J Neurosurg 119:1194–1207, 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 1Neurological Surgery and 2Otolaryngology, 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 2011. 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 28–82 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 1–135 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. (http://thejns.org/doi/abs/10.3171/2013.6.JNS122259)

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.

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C

raniopharyngiomas (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 on­line but in black-and-white in the print edition.

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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 overall16,20,31,32 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 2011. 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.

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 with-

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in 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 28–82 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 previ1195

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.

ministration, 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.

Imaging Findings

Surgical Management and Adjuvant Treatment

The average tumor volume in the whole cohort was 9.6 cm3 (range 0.96–68.5 cm3), and the maximum tumor diameter varied from 1.3 to 6.4 cm. In adults, the average tumor volume was 6.6 cm3 (range 0.96–31.4 cm3) 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 cm3 (range 1.5–68.5 cm3), 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 ad-

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 1–135 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 32P 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 no. of patients visual impairment pituitary dysfunction   hypogonadism   hypoadrenalism     GH deficit/growth retardation   hypothyroidism    hyperprolactinemia (stalk effect) headache DI obesity† increased ICP (HC/papilledema) nausea/vomiting CN palsy gait disturbance mental changes incidental finding

Previous Treatment Status

Adults

Children

47 38 (80.8%) 31 (66%) 19 (40.4%) 18 (38.3%) 6 (12.8%) 23 (48.9%) 6 (12.8%) 16 (34%) 16 (34%) 22/40 (55%) 5 (10.6%)‡ 2 (4.3%) 0 1 (2.1%) 1 (2.1%) 1 (2.1%)

17 6 (35.3%) 9 (52.9%) 4 (23.6%) 4 (23.6%) 5 (29.4%) 7 (41.2%) 0 11 (64.7%) 3 (17.6%) 7/16 (43.8%) 4 (23.6%) 3 (17.6%) 1 (5.9%) 0 0 2 (11.8%)

Primary Tumor 47 31 (66%) 27 (57.4%) 14 (29.8%) 10 (21.3%) 8 (17%) 18 (38.3%) 5 (10.6%) 23 (48.9%) 6 (12.8%) 18/41 (43.9%) 5 (10.6%) 5 (10.6%) 1 (2.1%) 0 1 (2.1%) 3 (6.4%)

Recurrent Tumor

Total

17 13 (76.5%) 13 (76.5%) 9 (52.9%) 12 (70.6%) 3 (17.6%) 12 (70.6%) 1 (5.9%) 4 (23.6%) 13 (76.5%) 11/15 (73.3%) 4 (23.6%)‡ 0 0 1 (5.9%) 0 0

64 44 (68.8%) 40 (62.5%) 23 (35.9%) 22 (34.4%) 11 (17.2%) 30 (46.9%) 6 (9.4%) 27 (42.2%) 19 (29.7%) 29/56 (51.8%) 9 (14.1%)‡ 5 (7.8%) 1 (1.6%) 1 (1.6%) 1 (1.6%) 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.

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Endoscopic endonasal surgery for craniopharyngiomas TABLE 2: Craniopharyngioma characteristics based on preoperative imaging findings* No. (%) Parameter

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

no. of patients tumor dimensions    mean vol (cm3)     mean max diameter (cm) tumor location   sellar   suprasellar tumor extension   ventricular system      intraventricular   sagittal plane     frontal lobe     sphenoid sinus   coronal plane     cavernous sinus         sylvian fissure     axial plane     prepontine cistern     interpeduncular cistern     CPA contrast enhancement   heterogeneous   homogeneous   ring enhancement

Adults 47 6.6 2.6

Children 17 17.7 3.4

Total 64 9.6 2.9

27 (57.4%) 47 (100%)

12 (70.6%) 39 (60.1%) 17 (100%) 64 (100%)

12 (25.5%)

9 (52.9%) 21 (32.8%)

1 (2.1%) 1 (2.1%)

0 1 (5.9%)

1 (1.6%) 2 (3.1%)

5 (10.6%) 0

1 (5.9%) 1 (5.9%)

6 (9.4%) 1 (1.6%)

1 (2.1%) 23 (48.9%) 0

2 (11.8%) 3 (4.7%) 11 (64.7%) 34 (53.1%) 2 (11.8%) 2 (3.1%)

41 (87.2%) 4 (8.5%) 2 (4.2%)

