Accepted Manuscript 3D Endoscopic endonasal approach and outcomes in sellar lesions: a single-center experience of 104 cases Valentina Pennacchietti, MD, Massimiliano Garzaro, MD, Silvia Grottoli, MD, Paolo Pacca, MD, Diego Garbossa, MD, Alessandro Ducati, MD, Francesco Zenga, MD PII:

S1878-8750(16)00137-6

DOI:

10.1016/j.wneu.2016.01.049

Reference:

WNEU 3653

To appear in:

World Neurosurgery

Received Date: 24 August 2015 Revised Date:

17 January 2016

Accepted Date: 19 January 2016

Please cite this article as: Pennacchietti V, Garzaro M, Grottoli S, Pacca P, Garbossa D, Ducati A, Zenga F, 3D Endoscopic endonasal approach and outcomes in sellar lesions: a single-center experience of 104 cases, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.01.049. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Pennacchietti

ACCEPTED MANUSCRIPT

3D Endoscopic endonasal approach and outcomes in sellar lesions: a single-center experience of 104 cases Valentina Pennacchietti, MD1, Massimiliano Garzaro, MD2, Silvia Grottoli, MD3, Paolo Pacca, MD 1

1

, Diego Garbossa, MD1, Alessandro Ducati, MD1, Francesco Zenga, MD1

Division of Neurosurgery, Department of Neurosciences, A. O. U. Città della Salute e della Scienza di Torino, Turin, Italy, 2

RI PT

Division of Ear, Nose and Throat 1, Department of Surgical Sciences, A. O. U. Città della Salute e della Scienza di Torino, Turin, Italy, 3 Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, A. O. U. Città della Salute e della Scienza di Torino, Turin, Italy.

Corresponding author: Valentina Pennacchietti, email [email protected], Department of Neurosciences, via

SC

Cherasco 15, 10126 Turin, Italy, Tel. +390116335430, Cell. +393397198857, Fax +390116334517.

M AN U

Abstract

Background: Pituitary tumors account for about 15% of primary intracranial neoplasms and are often diagnosed incidentally. Common sellar lesions are pituitary adenomas, craniopharyngiomas and Rathke’s cleft cysts.

TE D

Currently endoscopic transsphenoidal approaches are largely used, and many centers also use 3D technology, although additional results of long-term follow-up are still being accumulated. Methods: We present a retrospective analysis of 104 patients with sellar lesions (57 males and 47

EP

females, mean age 52 years) who underwent 3D endoscopic transsphenoidal surgery in our center from December 2011 to March 2015 and were followed up for a mean time of 18 months.

AC C

Results: 16 patients were diagnosed with GH-secreting adenomas, 9 with ACTH-, 5 with PRL- and 2 with TSH-secreting tumors and 58 with non-secreting pituitary adenomas. 5 patients were Rathke’s cleft cysts, 5 craniopharyngiomas, 2 fibrous solitary tumors, a metastasis and a chordoma. At baseline, 47 patients (45,2%) had hormonal changes and 52 (50%) had visual field changes. Complete resection was achieved in 73 patients (70,1%). Follow up evaluation detected hormonal remission in 7 patients with Cushing disease (77,7%) and in 11 patients with acromegaly (68,7%). Complications were in 5 cases (4,8%) cerebrospinal fluid leak and in 6 cases transient diabetes insipidus (5,7%). 55 patients (52,9%) were discharged less than 72 hours after surgery. Pagina 1

Pennacchietti

ACCEPTED MANUSCRIPT

Conclusions: The use of an endoscopic endonasal approach with 3D technology provides several advantages, as concerns length of stay, rate of complications, post-operative recovery and novice surgeons’ training. Advantages of 3D endoscopy and long-term follow-up still need further elucidation.

SC

- Rathke cleft cyst - transsphenoidal approach.

