seen in future literature [30]. There is also the difficulty of manipulating tools through a narrow corridor [8,21]. However, both these issues can be overcome with surgeon experience [8,21]. Using a binostril, bimanual technique may also address this [8,21]. The learning curve involved in endoscopic transsphenoidal surgery has been investigated in the series by Chao-Hung et al. where the authors stratified their patients temporally and reported greater recurrences in earlier cases [26]. This corroborates the presence of a learning curve in endoscopic transsphenoidal surgeries that required experience and training to be acquired [13,26].
Concerns have also been raised regarding its lack of maneuverability as surgeons can only manipulate tools with one hand unless a holder is used [7]. The use of an assistant may, however, crowd the operative field [7].
Another disadvantage that has been reported is the increased incidence of extracranial manifestations [20]. These include nasal crusting and synechiae formation [20]. This may be a direct result of the repetitive passage of instruments in the nasal cavity [20]. Postoperative nasal debridement is usually required [20].
There is also increased incidences of vascular complications and post-operative cerebrospinal fluid (CSF) leaks with the endoscope [13]. The increase in vascular complications may be attributed to the fact that the surgeon may attempt more radical tumor excision with the endoscope by virtue of the increased view.

Systemic review and meta-analysis
In our review of the literature, we found several systemic reviews and metanalysis that compared microscopic and endoscopic surgical techniques and prognostics in a heterogeneous population of patients with various pituitary adenomas [15,20,22,28]. We found two studies that were accessible as full-text articles that compared the two surgical techniques in the setting of Cushing's disease only [13,30]. The findings of all these studies are summarized in Table 2 [13,15,20,22,28,30].

Conclusions
According to the literature published to date, an endoscope is an effective tool in transsphenoidal surgeries. Its superior view along with better patient prognostics establish it as a superior modality for Cushing's disease when compared with the microscope. Significant limitations need to be considered, however, as there exists a learning curve for surgeons using the endoscope. Lack of maneuverability and extra-cranial complications need to be addressed as well. In the future, 3D endoscopes may perhaps become a mainstream modality. The operative microscope can till then be utilized upon the surgeon's discretion.

Conflicts of interest:
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