Endoscopic Approach to Pituitary Tumors
Omar Gasudraz Ahmed, M.D., Andrew Jacob Victores, M.D.
Masayoshi Takashima, M.D., F.A.C.S., F.A.A.O.A.
From the Bobby R. Alford Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, Houston, Texas (A.V., M.T.)
Pituitary tumors represent 10-15% of all intracranial tumors. Although they are often benign, surgical excision is indicated when they produce significant clinical symptoms through mass effect and hormonal hyper-secretion. The surgical approach to the pituitary has undergone significant changes since first being performed in the late 1800’s. Today the endoscopic nasal, transsphenoidal approach is commonly performed with a multidisciplinary team with Neurosurgeons and Otolaryngologists working together. This combined approach has led to improved outcomes and decreased complication rates as Otolaryngologists provide expertise in endoscopic techniques and knowledge in sinus and anterior skull-base anatomy while neurosurgeons perform the excision of pituitary tumor intracranially. Extensive pre-operative planning by reviewing the MRI and CT imaging allows the surgeons to anticipate any anatomic difficulties. The surgical technique involves four phases including the nasal phase (entering the nasal cavity and gaining adequate exposure to the sphenoid sinus), the sphenoid phase (entering the sphenoid sinus and visualizing the important anatomic landmarks), the sellar and excision of tumor phase (involving entering the sella and adequately resecting the tumor), and the reconstructive phase (adequately covering the skull base defect). Depending on the extent of the defect, different reconstructive methods can be used. The vascularized, pedicled nasoseptal flap is commonly used for larger defects and has been highly effective at decreasing post-op CSF leak rates. Post-operative hospital stays have decreased in length, as there has been improved patient education and close follow up by a multi-disciplinary team including involvingOtolaryngologyists, Neuro-ophthalmology, Endocrinologyists, and Neurosurgeryons. As technologyWith this shift toward treating pituitary tumors at well defined multidisciplinary centers, continueds to improvements are anticipated in the and more standardized pre, intra, and post-operative management of these patients. care given, we will continue to see decreased complication rates for surgical endoscopic resections of pituitary tumors.
Pituitary tumors are relatively common and represent 10-15% of all intracranial tumors (1). A vast majority of pituitary tumors are benign adenomas, while carcinomas are exceedingly rare and represent less than .5% of pituitary masses (1). Although pituitary adenomas are benign, they can produce significant clinical symptoms based on several factors including size and hormonal activity. Patients with non-secreting tumors often present with symptoms resulting from mass effect causing compression of the surrounding structures including the optic chiasm and cranial nerves. Those with secreting tumors typically present with hormonal hypersecretion, which can lead to hyperprolactinemia, acromegaly, Cushing’s disease, thyroid disease, or generalized hypopituitarism depending on the hormone secreted. Many patients, particularly those with endocrine-secreting tumors, are primarily treated medically. However, some patients may not respond to these medical treatments and surgical intervention should be considered.
Pre-operative assessment and surgical intervention for pituitary tumors requires a multidisciplinary approach. The critical role of the pituitary and hypothalamus in hormone regulation requires a careful assessment of endocrinologic function prior to surgery including baseline testing for prolactin, IGF-1, cortisol, ACTH, T4 and TSH and testosterone and other sex hormones. Formal visual field testing should also be performed if there is concern for visual symptoms. Imaging studies also serve a crucial role in the pre-operative assessment. High resolution computed tomography (CT) along with magnetic resonance imaging (MRI) delineate bony and soft tissue anatomy, respectively (3). These imaging studies can also be used for pre-operative planning and intra-operative guidance, which increases anatomic accuracy and identification of atypical anatomical variants including possible dehiscent or “kissing” carotid arteries, dehiscent optic nerves, and/or abnormal sphenoid pneumatization patterns. (4). CT is especially helpful in identifying the presence of a sinus infection which can then be treated prior to surgery. In addition, the CT also helps identify the shape and pneumatization of the sphenoid sinuses,. There are three pneumatization patterns of the sphenoid bone, including the sellar (80%), presellar 15-17% and conchal types (1-3%). While the “sellar” type is a fully pneumatized sinus with easy identification of the sella, presellar and conchal types can complicate surgical entry into the sella due to the lack of anatomical landmarks. Image guided surgery technology is helpful in these instances. MRI is used to assess the size of the tumor as well as possible extension into surrounding structures such as the cavernous sinus and the suprasellar regions.