RI PT

Keywords: craniopharyngioma - 3D endoscopy- endoscopic endonasal surgery - pituitary adenoma

Background

M AN U

Pituitary tumors constitute 10-15% of all primary intracranial neoplasms. Pituitary adenomas are the most common finding among sellar lesions, they affect both sexes equally and are more frequent in the third and fourth decades of life (19). Other common pathologic findings in the sellar region are craniopharyngiomas and Rathke’s cleft cysts (1).

TE D

Asymptomatic pituitary masses are often found incidentally and differential diagnosis includes pituitary adenomas, craniopharyngiomas, Rathke’s cleft cysts, meningiomas, gliomas, germinomas, cysts, hamartomas, metastases, focal areas of infarction, lymphocytic infiltrations and normal

EP

pituitary hypertrophy (9), (7), (25).

Pituitary adenomas can be classified in different ways, but they are mainly distinguished according

AC C

to dimensions (macroadenomas are more than 1 cm diameter, microadenomas are less than 1 cm diameter), hormonal activity (non-functioning, prolactin- or adrenocorticotropic hormone-, growth hormone-, thyroid stimulating hormone- or gonadotropin hormones-producing) and cavernous sinus invasion (Knosp 0-4) (24), (23), (27), (6). Surgery is the treatment of choice for most patients, although for prolactinomas the treatment of choice is medical, often with dopamine agonists (bromocriptine, cabergoline), because of their excellent response to these drugs. In some cases prolactinomas might need a surgical treatment, usually for patients presenting with CSF rhinorrea, pituitary apoplexy with neurological signs, Pagina 2

Pennacchietti

ACCEPTED MANUSCRIPT

failure of medical therapy or increasing tumor size with neurological deficits. Furthermore, some authors suggest that medically refractory prolactinomas and GH-secreting adenomas may offer a better response to drug after surgical debulking (5), (14). Surgical options to sellar lesions include transsphenoidal and transcranial approaches. At the

RI PT

present time, transsphenoidal approach is the method of choice to remove tumors of the sellar and parasellar region. Indications for a transsphenoidal approach have expanded with the development of extended transsphenoidal approaches that involve removal of additional bone to widen the

SC

surgical corridor, allowing access to skull base lesions. Although microscopic techniques are used, the endoscopic technique is gaining favor as the preferred approach in experienced hands. The

M AN U

endoscopic endonasal sphenoidotomy approach for resection of pituitary adenomas and other sellar lesions provides excellent exposure of the sella and adequate working space. Besides, the introduction of 3D endoscopes has given several additional advantages, such as depth perception, improved visualization of anatomical structures and their relations and a less steeper learning curve

Methods

TE D

for the surgeon (19), (13), (21).

EP

Our case series describes the preoperative and postoperative evaluation of a series of patients who underwent 3D endoscopic endonasal resection of pituitary functioning and non-functioning micro-

AC C

and macro-adenomas, Rathke’s cleft cysts and craniopharyngiomas between December 2011 and March 2015. In that period we performed 104 consecutive transsphenoidal operations in our center, the Neurosurgery Division of “Azienda Ospedaliero-Universitaria Città della Salute e della Scienza”, “Molinette”, University of Turin in Turin, Italy. All the patients were treated by the same surgeon, using 3D endoscope Visionsense (Visionsense, New York). We performed surgery using a “four hand-two nostrils” technique, with a stealth image guidance system (BrainLab, Germany). The patients were 57 males and 47 females. Mean age was 52 years in a range of 15-83 years. All the patients underwent preoperative endocrinological and neurophtalmologic assessment, and

Pagina 3

Pennacchietti

ACCEPTED MANUSCRIPT

neuroimaging (consisting of a MRI with and without contrast of the sellar region and/or a CT scan with and without contrast). These patients were followed-up for a mean time of 18 months (range 40-3 months), with a

RI PT

neurosurgical, radiological, endocrinological and neurophtalmologic evaluation.

