Endoscopic endonasal resection versus open surgery for pediatric craniopharyngioma: comparison of outcomes and complications

Peter J. Madsen Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia;

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Vivek P. Buch Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia;

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Jennifer E. Douglas Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania;

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Arjun K. Parasher Department of Otolaryngology–Head and Neck Surgery, University of South Florida, Tampa, Florida;

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David K. Lerner Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania;

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Erin Alexander Division of Neurosurgery, Children’s Hospital of Philadelphia, Pennsylvania;

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Alan D. Workman Department of Otorhinolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and

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James N. Palmer Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania;

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Shih-Shan Lang Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia;
Division of Neurosurgery, Children’s Hospital of Philadelphia, Pennsylvania;

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Benjamin C. Kennedy Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia;
Division of Neurosurgery, Children’s Hospital of Philadelphia, Pennsylvania;

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Arastoo Vossough Department of Radiology, Children’s Hospital of Philadelphia, Pennsylvania

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Nithin D. Adappa Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania;

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Phillip B. Storm Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia;
Division of Neurosurgery, Children’s Hospital of Philadelphia, Pennsylvania;

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OBJECTIVE

Craniopharyngioma represents up to 10% of pediatric brain tumors. Although these lesions are benign, attempts at gross-total resection (GTR) can lead to serious complications. More conservative approaches have emerged but require adjuvant radiation. Endoscopic endonasal surgery (EES) aimed at GTR has the potential to result in fewer complications, but there has been limited comparison to open surgery. The authors performed a review of these two approaches within their institution to elucidate potential benefits and complication differences.

METHODS

The authors performed a retrospective review of pediatric patients undergoing resection of craniopharyngioma at their institution between 2001 and 2017. Volumetric analysis of tumor size and postoperative ischemic injury was performed. Charts were reviewed for a number of outcome measures.

RESULTS

A total of 43 patients with an average age of 8.2 years were identified. Open surgery was the initial intervention in 15 and EES in 28. EES was performed in patients 3–17 years of age. EES has been the only approach used since 2011. In the entire cohort, GTR was more common in the EES group (85.7% vs 53.3%, p = 0.03). Recurrence rate (40% vs 14.2%, p = 0.13) and need for adjuvant radiation (20.0% vs 10.7%, p = 0.71) were higher in the open surgical group, although not statistically significant. Pseudoaneurysm development was only observed in the open surgical group. Volumetric imaging analysis showed a trend toward larger preoperative tumor volumes in the open surgical group, so a matched cohort analysis was performed with the largest tumors from the EES group. This revealed no difference in residual tumor volume (p = 0.28), but the volume of postoperative ischemia was still significantly larger in the open group (p = 0.004). Postoperative weight gain was more common in the open surgical group, a statistically significant finding in the complete patient group that trended toward significance in the matched cohort groups. Body mass index at follow-up correlated with volume of ischemic injury in regression analysis of the complete patient cohort (p = 0.05).

CONCLUSIONS

EES was associated with similar, if not better, extent of resection and significantly less ischemic injury than open surgery. Pseudoaneurysms were only seen in the open surgical group. Weight gain was also less prevalent in the EES cohort and appears be correlated with extent of ischemic injury at time of surgery.

ABBREVIATIONS

BMI = body mass index; DWI = diffusion-weighted imaging; EES = endoscopic endonasal surgery; EOR = extent of resection; FDCA = fusiform dilatation of the carotid artery; GTR = gross-total resection; RT = radiation therapy; STR = subtotal resection.

OBJECTIVE

Craniopharyngioma represents up to 10% of pediatric brain tumors. Although these lesions are benign, attempts at gross-total resection (GTR) can lead to serious complications. More conservative approaches have emerged but require adjuvant radiation. Endoscopic endonasal surgery (EES) aimed at GTR has the potential to result in fewer complications, but there has been limited comparison to open surgery. The authors performed a review of these two approaches within their institution to elucidate potential benefits and complication differences.

METHODS

The authors performed a retrospective review of pediatric patients undergoing resection of craniopharyngioma at their institution between 2001 and 2017. Volumetric analysis of tumor size and postoperative ischemic injury was performed. Charts were reviewed for a number of outcome measures.

RESULTS

A total of 43 patients with an average age of 8.2 years were identified. Open surgery was the initial intervention in 15 and EES in 28. EES was performed in patients 3–17 years of age. EES has been the only approach used since 2011. In the entire cohort, GTR was more common in the EES group (85.7% vs 53.3%, p = 0.03). Recurrence rate (40% vs 14.2%, p = 0.13) and need for adjuvant radiation (20.0% vs 10.7%, p = 0.71) were higher in the open surgical group, although not statistically significant. Pseudoaneurysm development was only observed in the open surgical group. Volumetric imaging analysis showed a trend toward larger preoperative tumor volumes in the open surgical group, so a matched cohort analysis was performed with the largest tumors from the EES group. This revealed no difference in residual tumor volume (p = 0.28), but the volume of postoperative ischemia was still significantly larger in the open group (p = 0.004). Postoperative weight gain was more common in the open surgical group, a statistically significant finding in the complete patient group that trended toward significance in the matched cohort groups. Body mass index at follow-up correlated with volume of ischemic injury in regression analysis of the complete patient cohort (p = 0.05).

CONCLUSIONS

EES was associated with similar, if not better, extent of resection and significantly less ischemic injury than open surgery. Pseudoaneurysms were only seen in the open surgical group. Weight gain was also less prevalent in the EES cohort and appears be correlated with extent of ischemic injury at time of surgery.

In Brief

The authors compared resection of pediatric craniopharyngioma, a tumor that develops near the base of the brain; endoscopic removal through the nose was compared to removal by open cranial surgery. The authors found that patients undergoing endonasal resection had similar if not more complete resections, had fewer vascular complications such as stroke, and were less likely to develop weight gain postoperatively, which is a common complication.

