SciELO - Scientific Electronic Library Online

 
vol.74 issue5The extended pterional approach allows excellent results for removal of anterior cranial fossa meningiomasPituitary macroadenoma: analysis of intercarotid artery distance compared to controls author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.74 no.5 São Paulo May 2016

http://dx.doi.org/10.1590/0004-282X20160042 

ARTICLE

Surgical outcomes of the endoscopic endonasal transsphenoidal approach for large and giant pituitary adenomas: institutional experience with special attention to approach-related complications

Resultados cirúrgicos do acesso endonasal endoscópico transesfenoidal para adenomas hipofisários grandes e gigantes: experiência institucional com ênfase às complicações relacionadas ao acesso cirúrgico

Edson Rocha Constantino1 

Rafael Leal1 

Christian Cândido Ferreira1 

Marcus André Acioly1 

José Alberto Landeiro1 

1Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Divisão de Neurocirurgia, Niterói RJ, Brazil.

ABSTRACT

Objective

In this study, we investigate our institutional experience of patients who underwent endoscopic endonasal transsphenoidal approach for treatment of large and giant pituitary adenomas emphasizing the surgical results and approach-related complications.

Method

The authors reviewed 28 consecutive patients who underwent surgery between March, 2010 and March, 2014.

Results

The mean preoperative tumor diameter was 4.6 cm. Gross-total resection was achieved in 14.3%, near-total in 10.7%, subtotal in 39.3%, and partial in 35.7%. Nine patients experienced improvement in visual acuity, while one patient worsened. The most common complications were transient diabetes insipidus (53%), new pituitary deficit (35.7%), endonasal adhesions (21.4%), and cerebrospinal fluid leak (17.8%). Surgical mortality was 7.1%.

Conclusions

Endoscopic endonasal transsphenoidal surgery is a valuable treatment option for large or giant pituitary adenomas, which results in high rates of surgical decompression of cerebrovascular structures.

Key words: endoscopic endonasal approach; giant pituitary adenomas; large pituitary adenomas; complication rates

RESUMO

Objetivo

Neste manuscrito investigamos a experiência institucional com o acesso endonasal endoscópico transesfenoidal no tratamento de adenomas hipofisários grandes e gigantes com ênfase às complicações relacionadas ao acesso cirúrgico.

Método

Foram incluídos neste estudo 28 pacientes consecutivos submetidos à cirurgia entre Março de 2010 e Março de 2014.

Resultados

O diâmetro médio pré-operatório dos tumores era 4,6 cm. Uma ressecção total foi obtida em 14,3%; quase total, em 10,7%; subtotal, em 39,3% e parcial, em 35,7%. Nove pacientes evoluíram com melhora na acuidade visual, enquanto um paciente apresentou piora da função visual. As complicações mais comuns foram diabetes insipidus transitório (53%), novo défice hipofisário (35,7%), sinéquias endonasais (21,4%) e fistula liquórica (17,8%). A mortalidade cirúrgica foi 7,1%.

Conclusões

A cirurgia por via endonasal endoscópica transesfenoidal é uma opção terapêutica extremamente útil para adenomas hipofisários grandes e gigantes, a resultar numa significativa descompressão das estruturas cerebrovasculares.

Palavras-Chave: acesso endoscópico endonasal; adenoma hipofisário gigante; adenoma hipofisário grande; índices de complicação

Introduced initially in the 1960s by Guiot et al.1 as an additional visualization tool to the microscope for sellar tumors, the endoscope has revolutionized the treatment of pituitary disorders because of improved visualization allowing ultimately the expansion of the surgical view2. At present, the purely endoscopic endonasal approach is widely used worldwide for the treatment of pituitary adenomas and other sellar tumors due to its similar safety, resection and complication rates, as well as surgical outcome in comparison to the traditional microscopic approach3,4. Large and giant pituitary adenomas comprise a different issue, which pose a significant surgical challenge5. The definition is based on a purely morphological criterion in the way that when the tumor achieves a diameter greater than 4 cm in any plane, it is considered giant5,6,7. There is no consensus, however, on the definition of large pituitary adenomas8,9. Juraschka et al.10 have considered large tumors as those having > 3 cm in the maximal diameter, while Cusimano et al.11 have introduced a new volumetric assessment (≥ 10 cm3) on the assumption of a better estimation of the tumor size and also for a better quantification of the extent of resection.

