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Skull Base Brain Tumor Research





By Joseph B. Eby M.D., Sung Tae Cha M.D., Hrayr K. Shahinian M.D.

Key words
Pituitary Surgery, Endoscopic, Microsurgery, Transsphenoidal

Summary

Objective: Microscopic transsphenoidal surgery is a widely accepted and highly effective therapy for pituitary adenomas. Over the past decade several centers have converted to an endoscopic transsphenoidal approach; suggesting that this technique provides more complete tumor resection and reduces complications. However, there have been few series to document the results of this procedure. This report presents the largest number of patients to date having undergone fully endoscopic transsphenoidal pituitary surgery, and compares these patient's outcomes with those published for the microscopic method.

Design/Patients: From 11/981/01, 75 patients underwent endoscopic pituitary adenoma resection. A retrospective review of the patient's records, and data from post-operative follow-up visits were used to ascertain patient's outcomes.

Measurements/Results: Of the 75 pituitary adenomas removed 30 were hormonally active, while 45 were non-functioning. Mean follow-up was 11.4 months. The average length of stay was 2.1 days. A total of 48 patients had post-operative hormonal or MRI studies to assess residual or recurrent disease. Remission was demonstrated in 92% of enclosed and 82% of invasive adenomas. Comparison of endoscopic vs. microscopic remission results revealed a trend toward improved outcomes using the endoscopic technique: ACTH (100% vs. 81%), PRL (69% vs. 66%) and GH (88% vs. 77%). The remission rate for non-functioning adenomas was 95%. Additionally, we noted a marked reduction in complications related to this procedure.

Conclusions: The endoscopic transnasal-transsphenoidal technique is a safe and effective method to remove pituitary adenomas. The results of this series suggest that the endoscope provides more complete tumor removal, and reduces complications. We believe that the advantages of the endoscopic technique will allow this procedure to become the future gold standard surgical therapy for pituitary adenomas.

Background

Significant advances in the recognition and management of pituitary adenomas has taken place over the last decade (Shimon & Melmed, 1998; Freda & Wardlaw, 1999). Highly sensitive hormonal assays and magnetic resonance imaging with gadolinium enhancement have led to earlier and more frequent diagnosis of pituitary adenomas (Shimon & Melmed, 1998; Freda & Wardlaw, 1999). New therapeutic agents (Cabergoline, Octreotide, and Ketoconazole) have been introduced, which may control hormonal symptoms and slow the growth of some functioning adenomas (Shimon & Melmed, 1998; Freda & Wardlaw, 1999). However, medical therapy is frequently unsuccessful for patients suffering from acromegaly, and no effective therapy is available for patients with Cushing's disease (Aron et al., 1995; Shimon & Melmed, 1998; Freda & Wardlaw, 1999). Moreover, a small but significant number of patients cannot tolerate the side effects of these medications, have hormonal tumors resistant to treatment, or have follow-up MRI scans demonstrating continued tumor growth (Aron et al., 1995; Shimon & Melmed, 1998; Freda & Wardlaw, 1999). Non-functioning adenomas do not respond to pharmacologic interventions, and frequently present as macroadenomas with symptoms of visual disturbance or hormonal deficiencies due to compression of adjacent structures (Aron et al., 1995; Shimon & Melmed, 1998; Freda & Wardlaw, 1999).

Stereotactic radiation and gamma-knife radiosurgery have been added to the list of treatment options, but these therapies often fail to completely control tumor growth or reduce hormone levels (Barkan et al., 1997; Powell et al., 1999).

Microscopic transsphenoidal surgical resection of pituitary tumors has demonstrated excellent results with minimal morbidity and almost no mortality; and has become the therapy of choice for many pituitary adenomas (Bushe & Halves, 1978; Wilson & Dempsey, 1978; Baskin et al., 1982; Smallridge & Martins, 1982; Boggan et al., 1983; Randall et al., 1983; Rodman et al., 1984; Wilson, 1984; Zervas, 1984; Ebersold et al., 1986; Tagliaferri et al., 1986; Laws, 1988; Mampalam et al., 1988; Ross & Wilson, 1988; van't Verlaat et al., 1988; Maira et al., 1989; Comtois et al., 1991; Yang et al., 1994; Carrau et al., 1996; Feigenbaum et al., 1996; Hardy, 1996; Molitch et al., 1997; Abosch et al., 1998; Freda et al., 1998; Freda et al., 1998; Lissett et al., 1998; Swearingen et al., 1998; Brucker-Davis et al., 1999; Freda & Wardlaw, 1999; Tyrrell et al., 1999). Continued attempts to improve surgical outcomes, reduce the incidence of complications, and hasten patient's post-operative recovery have led to the development of a minimally invasive fully endoscopic transsphenoidal approach to resect pituitary adenomas.