17 (100%) 0 0

58 (90.6%) 4 (6.2%) 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

M. Koutourousiou et al. TABLE 3: Summary of treatment in 64 patients with craniopharyngioma* Type of Treatment no. of patients initial treatment   EES only     single EES     staged EES    EES (single) + radiotherapy     radiosurgery     conventional radiotherapy     proton beam therapy no. of recurrences treatment for recurrence   reop only     EES     open approach (craniotomy)    radiotherapy only (radiosurgery)    reop + radiotherapy     EES     open approach     intracystic radiation (32P)     radiosurgery   interferon    no adjuvant treatment (close FU)

Adults

Children

Total

47

17

64

39 (83%) 36 (76.6%) 3 (6.4%) 8 (17%) 5 (10.6%) 2 (4.2%) 1 (2.1%) 15 (31.9%)

16 (94%) 14 (82.3%) 2 (11.8%) 1 (6%) 1 (6%) 0 0 7 (41.2%)

55 (86%) 50 (78.1%) 5 (7.8%) 9 (14%) 6 (9.4%) 2 (3.1%) 1 (1.6%) 22 (34.4%)

3 (20%) 2 (13.3%) 1 (6.7%) 1 (6.7%) 6 (40%) 6 (40%) 2 (13.3%) 2 (13.3%) 6 (40%) 0 5 (33.3%)

3 (42.8%) 3 (42.8%) 0 0 (0%) 2 (28.6%) 1 (14.3%) 1 (14.3%) 1 (14.3%) 1 (14.3%) 1 (14.3%) 1 (14.3%)

6 (27.3%) 5 (22.7%) 1 (4.5%) 1 (4.5%) 8 (36.4%) 7 (31.8%)† 3 (13.6%)‡ 3 (13.6%) 7 (31.8%) 1 (4.5%) 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

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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),

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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. Surgical Complications

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

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 = 0.0006): 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%

primary recurrent p value adults children p value intraventricular extraventricular p value intrasellar/suprasellar suprasellar only p value total

47 17

19 (40.4%) 5 (29.4%) 0.42 15 (31.9%) 9 (52.9%) 0.12 9 (42.9 %) 15 (34.9%) 0.54 16 (41%) 8 (32%) 0.47 24 (37.5%)

34 (72.3%) 12 (70.6%) 1.0 29 (61.7%) 17 (100%) 0.002 15 (71.4%) 31 (72.1%) 0.956 28 (71.7%) 18 (72%) 0.986 46 (71.9%)

47 17 21 43 39 25 64

Near-Total Resection (>95%)

Subtotal Resection (≥80%)

Partial 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 (%).

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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 pituitary dysfunction DI obesity (BMI >30) headache

38 31 16 22 16

19 (50%) 5 (16.1%) 0 0 12 (75%)

13 (34.2%) 2 (6.4%) 0 0 0

5 (13.2%) 16 (51.6%) 16 (100%) 9 (100%)§ 4 (25%)

1 (2.6%)† 8 (25.8%) 0 0 0

1/9 (11.1%)† 6/16 (37.5%) 10/31 (32.3%)‡ 2/18 (11.1%)¶ 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: 18.5–24.9) or overweight (BMI: 25–29.9) 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 1–135 months) for the entire cohort, 39 months (range 1–135 months) for adults, and 35.3 months (range 11–59 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 pituitary dysfunction DI obesity (BMI-for-age/-sex) headache

6 9 3 7 11

4 (66.7%) 0 0 0 11 (100%)

2 (33.3%) 1 (11.1%) 0 1/6 (16.7%) 0

0 3 (33.3%) 3 (100%) 5/6 (83.3%)‡ 0

0 5 (55.5%) 0 0 0

0 8/8 (100%) 11/14 (78.6%)† 3/9 (33.3%)§ 0

*  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.

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Endoscopic endonasal surgery for craniopharyngiomas TABLE 7: Complications after EES for craniopharyngioma* Age Group

Primary vs Recurrent Tumor

Complication

Adults

Children

Primary

Recurrent

Total

hypopituitarism (new) permanent DI CSF leakage hydrocephalus (new) meningitis transient CN palsy SIADH

14/37 (37.8%) 10/31(32.3%) 13/47 (27.7%) 5/42 (11.9%) 3/47 (6.4%) 2/47 (4.2%) 2/47 (4.2%)

13/15 (86.7%) 11/14 (78.6%) 2/17 (11.8%) 2/13 (15.4%) 2/17 (11.8%) 3/17 (17.6%) 1/17 (5.9%)

24/47 (51.1%) 19/41 (46.3%) 13/47 (27.7%) 5/42 (11.9%) 4/47 (8.1%) 4/47 (8.1%) 3/47 (6.4%)

3/5 (60%) 2/4 (50%) 2/17 (11.8%) 2/13 (15.4%) 1/17 (5.9%) 1/17 (5.9%) 0

27/52 (51.9%) 21/45 (46.7%) 15/64 (23.4%) 7/55 (12.7%) 5/64 (7.8%) 5/64 (7.8%) 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

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.