Traditionally, these tumors have been handled by the transcranial route, alone or in combination with the transsphenoidal resection7,9,11,12. Some recent reports have described the usefulness of the endoscopic endonasal route in the their management, even though its safety and effectiveness of treating large and giant pituitary adenomas is yet to be established in the literature6,8,10,11,13,14,15,16. Herein, we sought to investigate our institutional experience of patients who underwent endoscopic endonasal transsphenoidal approach for treatment of large and giant pituitary adenomas emphasizing the surgical results and approach-related complications.

METHOD

This study consists in a retrospective review of 28 consecutive patients who underwent endoscopic endonasal transsphenoidal surgery for treatment of large and giant pituitary adenomas between March, 2010 and March, 2014. Clinical presentation, endocrine status, neuroimaging, histopathological evaluation, extent of resection, clinical outcomes, and complication rates were analyzed. The institutional review board approved the terms and conditions of the present study.

Inclusion criteria

All patients undergoing endoscopic endonasal transsphenoidal resection for histologically proven pituitary macroadenomas with a maximal diameter > 3–4 cm (large) or > 4 cm (giant) were included in this analysis. Patients harboring smaller tumors, distinct histological diagnosis, or those who have been submitted to a previous transcranial resection were excluded.

Patient characteristics

The medical charts were reviewed to collect clinical data. The clinical characteristics included were gender, age, visual acuity (Humphrey visual field [HVF] testing), ophthalmoplegia, pituitary dysfunction (hypo- or hyperfunction syndromes), diabetes insipidus (DI), and prior surgery. All patients underwent preoperative magnetic resonance imaging (MRI) and computed tomography (CT) with navigation protocol. Neuroimaging were evaluated to measure the maximal tumoral diameter in any plane, and to assess suprasellar and parasellar extension based on the classification of Hardy17 and Mohr et al.18, as well as the occurrence of optic nerve compression, hydrocephalus, or haemorrhagic component. All patients were seen by an experienced endocrinological team being tested for serum growth hormone (GH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH), cortisol, insulin-like growth factor-I (IGF-1), prolactin, thyroid-stimulating hormone (TSH), T4, testosterone and estrogen levels.

Postoperatively, all patients performed cranial CT within 48 hours and cranial MRI at 2-, 12-months, and yearly thereafter. Gross-total resection (GTR) was assigned when the MRI scan showed no residual tumor, while near total resection (NTR) was attributed to the removal of ≥ 90%, subtotal resection (STR) with a tumor reduction from 70% to 89.9% and partial resection (PR) in the case of ≤ 70% of tumor resection. Follow-up imaging also addressed regrowth of a residual tumor or tumor recurrence in the case of GTR. The occurrence of postoperative complications, including DI (transient/permanent), new hypopituitarism, cerebrospinal fluid (CSF) leak, meningitis, ophthalmoplegia, endonasal synechiae, acute sinusitis, epistaxis, internal carotid artery injury, subarachnoid haemorrhage (SAH) and ischemic stroke were considered.

For hormone-secreting tumors, chemical remission was based on the following criteria: for prolactinomas, a prolactin level < 15ng/mL in men and < 20ng/mL in women; and for GH-secreting tumors, normalization of serum levels of IGF-1 matched for age and gender, random serum GH level of < 1ng/mL or a serum GH nadir of < 0.4 ng/mL following oral glucose tolerance test19,20.

Surgical approach

The operative technique used was the endoscopic endonasal transsphenoidal approach. All surgeries were performed primarily by the senior neurosurgeon (J.A.L.) during this time period. The primary objective was maximum decompression of the optic apparatus, the pituitary gland and surrounding brain structures12. Patients were positioned with their heads secured by a Mayfield head holder. Then, the patients were registered to a frameless stereotactic navigation system (Stealth; Medtronic, Jacksonville, Florida, USA) for intraoperative guidance and anatomical verification. Lumbar drains were not used routinely.

