International Journal of Pediatric Otorhinolaryngology 74 (2010) 1298–1302

Endoscopic endonasal transsphenoidal surgery for sellar tumors in children

Davide Locatelli a, Luca Massimi b,*, Mario Rigante c, Viola Custodi a, Gaetano Paludetti c,Paolo Castelnuovo d, Concezio Di Rocco b

a Department of Neurosurgery, San Matteo Hospital, Pavia, Italyb Pediatric Neurosurgery, A. Gemelli Hospital, Rome, Italyc ENT Surgery, A. Gemelli Hospital, Rome, Italyd Department of ENT, University of Insubria, Varese, Italy

A R T I C L E I N F O

Article history:

Received 1 July 2010

Received in revised form 9 August 2010

Accepted 12 August 2010

Available online 9 September 2010

Keywords:

Endoscopic endonasal approach

Transsphenoidal surgery

Microsurgery

Sellar region

Clivus

Pediatric age

A B S T R A C T

Objective: Endoscopic endonasal transsphenoidal surgery (EETS) is still rarely used in pediatric subjects

compared with adults. Reports on EETS in children appeared only recently in the literature, usually

regarding small series. The aim of the study is to assess the actual role and the limits of EETS in children

with sellar tumors by reporting a two-centers experience.

Methods: Twenty-seven children (mean age: 12.2 years) were operated on during the last decade.

Seventeen patients harbored a sellar mass, 7 a suprasellar tumor, and 3 a clival mass. Laboratory

investigations revealed hypopituitarism in 6 children and hormone hypersecretion in 9. All the

operations were carried out by a team including both ENT surgeon and neurosurgeon using a dedicated

18-cm long rigid endoscope (2.7 mm and 4 mm diameter) through the direct paraseptal or the

transethmoidal or the transpterygoid route.

Results: Overall, 29 operations were performed. Gross total tumor resection was obtained in 22 children

(81.5%) while a subtotal and a partial removal in 2 (7.5%) and 3 cases (11%), respectively. Pituitary

adenoma was the most common histotype (12 cases), followed by craniopharyngioma (5) and Rathke’s

cleft cyst (4). No surgical mortality or neurological morbidity or late nasal complications were observed.

Postoperative CSF fistula occurred in 3 patients. All children are alive at current follow-up (average: 8.6

years). Preoperative hypopituitarism disappeared or improved in 4 cases and was stable in the remaining

2 (no new hormone deficits appeared).

Conclusion: EETS is a safe and effective surgical option also in children. As for adults, it allows to manage

most of the tumor lesions of the sellar region with stable long-term results.

� 2010 Elsevier Ireland Ltd. All rights reserved.

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1. Introduction

In the last two decades, neuroendoscopy underwent animpressive development in terms of techniques and sophisti-cated surgical tools that currently permits to treat a wide rangeof diseases. Endoscopic endonasal transsphenoidal surgery(EETS) has become a relatively common surgical procedure totreat the anterior skull base tumors, especially in adult patients.EETS is less utilized in the pediatric population mainly becauseof the higher prevalence of such tumors in adults (namelypituitary adenomas and meningiomas) and the less favorableanatomical conditions in children (minute nostrils, narrow nasalcavities, reduced/absent pneumatization of the sphenoid sinus).However, some studies concerning EETS in small series of

* Corresponding author at: Institute of Neurosurgery – A. Gemelli Hospital, Largo

A. Gemelli, 8, 00168 Rome, Italy. Tel.: +39 0630154587; fax: +39 0630156660.

E-mail address: lmassimi@email.it (L. Massimi).

0165-5876/$ – see front matter � 2010 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ijporl.2010.08.009

children have recently appeared, showing an effectiveness of theprocedure comparable to that of the older counterpart [1–4].

We describe the results obtained with EETS in the largest seriesof children with tumors of the sellar and clival region reported sofar. The goal of this report is to evaluate whether EETS is a suitablesurgical option in pediatric subjects.

2. Methods

2.1. Series

The series is composed by 27 pediatric patients (11 boys and 16girls) operated on at the Neurosurgical Unit of the San MatteoHospital, Pavia, Italy, and at the Pediatric Neurosurgery of the A.Gemelli Hospital, Rome, Italy, during the last decade. The mean ageat surgery was 12.2 years, ranging from 4 to 18 years. Seventeenpatients harbored a purely sellar mass, 7 a sellar/supra- and para-sellar tumor, and 3 a clival mass. The conchal variant of thesphenoid sinus was found in one case.

