Pituitary DOI 10.1007/s11102-009-0195-x
Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center Jackson A. Gondim Æ Michele Schops Æ Joa˜o Paulo C. de Almeida Æ Lucas Alverne F. de Albuquerque Æ Erika Gomes Æ Taˆnia Ferraz Æ Francisca Andre´a C. Barroso
Ó 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 adenoma removal over an 10-year period. Pre- and postoperative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-
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]
secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormonesecreting 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 nonfunctioning adenomas was 83% and for functioning adenomas 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 complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome 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.
M. Schops J. P. C. de Almeida L. A. F. de Albuquerque School of Medicine, Federal University of Ceara, Fortaleza, Brazil
Keywords Endoscopic surgery Endonasal Transsphenoidal surgery Pituitary adenoma
E. Gomes Department of Ear, Nose and Throat Surgery, General Hospital of Fortaleza, Fortaleza, Brazil
Introduction
T. Ferraz F. A. C. Barroso Department of Endocrinology, General Hospital of Fortaleza, Fortaleza, Brazil
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
123
Pituitary
[1]. Hirsch in 1910 described a direct endonasal transsphenoidal 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 pituitary 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 transsphenoidal 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 consecutives patients who underwent 251 pure endoscopic endonasal treatment of pituitary adenomas. Any other lesion
123
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, insulin-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-stimulating hormone (TSH), free thyroxine, luteinizing hormone (LH) and follicle stimulating hormone (FSH), testosterone, and estradiol levels were studied. All tumors were submitted to immunohistochemical analysis of the tissue removed. Neuroradiology All patients underwent tumor evaluation by magnetic resonance 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 gadolinium-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
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 localized, 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. Intraoperative 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 adenomas and hormonal control in functioning adenomas (prolactinomas, GH-secreting adenomas, ACTH-secreting adenomas, TSH-secreting adenomas and FSH/LH-secreting 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 considered 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 current 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 measurement (\100 nmol/l requiring substitutive therapy) obtained in the first 48 h after surgery along with suppression 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 hormonal 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 microadenomas 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 Nonfunctioning adenomas
228 93
100 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
97
42.5
Localized perfuration of the sella floor
26
11.5
Diffuse perforation of the sella floor
67
29.4
48
21.1
[10 mm
Cystic component
123
Pituitary
Subgroup analysis
Table 3 Growth hormone secreting adenomas characteristics
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 components 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 resections); the two remain patients were referred to radiotherapy 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 acromegaly) of GH-prolactin co-secreting adenomas were
GH secreting adenomas
58
Mean size
20.8 ± 10.02 mm
Microadenomas Hormonal control Macroadenomas Hormonal control Second surgery Cure after the second procedure
11 (18.9%) 9 (81.8%) 47 (81.1%) 32(68%) 4 4
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 adenomas. 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 clinical 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
Table 4 Prolactinomas characteristics
Mean size
30.4 ± 15.1 mm
Prolactinomas
41
Microadenomas
0
Mean size
20.2 ± 10.8 mm
93 (100%)
Microadenomas
Macroadenomas Total resection
70 (75.2%)
Subtotal resection ([80%)
13 (13.9%)
Partial resection (\80%)
10 (10.7%)
123
Hormonal control Macroadenomas Hormonal control
7 (17.1%) 7 (100%) 34 (82.9%) 28 (82.3%)
Pituitary
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 endocrinological 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 evaluation after the second procedure. No patient was submitted 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 important 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%) endoscopic 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 secretion (SIADH) was presented in two cases of macroadenomas 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 6 Complications analysis n
%
Table 5 ACTH-secreting adenomas characteristics
SIADH
2
0.7
ACTH adenomas
28
Transient diabetes insipidus
6
2.3
Mean size
8.7 ± 8.3 mm
Permanent diabetes insipidus
2
0.7
Microadenomas
0.7
20 (71.4%)
Internal carotid lesion
2
Hormonal control
15 (75%)
Post-operative hemorrhage
7
2.7
Partial control
5 (25%)
Seizures
1
0.3
Second surgery (hemihypophisectomy)
5 (100%)
Brain parenchima lesion
1
0.3
5 (100%)
Addisonian crisis
1
0.3 0.3
Cure after the second procedure
8 (28.6%)
Hypertension
1
Hormonal control
5 (62.5%)
CSF leak
8
3.1
Partial control
3 (37.5%)
Second surgery
3 (100%)
Meningitis Death
2 2
0.7 0.7
Cure after the second procedure
0
Total
35
13.9
Macroadenomas
123
Pituitary
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 pneumonia 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 performed as a ‘‘pure’’ technique, with the endoscope as the sole visualizing tool along the whole procedure, as presented in our series; or as an ‘‘endoscope-assisted’’ procedure, 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 adenomas have been extensively compared to the results obtained by microsurgery [24, 28, 29]. However, no conclusive evidence of different results has been demonstrated [24, 28, 29]. Until the moment, no large randomized study has compared the results of these techniques.
