Craniopharyngiomas are rare, benign, and slow-growing intracranial neoplasms derived from the remnants of squamous epithelium along the craniopharyngeal duct.1 They can occur in both adult and pediatric age groups. Pediatric craniopharyngiomas account for between 30% and 50% of all craniopharyngiomas and between 1.2% and 4.6% of all pediatric intracranial tumors.2–4 Historically, transcranial microsurgery (TCM) with gross-total resection (GTR) was the mainstay treatment for craniopharyngiomas, but excess morbidities and mortality associated with hypothalamus injury make the management of craniopharyngiomas challenging.5,6
Over the last decade, endoscopic endonasal surgery (EES) has been widely used for sellar, para-, and suprasellar lesions. The advantages of EES over TCM include direct access to tumors without brain retraction and the manipulation of vital neurovascular structures, and exposure of tumors along their long axis, making it a sensible and alternative approach compared with TCM for sellar and suprasellar craniopharyngiomas, or even lesions extending into the third ventricle or cisterna interpeduncularis.7–9 However, increased CSF leakage and less-effective management of tumors extending laterally beyond the bifurcation of the internal carotid arteries are the main drawbacks of EES,9,10 although the former has been decreased after using vascularized nasoseptal flaps for endoscopic skull base reconstruction.11,12
Generally, both surgical modalities have advantages and limitations, rendering no clear consensus as to which one is superior. Directly comparing EES and TCM for specific tumors is the ideal way to resolve this issue. Several studies have compared EES and TCM for adult and mixed-age population craniopharyngiomas, demonstrating that EES has an equivalent GTR rate, tumor recurrence rate, and postoperative quality of life, but superior visual and endocrinological outcomes.10,13–16 In pediatric patients, although limited studies17–20 have demonstrated that EES is a safe and effective approach for midline craniopharyngiomas, studies comparing EES and TCM for pediatric craniopharyngiomas are sparse. To our knowledge, only one study has compared EES and TCM in the pediatric population, reporting that EES is associated with an equivalent recurrence rate, significantly increased rate of GTR, and less ischemic injury.21 However, the significantly different follow-up durations between the groups in that study may bias the comparison of long-term outcomes; additionally, a comparison of visual outcomes between the groups was missing. Thus, supplementing the current literature is warranted by comparing EES and TCM in pediatric cohorts, to provide insights into the surgical management of pediatric craniopharyngiomas and improvement of outcomes.
Herein, we compared the baseline characteristics of patients who underwent EES with those who underwent TCM for pediatric craniopharyngiomas, as well as surgical results and perioperative complications. Next, propensity-adjusted analysis was implemented to match covariables and compare surgical outcomes between the treatment groups.
Methods
After obtaining board approval from the local ethics committee, the medical files and imaging data of consecutive pediatric patients with craniopharyngiomas (aged < 18 years at diagnosis) who underwent surgery between February 2009 and June 2021 at our center were retrospectively reviewed. Patients meeting the following inclusion criteria were included: 1) a histologically confirmed diagnosis of craniopharyngioma; 2) EES or TCM for primary or secondary tumors; 3) complete medical records, including demographic data, pre- and postoperative imaging data, preoperative assessment, tumor characteristics, intraoperative notes, surgical results and complications, postoperative management, and imaging and clinical data during follow-up; and 4) midline tumors located in the sellar, sellar-suprasellar, or suprasellar regions, or lesions with extension to the roof of the third ventricle and those with extension into the prepontine cistern. Patients with tumors significantly extending laterally beyond the bifurcation of internal carotid arteries were excluded to ensure that the included tumors were amenable to both approaches. All the included patients were divided into an EES group and a TCM group according to the treatment modality received.
Tumor volume was estimated using the following equation: tumor volume = (A × B × C)/2, where A, B, and C represent the dimensions of the tumor in 3 orthogonal planes.10 Tumor location, tumor consistency, calcification, and hydrocephalus were determined by preoperative MRI and CT scans. Regarding the extent of resection (EOR), GTR was defined as resection with no residual tumor confirmed by intraoperative findings and postoperative contrast-enhanced MRI acquired within 72 hours after surgery. By contrast, cases in which ≥ 80% of the tumor was resected were deemed a subtotal resection (STR), and partial resection was defined as < 80% resection.13,22 Visual testing, including visual acuity and visual fields, was employed preoperatively and 2 weeks after surgery for all patients, except for patients who were too young to cooperate with the examination. Additionally, preoperative hypothalamic involvement was graded according to the classification system proposed by Puget et al., which is outlined as follows: grade 0, no hypothalamic involvement; grade 1, the tumor abutting or displacing the hypothalamus; and grade 2, hypothalamic involvement (the hypothalamus is no longer identifiable).23
Endocrinological Evaluation and BMI
The presurgical and postsurgical endocrinological statuses were evaluated as described previously.7 Deficiency was diagnosed when the serum levels of endocrinological tests were lower than the current reference values for the axis, and if patients had undergone hormone replacement therapy. Partial hypopituitarism was defined as hormone deficiencies in 1 or 2 axes, and panhypopituitarism was defined as hormone deficiencies in ≥ 3 axes. Patients were diagnosed with diabetes insipidus (DI) when they had polydipsia and polyuria with urine-specific gravity < 1.005 and urine osmolality < 300 mOsm/kg, as well as a positive response to desmopressin. Additionally, BMI was calculated as body weight (kg) divided by height (m) squared (kg/m2) and was measured preoperatively and during follow-up.
