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Pituitary Tumors and Transsphenoidal Surgery
Pituitary Tumors and Transsphenoidal Surgery Gail L. Rosseau, MD Introduction Pituitary adenomas are among the most common brain tumors, with an estimated prevalence of 16% on autopsy studies.1 The patient advocacy organization, Pituitary Network, recently conducted a “1 in 5” campaign, to increase public awareness of this common entity. While many patients harbor these adenomas, the lesions are nearly always benign and often asymptomatic. Pituitary adenomas are classified according to size, with those less than 10 mm considered microadenomas and those reaching 10 mm or greater in size considered macroadenomas. The vast majority of patients with macroadenomas will have headaches. The most common presenting symptom for large tumors is visual field loss, because of elevation and compression of the optic nerve(s) and chiasm from the tumor as it grows upward from the sella turcica. Diplopia may occur, because of cavernous sinus invasion, with compression or encasement of cranial nerves III, IV, and VI. Pituitary tumors are divided physiologically into secretory and nonsecretory tumors. The most common secretory tumors are prolactinomas, followed by growth hormone-secreting tumors (acromegaly) and adrenocorticotropin-producing tumors (Cushing’s syndrome). Other hormonally active tumors, including gonadotropin—and thyroid-stimulating hormone-producing tumors, are less common.
Treatment Patients with secretory tumors are generally referred for surgical removal. The exception to this recommendation is prolactinomas, where the initial treatment is often medical, with dopamine agonist medications, which reliably treat the hyperprolactinemia and frequently result in tumor shrinkage as well.2 The transsphenoidal surgical approach has been used for over a century to resect lesions of the sellar and parasellar regions. During the past decade, the sublabial, transseptal approach has been largely replaced by Dis Mon 2011;57:607-614 0011-5029/2011 $36.00 ⫹ 0 doi:10.1016/j.disamonth.2011.08.003 DM, October 2011
607
an endonasal approach, often with the very useful adjunct of the endoscope. This minimally invasive procedure for both the approach and the tumor resection improves patient comfort. The wide-angle, magnified visualization provided by the endoscope allows direct observation of critical surrounding structures of the central skull base and angled views for detecting tumor remnants not visualized with direct microscopic views. This report provides an update to current surgical management of these common tumors. The transsphenoidal approach to the pituitary was first performed by Schloffler in Vienna in 1907.1 The sublabial, transseptal version of this approach was initially popularized by Cushing,3 who abandoned the approach during the preantibiotic era and preferred a transscranial approach to pituitary lesions. Widespread and permanent adoption of the transphenoidal technique in the 1960s is credited to Guiot, Hardy, Laws, Wilson, and many others.4 By the 1970s, a sublabial approach to the sellar floor was generally employed for moderate-sized lesions of the region. During the 1990s, several teams built upon the ideas of endoscopic pituitary surgery initially advanced by Guiot.1 The use of the endoscope in transsphenoidal surgery gained momentum because of the advances in optical technology and widespread adoption for sinus surgery by otolaryngologists. Jho and Alfieri,5 Cappabianca and coworkers,6 and others advanced the concept of employing endoscopes to facilitate the transsphenoidal approach to the sellar floor. Several advantages were proposed. These included minimal dissection with elimination of the need for a sublabial incision; panoramic view of the central skull base anatomy, with greater control of important structures, including carotid arteries and optic nerves; and improved patient comfort by eliminating the need for packing. Disadvantages included loss of the depth perception and hands-free visualization provided by a binocular microscope, and the potentially problematic paramedian, rather than midline, approach provided by a completely endonasal route. From 1996 to 1997, we performed all transsphenoidal surgery done via the traditional sublabial microscopic route, but added the use of the rigid 4-mm, 18-cm sinus endoscope, and appropriate 0-degree, 30-degree, and 70-degree lenses. This was done in conjunction with applied cadaver dissection of sinus anatomy. The advantages provided by adjunctive use of endoscope and microscope led us in 1998 to begin using a totally endoscopic endonasal approach to the sella. A combination of endoscopic and microscopic removal of the sellar and parasellar pathology has proven to be effective and safe. In 2008, we reported our 10-year experience with the endoscopic endonasal approach.2 608
DM, October 2011
Surgical Procedure Operating Room Organization and Patient Position The patient is placed supine on the operating table, with neck extended and head turned slightly to the right. The endoscopic equipment, including monitor, light source, video camera, and recorder, is positioned above and behind the patient’s left shoulder. The frameless image guidance monitor is positioned alongside. The surgeon stands at the patient’s right shoulder; the anesthesiologist and his or her equipment are on the patient’s left side. The nurse is at the patient’s head, with a Mayo stand extending over patient’s left shoulder. The patient’s face and periumbilical region are prepped and draped. The nasal cavities are prepped with gauze pledgets of 5% chlorhexidine gluconate. Two cottonoids soaked in xylometazoline hydrochloride are gently and temporarily placed in each nare as nasal decongestants. The middle turbinate and septum are injected with diluted adrenaline (1:200,000). Broad spectrum antibiotics are given pre- and for 24 hours postoperatively.