123
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 distance between the reference center and the small towns in the country and the important delay between development of symptoms and admission in our neurosurgical department. 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 surgery 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 adenomas, 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 nonfunctioning 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 endoscopic 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
by the weighted average value of microscopic series calculated 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 literature [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 GHsecreting 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.
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 adenomas 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 presenting 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 adenomas, 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.
Prolactinomas
TSH-secreting adenomas
Our disease control results (85%) are similar to the previously 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 hormonal control was not achieved after surgery were submitted to pharmacological therapy based on cabergoline/ bromocriptine. The superiority of endoscopic surgery for hormonal control of prolactinomas has not been conclusively 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 randomized study comparing the results of the endoscopic endonasal technique versus the sublabial microsurgical approach demonstrated similar results in terms of prolactinoma resection and hormonal control [26]. However, endoscopic surgery was associated with fewer complications, shorter hospital stay and operative time [26].
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.
ACTH-secreting tumors In our 10 years of endoscopic experience, 28 cases of Cushing Disease have been treated. After the first surgery,
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
123
Pituitary
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.
non-randomized, single institutional study design. There was no direct comparison between the traditional microscopic and endoscopic procedures. We have no data to demonstrate that endoscopy provides a measurable difference in outcome as compared to the microsurgical transsphenoidal technique, and therefore, it is not possible to definitively prove the superiority of endoscopic visualization. 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 experience of the surgeon with the method. Use of the endoscope 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 analysis of the definitive role of endoscopy in the treatment of pituitary adenomas.
Endoscopy limitations The endoscopic approach presents some particular limitations, 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 surgeon 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 endoscopic 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
123
References 1. Schloffer H (1906) Zur frage der Operationen an der Hypophyse. Beitr Klin Chir 50:767–817 2. Hirsch O (1910) Endonasal method of removal of hypophyseal tumors. With a report of two successful cases. JAMA 55:772–774 3. Halstead AE (1910) Remarks on the operative treatment of tumors of the hypophysis. With the report of two cases operated on by an oro-nasal method. Surg Gynecol Obstet 10:494–502 4. Rosegay H (1981) Cushing’s legacy to transsphenoidal surgery. J Neurosurg 54:448–454 5. Cushing H (1912) The Pituitary Body and Its Disorders: Clinical States Produced by Disorders of the Hypophysis Cerebri. JB Lippincott, Philadelphia, pp 296–305 6. Cushing H (1914) The Weir Mitchell Lecture. Surgical experiences with pituitary disorders. JAMA 63:1515–1525 7. Zada G, Kelly DF, Cohan P, Wang C, Swerdloff R (2003) Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions. J Neurosurg 98:350–358 8. Liu JK, Das K, Weiss MH, Laws ER Jr, Couldwell WT (2001) The history and evolution of transsphenoidal surgery. J Neurosurg 95:1083–1096 9. Hardy J (1969) Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 16:185–217
