Imaging strategies for brain tumours

Growth factors have been shown to be associated with primary hypertrophic cardiomyopathy. Octreotide, a long acting somatostatin analogue, can prevent the stimulating effect of growth factors and decrease the left ventricular mass in patients with acromegaly. In the light of these results, three patients with primary hypertrophic cardiomyopathy were treated with subcutaneous octreotide (50 micrograms three times a day during the first week and 100 micrograms twice a day for the following three weeks). Initially, two patients were in New York Heart Association class II in and one was in class III. At the end of a four week treatment session all were in class I. There were significant decreases in left ventricular posterior wall thickness, interventricular septum thickness, and left ventricular mass in all three patients. Both left ventricular end diastolic and end systolic diameters had increased in all of the patients at the end of the fourth week. Two of three patients showed improved diastolic filling: their hyperdynamic systolic performance returned to normal. No side effects were observed during octreotide treatment. The considerable improvement obtained with the short term octreotide treatment in patients with primary hypertrophic cardiomyopathy seems promising.     

Secondary extradural spinal tumours in children

Secondary extradural spinal tumours are very rare, but they comprise most of the extradural neoplasms seen in infancy and childhood. Thirty-nine patients with this type of secondary tumour were treated in our hospital between 1965 and 1991. The diagnosis was proved by biopsy in every case. Following surgical decompression, all 35 survivors had radiotherapy and/or chemotherapy. Their outcome is reported.     

Information booklet for parents of children surviving cancer

With increasing survival rates in pediatric oncology, the medical and psychosocial costs of cure are becoming apparent for the child and his family. The focus of our concern is now how to prevent and to reduce these adverse late effects of cancer and its treatment. To reduce the late psychosocial consequences for the child and its family a booklet was written for parents. We decided to address parents because of the young age of many children when treatment is completed, the essential role of parents in alleviating late effects for the child and his siblings, and the possibility to discuss the whole range of psychosocial late effects: those for the patient, the siblings, and for the parents themselves. The booklet acknowledges the specific emotional problems in patients, parents, and siblings that results from surviving childhood cancer and provides information and support on how to deal with them. The booklet can enhance open communication with the health care team about late consequences. In this way the booklet supports the further integration of medical and psychosocial aftercare.     

Medulloblastoma: factors influencing the educational potential of surviving children

Twenty-five children with a histological diagnosis of medulloblastoma operated upon in our unit and who had then been treated with identical radiotherapy regimes were studied in an attempt to determine the academic potential of children who survive for more than two years following their initial presentation. Fourteen children were attending a mainstream school at which they required no special help or remedial classes and were in the appropriate year for their age while eleven required special help with their schooling. Seven of these attended a mainstream school, but required remedial classes for help with reading, writing and arithmetic while two were in a class a year below what would have normally been expected for their age group. Two children attended a special school for children with learning difficulties. These differences in academic potential can be related to the age of the child at presentation and the presence or absence of postoperative complications.     

Biology and genetics of malignant brain tumours

Conventional therapies such as surgery, radiotherapy and, to a lesser extent, chemotherapy have produced significant increases in survival in patients with some types of brain tumours such as medulloblastoma. However, in many other types of brain tumour in both adults and children, the effect of these modalities has been more modest. A thorough understanding of the biology of malignant brain tumours is likely to provide the background for the development of new leads that might be amenable to therapeutic exploitation. This review examines some aspects of glioma biology that have been reported in the past 12 months, and which might be translated into clinical application.     