The nasal cavity was prepared with adrenalin (1:1000) soaked cottonoids for at least 5 minutes in order to decrease bleeding. The surgical procedure started with the inventory of nasal cavity with a 0-degree 4-mm endoscope (Karl Storz GmbH & Co.KG, Tuttlingen, Germany). A right middle turbinate luxation or middle turbinectomy was developed before harvesting mucoperiosteal nasoseptal vascularized flap for skull base reconstruction after tumor resection. A posterior septectomy was undertaken for a two nostril bimanual technique. An anterior sphenoidotomy was then carried out. Inside the sphenoid sinus, the sellae borders were demarcated by the aid of image guidance. Its front wall was opened with a fine chisel and expanded with a Kerrison forceps or drilling. Dural exposure was limited by the tuberculum sellae superiorly, clival recess inferiorly, and laterally by the medial walls of the cavernous sinus. Tumor was debulked by piecemeal resection and suction and ultimately the tumor border was defined for bimanual preparation of the neurovascular structures (Figure 1). The reconstruction of the skull base was performed with autologous fat patch, which was placed in the resection cavity with a special care not to overpack, followed by placement of the nasoseptal mucous flap. Tissue glue (Beriplast, Behring) was applied to the flap edges and covered with Surgicel (Ethicon). A nasal Foley catheter was introduced for packing of the sphenoidal cavity in order to prevent flap migration only in the case of intraoperative CSF leakage.

Figure 1 Intraoperative imaging demonstrating the surgical steps involved in the resection of a giant pituitary adenoma. (A) Anterior sphenoidotomy. (B) Dural opening and initial preparation of the tumor capsule. (C) Intracapsular resection. 

RESULTS

Preoperative characteristics

Patients included 17 men (60%) and 11 women (40%). The mean age was 46 years (range, 15–62 years). The average tumor size was 4.6 cm (range, 3.9–9.7 cm). The most common presenting symptoms were endocrinopathy (57%), visual acuity deficits (42%), and headache (35%). There were 5 patients (17.8%) with preoperative hypogonadism, 4 patients (14.3%) had hypothyroidism, one patient (3.6%) had acromegaly and one patient (3.6%) was affected by galactorrhea. Gait apraxia and cognitive impairment were found in 7.1% of patients (2 patients) due to obstructive hydrocephalus (grade D of Hardy).

In 2 patients (7.1%), there was acute worsening of visual impairment and headache, which together with the imaging findings confirmed the diagnosis of tumor apoplexy. Prior to surgery, the imaging morphological characteristics of tumors are illustrated on Table 1. The majority of tumors were nonfunctioning pituitary adenomas (82%) (Figure 2).

Table 1 Imaging characteristics of large and giant pituitary adenomas. 

Tumor characteristic Nº of patients (%)
Optic nerve compression 22 (78.6)
Supra- and para-sellar extension 17 (60.7)
Hydrocephalus 2 (7.1)
Tumor apoplexy 2 (7.1)

Figure 2 Tumor classification according to the immunohistochemical profile. (GH – growth hormone; TSH – thyroid-stimulating hormone). 

Extent of resection and Clinical outcomes

The tumor resection rates were estimated by analysis of postoperative MRI exams, which were performed two months after surgery. Gross-total resection (GTR) was achieved in 14.3% (4 patients), near-total (NTR) in 10.7% (3 patients), subtotal (STR) in 39.3% (11 patients), and partial (PR) in 35.7% (10 patients). Nine (32.1%) patients experienced improvement in visual acuity, while only one patient (3.6%) worsened. Surgical resection alone achieved endocrinological remission in four of the five patients with hormone-secreting tumors (the remaining patient died after 30 days postoperatively).

Complications

The authors identified 11 different immediate/ short-term and late complications related to the endoscopic transsphenoidal resection of giant pituitary adenomas (Table 2). The most common complications were transient diabetes insipidus (53%), new pituitary deficit (35.7%), endonasal adhesions (21.4%), and CSF leak (17.8%). From the immediate/short-term group, nasosinusal disorders, such as acute sinusitis and epistaxis occurred in 7.1%, each. Intraoperatively, CSF leak was detected in 21% and corrected at the end of tumor resection, even though 17.8% of the patients experienced postoperative CSF leak. All patients were placed on a conservative regimen of bed rest, acetazolamide and lumbar drain for 5 days with total symptom remission. Two patients developed postoperative meningitis after treatment for CSF leak.

Table 2 Perioperative and postoperative complications of the endoscopic endonasal transsphenoidal approach. 

