Pituitary surgery was developed and has advanced on the basis of repeated innovations and exchanges between Europe and the New World. The first operation on a pituitary tumor was performed by Horsley in 1889, who published in 1906 ¹ the results obtained on a series of 10 patients, first by means of a frontal craniotomy and later through a temporal approach.² The first surgeon who reported on an operation specifically for a pituitary tumor was a British general surgeon, Paul; in 1893, he performed a temporal decompression in an acromegalic patient without actually reaching the tumor.^3,4

The next milestone was the first transsphenoidal approach achieved by the Viennese surgeon Schloffer in Innsbruck, Austria, in 1907.⁵ The use of a direct route through the nose toward the brain was not absolutely new: Many centuries ago, the Egyptians used to extract cerebral tissue transnasally in the mummification process by means of special hooked instruments, without disfiguring the face. Based on anatomic studies of the Italian physician Giordano, chief surgeon of the Hospital of Venice,^6,7 Schloffer performed a lateral rhinotomy, reflecting the nose to the right; removed the turbinates; and opened the maxillary, ethmoid, and sphenoid sinuses before reaching the sella. In the same year, von Eiselsberg,⁸ in Vienna, performed a similar, if even more extended, procedure. The next evolutionary step, approaching the modern transsphenoidal approach, was realized in 1909 by Kocher, professor of surgery in Berne, Switzerland, who was awarded the Nobel Prize for Medicine and Physiology in 1909 for his contributions concerning the thyroid; he performed a transseptal submucosal approach by means of an external midline incision on the nasal bridge,^9,10 but without exenteration of frontal, ethmoidal, and maxillary sinuses. Another remarkable contribution was that of Kanavel,^11,12 who proposed an approach through an infranasal skin incision. The first totally endonasal procedure, without complete dislocation of the nose, was achieved in 1910 in five stages with the patient under local anesthesia by Hirsch, a Viennese rhinologist, who was the first to incorporate a nasal speculum.¹³ He used the technique of his teacher Hajek,¹⁴ which was used previously for purulent infections of the sphenoid sinus, first opening the posterior ethmoid sinus, then enlarging the opening into the sphenoid sinus after a submucosal resection of the septum, according to Kocher’s and Kilian’s techniques,^9,15 beginning with a hemitransfixion incision in the right nasal cavity. Hirsch moved to the United States in 1938 to escape the Nazis, and worked in Boston with the neurosurgeon Hamlin.¹⁶

In 1910, Halstead 17,18 was a pioneer of the sublabial approach, which initially was performed as a multistage operation in Chicago. Cushing performed his first transsphenoidal procedure in 1909,¹⁹ but his classic sublabial, transseptal, transsphenoidal approach²⁰ was the evolution of his technique and a combination of different methods reported by other authors, such as Halstead, Hirsch, Kanavel, and Kocher (i.e., sublabial incision + submucosal paraseptal approach to the sphenoid sinus + use of the nasal speculum + use of an electric headlamp). Cushing later abandoned this procedure,^10,21,22 likely because of better recovery of vision in patients operated transcranially owing to difficulty with hemostasis and completeness of tumor removal in large suprasellar tumors and owing to difficulty in preoperative differential diagnosis. His advocacy of the transcranial option prompted most neurosurgeons to follow his recommendations. Another leading American neurosurgeon, Dandy, stated, “The nasal route is impractical and can never be otherwise.”²³ In 1918, at the Johns Hopkins Medical Society, Dandy had presented his experience in about 20 cases operated on through an intracranial intradural approach to the chiasm, according to a frontotemporal route to the pituitary along the sylvian fissure, originally conceived by Heuer in 1914.^24,25 The two main transcranial options—subfrontal and frontotemporal—are still used today, together with more recent skull base approaches.

The late 1920s to the 1960s was a relatively dark period for transsphenoidal surgery, because of the absence of antibiotics and replacement therapy for adrenocortical hormones, the lack of adequate illumination, and the opinions of the most authoritative opinion leader, Cushing. The only pupil of Cushing who did not abandon the transsphenoidal method was Dott, neurosurgeon of the Royal Infirmary at Edinburgh.10,26 He had learned the method from Cushing when he had been awarded a 1 year Rockefeller Fellowship at the Peter Bent Brigham Hospital in 1923. It is not clear why Dott did not publish his results, but he kept the procedure alive, improved the technique by adding two light bulbs to the speculum designed by Cushing, and taught the method to the French neurosurgeon Guiot during his visit to the Royal Infirmary in 1956. Guiot at the Hôpital Foch in Paris and Guiot’s trainee Hardy in Montreal deserve credit for the “transsphenoidal renaissance” in the late 1960s and 1970s. Modern transsphenoidal surgery takes advantage of the innovations of intraoperative image intensification and fluoroscopy, introduced by Guiot, and the use of the operating microscope according to Hardy,²⁷ who introduced the concept of microadenoma and selective microsurgical resection.