D. Locatelli et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1298–1302 1299

All children admitted during this period for sellar/suprasellar orclival masses were selected for EETS. When a Rathke’s cyst cleftwas suspected, it was followed up and treated only in case ofprogressive growth. Huge craniopharyngiomas extending into themiddle and/or the posterior cranial fossa were not considered forEETS.

The preoperative clinical picture was mainly characterized byraised intracranial pressure syndrome, endocrinologic imbalanceand cranial nerve palsy (Table 1). Laboratory investigationsrevealed hypopituitarism in 6 children and hormone hypersecre-tion in 9 (Table 1).

2.2. Pre-surgical assessment

The clinical preoperative work up consisted of physicalexamination, ophthalmologic and endocrinologic evaluation, andENT assessment of the nasal cavities to estimate the feasibility ofthe endonasal approach.

All the patients were investigated through hormonal screeningand brain MRI, as well as CT scan of the anterior skull base that wasutilized to point out possible anomalies of the anatomical bonelandmarks. Neuroimaging for neuronavigation was obtained inselected cases (e.g. non-pneumatized sphenoid sinus).

2.3. Surgical details

All the operations were carried out by a team including bothENT surgeon and neurosurgeon alternating as first operatoraccording to the different phases of the operation.

The surgical equipment included an 18-cm long rigid endo-scope (diameter: 4 mm and 2.7 mm), with 08, 308, 458 and 708optics, and a dedicated dissection and microsurgical instrumen-tarium.

The operation was realized with the patient in supine positionand the head elevated (10–308) and slightly tilted to the right. Themonitors for endoscopy and neuronavigation as well as the scrubnurse’s table were positioned in front of the surgeons, closed to theright side and the left side of the patient’s head, respectively.

The ‘‘two-nostrils-four-hands’’ technique was routinely utilizedas well as the so-called ‘‘diving technique’’, which was applied toimprove the visualization of the surgical field. It is based on the samedissection procedures of the ventricular endoscopy, which allow thesurgeon to optimize the vision with a dynamic fluid film that is usedto fill the surgical field and acts as a concave–convex lens [5].

The best surgical route to approach the sphenoid sinus (directparaseptal, transethmoid-sphenoidal, or transethmoid–transpter-ygoid-sphenoidal) was chosen according to the tumor extensionand the surgical anatomy, as described elsewhere [6,7]. Theunilateral removal of the middle turbinate was rarely required.

In case of conchal variant of the sphenoid sinus, the sphenoidbone was drilled to reach the sella. It was realized using high speeddrill and CT-guided neuronavigation.

Table 1Preoperative clinical picture.

Neurological

sign/symptoms

No. patients Endocrinological

alterations

No. patients

Raised ICP 8 Short stature 3

Cranial nerve palsy 3 Cushing disease 5

Epileptic seizuresa 1 Dysmenorrhoea 2

Galattorrhoea 2

Hypopituitarism 6

ACTH hypersecretion 6

PRL hypersecretion 3

Insipid diabetes 1

a Due to electrolytic imbalance.

An extended approach to the clivus was performed for clivalmasses.

When the sellar floor plastic was required at the end of thesurgical procedure, a multi-layered reconstruction with autogenicmaterials (fascia lata, septal or turbinate mucoperiosteum, septalcartilage, turbinate bone) and/or commercially available duralsubstitutes was done.

2.4. Post-surgical follow-up

All the patients underwent a strict clinical and radiologicalfollow-up, including: (1) endoscopic evaluation 2–3 weeks aftersurgery using the nasal endoscope to visualize the correctrecreation of the mucosal layer in the sphenoid sinus, theeffectiveness of the sinus ventilation, and the presence of sinechiasor crusts to be removed; (2) neuro-radiological follow-up,consisting of early CT scan (first to third postoperative day) andlate MRI (3–6–12 months after surgery, and then yearly); (3) serumand urinary hormonal dosages in the postoperative time followedby endocrinological follow-up, according to the patients’ char-acteristics; (4) early (1 month) and late (1 year) visual acuity andvisual field evaluation.

3. Results

Overall, 29 surgical procedures were performed (2 childrenrequired a second EETS; see below). The approach was carried outthrough a direct paraseptal route in 24 cases (bilateral in 18 andmonolateral in 6), through a transethmoidal approach in 4 andthrough a transpterygoid approach in the remaining one. Twochildren underwent EETS as secondary procedure following aprevious transcranial approach.