Complication Nº of patients (%)
Diabetes insipidus
transient 15 (53.6)
permanent 1 (3.6)
Adrenal insufficiency 10 (35.7)
Endonasal synechiae 6 (21.4)
CSF leak 5 (17.8)
Acute sinusitis 2 (7.1)
Meningitis 2 (7.1)
Epistaxis 2 (7.1)
SAH 1 (3.6)
Internal carotid artery injury 1 (3.6)
Stroke 1 (3.6)
Ophthalmoplegia 1 (3.6)

CSF: cerebrospinal fluid; SAH: subarachnoid haemorrhage.

Surgical mortality was 7.1% (2 patients). One patient had a severe subarachnoid/tetraventricular haemorrhage, which ultimately lead to diffuse cerebral vasospasm and brain death (Figure 3), while the second deceased from metabolic disorders as a result from DI. A third patient died more than 30 days postoperatively affected by nosocomial pneumonia and therefore was not considered surgical mortality. At the last follow-up, only one patient (3.6%) was affected by permanent DI. The ENT team monitored all endonasal adhesions in the outpatient clinic, but no surgery was necessary.

Figure 3 Preoperative axial (A) and coronal (B) T1-weighted gadolinium-enhanced MRI of a rounded giant pituitary tumor. (C, D) The patient underwent near-total resection of the adenoma, but experienced a severe subarachnoid/tetraventricular haemorrhage after cavernous sinus violation and internal carotid artery injury, which ultimately lead to diffuse cerebral vasospasm and brain death. 

Recurrences and Follow-Up

During the mean follow-up time of 30 months (range, 12–36 months), 9 (32.1%) patients were reoperated on for tumor regrowth. In total, 28 patients underwent 32 endoscopic endonasal transphenoidal procedures. Five of the 9 patients were given reoperation through open craniotomy. The mean time to regrowth was 2 years. All patients who underwent GTR (14.3%) remained free of tumor.

DISCUSSION

Giant pituitary adenomas are rare tumors with an estimated incidence between 5% and 16% of all pituitary tumors1,21,22 . Complete resection is often a technical challenge, even for experienced neurosurgeons, considering that this subgroup of tumors may present with a high degree of invasion of neurovascular structures and large areas of supra- and parasellar extension11,23. In this way, the primary objective of surgery includes relief of mass effect by obtaining maximal tumor resection in order to decompress visual pathways, neurovascular structures and the pituitary gland6,9,15.

The possible route to reach the sellar region in the management of giant pituitary adenomas can be divided into two main groups: the transcranial and the transsphenoidal approaches, either microscopic or endoscopic. A recent systematic review from the modern literature (1995–2010) was conducted to compare the benefits and limitations of the various surgical approaches7. Based on the collection of 478 patients affected of giant pituitary adenomas, Komotar et al.7 found that the endoscopic cohort had higher rates of gross total resection (GTR) (47.2%) and improved visual outcome (91.1%) than the transcranial (9.6% and 40%) and the microscopic transsphenoidal cohorts (30.9% and 34.8%), respectively.

It is worth emphasizing that only one purely endoscopic surgical series was included in their analysis, since the manuscript by de Paiva Neto et al.24 was mainly microscopic transphenoidal. Thereafter, few studies came out in the literature addressing the outcomes of patients undergoing resection for large and giant pituitary adenomas by the endoscopic approach6,8,10,11,13,14,15,16. Their main surgical outcomes and complications rates are detailed on Tables 3 and 4. Our group has recently analyzed the initial experience (2000–2010) in the management of 35 giant nonfunctioning pituitary adenomas operated on by the open and the endoscopic routes, but the main objective was to correlate Ki-67 expression with tumor recurrence12.

Table 3 Outcomes of main series of endoscopic endonasal transsphenoidal approach for large and giant pituitary adenomas. 