Craniopharyngioma, a rare neoplasm of the CNS, has an incidence of 0.5–2 cases per million persons per year.25,29 It has a bimodal age distribution, with children and adolescents making up 30%–50% of new diagnoses, accounting for 4%–10% of pediatric brain tumor diagnoses.9,24,29 Despite its benign histology and good survival rates, complications related to treatment can have significant impacts on quality of life.24 This is especially important in the pediatric group, given that comorbidities such as panhypopituitarism, hypothalamic dysfunction, obesity, behavioral disturbances, and learning disabilities can have effects over an entire lifetime.6,7,16,31,40

Historically, gross-total resection (GTR) by craniotomy was considered to be first-line treatment to minimize recurrence and avoid postoperative radiation.41 This approach has been challenged due to morbidities associated with aggressive resection, including panhypopituitarism, damage to the optic apparatus, stroke, hypothalamic injury, and vascular injuries such as pseudoaneurysm formation (often referred to as fusiform dilatation of the carotid artery [FDCA]).5,13,25,37 More conservative approaches, such as subtotal resection (STR) or cyst drainage followed by radiation therapy (RT), have therefore been pursued.5,15,23,34,35 Although they may decrease upfront morbidity, these less aggressive options are associated with shorter progression-free survival unless combined with RT, which introduces a host of nonnegligible, long-term risks (i.e., damage to the hypothalamic-pituitary axis and/or optic apparatus, secondary malignancy formation, etc.).5,9,18 However, modern conformal radiotherapy techniques may help to mitigate some of these concerns, especially changes in cognitive function.8,27

Endoscopic endonasal surgery (EES) has been used with success in various adult sellar and suprasellar pathologies, including craniopharyngioma. Studies of EES of adult craniopharyngioma performed to date have focused on small, suprasellar tumors, but they demonstrate an equivalent if not better extent of resection (EOR) and reduced rates of comorbidities than are typically associated with open approaches.19 Only a limited number of series of EES for craniopharyngioma have focused on or included children, but they have generally demonstrated feasibility.2,4,14,20,22,30,33,39 In this study we set out to better define the role that EES can play in the treatment of pediatric craniopharyngioma, with the specific aim of determining if EES can achieve similar rates of GTR compared to open surgery with fewer complications, especially those related to vascular insult.

Methods

Study Design, Data Collection, and Statistical Analysis

Institutional review board approval was obtained for data collection and analysis. Patients with craniopharyngioma who were younger than 18 years of age at diagnosis were retrospectively identified from the Children’s Hospital of Philadelphia from 2001 to 2017. Clinical data were extracted from chart and imaging review, including patient demographics, presenting signs and symptoms, pre- and postoperative imaging, complications and postoperative comorbidities, adjuvant therapies, recurrence rate, body mass index (BMI), and presence of significant psychosocial issues at follow-up (i.e., reported learning disabilities or significant behavioral abnormalities that interfere with school or other social function). Statistical analysis was performed using MATLAB software (MathWorks Inc., 2018). Medians were used instead of means, unless specified, due to the presence of nonnormal distributions within the data. The Wilcoxon rank-sum test and the chi-square test were used to determine significance of differences in medians and observed distributions, respectively. Comparative statistical measures were considered to be statistically significant if their p value was less than 0.05.

Volumetric Analysis

When available, preoperative and immediate postoperative MRI studies were analyzed for tumor volume, and postoperative volume of ischemia was determined from diffusion-weighted imaging (DWI) sequences. Volumes were calculated using the modified ellipsoid volume method: length × width × height × 0.52. Volumetric analysis was only performed on imaging studies performed immediately before or after the initial surgical encounter.

Results

A total of 43 patients were identified for the study; these individuals had undergone a total of 52 surgeries. The average age was 8.2 years, ranging between 1 and 17 years. Of these patients, 12 underwent only open surgery, 28 had only EES, and 3 had both types of resection during their treatment course. The cohort was then broken down based on initial surgery performed, resulting in 15 patients in the open surgical cohort and 28 in the EES group. Over the study period, open surgery in these cases was performed only until 2011, when a change in practice occurred. Since 2011, all surgeries for craniopharyngioma at our institution have been performed endonasally. Demographic data for the two groups can be found in Table 1. Patient age was similar between the two groups, but there was a male predominance in the EES cohort. The development of signs and symptoms of intracranial hypertension was the most common presentation in both groups, but evidence of hydrocephalus on preoperative imaging was seen more frequently in the open surgical group (75.0% vs 32.1%, p = 0.01). Growth hormone deficiency was seen as the primary presenting sign only in the EES group. Tumor location (i.e., sellar, suprasellar, or mixed sellar and suprasellar) and tumor quality (predominately cystic, predominately solid, or mixed cystic and solid) were not significantly different between the two groups, but there was a trend toward solid tumors being overrepresented in the EES cohort (Table 1).

TABLE 1.

Demographics and preoperative characteristics of patients undergoing open surgery and EES as the initial intervention

CharacteristicOpen Surgery, n = 15EES, n = 28p Value
Mean age in yrs6.6, range 1–118.9, range 3–17
Sex (% male)41.1%73.5%
Primary presenting sign or symptom
 Symptoms of elevated ICP9130.40
 Growth hormone deficiency060.05
 Loss of visual acuity340.63
 Cranial neuropathy (other than vision)221.0
 Other13
Hydrocephalus at diagnosis9/12 (75.0%)9/28 (32.1%)0.01
Tumor location
 Sellar01 (3.6%)0.46
 Mixed sellar & suprasellar6 (40.0%)12 (42.9%)0.86
 Suprasellar9 (60.0%)15 (53.6%)0.69
Tumor quality
 Predominately cystic6 (40.0%)6 (21.4%)0.20
 Predominately solid1 (6.7%)8 (28.6%)0.09
 Mixed cystic & solid8 (53.3%)14 (50.0%)0.84

ICP = intracranial pressure.

