Surgical management of selected pituitary macroadenomas using extended endoscopic endonasal transsphenoidal approach: Early experience
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.111114
Source of Support: None, Conflict of Interest: None
Background and Objectives: The endoscopic transsphenoidal approach is commonly used surgical approach for pituitary adenomas. However, adenomas with dumbbell configuration, pure suprasellar location, and fibrous consistency are difficult to remove by this approach. Recently, the extended endoscopic endonasal approach (EEEA) has been utilized to excise this subgroup of pituitary adenomas successfully. Materials and Methods: Between January 2009 and December 2011, 13 patients with pituitary macroadenomas were treated with EEEA. The tumor subgroups included: Dumbbell tumor configuration (4), pure suprasellar tumor location (2), and large suprasellar tumors with subfrontal extension (2). Five patients had fibrous/recurrent tumors and required addition of transtubercular-transplanum extension to the standard endoscopic endonasal exposure for radical resection. Results: The tumor removal was gross total in 8 (61.5%) patients, subtotal in 4 (30.7%), and partial in 1 (7.7%) patient. Clinical improvement was observed in almost all patients, immediate relief in headaches in 88% and normalization of vision in 90% of patients with pre-operative visual disturbances. Three patients with secreting adenomas, two with growth hormone-secreting adenomas and one with prolactin-secreting adenoma, had normalization of hormonal status. Three patients developed temporary diabetes insipidus two patients suffered transient ischemic attacks and one patient with a recurrent giant pituitary adenoma experienced a serious injury to the perforating artery. Four patients (30.7%) developed post-operative cerebrospinal rhinorrhea and two patients required surgical repair. Conclusions: Our early experience suggests that the EEEA offers a potentially viable treatment option in certain pituitary tumors which are difficult to remove by the standard endoscopic approaches. However, longer follow-up and larger series are needed to establish the efficacy of this approach.
Keywords: Dumbbell adenoma, extended endoscopic endonasal approach, extended suprasellar approach, fibrous adenoma, giant pituitary adenoma, pituitary adenoma, transsphenoidal surgery
Endoscopic transsphenoidal approach has evolved considerably in the last 10-15 years and is now the standard surgical technique for most pituitary adenomas. Recent studies with this approach have shown increased tumor resection rates with minimal complications ,,,,,,,,,,, [Table 1]. However, certain adenomas, such as those with dumbbell configuration, firm or fibrous consistency, or pure suprasellar components, and some large recurrent tumors are difficult to remove by the conventional endoscopic approach. As a result, alternative surgical procedures like staged-transsphenoidal, transcranial, or combination of transsphenoidal-transcranial approaches having been used for management of these subtypes of pituitary tumors. With growing experience in the endoscopic surgery for various skull base lesions, it has now become possible to remove a wide variety of anterior and middle fossa tumors safely and more effectively. ,,,,,,,,, Since past few years, we have employed the endoscopic endonasal transsphenoidal approach with extension to the tuberculum sellae (TS) and planum sphenoidale (PS) for removal of meningiomas, craniopharyngiomas, suprasellar cysts, and selected pituitary macroadenomas [Figure 1]. In this report, we present our surgical technique and early experience with the extended endoscopic endonasal approach (EEEA) for the management of pituitary adenomas.
This study was a retrospective outcome review of pituitary macroadenomas removed via EEEA. Data of the patients undergone EEEA for pituitary adenomas between January 2009 and December 2011 at two institutions with the same team of surgeons were collected. All patients underwent full pre-operative ophthalmic and endocrinological evaluation. The same tests were repeated 1 month and 6 months post-operatively, and subsequently thereafter as deemed necessary. Neuroradiological evaluation was performed with a pre- and post-contrast magnetic resonance imaging (MRI) pre-operatively and post-operatively within 24 h or a week and after 3 months. MRI study was repeated in the follow-up as per the clinical indications to detect any tumor regrowth or recurrence. Computed tomography scanning was carried out as a part of pre-operative evaluation and surgical planning in the majority of cases to examine the anatomy of the sphenoid sinus, sella turcica, and parasellar structures, and to assess the extent of bone removal required in case of repeat surgery.
