Endoscopic endonasal transsphenoidal surgery: procedure, endoscopic equipment and instrumentation

Endoscopic endonasal transsphenoidal surgery: surgical resultsof 228 pituitary adenomas treated in a pituitary center

Jackson A. Gondim Æ Michele Schops ÆJoao Paulo C. de Almeida Æ Lucas Alverne F. de Albuquerque ÆErika Gomes Æ Tania Ferraz Æ Francisca Andrea C. Barroso

� Springer Science+Business Media, LLC 2009

Abstract Pituitary tumors are challenging tumors in the

sellar region. Surgical approaches to the pituitary have

undergone numerous refinements over the last 100 years.

The introduction of the endoscope have revolutionized

pituitary surgery. The aim of this study is to report the

results of a consecutive series of patients undergoing

pituitary surgery using a pure endoscopic endonasal

approach and to evaluate the efficacy and safety of this

procedure. We reviewed the data of 228 consecutive

patients who underwent endonasal transsphenoidal ade-

noma removal over an 10-year period. Pre- and post-

operative hormonal status (at least 3 months after surgery)

were analyzed and compared with clinical parameters

presented by the patients. Tumor removal rate, endocri-

nological outcomes, and complications were retrospec-

tively assessed in 228 patients with pituitary adenomas

who underwent 251 procedures between December 1998

and December 2007. There were 93 nonfunctioning ade-

nomas, 58 growth hormone-secreting, 41 prolactin-

secreting, 28 adrenocorticotropin hormone secreting, 7

FSH-LH secreting and 1 thyroid-stimulating hormone-

secreting adenomas. Gross total removal was achieved in

79.3% of the cases after a median follow-up of

61.5 months. The remission results for patients with non-

functioning adenomas was 83% and for functioning ade-

nomas were 76.3% (70.6% for GH hormone-secreting,

85.3% for prolactin hormone-secreting, 71.4% for ACTH

hormone-secreting, 85.7% for FSH-LH hormone-secreting

and 100% for TSH hormone-secreting), with no recurrence

at the time of the last follow-up. Post-operative compli-

cations were present in 35 (13.9%) cases. The most fre-

quent complications were temporary and permanent

diabetes insipidus (six and two cases, respectively), syn-

drome of inappropriate antidiuretic hormone secretion (two

cases) and CSF leaks (eight cases). There was no death

related to the procedure in this series. The endoscopic

endonasal approach for resection of pituitary adenomas,

provides acceptable results representing a safe alternative

procedure to the microscopic approach. This less invasive

method, associated with a small number of complications,

provides excellent tumor removal rates and represents

an important tool for the achievement of good results in the

pituitary surgery, mainly for the complete removal of large

adenomas.

Keywords Endoscopic surgery � Endonasal �Transsphenoidal surgery � Pituitary adenoma

Introduction

The transsphenoidal approach for pituitary gland was first

successfully described by Schloffer, when he reported the

first transsphenoidal removal of a pituitary tumor in 1906

J. A. Gondim (&) � J. P. C. de Almeida �L. A. F. de Albuquerque

Department of Neurosurgery, General Hospital of Fortaleza,

Fortaleza, Brazil

e-mail: [email protected]; [email protected]

M. Schops � J. P. C. de Almeida � L. A. F. de Albuquerque

School of Medicine, Federal University of Ceara,

Fortaleza, Brazil

E. Gomes

Department of Ear, Nose and Throat Surgery, General Hospital

of Fortaleza, Fortaleza, Brazil

T. Ferraz � F. A. C. Barroso

Department of Endocrinology, General Hospital of Fortaleza,

Fortaleza, Brazil

123

Pituitary

DOI 10.1007/s11102-009-0195-x

[1]. Hirsch in 1910 described a direct endonasal trans-

sphenoidal approach, a procedure that involved resection of

the middle turbinate and part of the nasal septum. Such

operation was performed in five different steps at intervals

lasting days to 2 weeks [2]. In the same year, Halstead

described the sublabial gingival via [3]. Cushing in 1912

modified the sublabial transsphenoidal approach to the

sella turcica, making it essentially as it is used nowadays

[4–6]. Since then the approach, either via sublabial or via

septal has gain importance in surgical treatment for pitui-

tary adenomas [4].

