Epidemiology

Pituitary tumors are common lesions believed to account for 10% to 15% of all primary brain tumors.³² More precise estimates on their incidence and prevalence vary to some degree, depending on the means of survey, the population studied, and the period of the study. Data from academic medical centers suggest that pituitary tumors represent as many as 20% of surgically resected primary brain tumors.³³ Epidemiologic estimates indicate an annual incidence of 8.2 to 14.7 cases per 100,000 people.³⁴ A recent Belgian study reported a prevalence of 94 cases per 100,000.³⁵ By these measures, pituitary tumors are the third most common primary intracranial tumor, preceded in frequency only by gliomas and meningiomas. These data underestimate the true frequency of pituitary tumors, however. Unselected autopsy studies have repeatedly shown that 20% to 25% of the general population harbor small pituitary microadenomas. These lesions are clinically silent; occur in patients without apparent endocrine symptoms; have the morphology of null cell, gonadotroph, or lactotroph adenomas; and are identified only after careful microscopic postmortem examination of a serially sectioned pituitary gland.^32,36 The high subclinical prevalence of these so-called incidentalomas has also been validated with magnetic resonance imaging (MRI). When carefully sought, subtle signal changes in the pituitary gland indicative of a clinically occult microadenoma can be identified in 10% or more of routine MRI scans.^37–39 It therefore follows that neoplastic transformation is a frequent occurrence in the pituitary, although it reaches clinical attention and requires intervention in relatively few cases.

Although pituitary adenomas occur in all age groups, the highest incidence is between the third and sixth decades of life. As a general rule, functioning pituitary tumors tend to be more common among younger adults, whereas nonfunctioning adenomas become more prominent with increasing age.^40–42 Pituitary adenomas are uncommon in the pediatric population, representing only 2% of all primary pediatric brain tumors.⁴³ The relative rarity of these lesions in the pediatric population is also reflected in several large institutional series of pituitary adenomas. At the Centre Foch, the Mayo Clinic, and the University of San Francisco, the respective proportions of pediatric pituitary tumors were 2.1% (66 of 3200 patients), 2.03% (36 of 1776), and 5.34% (119 of 2330).^41,44,45 In most surgical series, pituitary tumors are distinctly more common among women, particularly premenopausal women. The basis of the higher prevalence in women is unclear, especially because incidental pituitary tumors are equally distributed between the sexes in autopsy series.³⁶ One plausible explanation is that the clinical manifestations of pituitary adenomas, most notably menstrual dysfunction, are more conspicuous in women and are more readily diagnosed in premenopausal women than in men. The fact that Cushing’s disease is much more prevalent in women than men may contribute to this phenomenon.

Genetic predisposition to pituitary tumors is restricted to a single uncommon condition: multiple endocrine neoplasia type 1 (MEN-1) syndrome. Only 3% of all pituitary tumors occur in the context of this disorder. An autosomal dominant condition, MEN-1 syndrome is characterized by tumors of the parathyroid glands, pancreatic islet cells, and pituitary. Because the condition is variably penetrant, only 25% of affected patients develop pituitary adenomas, and most of these are macroadenomas associated with excess levels of growth hormone (GH) or prolactin (PRL), or both.^46,47

Pathology

The pituitary gland is a bilobed, composite neuroendocrine structure. It is composed of an anterior adenohypophysial component in apposition with a morphologically, embryologically, and functionally distinct posterior neurohypophysial component. Either component can serve as a substrate for neoplastic transformation, but most pituitary tumors originate within the adenohypophysis, taking the form of histologically benign adenomas. Primary neurohypophysial tumors are rare and are generally less morphologically diverse; most are granular cell tumors, gliomas, or hamartomas, with each bearing histologic similarities to corresponding tumors found elsewhere in the neuraxis. The neurohypophysis is the favored intrasellar site for metastatic tumors.

Because pituitary adenoma is clinically and numerically the most significant neoplastic process affecting the pituitary gland, only this lesion is discussed in this chapter. However, a diverse collection of other abnormalities can occur in the sellar region. Often masquerading as nonfunctioning pituitary adenomas, these lesions include a wide variety of neoplasms, developmental lesions, cysts, inflammatory processes, and aneurysms (Table 134-1).

TABLE 134-1 Differential Diagnosis of a Sellar Mass

Clinical and Endocrine Classification

The simplest approach to classifying pituitary adenomas, one favored by clinicians, is the functional classification. This classification broadly distinguishes tumors as functional or nonfunctional, based on their secretory activity in vivo. Functional adenomas are those that secrete PRL, GH, TSH, or ACTH, producing their respective clinical phenotypes of amenorrhea-galactorrhea syndrome, acromegaly or gigantism, secondary hyperthyroidism, and Cushing’s disease or Nelson’s syndrome. Tumors unassociated with a clinical hypersecretory state (gonadotroph adenomas, null cell adenomas, oncocytomas, and various silent adenomas) are collectively designated as clinically nonfunctional.

Pathologic Classification

Of the pathologic classifications of pituitary tumors, the earliest and most enduring distinguished adenomas on the basis of cytoplasmic staining affinity. Now obsolete, this classification attempted to confine a clinically and pathologically heterogeneous group of tumors within elementary categories of acidophilic, basophilic, and chromophobic. Under such a scheme, it was assumed that acidophilic adenomas were exclusively GH-secreting tumors and basophilic adenomas were ACTH-secreting tumors. Tumors that failed to stain were collectively designated chromophobic and were believed to be hormonally inactive. Perhaps because of its simplicity and convenience, this three-tiered classification endured for decades. With the emergence of newer methods came the realization that the tinctorial characteristics of the cytoplasm correlate poorly with secretory activity, reliable cell type recognition, and cytogenesis. Not all acidophilic tumors produce GH, some basophilic tumors do not cause Cushing’s disease, and more than one half of all chromophobic tumors are endocrinologically active.

