Microscopic endonasal access in pituitary surgery for ... · be forgotten by ear, nose and throat...

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For citation purposes: Raja H, Upile T, Jerjes W, Charakias N, Dewan V, Redfern RM. Microscopic endonasal access in pituitary surgery for tumour removal: eight-year review of nasal complications. Head Neck Oncol. 2012 Nov 23;4(4):76.

Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY)

AbstractIntroductionTrans-sphenoidal pituitary resection is possible via the traditional micro-scopic trans-septal approach or newer endoscopic transnasal approach. There is little in the literature to describe the nasal complications of the endona-sal microscopic resection of pituitary lesions. We describe our experience of a single surgeon series and specifi-cally the nasal complications from this method.MethodWe preformed an 8-year retrospec-tive case notes review of transnasal endoscopic resections of 70 pituitary tumours. The data were collected on a proforma developed after consulta-tion with a multidisciplinary team and validated independently by ran-dom interval analysis.ResultsGross tumour removal rate was achieved in 77.1% (n = 54/70) cases by 24 months follow-up. One patient experienced a purulent nasal dis-charge, which required antibiotic intervention, whilst another had per-sistent maxillary nerve damage with paraesthesia. No patient experienced persistent epistaxis, septal perfora-tion, anosmia, cerebrospinal fluid

Microscopic endonasal access in pituitary surgery for tumour removal: eight-year review of nasal complications

H Raja1*, T Upile2, W Jerjes3, N Charakias4, V Dewan5, RM Redfern6

leaks or meningitis. Unfortu nately, one patient succumbed from the con-sequences of internal carotid artery damage.ConclusionNasal complication rates from this method were low. A microscope can be successfully used in an endonasal approach to the sella on its own. It can also be a useful adjunct to the endoscope and this skill should not be forgotten by ear, nose and throat surgeons and neurosurgeons. It ap-pears that the method of approaching the sella (transnasal vs trans-septal) rather than the instrument used helps to determine the rate of nasal complications.

IntroductionThere have been many advances in approaches to the pituitary gland over the past century. Having been first performed transcranially1, when-ever the anatomical configuration of the condition allows, the preferred approach for lesions of the sella is trans-sphenoidal (Figure 1). Access to the sphenoid sinus has generally been performed using a midline sub-mucosal resection. This trans-septal route uses either a sublabial ap-proach to the septum or an incision in the mucosa commencing within the anterior nares; both techniques usually involve resection of at least part of the nasal septum. Further-more, even in experienced hands, the incidence of nasal septum perfora-tion is reported to be 3.3%. A direct transnasal approach to the sphenoid sinus avoids potential complications of submucosal resection and, in case of a translabial approach, removal of the maxillary spine. To assess the ben-efits of the direct transnasal approach,

a retrospective study of complica-tions associated with this procedure was undertaken.

Access to the pituitary gland had been microscopic and via the trans-septal route following the work of Hardy in the 1960s and 1970s2,3. In recent years, however, the endoscope has started to establish itself as the option of choice because of improved visualisation offered to the operating surgeon and excellent short-term re-sults. However, long-term resection results of this technique are still awaited. Nevertheless, it carries a

* Corresponding authorEmail: [email protected] Department of ENT, University Hospital

Birmingham, UK2 Department of Otolaryngology, Bielefeld

University, Germany3 Leeds Institute of Molecular Medicine,

University of Leeds, UK4 Department of ENT, Lancashire Teaching

Hospitals, UK5 Department of Anatomy, University of

Birmingham, UK6 Department of Neurosurgery, Morriston

Hospital, UK

Figure 1: Clinico-pathological image showing the volume effect and loca-tion of a pituitary tumour. Note its intimate relationship to the sphenoid and basisphenoid region of the skull base. Also note the short distance to the cribiform plate and the superior aspect of the internal nasal anatomy indicating that transnasal approaches may have utility in the removal of these types of lesions. In addition, the circumscribed nature of the tumour and its intimate relationship to the location of the path of the internal ca-rotid arteries and optic chiasma can be appreciated.