Postoperative Management and Follow-Up
Vital signs, water electrolytes, and endocrinological status were closely observed after surgery. All patients underwent imaging and clinical evaluation at 3 months, 6 months, 12 months, and every 2 years subsequently after discharge. Recurrence was defined as the emergence of tumors detected on neuroimaging for patients who underwent GTR, or the regrowth of a residual tumor. Generally, patients who underwent STR routinely received radiotherapy 3 months after surgery, except for those younger than 5 years.23 Additionally, in patients with recurrence, observation, radiotherapy, or reoperation was performed during follow-up on a case-by-case bias. Postoperative hypothalamic dysfunction was evaluated using the 4-tiered grading scale created by De Vile et al.24 It was adapted and is outlined in Table 1.
Levels of hypothalamic function at follow-up*
| Level | Description |
|---|---|
| 1 | Normal hypothalamic function. |
| 2 | Postoperative obesity or excess weight gain is present w/o any other hypothalamic dysfunction. |
| 3 | An obvious period of hyperphagia, or an associated change in affective behavior or memory other than obesity or weight gain, is present. |
| 4 | Hyperphagia & weight gain are extreme, along with other clinical manifestations such as impaired thirst & rage behavior, or disturbances of thermoregulation, memory, & sleep-wake patterns. |
Adjusted based on the grading scale created by De Vile et al.24
Statistical Analysis
Continuous variables are reported as mean ± SD or median with interquartile range (IQR), determined by the Shapiro-Wilk test. Categorical data are reported as counts and proportions in each group. The data between the groups were compared using the chi-square test (Fisher’s exact test where appropriate) for categorical variables or 2-tailed Student t-test (Mann-Whitney U-test where appropriate) for continuous variables. Additionally, propensity-adjusted analysis (adjusted for the duration of follow-up, preoperative anterior pituitary function, surgery type, tumor location, tumor volume, and postoperative radiation) was performed.
IBM SPSS Statistics version 25.0 (IBM Corp.) and GraphPad Prism version 8.0.2 (GraphPad Software) were used to perform statistical analyses. The difference was considered statistically significant when p < 0.05 using two-tailed tests.
Results
Clinical Characteristics
Overall, 53 pediatric patients with craniopharyngiomas were identified at our center between February 2009 and June 2021. After excluding patients with incomplete medical records (n = 3) and those with tumors significantly extending laterally beyond the bifurcation of the internal carotid arteries (n = 1), 49 patients comprising 51 operative cases remained, including 35 cases treated with EES and 16 cases treated with TCM (Table 2). Of 51 surgeries, initial and repeated surgeries accounted for 72.5% and 27.5%, respectively. Among the 35 EES cases, 24 (68.6%) were initial surgeries and 11 (31.4%) were treatment for recurrent or progressive tumors, among which 10 had been preceded by TCM and 1 had been preceded by EES. Of the 16 TCM cases, 13 (81.3%) were initial surgeries and 3 (18.8%) were treatment for recurrent or progressive tumors, of which 2 had been preceded by TCM and 1 had been treated twice previously with TCM. The proportion of initial surgeries between the EES and TCM groups was comparable, without a significant difference (68.6% vs 81.3%, p = 0.546). Additionally, of 14 cases that were recurrent surgeries, 2 had been performed at at our center, and the others were performed at other centers. None of the included patients had received other treatments (e.g., adjuvant radiotherapy and ventriculoperitoneal shunt placement) before surgery. The difference between the groups in patient age, sex, clinical presentations before surgery, and tumor characteristics was not significant. Regarding preoperative anterior pituitary function, the groups only differed in that the proportion of hypogonadism was significantly higher in the EES group than in the TCM group (60% vs 18.8%, p = 0.006). Furthermore, the median duration of follow-up was 66.0 months (IQR 46.0–100.0 months) in the TCM group, which was significantly longer than that in the EES group (40.5 months, p = 0.007). Given the significant difference in the preoperative anterior pituitary function and duration of follow-up between the groups, we performed propensity adjustment to match covariables that may affect the comparison of long-term outcomes for pediatric patients with craniopharyngiomas. Table 3 shows that the baseline characteristics between the two treatment groups were similar without significant differences after score matching.