No new progress was made until the 1990s, when the latest innovation, the endoscope, was introduced. By analogy with the evolution of Picasso’s painting, the “cubist evolution” of transsphenoidal surgery occurred, from devastating transfacial approaches to minimally invasive contemporary procedures,²⁸ and with the endoscope used as a visualizing instrument for pituitary surgery. Used for the first time by Guiot in 1963²⁹ as an adjunct to the microscope to expand the field of vision (endoscope-assisted microneurosurgery), then abandoned for many years because it still was technically insufficient, the endoscope has come into regular use as a stand-alone visualizing and operating tool (pure endoscopic transsphenoidal surgery), thanks primarily to the work of Jho in Pittsburgh^30,31 and of our group in Naples, Italy^32,33; these workers standardized a unilateral endonasal anterior sphenoidotomy approach to the sella, without the use of the operating microscope or of a transsphenoidal retractor. Further advancement and evolution of the technique are expected through intraoperative magnetic resonance imaging (MRI), robotics, and miniaturization, as well as the rapidly emerging biomolecular frontiers, which are expected to change the world of pituitary surgery.

Surgical Anatomy

The pituitary gland, or the hypophysis cerebri, is situated within the hypophyseal fossa, a fibro-osseous compartment near the center of the cranial base (Fig. 12-1). This fossa is limited laterally and superiorly by reflections of dura mater, and anteriorly, posteriorly, and inferiorly by the sella turcica, a depression in the body of the sphenoid bone. At the superior edge of the anterior wall of the sella turcica is a bony protrusion called the tuberculum sellae, and its posterior wall is the dorsum sellae.

FIGURE 12-1 Frontal view: schematic drawing of the sellar region. a, Pituitary gland. b, Optic nerve. c, Optic chiasm. d, Optic tract. e, Internal carotid artery. f, Anterior cerebral artery. g, Middle cerebral artery. h, Oculomotor nerve. i, Trochlear nerve. j, Ophthalmic branch (V1) of the trigeminal nerve. k, Abducent nerve. l, Maxillary branch (V2) of the trigeminal nerve. m, Sphenoid sinus. n, Sphenoid septum. (Courtesy V. Valente, MD.)

The degree of pneumatization of the sphenoid bone and the thickness of the bone separating the sphenoid sinus from the hypophyseal fossa are highly variable. Three sinus types are distinguished by their shape and size: In the conchal type (≈3%), the area below the sella is a solid block of bone without an air cavity; in the presellar type (≈17%), the air cavity does not penetrate beyond a vertical plane parallel to the anterior sellar wall; and in the sellar type (≈80%), the air cavity extends into the body of the sphenoid below the sella and as far posteriorly as the clivus. The conchal type is most common in children before the age of 12 years, at which time pneumatization progresses within the sphenoid sinus. The greater the degree of pneumatization of the sphenoid sinus, the easier is the access to the sellar region through the transsphenoidal approach.

The space within the sphenoid sinus is subdivided by one or more septa. Single septa are not always located in the midline, and in 20% of cases, the posterior attachment of the sphenoid septum to the sphenoid sinus is on the carotid protuberance, serving as an important landmark for preventing injury to the carotid artery.

The diaphragma sellae, a fold of dura with a central aperture, forms an incomplete roof above the sella turcica. The diaphragma separates the anterior lobe from the overlying optic chiasm. The central opening of the diaphragma is of variable size and transmits the pituitary stalk and its blood supply. The subarachnoid space of the chiasmatic cistern can extend through the aperture of the diaphragma and into the sella turcica for varying distances above the gland. When there is an incompetent diaphragma sellae (i.e., wide central aperture of the diaphragma), the chiasmatic cistern herniates to fill the sella turcica partially, leading to remodeling and enlargement of the hypophyseal fossa and flattening of the pituitary gland, a condition called empty sella,³⁴ which is found in 5% to 23% of cases at autopsy.³⁵ When this condition is associated with the presence of an adenoma, usually a microadenoma, the surgeon must be careful to avoid entering the subarachnoid space (i.e., the chiasmatic cistern herniated into the sella), to prevent an intraoperative cerebrospinal fluid (CSF) leak, which could increase the difficulty of resecting the lesion.