TABLE 8: Recurrence compared between different parameters*

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

Parameter GTR near-total resection subtotal resection partial resection GTR non-GTR resection >95% resection 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 sequelae34 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

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. 1204

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

Endoscopic endonasal surgery for craniopharyngiomas tients concur with those in the transsphenoidal literature, it is worth noting the different endocrinological outcome in pediatric patients. Since children are more vulnerable to late treatment failures and side effects from radiation therapy, including endocrinopathies, vasculopathies, and secondary tumors,23 we remain surgically aggressive in this age group. This principle explains the higher pediatric rates of postoperative new hypopituitarism (86.7%) and new DI (78.6%).

Central Obesity. Central obesity due to hypothalamic eating disorders is a major adverse effect in children and adolescents with craniopharyngioma. Increased BMI at the diagnosis of craniopharyngioma is a significant risk factor for severe obesity and correlates with the severity of hypothalamic damage.30 All of our pediatric craniopharyngiomas had some degree of radiographic hypothalamic involvement, and the rate of obesity at diagnosis was 43.8%, which was similar to other reported rates.6,29 New-onset obesity in children has been documented at over 50% after transcranial surgery30 and 37% after TSS.17 The incidence of new obesity following EES was 33.3% in our experience. Obesity in adults with craniopharyngioma may not be exclusively associated with hypothalamic dysfunction but may represent an unhealthy lifestyle and/or genetic predisposition. Postoperative obesity in adults is rarely discussed in the literature. Chakrabarti et al.4 found hyperphagia in 61% of patients with craniopharyngioma after transcranial surgery and in 40% after transnasal surgery. In our experience, 11.1% of the adults with craniopharyngioma with available postoperative data were newly obese after EES, but it is unclear if this rate represents true hypothalamic damage or if it is the result of hypopituitarism or lifestyle factors. In any case, obesity confers significant morbidity and mortality and may further affect the quality of life of these patients. Surgical Complications

Evidence of new endocrinopathies and visual deterioration was discussed earlier and, based on the current literature, was higher in transcranial than in transsphenoidal studies.4,8,9 One of the major problems of transnasal approaches (either microscopic transsphenoidal or endoscopic) has been postoperative CSF leakage. Maira et al.,27 who used TSS, noted CSF leaks in 17.5% of their cases. In endoscopic studies, de Divitiis et al.5 and Campbell et al.2 reported CSF leak rates of 20% and 37.5%, respectively. Our early institutional experience12 with EES in treating 16 suprasellar craniopharyngiomas included a CSF leak rate of 58%. In the present study and after the introduction of the vascularized nasoseptal flap for skull base reconstruction,13,22,41 the overall CSF leak rate decreased dramatically to 23.4%. Indeed, among the patients with craniopharyngioma who underwent reconstruction with the vascularized nasoseptal flap (47 patients), only 5 experienced a CSF leak, which means a CSF leakage rate of 10.6% when this technique is used. The incidence of postoperative meningitis, usually associated with CSF leaks, remains low.2,4,9,12,17 J Neurosurg / Volume 119 / November 2013

Postoperative hydrocephalus requiring treatment has ranged from 0% to 21.4%.2,9,17,27 Our rate was consistent with that at 12.7%, and we treated hydrocephalus with ventriculoperitoneal shunt placement. Other surgical complications, such as hematoma, seizures, pneumocephalus, wound-healing problems, and SIADH, have been reported in the literature but are not clearly associated with the surgical route.2,9,17 Other than the evidence of new obesity in 3 children, none of our patients experienced postoperative hypothalamic dysregulation or cognitive decline, both of which have been described by other authors who perform more aggressive tumor resection to achieve higher GTR rates.4,9,17 Since hypothalamic damage can result in devastating sequelae, we continue to strongly support less aggressive dissection when the tumor infiltrates this vital neurological structure, even if doing so results in lower rates of complete tumor resection. Perioperative mortality has been directly associated with higher rates of GTR.10 Yasargil et al.40 had a perioperative mortality rate of 9% with a GTR of 90%, and Falbusch et al.9 reported rates of 10.5% for recurrent craniopharyngiomas and 2.1% for primary craniopharyngiomas. These rates have dramatically decreased in most recent publications,2,3,17 probably because of the increased awareness of surgeons and the general acceptance of adjuvant treatments for disease control. In agreement with recent literature, our perioperative mortality rate was 0%. Tumor Recurrence and Adjuvant Therapies