Tumor Volume Analysis

Volumetric analysis was performed in 11 patients in the open surgical group and 28 in the EES group (Fig. 1). Three patients from the initial group of 15 who underwent open surgery did not have sufficient imaging data for analysis, and 1 patient in the open group was excluded from volumetric analysis because of an extremely large tumor (7 times larger than the average of the open surgery group) to avoid skewing the cohort. On initial evaluation, the median preoperative tumor volume was larger in the open group (18,429 mm3 vs 6,244 mm3; Fig. 1A) and neared statistical significance (p = 0.06). There was no significant difference in median postoperative residual tumor volume between the groups (Fig. 1B). As shown in Fig. 1C, a distribution of preoperative tumor volumes shows a clustering of smaller tumors in the EES group that lowered the median preoperative tumor volume. Given the near-significant difference in preoperative tumor volume, a matched cohort analysis was performed to compare the patients with the largest tumors in the EES group (n = 11) with the open surgical group (n = 11). A distribution of preoperative tumor volumes for these matched patients revealed a more similar cohort for comparison (Fig. 1D). In the matched cohort analysis, the median preoperative tumor volumes of the groups were nearly identical (p = 1; Fig. 1E). The residual tumor volume in the matched cohorts was still similar between the groups (p = 0.28; Fig. 1F). In both the unmatched and matched analyses the open surgical group had a larger distribution of residual tumor volumes, whereas EES seemed to result more reliably in complete resections. The matched cohorts were similar in terms of tumor location and quality as well as a number of outcome measures, but differed significantly in their length of clinical and imaging follow-up (Table 2).

FIG. 1.
FIG. 1.

Box-and-whisker plots of preoperative (A) and residual postoperative (B) tumor volumes of the open surgical and EES groups showing a near-significant difference in preoperative tumor volumes but equivalent residual volumes. Plotting the preoperative tumor volumes of both groups (C) showed that the EES group had a large percentage of smaller tumors. Patients with the largest tumors in the EES group were then matched with the open surgical cohort, resulting in statistically similar median volumes (D). Box-and-whisker plots of preoperative (E) and postoperative (F) tumor volumes in the matched cohort analysis show no difference, but the range in residual volumes for the open surgical group was much larger (F).

TABLE 2.

Various characteristics and outcomes for the patients in the matched cohort analysis based on preoperative tumor volume

CharacteristicOpen Surgery, n = 11EES, n = 11p Value
Tumor location
 Sellar00
 Mixed sellar & suprasellar850.19
 Suprasellar360.19
Tumor quality
 Predominately cystic530.37
 Predominately solid111.0
 Mixed cystic & solid570.39
Median length of stay (days)13150.67
Median length of ICU stay (days)7.5100.23
EOR
 GTR790.65
 STR420.34
Reoperation for CSF leak020.14
Recurrence rate420.34
Median time to recurrence (mos)34150.18
Adjuvant RT100.31
Reoperation rate221.0
Median BMI at last follow-up (kg/m2)26.924.40.17
Median change in BMI (kg/m2)8.885.530.33
New-onset obesity4 (36.4%)3 (27.3%)0.65
Presence of significant psychosocial issues at follow-up520.17
Panhypopituitarism at follow-up11111.0
Death010.31
Median clinical follow-up (mos)7920<0.001
Median imaging follow-up (mos)8024<0.001

Medians were used unless otherwise stated due to nonnormal distributions in the data.

Cerebrovascular Complications

Postoperative MR images were also evaluated for volume of DWI signal change to assess the burden of ischemic injury following intervention. These data were not available in 2 of the patients in the open surgery group. Patients from the unmatched and matched volumetric analyses were also compared for volume of postoperative DWI signal change. This comparison showed a significantly larger median volume of ischemia in the open surgical group compared to the EES group in both the unmatched (p = 0.00001; Fig. 2A) and matched (p = 0.004; Fig. 2B) analyses. The anatomical distribution of ischemic injury was quite variable in the open surgical group, but was more often related to retraction injury, small-vessel injury, or ischemia of deep nuclei rather than large territorial infarcts. Hypothalamic ischemia was seen more often in the open surgical group than in the EES group used in the matched (5 vs 1, p = 0.06) and unmatched (5 vs 2, p = 0.005) volumetric analyses.

FIG. 2.
FIG. 2.

Box-and-whisker plots from unmatched (A) and matched (B) analysis of extent of ischemic injury as measured by DWI signal change in the open and EES groups. Both analyses reveal significant levels of ischemic injury in the open surgical group compared to the EES group. Presence of FDCA was extracted from chart and imaging review and only found to occur in the open surgical group, reaching statistical significance (C).

Given the prevalence of FDCA following open surgery of pediatric craniopharyngiomas, a comparison of the incidence of FDCA formation in the open surgical and EES groups was performed. Review of charts and postoperative imaging identified 4 patients in the open surgical group who developed FDCA and no patients in the EES group (p = 0.02; Fig. 2C). On average, FDCA was identified on imaging obtained at 19.5 months after surgery. Patients with FDCA did not require any further therapeutic interventions for the finding, but they did require surveillance imaging via additional MR images or even conventional angiography. The only other identified direct vascular injury was in 1 patient in the EES group who developed delayed cerebral ischemia secondary to angiographically confirmed vasospasm. This resulted in an ischemic stroke and hemiparesis, which had resolved at follow-up.

