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Surgical Management of Craniopharyngiomas inChildren: Meta-analysis and Comparison ofTranscranial and Transsphenoidal Approaches

BACKGROUND: Controversy persists regarding the optimal treatment of pediatriccraniopharyngiomas.

OBJECTIVE:We performed a meta-analysis of reported series of transcranial (TC) andtranssphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whethercomparisons between the outcomes in TS and TC approaches are valid.

METHODS: Online databases were searched for English-language articles reportingquantifiable outcome data published between 1990 and 2010 pertaining to the surgicaltreatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patientshaving TC surgery and 13 studies describing 373 patients having TS surgery met in-clusion criteria.

RESULTS:Before surgery, patients who had TC surgery had less visual loss, more fre-quent hydrocephalus and increased intracranial pressure, larger tumors, and more su-prasellar disease. After surgery, patients in the TC group had lower rates of gross totalresection (GTR), more frequent recurrence after GTR, higher neurological morbidity,more frequent diabetes insipidus, less improvement, and greater deterioration in vision.There was no difference in operative mortality, obesity/hyperphagia, or overall survivalpercentages.

CONCLUSION: Directly comparing outcomes after TC and TS surgery for pediatriccraniopharyngiomas does not appear to be valid. Baseline differences in patients whounderwent each approach create selection bias that may explain the improved rates of

disease control and lower morbidity of TS resection. Although TS approaches are be-coming increasingly used for smaller tumors and those primarily intrasellar, tumors moreamenable to TC surgery include large tumors with significant lateral extension, thosethat engulf vascular structures, and those with significant peripheral calcification.

KEY WORDS: Craniopharyngioma, Craniotomy, Pediatric, Radical resection, Transnasal, Transsphenoidal

Neurosurgery 69:630643, 2011 DOI: 10.1227/NEU.0b013e31821a872d www.neurosurgery-online.com

Craniopharyngiomas are the most commonchildhood nonglial brain tumor, com-prising 6% to 8% of pediatric brain

tumors.1

They are benign, epithelial neoplasmsthought to arise from embryological remnants ofsquamous epithelium of the craniopharyngeal

duct.2 The benign histology of craniophar-yngiomas, however, belies their rather malignantclinical course, especially in children. Described

by Harvey Cushing3

as one of the most bafflingproblems to the neurosurgeon, their closeproximity to the visual apparatus, circle of Willis,pituitary stalk, and hypothalamus predisposesthese patients to severe adverse sequelae inmultiple functional domains, both at pre-sentation and after treatment.

Improvements in surgical technique, radiationtherapy (RT) modalities, hormone replacement,and supportive care have resulted in improved

Robert E. Elliott, MD*

John A. Jane, Jr., MD

Jeffrey H. Wisoff, MD*

*Department of Neurosurgery, New York

University School of Medicine, New York,

New York; Department of Neurosurgery

and Pediatrics, University of Virginia,

Charlottesville, Virginia

Correspondence:Jeffrey H. Wisoff, MD,

Division of Pediatric Neurosurgery,

NYU Langone Medical Center,

317 East 34th Street, Suite 1002,

New York, NY 10016.

E-mail: [email protected]

Received,July 19, 2010.

Accepted,February 16, 2011.

Published Online,April 14, 2011.

Copyright 2011 by the

Congress of Neurological Surgeons

ABBREVIATIONS: DI, diabetes insipidus; GTR,

gross total resection; ICP, intracranial pressure;OS, overall survival; RT, radiation therapy; TC,

transcranial; TN, transnasal; TS, transsphenoidal;VA,visual acuity; VF,visual field

630 | VOLUME 69 | NUMBER 3 | SEPTEMBER 2011 www.neurosurgery-online.com

RESEARCHHUMANCLINICAL STUDIES

TOPIC RESEARCHHUMANCLINICAL STUDIES

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.


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survival for children with craniopharyngiomas.1,4-11Accordingly,outcome assessments have shifted from the length of survivaltoward analysis of the quality of survival. A major focus of recentefforts has been to determine the optimal treatment strategy forcraniopharyngiomas, and the 2 major schools of thought arelimited resection plus RT and radical resection with attempt at

surgical cure. Both offer similar rates of progression-free andoverall survival (OS),6,11-16 but the former strategy may tradeslightly less acute morbidity for possibly increased long-termmorbidity because of the late and unpredictable side effects ofRT, particularly in children.6,17

Although this debate persists, the evolution of endoscopic in-strumentation and techniques has fostered the rise ofmicroscopic transsphenoidal (TS) and transnasal (TN) endoscopicapproaches through the sphenoid sinus for the resection of para-sellar tumors, including craniopharyngiomas. Given the retro-spective nature of most surgical series and the limited number ofpatients accumulated by any 1 center, direct comparison of TS andtranscranial (TC) approaches is fraught with difficulty.5,18,19 Nu-merous centers have reported their experience with both ap-proaches, but such direct comparisons are prone to selectionbias.5,20-22 In contrast to the majority TC cases, most TS cases wereperformed on smaller tumors, tumors primarily intrasellar, andonly more recently for predominantly suprasellar disease.

In this report, we summarize the major TC and TS surgicalseries for primary craniopharyngiomas in children. We summa-rize oncological outcomes, operative morbidity (neurological,endocrinological, hypothalamic), visual outcomes, perioperativemortality, and long-term survival. We discuss the advantages anddisadvantages of the various surgical approaches and the nuancesof TS surgery in children. Moreover, we analyze the baseline

characteristics of children treated with TC and TS approaches todetermine whether significant differences exist that would pre-clude meaningful comparison in indications and outcomes.

METHODS

Article Selection

Online databases MEDLINE (PubMed) and Embase were searched forEnglish-language articles published between January 1990 and January 2010containing the following keywords alone or in combination: craniophar-

yngioma, craniopharyngiomas, pediatric, children, child, surgery,microsurgery, resection, treatment, transnasal, transsphenoidal,and endoscopic. We reviewed all abstracts, and each article of interest wasmarked for further review. The full text of the marked studies was retrieved,and studies that satisfied our inclusion criteria were included in this analysis.The references listed in each article of interest were also reviewed for pertinentarticles. Table 1 summarizes the inclusion and exclusion criteria for this meta-analysis.

