NEURO-ONCOLOGY

Developments in Oncology

Volume 66

The titles published in this series are listed at the end of this volume.

Neuro-Oncology

edited by

P. Paoletti Professor of Neurosurgery, University of Pavia, Pavia, Italy

K. Takakura Professor and Chairman, Department of Neurosurgery, University of Tokyo, Tokyo, Japan

M.D. Walker Director Division of Stroke and Trauma, National Institute ofNeurological Disorders and Stroke, National Institute of Health, Bethesda, U.S.A.

G. Butti Assistant Professor of Neurosurgery, University of Pavia, Pavia, Italy

and

S. Pezzotta Associated Professor of Neurosurgery, University of Pavia, Pavia, Italy

SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

Library of Congress Cataloging-in-Publication Data Neuro-oncology I edlted by P. Paolettl ... [et al . l.

p. cm . -- IDevelopments In oncology : v . 66) Proceed"lngs of the International Symposlum on Advances In Neurc

-Oncology, held Sept. 26-29, 1990 In San Remo, Italy: sponsored by the Unlversity of Pavla, I.R . C. C.S. Pol lcllnlco San Matteo, and the Giovanni Lorenzlni Medical Foundatlon .

Inc 1 udes 1 ndex . ISBN 978-94-010-5390-7 ISBN 978-94-011-3152-0 (eBook) DOI 10.1007/978-94-011-3152-0 1. Braln--Cancer--Congresses. 1 . Paolettl, Pletra, 1934-

II . International SympoSium on Advances In Neuro-Oncology (1990 San Ramo. Italy) III . Unlversita dl Pavla. IV. I.R.C . C. S. Policlinico San Matteo. V. Fondazione Giovanni Lorenzini. VI. Series.

[DNLM : 1. Brain Neoplasms--congresses. 2. Glioma--congresses. W1 DE998N v . 66 I WL 358 N49353 19901 RC280.B7N47 1991 616.99 · 481--dc20 DNLM/DLC for Library of Congress

ISBN 978~94-0rO-5390-7

Printed on acid-free paper

AII Rights Reserved © 1991 Springer Science+Business Media Dordrecht Originally published by K1uwer Academic Publishers in 1991 Softcover reprint of the hardcover 1 st edition 1991

91-7051

No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owner.

Placida notte, e verecondo raggio della cadente luna; e tu che spunti per la tacita selva in su la rupe nunzio del giorno

G. Leopardi, Maggio 1822

Table of Contents

Preface xiii

List of First Contributors xv

PART ONE BIOLOGY AND DIAGNOSIS

1. Pathology of brain tumors and its clinicobiological correlates D. Schiffer 3

2. Immunohistochemistry in brain tumor classification W. Wechsler and G. Reifenberger 11

3. Molecular biological events in the selection of chemotherapy resistant-cells in human malignant gliomas

J.R. Shapiro and A.C. Scheck 21 4. Expression of multiple activated cellular oncogenes in human brain tumors

M.A. Gerosa, G. Della Valle, M. Tognon, L. Faggioli, A. Nicolato, M. Vitale, L. Cristofori, C. Vivenza and A. Bricolo 27

5. Proliferative potential of astrocytomas and glioblastomas T. Hoshino 33

6. The biological relevance of Arachidonic Acid Metabolism in human brain tumors P. Gaetani, Ch. Chiabrando, M. Danova, F. Marzatico, V. Silvani, G. Butti and R. Rodriguez y Baena 41

7. Computed tomography and magnetic resonance in the diagnosis of brain tumors G. Scotti and S. Livian 49

8. The application of positron emission tomography in studies of human cerebral glioma D.G.T. Thomas 57

9. Angiography in brain tumours G.B. Bradac, A. Riva and M. Bracchi 63

10. Stereotactic approach in brain tumors F. Giunta, V. Scipione, F. Zorzi and G. Marini 69

11. Cellular localization of glucocorticoid receptor mRNAs in human CNS tumors by in situ hybridization

L. Magrassi, E. Silini, G.L. Brambilla, R. Assietti, G. Milanesi and G. Butti 77 12. Proto-oncogene expression and proliferative activity in human malignant gliomas

A. Riccardi, M. Danova, M. Giordano, P. Gaetani, G. Butti, C. Zibera and G. Mazzini 81

13. Coexpression of PDGF and PDGF-receptors genes in human astrocytic gliomas A. Mauro, A. Bulfone, A. Di Sapio, L. Sosso and D. Schiffer 85