Approach to the Sella The endoscope (4-mm diameter, 0-degree lens, 18-cm length) is introduced into the chosen nostril. The inferior and middle turbinate are identified, and the middle turbinate is compressed and mobilized laterally. This allows visualization of the superior turbinate, which is a guide to the sphenoid ostium. The size and position of the sphenoid ostia are variable. Entry into the sphenoid sinus via the ostia may be facilitated by visualization of the contralateral ostium and/or use of image guidance. The mucosa surrounding the ostia is gently coagulated to avoid bleeding from septal branches of the sphenopalatine artery. These steps are performed bilaterally. The nasal septum is then separated from the sphenoid rostrum. The entire anterior wall of the sphenoid sinus is thus visible. The anterior sphenotomy is performed by enlarging the 2 sphenoid sinus ostia in a medial and inferior direction. The sphenoid rostrum is completely removed. The anterior sphenoid wall is removed (Fig 1). For macroadenomas, special care is taken to adequately remove the rostrum inferiorly, to permit suprasellar visualization for tumor removal. Meticulous hemostasis is achieved using bone wax and bipolar cautery. Next, one or more intrasphenoid septa are generally encountered. All septa are removed, special care being taken when removing those that insert on the optic and/or carotid protuberances (Fig 2). The sellar floor is examined. Any bony dehiscence already created by the presence of the tumor is developed DM, October 2011
609
FIG 1. Panoramic view of sphenoid sinus, demonstrating sellar floor and left carotid canal. (Color version of figure is available online.)
FIG 2. Axial computed tomographic bone window image, demonstrating erosion of bony carotid canal within the sphenoid sinus by tumor. (Color version of figure is available online.)
along the epidural plane. An intact sellar floor is opened with a microdrill or osteotome. The epidural dissection is performed and complete removal of the sellar floor is achieved. Confirmation of structures and trajectory is aided by frameless stereotactic image guidance (Fig 3). 610
DM, October 2011
FIG 3. Intraoperative Image Guidance System. Note sphenoid sinus septa which inserts on right carotid canal. (Color version of figure is available online.)
Removal of the Lesion The dura is coagulated and incised; the dural leaflets are pushed or coagulated to produce a rectangular opening. A specimen trap is used if cystic or hemorrhagic degeneration of the tumor has been noted on preoperative images. Working first inferiorly, then laterally, and finally superiorly, the lesion is mobilized with curettes of various sizes and angles. Removal of sellar tumor may be performed under microscopic or endoscopic visualization. Once all sellar tumor has been removed, the 30-degree endoscope is used to explore the suprasellar space for additional tumor and to verify that the suprasellar cistern has not been violated. Valsalva maneuver is performed to deliver additional tumor inferiorly and challenge the watertight nature of the dissection cavity. This assures that hemostasis will remain secure with any postoperative coughing or straining that may occur.
Sellar Reconstruction Because the approach is a minimally invasive technique, there is generally not a large fragment of bone or cartilage to use for sellar reconstruction. A piece of autologous adipose is generally harvested from the abdomen. A small adipose graft is placed at the sellar floor and held in place with fibrin sealant. In the case of an intraoperative cerebrospinal fluid (CSF) leak, a lumbar drained may be placed postoperatively and DM, October 2011
611
FIG 4. Endoscopic view of closure after endonasal transsphenoidal approach: replacement of nasal septum in midline position and preserved superior turbinate. (Color version of figure is available online.)