Immunohistochemistry and electron microscopy represent the “gold standard” methods of classifying pituitary adenomas. Delineating tumors on the basis of hormonal content, ultrastructural morphology, and cellular derivation, these methods have led to a new classification of pituitary adenomas that reliably correlates structure with function and cytogenesis with biology.³² As outlined in Table 134-2, this classification recognizes 14 principal pituitary adenoma subtypes, each having its own immunohistochemical and ultrastructural profile. Adenomas are stratified first on the basis of cellular origin and hormonal content and secondarily on the basis of ultrastructure.^32,51–54 Subtypes that appear to have a higher recurrence rate include sparsely granulated GH adenomas, mammosomatotroph adenomas, acidophil stem-cell adenomas, and silent adenomas (especially silent ACTH adenomas and silent subtype 3 tumors).^32,53,54

The morphologic appraisal of pituitary adenomas has its limitations. Whether considered from the standpoints of routine histology, hormonal immunophenotype, or ultrastructural morphology, none of these techniques permits reliable inferences about tumor behavior or prognosis.⁵¹ Accordingly, pituitary adenomas are not amenable to any form of histopathologic grading, such as that available for astrocytic tumors, that could reliably distinguish aggressive variants from indolent ones. The usual morphologic markers of tumor aggressiveness—pleomorphism, nuclear atypia, increased cellularity, and mitotic activity—correlate poorly with an adenoma’s invasive tendency, proliferative capacity, potential for recurrence, and overall biologic behavior. In general, mitotic figures and other morphologic markers of aggressive behavior are neither sufficiently common among invasive tumors nor sufficiently rare among noninvasive tumors to be of routine prognostic use.⁵⁵ Nevertheless, pituitary adenomas are graded as “typical adenomas,” “atypical adenomas,” and “pituitary carcinomas.”⁵³ Atypical adenomas are characterized by atypical morphology, an elevated mitotic index, a Ki-67 (MIB-1) labeling index greater than 3%, and extensive p53 nuclear staining. Pituitary carcinoma is characterized by the presence of noncontiguous metastatic spread of an adenoma.^53,54

Imaging Classification

From a surgical standpoint, pituitary tumors can be classified on the basis of their size and growth characteristics, as determined by imaging studies. The simplest system, based purely on size, classifies tumors as microadenomas (<1 cm in diameter) or macroadenomas (>1 cm in diameter). This system fails to account for the tremendous variability in the size and growth characteristics of macroadenomas. The most enduring classification is that devised by Hardy^12,56 and modified by Wilson.⁵⁷ This five-tiered radiologic classification first differentiates tumors as microadenomas or macroadenomas. Microadenomas are designated grade 0 or grade I tumors, depending on whether the sellar appearance is normal or minor sellar changes are present, respectively. Macroadenomas causing diffuse enlargement, focal destruction, and extensive destruction of the sella are referred to as grade II, grade III, and grade IV tumors, respectively. In this system, macroadenomas are also staged according to the degree and direction of extrasellar extension—extending to the suprasellar cistern only (stage A), to third ventricle floor (stage B), or into the third ventricle (stage C). Tumors that have extensive lateral intradural or extradural extension are referred to as stage D and stage E, respectively.

With the advent of high-quality MRI, Knosp and colleagues⁵⁸ proposed a grading system that predicts cavernous sinus invasion based on the position of the tumor in relation to tangents drawn through the supra- and intracavernous carotid arteries in the coronal view. Tumors that encase the carotid artery are universally found to invade the cavernous sinus at surgery. Tumors that do not pass beyond a tangent along the medial border of the supra- and intracavernous sinus do not invade the cavernous sinus. However, no other radiographic findings can definitively predict cavernous sinus invasion or the lack thereof.⁵⁹

World Health Organization Classification

A variety of approaches can be used to classify pituitary tumors, ranging from simple to sophisticated, with each having its own merits and limitations. The management of pituitary tumors is a multidisciplinary endeavor, and nosologic preferences vary among specialties; the pathologist may favor a morphologic classification, the endocrinologist may favor one based on endocrine activity, and the neurosurgeon may favor one based on tumor size and invasiveness. In a bid to create a comprehensive classification scheme universally acceptable to clinicians, pathologists, and surgeons alike, a seven-tiered classification of adenohypophysial tumors has been proposed by the World Health Organization.⁵³ In this scheme, seven descriptive levels are applied to each adenoma:

This classification attempts to integrate the merits of all existing complementary classification schemes and provides a practical synopsis of all relevant clinical and pathologic aspects of any given adenoma.

Diagnostic Approach

For patients in whom a pituitary adenoma is suspected, a coordinated two-step diagnostic approach is required. The first step involves establishing an endocrine diagnosis, and the second is securing an anatomic diagnosis.

Therapeutic Approach

After a diagnosis of pituitary adenoma has been established on the basis of clinical examination, endocrinologic testing, and imaging studies, optimal therapy begins with a clear assessment of the treatment objectives. In general, therapy for pituitary tumors should be directed at the following goals:

Therapeutic options for pituitary tumors include surgical resection, receptor-mediated pharmacotherapy, and radiation therapy (conventional and stereotactic). Although each is effective to some degree in various situations, the merits and limitations of these modalities must be carefully considered, and a comprehensive, individualized plan of management must be provided to each patient.