Baseline characteristics of pediatric craniopharyngiomas treated via EES versus TCM before score matching
| Variable | Overall (n = 51) | EES (n = 35) | TCM (n = 16) | p Value |
|---|---|---|---|---|
| Median pt age, yrs (IQR) | ||||
| At diagnosis | 12.0 (8.0–16.0) | 12.0 (8.0–16.0) | 11.5 (5.2–15.8) | 0.737 |
| At last follow-up | 17.0 (10.0–20.0) | 17.0 (10.0–19.0) | 15.5 (10.3–22.8) | 0.611 |
| Pt sex | 0.201 | |||
| F | 22 (43.1) | 13 (37.1) | 9 (56.3) | |
| M | 29 (56.9) | 22 (62.9) | 7 (43.8) | |
| Mean preop BMI ± SD, kg/m2 | 18.4 ± 3.4 | 18.7 ± 3.4 | 17.7 ± 3.4 | 0.319 |
| Clinical presentation | ||||
| Visual impairment | 24 (47.1) | 15 (42.9) | 9 (56.3) | 0.374 |
| Headache | 32 (62.7) | 24 (68.6) | 8 (50) | 0.203 |
| Growth retardation | 24 (47.1) | 15 (42.9) | 9 (56.3) | 0.374 |
| Seizures | 3 (5.9) | 2 (5.7) | 1 (6.3) | >0.99 |
| Vomiting | 16 (31.4) | 11 (31.4) | 5 (31.3) | 0.990 |
| Balance instability | 4 (7.8) | 2 (5.7) | 2 (12.5) | 0.783 |
| Cognitive/personality change | 7 (13.7) | 5 (14.3) | 2 (12.5) | >0.99 |
| DI | 15 (29.4) | 11 (31.4) | 4 (25.0) | 0.892 |
| Type of op | 0.546 | |||
| Primary | 37 (72.5) | 24 (68.6) | 13 (81.3) | |
| Repeat | 14 (27.5) | 11 (31.4) | 3 (18.8) | |
| Median tumor vol, cm3 (IQR) | 15.0 (5.5–25.4) | 14.6 (4.6–25.2) | 16.7 (8.3–26.5) | 0.543 |
| Tumor location | 0.501 | |||
| Sellar | 3 (5.9) | 3 (8.6) | 0 (0) | |
| Sellar-suprasellar | 22 (43.1) | 16 (45.7) | 6 (37.5) | |
| Suprasellar | 26 (51.0) | 16 (45.7) | 10 (62.5) | |
| Hypothalamic involvement | ||||
| Grade 0 | 9 (17.6) | 7 (20.0) | 2 (12.5) | 0.798 |
| Grade 1 | 13 (25.5) | 8 (22.9) | 5 (31.3) | 0.770 |
| Grade 2 | 29 (56.9) | 20 (57.1) | 9 (56.3) | 0.952 |
| Tumor consistency | 0.572 | |||
| Solid | 6 (11.8) | 5 (14.3) | 1 (6.3) | |
| Mixed | 28 (54.9) | 20 (57.1) | 8 (50.0) | |
| Cystic | 17 (33.3) | 10 (28.6) | 7 (43.8) | |
| Calcification | 0.546 | |||
| Yes | 37 (72.5) | 24 (68.6) | 13 (81.3) | |
| No | 14 (27.5) | 11 (31.4) | 3 (18.8) | |
| Hydrocephalus at diagnosis | 0.485 | |||
| Yes | 11 (21.6) | 9 (25.7) | 2 (12.5) | |
| No | 40 (78.4) | 26 (74.3) | 14 (87.5) | |
| Preop anterior pituitary function | ||||
| Adrenal insufficiency | 17 (33.3) | 12 (34.3) | 5 (31.3) | 0.831 |
| Hypothyroidism | 14 (27.5) | 10 (28.6) | 4 (25.0) | >0.99 |
| Hypogonadism | 24 (47.1) | 21 (60.0) | 3 (18.8) | 0.006 |
| Growth hormone deficiency | 22 (43.1) | 15 (42.9) | 7 (43.8) | 0.952 |
| Median FU, mos (IQR)* | 47.0 (29.0–70.0) | 40.5 (23.0–56.8) | 66.0 (46.0–100.0) | 0.007 |
FU = follow-up; pt = patient.
Fifty-one surgeries were performed in 49 patients. Values are presented as the number of procedures (%) unless otherwise indicated. Boldface type indicates statistical significance.
Calculated after excluding perioperative mortality.