TABLE 1. Results—Symptom relief
Headache (502) Visual field deficit (350)
Improved or Preserved
Worse
502 344
0 6
allowed to drain for 2-4 days. Larger skull base defects may require autologous cartilage, adipose or fascia for reconstruction. Irrigation and final hemostasis of the nasal mucosa are performed. The medial turbinate and nasal septum are medialized (Fig 4). No nasal packing is used. A small triangular nasal drip pad is employed until drainage is minimal.
Results The results of symptom control are listed in Table 1. Of 502 patients who presented with headaches, all reported their headaches were improved by 3 months after surgery. Among the 350 patients who presented with visual complaints and/or field defects, vision was preserved or improved in 344 (98%) and worse in 6 (2%). Control of endocrinopathy with surgery alone was considerably more difficult. Results are listed in Table 2. Among 192 patients with prolactinomas, 120 (63%) experienced normalized prolactin levels and were normal, without need for dopamine agonist therapy, at most recent 612
DM, October 2011
TABLE 2. Results resolution of enocrinopathy Prolactinomas (n ⫽ 192) Acromegaly (n ⫽ 72) Cushing’s disease (n ⫽ 30)
Surgery alone
%
120 40 20
63 56 67
TABLE 3. Complications Transient hyponatremia postdischarge
7
Worsened visual field Cortisone replacement Epidural blood patch Subarachnoid hemorrhage, stroke Reoperation for CSF leak
6 4 1 1 0a
a
One patient had adjuvant stereotactic radiosurgery and developed spontaneous CSF rhinorrhea 18 months later, requiring surgical repair.
follow-up. For the 72 acromegalic patients, surgery was curative in 40 patients (56%) at most recent follow-up. The remaining patients were normalized with adjunctive radiosurgery. Three require ongoing additional suppressive medical therapy. Among the 30 patients with Cushing’s syndrome, 20 (67%) were normal at last evaluation with surgery alone. The remainder was treated with adjunctive radiosurgery and steroid inhibitors. One patient was treated with adrenalectomy. In addition, of the 264 patients with nonfunctional tumors, 14 (5.3%) have had recurrent, growing tumor on subsequent surveillance imaging. These patients were treated with a second debulking transsphenoidal resection, followed by radiosurgery.2 Complication rates were low in this series and are listed in Table 3. Major morbidity was well below 1%,2 in keeping with the observations of Ciric and coworkers,7 Hardy and Kurn,4 Laws,8 and others, who have documented small surgical risks for tumor resection via the transsphenoidal approach, compared with other neurosurgical procedures.
Discussion The endoscopic approach has been confirmed to be both a safe and an effective means of removing tumors and other pathologies in this region. The recurrence rate is compatible with those reported for standard sublabial resection of such tumors. The recurrence rate for secretory tumors remains undesirably high. This appears to be due to local invasion of the dura and cavernous sinuses, rendering complete removal of such DM, October 2011
613
tumors impossible without unacceptable neurologic deficit. For the foreseeable future, adjunctive therapy with antagonist medications and/or radiotherapy will be the norm for such lesions.
Conclusions Improvement in patient comfort with the direct endonasal transsphenoidal approach, while preserving and even advancing satisfactory tumor resection, has led to the widespread adoption of this approach for resection of sellar and parasellar lesions. Adjunctive therapies will continue to play a role in the management of recurrent and secretory lesions.
REFERENCES 1.
2. 3. 4. 5. 6. 7.
8.