Based on MRI, a gross total resection of the tumor was obtainedin 81.5% of the cases (22 children) (Fig. 1) while a subtotal and apartial removal were realized in the remaining 7.5% (2) and 11%(3), respectively. Pituitary adenoma was the most commonhistotype (12 cases), followed by craniopharyngioma (5) andRathke’s cleft cyst (4). Pituitary adenomas and Rathke’s cleft cystsresulted as the best removable tumors (Fig. 2). Details onhistological diagnosis and surgical resection are summarized inTable 2.

At current follow-up (average: 8.6 years, range: 1–12.4 years), 2children showed a tumor recurrence after a gross total removal oftheir neoplasm: one patient, harboring an epitheliod sarcoma thatrelapsed 9 months after surgery and 5 months after irradiation, isundergoing salvage chemotherapy for tumor progression; thesecond child had an ACTH secreting adenoma, which recurred 2years after surgery, and underwent a second EETS with completetumor excision. All the remaining patients are disease-free,including the child with clival chordoma who received proton-beam radiotherapy after surgery. Three patients with subtotally/partially excised craniopharyngiomas are receiving neuroimagingfollow-up since no tumor progression occurred so far. With regardsto the remaining 2 children with partially excised tumors,chemotherapy was administered to one of them because ofLangerhans histiocytosis, obtaining a progressive tumor regres-sion; second EETS was attempted to a young boy with a regrowingcraniopharyngioma, achieving a subtotal resection.

The series was not burdened by surgical mortality or byneurological morbidity. No early or late nasal complications werenoticed. Postoperative CSF fistula occurred in 3 patients (onepituitary adenoma and 2 craniopharyngiomas): in two cases, theCSF leakage was resolved with a multi-layered sellar repair and, inthe remaining one, by transient external lumbar drainage. Acutepostoperative hydrocephalus occurred in a 4-year-old boy treatedfor an epithelioid sarcoma possibly following a mild subarachnoid

[(Fig._1)TD$FIG]

Fig. 1. Preoperative (A) and postoperative sagittal MRI (B) showing the gross total removal of a clival sarcoma in a 4-year-old boy.

D. Locatelli et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1298–13021300

hemorrhage; it required only a transient external ventriculardrainage for its resolution.

All children are alive at current follow-up. Raised intracranialpressure syndrome promptly recovered after the operation in allpatients. Nor worsening of preoperative neurological deficit nornew alterations were noticed postoperatively. Cranial nerve palsydisappeared in two cases and improved in the remaining one.Epileptic seizures regressed. Preoperative hypopituitarism dis-appeared or improved in 4 cases but was stable in the remaining 2(see also Table 3); no new hormone deficits appeared in thepostoperative course. However, 3 patients currently rely onchronic hormone replacement. Hormone hypersecretion regressedin all cases. A moderate obesity is evident in one child operated onfor craniopharyngioma.

4. Discussion

In spite of the increasing application of EETS in the pediatricpopulation, only a few studies concerning this subject are currentlyavailable in the literature. Most of them consider small pediatricseries, alone or as part of mixed cohorts, or series where the youngpatients are treated by combined approaches (e.g. transnasal and/or transcranial endoscopically assisted surgery) [1,3,4,8,9]. Amongthe series of 22 children with craniopharyngioma operated on bytranssphenoidal route by Jane et al., only 6 patients underwent apure endoscopic endonasal approach [2].

The series here presented consists of 27 pediatric patients withsellar/suprasellar and clival tumors treated with EETS in twoCenters both devoted to endoscopy and pediatric neurosurgery.

[(Fig._2)TD$FIG]

Fig. 2. Preoperative (A) and postoperative coronal MRI (B) demonstr

Actually, the indications to surgery and the surgical routes andtechniques were developed in collaboration. The liaison in terms ofsurgical methods is the result of such a teamwork. Our experienceconfirms the effectiveness and safeness of EETS in the pediatric age,and the feasibility of these approaches even in small children.Differently from the other series described in the literature[1,2,4,10], the series here considered has a larger number ofpatients and is more homogeneous, being composed only bychildren, all treated by the same surgical procedure. Moreover,almost the whole spectrum of pediatric sellar tumors is hererepresented. Pituitary adenomas are rare tumors in children,accounting for about 3% of all supratentorial masses (incidence: 0.1per million) [11]. The relatively high number of pediatric patientswith pituitary adenomas in our series mainly results from theselective referral of these subjects to our tertiary level Centers. Theprevalent occurrence of functioning microadenomas and theabsence of macroadenomas involving the cavernous sinus givereason of our high rate of gross total resections and the lowincidence of late hormone dysfunctions.