In the 1950s and 1960s, Guiot, developed introperative

fluoroscopy for trassphenoidal surgery, and Hardy, that

combined fluoroscopy with microsurgical techniques,

importantly contributed to the development of the pituitary

surgery, reducing the risk of brain injure and improving the

rate of tumor resection and favorable outcome [7–10].

In 1970, Messerklinger [11] developed the endoscopic

technique. After it, the endoscope started to be used in skull

base surgery and in sellar and parasellar region [12, 13]. In

1992, Jankowski et al. [14] introduced the endoscope in the

pituitary surgery, describing the use of the endonasal

transsphenoidal endoscopic technique for removal of three

pituitary adenomas.

The transsphenoidal endoscopic guided pituitary surgery

was standardized in actual clinical practice by Carrau and

Jho [15, 16] and Cappabianca et al. [17]. The development

of neuroendoscopy and the popularization of transsphe-

noidal endoscopic guided pituitary surgery have been

associated with better tumor resection results. Although

presenting better illumination and visualization of the

lesions, no report has definitively proved the superiority of

endoscopy over microsurgery in pituitary surgery, so far.

We performed our first purely endoscopic resection of a

pituitary adenoma in 1998. Now, we report our 10 years

experience series of 228 patients treated with endoscopic

endonasal transsphenoidal surgery for pituitary adenomas.

We also compare our results with other endoscopy

and microscopy pituitary surgery series reported in the

literature.

Methods

Study design

Between May 1998 and December 2007, a total of 309

patients underwent endoscopic transsphenoidal procedures

for skull base lesions at the Neuroendocrinological

Department of General Hospital of Fortaleza, Brazil. This

retrospective study comprises the evaluation of 228 cons-

ecutives patients who underwent 251 pure endoscopic en-

donasal treatment of pituitary adenomas. Any other lesion

was excluded from the study. The authors reviewed the

patients’ files in order to collect clinical and surgical data

for the study.

All patients underwent neurologic, ophthalmologic and

endocrinologic examinations. The patient follow up varied

from 8 months to 11 years.

Endocrinological assessment

All the endocrinological investigation was performed at

our hospital. Multiple measurements of plasma GH, insu-

lin-like growth factor-I (IGF-I), GH level after oral glucose

tolerance test (OGTT), prolactin, adrenocorticotrophic

hormone (ACTH), cortisol, 24-h urinary free cortisol

(when Cushing’s disease was suspected), thyreoid-stimu-

lating hormone (TSH), free thyroxine, luteinizing hormone

(LH) and follicle stimulating hormone (FSH), testosterone,

and estradiol levels were studied. All tumors were sub-

mitted to immunohistochemical analysis of the tissue

removed.

Neuroradiology

All patients underwent tumor evaluation by magnetic res-

onance imaging (MRI), with and without administration of

intravenous contrast agent. We utilized a 1.5 Tesla MRI

with T1 and T2-weighted spin echo before and after gad-

olinium-base contrast medium. Tumor size was classified

according to maximum tumor diameter in two categories:

microadenoma (\10 mm), and macroadenomas (C10 mm).

A facial computed tomographic scan was used in all

patients to evaluate the paranasal sinuses (septal anatomy,

sphenoidal, and maxillofacial format) for surgical planning.

Follow-up MRI studies were obtained at 3 months and

every 6 months thereafter.

Surgical technique

All patients were treated by the same medical team, using

identical procedures. Under general anesthesia, the patient

is placed in the supine position on the operative table with

the back elevated 30�, the head tilted back 20�, and toward

the left shoulder 25�. The neurosurgeon is positioned on the

right side of the patient and the ear, nose and throat (ENT)

surgeon on the left side. Usually, the left nostril is used, but

the choice is based on nasal anatomy. Routinely a bilateral

approach affords significant improvement in exposure and

confort for the surgeon. A 30�, and less frequently 45 or

70�, rigid endoscope (180/4 mm) is used. The endoscope is

navigated into the nasal cavity. The floor of the sella is

located *1 cm above the inferior margin of the middle

turbinate. The space between the middle turbinate and the

nasal septum is gently widened, and a large opening is

Pituitary

123

made in the posterior internasal septum. Normally we do

not resect the middle turbinate by are gently lateralized but

preserved to promote normal post-operative middle meatus

physiology. The anterior wall of the sphenoidal sinus is

open. Inside the sphenoidal sinus, the sella is then local-

ized, the anterior wall of the sella and the dura mater are

largely opened with a highspeed drill or Kerrison rongeur.

