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REVIEW ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 7  |  Page : 66-71

Anatomical Correlates and Subtleties of Surgery for Pituitary Tumors- A Review of Personal Understanding


Department of Neurosurgery, Seth G.S. Medical College and K.E.M Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication24-Jun-2020

Correspondence Address:
Prof. Atul Goel
Department of Neurosurgery, K.E.M. Hospital and Seth G.S. Medical College, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.287662

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 » Abstract 


The authors review the anatomy of the pituitary gland on the basis of cadaver dissection studies and anatomy of dural relationships of pituitary tumors and its extensions on the basis of a 35-year-old experience of surgically treating pituitary tumors. Perfect understanding of anatomical correlates and nuances of pituitary tumor surgery is essential to achieve satisfactory surgical results. The pituitary gland is located in a specially enclosed cavity that is neither intracranial nor extracranial. It is covered strategically by meninges. Pituitary gland has a close relationship with cavernous sinuses and sphenoid air sinus. Pituitary tumors range widely in their size. Whilst microadenomas are generally associated with hormonally active tumors, large and giant sized tumors are usually hormonally non-functional. Surgical issues are unique for all sizes of pituitary tumors. Giant pituitary tumors grow in size, but a majority of them are confined to dural compartmental space. Recently proposed classification schemes have enhanced the understanding of anatomical subtleties and dural relationships of growing and giant pituitary tumors.


Keywords: Cavernous sinus, diaphragma sellae, pituitary tumors
Key Message: Understanding of the dural relationship with pituitary tumors can dictate the surgical strategy. Growing pituitary tumors elevate the dura of diaphragm sellae and only rarely transgress it. Pituitary tumors invade into the cavernous sinus but the lateral dural wall of cavernous sinuses cannot be transgressed. The tumours that involve cavernous sinus frequently elevate the dural roof.


How to cite this article:
Goel A, Jhawar S, Shah A. Anatomical Correlates and Subtleties of Surgery for Pituitary Tumors- A Review of Personal Understanding. Neurol India 2020;68, Suppl S1:66-71

How to cite this URL:
Goel A, Jhawar S, Shah A. Anatomical Correlates and Subtleties of Surgery for Pituitary Tumors- A Review of Personal Understanding. Neurol India [serial online] 2020 [cited 2020 Jul 5];68, Suppl S1:66-71. Available from: http://www.neurologyindia.com/text.asp?2020/68/7/66/287662




Pituitary tumors are a relatively common neurosurgical entity. Whilst smaller tumors are diagnosed early due to their hormonal manifestations, larger tumors are often diagnosed due to their compressive effects on the visual apparatus. A number of clinical and surgical issues need to be comprehensively evaluated and studied and elegantly executed to achieve a gratifying clinical outcome. Giant pituitary tumors are amongst the more complex neurosurgical challenges. Despite the histological benign nature, some of these tumors grow to a massive size. Due to the invasiveness and size of such tumors, surgical resection is difficult and on some occasions, dangerous.[1],[2],[3],[4],[5] Inadequate resection can lead to postoperative complications and even death. As the results of radiation therapy are inconsistent, surgery forms the mainstay of treatment.


