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Biomedical subjects

N K Foreman

Publications and source records attributed to N K Foreman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intracranial ependymomas: analysis of prognostic factors in a population-based series.

A retrospective study of 31 children presenting in the period 1976-1993 with intracranial ependymomas in the south-west region of the UK was performed. The diagnosis was confirmed by histological review and several histological variables recorded, including pleomorphism, cellularity, numbers of mitotic figures and extent of necrosis. Histological features, presentation and treatment were correlated with outcome. Eleven patients had supratentorial primaries and 20 infratentorial primaries. Seven patients had macroscopically complete resections of which 5 had supratentorial primaries. Eight patients had no other therapy apart from surgery. Six patients received craniospinal irradiation, 11 had involved-field irradiation and 14 did not have radical radiotherapy. Twelve patients received chemotherapy. Eleven patients are relapse-free at a median of 43 months. Of the 20 relapses, 19 were local and only 1 metastatic. The grade of the tumor assigned at presentation had no correlation with outcome. On histological review, the only feature that had a significant correlation (p = 0.05) with survival was tumor cellularity. There was a survival advantage for a supratentorial primary site (p = 0.04). The event-free survival was significantly longer for patients diagnosed after 1986 than before (p = 0.006). Survival was not significantly affected by radiotherapy or chemotherapy. Children who had had a macroscopically complete excision of the tumor had a 5-year survival of 69% as opposed to 47% for those who had incomplete surgery, but this difference is not significant (p = 0.13). The data suggest that: (1) the event-free survival rate has improved significantly with time; (2) there is little correlation between a variety of pathological features and outcome, and (3) failure at the primary site is the major obstacle to improved cure rates. The role of complete resection, including second-look surgery, needs further evaluation.

Adolescent↗
PubMed1995

Magnetic resonance imaging and magnetic resonance angiography in long term survivors of acute lymphoblastic leukemia treated with cranial irradiation.

BACKGROUND: Successful treatment of acute lymphoblastic leukemia (ALL) has resulted in an increasing number of patients whose disease is cured. This treatment includes cranial irradiation as prophylaxis against central nervous system relapse. The late effects of irradiation are well documented, but their incidence is unknown. The authors investigated the late effects of this treatment modality further by scanning 35 long term survivors of ALL who received cranial irradiation. METHODS: Thirty-five survivors of ALL with no known complication of treatment were included in this study. They were examined with magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the circle of Willis. A control group of 24 patients who were cured of other childhood malignancies without exposure to cranial irradiation also were scanned. RESULTS: Fifteen of 35 (43%) abnormalities were found in the study group versus 4/24 (17%) in the control group. Excluding minor atrophic changes that are known to be produced by irradiation and chemotherapy, there were 9/35 (26%) abnormalities in the study group and 1/24 (4%) in the control group (P < 0.05). These abnormalities included three tumors, a meningioma, a paranasal sinus rhabdomyosarcoma, and an anaplastic astrocytoma. In addition, there were two cases of large vessel vasculopathy, two small cystic infarcts, one diffuse white matter abnormality, and one cryptic vascular malformation. The abnormal control patient had a cerebellar infarct. CONCLUSION: Complications of cranial irradiation in the treatment of ALL appear to be more frequent than currently are appreciated. That these complications include tumors that are potentially treatable suggests that screening may be valuable for these patients.

Adolescent↗
PubMed1995

Intracranial large vessel vasculopathy and anaplastic meningioma 19 years after cranial irradiation for acute lymphoblastic leukaemia.

A child was diagnosed in 1969 as having acute lymphoblastic leukaemia (ALL) and received chemotherapy. On bone marrow relapse in 1973, he was treated with cranial irradiation (20 Gy) in addition to chemotherapy. He continues in complete remission 19 years after his relapse. At age 25 years, he presented with headaches and left hemiparesis. Computerised tomograph demonstrated a large, enhancing right-sided intracranial tumour. Angiography was performed and showed the right internal carotid artery was occluded. Most of the right hemisphere was supplied from the external carotid via the middle meningeal artery. The left posterior cerebral artery and the left anterior cerebral artery were absent presumably as a result of radiation-induced arteritis. A resection of an anaplastic meningioma arising from the right sphenoidal ridge was achieved. There was a rapid improvement in function and he returned to work. Vasculopathy of the large intracranial arteries has been described after high dose radiation. It may occur as in this case after moderate dose radiation. There is a correlation with meningioma. There is a possibility that large artery vasculopathy will be present in a proportion of patients irradiated for ALL. The long lag time between irradiation and the development of meningioma may mean that, as survivors of childhood ALL enter their third decade since cure, this tumour may be seen increasingly.