The folds of the dura mater form the lateral walls of the hypophyseal fossa and the medial wall of the so-called cavernous sinuses, these latter consisting of a series of compartmentalized venous channels separated by fibrous trabeculae and communicating with each other by means of the anterior and posterior intercavernous sinuses.36–40 The oculomotor nerve, the trochlear nerve, and the first two divisions of the trigeminal nerve are embedded in the lateral wall of the cavernous sinus, lying between the endothelial lining and the dura mater, whereas the abducens nerve is contained within the sinus itself. The cavernous sinus also envelops a portion of the internal carotid artery (ICA) and the sympathetic nerve plexus encircling it. The intracavernous segment of the ICA extends forward, adjacent to the superolateral surface of the body of the sphenoid bone, in a groove called the carotid sulcus. The carotid arteries and the bone layers overlying them in the sphenoid sinus form two protuberances, which represent important landmarks in the transsphenoidal approach, particularly at the level of the sellar floor, where they are considered the lateral margins of a correct opening of the sella.

The pituitary gland derives its blood supply from two groups of arteries. The superior hypophyseal artery primarily supplies the anterior lobe, the pituitary stalk, and the inferior surface of the optic nerve and chiasm, whereas the inferior hypophyseal artery is related primarily to the pars nervosa. The superior hypophyseal artery can arise from the supraclinoid portion of the ICA or from the posterior communicating artery, whereas the inferior hypophyseal artery arises from the meningohypophyseal trunk, a branch of the cavernous segment of the ICA.

The pituitary gland is overlaid by the visual pathways and the hypothalamus. The relationships between the pituitary gland, diaphragma sellae, sulcus chiasmatis, and optic apparatus are important determinants of the visual deficits produced by an expanding pituitary tumor.⁴¹ In some cases, the anterior border of the optic chiasm is closely applied to the sulcus chiasmatis of the sphenoid bone; this leads to a lower position of the optic chiasm, which is much nearer to the diaphragma sellae. This condition, called prefixed chiasm and present in 5% to 10% of cases,^42,43 must be considered during transcranial approaches and in the transsphenoidal opening of the upper portion of the sellar floor, as in the extended approaches to the planum sphenoidale, because of the possibility of producing iatrogenic damage to the optic chiasm. In other cases, the optic chiasm is located above the anterior part of the diaphragma sellae, making it extremely vulnerable to the suprasellar extension of a pituitary tumor. This pattern is found in about 12% of cases.^42,43 In most cases (75%), the optic chiasm is placed more posteriorly, lying over the posterior aspect of the diaphragma sellae, near the dorsum sellae,^42,43 which is a more favorable relationship for the removal of a sellar lesion because in such a circumstance, the suprasellar region is free from the optic chiasm. The remaining pattern is that of an optic chiasm located on and behind the dorsum sellae, called postfixed chiasm (4% to 11% of cases).^42,43 In such cases, the intracranial course of the optic nerves is longer, and the medial aspects of the optic nerves are more vulnerable to the suprasellar extension of the pituitary tumor.

Anatomy should represent an uninterrupted line in the surgeon’s mind. The surgeon must have a thorough knowledge of anatomy and must refer to it before, during, and after performing the surgical procedure. Only in this way can the surgeon determine the correct surgical approach, that is, the exact plan for each operation; perform the necessary intraoperative controls; and check the ultimate results of the intervention.