Pituitary 10. Guiot G (1973) Transsphenoidal approach in surgical treatment of pituitary adenomas. General principles and indications in nonfunctioning adenomas. In: Kolher PO, Ross GT (eds) Diagnosis and treatment of pituitary tumors, vol 303. Excepta Medica Congress Series, Amsterdam, pp 159–178 11. Messerklinger W (1970) Endoscopy of the nose. Monatsschr Ohrenheilkd Laryngorhinol 104:451–456 12. Kennedy DW, Cohn ES, Papel ID, Holliday MJ (1984) Transsphenoidal approach to the sella the Johns Hopkins experience. Laryngoscope 94:1066–1074. doi:10.1288/00005537-19840800000015 13. Draf W (1991) Endonasal micro-endoscopic frontal sinus surgery the Fulda concept. Operative Tech Otolaryngol Head Neck Surg 2:234–240 14. Jankovsky R, Auque J, Simon CMJC, Hepner H, Wayoff M (1992) Endoscopic pituitary surgery. Laryngoscope 102:198–202 15. Jho H, Carrau R (1996) Endoscopy assisted transsphenoidal surgery for pituitary adenoma. Acta Neurochir (Wien) 138:1416– 1425. doi:10.1007/BF01411120 16. Jho H, Carrau R (1997) Endoscopic endonasal transsphenoidal surgery: experience with fifty patients. J Neurosurg 87:44–51 17. Cappabianca P, Alfieri A, de Divitiis E (1998) Endoscopic endonasal transsphenoidal approach to the sella: towards functional endoscopic pituitary surgery (FEPS). Minim Invasive Neurosurg 41:66–73. doi:10.1055/s-2008-1052019 18. Hadad G, Bassagasteguy L, Carrau RL, Mataza JC, Kassam A, Snyderman CH et al (2006) A novel reconstructive technique following endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 116:1881–1885. doi: 10.1097/01.mlg.0000234933.37779.e4 19. Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A (2005) Consensus statement: medical management of acromegaly. Eur J Endocrinol 153:737–740. doi: 10.1530/eje.1.02036 20. Jho HD, Carrau RL, Ko Y, Daly MA (1997) Endoscopic pituitary surgery: an early experience. Surg Neurol 7:213–223. doi: 10.1016/S0090-3019(96)00452-1 21. Cappabianca P, Cavallo LM, de Divitiis E (2004) Endoscopic endonasal transsphenoidal surgery. Neurosurgery 55:933–940. doi:10.1227/01.NEU.0000137330.02549.0D 22. Perneczky A, Fries G (1998) Endoscope-assisted brain surgery: part 1—evolution, basic concept, and current technique. Neurosurgery 42:219–224. doi:10.1097/00006123-199802000-00001 23. Fries G, Perneczky A (1998) Endoscope-assisted brain surgery: part 2—analysis of 380 procedures. Neurosurgery 42:226–231; discussion 231–232. doi:10.1097/00006123-199802000-00008 24. Dehdashti AR, Ganna A, Karabatsou K, Gentili F (2008) Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 62:1006–1017. doi:10.1227/ 01.neu.0000325862.83961.12 25. Koren I, Hadar T, Rappaport ZH, Yaniv E (1999) Endoscopic transnasal transsphenoidal microsurgery versus the sublabial approach for the treatment of pituitary tumors: endonasal complications. Laryngoscope 109:1838–1840 26. Cho D-Y, Liau W-R (2002) Comparison of endonasal endoscopic surgery and sublabial microsurgery for prolactinomas. Surg Neurol 58:371–376. doi:10.1016/S0090-3019(02)00892-3 27. Sheehan MT, Atkinson JLD, Kasperbauer JL, Erickson BJ, Nippoldt TB (1999) Preliminary comparison of the endoscopic transnasal versus the sublabial transseptal approach for clinically nonfunctioning pituitary macroadenomas. Mayo Clin Proc 74:661–670. doi:10.4065/74.7.661
