From: Subject: Repeat Operations in Pediatric Patients with Recurrent Craniopharyngiomas Date: Tue, 6 Apr 2010 21:47:08 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CAD5D2.B4BAA620" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CAD5D2.B4BAA620 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000277620 =EF=BB=BF Repeat Operations in Pediatric Patients with = Recurrent Craniopharyngiomas Background: Controversy continues over the optimal = management of recurrent craniopharyngiomas. Our strategy for approaching = repeatedly recurrent craniopharyngiomas in pediatric patients has been = to decompress vital structures and relieve the symptoms as early as = possible. The purpose of this study was to present our experiences of = repeatedly recurrent craniopharyngiomas and the pattern of failure = associated with treatment. Methods: A retrospective review was = conducted on 7 pediatric patients who underwent resection >2 times in a = single institution between 1990 and 2004. Resections were performed = 3=E2=80=938 times for each patient. Variables including tumor size, = consistency and location, extent of resection, adjuvant therapy and = morbidity were evaluated. Results: Thirty-two operations were = performed in 7 pediatric patients. Total resection was not achieved by = the third surgery and thereafter, and the interval between each surgery = became shorter. Appetite disorders, neurocognitive disorders and = behavioral disorders occurred following repeat surgeries. = Conclusion: Repeat operations are associated with a high failure = rate of tumor control, even though they can help relieve neurologic = symptoms. It is suggested that the number of repeat operations should be = limited."=20 name=3Dcitation_abstract>

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Vol. 45, No.=20 6, 2009 =20

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Original Paper

Repeat Operations in = Pediatric=20 Patients with Recurrent Craniopharyngiomas
Woo = Young=20 Janga, Kwan-Sung Leea, Byung = Chul=20 Sonb, Sin-Soo Jeuna, Yong-Kil=20 Honga, Sang Won Leeb, Seung-Ho=20 Yangb

aDepartment of=20 Neurosurgery, Seoul St. Mary=E2=80=99s Hospital, = Catholic University=20 of Korea, Seoul, and
bDepartment of=20 Neurosurgery, St. Vincent=E2=80=99s Hospital, Catholic = University of=20 Korea, Suwon, Korea

Address=20 of Corresponding Author

Pediatr Neurosurg 2009;45:451-455 (DOI:=20 10.1159/000277620)

 Outline

  • Key=20 Words
  • Abstract=20
  • Introduction
  • Clinical=20 Material and Methods
  • Results
  • Discussion=20
  • References=20
  • Author=20 Contacts=20
  • Article=20 Information=20
  • Publication=20 Details=20
  • Drug=20 Dosage / Copyright

  Key = Words

  • Craniopharyngioma
  • Recurrence
  • Radiotherapy

  Abstract

Background: Controversy continues over the = optimal=20 management of recurrent craniopharyngiomas. Our = strategy for=20 approaching repeatedly recurrent craniopharyngiomas in = pediatric patients has been to decompress vital = structures and=20 relieve the symptoms as early as possible. The purpose = of this=20 study was to present our experiences of repeatedly = recurrent=20 craniopharyngiomas and the pattern of failure = associated with=20 treatment. Methods: A retrospective review was=20 conducted on 7 pediatric patients who underwent = resection=20 >2 times in a single institution between 1990 and = 2004.=20 Resections were performed 3=E2=80=938 times for each = patient.=20 Variables including tumor size, consistency and = location,=20 extent of resection, adjuvant therapy and morbidity = were=20 evaluated. Results: Thirty-two operations were=20 performed in 7 pediatric patients. Total resection was = not=20 achieved by the third surgery and thereafter, and the = interval=20 between each surgery became shorter. Appetite = disorders,=20 neurocognitive disorders and behavioral disorders = occurred=20 following repeat surgeries. Conclusion: Repeat=20 operations are associated with a high failure rate of = tumor=20 control, even though they can help relieve neurologic=20 symptoms. It is suggested that the number of repeat = operations=20 should be limited.

