Surgical Management of Pituitary Tumors
Reza Jarrahy, M.D., Hrayr Shahinian MD, FACS

Historical Background

The development of pituitary surgery over the past century is largely credited to the pioneering work of Harvey Cushing in the early 1900s.^{45, 106} Cushing's early experience with transsphenoidal approaches to the sella built upon the work of his mentor Halstead and his contemporaries, including Giordano, Schloffer, Kanavel, and Hirsch.^{21, 52, 53, 99} Similarly, Cushing's interpretation of the transcranial approach draws from the prior experiences of, among others, Caton, Paul, Horsley, Krause, and Kiliani.^{18, 21, 52, 55, 85} Cushing would ultimately focus his practice on the transcranial technique, citing its direct and wide exposure of the gland from a suprasellar perspective as paramount to the effective surgical management of pituitary disease.^{22, 23, 51, 106} Reports of Cushing's success with this procedure helped establish widespread acceptance of the transcranial method throughout Europe. Hirsch's continued practice of the transsphenoidal technique, however, contributed to a polarization of opinions on treatment options in pituitary surgery. Claiming that a transsphenoidal exposure of the gland was adequate for thorough resection of tumor, he argued that the less invasive nature of this procedure made it the technique of choice in pituitary surgery. His opinions were shared by other prominent surgeons, as were those of Cushing. Practice of both methods continued, as did lively discussions within the medical community regarding the indications, merits, and pitfalls of each.

Cushing's assistant Norman Dott sustained this debate. Dott acquired experience in both procedures under Cushing's tutelage. In his own practice at the University of Edinburgh he wrote and lectured in favor of the transsphenoidal technique.³⁰ He also began developing instruments designed specifically for use in the procedure. Among those who studied and applied Dott's experience to their own practice was Gerard Guiot, who credited his revival of the transsphenoidal hypophysectomy in France during the 1950s to Dott's influence.⁴⁵ Guiot's adaptation of the procedure is especially noteworthy in its correlation with the introduction of intraoperative radiofluoroscopic imaging.¹⁰⁶ Jules Hardy followed the work of Dott and Guiot and incorporated newly developed medical technology into his technique. His work is distinguished for his description of the use of the operating microscope, pictures of which he first presented in 1965.⁴⁸

The introduction of fluoroscopy and microscopy to pituitary surgery in effect ended the debate on how to maximally expose the gland with the least morbidity. With these instruments available, adequate exposure and thorough exploration of intrasellar and suprasellar extensions of the gland became possible without the need for a large frontal craniotomy or prolonged brain retraction. With these advances, the transseptal transsphenoidal approach came to be accepted as the procedure of choice for the surgical management of most pituitary lesions. Transcranial techniques were reserved for use in the resection of tumors with extensive invasion into the anterior and middle cranial cavities. With specific roles for these two procedures thus identified, the indications for microscopic transseptal transsphenoidal and transcranial pituitary surgery have remained relatively well defined for several decades.

Recently, however, discussion regarding the most effective and least invasive way to perform pituitary surgery has been renewed as the above-described standards have been challenged. Developments in the field of sinus endoscopy^{66, 80, 86, 95, 118} originally prompted surgeons to attempt endoscope-assisted surgery of the pituitary gland via the traditional transseptal approach.^{40, 50, 57, 95, 105, 109, 130, 131} Experimental and clinical models for fully endoscopic pituitary surgery via a transnasal transsphenoidal approach have since been described.^{16, 49, 58-61} This procedure is proving to be equally if not more effective than microscopy as the primary imaging modality in pituitary surgery. Additional experience with this procedure and its outcomes will determine its ultimate role in pituitary surgery.

Surgical Anatomy

Because of its position at the interface of the anterior and middle cranial fossae, frontal and lateral transcranial approaches to the pituitary gland require familiarity with the anatomical relationships between the critical structures that reside within these spaces as well as the surgical anatomy of the sella turcica. Moreover, the inferior microscopic and endoscopic approaches call for specific knowledge of the intra- and infra-nasal anatomy and architecture.

The anterior and middle cranial cavities

The embryological development of the anterior and middle cranial fossae is predicated upon the formation of ossification centers within the chondral template of the developing skull base. This sheet of cartilage provides the framework for the base of the cranium as well as parts of the midface and nose. Deposition of bone within this cartilage gives rise to the majority of the occipital, temporal, sphenoid, and ethmoid bones and determines their ultimate shapes.^{38, 69, 70, 75, 103}

The frontal bone defines the rostral limit of the anterior cranial cavity. The mature bone represents the fusion of separate ossification centers within the embryonic membranous neurocranium that articulate in the midline at the metopic suture.^{38, 111} An osseous projection called the frontal crest extends posteriorly from the inner surface of the frontal bone along the floor of the cavity. The frontal crest points to the cribriform plate and is separated from it by the foramen cecum.¹⁴ This foramen passes an emissary vein. The cribriform plate is a punctate bony surface that forms the roof of the nasal cavities bilaterally. Its perforate nature is derived from its formation around the differentiated nerves of the upper nasal passages, which pass into the anterior fossa to synapse on the olfactory bulbs.^{71, 73, 119, 126} These are the distal limits of the olfactory tracts, the purely sensory nerves that lie on the surface of the cribriform plate to provide the sense of smell. The cribriform plate is bisected by the falx cerebri and crista galli, which represents the intracranial extension of the perpendicular plate of the ethmoid bone.^{14, 24, 73, 87}

The remainder of the floor of the anterior fossa is made up of the thin orbital plates of the frontal bone.⁷ These irregularly surfaced platforms comprise the roofs of the orbits and support the frontal lobes. They articulate medially with the cribriform plate. At this interface the anterior and posterior ethmoidal arteries--distal branches of the ophthalmic artery--pass through foramina in the plate to supply the nasal septum and lateral nasal walls.¹⁵ Posterior to the cribriform plate, the body and lesser wings of the sphenoid mark the caudal limits of the anterior cavity and the anterior margin of the middle cranial fossa.

The middle fossa houses the temporal lobes laterally and the pituitary gland anteriorly. The majority of the floor of the cavity is made up of the sphenoid bone.¹⁰³ Various foramina in the floor of the middle fossa allow for passage of neurovascular structures into and out of the cranium. These include the carotid artery, the middle meningeal artery and vein, and the branches of the trigeminal nerve.^{65, 107} A gap at the medial junction of greater and lesser sphenoid wings—the superior orbital fissure—is occupied by the first branch of the trigeminal nerve, the oculomotor, trochlear, and abducens nerves, and the ophthalmic veins. The bony optic canal provides a route for passage of the optic nerve into the apex of the orbit.^{91, 103, 114}

The sella turcica and pituitary gland

The sella turcica, also commonly referred to as the hypophyseal fossa, contains the pituitary gland. Structurally, it represents a rounded excavation of the sphenoid bone that is flanked by numerous critical structures. The dorsum sellae is the uppermost extension of the clivus and forms the posterior wall of the sella. It has lateral protuberances that are referred to as the posterior clinoid processes. The anterior boundary of the sella is set by the tuberculum sellae, a raised prominence on the superior surface of the sphenoid bone immediately in front of the hypophyseal fossa.^{37, 103} The curving projections of the lesser wings of the sphenoid terminate medially in the anterior clinoid processes, which rest above and posterolateral to the tuberculum.⁹⁴ Anterior to the tuberculum sellae is a depression in the sphenoid called the prechiasmic groove, to either side of which lie the intracranial openings of the optic canals.¹¹⁹

The development and ultrastructure of the pituitary gland itself are thoroughly discussed elsewhere in this text. However, knowledge of its anatomical relationships is of paramount importance in the surgical management of hypophyseal disease. The hypophysis sits in the cavity of the sella turcica at the distal end of the hypophyseal stalk. The stalk serves as a direct conveyance of hormones to the posterior pituitary and as a conduit for hormone-releasing signals to the anterior pituitary via its portal vessels.³² It descends from the median eminence of the hypothalamus and passes through a central hiatus in the diaphragma sellae, a dural reflection between the anterior and posterior clinoid processes that covers the hypophyseal fossa.^{36, 37, 101, 102} Above the diaphragma, the hypophyseal stalk is anteriorly related to the optic chiasm. Most commonly, the chiasm directly overlies the sella and pituitary. (This is the anatomical basis of the incidence of visual symptoms—most notably bitemporal hemianopsia—seen in patients with pituitary tumors that have suprasellar extension.) Alternatively, the chiasm may lie over the tuberculum ("prefixed" position) or over the dorsum sellae ("postfixed" position).¹⁰¹ The optic nerves emerge from the optic canals anteromedial to the tips of the anterior clinoid processes to run posteromedially toward the chiasm. Knowledge of these normal and variant anatomical patterns is especially important when performing transcranial operations in which the approach to the sella is conducted along the floor of the anterior fossa directly towards the optic nerves and chiasm.