14. Diagnostic and prognostic significance of positron emission tomography in gliomas K. Mineura, T. Sasajima, M. Kowada, F. Shishido and K. Uemura 89

15. Brain haemodynamics in intracranial supratentorial tumors G. Acerbi, G. Liberti, A. Pieri and P. Caciagli 93

16. The glycosphingolipids of human astrocytomas B.L. Bauer, R. Jennemann, A. Rodden, H.-D. Mennel and H. Wiegandt 97

17. Findings of aberrant epidermal growth factor receptor in primary human malignant gliomas

N. Sugawa, AJ. Ekstrand, C.D. James and V.P. Collins 101

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18. Expression of epidermal growth factor receptor (EGF-R) and Erb-B2 (HER 2/NEU) in glioblastoma (GBM): prognostic relevance

E.M. Hiesiger, RL. Hayes, L. Thoron, G.N. Budzilovich, D.M. Pierz, A Wise and I. Ransohoff 105

19. Evaluation of the proliferative potential of gliomas by KI 67 immunolabelling of stereotactic biopsy samples

M. Parent, S. Blond, P. Gosset, F. Dubois, R Assaker, I.L. Christiaens and A Dupont 109

20. Immunobiology of visualizable brain tumor cells: gamma interferon induces changes in the immune environment in each compartment of brain tumor spread

L.A. Lampson and M.P. Sethna 113 21. Epidemiology of primary cerebral tumors. Results of a multi-center study in the

Veneto region of northern Italy P. Zampieri, G.B. Soattin, R Faggin, P.L. Longatti, M. Gerosa, C. Licata, L. Casentini, V. Fornezza, A. Agostini and S. Mingrino 117

22. Simvastatin, a blocker of cholesterol biosynthesis inhibits human glioma cell profileration

M.R Soma, P. Pagliarini, G. Butti, R Paoletti, P. Paoletti and R Fumagalli 121

PART TWO THERAPY OF GLIOMAS

23. Surgery of cerebral gliomas: state of the art P. Paoletti, G. Butti and G. Spanu 129

24. Advances in neuro-oncology for adult patients with supratentorial gliomas: from the window of radiation oncology

AB.M.F. Karim, I.H. Kralendonk and B.J. Slotman 137 25. Recent clinical results in the chemotherapy of brain tumors: BTCG studies

W.R Shapiro, S.B. Green, P.C. Burger, RG. Selker, M.S. Mahaley, I. Mealey, I.T. Robertson, F.H. Hochberg, I.D. Vangilder, 1. Ransohoff and R Young 147

26. Clinical application of radiolabeled human X human monoclonal antibody with interferon in the treatment of malignant glioma - preliminary report

M. Nagai, T. Arai, K. Watanabe, K. Ichikawa and T. Watari 153 27. Targeted therapy for CNS tumours with monoclonal antibodies (MAbs)

V. Papanastassiou, B.L. Pizer, R. Moseley, I.T. Kemshead and H.B. Coakham 161 28. Early or late surgery for supratentorial gliomas? A randomized study

R. Knerich, G. Ubezzi, P. Buoncristiani, B. Tanghetti, D. Adinolfi, R Assietti, M. Rolli, V. Silvani, L. Princi and D. Schiffer 167

29. Reoperation in the treatment of recurrent intracranial malignant astrocytomas M. Ammirati and lH. Galicich 171

30. Symptomatic subependymoma: a clinico-pathologic and flow cytometric study D. Lombardi, B. Scheithauer, F.B. Meyer, G.S. Forbes, E.G. Shaw, D.J. Gibney and I.A. Katzmann 175

31. Prognostic factors in anaplastic astrocytomas after surgery and conventional radiotherapy

R. Soffietti, A Chio, M.T. Giordana, R Ruda, S. Sales, E. Vasario and D. Schiffer 179

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32. Intraoperative radiation therapy (IORT) for cerebral glioblastoma M. Matsutani and O. Nakamura 181

33. Positron emission tomography (PET) applied to stereotactic interstitial brain brachytherapy for malignant glioma patients

H.W. Chin, J.M. Bertoni and A.H. Fruin 185 34. Radiosensitization of human glioma cells by buthionine sulfoximine-induced

glutathione depletion T. Yoshimine, A. Murasawa, H. Nakata and T. Hayakawa 189

35. Degenerative effects of the radiotherapy on the cerebral gliomas R. D'Avanzo, M. Natale, M. Lama and F.A. Cioffi 193

36. High dose ACNU chemotherapy with autologous bone marrow transplantation for human malignant brain tumors

I. Yamashita, K. Shoin and M. Soma 197 37. Intrathecal perfusion therapy with nitrosoureas against subarachnoid dissemination of

glioma: experimental and clinical studies M. Kochi, Y. Ushia, J. Kuratsu, Y. Mihara, S. Takaki and S. Uemura 201

