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Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 94-110

Giant pituitary adenomas: Operative strategies

Department of Neurosurgery, AIIMS, New Delhi, India

Date of Web Publication02-Nov-2021

Correspondence Address:
Dr. Ashish Suri
Department of Neurosurgery, All India Institute of Medical Sciencs(AIIMS), New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_415_21

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Giant pituitary adenomas (GPAs) are a subset of pituitary tumors characterized by their large size and invasive nature. Diverse surgical techniques including microscopic transsphenoidal, endoscopic transsphenoidal, transcranial transcavernous, and a combination of both suprasellar and infrasellar techniques have been developed to treat such giant tumors with extension into surrounding structures. In this review, we attempt to summarize the different operative strategies, nuances, the pearls and pitfalls of different techniques, and the outcome following surgery for GPAs..

Keywords: Edonasal, edoscopic, giant pituitary adenomas, pituitary tumors, resection, trans-sphenoidal, transcranial

How to cite this article:
Sharma R, Suri A. Giant pituitary adenomas: Operative strategies. Int J Neurooncol 2021;4, Suppl S1:94-110

How to cite this URL:
Sharma R, Suri A. Giant pituitary adenomas: Operative strategies. Int J Neurooncol [serial online] 2021 [cited 2022 Jun 27];4, Suppl S1:94-110. Available from: https://www.Internationaljneurooncology.com/text.asp?2021/4/3/94/329810

  Introduction Top

Pituitary adenomas are the third most common intracranial tumors comprising about 10%–15% of all tumors, with the gonadotrophic-secreting functional adenomas being the most common histological subtype of all the pituitary adenomas.[1] Symptomatology of pituitary tumors is related to hyper- or hypohormonal secretion or due to mass effect on adjacent structures or they may be discovered incidentally. Giant pituitary adenomas (GPAs) are a subset of pituitary tumors characterized by their large size and invasion into parasellar and suprasellar regions, leading to visual decline, hypothalamic dysfunction, and ocular movement dysfunction.

Transsphenoidal surgery is the standard treatment in the majority of GPAs. Due to the larger size, extension into suprasellar and parasellar structures, and invasion into surrounding crucial intracranial structures, surgery is quite challenging and associated with poor oncological outcome (decreased gross total resection [GTR] rates), higher recurrence rates, higher complication rates, and overall poor treatment outcome and long-term prognosis in lesser experienced hands.

Diverse surgical techniques including microscopic transsphenoidal, endoscopic transsphenoidal, transcranial transcavernous, and a combination of both suprasellar and infrasellar techniques have been developed to treat giant tumors with extension into surrounding structures, but still the gross total and near total resection rates vary between 14% and 91% in the literature.[2],[3] The primary goal of surgery is decompression of the optic apparatus and the secondary goal is to achieve maximum safe resection of the tumor. Keeping these goals in mind, the surgical technique should be selected to improve the long-term outcome of GPA.

The objective of this chapter is to discuss in detail the different operative strategies, nuances, the pearls and pitfalls of different techniques, and the outcome following surgery in tackling GPAs.

  Surgical Anatomy of Pituitary Gland and Sella Turcica Top

The pituitary gland (or hypophysis) is a bilobed pear-shaped neuroendocrine structure located as a downward protrusion from the hypothalamus in the middle cranial fossa. It is segregated into three divisions – an anterior adenohypophysis, a posterior neurohypophysis, and an intermediate lobe. Understanding the anatomy of adenohypophysis is extremely important in the surgeries of pituitary adenomas. Adenohypophysis is further divided into pars distalis (anterior lobe) and pars tuberalis (funnel-shaped extension of anterior lobe on the anterior surface of infundibulum), constituting about 80% of the gland.

  Topographic Distribution of Secreting Cells in the Anterior Lobe Top

Anterior lobe is composed of five principal hormone-secreting cells arranged in a specific and consistent location in the gland. Because of this specific and preferential arrangement of secreting clusters, different functional pituitary adenomas arise from their preferential sites in the intraglandular location. Neurosurgeon must be aware of the topographical location of different hormone-secreting cells as the surgeon occasionally needs to dissect through the normal pituitary to look for microadenoma. The topographic distribution of different hormone-secreting cells is depicted in [Figure 1].
Figure 1: Illustration depicting the topographic distribution of different hormone-secreting cells in a normal pituitary gland

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  Surgical Anatomy of Sellar Region Top

Pituitary gland is housed in the bony cavity of sphenoid bone in the floor of the middle cranial fossa known as sella turcica which is covered by dural fold called diaphragma sellae. The sella turcica is related to critical neurovascular structures – superiorly to optic nerves, optic chiasm, hypothalamus, third ventricle, and the circle of Willis. The sella is laterally flanked by cavernous sinus and internal carotid artery (ICA) on both sides, posteriorly it is related to brain stem, basilar artery , and anteriorly it is related to the nasal cavity via the ethmoid and sphenoid sinuses [Figure 2]. In GPAs, understanding the anatomy of tumor extensions with relation to dural layers of sella turcica, diaphragma sellae, and cavernous sinus is extremely crucial in planning the surgery.
Figure 2: Illustration depicting the relationship of pituitary gland with other neurovascular structures

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Giant pituitary adenoma and diaphragma sellae

The concept that pituitary tumors cause diaphragma sellae elevation rather than transgression causes significant changes in the implications of surgery.[4] In larger pituitary adenomas (GPA) with significant intracranial component, transcranial surgery was preferred, but this concept of diaphragma sellae elevation changed the perceptive toward more endonasal surgery due to the dural covering in the rostral part of the tumor. Radiological assessment of dural elevation or transgression is imperative in surgical planning.

