Historically, the first successful removal of a pituitary tumor was performed by Schloffer in 1907, using an extracranial transsphenoidal approach through a superolateral nasoethmoidal route. Although Hirsch from Vienna pioneered in 1909 an inferolateral endonasal approach, Harvey Cushing ingeniously introduced a new method that combined the advantages of previous technical modalities; he deserves the credit for having standardized an oronasal midline rhino septal transsphenoidal approach. He routinely used this method during a 20-year period for over 247 cases of pituitary tumor, remaining faithful to an early statement that "the important factor seems to me a direct extracranial midline approach by the shortest possible route."
Nevertheless, by 1929, Cushing began using the intracranial transfrontal operation, which was initially described by Frazier, who first performed it in 1912. The reason for changing from the transsphenoidal to the intracranial operation was not the operative results but rather a consideration of the indications. The occasional discovery of other kinds of lesions about the sella turcica, such as a meningioma or a craniopharyngioma, was so much emphasized that, noted Henderson: "The intracranial approach was eventually used. . . for nearly all pituitary tumors irrespective of whether the growth of the tumor was chiefly upwards or downwards as well (with a large sella)." Another reason was the higher incidence of recurrence with the transsphenoidal operation because of incomplete tumor removal; with this method, "in the average favourable case probably one-third or even two-thirds of the tumor was removed," wrote Cushing.
Norman Dott from Edinburgh remained faithful to Cushing's approach and used the transsphenoidal operation throughout his career in over 120 cases. Guiot of Paris learned the procedure from Dott and deserves the credit for reviving and popularizing the method in Europe by the early I 960s. 2 Until then, the indications for surgical treatment remained the classic criteria that had been used over the previous 40 years, chiefly the presence of visual disturbance caused by a large pituitary adenoma with suprasellar expansion. The procedure was a massive debulking of the tumor in order to relieve pressure on the optic nerves, which indeed was successful in most cases; the alternatives were subtotal removal of the tumor followed by radiation therapy, or total sellar cleanout, or nonselective tumor removal. The attempt to perform a complete radical excision of the tumor did not permit distinction between normal and pathologic tissues; both were excised, resulting in panhypopituitarism, which required total pituitary hormonal substitution therapy.
In 1962, Hardy of Montreal, returning from Paris where he had learned the transsphenoidal approach from Guiot, reintroduced the procedure in North America. He improved the technique by introducing the combined use of televised radiofluoroscopic control, optical magnification with the surgical microscope, and microsurgical techniques of dissection. He demonstrated the possibility of achieving complete removal of the tumor (including the suprasellar extension) by direct monitoring of the fluoroscopic control during surgery and by observing the refilling of the chiasmatic cistern with air after tumor removal. A direct magnified view with excellent illumination of the operative field overcame the major criticism in the past that the transsphenoidal approach was a blind procedure. The main advantage was to assure complete tumor removal in most of the cases, thus avoiding postoperative radiotherapy. Striking progress in microsurgery made it possible to clearly distinguish between normal and pathologic tissues, thus opening the field of histologic functional microsurgery. Selective microsurgical adenomectomy with preservation of the normal gland became possible, so that pituitary function could be preserved or even restored without hormonal substitution therapy. Hardy first reported the possibility of recognizing intrapituitary lesions measuring a few millimeters in diameter, which he called microadenomas. The concept of selective microadenomectomy has contributed to better understanding of the pathophysiology of hypersecretory pituitary disorders and of the causes of tumor formation and has cast new light on the therapeutic approach to pituitary endocrine disorders. Current refinements in technique have clarified the indications for the intracranial versus the transsphenoidal approach to sellar lesions.
