Craniopharyngiomas (from Greek: κρανίον, skull

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1 J Neurosurg 119: , 2013 AANS, 2013 Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients Clinical article Maria Koutourousiou, M.D., 1 Paul A. Gardner, M.D., 1 Juan C. Fernandez-Miranda, M.D., 1 Elizabeth C. Tyler-Kabara, M.D., Ph.D., 1 Eric W. Wang, M.D., 2 and Carl H. Snyderman, M.D., M.B.A. 1,2 Departments of 1 Neurological Surgery and 2 Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Object. The proximity of craniopharyngiomas to vital neurovascular structures and their high recurrence rates make them one of the most challenging and controversial management dilemmas in neurosurgery. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for both pediatric and adult craniopharyngiomas. The object of the present study was to present the results of EES and analyze outcome in both the pediatric and the adult age groups. Methods. The authors retrospectively reviewed the records of patients with craniopharyngioma who had undergone EES in the period from June 1999 to April Results. Sixty-four patients, 47 adults and 17 children, were eligible for this study. Forty-seven patients had presented with primary craniopharyngiomas and 17 with recurrent tumors. The mean age in the adult group was 51 years (range years); in the pediatric group, 9 years (range 4 18 years). Overall, the gross-total resection rate was 37.5% (24 patients); near-total resection (> 95% of tumor removed) was 34.4% (22 patients); subtotal resection ( 80% of tumor removed) 21.9% (14 patients); and partial resection (< 80% of tumor removed) 6.2% (4 patients). In 9 patients, EES had been combined with radiation therapy (with radiosurgery in 6 cases) as the initial treatment. Among the 40 patients (62.5%) who had presented with pituitary insufficiency, pituitary function remained unchanged in 19 (47.5%), improved or normalized in 8 (20%), and worsened in 13 (32.5%). In the 24 patients who had presented with normal pituitary function, new pituitary deficit occurred in 14 (58.3%). Nineteen patients (29.7%) suffered from diabetes insipidus at presentation, and the condition developed in 21 patients (46.7%) after treatment. Forty-four patients (68.8%) had presented with impaired vision. In 38 (86.4%) of them, vision improved or even normalized after surgery; in 5, it remained unchanged; and in 1, it temporarily worsened. One patient without preoperative visual problems showed temporary visual deterioration after treatment. Permanent visual deterioration occurred in no one after surgery. The mean follow-up was 38 months (range months). Tumor recurrence after EES was discovered in 22 patients (34.4%) and was treated with repeat surgery (6 patients), radiosurgery (1 patient), combined repeat surgery and radiation therapy (8 patients), interferon (1 patient), or observation (6 patients). Surgical complications included 15 cases (23.4%) with CSF leakage that was treated with surgical reexploration (13 patients) and/or lumbar drain placement (9 patients). This leak rate was decreased to 10.6% in recent years after the introduction of the vascularized nasoseptal flap. Five cases (7.8%) of meningitis were found and treated with antibiotics without further complications. Postoperative hydrocephalus occurred in 7 patients (12.7%) and was treated with ventriculoperitoneal shunt placement. Five patients experienced transient cranial nerve palsies. There was no operative mortality. Conclusions. With the goal of gross-total or maximum possible safe resection, EES can be used for the treatment of every craniopharyngioma, regardless of its location, size, and extension (excluding purely intraventricular tumors), and can provide acceptable results comparable to those for traditional craniotomies. Endoscopic endonasal surgery is not limited to adults and actually shows higher resection rates in the pediatric population. ( Key Words craniopharyngioma endoscopic endonasal approach endoscopic skull base surgery Abbreviations used in this paper: BMI = body mass index; CN = cranial nerve; DI = diabetes insipidus; EES = endoscopic endonasal surgery; GH = growth hormone; GTR = gross-total resection; HPA = hypothalamic-pituitary-adrenal; HPG = hypothalamic-pituitarygonadal; HPT = hypothalamic-pituitary-thyroid; TSS = transsphenoidal surgery; SIADH = syndrome of inappropriate antidiuretic hormone secretion. Craniopharyngiomas (from Greek: κρανίον, skull + ϕάρυξ, throat + -ωμα, growth) are benign, rare tumors arising from squamous epithelial remnants of the Rathke pouch. 16,35 Epidemiologically, they have a This article contains some figures that are displayed in color on line but in black-and-white in the print edition J Neurosurg / Volume 119 / November 2013

2 Endoscopic endonasal surgery for craniopharyngiomas bimodal age distribution pattern with a peak between 5 and 14 years in children and 50 and 74 years in adults, although the tumor has been reported in all age groups. 1,16,20 They account for 2% 5% of primary intracranial neoplasms overall 16,20,31,32 and 6% 13% of intracranial tumors in children. 1,14,16,20 Craniopharyngiomas rarely undergo malignant degeneration but are difficult to cure and pose significant difficulties in the establishment of an optimal therapeutic protocol. Treatment should focus on the relief of symptoms, avoidance of treatment-related morbidity, preservation of quality of life, and prevention of recurrence with extension of survival. Complete tumor removal can be curative, and excision followed by irradiation in cases of residual tumor is the main treatment option. 20,39 However, increased recurrence rates usually necessitate multimodality treatments (surgery, radiotherapy, stereotactic radiosurgery, intracystic irradiation, local/intracystic chemotherapy, or systemic chemotherapy). In every case, treatment should be tailored to the individual based on age, presenting symptoms, tumor characteristics, prior treatment, treatment tolerance, and comorbidities. For the last 12 years in our department, EES has been used for the treatment of every craniopharyngioma except purely intraventricular tumors. The aim of the present study was to describe the results of this surgical approach for the management of craniopharyngiomas and to analyze outcome in both the pediatric and the adult age groups. We also discuss the surgical success of the endonasal approach, compare its results with those for open and microscopic transsphenoidal approaches, and provide a review of the literature. Methods Patient Population With approval from the institutional review board, we retrospectively reviewed the medical files and imaging studies of patients with