Original Article
Endoscopic Endonasal Approach for Craniopharyngiomas with Intraventricular
Extension: Case Series, Long-Term Outcomes, and Review
Hanna Algattas1, Pradeep Setty1, Ezequiel Goldschmidt1, Eric W. Wang2, Elizabeth C. Tyler-Kabara1,
Carl H. Snyderman2, Paul A. Gardner1
- BACKGROUND: Traditionally, craniopharyngiomas with
intraventricular extension were approached transcranially;
however, endoscopic approaches are now increasingly
used. We sought to study the endoscopic endonasal
approach (EEA) in the setting of complex craniophar-
yngiomas with intraventricular extension and to compare it
with existing literature.
- METHODS: Patients undergoing EEA for resection of
craniopharyngioma with ventricular involvement from 2002
to 2015 were retrospectively reviewed. Outcomes were
compared with previously published EEA and transcranial
approach (TCA) studies for all craniopharyngioma
locations.
- RESULTS: Sixty-two patients were included. Average
tumor and intraventricular volume were 13.93 cm3 and 2.61
cm3, respectively. Patients presented with visual impair-
ment, endocrinopathy, and, headache. Gross total resection
(GTR) was achieved in 47% of all cases and increased to
77% after 2012 Approximately 98% experienced improve-
ment or stability of vision. Postoperative cerebrospinal
fluid (CSF) leak and meningitis rates were 19% and 8.1%,
respectively. However, nasoseptal flap (NSF) use reduced
CSF leak rate to 10%. Six (9.6%) patients required shunting
before resection and 25% were shunted postoperatively.
Seven of 10 patients (70%) treated before NSF use required
shunting, whereas only 7 of 46 (15%) required shunting
with NSF reconstruction. Review demonstrated similar
Key words
- Craniopharyngioma
- Endoscopic endonasal approach
- Intraventricular
Abbreviations and Acronyms
CI: Confidence interval
CSF: Cerebrospinal fluid
DI: Diabetes insipidus
EEA: Endoscopic endonasal approach
GTR: Gross total resection
MRI: Magnetic resonance imaging
NSF: Nasoseptal flap
RT: Radiotherapy
SRS: Stereotactic radiosurgery
WORLD NEUROSURGERY 144: e447-e459, DECEMBER 2020
outcomes between the present cohort and EEA or TCA for
all craniopharyngioma locations. TCA had a greater GTR,
however, with large study variation. EEA showed improved
visual outcomes but also increased CSF leaks.
- CONCLUSIONS: EEA for craniopharyngiomas with
intraventricular extension shows similar outcomes to TCA
and EEA for all craniopharyngiomas, expanding this
anatomic limit. Given ventricular involvement, CSF leak
rates are expectedly high. GTR increased and CSF leak
rates dramatically decreased with time, suggestive of the
steep learning curve to complex resection.
INTRODUCTION
A lthough histologically benign, craniopharyngioma’s rela-
tively deep location and tendency to adhere to critical
structures makes total resection challenging. Size and
degree of spread outside the suprasellar space drives choice of
surgical approach. Thus, given their propensity for suprasellar
spread, open, transcranial approach (TCA) often was used.1-3
However, craniopharyngiomas also may arise from the sella or
ventricle. The relationship of craniopharyngiomas to the optic
chiasm and the narrow corridor above the pituitary gland initially
precluded the transsphenoidal approach, but with growing
application and experience, the endoscopic endonasal approach
(EEA) has increasingly been used. EEA provides superior
STR: Subtotal resection
TCA: Transcranial approach
VPS: Ventriculoperitoneal shunt
From the Departments of 1Neurological Surgery and 2Otolaryngology, University of Pittsburgh
Medical Center, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania, USA
To whom correspondence should be addressed: Hanna Algattas, M.D.
[E-mail: algattash@upmc.edu]
Citation: World Neurosurg. (2020) 144:e447-e459.
https://doi.org/10.1016/j.wneu.2020.08.184
Journal homepage: www.journals.elsevier.com/world-neurosurgery
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HANNA ALGATTAS ET AL.
visualization to the undersurface of the chiasm and hypothal-
amus—a relative blind spot of the TCA.4 EEA may produce
similar, and in some regard superior, outcomes for
craniopharyngioma resection.5-10
Tumors with ventricular involvement may be approached via
open craniotomy; however, limited suprasellar access, risk of
forniceal, pericallosal artery, and/or internal cerebral vein injury
are serious limitations.4 Yet, craniopharyngiomas with
intraventricular extension occur frequently, given involvement of
the adjacent infundibulum and hypothalamus.11 Thus, the
ventricular cavity is considered an anatomic limit of EEA12 and
is often a surrogate for hypothalamic involvement. Kassam
et al.13 proposed an anatomic classification system for
craniopharyngiomas as: preinfundibular (type I),
transinfundibular (type II), retroinfundibular (III),
retroinfundibular/third ventricular (type IIIa), retroinfundibular/
interpeduncular cistern (type IIIb), and purely third ventricular
(type IV).12,13 However, multiple other classification schemes
exist, and ventricular extension also can be closely described
either as primarily intraventricular, infundibulotuberal,
secondarily intraventricular, and pseudointraventricular.14 These
nuanced schemes suggest the technical modifications necessary
in resecting these lesions based on relationship to the third
ventricular floor. These endoscopic resections require
appropriate endoscopic expertise. Thus, the limits of EEA can