Basically, there are two major clinical endocrinologic pituitary syndromes. The first involves hyposecretion secondary to a pituitary tumor: Progressive loss of pituitary hormone secretions secondary to compression of the gland by a nonfunctional tumor may result in panhypopituitarism, requiring lifelong multihormonal substitution therapy. Surgical decompression of the gland interrupts this process and may even favour restoration of function. Most often, this hyposecretion syndrome is found in association with a large intrasellar mass-a nonsecreting cystic or oncocytic pituitary adenoma, a Rathke's pouch cyst, or a craniopharyngioma; occasional meningiomas, germinomas, and epidermoid tumors are also found in the sella. Further tumor growth may even encroach upon the adjacent optic pathways and cranial nerves. An accurate final diagnosis can only be reached by exploratory biopsy, for which the transsphenoidal approach is the least traumatic and most convenient method. The incidental radiologic finding of a nonfunctional tumor in the sella without endocrinologic or visual disturbance does not require immediate surgical treatment. Progressive impairment of function, however, may render surgery mandatory.
The second major pituitary syndrome is the hypersecreting pituitary adenoma, which has now emerged as the most frequent tumor of the pituitary. It gives rise to well-known clinical pictures such as galactorrhea-amenorrhea and infertility in the female and sexual impotence and loss of libido in the male secondary to a prolactin-secreting adenoma; gigantism or acromegaly; and Cushing's disease. These hypersecretory syndromes are usually isolated but occasionally are combined. They can be detected early with radioimmunoassay methods for the measurement of pituitary hormones, methods that have clearly defined the association of the clinical syndromes with specific hormones. Refinement in neuroradiologic diagnostic procedures, which include high-resolution computed tomography (CT) and magnetic resonance imaging (MRI), now permits the detection of lesions smaller than the pituitary gland itself-those originally called microadenomas. In the present state of medical knowledge, a preoperative predicted pathologic diagnosis is accurate in over 90 percent of cases.
Pituitary adenomas are divided into two major groups: enclosed tumors and invasive lesions. These may be associated with suprasellar or parasellar extensions. The transsphenoidal approach is the recommended approach for most enclosed tumors even with large suprasellar extension, provided the tumor extends symmetrically in the midline above the sella turcica. Locally or diffusely invasive tumors with downward extension into the sphenoid sinus and lateral extension toward the cavernous sinus are also suitable for transsphenoidal surgery, since the procedure allows a massive debulking of the tumor prior to radiation therapy. Irregular multinodular, fungating tumors or eccentric extensions into the frontal, temporal, or posterior fossa dictate an intracranial transfrontal approach
Among the various approaches to the sphenoid sinus and sella turcica, such as the lateral orbital, lateral endonasal, and transmaxillary, the sublabial midline rhinoseptal trans-sphenoidal approach stands out as the most convenient and practical for neurosurgeons, as it is the safest and simplest procedure (devised and adopted by Harvey Cushing beginning in 1909). However, as Cushing wrote: The mere technical triumph of exposing the contents of the sella turcica by one or another method is far from the most important consideration. The "crux" of the situation lies in the manner of dealing with the pathologically modified gland when it has been brought into view.
The procedure described below can be learned and performed by a single neurosurgeon unless other considerations require the assistance of a nasal surgeon.
After anesthesia induction with intravenous thiopental sodium, an endotracheal tube placed in the angle of the mouth is used to produce light general anesthesia. To prevent bronchial aspiration, the oropharyngeal cavity is packed with moist sponges. The patient is placed in a semi sitting position, with the head firmly affixed to a horseshoe headrest and the neck slightly flexed at an angle of 15 degrees from the horizontal and then tilted 20 degrees onto the left shoulder. In this manner, the patient's body on the operating table is out of the way and the surgeon is in front of the face; the surgeon works in a strictly median sagittal plane.
A portable image intensifier is then positioned on the side of the patient's head in such a way that the horizontal beam is centered on the sella turcica. The monitor is placed behind and just above the patient's head. This enables the surgeon to look at the screen in line with the binocular of the microscope, so that only a slight head movement is needed to change between observing the operative field and the screen. Radiofluoroscopic control is used only as needed during the operation; its proper placement limits radiation to only a few seconds at each stage of the procedure. The image intensifier is switched on and off with a foot pedal controlled by the surgeon or an assistant. Lead shielding and aprons are used to protect operating room personnel from radiation. Television input from the microscope and radiofluoroscopy from the image intensifier can be monitored on two separate channels of a videotape recorder.