Positron emission tomography in primary brain tumours using cobalt-55

Primary brain tumours are usually assessed by computed tomography (CT) and magnetic resonance imaging (MRI), sometimes in conjunction with positron emission tomography (PET). We used cobalt-55 (55Co) as a calcium (Ca) tracer to visualize decaying tumour tissue, based on the fact that Ca-influx is essential in both cell death and leukocyte activation. Net 55Co uptake may be the result of cell decay, leukocyte infiltration, (re)perfusion and the pharmacological profile of 55Co. Three patients with primary malignant brain tumours (first presentation) were studied with CT, MRI and Co-PET after the intravenous administration of 0.5 mCi 55Co. Histopathological diagnosis was obtained by biopsy or resection. Co-PET demonstrated each of the brain tumours and showed good topographical agreement with CT and MRI. Co-PET provided additional detail as to the site and size of the necrotic core and the perinecrotic rim of decaying tumour. The 55Co uptake indices varied between 2.6 and 5.3. 55Co demonstrated uptake in decaying tissue, irrespective of the integrity of the blood-brain barrier. Neither necrotic nor viable tumour tissue showed affinity for 55Co. Since 55Co is readily applicable to both PET and single photon emission tomography (SPET), differences in the uptake mechanism and functional significance of the 55Co tracer are discussed in relation to 201Tl SPET. We present a (limited) pilot series of three patients to forward the claim of this new functional technique in nuclear neurology.     

Therapeutic approaches to primary and secondary brain tumours

INTRODUCTION: This study examined the long-term effects of hysterectomy, with and without bilateral oophorectomy, and treatment with estrogen replacement on bone mineral density in older hysterectomized women. METHODS: Subjects were 346 women 60-89 years of age, who were participants in the Rancho Bernardo Study and attended a follow-up clinic visit in 1988-1991. Bone density was measured at the ultradistal wrist, midshaft radius, lumbar spine and hip. RESULTS: Of these women, 182 had a hysterectomy with conservation of one or both ovaries and 164 had a hysterectomy with bilateral oophorectomy. Current estrogen users had the highest bone densities; those who never used estrogen replacement had the lowest. Only 9.1% of oophorectomized women, compared to 19.2% of those with ovarian conservation had never used estrogen (P < .01). After adjustment for covariates including estrogen replacement therapy, hysterectomized women with ovarian conservation had marginally higher bone densities at the wrist (P < .09) and spine (P < .06) than oophorectomized women. We found significant differences only among women currently using estrogen (P < .05 for wrist and P < .01 for spine densities, respectively). Bone density did not differ at any site by oophorectomy status among past or never users of estrogen. CONCLUSIONS: Hysterectomized women who use estrogen replacement therapy have better bone density, regardless of a bilateral oophorectomy. In addition, bilateral oophorectomy may not have a long-term negative effect on bone density; hysterectomized women who do not use estrogen appear to have equivalent bone density whether or not they had a bilateral oophorectomy.     

Monoamine acid metabolites in ventricular CSF of patients with brain tumours

Homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in ventricular CSF were determined in 19 patients (12 female 7 male) with brain tumours. No relationship was found between ventricular fluid pressure (VFP) and levels of HVA and 5-HIAA. A relationship was observed between ventricular CSF, HVA concentrations and tumour induced alterations in CSF dynamics. HVA concentrations were very high in patients whose tumours involved the third ventricle, the aqueduct, or the fourth ventricle, producing marked alterations in CSF flow. HVA concentrations significantly lower than in controls were observed in cases where tumours involved the lateral ventricles. Concentrations of acid metabolites in patients with little or no alteration in CSF dynamics corresponded with those in patients with other neurosurgical disorders.     

Rare pancreatic tumours in children (other than nesidioblastosis)

BACKGROUND: The rarity of pancreatic tumours other than nesidioblastosis in children is such that the experience of any one surgeon or institution is small. As a consequence, there is limited information on the appropriate management and outcome of these tumours. For this reason a review was conducted of the experience of a large paediatric surgical institution. METHODS: During a 23-year period, six patients with pancreatic tumours other than nesidioblastosis were treated at the Royal Children's Hospital, Melbourne. RESULTS: Despite the varied modes of presentation and surgery undertaken, all six patients with surgery alone, with follow-up from 1 to 18 years. Two of the tumours were malignant; the remaining four being islet cell adenomata. No form of adjuvant treatment (chemotherapy or radiotherapy) was used. CONCLUSION: These rare paediatric tumours appear to have a good prognosis, even when malignant, and respond well to radical surgical ablation. Adjuvant therapy appears to be unnecessary.     