Surgical Indications

The most urgent indication for surgical intervention is related to pituitary apoplexy.^71–74 Patients may present with hemorrhage into an existing pituitary tumor or with acute necrosis of the tumor and subsequent swelling. In either case, the presentation includes sudden headache, precipitous loss of vision, ophthalmoplegia, altered level of consciousness, and collapse from acute adrenal insufficiency. In such situations, urgent glucocorticoid replacement and surgical decompression constitute the most reliable and effective form of therapy. Nevertheless, clinical apoplexy should be distinguished from subclinical apoplexy. Many tumors undergo microhemorrhage or infarction without clinically devastating results. Other patients may present with headache and pituitary insufficiency but without visual decline. Supportive nonsurgical treatment with analgesia and appropriate hormone replacement can be considered for these patients. Indeed, some patients managed in this manner experience tumor involution with serial imaging.

Another clear surgical indication is progressive mass effect (usually manifesting as vision loss) from a large macroadenoma. These patients should always have a serum PRL determination because prompt and dramatic shrinkage of prolactinomas can occur with appropriate pharmacologic management. More often, the PRL level is only modestly elevated, and the patient has a clinically nonfunctioning pituitary tumor or other sellar mass. Such patients require decompression.

Among hyperfunctioning pituitary adenomas, surgery is the treatment of choice for Cushing’s disease, acromegaly, and secondary hyperthyroidism. In the case of Cushing’s disease, medical management is invariably suboptimal, and surgery provides the best means of obtaining prompt and lasting remission. In the case of somatotroph and thyrotroph adenomas, some latitude exists for the use of somatostatin analogues as the initial intervention, but surgery remains the preferred, primary, and definitive treatment for these conditions.^75–78 For most prolactinomas, medical therapy is the preferred option unless the tumor is unresponsive or the patient is intolerant of medical therapy.

Failure of prior therapy often represents an indication for surgical intervention and usually occurs in one of several situations. A minority of patients are intolerant of the side effects of medical therapy. Other patients treated with radiotherapy have a favorable initial response followed by recurrence of symptoms in the form of mass effect or recurrent hormonal hypersecretion. For others treated with pharmacologic therapy, the response might have been suboptimal. For example, in some patients with a presumed prolactinoma, medical therapy can normalize PRL levels, but tumor growth continues. At surgery, these patients are usually found to have lesions other than prolactinoma. In other patients with genuine prolactinomas, a suboptimal response to medical therapy may take the form of persistently elevated PRL levels. Surgery may reduce the tumor burden and lead to a more effective pharmacologic response.⁷⁹ The same also applies to acromegalic patients treated with somatostatin analogues.⁸⁰

A somewhat generic surgical indication is the need for tissue diagnosis. Although seldom required in the case of functioning pituitary adenomas, this indication may be important when the surgeon is confronted with a nonfunctioning sellar mass whose pathologic identity cannot be confirmed without histologic examination.⁵¹

Surgical Contraindications

Contraindications for surgery are few. The most important are related to the general medical condition of the patient. For instance, florid Cushing’s disease, acromegaly, or secondary hyperthyroidism can pose a significant anesthetic risk. In most cases, however, the patient’s medical condition can be stabilized without undue delay. Similarly, profound hypopituitarism can be a temporary contraindication to surgery, although it should be fully responsive to steroid and thyroid replacement. Active sinus infection may also contraindicate the transsphenoidal approach, although this condition is usually responsive to appropriate antibiotic therapy. Rarely, MRI may reveal ectatic and tortuous carotid arteries that protrude from the region of the cavernous sinus and obstruct transsphenoidal access.

Preoperative Evaluation

After anatomic and endocrine diagnoses have established the patient as a surgical candidate, a comprehensive preoperative evaluation is undertaken. Attention is first turned to optimizing the patient’s medical condition. The general medical examination should address issues such as hypertension, cardiac disease, diabetes, thyroid status, and pituitary endocrine function. Such perturbations commonly occur in pituitary tumor patients, and most are responsive to a significant degree to pharmacologic management. In all patients with pituitary adenomas, some consideration should be given to the possibility of MEN-1. Soliciting a family history and measuring serum calcium levels are important in this regard.

Because visual dysfunction frequently complicates the course of many pituitary tumors, a complete ophthalmologic evaluation is mandatory for all patients with visual complaints and for those whose tumors exhibit suprasellar extension. Serial assessments of visual fields and acuity are often necessary to document disease progression and response to therapeutic intervention.

Choice of Surgical Approach

Surgical approaches to the sellar region can be broadly divided into three groups: transsphenoidal approaches, conventional craniotomy, and alternative skull base approaches (Table 134-3). For historical completeness, stereotactic approaches constitute a fourth category, but this approach is seldom indicated. Within each of the three groups, there is at least one standard procedure, as well as a menu of technical variations and options that allow the operation to be precisely tailored to the situation at hand. The overwhelming majority of all pituitary adenomas can be accessed through a transsphenoidal approach. The remainder require transcranial approaches consisting of standard pterional or subfrontal craniotomy or various skull base approaches that may be transcranial, extracranial, or a combination of the two.

TABLE 134-3 Surgical Approaches for Pituitary Tumors

The choice of surgical approach depends on several factors. The most important of these include the size of the sella and its degree of mineralization, the size and pneumatization of the sphenoid sinus, the position and tortuosity of the carotid arteries, the presence and direction of any intracranial tumor extensions, the presence of any uncertainty about the pathology of the lesion, and whether prior therapy (surgical, pharmacologic, or radiotherapeutic) has been administered. As a rule, a transsphenoidal approach is preferred in all but the following circumstances:

If any of these features exist, a transcranial procedure should at least be considered.