Progress in diagnostic imaging techniques (computed tomography [CT] and MRI) has given the neurosurgeon preoperative detailed knowledge of the anatomy of each patient and of the surgical route to follow, rendering the surgical procedure safer and more comfortable for the patient and the surgeon. CT of the nasal and paranasal structures provides precise information on the surgical route to follow, which is particularly useful for the endoscopic transsphenoidal procedure and reveals the possible presence of turbinate hypertrophy; nasal septal deviation; concha bullosa; unusual sphenoid sinus type (sellar, presellar, or conchal type); single or multiple sphenoid septa; presence of an Onodi cell, which represents a potential risk for the optic nerve; and any bone structure alteration caused by the sellar lesion, such as thinning or erosion or both of the sellar floor. MRI of the sellar area, before and after intravenous administration of a paramagnetic contrast medium (gadolinium-diethylene-triamine-pentaacetic acid), is fundamental. Imaging permits precise localization of the lesion with its peculiar characteristics, localization of the anatomic endosellar and parasellar structures (cisterns, optic nerves, medial wall of the cavernous sinus with the ICA), and knowledge of their mutual relationships. In clinical practice, MRI is performed in the sagittal and coronal planes: The sagittal sections give good definition of the morphology and size of the lesion; of the pituitary gland and of the pituitary stalk, when recognizable; of the suprasellar cisterns; and of the optic chiasm. The coronal slices add an evaluation of symmetry at the sellar and parasellar level. In the axial plane, the images are obtained as completion, to define better the anterosellar and retrosellar extensions of the lesion.

The need to define intraoperatively the exact location of a lesion and its relationships with surrounding vascular and nervous structures has led to the development of neuronavigation and intraoperative MRI, which provide continuous anatomic information. The neuronavigator is a computer-based system that offers the surgeon real-time information related to the operating site. The basic function of the navigator is to determine the location of a probe tip within the surgical field and to translate it into CT/MRI coordinates. The patient’s head is related initially to the CT/MRI coordinates; this relationship is established preoperatively by a set of fiducial markers on the patient’s head. During transsphenoidal surgery, this relationship can obviate the need for intraoperative fluoroscopy, avoiding exposure of the operating room staff and the patient to radiation. Its employment is particularly useful in the presence of a conchal or presellar type of sphenoid sinus, in identifying the boundaries of the sella, and in some cases of recurrence in which prior surgery has altered the landmarks needed to reach the sella safely.44–49

Intraoperative MRI, with the use of a magnetic resonance magnet positioned in a specially designed operating room with a movable operating table that allows translation of the patient from the surgical equipment to the MRI imager, offers the opportunity of a second look during the same surgical procedure. In transsphenoidal surgery, intraoperative MRI allows documentation of the extent of surgical resection of the sellar lesion, and removal of the suprasellar portion of the tumor can be evaluated reliably.50–55

Surgery

Therapy for pituitary adenomas is targeted to achieve multiple goals, as follows:

• Normalization of excess hormone secretion

• Preservation or restoration of normal pituitary function

• Elimination of mass effect

• Preservation or restoration of normal neurologic function, usually with visual acuity or visual field (or both) affected more frequently

• Prevention of tumor recurrence

• Achievement of a complete histologic diagnosis

• Gathering of tissue for scientific studies

Despite advances in medical treatment for pituitary adenoma, most of these tumors are managed surgically. Indications for surgery for pituitary adenomas are as follows:

• Pituitary apoplexy, a relatively rare condition presenting with sudden headache, abrupt visual loss, ophthalmoplegia, altered level of consciousness, and collapse from acute adrenal insufficiency. It is caused by a hemorrhage into the tumor or its acute necrosis, with subsequent swelling and frequent spreading into the subarachnoid space, leading to other signs of meningeal irritation; the related acute and severe clinical syndrome demands glucocorticoid replacement and surgical decompression, usually transsphenoidal, if visual loss is severe and progressive.56–59 If the patient has a mild form of apoplexy and is clinically stable, it is prudent to measure the serum prolactin because some patients with prolactinoma present in this fashion and can be treated successfully with medical therapy.

• Progressive mass effect, producing compression of surrounding neurovascular structures and usually causing visual deficit (due to compression of the optic chiasm) or less frequently cranial nerve palsy (due to compression of cranial nerves inside the cavernous sinus). In cases of prolactin-secreting macroadenomas, dopamine agonist administration can be considered as the first treatment option because of predictable dramatic shrinkage of the lesion, with rapid recovery of neurologic deficits. In such circumstances, frequent visual field and imaging controls are necessary to monitor the clinical evolution.