The parasellar vascular anatomy must also be fully appreciated to minimize the chance of intraoperative vascular injury. Subfrontal approaches to the sella expose the carotid arteries and the anterior arc of the circle of Willis, as well as perforating branches from these major vessels. Vascular structures in the suprasellar area may be displaced by superior extensions of tumors, distorting normal anatomical relationships and making manipulation of these vessels extremely dangerous.^{12, 72, 90, 100}

The carotid artery emerges from the roof of the cavernous sinus positioned beneath the optic nerve and immediately gives off its ophthalmic branch, which turns into the optic canal on the underside of the nerve.⁶² The carotid turns back toward the posterior clinoid process, where it meets the posterior communicating artery and gives off the anterior cerebral artery.^{25, 94, 101, 102} This artery courses over the superior surface of the optic chiasm and gives off an anterior communicating branch to its contralateral counterpart. The length of this segment determines how tightly it is draped over the chiasm and any underlying tumor. Longer communicating arteries are generally related to the optic nerves rather than the chiasm.¹¹⁹ This anatomy must be fully identified in both midline and oblique transcranial subfrontal approaches. Surgeons employing these methods must carefully work around the optic nerves and chiasm and associated neurovascular structures while removing tumor from the sella and sphenoid.^{27, 28}

The carotid arteries are also at risk during transsphenoidal approaches to the sella. Their tortuous intracranial course carries them alongside the lateral margins of the sphenoid sinus.¹⁰¹ Here they are at risk when the anterior wall and mucosa of the sinus are dissected. The intracavernous segments of the arteries are susceptible to overly aggressive curettage of tumor from within the sphenoid or sella. This risk also applies to cavernous sinus injury without carotid artery involvement. The barriers between the lateral walls of the sella turcica and the medial boundaries of the cavernous sinuses are often negligible and therefore quite vulnerable to damage from dissecting instruments.^{26-28, 101, 102}

The nasal cavities

Pituitary surgeons must navigate the neurovascular anatomy of the anterior and middle cranial fossae in transcranial pituitary surgery as well as the length of the nasal septum in the transseptal transsphenoidal approach. The introduction of transnasal endoscopic pituitary surgery has further underscored the necessity for surgeons to become familiar with the relationships of the sella and pituitary gland to the bony, cartilaginous, and mucosal architecture of the nasal cavities and the paranasal sinuses.

During embryonic development, bilateral invaginations of ectoderm located superior to the opening of the mouth pass posteriorly through the mesoderm of the head to form the left and right nasal pits. These meet and fuse with the endoderm of the most cranial extension of the primitive foregut, creating a passageway from the external environment to the gut lumen. Thus connected, the nasal pits are referred to as the right and left nasal cavities and the part of involved foregut is called the nasopharynx.¹¹⁹ The common medial wall of each nasal cavity is the embryonic nasal septum and the floors of these cavities comprise the primary palate.^{9, 76, 103, 119}

Cartilage forms in the mesoderm of the roof of each nasal cavity and extends into the adjacent upper regions of the lateral walls and the septum. Connective tissue develops in the inferior lateral walls, inferior septum, and cavity floors. Bony deposition begins in ossification centers found throughout the cartilaginous and membranous portions of the nasal capsule.^{6, 70} The posterior and inferior parts of the nasal septum become ossified to form the perpendicular plate of the ethmoid and the vomer, respectively.⁴³ The crista galli—the superior extension of the perpendicular plate of the ethmoid—is also formed in this process.²⁴ The anterior extent of the septum remains cartilaginous. The roof of the nasal cavities ossifies around nerve fibers that communicate superiorly with the olfactory bulbs. The cribriform plate of the ethmoid is thereby formed, as previously discussed.

A "gap" in the deposition of cartilage in the lateral nasal cavity wall results in the hiatus semilunaris.^{6, 24, 87} In its mature form, it is identified as a depression in the lateral nasal wall at the level of the middle meatus. Cartilage formation resumes at the inferior aspect of this hiatus in the uncinate process, which invaginates to create the inferior turbinate. This in turn ossifies and runs nearly the entire anteroposterior distance of the nasal cavity. The remainder of the cartilage of the lateral wall ossifies to generate the ethmoid labyrinth.^{6, 24, 76, 87} As the paranasal air sinuses develop, the labyrinth is polarized into lateral and medial walls. The former makes up the medial wall of the orbit. The latter generates two additional invaginating bony processes. These are the precursors of the middle and inferior turbinates. Like the inferior turbinate, the middle spans nearly the entire length of the nasal cavity. The superior turbinate, however, is more limited in length and sits near the roof of the nasal cavity. The recesses created by the curvatures of the turbinates are referred to as meati; these are the sites of origin of the paranasal sinuses.^{24, 76, 87}

The mucous membranes lining the lateral nasal walls evaginate into the skeleton of the midface to create air pockets surrounded by bone.^{76, 87, 113} Posteriorly, the mucous membrane covering the anterior surface of the sphenoid bone pushes back to create the sphenoid sinus.⁷⁶ Formation of a thin bony septum divides the sinus into left and right cavities. While normally a midline structure, the nature of the septation may widely vary.¹⁰¹ The sphenoid sinus communicates with the nasal cavities via ostia that are anteriorly related to the spheno-ethmoid recesses behind the superior turbinates.¹⁰⁴ The mucous membranes of the superior meatus generate the posterior ethmoidal air cells while those of middle meatus contribute to the anterior ethmoidal air cells.^{6, 76, 87} The anterior ethmoidal air cells, frontal sinus, and maxillary sinus all communicate with the nasal cavity via the hiatus semilunaris.¹³

Not all of the cartilage of the external nose is ossified. The atrium is the intranasal space that lies anterior to the turbinates; it remains enclosed by cartilaginous walls after development is complete. That part of the anterior nasal cavity bounded by the alae of the nose is specifically referred to as the vestibule.

During endoscopic transnasal pituitary surgery, endoscopes are advanced into the vestibule to first identify the inferior turbinate and the anterior portion of the septum. As discussed above, the inferior and middle turbinates span almost the entire depth of the nasal cavity. Therefore, with slight superior and posterior advancement of the endoscope, the anterior limit of the middle turbinate comes into view. With further caudal progress, the remainder of the middle turbinate and the superior turbinate are appreciated. The goal of the intranasal portion of this procedure is to create a wide passage from the exterior to the sphenoid rostrum. The space of the middle meatus is therefore obliterated as the middle turbinate is outfractured. The sphenoid ostia may or may not be readily apparent until mucosa is dissected from the anterior surface of the body of the sphenoid. The superior and middle turbinates serve as valuable landmarks in identifying the approximate locations of the ostia until they are directly visualized.

Mucosal bleeding encountered intraoperatively may come from distal branches of either the internal or external carotid arteries.¹⁵ The maxillary branch of the external carotid artery feeds the sphenopalatine artery, which branches into posterior lateral nasal and posterior septal arteries. These ramify within the mucosa of the deep nasal cavities. As noted above, the anterior lateral nasal and anterior septal branches of the anterior ethmoidal artery provide rostral circulation. The posterior ethmoidal artery, although less constant in its anatomical course, also contributes to the posterior nasal vascular supply.^{15, 62}

Transcranial surgery of the pituitary gland

Indications

The majority of pituitary tumors, including those with parasellar and suprasellar extensions, can be successfully treated by microscopic transseptal or endoscopic transnasal approaches to the sella.^{28, 120, 121} These techniques are less invasive, less timely, and associated with fewer complications, as will be discussed below. They provide adequate exposure of the gland, even when tumor extends beyond the boundaries of the hypophyseal fossa. If tumor invasion of the middle or anterior cranial cavities is significant, however, transcranial approaches offer a greater chance of complete or near-complete tumor removal. Often a transcranial method will be reserved for the second stage of a two-stage operation.^{28, 121} The primary procedure is performed via microscopic or endoscopic exposure of the sella turcica in which the bulk of the tumor is removed transsphenoidally. Residual tumor is then targeted in a subsequent transcranial exploration.

The transcranial approach is well suited to the management of other lesions effecting the parasellar areas that tend to spread regionally. These include chordomas, craniopharyngiomas, meningiomas, and vascular lesions.^{34, 41, 82, 121}

Patient positioning

After the induction of general anesthesia and rotation of the patient so that the head is away from the anesthesiologist, the procedure begins. The patient is placed supine on the operating room table and the head of the bed is raised approximately 15 degrees. The position of the patient's head is determined by using the floor of the anterior cranial fossa as a guide to the surgical landmarks of the suprasellar area. In the midline subfrontal approach, the head is extended 30 degrees in a vertical plane toward the surgeon. At this angle the frontal lobes will fall back and the surgeon will have a direct path to the pituitary along the orbital plates of the frontal bone.^{27, 121} When adequate head position is achieved, the head is fixed in place with a three-pin horseshoe clamp.

The head is shaved from the hairline to the apex of the cranial vault and both the head and an area of the lower right quadrant of the abdominal wall are washed with aqueous iodine-based aseptic solution. The latter area is prepared in anticipation of intraoperative harvesting of an abdominal fat graft to fill the space of the sphenoid sinus once the tumor is removed.

Surgical technique

There are four variations upon the transcranial technique that remain in popular use. The midline subfrontal approach, the oblique subfrontal approach, the pterional approach, and the subtemporal approach. While the first two of these are still regularly used to reach pituitary tumors with extensive extrasellar involvement, the pterional and subtemporal methods are of greater benefit in the management of non-pituitary lesions that occur in the posterior parasellar areas.

Midline subfrontal approach

The midline subfrontal approach remains the most common method for transcranial pituitary surgery, as it affords a direct exposure of the optic nerves and carotid arteries while providing ready access to the hypophyseal stalk.¹²¹ A hemicoronal flap is developed on the ipsilateral side of the tumor in a subperiosteal plane superiorly and to the depth of the deep temporalis fascia laterally where the muscle overlies bone. The incision is carried from the level of the lateral canthus of the eye to just beyond the midline. The temporalis muscle is disinserted to reveal the juncture of the zygoma to the lateral orbital rim. A craniotomy is made based on burr holes placed at this site and in the midline at the level of the orbital roof.

