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Fully Endoscopic Transnasal vs. Transseptal Transphenoidal Pituitary Surgery
By Mohamed S. Kabil., Joseph B. Eby M.D., Hrayr K. Shahinian M.D.

Abstract

A long-term retrospective study of 300 patients who have undergone fully endoscopic transnasal pituitary adenoma resection betweenNovember 1998 and October 2004. These patients' records and data from postoperative follow-up visits were used to ascertain their outcomes. The data was then compared to mean values calculated from several transeptal-transsphenoidal reports.

From a total of 300 pituitary adenomas, 139 (46%) were hormonally active, while 161 (54%) were non-functioning. Mean follow-up period was 38.2 months. The average length of hospital stay was 1.4 days. All patients had postoperative MRI studies to assess residual or recurrent disease; all patients with hormonally active tumors had additonal postoperative hormonal studies. Remission, being defined as no hormonal or radiological evidence of recurrence within the time-frame of the follow-up. Remission was demonstrated in 127/134 (95%) of enclosed and 144/166 (87%) of invasive adenomas. Comparison of fully endoscopic transnasal vs. transseptal-transsphenoidal remission results, revealed an improved outcome using the fully endoscopic transnasal technique: ACTH (86% vs. 81%), PRL (89% vs. 66%) and GH (85% vs. 77%). The remission rate for non-functioning adenomas was 149/161 (93%). Additionally, we noted a marked reduction in complications related to this procedure.

There has been few series to document the results of this procedure; our results conclude that the fully endoscopic transnasal technique is a safe and effective method for removal of pituitary adenomas providing more complete tumor removal and reducing complications. This report presents the largest number of patients to date having undergone fully endoscopic transnasal pituitary surgery, and compares their outcomes with those published for the traditional transseptal-transsphenoidal method.

Keywords
Pituitary Surgery, Endoscopic, Microsurgery, Transsphenoidal

Introduction

Significant advances in the recognition and management of pituitary adenomas have taken place over the last decade. Highly sensitive hormonal assays and magnetic resonance imaging with gadolinium enhancement have led to earlier and more frequent diagnosis of pituitary adenomas. New therapeutic agents such as Cabergoline and Octreotide have been introduced which can control hormonal symptoms and may slow or stop the growth of some functioning adenomas.1,2

However, medical therapy is still frequently unsuccessful for patients suffering from acromegaly, and no effective therapy is available for patients with Cushing's disease. 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.1,2

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.1,2 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.3,4

The traditional transseptal-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.5-11 Continued attempts to improve surgical outcomes, reduce the incidence of complications, and hasten postoperative recovery have led to the development of a minimally invasive fully endoscopic transnasal approach for resection of 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.12-16 Over the past 10 years several centers have adopted the fully endoscopic transnasal procedure as an alternative to the traditional transeptal-transphenoidal approach. However, there has been few series to document the results of this procedure.

Our group began using a combined endoscope-assisted transsphenoidal approach to pituitary tumors in 1996 and have published our results.15 Using this technique we found that 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. 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.16 The advantages of the endoscopic technique convinced our group to convert to a fully endoscopic transnasal procedure in November of 1998.17

In this article we report the largest number of patients to date (300) having undergone fully endoscopic transnasal pituitary adenoma removal. We compare these patients' outcomes with those published in several transseptal-transsphenoidal series reports.

Patients and Methods

Between November 1998 and October 2004, 350 fully endoscopic transnasal operations were performed by surgeons at the Skull Base Institute in Los Angeles, California. 300 of which were for primary or recurrent pituitary adenomas. These patients' 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 (I-IV) was assessed using the pituitary tumor scale proposed by Hardy,18and was determined from preoperative magnetic resonance imaging results. 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, postoperative hormonal levels and MR imaging results. MR imaging studies were performed for all patients during the early postoperative period, to be repeated after 6-12 months and then annually for the rest of their follow-up period.