Giant pituitary adenoma and cavernous sinus

GPAs often cause transgression of medial wall of the cavernous sinus, but lateral wall transgression is rare.[4] They also cause elevation of roof of the cavernous sinus, and transgression is rare. Understanding these concepts of cavernous sinus invasion enhance the scope of endonasal approach to pituitary tumors.

  Definition and Epidemiology of Giant Pituitary Adenoma Top

Since the first description of GPA by Jefferson in 1969, various authors have tried to provide radiological criteria for defining GPA. Later Symon and Jakubowski[5] used the term GPA and provided the criteria as a tumor with an extension of more than 40 mm above the planum sphenoidale in any direction, less than 6 mm distance from the highest point of the tumor to the foramen of Monroe or those with the multi-compartmental spread. Recently, some of the authors defined GPA as the tumor with volume >10 cc[6],[7] or those with maximum dimension of 3 cm in one of the three axes (AP X TC X CC) of the tumor growth.[4]

GPA constitutes around 6%–10% of all the pituitary adenomas and are more common in males than females. The mean age of diagnosis is lower as compared to pituitary adenomas. Histologically, GPA does not correlate well with the gross appearance and is composed of benign cells. A nonfunctional adenoma is more common than functional GPA[3] (ratio of >2:1), and the more frequently encountered functional GPAs are medically refractory prolactinomas followed by somatotrophic adenomas.

  Classification of Pituitary Adenoma and Giant Pituitary Adenoma Top

Different approaches can be used to classify pituitary adenomas (clinical, endocrinological, pathological, and imaging), but from the surgical perspective, in assessing the neuroimaging classification helps in surgical planning and, degree of invasion of cavernous sinus. One of the most widely used classifications based on the imaging features was proposed by Hardy and Vezina[8] and later modified by Wilson[9] [Table 1] and [Figure 3].
Table 1: Modified Hardy-Wilson classification (imaging and operative features)[8],[9]

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Figure 3: Illustration depicting the various grades of invasion of the giant pituitary adenoma, according to modified Hardy–Wilson classification

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The most popular modified Knosp grading[10],[11] is based on the coronal magnetic resonance imaging (MRI) images that depict both the supra- and intracavernous ICAs, adjacent to sella [Table 2] and [Figure 4]. This grading system is useful to know the lateral extent of tumor into the cavernous sinus and thus helps in planning surgery and avoids complications following surgery.
Table 2: Modified Knosp grading (invasion into cavernous sinus)[10],[11]

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Figure 4: Illustration depicting the various grades of cavernous sinus extension according to modified Knosp classification

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Goel et al. in 2004 developed a classification system of GPAs [Table 3] and [Figure 5] based on the tumor growth and its relations with the dural layers of diaphragma sellae and cavernous sinus. This classification system helps in developing the surgical plan and predicts the surgical and long-term outcome.
Table 3: Goel et al. classification of giant pituitary adenomas (tumor relationship with dural layers)[4]

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Figure 5: Goel classification of giant pituitary adenomas. (a) Grade I with suprasellar extension without dural transgression, (b) Grade II with medial cavernous wall invasion and lateral wall of cavernous wall is intact, which can be recognized by smooth lateral wall of tumor taking the shape of cavernous sinus, (c) Grade III with elevation of left cavernous sinus, but wall is irregular which also suggests subarachnoid extension, (d) Grade IV with subarachnoid invasion in the supradiaphragmatic region

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  Clinical Presentation and Preoperative Evaluation of Giant Pituitary Adenoma Top

The clinical spectrum of GPA is diverse and secondary to compression of surrounding structures, hyposecretion of hormones, and tumoral excess hormone production [Table 4] and [Table 5].[12] Visual impairment and field defects are the most common presenting complaints in a majority of GPAs, followed by headache. Visual symptoms tend to occur in 72% of the cases of GPA. In majority of the cases of GPA, partial or panhypopituitarism can occur among which corticotrophin (adrenocorticotropic hormone) insufficiency is reported in 40% of the cases. Panhypopituitarism has been reported in 17%–33% of giant prolactinomas. Symptoms due to tumor hormone hypersecretion are related to the specific hormone secretion and the tumor type. An exception is that in some cases of thyroid-stimulating hormone (TSH)-secreting adenomas, TSH secretion can be accompanied by secretion of prolactin and growth hormone.
Table 4: Tumor growth and symptoms due to mass effect in giant pituitary adenomas

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Table 5: Preoperative evaluation and planning for surgery[3],[12]

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  Preoperative Evaluation of Giant Pituitary Adenoma Top

Surgical approaches of giant pituitary adenoma

The best approach for the resection of GPA is still a matter of debate. The more commonly preferred approaches include transcranial (bifrontal, pterional, and orbitozygomatic), transsphenoidal (microscopic and endoscopic), and combined (both transcranial and endonasal) approaches. In the past, transcranial approaches have been traditionally used to resect GPAs. Due to the advanced understanding of the anatomical relationships of the tumor with surrounding dural layers and development of advanced endoscopic techniques over the last two decades, the endoscopic endonasal approach is being widely used nowadays with improved results of visual outcome, resection rates, and reduced complication rates. Irrespective of the approach used, the major goals of surgery are described in [Table 6]. Adequate and safe tumor debulking is very crucial as inadequate debulking can lead to residual tumor apoplexy, which can cause neurological deterioration, hypohypothalamic dysfunction, and death.
Table 6: Goals of surgery in giant pituitary adenomas[3]

