CLINICAL STUDY
Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas Ercan Pinar, MD,* Nurullah Yuceer, MD,† Abdulkadir Imre, MD,* Gonul Guvenc, MD,† and Onur Gundogan, MD* Objective: The objective of this study was to report the efficacy, safety, and outcomes of endoscopic endonasal transsphenoidal techniques for pituitary adenomas. Patients and Methods: A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma between February 2011 and December 2013 was performed. The patients' demographic data, clinical presentations, radiologic findings, recurrence rates, and complications were analyzed. Results: There were 14 men and 18 women with age ranging from 23 to 74 years (mean age, 48.6 y). Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had growth hormone–secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone–secreting adenomas, 2 patients (6.2%) had follicle-stimulating hormone/luteinizing hormone–secreting adenomas, and 1 patient (3.1%) had thyroidstimulating hormone–secreting adenomas. Of the 32 patients, 20 (62.5%) had pituitary macroadenomas and 12 patients (37.5%) had microadenomas. Total-subtotal tumor resection was achieved in 75% and 45% of the microadenomas and macroadenomas, respectively. Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extension. Postoperative cerebrospinal fluid leaks occurred in 3 patients. Two patients developed temporary diabetes insipidus. Conclusions: Endoscopic transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in these patients. Key Words: Pituitary adenoma, endoscopic transsphenoidal surgery, complications (J Craniofac Surg 2015;26: 201–205)
generally performed either on the basis of visual impairment arising from the compression of the optic nevre by the tumor or on the basis of manifestations of excess hormone secretion; the specifics depend on the type of hormone. Pituitary adenoma can be divided into functioning and nonfunctioning tumors or according to size, namely, microadenomas or macroadenomas. Functioning pituitary adenomas can be clinically classified by means of the hormone they secrete.Pituitary adenomas can be differentiated by measuring the size of the tumor. Pituitary microadenomas are defined as intrasellar adenomas of less than 1 cm in diameter without sellar enlargement, whereas pituitary macroadenomas measure larger than 1 cm in diameter with generalized sellar enlargement and may cause symptoms of mass effect.In addition, giant pituitary adenomas are defined as tumors larger than 4 cm in maximum diameter in any direction. They comprise 5% to 16% of all pituitary adenomas in surgical series.3 The endoscopic transsphenoidal approach has become a standard procedure for the removal of pituitary tumors because it has numerous advantages compared with the transcranial approach; this is the least traumatic route to the sella turcica, it avoids the need for brain retraction, and it provides excellent visualization of the pituitary gland and related lesions.This technique, offering a panoramic wide-angled view with increased illumination, was first developed in the 1990s. Jankowski et al4 described the endoscopic endonasal removal of pituitary adenomas. Carrau and Jho5 further developed the pure endonasal endoscopic surgery of pituitary tumors. Different angles can be used, making it possible to effectively reach suprasellar and parasellar portions of the lesion and work around the corner. Because of these advantages, it has been suggested that the endoscopic technique may be preferable to the conventional technique, especially in patients with invasive macroadenomas.6–8 The purpose of this retrospective study was to evaluate the demographic data, clinical presentations, radiologic findings, and postoperative results of endoscopic endonasal transsphenoidal surgery in patients with pituitary tumor.
P
ituitary adenomas are benign, slow-growing tumors. Pituitary adenomas account for approximately 10% of intracranial neoplasms. They often remain undiagnosed, and small pituitary tumors have an estimated prevalence of 16.7%.1,2 The diagnosis is
From the Departments of *Otorhinolaryngology, and †Neurosurgery, Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey. Received April 7, 2014. Accepted for publication July 23, 2014. Address correspondence and reprint requests to Ercan Pinar, MD, Department of Otorhinolaryngology, Katip Celebi University Ataturk Training and Research Hospital, Koruturk mah. Cagdas cad. No. 11/9 35330 Balcova, Izmir, Turkey; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001240
PATIENTS AND METHODS Study Design A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma at the neurosurgery department of Katip Celebi University Hospital from February 2011 to December 2013 was performed. The patients’ demographic data, clinical presentations, radiologic findings, approaches, and complications were analyzed. All patients underwent neurologic,ophthalmologic, radiologic, and endocrinologic examinations before and after surgery. A minimum follow-up of 3 months postoperatively was required for inclusion into the study. Institutional review board approved this study.
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Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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TABLE 1. Clinical Presentation of 32 Patients With Pituitary Adenomas Clinical Signs Total no. patients Visual impairment Headache Amenorrhea Galactorrhea Cushing disease Pituitary insufficiency
Number
Percentage, %
32 10 22 8 6 5 1
100 31.2 68.8 25 18.8 15.6 3.1
Radiologic Evaluation Paranasal sinus computed tomographic (CT) scans were used in all patients for the evaluation of anatomic alterations in the sellar floor, nasal cavity, and paranasal sinuses. All CT scans were performed on a 64-row multislice CT scanner (Toshiba Aquilion; Tokyo, Japan) using axial and coronal images. The images were obtained in 5-mm thickness. Magnetic resonance imaging was performed on a 1.5-T superconductive unit (GE, Milwaukee, WI). Axial, coronal, and sagittal images were used to measure the size of the pituitary tumor preoperatively. Routinely, surgical field was analyzed through contrast-enhanced magnetic resonance imaging on the immediate postoperative first day, 3 months after the surgery, and then at yearly intervals to determine the presence of tumor recurrence.