be widened to the surgeon’s experience, tools available, and
then anatomic boundaries.
The anatomic limits of EEA have gradually expanded since its
initial application.8 This study describes outcomes after EEA for
craniopharyngiomas that extend into the third ventricle. These
outcomes are compared with a review of other studies regarding
EEA and TCAs for resection of craniopharyngiomas of all
locations.
METHODS
All pediatric and adult craniopharyngiomas resected from 2002 to
2016 via EEA at the University of Pittsburgh Medical Center were
retrospectively reviewed. Patient demographics were recorded.
Cases with intraventricular extension, defined as extension of a
cystic or solid component into a ventricular cavity based on pre-
operative magnetic resonance imaging (MRI), were included for
analysis. As such, infundibulotuberal and secondarily intraven-
tricular were predominantly selected. Where able, intraoperative
notes regarding violation of the third ventricular floor and infun-
dibular sacrifice were recorded; however, given this was a retro-
spective review, limited documentation made an accurate report of
these data challenging. Presentation, imaging characteristics,
previous treatment, histopathology, and follow-up were recorded.
Preoperative, postoperative, and intraventricular tumor volume
was calculated by the following formula (in centimeters): [(ante-
rior e posterior)*(medial e lateral)*(rostral e caudal)]/2.
Tumors were resected by 4 neurosurgeons with assistance of 3
otolaryngologists. The surgical technique has been extensively
described from our institution elsewhere.15,16
The electronic medical record was further queried for remaining
outcome data, including degree of resection, symptom improve-
ment, recurrence, endocrinopathy, cerebrospinal fluid (CSF) leak
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ORIGINAL ARTICLE
EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS
rate, ventriculoperitoneal shunt (VPS) placement, intraventricular/
intracerebral hemorrhage, Karnofsky Performance Status, menin-
gitis, hydrocephalus, pulmonary embolism, stroke, coma, and
mortality. Panhypopituitarism was defined as need for total
hormone-replacement postoperatively. Operative notes were
reviewed to determine the surgical goal, whether it be biopsy,
symptomatic relief, or gross total resection (GTR). Where no such
indication was made, the case goal was treated as GTR. Extent of
resection was strictly defined, with even question of residual tu-
mor capsule or anything greater being considered subtotal resec-
tion. Institutional review board approval was not necessary, given
deidentified patient data, and, given this fact, patient consent was
not necessary.
A literature search was performed via PubMed for craniophar-
yngiomas resected via EEA or TCA and provided 533 items. Search
terms included: “endoscopic endonasal craniopharyngioma,”
“EEA craniopharyngioma,” “transcranial craniopharyngioma,”
“microscopic craniopharyngioma,” “craniopharyngioma open
resection,” “craniopharyngioma subfrontal,” and “craniophar-
yngioma interhemispheric.” Inclusion criteria were studies pub-
lished after 2000 focusing on EEA and/or TCA for resection of
craniopharyngiomas of all locations with appropriately detailed
outcome measures. Exclusions were series with fewer than 10
patients, exclusively recurrent tumors, exclusively pediatric cases,
studies grouping EEA and TCA outcomes together, and micro-
scopic transsphenoidal approaches.
Statistical analysis was completed with a random effects model,
assuming heterogeneity between studies selected for inclusion.
The assumption of heterogeneity precludes the use of a fixed-
effects model for analysis and implies there may be variation in
the outcomes of interest when compared across studies in the
same group. Lack of heterogeneity suggests a tighter cluster of
data within subgroups and potentially a more robust comparison.
Analyses for binomial data were conducted for each outcome and
each procedure (EEA and open) separately. Heterogeneity of the
studies was evaluated by Cochran’s Q statistic and the variation in
the estimate attributable to heterogeneity was assessed by I2.
Random effects model, assuming the observed outcomes may vary
across studies, was used to generate the pooled proportion and its
95% confidence interval. Analyses were performed using STAT v14
(StataCorp LLC, College Station, Texas, USA). KaplaneMeier
survival curve for time to recurrence and log rank test via Bre-
slow analysis was completed using SPSS software version 18.0.
RESULTS
Craniopharyngiomas with Intraventricular Extension
A total of 62 craniopharyngiomas with intraventricular extension
were identified (40 male, 22 female) (Table 1). Patients ranged
from 3 to 82 years old with a mean age of 41 years at the time
of resection (17 pediatric cases, 45 adult). The most common
presenting symptoms were visual deficit (75.8%), partial or total
hypopituitarism (29.0%), headache (16.1%), diabetes insipidus
(DI) (16.1%), and altered mental status (8.1%). Radiographically,
9 of 62 (14.5%) craniopharyngiomas had homogenous features,
40 of 62 (64.5%) were heterogenous, and 13 of 62 (21.0%)
displayed rim enhancement. The average tumor volume
extending into a ventricle was 2.61 cm3 (17.3% of the average
 ORIGINAL ARTICLE
HANNA ALGATTAS ET AL. EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS

entire tumor volume). All tumors had third ventricular

Table 1. Patient Demographics and Characteristics involvement but 9 also extended into the lateral ventricles. There
Demographics N [ 62 Patients were both treatment-naïve (77.4%) and recurrence (22.6%)
patients included. Eight patients had previous craniotomies, 1
Female 22/62 (35.5%) only radiation, and 4 received both previous craniotomy and
Age, years, average 41 radiation. Adamantinomatous pathology accounted for 55 of 62
(89%) cases compared with 7 of 62 (11%) papillary. Two
Weight, kg, average 78.3
papillary cases were positive for the BRAFv600E mutation;
Body mass index, average 28.4 however, the other 5 cases occurred before routine BRAF
Intraventricular extension, volume/% total tumor volume 2.61 cm3/17.3% mutation analysis. The 2 cases with BRAFv600E mutations both
underwent GTR and did not demonstrate evidence of recurrence
Pathology
at follow-up.
Adamantinomatous 55 (88.7%) Improved vision was noted in 35 of 47 patients presenting with a
Papillary 7 (11.3%) deficit (74.5%), stable in 11 patients (23.4%), and worse in 1 pa-
tient (2.1%). Of the 15 patients who had normal vision preopera-
Treatment history
tively, none developed visual deficits postoperatively. A total of 18
Naïve 49 (79.0%) patients had normal pituitary function pre- and postoperatively, 1
Previous craniotomy 8 (12.9%) patient went from normal to partial panhypopituitarism, 6 patients
from partial to panhypopituitarism, 12 patients presented with
Previous radiation 1 (1.6%)
panhypopituitarism and remained so postoperatively, and 25 went
Previous craniotomy and radiation 4 (6.5%) from normal to panhypopituitarism postoperatively (Table 2).
Presentation Thus, of the 44 patients presenting without endocrinopathy
Visual deficit 47 (75.8%)
preoperatively, 25 developed panhypopituitarism, and 1
developed partial hypopituitarism (n ¼ 26/44, 59.1%). Of the
Headache 10 (16.1%) patients developing new postoperative panhypopituitarism, 19 of
Hypopituitarism 18 (29.0%) 26 (73%) had intraoperative evidence of stalk invasion by the
Diabetes insipidus 10 (16.1%) tumor. Of those 19 patients with stalk involvement, 9 noted
intraoperative stalk transection/compromise for tumor removal;
Altered mental status 5 (8.1%) in 4 patients, the stalk was preserved and in 6 patients the
Staged resection 2 (3.2%) integrity of the stalk by the end of the operation was not
Reconstruction commented on within operative records. Similarly, 10 patients
originally presented with DI and 19 other patients developed DI
Fat 10 (16.1%)
postoperatively (n ¼ 19/52; 36.5%). Regarding functional
Nasoseptal 52 (83.9%) outcomes, average Karnofsky Performance Status was 79.7
Intraoperative lumbar drainage 22 (35.5%) preoperatively and 82.6 postoperatively.
GTR was achieved in 46.8% of cases overall and in 55.6% of
Resection
patients GTR in whom GTR was the goal of surgery. As a function
GTR 29 (46.7%) of time, GTR increased linearly, notably to 77.4% after 2012
Non-GTR 33 (53.2%) (Figure 1). All other resection categories were grouped together
into subtotal resection (STR) with a rate of 53.2% achieved over
Postoperative radiation treatment
the entire study period. GTR was achieved in 46.8% of cases
Stereotactic radiosurgery 9 (14.5%) overall and in 55.6% of patients GTR in whom GTR was the
External beam radiation 1 (1.6%) goal of surgery. All other resection categories were grouped
together into STR with a rate of 53.2% achieved over the entire
Follow-up time, months, average 51
study period; this reflects anything from partial to near-total
Recurrence 24 (38.7%) resection. When GTR was the goal, the rate of STR was 44%.
Time to recurrence, months 39 However, the outcomes of our early experience with these patients
biased toward greater STR. Also, 14 patients had recurrent tumors
Treatment recurrence
where GTR in that group was 43% versus 48% among those with
Repeat EEA 17/24 (70.8%) primary tumors. GTR increased linearly over time, notably to
Craniotomy 1/24 (4.2%) 77.4% after 2012 (Figure 1). The linear increase in GTR
Stereotactic radiosurgery 8/24 (33.3%)
demonstrates the steep learning curve in advanced endoscopic
endonasal surgery which has been published previously.17 It is
GTR, gross total resection; EEA, endoscopic endonasal approach. thus essential that teams with appropriate experience undertake