 » Anatomical Corelates Top


Anatomy of the pituitary gland

The pituitary gland also called hypophysis, is small pea-shaped structure located at base of brain as a protrusion off the bottom of the hypothalamus. It is housed in the bony cavity of the sphenoid sinus in center of middle cranial fossa known as sella turcica, which is covered by a dural fold called diaphragma sella [Figure 1] and [Figure 2]. Sella turcica has important neurovascular relationships. Superiorly, it is related to optic nerves, chiasma, hypothalamus, third ventricle and circle of Willis, laterally it is related to cavernous sinuses and internal carotid arteries, posteriorly it is related to brainstem, basilar artery and anteriorly it is related to nasal cavity via sphenoid and ethmoid sinuses.
Figure 1: Stepwise demonstration of trans nasal endoscopic approach to sella and pituitary gland. (a) Endoscopic view of sphenoid ostia (arrow). On left side middle turbinate is preserved to demonstrate its relationship to ostium of sphenoid sinus. On right side sphenopalatine foramen is visible at root of inferior turbinate. (b) Panoramic view of sphenoid sinus cavity after anterior sphenoidectomy showing posterior wall of sphenoid sinus with sella floor, optic protuberance, tuberculum sella, planum sphenoidale, clival recess and internal carotid artery protuberance. Clival recess can be seen bordered by paraclival internal carotid artery laterally on both sides. (c) Endoscopic view after removal of bone of posterior wall of sphenoid sinus. Underlying periosteal dura can be seen covering sella, clivus and internal carotid artery. Sellar internal carotid artery appears to form a variable C-shaped curvature when viewed from endonasal endoscopic perspective. Basilar plexus or posterior intercavernous sinus can be seen between layers of clival dura. (d) Close up view of sellar compartment with pituitary gland. Inferior hypophyseal artery can be seen on right side going to posterior pituitary gland. Anteriorly direct branch from internal carotid artery can be seen supplying capsule of pituitary gland. These branches are also known as McConnel's capsular branches. (e) Overview of endoscopic dissection of sella, clival and suprasellar region. Dura covering anterior skull base, optic nerves, pituitary gland, cavernous sinus, internal carotid arteries and clival region has been removed to expose neurovascular structures. Pituitary gland can be seen in relation to optic chiasma and suprasellar arteries. Ophthalmic arteries can be seen arising from supraclinoid internal carotid arteries and going below optic nerves. Basilar artery with brainstem is visible in the background. (f) Close up view of pituitary gland with stalk and optic chiasma. Superior hypophyseal artery can be seen arising from internal carotid artery and supplying stalk and anterior lobe of pituitary gland. Anterior communicating artery complex is visible in supra-chismatic recess

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Figure 2: Superior view of sellar region. (a) Osseous anatomy of sellar cavity. Sella turcica extend from tuberculum sella anteriorly to dorsum sella posteriorly. Chiasmatic groove separates tuberculum sella from planum sphenoidale anteriorly, (b) Sagittal section showing nasal cavity in relation to skull base. Sella turcica with pituitary gland can be seen as a prominent bulge into sphenoid sinus. Superior, middle and inferior turbinates can be seen in lateral nasal wall, (c) Pituitary gland can be seen here with its dural relationships from superior aspect. Diaphragma sella covers the most of the pituitary gland superiorly except small opening in the center, which transmit pituitary stalk. Diaphragma can be seen extending laterally as roof of cavernous sinus. Internal carotid artery and optic nerves can be seen in relation to pituitary gland. Right optic nerve has been lifted to show ophthalmic artery, (d) Dura from roof is removed to expose pituitary gland. Pituitary gland has two distinct lobes, anterior is bigger and darker compared to posterior lobe. Pituitary stalk can be seen arising from top of the gland, and (e) Superior view of sella and parasellar region showing relationship of pituitary gland to cavernous sinuses. Cavernous sinuses have been dissected to show its neurovascular contents. Internal carotid artery takes a S-shaped course while travelling inside cavernous sinus and forms a groove along lateral wall of sphenoid sinus known as carotid sulcus. Inferior hypophseal artery can be seen going medially after origin to supply posterior pituitary gland. Dorsal clival artery can be seen arising from meningohypophseal trunk and giving supply to clival dura and abducens nerve. Oculomotor, trochlear and trigeminal nerve can be seen going in to lateral wall of cavernous sinus

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Anatomy of surgical 'routes'

A brief overview of sellar anatomy is elucidated with the help of cadaveric dissection. The focus is to show the anatomy of the region as it will be seen whilst operating by trans cranial and endoscopic trans nasal surgical routes.