Patient included in the study were subjects with dumbbell or hour-glass shaped or pure suprasellar adenomas, giant adenomas with large midline subfrontal extension, and large recurrent adenomas after initial surgery and/or radiation. The choice of EEEA in these patients was based on the information provided by the pre-operative MRI. The patients who had firm and fibrous tumors and those in whom the suprasellar tumors failed to descend into the surgical field also underwent EEEA, at the same time or at a later date, and were included in this study. The decision to perform EEEA was entirely based on the intraoperative findings in these patients.
Patients with tumor extensions in areas other than those described here were found unsuitable for this approach and were excluded from this study. Two patients who had giant pituitary adenomas with tumor extensions in the cavernous sinuses were the unlikely candidates for a radical tumor resection and were included in this study for removal of their midline tumor masses to achieve relief in symptoms. Outcome measures included the extent of resection, visual and hormonal outcomes, and surgical complications, including the rate of post-operative cerebrospinal fluid (CSF) fistula formation. The extent of resection was categorized as gross total (100% resection) near total (>90% resection), subtotal (>70% resection), and partial (<70% resection) based on the post-operative MRI.
After induction of general anesthesia, the patient is positioned supine on the operating Table with the head fixed in a 3-point Mayfield clamp. The head of the patient is extended by 5-10°, flexed by 15° toward the left shoulder, and rotated by 15° to the right side to achieve an appropriate trajectory and a comfortable access through the right nostril. The head end of the operating Table is elevated slightly above the heart level to facilitate venous return. The endotracheal tube is secured to the left side of the face, and a lumbar spinal catheter is placed under general anesthesia for temporary post-operative CSF drainage, if necessary. The nostrils are prepared externally with betadine, and the nasal cavity is packed with adrenaline-soaked pledgets for 7-10 min. The left thigh is also prepared to harvest autologous fascia lata and fat for closure and reconstruction of the sellar floor (SF).
Endoscopic endonasal transsphenoidal approach
The procedure is performed using a 3- or 4-handed binostril technique. The endoscope is placed in the superior corridor of the right nostril abutting and lifting up the ala of the right nostril. This allows the operating surgeon to use the remainder of the right nostril as well as the entire left nostril for instrument manipulation. The right middle turbinectomy, wide sphenoidotomy, and removal of the vomer and rostrum of sphenoid sinus provide an unrestricted view of the target area and its surrounding landmarks. The posterior septectomy additionally aids movement of the instruments towards the lateral most margins of the target areas. The surgery is generally performed with a 0° endoscope, 4 mm in diameter, and 18-cm long. A 30° endoscope is used some time to obtain a more versatile view during exposure and to inspect the cavity after tumor removal. The basic steps of the endoscopic approach include (a) removal of the middle turbinate on one side, (b) lateralization of the contralateral middle turbinate, (c) posterior septectomy, and (d) a wide anterior sphenoidotomy.
After a decongested surgical field is obtained, the root of the middle turbinate is bipolarized and cut sharply to remove it intact. Similarly, the superior turbinate is bipolarized at the base and excised bilaterally. This step exposes the sphenoid ostium on both sides. The sphenoid ostium is widened laterally and inferiorly, and the rostrum of sphenoid is excised by using a high speed diamond drill. The posterior half of the nasal septum including the vomer is then excised. This step is in keeping with the principle of creating extra space within the nasal cavity for the endoscope while the cavity itself helps in easy maneuverability of instruments in three or four hand technique. It also provides a straight trajectory to the sellar and suprasellar regions after dural opening. Further bone removal in all directions proceeds using a Kerrison rongeur forceps. In the majority of cases with pituitary macroadenoma, the bone of the SF is remarkably thin or disrupted and can be removed easily. The bone of the SF is removed inferiorly up to the inferior intercavernous sinus, and superiorly till the superior intercavernous sinus is visualized. The anterior bend of the parasellar internal carotid artery forms the lateral limit of sellar bone removal.