Author, year Nº of patients Extent of resection (%) Visual outcome Surgical Mortality


GTR NTR STR PR Improved Unchanged Worsened
Nakao and Itakura, 201116 43 47* - 53 - 97.7 2.3 0 0
Di Maio et al., 201113 20 60 20 15 5 85.7 7.1 7.1 0
Cusimano et al., 201211 29a 20.7 - 79.3a - 96.2 - 3.8a 0
Hofstetter et al., 201214 43b 48.8 - 51.2b - 85.7b 14.3 0 4.6
Koutourousiou et al., 201315 54 20.4 66.7 - 12.9c 80 13.3 4.4 0
Gondim et al., 20146 50 38 18 - 44** 76 22 0 4
Juraschka et al., 201410 66*** 24.2 16.7 36.4 22.7 73d 22.2 4.8 0
Chabot et al. 20158 39 56.4 28.2 15.4e - 53.6 46.4 0 0
Present Series 28 14.3 10.7 39.3 35.7 32.1 64.3 3.6 7.1

GTR: gross total resection; NTR: near total resection; PR: partial resection; STR: subtotal resection. *The extent of resection considered STR for any residual tumor; **The extent of resection considered PR for any residual tumor greater than 10%; ***Preoperative and postoperative MRI were available in 66 of the 72 patients reported; aPurely endoscopic transsphenoidal approach was done in 29 of the 72 patients reported. Residual tumor was not defined in NTR, STR or PR. One patient experienced no improvement on visual function, but it was not informed whether it was unchanged or worsened; bPurely endoscopic transsphenoidal approach for large (> 3 cm) and giant (> 10 cm3) adenomas was done in 43 of the 71 patients reported. Residual tumor was not defined in NTR, STR or PR. Visual acuity was not included in the analysis. The reported rates of visual outcomes reflect visual field defect of the patients suffering from giant tumors only. c The extent of resection considered PR for any residual tumor greater than 10%. dPostoperative visual fields were available for 55 patients, of whom 61.8% experienced improvement. eThe extent of resection considered STR for any residual tumor greater than 10%. Postoperative visual fields improved in 20 patients and remained unchanged in 6 patients.

Table 4 Immediate, short- and late postoperative complications of main series of endoscopic endonasal transsphenoidal approach for large and giant pituitary adenomas. 

Author, year Nº of patients Immediate & short-term (%) Late (%)


Trans. DI Sinusitis/ Epistaxis CSF leak Meningitis SAH /Hematoma Transient CN deficit Permanent DI Pituitary Insuf. Nasal Synechiae
Nakao and Itakura, 201116 43 25.6 - / - 0 - 0 / 4.7 - 0 4.7 2.3
Di Maio et al., 201113 20 - - / - 5 - - / - - - - -
Cusimano et al., 201211 29 - - / - 27.6 - - / 0 - 0.07 0.31 -
Hofstetter et al. 201214 43 - - / - 0 - - / - - 13.9 13.9 -
Koutourousiou et al., 201315 54 24.1 - / - 16.7 5.5 - / 3.7 11.1 9.6 16.7 -
Gondim et al., 20146 50 36 2 / 6 8 2 6 / - - 0.1 0.36 -
Juraschka et al., 201410 66 - 13.7 / 2.7 9.6 2.7 0 / 0 0 - 5.5 -
Chabot et al. 20158 39 - - / - 10.7 2.6 - 0 7.7 12.8 15.4*
Present Series 28 53.6 7.1 / 7.1 17.8 7.1 7.1 / 0 3.6 3.6 35.7 21.4

CN: cranial nerve; CSF: cerebrospinal fluid; DI: diabetes insipidus; Pituitary insuf.: new pituitary insufficiency of one or more axis; SAH: subarachnoid hemorrhage; Trans. DI: transient diabetes insipidus. *The authors described 15.4% of sinonasal symptoms, but they were not detailed.

Extent of resection of the endoscopic endonasal transsphenoidal approach

As aforementioned, GTR is not the goal for such large tumors because of neurovascular structures involvement and the recent success of adjuvant therapies8. Thus, the extent of resection is difficult to evaluate as an outcome for large and giant pituitary adenomas8. Moreover, there is no general consensus on the definition for near total (NTR), subtotal (STR), and partial resection (PR), as also noted by Chabot et al.8. Overall, the reported rate of GTR in the modern purely endoscopic series published after the systematic review by Komotar et al.7 ranges from 14% in our series to 60% in the Naples series13 (average of 36.7%) (Table 3).

Such higher rates of GTR are quite encouraging in comparison to the open and microscopic transsphenoidal groups (9.6% and 30.9%, respectively)7. It is worth discussing that cavernous sinus involvement is reported by most of the studies as the major limitation to GTR with the endoscopic approach6,8,14,16, whereas for the microscopic transsphenoidal approach is the suprasellar extension25. Besides cavernous sinus involvement, tumor size greater than 10 cm3,14 multilobular configuration and extension to the middle fossa15 are also reported to have a negative impact on surgical resection rates by the endoscopic technique.