Trans nasal/sphenoidal approach

Trans nasal approach can be broadly divided into three stages viz nasal stage, sphenoidal stage and sellar stage. For the nasal stage, one needs to be familiar with nasal anatomy and prominent nasal landmarks, like middle turbinate root, superior turbinate and sphenoethmoidal recess leading to sphenoid ostia on either side [Figure 1]a. Apart from that, one should also be aware of landmarks for locating sphenopalatine artery that supplies nasoseptal flap [Figure 1]a. Sphenoid ostia can be identified based on these landmarks and give access to sphenoid sinus, which is the main working area for pituitary tumor removal. Depending on the degree of pneumatisation, sphenoid sinus presents useful landmarks for identifying sella, optic nerve and internal carotid artery. An endoscopic view of posterior and lateral walls of sphenoid sinus provides consistent landmarks for orientation to the anatomy of sella and parasellar areas [Figure 1]b. Most consistent identifiable landmark is clival indentation bordered superiorly by floor of sella and ICA protuberance laterally [Figure 1]b. Another prominent bony landmark is optic carotid recess (OCR), which is ventral recess of optic strut. OCR is a space between the sellar ICA bulge and optic nerve impression. Area of bone rostral to sella is planum sphenoidale. A mild, narrow, central bulge just superior to the sella represents the tuberculum sella, which anchors the chiasmatic sulcus intra cranially and is bordered by the optic canals laterally. Thus, sella floor forms the central bulge in the sinus cavity bordered rostrally by planum sphenoidale and caudally by clival recess. Lateral to sella is carotid protuberance due to sellar segment of ICA.

Once sphenoid bone is removed sellar contents can be accessed by cutting dura of sella floor. Here one needs to understand dural layers and their relation to intercavernous sinuses [Figure 1]c. Rarely McConnel's capsular artery can be a source of bleeding while opening the dura in this region. In sella pituitary gland is separated from suprasellar cisterns by a double layer of dura called diaphragma sella. It has an opening for a stalk of pituitary gland which attaches the gland to hypothalamus. Laterally medial cavernous wall separates pituitary gland from contents of cavernous sinus [Figure 1]d. Medial cavernous wall also offers anatomical restriction to lateral extension of pituitary tumors. Suprasellar extension of pituitary tumor can affect optic apparatus, anterior communicating artery with perforators and third ventricle depending upon level of extension [Figure 1]e and [Figure 1]f.

Trans cranial approach

Superior view of sella

Pituitary fossa occupies the central part of the sphenoid body and is bounded anteriorly by the tuberculum sellae and posteriorly by the dorsum sellae [Figure 2]a. Planum sphenoidale is separated from tuberculum sellae by chiasmatic groove, a shallow groove between two optic foramina [Figure 2]a. Diaphragma sella is dural roof of sella cavity with a circular opening for pituitary stalk [Figure 2]b and [Figure 2]c. The pituitary gland has two distinct parts when viewed from above, a largely darker and thicker part is the anterior lobe and a smaller lighter and gelatinous part is the posterior lobe [Figure 2]d. The pituitary gland is related to optic chiasm and anterior cerebral artery complex superiorly [Figure 2]b. Laterally pituitary gland is related to cavernous sinuses on both sides, from which it is separated by medial cavernous wall. The medical cavernous wall is a thin translucent membrane.

Surgical concepts regarding dura and its relationship with pituitary tumors

Understanding of the anatomy of the tumor extensions and their relationships with the dural layers of sella, diaphragm sellae and walls of the cavernous sinus are crucially important for surgery, particularly when the tumors are large or giant in size.

Diaphragma sellae and pituitary tumors

Goel first described that the pituitary tumors elevate the diaphragma sellae and seldom transgress it.[1],[6] The concept that the diaphragma sellae is elevated and not transgressed had significant implications in the development of surgical concepts of these tumors. This understanding that the cranial component of the tumor is covered by the 'dural' layer of diaphragma sellae and is infradiaphragmatic in location evolutionized surgical approach to pituitary tumors.[7] Earlier, dumbbell shaped tumors were considered to be in the sella in its inferior aspect and in the intracranial subarachnoid compartment in its rostral component, the waist being formed by the edge of the defect in the diaphragma sellae. Trans cranial surgery was the favoured option in cases where the cranial component was significantly large. However, understanding of the fact that the dura of diaphragma sellae was elevated by the tumor and formed a barrier between the tumor and the brain permitted safe resection and allowed trans nasal surgery for such tumors.

Cavernous sinus dural walls – relevance to pituitary surgery

Transgression of the medial wall of the cavernous sinus is a frequent event in patients with pituitary tumors, but transgression of the lateral wall and the roof of the cavernous sinus is rare or not possible. The elevation of the dural roof of the cavernous sinus by the pituitary tumors was first described by Goel et al.[1],[6]

Surgical implications

Understanding of the extensions and relations of the dura in the region of the sella and of cavernous sinus helped in the development of surgery of pituitary tumors and enhanced the scope of surgery from the nasal route.[7] The tumors that were earlier considered to be suitable for trans cranial surgery could be operated by trans nasal route. These concepts of anatomy revolutionized surgical approaches to large and giant pituitary tumors in general and particularly those that extended above the sella and those that invaded into the cavernous sinus. Introduction of endoscope based surgery assisted in developing this concept further.