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10), whereas after NSF introduction the rate dropped to 9.8% (5/
Table 2. Preoperative Endocrine Symptoms and Postoperative 51). Otherwise, bacterial meningitis occurred in 4 of 62 (6.5%) and
Outcomes chemical meningitis in 1 of 62 (1.6%). One patient suffered a
Pituitary function putaminal infarct with good recovery (1.6%). Two patients had
(preoperative/postoperative) n tumor bed/intraventricular hemorrhage requiring EEA for evacu-
ation (3.2%). One pediatric patient had an epidural hematoma due
Normal/normal 18 to Mayfield pin placement requiring craniotomy. There were no
Normal/partial 1 30-day postoperative mortalities (Table 2).
Partial/total 6
Review
Total/total 12 The extant literature was surveyed for studies examining outcomes
Normal/total 25 after resection of craniopharyngiomas of any location via either
EEA or TCA. Seventeen studies met inclusion and exclusion
Outcome criteria: 8 studies on EEA, 8 on TCA, and 1 including both. In-
dividual study variables and outcomes are shown in Table 3.
VPS placement 14/56 (25.0)
Likewise, grouped proportions for variables and outcomes of
Pre-nasoseptal flap 7/10 (70.0) interest are seen in Table 4.
Post-nasoseptal flap 7/46 (15.2)
Review Comparison
Meningitis 5/62 (8.1)
Regarding preoperative presentation, pooled rates of symptomatic
Bacterial 4/62 (6.5) presentation were similar comparing the current study, to EEA for
Chemical 1/62 (1.6) craniopharyngioma of all locations, and to TCA for craniophar-
yngioma of all locations.
Intraventricular/resection bed hemorrhage 2/62 (3.2)
GTR was greater within the TCA group (82%; 95% confidence
Stroke 1/62 (1.6) interval [CI] 0.75e0.88) compared with the current study (47%
CSF leak 11/61 (18.0) 95% CI 0.35e0.59); however, when we accounted for cases in
Pre-nasoseptal flap 6/10 (60)
which GTR was the goal of surgery, that difference disappeared.
Rates of recurrence were greater among the group undergoing
Post-nasoseptal flap 5/51 (9.8) EEA for intraventricular craniopharyngioma compared with EEA
30-day mortality 0/62 (0.0) for all craniopharyngiomas, approximately 39% (95% CI 0.28e
0.51) versus 18% (95% CI 0.12e0.25), but not compared with TCA,
VPS, ventriculoperitoneal shunt; CSF, cerebrospinal fluid.
with significant heterogeneity in the random effects model.
(Importantly for clarification, heterogeneity in this sense suggests
a significant variability between studies, not necessarily a statis-
such complex resections. Postoperatively, 10 patients were tically significant difference.) However, again, when considering
additionally treated with radiation therapy, 9 receiving the rate of recurrence among patients undergoing EEA for intra-
stereotactic radiosurgery (SRS) (14.5%) and 1 external beam ventricular extension who received GTR, the recurrence rate is
radiation therapy (1.6%). Average follow-up time was 51 months. 15.6% and that difference disappears (95% CI 0.08e0.29).
Recurrence was noted in 24 of 62 patients (38.7%) at an average of The probability of improved visual outcome was superior in the
39 months postoperatively. Of the recurrences, 7 occurred in pa- group undergoing EEA for lesions with intraventricular extension
tients with GTR and the remainder in those with STR (15.6% vs. and EEA for all lesion locations compared with TCA, but with
51.5%, respectively). 60% of patients who received postoperative heterogeneity. There were fewer CSF leaks encountered in those
radiation had recurrence; however, none of those patients had patients undergoing TCA for craniopharyngioma rather than EEA,
GTR; among those without immediate postoperative radiation, but rates of meningitis did not significantly differ. Otherwise,
recurrence was 34.6%. Of patients with recurrence, 16 underwent outcomes were similar among the 3 groups; importantly, however,
repeat EEA, 1 TCA, 1 EEA and SRS, 1 TCA and SRS, and 5 SRS. there was significant heterogeneity within the subsets analyzed
KaplaneMeier time to recurrence analysis is shown based on GTR based on variability between studies contained within a group
and STR in Figure 2. Recurrence-free survival was longer in the (Table 4).
GTR group relative to STR (P ¼ 0.042).
There were 12 patients (19.3%) with preoperative hydrocephalus Representative Case
requiring either ventriculostomy (6/12; 50%) or VPS (6/12; 50%). An 8-year-old male patient presented with symptomatic hydro-
Fourteen patients required postoperative VPS, 3 of whom had a cephalus and temperature dysregulation. MRI noted a 4.9-  3.2-
ventriculostomy preoperatively. Notably, in mid-2006 the naso-  3.5-cm heterogeneous, contrast-enhancing suprasellar mass
septal flap (NSF) was used for reconstruction rather than non- with cystic components, third ventricular extension, and
vascularized grafts. Seventy percent of patients (7/10) treated obstructive hydrocephalus (Figure 3). Visual field testing noted a
before NSF introduction required postoperative VPS. After NSF mild left quadrantanopsia. He was started on hormone-
introduction, the rate of postoperative VPS decreased to 15.2% (7/ replacement therapy and given low cortisol and thyroid hormone
46). Similarly, CSF leak rate before NSF introduction was 60% (6/ levels preoperatively.

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HANNA ALGATTAS ET AL. EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS

Figure 1. Line graph representative of gross total resection (GTR) rates per year for craniopharyngiomas with
ventricular extension.

Given his hydrocephalus, the patient was initially taken to the merely Kassam IeIIIB. In the absence of intervening pathology,
operating room for an endoscopic septostomy, VPS, and accessing the third ventricle, let alone lateral ventricle, may be
endoscope-assisted biopsy. Pathology revealed an ada- exceedingly difficult. In the case of craniopharyngiomas, the
mantinomatous craniopharyngioma. Two weeks after shunt common origin in the infundibulum or hypothalamus and
placement, he underwent transplanum/transtubercular EEA with
NSF reconstruction (Figure 3—postoperative MRI; Figure 4—
intraoperative images). At follow-up, his hydrocephalus
improved and he continued total hormone replacement therapy.
After 7 years of recurrence-free survival, he developed an asymp-
tomatic, partially cystic recurrence that prompted an uncompli-
cated repeat EEA in 2019 for repeat resection (Figure 5).

DISCUSSION
This paper describes outcomes of a novel patient cohort under-
going EEA for resection of craniopharyngiomas with intraven-
tricular extension. These outcomes are compared with literature
on resection of craniopharyngiomas at any location via EEA or
TCA to see if outcomes are similar when there is intraventricular
extension.
Lesions extending into a ventricle stretch one of the limitations
of endoscopic endonasal surgery. Judicious preoperative planning
must be used before undertaking such a venture. Some authors
have suggested lesions violating both prechiasmatic and retro-
chiasmatic spaces may be better served by TCA, given these le-
sions are typically large and multilobulated.7 For instance, this is
suggested for Kassam type IV craniopharyngiomas, which are Figure 2. Time to recurrence survival analysis. Gross total resection (GTR)
and subtotal resection (STR) recurrence-free survival seen as function of
purely intraventricular. Of note, the current study did not time. Labeling of curves as per key.
contain any purely intraventricular craniopharyngiomas, but

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Table 3. Review: Resection of Craniopharyngioma