Patients that had tumors judged preoperatively as inaccessible from a transsphenoidal approach (tumor located cephalad to the optic chiasm or lateral to the cavernous sinus) underwent a two-stage operation with an average of 29 days in between both operations, this included a second stage transglabellar or supraorbital endoscopic operation to remove residual tumor; their postoperative data, MR imaging results and hormonal assays, were assessed after the second operation.

The data from this fully endoscopic series was compared to mean values calculated from several transseptal-transsphenoidal reports. 6 11, 19-26

Surgical Procedure

The fully endoscopic transnasal surgical procedure has been described in previous communications17 and will only be briefly discussed in this report. 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 is 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 a 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 vision; the fluoroscopy monitor is positioned above the patient's opposite shoulder to provide a simultaneous fluoroscopic image of the extent of dissection.

The endoscope is covered with an irrigating sheath, this obviaties 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 to allow for 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 field of view, the 00 endoscope is withdrawn and a 300 endoscope is inserted. The angled lens of this endoscope provides excellent exposure of the suprasellar and parasellar regions. Rotating the 300endoscope clockwise and counterclockwise provides visualization of suprasellar and 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, 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 or a step-down unit for overnight monitoring.

Results

A total of 300 patients underwent fully endoscopic transnasal removal of their pituitary adenomas during the 71 month period of this study. Mean operative time was 69 minutes. 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%. Twelve patients had preoperative panhypopituitarism, 4 of which recovered their pituitary function postoperatively.

Demographic information is presented in Table 1. 72 patients (24%) had recurrent pituitary tumors after prior transseptal-transsphenoidal surgery at other institutions. The majority of which (61%) were non-functioning adenomas. From the recurrent cases, 21 had an extra-sellar tumor extension judged preoperatively as inaccessible from a transsphenoidal approach (tumor located cephalad to the optic chiasm or lateral to the cavernous sinus) and were recommended to undergo a two-stage surgical approach beginning with an endoscopic transnasal resection, to be followed by an endoscopic transglabellar or supraorbital approach for removal of residual tumor.

The average length of stay was 1.4 days, with 237 patients (79%) discharged within 24 hours of the operation. The most common indications for longer hospitalization included temporary diabetes insipidus 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 Hardy18. There were 134 (45%) enclosed tumors (Grades I & II) and 166 (55%) invasive adenomas (Grades III & IV). Compared with prior transseptal-transsphenoidal series, our patient cohort appeared to contain a larger number of high-grade (III & IV) tumors with significant supra- and parasellar extension, including a 24% incidence of cavernous sinus invasion.

The extent of tumor resection was judged intraoperatively, 278/300 (93%) patients were believed to have undergone a total removal of their tumors. 32 patients were planned preoperatively for a two-stage operation, which included a second stage transglabellar or supraorbital approach to remove residual tumor (tumor extension located cephalad to the optic chiasm or lateral to the cavernous sinus) their postoperative data, the extent of tumor resection, their MR imaging results and hormonal assays, were assessed after their second operation.

Residual or recurrent disease was assessed by postoperative MR imaging and by hormonal assays in patients with hormonally active tumors. MR imaging was performed for all patients in the early postoperative period, repeated after 6-12 months, then annually for the rest of their follow-up period.

There were 139 (46%) patients with hormonally active tumors, 19 of which were scheduled for a two-stage operation. The 139 cases consisted of 63 prolactinomas, 48 growth hormone secreting tumors, and 28 corticotrophic adenomas.

Non-functioning adenomas numbered 161 (54%), they were on average larger and of higher grade than the functioning adenomas (107/161 (66%) non-functioning adenomas were of Grades III & IV vs. 59/139 (42%) hormonally active tumors that were of Grades III and IV).