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  Microscopic Versus Endoscopic Transsphenoidal Surgery in Giant Pituitary Adenoma Top

In the transsphenoidal approach, there was gradual transition from microscopic to endoscopic approach over the last two decades. In pituitary adenomas, confining to the sellar region, both microscopic and endoscopic transsphenoidal approaches show a similar outcome, whereas in giant adenomas, the endoscopic approach showed more promising results due to good visibility and wide exposure for extended approaches which are often necessary in GPA. These include the transtuberculum and transplanum or transcavernous transsphenoidal approaches used in cases with subfrontal or cavernous sinus extensions, respectively. A systemic review of 11 studies published by RJ Komotar et al., in 2012[2] comparing different approaches in GPA concluded that microscopic transsphenoidal surgery is associated with poor resection rates and visual outcome and also concluded that endoscopic endonasal approach is safe and effective in the treatment of majority of GPAs. Another large systemic review of 12 studies (431 patients) published in 2019 by Marigil Sanchez et al.,[3] on the endoscopic surgery in GPAs also showed similar results regarding the extent of resection (EOR) of GPA. In addition, this study also concluded that the pure endoscopic endonasal approach obtained better clinical outcome (visual and endocrine) and lesser rates of cerebrospinal fluid (CSF) leak (<5% with the implementation of Hadad flap) than the microscopic transsphenoidal approach.

Tumors extending to the parasellar and subfrontal region were initially considered inoperable by the classic endoscopic approach and were being operated by transcranial surgery. Development of extended approaches[13] (transtuberculum and transplanum or transcavernous transsphenoidal approaches) made endoscopic surgery surpass transcranial surgeries for such GPAs.

The comparison of different parameters between endoscopic and microscopic transsphenoidal approaches for pituitary adenomas is illustrated in [Table 7].
Table 7: Comparison of endoscopic versus microscopic transsphenoidal approach[3]

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  Endoscopic Transsphenoidal Versus Transcranial Approach For Giant Pituitary Adenoma Top

Surgery is the main stay of treatment for the majority of GPAs except for giant prolactinomas that show a good response to medical management in a majority of the cases. In the current era, GPAs are often operated by endoscopic approach or transcranial approach or combined endoscopic and transcranial approach [Figure 6].
Figure 6: The limit of resection in endoscopic and extended endoscopic approach and indication in transcranial approach. (a) Endoscopic approach is limited by four blue lines – cavernous sinus on both sides, anterior intercavernous sinus anteriorly, and inferior intercavernous sinus posteriorly. (b) Extended endoscopic approach (represented by 4 yellow lines) – anterolaterally orbital apex, anterior clinoid process; posteriorly posterior clinoid process, petrous apex; laterally by the lateral border of cavernous sinus. (c) Indications of transcranial approach for tumors with subarachnoid extension into temporal lobes or posterior fossa

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Despite the advancements in endoscopy, transcranial approach[14] remains a part of the surgical armamentarium in 1%–4% of the GPAs and requires specific indications, and in some cases, transcranial approach has been combined with endoscopic surgery when the desired result (adequate tumor debulking) could not be achieved or seemed difficult. Transcranial approach is quite useful in tumor decompression and decompression of the optic apparatus but often requires manipulation of optic nerves and perforators. The most important limitation of transcranial surgery is that intrasellar portion of the tumor is more difficult to visualize and remove, particularly in the setting of prefixed optic chiasm.

The factors which help to predict the surgical approach are[2],[3],[13] – tumor extension, elevation/transgression of dura, multicompartmental invasion, and tumor consistency (hypointensity on T2-weighted MRI sequence). The choice of approach in GPA depends on several factors as detailed in [Table 8], but the approach should be tailored in each patient weighing the risks and benefits of each approach in order to achieve the goals of surgery.
Table 8: Factors affecting the surgical approach for giant pituitary adenomas

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  Extended Endoscopic Approach in Giant Pituitary Adenoma – What is the Need? Top

In endoscopic approach to GPAs, generous bony exposure is the key maneuver to achieve optimal surgical debulking. Extracapsular dissection should be performed wherever feasible for optimal results. In classical endoscopic transsphenoidal approach, the traditional bone removal (between the medial borders of cavernous sinus, anteriorly superior intercavernous sinus and posteriorly inferior intercavernous sinus) would preclude the operating surgeon from reaching the lateral and anterior borders of giant tumors. Suboptimal removal of the lateral and anterior edges of the bone prevents the descent of suprasellar lesion into the sella and thus reduced resection rates. Extended endoscopic approaches[13] (transtubercular, transplanum for anterior tumor extension, transcavernous for lateral extension, and transclival for posterior extension) are routinely being used, especially for giant tumors, with increased resection rates.