614
Coldwell WT, Weiss MH. Transnasal transsphenoidal approach. In: Apuzzo MLJ, ed Surgery of the Third Ventricle. Baltimore, MD: Williams and Wilkins, 1998. p. 553-74. Rosseau GL, Becker SA. The endoscopic transsphenoidal approach: evolution and personal experience. Bras Neurocirurg J 2008;19(2):30-5. Cushing H. The Weir Mitchell lecture. Surgical experiences with pituitary disorders. JAMA 1914;63:1515-25. Hardy J. Transphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1969;16:185-217. Jho HD, Alfieri A. Endoscopic endonasal pituitary surgery: evolution of surgical technique and equipment in 150 operations. Minim Invas Neurosurg 2001;44:1-12. Cappabianca P, Cavallo LM, de Divitis E. Endoscopic endonasal transsphenoidal surgery. Neurosurgery 2004;55(4):933-40 [Discussion 940-1]. Ciric I, Ragin A, Baumgartner C, et al. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997;40:225-37. Laws ER, Kurn EB. Complications of transsphenoidal surgery. In: Tindall GT, Collins WF, editors. Clinical Management of Pituitary Disorders. New York: Raven, 1979. p. 435-45.
DM, October 2011
Treatment Patients with secretory tumors are generally referred for surgical removal. The exception to this recommendation is prolactinomas, where the initial treatment is often medical, with dopamine agonist medications, which reliably treat the hyperprolactinemia and frequently result in tumor shrinkage as well.2 The transsphenoidal surgical approach has been used for over a century to resect lesions of the sellar and parasellar regions. During the past decade, the sublabial, transseptal approach has been largely replaced by Dis Mon 2011;57:607-614 0011-5029/2011 $36.00 ⫹ 0 doi:10.1016/j.disamonth.2011.08.003 DM, October 2011
607
an endonasal approach, often with the very useful adjunct of the endoscope. This minimally invasive procedure for both the approach and the tumor resection improves patient comfort. The wide-angle, magnified visualization provided by the endoscope allows direct observation of critical surrounding structures of the central skull base and angled views for detecting tumor remnants not visualized with direct microscopic views. This report provides an update to current surgical management of these common tumors. The transsphenoidal approach to the pituitary was first performed by Schloffler in Vienna in 1907.1 The sublabial, transseptal version of this approach was initially popularized by Cushing,3 who abandoned the approach during the preantibiotic era and preferred a transscranial approach to pituitary lesions. Widespread and permanent adoption of the transphenoidal technique in the 1960s is credited to Guiot, Hardy, Laws, Wilson, and many others.4 By the 1970s, a sublabial approach to the sellar floor was generally employed for moderate-sized lesions of the region. During the 1990s, several teams built upon the ideas of endoscopic pituitary surgery initially advanced by Guiot.1 The use of the endoscope in transsphenoidal surgery gained momentum because of the advances in optical technology and widespread adoption for sinus surgery by otolaryngologists. Jho and Alfieri,5 Cappabianca and coworkers,6 and others advanced the concept of employing endoscopes to facilitate the transsphenoidal approach to the sellar floor. Several advantages were proposed. These included minimal dissection with elimination of the need for a sublabial incision; panoramic view of the central skull base anatomy, with greater control of important structures, including carotid arteries and optic nerves; and improved patient comfort by eliminating the need for packing. Disadvantages included loss of the depth perception and hands-free visualization provided by a binocular microscope, and the potentially problematic paramedian, rather than midline, approach provided by a completely endonasal route. From 1996 to 1997, we performed all transsphenoidal surgery done via the traditional sublabial microscopic route, but added the use of the rigid 4-mm, 18-cm sinus endoscope, and appropriate 0-degree, 30-degree, and 70-degree lenses. This was done in conjunction with applied cadaver dissection of sinus anatomy. The advantages provided by adjunctive use of endoscope and microscope led us in 1998 to begin using a totally endoscopic endonasal approach to the sella. A combination of endoscopic and microscopic removal of the sellar and parasellar pathology has proven to be effective and safe. In 2008, we reported our 10-year experience with the endoscopic endonasal approach.2 608
DM, October 2011
Surgical Procedure Operating Room Organization and Patient Position The patient is placed supine on the operating table, with neck extended and head turned slightly to the right. The endoscopic equipment, including monitor, light source, video camera, and recorder, is positioned above and behind the patient’s left shoulder. The frameless image guidance monitor is positioned alongside. The surgeon stands at the patient’s right shoulder; the anesthesiologist and his or her equipment are on the patient’s left side. The nurse is at the patient’s head, with a Mayo stand extending over patient’s left shoulder. The patient’s face and periumbilical region are prepped and draped. The nasal cavities are prepped with gauze pledgets of 5% chlorhexidine gluconate. Two cottonoids soaked in xylometazoline hydrochloride are gently and temporarily placed in each nare as nasal decongestants. The middle turbinate and septum are injected with diluted adrenaline (1:200,000). Broad spectrum antibiotics are given pre- and for 24 hours postoperatively.