Recurrence Rate and Adjuvant Therapies

Historically, open surgery for pediatric craniopharyngioma has been the most consistent approach for maximizing EOR and limiting recurrence.9 Evaluation of the cohort for EOR showed a significantly higher rate of GTR in the EES group compared to the open surgical group (85.7% vs 53.3%, p = 0.03; Table 3). As would be expected from this finding, the recurrence rate was higher although not statistically significant in the open surgical group (40% vs 14.2%, p = 0.13). The median time to recurrence, as indicated by growth of residual tumor or signs of new tumor on imaging, was longer in this group as well (29.0 vs 10.5 months, p = 0.26). Although not statistically significant, the need for adjuvant RT (either proton- or photon-based) was higher in the open surgical group (20.0% vs 10.7%, p = 0.71), presumably due to the higher rate of STR within the group. More patients in the open surgical group went on to require repeat surgery than did patients in the EES group, but this did not reach statistical significance (26.7% vs 10.7%, p = 0.36).

TABLE 3.

Various patient outcomes following either an initial open surgery or EES

VariableOpen Surgery, n = 15EES, n = 28p Value
Median length of stay (days)15.513.00.17
Median length of ICU stay (days)9.07.00.35
EOR
 GTR8 (53.3%)24 (85.7%)0.03
 STR7 (46.7%)4 (14.3%)0.05
Reoperation for CSF leak020.76
Recurrence rate6 (40.0%)4 (14.3%)0.13
Median time to recurrence (mos)2910.50.26
Adjuvant RT3 (20.0%)3 (10.7%)0.71
Reoperation rate4 (26.7%)3 (10.7%)0.36
Median BMI at last follow-up (kg/m2)26.923.00.03
Median change in BMI (kg/m2)7.953.700.03
New-onset obesity6/15 (40%)6/27 (22.2%)0.39
Presence of significant psychosocial issues at follow-up5/15 (33.3%)5/27 (18.5%)0.48
Panhypopituitarism at follow-up15 (100%)26 (92.8%)0.76
Death010.75
Median clinical follow-up (mos)83.014.0<0.001
Median imaging follow-up (mos)95.023.5<0.001

Medians were used unless otherwise stated, due to nonnormal distributions in the data.

Cerebrospinal Fluid Leakage

One concern often raised regarding the use of endonasal approaches is the issue of CSF leakage. The standard technique used by our group for skull base repair involves the placement of fat and tensor fascia lata graft harvested from the thigh, followed by a vascularized nasoseptal flap and fibrin sealant. We generally do not place lumbar drains at the time of the procedure. Although intraoperative CSF leaks were encountered in all patients in the EES group, the incidence of a significant postoperative CSF leak requiring further intervention occurred in 2 of 28 patients (7.1%; Table 3). Of note, our practice for postoperative CSF leakage is to revise the skull base repair. There were no recorded cases of meningitis in any of the patients who underwent EES, including the 2 with postoperative CSF leakage. One patient with persistent CSF leakage went on to require placement of a ventriculoperitoneal shunt.

Obesity Rate

Pediatric patients with craniopharyngioma often develop significant weight gain and obesity following resection, which is thought to be from manipulation or damage to the hypothalamic nuclei.7 Given the difference in the amount of ischemic injury observed between the open surgery and EES groups, the cohorts were assessed to determine if they also had a difference in the incidence of obesity and if the ischemic injury could be correlated to weight gain.

Data on patient BMI at most recent follow-up was obtained from chart review. The difference in median BMI at follow-up was found to be statistically significant between the open surgical and EES groups (26.9 vs 23.0 kg/m2, p = 0.03; Fig. 3A), as was the difference in median change in BMI before and after surgery between the groups (7.95 vs 3.70 kg/m2, p = 0.03; Table 3, Fig. 3C). In the matched cohort the median BMI at follow-up was also higher in the open surgical group, but it did not reach statistical significance (26.9 vs 24.4 kg/m2, p = 0.17; Table 2). Change in BMI was also higher in the open surgical group in the matched cohorts but again did not reach significance (8.88 vs 5.53 kg/m2, p = 0.33; Table 2). The rate of obesity, defined as BMI > 30 kg/m2 at most recent follow-up, was higher in the open surgery than the EES group (40.0% vs 22.2%; Fig. 3B) but did not reach significance (p = 0.39). Obesity rate was also higher among patients in the open surgery group in the matched cohort volumetric analysis, but was not statistically significant (36.4% vs 27.3% kg/m2, p = 0.65; Table 2). To assess the influence of ischemic injury on obesity development, a linear regression model was performed to correlate BMI and volume of DWI signal change on postoperative imaging in the entire patient cohort, independent of surgery performed (Fig. 3D). To perform the correlation, 2 patients in the open surgical group with large cortical infarcts were excluded to focus on ischemic events more representative of those leading to hypothalamic injury. This analysis resulted in a statistically significant (p = 0.05) positive correlation between BMI at last follow-up and volume of DWI signal change on postoperative imaging.

FIG. 3.
FIG. 3.

Box-and-whisker plot of patient BMI for the open surgical and EES groups (A) shows a significantly higher median BMI in the open group at last recorded follow-up. The rate of obesity (BMI > 30 kg/m2) was also found to be higher in the open group, but this did not reach significance (B). The change in BMI from preoperatively to the most recent postoperative visit was found to be significantly larger in the open surgical group (C). Regression analysis of BMI and volume of ischemic injury on postoperative MRI, irrespective of surgical type, demonstrated a significant positive correlation between the two variables (D, p = 0.05).