  Operative Technique and Nuances Of Endoscopic Transsphenoidal Approach Top

Endoscopic endonasal transsphenoidal approach for the resection of pituitary tumors can be described in three stages – (1) nasal stage, (2) sphenoid stage, and (3) Sellar stage [Figure 7]. This procedure is performed with endoscope of 4 mm with variable angled scopes (0°, 30°, and 45°). This procedure can be done by uninostril or binostril approach. At the author's institute, they routinely use binostril three- or four-handed approach for this procedure.
Figure 7: Endoscopic endonasal transsphenoidal approach in a 50-year-old female with a nonfunctional giant pituitary adenoma. (a) Preoperative contrast magnetic resonance imaging showing giant pituitary adenoma of Goel I/Knosp 1 with suprasellar extension, (b) Identification of sphenoid ostium after lateralizing middle turbinate, (c) Posterior septostomy, (d) Removal of keel of vomer, (e) Septum of sphenoid sinus, (f) Postsellar drilling between the four blue lines, (g) After dural opening from 5 o'clock to 7 o'clock position, tumor decompression, (h) Arachnoid bulge after complete removal of tumor, (i) Postoperative noncontrast computed tomography head showing no residual disease

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  Operative Room Setup and Patient Positioning Top

Patients are positioned to maximize exposure of the sellar region and to provide comfort and spatial orientation to the surgeon. Patient's head is fixed in Mayfield three-pin holder to allow for the use of neuronavigational system. The operating table is adjusted to lawn-chair position with torso elevated to 20°–30°. The patient is laid in supine position with neck slightly tilted to left, and the head is translated superiorly to avoid impingement of patient's thorax with endoscope and other surgical instruments. The head should be flexed or extended according to the extent of tumor in GPA (extension of 10°–15° to achieve more anterior trajectory [transtuberculum and transplanum approaches], slightly flexion of head for the posterior trajectory [transclival approach]). The operative room setup for GPA is the same as for other pituitary adenomas and is depicted in the picture.

  Nasal Preparation for Surgery Top

Nasal decongestants are used to facilitate pituitary surgery by reducing the bleeding from the mucosa. Using Killian's nasal speculum, cotton pledgets soaked in povidone-iodine solution are placed along the floor of the nasal cavities and in between the middle turbinate and nasal septum for approximately 5 min and then removed. Then, the cotton pledgets soaked in decongestant solution (2 ml of adrenaline, 5 ml of diluted lignocaine, and 4 ml of saline solution) are placed between the middle turbinate and nasal septum for 15 min, during which the patient is prepared for sterile draping.

  Preoperative Preparation of the Patient Top

The various components of preoperative preparation of a patient undergoing pituitary surgery are summarized in [Table 9].
Table 9: Components of preoperative preparation of the patient

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Surgical steps and nuances

Nasal stage

The goal of the nasal stage is to reach the sphenoid sinus through the sphenoid ostium, and a posterior nasal septostomy, which can be achieved through different strategies of nasal mucosa and septum manipulation (traditional transseptal submucosal, endonasal, and sublabial technique). In this section, we will be discussing about the endonasal technique.

This stage begins with the introduction of zero-angled endoscope in the right nostril to identify inferior turbinate laterally, nasal septum medially, and choanae posteroinferiorly for orientation. This step is followed by lateralization of middle turbinate to increase the exposure with blunt dissection and avoid excessive mucosal injury. After creating adequate working space, the next step is to identify sphenoethmoid recess and sphenoid ostium which is located at 1.5 cm above the choanae. These steps are repeated on the opposite nostril, and the sphenoid ostium is identified [Table 10].
Table 10: Operative nuances in the nasal stage for giant pituitary adenomas

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In giant adenomas which require an extended approach and wide exposure of sella and pose great risk of high-flow CSF leak, reconstruction of the defect is crucial. This can be achieved by pedicled nasoseptal flap based on posterior septal artery, a branch of sphenopalatine artery. This procedure was first described by Hirsch[15] in 1952 and was popularized by Hadad et al.[16] It has become the workhorse approach of skull base reconstruction after extended endoscopic approaches. After identifying sphenoid ostium, Hadad flap is elevated by giving two parallel incisions – along the maxillary crest inferiorly, caudal to the olfactory epithelium superiorly and connected by a vertical anterior incision. This flap is generally tucked into the nasopharynx or maxillary sinus for protection during the surgery.

The mucosa around the sphenoid ostia is coagulated and the posterior nasal septum, and the perpendicular plate of the vomer are removed to facilitate a wide exposure. This permits the use of both the nostrils from the sphenoid stage.

Sphenoidal stage

The nasal septum is detached from the anterior sphenoid exposing both the sphenoid ostia and after this maneuver it gives an owl's eye appearance in the endoscopic view. The anterior sphenoidectomy is performed in a V-shaped manner using microdrills or bone punches, and care should be taken in the inferolateral aspect to avoid injury to the sphenopalatine artery or its branches. Posterior septostomy is expanded using a backbiter to facilitate the binostril approach. Performing a wide sphenoidectomy is an important step in the surgery of GPA because it allows the maneuverability of the endoscopic instruments and prevents the debris from occluding the endoscope during surgery. As sphenopalatine arteries limit the inferior sphenoidectomy the procedure can be extended superiorly and laterally with the removal of superior turbinate and posterior ethmoidal cells, respectively. In cases of sphenoid sinus with minimal pneumatization (conchal and presellar type), the image guidance system helps in preventing misdirection. Mucosa of the sphenoid sinus should be cauterized and excised to prevent postoperative mucocele formation (avoid stripping as it can cause bleeding). Septations of the sphenoid sinus should be removed, and surgeons should be aware of the anomalous variant of sphenoid septa to prevent drilling over the carotid protuberance [Table 11].
Table 11: Operative nuances in the sphenoid stage for giant pituitary adenomas

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The boundaries of anterior sphenoidectomy include 1) cranially, corridors, the superior limit of sphenoid ostia ; 2) caudally, the vidian canal at 5 and 7 o'clock position; and 3) laterally, the crest marking the junction of the sphenoid and ethmoid sinuses till the visualization of the carotid artery protuberance. It is necessary to create a 5–6-mm space below the sellar floor for free manipulation of the instruments. These boundaries can be extended depending on the extension of the pituitary tumors.