Analysis was limited to articles that included patients younger than 21years of age at the time of primary TC microsurgery or microscopic/endoscopic TS/TN surgery and those published in 1990 or later giventhe advent of microsurgical techniques and the rise of magnetic reso-nance imaging (MRI). In articles that included adults older than 21 yearsof age in the analysis, results of younger patients were extracted separately

or notation was made when the results of adults and children could notbe disaggregated. Articles describing the management of other neoplasmsbesides craniopharyngiomas were included only if the results for cra-niopharyngiomas were reported separately. We excluded case reports andseries with fewer than 20 patients in TC series and fewer than 10 patientsin TS series to potentially account for the effect of surgical experience onoutcomes. Studies that reported the outcomes of only a single functionaldomain (eg, vision or endocrine) were also excluded. If centers reportedcombined results of TC and TS surgeries without segregation of out-comes, results were included and attributed to 1 approach if that ap-proach constituted 85% or more of the cases described. For series thatcombined TS and TC outcomes with one approach constituting less than85% of total cases, the results were not included in the summary statistics.For centers that published multiple studies on the patients described in

previous reports, the most recent and/or most comprehensive study wasused. Review articles of multiple series were excluded as were series withhigh percentages of planned subtotal resection (STR) + RT, simple cyst

TABLE 1. Inclusion and Exclusion Criteria for Studies Concerning the Surgical Management of Craniopharyngiomas in Children a

Inclusion Criteria Exclusion Criteria

TC and/or TS resection of craniopharyngiomas Studies reporting primarily on planned l imited resection + radiationtherapy

$20 patients for TC series Studies reporting primarily on cyst aspiration, intracavitary treatments,

biopsies, or CSF diversion procedures only$10 patients for TS series Reports describing outcomes of only a single functional domainFor reports that combined TC/TS outcomes, 1 approach must comprise$85% of cases

Combined reporting of craniopharyngioma resection with otherpathologies

For reports that combined craniopharyngiomas with other pathologies,outcomes of craniopharyngioma cases must be reported separately

Earlier reports of series that were republished by the same center

Includes patients ,21 years of age at time of surgery Review articles summarizing results of previous seriesPublished in 1990 or laterEnglish language

aCSF, cerebrospinal fluid; TC, transcranial; TS, transsphenoidal.

SURGERY FOR PEDIATRIC CRANIOPHARYNGIOMAS

NEUROSURGERY VOLUME 69 | NUMBER 3 | SEPTEMBER 2011 | 631



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decompressions, biopsies, intracavitary chemotherapy or irradiation, orprocedures for cerebrospinal fluid (CSF) diversion only.

After screening more than 2000 articles, 61 articles were analyzed,having satisfied our inclusion criteria. Forty-eight studies describing2955 patients who had TC surgery6,10,11,22-65 and 13 studies describing373 patients who had TS surgery5,12,18,31,66-74 met our inclusion criteriafor this study and serve as the basis of this report. Patients who had stagedTC-TS surgeries were included in the TC group.

Data Extraction and Analysis

Data from these articles were pooled to calculate the baseline char-acteristics of the patients and the prevalence of postoperative outcomes.

The baseline data recorded included the number of patients, inclusionof adult patients and their number if available, the incidence of pre-operative visual deficits, hydrocephalus, and signs of increased in-tracranial pressure (ICP) at presentation including nausea, vomiting,lethargy, and somnolence. Headache alone was not considered a de-finitive sign of high ICP. Postsurgical data recorded included follow-upduration, rate of gross total resection (GTR), tumor recurrence afterGTR, surgical mortality, new diabetes insipidus, (DI), visual de-

terioration, vision improvement, neurological deterioration, obesity and/or hyperphagia, OS, incidence of CSF leaks and meningitis. In nearly allstudies after the early 1990s, MRI was used postoperatively to determinethe extent of resection. For some patients reported in the studies in theearly to mid-1990s, extent of resection was based on surgeon impressionintraoperatively or computed tomography imaging. Perioperative mor-tality included deaths that occurred within 30 days of surgery. Patients

who underwent surgery for previously treated craniopharyngiomas wereexcluded from this analysis when disaggregation of the data was notpossible. Notation was made if and how many children with recurrenttumors were included in a given series. Table 2 summarizes the numberand percentage of patients with complete data reported for each of theabove pre- and postoperative variables.

Using the number of patients in each study with data available and thepercentage of cases for each variable collected, weighted averages werecalculated to determine the conglomerate values for all studies included.Follow-up duration was collected as mean follow-up in years. Rarely,follow-up was reported as a median value, and this has been noted in thetables. Tumor size was recorded as both mean and median values incentimeters in various studies and is noted as such in the tables.

Statistical Analysis

The raw data were entered into Microsoft Excel (Office 2008 forMac). The Fisher exact (x2) tests were used to compare proportionsbetween the TC and TS patient groups. All statistics were calculated withSSPS (17.0 for Mac; SSPS, Inc, Chicago, Illinois). A 2-tailedPvalue of,.05 was considered statistically significant for all analyses.

RESULTS

TC Surgical Series of Pediatric Craniopharyngiomas

Table 3 summarizes the baseline characteristics for 2955 pa-

tients treated via TC resection for craniopharyngiomas. Sixty-onepatients (2.1%) had TS procedures that were included in theresults of TC studies because the data could not be disaggregated.

Preoperative data concerning visual field (VF) and/or visualacuity (VA) status were reported in 1966 TC cases (66.5%).Before surgery, 1051 patients (53.5%) had VF and/or VA def-icits. Presence or absence of hydrocephalus and increased ICPwere reported in 1625 (55.0%) and 1713 (58.0%) TC cases,respectively. Hydrocephalus or signs of increased ICP werepresent in 678 (41.7%) and 729 (42.6%) patients, respectively.

Tumor size was reported in 10 of 48 TC studies for a total of957 patients (32.4%). Four studies (n = 198) reported tumor size

as a mean value for an average tumor size of 5.2 cm. In 6 otherstudies, size was reported as a median value or median range oftumors (3-6 cm). Tumor location was inconsistently reported buttended to have a high preponderance of suprasellar or pre-dominantly suprasellar craniopharyngiomas. Few purely intra-sellar tumors were treated with TC surgery.

Table 4 summarizes the oncological and functional outcomesfor patients after TC surgery for craniopharyngiomas. At anaverage follow-up time from surgery of 5.9 years, 90.3% ofpatients are alive (2039 of 2258). GTR was achieved in 60.9% ofsurgeries (1693 of 2780), and 17.6% of patients (261 of 1518)experienced disease recurrence after GTR. Perioperative deathsoccurred in 2.6% of surgeries (68 of 2622), and neurological

deterioration occurred in 9.4% of patients (200 of 2140). DI waspresent in 69.1% of cases after treatment (1437 of 2076), and32.2% of patients experienced obesity and/or hyperphagia (439of 1363). Visual status improved in 47.7% of patients (454 of1051) who had preoperative deficits, and 13% of patients (263 of2029) experienced new VF and/or VA deficits after treatment.

TS Surgical Series of Pediatric Craniopharyngiomas

Table 5 summarizes the baseline characteristics for 373patients treated with TS resection for craniopharyngiomas.

TABLE 2.Number of Patients With Complete Preoperative and

Postoperative Data in Major Transcranial and Transsphenoidal

Surgery for Primary Craniopharyngiomas in Childrena

Variable

No. (%) of Patients

With Complete Data

Transcranial

Series

Transsphenoidal

Series

Preoperative vision status 1667 (61.6) 181 (48.5)Preoperative hydrocephalus 1509 (55.7) 99 (26.5)Preoperative elevated ICP 1547 (57.1) 138 (37.0)Gross-total resection 2610 (96.4) 276 (74.0)Recurrence after GTR 1419 (52.4) 201 (53.9)

Operative mortality 2490 (92.0) 373 (100)Neurological morbidity 2012 (74.3) 325 (87.1)Diabetes insipidus 2028 (74.9) 318 (85.3)Vision improvement N/Ab N/Ab

Vision deterioration 2029 (75.0) 352 (94.4)Obesity or hyperphagia 1269 (46.9) 109 (29.2)Overall survival 2160 (79.8) 230 (61.7)

aICP, intracranial pressure; GTR, gross total resection; N/A, not available; TS,

transsphenoidal.bDenominator unknown.