Visualization of the sellar region is initially performed with

a 0� endoscope. Following tumor resection, both 0 and

angled (30, 45 and 70�) endoscopes are placed into the

surgical cavity to explore for any residual tumor. Intraop-

erative image guidance is used in adenomas with a retro

sellar component or adenomas presenting close contact to

the third ventricle. For the reconstruction of the sellar

region, we used a combination of fascia lata, abdominal fat,

mucoperiosteum, fibrin sealants and a vascularized nasal

septal mucosa flap as a final layer over the onlay graft,

followed by Foley catheter as a buttress that is removed in

48 h [18].

Tumor control

The aim of treatment was to remove the tumor in its totality

without causing hypopituitarism. The criteria for disease

control were tumor total removal in nonfunctioning ade-

nomas and hormonal control in functioning adenomas

(prolactinomas, GH-secreting adenomas, ACTH-secreting

adenomas, TSH-secreting adenomas and FSH/LH-secret-

ing adenomas).

The success of the tumor removal is based on both MRI

findings with contrast obtained 3 months after surgery and

the surgeon’s intraoperative vision. The tumor is consid-

ered to be totally removed when the surgeon’s vision and

MRI image examination documents no residual tumor. The

resection is considered subtotal when more than 80% of the

lesion has been removed and partial resection when less

than 80% has been removed.

The criteria for acromegaly control used were the cur-

rent internationally accepted criteria for biochemical

‘‘cure’’ of the disease [19]: the nadir GH level after oral

glucose should be less than 1 lg/l, and the IGF-1 should be

age and sex-matcher. The criteria for Cushing’s disease

control used were an early morning cortisol level mea-

surement (\100 nmol/l requiring substitutive therapy)

obtained in the first 48 h after surgery along with sup-

pression to the low-dose dexamethasone (1 mg) overnight

test and normalization of the 24-h urinary free cortisol

(both at 4 and 6 week follow-up). Prolactinomas were

considered under control when serum prolactin after

surgery was \20 ng/ml. In FSH/LH cases, normalization

of serum FSH and LH levels was required for hor-

monal control. Endocrinologically ‘‘cured’’ TSH-secreting

adenoma patients were those presenting normal levels of

T3, free T4 and TSH after surgery.

Statistical analysis

All data are expressed as mean ± standard deviation (SD).

Statistical software, SPSS 16.0 (SPSS Inc., Chicago, IL)

was used for statistical analysis, with P \ 0.05 considered

statistical significant.

Results

General analysis (see Table 1)

From 1998 to December 2007, 228 patients were admitted

in our center for surgical treatment of pituitary adenomas.

Males and females represented 44.7% (102 patients) and

55.3% (126 patients) of these, respectively. The mean age

of the studied population was 42.51 ± 15.25 years old

(range 13–79 years).

According to the size of the lesion, 190 (83.8%) tumors

were classified as macroadenomas (mean size of the

lesions: 24.68 ± 14.57 mm). Cystic components were

present in 48 cases (21.1%) and destruction of the sella

floor was detected in 93 patients (40.8%). Functioning

adenomas represented most of the lesions (135 cases,

59.3%). The most common hormone-secreting lesions were

GH secreting pituitary adenomas (58 adenomas, 25.4%),

followed by prolactinomas (41 adenomas, 17.9%). Disease

control was achieved in 33 (86.8%) cases of microadeno-

mas and 142 (74.7%) of macroadenomas.

Headache and visual complaints were present in 154

(67.5%) and 75 (32.9%) patients, respectively.