Endocrinologic Evaluation All the endocrinologic investigation was performed at our hospital. Multiple measurements of plasma growth hormone(GH), insulin-like growth factor 1, GH level after oral glucose tolerance test, prolactin, adrenocorticotrophic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free thyroxine, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone, and estradiol levels were evaluated.
Surgical Procedure All the operations were a combined otorhinological and neurosurgical team effort. We routinely used the binostril approach. Through the binostril approach, a wide field of vision is obtained, the introduction of multiple (3 or even 4) surgical instruments is possible, and resection of lesions with large suprasellar and parasellar components is therefore performed more easily.Under general anesthesia, the patient is placed in the supine position on the operative table, with the back elevated 30 degrees and the head tilted back 20 degrees. A 0-degree and 45-degree rigid endoscope (180/4 mm) is used. Preoperative preparation of the nasal mucosa consists of pledgets soaked in lidocaine HCl of 20 mg/mL and epinephrine HCl of 0.0125-mg/mL mixed solution, which are placed on the medial side of the turbinates through both nostrils for the mucosal decongestion and to decrease mucosal bleeding. The endoscope is navigated into the nasal cavity. The space between the middle turbinate and the nasal septum is gently widened, and a large opening is made in the posterior internasal septum. Normally, we do not resect the middle turbinate through gentle lateralization but through preservation to promote normal postoperative middle meatus physiology. The pure endoscopic transsphenoidal approach involves identifying the sphenoid ostium in the sphenoethmoidal recess. In this step, we usually see the posterior septal branch of the sphenopalatine artery and coagulate it to prevent the risk for the late-onset epistaxis. The sphenoid ostium is enlarged inferomedially with Kerrison punch forceps initially and subsequently enlarged
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maximally in all directions. Once the vital structures in the lateral wall of the sphenoid sinus are identified, a subtectomy (removal of the posterior nasal septum), along with the sphenoid rostrum, is performed to enhance bilateral exposure. In addition, the intersinus septum and the sphenoid air cells are exenterated. Inside the sphenoidal sinus, the sella is then localized and the anterior wall of the sella and the dura mater is largely opened with a high-speed drill or Kerrison rongeur. The sella dura is incised and the pituitary adenoma is removed through bilateral application of suction by the neurosurgeon. All tumors were subjected to pathologic and immunohistochemic analysis.
RESULTS Thirty-two patients met the inclusion criteria and were recruited into our study. There were 14 (43.8%) men and 18 women (56.2%) with age ranging from 23 to 74 years (mean age, 48.6 y). Most patients presented with headache and visual disturbances, followed by acromegaly, amenorrhea, galactorrhea, and Cushing disease. Headache and visual disturbances were present in 11 (34.3%) and 21 (65.6%) patients, respectively (Table 1). Eight patients had bitemporal visual field loss, 1 patient had color desaturation and diplopia, and 2 patients had ophthalmoplegia. Postoperatively, the vision improved in 8 patients and, in the rest, remained the same. Twenty patients (62.5%) had pituitary macroadenoma and 12 (37.5%) had pituitary microadenoma. Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had GH-secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone-secreting adenomas, 2 patients (6.2%) had FSH/LH–secreting adenomas, and 1 patient (3.1%) had thyroid-stimulating hormone–secreting adenomas. General characteristics and analysis of the patients are shown in Table 2.
Nonfunctioning Tumors The nonfunctioning adenomas were the most common single subgroup of pituitary adenomas operated in our patient series. Four of 10 patients (40%) had microadenomas and 6 patients (60%) had macroadenomas. Four of the 6 patients with macroadenomas had sellar extension and 2 patient had cavernous extension.
Growth Hormone–Secreting Adenomas Acromegaly was the most common clinical manifestation in hormone-secreting adenomas. The microadenomas and macroadenomas corresponded to 2 (25%) and 6 (75%) cases, respectively.
TABLE 2. General Characteristics and Analysis of 32 Patients With Pituitary Adenomas Adenoma Characteristics Total no. patients Nonfunctioning adenomas Hormone-secreting adenomas GH-secreting adenomas Prolactinoma ACTH-secreting adenomas FSH/LH-secreting adenomas TSH-secreting adenoma Macroadenomas Microadenomas
Number
Percentage, %
32 10 22 8 6 5 2 1 20 12
100 31.2 68.8 25 18.8 15.6 6.2 3.1 62.5 37.5
© 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery • Volume 26, Number 1, January 2015
Endoscopic Surgery for Pituitary Adenoma
TABLE 3. Surgical Results of 32 Patients With Pituitary Adenomas Clinical Signs
Total-Subtotal Resection
Microadenoma (n = 12) Macroadenoma (n = 20) Sellar (n = 8) Suprasellar extension (n = 8) CS extension (n = 4) Total no. patients (n = 32)
9 9 5 3 1 18
(75%) (45%) (62.5%) (37.5%) (25%) (56.2%)
Partial Resection 2 11 3 5 3 14
(25%) (55%) (37.5%) (62.5%) (75%) (43.8%)
CS, cavernous sinus extension.