Craniopharyngiomas have a tendency to recur even after apparent total removal, making adjuvant treatment essential. According to major literature studies,9,37 the rate of recurrence ranges from 0% to 53% in cases of total removal and from 30% to 100% in cases of subtotal or partial removal. Our recurrence rate following GTR was 25%, and the overall recurrence rate for the entire cohort was 34.4%, which agrees with rates in the literature. However, it is impressive that pediatric patients, despite their higher resection rate, had a higher recurrence rate (41.2% vs 31.9% in adults), indicating the increased difficulty in treating this disease in children. Although the goal of surgery was the removal of > 95% of the tumor when GTR was considered dangerous, this strategy led to a recurrence rate of 40% (16 of 40 cases) compared with only 25% (6 of 24 cases) among patients who underwent GTR. This is the tradeoff for incomplete resection. External beam irradiation is commonly used after partial resection and significantly improves the local tumor control rate.18,20,39 Tumors that are purely cystic can be treated stereotactically with cyst decompression and intracavitary therapy.16,18,20 Our experience with intracystic radiation (32P) in 3 patients was successful in 2, for total resolution of a recurrent cystic lesion in 1 patient and a decrease of the lesion in the other patient. Stereotactic radiosurgery is effective in patients with small-volume lesions and is particularly useful for a well-defined residual mass after surgery or for small solid recurrent tumors. We used stereotactic radiosurgery in 6 patients with small residual tumor after EES and in 8 patients with recurrent craniopharyngioma with good results. Sys1205

M. Koutourousiou et al. temic chemotherapy and interferon-a may be beneficial for craniopharyngiomas that have undergone malignant transformation.20 Our experience with 1 pediatric patient who received interferon for recurrent (benign) tumor was excellent, with total resolution of the mass. In any case, the management of craniopharyngioma must be individualized; treatment options must be tailored to the specific endocrine and neurological status, patient age, imaging features, and tumor consistency. Disease Prognosis

Craniopharyngiomas are associated with decreased survival, with mortality rates 3- to 6-fold higher than those for the general population.33 Recent studies have shown survival rates ranging from 83% to 93% at 10 years of follow-up.20,33 Besides the fatal surgical complications and deaths directly attributed to the tumor, low survival rates in the postoperative period are associated with cardiovascular, cerebrovascular, and respiratory problems in patients treated for craniopharyngioma.10 An explanation for this morbidity is the possible early postoperative pituitary insufficiency or hypothalamic dysfunction, which is more likely after aggressive resection and, in some cases, radiation therapy. Patients with recurrent craniopharyngioma have a significantly lower probability of survival than those with primary tumors (at 10 years: 70% vs 99%).20 Unfortunately, the recent application of EES for craniopharyngioma does not allow for long-term followup. Given this limitation in the current study, we cannot yet provide survival rates or long-term results for the patients with craniopharyngioma treated with EES.

Conclusions

The use of EES has been expanded to the treatment of large suprasellar craniopharyngiomas even with intraventricular extension. The goal of surgery should remain GTR or tumor removal > 95% when GTR is contraindicated. Regardless of the selected surgical approach, the high rate of recurrence often requires the use of adjuvant therapies. The surgical results of EES are acceptable and comparable to those for traditional approaches. Based on these results, EES can be considered an alternative to transcranial surgery for the management of craniopharyngioma. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Gardner, Koutourousiou. Acquisition of data: Koutourousiou. Analysis and interpretation of data: Koutourousiou. Drafting the article: Koutourousiou. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Gardner. Statistical analysis: Koutourousiou. Study supervision: Gardner. Acknowledgments The authors wish to thank Dr. Amin B. Kassam, Division of

