EDUCATIONAL REVIEW

D.C. MACARTHUR and N. BUXTON

Department of Neurosurgery, University Hospital, Queen’s Medical Centre, Nottingham, U.K.

Introduction Incidence and Aetiology Pathology Presentation Investigation and Diagnosis

Clinical Management Surgical Management Radiotherapy Chemotherapy Acknowledgements

Current knowledge on the biology and clinical features of brain tumours is reviewed with particular reference to the most commonly occurring tumours - gliomas, meningiomas and metastases. Unfortunately, the enormous increase in understanding of the biology of these tumours over recent years has not, as yet, been paralleled by advances in treatment or improvements in clinical outcome. Developing adjuvant therapies, ranging from novel means of delivery of radiotherapy and new chemotherapy agents to gene therapy and anti-angiogenic agents, are currently being explored and offer some hope for improvement in our ability to treat these tumours over the next few decades.

Keywords: brain tumour, surgery, radiotherapy, chemotherapy

J.R.Coll.Surg.Edinb., 46, December 2001, 341-348

INTRODUCTION

The public and medical perception of a brain tumour is generally of a dreadful disease with a dismal prognosis. Unfortunately, there is some justification for this as 30 years of considerable progress in the understanding of the biology and molecular genetics of brain tumours has done little to improve clinical outcomes, as yet, for the most common and aggressive tumour types. The advent of modern imaging techniques, with computerised tomography (CT) and magnetic resonance imaging (MRI) now being widely available, has made it possible for these tumours to be identified and to some extent diagnosed earlier and more easily than in the past with its dependence on angiography. Management has now become multidisciplinary with radiologist, surgeon and oncologist all contributing significantly to the process. Multidisciplinary meetings, where each case is discussed and a consensus treatment protocol agreed, are now becoming standard neuro-oncological practice. Indeed, such discussions are essential as many of these patients are treated within the context of trials. This article attempts to summarise the current state of knowledge and treatment of the commoner brain tumours, from a surgical viewpoint.

INCIDENCE AND AETIOLOGY

The incidence of brain tumours in this country is increasing and has recently been estimated at 21/100000/yr.¹ Brain tumours are now the second commonest group of tumours in children (after leukaemias) and the sixth commonest in adults. In 13% of deaths from cancer there is central nervous system involvement. Despite a considerable research effort, the aetiology of the great majority of brain tumours remains unclear. A small proportion of specific types of tumour arise in the context of a variety of genetic disorders (Neurofibromatoses 1 and 2, Von Hippel Lindau disease and Tuberous Sclerosis), prior childhood irradiation is implicated in the development of a few brain tumours and primary central nervous system (CNS) lymphoma is becoming commoner in the immunosuppressed patient. The role of environmental or occupational factors is unclear and, in particular, there is no good evidence, as yet, to link the increasing incidence of brain tumours with mobile phone use.² Cytogenetically, many brain tumours show multiple and characteristic abnormalities- for example amplification of the gene for c erb B1 on the short arm of chromosome 7 resulting in over-expression of epidermal growth factor receptor (EGFR) in up to 35% of glioblastomas or consistent losses of material from chromosomes 10 and 17 from areas which may include tumour suppresser genes.^3,4 To date, the exact role of these abnormalities in pathogenesis is not understood but it seems likely that a combination of several genetic and biological disturbances is important in the initiation and development of a brain tumour.

PATHOLOGY

The classification of brain tumours is complicated by the existence of a number of historical, often overlapping, classification schemes. A simplified version of the current WHO scheme, which is based upon the cell of origin, along with the numbers of new patients with each tumour type seen in a typical regional neurosurgical unit over a year, is shown below in Table 1.

Figures are for histologically proven cases only *This figure represents the proportion of intracranial metastases in a population undergoing surgery. The number of patients with metastases (frequently multiple) who do not undergo surgery is very much higher- perhaps 40% of all brain tumours are secondaries, most commonly from lung, kidney, breast and melanoma.