With the bone flap removed, the dura is incised and the brain is lifted from the floor of the fossa. Throughout the procedure, retraction must be kept to a minimum, as postoperative swelling of the frontal lobe can be problematic.^{78, 121, 123} Avulsion of the olfactory nerve is also a significant operative risk, resulting in postoperative anosmia.^{35, 39, 116} Dissection is carried out along the midline with the crista galli and invested falx cerebri serving as initial landmarks. Proceeding posteriorly along the cribriform plate, the optic nerve is seen emerging from the optic canal. Once the ipsilateral optic nerve is revealed it should be fully exposed and used as a guide to expose the contralateral optic nerve and the optic chiasm. The anatomy of the anterior circle of Willis is further defined in this dissection. Once the neurovascular anatomy is fully detailed, the surgeon can work around the relevant structures to remove tumor from the sella.^{98, 99, 112, 121} An assortment of dissecting curettes are used to accomplish this.

In the case of a prefixed chiasm or large tuberculum sellae, direct access to the sella is impeded. If so, the tuberculum may be removed or drilled to gain entry into the sphenoid sinus below.⁹⁹ The anterior wall of the sella is then removed and resection of tumor progresses. A fat graft may be placed within the space of the sinus after tumor resection is complete.

Following the resection the dura is reapproximated to achieve a water-tight seal. If it is compromised during the initial craniotomy, the frontal sinus is cranialized by removal of its posterior wall and obliteration of the fronto-nasal duct. The craniotomy bone flap is replaced and affixed with microplates and screws, and the soft tissues of the scalp are tightly reapproximated. The patient is extubated at the end of the procedure and transferred to the intensive care unit. In addition to monitoring for potential sequelae specific to pituitary surgery (diabetes insipidus, visual field deficits, etc.) particular attention is paid to the development of signs indicative of frontal lobe edema in the postoperative period.

Oblique subfrontal approach

The oblique subfrontal approach is identical to the midline subfrontal approach in the development of scalp and bone flaps. It also proceeds along the floor of the anterior fossa to reach the suprasellar area. However, this is undertaken at an angle to the midline in order to allow less aggressive retraction of the frontal lobe and minimize the risk of postoperative anosmia.⁹⁹ Unfortunately, this lateral approach yields incomplete access to the sella turcica, making thorough removal or contralateral tumor more difficult. In addition, the surgeon is forced to work over the optic nerves, increasing the likelihood of a major complication. The beneficial decrease in frontal lobe retraction that this procedure offers must be carefully weighed against the added risks to the regional neurovascular structures it entails.

The pterional approach

The pterional approach is most often used in the management of lesions such as chordomas or meningiomas that, in addition to pituitary lesions, also may occupy the extrasellar space. Exposure in this approach may be widened through wide retraction of the sylvian fissure.^{10, 34, 82, 121} Excellent exposure of most of the clivus is achieved. However, retraction of the frontal lobe in this technique may also place the olfactory nerve at risk for avulsion.¹¹

The subtemporal approach

Finally, the subtemporal approach is conducted along the floor of the middle fossa via a temporal craniotomy and middle fossa craniectomy. The retrosellar area is exposed in this procedure, but only with heavy and potentially deleterious retraction of the temporal lobe. At risk as well are the neurovascular structures that traverse the floor of the middle fossa.^{41, 54, 112, 121} Its usefulness in light of other less morbid options is therefore limited.

Transseptal transsphenoidal microsurgical pituitary surgery

In current practice, transseptal transsphenoidal surgery closely resembles Cushing's originally described method.⁴⁵ The development of intraoperative fluoroscopy and microscopy approximately one half-century after his initial contributions enabled surgeons to more precisely localize and visualize critical structures during surgery.^{66, 129} Today the success of this operation is vitally dependent upon these imaging modalities.

Indications

This procedure is indicated in the surgical management of pituitary lesions causing endocrinopathies characterized by hypo- or hyperfunction of the gland that have not adequately responded to medical treatment, lesions interfering with the optical apparatus and causing visual disturbances, or lesions invading the cavernous sinus causing cranial nerve palsies. Micro- and macroadenomas are amenable to resection by this method, including those with mild supra- and parasellar extension.^{5, 45, 74, 93, 128, 129}

In tumor-induced hypopituitarism, compression of the normal pituitary gland and hypophyseal stalk interferes with the synthesis and release of pituitary hormones.^{1, 5, 45, 97} The resultant clinical syndromes require hormonal replacement therapy that is costly, wrought with deleterious side effects, and usually of lifelong duration. Surgical intervention may completely eliminate the need for exogenous administration of hormone and restore the pituitary axis.

If the tumor is productive of one or more of the pituitary hormones, the histological diagnosis can usually be made prior to surgery with the use of serum hormonal assays.^{4, 5, 19, 64, 83} The patient's signs and symptoms guide physicians in choosing which laboratory analyses to perform. Excessive secretion from lactotrophs, somatotrophs, or corticotropes results in galactorrhea/amenorrhea (females) and decreased sexual function and libido (males), gigantism, and Cushing's disease, respectively. Correlation between clinical and hormonal profiles are similarly used to diagnose tumors of thyrotrope and gonadotrope origin. When medical therapy of these conditions fails, surgical intervention is called for to remove the source of the problem.

Regardless of the functional status of the tumor, ophthalmoplegia and visual field deficits signal its extension beyond the confines of the sella turcica to involve the optic nerves or the cavernous sinuses.^{20, 128, 129} Evidence of an optical or visual defect is cause for concern and calls for urgent tumor resection to decompress the involved structures. Compression of the optic chiasm may cause a mild deficit or complete bitemporal hemianopsia. Tumor invasion into the cavernous sinus may generate a clinical picture that suggests involvement of one or more of the associated cranial nerves. Tumor anatomy, as documented by CT or MRI scans, usually correlates with the patient's presentation.^{5, 63, 83, 127}

Suprasellar extensions of macroadenomas will naturally descend into the sella turcica as the tumors are removed through the sphenoid sinus.^{45, 47, 128} This may be facilitated by Valsalva maneuvers conducted by the anesthesiologist, which transiently raise intracranial pressure and cause inferior displacement of the mass. Parasellar extensions of pituitary tumors, however, are more difficult to manage, as the lateral perspectives offered by the microscope are greatly limited. Given the proximity of the optic nerves, optic chiasm, carotid arteries, and cavernous sinuses to the sella, blind curettage of any tumor remnants extending beyond the limits of the sella is potentially catastrophic. Patients with extrasellar extension of the tumor into the anterior and middle cranial fossae must be considered for two-stage procedures. In these cases, a primary transsphenoidal procedure serves to debulk as much of the tumor as possible from below, while a secondary operation via one of the aforementioned transcranial approaches allows resection of tumor remnants.^{2, 27, 28, 96} Such improvisation allows complete surgical removal of extensive lesions with minimal morbidity.

Patient positioning and operating room setup

The patient is placed supine on the operating room table. Following induction of general anesthesia and endotracheal intubation, the bed is rotated such that the head is opposite the anesthesiologist, who uses tubing of extended length to maintain the respiratory circuit. The anesthesiologist secures the endotracheal tube in place at the corner of the mouth, leaving the opening of the oral cavity free of obstruction. An absorbent sponge is passed through the mouth into the posterior oropharynx to collect blood and mucous secretions that collect intraoperatively. This must be done attentively so as not to disturb the position of the endotracheal tube.

The head of the bed is raised to make a twenty-degree angle with the floor. The patient's head is placed in a carbon horseshoe three-pin clamp. The neck is extended while the head is tilted slightly to the left and rotated approximately fifteen degrees to the right, toward the surgeon. The head clamp is then securely fastened to the bed. In this position, with the microscope in place, the surgeon will be operating along a direct anteroposterior axis toward the pituitary gland.⁴⁷ The fluoroscopic image intensifier is positioned so that the beam is perpendicular to a sagittal plane through the sella turcica. The contours of the sphenoid sinus and sella turcica must occupy the center of the monitor, which is placed over the patient's right shoulder. The surgeon need therefore only make a slight adjustment in position to view the fluoroscopic image while working under the microscope. Although fluoroscopy is only selectively necessary throughout the procedure, it must be readily and unobtrusively available.

With the patient thus positioned, attention is turned to preparing the surgical site. An aqueous antibacterial solution is applied to the nose and face and the upper gingival mucosa. Cotton-tipped applicators that have been soaked in the solution are placed in the nares. The upper gums are infiltrated with a solution of 1% lidocaine containing epinephrine (1:100,000). This maneuver both lifts the buccal mucosa off of the premaxilla and limits the amount of intraoperative bleeding from the oral incision site. A site on the lower right quadrant of the abdomen is also prepared with antibiotic scrub solution and draped with sterile towels. A fat graft is harvested from this site during the procedure. It is used to pack the sella and sphenoid sinus following extirpation of the tumor. An alternative site for fat harvesting is the periumbilicus, where the resultant scar is more discrete. The lateral thigh may also be used by surgeons who prefer muscle and fascia as graft substrates.¹³² The face is draped so that only the nose and upper lip remain uncovered. Following the administration of antibiotics, the procedure begins.

Surgical technique

While the upper lip is retracted by an assistant, an upper buccal sulcus incision is extended between the molar roots. The incision is carried down to the periosteum of the premaxilla. Appropriate placement of the incision is extremely important, as enough soft tissue must be left above the teeth to allow for adequate closure. However, if the incision is made too far above the cleft of the sulcus, scar contracture may lead to complaints of lip tightness as well as aesthetic changes in the appearance of teeth and gums during smiling. The soft tissues are elevated from the bone to reveal the anterior nasal spine centrally and the pyriform apertures bilaterally. The former may be removed using a rongeur and the apertures may be enlarged to facilitate visualization.