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clear advantage in the published data thus far over the microscopic trans-septal technique, with equivalent or better results and fewer complica-tions4. However, majority of the com-parative studies have not compared endoscopic transnasal technique with microscopic transnasal tech-nique, as the endoscopic technique has its own disadvantages.

Both techniques usually involve re-section of at least part of the nasal septum. Trauma to the nose and sub-sequent complications can form a significant basis of morbidity for pa-tients undergoing pituitary surgery. They may not be perceived as being as important as other life-threatening complications of sellar and parasellar regions, but they can leave the pa-tients with symptoms that often will require ear, nose and throat (ENT) input. Even in experienced hands, the incidence of nasal septum perfo-ration is reported to be 3.3%5. We present our retrospective series of the complications experienced by the direct transnasal microscopic ap-proach with no endoscopic assis-tance. This is the largest case series of its kind in Europe and the fifth largest overall.

Methods and materialsAll patients presenting with pituitary tumours (Figure 2) were managed in a multidisciplinary environment with teams including neuroendocrinology specialists with a neurosurgeon and two endocrinologists, supported by Departments of Neuropathology, Neuroradiology and Ophthalmology. The records of 70 consecutive pa-tients undergoing pituitary surgery via the transnasal route by a single surgeon during the preceding 8 years were obtained. There were 42 males and 28 females. The mean age was 56 years (range, 19–85 years). There were 66 pituitary adenomas, 3 cra-niopharyngiomas and 1 meningioma.

Pre-operative imaging included coronal magnetic resonance imaging (MRI) in all cases (Figures 3 and 4).

betadine solution and the right thigh was prepared, in expectation should a fascia lata graft be required. Surgery was undertaken via the right anterior nares in all cases using the operating microscope and with lateral screen-ing using an image intensifier (Figures 5–7). The sphenoid sinus was approached via a direct transna-sal approach. Any nasal polyps en-countered were reduced using bipolar coagulation or microdebrider. After coagulating the nasal mucosa overlying the right side of the vomer, a posterior right septotomy ± pos-terior septectomy was performed.

Figure 2: An image of a pathology slide stained with haematoxylin and eosin and immunostains showing a somatotrophinoma.

Figure 3: An intraoperative screen-ing plain X-ray image within a se-quence showing a localisation hook introduced via the nasal cavity and into the sphenoid paranasal sinus.

Figure 4: An intraoperative screen-ing plain X-ray image within a se-quence showing the localisation hook advanced into the region of the pitui-tary fossa.

In many cases, computed tomogra-phy (CT) imaging was also available. In addition to providing confirmation that a trans-sphenoidal approach was appropriate, the coronal images (MRI or CT) were used to define the position and characteristics of the sphenoid septum, an essential land-mark in establishing the position of the midline pre-operatively. Cefuroxime (1.5 g) was intravenously adminis-tered routinely with induction, to-gether with hydrocortisone (100 mg).

Once positioned on the operating table, the anterior nasal mucosa of both nostrils was liberally coated with benzoylmethylecgonine paste. The face was prepared using aqueous

Figure 5: An intraoperative screen-ing plain X-ray image within a se-quence showing the localisation hook retracted from the pituitary fossa.

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production, prior to discharge from hospital. Accordingly, all patients re-mained in hospital for 5–6 days after surgery. The first routine neuroendo-crine clinic follow-up appointment occurred within 4–8 weeks of surgery.

ResultsIn total, gross tumour removal rate was achieved in 54 of 70 cases (77.1%) at 24-month follow-up (Table 1).

EpistaxisThere were no cases of significant post-operative epistaxis. Most pa-tients had a light discharge of blood-stained mucus after removal of the nasal packs, but in all cases, this stopped the same day. Seven patients (10%) experienced a discharge suffi-cient to be documented in the medi-cal records, but no patients had to undergo re-packing of the nose or had frank blood discharging from the nostrils. There were no cases of de-layed (secondary) epistaxis during hospital stay nor was it recorded at follow-up.

