Endoscopic endonasal transsphenoidal surgery of 1,166 pituitary adenomas

A total of 1,166 pituitary adenoma patients that underwent pure endoscopic endonasal transsphenoidal surgery, conducted by the leading surgeon Zhou tao at the Neurosurgery Department of PLA general hospital between January 2007 and June 2013, were retrospectively studied. All patients underwent neurologic, ophthalmologic, and endocrine examinations prior to surgery. The patient follow-up period varied from 3 months to 5.6 years.

All endocrine examinations were performed prior to and after surgery and at the time of follow-up consultation. Multiple measurements of plasma growth hormone (GH), insulin-like growth factor-I (IGF-I), prolactin (PRL), adrenocorticotrophic hormone (ACTH), cortisol, 24 h urinary free cortisol (when Cushing’s disease was suspected), thyroid-stimulating hormone (TSH), free thyroxine, luteinizing hormone (LH) and follicle stimulating hormone (FSH), testosterone, and estradiol (E2) levels were investigated.

To evaluate the size and the invasion of the adenoma, all patients underwent magnetic resonance imaging (MRI), with and without administration of the intravenous contrast agent prior to surgery. Tumor size was classified in three categories according to maximum tumor diameter: microadenoma (<10 mm); macroadenomas (>10 mm); and giant adenoma (>40 mm). Conventional paranasal computerized tomography scans were used in 264 patients for surgical planning. Sphenoid sinus and septal anatomy were evaluated in detail. Follow-up MRI studies were obtained at 3 and 6 months following surgery.

All patients were treated by the same medical team, using identical procedures. Under general anesthesia, the patient was placed in the supine position on the operative table with the back elevated at a 30° angle and the head tilted back at a 20° angle. The neurosurgeon was positioned on the right side of the patient and the assistant on the left side. Preoperative preparation of the nasal mucosa consists of pledgets soaked in tetracaine HCl 20 mg/ml and epinephrine HCl 0.0125 mg/ml mix solution which are placed on medial side of the turbinate through both nostrils for the mucosal decongestion and to decrease mucosal bleeding during nasal phase of surgery. Briefly, after intubation, the endoscope (Karl Storz, Tuttlingen, Germany) was inserted into the nasal cavity. The middle turbinate is lateralized or fractured to promote normal postoperative middle meatus physiology. In the reported cases, the space between the middle turbinate and the nasal septum was gently widened. The unilateral nostril was commonly utilized for the majority of patients, while bilateral nostrils were utilized for patients with giant adenomas or when the tumors were located in the sphenoid sinus. Predominantly, in the cases reported in this study, the right nostril approach was chosen. If the right nostril was unsuitable due to septal deviation or adenoma extension to the right cavernous sinus or to the superior sellae region, the left nostril was utilized. The ostium was observed and widened to visualize entrance to the sphenoid sinus. Drilling of the base of the sphenoid and particularly removal of the sphenovomerine suture enabled exposure of the sellae floor and also significantly increased the maneuverability of surgical instruments, thus augmenting the efficacy and safety of endoscopic surgery by improving accessibility to the tumor and controlling any bleeding, similar to that achieved by microsurgery. Inside the sphenoid sinus, exposure of the sellae diaphragm floor from one carotid protuberance to the other and craniocaudally from the planum sphenoidale to the clivus was achieved. The point of attachment of the diaphragm sellae should not be compromised with dual incision, which can be identified by preoperative MRI T2 imaging. Intrasphenoidal septal variations and the anterior wall of the sellae are easily evaluated by both coronal and sagittal paranasal CT scans preoperatively. Intercarotid distance is measured in great care with MRI and CT scans and these measures are rechecked intraoperatively with the aid of designed 10 mm scaled-dissector by the leading author. In most cases, the neuronavigation was used to identify diaphragm sellae, the anterior wall of the sellae and the dura mater are opened with a highspeed drill or Kerrison rongeur. Visualization of the sellae region was initially performed with a 0° endoscope. If a macroadenoma was encountered directly beneath the dura, decompression was commenced immediately. The interior was debulked in the traditional fashion using curettes and suction. In the current study, if a cavity opened during surgery, the endoscope was inserted into the cavity, allowing direct visualization of the residual tumor. Following tumor resection, 45° angled endoscopes were inserted into the surgical cavity to explore for any residual tumor. In some cases, the intraoperative MRI scan was performed to detect the residual tumor for further resection in case of macro adenomas. For the reconstruction of the sellae region, a small piece of Surgicel (Ethicon Ltd., U.K.) was placed into the sellae cavity, and Duragen (Integra, Plainsboro, NJ, USA), positioned as an overlayer graft in the intradual space. A larger piece of Duraform was then placed into the sinus to sustain the Duragen graft and Bio Glue (CryoLife, Inc., Kennesaw, GA, USA), applied to fix the graft. The expanding sponge was inserted into the window of the anterior wall of the sphenoidal sinus as a buttress and removed 48 h after surgery. In some cases that postoperative CSF leakage was obvious, an external lumbar drainage system was applied and kept in place for 5 days after surgery. If the postoperative CSF leakage continues, a second dual fixation operation should be made, a combination of duraform, underlayer, and overlayer free fascia lata grafts was placed in the sellae floor. In the 24 h after the surgery, CT and endocrinological evaluations were conducted. Hormonal assessments, identical to the preoperative hormonal screenings, were performed on postoperative day 1 and 7 and in the first and third postoperative months.