Table 1 General characteristics and analysis of 228 pituitary

adenomas

Adenomas characteristics N %

Total of patients 228 100

Nonfunctioning adenomas 93 40.7

Hormone-secreting adenomas 135 59.3

GH secreting adenomas 58 25.4

Prolactinoma 41 17.9

ACTH secreting adenomas 28 12.2

FSH/LH secreting adenomas 7 3

TSH secreting adenoma 1 0.4

Microadenomas 38 16.6

Macroadenomas 190 83.8

[10 mm 97 42.5

Localized perfuration of the sella floor 26 11.5

Diffuse perforation of the sella floor 67 29.4

Cystic component 48 21.1

Pituitary

123

Subgroup analysis

Nonfunctioning adenomas (see Table 2)

Nonfunctioning adenomas were the most common single

subgroup of pituitary adenomas operated in this series

(93 cases, 40.8%). All the tumors were macroadenomas;

the mean size of the lesions in this group was

30.4 ± 15.1 mm. These lesions presented cystic compo-

nents in 24 cases (25.8%). Visual complaints secondary to

optic chiasm compression were referred by 50 patients

(53.8%). In 70 cases (75.2%), gross total resection was

possible and no residual tumor or tumor regrowth was

observed during the follow up. In 23 patients complete

resection was not achieved during the first procedure: 13

had subtotal resection ([80%) and 10 partial resection

(\80%). In the subgroup of partial resection a second

endoscopic surgery was performed in all patients and total/

subtotal removal of the residual lesions was obtained in

eight cases (four subtotal resections and four total resec-

tions); the two remain patients were referred to radiother-

apy for treatment of important cavernous sinus invasion.

The 13 cases with subtotal resection are under clinical

observation and have not presented any symptoms during

the follow up.

Growth hormone-secreting adenomas (see Table 3)

Acromegaly was the most common hormone-secreting

pituitary adenoma subgroup in our series (58 cases,

25.4%). The micro- and macroadenomas corresponded to

11 (18.9%) and 47 (81%) cases, respectively. Cystic

lesions were observed only in six cases (10.3%). Hormonal

control was achieved in 9 microadenomas (81.8%) and 32

macroadenomas (68%) (total hormonal control rate: 41

patients, 70.7%).

Seventeen patients did not achieve hormonal control:

four macrodenomas were submitted to a second endoscopic

procedure and obtained disease control; and 13 patients

have been using somatostin analogues post-operatively.

Three cases (1.3% of all adenomas and 5.17% of acro-

megaly) of GH-prolactin co-secreting adenomas were

present in this group: hormonal control after surgery was

obtained in two of these and one patient was submitted to

medical treatment based on cabergoline and somatostatin

analogue once complete endocrinological control was not

achieved after the endoscopic resection.

Prolactinomas (see Table 4)

Endoscopic resection of prolactinomas was performed in

selected cases: cystic chiasmatic compressive lesions, no

hormonal control with use of medical therapy, important

medical therapy side effects or refusal to clinical treatment.

Macroadenomas were present in 34 patients (82.9%). About

15 cases (36.6%) presented as predominantly cystic ade-

nomas. We achieved an overall hormonal control in 35

patients (85.3%). All the microprolactinomas (seven

patients) presented hormonal control after surgery and 28

macroprolactinomas were controlled after resection

(82.3%). The six patients who did not achieve hormonal

control after endoscopic resection were submitted to clini-

cal therapy based on cabergoline. Recurrence was observed

in three cases of macroprolactinomas during the follow up.

Such cases were successfully submitted to cabergoline

based treatment, with no side effects observed. No patient

was submitted to radiotherapy for adjuvant treatment.

ACTH-secreting hormone (see Table 5)

Twenty-eight cases (12.2%) of Cushing Disease were

treated by endoscopic resection in our series. Most of those

Table 2 Nonfunctioning adenomas characteristics

Nonfunctioning adenomas 93

Mean size 30.4 ± 15.1 mm

Microadenomas 0

Macroadenomas 93 (100%)

Total resection 70 (75.2%)

Subtotal resection ([80%) 13 (13.9%)

Partial resection (\80%) 10 (10.7%)

Table 3 Growth hormone secreting adenomas characteristics

GH secreting adenomas 58

Mean size 20.8 ± 10.02 mm

Microadenomas 11 (18.9%)

Hormonal control 9 (81.8%)

Macroadenomas 47 (81.1%)

Hormonal control 32(68%)

Second surgery 4

Cure after the second procedure 4

Table 4 Prolactinomas characteristics

Prolactinomas 41

Mean size 20.2 ± 10.8 mm

Microadenomas 7 (17.1%)

Hormonal control 7 (100%)

Macroadenomas 34 (82.9%)

Hormonal control 28 (82.3%)

Pituitary

123

tumors presented as microadenomas (20 patients, 71.4%).