craniopharyngiomas treated via EES at the University of Pittsburgh Medical Center in the period from June 1999 to April In every case, the diagnosis had been histologically confirmed. All patients had been preoperatively evaluated with MRI and CT scanning of the brain and skull base. Tumor volume was approximated by a modified ellipsoid volume, that is, (A B C)/2, where A, B, and C are the maximum diameters of the craniopharyngioma in each of the 3 dimensions. J Neurosurg / Volume 119 / November 2013 Evaluation of Outcome Clinical outcome after EES had been assessed with postoperative visual tests (visual acuity and visual fields), endocrinological studies, and clinical examination. Postoperative obesity was evaluated based on BMI and BMIfor-age/-sex charts for children; these results were available in only 20 adults but in 16 of the 17 children. We evaluated the degree of tumor resection by performing volumetric analysis of the postoperative MR images compared with preoperative images. In most cases, immediate postoperative MRI had been performed within a few days after surgery to be used as a baseline for further imaging follow-up. The degree of resection had been confirmed on the 3-month postoperative MRI study in all but 5 patients; 3 were lost to follow-up and 2 died within 3 months following surgery. During our review, the volume of residual craniopharyngioma was calculated with the same mathematic formula ([A B C]/2) used for the initial tumor measurement. In residual tumors, we considered the degree of resection to be near total when > 95% of the tumor was resected, subtotal when 80% of the tumor was resected, and partial when < 80% of the tumor was removed. Results were analyzed for the whole cohort and separately for the adult and pediatric populations. Resection and recurrence rates for every studied tumor characteristic were compared using the chi-square or Fisher exact test, as appropriate. A p value < 0.05 was considered statistically significant. Data were collected using Microsoft Excel 2010 (Microsoft Corp.) and analyzed using SAS, version 9.3 (SAS institute Inc.). Results Clinical Presentation Sixty-four patients (47 adults and 17 children) with craniopharyngioma were identified. The mean age of patients was 40 years (range 4 82 years) with a male/female ratio of 1.6:1. Forty-seven patients had presented with primary craniopharyngioma and 17 with recurrent. All of the 17 previously treated patients had undergone surgery elsewhere (multiple surgeries in 5 cases), including craniotomy (13 patients), transsphenoidal surgery (5 patients), and stereotactic cyst aspiration (2 patients); 8 of the 17 had had additional radiation therapy and 1 had received chemotherapy. In the adult population, the mean age was 51 years (range years) and there was a male predominance (male/female ratio of 1.5:1). Thirty-four adults (72%) had a primary craniopharyngioma. In the pediatric population, the mean age was 9 years (range 4 18 years) and there was a male predominance (male/female ratio of 1.8:1). Thirteen children (76%) had presented with a primary craniopharyngioma. The most common clinical presentation in the entire cohort was visual impairment, which occurred in 44 patients (68.8%), followed by complete or partial pituitary dysfunction (62.5%), obesity (51.8%), headache (42.2%), and DI (29.7%). In the adult population, visual impairment occurred in 80.8% of patients, hypopituitarism in 66%, and obesity in 55%. (In the adult group it was difficult to differentiate between hypothalamic obesity and obesity due to lifestyle or other factors.) In the pediatric population, besides visual deficit and hypopituitarism (35.3% and 52.9%, respectively), common symptoms were central obesity (43.8%) and headache (64.7%). As expected, patients who had presented with recurrent, previously treated tumors had a higher incidence of pituitary dysfunction (76.5% of patients vs 57.4% of those with primary craniopharyngiomas) and a higher rate of DI (76.5% of patients vs 12.8% of those with primary tumors). Moreover, obesity was remarkably higher in previ- 1195

3 M. Koutourousiou et al. ously treated patients (73.3% vs 43.9%). Table 1 summarizes the presenting symptoms in the different age groups (adults vs children), according to previous treatment status (primary vs recurrent tumor), and in the whole cohort. Imaging Findings The average tumor volume in the whole cohort was 9.6 cm 3 (range cm 3 ), and the maximum tumor diameter varied from 1.3 to 6.4 cm. In adults, the average tumor volume was 6.6 cm 3 (range cm 3 ) and the maximum tumor diameter ranged from 1.3 to 5.1 cm. Tumors were bigger in the pediatric group with an average volume of 17.7 cm 3 (range cm 3 ), and the maximum tumor diameter ranged from 1.8 to 6.4 cm. Tumor location and extension were quite irregular in many cases. All tumors had a suprasellar component, and 39 also occupied the sella (60.1%). All of the craniopharyngiomas also had some degree of hypothalamic involvement. Extension into the third ventricle, which was evaluated on preoperative MRI and confirmed intraoperatively, occurred in 21 cases (32.8%) in the entire cohort. In many cases, the preoperative MRI impression of tumor extension into the third ventricle was incorrect; usually the tumor expanded against the floor of the third ventricle, which remained intact (Fig. 1). Extension to the interpeduncular cistern was found in 34 cases (53.1%). Cavernous sinus involvement was rare and evident mainly in the adult group (10.6%), while extreme lateral extension to the cerebellopontine angle was found only in children (11.8%). Fifty-eight (91%) of the tumors showed heterogeneous enhancement on MRI after contrast administration, 4 showed homogeneous enhancement, and 2 had a purely cystic appearance. Table 2 summarizes the tumor imaging findings in adults, children, and the entire cohort. Surgical Management and Adjuvant Treatment All patients underwent EES as the initial treatment modality. The goals of surgery were symptom relief and the avoidance of surgery-related morbidity with GTR desired in every case possible. However, in many cases GTR was considered overly dangerous because of tumor infiltration of or adherence to vital neurovascular structures (for example, the hypothalamus or optic chiasm); in such cases, residual tumor was intentionally left behind. Fifty patients (78.1%) underwent a single EES; and 5 (7.8%), a staged EES. In 9 cases (14%), resection was followed by radiotherapy: radiosurgery in 6 cases, conventional radiotherapy in 2, and proton beam in 1. Endoscopic endonasal surgery combined with radiotherapy was more often used in the adult group than in the pediatric group (8 patients vs 1 