Baseline characteristics of pediatric craniopharyngiomas treated via EES versus TCM after score matching
| Variable | Overall (n = 24) | EES (n = 12) | TCM (n = 12) | p Value |
|---|---|---|---|---|
| Mean pt age ± SD, yrs | ||||
| At presentation | 11.6 ± 4.5 | 12.3 ± 4.0 | 11.0 ± 5.0 | 0.507 |
| At last follow-up | 16.0 ± 6.3 | 16.7 ± 5.4 | 15.5 ± 7.3 | 0.661 |
| Pt sex | 0.680 | |||
| F | 14 (58.3) | 6 (50.0) | 8 (66.7) | |
| M | 10 (41.7) | 6 (50.0) | 4 (33.3) | |
| Mean preop BMI ± SD, kg/m2 | 17.9 ± 3.8 | 17.9 ± 4.2 | 18.0 ± 3.5 | 0.971 |
| Clinical presentation | ||||
| Cognitive/personality change | 6 (25.0) | 4 (33.3) | 2 (16.7) | 0.640 |
| DI | 9 (37.5) | 5 (41.7) | 4 (33.3) | >0.99 |
| Type of op | >0.99 | |||
| Primary | 19 (79.2) | 10 (83.3) | 9 (75.0) | |
| Repeat | 5 (20.8) | 2 (16.7) | 3 (25.0) | |
| Median tumor vol, cm3 (IQR) | 16.7 (2.8–26.5) | 16.0 (2.0–21.7) | 16.7 (5.7–42.3) | 0.326 |
| Tumor location | >0.99 | |||
| Sellar-suprasellar | 8 (33.3) | 4 (33.3) | 4 (33.3) | |
| Suprasellar | 16 (66.7) | 8 (66.7) | 8 (66.7) | |
| Hypothalamic involvement | ||||
| Grade 0 | 3 (12.5) | 2 (16.7) | 1 (8.3) | >0.99 |
| Grade 1 | 8 (33.3) | 3 (25.0) | 5 (41.7) | 0.667 |
| Grade 2 | 13 (54.2) | 7 (58.3) | 6 (50.0) | >0.99 |
| Tumor consistency | >0.99 | |||
| Solid | 3 (12.5) | 2 (16.7) | 1 (8.3) | |
| Mixed | 11 (45.8) | 5 (41.7) | 6 (50.0) | |
| Cystic | 10 (41.7) | 5 (41.7) | 5 (41.7) | |
| Calcification | >0.99 | |||
| Yes | 19 (79.2) | 9 (75.0) | 10 (83.3) | |
| No | 5 (20.8) | 3 (25.0) | 2 (16.7) | |
| Hydrocephalus at diagnosis | 0.640 | |||
| Yes | 6 (25.0) | 4 (33.3) | 2 (16.7) | |
| No | 18 (75.0) | 8 (66.7) | 10 (83.3) | |
| Preop anterior pituitary function | ||||
| Adrenal insufficiency | 6 (25.0) | 2 (16.7) | 4 (33.3) | 0.640 |
| Hypothyroidism | 5 (20.8) | 2 (16.7) | 3 (25.0) | >0.99 |
| Hypogonadism | 9 (37.5) | 6 (50.0) | 3 (25.0) | 0.400 |
| Growth hormone deficiency | 11 (45.8) | 5 (41.7) | 6 (50.0) | >0.99 |
Values are presented as the number of procedures (%) unless otherwise indicated.
Surgical Results and Perioperative Complications
Of the TCM cases, 50% were treated via a pterional approach, followed by 31.3% via subfrontal approaches and 18.8% via interhemispheric approaches. By analyzing the surgical trends over time, a stably increasing proportion of EES was observed after 2012, when the EES technique was introduced to our center by the chief surgeon (T.H.) (Fig. 1).
Stacked bar charts showing the percentage of pediatric craniopharyngiomas treated with EES (blue) versus TCM (red) at our institution between 2009 and 2020. Figure is available in color online only.
The difference in the proportion of GTR between the groups did not reach statistical significance, despite a higher proportion of GTR observed in the EES group both before (94.3% vs 75%, p = 0.130; Table 4) and after (91.7% vs 83.3%, p > 0.99; Table 5) score matching. Improved and stable visual outcomes were more common in the EES group, although no significant difference was found (40.0% vs 25%, p = 0.298 and 60% vs 50%, p = 0.503). By contrast, TCM significantly increased the risk of worsened visual outcomes (25.0% vs 0.0%, p = 0.012); statistical significance was not found after score matching because of the small sample size (p = 0.217). CSF leakage exclusively occurred in the EES group, with no significant difference observed between the groups in this study (5.7% vs 0.0%, p > 0.99). Both patients who experienced CSF leakage recovered via lumbar drains. Additionally, in 6 cases (11.8%), the patients received adjuvant radiotherapy after surgery, 4 following STR and 2 following tumor recurrence, although the difference in adjuvant radiotherapy between the groups did not reach significance (p = 0.130). All other perioperative complications stratified by treatment modality are tabulated in Table 4, from which no significant difference was observed in intracranial infection, postoperative hydrocephalus, epilepsy, cranial nerve injury, or cerebral contusion between the groups.