Table 1: A simplified classification of brain tumours (after the WHO 1993 and 2000 schemes) along with their incidence in inpatients in a typical regional neurosurgical unit. [Statistics from Departments of Neurosurgery / Neuropathology, Queen’s Medical Centre, Nottingham over the period Jan - Dec 1998]

The commonest single tumour type is the astrocytoma arising from glial supporting cells. This may present either in a low grade form and then progress over a number of years to a higher pathological grade (additional features of mitoses, nuclear pleomorphism, endothelial proliferation and necrosis observed) or more commonly present de novo in its most malignant form as a glioblastoma (Figure 1). These tumours are diffusely infiltrative within the brain and the radiological impression of a defined margin on imaging is not usually borne out histologically where tumour cells can be seen up to several centimetres away from the main tumour mass, and in some cases, even in the other hemisphere. The realisation that this is not a localised disease is a key in developing strategies for its management. In contrast, metastases and meningiomas, arising extrinsic to the brain from the meninges, commonly do have a clear demarcation from brain tissue and in these circumstances attempts at resection and other localised treatments are more appropriate.

Figure 1: Macroscopic view of an infiltrative high grade glioma close to the sylvian fissure on the right of the figure

PRESENTATION

Most brain tumours present in one of three ways: seizures, focal signs or signs of raised intracranial pressure (headache, typically frontal or generalised and worse on waking, nausea and vomiting and reduced conscious level). Seizures result from irritation of cortical tissue. Focal deficits are a result of infiltration or compression of normal brain structures while infiltration of the dura can cause well-localised pain. The presence of papilloedema is suggestive of raised intracranial pressure (ICP) but it is not always seen and may even be supervened by optic atrophy. The specific mode of presentation depends on the exact site and rate of growth of the tumour. Early symptoms are often non specific (forgetfulness, word-finding difficulties, headaches) and, in many cases, a history going back several months is obtained in retrospect. By the time of presentation, however, clinical signs are usually overt and even rudimentary examination of the motor or sensory systems, speech function and visual fields will reveal significant abnormalities.

INVESTIGATION AND DIAGNOSIS

The differential diagnosis, when there is one, will include other causes of raised ICP or progressive neurological deficit such as chronic subdural haematoma (in the more elderly population), cerebrovascular events, herpes simplex encephalitis and hydrocephalus. A CT head scan with contrast will usually make the diagnosis of a brain tumour with some degree of certainty. The most likely tumour type can often be made on the basis of CT appearances (Figure 2).

        Figure 2a: CT scan of glioblastoma                                        Figure 2b: CT scan of meningioma

        Figure 2c: Ct scan of multiple intracranial 
        metastases

The one important differential diagnosis is that of cerebral abscess, which radiologically can be difficult to differentiate from a rounded necrotic high grade tumour, and in some cases, this is only resolved by an urgent biopsy/ aspiration of the lesion. This then allows appropriate treatment to be commenced in such cases. Magnetic resonance imaging is more sensitive (for example in showing multiple small metastases), provides higher resolution images in three planes and is particularly useful in evaluating tumours in the cerebellum, brainstem and pituitary fossa regions where CT detail is very poor. There is some evidence that advanced MR techniques such as spectroscopy, to look at the chemical constituents of the tumour tissue, can be used to improve accuracy in noninvasive diagnosis of tumour type and grade. One group has reported a diagnostic accuracy for MR spectroscopy of 99% and this, along with other modalities of MRI such as perfusion and tensor diffusion imaging, may have clinical application in the future.6 For the present, however, the key to further management of almost all patients with brain tumours remains the establishment of an exact histological diagnosis.

CLINICAL MANAGEMENT

While an operative procedure is being arranged the majority of patients are commenced on dexamethasone at a dose of 4mg qds (orally or IV). The introduction of dexamethasone in the management of tumour-related raised intracranial pressure in the early 1960s was, perhaps, the last great advance in clinical management of these patient.⁷ Whilst the mechanism of action remains unclear (but possibly related to reduction in local cerebral blood volume rather than as was previously supposed reduction in oedema) dexamethasone can very significantly reduce focal neurological deficit.⁸ A maximal clinical effect is usually seen within two or three days. Not only does this result in symptomatic improvement for the patient and contribute to the safety of surgery, by reducing the degree of brain swelling, but also can help predict (depending on response to dexamethasone) which patients might benefit most from more extensive surgery. Failure to improve with dexamethasone (“fixed deficit”) suggests that the appropriate area of brain has been extensively and irremediably infiltrated with tumour, as opposed to simply being compressed by an adjacent tumour. Those patients whose brain deficits improve to near normal with steroids may have a similar but more long lasting benefit if the volume of tumour tissue can be significantly reduced. In the occasional extreme setting of a patient presenting with a very impaired conscious level, a bolus dose of 16mg of dexamethasone intravenously may substantially improve clinical status and allow time for further imaging and proper planning of surgery. Other appropriate symptomatic treatments will include codeine phosphate for headache (good analgesia with minimal effect on Glasgow coma scale assessment) and cyclizine or metaclopramide for nausea and vomiting.