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Neurosurgery, University of Ottawa, Ottawa, Ontario, Canada; Dr. Daniel M. Prevedello, Department of Neurological Surgery, The Ohio State University Medical College, Columbus, Ohio; and Dr. Ricardo L. Carrau, Department of Otolaryngology-Head & Neck Surgery, The Ohio State University Medical College, Columbus, Ohio, for their involvement in the clinical and operative management of many of these patients. References   1.  Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM: The descriptive epidemiology of craniopharyngioma. J Neurosurg 89:547–551, 1998   2.  Campbell PG, McGettigan B, Luginbuhl A, Yadla S, Rosen M, Evans JJ: Endocrinological and ophthalmological consequences of an initial endonasal endoscopic approach for resection of craniopharyngiomas. Neurosurg Focus 28(4):E8, 2010   3.  Cavallo LM, Prevedello DM, Solari D, Gardner PA, Esposito F, Snyderman CH, et al: Extended endoscopic endonasal transsphenoidal approach for residual or recurrent craniopharyngiomas. Clinical article. J Neurosurg 111:578–589, 2009   4.  Chakrabarti I, Amar AP, Couldwell W, Weiss MH: Long-term neurological, visual, and endocrine outcomes following transnasal resection of craniopharyngioma. J Neurosurg 102: 650–657, 2005   5.  de Divitiis E, Cappabianca P, Cavallo LM, Esposito F, de Divitiis O, Messina A: Extended endoscopic transsphenoidal approach for extrasellar craniopharyngiomas. Neurosurgery 61 (5 Suppl 2):219–228, 2007   6.  de Vile CJ, Grant DB, Hayward RD, Kendall BE, Neville BG, Stanhope R: Obesity in childhood craniopharyngioma: relation to post-operative hypothalamic damage shown by magnetic resonance imaging. J Clin Endocrinol Metab 81:2734– 2737, 1996   7.  Elliott RE, Hsieh K, Hochm T, Belitskaya-Levy I, Wisoff J, Wisoff JH: Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. Clinical article. J Neurosurg Pediatr 5:30–48, 2010   8.  Elliott RE, Jane JA Jr, Wisoff JH: Surgical management of craniopharyngiomas in children: meta-analysis and comparison of transcranial and transsphenoidal approaches. Neurosurgery 69:630–643, 2011   9.  Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M: Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 90:237–250, 1999 10.  Fernandez-Miranda JC, Gardner PA, Snyderman CH, Devaney KO, Strojan P, Suárez C, et al: Craniopharyngioma: a pathologic, clinical, and surgical review. Head Neck 34:1036–1044, 2012 11.  Frank G, Pasquini E, Doglietto F, Mazzatenta D, Sciarretta V, Farneti G, et al: The endoscopic extended transsphenoidal approach for craniopharyngiomas. Neurosurgery 59 (1 Suppl 1):ONS75–ONS83, 2006 12.  Gardner PA, Prevedello DM, Kassam AB, Snyderman CH, Carrau RL, Mintz AH: The evolution of the endonasal approach for craniopharyngiomas. J Neurosurg 108:1043–1047, 2008 13.  Hadad G, Bassagasteguy L, Carrau RL, Mataza JC, Kassam A, Snyderman CH, et al: A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 116:1882–1886, 2006 14.  Haupt R, Magnani C, Pavanello M, Caruso S, Dama E, Garrè ML: Epidemiological aspects of craniopharyngioma. J Pediatr Endocrinol Metab 19 (Suppl 1):289–293, 2006 15.  Honegger J, Buchfelder M, Fahlbusch R: Surgical treatment of craniopharyngiomas: endocrinological results. J Neurosurg 90:251–257, 1999 16.  Jane JA Jr, Laws ER: Craniopharyngioma. Pituitary 9:323– 326, 2006 17.  Jane JA Jr, Prevedello DM, Alden TD, Laws ER Jr: The trans-