Surgical outcomes and perioperative complications of pediatric craniopharyngiomas treated via EES versus TCM before score matching
| Variable | Overall (n = 51) | EES (n = 35) | TCM (n = 16) | p Value |
|---|---|---|---|---|
| EOR | 0.130 | |||
| GTR | 45 (88.2) | 33 (94.3) | 12 (75.0) | |
| STR | 6 (11.8) | 2 (5.7) | 4 (25.0) | |
| Visual outcomes | ||||
| Improved | 18 (35.3) | 14 (40.0) | 4 (25.0) | 0.298 |
| Unchanged | 29 (56.9) | 21 (60.0) | 8 (50.0) | 0.503 |
| Worsened | 4 (7.8) | 0 (0.0) | 4 (25.0) | 0.012 |
| Postop anterior pituitary function* | ||||
| Adrenal insufficiency | 31 (63.3) | 19 (55.9) | 12 (80.0) | 0.107 |
| Hypothyroidism | 31 (63.3) | 19 (55.9) | 12 (80.0) | 0.107 |
| Hypogonadism | 27 (55.1) | 22 (64.7) | 5 (33.3) | 0.042 |
| Growth hormone deficiency | 20 (40.8) | 9 (26.5) | 11 (73.3) | 0.002 |
| Partial hypopituitarism | 15 (30.6) | 12 (35.3) | 3 (20.0) | 0.463 |
| Panhypopituitarism | 28 (57.1) | 16 (47.1) | 12 (80.0) | 0.032 |
| Normal to partial hypopituitarism | 3 (6.1) | 1 (2.9) | 2 (13.3) | 0.218 |
| Normal to panhypopituitarism | 7 (14.3) | 3 (8.8) | 4 (26.7) | 0.229 |
| Partial to panhypopituitarism | 14 (28.6) | 9 (26.5) | 5 (33.3) | 0.883 |
| Partial hypopituitarism to normal | 4 (8.2) | 4 (11.8) | 0 (0.0) | 0.412 |
| Panhypopituitarism to partial | 2 (4.1) | 2 (5.9) | 0 (0.0) | >0.99 |
| Panhypopituitarism to normal | 1 (2.0) | 1 (2.9) | 0 (0.0) | >0.99 |
| Recurrence* | 4 (8.2) | 2 (5.9) | 2 (13.3) | 0.755 |
| Permanent DI* | 19 (38.8) | 10 (29.4) | 9 (60.0) | 0.043 |
| CSF leak | 2 (3.9) | 2 (5.7) | 0 (0.0) | >0.99 |
| Intracranial infection | 3 (5.9) | 2 (5.7) | 1 (6.3) | >0.99 |
| Postop hydrocephalus | 3 (5.9) | 1 (2.9) | 2 (12.5) | 0.229 |
| Postop epilepsy | 2 (3.9) | 0 (0.0) | 2 (12.5) | 0.094 |
| Periop mortality | 2 (3.9) | 1 (2.9) | 1 (6.3) | 0.533 |
| Postop radiotherapy | 6 (11.8) | 2 (5.7) | 4 (25.0) | 0.130 |
| Cranial nerve injury (nonoptic nerve) | 1 (2.0) | 0 (0.0) | 1 (6.3) | 0.314 |
| Cerebral contusion | 1 (2.0) | 0 (0.0) | 1 (6.3) | 0.314 |
Fifty-one surgeries were performed in 49 patients. Values are presented as the number of procedures (%) unless otherwise indicated. Boldface type indicates statistical significance.
Data are not available for 2 procedures in which the patients died perioperatively (EES, n = 1 and TCM, n = 1).
Outcomes of pediatric craniopharyngiomas treated via EES versus TCM after score matching
| Variable | Overall (n = 24) | EES (n = 12) | TCM (n = 12) | p Value |
|---|---|---|---|---|
| EOR | >0.99 | |||
| GTR | 21 (87.5) | 11 (91.7) | 10 (83.3) | |
| STR | 3 (12.5) | 1 (8.3) | 2 (16.7) | |
| Recurrence | 2 (8.3) | 1 (8.3) | 1 (8.3) | >0.99 |
| Permanent DI | 12 (50.0) | 4 (33.3) | 8 (66.7) | 0.220 |
| Visual outcomes | ||||
| Improved | 5 (20.8) | 2 (16.7) | 3 (25.0) | >0.99 |
| Unchanged | 16 (66.7) | 10 (83.3) | 6 (50.0) | 0.193 |
| Worsened | 3 (12.5) | 0 (0.0) | 3 (25.0) | 0.217 |
| Postop anterior pituitary function | ||||
| Adrenal insufficiency | 15 (62.5) | 5 (41.7) | 10 (83.3) | 0.089 |
| Hypothyroidism | 16 (66.7) | 7 (58.3) | 9 (75.0) | 0.667 |
| Hypogonadism | 13 (54.2) | 8 (66.7) | 5 (41.7) | 0.414 |
| Growth hormone deficiency | 12 (50.0) | 3 (25.0) | 9 (75.0) | 0.039 |
| Partial hypopituitarism | 9 (37.5) | 7 (58.3) | 2 (16.7) | 0.089 |
| Panhypopituitarism | 14 (58.3) | 4 (33.3) | 10 (83.3) | 0.036 |
| Normal to partial hypopituitarism | 1 (4.2) | 0 (0.0) | 1 (8.3) | >0.99 |
| Normal to panhypopituitarism | 5 (20.8) | 2 (16.7) | 3 (25.0) | >0.99 |
| Partial to panhypopituitarism | 7 (29.2) | 2 (16.7) | 5 (41.7) | 0.371 |
| Partial hypopituitarism to normal | 2 (8.3) | 2 (16.7) | 0 (0.0) | 0.478 |
| Panhypopituitarism to partial | 1 (4.2) | 1 (8.3) | 0 (0.0) | >0.99 |
| Panhypopituitarism to normal | 0 | 0 | 0 | |
| Median BMI gain, kg/m2 (IQR) | 4.2 (0.4–9.0) | 1.5 (0.3–6.2) | 7.5 (1.7–10.0) | 0.046 |
| Hypothalamic function | ||||
| Level 1 | 8 (33.3) | 7 (58.3) | 1 (8.3) | 0.027 |
| Level 2 | 8 (33.3) | 3 (25.0) | 5 (41.7) | 0.667 |
| Level 3 | 6 (25.0) | 2 (16.7) | 4 (33.3) | 0.640 |
| Level 4 | 2 (8.3) | 0 (0.0) | 2 (16.7) | 0.478 |
Values are presented as the number of procedures (%) unless otherwise indicated. Boldface type indicates statistical significance.