ELLIOTT ET AL




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TABLE 3.Major Transcranial Surgical Series of Primary Craniopharyngioma in Children: Presenting Characteristics and Follow-up Duration a

Study

No. of

Patients Age Groups

No. of

Patients

With TS-Only

Surgeries

Mean

Follow-up, y

Mean Tumor

Size, cm

Preoperative

HCP, %

Preoperative

Increased

ICP, %

Preoperative

Vision

Deficits, %

Colangelo et al, 26 1990 32 C 0 4.6 N/A 81.3 N/A N/AFischer et al,32 1990 37 C 0 10.5 N/A N/A N/A N/AYasargil et al,63 1990 144 70C & 74A 14 N/A N/A N/A N/A 30.6Samii and Bini,65 1991 34 11C & 23A 0 N/A N/A N/A N/A N/ASymon et al,58 1991 50 10C & 40A 0 2.5 N/A N/A 22 68Hoffman et al,37 1992 50 C 0 4.9 N/A 48 N/A 58Tomita and McLone,61 1993 27 C 0 6.7 N/A 48.1 33.3 44.4Pierre-Kahn et al,50 1994 30 C 0 3.2 N/A N/A N/A 46.7Maira et al,22 1995 22 C & A 0 7.5 N/A N/A N/A N/AMark et al,45 1995 49 15C & 34A 0 8 N/A N/A 45 N/ADe Vile et al,27 1996 75 C 0 6.4 3.5 54.1 N/A N/AShibuya et al,54 1996 22 9C & 13A 0 2.75 4.1 N/A N/A 81.8Bulow et al,24 1998 26 C 0 12.5 N/A 40 27 N/AFisher et al,33 1998 30 C 0 N/A N/A 31 N/A N/A

Khafaga et al,41

1998 44 C 0 2 4 N/A N/A 40.9Fahlbusch et al,31 1999 94 C & A 0 5.4 2-3 (median) 20.2 N/A 79.8Kim et al,42 2001 36 C 0 4.3 All .3 69.4 N/A N/AMerchant et al,46 2002 30 C 0 6.1 N/A 23 43 N/AVan Effenterre and Boch,10 2002 122 29C & 93A 10 7 N/A 20 20 86.1Chen et al,25 2003 36 17C & 19A 0 10.25 N/A N/A N/A 66.7Kalapurakal et al,38 2003 25 C 0 10 N/A 80 56 N/AGonc et al,34 2004 66 C 0 5.1 N/A 46.2 74.2 N/AStripp et al,57 2004 76 C 0 7.6 N/A N/A 57.9 56.6Albright et al,23 2005 27 C 0 9 N/A N/A N/A N/AErsahin et al,30 2005 87 C 2 3.2 N/A 31 24.1 N/AKaravitaki et al,39 2005 42 C 2 7.8 N/A N/A 54 N/ALena et al,44 2005 47 C 1 9.5 N/A 14.9 14.9 68.1Minamida et al,47 2005 37 8C & 29A 4 11.1 N/A N/A N/A N/AMotollese et al,48 2005 36 C 0 N/A N/A N/A 55 N/A

Saint-Rose et al,52 2005 66 C 0 7 N/A N/A 68 44Shirane et al,55 2005 42 20C & 22A 0 N/A N/A N/A 19 N/ASosa et al,56 2005 35 C 4 4.6 N/A N/A N/A N/AThompson et al,59 2005 48 C 5 5.6 N/A N/A N/A 58.3Tomita and Bowman,60 2005 54 C 3 N/A N/A 50 29.6 42.6Zuccaro,11 2005 153 C 1 N/A 4-6 (median) 54 40 43.8Xu et al,62 2005 51 C & A 0 2.3 .4 (median) 80.4 81 N/ADhellemmes and Vinchon,28 2006 37 C 0 10.1 N/A N/A 38 73Di Rocco et al,29 2006 54 C 6 8.7 N/A 33 61 33.3Gupta et al,35 2006 116 C N/A 1.5 2-4 (median) 42.2 46.5 65.5Hafez et al,36 2006 62 C 1 3.5 N/A N/A N/A 59.7Ohmori et al,49 2007 27 C 1 N/A N/A N/A N/A N/APuget et al,51 2007

(retrospective group)66 C 0 7 N/A 53 68 43.9

Puget et al,

51

2007(prospective group) 22 C 0 1.2 N/A 45 59 N/A

Lee et al,43 2008 66 C 0 7.2 N/A N/A 45.5 N/AShi et al,53 2008 309 58C & 251A 0 2.1 3-6 (median) 37.8 34.6 43Zhang et al,64 2008 202 C 1 N/A N/A N/A N/A 55.9Elliott et al,6 2010 57 C 0 10.7 4.1 29.1 N/A 40.4Kawamata et al,40 2010 55 27C & 28A 6 14.8 N/A N/A N/A N/AAverage values 2.0 5.9 5.2b 41.7 42.6 53.5

aA, adults; C, children; HCP, hydrocephalus; ICP, intracranial pressure; N/A, not available; TS, transsphenoidal.bAverage value includes only the studies that reported mean values of tumor size (n = 198).





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TABLE 4. Major Transcranial Surgical Series of Primary Craniopharyngiomas in Children: Surgical Outcomes, Morbidity, and Mortality a

Study

No.

of

Patients

GTR,

%

STR,

%

Recurrence

After

GTR, %

Operative

Mortality,

%

Neurological

Morbidity,

%

DI,

%

Vision

Improvement,

%

Vision

Worsening,

%

Obesity or

Hyperphagia,

%

Overall

Survival,

%

Colangelo et al,

26

1990 32 22 78 14 12 12 N/A N/A N/A N/A 75Fischer et al,32 1990 37 19 81 57 0 N/A 34 N/A N/A N/A 92Yasargil et al,63 1990 144 90 10 7 2.9 N/A 90 36 13 N/A 80Samii and Bini,65 1991 34 100 0 3 0 0 .80 N/A N/A N/A N/ASymon et al,58 1991 50 60 40 10 4 10.9 .50 N/A N/A 8.7 76Hoffman et al,37 1992 50 90 10 29 2 6 93 36 41 52 98Tomita and McLone,61 1993 27 78 22 14 0 N/A 81 80 19 N/A 93Pierre-Kahn et al,50 1994 30 83 17 N/A 0 N/A N/A 31 29 N/A N/AMaira et al,22 1995 22 71 29 0 0 4.5 N/A N/A N/A N/A 86.4Mark et al,45 1995 49 39 61 37 10 10.2 N/A N/A N/A N/A N/ADe Vile et al,27 1996 75 40 60 10 0 13 80 N/A N/A 15 88Shibuya et al,54 1996 22 N/A N/A N/A 0 7% 97 72 9 N/A 90Bulow et al,24 1998 26 73 27 N/A 8 N/A N/A N/A N/A N/A 88Fisher et al,33 1998 30 27 73 N/A 0 N/A 83 N/A N/A N/A 93Khafaga et al,41 1998 44 39 61 N/A 16 N/A N/A N/A N/A N/A 73