Taking together the results of GTR, NTR and STR as an arbitrary threshold to provide satisfactory neurovascular structures decompression, the endoscopic cohort was able to achieve decompression rates of 78.9% (range 63–95%)10,13,Present. Even though a fair comparison cannot be performed, because of a different definition for STR (residual tumor > 10–20%)7, the endoscopic rates of decompression are at least similar to open and microscopic transsphenoidal groups (78.8% and 81.2%, respectively)7.

Finally, the surgical technique used by most of the endoscopic endonasal series is the standard approach, in which a wide exposure of the sellar floor is obtained from the medial walls of the cavernous sinus laterally, the tuberculum sellae cranially and the dural indentation of the clivus/inferior transcavernous sinus caudally6,8,10,11,14,16. Some studies have used the extended transplanum/transtuberculum endonasal approach to address some dumbbell-shaped or suprasellar adenomas or even fibrous tumors6,8,10,13,14,15. The role of the extended approach is yet to be defined, but the results are promising taken into consideration the higher rates of GTR in comparison to the standard endonasal approach (average of 41.3% vs. 27.3%, respectively; Table 3). Further studies are, however, necessary to clarify this issue.

Clinical outcomes of the endoscopic endonasal transsphenoidal approach

Nine patients in our series experienced visual acuity improvement and only one patient had visual deterioration. Similar results were described by recent endoscopic endonasal series, in which the rates of visual improvement achieved a mean of 75.5% (range 32.1%–97.7%; Table 3). Given that visual improvement is observed in up to 40% in the open and microscopic transsphenoidal cohorts7, visual outcomes are by far the major advantage of the endoscopic endonasal approach over the remaining surgical techniques8. Chabot et al.8 hypothesized that the endoscope provides a better visualization and therefore protection of the optic apparatus and its blood supply, which ultimately leads to such improved outcomes.

Conversely, the endocrine outcomes are generally not so encouraging as observed with visual outcomes. Our results indicate the occurrence of 35.7% of new postoperative pituitary insufficiency, which is similar to other endoscopic endonasal series (mean 17.2%; range 4.7%–36%; Table 4). The open and microscopic cohorts revealed better outcomes, however (9.1% and 9.5%, respectively)7. Even though Nakao and Itakura16 and Juraschka et al.10 reported lower rates of new postoperative hypopituitarism, the endocrine outcomes seems to correlate inversely with the greater extent of resection and therefore with the greater surgical manipulation provided by the endoscope.

Complications of the endoscopic endonasal transsphenoidal approach

The complications related to the endoscopic transsphenoidal surgery in our series show converging rates with published studies (Tables 3 and 4), suggesting the technical safety and efficacy compared to the open transcranial and microscopic transsphenoidal approaches. We have didactically divided postoperative complications into two major groups, namely the immediate/short-term and late complications. From the first group the occurrence of CSF leak, transient DI and nasosinusal disorders (sinusitis/epistaxis) are the most frequent.

CSF leak has been considered one of the major disadvantages of the endoscopic endonasal approach, especially in the case of extended approaches8. As the matter in fact, it should be noted that it is extremely difficult to resect such complex tumors without violating the arachnoid layer8. The advent of nasoseptal flaps has contributed enormously to decrease its incidence10,15. But, even after the routine use of nasoseptal flaps, 17.8% of our patients experienced a CSF leak postoperatively. The overall rates of postoperative CSF leaks among the endoscopic surgical series are 10.6% (range 0%–27.6%; Table 4). Several different reconstruction techniques were used by the endoscopic reports in the way that a direct comparison cannot be done. However, we did not use routinely any inlay besides abdominal fat, which could be a potential source for our increased rates of CSF leak. Further studies are necessary to address this issue definitely. Open and microscopic cohorts rendered CSF leak rates of 7.1% and 5.1%, respectively7.