Early reports using this technique highlighted the endoscope's superior visualization over the operating microscope, and have suggested that this minimally invasive technique allows for more complete tumor resection, and a reduced incidence of complications (Jankowski et al., 1992; Gamea et al., 1994; Helal, 1995; Carrau et al., 1996; Jho & Carrau, 1996; Heilman et al., 1997; Jho & Carrau, 1997; Jho et al., 1997; Jho, 1999; Jarrahy et al., 2000; Jarrahy & Shahinian, 2000). Over the past 10 years several centers have adopted an endoscopic transnasal-transsphenoidal procedure as an alternative to the microscopic approach. However, there have been very few endoscopic series to document the results of this procedure (Jho & Carrau, 1997).

Our group began using a combined endoscope-assisted transsphenoidal approach to pituitary tumors in 1996 and have published our results (Jarrahy et al., 2000). Using this technique we found the endoscope enhanced our ability to differentiate normal pituitary gland from tumor, and provided unparalleled exposure of suprasellar and parasellar tumor extension, including tumor not identified using the operating microscope alone (Jarrahy et al., 2000). To allow for further development of this technique and provide instruction on the endoscopic procedure, we subsequently developed a pig model for fully endoscopic pituitary surgery (Jarrahy et al., 1999). The advantages of the endoscopic technique convinced our group to convert to a fully endoscopic transnasal-transsphenoidal procedure in November of 1998 (Jarrahy & Shahinian, 2000).

In this article we report the largest number of patients to date (75) having undergone fully endoscopic transnasal-transsphenoidal pituitary adenoma removal. We then compare these patients outcomes with those published in several microscopic transsphenoidal series reports.

Materials and Methods

Prior to performing fully endoscopic pituitary surgery on human subjects, the entire surgical protocol including the consent forms were reviewed and approved by the Cedars-Sinai Medical Center Institutional Review Board.

From November 1998 to January 2001 the senior surgeon (HKS) has performed more than 120 fully endoscopic transsphenoidal operations 75 of which were for primary or recurrent pituitary adenomas. These patient's charts were retrospectively reviewed and information from follow-up visits collected to assess operative success rates, and the incidence of complications. Pre-operative information collected included: age, sex, presenting symptom(s), prior surgical procedure(s), and pre-operative laboratory results. Tumor grade was (I-IV) assessed using the pituitary tumor scale proposed by Hardy, and was determined from pre-operative magnetic resonance imaging results (Hardy, 1969). Follow-up data was compiled regarding the length of hospitalization, and the incidence of complications including: CSF fistulae, diabetes insipidus, anterior pituitary insufficiency, intrasellar hematoma formation, loss of vision, CNS injury (epidural, subdural, hypothalamic injury), meningitis, carotid artery injury, and death. Patient outcomes were determined from intra-operative assessment of tumor resection, post-operative hormone levels and MRI imaging results. The data from this endoscopic series was then compared to mean values calculated from several microscopic transsphenoidal reports (Wilson & Dempsey, 1978; Smallridge & Martins, 1982; Boggan et al., 1983; Randall et al., 1983; Wilson, 1984; Ebersold et al., 1986; Tagliaferri et al., 1986; Mampalam et al., 1988; Ross & Wilson, 1988; van't Verlaat et al., 1988; Maira et al., 1989; Comtois et al., 1991; Yang et al., 1994; Abosch et al., 1998; Tyrrell et al., 1999).

Surgical Procedure

The fully endoscopic transnasal-transsphenoidal surgical procedure has been described in previous communications and will be only briefly discussed in this report (Jarrahy & Shahinian, 2000). The operation takes place with the patient supine with their head secured in a carbon fiber three-pin Mayfield Clamp. The head of the bed is elevated and the patient's neck slightly extended and rotated toward the nostril to be used for the procedure. The C-arm fluoroscopy image intensifier is then positioned so that the beam yields centrally positioned sphenoid and sellar contours. Depending on the pre-operative assessment of the patients nasal passageway either 4mm or 2.7mm StortzR (Culver City, CA) endoscope is used. The video monitor is positioned behind the patient's shoulder directly opposite the surgeon's line of site; the fluoroscopy monitor is positioned above the patient's opposite shoulder to provide a simultaneous fluroscopic image of the extent of dissection.