The patient's face, mouth, and nasal cavities are prepared with an aqueous antiseptic solution. Infiltration of the nasal mucosa and upper gum with 0.5% procaine containing epinephrine (1:200,000) facilitates the subsequent elevation of the mucosa and diminishes oozing of blood. An adhesive plastic drape is used to cover the face, and additional draping of the entire operative field ensures complete isolation and sterility. A hole is made in the drape at the level of the upper lip, and sterile sponges are introduced into the mouth so that only the upper gingival margin is exposed.
The surgical procedure begins with a horizontal sublabial incision above the gingival margin, extending from one canine fossa to the other . After the incised upper lip and submucosal tissues are elevated to expose the nasal bony cavity, the mucosa of the floor of the nose is elevated on both sides. The anterior spinous process is resected and the sharp edge of the maxilla sheared off. The mucosa of the nasal septum is elevated on one side until the entire nasal septum is exposed. At this point there is a unilateral rhinoseptal submucosal cavity, which can be used whenever possible in the absence of septal deviation. The plane of cleavage is on the left side for a right-handed surgeon, and the mucosa is further detached from the posterior wall and the lateral edge of the vomer. The base of the septal cartilage is separated from the palatine crest, and the posterior vertical attachment to the vomer is separated with sharp dissection or a swivel knife, moving in an upward direction.
Then the entire nasal septum is tilted laterally toward the right side, although it remains attached to the upper part of the perpendicular plate of the ethmoid bone, which serves as a hinge. When there is marked septal deviation or when the cartilaginous septum breaks in pieces at the lower portion, it is preferable to remove the loose parts or the inferior third (resected with a swivel knife) and preserve the pieces for further use in closure of the sella floor.
The sphenoid rostrum or the vomer comes into view, having the appearance of the keel of a boat. A special double-bladed nasal speculum is introduced into the newly formed submucosal cavity, and the blades are opened widely to hold the retracted mucosa out of the field . Ordinarily, only minimal pressure is required to open the blades of the speculum; additional pressure with a dilator is not required. When the blades cannot be opened widely enough because of a narrow bony nasal orifice, the latter should be enlarged by shearing off the ascending branches of the maxilla.
Occasional hypertrophy of the turbinates in acromegalic patients may require the use of a dilator. The vomer is then detached, and further resection of the sphenoid floor gives wide exposure of the entire sinus cavity. After the mucosa is pierced and deflected and the bony septa are removed, the entire posterior aspect of the sinus and the floor of the sella turcica are brought into view. The boundaries of the sella are determined carefully under direct vision and on lateral views with fluoroscopic control. At this stage, the binocular surgical microscope is moved into place.
After the main portion of the procedure within the sella is accomplished, the rhinoseptal closure is simple. Nasopharyngeal tubes are placed in the patient's nostrils to ensure free nasal airways. Then the septal mucosa is reapproximated and maintained with endonasal Merocel tampons impregnated with steroids and antibiotic ointment. A few loose catgut sutures are placed along the sublabial gingival incision; these are well tolerated and painless because of the temporary numbness due to the section of small nerve endings. With this approach there is no visible postoperative scar. The procedure described here can be carried out by a single surgeon, although other considerations may make the assistance of a nasal surgeon desirable.
Removal of Microadenoma
In patients suffering from a hypersecretory pituitary syndrome with a normal-size sella turcica (Cushing's disease, gigantismacromegaly, galactorrhea-amenorrhea), transsphenoidal microsurgical exploration makes it possible to identify an intrapituitary lesion smaller than 10 mm in diameter (microadenoma). These lesions are located in specific areas of the gland: growth hormone microadenomas are usually located in the anterior portion of the lateral wing. prolactin-secreting microadenomas in the posterior inferior portion of the lateral wing. and adrenocorticotropic hormone-secreting microadenomas in the central portion of the mucoid zone of the gland, deep in the parenchyma, just in front of the posterior lobe.