Results

In our series, 83 patients had a pituitary macroadenoma, 7 microadenomas. Among them, 16

SC

patients were diagnosed with a GH-secreting adenoma, 9 with an ACTH-, 5 with a PRL- and 2 with a TSH-secreting tumor. In 58 cases, non-secreting pituitary adenomas were found. We also treated

M AN U

5 patients with Rathke’s cleft cysts and 5 with craniopharyngiomas. In one case pathology report revealed a sellar chordoma, in one case a colorectal cancer metastasis and in two cases a solitary fibrous tumor involving the sellar region (Table 1). Patients were evaluated at baseline with a brain MRI with and without contrast and/or a CTA scan, hormonal examination (prolactin, α-subunit, TSH, fT3, fT4, IGF-1, GH, ACTH, cortisol, testosterone or 17-β-estradiol, FSH-LH, electrolytes assessment, which consisted of visual field testing

TE D

and diuresis) and a neuroophtalmologic

(Humphrey or Goldmann perimetry), optic disc examination, eye movements, pupillary responses

EP

and visual evoked potentials.

Hormonal alterations were detected in 47 patients (45,2%), whereas visual field changes were

AC C

observed in 52 patients (50%). Main symptoms at diagnosis were visual impairment (blurry vision, diplopia, visual field deficit in 37 patients, 35,6%), headache (26 patients, 25%), hormonal disturbances (amenorrhea, galactorrhea, Cushing’s disease- and acromegaly) in 27 patients, 25,9%. In 17 patients diagnosis was incidental (16,3%). 5 patients (4,8%) were directly admitted to the emergency department, with a new onset of drug-resistant headache, nausea and vomiting, sudden visual deficits, hyponatriemia and hypopituitarism (hypocortisolism), suggesting the diagnosis of pituitary apoplexy, then confirmed by MRI features of the tumors (enlargement of the pituitary

Pagina 4

Pennacchietti

ACCEPTED MANUSCRIPT

gland, signs of hemorhage within the mass, peripheral enhancement, non-enhancing infarcted core, compression of optic nerves and chiasm with eventual edema), (Table 2). At imaging, macroadenomas were described based on cavernous sinus and parasellar invasion: 19,3% of macroadenomas were Knosp Grade 1 (16 patients), 37,3% Grade 2 (31 patients), 32,5%

RI PT

Grade 3 (27 patients) and 10,8% Grade 4 (9 patients). After surgery, patients were evaluated with a 3-month brain MRI with gadolinium and with a neuroophtalmologic and endocrinological assessment. Complete resection of the tumor was

SC

achieved in 73 patients (70,1%), whereas a subtotal resection was accomplished in 30 patients (28,8%). In two cases we performed a biopsy of the lesion and then decided for a transcranial

M AN U

approach to the mass (1,9%).

Hypopituitarism occurred in 16,3% of cases in our serie (17 patients). Complications, such as cerebrospinal fluid leak and transient diabetes insipidus or SIADH/hyponatremia were observed, respectively, in 5 (4,8%) and 6 (5,7%) patients (Table 3).

TE D

In functioning tumors, hormonal remission was achieved in 77,7% of patients with Cushing disease

(11 patients).

AC C

Discussion

EP

(7 patients), 80% of patients with prolactinoma (4 patients), and 68,4% of patients with acromegaly

We present a single-center experience in the use of 3D endoscopic technique for the treatment of sellar and parasellar lesions. All the patients considered in this series were operated by the same surgeon, using an endoscopic techinique to perform an endonasal transsphenoidal approach to the sellar lesions. In this series 5 patients with prolactinoma were treated surgically. In two cases surgery was indicated because of the onset of CSF leak after medical treatment with Cabergoline. 2 patients with Pagina 5

Pennacchietti

ACCEPTED MANUSCRIPT

macroprolactinomas showed no significant response to dopamine-agonists and underwent surgery. One patient didn’t show biochemical signs of hyperprolactinemia, but was diagnosed as a prolactinoma by the pathologist. The postoperative outcomes and the rate of complications described in the manuscript are