The endoscope is covered with an irrigating sheath, obviating the need to remove and reinsert the endoscope to clear debris from the lens. The endoscope is then secured in position using a pneumatically powered endoscope-holding arm, allowing bimanual surgical dissection. The 00 endoscope is used to guide the intranasal dissection and initial tumor resection. No intranasal retractor or speculum is used for this procedure. Tumor resection is carried out in a manor similar to that performed during the microscopic procedure using a suction device and ring curettes of varying diameter and orientation. All operations are performed via a single nostril approach. Once tumor resection is complete or residual tumor is outside the view of the 00 endoscope, this instrument is removed and the 300endoscope is inserted. The angled lens of this endoscope provides excellent exposure of the suprasellar region. Rotating the 300endoscope clockwise and counterclockwise provides visualization of parasellar tumor extension, including invasion into the cavernous sinus if present. Any residual tumor is resected, eliminating areas of potential tumor recurrence. Once tumor resection is complete using the 300endoscope, the area is irrigated and hemostasis is obtained.

An abdominal fat graft is harvested and used to reconstruct the sellar defect, which is then sealed using fibrin adhesive. No nasal packing is required, and only a small gauze dressing is placed below the nares to collect any residual blood or debris. All patients are admitted to the surgical intensive care unit for overnight monitoring.

Results

A total of 75 patients underwent endoscopic removal of their pituitary adenomas during the 29-month period of this study. Other than hormonal symptoms the most common presenting complaints included headache in 35% of patients and changes in visual acuity or visual field deficits in 32%. Three patients had pre-operative panhypopituitarism, 1 patient recovered their pituitary function post-operatively.

Demographic information is presented in Table 1. Eighteen patients (24%) had recurrent pituitary tumors, the majority of which (61%) were non-functioning adenomas. All 18 patients had undergone prior microscopic transsphenoidal surgery at other institutions. A total of 9 patients with massive suprasellar tumor extension judged preoperatively as inaccessible from a transsphenoidal approach (tumor located cephalad to the optic chiasm) and were recommended to undergo a two-stage surgical approach beginning with an endoscopic transsphenoidal resection, followed by a transglabellar approach to remove any residual suprasellar tumor. This endoscopic transglabellar procedure has also been described in a previous communication (Jarrahy et al., 2000). Five of these patients have since undergone a second-stage transglabellar procedure. One patient died of unrelated causes prior to his second operation. The 3 remaining patients are scheduled to undergo their second-stage procedure within the next 2 months.

The average length of stay was 2.1 days, with 22 patients (29%) discharged within 24 hours post-op. The most common indications for longer hospitalization included temporary diabetes insipidus, CSF leak, and prior co-morbid conditions which required extended monitoring or rehabilitation.

Tumor characteristics including grade are depicted in Table 2 (classified according to a scheme originally proposed by Hardy (Hardy, 1969). There were 34 (45%) enclosed tumors (Grades I & II) and 41 (55%) invasive adenomas (Grades III & IV). Compared with prior microscopic series, our patient cohort appeared to contain a larger number of high-grade (III & IV) tumors with significant supra- and parasellar extension, including a 33% incidence of cavernous sinus invasion. There were 30 (40%) hormonally active tumors consisting of 14 prolactinomas, 9 growth hormone secreting tumors, and 7 corticotrophic adenomas. Non-functioning adenomas numbered 45 (60%) and were on average larger and of higher grade than the functioning adenomas (64% vs. 40% Grades III & IV).

Residual or recurrent disease was assessed by post-operative hormonal assays in 27/30 patients with hormonally active tumors, while 13 had post-operative MRI scans. Additionally, 19/45 patients with non-functioning adenomas had post-operative MRI studies.

There were 14 patients with prolactinomas (Table 3), 9/14 (64%) had pre-operative prolactin (PRL) levels > 200ng/ml. Four of the 5 patients with pre-operative PRL levels < 200ng/ml were taking dopamine agonist medication at the time the PRL level was measured. One patient with a grade II prolactinoma is to undergo a second-stage transglabellar operation. Post-operative PRL levels were available for 12 of the remaining 13 patients, documenting hormonal cure in 9 patients. Two patients were restarted on medication post-operatively, one of which is scheduled for a two-stage procedure. Post-operative MRI scans were available for 6/14 patients, including 1 from a patient without post-operative PRL levels. One patient with a post-operative PRL level of 23ng/ml (on Bromocriptine) demonstrated evidence of recurrent tumor on their MRI scan. Another MRI scan revealed no evidence of residual or recurrent disease in a patient with a post-operative PRL level of 36ng/ml (This was not considered a curative result).

All patients demonstrated significant reductions in their mean PRL level, with a mean decrease of 94%. The overall remission rate in this series for endoscopically removed prolactin secreting adenomas was 9/13 (69%).

Nine patients had growth hormone secreting tumors (Table 4). One patient was scheduled for a two-stage surgical procedure. Pre-operative and post-operative IGF1 levels were available for the 8 remaining patients, demonstrating hormonal cure in 7/8 patients. The one patient not demonstrating hormonal cure had a recurrent Grade IV GH secreting adenoma with suprasellar extension. This patient's IGF1 level was reduced from 1020ug/ml pre-operatively to 465ug/ml post-operatively (normal < 360ug/ml). Four patients with normal post-operative IGF1 levels also underwent MRI scans, all of which showed no evidence of recurrent tumor.