Other Outcome Measures

Aggressive resection of pediatric craniopharyngioma has been associated with long-term psychological and cognitive deficits.7,12,28 To look for differences in the cohorts, charts were reviewed for descriptions of patients’ longitudinal psychological and cognitive functional levels. The presence of concerns such as learning disabilities, difficulty with school, aggressive behavior, significant anxiety, and/or depression was noted. Although they were a crude measure of behavioral, learning, or psychosocial issues, these qualitative data were obtainable for the vast majority of patients given the high quality of follow-up and documentation throughout the electronic medical record. Following data extraction, patients in the open surgical group were noted to have a 33.3% rate of developing such issues during follow-up compared to 18.5% of the EES group (Table 3). Given the small sample size, this difference did not reach statistical significance (p = 0.48).

The presence of panhypopituitarism in the postoperative period was nearly uniform across the groups (Table 3). Only 2 patients in the EES group did not require full hormone replacement. One death occurred during the follow-up period (Table 3). A patient in the EES group with postoperative panhypopituitarism and obstructive sleep apnea was found to have died in their sleep 26 months after surgery. No clear cause of death was identified.

Discussion

Recently, endoscopic endonasal approaches to the skull base have started to make inroads into treatment choices for the pediatric population. Historically, concerns about this approach in children due to the frequent lack of pneumatization of their sinuses and small working corridors have been raised.17 In our experience, these factors have not been limitations.21 Our experience is also supported by other groups.1,39 As this approach becomes more frequently used, it is important to fully understand how it may be most beneficial in patients with a variety of pathologies and to compare it to historical predecessors. For pediatric craniopharyngioma, open surgeries, especially of tumors of substantial size, carry significant risks that are often further magnified in the setting of recurrent disease. Conservative approaches such as planned STR or cyst drainage followed by radiation targeted to residual disease have been pursued, but this adds a nonnegligible risk associated with radiation. With these factors in mind, the preferred surgical approach would be one that avoids brain retraction and injury but is capable of achieving a GTR to avoid RT. EES has the potential to allow for GTR while satisfying this desire, because it allows the surgeon to come directly at the tumor without the need for brain retraction. A transsphenoidal approach also theoretically allows for the decompression of critical structures—optic chiasm, anterior communicating artery complex, distal A2 vessels, and end artery perforators—prior to any manipulation or stretching. We hypothesized that these potential advantages of EES may decrease the risk of cerebrovascular injury or ischemic insults, and ultimately the amount of functional complications, without sacrificing the ability to achieve a GTR.

Extent of Resection

A recent case series by Yamada et al. and their accompanying review of the literature has shown that GTR is readily feasible with an EES approach.39 Their rate of GTR, 91% in patients with either primary or recurrent disease, is comparable to the rate of GTR reported in this study (86%; Table 3). Furthermore, when compared to open surgery in our study, EES, unexpectedly, was significantly more likely to result in GTR. Preoperative tumor volume was smaller in the EES group, a potential confounder that was nearly significant (p = 0.06), so a matched cohort analysis between the 11 largest tumors in the EES group and 11 patients in the open surgical group was performed. This resulted in a near-identical median tumor volume between the groups (Fig. 1E), and the residual tumor volumes following either approach remained equivalent. Furthermore, the range of residual tumor volumes in both the matched and unmatched analyses showed a much narrower distribution for EES (Fig. 1B and 1F), suggesting that EES is more reliable in delivering a larger EOR. When our results are taken together with recent series describing EES for pediatric craniopharyngioma, there seems to be growing evidence that EES is a reliable approach to this tumor for the purpose of achieving a GTR.

Cerebrovascular Complications

To evaluate the hypothesis that EES has the potential to reduce cerebrovascular-related complications, such as ischemic insults and FDCA, we performed a volumetric analysis of the area of restricted diffusion on postoperative MRI, in both the unmatched and matched preoperative tumor volume scenarios, and reviewed charts for the rate of FDCA formation. This showed a significantly lower volume of ischemia in the EES group compared to the open surgical group (Fig. 2A and B), supporting the theory that shifting the operative corridor to the midline and avoiding brain retraction and reducing arterial manipulation decreases ischemic insults.

FDCA is a well-described complication after resection of pediatric craniopharyngioma.3,10,13,38 The natural history of this entity has been investigated, and although the risk of complications secondary to its development is very low over time, significant resources are still allocated to monitoring patients who develop it.10 In our series, this entity was observed in the open surgical group at a rate of 26.7%, which is in the range of its reported incidence.25 These patients did not require direct intervention for their FDCA, which is in keeping with its natural history, but they all required subsequent vascular imaging, a resource-intensive and nontrivial task in most children. There were no instances of FDCA in the EES cohort, which is presumably secondary to the fact that EES approaches require significantly less manipulation of the cerebral vessels than open procedures. It is possible that no cases of FDCA were identified in the EES group because of the group’s shorter length of follow-up, but the median time to the development of FDCA in the open group, 19.5 months, is within the median imaging follow-up for the EES group (23.5 months). There was 1 patient in the EES group who suffered an ischemic stroke secondary to vasospasm, highlighting the fact that this approach still poses some risk to vascular structures.