TSH-Secreting Adenomas FIGURE 1. Magnetic resonance image demonstrates a giant pituitary adenoma with a significant suprasellar extension and the partial resection of the tumor after the endoscopic endonasal approach. A, Coronal T1 contrast-enhanced image demonstrating the suprasellar extension of the lesion and the absence of cavernous sinus invasion. B, Sagittal T1 contrast-enhanced image demonstrating the suprasellar extension of the tumor and the compression of the optic chiasm. C, Coronal T1 contrast-enhanced image after the partial resection of the tumor. D, Sagittal T1 contrast-enhanced image after the partial removal of the lesion. Residual tumor was observed in the clivus.
Three of the 6 patients with macroadenomas had suprasellar extension and 1 patient had cavernous sinus invasion.
Prolactinoma Amenorrhea and galactorrhea were the most common clinical manifestation in prolactioma. The microadenomas and macroadenomas corresponded to 2 (16.6%) and 4 (83.4%) patients, respectively. Three of the 4 patients with macroadenomas had suprasellar invasion and 1 patient had cavernous sinus invasion.
ACTH-Secreting Adenomas There were 9 patients with confirmed Cushing disease on the basis of clinical, endocrinologic, and immunohistochemical evaluations. Most of these tumor presented as microadenomas (4 patients, 80%). Only 1 patient had sellar macroadenomas.
Only 1 patient in our series presented with a TSH-secreting adenoma. The patient had a macroadenoma that caused important chiasm compression.
Surgical Outcome Total-subtotal tumor resection was achieved in 18 patients (56.2%); partial resection, in 14 patients (43.8%) (Fig. 1). Microadenomas were completely and subtotally removed in 9 patients (75%). Total resection and subtotal resection were achieved in 9 (45%) of 20 patients with macroadenomas (Fig. 2). Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extensions. Total resection and subtotal resection rates were decreased, especially in macroadenomas with suprasellar and cavernous sinus extensions (Table 3).
Complications The most common surgical complication was postoperative cerebrospinal fluid (CSF) leak, which occurred in 3 patients (9.3%). The CSF leaks were treated successfully with 3 days of lumbar drainage. There was 1 patient with meningitis associated with the occurrence of CSF leak. These patients were successfully treated with intravenous antibiotics. Two patients had diabetes insipidus, both of them permanent. Two transient cranial nerve palsies occurred: these 2 patients had a left third cranial nerve palsy in cases with tumor extension in the cavernous sinus. All of the iatrogenic cranial nerve palsies resolved within days or weeks. There was no postoperative nasal bleeding or other significant nasal disturbances (Table 4).
FSH/LH–Secreting Adenomas Follicle-stimulating hormone/LH adenomas were observed in 2 patients (3%) treated by our group. All these were macroadenomas. One of the 2 patients had suprasellar extension, and the other patient had cavernous sinus extension.
DISCUSSION The use of the endoscope for pituitary tumor resection represents significant advancement in pituitary surgery. It allows the surgeon a wide panoramic view independent of the width and depth
TABLE 4. Complication Analysis of 32 Patients Complications Intraoperative CSF leak
FIGURE 2. Magnetic resonance images of pituitary macroadenoma without suprasellar and cavernous sinus extension. A, Preoperative coronal T1 contrast-enhanced image. B, Coronal T1 contrast-enhanced image after the total resection of the tumor.
Postoperative CSF leak Meningitis Transient CN palsy Transient diabetes insipidus Sinusitis
Number (%) 7 3 1 2 2 1
(21.8) (9.3) (3.1) (6.2) (6.2) (3.1)
CN, cranial nerve; CSF, cerebrospinal fluid.