A total of 1,166 pituitary adenomas were treated by one surgeon in one medical center. Males and females represented 44.3 and 55.7 % of patients, respectively. The mean age of the population was 40.3 ± 15.25 years (Table 1). According to the size of the lesion, 245 (21.0 %) of tumors were classified as microadenomas, 806 (69.1 %) tumors as macroadenomas, and 115 (10 %) tumors as giant adenomas. Hormone-secreting adenomas represented the majority of lesions (589 cases, 50.6 %). The most common of functioning lesions was PRL secreting pituitary adenomas (26.4 %), followed by GH-secreting pituitary adenomas (15.4 %), mixed GH/PRL secreting pituitary adenomas (2.2 %), and ACTH-secreting adenomas (5.8 %), followed by TSH secreting adenomas (0.6 %) (Table 2).

Gross total resection as ascertained by MRI results 3 months after surgery was achieved in 240 (98 %) cases of microadenomas, 742 (92 %) cases of macroadenomas, and 87 (76 %) cases of giant adenomas (Table 3). Visual recovery was acquired in 105 (92 %) cases, with the III and VI cranial nerve function restored in 22 (88 %) patients. Hormonal control, determined in the 3 months after surgery, was achieved in 47 (69 %) cases of ACTH-secreting pituitary adenomas, 119 (66 %) cases of GH-secreting pituitary adenomas, 262 (85 %) cases of PRL secreting pituitary adenomas, and 6 (86 %) cases of TSH secreting adenomas (Table 4).

Complications were observed in 157 (13.5 %) patients (Table 5). Diabetes insipidus (DI) was observed in 82 patients following surgery, 74 of them (6.3 % of all patients) presented with only transient dysfunction, while 8 patients presented with permanent DI, requiring vasopressin therapy and clinical follow-up. Postoperative CSF leakage was observed in 7 cases (0.6 %). A second operation was performed in these patients to reconstruct the sellae and the double layer of duraform and free fascia lata grafts placed in both the intradural and epidural space supported by fat tissue. Lumbar drainage was maintained for 5–7 days after the operation. Twelve patients that suffered from meningitis were adequately treated, and recovered well. Twenty patients suffered from postoperative epistaxis, 17 of which required coagulation by packing of the nasal cavity. One case was treated by the ENT colleagues, while 2 cases that did not respond to the above-mentioned method were treated with endovascular embolization of maxillary artery branches. Out of seventeen patients that suffered from transient hyposmia, 8 patients recovered after 3 months and 9 patients with giant nonfunctioning adenoma recovered after 6 months. Fifteen patients experienced hypopituitarism and consequently required thyroid replacement therapy and/or steroid replacement therapy. One patient presented with headache and transient III cranial nerve palsy. The CT scan of this patient showed SAH and consequently CTA was performed to exclude the aneurysm. One giant non-functional patient suffered coma after surgery and was lost when follow-up. Eight cases of intrasellae bleeding following surgery were observed. Evacuation of the hematoma via an endoscopic approach was performed in 7 cases, and a third operation was performed in one patient with residual hematoma after second evacuation surgery. Normal visual acuity was restored in 3 out of these 8 patients while 5 patients had poor visual acuity.