A suboptimal opening in the SF during prior operation needs specific attention and a careful circumferential bone removal is carried out to improve endosellar exposure. We prefer to harvest a pedicled, vascularized nasoseptal flap, which is rotated inferiorly and placed temporarily into the nasopharynx. For extracapsular access to the tumor in suprasellar space, it is essential to remove TS and PS in addition to the bone of SF [Figure 2]a.
The primary steps of the extended endoscopic endonasal technique that we used in these cases have been described in detail in other publications. ,,, The bone of the SF, TS, and PS is first thinned down with a high-speed diamond drill and is then removed carefully in standard fashion using Kerrison rongeur forceps [Figure 1]. It is, however, crucial to identify the anatomical landmarks in the sphenoid sinus such as the optic and carotid protuberances and the medial and lateral optico-carotid recesses before drilling of the bone is commenced [Figure 2]a and b. The medial optico-carotid recess is an essential structure as it represents pneumatization of the middle clinoid process and indicates lateral aspect of the TS. The bone over the tuberculum strut and both medial optico-carotid recesses is thinned down and then removed with a blunt hook or angled curette. With removal of the bone of medial optico-carotid recesses, unroofing of the medial aspect of the optic canals is accomplished, which facilitates exposure of the optic nerves (ONs) and paraclinoid carotid arteries in the optico-carotid cistern. 
Utmost care should be taken to avoid thermal injury to the ONs by using copious saline irrigation during bone drilling. Venous bleeding from the cavernous and inter-cavernous sinuses can be controlled with surgicel or surgiflo (Ethicon, Inc.). The optimal exposure usually includes bone removal of sella, from one optic protuberance to the other, and from the carotid artery on one side to the carotid on the other side in lateral extent. In case of tumors lateral to the internal carotid artery, the bone over the internal carotid artery is gently thinned with diamond drill and then removed using Kerrison forceps. Bone removal inferiorly should include the entire floor of the sella so that it is flush with the upper clivus. Superiorly, it should include exposure of the superior intercavernous sinus, and dura of the tubercular and planum [Figure 2]b.
The dura is opened in a transdiaphragmatic fashion with two incisions parallel to each other in the dura, immediately superior and inferior to the superior intercavernous sinus. It allows coagulation and division of the superior intercavernous sinus under direct vision. The inferior transverse incision is then extended down in the midline to the sellar region. Using micro-scissors under direct vision, the midline sellar incision is extended laterally until medial margin of the cavernous sinus is visualized on both sides. Although, the superior intercavernous sinus is often found obliterated due to compression by the suprasellar tumors, it is always safer to coagulate it before dividing at the time of dural opening. , Opening the dura of the sella turcica and planum in this manner exposes the entire sellar cavity and suprasellar cistern and provides two distinct surgical routes to access the tumor, the inferior or extra-arachnoidal or endosellar route, and the superior or intra-arachnoidal or suprasellar route.
Except for a purely suprasellar pituitary adenoma, the endosellar intracapsular tumor is usually debulked first using the same principles of standard transsphenoidal technique [Figure 2]c. However, the conventional maneuvers such as curettage and suction are usually ineffective in cases with firm and fibrous tumors which require microsurgical techniques using sharp dissection with microscissors alternating with blunt dissection using microdissectors in a manner similar to open microsurgical procedures used for piece-meal removal of other intracranial tumors.