RI PT

comparable to other studies in literature. Surgery was complicated in 5 cases (4,8%) with cerebrospinal fluid leak, requiring further treatment with bed rest, lumbar drain and additional surgery (nasoseptal flap, abdominal fat graft and/or iliotibial tract graft harvesting). In 6 cases our

SC

patients developed transient diabetes insipidus or SIADH/hyponatremia (5,7%). There were no procedure-related deaths, 55 patients (52,9%) were discharged from the hospital less than 72 h after

M AN U

surgery. The mean length of stay at our Division was 3,9 days (2-15 days), being 5 days the mean length for patients operated until December 2013, and 3 days the mean length of stay for patient with a more recent admission (after January 2014). The length of stay significantly decreased after an initial period (from December 2011 to December 2013), both because of a better management of

TE D

the postoperative recovery and a lower incidence of postoperative complications. Concerning functioning pituitary adenomas treated in our series, biochemical remission for ACTH-

EP

secreting tumors was diagnosed at 3 months post-operatively, with hypocortisolemia, low or normal 24-hours urinary free cortisol or salivary cortisol and/or cortisol suppression < 1,8 µg/dl after 1 mg

AC C

dexamethasone (2), (8), (22). In GH-secreting adenomas post-operative biochemical remission was observed at 3 months normalized levels of IGF-1 and postglucose GH levels < 0,4 µg/l (18), (20). Concerning visual outcome, 85% of the patients with a pre-existing impairment presented a significant improvement of the visual field tests. Interestingly, postoperative visual evoked potentials showed a similar trend in comparison to the preoperative evaluations, with an improvement of amplitudes and prolongation of latencies of the visual evoked potential response. As already stated by Jayamaran et al (2010), this suggests that visual evoked potentials are useful to

Pagina 6

Pennacchietti

ACCEPTED MANUSCRIPT

determine the topography of the deficit in compressive optic neuropathy secondary to pituitary adenomas (15). Since 2011 the use of 3D endoscopes spread in our Center and gradually took the place of the microscopic technique. In our Division we switched directly from the classic microscopic vision to

RI PT

a totally “microendoscopic” vision with a 3D perspective. Classic 2D endoscopes do not give a good perception of depth because of a disproportion between the position observed on the monitor and the real position of the surgical instruments. This affects

SC

the precision of movements in the anteroposterior direction. In the 1990s 3D endoscopes were introduced to fix this issue with important lacks in image definition. Some authors compared the

M AN U

use of 2D and 3D scopes as concerns operative time, bleeding, hospital stay, and complications and no relevant variation was observed. 3D endoscopes enable the surgeon to perceive anatomical details in an anteroposterior fashion and allow a good precision of surgical maneuvers (16), (26), (30). “Hand-eye” coordination is therefore improved, with a better understanding of tissue characteristics and anatomy. This accurate and defined vision is of particular relevance for novice

TE D

surgeons, because anatomic details and depth perception gained with 3D endoscopes allow the naive operator to train with faster and better results (30). When performing the initial step of

EP

surgery, the benefits of 3D endoscopes are of little significance, because of the narrow space represented by the nasal fossae. On the other hand, the intrasellar and, mostly, the intradural parts of

AC C

surgery achieve an increased depth perception. Advantages with the use of 3D technology are also evident in the recostructive step. In our series, as in other papers, the procedures were conducted using 3D vision without causing discomfort in the surgical team (12), (11), (29). Some studies also showed a shorter learning curve for 3D endoscopy rather than 2D endoscopy. In fact, for residents and novice operators surgical maneuvers were faster and with lower error rates. In our experience, according to those data in literature, residents easily became familiar with 3D technology and were able to perform increasingly more complex tasks (10), (11). New generation endoscopes use an “insect eye” technology, with a single video chip. High Definition images are the newest advantage

Pagina 7

Pennacchietti

ACCEPTED MANUSCRIPT

of 3D technology. This allows a better distinction between the normal pituitary mass and the pathologic tissue. In the suprasellar area the HD definition is of a greater help to perform a precise and meticulous sharp dissection from the lesion the surrounding structures.