Although craniopharyngiomas are the most common lesions ofthe sellar and para-sellar region in the pediatric population as wellas in our clinical experience [12,13], they account for only onefourth of the series since in children they are usually representedby huge mass extending into the middle and/or the posteriorcranial fossa that we remove by a craniotomic approach. However,craniopharyngioma was the most challenging tumor of the seriesas well, as demonstrated by the lower rate of gross total resections,the need of re-operation, and the higher incidence of lateendocrinological sequelae. A gross total tumor resection was

ating the resection of a Rathke’s cyst in a young girl (14 years).

Table 2Pathology versus surgical resection.

Histotype No. Mean age (years) Gross total resection Subtotal resection Partial resection

Pituitary adenomaa 12 13.6 12/12 / /

Craniopharyngioma 7 9.2 3/7 2/7 2/7

Rathke’s cyst 4 10.5 4/4 / /

Clivus chordoma 1 9 1/1 / /

Clivus epithelioid sarcoma 1 4 1/1 / /

Histiocytosis (clival region) 1 4 / / 1/1

Sellar epidermoid cyst 1 13 1/1 / /

Total 27 12.2 22/27 (81.5%) 2/27 (7.5%) 3/27 (11%)

a 8 microadenomas + 4 macroadenomas, 9 functioning + 3 non-functioning.

D. Locatelli et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1298–1302 1301

actually achieved in 81.5% of the cases in the whole series but,when only craniopharyngiomas are considered, this rate droppedto 43%, as experienced also by other authors [2,9,14]. As expected[15], Rathke’s cleft cysts showed a significantly better surgicaloutcome that craniopharyngiomas.

Overall, our surgical and clinical results (Tables 2 and 3) overlapor even overcome those obtained with a craniotomic and/or atraditional microscopic transsphenoidal approaches in children,either according to our previous experience and the literature[2,14,16–19]. Such a good trend is further confirmed by the lowrate of tumor recurrence (9%) following a gross total tumorresection (2 out of 22 cases) after 8.6-year mean follow-up. Ofcourse, these satisfying surgical results as well as the relatively lowrate of endocrinological sequelae in part result from the smallnumber of secondary procedures we had to carry out and from ourselection criteria. However, the use of EETS has certainlycontributed to the good surgical outcome, especially the relativelylow rate of early and late complications, as confirmed in adults byseveral authors [20–22]. With regards to nasal complications, EETSdecreases the risk of their occurrence [23], ensuring a comfortablepostoperative course and not significantly affecting the naso-facialgrowth, which is necessary for a regular maxillo-facial develop-ment in children.

The use of the ‘‘two-nostrils-four-hands’’ surgery deserves aspecial mention due to the advantages that it offers in the pediatricpatients. Since the first experience during the late eighties [24], thebinostril-bimanual technique has been more and more utilized forboth the standard and the expanded endoscopic endonasalapproaches to the anterior skull base [6,25], showing high efficacyand short surgical times [26]. In children, the small nostrils and thenarrow nasal cavities make the binostril route the best (andsometimes the only) way to simultaneously introduce theendoscope together with 2 or 3 surgical instruments and tomanipulate them throughout the ‘‘sellar’’ phase of the procedure.Moreover, the opportunity to change the working angle of theendoscope during the operation by alternating the nostrils,combined with the use of different optics, significantly enlargesthe visualization of the surgical field, thus improving the chance to

Table 3Endocrinological outcome.