Surgical History and Surgical Approaches
Today, a purely transnasal, transsphenoidal approach is used in over 90% of pituitary tumor resections and has become the standard surgical therapy (5). This approach has only recently become the primary surgical modality. The earliest pituitary surgeries were performed transcranially. In 1889, Sir Victor Horsely performed the first pituitary surgery using a transcranial approach. Over the course of the early 1900s, the transcranial approach to pituitary resection was modified with the goal of lowering recurrence rates and allowing for a wider surgical exposure. This approach has since fallen out of favor. Today the transcranial approach is rarely used in pituitary tumor surgery with limited indications including significant parasellar extension into the cavernous sinuses, inaccessible suprasellar extension, and intrasellar “kissing” carotid arteries (6).
The first transsphenoidal approach was performed by Schloffer in 1907 and initially advanced by Cushing in 1909 (7). Cushing performed over 200 sublabial, transseptal transsphenoidal approaches to the sella turcica with a low mortality rate of 5.6% at the time. However, he eventually favored the transcranial approach because of the high tumor recurrence. It wasn’t until 1960 when the sublabial transeptal transphenoidal approach reemerged with the use of Jules Hardy’s intraoperative microscope (8). This approach was performed through a gingivo-labial incision dissecting mucosa along the inferior margin of the pyriform aperture medial to the septal mucoperiochondrium to eventually reach the sphenoid rostrum. This approach, with the use of the microscope, was predominantly used to access pituitary tumors from the 1960’s to the 1990’s. (9). During this time period, the nasal endoscope was being advanced and used by Otolaryngologists for functional endoscopic sinus surgery. (10). This led way to the modern day purely nasal endoscopic transsphenoidal pituitary approach. In 1995, Carrau and Jho from Pittsburg were the first to advance and popularize this modern day technique. (11). This approach since has gained widespread use and has been associated lower length of stay, lower hospital costs, lower complication rates, quicker postoperative recovery rates, and decreased patient discomfort. (12).
The primary focus of the discussion of surgical technique will be on the endoscopic transnasal approach. Prior to beginning the surgery, it is important to ensure the proper instrumentation and equipment is both present and functional. Some of the essential equipment include an endoscope (4mm in diameter, 18 cm in length), a fiberoptic cable, a light source, high definition camera and monitor and the image guidance navigation system. While a majority of the surgery will be performed using a 0-degree endoscope, it is important to also have angled (30 or 45 degree) scopes to inspect the corners of the sella for tumor remnants after tumor resection and to help visualize larger parasellar or suprasellar lesions. Detractors of the endoscopic technique criticize the two dimensional nature of the surgical field with lack of depth perception. Otolaryngologists, through their experience with sinus surgery, utilize constant movement of the endoscope in different depths and angles to create a quasi-3D environment. Although 3D endoscopes are available for commercial use, the image quality at this time is not as sufficient to outweigh the advantages of the 2D high definition systems. Endoscopic pituitary surgery is divided into 4 phases: nasal, sphenoid, tumor excision, and reconstructive.
The patient is first placed under general anesthesia with orotracheal intubation. Next, lidocaine with epinephrine (1 to 100,000) is be injected under endoscopic guidance along the septum and inferior turbinates. Cottonoid pledgets soaked in a topical vasoconstriction agent such as .05% oxymetazoline or 1:1000 epinephrine is placed between the middle turbinate and the septum, underneath the middle turbinate, and along the nasal floor for several minutes, which helps to decongest the nasal mucosa as well as decrease bleeding. When initially entering the nasal cavity, the inferior turbinate appears laterally and the nasal septum medially (figure-1) As the endoscope is advanced along the floor, the head of the middle turbinate will appear posterior and superior to the inferior turbinate. The choana will eventually be encountered which marks the opening of the nasopharynx. Here, the medial border is the vomer of the nasal septum and the superior border is marked by the floor of the sphenoid sinus. The inferior and middle turbinates are lateralized without disrupting the mucosa. The sphenoid os can be found 1.5-2 cm superior to the choana in the sphenoethmoidal recess between the superior turbinate and the nasal septum (Figure-2). There are several common anatomic obstacles encountered which can make this phase technically difficult including a deviated septum, concha bullosa (an air cell located in the middle turbinate) and superior turbinate hypertrophy. The superior turbinate can be lateralized or removed in order to gain better access to the sphenoid os, however this may result in hyposmia or anosmia. Careful attention should be placed when entering into the sphenoid sinus as a dehiscent carotid artery or optic nerve along the lateral wall of the sphenoid sinus can be injured.