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Endoscopic endonasal surgery for craniopharyngiomas sphenoidal resection of pediatric craniopharyngiomas: a case series. Clinical article. J Neurosurg Pediatr 5:49–60, 2010 18.  Karavitaki N: Radiotherapy of other sellar lesions. Pituitary 12:23–29, 2009 19.  Karavitaki N, Brufani C, Warner JT, Adams CBT, Richards P, Ansorge O, et al: Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin Endocrinol (Oxf) 62:397–409, 2005 20.  Karavitaki N, Cudlip S, Adams CB, Wass JA: Craniopharyngiomas. Endocr Rev 27:371–397, 2006 21.  Kassam A, Snyderman CH, Mintz A, Gardner P, Carrau RL: Expanded endonasal approach: the rostrocaudal axis. Part I. Crista galli to the sella turcica. Neurosurg Focus 19(1):E3, 2005 22.  Kassam AB, Thomas A, Carrau RL, Snyderman CH, Vescan A, Prevedello D, et al: Endoscopic reconstruction of the cranial base using a pedicled nasoseptal flap. Neurosurgery 63 (1 Suppl 1):ONS44–ONS53, 2008 23.  Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28(4):E10, 2010 24.  Komotar RJ, Roguski M, Bruce JN: Surgical management of craniopharyngiomas. J Neurooncol 92:283–296, 2009 25.  Kouri JG, Chen MY, Watson JC, Oldfield EH: Resection of suprasellar tumors by using a modified transsphenoidal approach. Report of four cases. J Neurosurg 92:1028–1035, 2000 26.  Laws ER Jr: Surgical outcome in 90 patients with craniopharyngiomas: an evaluation of the transsphenoidal approach. World Neurosurg 74:254–255, 2010 27.  Maira G, Anile C, Albanese A, Cabezas D, Pardi F, Vignati A: The role of transsphenoidal surgery in the treatment of craniopharyngiomas. J Neurosurg 100:445–451, 2004 28.  Merchant TE, Kiehna EN, Sanford RA, Mulhern RK, Thompson SJ, Wilson MW, et al: Craniopharyngioma: the St. Jude Children’s Research Hospital experience 1984-2001. Int J Radiat Oncol Biol Phys 53:533–542, 2002 29.  Müller HL, Bueb K, Bartels U, Roth C, Harz K, Graf N, et al: Obesity after childhood craniopharyngioma—German multicenter study on pre-operative risk factors and quality of life. Klin Padiatr 213:244–249, 2001 30.  Müller HL, Emser A, Faldum A, Bruhnken G, Etavard-Gorris N, Gebhardt U, et al: Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 89:3298–3305, 2004 31.  Nelson JS (ed): Principles and Practice of Neuropathology, ed 2. New York: Oxford University Press, 2003 32.  Parisi JE, Mena H: Nonglial tumors, in Nelson JS, Parisi JE, Schochet SS Jr (eds): Principles and Practice of Neuropathology. St. Louis: Mosby, 1993, pp 203–266

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33.  Pereira AM, Schmid EM, Schutte PJ, Voormolen JH, Biermasz NR, van Thiel SW, et al: High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma. Clin Endocrinol (Oxf) 62:197–204, 2005 34.  Puget S, Garnett M, Wray A, Grill J, Habrand JL, Bodaert N, et al: Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg 106 (1 Suppl):3–12, 2007 35.  Rennert J, Doerfler A: Imaging of sellar and parasellar lesions. Clin Neurol Neurosurg 109:111–124, 2007 36.  Scott RM, Hetelekidis S, Barnes PD, Goumnerova L, Tarbell NJ: Surgery, radiation, and combination therapy in the treatment of childhood craniopharyngioma—a 20-year experience. Pediatr Neurosurg 21 (Suppl 1):75–81, 1994 37.  Van Effenterre R, Boch AL: Craniopharyngioma in adults and children: a study of 122 surgical cases. J Neurosurg 97:3–11, 2002 38.  van Overbeeke JJ: Craniopharyngiomas, in Sekhar LN, Fessler RG (eds): Atlas of Neurosurgical Techniques: Brain. New York: Thieme Medical Publishers, 2006, pp 680–686 39.  Yang I, Sughrue ME, Rutkowski MJ, Kaur R, Ivan ME, Aranda D, et al: Craniopharyngioma: a comparison of tumor control with various treatment strategies. Neurosurg Focus 28(4): E5, 2010 40.  Yaşargil MG, Curcic M, Kis M, Siegenthaler G, Teddy PJ, Roth P: Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg 73:3–11, 1990 41.  Zanation AM, Carrau RL, Snyderman CH, Germanwala AV, Gardner PA, Prevedello DM, et al: Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery. Am J Rhinol Allergy 23:518–521, 2009 Manuscript submitted November 26, 2012. Accepted April 4, 2013. Portions of this work were presented in abstract form at the 14th European Congress of Neurosurgery held in Rome, Italy, on October 9–14, 2011, and the 6th International Congress of the World Federation of Skull Base Societies and the 10th European Skull Base Society Congress held in Brighton, United Kingdom, in May 2012. Please include this information when citing this paper: published online August 2, 2013; DOI: 10.3171/2013.6.JNS122259. Address correspondence to: Paul A. Gardner, M.D., Department of Neurosurgery, UPMC Presbyterian, 200 Lothrop St., Ste. B400, Pittsburgh, PA 15213. email: [email protected]

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Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients.

The proximity of craniopharyngiomas to vital neurovascular structures and their high recurrence rates make them one of the most challenging and contro...
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