EEA/
Intraventricular EEA

Leng Cavallo Gardner Park Yadav Jeswani

Koutourousiou Fomichev et al., et al., et al., et al., Moussazadeh et al., et al.,
Present study et al., 201318 et al., 20168 20126 20147 200815 201710 et al., 20169 201521 201622

N 62 64 136 24 103 16 116 21 44 19

Intraventricular extension, % 100 e 18 25 38 e e e e e
Extent of Resection, %
GTR, % 47 56* 38 72 67 69 73 47 91 59 e
Presentation, %
Visual deficit, % 76 69 82 79 77 88 83 48 84 55
Hypopituitarism, % 29 63 54 83 16 31 25 e 9 e
DI, % 16 30 e e 23 e 15 e 66 e
Postoperative
Vision improved, % 75 86 89 77 75 93 76 63 77 e
Vision stable, % 23 11 e 7 18 7 17 40 23 e
Vision improved/stable, % 98 98 e 83 92 100 7 e e e
Vision worse, % 2 2 11 13 3 0.0 e 10 e e
Hypopituitarism, % 71 e e 38 e e e 52 e 42
New hypopituitarism, % 58 58 e e e 18 e e e e
DI, % 48 e e 42 e e e 14 e 32
New DI, % 38 47 e e 48 e 26 e e e
Recurrence, % 39 16y 34 20 25 22 e 16 0 14 e
CSF leak, %, total 19 23 9 4 15 58 11 5 9 26
CSF leak, %, post-enasoseptal flap 10 11 e e e e e e e e
Meningitis, % 8 8 16 e 1 0 6 e 2 5
Postoperative infection, % e e e e e e e e e e
ICH/IVH, % 3 e e e e e e e e 5
Medical complications, % 13 e e e e e 5 e e e
PE, % 2 e e e e e e 5 e 0
Stroke, % 2 e e e e e 1 10 e 0
30-day mortality, % 0 e e e 2 e 0 e 2 5

EEA, endoscopic endonasal approach; TCA, transcranial approach; GTR, gross total resection; DI, diabetes insipidus; CSF, cerebrospinal fluid; ICH, intracerebral hemorrhage; IVH, intraventricular
hemorrhage; PE, pulmonary embolism.
*GTR where goal of surgery was GTR.
yRecurrence where GTR was obtained.

expansion of these spaces can create a widened corridor, thus
facilitating resection. In this vein, craniopharyngiomas may even
displace the chiasm anteriorly into a prefixed position, again
widening the corridor and subchiasmatic space.27
Visual deficit was the most common presentation; however,
endocrinopathy showed the greatest variability among studies.
Presentation with DI and/or panhypopituitarism ranged from 0%
to 65.9% and 9.1% to 83.3%, respectively. Postoperative DI and
panhypopituitarism also ranged from 29.7% to 66.7% and 8.3% to
58.3%, respectively. Among the patients who developed post-
operative hypopituitarism, 73% had intraoperative evidence of
stalk invasion by the tumor, and one-half required stalk

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Table 3. Continued

TCA

Jeswani Shi et al., Mortini Shirane Feng Wannemuehler Shirane Shi Yu

et al., 201622 200824 et al., 201119 et al., 20052 et al., 201825 et al., 201626 et al., 200223 et al., 201720 et al., 201411

34 309 112 42 159 12 24 1054 24

e e 6 e e e e e e

e 89 e 71 81 58 71 90 79

55 e 73 73 e 83 e 37 42
e e e e e 33 55 e e
e e 38 38 16 e 29 8 21

e 42
e 45
e 87
e 13
38 e e
e e
53 53
e e
e 23
0 e
e e
0 e
e e
0 0
e e
3 e
3 e
3 4
e e e 25 63 60 29
e e e 50 e 16 13
e e e 75 e 76 32
21 e e 25 e 1 e
e e e e e e
e e e 17 e e 33
e e e 50 e e e
e e 60 50 e 30 63
e 38 e e 32 21 25
4 e 1 0 e 0 e
e e e e e e e
1 e e 8 e e e
e e 6 8 e 8 e
e e 4 0 e e e
e e e e e e e
1 e e e e 2 e
e e e 8 e e e
3 e e 0 e e e

transection. The degree of stalk and hypothalamic involvement are
certainly factors that significantly affect rates of postoperative
endocrinopathy and extent of resection. In a review by Komotar
et al.,28 permanent DI and hypopituitarism occurred in 55% and
48% of transcranial cases, respectively, compared with 28% and
48%, respectively, for EEA cases. In that study, EEA had
reduced risk of postoperative DI; however, more patients in the
EEA group presented with endocrinopathy initially compared
with TCA.28 In our study, the overall rate of postoperative
panhypopituitarism was larger in the EEA group for
intraventricular lesions compared with EEA for all
craniopharyngiomas. However, there was no difference in the

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Table 4. EEA (Intraventricular Lesion) Versus EEA (All Locations) Versus TCA (All Locations)
EEA (Intraventricular Location, EEA (All Locations) TCA (All Locations) Heterogeneity
Present Study) Proportion (95% CI) Proportion (95% CI) Proportion (95% CI) (P Value)