Preoperative alteration No. patients Postoperative r

Hypostaturalism 3a Improved: 2

Stable: 1

High ACTH levels/Cushing disease 6 Disappeared: 6

High PRL levels/dysmenorrhoea/galattorrhoea 4 Disappeared: 4

Hypopituitarism 6b Regressed: 3

Improved: 1

Stable: 2

Insipid diabetes 1a Disappearance:

New cases: 1

Obesity 0 New cases: 1

a All craniopharyngiomas.b 5 craniopharyngiomas, 1 macroadenoma.

control possible bleedings and remove even small tumorremnants. The deep surgical vision is further improved bysynchronizing the movements of the endoscope according to thefirst operator’s movements and by continuous irrigation andsuctioning, all these manoeuvres being performed by the secondoperator. The assistant surgeon actually plays an active role thewhole time of the operation, what is of paramount importance forher/his learning curve. The elevation of the suprasellar cistern,which frequently protrudes downwards and interposes in thesurgical field, is another key-step allowed by the four-handsprocedure to be considered when dealing with children whoseintrasellar space is particularly narrowed. Finally, this techniqueallows the surgeons to alternate in case of long operations.

As mentioned, we are used to integrate the two-nostrils-four-hands technique with the so-called ‘‘diving technique’’ [5]. It isabout a sort of ‘‘hydroscopy’’ that can enhance the chances oftumor resection: the surgical field (sellar cavity, cavernous sinus,cavity obtained after clivectomy) is actually filled with salinesolution so that the potential small tumor residues are dissected bythe fluid injection and then removed. Also small dehiscence of thesellar diaphragm and the arachnoid can be identified and the risk ofpostoperative CSF leakage reduced. Furthermore, the abundantirrigation decreases the risk of visual impairment due to the bloodproducts and allows to use the nasal endoscope like in theintraventricular neuroendoscopy with a direct visualization of thetumor remnants or the bleeding sources. The use of such atechnical variant together with the two-nostrils-four-handssurgery significantly improved our confidence with EETS overthe time, thus allowing us to face even very rare tumors in children,like clival masses [27,28]. Furthermore, thanks to these twotechniques and to the use of hemostatic agents (namely, fibrin-based products), we were able to reduce the intraoperativebleeding, which is a major concern especially when dealing withyoung children. In these subjects, moreover, the bone is richlyvascularized, thus representing a further problem in case ofconchal or juvenile sphenoid sinus, or transclival approach. The useof the diamond drill is very useful to control the bone hemostasis.In addition, hemostatic powders can be successfully utilized.

esult Outcome details

GH administered to all cases:

one child <3rd percentile, 2 children along 10th and 25th percentile

–

–

ACTH replacement: 3

TSH replacement: 2

1 Both transient, no therapy required

Weight along 97th percentile, normal daily life not affected

D. Locatelli et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1298–13021302

Possible limitations of EETS in children are represented by thenarrow sino-nasal pathways and, until recently, the lack ofdedicated surgical instruments [29]. With regards to the firstissue, the binostril approach together with the use of 2.7-mmdiameter optics and 3-mm diameter optics recently developedallows to overcome the problem of the small nostrils in severalcases. The involvement of both nostrils, however, does not increasethe risk of nasal morbidity. As to the pneumatization of thesphenoid sinus, we did not observe an augmented risk of not/partially pneumatized sinus (only one conchal variant). Actually,although traditionally considered to start from the 3rd to 4th yearof age and to be completed during the second decade of life [30,31],several studies based on anatomical, CT and MR imagingdemonstrated that the sphenoid pneumatization begins as earlyas the first months of age and usually finishes within the firstdecade [32–34]. A correct preoperative radiological assessment,which should include the nose and the paranasal sinuses, and theuse of neuronavigation make easier and safe to manage suchanatomical variations. When the drilling of the sphenoid sinus isrequired, we are used to perform it by means of a high speed drillwith diamond drilling tip, which allows the surgeon to remove thebone and, at the same time, to proceed cautiously within the non-pneumatized sphenoid bone. In such a circumstance, theneuronavigation is very helpful to maintain the correct trajectory.

Due to the infrequent occurrence of skull base lesions inchildren, a surgical instrumentation specific for pediatricpatients was only recently developed, parallel to the continuoustechnological progress in EETS, improving effectiveness andsafeness of this technique in this subgroup of patients. Forexample, dedicated 3 mm optics have been designed togetherwith new cutting instruments, such as shorter drill handpieces,new shavers and ultrasonic aspirators, giving the pediatricneurosurgeons the chance to take advantage of all technologiesand techniques currently available.

In conclusion, we recommend EETS for the management ofsellar/suprasellar tumors in children. The efficacy, the poorinvasiveness against the growing maxillo-facial structures, andthe relatively low rate of complications make EETS among thetechnical acquisitions that each surgeon dealing with this group ofpatients should have.

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