When the floor of the sella is exposed, it is usually opened only on the side on which the lesion is expected to be located (on the basis of tomographic, CT, or MRI studies). Usually the floor appears slightly lower and thinner on the side of the lesion. After a cruciform incision is made in the dura, a growth hormone microadenoma is readily exposed, since it usually is bulging at the surface of the lateral wing of the gland. Gentle pressure on the gland will squeeze out the microadenoma. Residual tumor tissue is further removed with a small pituitary spoon and microcurettes especially designed with 45- and 90-degree angles to allow scraping of the lateral walls of the sella and particularly of the anterior corner, where some abnormal tissue can be hidden and easily overlooked.
A prolactinoma that is smaller than 5 mm in diameter is not readily visible at the surface, because it is usually located deep in the posteroinferior portion of the lateral wing of the gland. A vertical incision is therefore made lateral to the midline, and the pituitary parenchyma is opened and dissected gently until the tumor tissue is found posteriorly. The microcurette is introduced under televised control, and upon withdrawal the greyish purple tissue of the tumor is identified and resected. This manoeuvre often results in separation, of the anterior portion of the lateral wing, which is also removed and serves as a control biopsy of the normal gland. This allows better exposure and facilitates removal of the remaining tumor tissue.
An ACTH microadenoma is more difficult to find and to remove completely. When the tumor is not visible at the surface, it is located most often, in the central core of the midportion of the gland in front of the posterior lobe; only occasionally is it eccentric. The exploration of the pituitary in such cases is more tedious. A stepwise procedure is recommended. First, a horizontal incision is made in the midportion of the anterior lobe deep into the parenchyma. Second. a vertical incision is made on the midline from the superior to the inferior surface of the gland, and a fragment of anterior lobe is taken for frozen histologic study. As the parenchyma is further dissected deeply, the microadenoma will be encountered and identified as a greyish purple tissue. After it is removed with a microcurette. the cavity is further examined at 25-power magnification. and any doubtful residual tumor tissue further excised; the margin of the tumor cavity is then biopsied. As the posterior lobe is difficult to distinguish clearly from the tumor tissue. the last fragment biopsied should be normal neural lobe tissue. The normal adenohypophyseal tissue is yellowish orange and is usually firmer than the tumor tissue, so it is not readily removed by low-pressure suction. Occasionally the margin of the tumor cavity is composed of a thin layer resembling a pseudocapsule between the tumor and the normal tissue. This membrane is also peeled off in one or several pieces.
If the surgeon is in doubt about having achieved total tumor removal, it is recommended that intraoperative frozen biopsies be performed with histologic verification. It must be stressed that for complete and selective functional histologic microsurgical removal of pituitary hypersecretory lesions, the help of a qualified neuropathologist is indispensable in the operating room during surgery. The risk of leaving pathologic tissue or removing too much of the normal gland requires immediate histologic tissue examination during surgery. Additional sterilization of the tumor bed may be accomplished by the temporary application of a cotton pad soaked in sterile 90%' alcohol.
After removal of the microadenoma, the tumor cavity can be measured by placing in it a piece of Gelfoam soaked in barium sulphate solution and making an x-ray film of it. Incidentally, this contrast substance has been found to be also useful in achieving hemostasis. After removal of the barium-impregnated Gelfoam, the cavity is packed with plain Gelfoam. If a CSF leak is present, a watertight closure can be achieved with a piece of fascia and muscle or lyophilized dura. Tissue fibrin sealant may also be used. The sellar window should be closed with a small piece of cartilage from the nasal septum.
Removal of Macroadenoma with Suprasellar Extension
Before the patient is positioned, a catheter is inserted into the lumbar subarachnoid space so that air may be injected as desired to outline the suprasellar contour of the tumor during the operation.
Once the floor of the sphenoid sinus has been opened, the sinus is frequently noted to be partially or completely filled by the bulging sellar floor. The floor is usually thinned and can be opened easily, producing a large window into the sella. The dural sheet also has been thinned by pressure from the growing tumor. At this step, a transdural puncture, using a 22-gauge needle mounted on a syringe, may be carried out to aspirate a possible cystic or semiliquid necrotic adenoma. lntratumoral metrizamide injection is also useful at this point to outline the tumor contour. Rupture of the superior dural capsule may also be detected by the extension of the contrast medium outside the tumor into the subarachnoid space. When the dura is incised in cruciform fashion, the gelatinous grey-purple tissue of the tumor will burst forth into the sphenoid sinus, to be removed by further aspiration.