38. The potential role of lonidamine in the combined treatment of malignant gliomas. A randomized study

C.M. Carapella, M.G. Paggi, F. Calvosa, F. Cattani, A. Floridi, B. Iandolo, L. Raus and A. Riccio 205

39. Rabbit brain concentrations of doxorubicin during intraarterial infusions SJ. Hassenbusch 209

40. 8-chloro-cyclic adenosine monophosphate is a potent inhibitor of human glioma cell proliferation in vitro

C.H. Langeveld, M.P. van Waas, I.J. Heimans and J.C. Stoof 213 41. Radiosensitization with carotid arterial infusion of bromodeoxyuridine (BUdR) ± 5

fluorouracil (5FU) biomodulation with focal external beam radiation (FEBT) for malignant gliomas

H.S. Greenberg, W.F. Chandler, W.D. Ensminger, L. Junck, A. Thornton, H. Sandler, M.A. Page, P. McKeever, S. Gebarski, B. Liang and R. Tankanow 217

42. Interstitial chemotherapy with drug impregnated polymer implants to treat brain tumors: pre-clinical and clinical studies

A. Olivi, A. Domb, D. Lenartz, R. Tamargo and H. Brem 221 43. Biologic response to intracavitary interleukin-2/lymphokine activated killer (LAK)

cells in the treatment of primary malignant brain tumors R.L. Hayes, M. Koslow, E.M. Hiesiger, H. Hochster, K. Hymes, E. Moore, D.M. Pierz, A. Wise and J. Ransohoff 225

PART THREE STEROID IN BRAIN TUMORS

44. Role of oxygen radicals in cerebral edema mechanisms: rationale for the use of steroids

E.D. Hall and R.M. Del Maestro 231 45. Comparative effects of dexamethasone and methylprednisolone on peritumoral brain

edema M. Zuccarello, D. Zerbi, G. Macchia, G.C. Andrioli and G. Schmitt 235

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46. Oral methylprednisolone megadose in the treatment of recurrent gliomas and in­tracranial metastases. Preliminary report

M.A. Gerosa, C. Licata, A. Nicolato, L. Cristofori, M. Vitale, J.C. Grosslercher, e. Vivenza and A. Bricolo 243

47. Effects of methyl-prednisolone on cerebral neoplasms: clinical and radiological evaluation

S. Mingrino, S. FerIa, R. Faggin and G. Dalla Pieta 249 48. Role of glucocorticoid receptors in intracranial tumors

G. Butti, C. Zibera, M. Scerrati, G. Sica, N. Gibelli, L. Magrassi, M. Rolli, G. Introzzi, G. Rossi and G. Robustelli della Cuna 253

PART FOUR NEURINOMAS, MENINGIOMAS AND OTHER TUMORS

49. Intracranial meningiomas: state of the art F. D' Andrea and F. Maiuri 261

50. Endocrine manipulation of meningiomas with medroxyprogesterone acetate T-M. Markwalder and E.R. Waelti 267

51. Controversies on craniopharyngioma P. Conforti, M. Rotondo and e. Parlato 275

52. Diagnosis and treatment of pineal region tumors K. Takakura, M. Matsutani and N. Shitara 283

53. Primary considerations in an integrated microsurgical-stereotactic approach to lesions affecting the third ventricular chamber

M.L.J. Apuzzo and M.L. Levy 291 54. Optic and chiasm tumors: present perspectives in diagnosis and treatment

R.M. Villani, G. Miserocchi, S. Balbi, M. Caroli, M. Egidi, S.M. Gaini and G. Tomei 301

55. Intracranial metastatic tumors: an overview K. Sano 309

56. Petroclival meningiomas: their surgical treatment G.P. Cantore, R. Delfini and P. Ciappetta 321

57. Pathology of pinealomas: an immunohistochemical and ultrastructural study H. Cravioto, S. Cortesi, M.T. Giordana, A. Migheli, T. Pezzulo, B. Pollo and M.e. Vigliani 325

58. Statistical analysis of operative mortality and recurrence in intracranial meningiomas R. Assietti, G. Pinna, G. Introzzi, P. Gaetani, A. Tangenti, R. Rodriguez y Baena, G. Sangiovanni, L. Magrassi, F. Rainoldi and G. Butti 329