There were seven patients suffering from Cushing's disease in this series (Table 5). Pre-operative and post-operative hormonal assays were available in all patients. Hormonal cure was documented in 7/7 patients with ACTH secreting tumors, of which 6 were grade I, and 1 was a grade IV tumor. Three of these patients also underwent post-operative MRI scans demonstrating no evidence of recurrent tumor.

Table 7 contains the tumor characteristics and post-operative results for non-functioning adenomas. A total of 45/75 patients had non-functioning adenomas, 7 of these patients were scheduled for two-stage operations. Of the remaining 38 patients 19 have undergone post-operative MRI scans. These scans were performed on average 10 months post-operatively and reveled no recurrent tumor in 18/19 patients (95%). The one patient demonstrating recurrent tumor had a 6mm mass located in left cavernous sinus on an MRI scan performed one year post-operatively.

Table 8 summarizes the overall post-operative results for patients undergoing endoscopic pituitary adenoma removal, and compares these results to those from several large microscopic pituitary series. Overall, the endoscopic technique demonstrated remission in 23/25 (92%) of enclosed tumors and in 18/22 (82%) of invasive tumors, for a combined remission rate of 41/47 (87%).

The incidence of complications related to the endoscopic procedure was recorded and the results are depicted in Table 9. This table also contains results from a national survey regarding complications related to the microscopic transsphenoidal procedure (Ciric et al., 1997). Complications related to glandular injury were markedly reduced in this endoscopic series, this is reflected by the low incidence of anterior pituitary insufficiency (2.7%) and diabetes insipidus (2.7%). Only the incidence of CSF leak was noted to be slightly elevated in this endoscopic series 5/75 (6.7%). However, 3/5 leaks occurred during the first 10 procedures, while only 2 CSF leaks were observed in the last 65 operations for an incidence of only (3.1%).

Discussion

Since Professor Pierre Marie first described acromegaly in 1886 progress in the diagnosis and treatment of pituitary tumors has paralleled advances in technology (Marie, 1886; Welbourn, 1986). Surgical approaches to pituitary adenomas have undergone significant adaptation since the first attempted transcranial and transsphenoidal decompression operations of the early 19th century.

In 1889 Horsley, using a transcranial approach is credited with performing the first operation for a pituitary tumor (Horsley, 1906; Horsley, 1906; Welbourn, 1986). In 1906 Schloffer reported the first removal of a pituitary tumor through an extracranial transsphenoidal approach (Schloffer, 1906; Welbourn, 1986; Hardy, 1996). Hirsch later modified this approach in 1909 (Welbourn, 1986; Hardy, 1996). However, it was Cushing's transseptal-transsphenoidal method introduced in 1910, which standardized this approach to pituitary tumors (Cushing, 1914). The transseptal-transsphenoidal technique gained popularity throughout the early 1900's. Cushing himself reported on 247 pituitary tumors removed by this method between 1910 and 1929 (Cushing, 1932; Hardy, 1996). Inability to reach suprasellar tumor extension, poor illumination, CSF leakage, meningitis, and a high recurrence rate all led Cushing and his contemporaries to abandoned the transsphenoidal approach by the early 1930's in favor of the transcranial procedure (Cushing, 1932; Welbourn, 1986; Hardy, 1996; Spencer et al., 1999).

It wasn't until the late 1950's when Guiot who learned Cushing's transseptal-transsphenoidal method from Dott reintroduced this approach (Welbourn, 1986; Hardy, 1996). Guiot improved the transsphenoidal approach with the addition of intra-operative fluoroscopy to guide the insertion of instruments into the sella, allowing for safer and more complete tumor removal (Guiot, 1958; Guiot & Thebaul, 1959; Welbourn, 1986; Hardy, 1996). It is Hardy however, who deserves much of credit for reestablishing the validity of the transsphenoidal approach, when in the 1960's he combined fluoroscopy and microsurgical techniques to further augment transsphenoidal pituitary tumor resection (Hardy, 1962; Hardy, 1969; Hardy & Vezina, 1976; Welbourn, 1986; Hardy, 1996). These new technologies provided the transsphenoidal approach with significant advantages over the transcranial procedure. The improved visualization, allowed for more complete tumor removal, and reduced the incidence of complications. In the ensuing 40 years several large series have established the transsphenoidal approach as the procedure of choice for all but the most massive pituitary adenomas, demonstrating outcomes equivalent or better than those reported for the transcranial procedure with fewer complications (Bushe & Halves, 1978; Wilson & Dempsey, 1978; Baskin et al., 1982; Smallridge & Martins, 1982; Boggan et al., 1983; Randall et al., 1983; Rodman et al., 1984; Wilson, 1984; Zervas, 1984; Ebersold et al., 1986; Tagliaferri et al., 1986; Laws, 1988; Mampalam et al., 1988; Ross & Wilson, 1988; van't Verlaat et al., 1988; Maira et al., 1989; Comtois et al., 1991; Yang et al., 1994; Carrau et al., 1996; Feigenbaum et al., 1996; Hardy, 1996; Molitch et al., 1997; Abosch et al., 1998; Freda et al., 1998; Freda et al., 1998; Lissett et al., 1998; Swearingen et al., 1998; Brucker-Davis et al., 1999; Freda & Wardlaw, 1999; Tyrrell et al., 1999).