Transient DI is a common complication in the immediate postoperative period with a reported incidence of 24.1%–53.6% of the patients (Table 4). It is considered to occur as a result of direct surgical manipulation, especially associated to hypothalamic injury6. Still in the immediate/short-term complication group, we have faced a cavernous sinus violation and consequently internal carotid artery injury, which lead to subarachnoid/tetraventricular haemorrhage followed by severe cerebral vasospasm and death. This is a rare complication of the transsphenoidal surgery with an estimated incidence of 1.58%–4.6%15,26.

From the late complication group, permanent DI and nasosinusal disorders are a common occurrence. Of note, however, is the frequent underreported description of nasosinusal complications. Only two previous studies addressed this complication8,16, which has a significant negative impact on patient’s quality of life27. Nakao and Itakura16 reported an incidence of 2.3% of nasal synechiae without the development of a nasoseptal flap, while Chabot et al.8 use the nasoseptal flap for skull base reconstruction rendering a rate of 15.4% of late nasosinusal symptoms, which is very similar to our results (Table 4).

Limitations

The retrospective data analysis and a reduced sample were the main limiting factors of this study.

In conclusion, endoscopic endonasal transsphenoidal surgery is a valuable treatment option for large or giant pituitary adenomas, which results in high rates of surgical decompression of cerebrovascular structures. Immediate, short-term and late complication rates are at least similar, if not less, to other surgical techniques, and well accepted in terms of disease complexity. Postoperative nasosinusal symptoms are frequently overlooked, but carry a significant negative impact on patient’s quality of life.

References

1. Guiot J, Rougerie J, Fourestier M, Fournier A, Comoy C, Vulmiere J et al. [Intracranial endoscopic explorations]. Presse Med. 1963;71:1225-8. French. [ Links ]

2. Xue-Fei S, Yong-Fei W, Shi-Qi L, Jing-Song W, Yao Z, Ying M et al. Microsurgical treatment for giant and irregular pituitary adenomas in a series of 54 consecutive patients. Br J Neurosurg. 2008;22(5):636-48. doi:10.1080/02688690802346083 [ Links ]

3. Berker M, Hazer DB, Yücel T, Gürlek A, Cila A, Aldur M, et al. Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature. Pituitary. 2012;15(3):288-300. doi:10.1007/s11102-011-0368-2 [ Links ]

4. Santos RP, Zymberg ST, Abucham Filho JZ, Gregório LC, Weckx LLM. Endoscopic transnasal approach to sellar tumors. Rev Bras Otorrinolaringol. 2007;73(4):463-75. doi:10.1590/S0034-72992007000400005 [ Links ]

5. Agrawal A, Cincu R, Goel A. Current concepts and controversies in the management of non-functioning giant pituitary macroadenomas. Clin Neurol Neurosurg. 2007;109(8):645-50. doi:10.1016/j.clineuro.2007.06.007 [ Links ]

6. Gondim JA, Almeida JP, Albuquerque LA, Gomes EF, Schops M. Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach. World Neurosurg. 2014;82(1-2):e281-90. doi:10.1016/j.wneu.2013.08.028 [ Links ]

7. Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of giant pituitary adenomas. Pituitary. 2012;15(2):150-9. doi:10.1007/s11102-011-0359-3 [ Links ]

8. Chabot JD, Chakraborty S, Imbarrato G, Dehdashti AR. Evaluation of outcomes after endoscopic endonasal surgery for large and giant pituitary macroadenoma: a retrospective review of 39 consecutive patients. World Neurosurg. 2015;84(4):978-88. doi:10.1016/j.wneu.2015.06.007 [ Links ]

9. Cappabianca P, Cavallo LM, de Divitiis O, de Angelis M, Chiaramonte C, Solari D. Endoscopic Endonasal Extended Approaches for the Management of Large Pituitary Adenomas. Neurosurg Clin N Am. 2015;26(3):323-31. doi:10.1016/j.nec.2015.03.007 [ Links ]

10. Juraschka K, Khan OH, Godoy BL, Monsalves E, Kilian A, Krischek B, et al. Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection. J Neurosurg. 2014;121(1):75-83. doi:10.3171/2014.3.JNS131679 [ Links ]

11. Cusimano MD, Kan P, Nassiri F, Anderson J, Goguen J, Vanek I, et al. Outcomes of surgically treated giant pituitary tumours. Can J Neurol Sci. 2012;39(4):446-57. doi:10.1017/S0317167100013950 [ Links ]