Fahlbusch et al,31

1999 94 46 54 19 0 0 N/A 71 15 6.7 91.5Kim et al,42 2001 36 100 0 39 0 42 94 N/A 25 6 89Merchant et al,46 2002 30 27 73 38 0 10 50 N/A 17 N/A 97Van Effenterre and Boch,10 2002 122 79 21 13 2.5 8 57 70 11 36 89Chen et al,25 2003 36 19 81 N/A 5.6 14 67 50 31 N/A N/AKalapurakal et al,38 2003 25 76 24 32 0 N/A 100 N/A N/A 32 100Gonc et al,34 2004 66 33 67 41 2 10.6 52 N/A N/A N/A 80Stripp et al,57 2004 76 62 38 N/A 1 N/A 80 21 15 49 89Albright et al,23 2005 27 67 33 11 0 11 N/A N/A 19 N/A N/AErsahin et al,30 2005 87 43 57 5 7 15 33 N/A 5 N/A 89Karavitaki et al,39 2005 42 17 83 0 0 12.9 65 N/A 6 39 80Lena et al,44 2005 47 66 34 26 2.4 N/A 86 16 16 48 94Minamida et al,47 2005 37 70 30 15 0 2.7 N/A N/A 2.7 N/A 94Motollese et al,48 2005 36 74 26 16 6 N/A 100 N/A 14 N/A 89Saint-Rose et al,52 2005 66 50 50 36 N/A N/A N/A 68 21 70 N/A

Shirane et al,55 2005 42 71 29 20 0 6.7 Most N/A N/A N/A 93Sosa et al,56 2005 35 83 17 41 0 20 91 N/A 17 N/A 97Thompson et al,59 2005 48 33 67 50 0 15 84 61 N/A 20 96Tomita and Bowman,60 2005 54 61 39 27 0 9 87 43 13 28 90Zuccaro,11 2005 153 69 31 0 3 10 50 45 8.5 35 87.5Xu et al,62 2005 51 92 8 17 0 8 N/A N/A N/A N/A 94Dhellemmes and Vinchon,28 2006 37 65 35 43 0 8 N/A 7 24 48 89Di Rocco et al,29 2006 54 78 22 7 3.7 18 56 44 11 18 93Gupta et al,35 2006 72b 26 74 11 N/A N/A N/A N/A N/A N/A N/AHafez et al,36 2006 62 50 50 20 6 6 85 68 5 N/A N/AOhmori et al,49 2007 27 93 7 14 3.7 N/A N/A N/A N/A N/A 93Puget et al,51 2007

(retrospective group)66 50 50 36 1.5 6 94 68 21 70 94

Puget et al,51 2007

(prospective group)

22 23 77 0 0 14 100 N/A 0 27 100

Lee et al,43 2008 66 N/A N/A N/A 0 6 66.7 N/A N/A 18 97Shi et al,53 2008 309 89.3 10.7 14 3.9 6 53 42 5.5 N/A 94Zhang et al,64 2008 202 40 60 0 1 5.4 81 42 5 22 ,70Elliott et al,6 2010 57 100 0 20 3.5 12 78 56.5 25 15 93Kawamata et al,40 2010 55 22 78 N/A 0 N/A 45 N/A 33 N/A 89Average values 60.9 39.1 17.6 2.6 9.4 69.1 47.7 13.0 32.2 90.3

aGTR, gross total resection; DI, diabetes insipidus; STR, subtotal resection; N/A, not available.bExtent of resection data based on 72 patients who had .12 months of follow-up.

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Preoperative data concerning VF and/or VA status was re-ported in 181 TS cases (48.5%). Before surgery, 124 patients(68.5%) had VF and/or VA deficits. Presence or absence ofhydrocephalus and increased ICP were reported in 99 (26.5%)and 138 (37.0%) TS cases, respectively. Hydrocephalus or signsof increased ICP were present in 5 patients (5.1%) and 0 (0%)

patients, respectively, before TS surgery.Tumor size was reported in 7 of 13 TS studies for a total of

115 patients (39.8%). In 6 of 7 of these studies (n = 80), size wasreported as a mean value with an overall average of 2.5 cm.Tumor location was inconsistently reported but tended to havea high preponderance of purely or mostly intrasellar cranio-pharyngiomas and intrasellar tumors with suprasellar extension.There was a minority of purely suprasellar tumors treated withTS surgery.

Table 6 summarizes the oncological and functional out-comes for patients after TS surgery for craniopharyngiomas.At an average follow-up time from surgery of 5.5 years, 93.9%of patients are alive (216 of 230). GTR was achieved in 72.1%of surgeries (199 of 276) and 8.0% of patients (16 of 201)experienced disease recurrence after GTR. Perioperativedeaths occurred in 1.3% of surgeries (5 of 373) and neuro-logical deterioration occurred in 3.1% of patients (10 of 325).DI was present in 36.0% of cases after treatment (112 of 311),and 32.1% of patients experienced obesity and/or hyper-phagia (35 of 109). Visual status improved in 85.5% ofpatients who had preoperative deficits (106 of 124), and 2.3%of patients experienced new VF and/or VA deficits aftertreatment (8 of 352).

Comparison of TC and TS Surgery for

Pediatric Craniopharyngiomas

Table 7 compares the average values for baseline characteristicsand outcomes between patients who had TC and TS cranio-pharyngioma surgery. Before surgery, patients who had TC surgeryhad less visual loss (P, .0001), a greater proportion of hydro-cephalus (P , .0001), and increased ICP (P , .0001), largertumors and more suprasellar disease compared with patients whounderwent TS procedures. Follow-up was slightly longer for pa-tients who had TC surgery, but this was not directly comparable(5.9 years vs 5.5 years). After surgery, patients in the TC surgerygroup had lower rates of GTR (P= .0003), more frequent tumorrecurrence after GTR (P= .0005), higher neurological morbidity(P , .0001), more frequent DI (P , .0001), less visual im-provement (P , .0001), and greater deterioration in vision(P, .0001). There were trends toward improved OS (P= .075)and less perioperative mortality in TS surgery (P= .21) but nodifference in the incidence of obesity and/or hyperphagia (P= 1.0).

DISCUSSION

The optimal management of pediatric craniopharyngiomasremains a contentious issue in pediatric neurosurgery. In thismeta-analysis of the major surgical series for the treatment ofcraniopharyngiomas, we demonstrated that patients treated withTS surgery had superb outcomes. Compared with patients whohad formal craniotomies, TS patients had better visual, neuro-logical, endocrinological, and oncological outcomes.

TABLE 5. Major Surgical Series of Endoscopic and Microscopic Transsphenoidal Resection of Primary Pediatric Craniopharyngiomas:

Presenting Characteristics and Follow-up Durationa

Study

No. of

Patients

Age

Group

Average

Follow-up, y

Mean Tumor

Size, cm

Preoperative

HCP, %

Preoperative

Increased ICP, %

Preoperative Vision

Deficits, %

Landolt and Zachmann,72 1991 10 3C & 7A 8.5 2.2 N/A 0 N/AHonegger et al,70 1992 19 3C & 16A 3 N/A N/A 0 42.1Laws,73 1994 76 23C & 56A N/A N/A N/A N/A N/AAbe and Ludeke,66 1999 11 C 2.9 1.7 0 0 N/AFahlbusch et al,31 1999 35 C & A 5.4 1-2 (median) N/A N/A 42.9Maira et al,74 2004 57 C & A 6 N/A N/A N/A N/A

Couldwell et al,67

2004 27 C & A 10.2 N/A N/A N/A N/ACaldarelli et al,12 2005 11 C N/A N/A N/A N/A N/AChakrabarti et al,5 2005 68 C & A .5 y N/A 2.9 0 91.2Frank et al,69 2006 10 1C & 9A 3.1 2.8 N/A 0 80.0Fatemi et al,68 2009 18 5C & 13A 1.7 3.1 N/A N/A 66.7Kitano and Taneda,71 2009 20 5C & 15A 4.6 2.9 15.0 0 75.0Jane et al,18 2010 11 C 7 2.3 N/A N/A 36.4Average values 5.5 2.5b 5.1 0 68.5

aA, adults; C, children; HCP, hydrocephalus; ICP, intracranial pressure; N/A, not available.bAverage value included the 6 of 7 studies that reported mean values of tumor size (n = 80).