28. Tabaee A, Anand VK, Barro´n Y, Hiltzik DH, Brown SM, Kacker A, Mazumdar M, Schwartz TH (2008) Predictors of short-term outcomes following endoscopic pituitary surgery. Clin Neurol Neurosurg 2:119–122 29. Frank G, Pasquini E, Farneti G, Mazzatenta D, Sciarretta V, Grasso V, Faustini Fustini M (2006) The endoscopic versus the traditional approach in pituitary surgery. Neuroendocrinology 83:240–248. doi:10.1159/000095534 30. Jain AK, Gupta AK, Pathak A, Bhansali A, Bapuraj JR (2008) Endonasal transsphenoidal pituitary surgery: is tumor volume a key factor in determining outcome? Am J Otolaryngol 29(1):48– 50. doi:10.1016/j.amjoto.2007.01.006 31. Jho HD (2001) Endoscopic transsphenoidal surgery. J Neurooncol 54:187–195. doi:10.1023/A:1012969719503 32. Kabil MS, Eby JB, Shahinian HK (2005) Fully endoscopic endonasal versus transseptal transsphenoidal pituitary surgery. Minim Invasive Neurosurg 48:348–354. doi:10.1055/s-2005-915635 33. Shen CC, Wang YC, Hua WS, Chang CS, Sun MH (2000) Endoscopic endonasal transsphenoidal surgery for pituitary tumors. Chin Med J Taipei 63:301–310 34. Davis DH, Laws ER Jr, Ilstrup DM, Speed JK, Caruso M, Shaw EG, Abboud CF, Scheithauer BW, Root LM, Schleck C (1993) Results of surgical treatment for growth hormone-secreting pituitary adenomas. J Neurosurg 79:70–75 35. Freda PU, Wardlaw SL, Post KD (1998) Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 89:353–358 36. Sheaves R, Jenkins P, Blackburn P, Huneidi AH, Afshar F, Medbak S, Grossman AB, Besser GM, Wass JA (1996) Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure. Clin Endocrinol (Oxf) 45:407–413. doi:10.1046/ j.1365-2265.1996.8370847.x 37. Gondim JA, Ferraz T, Mota I, Studart D, Almeida JP, Gomes E, Schops M (2009) Outcome of surgical intrasellar growth hormone tumor performed by a pituitary specialist surgeon in a developing country. Surg Neurol 72:15–29; discussion 19 38. Charpentier G, de Plunkett T, Jedynak P, Peillon F, Le Gentil P, Racadot J, Visot A, Derome P (1985) Surgical treatment of prolactinomas. Short- and long-term results, prognostic factors. Horm Res 22:222–227. doi:10.1159/000180098 39. Derome P (1985) Surgical treatment of prolactinomas. Short and long-term results, prognostic factors. Horm Res 22:222–227. doi: 10.1159/000180098 40. Scanlon MF, Peters JR, Thomas JP, Richards SH, Morton WH, Howell S et al (1985) Management of selected patients with hyperprolactinaemia by partial hypophysectomy. Br Med J (Clin Res Ed) 291:1547–1550 41. Fahlbusch R, Buchfelder M, Muller OA (1986) Transsphenoidal surgery for Cushing’s disease. J R Soc Med 79:262–269 42. Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, Rahl R, Lu A, Wilson CB (2004) Transsphenoidal microsurgery for Cushing’s disease: initial outcome and longterm results. J Clin Endocrinol Metab 89:6348–6357. doi: 10.1210/jc.2003-032180 43. Netea-Maier RT, van Lindert EJ, den Heijer M, van der Eerden A, Pieters GF, Sweep CG, Grotenhuis JA, Hermus AR (2006) Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing’s disease. Eur J Endocrinol 154:675–684. doi:10.1530/eje.1.02133 44. Cappabianca P, Cavallo LM, Colao A, de Divitiis E (2006) Surgical complications associated with the endoscopic endonasal transsphenoidal approach for pituitary adenomas. J Neurosurg 97:293–298 45. de Divitiis E, Cappabianca P, Cavallo M (2003) Endoscopic endonasal transsphenoidal approach to the sellar region. In: de
123
Pituitary Divitiis E, Cappabianca P (eds) Endoscopic Endonasal Transsphenoidal Surgery. Springer, Wien, pp 91–130 46. Ciric I, Ragin A, Baumgartner C, Pierce DB (1997) Complications of transsphenoidal surgery: results of a national survey, review of the literature and personal experience. Neurosurgery 40:225–237. doi:10.1097/00006123-199702000-00001 47. Semple PL, Laws ER Jr (1999) Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing’s disease. J Neurosurg 91:175–179
123
48. Gondim J, Schops M, Tella OI Jr (2003) Transnasal endoscopic surgery of the sellar region: study of the first 100 cases. Arq Neuropsiquiatr 61:836–841. doi:10.1590/S0004-282X20030005 00024 49. Cappabianca P, Divitiis E (2004) Endoscopy and transsphenoidal surgery. Neurosurgery 54:1043–1050. doi:10.1227/01.NEU.000 0119325.14116.9C