 » Giant Pituitary Tumors Top


Giant and 'invasive' pituitary tumors are amongst the more formidable neurosurgical challenges. Despite the histological benign nature, some of these tumors grow into a massive size and invade into diverse anatomical structures.[1],[2],[3],[4],[5] Due to the size of such tumors, surgical resection is difficult and on occasion dangerous. At one time, these tumors were considered to be a contraindication for any surgery. Wirth et al. reported a mortality rate of 18% when dealing with these giant pituitary adenomas.[7] In 1969, Jefferson's view was that surgery was contraindicated when the surface area of a suprasellar extension as shown on an unmagnified lateral projection pneumoencephalogram exceeded seven square centimetres and when the summit of the tumour was within six millimetres of the foramen of Monro.[7],[8] It was only much later that radical surgery was adopted for these tumors.

Giant pituitary tumors have been described as invasive adenoma,[9] malignant adenoma[10] and carcinoma.[11] Mohr and Hardy classified pituitary tumors on the basis of their biological behaviour.[8] Some authors refer to pituitary tumors with size in excess of 40 mm, or those extending less than 6 mm from the foramen of Monro as 'giant' irrespective of their invasiveness.[9] Jefferson observed an incidence of giant pituitary tumors in about 6% of all cases.[10] The histological characters of giant pituitary tumors do not usually correlate well with the gross features and generally comprise of benign cells.[4],[11] In our earlier article on the subject we identified tumors over 40 mm in their maximum dimension as giant.[2] However, it now appears that tumor that measured more than 30 mm in their maximum or 'total (sellar + suprasellar component) height' can be labelled as 'giant'.[12] These tumors constituted approximately 15% of the total number of pituitary tumors seen during the period. Surgical difficulties and outcome significantly differs in tumors having 30 mm height and those having 40 mm or more height.

Hardy classification of pituitary tumors

Hardy (1979)[5] classified pituitary tumors on the basis of their biologic behaviour. According to this classification, grade III refers to tumors having localized invasion of the floor of the sella, grade IV indicates diffuse invasion and grade V indicates diffuse metastases.

Knosp classification of pituitary tumors

Knosp et al. in 1983 presented a classification scheme to describe the invasion of the pituitary adenoma into the cavernous sinus.[13] The classification is based on three lines in relation to the supracavernous and intracavernous carotid artery as seen on coronal views of MRI. These lines are the medial, median and lateral carotid lines. The medial line passes through the medial walls of the supra and intracavernous sinus ICA. The median line crosses the centres of the ICAs and the lateral carotid line is tangential to the lateral walls of the ICAs.

According to the classification, the tumor invasion into the cavernous sinus can be classified as follows:

Grade 0: The adenoma does not extend beyond the medial carotid line.

Grade 1: The adenoma crosses the medial line, but doesn't extend past the median line, or the so-called “intercarotid” line.

Grade 2: The adenoma extends beyond the median line, but doesn't extend beyond the lateral line.

Grade 3: The adenoma extends beyond the lateral carotid line.

Grade 4: The adenoma totally wraps around the intracavernous carotid artery.

Goel classification of giant pituitary tumors[1],[6]

We discussed a classification scheme for giant pituitary tumors on the basis of their dural relationships. The classification helped in characterizing these tumors, assisted in developing a surgical plan and predicted the surgical and long-term outcome.[6],[14],[15],[16],[17],[18]

Grade I giant pituitary tumors

This group of tumors is confined inferiorly to the sellar dura, is underneath the elevated diaphragma sellae and laterally is bordered by an intact medial wall of the cavernous sinus [Figure 3]. Diaphragma sellae can sometimes be elevated up to or even beyond the corpus callosum. Diaphragma sellae is markedly thinned out at places and frequently forms big or small daughter balloons. The rounded superior wall or dome of the tumor is suggestive of the fact that the diaphragma sellae is intact. The diaphragma sellae is elevated superiorly to varying extent. The fact that diaphragma sellae is elevated and not transgressed is identified by the fact that the arteries of the circle of Willis are not encased by the tumor. The presence of an intact diaphragma sellae is confirmed during surgery and this feature has significant surgical relevance as it forms an important protective barrier and such tumors can be resected radically through a relatively small exposure by a trans-nasal transsphenoidal route.
Figure 3: Sagittal T1 weighted contrast image shows Goel Grade I pituitary tumor. The diaphragma sellae is elevated superiorly