patient). During a mean follow-up of 38 months (range months), 22 patients (34%) had a tumor recurrence (15 adults and 7 children) and were treated with reoperation in 6 cases (EES in 5 and open craniotomy in 1), radiosurgery alone in 1, surgery (EES in 7 and craniotomy in 1) combined with radiotherapy (intracystic irradiation with 32 P in 3 patients and radiosurgery in 7) in 8 patients, systemic interferon in 1 pediatric patient, and close follow-up (no adjuvant treatment so far) in 6 clinically asymptomatic patients. Open craniotomies, although never used as the initial ap- TABLE 1: Clinical presentation of patients with craniopharyngioma* Age Group Previous Treatment Status Adults Children Primary Tumor Recurrent Tumor Total no. of patients visual impairment 38 (80.8%) 6 (35.3%) 31 (66%) 13 (76.5%) 44 (68.8%) pituitary dysfunction 31 (66%) 9 (52.9%) 27 (57.4%) 13 (76.5%) 40 (62.5%) hypogonadism 19 (40.4%) 4 (23.6%) 14 (29.8%) 9 (52.9%) 23 (35.9%) hypoadrenalism 18 (38.3%) 4 (23.6%) 10 (21.3%) 12 (70.6%) 22 (34.4%) GH deficit/growth retardation 6 (12.8%) 5 (29.4%) 8 (17%) 3 (17.6%) 11 (17.2%) hypothyroidism 23 (48.9%) 7 (41.2%) 18 (38.3%) 12 (70.6%) 30 (46.9%) hyperprolactinemia (stalk effect) 6 (12.8%) 0 5 (10.6%) 1 (5.9%) 6 (9.4%) headache 16 (34%) 11 (64.7%) 23 (48.9%) 4 (23.6%) 27 (42.2%) DI 16 (34%) 3 (17.6%) 6 (12.8%) 13 (76.5%) 19 (29.7%) obesity 22/40 (55%) 7/16 (43.8%) 18/41 (43.9%) 11/15 (73.3%) 29/56 (51.8%) increased ICP (HC/papilledema) 5 (10.6%) 4 (23.6%) 5 (10.6%) 4 (23.6%) 9 (14.1%) nausea/vomiting 2 (4.3%) 3 (17.6%) 5 (10.6%) 0 5 (7.8%) CN palsy 0 1 (5.9%) 1 (2.1%) 0 1 (1.6%) gait disturbance 1 (2.1%) (5.9%) 1 (1.6%) mental changes 1 (2.1%) 0 1 (2.1%) 0 1 (1.6%) incidental finding 1 (2.1%) 2 (11.8%) 3 (6.4%) 0 3 (4.7%) * Unless otherwise stated, values represent numbers of patients (%). HC = hydrocephalus; ICP = intracranial pressure. Note that preoperative obesity was evaluated based on BMI and BMI-for-age/-sex charts for children and BMI for adults, and these data were available in only 40 adults and 16 children (41 primary and 15 recurrent cases). Among these patients, 2 had a shunt after previous treatment J Neurosurg / Volume 119 / November 2013

4 Endoscopic endonasal surgery for craniopharyngiomas TABLE 2: Craniopharyngioma characteristics based on preoperative imaging findings* Fig. 1. Left: Preoperative sagittal postcontrast T1-weighted MR image showing a craniopharyngioma with solid (lower) and cystic (upper) compartments. The cystic compartment extends up to the floor of the third ventricle, giving the impression of invading the ventricle (arrow). Right: Sagittal postcontrast T1-weighted MR image obtained after GTR. During surgery, the tumor capsule was dissected from the floor of the third ventricle, which was intact and not penetrated (arrow). The pituitary gland and stalk were also preserved, as demonstrated on MRI. The contrast-enhancing linear structure at the posterior aspect of the sphenoid sinus represents the vascularized nasoseptal flap that was used for reconstruction (arrowheads). proach in this cohort, were performed in 3 cases of craniopharyngiomas that recurred either in the third ventricle or lateral to the optic nerve/supraclinoid carotid artery. Table 3 summarizes all treatment modalities used for the management of craniopharyngioma both initially and for recurrences in adults, children, and the entire cohort. Degree of Tumor Resection As previously mentioned, the goals of surgery are symptom relief, the avoidance of surgery-related morbidity, and GTR whenever possible. When GTR is considered harmful, we intentionally leave tumor capsule attached to vital surrounding neurovascular structures with the aim of resecting > 95% of the tumor; we have found that this degree of resection can provide good results while limiting major morbidity. For adults in whom GTR may be dangerous, we believe that near-total surgical removal combined with postoperative irradiation represents a better alternative than aggressive surgery with the aim of GTR. We have probably been more aggressive with the pediatric population given the radiotherapy restrictions in this age group. As a result, the GTR rate after EES was 37.5% (24 patients) overall and was higher in children (9 patients [52.9%]) than in adults (15 patients [31.9%]; p = 0.12; Fig. 2). Analyzing our results based on the goal of maximum safe resection (> 95% of the tumor), the overall success rate was 71.9% (46 patients) and, more specifically, 61.7% in adults (29) and 100% in children (17; p = 0.002). Besides this significant difference in resection rates; tumor location, tumor extension, and previous treatment did not influence the success rates of EES when we analyzed the data with the goal of either GTR or maximum safe resection (Table 4). Clinical Outcome Whole Cohort. Overall, improvement in or normalization of vision occurred in 86.4% of the patients (38 of the 44 who presented with visual impairment). In the entire J Neurosurg / Volume 119 / November 2013 Parameter No. (%) Adults Children Total no. of patients tumor dimensions mean vol (cm 3 ) mean max diameter (cm) tumor location sellar 27 (57.4%) 12 (70.6%) 39 (60.1%) suprasellar 47 (100%) 17 (100%) 64 (100%) tumor extension ventricular system intraventricular 12 (25.5%) 9 (52.9%) 21 (32.8%) sagittal plane frontal lobe 1 (2.1%) 0 1 (1.6%) sphenoid sinus 1 (2.1%) 1 (5.9%) 2 (3.1%) coronal plane cavernous sinus 5 (10.6%) 1 (5.9%) 6 (9.4%) sylvian fissure 0 1 (5.9%) 1 (1.6%) axial plane prepontine cistern 1 (2.1%) 2 (11.8%) 3 (4.7%) interpeduncular cistern 23 (48.9%) 11 (64.7%) 34 (53.1%) CPA 0 2 (11.8%) 2 (3.1%) contrast enhancement heterogeneous 41 (87.2%) 17 (100%) 58 (90.6%) homogeneous 4 (8.5%) 0 4 (6.2%) ring enhancement 2 (4.2%) 0 2 (3.1%) * Unless otherwise stated, values represent numbers of patients (%). CPA = cerebellopontine angle. cohort a postoperative visual deficit developed in 1 patient whose preoperative vision was intact, although the deficit was completely resolved within 6 months. Improvement in or normalization of preexisting pituitary dysfunction occurred in 20% of the patients overall (8 of the 40 who presented with some degree of hypopituitarism). In 19 patients (47.5%), preoperative pituitary insufficiency remained unchanged following EES; in 13 patients (32.5%), a further deficit in 1 or more hypothalamopituitary axes occurred (adrenal insufficiency in 11 [27.5%], hypothyroidism in 5 [12.5%], hypogonadism in 3 [7.5%], and GH deficit in 3 [7.5%]). New hypopituitarism in those with normal pituitary function preoperatively (24 patients) occurred in 14 cases (58.3%) and included adrenal insufficiency (13 patients [54.2%]), thyroid dysfunction (14 patients [58.3%]), hypogonadism (3 patients [12.5%]), and GH deficit (4 patients [16.7%]). Preexisting DI remained unchanged in all 19 patients. Among the 45 patients without preoperative DI, 12 (26.7%) experienced transient DI requiring short-term treatment with desmopressin and 21 (46.7%) had permanent DI after surgery. Headache at presentation (27 patients) resolved in 23 patients (85.2%) and persisted in 4 (14.8%). Postoperative weight changes were not available 1197