The anterior nasal spine is followed superiorly to the anteroinferior border of the septal cartilage. Once this is identified, attention is turned to the development of mucoperichondrial and mucoperiosteal flaps. An elevator is used to free the septal mucosa bilaterally from the level of the nasal spine to a point above the attachment of the cartilaginous septum to the maxillary crest. This dissection is continued caudally along the entire face of the septum on one side until the articulation of the septum with the perpendicular plate of the ethmoid bone is reached. Elevators are also used to lift the mucosa from the floor of both nasal cavities. On the side of the septum from which the surgeon will approach the sella, the inferior mucoperiosteal flap is joined to the septal flap to create a large submucosal tunnel. The choice of side depends upon the observed septal architecture. The preferred nasal cavity through which a right-handed surgeon should operate is the left. Alterations in this plan may be required in the event of significant septal deviation.^{34, 124} The integrity of the mucosa is maintained during this dissection and the nares are not violated. Bleeding from distal septal branches of the sphenopalatine artery may be controlled by packing the submucosal spaces with strips of dense cotton sponges.

Once the interface between septal cartilage and ethmoid bone is identified, the base of the septum is gently liberated from the maxillary crest and retracted to the side opposite the developed rhinoseptal submucosal tunnel. The posterior edge of the septum is cut with a swivel knife to facilitate this maneuver. However, the superior attachments of the septum to the ethmoid bone and lateral nasal cartilages are left intact. Separation of these attachments leads to a loss of projection of the nasal tip and must be avoided.^{67, 110} The inferior part of the perpendicular plate of the ethmoid bone is then removed and preserved in saline for later use in reconstruction of the floor of the sella. Submucosal dissection is again continued until the vomer comes into view.

Until this point, dissection is performed under direct vision with the aid of magnifying loupes and a headlamp. Following the removal of the perpendicular plate of the ethmoid and identification of the vomer, however, microscopic dissection begins. First an adjustable bivalve retractor is placed into the nasal cavity. Its blades are advanced to the rostrum of the sphenoid bone and are positioned so that they retract the mucosal flaps off of this surface. Excessive retraction of the blades should be avoided, as fractures to the bony nasal walls, the pyriform apertures, the pterygoid plates, or the palate may result. All subsequent operative maneuvers are conducted through the space between the blades of this retractor.

The vomer is removed with the use of a rongeur and the rostral surface of the sphenoid bone is exposed. Using the sphenoid ostia as reference points, the anterior wall of the sphenoid sinus is resected using a combination of rongeurs and graspers. Subsequent examination of the sella is entirely dependent upon this exposure. Caution must be used at the lateral boundaries of the sphenoid where the carotid arteries ascend. Additionally, superior dissection must be guarded as injury to the cribriform plate introduces the likelihood of a subsequent cerebrospinal fluid leak.^{87, 126}

The anatomy of the sphenoid sinus will depend on the age of the patient as well as the pituitary pathology.⁴⁷ It may be non-aerated in pediatric patients, multi-septated, or completely filled with tumor that has invaded through the floor of the sella. Imaging studies provide useful clues to its anatomy prior to surgery. Once the sphenoid is completely exposed, its mucosal lining is stripped to minimize the risk of postoperative mucocele.³⁴ The posterior wall of the sinus, which makes up the floor of the sella turcica, is immediately recognizable. Usually, with benign adenomas, the floor of the sella is intact. However, the bony border between the pituitary gland and the sphenoid may be thinned, fractured, or even completely obliterated by expanding tumor.^{34, 128} In the most common instance of an intact sella, however, the bone must be resected to provide access to the gland.

The first step in accomplishing this is to carefully fracture the floor of the sella using an osteotome. Once a bone flap is removed, rongeurs can be inserted in the space between bone and dura and remove the remainder of the floor in a piecemeal manner. Maximal exposure of the gland is only achieved with thorough removal of bone. Again, as in dissection of the wall of the sphenoid, serious consideration must be given to surrounding structures, including the carotid arteries and cavernous sinuses laterally and the optic nerves and chiasm superiorly.³⁴

Deep to the floor of the sella is the dura, identifiable by its azure hue. The dura must be incised to gain access to the pituitary gland and tumor. A sharp hook or blade is used to make a cruciate incision. Through this incision ring curettes of different diameters and spatial orientation are introduced to resect of tumor.

The appearance and consistency of tumor tissue is determined by several variables. Histology type, preoperative therapies (e.g., radiation), tumor age, and other variables (e.g., hemorrhage) can all potentially effect tumor phenotype.⁸⁸ A high quality contrast-enhanced MRI scan of the pituitary gland helps the surgeon differentiate between normal and abnormal tissue. The MRI should allow the surgeon to identify the presence of the hypophyseal stalk and normal pituitary gland as well as the mass effect of the tumor on the gland's position.^{3, 63, 83, 117, 127} Knowledge of the quadrant in the sella where the normal gland is located must be incorporated into the surgical plan. The histology of tissue of questionable appearance near surgical margins can be confirmed via intraoperative frozen section pathological analysis.

Resection of tumor is carried out until all grossly identifiable parts of the lesion are removed. As the sella is emptied of tumor, the boundaries of normal pituitary gland are identified, as are the diaphragma sellae, arachnoid, and optic chiasm. Supra- and parasellar extensions of tumor must be approached cautiously. The locations of dissecting curettes placed into the supra- and parasellar spaces can be confirmed fluoroscopically by using the bony parasellar structures as radiographic landmarks.⁴⁵ Extreme care must be taken to avoid the cavernous sinuses, carotid arteries, or optic chiasm, as dire complications may ensue if these are damaged. Similarly, trauma to the arachnoid membrane increases the risk of damage to neural structures and of postoperative cerebrospinal fluid leak.¹²⁸ Preoperative radiological studies should be available for intraoperative review; as the surgical "roadmaps" they help the surgeon define relevant anatomical relationships at the time of surgery.

While the surgeon is conducting a final survey of the operative site for any remaining fragments of tumor, an assistant harvests a fat graft from the abdomen or a graft of muscle and fascia from the lateral thigh. There are several models of graft design,^{20, 33, 67, 68, 88, 129} but each has as a common goal prevention of subsequent leakage of cerebrospinal fluid. A fragment of the perpendicular plate of the ethmoid bone or a piece of septal cartilage may be used as supportive struts in the reconstruction of the floor of the sella, in conjunction with either fat, muscle, fascia, or synthetic material.^{20, 128, 129} In most cases, however, a simple fat graft that plugs the hole in the floor of the sella and obliterates the space of the sphenoid sinus will suffice.¹²⁸ The graft is held in place by a fibrin-based sealant, which is liberally applied around the graft in liquid form. Within seconds it congeals into a firm gelatinous matrix.

With the graft in place, the retractor is removed, the septum and mucosal flaps are repositioned, and the gingival incision is reapproximated using absorbable sutures. Both nares are packed with Vaseline-impregnated gauze strips. This packing remains in place for up to 48 hours postoperatively, absorbing any draining fluid and providing structural support to the nose as it heals internally.

Postoperative monitoring

Following the operation, the patient is extubated and taken to the intensive care unit for overnight monitoring. Medical staff specifically look for evidence of developing neurological impairment, visual field deficits, cerebrospinal fluid leak, or diabetes insipidus. Barring any such complications, the patient is transferred to the ward on the day following surgery and is generally transferred home within 72 hours.

Follow-up is dependent upon the nature of the tumor and extent of resection, and should always be planned in concert with the referring endocrinologist.

Outcomes

Outcomes of microscopic transsphenoidal pituitary surgery are measured along several lines, first and foremost of which are complications related to surgery. Mortality rates are low, generally occurring at a rate of less than 1 percent.^{20, 33, 74} Morbidities arise from damage to neurovascular structures in or proximal to the surgical field. These include both the anterior and posterior lobes of the normal pituitary gland, optic chiasm, cavernous sinuses, and carotid arteries. Damage to these structures can in general be entirely avoided with scrupulous and meticulous surgical technique.

The most common complication of this procedure is cerebrospinal fluid leak, occurring in approximately 1-3 percent of patients.^{20, 33, 122, 129} When tumor involves the diaphragma sellae it should be included in the margins of resection. Doing so unfortunately increases the likelihood of a cerebrospinal fluid leak; intraoperative manifestations of this may become apparent immediately after the diaphragma is removed. In such cases, thorough packing of the sella and sphenoid sinus is paramount. Persistent leaks may be treated by placement of a lumbar drain^{33, 128, 129} or, when more aggressive intervention is required, by re-exploration and packing of the sphenoid and sella.^{20, 95, 132}

The next most common type of complication is related to glandular injury. Damage to the posterior lobe results in diabetes insipidus of either a transient or permanent nature.^{33, 88, 129} Administration of desmopressin acetate (DDAVP) is the indicated treatment. Treatment of anterior pituitary failure depends upon the postoperative pituitary deficiencies that are observed, but in majority of cases requires exogenous steroid delivery perioperatively.^{33, 88} Again, a well-devised surgical plan and careful surgical technique, including the use of intraoperative frozen pathology to aid in the demarcation of surgical margins, should enable surgeons to resect tumor while leaving normal gland behind.