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Critical to this analysis, however, is the identification ofbaseline differences between the populations of patients who wereselected for each surgical approach. Craniopharyngiomas treatedtranssphenoidally tended to be smaller, more often completely orpredominantly intrasellar, and often cystic in nature.5,22,31

Patients undergoing TS surgery also had less hydrocephalus and

no reported instances of increased ICP. Previous studies reportedworse outcomes in patients with hydrocephalus, larger tumors,and poor preoperative functional status.6,27,63,75 Moreover, largetumor size has been associated with increased operative mortality,63

neurological and hypothalamic morbidity,27,30,63 a lower prob-ability of GTR,21,27,31 and higher recurrence rates.27,30,35,59 Theselection bias caused by these baseline differences may explain theimproved outcomes in the TS surgery group. Regardless of thesefindings, further experience with TS approaches will undoubtedlycontinue to expand the indications for TS surgery and, ulti-mately, limit patient morbidity and improve overall outcomesand quality of life.

Oncological ControlAs our review discovered and as reported by centers comparing

their own experience with both TS and TC removal of cranio-pharyngiomas, there was a higher rate of complete excision andfewer recurrences after GTR in patients treated with the TSapproach. This difference in the rate of GTR may be explained bythe fact that some patients, specifically in the TC group, receivedintended STR followed by planned RT. Regardless of approach,however, certain anatomic factors may account for much of theability to completely resect a given craniopharyngioma, and caseselection for TS surgery may explain many of the differences insurgical outcomes.

In the series of 168 adults and children with craniophar-yngiomas who underwent resection, Fahlbusch et al31 performedTS surgery on 29% of their patients. Compared with TC surgerycases, they reported a higher rate of GTR (86% vs 46%), morevisual improvement (73% vs 67%), less morbidity (8% vs 13%),and a higher rate of functional independence without impairment(91% vs 78%) after TS surgery. However, they also noted that atleast 60% of the tumors treated transsphendoidally were less than2 cm in size, markedly smaller than those treated via TC surgery.Moreover, the pituitary fossa was enlarged in more than 90% ofcases treated with TS surgery, suggesting an intrasellar origin in thevast majority of those cases. Chakrabarti et al5 analyzed their ex-perience using TS and TC surgery for 86 patients with cranio-

pharyngiomas, 79% of whom were treated transsphenoidally.Using the TS approach, they had a higher rate of GTR (90% vs61%), greater visual improvement (87% vs 61%), fewer compli-cations, and shorter hospital stays (4.2 days vs 7.8 days). Only 16%of TS cases in their series were purely suprasellar (vs 100% of TCcases), and 88% had cystic components compared with 44% ofTC cases. They preferred the TC approach for tumors that werepredominantly solid, suprasellar, or lateral to midline. Consistentwith the anatomic location of a tumor explaining many cases ofSTR, Maira et al74 reported on 57 adults and children operated on

TABLE6.MajorSurgicalSeriesofEndoscopicandMicroscopicTranss

phenoidalResectionofPrimaryPediatricCraniopharyngiomas:SurgicalOutcome

s,Morbidity,and

Mortalitya

Study

No.of

Patients

GTR,

%

STR,%

Recurrence

AfterGTR,%

Ope

rative

Mortality,%

Neurological

Morbidity,%

DI,

%

Visual

Improvement,

%

Vision

Worsening,

%

Obesityor

Hyperphagia,

%

CSF

Leak,

%

Meningitis,

%

Overall

Survival,

%

LandoltandZachmann,7

2

1991

10

N/A

N/A

N/A

10

N/A

50

N/A

N/A

N/A

N/A

N

/A

86

Honeggeretal,70

1992

19

79

21

0

0

5

8

87.5

5

N/A

N/A

5

.3

95

Laws,73

1994

76

N/A

N/A

7

2.6

4.9

30

N/A

1.3

N/A

16

8

92.1

AbeandLudeke,6

6

1999

11

27

73

0

0

0

50

N/A

0

N/A

0

N

/A

N/A

Fahlbuschetal,31

1999

35

86

14

0

0

0

N/A

87

0

N/A

3

3

91.4

Mairaetal,74

2004

57

56

44

N/A

0

0

14

N/A

0

N/A

17.5

0

96

Couldwelletal,67

2004

27

74

26

20

0

N/A

4

N/A

0

N/A

6

0

N/A

Caldarellietal,12

2005

11

N/A

N/A

N/A

18

N/A

Rare

N/A

N/A

N/A

N/A

N

/A

N/A

Chakrabartietal,5

2005

68

90

10

10

0

0

67

87

3

40

1.5

0

N/A

Franketal,69

2006

10

70

30

0

0

0

30

75

0

20

30

10

N/A

Fatemietal,6

2009

18

17

83%

0

0

0

46

92

0

N/A

6

6

100

KitanoandTaneda,7

1

2009

20

86

14

11

0

20

50

80

15

15

15

0

N/A

Janeetal,18

2010

11

100

0

18

0

9

71

75

9

27

0

0

100

Averagevalues

72.1

27.9

8

1.3

3.1

23.9

85.5

2.3

32.1

9.4

2

.9

93.9

aGTR,grosstotalresection;STR,sub

totalresection;DI,diabetesinsipidus;CSF,cerebrospinalfluid;N/A,notavailable.

ELLIOTT ET AL




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via the TS route. GTR was successful in 91% of 11 intrasellartumors, 54% of 37 lesions with intra- and suprasellar components,and only 22% of 9 tumors entirely suprasellar. In their series of 121craniopharyngiomas, Duff et al20 reported better outcomes and lesstumor recurrence in patients with intrasellar tumors and betteroutcomes in patients treated transsphenoidally compared withthose who underwent craniotomy. However, pre- and post-operative clinical and imaging data segregating the TS and TCsurgery cohorts were not provided.