Occasionally, the configuration of the tumor is such that a single approach, transsphenoidal or transcranial, is insufficient to achieve complete tumor removal (Fig. 134-1). This situation is uncommon and is typically associated with giant tumors having a significant intracranial component that may be inaccessible from below. In such situations, a combined transsphenoidal-transcranial approach can be used. Barrow and colleagues⁸¹ described the simultaneous performance of both approaches by two surgical teams. Alternatively, the two can be performed in a staged fashion. When considering such combined approaches, it is important to ascertain that the risks of aggressive surgery are justified by the benefits of radical tumor removal. In some instances, particularly those involving elderly patients with large, slow-growing, nonfunctioning tumors, a less radical and safer subtotal decompression may be preferable. However, in carefully selected patients, the combined approach represents an effective alternative.

FIGURE 134-1 Coronal T1-weighted image of a large, invasive, nonfunctioning pituitary macroadenoma.

Transsphenoidal Approaches

Details of anesthetic management have been described elsewhere.⁸² Special consideration must be given to the intubation of acromegalic patients, who may require awake intubation to safely secure an airway. Perioperative prophylactic antibiotics are routinely employed. Traditionally, perioperative “stress dose” exogenous corticosteroids were administered to all patients except those with Cushing’s disease whose serum cortisol was to be monitored in the postoperative period. However, routine administration appears to be required only in those patients who are adrenally insufficient preoperatively; in others, we no longer administer perioperative exogenous steroids. Instead, patients are monitored for clinical symptoms of adrenal insufficiency, and morning serum cortisol levels are drawn on each postoperative day to determine hypothalamic-pituitary-adrenal axis reserve. Levels less than 8 µg/dL are considered low and are replaced accordingly.

For most pituitary tumors, some variation of the transsphenoidal approach is the most appropriate route.^25,83–85 All the variations (e.g., endonasal versus sublabial, endoscopic versus microscopic, submucosal versus direct sphenoidotomy) are minimally invasive, and the true standard of care is simply some route involving the transsphenoidal corridor. The virtues of the transsphenoidal approach are many. Most important, it 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. This is true regardless of which variation is used. The techniques described here do not represent a compendium of all variations; they include the approaches we use in the treatment of pituitary adenomas and the relative indications for each. Virtually all tumors can be resected using these techniques, although each technique (and its variations) has particular advantages and disadvantages.

Advantages of the microscope include its familiarity to the neurosurgeon and its three-dimensional view. The microscope itself is outside the surgical field and does not impair the maneuverability of instruments. Once the speculum is in place and confirmed to be in the appropriate trajectory to the sphenoid sinus and sella, the microscope (which can be fixed in space) maintains that safe trajectory. The speculum also protects the mucosa during the operation. Instruments can be brought in and out of the field easily without injuring the mucosa or nares. Disadvantages include the limitations created by line of sight. With the tumor out of view, removal is performed by feel, which requires not only surgical skill but also experience.

Advantages of the endoscope include the panoramic and angled views that allow the surgeon to remove a greater portion of the tumor by direct visualization. Endoscopic macroadenoma resection relies on sight more than feel (in contradistinction to the microscopic removal of macroadenomas). This improves the surgeon’s comfort and the certainty of resection. Indeed, the advantages of the endoscope are most apparent with macroadenomas; with smaller tumors, the advantages are less appreciable. The endoscopic approach is also well tolerated and rarely requires nasal packing. Anterior sinonasal complications are almost completely avoided. However, the surgeon must create enough room not only for the suction and dissector-curet (as in the microscopic approach) but also for the endoscope itself. Because more instruments are in place than with the microscopic approach, the exposure must be larger to accommodate the addition of the endoscope. This larger exposure may include a unilateral or bilateral middle turbinectomy, which increases the potential for posterior sinonasal complications and requires more postoperative nasal care.

Positioning

The patient’s head is supported by a Mayfield headrest with a horseshoe (Fig. 134-2). Because the head is not fixed, gentle lateral movements of the head can be used to optimize intraoperative visualization, especially of the cavernous sinus area. This is particularly useful in microscopic cases because it allows the surgeon to move the patient’s head instead of stopping the operation to move the microscope. Although this is not a factor when the endoscope is used (because it provides a panoramic view), we do not fix the patient’s head in endoscopic cases either, to avoid the postoperative scalp discomfort associated with the cranial clamp. Fixation of the head may be necessary when certain forms of semirecumbent guidance are used.

FIGURE 134-2 Patient positioning and surgical team. 1, The patient’s right shoulder is positioned in the top right-hand corner of the operating table. 2, The headrest frame is positioned to the far left. 3, The horseshoe headrest is rotated so that the patient’s head is oriented toward the surgeon. 4 and 5, The patient’s head is oriented at a right angle to the walls of the room to facilitate lateral intraoperative videofluoroscopy of the draped patient. 6, The head is positioned so that the trajectory is toward the sella. This is most easily accomplished by positioning the neck such that the dorsum of the nose is parallel to the floor. 7, The beach-chair position is used with the table angled approximately 20 degrees. 8, The patient’s right hand is carefully positioned in an unobtrusive manner under the buttocks. ASST, assistant; SCRUB, scrub nurse; SGN, surgeon.

(From Jane JA Jr, Thapar K, Kaptain GJ, et al. Pituitary surgery: transsphenoidal approach. Neurosurgery. 2002;51:435.)