59. Surgical management of lateral ventricular tumors J.M. Piepmeier and K.J. Sass 333

PART FIVE BRAIN TUMORS IN CHILDREN

60. Supratentorial brain tumors in children C. Di Rocco, A. Ceddia and A. Iannelli

61. Brain stem gliomas G. Magram and L. Schut

62. Current management of neonatal tumors

339

347

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S. Pezzotta and D. Locatelli 359 63. Brain tumors as second malignancies in children treated for acute lymphoblastic

leukemia M. Jankovic, G. Masera, M.L. Cristiani, E. Nardi and A. Arrighini 365

PART SIX INTRACRANIAL PRESSURE MANAGEMENT: AN IDEAL VALVE

64. The treatment of hydrocephalus in pediatric patients with a variable resistance valve S. Pezzotta and D. Locatelli 373

65. The treatment of tumoral hydrocephalus in adults by means of a variable resistance valve

R. Spaziante 379 66. Advantages of the Orbis-Sigma valve in the treatment of triventricular hydrocephalus

P.M. Rampini, M. Caroli, M. Zavanone, E. Sganzerla and M. Farabola 387 67. Reliability and efficacy of different CSF-shunting devices in the treatment of CSF­

dynamics disturbances C. Anile, G. Maira, A. Puca and G.F. Rossi 393

Index 399

Preface

This volume contains the proceedings of the latest in a series of international symposia on advances in neuro-oncology, held September 26-29, 1990, in San Remo, Italy and sponsored by the University of Pavia, I.R.C.C.S. Policlinico San Matteo (Pavia, Italy) and the Giovanni Lorenzini Medical Foundation (Milan-Houston). It drew papers from six continents of the world, was attended by over 500 investigators, and demonstrated the extraordinary vitality, depth and breadth of research which characterizes modem neuro-oncology.

Over the course of the last decade, there has been a remarkable shift in research carried out in the heterogeneous field of neuro-oncology, which appears to be away from clinical descriptive studies, and toward more basic and fundamental investigation of the pathology, immunohis­tochemistry, biochemical and cellular subsets of brain tumors. Besides the traditional fields of neurology, neurosurgery, neuropathology, and radiation therapy, there has been an increased interest and involvement by investigators in the fields of medical oncology, neuroradiology, immunology, and many areas of fundamental neurobiology. It has become evident that interest has also been exhibited in a broader spectrum of tumors than just the malignant glial series, and studies in meningioma, craniopharyngioma, neurinomas, and the pituitary tumors were reported. Several sessions were devoted to the special problems of pediatric brain tumors.

In several presentations and during the question and answer period, there was considerable discussion regarding the value of an extensive surgical resection. With new diagnostic methods that make possible the ability to define small tumors at a time when they are asymptomatic, surgeons were actively debating the appropriate course of treatment. The employment of stereotoxic biopsy, minor resection, major resection, or no operations at all were vigorously debated. While no resolution was achieved during this Symposium, our attention has been focused on this important issue.

The great interest in clinical trials has been so evident in previous conferences has abated, as clinicians have found that continuous improvement in outcome and survival has not been so easy to achieve. However, the characteristics of patients with these tumors have been well defined and the prognostic factors of outcome identified and described. The realization that once the efficacy of radiotherapy, the nitrosoureas and a few other compounds had been demonstrated, and that large therapeutic gains have not been found in single or multiple drug treatment approaches, we have had to redirect attention to the basic biologic activities of the cancer cell and how it proliferates. The explosion of new technology capable of revealing the genetic, biochemical and molecular nature of brain tumors is being aggressively used. The oncogenic expression, metabolic abnonnalities and identification of a wide variety of receptor sites indicate the extraordinary complexity of these tumors and may provide some of the explanation for the difficulties encoun­tered in treatment. New diagnostic imaging methodology, better operative techniques and approaches to the management of intracranial pressure were highlights of improvement. An extraordinary array of radiotherapeutic techniques radiation sensitizers and radioprotectors show promise, but now need to be subjected to controlled prospective random clinical trials to demonstrate their actual efficacy.

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This Symposium can be characterized as having presented an extraordinarily diverse amount of material in a great many areas of importance to brain tumor treatment and research. It has left the participants with a wealth of information, but more important, it has posed a large number of unanswered questions for further research into how we can better diagnose, treat and manage our patients with brain tumor. These will be answered in future conferences.