In many studies that reported the reasons for incomplete re-

sections, tumoral adherence to vascular structures, optic apparatus,or the hypothalamus was the most common explanation.6,21,31

Such factors intrinsic to the tumor make complete resection dif-ficult, if not impossible, regardless of approach. Vascular injuryduring craniopharyngioma resection is one of the most dreadedand life-threatening complications and has been reported in bothTS and TC surgeries.6,29,67,72,76,77 Given the limitations in thefield of view and the tools necessary to halt significant bleeding, webelieve that TS surgery is contraindicated if complete resection isthe goal when tumors engulf or extend lateral to the carotid arteriesand those with significant suprasellar calcification (an indicator ofadhesiveness to surrounding structures).5,18,78

Recurrence of a craniopharyngioma is a relatively common and

frustrating event after even definitive treatment. Compiling theoutcomes of surgical series before 1991, Choux et al13 estimatedrecurrence rates of 19% after complete resection and nearly 30%after limited surgery plus RT. Although initial surgery appears toprovide the best chance at total excision and surgical diseasecontrol, our review found a recurrence rate after GTR of 17.6%in patients who had TC surgery in contrast to only 8% after TSresection. Given that the risk of craniopharyngioma recurrenceincreases with longer follow-up, shorter follow-up in the TSgroup may account for this difference. Most recurrences,

however, occur within the first 3 to 4 years after treat-ment,6,11,28,31,60,63 well before the average follow-up time of5.5 years for the TS group. This difference may reflect bettertumor control provided by TS surgery and may be explained bythe excellent direct visualization of the entire surgical field pro-vided by current endoscopic technology, ensuring removal of alltumor remnants. Such visualization of the entire field from belowoften contrasts with the blind spots that can occur in TC surgery(eg, the lateral trajectory of the pterional approach), such asextension into the third ventricle or sella. Chakrabarti et al5

postulate the lower recurrence rate with TS surgery may also beattritubed to the extrapial location and smaller size of manycraniopharyngiomas treated transsphenoidally.

As demonstrated by our review and using single-center seriesdescribing both approaches, craniopharyngiomas appropriate forTS surgery tend to be anatomically different from those appro-priate for TC surgery, rendering meaningful comparison ofsurgical outcomes confounded by selection bias.

Visual Outcomes

As Laws et al79 noted in 1977, TS surgery is the quickest, mosteffective, and least dangerous mode of therapy for lesions pro-ducing visual impairment by compression of the optic nerves and

chiasm. Approaching craniopharyngiomas from below allows fordecompression of the tumor before manipulation of the opticapparatus. In contrast, the majority of TC approaches requiremanipulation of the optic apparatus and extracapsular dissectionbefore decompression of the tumor. These observations areconcordant with the higher rates of visual improvement and lowerrates of deterioration after TS compared with TC resection ofcraniopharyngiomas.

In our own series of 86 children treated with craniotomy,6 wefound that the most common new visual deficit was contralateral

TABLE 7.Comparison of Baseline Characteristics and Outcomes Following Resection of Pediatric Craniopharyngiomas via Transcranial and

Transsphenoidal Approachesa

Variable

Transcranial

Series, % (no.)

Transsphenoidal

Series, % (no.)

P

value

Preoperative vision deficits 53.5 (1051 of 1966) 68.5 (124 of 181) ,

.001Preoperative hydrocephalus 41.7 (678 of 1625) 5.1 (5 of 99) ,.001Preoperative increased ICP 42.6 (729 of 1713) 0 (0 of 138) ,.001GTR 60.9 (1693 of 2780) 72.1 (199 of 276) .0003Recurrence after GTR 17.6 (261 of 1518) 8.0 (16 of 201) .001Operative mortality 2.6 (68 of 2622) 1.3 (5 of 373) .21Neurological morbidity 9.4 (200 of 2140) 3.1 (10 of 325) ,.001Diabetes insipidus 69.1 (1437 of 2076) 23.9 (76 of 318) ,.001Vision improvement 47.7 (454 of 1051) 85.5 (106 of 124) ,.001Vision deterioration 13 (263 of 2029) 2.3 (8 of 352) ,.001Obesity or hyperphagia 32.2 (439 of 1363) 32.1 (35 of 109) 1.00Overall survival 90.3 (2039 of 2258) 93.9 (216 of 230) .075

aGTR, gross total resection; ICP, intracranial pressure.





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homonymous hemianopia, likely from manipulation of theipsilateral optic tract during resection of the retrochiasmaticportion of the tumor coming from the lateral (pterional) tra-jectory. Although many of these immediate deficits resolvedcompletely by 2 to 3 months, some children were left witha permanent, although rarely debilitating, superior quad-

rantanopsia. Most series of TS treatment of craniopharyngiomas,however, included few retrochiasmatic tumors, precluding directcomparison. As more centers gain experience with endoscopictechniques and mobilization of the pituitary gland, visual out-comes may be improved in children with these difficult retro-chiasmatic craniopharyngiomas, avoiding some of the morbidityof TC surgery.

Pituitary Dysfunction

Hypopituitarism and DI are some of the most prevalentdeficits that patients with craniopharyngiomas can have at pre-sentation and certainly after treatment. Many centers believe thatsome level of endocrinopathy should be accepted as a nearlyuniversal sequela to definitive craniopharyngioma treatment,5,6,20

but these deficits are often not a major source of significantmorbidity to patients in the modern era and in areas with readyaccess to medical care.20,80

In our review, postsurgical DI occurred in only 36% ofpatients treated transsphenoidally in contrast to 69% of TC cases.The underlying explanation may lie in the improved visualizationof the pituitary gland and stalk that allows a more controlled andsharp dissection of the tumor from the stalk. Moreover, anatomicdifferences may be partially responsible given the more distalinvolvement of the stalk in intrasellar tumors compared withprimarily suprasellar tumors that intimately involve the tuber

cinereum and proximal infundibulum.Given the high rates of DI with radical resection, regardless ofpituitary stalk integrity, in our TC experience6 and that ofothers,10,47,48,63,81 we stress that attempted stalk preservationshould not preclude GTR. Long-term management of post-operative DI did not appear to have a negative impact on OS orquality of life in our TC experience. In all cases of necessary stalksacrifice, we section as distal to the hypothalamus as possiblewithout compromising negative margins.

The reporting of adenohypophysis function before and aftersurgery was inconsistent and incomplete; therefore, direct com-parison between TS and TC surgery was not attempted. Most TSseries reported new anterior pituitary dysfunction in approxi-

mately one third of patients,68,82

and, in general, higher rates(.50%) were reported in the TC literature.39,63,83 Chakrabartiet al5 compared endocrinological outcomes of 68 patients whounderwent TS resection and 18 patients who underwent TCresection of craniopharyngiomas. They reported similar incidenceof new postoperative DI (67% vs 56%) but higher rates of newgrowth hormone deficiency (57% vs 22%), hypothyroidism(79% vs 22%) and hypocortisolemia (53% vs 17%) in the TCgroup after surgery. They attributed their higher rate of DI incomparison with other TS surgical series to their aggressive

approach aimed at complete resection. This is in accord with thetrend that we found in the literature in which higher rates of GTRwere associated with a higher incidence of permanent DI andanterior pituitary dysfunction after surgery.63,83,84

Craniopharyngiomas most commonly arise along the corridorfrom the floor of the third ventricle along the infundibulum

toward the sella. Given their anatomic origin, the pituitary glandis found ventral and anterior to the tumor in as many as 50% to60% of cases.22,31 To gain sufficient access to the dorsally locatedtumor when approaching from below, numerous centers havereported on successful mobilization of the gland using a verticalincision31,66,70,74 or en bloc mobilization85 with a low incidenceof iatrogenic hypopituitarism. Maira et al74 reported that incisionof the normal pituitary gland to reach a craniopharyngioma neverresulted in major functional damage to the anterior pituitary. Abeet al86 reported hypopituitarism in a least 1 domain in 6 of 25patients (24%) in whom a vertical incision of the pituitary wasmade to reach a dorsally located tumor (most commonly adre-nocorticotropic dysfunction). Therefore, despite the frequentneed for mobilization and manipulation of the pituitary glandwith TS-TN approaches and the high proportion of intrasellartumors treated via these approaches, the rate of new, severe en-docrinological deficits with TS surgery appears to be low.