Three cases presented clinical characteristics but negative

MRI results. Those cases were diagnosed based on inferior

petrosal sinus sampling and then, submitted to endoscopic

surgery. The total hormonal control rate: 20 patients,

71.4%. In the microadenoma group, complete hormonal

control was achieved in 15 (75%) patients after surgery.

The five patients that did not obtain disease control were

submitted to a second surgery, in which hypophisectomy

was performed routinely. All of then achieved endocrino-

logical control after it. There were no cystic lesions in this

group.

It was possible to obtain endocrinological control of the

disease in five cases of macroadenomas (62.5%). In three

cases (27.5%), presenting important cavernous sinus

invasion, a second surgery was performed; however, the

second procedure did not achieve hormonal control in any

of these cases. One of these was submitted to radiotherapy

treatment and two patients did not return to clinical eval-

uation after the second procedure. No patient was sub-

mitted to adrenalectomy.

FSH-LH-secreting adenomas

FSH-LH adenomas were observed in seven patients (3%)

treated by our group. All these were macroadenomas (mean

size: 43.3 ± 11.37 mm). Three of them presented impor-

tant optic chiasm compression and one of the adenomas

was predominantly a cystic lesion. No cavernous sinus

invasion was present in any of these cases. Five cases

achieved hormonal control after surgery (71.4%). There

was one death in the fifth post-operative day secondary to

development of cardiac arrhythmia and cardiopulmonary

failure, not directly related to the surgical procedure. In one

case, a second endoscopic resection was required for

endocrinological control.

TSH-secreting adenomas

Only one patient in our series presented a TSH-secreting

adenoma. The patient was a 53 years old man with a

macroadenoma (3.0 9 3.0 9 2.8 cm), which caused

important chiasm compression and destruction of the sella

floor. Endoscopic resection was performed successfully

and the patient obtained hormonal disease control with no

recurrences observed in the follow up evaluations.

Complications (see Table 6)

Complications were observed after 35/251 (13.9%) endo-

scopic procedures. Diabetes insipidus (DI) was observed in

eight patients after the surgery. Six of them (2.3% of all

patients) developed only transient disfunction, while two

patients (0.7%) presented permanent DI, requiring rigorous

medical therapy and clinical follow up.

Syndrome of inappropriate antidiuretic hormone secre-

tion (SIADH) was presented in two cases of macroadeno-

mas with important suprasellar extension. These patients

were submitted to clinical treatment after surgery and

recovered with no secondary deficits.

Important CSF leak was present in eight cases (3.1%).

These cases were diagnosed in the post-operative period

(first week) and were submitted to reconstruction with a

vascularized nasal septal mucosa flap, fascia lata and fibrin

sealant. Two cases of meningitis, with no CSF leak

observed in the surgery, were present in our series. These

cases were adequately treated in our neurocritical care unit,

with complete recovering of these patients.

Seven cases of nasal post-operative bleeding were

observed. In one case, a patient with acromegaly was

reoperated and a sphenoidal bone hemorrhage was

Table 5 ACTH-secreting adenomas characteristics

ACTH adenomas 28

Mean size 8.7 ± 8.3 mm

Microadenomas 20 (71.4%)

Hormonal control 15 (75%)

Partial control 5 (25%)

Second surgery (hemihypophisectomy) 5 (100%)

Cure after the second procedure 5 (100%)

Macroadenomas 8 (28.6%)

Hormonal control 5 (62.5%)

Partial control 3 (37.5%)

Second surgery 3 (100%)

Cure after the second procedure 0

Table 6 Complications analysis

n %

SIADH 2 0.7

Transient diabetes insipidus 6 2.3

Permanent diabetes insipidus 2 0.7

Internal carotid lesion 2 0.7

Post-operative hemorrhage 7 2.7

Seizures 1 0.3

Brain parenchima lesion 1 0.3

Addisonian crisis 1 0.3

Hypertension 1 0.3

CSF leak 8 3.1

Meningitis 2 0.7

Death 2 0.7

Total 35 13.9

Pituitary

123

observed and then controlled. The other six cases presented

no important clinical manifestations.