The use of rigid endoscopes for sinus surgery provided the inspiration for their application to pituitary surgery (Gamea et al., 1994; Jho & Carrau, 1996; Jho et al., 1997). Isolated reports of the use of endoscopes to resect pituitary tumors appeared in the literature as early as the 1970's (Bushe & Halves, 1978). However, it wasn't in the early 1990's that technologic advances in optics, digital cameras, light sources, holding arms, and monitors have allowed endoscopes < 5 mm to provide high-quality panoramic exposure that surpasses the visualization provided by operating microscopes (Jankowski et al., 1992; Gamea et al., 1994). Spencer recently compared and quantified the exposure provided by the 00 endoscope vs. the operating microscope (Spencer et al., 1999). This report found that even the 00 endoscope provides 1.5-2.5X greater volume of view of the sellar, parasellar and suprasellar region (Spencer et al., 1999).

In 1992 Jankowski provided the first description of fully endoscopic transnasal-transsphenoidal technique (Jankowski et al., 1992). Since then experience with this approach has for the most part been limited to a few subspecialty centers, while outcomes data for patients undergoing this procedure is just beginning to be reported (Helal, 1995; Carrau et al., 1996; Heilman et al., 1997; Jho & Carrau, 1997; Sheehan et al., 1999; Jarrahy et al., 2000). Jho has published the largest series to date describing his experience with 44 pituitary adenomas and 6 other parasellar lesions (Jho & Carrau, 1997). This report along with several other small series have suggested that in addition to providing more complete tumor removal, the endoscopic technique may also result in a lower incidence of complications related to blind dissection (Helal, 1995; Carrau et al., 1996; Heilman et al., 1997; Jho & Carrau, 1997; Sheehan et al., 1999; Jarrahy et al., 2000).

Just as the improved exposure of fluoroscopy and operating microscope ushered in the resurgence of the transsphenoidal technique, the endoscope's superior visualization has largely been responsible for its success in pituitary surgery. This report set out to document the largest series of patients having undergone endoscopic pituitary tumor removal and to compare outcomes for the endoscopic approach to the widely accepted microscopic transsphenoidal technique.

Tumor Remission

Endoscopic surgical outcomes for the various pituitary tumor types as well as comparative data from several large microscopic series are depicted in Table 7. Despite the fact that 55% of the 75 patients in our endoscopic series had invasive (Grade III or IV) tumors, and 24% had undergone prior pituitary surgery; we were still able to demonstrate improved early remission rates when compared to those reported using the microscopic technique. Comparison of endoscopic vs. microscopic results for functioning adenomas revealed early remission in 7/7 (100%) of ACTH secreting adenomas vs. (81%), 9/13 (69%) of prolactin secreting adenomas vs. (66%), and in 7/8 (88%) of growth hormone secreting adenomas vs. (77%) (Wilson & Dempsey, 1978; Smallridge & Martins, 1982; Boggan et al., 1983; Randall et al., 1983; Wilson, 1984; Tagliaferri et al., 1986; Mampalam et al., 1988; Ross & Wilson, 1988; van't Verlaat et al., 1988; Maira et al., 1989; Yang et al., 1994; Abosch et al., 1998; Tyrrell et al., 1999).

There are no published reports documenting early post-operative tumor remission rates for non-functioning adenomas, as only recently have physicians begun to perform early post-operative MRI studies to ascertain residual disease and look for tumor recurrence. With a mean follow-up of only 11.4 months, post-operative MRI imaging for this endoscopic series revealed the remission rate for non-functioning adenomas to be 95% (18/19). Two long-term reports documenting outcomes for non-functioning adenomas with an average of 72 months follow-up noted an 82% remission rate (based on tumor recurrence) (Ebersold et al., 1986; Comtois et al., 1991).

The results from this fully endoscopic series are in line with previous reports demonstrating improved outcomes for patients with lower grade tumors. Remission was noted in (23/25) 92% of Grade I & II tumors, and in (18/22) 82% Grade III & IV tumors. Overall, the early post-operative hormonal and imaging results for the endoscopic series demonstrated remission in (41/47) 87% of patients.