Regardless of approach, patients, families, and primary physiciansshould still be counseled on the likelihood of postoperative hypo-pituitarism and DI. Modern endocrinological care is very successfulat supplementing endocrine deficiencies, guiding catch-up growthand nearly eliminating the risk of fatal endocrine crises. The successand safety of all treatment paradigms for craniopharyngiomas,however, depend rather heavily on regular postoperative endocri-nological support and the familial and societal resources to cope with

these common endocrine deficiencies.

87

In regions with limitedaccess to endocrine follow-up and acute care for emergencies, a moreconservative treatment paradigm may be warranted.

Hypothalamic Morbidity

Arguably the most physically, psychologically, and socially dev-astating sequela of craniopharyngioma treatment is hypothalamicinjury, a spectrum of dysfunction that can include hyperphagia,obesity, memory deficits, problems with social interaction, rage be-havior, and sleep-wake cycle and thermoregulatory disturbances.27,51

Some centers have identified preoperative risk factors that can predicthypothalamic morbidity and serve as a guide to limit aggressiveresection.27,51 De Vile et al27 reported a vertical tumor height of 3.5

cm, the presence of preoperative hypothalamic disturbance, andintraoperative adherence of the tumor to the floor of the thirdventricle to be predictive of hypothalamic morbidity. They recom-mend limited resection plus RT in those instances. Similarly, Puget etal51 developed an MRI-based grading scale that evaluated hypotha-lamic involvement by the tumor and recommend a stratified treat-ment strategy in accordance with the grade.

Regardless of the surgical approach, however, suprasellar cranio-pharyngiomas tend to adhere to the floor of the third ventricle.Describing TS surgery, Laws et al88 note the apex of the tumor

ELLIOTT ET AL




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represents the most difficult aspect of removal and, in many cases ofcraniopharyngiomas, there is significant adherence to the brain at themost dorsal aspect of the tumor. Although many authors havenoted the presence of a gliotic pseudocapsule that separates cra-niopharyngiomas from the floor of the third ventricle,11,47,61,63

neither TS nor TC surgery can avoid this dissection of the adherent

suprasellar tumor from the hypothalamus and its potentialmorbidity.

Although many studies did not define obesity and the re-porting of obesity and hyperphagia was available in less than 50%of patients in this review, we found no significant difference in therate of obesity between TS and TC studies. These trends maylikely be due to reporting bias and subjective assessments ofweight gain. Another possible explanation for the similar hypo-thalamic morbidity may be because of the typical anatomiclocation of craniopharyngiomas and their adherence to the floorof the third ventricle. However, many of the patients in the TSgroup had primarily intrasellar tumors, making the latter expla-nation unlikely. Comparing intrasellar and suprasellar cranio-pharyngiomas, Lee et al43 reported greater hypothalamicdisturbance, higher rates of obesity and hyperphagia, headache,and increased ICP in the suprasellar tumor group and a higherprevalence of visual deficits and hypopituitarism in the group ofpatients with intrasellar tumors. In agreement with other cen-ters,34,51 they contend that tumor location at presentation wasthe largest determinant of hypothalamic-pituitary dysfunctionbefore and after treatment. For those tumors that involve thesuprasellar region near the tuber cinereum, however, we believethat injury to the hypothalamus is not attributable to the type ofapproach per se, but rather a consequence of the involvement andadherence of the tumor to the walls of the third ventricle. Pre-

operative counseling of patients, families, and referring physiciansshould include discussing this risk before surgery, and surgery, viawhichever route, should proceed according to the wishes of theinvolved parties.

Determining the Optimal Approach

The morphology and directional growth of craniophar-yngiomas can vary widely and the surgical approach depends onthe origin of the tumor in relation to the diaphragma sella and thefloor of the third ventricle.70,84,89-92 Approximately one third ofall craniopharyngiomas involve the pituitary fossa.4,13,66,70,72,93

Expansion of the sella is the major preoperative imaging clue to anintrasellar origin of the tumor.73,94 The overlying diaphragm

serves as a barrier to entry into the intradural space and permitstraction on the capsule, making these tumors ideal candidates forTS resection. In contrast, tumors that arise supradiaphragmati-cally or have dumbbell-like configurations traversing the di-aphragm tend to directly adhere to the undersurface of the brain,making traction from below more dangerous.

Traditionally, indications for the TS approach were limitedto sellar or intra- and suprasellar, infradiaphragmatic cranio-pharyngiomas, preferably in patients with a well-pneumatizedsphenoid sinus and enlargement of the pituitary

fossa.31,63,66,70,73,93,95,96 However, variations on the standard TSapproach are becoming increasingly and successfully used toremove craniopharyngiomas completely or partially outside of theconfines of the sella. Advantages of TS approaches for cranio-pharyngiomas include direct access to the lesion, minimal or nobrain retraction, early bony decompression of the optic nerves

and chiasm with minimal direct manipulation, lower overallmorbidity, and shorter hospital stays.5,97 The transsellar trans-diaphragmatic approach can be used for tumors with significantportions above and below the diaphragm.5,31,74 Originally de-scribed by Weiss98 in 1987, the extended TS approach involvesremoval of the tuberculum sellae and was designed to removetumors lying completely within the suprasellar region. Somecenters have described the successful resection of craniophar-yngiomas located completely within the third ventricle via anendoscopic approach through the lamina terminalis.71

All extended TS approaches have been advanced by theadoption of the endoscope, used alone or in conjunction with themicroscope. As optics, video equipment, image guidance systems,endoscopic instrumentation, and our understanding of parasellaranatomy have improved,85,88,97 many surgeons are now per-forming these procedures entirely endoscopically via a TN cor-ridor. Visualization is reported to be superior with the endoscopecompared with the microscope and offers both close-up andwide-angle views of the pertinent anatomy and field of dissec-tion.97,99 In addition to the technical benefits, Dusick et al82

reported better patient satisfaction (less pain, better nasal airflow)and shorter hospital stays in patients who had endonasal surgerycompared with the traditional sublabial approach.

One major obstacle to successful TS tumor resection ispostoperative CSF leak and resultant meningitis. The initial

series describing TS resection of suprasellar tumors had ratherhigh rates of rhinorrhea.73,74,84,100 With or without the use oflumbar drainage, the rate of CSF leaks has markedly decreased overtime with advancements in reconstructive techniques of the an-terior cranial base including multilayered closures,101,102 pediclednasoseptal flaps,103,104 pedicled pericranial flaps,105,106 and endo-scopic suturing of facial grafts.107 In most series, the rate of CSFleak has decreased dramatically with surgical experience andadoption of these closure techniques.5,18,68,108 Further advancesthat will undoubtedly expand the utility of TS approaches forparasellar tumors include 3-dimensional109 and angled110 endo-scopes, a micro-Doppler probe to identify the carotid artery,88,108

binasal techniques with greater instrumentation maneuverability,

and the use of 2 surgeons simultaneously.85,95

Not all craniopharyngiomas, however, are appropriate for TSresection. Table 8 summarizes the relative indications and contra-indications to TC and TS surgery and the advantages and dis-advantages of each approach. Given the limitations in the field ofview and the tools necessary to halt significant bleeding, we and othercenters believe that the TS is contraindicated if complete resection isthe goal when tumors engulf or extend laterally to the carotid arteriesand those with significant suprasellar calcification (an indicator oftumoral adhesiveness to surrounding structures).5,18,66,78





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Ultimately, the decision on which approach and the plannedaggressiveness of resection must be determined on an individualbasis after considering the imaging findings and wishes and ex-pectations of the patient and family. TS and TC approaches canbe combined in a staged fashion to completely and most safelyresect the intrasellar and suprasellar portions. Moreover, TSsurgery can provide prompt and effective decompression ofcritical suprasellar structures; TS approaches should be consideredwhen STR is the goal and adjuvant RT planned. This strategymay spare children the potential morbidity of formal craniotomy.