Obesity and Other Complications

The development of obesity is intimately intertwined with the outcomes of pediatric craniopharyngioma surgery.7 This phenomenon is thought to be mediated by damage to the ventromedial hypothalamic nuclei.32 With this in mind, we hypothesized that the difference in vascular insults observed between the open surgical and EES groups may translate into a difference in postoperative weight gain. Analysis of the most recent BMI at follow-up showed a significantly higher median value and a larger increase in BMI in the open surgical group (Table 3). These differences were seen in the matched cohort volumetric analysis but did not hold statistical significance (Table 2), potentially due to the limited number of patients in the analysis. To link volume of ischemia with the BMI results, we performed a regression analysis that showed a significant positive correlation in the two variables regardless of which surgical intervention was performed, suggesting that the volume of ischemia played a role in the observed BMI differences. One potential source of bias in these data is the difference in length of follow-up between the groups. Although the follow-up is greater in the open surgical group, the time period over which obesity generally develops following resection is rather rapid, on the order of 6–12 months.7

Many authors have reported a spectrum of behavioral and learning disabilities following the resection of pediatric craniopharyngioma.7,25 We hypothesized that the benefits of EES—mainly diminished vascular insults—may translate to benefits in this regard as well. After extracting qualitative data about behavioral and learning function at last follow-up, we found a higher rate of these psychosocial issues in the open group compared to the EES group (33.3% vs 18.5%; Table 3), but this did not reach significance. This result is in line with anecdotal observations that we and our colleagues have made regarding children after EES as opposed to those who have undergone open resections. Observations concerning psychosocial outcomes require larger sample sizes and longitudinal studies before meaningful conclusions can be reached.

A common concern regarding EES is that of CSF leakage. Our group has previously published on our technique for nasoseptal flap reconstruction in this age group and its feasiblity.11 As suggested by the results of this study, techniques for skull base reconstruction in this patient population have an acceptable success rate; only 2 of 28 patients (7.1%) required revision of a reconstruction for persistent postoperative leakage. This rate is similar to other recent reports.26,30 Given this rate, the nontrivial complications associated with lumbar drain use, and the unclear utility of its use in even high-flow CSF leak cases when using a nasoseptal flap,36 we do not routinely place lumbar drains at the time of initial surgery or revision of a repair if needed.

Study Limitations

The retrospective, longitudinal nature of this type of study is a clear source of potential bias. Surgeries were performed by two surgeons over the period, one of whom performed only open surgeries in early cases in the cohort and another who performed some of the open surgeries and all of the EES cases. Differences in techniques over time have the potential to influence findings and are challenging to account for. One attempt to minimize the bias of retrospective review involved the use of an independent review of the imaging for volumetric analysis by the neuroradiologist involved, who was blinded to patient outcomes. Differences in clinical and imaging follow-up between the groups may also play a role in observed longitudinal outcome measures, such as recurrence rate. The median imaging follow-up for the EES group, though, was similar to the median time to recurrence. Also, in our series most recurrences were in patients who had STRs, a factor that would be independent of length of imaging or clinical follow-up. Furthermore, small sample sizes, a common issue with studies regarding rare diseases, also limited the ability to achieve significance in a number of comparisons.

Conclusions

In this single-institution study, we describe our experience with pediatric craniopharyngioma resection by EES compared to open surgery, adding to the growing evidence that this technique is safe and feasible regardless of age, extent of sphenoid sinus aeration, or tumor size. Results showed that EES was capable of achieving a comparable or superior EOR over open surgery while having a significantly lower level of associated cerebrovascular injury, even when accounting for differences in preoperative tumor volume. Additionally, the recurrence rate and need for adjuvant RT were lower in the EES group. Furthermore, the observed positive correlation between ischemic injury and postoperative BMI supports the theory that hypothalamic dysfunction secondary to ischemic injury can be mitigated by procedures that cause less ischemia, a finding significantly associated with EES cases in our series.

These experiences and findings have altered our practice, and we believe that the vast majority of these tumors can be safely and effectively removed via an EES approach, even those involving the hypothalamus. An exception may be those cases of extremely large, solid tumors with significant lateral extent beyond the carotid arteries, which may require combined craniotomy and EES approaches for maximal debulking. For the majority of cases, though, these findings add to the growing body of literature in support of using purely endoscopic endonasal techniques for the surgical management of pediatric craniopharyngioma.

Acknowledgments

This work was supported by the Abrahams Family Innovation Fund.

Disclosures

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

Conception and design: Storm, Adappa. Acquisition of data: Storm, Madsen, Douglas, Parasher, Lerner, Alexander, Workman, Palmer, Lang, Kennedy, Adappa. Analysis and interpretation of data: Storm, Madsen, Buch, Douglas, Lerner, Kennedy, Vossough. Drafting the article: Storm, Madsen, Buch, Douglas. Critically revising the article: Storm, Madsen, Buch, Parasher, Adappa. Reviewed submitted version of manuscript: Storm, Madsen, Buch, Douglas, Parasher, Lerner, Workman, Palmer, Lang, Kennedy, Vossough, Adappa. Approved the final version of the manuscript on behalf of all authors: Storm. Statistical analysis: Madsen, Buch. Administrative/technical/material support: Storm, Alexander, Palmer, Lang, Kennedy, Vossough, Adappa. Study supervision: Storm, Adappa.

Supplemental Information

Previous Presentations

Portions of this work were presented at the 45th and 46th Annual AANS/CNS Section Meetings on Pediatric Neurological Surgery in December 2016 and November 2017, respectively, and to the American Society of Pediatric Neurosurgeons in January 2019.

References

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    Ali ZS, Lang SS, Kamat AR, Adappa ND, Palmer JN, Storm PB, et al.: Suprasellar pediatric craniopharyngioma resection via endonasal endoscopic approach. Childs Nerv Syst 29:20652070, 2013

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    Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, et al.: The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg 121:100113, 2014

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    • PubMed
    • Search Google Scholar
    • Export Citation
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    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. J Neurosurg Pediatr 5:3048, 2010

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    Elliott RE, Wisoff JH: Fusiform dilation of the carotid artery following radical resection of pediatric craniopharyngiomas: natural history and management. Neurosurg Focus 28(4):E14, 2010

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    Ghosh A, Hatten K, Learned KO, Rizzi MD, Lee JY, Storm PB, et al.: Pediatric nasoseptal flap reconstruction for suprasellar approaches. Laryngoscope 125:24512456, 2015