RI PT

Conclusions The data we obtained and reported in this study consider a 4 year experience with the use of 3D endoscope and are comparable to other similar studies on neuroendoscopy present in literature (28),

SC

(17), (1), (4).

The gold standard treatment for pituitary adenomas, except for prolactinomas, is transsphenoidal

M AN U

surgical removal of the tumor. Some studies looked at the difference between an endoscopic versus a microscopic approach. Most studies indicate no difference in surgical outcomes regarding the two approaches. However, some studies indicate that length of stay and postoperative complications seem to be less with the endoscopic approach (17).

The choice of an endoscopic endonasal route requires a detailed anatomic knowledge, a specific

TE D

training to learn the technique and the ability to manage the pathology and its possible complications in a multidisciplinary team. Furthermore, this technique allows the surgeon to have a

EP

close visualization of the surgical target and, at the same time, provides an expanded approach to the sellar and parasellar regions (3).

AC C

Based on our observations and results, the use of a 3D endoscopic endonasal transsphenoidal approach is another good option, alternative to the microscopic technique and to the classic 2D endoscope for the treatment of sellar lesions, since it presents many advantages, concerning both surgical outcomes and training. Currently, there is accumulating, but insufficient data in literature to demonstrate the real advantages of 3D endoscopic surgery over microscopic approaches to pituitary tumors. Further studies, in particular detailed long-term follow-up, are still necessary to support the evidence that the use of endoscopes is the future in approaching sellar and parasellar masses.

Pagina 8

Pennacchietti

ACCEPTED MANUSCRIPT References

1.

Barkhoudarian G, Zada G, Laws ER. Endoscopic endonasal surgery for nonadenomatous

2.

RI PT

sellar/parasellar lesions. World neurosurgery. 2014;82(6 Suppl):S138-146. Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent

2008;93(7):2454-2462. 3.

Cappabianca P, Cavallo LM, de Divitiis O, Solari D, Esposito F, Colao A. Endoscopic

M AN U

pituitary surgery. Pituitary. 2008;11(4):385-390. 4.

SC

Cushing's syndrome: a consensus statement. The Journal of clinical endocrinology and metabolism.

Cappabianca P, Cavallo LM, Solari D, Stagno V, Esposito F, de Angelis M. Endoscopic

endonasal surgery for pituitary adenomas. World neurosurgery. 2014;82(6 Suppl):S3-11. 5.

Colao A, Attanasio R, Pivonello R, et al. Partial surgical removal of growth hormone-

secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. The

6.

TE D

Journal of clinical endocrinology and metabolism. 2006;91(1):85-92. Dallapiazza R, Bond AE, Grober Y, et al. Retrospective analysis of a concurrent series of

EP

microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0-2 nonfunctioning pituitary macroadenomas at a single institution. Journal of neurosurgery. 2014;121(3):511-517. Donckier JE, Gustin T. Pituitary incidentaloma: to operate or not to operate? Acta

AC C

7.

chirurgica Belgica. 2012;112(4):255-260. 8.

Esposito F, Dusick JR, Cohan P, et al. Clinical review: Early morning cortisol levels as a

predictor of remission after transsphenoidal surgery for Cushing's disease. The Journal of clinical endocrinology and metabolism. 2006;91(1):7-13. 9.

Esteves C, Neves C, Augusto L, et al. Pituitary incidentalomas: analysis of a

neuroradiological cohort. Pituitary. 2015.

Pagina 9

10.

Pennacchietti

ACCEPTED MANUSCRIPT

Felisati G, Lenzi R, Pipolo C, et al. Endoscopic expanded endonasal approach: preliminary

experience with the new 3D endoscope. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale. 2013;33(2):102-106. 11.