© 2014 Mutaz B. Habal, MD
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of the access. A wide-angled panoramic view is useful for pituitary tumor surgery because it allows excellent anatomic visualization at the posterior wall of the sphenoidal sinus, whereas angled-lens views such as 30-, 45-, and 70-degree endoscopes allow direct visualization at the suprasellar region or various anatomic corners. Endoscopic techniques also have greater advantages for the removal of pituitary macroadenoma extending to the suprasellar region or invading into the cavernous sinus or engulfing the carotids, thus reducing the incidence of residual tumor.9 In this series of patients, we present clinical presentation and surgical outcome of pituitary adenomas after a purely endoscopic endonasal transsphenoidal surgery. Pituitary adenoma can be divided into functioning and nonfunctioning tumors or according to size, namely, microadenomas or macroadenomas. Pituitary adenomas may reach such large dimensions without being detected for several reasons. Patients with silent corticotrophic adenoma, patients with nonfunctional adenoma, and male patients with prolactinomas have tumors that grow slowly without significant symptoms for a long time. When symptoms are present, visual symptoms or headaches are the main complaints.6,10,11 The visual symptoms depend on the anatomic relationship between the tumor and the optic chiasm. In our series, visual symptoms and headache are also the most common clinical symptoms. Pituitary macroadenomas usually compress surrounding structures, commonly resulting in sella enlargement and suprasellar extension. Cavernous sinus invasion has been reported in 6% to 10% of all pituitary adenomas in the literature.12 However, in more recent reports of extended microscopic and endoscopic approaches, authors have reported cavernous sinus invasion in greater than 10% of lesions.13,14 In the current study, 62.5% tumors were classified as macroadenomas. Twelve (60%) of 20 macroadenomas had suprasellar and cavernous sinus extensions. Four patients had cavernous sinus invasion. The incidence of cavernous sinus invasion in the macroadenomas and in all pituitary adenomas were 20% and 12.5% in our study, respectively. Similarly, Hofstetter et al15,16 reported a 29.6% rate of cavernous sinus invasion in macroadenomas and 20.9% in functional adenomas. The endoscopic surgical control of pituitary adenomas, based on gross total resection analysis, varies from 62% to 93%. The large difference between the results reported is partially secondary to the learning curve required to master the procedure and size of the tumor. The incidence of residual tumor is higher in pituitary macroadenoma. This is probably caused by the size and extension of tumor to surrounding structures, namely, suprasellar extension to optic chiasm and lateral extension to engulf the internal carotid artery. In our patient series, the rates of total-subtotal resection in microadenomas and macroadenomas were 75% and 45%, respectively. Surgical results of the macroadenomas with suprasellar and cavernous sinus extensions were associated with lower rates of total-subtotal resection. Although cavernous sinus invasion is the main limitation of open and microscopic transsphenoidal approaches, with wider exposures and angled endoscopes, invasion of the medial wall of the cavernous sinus does not restrict tumor resection. The limitation of endoscopic transsphenoidal surgery is invasion of the lateral wall of the cavernous sinus and extension of the tumor to the temporal lobe. The rate of total-subtotal resection was 25% in the cavernous sinus invasion in our patient series, and this was similar to the rates (38.1%) reported by Hofstetter et al.15 A similar rate of cure (27.2%) was achieved by Santos et al.17 Endoscopy series report rates of complications that vary from 10% to 26.9%.8,9,16,18 The most common complications are permanent diabetes insipidus, new pituitary insufficiency, and postoperative CSF leaks. The rate of CSF leaks after endoscopic endonasal surgery for pituitary adenomas varies in the literature. The rate of
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CSF leaks ranges from 1.2% to 14%.18–20 There is also a greater risk for intraoperative complications such as CSF leak with pituitary macroadenomas, especially if there is significant extrasellar extension. We had 3 patients with postoperative CSF leak (9.3%). The CSF leaks were treated successfully with 3 days of lumbar drainage. These 3 patients had pituitary macroadenoma. There was 1 patient with meningitis associated with the occurrence of CSF leak. This patient was successfully treated with intravenous antibiotics. Diabetes insipidus is usually reported as a complication of pituitary surgery, with reported incidences of transient diabetes insipidus of 2.5% to 20% and permanent diabetes insipidus in 1% to 14.8% in endoscopic series.8,19,21
CONCLUSIONS In conclusion, this study shows that patients with pituitary macroadenomas had lower rates of total-subtotal resection compared with those with pituitary microadenomas. This is most likely caused by difficulties encountered in complete tumor removal, more so with suprasellar extension involving optic chiasm and lateral extension engulfing the carotid artery and carvenous sinus. On the basis of the results of our series and the reports in the literature, transsphenoidal endoscopic surgery is a safe and effective procedure for the treatment of patients with pituitary tumor, if performed by a group of surgeons who specialize in pituitary surgery.