A semirecumbent position is used, with the patient’s back at a 20-degree angle from the horizontal and the head above the heart (see Fig. 134-2). This facilitates venous drainage and decreases venous pressure within the cavernous sinus. The right shoulder is placed at the upper right-hand corner of the table; the patient’s left ear is pointed toward the left shoulder, and the table is turned so that the patient’s head remains parallel to the wall of the room. This moves the foot of the table away from the surgeon and allows him or her to stand or sit in close proximity to the surgical field without bending over the patient. It also provides a spatial cue regarding the midline during a microscopic approach. If both the patient’s head and the microscope are perpendicular to the wall, the operative line of sight is in the midline. The head may be tilted to the right in some endoscopic approaches.

Nasal Preparation

All surgeries can benefit from some degree of nasal decongestion, with the possible exception of patients with a history of hypertension and coronary artery disease. Before and immediately after induction of anesthesia, patients are given oxymetazoline intranasally. During positioning, oxymetazoline-soaked patties are placed between the middle turbinates and septum using a nasal speculum and bayonet forceps. The pledgets are allowed to remain in contact with the nasal mucosa for 5 to 10 minutes, during which draping of the patient is completed. The patties are removed after prepping and draping, and the nasal mucosa can be injected with 0.2% ropivacaine with 1 : 200,000 epinephrine. In microscopic cases, 10 to 20 mL of the solution is infiltrated, first along the upper gingiva, then along the inferior portion of the nasal septum, and finally along the lateral aspects of the nasal septum. A conscious effort is made to dissect the nasal mucosa away from the cartilaginous septum with the injection solution (Fig. 134-3A and B). This step is performed under direct vision with the aid of a nasal speculum, headlight, and loupes. In endoscopic cases, the middle turbinate, posterior septum, and sphenoid rostrum are injected (Fig. 134-4).

FIGURE 134-3 Endonasal approaches. A and B, Submucosal endonasal approach. C, Septal displacement approach.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

FIGURE 134-4 Endoscopic views of mucosal injection in the right nostril just before (A) and after (B) injection of the middle turbinate (MT). S, nasal septum.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

Sphenoid Sinus Access and Exposure

Microscopic Approaches

The next major consideration in the transsphenoidal procedure is the precise route of entry into the sphenoid sinus. For microscopic approaches, the two basic options are the endonasal approach and the sublabial approach. Selection of one over the other depends on the size of the nostril, the size of the lesion, and the preference of the surgeon. We tend to favor endonasal approaches in most instances, reserving the sublabial incision for pediatric patients or adults with small nostrils in whom the broader corridor afforded by the piriform aperture improves the visualization of the surgical field and the maneuverability of the surgical instruments. The endonasal microscopic approaches include the transseptal submucosal, septal pushover, and direct sphenoidotomy (see Fig. 134-4). These differ based on the location of the initial incision. With the transeptal submucosal technique, the incision is made just within the nostril, posterior to the columella; with the septal pushover, it is fashioned at the junction of the bony and cartilaginous septum; and with direct sphenoidotomy, the incision is made at the junction of the septum and the rostrum of the sphenoid. As the incision is carried farther back, the amount of septal dissection, and therefore the number of nasal complications, necessarily decreases. This decrease in septal dissection comes at the cost of a progressively narrower and potentially off-midline trajectory to the sella.

Endonasal Microscopic Approaches

The endonasal submucosal transseptal approach begins with a right-sided hemitransfixion incision in the nostril, with the columella retracted to the patient’s left and the ala retracted toward the right (see Fig. 134-3A). The inferior border of the cartilaginous septum is exposed with sharp dissection, and one side of the septum is exposed submucosally with a combination of sharp and blunt dissection, thereby creating a unilateral anterior tunnel (Fig. 134-5). The dissection continues posteriorly, elevating the nasal mucosa away from the cartilaginous septum back to its junction with the bony septum. A vertical incision is made at this junction, and bilateral posterior submucosal tunnels are created on either side of the perpendicular plate of the ethmoid. The articulation of the cartilaginous septum with the maxilla is then dissected free, and an attempt is made to raise the inferior mucosal tunnel on the opposite side so that the cartilaginous septum can be displaced laterally without creating inferior mucosal tears. A self-retaining nasal speculum can be introduced to straddle the perpendicular plate of the ethmoid, exposing the face of the sphenoid sinus.

FIGURE 134-5 Submucosal tunnels. A, Axial views: anterior submucosal tunnel (1); septal displacement and posterior submucosal tunnels (2). T, T-tumor. B, Coronal views: anterior submucosal tunnel (1); posterior and inferior submucosal tunnels before (2) and after (3) septal displacement.

(From Jane JA Jr, Thapar K, Kaptain GJ, et al. Pituitary surgery: transsphenoidal approach. Neurosurgery. 2002;51:435.)

In some patients, particularly those who have had previous nasal, septal, or transsphenoidal surgery, we have used an alternative endonasal approach called the endonasal septal pushover technique (Fig. 134-3C).^83,87,88 Instead of a submucosal incision for the creation of an anterior nasal tunnel, the nostril is entered, and an incision is made through the lateral mucous membrane of the nasal septum at the base of the septal insertion onto the maxillary ridge. The incision is carried back to the junction of the cartilaginous and bony septa or back to the face of the sphenoid if this bone has previously been removed. The nasal septum is carefully disarticulated, an opposite-side inferior tunnel is developed, and the septum together with the two layers of attached mucous membrane is reflected laterally to expose the perpendicular plate of the ethmoid and the sphenoid face. This rapid method may lack the elegance of the standard submucosal approach, but it can be very effective when the conventional approach proves difficult. If necessary, it can also be converted to a sublabial approach.