P. Paoletti K. Takakura

M.D. Walker G. Butti

S. Pezzotta

LIST OF FIRST CONTRIBUTORS

Giovanni Acerbi Strada 169 65016 Montesilvano PE Italy

Mario Ammirati Ass. Professor of Neurosurgery Department of Surgery University of California 1033 Le Conte Avenue Los Angeles, CA 90024-6901 U.S.A.

Giancarlo Andrioli Div. di Neurochirurgia Ospedale Galliera Mura Cappuccine, 14 16128 Genova Italy

Carmelo Anile Istituto di Neurochirurgia Universita Cattolica Largo Gemelli, 8 00168 Roma Italy

Michael L.J. Apuzzo Neurological Surgery University of Southern Califomia School of Medicine 1200 N. State Street, Room 5046 Los Angeles, CA 90033 U.S.A.

Roberto Assietti Clinica Neurochirurgica Universita di Pavia Piazzale Golgi, 2 27100 Pavia Italy

B. L. Bauer Department of Neurosurgery Philipps University Baldingerstrasse DW-3550 Marburg Germany

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Gianni Boris Bradac Neuroradiologia Universita di Torino Via Cherasco, 15 10126 Torino Italy

Giorgio Butti Dip. di Chirurgia Neurochirurgia Universita di Pavia Policlinico S. Matteo 27100 Pavia Italy

Giampaolo Cantore Dip. di Scienze Neurologiche Universita "La Sapienza" Viale del1' Universita, 30/a 00185 Roma Italy

Carmine M. Carapel1a Divisione di Neurochirurgia Istituto Regina Elena per 10 Studio e la Cura dei Tumori Viale Regina Elena, 291 00161 Roma Italy

HongW. Chin Overton Brooks Medical Center Shreveport, LA 71101 U.S.A.

Hugh Coakham Imperial Cancer Research Fund. Paediatric & Neuro-oncology Group Frenchay Hospital Bristol U.K.

Paolo Conforti Istituto di Neurochirurgia la Fac. di Medicina e Chirurgia Universita di Napoli c/o CTO - Viale Colli Aminei, 21 80131 Napoli Italy

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Humberto Cravioto Dept. of Pathology (Neuropathology) New York University 550 First Avenue New York, NY 10016 U.S.A.

Faust D'Andrea Istituto di Neurochirurgia 2a Scuola di Medicina Via Pansini, 5 80100 Napoli Italy

Raffael D'Avanzo Via A. De Gasperi 80133 Gicciano NA Italy

Concezio Di Rocco Sez. di Neurochirurgia Pediatrica Istituto di Neurochirurgia Fac. di Medicina Universita Cattolica del Sacro Cuore 00198 Roma Italy

Paolo Gaetani Dip. di Chirurgia Neurochirurgia IRCCS Policlinico S. Matteo 27100 Pavia Italy

Massimo A. Gerosa Servizio di Neurochirurgia Universita di Verona Ospedale Civile Maggiore Piazzale Stefani, 1 37128 Verona Italy

F. Giunta Neurochirurgia Spedali Civili 25123 Brescia Italy

Harry S. Greenberg Department of Neurology University of Michigan 1500 E. Medical Center Drive 1914 Taubman Center

Ann Arbor, MI 48109-0316 U.S.A.

Edward D. Hall CNS Diseases Research The Upjohn Company Kalamazoo, MI 49001 U.S.A.

S. Hassembusch Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland OH 44195-5226 U.S.A.

Roberta Hayes Dept. of Neurosurgery NYU Medical Center 550 First Avenue New York, NY 10016 U.S.A.

Emile M. Hiesiger Dept. of Neurology New York University Medical Ctr. 550 First Avenue New York, NY 10016 U.S.A.

Takao Hoshino Dept. of Neurosurgery Kyorin University School of Medicine Shinkawa, Mitaka Tokyo 181 Japan

Momcilo Jankovic Clinica Pediatrica Ospedale S. Gerardo Via Doninzetti, 106 20052 Monza (MI) Italy

A. B. M. F. Karim Afdeling Radiotherapie VU Ziekenhuis Postbus 7057 1007 MB Amsterdam The Netherlands

Roberto Knerich Dip. di Chirurgia Neurochirurgia Universita di Pavia 27100 Pavia Italy

Lois A. Lampson Neurology!Thom 12 Brigham and Women's Hospital 75 Francis St. Boston, MA 02115 U.S.A.