GTR 0.47 (0.35e0.59) 0.64 (0.52e0.75) 0.82 (0.75e0.88) 0.00

Postoperative
Improved vision 0.74 (0.60e0.85) 0.81 (0.75e0.87) 0.45 (0.32e0.59) 0.00
Stable vision 0.23 (0.14e0.37) 0.17 (0.11e0.23) 0.28 (0.1e0.50) 0.44
Improved/stable vision 0.98 (0.89e1.00) 0.80 (0.19e1.00) 0.81 (0.70e0.90) 0.00
Worse vision 0.02 (0.00e0.11) 0.05 (0.01e0.10) 0.11 (0.01e0.29) 0.62
Hypopituitarism 0.71 (0.59e0.81) 0.44 (0.32e0.57) 0.50 (0.34e0.65) 0.00
New hypopituitarism 0.58 (0.43e0.71) 0.45 (0.28e0.62) 0.27 (0.13e0.44) 0.17
DI 0.48 (0.36e0.61) 0.28 (0.13e0.46) 0.53 (0.47e0.58) 0.00
New DI 0.38 (0.26e0.51) 0.39 (0.24e0.56) 0.50 (0.28e0.72) 0.76
Recurrence 0.39 (0.28e0.51) 0.18 (0.12e0.25) 0.25 (0.19e0.30) 0.01
Recurrence (GTR*) 0.16 (0.08e0.29) NA 0.18 (0.10e0.28) 0.00
CSF leak 0.19 (0.11e0.31) 0.15 (0.09e0.22) 0.00 (0.00e0.02) 0.00
Meningitis 0.08 (0.03e0.18) 0.04 (0.01e0.09) 0.01 (0.00e0.05) 0.20
ICH/IVH 0.03 (0.01e0.11) 0.05 (0.00e0.15) 0.00 (0.00e0.03) 0.10
PE 0.02 (0.00e0.09) 0.02 (0.00e0.10) 0.02 (0.01e0.02) 0.76
Stroke 0.02 (0.00e0.09) 0.01 (0.00e0.08) 0.04 (0.00e0.12) 0.22
30-day mortality 0.00 (0.00e0.06) 0.01 (0.00e0.04) 0.02 (0.01e0.04) 0.25

Bold indicates significant difference with heterogeneity present.

EEA, endoscopic endonasal approach; TCA, transcranial approach; CI, confidence interval; GTR, gross total resection; DI, diabetes Insipidus; CSF, cerebrospinal fluid; ICH, intracerebral
hemorrhage; IVH, intraventricular hemorrhage; PE, pulmonary embolism.
*Recurrence among patients with GTR.

rate of new postoperative hypopituitarism between the 2 groups.
Likewise, rates of DI both overall and new postoperatively were
similar. Yet, increased incidence of preoperative and
postoperative endocrine dysfunction may not be unexpected
with intraventricular extension; pituitary gland dysfunction is
more common in subdiaphragmatic craniopharyngiomas,
whereas hypothalamic dysfunction is more frequent with tumors
involving the third ventricle.19,29,30 However, lesions with
extensive hypothalamic involvement may cause postoperative
hypopituitarism in the absence of subdiaphragmatic extension.
Prechiasmatic, transinfundibular, and retrochiasmatic
craniopharyngiomas place the infundibulum at varying degrees
of risk during resection, often times prompting deliberate
transection of the stalk to achieve GTR. Anecdotally, it can be
more difficult to preserve the stalk when tumors are centered at
the tuber cinereum/hypothalamus compared with tumors of
purely stalk origin. Thus, from both anatomic involvement and
the pathway of the designed surgical approach, increased rates
of endocrinopathy may be expected. However, given the
variability among both preoperative and postoperative endocrine
abnormalities and intragroup variation, this may suggest
differences in data collection rather than purely surgical effect.20
Important to note, hypothalamic involvement of
craniopharyngiomas adds more to the morbidity of these
resections than purely ventricular involvement alone and can be
the limiting factor.
GTR exhibited a large degree of variation among studies. In the
present study, the average GTR in patients in whom GTR was the
goal was 55.6%, even substantially increasing over time, demon-
strating a learning curve. Another study from our same institution
similarly identified GTR as 73% in a case series of EEA for all
craniopharyngiomas.15 In addition, a recently published
retrospective analysis of 43 EEAs for suprasellar
craniopharyngiomas noted a GTR of 43% between 2006 and
2012, a similar rate and interval to our findings.31 Among
studies included in the review, GTR in EEA studies ranged from
37.5% to 90.5%.5-10,15,21,22 Similarly, among TCA, GTR ranged
from 58.3% to 89.6%.2,11,19,20,22-26 There are no reports in the
literature of TCA purely focused on craniopharyngiomas with
intraventricular extension, which would provide a helpful direct
comparison. Yet even so, recent GTR data from the present study
is similar to pooled rates for EEA and TCA approaches (Table 4).
An interesting observation was the steep decline in shunting
and CSF leak after the introduction of an NSF.32 Only one case