Surgeons should be aware of the midline while performing anterior sphenoidectomy which can by identified by following the remnant of the vomer, the midpoint between the carotid protuberances.

By the end of anterior sphenoidectomy, the second surgeon holds the endoscope so that the operating surgeon can perform surgery bimanually from both the nostrils and provide three-dimensional perception to the operating field.

Sellar stage

After an adequate anterior sphenoidectomy, the floor of the sella should be assessed as it can be thinned out or eroded due to the longstanding tumor. Endoscopic view of the sella resembles a fetal face after adequate sphenoidectomy. The boundaries of the sella are confirmed by neuronavigation. A medium-sized diamond drill at low speed under continuous irrigation is used to drill the sellar floor to eggshell thickness in a circumferential manner, and then, the thin bone is broken and removed with a Kerrison punch no. 1 or fine dissector. The drilling of the sellar floor can be continued circumferentially till the four blue lines are seen (both the superiorly and inferiorly located intercavernous sinuses and the laterally located cavernous sinuses) in cases of classic endoscopic approach for micro- and macroadenomas [Table 12]. In extended endoscopic approaches, floor of the sella drilling should be tailored according to the extension of the tumor.
Table 12: Operative nuances in the floor of the sella drilling for giant pituitary adenomas

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In giant adenomas, drilling should be adequate to help provide good resection rates.

In extended transtuberculum/transplanum approach, the sellar floor drilling can be extended to 1.5–2 cm and not beyond the anterior border of sphenoid sinus. Laterally, drilling is limited by the optic nerve protuberance on both sides. Drilling of planum sphenoidale gives the shape of trapezium with a narrow base posteriorly due to the course of optic protuberance (at the level of tuberculum sellae, optic nerves are in proximity [14 mm] and they diverge anteriorly after piercing the optic canal).

In extended transcavernous approach, two surgical corridors in relationships to cavernous ICA can be used to resect the intracavernous portion of the tumor – one permits the removal of tumor medial to ICA and the other permits the removal of tumor lateral to ICA. Drilling of the sellar floor should also be based on the tumor relationship with ICA in the cavernous sinus. Drilling can be extended laterally for the first surgical corridor to resect the tumors medial to ICA, whereas drilling can be done separately leaving behind a thin bone over the ICA which is pushed medially by the tumor on its lateral aspect.

Dural opening

After adequate exposure of the sellar bulge, dura can be opened in several ways based on the tumor extension. In the classical approach, dural incision is sufficient from 5 o'clock to 7 o'clock position, but in extended approaches, dural opening can be inverted “T” shaped or lying “H” shaped with the vertical limb extending to the tuberculum sella and planum region coagulating the margins of anterior intercavernous sinus. Sometimes, dura can be opened in a cruciate fashion and the dural edges are retracted using bipolar coagulation [Figure 8], [Table 13].
Figure 8: Patterns of dural opening in classical (a,b) and extended endoscopic approach (c) in giant pituitary adenoma. In extended endoscopic approach, the dural opening is extended anteriorly by coagulating anterior intercavernous sinus

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Table 13: Operative nuances in the tumor resection for giant pituitary adenomas

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Tumor resection

Location of the normal pituitary gland should be estimated based on the MRI imaging, and dural incision should be planned to avoid injury to the pituitary gland and the carotid arteries. After opening the dura, extracapsular dissection is done followed by piecemeal resection of the tumor.

  Extracapsular dissection Top

Complete extracapsular dissection is extremely difficult in GPAs with lateral extension. In tumors with only suprasellar extension (Knosp 1 or Goel I), extracapsular dissection can be performed by selectively opening and reflecting the outer layer of dura and a ball dissector is used between the two layers of dura all around to free the tumor capsule.

  Piecemeal excision of the tumor Top

Tumor should be mobilized and removed in a piecemeal fashion using suction and ring curettes. The order of removal of tumor is important to prevent the premature bulge of arachnoid and diaphragma sellae blocking the view and reducing the extent of tumor resection.

First, the inferior and basal portion of the tumor is removed from caudal to cranial aspect in a posterior trajectory toward the dorsum sella-clivus junction. During this time, the superior dural flap acts as a retractor and prevents the descent of tumor and arachnoid bulge. Inferior part removal is followed by lateral portions of the tumor with upward angled ring curette. Finally, the superior portion of the tumor is removed after extending the dural incision upward. The tumor resection is done bimanually – with curette in the right hand for dissection and suction in the left hand to remove the tumor.