Felisati G, Pipolo C, Maccari A, Cardia A, Revay M, Lasio GB. Transnasal 3D endoscopic

RI PT

skull base surgery: questionnaire-based analysis of the learning curve in 52 procedures. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-RhinoLaryngological Societies. 2013;270(8):2249-2253.

Garzaro M, Zenga F, Raimondo L, et al. Three-dimensional endoscopy in transnasal

SC

12.

transsphenoidal approach to clival chordomas. Head & neck. 2015.

Gondim JA, Schops M, de Almeida JP, et al. Endoscopic endonasal transsphenoidal surgery:

M AN U

13.

surgical results of 228 pituitary adenomas treated in a pituitary center. Pituitary. 2010;13(1):68-77. 14.

Hamilton DK, Vance ML, Boulos PT, Laws ER. Surgical outcomes in hyporesponsive

prolactinomas: analysis of patients with resistance or intolerance to dopamine agonists. Pituitary. 2005;8(1):53-60.

Jayaraman M, Ambika S, Gandhi RA, Bassi SR, Ravi P, Sen P. Multifocal visual evoked

TE D

15.

potential recordings in compressive optic neuropathy secondary to pituitary adenoma. Documenta

16.

EP

ophthalmologica. Advances in ophthalmology. 2010;121(3):197-204. Kari E, Oyesiku NM, Dadashev V, Wise SK. Comparison of traditional 2-dimensional

AC C

endoscopic pituitary surgery with new 3-dimensional endoscopic technology: intraoperative and early postoperative factors. International forum of allergy & rhinology. 2012;2(1):2-8. 17.

Karppinen A, Kivipelto L, Vehkavaara S, et al. Transition From Microscopic to Endoscopic

Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas. World neurosurgery. 2015;84(1):48-57. 18.

Katznelson L, Atkinson JL, Cook DM, et al. American Association of Clinical

Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly--2011 update: executive summary. Endocrine practice : official journal of the

Pagina 10

Pennacchietti

ACCEPTED MANUSCRIPT

American College of Endocrinology and the American Association of Clinical Endocrinologists. 2011;17(4):636-646. 19.

Kopczak A, Renner U, Karl Stalla G. Advances in understanding pituitary tumors.

F1000prime reports. 2014;6:5. Krieger MD, Couldwell WT, Weiss MH. Assessment of long-term remission of acromegaly

following surgery. Journal of neurosurgery. 2003;98(4):719-724. 21.

RI PT

20.

Laws ER, Jr., Barkhoudarian G. The transition from microscopic to endoscopic

SC

transsphenoidal surgery: the experience at Brigham and Women's Hospital. World neurosurgery. 2014;82(6 Suppl):S152-154.

Lindsay JR, Oldfield EH, Stratakis CA, Nieman LK. The postoperative basal cortisol and

M AN U

22.

CRH tests for prediction of long-term remission from Cushing's disease after transsphenoidal surgery. The Journal of clinical endocrinology and metabolism. 2011;96(7):2057-2064. 23.

Mert A, Micko A, Donat M, et al. An advanced navigation protocol for endoscopic

transsphenoidal surgery. World neurosurgery. 2014;82(6 Suppl):S95-105. Micko AS, Wohrer A, Wolfsberger S, Knosp E. Invasion of the cavernous sinus space in

TE D

24.

pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification.

25.

EP

Journal of neurosurgery. 2015:1-9.

Molitch ME. Management of incidentally found nonfunctional pituitary tumors.

26.

AC C

Neurosurgery clinics of North America. 2012;23(4):543-553. Ogino-Nishimura E, Nakagawa T, Sakamoto T, Ito J. Efficacy of three-dimensional

endoscopy in endonasal surgery. Auris, nasus, larynx. 2015;42(3):203-207. 27.

Raverot G, Jouanneau E, Trouillas J. Management of endocrine disease: clinicopathological

classification and molecular markers of pituitary tumours for personalized therapeutic strategies. European journal of endocrinology / European Federation of Endocrine Societies. 2014;170(4):R121-132.