Five cases were listed (Table 6): 1 nonfunctioning adenoma (Fig. 1), 1 nonfunctioning adenoma invading cavernous sinus (Fig. 2), 1 PRL adenoma (Fig. 3), 1 ACTH adenoma (Fig. 4), and 1 TSH adenoma (Fig. 5). All the adenomas got gross total resection.

In recent years, endoscopic endonasal transsphenoidal surgery has a wide application in the treatment of pituitary adenomas. It has been used in our medical center where the correspondence author (Doctor Zhou) of this manuscript is since 2007 because the endoscopic surgery can provide better vision and result in less nasal cavity injuries than the microsurgical approach.

Exclusive endoscopic transsphenoidal resection of pituitary adenomas is safe and efficacious when compared to the traditional microscopic approach. The endoscopic transsphenoidal approach provides a panoramic vision inside the surgical area, a superior close up of the anatomy, an improved working angle and less nasal cavity injuries. D’Haens et al. [5] reported the endocrinologic outcome in 2 series of patients using these 2 different techniques, the overall remission rate of hypersecretion was 63 % in the endoscopic group compared to 50 % in the microsurgical group; in noninvasive macroadenomas, the remission rate of hypersecretion obtained using endoscopy was 78 % compared with 43 % using microsurgery; the endocrinological results achieved for microadenomas were similar in the 2 groups; postoperative CSF leaks occurred more frequently in the endoscopic group (6 cases). Strychowsky et al. [6] made a systematic review included one prospective and nine retrospective articles, and demonstrated that the pure endoscopic approach was associated with less mean blood loss, shorter hospital stays and operative times, and fewer nasal complications, and a trend toward better gross total resection and decreased incidence of postoperative DI.

The removal rate of pituitary adenomas is closely related with tumor volume [7, 8], which was a predicting factor for the surgical outcome. Compared with traditional open or transsphenoidal microscopic methods, the endoscopic endonasal transsphenoidal approach offers the potential for aggressive resection via a minimal access corridor. In the current study, the majority of tumors were macroadenomas (69.1 %) and giant adenomas (10 %), and the gross total of resections of macroadenomas was 92 %, which was comparable to the results (96 %) reported by Dehdashti et al. [9]; the gross total of resections of giant adenomas was 76 %, which was higher than the results (47.2 %) of a systematic review conducted by Komotar et al. [10]. The higher gross total resection in the present study may be attributed to the use of intraoperative MRI and neuronavigation during the surgery. In our medical center, the intraoperative MRI and neuronavigation are often used during the treatment of macroadenomas bigger than 3 cm. After the initial resection, the intraoperative MRI scans can be used for assessing if there is residual tumors and determining if a second or third surgery is required for safe resection of the lesion. The surgery should not be continued if the tumor residue is out of reach, the access corridor is very narrow for the operation, or when most parts of some giant adenoma were removed to achieve the decompression. A second transcranial surgery or radiotherapy or radiosurgery may be considered for tumors invading into cavernous sinus and neighboring cranial base that cannot be totally removed by the first surgery.

The exclusive endoscopic approach is a safe, efficacious, and minimally invasive technique for treatment of pituitary adenoma. A higher gross total resection rate is vital for non-functional and functional adenomas. For functional adenomas, hormonal remission is unlikely to be achieved by surgery alone, indicating that the use of adjuvant therapy be introduced to obtain long-term hormonal control. The progression of endoscopy instruments, more experienced doctors, and the development of more effective drugs are all important factors for the good outcome of pituitary adenoma.