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HANNA ALGATTAS ET AL.
Figure 3. (A) Preoperative sagittal T1 post-gadolinium
magnetic resonance imaging (MRI) demonstrating a
large, heterogeneously enhancing partially cystic mass
emanating from the suprasellar space with third
ventricular involvement and resultant hydrocephalus.
(B) Preoperative coronal T1 post-gadolinium MRI again
notes the heterogeneous, mixed-density mass that
largely remains medial to bilateral cavernous carotids
after 2006 did not employ NSF reconstruction. The CSF leak rate
dropped from 60% to 9.8% after the introduction of an NSF.
Before the use of NSF, VPS placement was largely due to CSF
leak (6/7; 86%) and not pre-existing hydrocephalus (1/7; 14%).
The rate of shunting dropped from 70% to 15.2% after the
introduction of NSF. The use of NSF does reduce rates of post-
operative hydrocephalus and can also resist mild or transient
intracranial hypertension which can be seen in this patient pop-
ulation. From the literature, NSF has led to successful recon-
struction in 94% of all high-flow cases.33 Craniopharyngiomas
with ventricular extension certainly represent one of the greatest
flows and greatest challenges in the pre-NSF era. In this review,
the leak rate among other EEA studies for all craniopharyngiomas
was 5.0% to 57.9%.9,15 Leak rates vary broadly by location and
pathology, from 2.9% for adenomas to 32.6% for posterior fossa
tumors.34,35 Dural defect size is associated with the greatest leak
rates.36 Craniopharyngiomas with intraventricular extension
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EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS
and extends superiorly. (C) Follow-up sagittal T1
post-gadolinium MRI demonstrating gross total
resection with no residual enhancement seen. (D)
Follow-up coronal T1 post-gadolinium MRI
demonstrating gross total resection with no residual
enhancement seen. Mild dysmorphic right lateral
ventricle is seen related to tumor involvement and
resection.
represent a unique combination with a smaller dural defect but
high flow’ given ventricular involvement, NSF proves most
effective in this setting.
Total recurrence in the current study was 39%. With GTR, this
rate dropped to 16% compared with 52% for STR; recurrence for
all locations (EEA and TCA) ranged from 14% to 38%.2,21
Importantly, the average follow-up for all reviewed studies was
41 months, whereas the present study had longer follow-up of 51
months. In our cohort, the average time to recurrence was
approximately 39 months, which is similar to the average total
follow-up times of 41 months seen among studies in this review.
The cohort examined in this study included 23% patients who had
previous treatment and 77% who were treatment-naïve. Attempted
GTR in patients with recurrent disease is recognized as more
challenging and leads to GTR in fewer cases with increased
mortality.1 This needs to be considered when comparing results.
However, of the studies in this review, inclusion of treatment-
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HANNA ALGATTAS ET AL.
Figure 4. (A) Endoscopic view with third ventricle in
line of sight and suction tip on left of image
demonstrating tumor. A cottonoid paddy can be seen
on the right of the image draped over the left optic
nerve. The anterior cerebral artery complex is seen at
the top of the image above the optic chiasm. Black
arrowhead indicates right A2; white arrowhead, left
A2; black arrow, anterior communicating artery; white
arrow, optic chiasm; and black diamond, third
ventricle. (B) Endoscopic view inferior to the optic
chiasm with cottonoid paddies being seen at the upper
left and lower left quadrants of the image. View into
the third ventricle is seen with bilateral foramina of
Monroe evident as well as tumor and choroid seen
along bilateral foramina and favoring the roof of the
naïve patients versus patients with recurrence was also
heterogeneous. Second, the literature over time contained
variable opinions regarding preferred GTR versus STR with
radiotherapy. There are data to suggest GTR allows lower rates
of recurrence (32.8%) compared with STR alone (73.3%) and
STR with radiotherapy (RT) (50%).37 A recent, large meta-
analysis identified similar survival outcomes between GTR and
STR þ RT.38 This study was retrospectively conducted over a
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EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS
third ventricle. White arrowhead indicates right
foramen of Monroe, black arrowhead, left foramen of
Monroe; and white arrow, tumor. (C) Deep endoscopic
view into third ventricle with outline of mammillary
bodies seen at the inferior aspect of the image and
beneath that part of the basilar artery complex being
seen. White arrow indicates the aqueduct of Sylvius;
white arrowhead, mammillary body; and black arrow,
basilar artery complex. (D) View into third ventricle
demonstrating removal of tumor and bilateral foramina
of Monroe with choroid plexus present. Third ventricle
appears clear of residual tumor. Looking within the
foramina the lateral ventricle is seen. White diamond
indicates view into left lateral ventricle.
period longer than others included in the review, so changing
attitudes toward goals of surgery for craniopharyngioma over
that time also should be considered. The selection of GTR
versus STR with RT relies on several factors, including pediatric
versus adult, adamantinomatous versus papillary pathology,
location/extent, and preoperative endocrinopathy.39 One
discrepancy within our retrospective series was that 53% of
patients did not undergo a GTR; however, only 15% received

HANNA ALGATTAS ET AL.
Figure 5. (A) Preoperative sagittal T1 sagittal magnetic
resonance imaging (MRI) with contrast demonstrating
cystic and nodular sellar/suprasellar component that
increased from previous follow-up imaging, becoming
more conspicuous. (B) Preoperative coronal T1 MRI
with contrast again denoting cystic, nodular recurrence
adjuvant radiotherapy. Although our institutional protocol is to
generally administer radiation to patients with STR, there were
some confounding features to explain the discrepancy between
STR and administration of RT. For one, nearly one-quarter of
patients in this series were not treatment-naïve and thus likely
already received RT. Second, for this analysis, our description of
STR entails anything from debulking to a near-total resection to
only residual capsule, which may be considered GTR by others,
which potentially inflates the STR value; this was done to simplify
comparison, given the various terminologies and reports used in
the literature review.
Recent developments in the treatment of papillary craniophar-
yngioma with BRAF or BRAK þ MEK inhibitors is a topic of recent
interest and adds a clear option for short-term treatment of cystic
tumors, especially with third ventricular extension.39 This could be
used to decrease cyst size and perhaps provide a lower risk surgery
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EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS
with enhancing nodule toward the floor of sella and
favoring the midline with the cystic portion favoring
the left lateral suprasellar region. (C) Postoperative
sagittal T1 MRI with contrast demonstrating gross
total resection. (D) Postoperative coronal T1 MRI with
contrast demonstrating gross total resection.
after treatment. In this series, only 11% of patients with
intraventricular extension were of the papillary type. Although
81%e100% of papillary craniopharyngiomas have been posited
to hold BRAF mutations, only a few studies have demonstrated
successful inhibition and only in small series.40-42
Similar results to this study were noted by a group examining 10
patients with intrinsic intraventricular craniopharyngiomas.43 That
group achieved GTR in 90%, recurrence in 20% (mean follow-up
47 months) and CSF leak in 10% of cases. However, third ven-
tricular tumors were purely intraventricular rather than infundi-
bulotuberal, extraintraventricular, and pseudointraventricular, as
delineated by the Pascual criteria.14 Unfortunately, the present
study did not contain cases of purely intraventricular
craniopharyngiomas (not out of exclusion, but none
retrospectively identified); otherwise, comparing with these
recently published findings would be interesting. Nevertheless,
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HANNA ALGATTAS ET AL. EEA INTRAVENTRICULAR CRANIOPHARYNGIOMAS