Surgical Outcomes at the Last Follow-Up
Four (8.2%) of the 49 patients exhibited tumor recurrence, of whom 2 underwent reoperations and 2 were treated with radiotherapy (Table 5). Compared with TCM, EES achieved a similar tumor recurrence rate both before (5.9% vs 13.3%, p = 0.755; Table 4) and after (8.3% vs 8.3%, p > 0.99; Table 5) score matching. Additionally, despite a significantly higher rate of permanent DI in the TCM group before score matching (60.0% vs 29.4%, p = 0.043), the difference did not reach statistical significance after score matching (66.7% vs 33.3%, p = 0.220). The proportion of postoperative hypogonadism was significantly higher in the EES group before score matching (64.7% vs 33.3%, p = 0.042); however, a significant difference was not found after score matching (p = 0.414). Postoperative panhypopituitarism and growth hormone deficiency were more often encountered in the TCM group both before (80.0% vs 47.1%, p = 0.032 and 73.3% vs 26.5%, p = 0.002) and after (83.3% vs 33.3%, p = 0.036 and 75% vs 25.0%, p = 0.039) score matching. Additionally, the median gain in BMI from before surgery to the last follow-up was more pronounced in the TCM group (7.5 kg/m2 vs 1.5 kg/m2, p = 0.046). Regarding hypothalamic function at the last follow-up, the proportions of level 2, level 3, and level 4 were not significantly different between the groups. However, normal hypothalamic function (level 1) was more often encountered in the EES group (58.3% vs 8.3%, p = 0.027).
Discussion
By comparing EES and TCM for pediatric craniopharyngiomas, we found that TCM was associated with a comparable rate of GTR and perioperative complications, but a higher risk of visual deterioration. Propensity-adjusted analysis revealed that, compared with TCM, EES was associated with a similar rate of tumor recurrence and permanent DI but a significantly lower rate of growth hormone deficiency and panhypopituitarism, less gain of BMI from before surgery to the last follow-up, and better hypothalamic function at the last follow-up.
Patient and Tumor Characteristics
Of the clinical presentations reported in this study, headache was the most common symptom, and the rate of visual impairment was slightly lower than that reported by the latest published studies regarding pediatric craniopharyngiomas.10,18,19 Consistent with other studies,10,13,16,21 the tumor volume in the TCM group was larger despite no significant difference. Additionally, in the current study, the similar baseline characteristics of patients and tumors in both groups make the comparison of perioperative complications and surgical results feasible, suggesting that the difference derives from the surgical modality received rather than from the selected patients or tumors. However, significantly different durations of follow-up and preoperative anterior pituitary function make the comparison of long-term outcomes challenging, suggesting that propensity-adjusted analysis is required.