REFERENCES 1. Komotar RJ, Starke RM, Raper DM, et al. Endoscopic endonasal compared with microscopic transsphenoidal and opentranscranial resection of giant pituitary adenomas. Pituitary 2012;15:150–159 2. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: a systematic review. Cancer 2004;101: 613–619 3. Agrawal A, Cincu R, Goel A. Current concepts and controversies in the management of non-functioninggiant pituitary macroadenomas. Clin Neurol Neurosurg 2007;109:645–650 4. Jankowski R, Auque J, Simon C, et al. Endoscopic pituitary tumor surgery. Laryngoscope 1992;102:198–202 5. Carrau RL, Jho HD, Ko Y. Transnasal-transsphenoidal endoscopic surgery of the pituitary gland. Laryngoscope 1996;106:914–918 6. Koutourousiou M, Gardner PA, Fernandez-Miranda JC, et al. Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations. J Neurosurg 2013;118:621–631 7. de Divitiis E, Cappabianca P, Cavallo LM. Endoscopic transsphenoidal approach: adaptability of the procedure to different sellar lesions. Neurosurgery 2002;51:699–705 8. Tabaee A, Anand VK, Barro Y, et al. Endoscopic pituitary surgery: a systematic reviewand meta-analysis. J Neurosurg 2009;111: 545–554 9. Gondim JA, Almeida JPC, Albuquerque LAF, et al. Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients. Pituitary 2011;14:174–183 10. Gondim AJ, Schops M, Almedia JPC, et al. Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center. Pituitary 2010;13:68–77 11. Ceylan S, Koc K, Anık I. Endoscopic endonasal transsphenoidal approach for pituitary adenomas invading the cavernous sinus. J Neurosurg 2010;112:99–107 12. Knosp E, Steiner E, Kitz K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993;33:610–618
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Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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13. Dehdashti AR, Gentili F. Current state of the art in the diagnosis and surgical treatment of Cushing disease: early experience with a purely endoscopic endonasal technique. Neurosurg Focus 2007;23:E9 14. Kitano M, Taneda M, Shimono T, et al. Extended transsphenoidal approach for surgical management of pituitary adenomas invading the cavernous sinus. J Neurosurg 2008;108:26–36 15. Hofstetter CP, Nanaszko MJ, Mubita L, et al. Volumetric classification of pituitary macroadenomas predicts outcome and morbidity following endoscopic endonasaltranssphenoidal surgery. Pituitary 2012;15:450–463 16. Hofstetter CP, Shin BJ, Mubita L, et al. Endoscopic endonasal transsphenoidal surgery for functionalpituitary adenomas. Neurosurg Focus 2011;30:E10
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17. Santos AR, Fonseca Neto RM, Veiga JC, et al. Endoscopic endonasal transsphenoidal approach for pituitary adenomas: technical aspects and report of casuistic. Arq Neuropsiquiatr 2010;68:608–612 18. Berker M, Hazer DB, Yücel T, et al. Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature. Pituitary 2012;15:288–300 19. Cappabianca P, Cavallo LM, Colao A, et al. Surgical complications associated with the endoscopic endonasaltranssphenoidal approach for pituitary adenomas. J Neurosurg 2006;97:293–298 20. Loyo-Varela M, Herrada-Pineda T, Revilla-Pacheco F, et al. Pituitary tumor surgery: review of 3004 cases. World Neurosurg 2013;79:331–336 21. Jho HD. Endoscopic transsphenoidal surgery. J Neurooncol 2001;54:187–195
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Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas Ercan Pinar, MD,* Nurullah Yuceer, MD,† Abdulkadir Imre, MD,* Gonul Guvenc, MD,† and Onur Gundogan, MD* Objective: The objective of this study was to report the efficacy, safety, and outcomes of endoscopic endonasal transsphenoidal techniques for pituitary adenomas. Patients and Methods: A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma between February 2011 and December 2013 was performed. The patients' demographic data, clinical presentations, radiologic findings, recurrence rates, and complications were analyzed. Results: There were 14 men and 18 women with age ranging from 23 to 74 years (mean age, 48.6 y). Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had growth hormone–secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone–secreting adenomas, 2 patients (6.2%) had follicle-stimulating hormone/luteinizing hormone–secreting adenomas, and 1 patient (3.1%) had thyroidstimulating hormone–secreting adenomas. Of the 32 patients, 20 (62.5%) had pituitary macroadenomas and 12 patients (37.5%) had microadenomas. Total-subtotal tumor resection was achieved in 75% and 45% of the microadenomas and macroadenomas, respectively. Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extension. Postoperative cerebrospinal fluid leaks occurred in 3 patients. Two patients developed temporary diabetes insipidus. Conclusions: Endoscopic transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in these patients. Key Words: Pituitary adenoma, endoscopic transsphenoidal surgery, complications (J Craniofac Surg 2015;26: 201–205)
generally performed either on the basis of visual impairment arising from the compression of the optic nevre by the tumor or on the basis of manifestations of excess hormone secretion; the specifics depend on the type of hormone. Pituitary adenoma can be divided into functioning and nonfunctioning tumors or according to size, namely, microadenomas or macroadenomas. Functioning pituitary adenomas can be clinically classified by means of the hormone they secrete.Pituitary adenomas can be differentiated by measuring the size of the tumor. Pituitary microadenomas are defined as intrasellar adenomas of less than 1 cm in diameter without sellar enlargement, whereas pituitary macroadenomas measure larger than 1 cm in diameter with generalized sellar enlargement and may cause symptoms of mass effect.In addition, giant pituitary adenomas are defined as tumors larger than 4 cm in maximum diameter in any direction. They comprise 5% to 16% of all pituitary adenomas in surgical series.3 The endoscopic transsphenoidal approach has become a standard procedure for the removal of pituitary tumors because it has numerous advantages compared with the transcranial approach; this is the least traumatic route to the sella turcica, it avoids the need for brain retraction, and it provides excellent visualization of the pituitary gland and related lesions.This technique, offering a panoramic wide-angled view with increased illumination, was first developed in the 1990s. Jankowski et al4 described the endoscopic endonasal removal of pituitary adenomas. Carrau and Jho5 further developed the pure endonasal endoscopic surgery of pituitary tumors. Different angles can be used, making it possible to effectively reach suprasellar and parasellar portions of the lesion and work around the corner. Because of these advantages, it has been suggested that the endoscopic technique may be preferable to the conventional technique, especially in patients with invasive macroadenomas.6–8 The purpose of this retrospective study was to evaluate the demographic data, clinical presentations, radiologic findings, and postoperative results of endoscopic endonasal transsphenoidal surgery in patients with pituitary tumor.