5 M. Koutourousiou et al. TABLE 3: Summary of treatment in 64 patients with craniopharyngioma* Type of Treatment Adults Children Total no. of patients initial treatment EES only 39 (83%) 16 (94%) 55 (86%) single EES 36 (76.6%) 14 (82.3%) 50 (78.1%) staged EES 3 (6.4%) 2 (11.8%) 5 (7.8%) EES (single) + radiotherapy 8 (17%) 1 (6%) 9 (14%) radiosurgery 5 (10.6%) 1 (6%) 6 (9.4%) conventional radiotherapy 2 (4.2%) 0 2 (3.1%) proton beam therapy 1 (2.1%) 0 1 (1.6%) no. of recurrences 15 (31.9%) 7 (41.2%) 22 (34.4%) treatment for recurrence reop only 3 (20%) 3 (42.8%) 6 (27.3%) EES 2 (13.3%) 3 (42.8%) 5 (22.7%) open approach (craniotomy) 1 (6.7%) 0 1 (4.5%) radiotherapy only (radiosurgery) 1 (6.7%) 0 (0%) 1 (4.5%) reop + radiotherapy 6 (40%) 2 (28.6%) 8 (36.4%) EES 6 (40%) 1 (14.3%) 7 (31.8%) open approach 2 (13.3%) 1 (14.3%) 3 (13.6%) intracystic radiation ( 32 P) 2 (13.3%) 1 (14.3%) 3 (13.6%) radiosurgery 6 (40%) 1 (14.3%) 7 (31.8%) interferon 0 1 (14.3%) 1 (4.5%) no adjuvant treatment (close FU) 5 (33.3%) 1 (14.3%) 6 (27.3%) * Unless otherwise stated, values represent numbers of patients (%). FU = follow-up. Two patients had multiple EESs for multiple recurrences. Open approaches in the 3 patients included craniotomy (2), stereotactic cyst aspiration (2), and Ommaya cyst aspiration (1). in the majority of adult patients, so it is difficult to have conclusions as regards the overall study. However, weight changes were well studied in the pediatric population and the results are analyzed below. Adult Population. The majority of adults (38 patients) presented with visual deficits, which improved or resolved in 32 (84.2%). In 5 adults (13.2%), preoperative visual deficits remained unchanged after EES, and 1 elderly patient (2.6%) experienced a temporary deterioration of his preexisting impaired vision in the immediate postoperative course. Further deterioration or new visual impairment in this cohort was transient. Improvement or normalization of preexisting hypopituitarism occurred in 7 adults (22.6%) and affected thyroid function in 2, gonadal function in 4, GH restoration in 2, and normalization of elevated prolactin levels in 3. The condition in over half of the adults (51.6%) with preoperative pituitary insufficiency remained unchanged, including 10 who had presented with recurrent craniopharyngiomas and panhypopituitarism after previous treatment. Worsening of preexisting hypopituitarism occurred in 8 cases (25.8%), affecting the HPA axis in 7 cases, the HPT axis in 3, the HPG axis in 1, and GH secretion in 2. New pituitary insufficiency in adults with normal pituitary function preoperatively was found in 6 cases (37.5%) and included a deficit in the HPA axis in 6 (37.5%), the HPT axis in 6 (37.5%), the HPG axis in 3 (18.7%), and GH secretion in 1 (6.2%). Preexisting DI was never resolved; transient DI occurred in 11 patients, permanent DI developed in 10 (32.3%) after surgery. Five patients presented with increased intracranial pressure, and 2 of them had received a shunt after previous treatment; shunt placement was necessary in the other 3 patients as well. As mentioned above, obesity is difficult to exclusively associate with hypothalamic dysfunction in this age group and thus we did not closely track adults for weight changes after EES. With the available data, however, we did find that all obese adults remained obese following surgery (9 patients), and 2 overweight adults (11.1%) became obese postoperatively. Table 5 provides a summary of the clinical outcomes in the adult population. Pediatric Population. Children with craniopharyngioma presented mainly with headache (11 patients), which was resolved in every case after EES. Six children had preoperative visual impairment that improved or even normalized after treatment; there was no visual worsening or new deficit in this cohort. Improvement of preexisting hypopituitarism occurred in only 1 patient (11.1%) and affected both the HPG axis and GH secretion. Preexisting hypopituitarism remained unchanged in one-third of the patients after EES, including 2 who had presented with recurrent craniopharyngioma and panhypopituitarism after previous treatment. Five patients (55.5%) showed further pituitary dysfunction in the HPA axis (4 patients), 1198 J Neurosurg / Volume 119 / November 2013

6 Endoscopic endonasal surgery for craniopharyngiomas in 8 (100%), and GH secretion in 3 (37.5%). Preexisting DI was never resolved; transient DI occurred in 1 patient (7.1%) and permanent DI developed in 11 (78.6%) after surgery. Four patients presented with hydrocephalus (2 of them had received a shunt after previous treatment); after EES, hydrocephalus resolved in every case but required shunt revision in 1 of the previously treated cases. One patient who presented with CN VI palsy showed complete recovery 6 months after EES. Among the 7 children who presented with central obesity, 6 had available postoperative data on their BMI-for-sex/-age. Five (83.3%) showed unchanged weight, and 1 (16.7%) lost weight and was moved to the overweight category. Among the 9 children who were either normal (8 patients) or overweight (1 patient) before surgery, 3 (33.3%) became obese, 5 (55.5%) maintained their weight, and 1 (11.1%) became overweight after surgery. Table 6 provides a summary of clinical outcomes in the pediatric population. Fig. 2. Coronal and sagittal postcontrast T1-weighted MR images obtained in an adult with a suprasellar craniopharyngioma. Upper: Preoperative images demonstrating a solid suprasellar craniopharyngioma with extension to the interpeduncular cistern and displacement of the optic chiasm. The pituitary stalk cannot be identified in these images. Lower: Postoperative images obtained after GTR via EES. The optic chiasm was totally decompressed. The pituitary stalk was preserved, as shown in both images. The pituitary gland was intact. Note the vascularized nasoseptal flap at the posterior aspect of the sphenoid sinus on the sagittal image. the HPT axis (2 patients), the HPG axis (2 patients), and GH secretion (1 patient). All of the previously endocrinologically intact children (8 patients) showed some degree of postoperative pituitary dysfunction requiring hormonal replacement therapy. New