We believe these improved outcomes are the result of the superior illumination, visualization, and angled view provided by the endoscope. Angled endoscopes allow for complete resection of high-grade (invasive) tumors, visualizing parasellar and suprasellar tumor extension, and allowing for rapid decompression of the optic chiasm. Often, the full extent of extrasellar tumor growth is not visible with the direct line of site of the operating microscope. This finding was first documented in 2 previous reports utilizing a combined micro-endoscopic technique, in which researchers demonstrated that the improved visualization provided by the endoscope located residual tumor after what was deemed to be complete microscopic resection in (24%) and (49%) of patients (Helal, 1995; Jarrahy et al., 2000).

Patients with massive suprasellar tumor extension are pre-operatively recommended to undergo a two-stage approach beginning with the endoscopic transsphenoidal resection, followed by a transglabellar approach to remove any residual suprasellar tumor.

Complications

Complications in transsphenoidal pituitary surgery are typically related to blind dissection, inability to determine normal gland from tumor, injury of the optic tracts and chiasm, or aggressive tumor dissection near the lateral and posterior aspects of the sella turcica (Laws & Kern, 1976; Laws & Kern, 1979; Laws, 1982; Laws & Kern, 1982; Landolt, 1984; Black et al., 1987; Candrina et al., 1988; Ahuja et al., 1992).

Improved visualization allows the surgeon to identify and avoid injury to the normal pituitary gland, carotid prominences, hypothalamus, and optic chiasm or bulbs. Recognizing these structures during pituitary tumor removal is critical to avoid catastrophic complications, which have been reported in several microscopic series (Laws & Kern, 1976; Laws & Kern, 1979; Laws, 1982; Laws & Kern, 1982; Landolt, 1984; Black et al., 1987; Candrina et al., 1988; Ahuja et al., 1992).

Table 8 depicts the incidence of various complications we recorded using the endoscopic approach and compares these results to those from a national survey by Ciric of over 1162 surgeons who perform microscopic transsphenoidal pituitary surgery (Ciric et al., 1997). Our results demonstrated a marked reduction in the incidence of complications including: anterior pituitary insufficiency (2.7% vs. 19.4%), diabetes insipidus (2.7% vs. 17.8%), visual loss (0% vs. 1.8%), CNS injury (0% vs. 1.3%), carotid injury (0% vs.1.1%), meningitis (0% vs. 1.5%), post-operative tumor hemorrhage (2.7% vs. 2.9%), and death (0% vs. 0.9%) (Ciric et al., 1997).

Only the incidence of CSF leak was slightly higher for the endoscopic series (6.7% vs. 3.9%). However, 3/5 leaks occurred during the first 10 procedures, while only 2 CSF leaks were observed in the last 65 operations (3.1%). Of note no patients in this series had pre-operative lumbar drains placed.

Other cited advantages of the endoscopic technique include the completely transnasal approach obviating the need for post-operative nasal packing, eliminating the risk of a nasal-oral fistulae and lip numbness which are potential complications of the sublabial-transsphenoidal approach.

Conclusion

Currently, the microscopic transsphenoidal approach represents the standard approach by which the vast majority of pituitary adenomas are surgically resected. This report suggests that the demonstrates that the fully endoscopic transnasal-transsphenoidal procedure may result in improved rates of complete tumor removal and a reduced incidence of complications, when compared to the microscopic transsphenoidal approach.

The early results of this endoscopic series are quite encouraging. However, long-term outcomes data are needed to confirm the efficacy of this procedure. We believe that the inherent advantages of endoscopic visualization, along with continued refinement of the endoscopic technique and instruments will allow this method to become the future gold standard surgical approach to pituitary adenomas.

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Table 1. Patient Demographics
Feature Number
Total number of patients 75
Age (years)
Mean
Range
 
46
16-75
Sex F:M 1.7:1
Prior transsphenoidal tumor resection 18
LOS (days)
Mean
Range
 
2.1
1-11
Follow-up period (months)
Mean
Range
 
11.4
4-29


Table 2. Tumor Characteristics
Tumor type   Number of Patients (%)
Nonfunctioning Adenoma 45 (60)
Functioning Adenoma 30 (40)
PRL Adenoma 14 (19)
GH Adenoma 9 (12)
ACTH Adenoma 7 (9)
Tumor Grade Enclosed 34 (45)
I: Sella normal or focally expanded tumor < 10mm 17 (22.5)
II: Sella enlarged or tumor > 10mm 17 (22.5)
Invasive 41 (55)
III: Localized perforation of sellar floor 16 (21.3)
IV: Diffuse destruction of sellar floor 25 (33.3)
Suprasellar extension 44 (59)
Compression of optic chiasm 36 (48)
Cavernous Sinus invasion 25 (33)