Because pituitary tumors are biologically, endocrinologically, and pathologically a heterogeneous group of lesions, the role of surgery differs for the different pituitary tumor subtypes. The primary role of surgery is established in the following conditions:

• Nonfunctioning pituitary tumors

• Cushing’s disease, because of the present inadequacy of pharmacologic agents

• Acromegaly, in combination with medical treatment (preoperative and postoperative, if necessary)

• Thyroid-stimulating hormone–secreting adenomas

The role of surgery in prolactinoma is secondary, but it still is necessary in selected conditions. Indications for surgery include the following:

• Failure of or resistance to medical treatment or intolerable side effects of medical therapy

• Recurrence, in combination or in association with the other therapeutic options, medical or radiotherapeutic or both

Indications for surgery have changed over time and with the refinement of surgical techniques and according to the evaluation of results and experiences, the development of knowledge about the biology of pituitary tumors, and the use of effective new pharmacologic agents 60–62 and radiation techniques. Large invasive pituitary tumors are difficult to cure regardless of the approach because removal of every fragment of the tumor is often impossible. Extended transsphenoidal approaches sometimes can represent a valid alternative to transcranial options; excellent visual outcomes derive from the transsphenoidal method.^58,63 Visual impairment does not indicate the need for a transcranial operation, as Cushing believed at one time.⁶⁴

The surgical approach, with respect to basic principles for resecting pituitary adenomas, can be performed by two main approaches, each of them with several subcategories:

a. Subfrontal unilateral

b. Frontolateral or pterional

c. Subfrontal bilateral interhemispheric

After an initial flourishing of transsphenoidal surgery in the early 1900s, transcranial approaches attained success and were popular in the first half of the twentieth century. This fundamental debate lasted for decades, until the introduction of intraoperative fluoroscopy and microscopy effectively put it to rest. With these new imaging techniques, adequate exposure and thorough exploration of the sella turcica became possible without the need for a craniotomy and associated brain retraction. As a result, the transseptal transsphenoidal approach came to be accepted as the procedure of choice for the surgical management of most pituitary lesions.65,66

The success of the transsphenoidal approach is based on solid foundations: It is the least traumatic route to the sella, it lacks visible scars, it provides excellent visualization of the pituitary gland and adjacent pathology, it offers lower morbidity and mortality rates compared with transcranial procedures, and it requires only a brief hospital stay. Indications for transsphenoidal surgery today include more than 95% of the surgical indications in the sellar area and approximately 96% of all pituitary adenomas.⁶⁷ The well-established indications for this route are as follows:

• Almost all adenomatous lesions ⁶⁸

• Non-neoplastic intrasellar cysts 34,69–71

• Craniopharyngiomas, preferably cystic, extra-arachnoidal,⁷² and infradiaphragmatic,⁷³ with an enlarged sella^74–76

Absolute indications were established in the 1970s and still are valid today; they include the following ⁷⁷:

• Elevated surgical risk of the transcranial route

• In the elderly

• In long-standing compression of the chiasm, not able to tolerate additional trauma

• In cases of acute endosellar hypertension

• In most cases of pituitary apoplexy

• In pan-invasive, not radically removable adenomas

• Adenomas with downward development

• Microadenomas

To these classic guidelines for the transsphenoidal option, in more recent decades the following can be added:

• The extended transsphenoidal approaches to the sphenoethmoid planum, for suprasellar craniopharyngiomas, Rathke’s cleft cysts, some tuberculum sellae meningiomas, and anterior cranial base CSF leaks 78–88; to the clival area, for chordomas^79,89–93; and to the parasellar compartment,^{37,79,91,94–99} for invasive adenomas and chordomas. The development of extended transsphenoidal approaches has provided transsphenoidal access to several lesions that previously would have been considered accessible by transcranial approaches only. The spectrum of lesions accessible to transsphenoidal surgery is widening. Extended approaches today represent standard procedures in selected centers and in experienced hands and are expected to progress further in the near future with additional technical and instrumental development.

• A sequential transsphenoidal approach, in intrasuprasellar adenomas, as an intentionally two-staged transsphenoidal operation. This operation is designed to encourage the descent of a suprasellar remnant of the adenoma incompletely removed in the first step, to limit the risks for brisk decompression of huge lesions, and to manage lesions with a second surgery.¹⁰⁰

The striking figure indicating that 19% of primary brain tumors treated in academic centers in the United States are operated transsphenoidally provides testimony to what we have reported about evolving modern and contemporary indications for the transsphenoidal approach. Conditions may limit and sometimes contraindicate the choice of the transsphenoidal approach in favor of the transcranial, because of either the anatomy of the surgical pathway or the morphology and consistency of the lesion. The size of the sella, its degree of mineralization, the size and pneumatization of the sphenoid sinus, and the position and tortuosity of the carotid arteries can increase remarkably the difficulty of the transsphenoidal procedure and the final surgical result and may determine the opportunity or even the necessity for the transcranial alternative.