The suprasellar part of the tumor is then approached through the superior intra-arachnoidal or extracapsular route [Figure 2]d. In case of a softer tumor, the opening in the intrasellar part of the tumor capsule is enlarged superiorly, and intracapsular tumor decompression is continued using curettage and suction technique [Figure 2]e. Intermittent gentle push to the capsule from above often helps descent of the suprasellar portion of the tumor down into the sellar cavity from where it can be removed easily. When the tumor is firm or purely suprasellar, its removal can be accomplished in piece meal fashion using sharp microsurgical techniques [Figure 2]f. After the tumor has been debulked adequately, an arachnoid plane is identified, and the tumor capsule is dissected and mobilized from the surrounding neurovascular structures under direct vision. [Figure 2]f Total tumor removal is ensured by exploring both sellar and suprasellar regions using 0, 30, and occasionally 45 endoscopes [Figure 2]g and h.
Closure of the cranial base defect after tumor removal is of critical importance in preventing a post-operative CSF leak and its complications. We use a multi-layered reconstruction technique to achieve a water-tight closure of the defect. Firstly, the intradural space is filled with a thin layer of Tisseel (Baxter Healthcare Corp.) fibrin glue to seal the arachnoid space. An autologous fascial graft, taken from patient's thigh, is then placed intradurally as an underlay graft, which is held in place by a layer of fibrin glue. The final layer of a previously prepared vascularized pedicled nasoseptal flap is then glued to cover the entire defect and is supported by the nasal Merocel (Medtronic Xomed) packs. A controlled drainage of CSF using a lumbar drain is continued post-operatively for 5 days.
A total of 13 patients, who underwent surgery via EEEA between January 2009 and December 2011, were identified [Table 2]. All patients were symptomatic because of their tumors, which included growth hormone (GH)-secreting adenomas in three, prolactin (PRL)-secreting adenoma in one, and non-secreting adenomas in the remaining nine patients. Three patients presented with recurrence of tumors, including two patients who had prior transsphenoidal surgery and one patient had transsphenoidal and transcranial surgeries. Two patients had received radiotherapy previously. Two other patients had been treated with pharmacological therapy (bromocriptine) prior to surgery.
According to the pre-operative MRI, five patients had large intra- and suprasellar tumors, four had large dumbbell shaped tumors, and two patients had purely suprasellar residual tumors without any intrasellar extensions. Two other patients with giant pituitary adenomas had large suprasellar-subfrontal tumor extensions. Firm and fibrous tumor consistency was observed during surgery in five patients. Four patients had their tumors invading the cavernous sinus, including one with bilateral involvement. All patients in this series underwent removal of their tumors via EEEA as described above, as a planned procedure based on the pre-operative MRI in eight patients and as an extension of the standard endoscopic approach on the basis of the intraoperative findings of the firm or fibrous tumor consistency or the suprasellar tumor failing to descent in the remaining five patients. The extent of tumor removal was gross total in 8 (61.5%) patients [Figure 3], subtotal in 4 (30.7%), and partial in 1 (7.7%).
Improvement in the pre-operative clinical condition was observed in almost all patients. Headaches resolved immediately after surgery in 88% and gradually during follow-up in the remaining 12% of patients. Vision in almost 90% of the patients who presented with visual impairment pre-operatively improved after surgery, while in the remaining 10% of patients, visual field defects remained unchanged. None of these patients reported worsening of vision after surgery except one patient who had developed transient diminution of vision transiently in one eye and recovered totally. Hormonal resolution was observed in all three patients with GH-secreting adenomas and one with PRL-secreting adenoma. Three patients developed temporary diabetes insipidus and required a short-term treatment with desmopressin (DDAVP) and fluid management. Two patients developed transient ischemic attacks and one patient with a recurrent giant pituitary adenoma suffered a serious ischemic injury to the hypothalamus due to an intraoperative injury to the perforating artery.
Four patients (30.7%) experienced post-operative CSF rhinorrhea which resolved with conservative management, including complete bed rest and lumbar CSF drainage for 5-7 days in two patients. The other two patients required surgical repair of their CSF fistulae. The incidence of CSF leak has reduced dramatically since we have started using the pedicled nasoseptal flap as a part of the reconstruction procedure and had a minor leak in only one patient in the last six cases who have been treated with this modified reconstruction technique.