pituitary insufficiency affected the HPA axis in 7 cases (87.5%), the HPT axis Surgical Complications New hypopituitarism and permanent DI have already been described in detail above. Overall, CSF leakage occurred in 23.4% of patients (27.7% in adults and 11.8% in children). It is important to note that EES began being used in children after 2007 when the skull base defect was routinely reconstructed with the vascularized nasoseptal flap, which is probably the reason for the difference in leakage rates. The CSF leakage rates in adults were significantly different between the flap and no-flap EES groups (p = ): among 17 adults who underwent no-flap reconstruction, 58.8% (10) had a CSF leak, whereas a leak occurred in only 10% (3) of the 30 adults who had vascularized flap reconstruction (essentially the same as in the pediatric group). Cerebrospinal fluid leakage was treated with reoperation alone (6 patients), lumbar drain placement alone (2 patients), or reoperation combined with lumbar or external ventricular drain placement (7 patients). Meningitis developed in 2 of the TABLE 4: Resection rates evaluated for different parameters* Parameter & p Value Total No. GTR (100%) Resection >95% Near-Total Resection (>95%) Subtotal Resection ( 80%) Partial Resection (<80%) primary (40.4%) 34 (72.3%) 15 (31.9%) 10 (21.3%) 3 (6.4%) recurrent 17 5 (29.4%) 12 (70.6%) 7 (41.2%) 4 (23.5%) 1 (5.9%) p value adults (31.9%) 29 (61.7%) 14 (29.8%) 14 (29.8%) 4 (8.5%) children 17 9 (52.9%) 17 (100%) 8 (47.1%) 0 0 p value intraventricular 21 9 (42.9 %) 15 (71.4%) 6 (28.6%) 2 (9.5%) 4 (19%) extraventricular (34.9%) 31 (72.1%) 16 (37.2%) 12 (27.9%) 0 p value intrasellar/suprasellar (41%) 28 (71.7%) 12 (30.8%) 7 (17.9%) 4 (10.3%) suprasellar only 25 8 (32%) 18 (72%) 10 (40%) 7 (28%) 0 p value total (37.5%) 46 (71.9%) 22 (34.4%) 14 (21.9%) 4 (6.2%) * The goal of surgery was GTR or resection > 95% of the tumor when GTR was dangerous, and p values were evaluated for these results. The additional columns show more analytically the resection rates that were achieved with EES. Unless otherwise stated, values represent numbers of patients (%). J Neurosurg / Volume 119 / November

7 M. Koutourousiou et al. TABLE 5: Clinical outcomes of 47 adults with craniopharyngioma following EES Initial Deficit Total Preop No. Resolved Improved Unchanged Worsened New Deficit* visual impairment (50%) 13 (34.2%) 5 (13.2%) 1 (2.6%) 1/9 (11.1%) pituitary dysfunction 31 5 (16.1%) 2 (6.4%) 16 (51.6%) 8 (25.8%) 6/16 (37.5%) DI (100%) 0 10/31 (32.3%) obesity (BMI >30) (100%) 0 2/18 (11.1%) headache (75%) 0 4 (25%) 0 3/31 (9.7%) * New deficit in patients without that particular symptom preoperatively. Unless otherwise stated, values represent numbers of patients (%). Refers to transient deficit. Refers to permanent deficit. Postoperative BMI was available in only 9 adults of the 22 who presented with obesity. Two new cases of obesity following EES among 18 patients who were normal (BMI: ) or overweight (BMI: ) before surgery. patients with a CSF leak. Signs and symptoms of meningitis developed in 5 patients and were managed with antibiotics without further complications. Hydrocephalus after EES occurred in 7 patients (12.7%) who were all treated with ventriculoperitoneal shunt placement; 3 of the 7 experienced postoperative CSF leakage. Only 1 of these 7 patients had preoperative papilledema, and none had preoperative radiographic evidence of hydrocephalus. Most of the patients with postoperative hydrocephalus had relatively large tumors (exceeding 3.2 cm in their maximum diameter in 5 cases), and 5 of the 7 had tumor extension into the third ventricle. Postoperative CN palsies (affecting CN VI in 3 cases and CN III in 2 cases) were all transient and occurred more often in children (17.6% vs 4.2% in adults), which may be a result of a larger tumor size or more aggressive surgical manipulation to achieve higher rates of tumor resection. Transient SIADH developed in 3 patients and was managed with water restriction. Some more rare complications occurred in the pediatric group and included 1 case of epidural hematoma from pin placement, requiring craniotomy for hematoma evacuation; 1 case of intraventricular hematoma and resultant hydrocephalus, managed with reoperation and shunt placement; and 1 case of subdural hematoma following external ventricular drain removal, managed via observation without further complications. No death occurred in the immediate postoperative course, that is, within 1 month after EES. Table 7 summarizes the main complications after EES in adults, children, and the entire cohort. Adjuvant Treatment, Recurrences, and Follow-Up The mean follow-up was 38 months (range months) for the entire cohort, 39 months (range months) for adults, and 35.3 months (range months) for children. During this period, 22 patients (34.4%) had tumor recurrence. Although resection rates after initial EES were higher in children, this age group showed a slightly higher recurrence rate than adults in the same time period (41.2% and 31.9%). In evaluating recurrence rates based on the degree of resection, we found no statistical significance (p = 0.43). Comparing recurrence rates between GTR and non-gtr cases revealed no significant difference (p = 0.22). Additionally, age, tumor location, or previous treatment did not have an important influence on recurrence, as shown in Table 8. However, it is important to note that the relatively short follow-up in this study may have resulted in a small number of recurrences at the present time and moderate power for a safe statistical analysis. The recurrence-free period was 17.1 months (range 3 52 months) in the entire cohort, 15.1 months (range 3 33 months) in adults, and 19.6 months (range 4 52 months) in children. Adjuvant treatment either initially or for the management of recurrent craniopharyngioma has already been summarized in Table 3. Radiotherapy following EES was TABLE 6: Clinical outcome in pediatric patients with craniopharyngioma following EES Initial Deficit Total Preop No. Resolved Improved Unchanged Worsened New Deficit* visual impairment 6 4 (66.7%) 2 (33.3%) pituitary dysfunction (11.1%) 3 (33.3%) 5 (55.5%) 8/8 (100%) DI (100%) 0 11/14 (78.6%) obesity (BMI-for-age/-sex) 7 0 1/6 (16.7%) 5/6 (83.3%) 0 3/9 (33.3%) headache (100%) * New deficit in patients without that symptom preoperatively. Unless otherwise stated, values represent numbers of patients (%). Refers to permanent deficit. Postoperative BMI was available in 6 patients among 7 who presented with obesity. Three new cases of obesity following EES of 9 patients who were normal (8) or overweight (1) based on BMI-for-age/sex before surgery J Neurosurg / Volume 119 / November 2013