  Giant pituitary adenoma with lateral extension (Knosp 2, 3, or 4/Goel II/III) Top

After decompression of the intrasellar portion of the tumor, lateral cavernous sinus extensions can be “chased after” with stepwise debulking of the tumor in the cavernous sinus. Micro-Doppler tracking is necessary to prevent injury to ICA. Tumors lateral to ICA in the cavernous sinus can be dealt by opening dura lateral to ICA and should be done with caution [Figure 9]. Surgeons should follow a “conservative strategy” while removing the tumor in the cavernous sinus.[6],[17] Neurophysiology monitoring and stimulation strategy for the identification of oculomotor nerve and abducens nerve can act as an important adjunct in the transcavernous approach because the intracavernous septations can be mistaken for nerves which can bring early end to the resection.
Figure 9: Extended endoscopic approach in a 45-year-old female with giant pituitary adenoma (Goel II/Knosp 3b, extending to cavernous sinus on right side). (a) Preoperative contrast magnetic resonance imaging showing giant pituitary adenoma Knosp 3b extending to right side, (b) Hadad flap, (c) Owl-eye appearance on posterior septostomy, (d) Planum sphenoidale drilling (e) Drilling of sellar floor overlying the cavernous sinus (f) The extent of drilling in extended endoscopic approach beyond the four blue lines in classic approach, (g) Removal of the tumor in the sellar portion, (h) Tumor decompression in the cavernous sinus after incising dura lateral to cavernous internal carotid artery, and (i) Postoperative noncontrast computed tomography head showing no residual disease

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  Giant pituitary adenoma with suprasellar extension (Knosp 1/Goel I/II) Top

After adequate removal of the sellar and lateral margins of the tumor, debulking of the suprasellar portion of the tumor is done, which leads to descent of tumor capsule into the sella. Inadequate central debulking is one of the most important causes for inadequate descent of suprasellar tumor. If the tumors fail to descent despite adequate central decompression, transtuberculum/transplanum approaches help in visualizing anterior/superior edge of the tumor capsule and mobilization it into the sella.

Dumbbell tumors with a narrow diaphragm offer a great challenge to the surgeon as the tumor underneath the patulous diaphragmatic folds is difficult to remove. Two techniques are described to remove tumor in these folds – first by atraumatic manipulation of diaphragmatic folds and the other by using four-handed technique, which is useful in this location for tumor removal. In the four-handed technique, the assisting surgeon holds the scope in one hand and a curette to retract the diaphragmatic fold away from the operative field in the other hand, so that the operating surgeons hold the suction and ring curette to work around these diaphragmatic folds to remove the tumor. Using a 30° angled endoscope is necessary to prevent the “swording effect” due to the overcrowding of the instruments in the limited field.

Inspection of the tumor cavity[18] is performed by 30° angled endoscope at the end of resection (pushing the diaphragma sellae with cotton patties) to look for tumor remnants, and this inspection is performed in a systematic clockwise fashion starting at 6 o'clock position. Visible pulsations through the diaphragma sellae suggest near total removal of the tumor. The more common locations of the tumor remnant are at – (a) insertion of the pituitary stalk, (b) beneath the diaphragmatic folds, (c) angle between the optic nerve and ICA at the medial opticocarotid recess, and (d) at the level of anterior intercavernous sinus beneath the anterior lip of dura, and these areas should be carefully inspected.

Reconstruction of skull base defect

CSF leak is the most common reported complication following surgery in GPA. Surgery for GPA creates a large cavity with skull base defect which causes high-flow CSF leak, and proper reconstruction of the skull base defect is necessary to prevent the complication. Large defects following the resection of suprasellar extension require a multilayered gasket seal technique with Hadad flap for reconstruction, whereas small defects can be reconstructed using fat globules, gel foam, and fibrin sealant. After tumor resection, Valsalva is performed to look for CSF leak [Table 14]. In GPA, irrespective of CSF leak, reconstruction is done by “multilayered gasket seal technique with Hadad flap” in larger defects. The diagrammatic representation of steps of harvesting a Hadad flap is shown in [Figure 10].
Table 14: Operative nuances in the skull base reconstruction of giant pituitary adenomas

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Figure 10: Illustration depicting steps of harvesting a Hadad flap - (a) Endoscopic view, (b) Lateral nasal view

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Multilayered gasket seal technique with Hadad flap

In this technique, fat globules are placed in the tumor cavity and surgeon should make sure of adequate pulsations of the fat globules and avoid overzealous packing of the tumor cavity. In the next layer, fascia lata harvested from the thigh is packed subdurally to cover the fat layer (inlay technique), followed by Hadad flap (pedicled nasoseptal flap) over the fascia lata covering all the edges of the sella (onlay technique). The next layer is packing of the sphenoid sinus with fat globules, and the final layer by Gelfoam reinforced with fibrin glue which acts as support for the fat layer. The bone pieces removed from the nasal septum/vomer can also be used to support the fat layer along with glue [Figure 11].[16],[19]
Figure 11: (a-f): Reconstruction of skull base defect using multilayered gasket seal technique and Hadad flap in larger defects following extended endoscopic approach for giant pituitary adenoma

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In giant pituitary tumors with significant intracranial extension or in cases with arachnoid tear in the suprasellar region, the exact site of the leak should be identified and packed with fat globules. In GPA extending into the third ventricle, care should be taken while packing fat in the tumor cavity to prevent fat from entering the ventricle because it can lead to fat globule migration and cause obstruction of the CSF flow in the ventricles.