Among the 63 patients with prolactinomas, 44/63 (70%) had preoperative prolactin (PRL) levels > 200ng/ml, while nineteen (that were taking dopamine agonist medication at the time PRL was measured) had PRL levels < 200ng/ml. 3 patients with a postoperative PRL level of <23ng/ml (on Bromocriptine) demonstrated evidence of recurrent tumor on their MRI scan. Another 2 patients with a postoperative MRI scan that revealed no evidence of residual or recurrent disease had a postoperative PRL level of >36ng/ml (this was not considered a curative result). All patients demonstrated significant reductions in their mean PRL level. The overall remission rate for prolactin secreting adenomas was 56/63 (89%).

Forty eight patients had growth hormone secreting tumors. Preoperative and postoperative IGF1 levels demonstrated hormonal and radiological cure in 41/48 (85%) of the patients. Two patients showed evidence of radiological cure but not hormonal and one patient had hormonal cure only (were not considered curative results). Patients that did not demonstrate hormonal cure had a variable but considerable decrease in their postoperative IGF1 levels (normal < 360ug/ml).

There were 28 (9%) patients suffering from Cushing's disease in this series, 24 of which were grade I, and 4 were grade IV tumor. Hormonal and radiological cure was documented in 24/28 (86%) of patients with ACTH secreting tumors.

A total of 161 (54%) patients had non-functioning adenomas, 14 of these patients were scheduled for a two-stage operation. Postoperative MR imaging revealed no recurrent tumor in 149/161 patients (93%). Five of the patients demonstrating recurrent tumor had a mass ranging from 5-8 mm located in the cavernous sinus on an MRI scan performed postoperatively.

Table 3 summarizes the overall postoperative results for patients who have undergone fully endoscopic transnasal pituitary adenoma removal, and compares their results to those from several large transseptal-transsphenoidal pituitary series. Overall, the fully endoscopic transnasal technique demonstrated remission (being defined as no hormonal or radiological evidence of recurrence within the time-frame of follow-up) in 127/134 (95%) of enclosed tumors and in 144/166 (87%) of invasive tumors, for a combined remission rate of 271/300 (90%).

The incidence of complications related to the endoscopic procedure was recorded and the results are depicted in Table 4. This table also contains results from a national survey27 regarding complications related to the traditional transseptal-transsphenoidal procedure. The fully endoscopic transnasal series showed a marked reduction in complications related to glandular injury as well as all other complications.

Discussion

Since Professor Pierre Marie 28 first described acromegaly in 1886 progress in the diagnosis and treatment of pituitary tumors has paralleled advances in technology. 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.29 In 1906 Schloffer reported the first removal of a pituitary tumor through an extracranial transsphenoidal approach.30 Hirsch later modified this approach in 1909.31,32 However, it was Cushing's transseptal-transsphenoidal method introduced in 1910, which standardized this approach to pituitary tumors.33 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 192931,34. Inability to reach suprasellar tumor extension, poor illumination, CSF leakage, meningitis, and a high recurrence rate all led Cushing and his contemporaries to abandon the transseptal-transsphenoidal approach by the early 1930's in favor of the transcranial procedure.31-34

It wasn't until the late 1950's when Guiot who learned Cushing's transseptal-transsphenoidal method from Dott reintroduced this approach. 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.35,36 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.18,31,37,38 These new technologies provided the transseptal-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.5-27

The use of rigid endoscopes for sinus surgery provided the inspiration for their application to pituitary surgery.14,39,40 Isolated reports of the use of endoscopes to resect pituitary tumors appeared in the literature as early as the 1970's.5 However, it was not until the early 1990's that technologic advances in optics, digital cameras, light sources, holding arms, and monitors allowed endoscopes < 5 mm in size to provide high-quality panoramic exposure that surpasses the visualization provided by operating microscopes.12,40 Spencer recently compared and quantified the exposure provided by the 00 endoscope vs. the operating microscope. This report found that even the 00 endoscope provides 1.5-2.5X greater volume of view of the sellar, parasellar and suprasellar region.41

In 1992 Jankowski provided the first description of fully endoscopic transnasal-technique.12 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.13,15,42,43 Jho has published relatively large series describing his experience with 44 pituitary adenomas and 6 other parasellar lesions.42 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.13,15,42-45

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 fully endoscopic transnasal pituitary tumor removal and to compare outcomes for the fully endoscopic transnasal approach to the widely accepted transseptal-transsphenoidal technique.