Copyright =C2=A9 2010 S. Karger AG, Basel

 Introduction

Craniopharyngiomas are rare intracranial tumors in=20 childhood, representing 1.2=E2=80=934.4% of tumors of = the central=20 nervous system. Although the histology is benign and = the=20 mortality rate low, craniopharyngiomas are associated = with a=20 high rate of recurrence, which, in turn, is associated = with a=20 high rate of morbidity [1]. Although=20 the optimal management of craniopharyngiomas remains=20 controversial, the extent of surgical resection has = been=20 considered the most significant predictive factor of = tumor=20 cure and good functional outcome [2,3]. The=20 rationale for maximal resection has been challenged = because=20 surgical complications such as hypothalamo-pituitary=20 dysfunction or optic nerve damage are serious = morbidities.=20 Therefore, studies have supported the trend toward = less=20 surgical aggressiveness and the broad use of = irradiation after=20 subtotal resection or at the time of progression [4,5]. However,=20 subtotal resection is associated with a higher number = of=20 recurrences, which bear a poor prognosis [6,7].=20 Morbidity caused by recurrence and the surgical = results after=20 repeat procedures are thus an important parameter for = the=20 long-term evaluation of the management of = craniopharyngiomas=20 [8,9].

Repeat operations for recurrent craniopharyngiomas = have=20 been the subject of only few studies. In cases of = recurrent=20 craniopharyngiomas after primary surgery and radiation = therapy, we performed repeat surgeries for the relief = of=20 symptoms such as increased intracranial pressure, = visual=20 disturbances and mental deterioration. Based on our = strategy,=20 we have operated on 87 patients with = craniopharyngiomas since=20 1990. In this study, we focused on pediatric patients = with=20 repeatedly recurrent tumors who underwent surgery more = than 2=20 times. We evaluated the failure pattern and associated = factors=20 of repeated recurrences.

 

 Clinical = Material and=20 Methods

We conducted a database search for patients who had = been=20 diagnosed with craniopharyngiomas at a single = institution=20 since 1990 after the advent of MR imaging. = Eighty-seven=20 patients underwent surgery for the initial treatment = of=20 craniopharyngiomas. The purpose of the initial surgery = was=20 total resection whenever possible without risking = damage to=20 the hypothalamus or visual pathway. In cases resulting = in=20 subtotal resection at the first operation, we = subsequently=20 performed radiotherapy. When recurrence was = accompanied by=20 signs and symptoms such as intracranial hypertension, = focal=20 neurologic deficits, seizures and mental = deterioration, we=20 opted to perform a reoperation. The purpose of the = reoperation=20 was total tumor resection with the preservation of = functioning=20 and the relief of symptoms. In cases involving tumor=20 recurrence or progression, even following reoperation = and=20 radiotherapy, a repeat reoperation was performed with = the goal=20 of maximal resection and relief of symptoms. The = extent of=20 resection was determined based on the = surgeon=E2=80=99s report and=20 postoperative MR images.

Based on our policy, 7 (5 males and 2 females) of = 87=20 patients underwent operations >2 times. Data were = extracted=20 from clinical notes, surgical reports and radiologic = reports.=20 The ages of the 7 patients ranged from 6 to 16 years = (mean: 12=20 years). The median number of surgeries was 4 (range: = 3=E2=80=938). The=20 median follow-up duration was 10 years (range: = 5=E2=80=9314=20 years).

 

 Results

Between 1990 and 2004, we operated on 87 patients = with the=20 diagnosis of craniopharyngioma; 61 were adult and 26 = pediatric=20 patients. The age ranged between 5 and 80 years. = During=20 craniopharyngioma surgery, gross total resection was = achieved=20 in 28 patients (32.2%). Three of the 28 patients = (10.7%) had=20 tumor recurrences, and the mean time between the first = surgery=20 and recurrence was 84 months. Of the other patients (n = =3D 59)=20 with subtotal and partial resections, adjuvant = radiotherapy=20 and radiosurgery was performed in 34 and 4 patients,=20 respectively. Fifteen patients were followed without = adjuvant=20 therapy. Six patients were treated with bleomycin via = an=20 Ommaya valve reservoir. Eighteen of the 59 patients = (30.5%)=20 had tumor recurrences, and the mean time between the = first=20 surgery and recurrence was 11.5 months. In our = institution,=20 symptomatic recurrence has been an indication for = reoperation=20 irrespective of adjuvant therapy.

Seven pediatric patients with tumor recurrences = underwent=20 craniotomies >2 times. The patient characteristics = are=20 summarized in table 1.=20 The tumor height in the midline ranged from 2.8 to 6.3 = cm. The=20 consistency of tumors included 2 cystic, 1 solid and 4 = mixed=20 components. Calcifications and hydrocephalus = accompanied 57.1%=20 and 71.4% of the tumors at the time of initial = presentation,=20 respectively. The extent of the first surgical = resection was a=20 gross total resection in 2 patients, a subtotal = resection in 4=20 patients and a partial resection in 1 patient (table = 2).=20 Adjuvant radiotherapy was delivered within 5 months = after the=20 initial operation; the radiation dosage ranged from = 4,500 to=20 5,040 cGy. Radiotherapy was performed following the = second=20 operation in 2 patients. The indications for radiation = after=20 the second operation were a rapid growth of a remnant = tumor in=20 case 1, and a staged operation in case 3. In the = second=20 operation, gross total, subtotal and partial = resections were=20 achieved in 2 and 4 patients, and 1 patient, = respectively. In=20 the third operation, subtotal and partial resections = were=20 achieved in 5 and 2 patients, respectively. Gross = total=20 resection was not achieved with the third operation = and=20 beyond.