The sphenoid phase consists of entering the sphenoid sinus and identifying the important anatomic landmarks. When performing the sphenoidotomy the posterior septal branch of the sphenopalatine artery crosses the inferior aspect of the sphenoethmoidal recess. Careful attention should be given to this artery and preservation is important as it may be needed for skull base reconstruction utilizing a pedicled nasoseptal flap. In order to gain better access to the sphenoid, the sphenoid rostrum and posterior nasal septum is resected. The anterior sphenoid wall should be taken down using bone punches, Kerrison ronguers, or a microdrill in order to allow for adequate working room for instrumentation (figure 3). In order to obtain a wider exposure, a posterior ethmoidectomy will allow access to the lateral aspects of the anterior sphenoid wall. (13) Careful attention should be given when extending the sphenoidotomy laterally to ensure the optic nerve and the carotid artery are not injured.
Once inside the sphenoid sinus, the intersinus septum is removed with caution because the posterior attachment can lie on the carotid protuberance in 20% of patients. If the patient has a sellar sphenoid sinus with a favorable pneumatization pattern, the posterior and lateral walls should be visible with the sellar floor at the center, the planum sphenoidale above, the clival indentation below, and the bony protuberance of the intracavernous carotid artery lateral. The bony outline of the optic nerve canal, the carotid canal, and the opticocarotid recess are frequently visualized along the lateral limits of the sphenoid cavity (figure-4). For patients with a presellar or a conchal type sphenoid sinus, landmarks may be difficult to distinguish and image guidance system can be helpful.
Sellar and Tumor Excision Phase
The sellar and tumor excision phase begins with entry into the sella and eventual removal of the pituitary tumor. During this phase of the surgery, it is vital that the neurosurgeon is able to use both hands while the endoscope and another instrument is held by a second surgeon in a manner commonly referred as the 4 hands technique.
Depending on the thickness of the sella,, a 4 mm chisel, microdrill, or other pituitary microdissection instruments can be used to open the sphenoid bone (figure 5). This opening should be expanded using bone punches or Kerrison ronguers in order to visualize the dura and expose the sella extensively with the cavernous sinuses as the lateral border. If needed, the surgeon can extend exposure by opening the clival indentation or the planum sphenoidale, which may be necessary in suprasellar macroadenomas.
Before incising into dura, if needed, the surgeon can use an endoscopic doppler ultrasound to help assess the exact location of the carotid arteries (14) Image guidance can also be used. The dura is then incised with a retractable pituitary sickle knife and bipolar cautery used to coagulate areas of bleeding. Less bleeding can be expected when excising macroadenomas compared to microadenomas because of mass effect compressing the superior and inferior cavernous sinuses. If there is decreased visibility secondary to bleeding, it is important to achieve hemostasis before excising the pituitary tumor, which can be achieved with cottonoid pledgets, coagulants, compression, and irrigation.
Once through the dura, the pituitary tumor should be visualized. Careful microdissection techniques should be used and the surgeon distinguishes normal tissue from tumor. An emphasis is placed on leaving as much normal pituitary tissue in order to maintain physiologic function. There is often a pseudocapsule surrounding adenomas, which can be utilized as a plane separating adenoma from the normal pituitary tissue (figure-6.) For macroadenomas, the lateral and inferior aspects of the tumor should be resected prior to removing the superior portion in order to prevent prolapse of the diaphragm sella and arachnoid. If the diaphragm sella descends, endoscopic visualization is frequently diminished. The superior portion of the tumor is in close anatomic relationship with the pituitary stalk, and the optic chiasm and aggressive handling in this area can lead to post-operative diabetes insipidus or vision loss, respectively. It is of utmost importance to ensure careful removal of all of the tumor for secreting adenomas as leaving any hormonally secreting cells could lead to failure of the surgical procedure. After removal of the tumor, a 30 and 45-degree scope should be inserted into the sella to evaluate for any residual tumor. The tumor is frequently sent as a frozen and permanent section specimen for pathological diagnosis.