P
ituitary adenomas are benign, slow-growing tumors. Pituitary adenomas account for approximately 10% of intracranial neoplasms. They often remain undiagnosed, and small pituitary tumors have an estimated prevalence of 16.7%.1,2 The diagnosis is
From the Departments of *Otorhinolaryngology, and †Neurosurgery, Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey. Received April 7, 2014. Accepted for publication July 23, 2014. Address correspondence and reprint requests to Ercan Pinar, MD, Department of Otorhinolaryngology, Katip Celebi University Ataturk Training and Research Hospital, Koruturk mah. Cagdas cad. No. 11/9 35330 Balcova, Izmir, Turkey; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001240
PATIENTS AND METHODS Study Design A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma at the neurosurgery department of Katip Celebi University Hospital from February 2011 to December 2013 was performed. The patients’ demographic data, clinical presentations, radiologic findings, approaches, and complications were analyzed. All patients underwent neurologic,ophthalmologic, radiologic, and endocrinologic examinations before and after surgery. A minimum follow-up of 3 months postoperatively was required for inclusion into the study. Institutional review board approved this study.
The Journal of Craniofacial Surgery • Volume 26, Number 1, January 2015
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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TABLE 1. Clinical Presentation of 32 Patients With Pituitary Adenomas Clinical Signs Total no. patients Visual impairment Headache Amenorrhea Galactorrhea Cushing disease Pituitary insufficiency
Number
Percentage, %
32 10 22 8 6 5 1
100 31.2 68.8 25 18.8 15.6 3.1
Radiologic Evaluation Paranasal sinus computed tomographic (CT) scans were used in all patients for the evaluation of anatomic alterations in the sellar floor, nasal cavity, and paranasal sinuses. All CT scans were performed on a 64-row multislice CT scanner (Toshiba Aquilion; Tokyo, Japan) using axial and coronal images. The images were obtained in 5-mm thickness. Magnetic resonance imaging was performed on a 1.5-T superconductive unit (GE, Milwaukee, WI). Axial, coronal, and sagittal images were used to measure the size of the pituitary tumor preoperatively. Routinely, surgical field was analyzed through contrast-enhanced magnetic resonance imaging on the immediate postoperative first day, 3 months after the surgery, and then at yearly intervals to determine the presence of tumor recurrence.
Endocrinologic Evaluation All the endocrinologic investigation was performed at our hospital. Multiple measurements of plasma growth hormone(GH), insulin-like growth factor 1, GH level after oral glucose tolerance test, prolactin, adrenocorticotrophic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free thyroxine, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone, and estradiol levels were evaluated.
Surgical Procedure All the operations were a combined otorhinological and neurosurgical team effort. We routinely used the binostril approach. Through the binostril approach, a wide field of vision is obtained, the introduction of multiple (3 or even 4) surgical instruments is possible, and resection of lesions with large suprasellar and parasellar components is therefore performed more easily.Under general anesthesia, the patient is placed in the supine position on the operative table, with the back elevated 30 degrees and the head tilted back 20 degrees. A 0-degree and 45-degree rigid endoscope (180/4 mm) is used. Preoperative preparation of the nasal mucosa consists of pledgets soaked in lidocaine HCl of 20 mg/mL and epinephrine HCl of 0.0125-mg/mL mixed solution, which are placed on the medial side of the turbinates through both nostrils for the mucosal decongestion and to decrease mucosal bleeding. The endoscope is navigated into the nasal cavity. The space between the middle turbinate and the nasal septum is gently widened, and a large opening is made in the posterior internasal septum. Normally, we do not resect the middle turbinate through gentle lateralization but through preservation to promote normal postoperative middle meatus physiology. The pure endoscopic transsphenoidal approach involves identifying the sphenoid ostium in the sphenoethmoidal recess. In this step, we usually see the posterior septal branch of the sphenopalatine artery and coagulate it to prevent the risk for the late-onset epistaxis. The sphenoid ostium is enlarged inferomedially with Kerrison punch forceps initially and subsequently enlarged
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maximally in all directions. Once the vital structures in the lateral wall of the sphenoid sinus are identified, a subtectomy (removal of the posterior nasal septum), along with the sphenoid rostrum, is performed to enhance bilateral exposure. In addition, the intersinus septum and the sphenoid air cells are exenterated. Inside the sphenoidal sinus, the sella is then localized and the anterior wall of the sella and the dura mater is largely opened with a high-speed drill or Kerrison rongeur. The sella dura is incised and the pituitary adenoma is removed through bilateral application of suction by the neurosurgeon. All tumors were subjected to pathologic and immunohistochemic analysis.
RESULTS Thirty-two patients met the inclusion criteria and were recruited into our study. There were 14 (43.8%) men and 18 women (56.2%) with age ranging from 23 to 74 years (mean age, 48.6 y). Most patients presented with headache and visual disturbances, followed by acromegaly, amenorrhea, galactorrhea, and Cushing disease. Headache and visual disturbances were present in 11 (34.3%) and 21 (65.6%) patients, respectively (Table 1). Eight patients had bitemporal visual field loss, 1 patient had color desaturation and diplopia, and 2 patients had ophthalmoplegia. Postoperatively, the vision improved in 8 patients and, in the rest, remained the same. Twenty patients (62.5%) had pituitary macroadenoma and 12 (37.5%) had pituitary microadenoma. Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had GH-secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone-secreting adenomas, 2 patients (6.2%) had FSH/LH–secreting adenomas, and 1 patient (3.1%) had thyroid-stimulating hormone–secreting adenomas. General characteristics and analysis of the patients are shown in Table 2.