SURGICAL MANAGEMENT

As mentioned above, the key aim of surgery with many brain tumours is the achievement of a histological diagnosis. The extent of surgery performed depends on various factors including the expected type and grade of the tumour, its proximity to eloquent areas of the cortex or other crucial structures such as cranial nerves, and the clinical status of the patient. The general approach is to remove the maximum amount of tumour possible without producing or adding to the neurological deficit. Certain tumours, such as some meningiomas, can realistically be completely excised (although still with a local recurrence rate of up to 10% many years later).⁹ Solitary metastases may be well demarcated and again can be removed from accessible areas. However, for many tumours it must be accepted that microscopic disease extends beyond any apparent visual or radiological “edge” of the tumour and that surgical cure is simply not possible. Options then range from a simple biopsy to a more extensive “debulking procedure” or even a macroscopic clearance (Figure 3). Patients with symptoms of raised ICP may benefit from a debulking of their tumour, but there is no good evidence from randomised trials as to the potential value of more extensive surgery.¹⁰ In the USA, in particular, great importance is placed on the extensive use of image guidance systems in mapping out the extent of the pre-operative tumour. This is usually done by MRI and then, having registered certain fixed points on the head to their equivalents on the scan once in theatre, using the scan information to guide a resection from all “involved” areas.¹¹ Some of the many limitations of such techniques include technical inaccuracies in the registration process; sometimes substantial shifts of the brain occurs in the middle of the process once the skull and dura have been opened and the operation commenced. Also, the inherent limitations of the scan to accurately delineate the extent of disease. Some of these problems may be overcome in the future with the use of small intra-operative MRI scanners, which can be used to give real time information as the operation progresses.¹² Ultrasound probes have also been advocated for their ability to provide real time information, as the tumour and brain are resected. It is important to remember, when appraising all such impressive technological tools, that there is often a lack of concrete evidence that their use to maximise resection actually affects outcome for the patient.¹³ Alternative approaches to avoiding the resection of eloquent tissue are to perform craniotomies either with “cortical mapping,” where electrophysiological correlation of brain and peripheral nerve activity is carried out, or to perform awake craniotomies, where the patient is able to communicate verbally and undergo constant clinical testing of motor and sensory functions during resection of an area of tissue.

Figure 3a: Frame based stereotactic biopsy

When it is decided that a biopsy alone is the most appropriate form of surgery, usually because the tumour is located very deeply or is in an eloquent area of brain, this is generally performed in a carefully targetted manner. The latter uses either an immediate pre-operative scan and then an image guidance system of the type mentioned above or a frame-based stereotactic system, where the patient has a scan and then their operation with a frame fixed to their head throughout, which accurately establishes a 3D coordinate system (Figure 3). There are risks associated with a biopsy such as haemorrhage or swelling of the tumour resulting in neurological deterioration. There is also the possibility of obtaining an inaccurate diagnosis, as some tumours are heterogeneous in their grade, or of failing to obtain a definite diagnosis at all. Many published series of stereotactic biopsies, particularly from the USA, report very low rates of postoperative deterioration (1%) and nondiagnostic biopsy (4-5%).^14,15 In a recent audit of 215 unselected stereotactic biopsies over three years in our unit the rate of postoperative deterioration was 6.4% and of nondiagnostic biopsy 9.3%. Similar results are obtained in other large units in this country and it is figures such as these, which must be used when balancing up the potential risks and benefits of carrying out a stereotactic brain biopsy. Nonetheless, a large number of patients, for example approximately half of those with highgrade gliomas, are managed from the surgical point of view simply by biopsy.