Outcome measures used to evaluate surgical efficacy most commonly include clinical parameters such as improvement in preoperative visual deficits and improvement in endocrine function. A review of clinical series indicates that, on average, visual disturbances are improved in approximately 80 percent of cases.^{20, 74, 129} Reported rates of normalization of endocrine function vary widely, ranging from 50 to 90 percent,^{5, 20, 74, 122, 129} depending upon tumor size and histology, the hormonal parameters studied and the criteria used in analysis.

Fully endoscopic pituitary surgery

The design of endoscopes has been revolutionized over the past several decades, leaving us with endoscopes of varying lengths, diameters, and directions of view. In turn, sophisticated light sources, video cameras, digital processors, and lens cleansing and irrigation systems have been developed.⁸¹ The availability of this equipment, without which this procedure cannot be performed safely or effectively, has made the next step in the evolution of pituitary surgery possible.

Indications

Indications for fully endoscopic pituitary surgery are identical to those for the traditional transseptal transsphenoidal microscopic approach, including the surgical management of productive and non-productive pituitary micro- and macroadenomas that either fail medical management or cause visual or cranial nerve deficits.^58-61 Additional indications for this procedure stem from its minimally invasive nature. Because the fully endoscopic approach to the sella and pituitary is less invasive than transseptal microscopic surgery, there are instances in which it should be considered as the first line of surgical therapy. A minimally invasive technique provides a distinct benefit over traditional methods in terms of operating time, perioperative morbidity, and recovery for biopsies of intrasellar lesions, pediatric patients, and patients with pituitary tumors whose medical histories put them at greater risk for complications of general anesthesia.

Instruments

Endoscopes

The rod lens design of endoscopes, first introduced in the 1960s by English physicist H. H. Hopkins,^{31, 77} provided the basis for the future manufacture of endoscopes and continues to set the standard for the industry. By integrating a series of lens systems within the rod, the endoscope could be lengthened and could yield an image of unparalleled depth and resolution.^{31, 77} The development of endoscopes of varying directions of view has provided for visualization of structures previously hidden from the direct anteroposterior imaging capability of the microscope. Zero, 30, 70, and 120 degree endoscopes offer panoramic perspectives of structures once completely obscured by anatomical "corners." Scopes of different diameters (4.0-mm and 2.7-mm) also provide valuable options to the surgeon faced with variations in surgical anatomy.⁸¹

Light sources

Illumination of tungsten halogen, metal halide, or xenon arc origin is generated by a light source and transmitted to the telescope via a fiberoptic cable. Light then travels along the length of the telescope—also fiberoptically—to illuminate the surgical field.^{31, 77, 81} The different types of devices offer light of varying brightness and whiteness and also offer hardware in a range of prices and sizes.

Cameras

Hopkins rod telescopes are manufactured with standard eyepieces through which the endoscopic image can be directly viewed or to which video cameras can be attached. The image can then be projected onto one or several monitors or electronically processed and recorded. Three-chip cameras contain individual chips for each of the primary colors. These produce the highest quality images and feature automatic control over color, exposure, white balance, and digital contrast enhancement. Single-chip cameras, while less expensive and offering fewer options, also produce high quality images that are more than adequate for the operating room.^{31, 81}

Other devices geared toward improving the quality and flexibility of the images derived from the endoscope are regularly appearing on the market. Devices that digitally process the video image allow detail enhancement and image manipulation. Video processing systems have also made "picture-in-picture" viewing--simultaneous viewing of endoscopic and microscopic images on one monitor—possible.^{92, 125} All of these options contribute to the great versatility of endoscopy as a surgical tool and make it easily adaptable to highly specialized and intricate procedures.

Holding arms

Bimanual operating is a necessity in endoscopic pituitary surgery. Multiple instruments are needed during the intranasal approach to the gland and during resection of the tumor. The development of different models of holding arms has obviated the need for surgeons to dedicate one hand to wield the camera, freeing both hands for operating.

In general, holding arms must be sturdy, stable, and adjustable. They must be able to hold the endoscopes securely in place but must allow the surgeon to manipulate them at will and with ease. Originally derived from existing surgical instruments adapted to a new applications, early designs combined long metallic rods at movable joints and placed clamps on each end: one to grip the operating table and the other to hold the endoscope. The latest generation of holding arms is designed to work using ball bearing joints that are pneumatically powered. These devices are remarkably flexible and extremely reliable.

Irrigation sheaths

Invariably, blood, debris, mucous, and mist will cover the lens of the endoscope during operation and obscure the image. Without a device to clean the surface of the lens in situ, the entire endoscope must be removed from the nasal cavity, wiped clean, and replaced. This must be repeated as many times as necessary to maintain a clear image.

Irrigation sheaths are available in different diameters to accommodate different sized endoscopes. They are connected to a reservoir of sterile saline via tubing that threads through a motorized pedal-activated gear system. Upon demand, the sheath delivers a cleansing stream of saline over the tip of the endoscope. This is immediately followed by a brief period of suction whereby any remaining drops of saline that would otherwise blur the resolution of the image are removed from the lens. With this system in place, continuity of the procedure is guaranteed.

Positioning and operating room setup

Patient positioning in the fully endoscopic procedure is similar to that used in the traditional transseptal transsphenoidal microscopic technique. However, the addition of the endoscopic tower must be considered when organizing the operating room. (The viewing monitor sits atop a movable "tower." The tower combines the camera, light source, and video recording and processing equipment in a single unit.)

The patient is placed supine with the head of the bed raised, the neck extended, and the head rotated and fixed in position with a carbon horseshoe three-pin clamp. Thus situated, the operating instruments and imaging hardware are positioned appropriately. The C-arm fluoroscopy image intensifier is brought to the head of the table and rotated so that the trajectory of the beam yields centrally positioned sphenoid and pituitary contours on the fluoroscopy monitor. Next, the endoscopic tower is placed over the patient's left shoulder, directly in the line of vision of the surgeon, while the fluoroscopy monitor is placed over the patient's right shoulder. This setup provides the surgeon with an unobstructed view of the visual information provided by the endoscope and ready access to real-time and still fluoroscopic imaging. Because the surgeon is not looking down into the eyepieces of a microscope, and instead directly forward at the video screen, proper alignment of these components is essential to keeping the surgeon oriented to a surgical plane that is perpendicular to the sphenoid rostrum.

Finally, an endoscope holding arm is affixed to the bed on the side opposite the surgeon and wrapped in a sterile drape. The arm reaches over the patient's upper body and the grasping end rests above the patient's nose. Its orientation can be adjusted to alter the position of the endoscope as necessary.

This standard of positioning is appropriate for all cases where the operation is conducted through the patient's right nostril. As the surgeon stands to the patient's right, use of the right nostril creates a natural axis along which the long, slender endoscopes and surgical instruments can be used comfortably and effectively. The extension and rotation of the patient's neck provides for easy intranasal access to the sphenoid sinus as well as the bilateral cavernous sinuses and suprasellar areas. A left-sided approach, by comparison, should be considered in patients with significantly deviated nasal septa that effectively obliterate the working space of the right naris, or those with histories of right-sided sinus surgeries or structural abnormalities.^{16, 60}

The face, nares, and abdomen or thigh are prepared with antibacterial surgical scrub, as in the transseptal transsphenoidal technique. Some authors^{49, 58, 105, 108} support the use of intranasal epinephrine- or cocaine-soaked sponges in order to obtain mucosal vasospasm. Sterile towels are used to cover the face, leaving only the nose exposed during surgery. After the intravenous administration of a third-generation cephalosporin for surgical prophylaxis, the operation is begun.

Surgical technique

The first step in the endoscopic procedure is to choose the appropriate endoscope. The initial dissection is invariably performed with a 0 degree lens, but the diameter of the scope may vary. The advantages of the 4.0-mm endoscope over the 2.7-mm include higher resolution of the image and better illumination of the surgical field. The 4.0-mm endoscope, however, occupies a significantly greater amount of space in a region that is already confined. Preoperative physical examination of the nasal passages provides the surgeon with an idea of which will be more appropriate. Nevertheless, nasal passages that may initially appear sufficiently large may front a deeper surgical anatomy that precludes the advancement of multiple surgical instruments alongside a 4-mm endoscope. The surgeon must have scopes of both diameters available and must be able to improvise intraoperatively, depending upon the intranasal and skull base anatomy of the patient.

Furthermore, every endoscope must be fitted with an irrigation sheath prior to use. As described above, these sheaths bathe the endoscope lenses with streams of saline when they become clouded with blood or debris. Operation without a properly functioning lens irrigation system is extremely difficult, as the redundant removal and replacement of endoscopes for cleaning is both tedious to the surgeon and hazardous to the patient.

When the appropriate endoscope is chosen, it is attached to the grasping end of the holder, advanced into the right naris, and used to conduct a brief survey of the anterior nasal vestibule. The middle turbinate and the architecture of the nasal septum are identified. As the ultimate target of the endoscope is the sphenoid ostium, the goal of the intranasal portion of the procedure is to create a passage to the ostium that is wide enough to accommodate the endoscope and accompanying instruments. This goal can be achieved rapidly, but should be meticulously and atraumatically performed, as bleeding from traumatized mucosa anteriorly can obscure visualization throughout the procedure posteriorly.