3DTAB01=20
Table 1. Patient=20 = characteristics

3DTAB02=20
Table 2. Extent of = repeated=20 surgery and timing of radiation=20 therapy

A total of 32 operations were performed in 7 = pediatric=20 patients. The median interval between the first and = second=20 operations was 58 months; between the second and third = operations it was 11 months, and between the third and = fourth=20 operations 12.5 months. The interval between the = fourth and=20 fifth operations was 8.5 months (table 3).=20 A longer interval between the first and second = surgeries was=20 associated with total resection (cases 2 and 5) and = early=20 irradiation (cases 6 and 7).

3DTAB03=20
Table 3. Surgical = approaches=20 and intervals between each=20 surgery

After the first and second surgeries, all 7 = patients=20 developed panhypopituitarism, requiring lifelong = hormone=20 supplementation of all pituitary hormones including=20 vasopressin, cortisol, and thyroxine. The other = complications=20 associated with repeat surgeries included appetite = disorders=20 and hypothalamic obesity (100%), neurocognitive = disorders and=20 learning disabilities (100%), neuropsychological and=20 behavioral disorders (42.9%), and sleep disorders = (42.9%).=20 Four of 5 patients presenting with visual disturbances = had=20 visual deterioration at the last follow-up visit. = There were=20 no surgery-related mortalities.

 

 Discussion

The treatments available for the recurrence of=20 craniopharyngiomas include reoperation, irradiation = and=20 radiosurgery [10,11]. In the=20 case of a cystic recurrence, intracystic bleomycin or=20 intracystic irradiation is effective [12].=20 Radiotherapy has been the proposed management either = after=20 subtotal resection or at the time of recurrence [13].=20 However, there is no consensus on the optimal = management of a=20 recurrence or progression after maximal resection and=20 irradiation. Our strategy for approaching repeatedly = recurrent=20 craniopharyngiomas in pediatric patients has been to=20 decompress close anatomic structures and relieve the = symptoms=20 as early as possible.

Recurrent craniopharyngiomas grow along the path of = least=20 resistance, extending into the basal cisterns, third = ventricle=20 and cerebral hemispheres. The tumor can also displace = the=20 optic nerves and chiasm and grow superiorly into the=20 hypothalamus and brain stem. At the first surgery, = there is=20 usually a natural cleavage plane between the tumor and = the=20 surrounding normal brain that results from a dense = peritumoral=20 gliotic reaction. However, at recurrence after radical = surgery, this gliotic reaction is not present, and = this=20 renders further surgical resection very challenging, = with a=20 high risk of complications and a low rate of local = control [14]. In our=20 series, total resection was not achieved with the = third=20 surgery and thereafter, and the interval between each = surgery=20 became shorter. Most surgical complications occurred = after the=20 first and second surgeries, which were performed in = order to=20 achieve total or radical resection. The purpose of a = repeat=20 reoperation was maximal resection and a relief of = symptoms,=20 which was different from that of the first and second=20 operation. A candidate for repeat reoperation was a = patient=20 who developed a rapid regrowth of tumor accompanied by = neurological symptoms.

Repeat surgeries after the second surgery were not = related=20 to serious morbidities, except for wound = complications. There=20 was no evidence of tumor seeding during repeat = surgeries.=20 Repeat operations were better tolerated than the first = and=20 second attempts in terms of symptom relief and = surgical=20 morbidity because endocrine disturbances were already=20 established and balanced by medical treatments. In our = series,=20 all patients were followed up for >5 years. Tumor=20 progression itself was not the main cause of death. = The=20 quality of life of long-term survivors was less = because of=20 visual disturbances and endocrinopathies such as = obesity and=20 diabetes insipidus. Obesity has a marked impact on the = patient=E2=80=99s quality of life and is associated = with diminished=20 motility and impaired schooling. The relation of = obesity to=20 surgical damage has been debated. Obesity, unlike=20 hypopituitarism, results from preoperative damage = rather than=20 from surgery itself [15]. In our=20 series, subtotal resection, tumor recurrence and = obesity are=20 closely correlated. Although no patients died during = the=20 perioperative period, 3 patients died after the = perioperative=20 period of endocrine disorders caused by hypothalamic=20 damage.