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Grade II giant pituitary tumors

This group is where the tumors crossed the boundary formed by the medial wall of the cavernous sinus and invade into the confines of the cavernous sinus [Figure 4]. Cavernous sinus invasion could be confirmed on MR imaging if the tumor extended on both sides of the carotid artery. Although bulged out laterally, a transgression of the lateral dural wall of the cavernous sinus is not observed, suggesting the relative firmness and the resistance offered by the lateral dural wall of the cavernous sinus.
Figure 4: (a) Coronal image showing Goel Grade II giant pituitary tumor with bilateral tumor invasion into the cavernous sinus. (b) Axial MRI shows internal carotid artery relationship with the tumor within the cavernous sinus

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Grade III giant pituitary tumors

'Weakness' of the superior wall or roof of the cavernous sinus and its elevation as a result of the presence of an intracavernous sinus meningioma has been described by Goel earlier.[18] It was observed that a significant number of giant pituitary tumors, which invaded into the cavernous sinus, elevated the superior dural wall of the cavernous sinus. Such tumors, which selectively elevated the roof of the cavernous sinus, were labelled as Grade III pituitary tumors [Figure 5]. The superior wall of the cavernous sinus matches in the elasticity but is relatively thinner than the diaphragma sellae. Trans-sphenoidal surgery was used to resect majority of these tumors. An attempt was made to remove the portion of the tumor extending into the cavernous sinus and along its superior wall. However, the radical resection of the part of the tumor along the superior wall of cavernous sinus was relatively complex due to difficulty in adequate exposure of the tumor mass and the narrowness of the dural neck at the level of the roof of the cavernous sinus. Moreover, manipulations in the region of the roof of the cavernous sinus placed the oculomotor nerve in danger of injury due to its anatomical proximity.
Figure 5: Coronal T1 weighted MRI image shows the Goel Grade III pituitary tumor. The elevation of the roof of cavernous sinus and diaphragma sellae can be noted. There is evidence of haemorrhage within the tumor confines

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Grade IV giant pituitary tumors

The giant pituitary tumors, which transgressed the diaphragmasellae boundary and encased the arteries of the circle of Willis, were labelled as Grade IV [Figure 6]. In these cases, it appeared that the tumor extended into the subarachnoid space of the brain and encased arteries and perforators. The exact site of dural dehiscence could not be confirmed. Invasiveness of such tumors matches an epidermoid tumor, wherein it spreads into the available spaces, engulfs or encircles the blood vessels and cranial nerves without actually invading these structures, rarely compromising the lumen of the artery and resulting in only moderate displacements. In such cases, surgery and attempts towards radical tumor resection can be dangerous as perforator injury can be an issue.[19] Tumor invading through the sellar floor dura, sella turcica and the adjacent bones may extend into the nasopharynx or sphenoid and/or ethmoid sinuses. Extension of the tumor may occur posteroinferiorly in the retropharyngeal space by erosion of the clivus and petrous apices. Larger tumors may extend up to the foramen magnum.
Figure 6: Goel Grade IV giant pituitary tumor showing transgression of the diaphragma sellae by the tumor. There is encasement of both anterior cerebral arteries and anterior communicating artery complex

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Surgical issues

Pituitary tumors are common neurosurgical lesions. The surgery is usually safe and can be remarkably quick. Pituitary tumors are usually soft and necrotic and sometimes vascular. They are sometimes relatively firm and 'elastic' in consistency. They are never hard or even very firm in nature. It appears that if dural relationships are appropriately understood, particularly as they relate to pituitary tumors and their potential to invade the cavernous sinus, surgery can if appropriately learned and practiced provide satisfactory lateral vision to explore the tumor inside the corners of the cavernous sinus in general and also the part of the tumor that is lateral to the internal carotid artery. The radicality of the resection of the part of the tumor within the cavernous sinus depends more on tumor characteristics like fragility and vascularity.