Septal complicationsThere were no cases of septal perfo-ration or deformity at 3, 6 and 12 months follow-up. A number of pa-tients, particularly those with acro-megaly, reported improvement in their breathing and reduced ten-dency to snoring after surgery.

Anosmia/hyposmiaPatients were specifically asked about change in their sense of smell and taste. None reported any abnor-mality immediately after operation and at follow-up.

Other symptomsOne patient developed numbness of the right cheek because of damage to the maxillary division of the trigemi-nal nerve resulting from inadvertent straying from the correct trajectory in a procedure undertaken by an experi-enced trainee. This unfortunate com-plication emphasises the importance

the bone may be hyperostotic, a small hammer and chisel. Use of a high-speed hand drill for this stage of the procedure has been advocated but was not used in this series. After gaining access to the sphenoid sinus, its mucosa would be stripped and the sella floor opened. The procedure was undertaken under X-ray control.

At the conclusion of the procedure, a Valsalva manoeuvre was performed in all cases. If cerebrospinal fluid (CSF) leakage was evident, then a fas-cia lata graft was used to seal the sella floor supplemented with tissue glue. In such cases, adjunctive spinal drain-age would be used for 3 days post-operatively. Prior to closure (and, where used, insertion of the myofas-cial graft), meticulous haemostasis would be established within the pitu-itary fossa, often by packing and gen-tle irrigation with saline and/or hydrogen peroxide, and always by pa-tient observation. After removing the retractor from the right anterior na-res, a Killian’s retractor would be passed into the left side to reposition the septum. In three cases, a small re-leasing incision was required in the right anterior nares to pass the Hardy retractor, and this incision would then be closed with one or two inter-rupted 5/0 nylon sutures. The nose was packed bilaterally using saline-soaked 7.5-cm Merocel packs within two fingers of a standard surgical glove, retained in place by a pack se-cured by ties passed behind the head. Antibiotic prophylaxis was given to all cases for 24 hours post-opera-tively by administering cefuroxime (750 mg) intravenously every 8 hours (3 doses). Throughout most of this series, the nasal packs were removed on the second post-operative day; more recently, the packs have been removed the following morning (about 18 hours post-operatively) without obvious adverse sequelae. The service uses a well-established post-operative protocol for adminis-tration of hydrocortisone, and as-sessment of endogenous cortisol

Muco-periosteal flaps were raised on both sides through the right sided posterior incision to expose both sides of the vomer. Whenever acces-sible, further access to the sphenoid sinus would be obtained via the adi-tus located high up to the right of the midline. Exposure would then be fa-cilitated using pituitary rongeurs or, particularly in acromegalics when

Figure 6: A T1-weighted MRI scan with contrast showing a pituitary le-sion showing its intimate relation-ship with the sphenoid sinus and cavernous sinus.

Figure 7: A T1-weighted MRI scan with contrast showing a pituitary le-sion (1.31 cm in diameter) showing its intimate relationship with the sphenoid sinus and cavernous sinus. The close approximation of the lesion to the posterior aspect of the nasal cavity again showing the utility of transnasal approaches for the re-moval of these lesions.


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the microscope can be associated with a high incidence of nasal compli-cations depending on the approach used. A literature search revealed that rhinological complications after sublabial trans-septal trans-sphenoi-dal surgery have ranged as high as 28%–35%8,9. Nasoseptal perfora-tions have been reported in 1%–13% of patients9, upper lip anaesthesia in 5%–28% and post-operative anos-mia in 5.5%8.

A study performed by Marquardt et al.10,11 reported post-operative complications of epistaxis (11.5%), facial swelling (9.6%), ecchymotic cheeks (15.4%) and raccoon eyes (3.8%). Watson et al.11 and Wilson et al.12 found that the sublabial ap-proach to the sphenoid can cause de-nervation or pulp death of some of the anterior teeth.