The appropriate time point and dose of irradiation = after=20 incomplete resection are controversial in the = literature as=20 well as in the clinical setting. Moon et al. [16]=20 suggested that early radiation therapy should be = highly=20 recommended for a better quality of life and longer = survival.=20 In this series, the total radiation dose ranged from = 45 to=20 55.8 Gy, with a median dose of 54 Gy using a = conventional=20 fractionation dose (1.8 Gy per fraction a day, 5 days = a week).=20 Habrand et al. [17] showed=20 that a high dose of radiation (=E2=89=A755 Gy) = significantly=20 influenced the outcome of patients who were irradiated = with a=20 total dose between 45 and 56 Gy (median: 50 Gy). = Regine et al.=20 [18]=20 reported a 44% risk of relapse below 54 Gy versus 16% = above 54=20 Gy. In our series, radiation therapy was given within = 5 months=20 after the first surgery. A relatively low dose of = radiation=20 (<50.4 Gy) has been suggested to lead to poor tumor = control. Conversely, other series have found no such=20 dose-effect relationship [19].

From this limited experience, it is crucial to = reduce the=20 number of repeat surgeries in the management of=20 craniopharyngiomas. To accomplish this goal, the = initial=20 operation to remove the tumor needs to be as = aggressive as=20 possible so as not to develop critical, irreversible = or=20 uncontrollable complications such as visual = deterioration and=20 hypothalamus-related neurologic dysfunctions. In = conclusion,=20 repeat operations for recurrent craniopharyngiomas are = associated with a high failure rate of tumor control, = even=20 though repeat operations can help relieve neurologic=20 symptoms.

  References



1
Raimondi AJ, Rougerie J: A critical review of = personal=20 experiences with craniopharyngioma: clinical = history,=20 surgical technique and operative results. Pediatr = Neurosurg=20 1994;21:151=E2=80=93154. 3D"External

2
Hoffman HJ, de Silva M, Humphreys RP, Drake JM, = Smith=20 ML, Blaser SI: Aggressive surgical management of=20 craniopharyngiomas in children. Childs Nerv Syst=20 1992;76:47=E2=80=9352. 3D"External

3
Fahlbusch R, Honegger J, Paulus W, Huk W, = Buchfelder M:=20 Surgical treatment of craniopharyngiomas: experience = with=20 168 patients. J Neurosurg = 1999;90:237=E2=80=93250. 3D"External

4
Merchant TE, Kiehna EN, Sanford RA, Mulhern RK, = Thompson=20 SJ, Wilson MW, Lustig RH, Kun LE: Craniopharyngioma: = the St.=20 Jude Children=E2=80=99s Research Hospital experience = 1984=E2=80=932001. Int=20 J Radiat Oncol Biol Phys = 2002;53:533=E2=80=93542. 3D"External

5
Sainte-Rose C, Puget S, Wray A, Zerah M, Grill = J,=20 Brauner R, Boddaert N, Pierre-Kahn A: = Craniopharyngioma: the=20 pendulum of surgical management. Childs Nerv Syst=20 2005;21:691=E2=80=93695. 3D"External

6
Regine WF, Kramer S: Pediatric = craniopharyngiomas:=20 long-term results of combined treatment with surgery = and=20 radiation. Int J Radiat Oncol Biol Phys=20 1992;24:611=E2=80=93617. 3D"External

7
Sands SA, Milner JS, Goldberg J, Mukhi V, = Moliterno JA,=20 Maxfield C, Wisoff JH: Quality of life and = behavioral=20 follow-up study of pediatric survivors of = craniopharyngioma.=20 J Neurosurg 2005;103:302=E2=80=93311. 3D"External

8
M=C3=BCller HL, Gebhardt U, Pohl F, Flentje M, = Emser A,=20 Warmuth-Metz M, Kolb R, Calaminus G, S=C3=B6rensen = N: Relapse=20 pattern after complete resection and early = progression after=20 incomplete resection of childhood craniopharyngioma. = Klin=20 Padiatr 2006;218:315=E2=80=93320. 3D"External

9
Vinchon M, Dhellemmes P: Craniopharyngiomas in = children:=20 recurrence, reoperation and outcome. Childs Nerv = Syst=20 2008;24:211=E2=80=93217. 3D"External

10
Caldarelli M, di Rocco C, Papacci F, Colosimo C: = Management of recurrent craniopharyngioma. Acta = Neurochir=20 1998;140:447=E2=80=93454. 3D"External