Comelis Langeveld Dept. of Neurology Free University Hospital Van der Boechorststraat 7 1081 BT Amsterdam The Netherlands

Daniela Lombardi Neurochirurgia Dip. di Chirurgia IRCCS Policlinico S. Matteo 27100 Pavia Italy

Lorenzo Magrassi Clinica Neurochirurgica Universita di Pavia Via Montebello della Battaglia, 4 27100 Pavia Italy

Thomas-Marc Markwalder Spezialartz f. Neurochirurgie FMH Krayigenweg 2 CH-3074 Muri - Bern Switzerland

Masao Matsutani Dept. of Neurosurgery University of Tokyo Hospital Hongo 7-3-1, Bunkyo Tokyo 113 Japan

Alessandro Mauro Clinica Neurochirurgica 2a Universita di Torino Via Cherasco, 15 10126 Torino Italy

Katsuyoshi Mineura Neurosurgical Service Akita University Hospital 1-1-1 Hondo Akita 010 Japan

Salvatore Mingrino Divisione di Neurochirurgia Ospedale Civile di Padova Via Giustiniani 35100 Padova Italy

Masakatsu Nagai Dept. of Neurosurgery Dokkyo University School of Medicine Mibu Tochigi 321-02 Japan

Alessandro Olivi Johns Hopkins Hospital Mever 7-113 600 N. Wolfe Street Baltimore, MD 21205 U.S.A.

Pietro Paoletti Dip. di Chirurgia Sezione di Neurochirurgia Universita di Pavia 27100 Pavia Italy

M. Parent C.H.R. - Faculte de Medecine Laboratoire d' Anatomopathologie 59037 Lille Cedex France

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Stefano Pezzotta Clinica Neurochirurgica Univ. degli Studi di Pavia Piazza Golgi 27100 Pavia Italy

Joseph Piepmeier Yale University School of Medicine 333 Cedar Street New Haven, CT 06510 U.S.A.

Paolo Rampini Istituto di Neurochirurgia Univ. di Milano Via Francesco Sforza, 28 20122 Milano Italy

Alberto Riccardi Clinica Medica II Policlinico S. Matteo 27100 Pavia Italy

Keiji Sano Dept. of Neurosurgery Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku Tokyo 173 Japan

Davide Schiffer 2a Neurologia Universita di Torino Via Cherasco, 15 10126 Torino Italy

Luis Schut Division of Neurosurgery Children's Hospital of Philadelphia 34th St. and Civic Ctr. Blvd Philadelphia, PA 19104 U.S.A.

G. Scotti Servizio di Neuroradiologia Ospedale S. Raffaele Via Olgettina 20090 Segrate MI Italy

Joan Rankin Shapiro Laboratory of Neuro-Oncology Barrow Neurological Institute 350 West Thomas Road Phoenix, AZ 85013 U.S.A.

William Richard Shapiro Barrow Neurological Institute 350 West Thomas Road Phoenix, AZ 85013 U.S.A.

Riccardo Soffietti 2a Clinica Neurochirurgica Universita di Torino Via Cherasco, 15 10126 Torino Italy

Maurizio Soma Institute of Pharmacological Sciences Via Balzaretti 9 1-20133 Milan Italy

Renato Spaziante 1st. di Neurochirurgia 2a Facolta di Medicina e Chirurgia Via Pansini, 5 80131 Napoli Italy

Noriaki Sugawa Ludwig Institute for Cancer Research Clinical Group P.O. Box 60004 S-104 01 Stockholm Sweden

Kintomo Takakura Dept. of Neurosurgery University of Tokyo 7-3-1 Hongo, Bunkyo-ku Tokyo 113 Japan

David G. T. Thomas Dept. of Neurological Surgery Institute of Neurology Queen Square London WCIN 3BG U.K.

Yukitaka Ushio Department of Neurosurgery Kumamoto University Medical School 1-1-1 Honjyo Kumamoto 860 Japan

Roberto Villani Istituto di Neurochirurgia Universita di Milano Via Francesco Sforza, 28 20122 Milano Italy

Wolfgang Wechsler Dept. of Neuropathology Heinrich-Heine-University Moorenstr. 5 DW-4000 Diisseldorf 1 Germany

Junkoh Yamashita Department of Neurosurgery Kanazawa University 13-1 Takaramachi Kanazawa 920 Japan

Toshiki Y oshimine Dept. of Neurosurgery Osaka Univ. Medical School 1-1-50 Fukushima Fukushima, Osaka 553 Japan

Paolo Zampieri Dipartimento di Chirurgia Policlinico Via Giustiniani, 5 35100 Padova Italy

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