The most rapid of all endonasal approaches is the direct sphenoidotomy.^89,90 In this approach, the speculum is inserted under fluoroscopic guidance directly anterior to the sphenoid rostrum. A sharp incision is made at the attachment of the septum to the sphenoid rostrum, and the septum is reflected laterally, exposing the rostrum of the sphenoid. Because there is no submucosal septal dissection, there is rarely any need for nasal packing with its resultant postoperative discomfort. The primary advantages of the septal pushover and direct sphenoidotmy techniques are the rapidity of the approaches and the avoidance of anterior septal dissection and its potential complications. However, these more direct approaches provide a narrower exposure and an off-midline trajectory—factors that should be considered when choosing the endonasal technique.

Sublabial Microscopic Approach

Under loupe magnification, the upper lip is retracted, and an incision is made in the buccogingival junction from one canine tooth to the other. Subperiosteal dissection is used to carefully elevate the mucosa from the maxillary ridge and the anterior nasal spine until the inferior border of the piriform aperture is exposed. Using curved dissectors and working from the lateral border medially, the two inferior nasal tunnels are created by dissecting the mucosa away from the superior surface of the hard palate. With sharp dissection, the right anterior tunnel is created and connected with the right inferior tunnel, and the entire right side of the nasal septum is exposed back to the perpendicular plate of the ethmoid. Using firm, blunt dissection along the right side of the base of the nasal septum, the cartilaginous portion of the nasal septum is dislocated and reflected to the left, and a left posterior mucosal tunnel is developed along the left side of the bony septum. At this point, it should be possible to insert the transsphenoidal retractor. It should be spread gently, and care should be taken to place all mucosal tears lateral to the retractor blades. As the retractor is opened, the turbinates are compressed, and it is unwise to apply too much force in opening the retractor. After the retractor is in place, the vomer, with its distinctive keel shape, should be visualized.

Endoscopic Approaches

Although the transsphenoidal approach has always been considered minimally invasive, particularly when compared with conventional transcranial approaches, the concept has been redefined in the context of endoscopic approaches to the sella.^{21,25,28,31,91} These approaches use straight and angled endoscopes as the sole visualization tools (a pure endoscopic approach) or as a supplement to the operating microscope (an endoscopic-assisted microscopic approach).

Several endoscopic approaches to the sella are used. The iterations include mono- or binarial techniques, two-handed approaches with or without the endoscope holder, and three-handed or four-handed approaches without the holder. Some surgeons advocate a unilateral partial middle turbinectomy to improve the maneuverability of instruments. Our preference is to perform a three-handed binarial technique with a partial posterior septectomy without routine middle turbinectomy.

The 0-degree endoscope is used for the majority of exposure and tumor resection. The endoscope is brought within the nostril, and the sinonasal anatomy is identified, including the nasal floor and both the inferior and middle turbinates. The middle turbinate is lateralized, and the choana and sphenoethmoid recess are identified. The sphenoid ostium is then identified posterior to the inferior third of the superior turbinate (Fig. 134-6). Once identified, the posterior septum can be incised and reflected contralaterally to identify the contralateral sphenoid ostium (Figs. 134-7 and 134-8). The bone between the two ostia is then removed, providing the initial sphenoidotomy. A posterior septectomy is then completed, with care taken not to remove the septum more anterior than the anterior limit of the middle turbinate.

FIGURE 134-6 Endoscopic view of the right sphenoid ostium (SO) at the inferior third portion of the superior turbinate (ST). SER, sphenoethmoid recess.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

FIGURE 134-7 Endoscopic view of the right nasal cavity. After the sphenoid ostium is identified, the nasal septal mucosa can be incised (dotted lines) before performing the posterior septectomy. Arrow shows midline vomer. MT, middle turbinate; S, nasal septum.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

FIGURE 134-8 Endoscopic view after the posterior septectomy but before the anterior sphenoidotomy. Both sphenoid ostia (arrows) are visible with the endoscope in the right nasal cavity. An instrument placed through the left nostril can be seen above the left sphenoid ostium (SO). MT, middle turbinate; S, nasal septum; SR, sphenoid rostrum; ST, superior turbinate.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

Sphenoidotomy

Microscopic

With the microscopic approaches, once the anterior face of the sphenoid sinus is reached, videofluoroscopy or neuronavigational image guidance is used to make any necessary adjustments to the final position and trajectory of the retractor blades. Midline orientation is crucial at this stage, and CT images of the sphenoid region are extremely helpful in delineating the bony anatomy and planning sphenoid entry. Portions of the bony nasal septum present in the operative field should be resected with a Lillie-Koffler tool or a Ferris-Smith punch. Any cartilage and bone that has been resected should be preserved so it can be used during closure. For experienced surgeons, the nasal spine does not represent a major obstacle anteriorly, and from a cosmetic standpoint, it is preferable to preserve this structure rather than chisel it away. With the sphenoid retractors in position, the keel of the vomer and the face of the sphenoid are seen. On either side of the central ridge, the ostia of the sphenoid sinuses can be identified.

After the operating microscope is introduced, the anterior wall of the sphenoid is opened. Fracturing into the sphenoid sinus is usually possible by grasping the vomer with a Lillie-Koffler forceps, Ferris-Smith punch, or chisel, if necessary. Once within the sphenoid sinus, the exposure is widened with a right-angled punch. The mucosa within the sinus is resected with a cup forceps. Resection of the mucosa aids in reducing bleeding and decreases the risk of postoperative mucocele formation. With all internal bony landmarks clearly visible, the surgeon reorients himself or herself with respect to the position of the carotid arteries, sellar floor, anterior fossa floor, and clivus, correlating the operative anatomy with imaging studies and navigational adjuncts to ensure that the appropriate midline trajectory is maintained.