The endoscope is advanced to the anteroinferior border of the middle turbinate. An elevator is passed under the shaft of the endoscope until it is visualized on the monitor. A long straight suction device may also be introduced to clear the naris of any blood or mucoid secretions that accumulate during the subsequent steps. The elevator is placed flatly against the surface of the septum and firm, sustained pressure is applied in a medial direction. The spongy septal mucosa is flattened and the underlying cartilage is moved. The elastic nature of the cartilage gives it a tendency to recoil to its native position following each thrust. The maneuver is therefore repeated along the entire face of the septum until it yields and is definitively displaced. The elevator is then carefully rotated intranasally and a similar force is applied to the middle turbinate in a lateral direction. The fragile skeleton of the middle nasal turbinate will often crack as it yields, but fracturing the bone is not explicitly necessary. As the nasal passage is widened, the holding arm is released and the endoscope advanced further posteriorly, where medial and lateral displacement of the septum and turbinate continues. Ultimately, the posterior nasopharyngeal wall and the right sphenoid ostium are revealed, marking the caudal extent of the intranasal dissection. This is confirmed radiographically by passage of a long suction tip through the nostril into the nasopharynx. Placement of the metallic tip against the bony contour of the anterior wall of the sphenoid sinus is confirmed fluoroscopically.

The sphenoid ostium is often difficult to detect. This may be due to a diminutive size or to mucosal inflammation. However, fluoroscopic identification of surgical instruments against the anterior wall of the sphenoid sinus serves as an adequate test of localization. Some authors have described alternative localization techniques, including the employment of various imaging modalities and frame-based stereotactically guided methods.^{8, 29, 42}

The mucosal lining of the anterior wall of the sphenoid sinus must be dissected before the sinus can be entered. The mucosa is cauterized with a combination suction-cautery device and then lifted from the surface of the bone using an elevator. This dissection is carried out bilaterally to expose both sphenoid ostia and to the superior and inferior limits of the anterior sphenoid, as defined by the cribriform plate and vomer, respectively. Again, fluoroscopic examination of the bony contours of these structures confirms these limits. The vomer may be removed with a rongeur to more completely expose the surface of the sphenoid bone.

Endoscopic resection of the rostral surface of the sphenoid, the mucosal lining of the sinus, and the floor of the sella proceeds as described above for the microscopic transseptal procedure. The holding arm is released and the endoscope is advanced further toward the pituitary with each subsequent step. The same rongeurs, graspers, and osteotomes are passed through the nostril, below the shaft of the endoscope, and into the surgical field to gain access to the sphenoid sinus and sella turcica. Similarly, the same principles of awareness for the limits of dissection apply.⁵⁷ Under endoscopic imaging, the distal recesses of the sphenoid sinus are better visualized. However, injuries to the cavernous sinuses, carotid arteries, optic nerves and chiasm, and cribriform plate are still possible if caution is not exercised while working within the sinus or sella.

When the sphenoid sinus is completely exposed, the endoscope is advanced into the cavity. There it remains until the majority of tumor resection is completed. The floor of the sella, if intact, is fractured and removed to reveal the dural covering of the pituitary gland. Incision of the dura and removal of tumor is conducted as previously described, using suction and ring curettes of varying diameters and orientations. Consideration must be given to the displacement of the normal gland by tumor as observed on MRI scans. Valsalva maneuvers are implemented in the attempt to deliver suprasellar extensions of tumor into the sella.⁶⁰

Until this point all procedures are carried out under the 0º endoscope. Its lens provides near complete exposure of the sella turcica and a partial view of the suprasellar structures, including the optic chiasm and the arachnoid membrane investing the median eminence. This panorama is remarkably more comprehensive than the microscopic view of the same region.¹¹⁵ However, the extent of visualization under this scope is limited by its optical capabilities. Therefore, once tumor resection under the 0º endoscope is deemed complete, it is replaced with a 30º endoscope. By advancing the 30º scope into the sella turcica and then rotating it in clockwise and counterclockwise directions about the anteroposterior axis, the parasellar and suprasellar areas are thoroughly visualized.^{60, 61} This maneuver reveals the strength of the endoscope in pituitary surgery: areas that are not revealed during microscopic examination are directly exposed. Tumor remnants in these areas are removed and sources of potential tumor recurrence are thereby eliminated. All of this is accomplished with a superb visual appreciation of the critical surrounding structures.

A 70º endoscope may also be implemented in this examination. However, the information obtained under a 30º lens is in most cases sufficient to identify any remaining tumor fragments. (While available to the surgeon, the 120º endoscope adds little to this application. Due to its viewing angle, its progress cannot be directly viewed as it is passed through the nostril. This blind insertion and advancement poses a significant threat to the patient and therefore severely limits the usefulness of this particular endoscope in this procedure.)

Tumor resection is considered to be complete only after examination with the angled endoscopes is performed and all residual tumor removed. A fat graft from the abdomen or a graft of muscle and fascia lata from the lateral thigh is harvested and used to reconstruct the floor of the sella and fill the sphenoid sinus.^{16, 49, 58-61, 108} Fibrin sealant is also used to secure its position.

With no mucoperichondrial or mucoperiosteal dissection to speak of, the need for postoperative nasal packings is eliminated.^{16, 58, 105} A thin sheet of Telfa absorbent sponge material is placed loosely in the nasal vestibule to collect residual secretions from the naris. A small gauze sponge fastened beneath the nose (a "mustache" dressing) serves a similar purpose. Both of these are extremely well tolerated by patients and are removed the morning following surgery.

Postoperative monitoring

The patient is extubated in the operating room and observed in the intensive care unit overnight. Again, particular attention is paid to the development of any neurological sequelae, alterations in vision, evidence of rhinorrhea, or signs of diabetes insipidus. In the absence of any such problems, patients are moved out of the I.C.U. the day after surgery and may be discharged home on the same or following day.

Outcomes

Because this procedure is relatively new, the amount of data generated by centers using this technique to perform pituitary tumor resection must increase before meaningful comparisons to the microscopic technique can be drawn. However, some general statements and preliminary conclusions can be made. As in the microscopic technique, complications in the fully endoscopic procedure can be almost be completely be avoided with careful technique. Incidence of morbidity is related to injuries to the normal gland or to surrounding neurovascular structures.

Preliminary evidence suggests that complication rates and surgical outcomes compare favorably to those that have been reported in large series of transseptal transsphenoidal microscopic pituitary surgeries.^{16, 49, 58, 60} More extensive data over longer follow-up is required to substantiate these early trends. However, it is currently clear that transnasal endoscopic pituitary surgery does offer a minimally invasive and effective means of addressing pituitary lesions requiring surgical intervention.