Radiotherapy treatment planning of brain tumours using MRI alone

MRI of the brain can provide images of very high quality revealing detailed information especially concerning the extent of abnormalities. As such MRI has great potential in the radiotherapy (RT) planning of brain tumours. However MRI has rarely been used alone as the basis for treatment planning primarily due to concern over potential geometric distortions. Treatment planning using MRI has therefore usually been carried out in conjunction with CT images. This work demonstrates that geometric distortions can be minimized by using a relatively small field-of-view, an increased receiver bandwidth, and a fast spin echo acquisition sequence, and that it is thus possible to perform RT planning using MRI.     

MR of the brain in children

MR imaging has firmly established its place as the cornerstone of pediatric neuroimaging. Recent advances in MR imaging have led to decreased imaging time, high resolution studies, and new methods for obtaining tissue contrast. Magnetic resonance angiography (MRA) now obviates the need for angiography in some children, although its extended role is still to be defined. Normal and abnormal development and myelination patterns have been further defined with MR imaging. The patterns of brain injury resulting from hypoxia and ischemia vary with the degree of the insult as well as the gestational age of the child. These patterns of hypoxic-ischemic encephalopathy can be analyzed to determine when the insult occurred. Neuronal migration disorders and phakomatoses can be diagnosed with confidence at an early age, thus facilitating genetic counseling. MR imaging can detect the most common lesions associated with childhood epilepsy, such as hippocampal sclerosis, focal cortical dysplasias, and low-grade tumors. Other areas, including pediatric AIDS, toxicity-related injury, metabolic/mitochondrial conditions, and disorders associated with iatrogenic injury, can be diagnosed with MR. Spectroscopy provides information that should prove useful in evaluating and monitoring neuronal and other brain tissue disorders in children.     

The creation of protection and hope in patients with malignant brain tumours

The malignant brain tumour disease condenses much of the anguish of cancer diseases. The brain is a vital and delicate organ, and the prognosis is generally unfavourable. The patient is exposed and has to rely on cognitive manoeuvres to manage the mental stress. The purpose of this study was to generate new insights into how the patient constructs a new sense of reality when confronted with the malignant brain tumour diagnosis. Within grounded theory methodology, 30 patients with malignant gliomas were interviewed twice, in direct connection with diagnosis, surgery and radiotherapy. In addition, their partners were interviewed, and quantitative instruments (SMMSE, RDCQ) were used as additional references for assessing the patients cognitively and emotionally. Eleven patients were excluded from the final analysis because of cognitive impairment of personality change. Most of the patients were aware of the fact that the brain tumour exposed them to grave danger, but they were also able to use various cognitive manoeuvres to create protection and hope. This process originated from different sources: the body; helpful relations; cognitive schemata; and the handling of information. The importance of the body to raise hope is emphasized. In the discussion we consider this process as an expression of how the patient brings together reality and hope, thus creating her/his own illusion. These findings are also related to adjacent psychoanalytic theory, proposing a theoretical reference with clinical implications when discussing "What to tell cancer patients."     

The origin of experimental brain tumours: a sequential study

A sequential study of rat brains treated transplacetally with the neurotropic carcinogen ethylnitrosourea reveals small foci of cell proliferations from the age of 8 weeks. These lesions consist mainly of undifferentiated cells of the subependymal plate type. They occur in those areas in which gliomas develop and represent the earliest, histologically detectable, changes in the development of brain tumours.     

Neuropsychological outcome of children after radiotherapy for intracranial tumours

With the aim of determining the neuropsychological disturbances associated with cranial radiotherapy in the child, a cross-sectional study was carried out on 25 survivors of medial-edge intracranial tumours. Children irradiated for intracranial tumours experienced deterioration mainly in visual attention and memory, but also in verbal fluency, full-scale IQ, and performance IQ and all its subtests, compared with control groups. This deterioration progressed with time, finally involving at least abstract thought and verbal skills. The pattern of damage by irradiation varied according to the degree of brain maturity, therefore the younger the child at irradiation, the greater the decline in IQ and visual-constructive abilities, and the earlier the deterioration of visual memory and verbal skills.     

Phase I study of interleukin-6 in children with solid tumours in relapse

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.