Surgical Considerations of TS Approaches in Children

Originally used in adult patients with enlarged sellae, the TSapproach has been adapted for use in patients with normal sellaeand children, who often have non- or minimally aerated sinuses(conchal type). Thick bones of the sinuses and cranial base mayrequire drilling near the sella, planum, and the optic nerves. Abeand Ludeke66 reported that incompletely pneumatized sphenoidsinuses required drilling in 46% of patients in their series of 11children, but this did not hinder resection in any case. Werecommend using an irrigating drill with a diamond burr whendrilling the bones of cranial base to decrease the risk of thermal ormechanical injury to the optic nerves, chiasm, or internal carotidarteries. Other useful adjuncts include a micro-Doppler probe tobetter identify the carotid artery and stereotactic image guidance

with high-resolution computed tomography imaging in additionto the standard preoperative MRI.

As noted by Im et al,84 the poorly pneumatized sinuses andsmaller facial structure of children create an even narrowerworking corridor. They accomplished GTR of 6 large cranio-pharyngiomas via the TS approach by reliance on the cysticnature of all 6 tumors, the infradiaphragmatic origin of the tu-mor, and the use of micromirrors for lateral visualization. Theynote that predominantly cystic tumors are more common inadults than children, and early decompression can aid in the

extirpation of such tumors and removal of the capsule fromsurrounding structures. With the advent of angled endoscopesand improved optics, micromirrors will likely become obsolete.Nevertheless, taking advantage of the cystic nature of cranio-pharyngiomas is a critical surgical pearl that facilitates TS surgeryvia a long, narrow corridor.

Study Limitations

This meta-analysis is inherently limited by combining theexperience of multiple centers with different surgical experiencesand varying biases concerning the optimal extent of resection.The groups compared are not the same size (2955 patients in the

TC group vs 373 in the TS group). Discounting a handful ofpatients in this review, all studies included are retrospective innature and prone to the bias such methods of data collectionoffer. The functional outcomes were usually reported by thetreating surgeons, which may cause underreporting of complica-tions. Moreover, incomplete and inconsistent recording of thecollected data points in each study causes gaps in the tabulation andcalculation of the incidence of various outcome measures. This isreflected in the varying denominators shown for each variable inTable 2. Although we tried to limit the review to children withprimary craniopharyngiomas, there was a significant number ofadults included in many studies and a small number of recurrenttumors, factors that could skew the results and comparisons.

The stated goal of this meta-analysis was to analyze the pre-operative characteristics and outcomes of children treated withTC and TS surgery for craniopharyngiomas and, secondarily, todetermine whether comparison of surgical approaches was evenpossible. Determination of the optimal treatment strategy forpediatric craniopharyngiomas is beyond the scope of this study.Future studies are needed to determine the role of radiosurgery,fractionated radiotherapy, intracavitary therapies, and open sur-gery in the management of craniopharyngiomas of different sizesand disparate locations.

TABLE 8.Relative Indications and Contraindications to Transcranial and Transsphenoidal Resection of Craniopharyngiomas

Transcranial Approaches Transsphenoidal Approaches

Indications Large or giant tumors Purely intrasellar tumorsCystic or solid suprasellar tumors Intra- and surprasellar subdiaphragmatic tumors

Tumor entirely within the third ventricle Predominantly cystic tumorsAdvantages Excellent visualization and control of major arteries Early decompression of tumor before optic apparatus manipulationShorter hospital staysLess tissue trauma and brain retractionLess pain

Contraindications Intrasellar tumors Tumors with ex tension lateral to the internal carotid arteryLarge or giant tumorsEncasement of arteries of circle of Willis or optic apparatusSuprasellar lesions with peripheral calcifications

Disadvantages Brain retraction Immature (conchal) sphenoid sinusManipulation of optic apparatus before tumor removal Poor control of hemorrhage (arterial injury)

Risk of cerebrospinal fluid leak

ELLIOTT ET AL




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Nevertheless, the strength of this report lies in the large numberof cases in each treatment class. We used strict criteria for inclusion.We included studies after 1990 to better use the benefits offered bymultiplanar MRI and microsurgical techniques in surgical plan-ning and treatment. Surgical success and the incidence of com-plications have been correlated with surgeon experience.51,111 We

attempted to control for surgeon experience by creating a minimalnumber of surgeries performed for inclusion in this study.

We believe that this meta-analysis does provide guidance as tothe safety and efficacy of TC and TS surgery in children. Thesedata are critical when discussing the risks of aggressive treatmentof craniopharyngiomas with patients, their families, and referringphysicians. Improved outcome measures and prospective re-porting are essential to determine the role of aggressive surgery inthe management of pediatric craniopharyngiomas.

CONCLUSION

Directly comparing outcomes after TC and TS surgery for

pediatric craniopharyngiomas may not be valid. The patientpopulations with craniopharyngiomas treated with TS ap-proaches tended to have less hydrocephalus and ICP increase,greater visual deficits, smaller and more cystic tumors, and moreintrasellar disease than those who had TC surgery. These dif-ferences create selection bias that may explain the improved ratesof disease control and lower morbidity of TS craniopharyngiomaresection. However, these findings do not diminish the excellentresults afforded by TS removal of craniopharyngiomas in adultsand children. The TS approach is commonly used for cranio-pharyngiomas that are purely intrasellar. There is growing ex-perience using the TS approach for select tumors that have bothsellar and suprasellar components. Craniotomy is indicated for

larger tumors, suprasellar tumors with significant lateral exten-sion, those that engulf vascular structures, and those with sig-nificant peripheral calcification. Nevertheless, as TS techniquesand instrumentation continue to advance, there will be continuedexpansion of the indications for its use and undoubtedly con-tinued improvements in functional outcomes for children withcraniopharyngiomas.

Disclosure

The authors have no personal financial or institutional interest in any of the

drugs, materials, or devices described in this article.

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COMMENT

In this systematic review, the authors synthesize findings from 61studies that report on preoperative characteristics and postoperative

outcomes after transcranial (TC) or transsphenoidal (TS) surgery for

craniopharyngiomas in children. They report that patients who had TCsurgery had larger tumors, more hydrocephalus, and more suprasellardisease. Hence, at present, selection bias precludes comparison of out-comes between these 2 approaches. As TS surgery continues to evolve

with expanded TS approaches, more surgeons are beginning to use thisapproach for larger tumors that are midline and suprasellar in location.Therefore, a careful selection of TC and TS cases may yield a faircomparison of the 2 approaches in the future.

Chirag G. PatilLos Angeles, California



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