Tumor Remission

Outcomes for the fully endoscopic surgical approach for the various pituitary tumor types as well as comparative data from several large transseptal-transsphenoidal series are depicted in Table 3. Despite the fact that 166 (55%) of the patients in this series had invasive (Grade III or IV) tumors, and 72 (24%) had undergone prior pituitary surgery; we were still able to demonstrate improved early remission rates when compared to those reported using the traditional transeptal-transsphenoidal technique. Comparison of the results for functioning adenomas revealed remission in (86%) of ACTH secreting adenomas vs. (81%), (89%) of prolactin secreting adenomas vs. (66%), and in (85%) of growth hormone secreting adenomas vs. (77%).6-11, 19-26

With a mean follow-up of 38.2 months, postoperative MR imaging for this endoscopic series revealed the remission rate for non-functioning adenomas to be 149/161 (93%). 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)10,26.

The results from this series are in line with previous reports demonstrating improved outcomes for patients with lower grade tumors. Remission was noted in 127/134 (95%) of Grade I & II tumors, and in 144/166 (87%) Grade III & IV tumors. Overall, the early post-operative hormonal and imaging results for the endoscopic series demonstrated remission in 271/300 (90%) of patients.

We believe that 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.13,15

Patients with massive suprasellar tumor extension are preoperatively recommended to undergo a two-stage approach beginning with the fully endoscopic transnasal resection, followed by an endoscopic transglabellar or a supraorbital approach to remove any residual supra- or parasellar tumor.

Complications

Complications in transsphenoidal pituitary surgery are typically related to blind dissection, inability to differentiate normal gland from tumor, injury to the optic tracts and chiasm, or aggressive tumor dissection near the lateral and posterior aspects of the sella turcica.

Improved visualization allows the surgeon to identify and avoid injury to the normal pituitary gland, carotid prominences, hypothalamus, and optic chiasm. Recognizing these structures during pituitary tumor removal is critical to avoid catastrophic complications, which have been reported in several transseptal-transsphenoidal series.46-49

Table 4 depicts the incidence of various complications we recorded using the endoscopic approach and compares these results to those from a national survey by Ciric27 of over 1162 surgeons who perform transseptal-transsphenoidal pituitary surgery. Complications related to glandular injury were markedly reduced in this fully endoscopic transnasal series, this is reflected by the low incidence of anterior pituitary insufficiency 8/300 (2.7%) and diabetes insipidus 16/300 (5.3%) (12/16 had transient DI vs. 4/16 who developed permanent DI). The incidence of CSF leak was 5/300 (1.7%), however, 3/5 leaks occurred during the first 75 procedures, while only 2 CSF leaks were observed in the last 225 operations for an incidence of only (0.9%). Of note no patients in this series had lumbar drains placed. Septal perforations occurred in only two patients (0.7%) and were small and posterior and caused no subjective complaints.

Apart from the neurological and endocrinological results of surgery, mean operative time was 69 minutes; this was longer in all the compared transseptal-transsphenoidal series. None of the patients who underwent fully endoscopic transnasal surgery had denture problems, snoring (of new onset), reduction of smell sensation, lip numbness, breathing problems, loss of nasal tip projection, as opposed to the other transseptal-transsphenoidal surgical groups who have reported the occurrence of these complications.46-49

Other cited advantages of the fully endoscopic transnasal technique include the completely transnasal approach, eliminating the need for extensive mucosal dissection or postoperative nasal packing.

Conclusion

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

The results of this fully endoscopic transnasal series are quite encouraging. 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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