Table 3. Summary of 14 prolactin secreting adenomas
Patient Age Sex Tumor Characteristics
GR, SS, CS, R a
Pre-operative

Prolactin ng/mL
(normal range)
Post-operative
Prolactin ng/mL
(normal range)
% Decrease in Prolactin Level Post-operative MRI Result Adjunctive Treatments
1 21 F I 57b (4-23) 23d (3-24) - Recurrent Tumor Bromocriptine
2 35 F I 270 (3-24) 16 (3-24) 94 - None
3 51 F I 160 (3-30) 24 (3-30) 85 None None
4 43 F II 146b(1-14) 3.8 (3-24) 97 None None
5 31 M II 487 (2-16) 4 (2-16) 99 No Recurrent Tumor None
6 29 F II, SS 100 (3-24) 80 (3-24) - - None
7 22 M II, SS, R 419 (3-19) - - - TSTCR e, bromocriptine
8 30 F III, SS 105b (3-19) 7 (3-19) 93 No Recurrent Tumor None
9 39 F III, SS 528 (3-30) 36 (3-30) 93 No Recurrent Tumor None
10 21 F III, SS 2190 (3-24) 17 (3-24) 99 - None
11 38 F IV, SS, CS, R 567 (3-19) 64 (3-24) 89 - None
12 38 F IV, SS 818c (3-24) 24 (4-27) 97 No Recurrent Tumor None
13 66 M IV, CS 970 (3-18) 11 (3-18) 89 - None
14 55 M IV, CS 1216 (2-19) - - No Recurrent Tumor None


a Tumor Characteristics: GR Tumor grade, SS Suprasellar tumor extension, CS Tumor invasion into cavernous sinus, R Recurrent tumor

b Patient was taking Bromocriptine pre-operatively

c Patient was taking Cabergoline pre-operatively

d Patient was restarted on Bromocriptine post-operatively

e TSTCR Two stage planned operation, transcranial resection of residual tumor as second procedure to be scheduled

Table 4. Summary of 9 GH secreting adenomas
Patient Age Sex Tumor Characteristics
GR, SS, CS, R a
Pre-operative

IGF1 ug/mL
(normal range)
Post-operative
IGF1 ug/mL
(normal range)
Post-operative MRI Result Adjunctive Treatments
1 51 F I 510 (90-360) 308 (90-360) - None
2 54 M I 1095 (76-377) 350 (76-377) - None
3 59 F I, R 575 (53-287) 288 (53-287) No Recurrent Tumor None
4 52 F II, R 473 (160-367) 252 (160-367) No Recurrent Tumor None
5 55 M II 898 (90-360) 249 (90-360) No Recurrent Tumor None
6 50 F III, CS 893 (53-287) 193 (53-287) No Recurrent
Tumor
None
7 35 F III, SS 534 (53-287) 262 (106-368) - None
8 36 F IV, CS, R 670 (114-492) - - TSTCRb
9 51 M IV, SS, R 1020 (90-360) 465 (90-360) - None


a Tumor Characteristics: GR Tumor Grade, SS Suprasellar tumor extension, CS Tumor invasion into cavernous sinus, R Recurrent tumor

b TSTCR Two-stage planned operation, transcranial resection of residual tumor as second procedure to be scheduled.

Table 5. Summary of 7 ACTH secreting adenomas
Patient Age Sex Tumor Characteristics
GR, SS, CS, R a
Pre-operative Test Results Post-operative Test Results
24 hr UFC
ug/24 hr
(nl.)
Am Cortisol
ug/mL
(nl.)
Dexamethasone Suppression Test ACTH Level
pg/mL
(nl.)
Peripheral / Petrosal Sinus Sampling 24 hr
UFC
ug/24 hr
(nl.)
Am
Cortisol
ug/mL
(nl.)
ACTH Level
pg/mL
(nl.)
Post-op
MRI
Result
Baseline
ug/mL
LD
ug/mL
HD
ug/mL
   
1 59 F I 57
(10-34)
18
(3-14)
- - - 61
(9-52)
38/382 - 4
(3-14)
10
(9-52)
-
2 52 F I 112
(12-104)
32
(3-22)
- - - 92
(9-52)
- - 14.2
(3-17)
16
(9-52)
-
3 34 F I 186
(24-108)
18
(2-17)
18
(8-24)
4 2 50
(5-30)
- 9
(5-55)
5
(3-22)
12
(10-60)
No Recurrent Tumor
4 33 F I 194
(10-80)
38
(6-30)
45
(6-30)
5 1 131
(9-52)
- - 5
(6-29)
- -
5 21 F I 348
(<108)
44
(3-22)
348
(<108/24hr)
109
(24 hr)
ND
(24 hr)
50
(0-46)
- - 10
(3-22)
- No Recurrent Tumor
6 41 F I 641
(42-90)
32
(3-25)
14
(2-7)
8 1 - - 68
(42-90)
17
(3-25)
22
(9-52)
-
7 63 M IV, SS, CS 177
(<50)
34
(8-20)
- - - 129
(9-52)
- 45
(<50)
- - No Recurrent Tumor


a Tumor Characteristics: GR Tumor Grade, SS Suprasellar tumor extension, CS Tumor invasion into cavernous sinus, R  Recurrent tumor