Extent of Resection
Currently, radical resection of craniopharyngiomas is debatable, particularly for pediatric patients. Some investigators have advocated for less-aggressive resections combined with adjuvant radiotherapy, with a similar tumor relapse rate but better postoperative endocrinological and hypothalamic functions.1,25–27 However, the risks of long-term vasculopathy, secondary malignancies, and neurocognitive dysfunction–associated radiotherapy cannot be neglected.28,29 Additionally, radiotherapy following STR makes the management of recurrent craniopharyngiomas more challenging because of tight adhesions to surrounding pivotal structures caused by radiation. At our center, GTR of tumors is always pursued, except for tumors with extensive and tight adhesion to the hypothalamus and surrounding vital vessels. Thus, the GTR rate of 88.2% in our whole pediatric cohort was higher than reported rates of 56.7% to 72.7%,14–16,21 and comparable to the reported rates (88.8% and 90.8%) in two other studies.10,13 In the present study, despite a higher proportion of GTR observed in the EES group, the difference did not reach statistical significance (94.3% vs 75.0%, p = 0.130). Consistent with our results, in other studies comparing EES and TCM, the authors reported a similar rate of GTR between the groups.10,13–16,21 However, Ozgural et al.30 compared 13 patients treated via TCM with 11 patients treated via EES and found that a significantly higher proportion of GTR was achieved in patients in the EES group (81.8% vs 30.8%, p = 0.019). One possible explanation is that in their study the preoperative tumor volume was larger in the TCM group, a potential confounder that was nearly significant (p = 0.082). Another reason may be the relatively small sample size in our study, making it difficult to find statistical significance.
Visual Outcomes
In this study, despite the higher proportion of postoperative visual improvement observed in the EES group, the difference did not reach statistical significance (40.0% vs 25.0%, p = 0.298). However, relative to TCM, a significantly higher proportion of postoperative visual improvement (88.9% vs 25.0%, p = 0.0075) was reported in the EES group in the study by Wannemuehler et al.16 Similarly, Fan et al.13 and Marx et al.15 found that the proportion of postoperative visual improvement in the EES group was significantly higher than that in the TCM group. One possible explanation is that, in our study, the rate of preoperative visual impairment was much lower and the sample size was relatively small, making it difficult to achieve statistical significance. Additionally, consistent with previous studies comparing EES and TCM for mixed-age population craniopharyngiomas,13,31 our results found that TCM could lead to a significantly higher risk of visual deterioration (25.0% vs 0.0%, p = 0.012), although the difference did not reach statistical significance after score matching, presumably because of the small sample size.
In general, our study supports the conclusion that EES could decrease the risk of visual deterioration and increase the chance of visual improvement for pediatric craniopharyngiomas. The following reasons may account for this conclusion. First, EES allows early identification of branches of the superior hypophyseal arteries, the protection of which is crucial for visual improvement. Additionally, rather than dissecting the cleavage plane between the tumor and optic apparatus under direct visualization via EES, TCM has the dilemma that the optic apparatus is situated between the tumor and the surgeon, making manipulation of the optic apparatus when removing the tumors inevitable and, thus, leading to a visual decline.
Perioperative Complications
As expected in our study, CSF leakage only occurred in the EES group, accounting for 5.7% of patients in the EES group. A low rate of CSF leakage and limited sample size make it challenging to find a significant difference. In accordance with our results, most studies comparing EES and TCM found that the CSF leakage rate was significantly lower in the TCM group or occurred exclusively in the EES group.10,13,16,21 Additionally, our low rate of CSF leakage, possibly due to routinely using vascularized nasoseptal flaps for endoscopic skull base reconstruction, is comparable to the reported rate in other studies, ranging from 4%11 to 3.8%32 to 7.1%.21 By contrast, complications such as postoperative epilepsy, cranial nerve injury, and cerebral contusion are too rare to provide grounds for determining significant differences between groups, despite exclusively occurring in the TCM group at rates of 12.5%, 6.3% and 6.3%, respectively. Consistent with our results, a meta-analysis conducted by Komotar et al. reported postoperative epilepsy in 8.5% of patients in the TCM group and 0.0% in the EES group, whereas the difference was statistically significant.31 Additionally, in the current study, the rates of other complications such as intracranial infection, hydrocephalus, and perioperative mortality were similar between the groups and comparable to those reported by other studies.10,13,15 Despite the lack of a significant difference, the need for adjuvant radiotherapy was higher in the TCM group (25% vs 5.7%, p = 0.130), presumably secondary to the higher rate of STR within the group.
Long-Term Outcomes
The recurrence rate was similar between the groups both before (5.9% vs 13.3%, p = 0.755) and after (8.3% vs 8.3%, p > 0.99) score matching. In accordance with our observations, several studies have reported a similar recurrence rate between the groups.13,16,21,31 Additionally, the rates of recurrence in the groups in our study were comparable to those of 6.4% in the EES group and 8.9% in the TCM group reported by Fan et al.13 Similarly, Wannemuehler et al. reported recurrence rates of 11.1% in the EES group and 8.3% in the TCM group; these values were equivalent to the rates of recurrence in the two groups in our study.16
Permanent DI and panhypopituitarism are often encountered in patients who have undergone craniopharyngioma resection. Our rate of permanent DI in the two treatment groups was comparable to that reported in the meta-analysis by Komotar et al., with a 27.7% rate of permanent DI in the EES group and 54.8% in the TCM group.31 Additionally, consistent with our results before score matching, the authors found that this difference reached statistical significance. However, the difference in permanent DI between the groups after score matching did not reach significance, a finding supported by other studies.13,15,16 The small sample size after score matching in our study may account for this discrepancy. Compared with the ESS group, panhypopituitarism and growth hormone deficiency at the last follow-up occurred more often in the TCM group both before and after score matching. This result is consistent with the situation in which to achieve GTR for tumors extending to the third ventricle or the sellar, EES provides better visualization of the hypothalamus-pituitary axis when removing tumors. However, most other studies comparing TCM with EES did not find this significant difference.10,13,16 Furthermore, the rates of panhypopituitarism reported in patients treated via TCM in those findings were much lower than those in our study. Intriguingly, Madsen et al. found the rate of panhypopituitarism to be as high as 100.0% and 92.8% in the TCM and EES groups in their pediatric cohort, respectively.21 One possible explanation is that preoperative anterior pituitary function and the EOR of tumors are different among these studies.