Lesion of the internal carotid artery occurred in two

patients. Both happened during a reoperation for resection

of a lateral extension of macroadenomas with important

cavernous sinus invasion. In both cases, obstruction of the

vessel was performed by the interventional radiology team

of our center. One of the patients presented mild left

hemiparesis at the last follow up evaluation; the other one

did not return to the follow up evaluation.

Fatal outcome was present in two cases after surgery

(0.7%). One patient died at the fifth post-operative day

secondary to cardiac arrhythmia and cardiopulmonary

failure; in the second case, the patient developed pneu-

monia after surgery and died at the 20th post-operative

day. No death was directly related to the endoscopic

surgery.

Discussion

The development of the endonasal endoscopic approach to

the resection of pituitary adenomas has been one of the

most remarkable advances for the treatment of these

tumors in the last decades. Since 1997, after the initial

reports of large series of endoscopic pituitary surgery by

Jho and Carrau [15, 16] and Cappabianca et al. [17], the

technique has been disseminated worldwide and represents,

nowadays, the main surgical approach for sellar lesions in

different neurosurgical centers.

The endoscopic transsphenoidal approach can be per-

formed as a ‘‘pure’’ technique, with the endoscope as the

sole visualizing tool along the whole procedure, as pre-

sented in our series; or as an ‘‘endoscope-assisted’’ pro-

cedure, where the endoscope is used in association with the

microscope [16, 17, 20–23].

A panoramic vision inside the surgical area, a superior

close up of the anatomy and an improved working angle

represent some of the advantages brought by the use of the

endoscope to the pituitary surgery [24]. Nevertheless, less

nasal cavity injuries, without the use of nasal speculum or

fluoroscopy and patients fast recovering also are benefits

reported in the literature [21, 25, 26]. Comparing it to the

sub-labial incision, there is an important reduction in

morbidity, mainly related to the reduction of upper lip and

nasal complications [25, 27].

The results of the pure endoscopic pituitary surgery for

tumor resection and hormonal control of pituitary adeno-

mas have been extensively compared to the results

obtained by microsurgery [24, 28, 29]. However, no con-

clusive evidence of different results has been demonstrated

[24, 28, 29]. Until the moment, no large randomized study

has compared the results of these techniques.

In our series, most of the tumors were macroadenomas

(81%). The size of the lesions treated in our center (mean

tumor size, 24.6 ± 15.1 mm) is larger than the size of the

adenomas treated by other groups [28, 30]. We attribute the

occurrence of larger lesions in our study to the long dis-

tance between the reference center and the small towns in

the country and the important delay between development

of symptoms and admission in our neurosurgical depart-

ment. We believe this explain why our total resection

results (76.7%) are slightly inferior to the results presented

by Dehdashti et al. [24], that report levels of overall gross

total resection of 88%. Jain et al. [30] analyzed the relation

between the size of pituitary adenomas and outcome in a

series of 20 patients treated by the endonasal endoscopic

approach. They observed that tumor volume of less than

5 ml (P \ 0.05) and no parasellar or suprasellar extension

are favorable variables for total removal. Tabaee et al. [28]

submitted 57 patients to purely endoscopic pituitary sur-

gery obtaining gross tumor removal in 89% and hormonal

control in 90% of the cases. He observed that the only

significant predictor of the extent of tumor removal was

maximum tumor size. Larger tumors were associated with

visual dysfunctions (P = 0.02), longer procedures (P =

0.03) and duration of hospital stay (P = 0.0005) [28].

Nonfunctioning adenomas

The endoscopic surgical control of nonfunctioning adeno-

mas, based on gross total resection analysis, varies from 62

to 93% [21, 24, 26, 28, 29, 31, 32]. The large difference

between the results reported is partially secondary to the

learning curve required to master the procedure and to the

development of new endoscopic instruments. Therefore,

more access to tumors with extensions to the suprasellar

and parasellar regions is possible nowadays, what reduces

the percentage of subtotal resections.

The main limitation for gross total removal of non-

functioning adenomas was the presence of cavernous sinus

invasion. Twelve of the 23 patients (52.2%) who did not

experience total tumor resection after the first endoscopic

procedure in our series presented cavernous sinus invasion.

Two of them were referred to radiotherapy once presented

important nerve compression signs; the other ten patients

have been asymptomatic since surgery and are under

clinical follow up.