Nonfunctioning Tumors The nonfunctioning adenomas were the most common single subgroup of pituitary adenomas operated in our patient series. Four of 10 patients (40%) had microadenomas and 6 patients (60%) had macroadenomas. Four of the 6 patients with macroadenomas had sellar extension and 2 patient had cavernous extension.
Growth Hormone–Secreting Adenomas Acromegaly was the most common clinical manifestation in hormone-secreting adenomas. The microadenomas and macroadenomas corresponded to 2 (25%) and 6 (75%) cases, respectively.
TABLE 2. General Characteristics and Analysis of 32 Patients With Pituitary Adenomas Adenoma Characteristics Total no. patients Nonfunctioning adenomas Hormone-secreting adenomas GH-secreting adenomas Prolactinoma ACTH-secreting adenomas FSH/LH-secreting adenomas TSH-secreting adenoma Macroadenomas Microadenomas
Number
Percentage, %
32 10 22 8 6 5 2 1 20 12
100 31.2 68.8 25 18.8 15.6 6.2 3.1 62.5 37.5
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The Journal of Craniofacial Surgery • Volume 26, Number 1, January 2015
Endoscopic Surgery for Pituitary Adenoma
TABLE 3. Surgical Results of 32 Patients With Pituitary Adenomas Clinical Signs
Total-Subtotal Resection
Microadenoma (n = 12) Macroadenoma (n = 20) Sellar (n = 8) Suprasellar extension (n = 8) CS extension (n = 4) Total no. patients (n = 32)
9 9 5 3 1 18
(75%) (45%) (62.5%) (37.5%) (25%) (56.2%)
Partial Resection 2 11 3 5 3 14
(25%) (55%) (37.5%) (62.5%) (75%) (43.8%)
CS, cavernous sinus extension.
TSH-Secreting Adenomas FIGURE 1. Magnetic resonance image demonstrates a giant pituitary adenoma with a significant suprasellar extension and the partial resection of the tumor after the endoscopic endonasal approach. A, Coronal T1 contrast-enhanced image demonstrating the suprasellar extension of the lesion and the absence of cavernous sinus invasion. B, Sagittal T1 contrast-enhanced image demonstrating the suprasellar extension of the tumor and the compression of the optic chiasm. C, Coronal T1 contrast-enhanced image after the partial resection of the tumor. D, Sagittal T1 contrast-enhanced image after the partial removal of the lesion. Residual tumor was observed in the clivus.
Three of the 6 patients with macroadenomas had suprasellar extension and 1 patient had cavernous sinus invasion.
Prolactinoma Amenorrhea and galactorrhea were the most common clinical manifestation in prolactioma. The microadenomas and macroadenomas corresponded to 2 (16.6%) and 4 (83.4%) patients, respectively. Three of the 4 patients with macroadenomas had suprasellar invasion and 1 patient had cavernous sinus invasion.
ACTH-Secreting Adenomas There were 9 patients with confirmed Cushing disease on the basis of clinical, endocrinologic, and immunohistochemical evaluations. Most of these tumor presented as microadenomas (4 patients, 80%). Only 1 patient had sellar macroadenomas.
Only 1 patient in our series presented with a TSH-secreting adenoma. The patient had a macroadenoma that caused important chiasm compression.
Surgical Outcome Total-subtotal tumor resection was achieved in 18 patients (56.2%); partial resection, in 14 patients (43.8%) (Fig. 1). Microadenomas were completely and subtotally removed in 9 patients (75%). Total resection and subtotal resection were achieved in 9 (45%) of 20 patients with macroadenomas (Fig. 2). Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extensions. Total resection and subtotal resection rates were decreased, especially in macroadenomas with suprasellar and cavernous sinus extensions (Table 3).
Complications The most common surgical complication was postoperative cerebrospinal fluid (CSF) leak, which occurred in 3 patients (9.3%). The CSF leaks were treated successfully with 3 days of lumbar drainage. There was 1 patient with meningitis associated with the occurrence of CSF leak. These patients were successfully treated with intravenous antibiotics. Two patients had diabetes insipidus, both of them permanent. Two transient cranial nerve palsies occurred: these 2 patients had a left third cranial nerve palsy in cases with tumor extension in the cavernous sinus. All of the iatrogenic cranial nerve palsies resolved within days or weeks. There was no postoperative nasal bleeding or other significant nasal disturbances (Table 4).
FSH/LH–Secreting Adenomas Follicle-stimulating hormone/LH adenomas were observed in 2 patients (3%) treated by our group. All these were macroadenomas. One of the 2 patients had suprasellar extension, and the other patient had cavernous sinus extension.
DISCUSSION The use of the endoscope for pituitary tumor resection represents significant advancement in pituitary surgery. It allows the surgeon a wide panoramic view independent of the width and depth
TABLE 4. Complication Analysis of 32 Patients Complications Intraoperative CSF leak
FIGURE 2. Magnetic resonance images of pituitary macroadenoma without suprasellar and cavernous sinus extension. A, Preoperative coronal T1 contrast-enhanced image. B, Coronal T1 contrast-enhanced image after the total resection of the tumor.