Figure 3b: Craniotomy

RADIOTHERAPY

Most patients with malignant brain tumours and many in which it is known that residual tumour tissue has been left behind will undergo post-operative radiotherapy. This typically involves fractionated delivery of 60 Gy focally to the tumour region in 30 fractions over 6 weeks. Large trials suggest that this increases the median survival time of patients with high-grade gliomas from 3 to 9 months from the time of diagnosis.¹⁶ As well as some local hair loss and minor degree of radiation injury to the scalp, side effects are usually limited and include fatigue and somnolence during the period of therapy. Focal radiotherapy is also used to attempt to reduce the rate of clinically significant recurrences following incomplete resections of meningiomas and pituitary tumours. Whole brain radiotherapy is usually nowadays reserved for the treat-ment of cerebral metastases with longest survival times coming after removal of an apparently solitary metastasis. Certain tumours, particularly those seen in children, have a tendency to seed throughout the central nervous system and detailed imaging of the spinal cord and, in some cases; spinal irradiation is carried out in these patients. Very focussed radiotherapy has a role in the treatment of certain well-localised tumours. For example, stereotactic radiosurgery (with a Cobalt-60 “gamma knife”) is very effective with small (under 3cm) targets and is used in the management of metastases and also for treating acoustic neuromas.¹⁷ The latter’s critical location in the cerebellopontine angle adjacent to a number of cranial nerves, can make open surgical results disappointing with facial nerve injury being a common outcome. An alternative approach to very focal radiotherapy is interstitial brachytherapy: 125-iodine seeds in Teflon rods can be stereotactically implanted into small, well localised tumours, such as metastases and left in situ for a specified duration (determined by the desired local dose of radiation) before being removed.

Unfortunately, in general, brain tumours are not particularly radiosensitive (with the notable exception of the germinoma, a tumour of the pineal region, which can virtually melt away with radiotherapy) and the tissue tolerance of the CNS to radiation is low so that a cure is rarely achieved. A proportion of patients go on to develop radionecrosis (areas of swollen necrotic tissue causing mass effect on the surrounding brain) and there is a risk of inducing second tumours or arguably causing progression of existing tumours to a higher grade with radiotherapy.

CHEMOTHERAPY

Lack of chemosensitivity of the commoner brain tumours, neurotoxic side-effects of many drugs and difficulties in delivering an adequate volume of a systemic drug across the blood-brain barrier means that the majority of patients with brain tumours do not receive chemotherapy. An exception are patients with oligodendrogliomas where good response to PCV (Procarbazine, CCNU and Vincristine) is likely and patients will usually be offered this form of drug therapy. There has been a tendency to use a similar regimen for high-grade gliomas either after radiotherapy or at the time of recurrence of symptoms. Unfortunately, the large MRC BR5 trial failed to show any benefit in survival time with adjuvant chemotherapy.¹⁸ Newer systemic agents, such as Temozolamide and Liposomal Daunorubicin, are undergoing evaluation at present. Alternative approaches to delivering the drug to the tumour have included intra-arterial chemotherapy (possibly negated by a marked degree of arteriovenous shunting in high grade gliomas) and the implantation of wafers impregnated with Carmustine (BCNU: 1,3-bis [2-chloroethyl]-1-nitrosourea, one of the first and still one of the most effective antiglioma agents) directly into the resection cavity at the time of operation. Early trial results suggest that chemotherapy combined with subsequent radiotherapy produces a modest improvement in survival time and also, importantly, in quality of life during that time.¹⁹ It is certainly intuitively attractive to leave behind an active agent, which will limit growth of the tumour in the interval between surgery and radiotherapy.