Indications for transcranial surgery include the following 68,73:

• Tumors with extensive intracranial invasion, into the anterior cranial fossa or lateral or posterior extension, into the middle and posterior cranial fossae ¹⁰¹

• Tumors with asymmetric suprasellar development, particularly if major vessel involvement is present

• Tumors with intracranial extension separated from the intrasellar portion by a narrow neck (dumbbell adenoma) and showing an hourglass configuration ¹⁰²

• Suprasellar tumors not completely resectable through the transsphenoidal route ¹⁰³

• Recurrent or residual pituitary tumors in patients who already have had unsuccessful transsphenoidal surgery

• When preoperative MRI assessment, on the basis of long repetition time (TR) signal, suggests a firm consistency of the adenoma, preventing easy debulking with subsequent collapse and descent into the sella, when resected from below.104–106 This may occur after radiotherapy¹⁰⁷; increased fibrosis also has been reported after treatment with dopamine agonists¹⁰⁸ or somatostatin analogues,^109,110 but these reports do not reflect our experience.

• When the sphenoid sinus is not pneumatized and the sella is small or does not make it easy to reach the suprasellar extension of the tumor ¹¹¹

• When coexisting vascular 96,112 and tumoral surgical pathology is evident and one-time surgical treatment for both conditions is chosen

Transsphenoidal Approaches

One or another variation of the transsphenoidal approach represents the most physiologic and minimally traumatic corridor of surgical access to the sella, providing direct and superior visualization of the pituitary gland and adjacent pathology.92,113 The transsphenoidal approach represents a midline approach that has been performed since the 1960s with use of the operating microscope as a visualizing tool, through transnasal transseptal, sublabial transseptal, or endonasal procedures (microsurgical transsphenoidal procedures). The transsphenoidal approach also can be performed by using the endoscope as the sole visualizing tool during the entire surgical procedure, realizing a “pure” endoscopic endonasal transsphenoidal approach. The combined use of the microscope and the endoscope during the same approach defines the condition of endoscope-assisted microsurgery.

Microsurgical Transsphenoidal Approaches: Although many different transsphenoidal procedures and variations have been described, three basic microsurgical transsphenoidal approaches to pituitary tumors are used: the transnasal transseptal transsphenoidal approach, the sublabial transseptal transsphenoidal approach, and the endonasal transsphenoidal approach. The patient can be positioned on the operating table supine, as originally proposed by Cushing, with the surgeon behind the patient’s head, or in the semisitting position, as favored by Guiot, with the surgeon standing in front of the patient. The procedure is performed with an operating microscope for visualization, illumination, and magnification of the surgical field. Intermittent fluoroscopy is used for trajectory guidance, or, more recently, neuronavigational systems permit the surgeon to gather information about the current position of anatomic structures or instruments during the procedure iself.44–49 Intraoperative MRI is capable of enhancing safety and providing additional knowledge about the completeness of lesion removal.^{50,51,53–55} The three main transsphenoidal methods differ slightly one from each other primarily in the initial phase up to the exposure of the sphenoid sinus; they then follow the same surgical sphenoidal and sellar steps.

Microsurgical Transnasal Transseptal Transsphenoidal Approach: In a diffused version of the transnasal approach (Fig. 12-2), the operation starts in the right nostril, with retraction of the columella to the patient’s left to expose through the incision in the nostril the anterior edge of the septal cartilage, 2 to 3 cm behind the mucosal-cutaneous junction. The nasal mucosa usually adheres tightly to the most anterior region of the septum: Its dense, fibrous strands are divided through a combination of sharp and blunt dissection. The submucosal dissection is extended posteriorly, elevating the nasal mucosa away from the septal cartilage up to its junction with the bony septum. The cartilaginous septum is dissected from the mucoperichondrium along its right side, then is laterally pushed on the left side, at the junction point, to free the cartilaginous septum from the bony septum. Posterior submucosal tunnels are created along both sides of the bony septum, which is partially removed to facilitate the introduction of a self-retaining transsphenoidal retractor, following the use of a nasal speculum in the dissection of the nasal septum. Care must be taken to avoid mucosal perforation during these maneuvers.

FIGURE 12-2 Sagittal view: schematic drawing of the microsurgical transnasal transseptal transsphenoidal approach. (Courtesy V. Valente, MD.)