Although endoscopic pituitary sur-gery is proving to have clear advan-tages in terms of complications and visualisation over the traditional trans-septal approach and, at least in the short-term, it is proving as effective in tumour removal, however, it has its own disadvantages. Gondim et al.13 reported reduction of field depth, constant need of manual control of the endoscope and required experi-ence of the endoscope technique. In addition to this, a higher incidence of post-operative CSF leaks is re-ported14. Anatomical variations may also hinder access to the sphenoid si-nus. A prospective study of anatomi-cal variations in patients undergoing this procedure found that septal de-viation was the most commonly visu-alised variation15. The incidence of this may be 63% in patients with si-nonasal symptoms16. Nevertheless, a recent meta-analysis by Tabee et al.4, looking at 9 studies (821 patients), showed gross tumour removal rate and hormone resolution of 78%–84%. Mortality rate was 0.24% (2/821—both because of vascular injury) with a CSF leak rate of 2%.

There has, however, been less comparison in the literature of the

complications. Microscopic pituitary surgery has the advantage of being easily used by a single surgeon and affords a stereoscopic three-dimen-sional view. Inevitably, when compared with the endoscopic technique, visu-alisation of the surgical field as well as manoeuvrability is restricted4,6.

A recent meta-analysis of the endo-scopic technique showed it to be a safe and viable procedure when as-sessing gross tumour removal rates, endocrine function and complication rates4. In fact, endocrine outcomes in the short-term have been shown to be better with the endoscopic tech-nique when compared with the mi-croscopic technique7. Long-term results for endoscopic surgery, how-ever, are not yet available despite these promising short-term results. For this reason, microscopic pituitary surgery still has an important role to play in this domain.

The major complications for pitu-itary surgery include CSF leaks, vas-cular injury, intracranial injury, endocrine abnormalities and infec-tion. Complication rates in both meth-ods have been found to be comparable6. Otolaryngologists are becoming in-creasingly involved in the care of this population of patients because of es-tablished familiarity with nasal anat-omy and with the endoscope.

In theory, the endoscopic approach has a decreased potential for nasal complications because of limited sep-tal dissection7. However, the use of

of paying careful attention to ana-tomical landmarks and to the periop-erative lateral radiological screening.

One patient had a purulent nasal discharge at outpatient follow-up, which responded to a course of broad spectrum antibiotics prescribed by an ENT surgeon.

There were no complaints of nasal or facial pain resulting from the pro-cedure, and no cases of anosmia. There were no complaints of intra-oral pain or numbness. However, there was one death resulting from intrasellar haemorrhage from the in-ternal carotid artery [mortality rate (n = 1/70), 1.4%; overall complica-tion rate (n = 3/70), 4.2%].

DiscussionThe use of the microscope for pitu-itary surgery has been established as the gold standard for the latter part of the 20th century following the work of Hardy2,3. However, in the 1990s, the use of the endoscope be-came increasingly prevalent due to the unparalleled view of the surgical field it afforded. There has been a substantial amount of work done re-cently to compare these two tech-niques to establish the gold standard.

However, both of these techniques are not without their advantages and disadvantages. Endoscopic pituitary surgery is slowly becoming the procedure of choice because of im-proved visualisation of the surgical field, reduced length of stay and

Table 1 Total complication rateComplication rates At 24 months follow-up (%)Epistaxis 0Septal perforation 0Anosmia 0CSF leak 0Meningitis 0Purulent nasal discharge 1.4 (n = 1/70) resolved with antibioticsMaxillary nerve damage 1.4 (n = 1/70)Mortality 1.4 (n = 1/70) internal carotid artery damage

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assistance was utilised in 163 cases. Our results for nasal complications are extremely favourable when com-pared with all the aforementioned series. The mortality rate of 1.4% is higher than that in the Fatemi (0.2%) series20 and in the recent meta-analysis of endoscopic work (0.24%)4. How-ever, Ciric et al.5 in a survey concluded that there was significant reduction in the complication rates with increasing experience at thresholds of 200 and 500 cases. Our series only has 70 cases, but it is one of the few studies of pure transnasal microscopic work without the assistance of an endoscope.