  Operative Technique and Nuances Of Transcranial Approach in Giant Pituitary Adenoma Top

Transcranial approaches, although rarely used for pituitary tumors, continues to play a key role in the surgical management of GPAs with significant intracranial extension into frontal or temporal regions or dumb bell-shaped tumors with a very narrow neck and large suprasellar component, or intumors with extensive cavernous sinus extension beyond the lateral wall and in multicompartmental giant adenomas. The commonly performed transcranial approaches in GPAs are[14] – transsylvian approach, subfrontal approach, and transcavernous approach (purely extradural/combined extradural and intradural) )[Table 15].
Table 15: Operative nuances in the transcranial approach for giant pituitary adenomas

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  Pterional Craniotomy and Transsylvian Approach For Giant Pituitary Adenoma Top

This is the most common transcranial approach performed for GPAs, and the indications are tumors with subarachnoid extension into temporal lobes or frontal lobes with less cavernous sinus invasion, multicompartmental GPA where adequate tumor decompression is the main goal of surgery, and in tumors where transsphenoidal approach is contraindicated. The major limitation of this approach is difficulty in reaching sellar portion of the tumor, manipulation of optic nerves, and high risk of perforator injury.

The patient is positioned with the head turned 30° to the opposite side of the craniotomy, with the vertex tilted down, so that the malar eminence forms the uppermost point. The neck is positioned to avoid any compromise of venous drainage. A classical pterional craniotomy is performed and orbitozygomatic/zygomatic osteotomies can be added to improve the operative view and reduce the working distance. After craniotomy, dura is opened in a curvilinear fashion and anterior Sylvian fissure is dissected. Sylvian fissure can be widely split to reduce brain retraction. CSF released from the opticocarotid cistern helps in relaxation of brain and reduces overzealous brain retraction. Tumor capsule can be visualized medial to ipsilateral optic nerve and diaphragma sellae encasing it in the superior aspect. The internal tumor decompression is done using the opticocarotid corridor and care should be taken to prevent perforator injury while performing extracapsular dissection. In tumors with adherent capsule, subtotal excision is prudent, and surgeon should focus on decompressing optic structures and adequate tumor removal. Adjuvant therapy is a reasonable option for the residual tumor.

  FTOZ Craniotomy and Pure Extradural Transcavernous Approach For Giant Pituitary Adenoma Top

In an attempt to improve the understanding of the transcavernous approach, we have detailed the relevant anatomy of this region in [Figure 12]. This approach is also being routinely performed in the current era for cases with significant residual disease after endoscopic transsphenoidal surgery, especially for functional adenomas, to achieve adequate tumor removal for adjuvant therapy and tumors with multicompartmental GPA with extensive cavernous sinus extension.[20] The major limitation of this approach is transient cranial nerve (CN) palsy after surgery due to the manipulation of CNs in the lateral wall of cavernous sinus and the risk of injury to ICA during surgery. The surgical nuances of this approach have been detailed with a representative case shown in [Figure 13].
Figure 12: Diagrammatic representation of bony(a) and neurovascular (b) anatomy of the cavernous sinus region relevant for extradural transcavernous approach for giant pituitary adenoma

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Figure 13: Pure extradural transcavernous approach in a 40-year-old female with residual giant pituitary adenoma. (a) Contrast magnetic resonance imaging showing giant pituitary adenoma Goel Grade 3, Knosp 4 on left side, (b) Incision marking on left side for left FTOZ craniotomy, (c) Left FTOZ single-piece craniotomy done, and sphenoid ridge drilled, (d) Deroofing of superior orbital fissure, (e) Foramen spinosum and coagulation of middle meningeal artery, (f) Interdural dissection between endosteal and meningeal layers of lateral wall of cavernous sinus, (g) Dural incision in the Parkinson's triangle, (h) Tumor decompression, (i) Postoperative magnetic resonance imaging showing adequate tumor debulking with residual disease

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This approach can be performed through Fronto-Temporal-Orbito-Zygomatic(FTOZ) craniotomy. The sphenoid ridge was removed using a high-speed drill and the superior orbital fissure was opened. The meningeal-orbital band over the base of anterior clinoid was removed and extradural anterior clinoidectomy was performed. The posterior third of the optic canal was deroofed, and the extracavernous extradural ICA was exposed. The temporal base was drilled, the foramen spinosum was opened, and the middle meningeal artery was coagulated and cut. The meningeal layer of the lateral wall of the cavernous sinus was peeled away from the inner endosteal layer using sharp and blunt dissection, and CNs on the lateral wall of cavernous sinus are exposed (III, IV, V1, V2, and V3). Tumor bulge can be seen through the lateral wall of cavernous sinus and can be approached either through the lateral triangle (Parkinson's triangle, between CN IV and V1) or the anterolateral triangle (Mullan's triangle, between the V1 and V2 nerves). Tumor decompression can be done inside the cavernous sinus; VI CN can be identified lateral to cavernous ICA. The medial extent of the lesion into the sella can also be removed through this approach. Bleeding from the cavernous sinus can be controlled using Floseal and Gelfoam. The common postoperative morbidity following this approach is transient VI nerve palsy, which recovers in days to weeks.