Endoscopic

The endoscopic anterior sphenoidotmy is generally larger than that required for microscopic approaches. This relates to the fact that endoscopic exposures must account for the added instrument in the operative field (the endoscope). Once the initial sphenoidotomy has been performed, the intersphenoid sinus septae should be removed so that the sella can be identified. The extent of the sphenoidotomy can then be tailored to the location of the sella. The inferior extent of the sphenoidotomy should allow a sucker to be placed on the clivus below the level of the tumor. The proximal vomer should be protected as a reference point for the anatomic midline. Care must also be taken not to injure the posterior nasal branches of the sphenopalatine artery at the inferolateral margins of the sphenoidotomy. The superior extent of the sphenoidotomy provides room for the endoscope during tumor resection. The sphenoidotomy should continue superiorly until the tuberculum sellae, lateral opticocarotid recesses, and planum sphenoidale are readily observed (Fig. 134-9).

FIGURE 134-9 Endoscopic view of the sphenoid sinus as the intersphenoid sinus septum is being removed. Note the panoramic view of the sphenoid anatomy with the optic and carotid protuberances (OP and CP, respectively), opticocarotid recess (OCR; arrow), clivus (Cl), planum sphenoidale (PS), and sellar floor (SF).

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

Sellar Entry

The sellar floor should be clearly visible. With some tumors, the sellar floor is eroded or extraordinarily thin, and it can be fractured with a blunt hook. Occasionally, a midline septum within the sphenoid sinus can be used to gain entry into the sella by grasping its base and gently twisting as the bone is removed. If the floor of the sella is thick, a small chisel can be used to remove a square of bone. In cases of an even thicker sellar floor, and when the sphenoid sinus is poorly pneumatized, a high-speed drill can be used to provide exposure. In the setting of recurrence, the appearance of the sellar floor can vary considerably. In more difficult cases, it may consist entirely of scar tissue, seemingly in continuity with the scarring encountered in the sphenoid sinus. In other cases, the sellar floor may have been fully reconstituted, appearing as if no prior procedure had been performed. In microscopic cases, the surgeon should use careful videofluoroscopic control or image guidance to continually monitor sellar entry, exposure, and trajectory. The panoramic endoscopic views generally provide adequate information regarding the anatomic midline and trajectory, except in repeat surgery or tumors with significant sphenoid sinus invasion.

After the sellar floor has been penetrated, the opening is widened with a Kerrison-type punch. An adequate bony exposure is crucial to the success of the transsphenoidal approach, particularly when dealing with large tumors. For recurrent tumors in particular, a wide bony opening can allow virgin dura to be uncovered. Identification of the latter greatly assists in establishing a plane between dura and scar tissue. We favor a wide removal of the sellar floor in virtually every case, extending from one cavernous sinus to the other. A small, bony margin of the sellar floor should be left, because this facilitates sellar reconstruction at the end of the procedure (Fig. 134-10).

FIGURE 134-10 Endoscopic views of the extent of sellar opening. A, Sellar opening before resection of an intrasellar microadenoma. B, Sellar opening before resection of a macroadenoma. Cl, clivus; CP, carotid protuberance; OP, optic protuberance; PG, pituitary gland; PS, planum sphenoidale.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

An invasive tumor may erode through the anterior dura of the sella, but in most cases the dura is intact. It is exposed as widely as feasible, and careful attention is paid to its appearance. Transverse, blue intracavernous sinuses traversing the sella at the top and bottom of the anterior dura are common, particularly in cases of microadenomas. The anterior dura may appear totally blue and very thin, indicating the possible presence of a cyst or an empty sella. After the dura is exposed completely, it should be opened with great care. A partial empty sella is sometimes present, and a CSF leak early in the operation can be a major deterrent to success. Before the dural incision is made, it is prudent to use Doppler ultrasonography and to review the imaging studies to assess the position of the carotid arteries so they are not injured during durotomy. In dealing with some cystic pituitary adenomas, it is helpful to use a long needle to evacuate and evaluate cyst contents before dural opening.

Having considered these issues, the site of dural opening is selected and incised in a cruciate or X-shaped fashion or with the excision of a dural window. Next, an attempt is made to establish a definite subdural cleavage plane between the pituitary gland or tumor and the underlying dura. A plane of dissection between the two leaves of the dura should be carefully avoided, because this practice allows entrance into the cavernous sinus, and heavy venous bleeding will result. The dural perimeter is widened by shrinking the dural margins with cautery, providing an unobstructed view into the sella.

Tumor Removal

For the typical macroadenoma, the tumor is entered with a ring curet; tissue is loosened and then removed with a relatively blunt curet and forceps. Regardless of whether a micrscopic or endoscopic surgery is performed, the surgeon should attempt tumor removal in an orderly fashion (Fig. 134-11). Our practice is to first remove tumor in the inferior aspect and then proceed laterally, from inferior to superior aspects on both sides, removing tumor along the medial side of the cavernous sinus. The main distinction during endoscopic removal is the ability to directly visualize tumor removal from the cavernous sinus walls and suprasellar space (Fig. 134-12). The surgeon must resist coring out the central and most accessible portion of the tumor first, because this may cause premature descent of the diaphragma and entrapment of more laterally situated tumor. It is also important to delay the superior dissection until the lesion is relatively free elsewhere, because this minimizes trauma to the pituitary stalk and secondarily transmitted trauma to the hypothalamus. The surgeon may occasionally be required to follow a tumor into a cavernous sinus or deal with a tumor directly involving the diaphragma. In either case, any maneuver more forceful than gentle cureting may be dangerous; pulling of adherent fragments must be avoided. Decompression of the intrasellar portion of the tumor frequently permits a suprasellar extension to prolapse into view within the sella. After this has been resected, the diaphragma prolapses and generally signifies that the resection is complete. When spontaneous prolapse of the tumor capsule or diaphragma does not occur, instillation of 15 to 20 mL of air or lactated Ringer’s solution into a lumbar subarachnoid catheter may facilitate descent. Alternatively, bilateral jugular vein compression or application of positive end-expiratory pressure can help in delivering a suprasellar tumor. If the tumor still fails to descend, a ring curet can be used cautiously in the intracranial space. These maneuvers are well suited for the endoscopic technique, which allows both cavernous sinus and suprasellar portions of tumors to be removed under direct visualization. Bleeding from the tumor bed can usually be controlled by precise tamponade with cotton patties or Gelfoam.