Reconstruction and Post-Operative follow up
The main goals of reconstruction after endoscopic transsphenoidal pituitary surgery are to ensure hemostasis and prevent a CSF leak. After removal of the tumor, the presence of a CSF leak may not be obvious. The anesthesiologist can be requested to valsalva the patient in order to help detect a subtle leak. Based on the degree of the leak as described by Esposito et al (15) different reconstructive options are available including autologous or artificial grafts, rotational vascularized nasoseptal flaps and multi layered closure using dural and bone substitutes (16). For an uncomplicated transsphenoidal pituitary removal without obvious diaphragmatic defects, simple measures such as cellulose can be placed as inlay and onlay along the dura without need for packing the sphenoid sinus. However, if a low-grade CSF leak is detected, either abdominal fat grafting, an allograft, or a dural substitute can be used to help seal the defect. In larger defects, with high flow intraoperative CSF leaks, vascularized pedicle nasoseptal flaps (NSF) have been used with great success (17). The traditional pedicled NSF flap, introduced by Hadad and Bassagaisteguy reduced post-operative CSF leak rates from greater than 20% to less than 5% following reconstruction of high flow intraoperative CSF leaks. (18). This flap is harvested along the posterior nasoseptal neurovascular pedicle and its size adjusted based on the defect (figure 7). The flap can be raised in the mucoperiosteal or mucoperichondrial plane and rotated to cover the defect. Modifications of this technique including the nasoseptal rescue flap (NSRF) can also be used in cases where CSF leak is possible, but not likely (19). This technique is performed by only partially incising the pedicled nasoseptal flap (the superior posterior aspect) and inferiorly reflecting this tissue until it is certain it is needed.
Post-operatively, patients are admitted for observation anywhere from 24-48 hours. Patients are monitored closely for signs of visual changes, other neurological deficits, CSF leak, and diabetes inspidus. Yoshor et al. demonstrated in a series of 50 patients, that close monitoring and follow up as well as proper pre-op and post-op education can reduce hospital length of admission (20). Routine post operative follow-up by the otolaryngologist ensures that the sinuses are healing well without infection or evidence of CSF rhinorrhea and provides patient comfort with routine nasal debridement. A repeat MRI can be performed after three months to evaluate tumor resection. If a patient had pre-operative visual symptoms, he or she must also follow up in an ophthalmology clinic for vision evaluation 6-12 weeks after surgery.
Sir Victor Horsely performed the first pituitary surgery transcranially in 1889. Since that time, there have been many advances in pituitary surgery including endoscopic transsphenoidal pituitary surgery. Over the past 20 years, as equipment and reconstructive techniques have improved, endoscopic pituitary surgery has become increasingly used as an effective and safe surgical approach... There have been several meta-analyses, which have demonstrated the success of this approach. Tabaee and colleagues (21) collected data from 821 patients from previous studies and found the gross pituitary tumor removal in 78% of patients and resolution of hormonal dysfunction in 81% of patients. Complications include CSF leak (2%), permanent DI (1%), epistaxis (<1%), anterior pituitary dysfunction (<1%), and death (.24%) secondary to vascular injury. Villlwock et al.(22) retrospectively examined 8543 patients from the National Inpatient Database and found comparable outcomes to Tabaee except for complications related to diplopia, ptosis, and cranial nerve defects (4%). As more centers both nationally and internationally adopt a multi-disciplinary approach to pituitary tumors and their surgical resection, there will likely be improved outcomes in resection rates, complications, quality of life measures, and overall costs.
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Send correspondence to Masayoshi Takashima, M.D., Bobby R. Alford Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, One Baylor Plaza, Mail Stop: NA-102, Houston, Texas 77030. E-mail: firstname.lastname@example.org, Phone: 713-798-3235, Fax: 713-798-5078