It should be emphasized that no capsule other than the previously opened dura is found around the pituitary adenoma. The dura is in fact the "capsule" of the tumor. It is contiguous with the lateral wall of the sella, it forms the inner layer of the cavernous sinus, and it is continuous with the diaphragma sellae. No attempt should be made to remove the "capsule," since any tear in the cavernous sinus wall will result in profuse bleeding. Further removal of the tumor is by curettage in all directions, using a malleable spoon and various types of curettes and suction tubes.
In large tumors, some pathologic tissue may be hidden in the lateral corners of the sella. Using a 45-degree angle fiberoptic mirror, this tissue can be identified and removed with a 90-degree angle curette and suction tube. Once the enlarged sella has been partially emptied of tumor, the suprasellar extension usually collapses into the sella as a result of normal intracranial pulsations. If this does not occur, curettes should be introduced under televised radiofluoroscopic control and the suprasellar bulge detached piecemeal until the diaphragm or superior capsule is seen to collapse downward, pulsating and hanging freely in the sella. The gradual passage of air into the suprasellar cistern is seen on the television screen, while the anterior third ventricle returns to its normal position above the sella. Thus, immediate pneumographic control is obtained during surgery, proving the completeness of tumor removal.
In the unusual circumstance of a fibrous adenoma (accounting for about 5 percent of cases), it is necessary to use the electrical loop to remove the lesion because of its firm consistency. Oozing may occur during tumor removal and may persist until the last fragment has been detached. It stops after the temporary packing of Gelfoam into the cavity. This oozing is of no real consequence, since it drains into the sphenoid sinus and the submucosal nasal opening.
Cerebrospinal fluid leakage rarely occurs during tumor removal, since the distention produced by the tumor generally causes the diaphragm to adhere to the arachnoid. The diaphragm is itself a natural protection against fistula formation, which will not occur if surgical manoeuvres are performed gently under radiofluoroscopic control.
If blood oozing persists after complete removal of the tumor, a catheter is left in the sphenoid cavity, fixed in place with a silk ligature at the gum margin. The catheter is connected to a low-pressure suction apparatus and is removed on completion of drainage.
Ordinarily, the larger the pituitary tumor extending downward into the sphenoid sinus, the easier it is to remove. For this reason, neurosurgeons with little or no experience in transsphenoidal pituitary surgery would do well to try to remove this type of lesion as their first attempt- even before attempting ablation of a normal gland (or a microadenoma, which is a much more difficult procedure). With tumors extending above the sella, considerable experience is needed to properly assess the amount of curettage needed to accomplish the required manipulation of the superior "capsule" without producing a tear. It must be emphasized that no attempt should be made to pull down the "capsule." It will come down of its own accord, as a result of intracranial pulsation, once the tumor has been totally removed. In accomplishing this, assistance may be obtained from the anesthesiologist, who can produce a temporary increase in the thoracic pressure (Valsalva manoeuvre) or can inject fluid through the lumbar catheter; either will increase the pressure in the cranial cavity and will help to push the capsule down into the sella.
In the case of large tumors with considerable suprasellar extension, collapse of the' 'capsule" far down in the sella may give rise to the empty sella syndrome. This can be prevented by placing a piece of muscle in the cavity to prevent downward herniation of the relaxed diaphragm, a procedure called preventive chiasmapexy.
If the suprasellar extension does not come down into the sellar cavity after Valsalva manoeuvres, it should not be pulled and the procedure should be interrupted. Postoperative follow-up with CT scans or MRI at 3- to 6-weyk intervals will show a progressive descent of the residual mass. When it has reached the bottom of the sella, a second operation can be carried out to remove the remaining portion of tumor. When the suprasellar portion does not come down, it should be removed by an intracranial subfrontal approach.