Although the nonfunctioning adenomas studied in this

series presented larger mean size (30.4 ± 15.1 mm) than

those presented by other groups [28, 30], we obtained

75.2% (70 cases) of disease control after the first endo-

scopic procedure, similarly to recent published reports

[29]. We attribute the difference between our results and

those presented by the endoscopic series of Dehdashti et al.

[24] (88% of gross total removal) and the results obtained

Pituitary

123

by the weighted average value of microscopic series cal-

culated in that paper (82% of gross total removal) to the

large size of the lesions presented in our study. Tumor size

has been demonstrated to be closely related to the extent of

resection obtained by the endoscopic pituitary surgery.

According to Tabaee et al. [28] there is a three folder

decrease in complete tumor removal for every 1 cm

increase in tumor size (P = 0.047).

Functioning adenomas

Acromegaly

Hormonal control results after the endoscopic resection of

GH-secreting adenomas varies from 65 to 85% in the lit-

erature [24, 28, 29, 31–33], presenting superior results

when compared to microsurgery series (52–85%) [24, 34–

36]. We obtained 70.1% of hormonal control after the first

endoscopic procedure and a level of 77.5% of control when

patients submitted to a second endoscopic procedure were

also analyzed. Previously, analyzing only intrasellar GH-

secreting tumors, our group reported a level of 84.84% of

disease control secondary to the endoscopic surgery [37].

Therefore, we believe that the suprasellar and parasellar

extension of the tumor represent the main cause of the

difference between these results.

Prolactinomas

Our disease control results (85%) are similar to the previ-

ously presented by other endoscopic series (64–100%) [24,

26, 28, 29, 31–33]. Gross total resection of prolactinomas

was not performed in six cases (15%) who presented

important parasellar extension. All cases in which hor-

monal control was not achieved after surgery were sub-

mitted to pharmacological therapy based on cabergoline/

bromocriptine. The superiority of endoscopic surgery for

hormonal control of prolactinomas has not been conclu-

sively demonstrated. In the literature, a wide range of

different results are presented for tumors operated by the

microsurgery technique (54–86%) [24, 32, 38–40]. A ran-

domized study comparing the results of the endoscopic

endonasal technique versus the sublabial microsurgical

approach demonstrated similar results in terms of prolac-

tinoma resection and hormonal control [26]. However,

endoscopic surgery was associated with fewer complica-

tions, shorter hospital stay and operative time [26].

ACTH-secreting tumors

In our 10 years of endoscopic experience, 28 cases of

Cushing Disease have been treated. After the first surgery,

20 patients (71.4%) achieved hormonal control. If the

results obtained after a second endoscopic procedure are

considered, 25 patients (89.2%) obtained disease control.

The results of hormonal control for ACTH-secreting ade-

nomas operated by endoscopic and microsurgery technique

varies from 67.8 to 86% [24, 28, 29, 31, 32] and from 70 to

86% [24, 41, 42], respectively. The largest series of

Cushing’s disease operated via the endoscopic technique

has been reported by Netea-Maier et al. [43]. In that study

the authors report remission of hypercortisolism in 77% of

the patients after the first pituitary operation and in 83% of

the patients after the first and the second pituitary operation

taken together. Similarly, to that group, we try to perform

the tumor resection preserving as much as possible the

normal parenchyma of the gland. In cases of patients pre-

senting negative MRI studies, hemihypophysectomy was

performed according to the results of the inferior petrosal

sinus sampling. Hypophysectomy was only performed in

cases of relapsing microadenomas in which the tumor was

not identified intraoperatively.

FSH-LH-secreting adenomas

We treated seven patients with FSH-LH-secreting adeno-

mas, and achieved hormonal control after the first procedure

in 71.4%. Considering the second procedure, the hormonal

control was 85.7%. All cases were macroadenomas.

TSH-secreting adenomas

Because of the rarity of such adenoma, our experience in

TSH-secreting adenomas is limited to just on case. Although

treated with success, we can not take any conclusion.

Complication analysis

As in other endoscopic series, the nasal complications are

reduced, mainly because the endoscopic approach skips the

nasal phase and the surgery really begins in the sphenoidal

ostium. Nasal complications in our series were resumed to

seven patients (2.7%) who presented epistaxis after surgery.