  Complications and Outcome Following Endoscopic Surgery in Giant Pituitary Adenoma Top

Endoscopic and extended endoscopic surgical approaches for GPAs show promising results in the published literature as compared to microscopic transsphenoidal or transcranial surgical approaches in terms of extent of resection rates (EOR), endocrinological outcome, visual outcome, and complication rates following surgery. Postoperative mortality following endoscopic surgery is reported to be <1%[17],[18],[23],[24] and is attributable to ICA injury, hypothalamic injury, and meningitis due to CSF fistula [Table 16]. The most common complication following endoscopic surgery is CSF leak which is in decreasing trend owing to the advancements in the techniques of skull base reconstruction. Recently published systemic review in 2019 by Marigil Sanchez et al.,[3] reported CSF leak rate of 8.8% (38) in 431 patients of GPAs, but these values are overestimated as pedicled nasoseptal flap was not used in all studies in the study. The same systemic review also reported mortality of 1.9% in GPAs, and 20.88% (90 of 431) of the patients developed a new endocrinological deficit either due to adenohypophyseal deficit or diabetes insipidus.
Table 16: Complications - Etiological factors and preventive and treatment strategies[3],[21]

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  Outcome Following Endoscopic Surgery For Giant Pituitary Adenoma Top

Oncological outcome

Literature shows variability regarding the EOR following endoscopic surgery in GPAs with gross total resection (GTR) rates reported between 14% and 41% and near total resection rates close to 91%.[2],[3],[13],[17],[21] The generally accepted principle is that GTR is not possible in GPAs. The aim of surgery is to reduce the tumor burden to as minimum as possible to prevent the recurrence. In the systemic review published in 2019 by Marigil Sanchez et al., of 431 patients, GTR rates of 34% and NTR rates of 18% are reported after endoscopic approach. The important factors which limit the resection rate of endoscopic surgery are subfrontal, retrosellar extension of the tumor, Knosp 3 or 4 tumors, and hypointensity on T2-weighed MRI sequence, and these patients should be counseled regarding the increased risk of postoperative residual tumor hemorrhage, need for second-stage surgery, and need for adjuvant therapy. The factors affecting the EOR in GPA are described in [Table 17].
Table 17: Factors affecting extent of resection in giant pituitary adenoma

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Recurrence rates

After the surgery of GPAs, many patients have small residual disease. Literature reported the recurrence rate of 0%–25%[3],[21],[22],[26] in different studies. The main factor predicting the recurrence following surgery is the degree of resection, and literature is scarce regarding the long-term residual tumor progression following endoscopic surgery and the factors to predict the progression of residual disease. Goel et al.,[4] suggested clinical and radiological follow-up for small, asymptomatic residual, and re-exploration for large residual tumors. Patients showing the growth of small residual tumors were advised adjuvant Gamma Knife radiosurgery (GKRS). In the case of recurrent tumors close to optic chiasm or of a large size, re-exploration was preferred.

Visual outcome

Endoscopic and extended endoscopic approach provides better visual outcome as compared to microscopic transsphenoidal and transcranial approaches for GPA. In the literature, the improvement in visual outcome is reported between 71% and 97.4%[2],[3],[21],[22],[26] following endoscopic surgery as compared with 40% and 34.8% with transcranial and microscopic transsphenoidal approach, respectively. The factors to predict the visual improvement following endoscopic approach are mentioned in [Table 18].
Table 18: Factors affecting the visual improvement following endoscopic approach to GPAs

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Endocrinological outcome

Patients with large and giant nonfunctional pituitary adenomas are reported to have higher incidence of partial or complete pituitary dysfunction in the preoperative period when compared with macroadenomas (60%–93% vs. 40%–70%). After surgery in GPA, endocrinological status can remain same as preoperative in 70%–90%, whereas endocrinological improvement is reported between 0% and 12% in most of the series. None of the risk factors could be identified to predict the worse/good endocrinological outcome following surgery.

In giant functional pituitary adenomas, endocrinological remission rates are lower due to the lower GTR rates and literature is sparse to determine the exact rates of remission following endoscopic surgery for GPA. In patients who failed to achieve remission after surgery, redo surgery should be planned, if feasible, along with medical management, whereas in the presence of a small residual tumor, GKRS is a valid option to achieve endocrinological remission.

  Conclusion Top

Endoscopic transsphenoidal surgery is a good modality for most cases of GPA. Factors influencing EOR following transsphenoidal surgery include retrosellar, subfrontal, Knosp 3 and 4 cavernous sinus extension, and T2 hypointense tumors. In experienced hands, endoscopic transsphenoidal surgery offers favorable results and allows tackling of T2 hypointense tumors and cavernous sinus extension of tumor. Extended endoscopic approaches have improved the resection rates of tumors spreading to subfrontal and parasellar locations. Transcranial approach is still an important part of the surgical armamentarium in some cases where adequate debulking cannot be achieved by endoscopic approach.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

  Suggested Readings Top

  1. 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.
  2. Marigil Sanchez M, Karekezi C, Almeida JP, Kalyvas A, Castro V, Velasquez C, et al. Management of giant pituitary adenomas: Role and outcome of the endoscopic endonasal surgical approach. Neurosurg Clin N Am 2019;30:433-44.
  3. Rahimli T, Hidayetov T, Yusifli Z, Memmedzade H, Rajabov T, Aghayev K. Endoscopic endonasal approach to giant pituitary adenomas: Surgical outcomes and review of the literature. World Neurosurg 2021;149:e1043-55.
  4. Suri A, Ahmad FU, Mahapatra AK. Extradural trans-cavernous approach to cavernous sinus hemangiomas. Neurosurgery 2007;60:483-8.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15], [Table 16], [Table 17], [Table 18]


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Surgical Anatomy...
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Definition and E...
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Clinical Present...
Preoperative Eva...
Microscopic Vers...
Endoscopic Trans...
Extended Endosco...
Operative Techni...
Operative Room S...
Nasal Preparatio...
Preoperative Pre...
Extracapsular di...
Piecemeal excisi...
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Giant pituitary ...
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Pterional Cranio...
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