Microsurgical Sublabial Transseptal Transsphenoidal Approach: The upper lip is retracted, and an incision is made along the buccogingival junction, between the two canine fossae (Fig. 12-3). The upper lip and the periosteum are elevated to expose the anterior nasal spine and the inferior border of the pyriform aperture of the nasal cavities. The mucosa of the floor of the nose is elevated first on both sides with a small periosteal elevator, which is introduced along the nasal septum to detach the mucosa from the cartilage. The elevated mucosa is held in place by a nasal speculum, which allows further mucosal elevation from the bony nasal septum. The inferior and posterior portion of the cartilaginous septum is dissected from the bony nasal septum and is deflected laterally. The self-retaining nasal speculum is introduced and opened widely to hold the retracted mucosa out of the field. The sublabial approach permits a more anterior trajectory with respect to the transnasal option; this can be useful in lesions that extend into the suprasellar area or toward the planum sphenoidale.

FIGURE 12-3 Sagittal view: schematic drawing of the microsurgical sublabial transseptal transsphenoidal approach. See detail of the sublabial incision on the right. (Courtesy V. Valente, MD.)

Microsurgical Endonasal Transsphenoidal Approach: A handheld speculum is inserted into the nostril along the middle turbinate, which reliably leads to the sphenoid sinus (Fig. 12-4). In the posterior nasal cavity, an elevator is used to make a vertical mucosal incision at the junction of the keel of the sphenoid bone and the posterior nasal septum. The septum, with its intact mucosa, is pushed off the midline by the medial blade of the handheld speculum. Bilateral mucosal flaps over the keel of the sphenoid bone are elevated and reflected laterally, with identification of the sphenoid ostia. The handheld speculum is replaced by a thin nasal speculum, which is placed up to the face of the sphenoid bone. After lesion removal, the speculum is withdrawn, the nasal septum is returned to the midline, and the ipsilateral outfractured middle turbinate may be moved toward the midline to prevent a maxillary sinus mucocele. Nasal packing is placed for 24 hours in selected cases but is not used routinely.^114,115

FIGURE 12-4 Sagittal view: schematic drawing of the microsurgical endonasal transsphenoidal approach. (Courtesy V. Valente, MD.)

When the anterior wall of the sphenoid sinus has been reached by one of the aforementioned three routes, bone punches are used to make a large opening in the anterior wall of the sphenoid sinus, which extends beyond the sphenoid ostia to provide adequate sellar floor exposure. After the anterior wall of the sphenoid sinus has been opened, one or more septa can be identified. The surgeon should review the anatomy of the sphenoid sinus on preoperative nasal and paranasal cavity CT scans and should compare them with the intraoperative scans, particularly when the septa are implanted on one of the carotid prominences and the sphenoid sinus is of a presellar type. Insertion of the septum along the posterior wall of the sphenoid sinus may produce a useful anatomic landmark for identifying the sellar floor and for defining the medial extent of the cavernous sinus. Even if in selected cases it is not necessary to remove all the sphenoid septa, their removal must allow exposure of all crucial anatomic findings that are visible inside the sphenoid cavity.

Usually, the sphenoid mucosa is displaced laterally as much as necessary to open the sellar floor, unless adenomatous infiltration is evident or suspected, and the mucosa is resected in such cases. Its preservation is thought to ensure adequate mucociliary transport, along with its associated function in maintaining the physiology of nasosinusal ventilation.

After the sphenoid septa have been removed completely, the sella is recognizable on the posterior wall of the sphenoid sinus; its anatomic boundaries, when not clearly visible, are confirmed by C-arm fluoroscopy or neuronavigation. Adequate bony exposure of the sellar floor is crucial to the success of the approach, particularly when one is dealing with large tumors.

With a presellar or a conchal type of sphenoid sinus, the sphenoidotomy calls for some precautions.¹¹⁶ With these two variants of incomplete sphenoid sinus pneumatization, a microdrill is used to open the sellar floor. In these cases, fluoroscopy or neuronavigation is extremely useful, if not essential, for identification of the superior and inferior edges of the sella, even in experienced hands. The method used to open the sellar floor depends on its consistency: If it is intact, opening is achieved by means of a microdrill or bone punches or both; if it is eroded or thinned, opening is achieved by means of a dissector, sometimes realizing an osteoplastic opening useful for sellar repair.¹¹⁷

The dura is incised in a midline position, in a linear or cross fashion, and a fragment of dura can be taken for histologic examination if it appears infiltrated.¹¹⁸ When the dura is incised, the surgeon must keep in mind that the perisellar sinuses,¹¹⁹ and particularly the superior and inferior intercavernous sinuses, are compressed and usually are obliterated by macroadenomas, making the dural incision bloodless. The situation is different with microadenomas, particularly in cases of Cushing’s disease, in which it is not unusual to find the entire sellar dura covered by one or two venous channels that can bleed during tumor resection. Caution is necessary when incising the dura in microadenomas to avoid damaging a possibly ectatic carotid artery, which may be located within the sella, especially in acromegalic patients.