8 Endoscopic endonasal surgery for craniopharyngiomas TABLE 7: Complications after EES for craniopharyngioma* Complication Age Group Primary vs Recurrent Tumor Adults Children Primary Recurrent Total hypopituitarism (new) 14/37 (37.8%) 13/15 (86.7%) 24/47 (51.1%) 3/5 (60%) 27/52 (51.9%) permanent DI 10/31(32.3%) 11/14 (78.6%) 19/41 (46.3%) 2/4 (50%) 21/45 (46.7%) CSF leakage 13/47 (27.7%) 2/17 (11.8%) 13/47 (27.7%) 2/17 (11.8%) 15/64 (23.4%) hydrocephalus (new) 5/42 (11.9%) 2/13 (15.4%) 5/42 (11.9%) 2/13 (15.4%) 7/55 (12.7%) meningitis 3/47 (6.4%) 2/17 (11.8%) 4/47 (8.1%) 1/17 (5.9%) 5/64 (7.8%) transient CN palsy 2/47 (4.2%) 3/17 (17.6%) 4/47 (8.1%) 1/17 (5.9%) 5/64 (7.8%) SIADH 2/47 (4.2%) 1/17 (5.9%) 3/47 (6.4%) 0 3/64 (4.7%) * Unless otherwise stated, values represent numbers of patients (%). The denominator in each column represents patients who were intact before surgery. The numerator in each column represents new or worsened cases. New hypopituitarism was counted among patients who had some degree of pituitary function before surgery; cases that presented with panhypopituitarism were excluded from the calculations. more often used in adults than in children (17% vs 6% for primary tumors and 40% vs 28.6%, respectively, for recurrent tumors; Fig. 3). As with primary tumors, recurrences in children were more often treated with surgery alone (42.8% vs 20% in adults). One child with a multiply recurrent craniopharyngioma received systemic chemotherapy with interferon and has remained free of disease for more than 2 years. Among the 7 adults who received adjuvant radiotherapy after EES, 2 with near-total tumor resection demonstrated no evidence of tumor on the most recent MRI and 5 showed a decrease in residual tumor. At the most recent follow-up for each patient, 24 patients (37.5%) were free of tumor, 6 (9.4%) had decreased residual tumor, 30 (46.9%) had stable residual tumor, and 4 (6.2%) had increased tumor; repeat surgery was TABLE 8: Recurrence compared between different parameters* Parameter Total No. Recurrence p Value GTR 24 6 (25%) 0.43 near-total resection (45.4%) subtotal resection 14 4 (28.6%) partial resection 4 2 (50%) GTR 24 6 (25%) 0.22 non-gtr (40%) resection >95% (34.8%) 0.70 resection <95% 20 6 (30%) EES + radiotherapy 9 3 (33.3%) 1.00 EES alone (34.5%) adults (31.9%) 0.49 children 17 7 (41.2%) primary (34%) 0.93 recurrent 17 6 (35.3%) intraventricular 21 8 (38.1%) 0.66 extraventricular (32.6%) intrasellar/suprasellar (30.8%) 0.45 suprasellar only (40%) total (34.4%) * Unless otherwise stated, values represent numbers of patients (%). J Neurosurg / Volume 119 / November 2013 planned for 2 of the latter 4 patients, whereas observation with further imaging studies was planned for the other 2. Although there was no operative mortality (death in the immediate postoperative course or within 1 month after EES) during the follow-up, 9 patients have died. An elderly patient died 2 months after EES as a result of the late complications of pneumonia and acute respiratory distress syndrome, although his surgery had been uneventful and he had been discharged on the 6th postoperative day without complaints. Another elderly patient died within 3 months after EES as a result of a fall that caused a subdural hematoma. All other deaths occurred years after EES and were not associated with the tumor. Discussion The surgical challenge that craniopharyngiomas represent and the frequent need for adjuvant treatment has been extensively discussed in the literature. 9,12,17,19,20,27,39 Traditionally, transsphenoidal or transcranial surgery is chosen based on the location (intrasellar or suprasellar) of the mass, its consistency, the degree of calcification, and the shape and size of the tumor. 16,20,27 The standard procedure for many years has been the transcranial route, which provides access to the suprasellar cisterns and direct visualization of the vital structures surrounding the tumor. 16 In selected cases, transsphenoidal or extended transsphenoidal surgery has been used to achieve tumor excision. 4,9,17,25 27 Endoscopic endonasal surgery has been used for the treatment of craniopharyngiomas in a few institutions over the last decade with good results. 2,3,5,11,12,21 Initially, it was applied to selected tumors with a purely sellar location, but as surgical experience and technology have advanced, EES has been used in our department for every suprasellar craniopharyngioma regardless of its extension (Fig. 4), except for purely intraventricular tumors. The surgery requires a multidisciplinary team with significant EES experience and advanced equipment (angled endoscopes, endoscopic surgery instruments, image guidance, and neurophysiological monitoring) for safe results. This approach provides direct access to the skull base, the suprasellar and parasellar regions, the interpeduncular 1201

9 M. Koutourousiou et al. Fig. 3. Coronal and sagittal postcontrast T1-weighted MR images obtained in a pediatric patient with invasive craniopharyngioma. A: Preoperative images showing a sellar/suprasellar tumor that erodes the anterior skull base and extends into the sphenoid sinus, invades the left cavernous sinus (arrow), erodes the clivus and extends into the prepontine cistern deforming the brainstem. B: Postoperative images demonstrating extensive, safe resection of the tumor. The pituitary stalk was identified during surgery and preserved, as seen in both images. The preexisting hypopituitarism improved postoperatively. The intracavernous tumor was deemed not safely resectable (arrow). Extensive erosion of the skull base was repaired with a vascularized nasoseptal flap (arrowheads). Residual tumor showed regrowth, and the patient underwent reoperation (EES) and Gamma Knife surgery 2.5 years after the initial EES. C: Most recent images obtained after reoperation and radiosurgery, showing resolution of the left intracavernous tumor (arrow). However, an area suspicious for new recurrence is visible on the right cavernous sinus. Four years after the initial diagnosis, the patient was under close observation. cistern, and the third ventricle. It allows direct visualization for dissecting the optic apparatus, hypothalamus, and pituitary stalk, maintaining their blood supply and functional integrity and avoiding complications associated with brain retraction and extensive craniotomies. 