Approach to the Sella The endoscope (4-mm diameter, 0-degree lens, 18-cm length) is introduced into the chosen nostril. The inferior and middle turbinate are identified, and the middle turbinate is compressed and mobilized laterally. This allows visualization of the superior turbinate, which is a guide to the sphenoid ostium. The size and position of the sphenoid ostia are variable. Entry into the sphenoid sinus via the ostia may be facilitated by visualization of the contralateral ostium and/or use of image guidance. The mucosa surrounding the ostia is gently coagulated to avoid bleeding from septal branches of the sphenopalatine artery. These steps are performed bilaterally. The nasal septum is then separated from the sphenoid rostrum. The entire anterior wall of the sphenoid sinus is thus visible. The anterior sphenotomy is performed by enlarging the 2 sphenoid sinus ostia in a medial and inferior direction. The sphenoid rostrum is completely removed. The anterior sphenoid wall is removed (Fig 1). For macroadenomas, special care is taken to adequately remove the rostrum inferiorly, to permit suprasellar visualization for tumor removal. Meticulous hemostasis is achieved using bone wax and bipolar cautery. Next, one or more intrasphenoid septa are generally encountered. All septa are removed, special care being taken when removing those that insert on the optic and/or carotid protuberances (Fig 2). The sellar floor is examined. Any bony dehiscence already created by the presence of the tumor is developed DM, October 2011
609
FIG 1. Panoramic view of sphenoid sinus, demonstrating sellar floor and left carotid canal. (Color version of figure is available online.)
FIG 2. Axial computed tomographic bone window image, demonstrating erosion of bony carotid canal within the sphenoid sinus by tumor. (Color version of figure is available online.)
along the epidural plane. An intact sellar floor is opened with a microdrill or osteotome. The epidural dissection is performed and complete removal of the sellar floor is achieved. Confirmation of structures and trajectory is aided by frameless stereotactic image guidance (Fig 3). 610
DM, October 2011
FIG 3. Intraoperative Image Guidance System. Note sphenoid sinus septa which inserts on right carotid canal. (Color version of figure is available online.)
Removal of the Lesion The dura is coagulated and incised; the dural leaflets are pushed or coagulated to produce a rectangular opening. A specimen trap is used if cystic or hemorrhagic degeneration of the tumor has been noted on preoperative images. Working first inferiorly, then laterally, and finally superiorly, the lesion is mobilized with curettes of various sizes and angles. Removal of sellar tumor may be performed under microscopic or endoscopic visualization. Once all sellar tumor has been removed, the 30-degree endoscope is used to explore the suprasellar space for additional tumor and to verify that the suprasellar cistern has not been violated. Valsalva maneuver is performed to deliver additional tumor inferiorly and challenge the watertight nature of the dissection cavity. This assures that hemostasis will remain secure with any postoperative coughing or straining that may occur.
Sellar Reconstruction Because the approach is a minimally invasive technique, there is generally not a large fragment of bone or cartilage to use for sellar reconstruction. A piece of autologous adipose is generally harvested from the abdomen. A small adipose graft is placed at the sellar floor and held in place with fibrin sealant. In the case of an intraoperative cerebrospinal fluid (CSF) leak, a lumbar drained may be placed postoperatively and DM, October 2011
611
FIG 4. Endoscopic view of closure after endonasal transsphenoidal approach: replacement of nasal septum in midline position and preserved superior turbinate. (Color version of figure is available online.)
TABLE 1. Results—Symptom relief
Headache (502) Visual field deficit (350)
Improved or Preserved
Worse
502 344
0 6
allowed to drain for 2-4 days. Larger skull base defects may require autologous cartilage, adipose or fascia for reconstruction. Irrigation and final hemostasis of the nasal mucosa are performed. The medial turbinate and nasal septum are medialized (Fig 4). No nasal packing is used. A small triangular nasal drip pad is employed until drainage is minimal.