12. Landeiro JA, Fonseca EO, Monnerat AL, Taboada GF, Cabral GA, Antunes F. Nonfunctioning giant pituitary adenomas: invasiveness and recurrence. Surg Neurol Int. 2015;6:179. doi 10.4103/2152-7806.170536 [ Links ]

13. Di Maio S, Cavallo LM, Esposito F, Stagno V, Corriero OV, Cappabianca P. Extended endoscopic endonasal approach for selected pituitary adenomas: early experience. J Neurosurg. 2011;114(2):345-53. doi:10.3171/2010.9.JNS10262 [ Links ]

14. Hofstetter CP, Nanaszko MJ, Mubita LL, Tsiouris J, Anand VK, Schwartz TH. Volumetric classification of pituitary macroadenomas predicts outcome and morbidity following endoscopic endonasal transsphenoidal surgery. Pituitary. 2012;15(3):450-63. doi:10.1007/s11102-011-0350-z [ Links ]

15. Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Paluzzi A, Wang EW, Snyderman CH. Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations. J Neurosurg. 2013;118(3):621-31. doi:10.3171/2012.11.JNS121190 [ Links ]

16. Nakao N, Itakura T. Surgical outcome of the endoscopic endonasal approach for non-functioning giant pituitary adenoma. J Clin Neurosci. 2011;18(1):71-5. doi:10.1016/j.jocn.2010.04.049 [ Links ]

17. Hardy J. Transphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg. 1969;16:185-217. [ Links ]

18. Mohr G, Hardy J, Comtois R, Beauregard H. Surgical management of giant pituitary adenomas. Can J Neurol Sci. 1990;17(1):62-6. [ Links ]

19. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva F et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010;95(7):3141-8. doi:10.1210/jc.2009-2670 [ Links ]

20. Colao A, Attanasio R, Pivonello R, Cappabianca P, Cavallo LM, Lasio G, et al. Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2006;91(1):85-92. doi:10.1210/jc.2005-1208 [ Links ]

21. Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg. 1997;87(1):44-51. doi:10.3171/jns.1997.87.1.0044 [ Links ]

22. Tabaee A, Anand VK, Barrón Y, Hiltzik DH, Brown SM, Kacker A, et al. Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg. 2009;111(3):545-54. doi:10.3171/2007.12.17635 [ Links ]

23. Cappabianca P, Cavallo LM, Esposito F, De Divitiis O, Messina A, De Divitiis E. Extended endoscopic endonasal approach to the midline skull base: the evolving role of transsphenoidal surgery. Adv Tech Stand Neurosurg. 2008;33:151-99. doi:10.1007/978-3-211-72283-1 [ Links ]

24. Paiva Neto MA, Vandergrift A, Fatemi N, Gorgulho AA, Desalles AA, Cohan P et al. Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas. Clin Endocrinol (Oxf). 2010;72(4):512-9. doi:10.1111/j.1365-2265.2009.03665.x [ Links ]

25. McLaughlin N, Eisenberg AA, Cohan P, Chaloner CB, Kelly DF. Value of endoscopy for maximizing tumor removal in endonasal transsphenoidal pituitary adenoma surgery. J Neurosurg. 2013;118(3):613-20. doi:10.3171/2012.11.JNS112020 [ Links ]

26. Zhao B, Wei YK, Li GL, Li YN, Yao Y, Kang J, et al. Extended transsphenoidal approach for pituitary adenomas invading the anterior cranial base, cavernous sinus, and clivus: a single-center experience with 126 consecutive cases. J Neurosurg. 2010;112(1):108-17. doi:10.3171/2009.3.JNS0929 [ Links ]

27. Little AS, Kelly D, Milligan J, Griffiths C, Prevedello DM, Carrau RL, et al. Predictors of sinonasal quality of life and nasal morbidity after fully endoscopic transsphenoidal surgery. J Neurosurg. 2015;122(6):1458-65. doi:10.3171/2014.10.JNS141624 [ Links ]

Received: January 5, 2016; Accepted: February 17, 2016

Correspondence: Marcus André Acioly; Departamento de Especialidades Cirúrgicas, Divisão de Neurocirurgia; Rua Marquês de Paraná, 303, 3º andar; 24033-900 Niterói RJ, Brasil; E-mail: marcusacioly@yahoo.com.br

Conflict of interest: There is no conflict of interest to declare.

Creative Commons License  This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.