11
Kalapurakal JA, Goldman S, Hsieh YC, Tomita T, = Marymont=20 MH: Clinical outcome in children with recurrent=20 craniopharyngioma after primary surgery. Cancer J=20 2000;6:388=E2=80=93393. 3D"External

12
Jiang R, Liu Z, Zhu C: Preliminary exploration = of the=20 clinical effect of bleomycin on craniopharyngiomas.=20 Stereotact Funct Neurosurg = 2002;78:84=E2=80=9394. 3D"External

13
Rajan B, Ashley S, Gorman C, Jose CC, Horwich A, = Bloom=20 HJG, Marsh H, Brada M: Craniopharyngioma: long-term = results=20 following limited surgery and radiotherapy. = Radiother Oncol=20 1993;26:1=E2=80=9310. 3D"External

14
Dhellemmes P, Vinchon M: Radical resection for=20 craniopharyngiomas in children: surgical technique = and=20 clinical results. J Pediatr Endocrinol Metab=20 2006;19:329=E2=80=93335. 3D"External

15
Vinchon M, Weill J, Delestret I, Dhellemmes P:=20 Craniopharyngioma and hypothalamic obesity in = children.=20 Childs Nerv Syst 2009;25:347=E2=80=93352. 3D"External

16
Moon SH, Kim IH, Park SW, Kim I, Hong S, Park = CI, Wang=20 KC, Cho BK: Early adjuvant radiotherapy toward = long-term=20 survival and better quality of life for = craniopharyngiomas:=20 a study in single institute. Childs Nerv Syst=20 2005;21:799=E2=80=93807. 3D"External

17
Habrand JL, Ganry O, Couanet D, Rouxel V, = L=C3=A9vy-Piedbois=20 C, Pierre-Kahn A, Kalifa C: The role of radiation = therapy in=20 the management of craniopharyngioma: a 25-year = experience=20 and review of the literature. Int J Radiat Oncol = Biol Phys=20 1999;44:255=E2=80=93263. 3D"External

18
Regine WF, Mohiuddin M, Kramer S: Long-term = results of=20 pediatric and adult craniopharyngiomas treated with = combined=20 surgery and radiation. Radiother Oncol=20 1993;27:13=E2=80=9321. 3D"External

19
Wen BC, Hussey DH, Staples J, Hitchou PW, Jani = SK,=20 Vigliotti AP, Doornos JF: A comparison of the roles = of=20 surgery and radiation therapy in the management of=20 craniopharyngioma. Int J Radiat Oncol Biol Phys=20 1989;17:1313=E2=80=931321. 3D"External

  Author = Contacts

Seung-Ho Yang, MD
Department of Neurosurgery, = St.=20 Vincent=E2=80=99s Hospital
Catholic University of = Korea, 93-6=20 Chi-dong
Paldal-gu, Suwon 442-723 (Korea)
Tel. = +82 31=20 249 8304, Fax +82 31 245 5208, E-Mail 72ysh@catholic.ac.kr

  Article=20 Information

Received: April 14, 2009
Accepted after = revision:=20 October 26, 2009
Published online: January 26,=20 2010
Number of Print Pages : 5
Number of = Figures=20 : 0, Number of Tables : 3, Number of = References=20 : 19

  Publication=20 Details

Pediatric Neurosurgery

Vol. 45, No. 6, Year 2009 (Cover Date: March = 2010)

Journal Editor: Frim D.M. (Chicago, Ill.)
ISSN:=20 1016-2291 (Print), eISSN: 1423-0305 (Online)

For additional information: = http://www.karger.com/PNE

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Drug Dosage: The authors and the publisher have = exerted=20 every effort to ensure that drug selection and dosage = set=20 forth in this text are in accord with current = recommendations=20 and practice at the time of publication. However, in = view of=20 ongoing research, changes in goverment regulations, = and the=20 constant flow of information relating to drug therapy = and drug=20 reactions, the reader is urged to check the package = insert for=20 each drug for any changes in indications and dosage = and for=20 added warnings and precautions. This is particularly = important=20 when the recommended agent is a new and/or = infrequently=20 employed drug. Copyright: All rights reserved. No part = of this=20 publication may be translated into other languages, = reproduced=20 or utilized in any form or by any means, electronic or = mechanical, including photocopying, recording, = microcopying,=20 or by any information storage and retrieval system, = without=20 permission in writing from the publisher or, in the = case of=20 photocopying, direct payment of a specified fee to the = Copyright Clearance Center.

  


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