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    Hoffmann A, Warmuth-Metz M, Lohle K, Reichel J, Daubenbüchel AMM, Sterkenburg AS, et al.: Fusiform dilatation of the internal carotid artery in childhood-onset craniopharyngioma: multicenter study on incidence and long-term outcome. Pituitary 19:422428, 2016

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    Jane JA Jr, Prevedello DM, Alden TD, Laws ER Jr: The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr 5:4960, 2010

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    Kanesaka N, Mikami R, Nakayama H, Nogi S, Tajima Y, Nakajima N, et al.: Preliminary results of fractionated stereotactic radiotherapy after cyst drainage for craniopharyngioma in adults. Int J Radiat Oncol Biol Phys 82:13561360, 2012

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    • Search Google Scholar
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    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) 62:397409, 2005

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    • Search Google Scholar
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    Kassam A, Thomas AJ, Snyderman C, Carrau R, Gardner P, Mintz A, et al.: Fully endoscopic expanded endonasal approach treating skull base lesions in pediatric patients. J Neurosurg 106 (2 Suppl):7586, 2007

    • PubMed
    • Search Google Scholar
    • Export Citation
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    Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28(4):E10, 2010

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    Komotar RJ, Starke RM, Raper DMS, Anand VK, Schwartz TH: Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of craniopharyngiomas. World Neurosurg 77:329341, 2012

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    • PubMed
    • Search Google Scholar
    • Export Citation
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    Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Tyler-Kabara EC, Wang EW, Snyderman CH: Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients. J Neurosurg 119:11941207, 2013

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    • PubMed
    • Search Google Scholar
    • Export Citation
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    Kuan EC, Kaufman AC, Lerner D, Kohanski MA, Tong CCL, Tajudeen BA, et al.: Lack of sphenoid pneumatization does not affect endoscopic endonasal pediatric skull base surgery outcomes. Laryngoscope 129:832836, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Leng LZ, Greenfield JP, Souweidane MM, Anand VK, Schwartz TH: Endoscopic, endonasal resection of craniopharyngiomas: analysis of outcome including extent of resection, cerebrospinal fluid leak, return to preoperative productivity, and body mass index. Neurosurgery 70:110124, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Moussa AH, Kerasha AA, Mahmoud ME: Surprising outcome of Ommaya reservoir in treating cystic craniopharyngioma: a retrospective study. Br J Neurosurg 27:370373, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Müller HL: Childhood craniopharyngioma. Pituitary 16:5667, 2013

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    Müller HL: Craniopharyngioma. Endocr Rev 35:513543, 2014

  • 26

    Nation J, Schupper AJ, Deconde A, Levy M: CSF leak after endoscopic skull base surgery in children: A single institution experience. Int J Pediatr Otorhinolaryngol 119:2226, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Netson KL, Conklin HM, Wu S, Xiong X, Merchant TE: Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 85:13011306, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Ondruch A, Maryniak A, Kropiwnicki T, Roszkowski M, Daszkiewicz P: Cognitive and social functioning in children and adolescents after the removal of craniopharyngioma. Childs Nerv Syst 27:391397, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al.: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol 17 (Suppl 4):iv1iv62, 2015

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    • PubMed
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    Patel VS, Thamboo A, Quon J, Nayak JV, Hwang PH, Edwards M, et al.: Outcomes after endoscopic endonasal resection of craniopharyngiomas in the pediatric population. World Neurosurg 108:614, 2017

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    • PubMed
    • Search Google Scholar
    • Export Citation
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    • PubMed
    • Search Google Scholar
    • Export Citation
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    • PubMed
    • Search Google Scholar
    • Export Citation
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    Sankhla SK, Jayashankar N, Khan GM: Extended endoscopic endonasal transsphenoidal approach for retrochiasmatic craniopharyngioma: Surgical technique and results. J Pediatr Neurosci 10:308316, 2015

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    • PubMed
    • Search Google Scholar
    • Export Citation
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    • Export Citation
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  • Collapse
  • Expand
  • Box-and-whisker plots of preoperative (A) and residual postoperative (B) tumor volumes of the open surgical and EES groups showing a near-significant difference in preoperative tumor volumes but equivalent residual volumes. Plotting the preoperative tumor volumes of both groups (C) showed that the EES group had a large percentage of smaller tumors. Patients with the largest tumors in the EES group were then matched with the open surgical cohort, resulting in statistically similar median volumes (D). Box-and-whisker plots of preoperative (E) and postoperative (F) tumor volumes in the matched cohort analysis show no difference, but the range in residual volumes for the open surgical group was much larger (F).

  • Box-and-whisker plots from unmatched (A) and matched (B) analysis of extent of ischemic injury as measured by DWI signal change in the open and EES groups. Both analyses reveal significant levels of ischemic injury in the open surgical group compared to the EES group. Presence of FDCA was extracted from chart and imaging review and only found to occur in the open surgical group, reaching statistical significance (C).

  • Box-and-whisker plot of patient BMI for the open surgical and EES groups (A) shows a significantly higher median BMI in the open group at last recorded follow-up. The rate of obesity (BMI > 30 kg/m2) was also found to be higher in the open group, but this did not reach significance (B). The change in BMI from preoperatively to the most recent postoperative visit was found to be significantly larger in the open surgical group (C). Regression analysis of BMI and volume of ischemic injury on postoperative MRI, irrespective of surgical type, demonstrated a significant positive correlation between the two variables (D, p = 0.05).