ND: Not Detectable

Table 6. Summary of 19 Non-functioning Adenomas with Post-operative MRI Results
Patient Age Sex Tumor Characteristics
GR, SS, CS, R a
Post-operative MRI Result
1 31 F I No Recurrent tumor
2 26 M I No Recurrent tumor
3 36 F II No Recurrent tumor
4 54 F II No Recurrent tumor
5 39 F II No Recurrent tumor
6 37 F II No Recurrent tumor
7 35 F II No Recurrent tumor
8 36 M III No Recurrent tumor
9 45 F III, SS No Recurrent tumor
10 51 M III, SS No Recurrent tumor
11 47 F III, SS No Recurrent tumor
12 74 F IV, SS No Recurrent tumor
13 38 F IV, SS No Recurrent tumor
14 49 F IV, SS, CS, R No Recurrent tumor
15 16 F IV, SS, CS, R 0.6 cm Lt Cavernous sinus
16 69 F IV, SS, CS No Recurrent tumor
17 34 M IV, SS, CS No Recurrent tumor
18 45 M IV, SS, CS No Recurrent tumor
19 58 M IV, SS, CS No Recurrent tumor


a Tumor Characteristics: GR Tumor Grade, SS Suprasellar tumor extension, CS Tumor invasion into cavernous sinus, R  Recurrent tumor

Table 7. Endoscopic vs. Microscopic Early Post-operative Results by Tumor Grade
  Tumor Grade Number of Patients Tumor Resection Judged Complete Intra- operatively Two Stage Operations Hormonally Active Adenomas - Remission by Hormonal assay and/or MRI Non-functioning Adenomas -
No Residual Tumor on
Post-op MRI (%)
Endoscopic Series Overall Remission Rate by Grade (%)
ACTH
(%)
PRL
(%)
GH
(%)
Enclosed Tumors I 17 17 - 6/6 (100) 2/3 (66) 3/3 (100) 2/2 (100) 13/14 (93)
  II 17 16 1 - 2/3 (66) 3/3 (100) 5/5 (100) 10/11 (91)
Invasive Tumors III 16 16 - - 2/3 (66) 1/1 4/4 (100) 7/8 (88)
  IV 25 17 8 1/1 3/4 (75) 0/1 7/8 (88) 11/14 (79)
Endoscopic Totals - 75 66 9 7/7 (100) 9/13 (69) 7/8 (88) 18/19 (95) 41/47 (87)
Microscopic Series - - -   (81) a (66) b (77) c (82) d -


a Immediate post-operative remission rate (mean value) calculated from microscopic series. (Boggan et al., 1983; Tagliaferri et al., 1986; Mampalam et al., 1988)

b Immediate or < 1yr follow-up, post-operative remission rate (mean value) calculated from microscopic series.(Smallridge & Martins, 1982; Randall et al., 1983; Maira et al., 1989; Yang et al., 1994; Tyrrell et al., 1999)

c Immediate or < 1yr follow-up, post-operative remission rate (mean value) calculated from microscopic series. (Wilson & Dempsey, 1978; Wilson, 1984; Ross & Wilson, 1988; van't Verlaat et al., 1988; Abosch et al., 1998)

d Post-operative remission rate (mean value) calculated from microscopic series with an average of 72 months of follow-up (excluding patients who received post-operative radiation therapy). (Ebersold et al., 1986; Comtois et al., 1991)

Table 8. Complications Endoscopic vs. Microscopic Transsphenoidal Pituitary Tumor Removal
Surgical Approach Anterior Pituitary Insufficiency Diabetes
Insipidus
Loss of Vision Carotid Injury CNS Injury Intrasellar Hemorrhage Cerebrospinal Fluid Leak Meningitis Death
Endoscopic 2.7 2.7 0 0 0 2.7 6.7 (3.1) b 0 0
Microscopic a 19.4 17.8 1.8 1.1 1.3 2.9 3.9 1.5 0.9


a Results of a national survey (Ciric et al., 1997)

b 3/5 CSF leaks occurred among the first 10 operations, while only 2 have occurred in the last 65 operations for an incidence of 3.1%.