References

1. Abboud CF. Anterior pituitary failure. In Melmed S (ed): The Pituitary, 1^st edition, pp 341-410. Cambridge, Blackwell Scientific, Inc., 1995.
2. Abe T, Iwata T, Kawamura N, et al. Staged transsphenoidal surgery for fibrous nonfunctioning pituitary adenomas with suprasellar extension. Neurol Med Chir (Tokyo) 1997;37(11):830-5.
3. Ahmadi H, Larsson EM, Jinkins JR. Normal pituitary gland: coronal MR imaging of infundibular tilt. Radiology 1990;177(2):389-92.
4. Annegers JF, Coulam CB, Abboud CF, et al. Pituitary adenoma in Olmsted County, Minnesota, 1935-1977. A report of an increasing incidence of diagnosis in women of childbearing age.Mayo Clin Proc1978;53(10):641-3.
5. Aron DC. Tyrrell JB. Wilson CB. Pituitary tumors. Current concepts in diagnosis and management. West J Med 1995;162(4):340-52.
6. Arredondo de Arreola G, Lopez Serna N, de Hoyos Parra R, et al. Morphogenesis of the lateral nasal wall from 6 to 36 weeks. Otolaryngol Head Neck Surg 1996;114(1):54-60.
7. Asano T, Ohno K, Takada Y, et al. Fractures of the floor of the anterior cranial fossa. J Trauma 1995;39(4):702-6.
8. Auer LM. Ultrasound stereotaxic endoscopy in neurosurgery. Acta Neurochir Suppl (Wien) 2;54:34-41.
9. Avery JA (ed): Oral Development and Histology, 1^st ed. Los Angeles, Williams & Wilkins, 1987.
10. Aydin IH, Tuzun Y, Takci E, et al. The anatomical variations of sylvian veins and cisterns. Min Invas Neurosurg 1997;40(2):68-73.
11. Aydin IH, Kadioglu HH, Tuzun Y, et al. Postoperative anosmia after anterior communicating artery aneurysms surgery by the pterional approach. Min Invas Neurosurg 1996;39(3):71-3.
12. Batjer HH, Kopitnik TA, Giller CA, et al. Surgery for paraclinoidal carotid artery aneurysms. J Neurosurg 1994;80(4):650-8.
13. Becker SP. Anatomy for endoscopic sinus surgery. Otolaryngol Clin N Am 1989;22(4):677-82.
14. Belden CJ, Mancuso AA, Kotzur IM. The developing anterior skull base: CT appearance from birth to 2 years of age. AJNR 1997;18(5):811-8.
15. Caliot P, Plessis JL, Midy D, et al. The intraorbital arrangement of the anterior and posterior ethmoidal foramina. Surg Radiol Anat 1995;17(1):29-33.
16. Cappabianca P, Alfieri A, de Divitiis E. Endoscopic endonasal transsphenoidal approach to the sella: towards functional endoscopic pituitary surgery (FEPS). Min Invas Neurosurg 1998;41(2):66-73.
17. Carrau RL, Jho HD, Ko Y. Transnasal-transsphenoidal endoscopic surgery of the pituitary gland. Laryngoscope 1996;106(7):914-8.
18. Caton R, Paul FT. A case of acromegaly treated by operation. Br Med J 1893;2:1421-1423.
19. Chang-DeMoranville BM, Jackson IM. Diagnosis and endocrine testing in acromegaly. Endocrinol Metab Clin North Am 1992;21(3):649-68.
20. Ciric I, Mikhael M, Stafford T, et al. Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results. J Neurosurg 1983;59(3):395-401.
21. Cope VZ. The pituitary fossa, and the methods of surgical approach thereto. Br J Surg 1916;4:107-144.
22. Cushing H. Disorders of the pituitary gland. Retrospective and prophetic. JAMA 1921;76(25):1721-1726.
23. Cushing H. Surgical experiences with pituitary disorders. JAMA 1914;63(18):1515-1525.
24. Davis WE, Templer J, Parsons DS. Anatomy of the paranasal sinuses. Otolaryngol Clin N Am 1996;29(1):57-74.
25. De Jesus O. The clinoidal space: anatomical review and surgical implications. Acta Neurochir (Wien) 1997;139(4):361-5.
26. Dietemann JL, Kehrli P, Maillot C, et al. Is there a dural wall between the cavernous sinus and the pituitary fossa? Anatomical and MRI findings. Neuroradiology 1998;40(10):627-30.
27. Dolenc VV. Surgery of tumors originating in or invading the cavernous sinus. In Long DM (ed): Surgery for Skull-Base Tumors, 1^st edition, pp 211-221. Boston, Blackwell Scientific Publications, 1992.
28. Dolenc VV. Transcranial epidural approach to pituitary tumors extending beyond the sella. Neurosurgery 1997;41(3):542-50.
29. Dorward NL, Alberti O, Zhao J, et al. Interactive image-guided neuroendoscopy: development and early clinical experience. Min Invas Neurosurg 1998;41(1):31-4.
30. Dott NM, Bailey P, Cushing H. A consideration of the hypophyseal adenomata. Br J Surg 1925;13:314-365.
31. Eaves FF 3^rd, Bostwick J 3^rd, Nahai F, Instrumentation and setup for endoscopic plastic surgery. Clin Plast Surg 1995;22(4):591-603.
32. Elster AD. Modern imaging of the pituitary. Radiology 1993;187(1):1-14.
33. Fahlbusch R, Buchfelder M. The transsphenoidal approach to invasive sellar and clival lesions. In Sekhar LN, Janecka IP (eds): Surgery of Cranial Base Tumors, 1^st edition, pp 337-349. New York, Raven Press, 1993.
34. Fahlbusch R, Honegger J, Paulus W, et al. Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 1999;90(2):237-50.
35. Favre JJ, Chaffanjon P, Passagia JG, et al. Blood supply of the olfactory nerve. Meningeal relationships and surgical relevance. Surg Radiol Anat 1995;17(2):133-8.
36. Ferreri AJ, Garrido SA, Markarian MG, et al. Relationship between the development of diaphragma sellae and the morphology of the sella turcica and its content. Surg Radiol Anat 1992;14(3):233-9.
37. FitzPatrick M, Tartaglino LM, Hollander MD, et al. Imaging of sellar and parasellar pathology. Radiol Clin N Am 1999;37(1):101-21.
38. Friede H. Normal development and growth of the human neurocranium and cranial base. Scand J Plast Reconstr Surg 1981;15(3):163-9.
39. Fukuta K, Saito K, Takahashi M, et al. Surgical approach to midline skull base tumors with olfactory preservation. Plast Reconstr Surg 1997;100(2):318-25.
40. Gamea A et al: The use of the rigid endoscope in transsphenoidal pituitary surgery. J Laryngol Otol 1994;108:19-22.
41. Goel A. Middle fossa sub-Gasserian ganglion approach to clivus chordomas. Acta Neurochir (Wien) 1995;136(3-4):212-6.
42. Goodman RR. Magnetic resonance imaging-directed stereotactic endoscopic third ventriculostomy.Neurosurgery1993;32(6):1043-7.
43. Gruber R, Lesavoy M. Closed septal osteotomy. Ann Plast Surg 1998;40(3):283-6.
44. Hardy J: La chirurgie de l'hypophyse par voie transsphénoïdale. Union Med Can 1967;96:702-712.
45. Hardy J. Trans-sphenoidal approach to the pituitary gland. In Wilkins RH, Rengachary SS (eds): Neurosurgery, 2^nd Edition, vol I, pp 1375-1384. New York, McGraw-Hill, 1996.
46. Hardy J. Transsphenoidal hypophysectomy. J Neurosurg 1971;34:582-594.
47. Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1969;16:185-217.
48. Hardy J, Wisger SM. Transsphenoidal surgery of pituitary fossa tumors with televised radiofluoroscopic control. J Neurosurg 1965;23:612-620.
49. Heilman CB, Shucart WA, Rebeiz EE. Endoscopic sphenoidotomy approach to the sella. Neurosurgery 1997;41(3):602-7.
50. Helal MZ: Combined micro-endoscopic trans-sphenoid excisions of pituitary microadenomas. Eur Arch Otorhinolaryngol 1995;252:186-189
51. Henderson WR. The pituitary adenomata. Br J Surg 1939;26:811-921.
52. Heuer GJ. The surgical approach and treatment of tumors and other lesions about the optic chiasm. Surg Gynecol Obstet 1931;53:489-518.
53. Hirsch O. Pituitary tumors. A borderland between cranial and trans-sphenoidal surgery. N Engl J Med 1956;254(20):937-939.
54. Holliday MJ. Lateral subtemporal approach to the management of sphenoid and temporal-infratemporal fossa lesions. In Long DM (ed): Surgery for Skull-Base Tumors, 1^st edition, pp 191-203. Boston, Blackwell Scientific Publications, 1992.
55. Horsley V. On the techniques of operations on the central nervous system. Br Med J 1906;2:411-423.
56. Ikeda K, Watanabe K, Suzuki H, et al. Nasal airway resistance and olfactory acuity following transsphenoidal pituitary surgery.Am J Rhinol1999;13(1):45-8.
57. Jankowski R, Auque J, Simon C, et al. Wayoff M. Endoscopic pituitary tumor surgery. Laryngoscope 1992;102(2):198-202.
58. Jarrahy R, Young J, Berci G, et al. Endoscopic skull base surgery I: a new animal model for pituitary surgery. J Invest Surg 1999;12:1-6.
59. Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 1997;87(1):44-51.
60. Jho HD, Carrau RL. Endoscopy assisted transsphenoidal surgery for pituitary adenoma. Technical note. Acta Neurochir (Wien) 1996;138(12):1416-25.
61. Jho HD, Carrau RL, Ko Y. Endoscopic pituitary surgery. In Rengachary SS, Wilkins RH (eds): Neurosurgical Operative Atlas, vol V, pp 1-12. Baltimore, Williams & Wilkins, 1996.
62. Jimenez-Castellanos J. Carmona A. Castellanos L. Catalina-Herrera CJ. Microsurgical anatomy of the human ophthalmic artery: a mesoscopic study of its origin, course and collateral branches. Surg Radiol Anat 1995;17(2):139-43.
63. Johnson MR, Hoare RD, Cox T, et al. The evaluation of patients with a suspected pituitary microadenoma: computer tomography compared to magnetic resonance imaging. Clin Endocrinol (Oxf) 1992;36(4):335-8.
64. Kaye TB. Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med 1990;112(6):434-44.
65. Kehrli P, Ali M, Reis M Jr, et al. Anatomy and embryology of the lateral sellar compartment (cavernous sinus) medial wall. Neurol Res 1998;20(7):585-92.
66. Kennedy DW et al: Functional endoscopic sinus surgery: theory and diagnostic evaluation. Arch Otolaryngol 1985;111:576-582.
67. Kern EB. Grand rounds: transnasal pituitary surgery.Arch Otolaryngol1981;107(3):183-90.
68. Kern EB, Laws ER Jr. The rationale and technique of selective transsphenoidal microsurgery for the removal of pituitary tumors. In  Laws ER, Randall RV, Kern EB, Abboud CF (eds): Management of Pituitary Adenomas and Related Lesions with Emphasis on Transsphenoidal Microsurgery, pp 219-233. New York, Appleton-Century-Crofts, 1982.