10 Finally, the endoscopic endonasal approach allows direct access to the long axis of craniopharyngiomas, a factor well recognized as critical for maximal, safe tumor resection. It is important to note some limitations of our study. Fig. 4. Coronal and sagittal postcontrast T1-weighted MR images of a pediatric suprasellar craniopharyngioma. Upper: Preoperative images demonstrating a suprasellar multicystic craniopharyngioma with invasion of the third ventricle and interpeduncular cistern, extension back to the level of the pineal region, and coexisting hydrocephalus. Lower: Images obtained after EES. Hydrocephalus was resolved with the placement of an external ventricular drain before surgery and did not necessitate a permanent shunt. No remnants of the tumor appear in the third ventricle. However, the tumor adhered to the hypothalamus, and thus further dissection was not attempted. Although not shown in these images, a minimal residual tumor capsule remained attached to the hypothalamus, and the case was considered a near-total resection. First of all, the recent application of EES for the resection of craniopharyngiomas means there is a relatively short follow-up (mean 38 months). Given this limitation, we cannot provide long-term results and survival rates for patients with craniopharyngioma who have undergone EES. Additionally, this study is retrospective and nonrandomized. However, given that all patients with craniopharyngioma, with the rare exception of those with purely intraventricular tumors, are subjected to EES at our institution, we believe that this study lacks selection bias. Resection Rates Defining the Goals of Surgery Irregular tumor extension and adherence to or infiltration of vital surrounding neurovascular structures do not allow a clear line of cleavage, making complete resection difficult and potentially hazardous to critical brain areas. The rates of GTR in the literature are variable among the different approaches and range from 16% 20 to 90%. 40 Although Yaşargil et al. 40 have reported a 90% GTR rate, that rate was based on the surgeon s impression alone given that postoperative MRI was not available in the majority of cases. Additionally, their intraoperative/early postoperative mortality rate was 9% and overall mortality was 16.7%. Indeed, there appears to be a clear relation between the rate of GTR and perioperative mortality. 10 Yang et al. 39 found that, regardless of the 1202 J Neurosurg / Volume 119 / November 2013

10 Endoscopic endonasal surgery for craniopharyngiomas approach, the overall GTR rate after craniopharyngioma surgery is 58%. In our cohort, the overall GTR rate was only 37.5%; however, GTR was not considered safe and was therefore not attempted in every patient. We believe that the optimal surgical approach should minimize the risk of damage to vital structures, and thus when the tumor capsule cannot be separated from vital neurovascular structures, we prefer to leave it behind and perform postoperative radiosurgery in adults and close follow-up in children. When GTR becomes dangerous, we consider surgical success a resection rate of at least 95% of the initial tumor mass, which was achieved in 71.9% of our patients along with perioperative mortality of 0%. This strategy that is, of near-total resection combined with subsequent radiation as an alternative to GTR when the surgical risks overpower the potential benefit has already been advocated by other surgeons. 24,28,36 In fact, a recent meta-analysis 39 has confirmed that subtotal resection with adjuvant irradiation results in similar rates of long-term disease control and recurrence as compared with those for primary GTR. Besides this recent trend in the surgical management of craniopharyngiomas that supports less aggressive approaches, there is no consensus in the literature on the acceptable amount of tumor to leave behind. We believe that GTR should remain the goal of surgery, and when this is not safe we should attempt the maximum (> 95%, if possible) tumor resection and apply radiation therapy for any residual tumor. However, to avoid the side effects of radiation in the young brain, 23 we have offered radiosurgery after initial EES to only one 16-year-old patient with residual tumor, and we closely followed up the rest of the children to offer adjuvant treatment in cases of recurrence. As illustrated in Table 4, EES is equally effective for primary and recurrent craniopharyngiomas. The safety and efficacy of EES for residual or recurrent craniopharyngiomas, regardless of the previous surgical route, has already been described by Cavallo et al. 3 This equivalent efficacy contrasts with the effectiveness of open approaches for recurrent tumors in which scar tissue and adhesions along the surgical path from previous surgeries and radiation decrease the possibility of successful excision at reoperation; the rates of total tumor removal in such cases decrease dramatically to 0% 25% and increase perioperative morbidity and mortality to 10.5% 24%. 20 Clearly, scarring that occurs within any tumor can increase the difficulty of resection upon recurrence. In the case of repeat endonasal surgery, however, the cavity for approach remains widely open and, if a patient previously underwent craniotomy, provides fresh access. We found that EES can provide equivalent resection rates between intrasellar tumors with suprasellar extension and purely suprasellar craniopharyngiomas. This finding contradicts the generally accepted notion that suprasellar craniopharyngiomas should be approached transcranially. 9,17,19,27,40 Moreover, intraventricular tumor extension is not a limitation for EES. Indeed, the GTR rate was higher for intraventricular tumors than for extraventricular ones (42.9% vs 34.9%). The tumor, growing in the cranial direction, creates a corridor to the third ventricle; therefore, manipulation of the surrounding vital J Neurosurg / Volume 119 / November 2013 neurovascular structures can be avoided (Fig. 5). Furthermore, with the view from below, it is possible to identify and dissect the arachnoid layer between the dome of the craniopharyngioma and the floor of the third ventricle in the numerous cases in which the tumor expands against the floor of the ventricle without penetrating it. 38 Finally, the walls of the third ventricle and the dissection plane (or lack thereof) with the hypothalamus can be well visualized to determine the safety of resection. 10 This ability to visualize critical interfaces further supports the resection philosophy espoused above. The single significant factor affecting resection rates is patient age (p = 0.002). Children are very vulnerable to recurrences, and this fact led us to pursue the intentional surgical aggressiveness that we apply based on age. As other authors have advocated, radical resection at presentation offers the best chance of disease control and potential cure with acceptable morbidity in pediatric craniopharyngiomas. 