FIGURE 134-11 Resection and reconstruction. A, Dural incision. B, Subdural plane developed. C, Sequential removal of tumor. D, Reconstruction of sellar floor.

(From Jane JA Jr, Thapar K, Kaptain GJ, et al. Pituitary surgery: transsphenoidal approach. Neurosurgery. 2002;51:435.)

FIGURE 134-12 Intrasellar endoscopic views. Using the endoscope, the resection cavity can be fully inspected. A, View using the 30-degree endoscope looking toward the right cavernous sinus wall. The redundant diaphragma sellae (D) obstructs the full view. B, Still using the 30-degree endoscope with the same vantage point, the diaphragma is elevated, which exposes residual tumor (asterisk). C, View after the residual tumor has been removed. Note the compressed pituitary gland (PG) against the diaphragma. D, Endoscopic view of the left cavernous sinus wall and a portion of the sellar floor using the 30-degree endoscope after tumor resection. The cavernous sinus wall appears to be intact and free of tumor residue. CSD, cavernous sinus dura; SFD, sellar floor dura.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

In all cases, a concerted effort is made to preserve normal pituitary tissue. In a large, diffuse adenoma, normal glandular tissue usually appears as a thin membrane situated superolaterally against the sellar wall. The orange-yellow gland, together with its firm consistency, distinguishes it from the grayish color and finely granular texture typical of the tumor (see Fig. 134-12). A biopsy of the suspected glandular remnant may be taken for confirmation, but the appearance is often so typical that this tissue can be left behind with confidence.

Microadenomas necessitate a different operative strategy because many are not immediately visualized on opening the dura. A systematic search through a seemingly normal-appearing gland is often required. We begin with a transverse glandular incision, followed by subdural dissection and mobilization of the lateral wings. If the incision in the gland is deep enough, lateral pressure with a Hardy dissector usually causes the microadenoma to herniate into the operative field. Its location can therefore be delineated, its cavity entered, and its removal completed by use of a small ring curet and cup forceps. All suspicious tissue is removed, and a biopsy specimen is occasionally obtained from the residual and presumably normal pituitary gland. It is also possible to search for and find the pseudocapsule in many cases. If preserved, an extracapsular resection ensures complete removal of the tumor.^50,92

Reconstruction and Closure

After the tumor has been removed and hemostasis has been achieved, the sella must be carefully evaluated with regard to reconstruction and closure. We prefer not to leave dead space in the sella. If no CSF leak has occurred, the sella is loosely packed with Gelfoam. If a CSF leak has occurred, some form of tissue graft becomes mandatory. Reconstruction of the sellar roof can be attempted with a piece of homologous dural graft material or fascia lata; however, this step probably adds little to the security of the seal. Current practice favors simple packing of the sella with fat taken from the right lower quadrant or subumbilical region of the abdomen. The fat is soaked in a chloramphenicol solution, may be rolled in Avitene, is trimmed to appropriate size, and is snugly placed within the sella. In either case, the sellar floor is then carefully reconstructed using a suitably trimmed piece of cartilage, bone, or tailored artificial grafts (Fig. 134-13; see Fig. 134-11). Some surgeons use fibrin glue as part of the closure in patients who have had CSF leaks, but we have found that an impressive mound of fibrin glue is a poor substitute for an inadequate structural repair; the integrity of the latter and not the adhesive properties of the former is the essential deterrent to postoperative CSF leaks. Likewise, we seldom use continuous lumbar drainage in patients who have had postoperative CSF leaks. Instead, we have adopted a policy of immediate reexploration, repacking of the sella, and reconstruction of the floor.

FIGURE 134-13 Endoscopic view of sellar reconstruction using a polyethylene implant. C, clivus; OCR, optico-carotid recess; OP, optic canal; PS, planum sphenoidale.

(From Jane JA Jr, Han J, Prevedello DM, et al. Perspectives on endoscopic transsphenoidal surgery. Neurosurg Focus. 2005;19:E2.)

In closing the nasal portion of the procedure, careful attention is paid to achieving anatomic and physiologic restoration. If a large intraoperative CSF leak has occurred, the sphenoid sinus may also be packed with fat, but in the absence of such a leak, it is left free of foreign material. After endonasal or sublabial transseptal operations, the posterior septal space may be reimplanted with crushed nasal bone and cartilage. The septal flaps are reapproximated, and the nasal septum is returned to its midline insertion. Any accessible mucosal tears are repaired with fine catgut sutures. Bilateral endonasal packs, consisting of gauze packing within the “fingers” of a rubber glove that have been lubricated with petroleum jelly or antibiotic ointment, are placed in the nostrils. The nasal or gingival incisions, or both, are closed with interrupted 4-0 catgut sutures, and a gauze moustache dressing is applied. After the septal pushover, direct microscopic sphenoidotomy, or endoscopic approaches, nasal packs are used only if the sphenoid sinus has been packed with fat. Otherwise, nasal packing does not appear to be necessary.

Transcranial Approaches