Excess weight gain is often associated with aggressive resection of craniopharyngiomas, particularly in children.25,33 Our findings revealed that the median gain of BMI in the TCM group was significantly higher than that in the EES group (7.5 kg/m2 vs 1.5 kg/m2, p = 0.046). Consistent with our findings, Madsen et al. found a significantly higher median change in BMI in the TCM group than in the EES group (7.95 kg/m2 vs 3.70 kg/m2, p = 0.03).21 Similarly, Marx et al. found a significant gain in BMI from before surgery to the last follow-up in the TCM group (p = 0.008), while the change in BMI in the EES group did not reach statistical significance (p = 0.14).15 Compared with TCM, the priority of EES in decreasing weight gain is likely attributed to diminished vascular insults.21 Another possible reason is that via EES, surgeons can dissect the cleavage plane between the tumor and hypothalamus under direct visualization, avoiding pulling blindly, which may diminish the damage of the hypothalamus.
Hypothalamic dysfunction after craniopharyngioma resection is usually qualitatively analyzed.13,24,34 We hypothesized that the priority of EES may translate to benefits in this regard as well. As expected, EES had a significantly higher proportion of normal hypothalamic function (58.3% vs 8.3%, p = 0.027). Consistent with our findings, Madsen et al. found a lower rate of psychosocial issues in the EES group than in the TCM group (33.3% vs 18.5%) in their pediatric cohort, although no statistical significance was observed.21 Similarly, Moussazadeh et al.9 found that, compared with EES, postoperative cognitive loss was significantly more often encountered in the TCM group (80% vs 0%, p < 0.0001).
Limitations
First, because of the retrospective nature of the study, selection bias inevitably exists. Second, our sample size was limited, particularly after score matching, making the ability to reach statistical significance between the groups less powerful. Additionally, although most of the surgeries, including all EESs and some TCMs, were performed by the chief surgeon (T.H.), the remaining surgeries were performed by two other surgeons with at least 10 years of experience in microsurgery. Differences in surgical techniques and preferences for special surgical modalities among surgeons potentially exist and may affect surgical strategies and surgical outcomes. In a study comparing EES and TCM, Jeswani et al.10 demonstrated that the choice of surgical modalities appeared mostly to reflect surgeon preference rather than specific tumor characteristics. Thus, while a well-designed, prospective, and randomized study would potentially eliminate this bias, it may not be possible because of the infrequent disease incidence and ethical considerations. In addition, because of the relatively low overall number of pediatric patients, we did not exclude patients undergoing repeated surgeries. No significant difference was found in the proportion of repeated surgeries between the groups (31.4% for EES vs 18.8% for TCM, p = 0.546), particularly after score matching (16.7% for EES vs 25.0% for TCM, p > 0.99). Thus, we believe that this is well balanced and should not bias the results. Finally, we did not examine the sinonasal quality of life. However, a previous study reported that the sinonasal quality of life was not inferior after EES during follow-up.15
Conclusions
For primary or secondary craniopharyngiomas in pediatric patients, EES can achieve a similar GTR rate and decreased risk of visual deterioration with a comparable risk of postoperative complications compared with TCM. Additionally, the rate of recurrence and permanent DI in the EES cohort was equivalent to, if not lower than, that in the TCM cohort, while growth hormone deficiency and panhypopituitarism at the last follow-up were significantly more often encountered in patients treated with TCM. Furthermore, EES can lead to significantly better hypothalamic function. Our findings favor the view that EES is a safe and effective surgical modality and can be a viable alternative to TCM for pediatric midline craniopharyngiomas.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (grant nos. 82060246 and 81460381), Ganpo555 engineering excellence of Jiangxi Science and Technology Department (2013), and the Key research and invention plan of Jiangxi Science and Technology Department (20192BBG70026).
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: Hong. Acquisition of data: J Wu, Pan, Xie, Tang, Fu, X Wu, Tong, B Wu, Yang, Ding, Li. Analysis and interpretation of data: Hong, J Wu, Pan. Drafting the article: J Wu. Critically revising the article: Hong, J Wu, Pan, Xie, Tang. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Hong. Statistical analysis: J Wu, Pan. Administrative/technical/material support: Hong. Study supervision: Hong.
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