7 Thus, when tumor infiltrates the infundibulum and cannot be fully dissected, we prefer to sacrifice pituitary function to achieve radical resection (unless the child is at or near puberty). Indeed, the GTR rate in children was 52.9%, the highest in our cohort. However, the same surgical aggressiveness cannot be applied when infiltration of the hypothalamus occurs, risking permanent and devastating neurological sequelae 34 or hypothalamic dysfunction. This limitation led to near-total resection in the rest of the pediatric cases (47.1%). Although surgical aggressiveness in pediatric cases has resulted in significantly higher resection rates in children (> 95% in 100% of children vs 61.7% of adults), it has also caused higher rates of new pituitary dysfunction and DI in this age group, as discussed below. Clinical Outcome Direct comparison of the results of transcranial surgery with those of TSS and EES is probably not valid because of selection bias. Transsphenoidal surgery and EES (based on limited reports) have traditionally been reserved for small sellar tumors and/or sellar enlargement, and purely suprasellar craniopharyngiomas have generally been considered to be unmanageable by TSS. 4,9,17,19,27 Thus, the favorable results of TSS are often attributed to limited case selection, which excludes the more demanding large, purely suprasellar craniopharyngiomas with intraparenchymal and intraventricular extension. In the present study, all patients were treated with EES. We used open craniotomies in only 3 tumors that recurred either in the third ventricle or lateral to the optic nerve/supraclinoidal carotid artery. Visual Outcome. In general, the published literature has shown that transcranial surgery is associated with worse visual outcomes in comparison with those for TSS and EES. 8,10 According to the extensive experience of Fahlbusch et al. 9 with 168 craniopharyngiomas, visual improvement occurred in 63% of patients after transcranial surgery and 73% after TSS; visual deterioration occurred only in the transcranial group and accounted for 14.3% of these cases. Similarly, after managing 86 craniopharyngiomas, Chakrabarti et al. 4 noticed visual improvement in 61% of the transcranial cases versus 87% 1203

11 M. Koutourousiou et al. Fig. 5. Images of a suprasellar craniopharyngioma with intraventricular extension treated with GTR via EES. A and B: Preoperative coronal and sagittal postcontrast T1-weighted MR images demonstrating a mixed suprasellar tumor with a lower solid and an upper cystic component, invading the floor of the third ventricle. C: Intraoperative view with a 0 endoscope after bony resection of the planum, tuberculum, and anterior wall of the sella. The pituitary gland (pg) is covered by the sellar dura. The suprasellar dura has been incised in a V fashion, and the underlying arachnoid has been exposed. D: After opening the suprasellar arachnoid, the optic chiasm (oc) is identified and the solid compartment of the tumor (tu) is visualized between the optic chiasm and the pituitary gland (pg). The arachnoid above the optic chiasm covers the A 2 branches of the 2 anterior cerebral arteries and is left intact. E: The tumor (tu) is dissected and removed from the suprasellar cistern. The optic nerves (on) are lying under the dura, which has been left intact to protect the nerves. F: A closer view with the 0 endoscope provides direct visualization of the third ventricle (3rd v), whose floor was eroded by the tumor. Once the tumor is removed, the pituitary stalk (ps) can be identified with deviation to the left. The optic chiasm (oc) and pituitary gland (pg) remain intact. G and H: Postoperative coronal and sagittal T1-weighted MR images obtained after contrast administration, confirming GTR of the craniopharyngioma. The pituitary stalk does not appear in the midline sagittal image (H) because of its deviation, but it does appear deviated to the left (G, upper arrow) on the coronal image, just above the pituitary gland (G, lower arrow). The linear contrast-enhancing area on the sagittal MR image (H, arrow) represents the vascularized nasoseptal flap that was used for skull base reconstruction, and the enhancing spot behind the flap is the intact pituitary gland. of TSS cases; vision worsened postoperatively in 17% of the transcranial cohort versus 3% of the transsphenoidal cohort. In a microscopic TSS study of 57 cases, Maira et al.27 noted vision improvement in 84.2% of the patients, which was similar to the 85.7% of patients in the EES experience of Campbell et al.2 Note that the latter study had a vision deterioration rate of 7.1%. In an account of their experience with TSS for pediatric craniopharyngiomas, Jane et al.17 documented visual improvement in 64% of children and deterioration in 14%. In an earlier report of our initial experience with EES for the treatment of suprasellar craniopharyngiomas,12 93% of the patients showed postoperative visual improvement and 0% had visual deterioration. In keeping with our surgical principles, visual improvement in the current study overall was 86.4% with 0% permanent visual deterioration. Notably, 100% of the pediatric population had visual improvement versus 84.2% of adults; the lower success rate in adults may represent the higher rate of previously treated patients in this group (27.7% with surgery and/or radiotherapy) who presented with permanent visual deficits or the resiliency of children Endocrinological Outcome. Based on a recent review of the craniopharyngioma literature,10 rates of new endocrinopathy in transcranial studies have ranged from 24% to 66% for panhypopituitarism and from 43% to 79% for DI; in transsphenoidal studies, 18% 67% of patients demonstrated panhypopituitarism and 8% 48% exhibited permanent DI. Again, the favorable transsphenoidal results may reflect selection bias. While sellar craniopharyngiomas usually displace the pituitary stalk, suprasellar craniopharyngiomas infiltrate the stalk and are more likely to present with postoperative pituitary dysfunction due to surgical manipulation. The latter tumors are usually counted among transcranial series. Some authors believe that pituitary stalk transition and resultant DI are acceptable to accomplish total tumor removal.15 We have adopted the new trend of near-total tumor resection combined with radiotherapy when GTR is contraindicated. The outcome in adults in the present study was 37.5% with new anterior pituitary dysfunction and 32.3% with permanent DI, without any bias for tumor selection. Although these results and the overall incidence of new hypopituitarism in 51.9% of patients and permanent DI in 46.7% of paj Neurosurg / Volume 119 / November 2013

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