the results of this study and others support the use of EEA for
these tumors.
By comparing the transcranial and endonasal corridors, the data
may help guide clinical judgment in selection of surgical approach
and management. Based on data (Table 4), the endonasal
approach provides superior visual outcomes, similar rates of
resection with experience, but increased risk of CSF leak.
Patients presenting with visual changes may be better served by
the endonasal approach, given the direct inferomedial access
and ability to decompress early and not manipulate the optic
apparatus during resection. In addition, the visualization and
the inferomedial trajectory offered via EEA may have less risk of
injury to critical optic nerve perforators (superior hypophyseal
branches) relative to the TCA. Also, patients with recurrence
after craniotomy may be better suited for endonasal resection to
avoid sites of scar tissue formation and use virgin arachnoid
planes. Other patient-specific features are essential as well. Tu-
mors with significant non-cystic extension lateral to the cavernous
carotids are difficult and potentially dangerous to resect endona-
sally and favor open cranial approach. Second, patients with high
body mass index (not uncommon, given the endocrinologic
involvement of craniopharyngiomas) may have further elevated
risk of postoperative CSF leak given greater baseline intracranial
pressures.
There are several limitations to this current study, starting with
its retrospective nature. The retrospective nature also made ac-
curate comment on other interesting associations difficult, such as
any association between recurrence rates and hypopituitarism.
The retrospective nature and limited documentation over a 14-year
course (particularly the earlier years) also made difficult the ac-
curate recording of how often the stalk was sacrificed. Given
identification of ventricular extension was based on preoperative
MRI and some cases did not explicitly note third ventricular floor
violation, it is possible some pseudointraventricular craniophar-
yngiomas are included. It also contains heterogeneous outcomes
on both primary and recurrent craniopharyngiomas. Importantly,
this study was conducted over a 14-year period, which is longer
than most other published. Attitudes toward ideal resection
strategy of craniopharyngiomas have certainly changed over time
and may be surgeon dependent. True comparisons with the
literature are challenging, given considerable heterogeneity even
among studies within each group, as noted here. Another critique
may be that a previous series of patients with craniopharyngiomas
was published by our institution.15,18 However, more than one-half
the cases from that review were not included in this analysis, given
their lack of ventricular involvement. In addition, that study only
analyzed patients from 1999 to 2011, whereas the current study
includes an additional 23 novel cases with intraventricular exten-
sion. Thus, these 2 series reflect quite-different patient pop-
ulations with very little overlap. In addition, we include the
present review to provide a more meticulous comparison of our
results with those of other historical reports and provide novel
analysis of long-term outcomes/follow-up as well as CSF leak and
shunting.
CONCLUSIONS
We present a large series of craniopharyngiomas with intraven-
tricular extension in addition to incorporating the data into a re-
view. Indeed, EEA for craniopharyngiomas with intraventricular
extension provides similar outcomes to EEA for any craniophar-
yngioma location and, may be better than TCA in particular in-
stances. In addition, this study provides dramatic insight into the
learning curve associated with complex endoscopic endonasal
surgery, as demonstrated by the GTR rate over time. In addition,
CSF leak fell dramatically over time with NSF reconstruction. In
this setting, EEA for craniopharyngiomas extending into a ven-
tricular cavity may provide outcomes comparable with other
methods of resection and does not represent an absolute contra-
indication to the approach.
CRediT AUTHORSHIP CONTRIBUTION STATEMENT
Hanna Algattas: Conceptualization, Methodology, Validation,
Formal analysis, Investigation, Data curation, Writing - original
draft, Visualization. Pradeep Setty: Data curation, Resources,
Validation. Ezequiel Goldschmidt: Resources, Validation, Writing
- review & editing. Eric W. Wang: Resources, Writing - review &
editing, Supervision, Project administration. Elizabeth C. Tyler-
Kabara: Resources, Validation, Supervision. Carl H. Snyderman:
Resources, Validation, Supervision, Writing - review & editing.
Paul A. Gardner: Conceptualization, Methodology, Investigation,
Validation, Resources, Writing - review & editing, Supervision,
Project administration.
ACKNOWLEDGMENTS
We acknowledge Benita Valappil, MPH, for her assistance with
data collection, recording, and overseeing research and institu-
tional review board efforts; Amin Kassam, Ricardo Carrau, Juan
Fernandez-Miranda, and Daniel Prevedello for their surgical and
clinical expertise in care of patients included in this series; and
Yue-Fang Cheng, PhD, and Ian Chow, MD, for statistical
assistance.

3. Shi X, Zhang Y, Wu B. Surgical experience of 179 5. Koutourousiou M, Gardner PA, Fernandez-

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Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 5 June 2020; accepted 25 August 2020
Citation: World Neurosurg. (2020) 144:e447-e459.
https://doi.org/10.1016/j.wneu.2020.08.184
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter Published by Elsevier Inc.
e459