 » Conclusions Top


Surgery on pituitary tumors is necessarily based on a high degree of understanding of the anatomy of the region in general and dural relationships of growing tumor in particular.[20]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Goel A, Nadkarni T. Surgical management of Giant pituitary tumors – A review of 30 cases. Acta Neurochir (Wien) 1996;138:1042-49.  Back to cited text no. 1
    
2.
Krisht AF. Giant invasive pituitary adenomas: Management plan. Contemp Neurosurg 1999;21:1-6.  Back to cited text no. 2
    
3.
Symon L, Jakubowski J, Kendall B. Surgical treatment of giant pituitary adenomas. J Neurol Neurosurg Psychiatry 1979;42:973-82.  Back to cited text no. 3
    
4.
Martins AN, Hayes GJ, Kempe LG. Invasive pituitary adenomas. J Neurosurg 1965;22:268-76.  Back to cited text no. 4
    
5.
Mohr G, Hardy J, Comtois R, Beauregard H. Surgical management of giant pituitary adenomas. Can J Neurol Sci 1990;17:62-6.  Back to cited text no. 5
    
6.
Goel A, Nadkarni T, Muzumdar D, Desai K, Phalke U, Sharma P. Giant pituitary tumors: A study based on surgical treatment of 118 cases. Surg Neurol 2004;61:436-45.  Back to cited text no. 6
    
7.
Shah A, Mohamed Elsanafiry MS. Diaphragma sellae: Anatomical and surgical implication in surgery for pituitary adenomas-Highlighting contributions by Goel. J Craniovertebr Junction Spine 2018;9:135-9.  Back to cited text no. 7
    
8.
Jefferson G. Extrasellar extensions of pituitary adenomas. Proc R Soc Med 1940;33:433-58.  Back to cited text no. 8
    
9.
Martins AN, Hayes GJ, Kempe LG. Invasive pituitary adenomas. J Neurosurg 1965;22:268-76.  Back to cited text no. 9
    
10.
Bailey OT, Cutler EC. Malignant adenomas of the chromophobe cells of the pituitary body. Arch Pathol 1940;29:368-99.  Back to cited text no. 10
    
11.
Feiring EH, Davidoff LM, Zimmerman HM. Pituitary carcinoma of the pituitary. Neuropathol Exp Neurol 1953;12:205-23.  Back to cited text no. 11
    
12.
Russel DS, Rubenstein LJ. Tumors of adenohypophysis. In: Pathology of Tumors of the Nervous System. 4th ed. Baltimore: Williams and Wilkins; 1977. p. 312-23.  Back to cited text no. 12
    
13.
Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomaswith invasion of the cavernous sinus space: A magnetic resonanceimaging classification compared with surgical findings. Neurosurgery 1993;33:610-8.  Back to cited text no. 13
    
14.
Agrawal A, Cincu R, Goel A. Current concepts and controversies in the management of non-functioning giant pituitary macroadenomas. Clin Neurol Neurosurg 2007;109:645-50.  Back to cited text no. 14
    
15.
Goel A. Challenge of giant pituitary tumors. World Neurosurg 2014;82:e121-4.  Back to cited text no. 15
    
16.
Goel A. Letter to the editor: Surgical management of pituitary macroadenomas. J Neurosurg 2016;125:516-8.  Back to cited text no. 16
    
17.
Goel A. Letter to the editor: Pituitary tumors and cavernous sinus extension. J Neurosurg 2016;124:1129-30.  Back to cited text no. 17
    
18.
Goel A. Meningeal architecture of the cavernous sinus: Clinical and surgical implications. Neurosurgery 1998;42:430-31.  Back to cited text no. 18
    
19.
Goel A, Deogaonkar M, Desai K. Fatal postoperative 'pituitary apoplexy': its cause and management. Br J Neurosurg 1995;9:37-40.  Back to cited text no. 19
    
20.
Jonathan GE, Sarkar S, Singh G, Mani S, Thomas R, Chacko AG. A randomized controlled trial to determine the role of intraoperative lumbar cerebrospinal fluid drainage in patients undergoing endoscopic transsphenoidal surgery for pituitary adenomas. Neurol India 2018;66:133-138.  Back to cited text no. 20
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