In our review of the literature, we found only two other sizable recent series looking at this method of exci-sion with respect to nasal complica-tions reported by Marquardt et al.10 (104 patients) and Zada et al.21 (78 patients). The findings of these stud-ies are summarised in Table 2.

Further, subgroup analysis in the series by Zada et al.21 and Dusick et al.22 demonstrates that of the sub-jects who had previously undergone trans-septal surgery, approximately 87% preferred the endonasal micro-scopic approach.

Cooke and Jones18 reported no septal, sinus or dental complications, but they had a major complication rate of 5.8%. There followed a series of smaller studies (such as those by Tan and Jones19) which reported no septal perforation and only 0.5% of nasal pain, which resolved after 1 week.

To date, the largest series on the endonasal microscopic approach to the sella has been by Fatemi et al.20 involving 812 patients. Surgical com-plications included 19 post-operative CSF leaks (2%), 6 post-operative hae-matomas (0.7%), 4 carotid artery in-juries (0.4%), 4 new permanent neurological deficits (0.4%), 3 cases of bacterial meningitis (0.3%) and 2 deaths (0.2%). The overall complica-tion rate was higher in the first 500 cases in the series and in extended approach cases. When we specifically look at nasal complications, the rates were 1% for delayed epistaxis requir-ing embolisation and 1.5% for delayed sinusitis requiring sinus endoscopy. The authors have chosen not to men-tion how sinusitis was defined and whether sinus washout or surgery was required. Here the endoscopic

endoscopic endonasal approach with the microscopic endonasal approach to the sella. The first reported method of the direct transnasal approach was by Griffith and Veerapen17. Whilst submucous trans-septal approaches to the sphenoid sinus afford the ad-vantage of remaining directly in the midline during the approach to the sella and also confer a slightly better exposure, the reported incidence of nasal complications from such tech-niques is high.

A literature search revealed that rhinological complications after sub-labial trans-septal trans-sphenoidal surgery have ranged as high as 28%–35%2,3. Nasoseptal perforations have been reported in 1%–13% of patients3, upper lip anaesthesia in 5%–28% and post-operative anos-mia in 5.5%2.

The first reported series of the di-rect transnasal approach was by Griffith and Veerapen17, who in a se-ries of 150 patients showed no septal perforations; 2 of 150 patients had secondary epistaxis and both were treated conservatively with no other major rhinological complications. Hyposmia was also noticed in 0.5% of patients. In the aforementioned study, only one patient was admitted for a secondary haemorrhage 10 days post-operatively.

It may be argued that better out-comes are to be expected following surgery that adopts a strictly midline approach, but in our retrospective study of 70 cases, the outcomes com-pared very favourably with those re-ported by Ciric et al. For example, we achieved a biochemical cure rate in acromegaly of 75% (9/12 cases) from surgery alone compared with 60% in Ciric’s study, and an almost identical rate of production of hypo-pituitarism of 19%5. Furthermore, a direct transnasal approach is easily adaptable to endoscopic techniques and to image-guided or frameless stereotactic assistance.

A subsequent study of 104 patients using the direct technique done by

Table 2 Summary of nasal complications from endonasal microscopic surgery from previous series in the literatureAuthor Number

of casesNasal complications following microscopic endonasal surgery

Fatemi et al.20

812 Incidence of epistaxis requiring embolisation was 1% and delayed sinusitis requiring sinus endoscopy was 1.5%

Zada et al.21 78 Sinonasal problemsComplication No problem

(%)Severe

difficulty (%)Facial pain 83 4Nasal congestion 74 3Decreased nasal airflow 77 4Decreased sense of smell 73 4

Marquardt et al.10

104 Epistaxis was reported in 1 case

Cooke et al.18 104 Major complication rate of 5.8% with no reported long-term nasal complications