Such complication has been reported to occur in 0.7–1.7% of

the patients treated by this technique [24, 29, 31, 44, 45].

Permanent DI was observed in 0.7%, an inferior rate

than that observed in the literature (1.0–3.42%) [24, 29, 31,

44, 45]. Transient DI and SIADH were observed in 2.3 and

0.7% of the patients, respectively. All patients presented

good outcome after intensive care management.

CSF leak is one of the most important complications of

pituitary surgery. It was present in 3.1% of the patients in

our 150 first cases of this series. In the last 78 cases we

have no CSF leak. The variation of endoscopic surgery

series is: 1.2–6% [24, 29, 31, 44, 45], and the microsurgery

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series reports: 0.9–3% [7, 46, 47]. The absence of CSF leak

in the last 78 cases is do to a vascularized nasal septal

mucosa flap as a final layer over the onlay graft, followed

by Foley catheter as a buttress that is removed in 48 h [18].

No case of CSF leak was associated with the development

of meningitis. Two cases of meningitis were observed

(0.7%), comparable to results previously published (0.4–

1.2%) [24, 29, 31, 44, 45].

Lesions of the internal carotid artery is reported in the

literature in 0–0.68% of patients treated by the endoscopic

approach. In our series we observed two cases (0.7%). The

two cases were reoperation and happened at the beginning of

the series when we did not use neuronavigation. After this, all

reoperations are done with this method [24, 29, 31, 44, 45].

Other frequent complications mentioned in literature [24,

29, 31, 44, 45], as sinusistis, mucocele, septum perforation,

ischemia, hematoma, vision deterioration, ophtalmoplegia

and intracerebral hemorrhage, were not observed in our series.

In this series, a total of 35 patients (13.9%) developed

complications, a result comparable to the literature data:

10–26.3% [24, 29, 31, 44, 45]. Our mortality rate was 0.7%

and in the literature it varies from 0 to 0.68% [24, 29, 31,

44, 45]. The microscopic endonasal approach present 37.6–

47% of complications and 0–0.6% of mortality; and the

microscopic transnasal approach presents 8.2–11% of

complication and 0.3–0.9% of mortality [7, 46, 47]. We

present a mortality rate slightly higher than other series.

However, none of the deaths was directly secondary to the

surgical procedure.

Endoscopy limitations

The endoscopic approach presents some particular limita-

tions, such as a narrow channel to the sella, necessity of

special instrumentation, different kind of view what

requires different skills, and some experience of the sur-

geon with the use of the endoscope [48]. Another potential

disadvantage is related to the difficult management of

bleeding complications during the procedure.

The loss of the three-dimensional vision in the endo-

scopic surgery has been advocated as one of the most

important disadvantages of the technique As Cappabianca

et al. [49] we do not consider the endoscopic bidimensional

vision lacking in depth of field. It is undeniable that there is

a remarkable difference when compared to the microscopic

view, but we believe the surgeon can perfectly overcome it

based on the knowledge of anatomic landmarks and with

movements of the endoscope.

Limitations of the study

Our study presents some limitations: it is a retrospective

experience, the data are largely descriptive and it is a

non-randomized, single institutional study design. There

was no direct comparison between the traditional micro-

scopic and endoscopic procedures. We have no data to

demonstrate that endoscopy provides a measurable differ-

ence in outcome as compared to the microsurgical trans-

sphenoidal technique, and therefore, it is not possible to

definitively prove the superiority of endoscopic visualiza-

tion. Another limitation is the short follow up period of

some patients in our series, considering that recurrence of

functioning adenoma may occur after many years.

Conclusion

Nowadays there is a tendency in favor of minimally

invasive technique as the pure endoscopic approach,

because of faster recovery of patient and less complication

and hospitalization time. An important aspect is the expe-

rience of the surgeon with the method. Use of the endo-

scope for sellar lesions is safe and effective, and it is clear

that the endoscope provides important intraoperative data

that are not obtainable with the tunnel vision of the

microscope. Gross total resection of large lesions may be

adequately achieved by the technique, without higher rates

of complications.

Although presenting important advantages, endoscopy

has not been proved to be superior to microsurgery. We

believe larger, randomized, studies are required for analy-

sis of the definitive role of endoscopy in the treatment of

pituitary adenomas.

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