Before removing an adenoma, the surgeon must keep in mind that the pituitary gland is an extra-arachnoid structure, situated below the diaphragma sellae. During the removal of a pituitary adenoma, surgical maneuvers must respect these structures, to avoid postoperative CSF leaks and other major complications. Concerning the removal of a microadenoma, if it is visible on the surface of the gland, a cleavage plane between the microadenoma and the residual anterior pituitary should be found, with the aim of delimiting the lesion. When the microadenoma is not superficial, and no change in the appearance of the overlying anterior pituitary is evident, such as discoloration or attenuated texture, a small incision can be made in the normal pituitary gland on the same side of the microadenoma, and the lesion can be removed with the help of small ring curettes. After curettage of the adenoma, a small cottonoid is inserted inside the tumor cavity and with a forceps is turned in alternate directions to mobilize fragments of the lesion or of the neoplastic capsule. Concerning the removal of macroadenomas, the surgeon first must try to remove the tumor tissue from the interior of the sella and from any lateral extension, to avoid cumbersome obstruction of the surgical field by a down-hanging, inverted diaphragma sella. If a gradual descent of the suprasellar portion of the lesion is not observed, it is useful to ask the anesthetist to perform the Valsalva maneuver, which may cause protrusion into the sellar cavity of a part of the dura and arachnoid covering the suprasellar tumor extension (suprasellar cistern), or to inject air through a lumbar drain preoperatively positioned for the same purpose.¹²⁰

After intracapsular emptying of the adenoma, its capsule can be dissected from the suprasellar cistern, when possible. As the macroadenoma grows, it sometimes distends the residual normal anterior pituitary, which appears as a thin layer of tissue surrounding the adenoma capsule, sometimes seen on MRI, the removal of which could cause postoperative hypopituitarism. It is also important to recognize the neurohypophysis, sometimes present in front of the dorsum sellae, where curettage or aspiration must be avoided, to prevent the development of postoperative diabetes insipidus.

After lesion removal, closure of the sellar floor is performed, especially when an intraoperative CSF leak has occurred, using a variety of techniques (intradural or extradural closure of the sella, packing of the sella with or without packing of the sphenoid sinus) and different autologous and synthetic materials.121,122 Overpacking of the sella must be avoided to prevent compression of the optic system.

As with removal of lesions that often originate or develop inside the intra-arachnoid compartment, such as craniopharyngiomas or Rathke’s cleft cysts, additional considerations are appropriate. These lesions develop primarily in the suprasellar region, with an intact or only slightly enlarged sellar cavity. In such cases, an extended approach is often necessary to manage the lesion. The anterior sellar wall, the tuberculum sellae, and the posterior portion of the planum sphenoidale are drilled away, according to the circumstances, with the use of a microdrill with a diamond bur. The superior intercavernous sinus is identified, coagulated, and divided in a midline position. When the lesion is exposed, it is removed, with as much respect as possible given to the arachnoid membrane, to avoid intraoperative and postoperative complications, which seem to be more frequent than with conventional transsphenoidal surgery.⁸³

Endoscopic Endonasal Transsphenoidal Approach: Endoscopic endonasal transsphenoidal surgery (Fig. 12-5) is a novel, minimally invasive transsphenoidal approach performed with the endoscope as a stand-alone visualizing and operating instrument, without the need for the transsphenoidal retractor. It has the same indications as the conventional microsurgical technique,^33,123 and since the 1990s, it has enjoyed progressive acceptance among surgeons and patients for its minimal invasiveness and for the excellent surgical view it provides.^{30–33,124–127} This procedure requires specific endoscopic skills and is based on a different concept because the endoscopic view that the surgeon receives on the video monitor is not a transposition of the real image, as it would be if looking through the eyepiece of a microscope, but is the result of a microprocessor’s elaboration.