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the pituitary gland. Neurosurgery. 1982 Feb;10(2):236–41.12. Wilson WR, Khan A, Laws ER Jr. Trans-septal approaches for pituitary surgery. Laryngoscope. 1990 Aug;100(8):817–9.13. Gondim J, Schops M, Tella OI Jr. Transnasal endoscopic surgery of the sel-lar region: study of the first 100 cases. Arq Neuropsiquiatr. 2003 Sep;61(3B): 836–41.14. D’Haens J, Van Rompaey K, Stadnik T, Haentjens P, Poppe K, Velkeniers B. Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: a retro-spective comparison with traditional transsphenoidal microsurgery in the same institution. Surg Neurol. 2009 Oct; 72(4):336–40.15. van Lindert EJ, Ingels K, Mylanus E, Grotenhuis JA. Variations of endonasal anatomy: relevance for the endoscopic endonasal transsphenoidal approach. Acta Neurochir (Wien). 2010 Jun;152(6): 1015–20.16. Sazgar AA, Massah J, Sadeghi M, Bagheri A, Rasool E. The incidence of con-cha bullosa and the correlation with nasal septal deviation. B-ENT. 2008;4(2):87–91.17. Griffith HB, Veerapen R. A direct trans-nasal approach to the sphenoid sinus. Technical note. J Neurosurg. 1987 Jan; 66(1):140–2.18. Cooke RS, Jones RA. Experience with the direct transnasal transsphenoidal approach to the pituitary fossa. Br J Neurosurg. 1994;8(2):193–6.19. Tan LK, Jones RA. Nasal complications of the direct transnasal approach to the pituitary fossa. Br J Neurosurg. 1995; 9(6):739–42.20. Fatemi N, Dusick JR, de Paiva Neto MA, Kelly DF. The endonasal microscopic ap-proach for pituitary adenomas and other parasellar tumors: a 10-year experience. Neurosurgery. 2008 Oct;63(4 Suppl 2): 244–56.21. Zada G, Kelly DF, Cohan P, Wang C, Swerdloff R. Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of ef-ficacy, safety, and patient impressions. J Neurosurg. 2003 Feb;98(2):350–8.22. Dusick JR, Esposito F, Mattozo CA, Chaloner C, McArthur DL, Kelly DF. Endonasal transsphenoidal surgery: the patient’s perspective-survey results from 259 patients. Surg Neurol. 2006 Apr; 65(4):332–41.

the rate of nasal complications. A full comparative trial of both endonasal methods is needed.

Abbreviations listCSF, cerebrospinal fluid; CT, com-puted tomography; ENT, ear, nose and throat; MRI, magnetic resonance imaging.

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The advent of the endoscope has heralded a new age in pituitary sur-gery with extremely promising short-term results. However, microscopic surgery, which has been the gold standard, still has a role to play in this arena. Major complication rates have been shown to be similar for both techniques. Our results, along with those of other series of the endonasal microscopic approach, show that na-sal complication rates are low and the perception that this may be fur-ther reduced by endoscopic surgery may not be founded.

A full comparative trial of endona-sal endoscopic vs endonasal micro-scopic pituitary surgery is needed, along with the long-term data on en-doscopic cure rates. As long as these long-term cure rates are equivalent to microscopic resection, the endo-scope is likely to be the preferred instrument of choice. However, the endonasal microscopic method should not be totally forgotten to en-sure that the skill of this relatively safe method is not lost.

ConclusionOur findings add weight to those of other authors that a direct transnasal approach provides safe trans-sphe-noidal access to the sella with a very low rate of nasal complications. We would again emphasise the impor-tance of strict adherence to anatomi-cal landmarks and to the role of lateral radiological screening.

1. Nasal complication rates from this method are low.

2. A microscope can be successfully used in an endonasal approach to the sella on its own.

3. It can also be a useful adjunct to the endoscope and this skill set should not be forgotten by ENT surgeons and neurosurgeons.

4. It appears that the method of approaching the sella (transnasal vs trans-septal) rather than the instrument used helps determine

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