Removal of Craniopharyngiomas and Other Sellar Tumors
The surgical management of craniopharyngioma will remain a challenging problem. Although usually a benign tumor, it is deceptive in that subtotal removal is often followed by recurrence. The only curative approach is total excision of the tumor at the time of the first operation. With the present medical knowledge of the clinical picture and radiographic features of this tumor, the surgical anatomy of the growing lesion has been clarified so that the indications for transsphenoidal versus intracranial approach are now better defined.
There are three anatomic varieties of craniopharyngioma. A pure intrasellar lesion, as evidenced by intrasellar calcification and a long history of hypopituitarism, suggests that the neoplasm is located beneath the diaphragma sellae and has extended into the sphenoid sinus, with enlargement of the floor of the sella turcica.
This is the major indication for the transsphenoidal approach in an attempt to achieve total excision of the tumor. The striking difference between a pituitary adenoma and a craniopharyngioma is evident as soon as the dural sheet of the floor of the sella has been opened. With a craniopharyngioma. a second membrane abuts on the inner surface of the dura. This is the capsule of the craniopharyngioma. Once the capsule has been punctured and the brownish fluid containing cholesterol crystals drained, the capsule collapses.
The tumor contents are further removed with various curettes. Then the capsule is grasped with a forceps, and a blunt enucleator is used to gently separate it from its attachment to the dura. Slight traction and dissection with cotton pledgets are used to detach the superior reflection of the capsule, particularly when it is attached to the inferior aspect of the diaphragm a sellae
When dealing with craniopharyngiomas, it is important to be aware of the fact that the normal pituitary gland is outside of the capsule and can be identified with the microscope. It can therefore be left in the sella to prevent further hypopituitarism and even favour restoration of hormonal secretion. Because of its firm adherence to the diaphragma sellae and the arachnoidal sheet of the chiasmatic cistern, the detachment of tumor at this point may occasionally produce a tear in the arachnoid, resulting in a cerebrospinal fluid leak. The tear is closed with a piece of fascia lata and the sellar cavity packed with muscle; further closure can be achieved with a cartilaginous septal graft applied with biological glue.
The second variety of craniopharyngioma is the one that is located only intracranially, above the diaphragm a sellae, extending and optic nerves. In this case, the transcranial subfrontal approach is absolutely mandatory.
The third variety of craniopharyngioma is the one that has its origin within the sellar cavity, as evidenced by a long history of hypopituitarism, but extends upward to result in a recent visual disturbance. This lesion is associated with a large sella turcica; its suprasellar extension is most often covered by the diaphragma sellae. This case presents a controversial indication. In some cases, it has been possible to approach the lesion by a transsphenoidal route and achieve total excision. However, if the suprasellar extension does not collapse down into the sella during the first procedure, a second must be tried approximately 1 month later, after repeated radiographic studies. If the capsule has collapsed down into the sella, it is still possible to achieve total excision by a transsphenoidal route. If the capsule remains attached to the hypothalamus and the surrounding neurovascular structures, however, the second operation should use an intracranial transfrontal approach.
Finally, occasionally an emergency procedure is required because of development of an acute intracranial pressure effect before an endocrine workup has been completed. Using intravenous cortisone replacement, a transsphenoidal approach can be carried out rapidly and a large cystic craniopharyngioma punctured and evacuated. Residual fluid will eventually drain into the sphenoid sinus, preventing recurrence of cystic dilatation and pressure on neurovascular structures. A decision concerning the ideal surgical treatment and further radical excision of the lesion can be postponed until after this temporary relief has been obtained and the endocrine workup completed.
Other nonpituitary lesions of the sella turcica can also be approached transsphenoidally: meningiomas, germinomas, granulomas, and intrasellar cystic lesions are best so approached. Tumors destroying the posterior wall of the sella turcica and the clivus, such as chordomas, are located just below the sella turcica in the posterior wall of the sphenoid sinus. After the usual transsphenoidal approach is carried out, the manoeuvres along the posterior clivus are performed under radiofluoroscopic control, making possible extensive removal of the tumor, although most often this is incomplete. Nevertheless, radiation therapy may prevent or delay recurrence of this unusual lesion.