Postoperative CSF leak Meningitis Transient CN palsy Transient diabetes insipidus Sinusitis
Number (%) 7 3 1 2 2 1
(21.8) (9.3) (3.1) (6.2) (6.2) (3.1)
CN, cranial nerve; CSF, cerebrospinal fluid.
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Pinar et al
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of the access. A wide-angled panoramic view is useful for pituitary tumor surgery because it allows excellent anatomic visualization at the posterior wall of the sphenoidal sinus, whereas angled-lens views such as 30-, 45-, and 70-degree endoscopes allow direct visualization at the suprasellar region or various anatomic corners. Endoscopic techniques also have greater advantages for the removal of pituitary macroadenoma extending to the suprasellar region or invading into the cavernous sinus or engulfing the carotids, thus reducing the incidence of residual tumor.9 In this series of patients, we present clinical presentation and surgical outcome of pituitary adenomas after a purely endoscopic endonasal transsphenoidal surgery. Pituitary adenoma can be divided into functioning and nonfunctioning tumors or according to size, namely, microadenomas or macroadenomas. Pituitary adenomas may reach such large dimensions without being detected for several reasons. Patients with silent corticotrophic adenoma, patients with nonfunctional adenoma, and male patients with prolactinomas have tumors that grow slowly without significant symptoms for a long time. When symptoms are present, visual symptoms or headaches are the main complaints.6,10,11 The visual symptoms depend on the anatomic relationship between the tumor and the optic chiasm. In our series, visual symptoms and headache are also the most common clinical symptoms. Pituitary macroadenomas usually compress surrounding structures, commonly resulting in sella enlargement and suprasellar extension. Cavernous sinus invasion has been reported in 6% to 10% of all pituitary adenomas in the literature.12 However, in more recent reports of extended microscopic and endoscopic approaches, authors have reported cavernous sinus invasion in greater than 10% of lesions.13,14 In the current study, 62.5% tumors were classified as macroadenomas. Twelve (60%) of 20 macroadenomas had suprasellar and cavernous sinus extensions. Four patients had cavernous sinus invasion. The incidence of cavernous sinus invasion in the macroadenomas and in all pituitary adenomas were 20% and 12.5% in our study, respectively. Similarly, Hofstetter et al15,16 reported a 29.6% rate of cavernous sinus invasion in macroadenomas and 20.9% in functional adenomas. The endoscopic surgical control of pituitary adenomas, based on gross total resection analysis, varies from 62% to 93%. The large difference between the results reported is partially secondary to the learning curve required to master the procedure and size of the tumor. The incidence of residual tumor is higher in pituitary macroadenoma. This is probably caused by the size and extension of tumor to surrounding structures, namely, suprasellar extension to optic chiasm and lateral extension to engulf the internal carotid artery. In our patient series, the rates of total-subtotal resection in microadenomas and macroadenomas were 75% and 45%, respectively. Surgical results of the macroadenomas with suprasellar and cavernous sinus extensions were associated with lower rates of total-subtotal resection. Although cavernous sinus invasion is the main limitation of open and microscopic transsphenoidal approaches, with wider exposures and angled endoscopes, invasion of the medial wall of the cavernous sinus does not restrict tumor resection. The limitation of endoscopic transsphenoidal surgery is invasion of the lateral wall of the cavernous sinus and extension of the tumor to the temporal lobe. The rate of total-subtotal resection was 25% in the cavernous sinus invasion in our patient series, and this was similar to the rates (38.1%) reported by Hofstetter et al.15 A similar rate of cure (27.2%) was achieved by Santos et al.17 Endoscopy series report rates of complications that vary from 10% to 26.9%.8,9,16,18 The most common complications are permanent diabetes insipidus, new pituitary insufficiency, and postoperative CSF leaks. The rate of CSF leaks after endoscopic endonasal surgery for pituitary adenomas varies in the literature. The rate of
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CSF leaks ranges from 1.2% to 14%.18–20 There is also a greater risk for intraoperative complications such as CSF leak with pituitary macroadenomas, especially if there is significant extrasellar extension. We had 3 patients with postoperative CSF leak (9.3%). The CSF leaks were treated successfully with 3 days of lumbar drainage. These 3 patients had pituitary macroadenoma. There was 1 patient with meningitis associated with the occurrence of CSF leak. This patient was successfully treated with intravenous antibiotics. Diabetes insipidus is usually reported as a complication of pituitary surgery, with reported incidences of transient diabetes insipidus of 2.5% to 20% and permanent diabetes insipidus in 1% to 14.8% in endoscopic series.8,19,21
CONCLUSIONS In conclusion, this study shows that patients with pituitary macroadenomas had lower rates of total-subtotal resection compared with those with pituitary microadenomas. This is most likely caused by difficulties encountered in complete tumor removal, more so with suprasellar extension involving optic chiasm and lateral extension engulfing the carotid artery and carvenous sinus. On the basis of the results of our series and the reports in the literature, transsphenoidal endoscopic surgery is a safe and effective procedure for the treatment of patients with pituitary tumor, if performed by a group of surgeons who specialize in pituitary surgery.
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