69. Kjaer I. Human prenatal craniofacial development related to brain development under normal and pathologic conditions. Acta Odontol Scand 1995;53(3):135-43.
70. Kjaer I. Ossification of the human fetal basicranium. J Craniofac Genet Dev Biol 1990;10(1):29-38.
71. Kral T, Zentner J, Vieweg U, et al. Diagnosis and treatment of frontobasal skull fractures. Neurosurg Rev 1997;20(1):19-23.
72. Krisht AF, Barrow DL, Barnett DW, et al. The microsurgical anatomy of the superior hypophyseal artery. Neurosurgery 1994;35(5):899-903.
73. Krmpotic-Nemanic J, Padovan I, Vinter I, et al. Development of the cribriform plate and of the lamina mediana. Anat Anz 1998;180(6):555-9.
74. Laws ER Jr. Pituitary surgery. Endocrinol Metab Clin North Am 1987;16(3):647-65.
75. Lee SK, Kim YS, Jo YA, et al. Prenatal development of cranial base in normal Korean fetuses. Anat Rec 1996;246(4):524-34.
76. Libersa C, Laude M, Libersa JC. The pneumatization of the accessory cavities of the nasal fossae during growth. Anat Clin 1981;2:265-273.
77. Linder TE, Simmen D, Stool SE. Revolutionary inventions in the 20th century. The history of endoscopy. Arch Otolaryngol Head Neck Surg 1997;123(11):1161-3.
78. Long DM. Subfrontal approach to the frontal meningioma. In Long DM (ed): Surgery for Skull-Base Tumors, 1^st edition, pp 93-103. Boston, Blackwell Scientific Publications, 1992.
79. Luft R, Olivecrona H. Experiences with hypophysectomy in man. J Neurosurg 1953;10:301-316.
80. Lund VJ: Extended applications of endoscopic sinus surgery—the territorial imperative. J Laryngol Otol 1997;111:313-315.
81. Magnan J, Sanna M (eds): Endoscopy in Neuro-Otology, 1^st edition. New York, Thieme, 1999.
82. Maira G, Anile C, Rossi GF, et al. Surgical treatment of craniopharyngiomas: an evaluation of the transsphenoidal and pterional approaches. Neurosurgery 1995;36(4):715-24.
83. Maroldo TV, Dillon WP, Wilson CB. Advances in diagnostic techniques of pituitary tumors and prolactinomas. Curr Opin Oncol 1992;4(1):105-15.
84. Matula C, Tschabitscher M, Day JD, et al. Endoscopically assisted microneurosurgery.Acta Neurochir1995;134(3-4):190-5.
85. McArthur LL. An aseptic surgical access to the pituitary body and its neighborhood. JAMA 1912;58(26):2009-2011.
86. Metson R, Gliklich RE: Endoscpic treatment of sphenoid sinusitis. Otolaryngol Head Neck Surg 1996;114:736-744.
87. Miller AJ, Amedee RG. Functional anatomy of the paranasal sinuses. J La State Med Soc 1997;149(3):85-90.
88. Mohr G, Hardy J, Comtois R, et al. Surgical management of giant pituitary adenomas. Can J Neurol Sci 1990;17(1):62-6.
89. Nabe-Nielsen J: Nasal complications after transsphenoidal surgery for pituitary pathologies. Acta Neurochir (Wien) 1989;96:122-125.
90. Nagai H. Moritake K. Nagao S. Yamasaki T. Ultrasonic bruits in the circle of Willis due to a large nonfunctioning pituitary adenoma.J Neuroimaging1997;7(4):251-4.
91. Natori Y, Rhoton AL Jr. Microsurgical anatomy of the superior orbital fissure. Neurosurgery 1995;36(4):762-75.
92. Nishioka NS, Mycek MA. Initial experience with a real-time video processor for enhancing endoscopic image contrast. Gastrointest Endosc 1998;48(1):62-6.
93. Nishizawa S, Yokoyama T, Ohta S, et al. Surgical indications for and limitations of staged transsphenoidal surgery for large pituitary tumors. Neurol Med Chir ( Tokyo) 1998;38(4):213-9.
94. Oikawa S, Kyoshima K, Kobayashi S. Surgical anatomy of the juxta-dural ring area. J Neurosurg 1998;89(2):250-4.
95. Papay FA, Benninger MS, Levine HL, et al. Transnasal transseptal endoscopic repair of sphenoidal cerebral spinal fluid fistula. Otolaryngol Head Neck Surg 1989;101(5):595-7.
96. Patterson RH. The role of transcranial surgery in the management of pituitary adenoma. Acta Neurochir [Suppl] 1996;65:16-7.
97. Randall RV. Clinical presentation of pituitary adenomas. In  Laws ER, Randall RV, Kern EB, Abboud CF (eds): Management of Pituitary Adenomas and Related Lesions with Emphasis on Transsphenoidal Microsurgery, pp 15-30. New York, Appleton-Century-Crofts, 1982.
98. Ray BS. Intracranial hypophysectomy. J Neurosurg 1968:28(2):180-6.
99. Ray BS, Patterson RH Jr. Surgical treatment of pituitary adenomas. J Neurosurg 1962;19:1-8.
100. Reisch R, Vutskits L, Patonay L, et al. The meningohypophyseal trunk and its blood supply to different intracranial structures. An anatomical study. Min Invas Neurosurg 1996;39(3):78-81.
101. Rhoton AL Jr. Microsurgical anatomy of the sellar region. In Wilkins RH, Rengachary SS (eds): Neurosurgery, 2^nd Edition, vol I, pp 1243-1253. New York, McGraw-Hill, 1996.
102. Rhoton AL Jr. Hardy DG. Chambers SM. Microsurgical anatomy and dissection of the sphenoid bone, cavernous sinus and sellar region.Surg Neurol1979;12(1):63-104.
103. Ricciardelli EJ. Embryology and anatomy of the cranial base. Clin Plast Surg 1995;22(3):361-72.
104. Rice DH, Schaefer SD (eds): Endoscopic Paranasal Sinus Surgery, 2^nd edition. New York, Raven Press, 1993.
105. Rodziewicz GS, Kelley RT, Kellman RM, et al. Transnasal endoscopic surgery of the pituitary gland: technical note. Neurosurgery 1996;39(1):189-92.
106. Rosegay H: Cushing's legacy to transsphenoidal surgery. J Neurosurg 1981;54:448-454.
107. Sejrsen B, Jakobsen J, Skovgaard LT, et al. Growth in the external cranial base evaluated on human dry skulls, using nerve canal openings as references. Acta Odontol Scand 1997;55(6):356-64.
108. Sethi DS, Pillay PK. Endoscopic management of lesions of the sella turcica. J Laryngol Otol 1995;109(10):956-62.
109. Sethi DS, Stanley RE, Pillay PK. Endoscopic anatomy of the sphenoid sinus and sella turcica. J Laryngol Otol 1995;109(10):951-5.
110. Sharma K, Tyagi I, Banerjee D, et al. Rhinological complications of sublabial transseptal transsphenoidal surgery for sellar and suprasellar lesions: prevention and management. Neurosurg Rev 1996;19(3):163-7.
111. Silau AM, Hansen BF, Kjaer I. Normal prenatal development of the human parietal bone and interparietal suture. J Craniofac Genet Dev Biol 1995;15(2):81-6.
112. Sloan AE, Black KB, Becker DP. Lesions of the sella turcica. In Donald PJ (ed): Surgery of the Skull Base, 1^st edition, pp 555-582. Philadelphia, Lippincott-Raven, 1998.
113. Smith TD, Siegel MI, Mooney MP, et al. Formation and enlargement of the paranasal sinuses in normal and cleft lip and palate human fetuses. Cleft Pal Craniofac J 1997;34(6):483-9.
114. Spektor S, Piontek E, Umansky F. Orbital venous drainage into the anterior cavernous sinus space: microanatomic relationships.Neurosurgery1997;40(3):532-9.
115. Spencer WR, Das K, Nwagu C, et al. Approaches to the sellar and parasellar region: anatomic comparison of the microscope versus endoscope. Laryngoscope 1999;109(5):791-4.
116. Spetzler RF, Herman JM, Beals S, et al. Preservation of olfaction in anterior craniofacial approaches. J Neurosurg 1993;79(1):48-52.
117. Stadnik T, Stevenaert A, Beckers A, et al. Pituitary microadenomas: diagnosis with two-and three-dimensional MR imaging at 1.5 T before and after injection of gadolinium.Radiology1990;176(2):419-28.
118. Stankiewicz JA: The endoscopic approach to the sphenoid sinus. Laryngoscope 1989;99:218-221.
119. Stern JT (ed): Essentials of Gross Anatomy, 1^st edition. Philadelphia, Davis, 1988.
120. Sullivan LJ, O'Day J, McNeill P, Visual outcomes of pituitary adenoma surgery. St. Vincent's Hospital 1968-1987. J Clin Neuroophthalmol 1991;11(4):262-7.
121. Taub E, Patterson RH. Transcranial approaches to the pituitary gland and sellar region. In Wilkins RH, Rengachary SS (eds): Neurosurgery, 2^nd Edition, vol I, pp 1385-1388. New York, McGraw-Hill, 1996.
122. Tyrrell JB, Lamborn KR, Hannegan LT. Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results. Neurosurgery 1999;44(2):254-61.
123. Tzortzidis F, Bejjani G, Papadas T, et al. Craniofacial osteotomies to facilitate resection of large tumours of the anterior skull base. J Craniomaxillofac Surg 1996;24(4):224-9.
124. Urquhart AC, Bersalona FB, Ejercito VS, et al. Nasal septum after sublabial transseptal transsphenoidal pituitary surgery. Otolaryngol Head Neck Surg 1996;115(1):64-9.
125. Vakil N, Bourgeois K. A prospective, controlled trial of eight-bit, 16-bit, and 24-bit digital color images in electronic endoscopy. Endoscopy 1995;27(8):589-92.
126. Vinter I, Krmpotic-Nemanic J, Hat J, et al. The frontal sinus and the ethmoidal labyrinth. Surg Radiol Anat 1997;19(5):295-8.
127. Webb SM, Ruscalleda J, Schwarzstein D, et al. Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology. Clin Endocrinol (Oxf) 1992;36(5):459-65.
128. Wilson CB. Neurosurgical management of large and invasive pituitary tumors. In Tindall GT, Collins WF (eds): Clinical Management of Pituitary Disorders, pp 335-342. New York, Raven Press, 1979.
129. Wilson CB, Dempsey LC. Transsphenoidal microsurgical removal of 250 pituitary adenomas. J Neurosurg 1978;48(1):13-22.
130. Wurster CF, Smith DE: The endoscopic approach to the pituitary gland. Arch Otolaryngol Head Neck Surg 1994;120:674.
131. Yaniv E, Rappaport H: Endoscopic transseptal transsphenoidal surgery for pituitary tumors. Neurosurgery 1997;40:944-946.
132. Yoon JH, Lee JG, Kim SH, et al.Microscopical surgical management of cerebrospinal fluid rhinorrhoea with free grafts. Rhinology 1995;33(4):208-11.