The degree of surgical removal of pituitary macroadenoma using transsphenoidal route essentially depends on the configuration, location, and consistency of the tumors. Certain tumors, such as those with dumbbell configuration, firm or fibrous consistency, large subfrontal extension, and purely suprasellar location, are difficult to remove completely by the standard transsphenoidal approach. , The pituitary tumors with extensive scarring due to previous surgery or irradiation also pose severe difficulties with this approach. Because of the serious technical limitations in tumor resection, the transsphenoidal approach has often been considered in the past as a relative contraindication in these patients.  The surgical options for these tumors, thus, remain limited to either staged transsphenoidal resections after residual tumor descends into the sella, or transcranial removal, or combined/staged transsphenoidal-transcranial approaches. ,,,
The extended endonasal transsphenoidal approach has recently been used in the surgical treatment of a variety of midline skull base tumors, ,,,,,,,,, including craniopharyngiomas, Rathke cleft cysts, and meningiomas. However, this approach is not commonly used for removal of pituitary adenomas and only a few reports are available in the literature. ,,, Recently, we employed the extended endoscopic endonasal transsphenoidal approach (EEEA) as described above in detail, in a subgroup of patients who had pituitary macroadenomas with dumbbell (hour-glass) configuration, firm or fibrous consistency, complete suprasellar location, larger subfrontal extension, or recurrent tumors after previous surgery/radiation.
The advantages of EEEA are many and are mainly because of the wider exposure that it provides after removal of SF and the bone of the TS and PS. The intradural exposure achieved by this approach offers a simultaneous and direct endosellar and extraarachnoidal (intracapsular) access to the tumor in the sellar region, and a suprasellar and intraarachnoidal (extracapsular) access to the suprasellar part of the tumor. The intracapsular tumor removal is carried out via the endosellar route, and using the suprasellar corridor at the same time, the tumor capsule is dissected from overlying suprasellar cistern, OPs and chiasm, and the anterior cerebral arteries under direct vision.
By providing greater exposure at the skull base and a better opportunity to achieve increased tumor resection, the EEEA obliviates the need for extensive open skull base or transcranial approaches or staged/combined transsphenoidal surgical procedures. Our results indicate clearly that the rate of total or nearly-total resection of non-infiltrating pituitary tumors is higher (89%) with EEEA than the average rate of total resection using standard endoscopic transsphenoidal (78%) ,,,,,,,, and transsphenoidal microscopic (50%) ,,,, approaches. All our patients experienced immediate and progressive relief in their symptoms and signs of meningeal stretching, and pressure on the optic apparatus and pituitary stalk (ST) due to tumor mass.
The basic technique of pituitary macroadenoma surgery involves tumor removal by curettage and suction method. ,,, Although it works well for the majority of pituitary tumors, the maneuver is totally ineffective when the tumor is firm and fibrosed. A blind curettage to remove suprasellar mass from the endosellar route has been found potentially dangerous and is associated with a high incidence of incomplete tumor removal from the suprasellar region.
The standard transsphenoidal surgery for pituitary adenomas also relies mainly on spontaneous descent of the suprasellar portion of tumor into sellar cavity after initial tumor debulking by endosellar route. ,,,,,, Occasionally, the suprasellar tumor does not fall into the sella and causes a large tumor mass to remain in the suprasellar region as a residue. A blind dissection in this situation may cause transgression of surgical instruments into the subarachnoid space resulting into CSF leak and/or injury to the optic apparatus or adjacent perforating vessels. The EEEA provides different corridors, endosellar and suprasellar, to dissect the tumor safely from the surrounding structures under direct vision. It also provides direct visualization and accessibility to suprasellar, subchiasmal, retrochiasmal, and retrosellar regions which are generally poorly visible in the standard transsphenoidal surgery.