OTHER THERAPIES AND FUTURE DEVELOPMENTS

In an unselected series of all patients with high-grade gliomas treated in our unit, median survival time was recently measured at 6 months and only a small percentage of patients were alive at one year. Survival time was not significantly different in the subgroup of patients who had a more extensive resection of the tumour than those who simply had a biopsy. There is evidence that radiotherapy and chemotherapy can lengthen median survival time by a few months, at most, but some caution must be exercised in generalising from data from the often highly selected patients who participate in trials. These current deplorable survival statistics for high grade brain tumours with conventional treatments and the fact that they ought to be an ideal tumour to treat - a population of dividing cells in the midst of a tissue whose cells for the most part do not divide - has led to major research effort into novel therapies. The last 10 years has seen the development of gene therapy techniques which rely on the incorporation of the herpes simplex virus thymidine kinase gene into tumour cells, thus, conferring upon themselves the ability to phosphorylate ganciclovir and be destroyed by subsequent exposure to it.²⁰ Different mechanisms of transduction have been explored, typically involving a retroviral vector to target dividing cells. Early clinical trials in glioblastoma are producing encouraging results in some smaller tumours.²¹ However, there have been difficulties in achieving a significant rate of transduction of the tumour cells in vivo and there is, as yet, a high reliance on the poorly understood “bystander effect”, whereby adjacent tumour cells are fortuitously destroyed not having been directly involved in the transduction process. Future work will undoubtedly aim at the insertion of genes to enhance immune response, promote radiosensitivity, promote apoptosis or limit angiogenesis or invasive capacity of tumour cells.

All gliomas, particularly those of higher grades, produce angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor/ scatter factor (HGF/SF). It is increasingly recognised that the process of angiogenesis and progressive development of tumour vasculature is of great importance to tumour growth and spread and a key potential target for therapeutic intervention.22 Various antiangiogenic drugs are under development; analogues of thalidomide inhibit the angiogenic action of bFGF and these may be seen in clinical trials over the next decade.²³

The potentially interesting technique of Boron Neutron Capture Therapy is undergoing evaluation for treatment of malignant glioma in a number of centres at present.²⁴ As the name suggests, the process depends upon the addition of a low energy thermal neutron to Boron-10 which then disintegrates in a “capture reaction” as a cleanly localised nuclear reaction, effectively destroying all cells in a 5-10 micron vicinity. Tumours can be encouraged to take up certain boron containing compounds but there are difficulties in getting sufficient amounts of boron into large numbers of cells for the technique to have a clinically useful effect. ²⁵ Previous experience in Japan suggests that it may be no more effective than conventional treatments.

CURRENT INITIATIVES AND PATIENT SUPPORT

Survival statistics for the commoner brain tumours have not significantly improved in the last 30 years and it can be argued that many of the technical advances in imaging and localisation of tumours have failed to make progress in treating the disease. It continues to be important to explore new adjuvant therapies but not at the expense of inflicting additional morbidity and distress on patients with what remains a fairly rapidly terminal disease. While progress in some of the newer potential therapeutic strategies is awaited, clinical neuro-oncology has seen a rather reflective last decade with an emphasis on quality of life and standards of care for malignant glioma patients.²⁶ There has been a drive to develop better organised neuro-oncology services, based around multidisciplinary meetings and clinics, and the increased involvement of brain tumour liason nurses to support patients throughout the whole cancer journey from the time of initial diagnosis and treatment to their care in the community.²⁷

ACKNOWLEDGEMENTS

Mr Paul Byrne, Mr Richard Ashpole and Prof Jim Lowe provided the illustrations.

KEY POINTS

. Incidence increasing

. Aetiology unknown for most cases

. Increased knowledge of cytogenetic abnormalities

. Commonest tumour types -astrocytomas, meningiomas, metastases

. Present with seizures, focal signs or raised intracranial pressure

. Potential temporary symptomatic improvement with dexamethasone

. Operations range from biopsy debulking to complete resection

. Radiotherapy used for malignant tumours or residual disease

. Chemotherapy used less commonly in selected tumour types and recurrent disease

. Developing adjuvant therapies include viral gene therapy techniques and anti-angiogenic agents

. Contemporary emphasis is on multidisciplinary neuro-oncology teams and support for patients and their families