Pagina 11

28.

Pennacchietti

ACCEPTED MANUSCRIPT

Torales J, Halperin I, Hanzu F, et al. Endoscopic endonasal surgery for pituitary tumors.

Results in a series of 121 patients operated at the same center and by the same neurosurgeon. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion. 2014;61(8):410-416. Wasserzug O, Margalit N, Weizman N, Fliss DM, Gil Z. Utility of a three-dimensional

RI PT

29.

endoscopic system in skull base surgery. Skull base : official journal of North American Skull Base Society ... [et al.]. 2010;20(4):223-228.

Zaidi HA, Zehri A, Smith TR, Nakaji P, Laws ER, Jr. Efficacy of Three-Dimensional

SC

30.

Endoscopy for Ventral Skull Base Pathology: A systematic review of the literature. World

AC C

EP

TE D

M AN U

neurosurgery. 2015.

Pagina 12

ACCEPTED MANUSCRIPT

Table 1: general characteristics of the sellar lesions in our series. Lesion

Number of Patients

Additional Information 58 Macroadenoma: 82 Microadenoma: 7 Giant Pituitary Adenoma: 1 16

Non-functioning Pituitary Adenoma GH-secreting Adenoma

5

ACTH-secreting Adenoma

9

TSH-secreting Adenoma

2

Craniopharyngioma

5 1 Granular Cell Tumor

Rathke’s Cleft Cysts

5

Solitary Fibrous Tumor

2 1 Fat-forming variety

SC

RI PT

PRL-secreting Adenoma

1 Colorectal Cancer Metastasis

Metastasis

1

AC C

EP

TE D

M AN U

Chordoma

ACCEPTED MANUSCRIPT

Table 2: preoperative assessment and relative percentage. Preoperative Evaluation

Number of Patients

% 5

4,8

Visual Field Deficit

52

50

Hormonal changes

47

45,2

Headache

26

25

CSF leak

2

AC C

EP

TE D

M AN U

SC

RI PT

Pituitary Apoplexy

1,9

ACCEPTED MANUSCRIPT

Table 3: postoperative complications and relative percentage. Postoperative Complications

Number of Patients

% 5

4,8

Diabetes Insipidus/SIADH

6

5,7

Vascular injury

2

1,9

Epistaxis

1

0,9

17

AC C

EP

TE D

M AN U

SC

Hypopituitarism

RI PT

CSF leak

16,3

ACCEPTED MANUSCRIPT

Highlights • A retrospective description of our 4 years-experience with 3D endoscopic endonasal approach to sellar lesions is described.

RI PT

• Patients outcomes and complications are discussed, with a maximum of 46 months follow-up.

AC C

EP

TE D

M AN U

SC

• We registered a short length of stay at the hospital, especially after an initial “training” period.

ACCEPTED MANUSCRIPT

The authors of this manuscript , Valentina Pennacchietti, Massimiliano Garzaro, Silvia Grottoli, Paolo Pacca, Diego Garbossa, Alessandro Ducati and Francesco Zenga declare that there is no conflict of interest

AC C

EP

TE D

M AN U

SC

RI PT

regarding the publication of this paper.

ACCEPTED MANUSCRIPT

Abbreviation List:

- ACTH: adrenocorticotropic hormone - CSF: cerebrospinal fluid

RI PT

- CT: computed tomography - FSH: follicle stimulating hormone

SC

- fT3: free triiodothyronine

- GH: growth hormone - IGF-1: insulin-like growth factor-1

TE D

- LH: luteinizing hormone

M AN U

- fT4: free thyroxine

- MRI: magnetic resonance imaging

EP

- PRL: prolactin

AC C

- SIADH: syndrome of inappropriate antidiuretic hormone secretion - 3D: three-dimensional

- TSH: thyroid stimulating hormone