  • 1

    Alalade AF, Ogando-Rivas E, Boatey J, Souweidane MM, Anand VK, Greenfield JP, et al.: Suprasellar and recurrent pediatric craniopharyngiomas: expanding indications for the extended endoscopic transsphenoidal approach. J Neurosurg Pediatr 21:7280, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Ali ZS, Lang SS, Kamat AR, Adappa ND, Palmer JN, Storm PB, et al.: Suprasellar pediatric craniopharyngioma resection via endonasal endoscopic approach. Childs Nerv Syst 29:20652070, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Bendszus M, Sörensen N, Hofmann E, Röll E, Solymosi L: Fusiform dilatations of the internal carotid artery following surgery for pediatric suprasellar tumors. Pediatr Neurosurg 29:304308, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, et al.: The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg 121:100113, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Clark AJ, Cage TA, Aranda D, Parsa AT, Sun PP, Auguste KI, et al.: A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst 29:231238, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Cohen M, Guger S, Hamilton J: Long term sequelae of pediatric craniopharyngioma—literature review and 20 years of experience. Front Endocrinol (Lausanne) 2:81, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Daubenbüchel AMM, Müller HL: Neuroendocrine disorders in pediatric craniopharyngioma patients. J Clin Med 4:389413, 2015

  • 8

    Di Pinto M, Conklin HM, Li C, Merchant TE: Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 84:e363e369, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    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. J Neurosurg Pediatr 5:3048, 2010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Elliott RE, Wisoff JH: Fusiform dilation of the carotid artery following radical resection of pediatric craniopharyngiomas: natural history and management. Neurosurg Focus 28(4):E14, 2010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ghosh A, Hatten K, Learned KO, Rizzi MD, Lee JY, Storm PB, et al.: Pediatric nasoseptal flap reconstruction for suprasellar approaches. Laryngoscope 125:24512456, 2015

  • 12

    Hoffman HJ, De Silva M, Humphreys RP, Drake JM, Smith ML, Blaser SI: Aggressive surgical management of craniopharyngiomas in children. J Neurosurg 76:4752, 1992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Hoffmann A, Warmuth-Metz M, Lohle K, Reichel J, Daubenbüchel AMM, Sterkenburg AS, et al.: Fusiform dilatation of the internal carotid artery in childhood-onset craniopharyngioma: multicenter study on incidence and long-term outcome. Pituitary 19:422428, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Jane JA Jr, Prevedello DM, Alden TD, Laws ER Jr: The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr 5:4960, 2010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Kanesaka N, Mikami R, Nakayama H, Nogi S, Tajima Y, Nakajima N, et al.: Preliminary results of fractionated stereotactic radiotherapy after cyst drainage for craniopharyngioma in adults. Int J Radiat Oncol Biol Phys 82:13561360, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    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) 62:397409, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Kassam A, Thomas AJ, Snyderman C, Carrau R, Gardner P, Mintz A, et al.: Fully endoscopic expanded endonasal approach treating skull base lesions in pediatric patients. J Neurosurg 106 (2 Suppl):7586, 2007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28(4):E10, 2010

  • 19

    Komotar RJ, Starke RM, Raper DMS, Anand VK, Schwartz TH: Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of craniopharyngiomas. World Neurosurg 77:329341, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Tyler-Kabara EC, Wang EW, Snyderman CH: Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients. J Neurosurg 119:11941207, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Kuan EC, Kaufman AC, Lerner D, Kohanski MA, Tong CCL, Tajudeen BA, et al.: Lack of sphenoid pneumatization does not affect endoscopic endonasal pediatric skull base surgery outcomes. Laryngoscope 129:832836, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Leng LZ, Greenfield JP, Souweidane MM, Anand VK, Schwartz TH: Endoscopic, endonasal resection of craniopharyngiomas: analysis of outcome including extent of resection, cerebrospinal fluid leak, return to preoperative productivity, and body mass index. Neurosurgery 70:110124, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Moussa AH, Kerasha AA, Mahmoud ME: Surprising outcome of Ommaya reservoir in treating cystic craniopharyngioma: a retrospective study. Br J Neurosurg 27:370373, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Müller HL: Childhood craniopharyngioma. Pituitary 16:5667, 2013

  • 25

    Müller HL: Craniopharyngioma. Endocr Rev 35:513543, 2014

  • 26

    Nation J, Schupper AJ, Deconde A, Levy M: CSF leak after endoscopic skull base surgery in children: A single institution experience. Int J Pediatr Otorhinolaryngol 119:2226, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Netson KL, Conklin HM, Wu S, Xiong X, Merchant TE: Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 85:13011306, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Ondruch A, Maryniak A, Kropiwnicki T, Roszkowski M, Daszkiewicz P: Cognitive and social functioning in children and adolescents after the removal of craniopharyngioma. Childs Nerv Syst 27:391397, 2011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al.: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol 17 (Suppl 4):iv1iv62, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Patel VS, Thamboo A, Quon J, Nayak JV, Hwang PH, Edwards M, et al.: Outcomes after endoscopic endonasal resection of craniopharyngiomas in the pediatric population. World Neurosurg 108:614, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Poretti A, Grotzer MA, Ribi K, Schönle E, Boltshauser E: Outcome of craniopharyngioma in children: long-term complications and quality of life. Dev Med Child Neurol 46:220229, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Rosenfeld A, Arrington D, Miller J, Olson M, Gieseking A, Etzl M, et al.: A review of childhood and adolescent craniopharyngiomas with particular attention to hypothalamic obesity. Pediatr Neurol 50:410, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Sankhla SK, Jayashankar N, Khan GM: Extended endoscopic endonasal transsphenoidal approach for retrochiasmatic craniopharyngioma: Surgical technique and results. J Pediatr Neurosci 10:308316, 2015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Scarzello G, Buzzaccarini MS, Perilongo G, Viscardi E, Faggin R, Carollo C, et al.: Acute and late morbidity after limited resection and focal radiation therapy in craniopharyngiomas. J Pediatr Endocrinol Metab 19 (Suppl 1):399405, 2006

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

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