REFERENCES

1. Pobereskin LH , Chadduck JB. Incidence of brain tumours in two English counties: a population based study. J Neurol Neurosurg Psychiatry 2000; 69: 464-71
2. Inskip PD, Taronie RE, Hatch EE et al. Cellular-Telephone Use and Brain Tumours. N Engl J Med 2001; 344: 79-86 
3. Libermann TA, Nusbaum HR, Razon N et al. Amplification, enhanced expression and possible rear-rangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985; 313:144 - 7
4. Collins VP. Progression as exemplified by human astrocytic tumours. Seminars in Cancer Biology 1999: 9; 267 - 76
5. Kleihues P, Burger PC, Scheithauer BW. Histological typing of tumors of the central nervous system. 2nd edition. World Health Organization. International histological classification of tumors. New York:Springer-Verlag, 1993
6. Preul MC, Caramanos Z, Collins DL et al. Accurate, non-invasive diagnosis of human brain tumours by using proton magnetic resonance spectroscopy. Nature Medicine 1996; 2: 323-5
7. Galicich JH, French LA, Melby JC. Use of dexamethasone in the treatment of cerebral edema associated with brain tumours. Lancet 1961; 81: 46 -53
8. Ostergaard L, Hochberg FH, Rabinov JD et al. Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumours. J Neurosurgery 1999; 90: 300 -5
9. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957; 20: 22 - 39
10. Metcalfe SE. Biopsy versus resection for malignant glioma. Cochrane Database of Systematic Reviews 2000: Vol 2.
11. Bohinski RJ, Kokkino AK, Warnick RE et al. Glioma Resection in a Shared-resource Magnetic Resonance Operating Room after Optimal Image-guided Frameless Stereotactic Resection. Neurosurgery 2001; 48: 731 -744
12. Hadani M, Spiegelman R, Feldman Z et al. Novel, Compact, Intraoperative Magnetic Resonance Imagingguided System for Conventional Neurosurgical Operating Rooms. Neurosurgery 2001; 48: 799 - 809
13. Whittle IR. Neuronavigation: where is the evidence and will there ever be any? Br J Neurosurg 1998; 12: 69 - 71
14. Apuzzo MLJ, Chandrasoma PT, Cohen D, et al. Computed imaging stereotaxy: Experience and persepective related to 500 procedures applied to brain masses. Neurosurgery 1987; 20: 930 -7
15. Field M, Witham TF, Flickinger JC et al. Comprehensive assessment of haemorrhage risks and outcomes after stereotactic brain biopsy. J Neurosurg 2001; 94: 545-51
16. Walker MD, Alexander E, Hunt WE et al. Evaluation of BCNU and / or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978; 49: 333-43
17. Flickinger JC, Kondziolka D, Niranjan A et al. Results of acoustic neuroma radiosurgery: an analysis of 5 years’ experience using current methods. J Neurosurg 2001; 94: 1-6
18. Thomas DGT, Bleehan NM, Roberts JT et al. MRC Randomised trial of adjuvant chemotherapy in high grade glioma (HGG-BR5). J Neurooncol 1998; 39: 102
19. Whittle IR, Westphal M, Ram Z et al. Are Gliadel wafers a useful adjunct to first surgery for malignant glioma? Presented to Society of British Neurological Surgeons meeting, Newcastle, 2001
20. Culver KW, Ram Z, Walbridge S et al. In vivo gene transfer with retroviral vector producing cells for the treatment of experimental brain tumours. Science 1992; 256: 1550 -2
21. Ram Z, Culver KW, Oshiro EM et al. Therapy of malignant brain tumours by intratumoural implantation of retroviral vector-producing cells. Nature Med 1997; 3: 1354-61
22. Schmidt NO, Westphal M, Hagel C et al. Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 1999; 84: 10 -18
23. Moreira AL, Friedlander DR , Shif B et al. Thalidomide and a thalidomide analogue inhibit endothelial cell proliferation in vitro. J Neurooncol 1999; 43: 109-14
24. Barth RF, Solway AH, Goodman JH et al. Boron neutron capture therapy of brain tumors: an emerging therapeutic modality. Neurosurgery 1999; 44: 433-51
25. Goodman JH, Yang W, Barth RF et al. Boron neutron capture therapy of brain tumors: biodistribution, pharmacokinetics and radiation dosimetry of sodium borocaptate in patients with gliomas. Neurosurgery 2000; 47: 608-22
26. Davies E and Hopkins A (eds) Improving care for patients with malignant cerebral Glioma. London: Royal College of Physicians of London, 1997.
27. Whittle IR. Brain tumour surgery: triumphs and tragedies

Correspondence: D.C. Macarthur, Department of Neurosurgery, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, U.K. 
E-mail donaldmacarthur@nottingham.ac.uk

Copyright date: 12th October 2001

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