In cases of dumbbell tumors, a narrow diaphragma opening prevents descent of the suprasellar portion of tumor into the sellar cavity. The fibrous tumors, recurrent tumors after initial surgery or irradiation, and some medically treated large tumors fail to fall into the sellar cavity because of their firm consistency and are, therefore, less likely to be removed totally by the routine transsphenoidal route. Attempts to use lumbar infusions or air injection to facilitate descent of the suprasellar tumor component are usually unsuccessful and frequently associated with significant complications. , The EEEA is advantageous in these cases because it offers larger tumor exposures through two different routes, endosellar or extraarchnoidal, and suprasellar or intraarachnoidal, which facilitates entire tumor removal in a single-stage surgery.
Purely suprasellar tumors and some giant tumors with large midline extensions in the subfrontal regions are not adequately visualized via the endosellar route and are, therefore, clearly unsuitable for the standard transsphenoidal approach. By adding a transtubercular-transplanum extension to the regular transsphenoidal endosellar approach, the possibility of tumor removal from these areas can be increased considerably. Both patients in our series with primary suprasellar residual tumors and one of the two patients, who had giant pituitary tumors with large subfrontal extensions, had a complete resection of their adenomas. For patients who have undergone prior craniotomy, the EEEA offers a virgin surgical route away from the area of fibrotic or gliotic reaction secondary to the previous surgery. In cases, in whom, a conventional transsphenoidal operation had been previously performed, the EEEA provides a relatively well-preserved route to access the tumor extensions that might not have been accessed in the earlier operation, such as the retrochiasmatic, subchiasmatic, and in some cases sellar components, without disruption by scarring.
Similarly, visualization of the ST and gland is usually difficult through the regular endoscopic transshenoidal exposure. The EEEA provides better visualization of the tumor-gland interface, and thereby, offers a great opportunity to preserve both, the ST and the gland during tumor removal. , A complete hormonal resolution was observed post-operatively in all our patients who had hormonally active tumors; in contrast to the hormonal resolution rate estimated as 79% (84% in GH-secreting, 82% in PRL-secreting, and 81% in adrenocorticotrophic hormone ACTH- secreting adenomas) with routine endoscopic transsphenoidal approach ,,,,,,,, and as 25-49.7% with traditional transsphenoidal microscopic approach. ,,,,
With regards to surgical complications of transsphenoidal surgery, the CSF leak remains to be the most common and disturbing post-operative morbidity. However, it should be noted that most CSF leaks are minor and easily managed with packing and CSF diversion. In a series of 592 pituitary macroadenomas and giant pituitary adenomas removed via the microscopic technique, Han et al.  reported post-operative CSF leaks in 4.4% of patients and described a correlation between the risk of CSF leaks and the type of adenoma, its consistency, margins, and size. In the largest endoscopic study in the literature, the percentage of CSF leaks ranged from 1.6% to 5.2%. ,, In a meta-analysis of endoscopic pituitary surgery, Tabee et al.  described 1-4% incidence of CSF leak.
The main drawback of EEEA for these selected pituitary macroadenomas is the considerably higher risk of CSF leak (5-13.6%) as compared with a simpler standard transsphenoidal technique. , Four patients (30.7%) in our study developed post-operative CSF rhinorrhea, and two of them required surgical repair. However, occurrence of this complication has reduced in our experience since the time we have started using a vascularized and pedicled nasoseptal flap  and meticulous multilayer reconstruction of the cranial base defect. , The results of literature review and our own experience in this study clearly demonstrate that the percentage risk of CSF leakage can be dramatically decreased with experience and this learning curve is unavoidable whatever may be the surgical technique. , There is no evidence of any significant increase in the incidence of other common complications like epistaxis, meningitis, and diabetes insipidus with EEEA as compared with the transsphenoidal microscopic and standard endoscopic approaches. ,,,,
The high rates of gross tumor removal, hormone resolution for secreting tumors, and improvement in pressure symptoms due to tumor mass, can be achieved with EEEA in the selected group of pituitary macroadenomas, which are difficult to be removed by the standard endoscopic transsphenoidal approach. Although, our early experience with this approach is encouraging, longer follow-up and larger published series is needed to establish the efficacy of this approach.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]