Results The results of symptom control are listed in Table 1. Of 502 patients who presented with headaches, all reported their headaches were improved by 3 months after surgery. Among the 350 patients who presented with visual complaints and/or field defects, vision was preserved or improved in 344 (98%) and worse in 6 (2%). Control of endocrinopathy with surgery alone was considerably more difficult. Results are listed in Table 2. Among 192 patients with prolactinomas, 120 (63%) experienced normalized prolactin levels and were normal, without need for dopamine agonist therapy, at most recent 612
DM, October 2011
TABLE 2. Results resolution of enocrinopathy Prolactinomas (n ⫽ 192) Acromegaly (n ⫽ 72) Cushing’s disease (n ⫽ 30)
Surgery alone
%
120 40 20
63 56 67
TABLE 3. Complications Transient hyponatremia postdischarge
7
Worsened visual field Cortisone replacement Epidural blood patch Subarachnoid hemorrhage, stroke Reoperation for CSF leak
6 4 1 1 0a
a
One patient had adjuvant stereotactic radiosurgery and developed spontaneous CSF rhinorrhea 18 months later, requiring surgical repair.
follow-up. For the 72 acromegalic patients, surgery was curative in 40 patients (56%) at most recent follow-up. The remaining patients were normalized with adjunctive radiosurgery. Three require ongoing additional suppressive medical therapy. Among the 30 patients with Cushing’s syndrome, 20 (67%) were normal at last evaluation with surgery alone. The remainder was treated with adjunctive radiosurgery and steroid inhibitors. One patient was treated with adrenalectomy. In addition, of the 264 patients with nonfunctional tumors, 14 (5.3%) have had recurrent, growing tumor on subsequent surveillance imaging. These patients were treated with a second debulking transsphenoidal resection, followed by radiosurgery.2 Complication rates were low in this series and are listed in Table 3. Major morbidity was well below 1%,2 in keeping with the observations of Ciric and coworkers,7 Hardy and Kurn,4 Laws,8 and others, who have documented small surgical risks for tumor resection via the transsphenoidal approach, compared with other neurosurgical procedures.
Discussion The endoscopic approach has been confirmed to be both a safe and an effective means of removing tumors and other pathologies in this region. The recurrence rate is compatible with those reported for standard sublabial resection of such tumors. The recurrence rate for secretory tumors remains undesirably high. This appears to be due to local invasion of the dura and cavernous sinuses, rendering complete removal of such DM, October 2011
613
tumors impossible without unacceptable neurologic deficit. For the foreseeable future, adjunctive therapy with antagonist medications and/or radiotherapy will be the norm for such lesions.
Conclusions Improvement in patient comfort with the direct endonasal transsphenoidal approach, while preserving and even advancing satisfactory tumor resection, has led to the widespread adoption of this approach for resection of sellar and parasellar lesions. Adjunctive therapies will continue to play a role in the management of recurrent and secretory lesions.
REFERENCES 1.
2. 3. 4. 5. 6. 7.
8.
614
Coldwell WT, Weiss MH. Transnasal transsphenoidal approach. In: Apuzzo MLJ, ed Surgery of the Third Ventricle. Baltimore, MD: Williams and Wilkins, 1998. p. 553-74. Rosseau GL, Becker SA. The endoscopic transsphenoidal approach: evolution and personal experience. Bras Neurocirurg J 2008;19(2):30-5. Cushing H. The Weir Mitchell lecture. Surgical experiences with pituitary disorders. JAMA 1914;63:1515-25. Hardy J. Transphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1969;16:185-217. Jho HD, Alfieri A. Endoscopic endonasal pituitary surgery: evolution of surgical technique and equipment in 150 operations. Minim Invas Neurosurg 2001;44:1-12. Cappabianca P, Cavallo LM, de Divitis E. Endoscopic endonasal transsphenoidal surgery. Neurosurgery 2004;55(4):933-40 [Discussion 940-1]. Ciric I, Ragin A, Baumgartner C, et al. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997;40:225-37. Laws ER, Kurn EB. Complications of transsphenoidal surgery. In: Tindall GT, Collins WF, editors. Clinical Management of Pituitary Disorders. New York: Raven, 1979. p. 435-45.
DM, October 2011