Adult↗
PubMed1995

Cystic metastatic cerebral neuroblastoma.

Intracerebral neuroblastoma is an exceedingly rare manifestation of intracranial neuroblastoma and has been described as a solid lesion. Cystic metastatic intracerebral neuroblastoma has not been described. We report a case of histologically proven metastatic intracerebral neuroblastoma presenting in a cystic form 1 year after diagnosis and treatment of a solid intra-abdominal neuroblastoma. The imaging and clinical appearance of this case was indistinguishable from that of intracerebral cystic lesions caused by infection or inflammation. It has been suggested that, due to more aggressive treatment of neuroblastoma, patients are surviving longer and consequently intracranial involvement is becoming more frequent. It is important to be aware of this cystic manifestation of the disease.

Abdominal Neoplasms↗
PubMed1994

Decline in incidence of medulloblastoma in children.

BACKGROUND: Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. METHODS: A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. RESULTS: In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. CONCLUSIONS: In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma.

Adolescent↗
PubMed1994

Childhood malignancies in the south-west region of England, 1976-1985.

The incidence and pattern of childhood cancer in the South-West Region of the United Kingdom was studied in the period 1976-1985 to see if there was any unevenness in distribution. This region consists of five counties with considerable variation in radon exposure and urbanisation. Cases were identified from multiple sources and the basis of the diagnosis reviewed. Internationally accepted diagnostic categories were used. Six hundred seventy-eight cases were found, giving an age standardised incidence rate of 114.2 per million childhood years. The incidence of different cancers by sex was strikingly similar to the Manchester Children's Tumour Registry, from a noncontiguous region, with three exceptions. In the South-West, there was a higher rate of soft tissue sarcoma in boys (P = 0.01) and lower rates of sympathetic nervous system and germ-cell tumours in girls (P = 0.01 and P = 0.04, respectively). There was no significant variation in cancer incidence among the five counties or with time. The incidence rate in counties of high radon exposure was not higher than with low radon exposure. The overall incidence in counties with urban districts was not significantly increased compared to those without, although there was a nonsignificant trend towards a higher incidence of leukaemia (P = 0.08). The incidence and type of childhood cancer are similar to those in a noncontiguous region. Geographical and temporal incidence are remarkably stable. Local environmental variation may not play a major role in the causality of childhood cancer.

Adolescent↗
PubMed1993

Mechanisms of selective killing of neuroblastoma cells by natural killer cells and lymphokine activated killer cells. Potential for residual disease eradication.

Widely disseminated neuroblastoma in children older than infancy remains a very poor prognosis disease. Even the introduction of marrow ablative chemotherapy with autologous rescue has not significantly improved the outlook for these children, presumably because of a failure to eradicate minimal residual disease. One additional approach which may hold promise is the use of immunomodulation with cytokines such as IL2 in the setting of minimal residual disease (MDR), for example after intensive chemotherapy and ABMT. However, considerable variability in the susceptibility of neuroblastoma cells to natural killer (NK) and lymphokine-activated (LAK) killing has been observed, and it is presently unclear how NK and LAK cells recognise neuroblastoma cells. In this paper we examine expression of cell adhesion molecules on neuroblastoma to determine which of these modify interaction with NK and LAK cells. We find that LFA-3 (CD58), the ligand for CD2 is of predominant importance in predicting susceptibility of neuroblastoma to the cytotoxic actions of NK and LAK cells, while expression of ICAM-1 (CD54) may also modify susceptibility. These findings were confirmed by blocking experiments in which co-culture of target cells with ICAM-1 and LFA-3 reduced LAK and NK cytotoxicity. Study of the immunophenotypic features of each patient's neuroblastoma cells before induction of MRD may be valuable in determining the likely effect of IL2 in predicting disease reactivation.

Cell Adhesion Molecules↗
PubMed1992

An approach for the analysis of relapse and marrow reconstitution after autologous marrow transplantation using retrovirus-mediated gene transfer.

Autologous bone marrow transplantation (ABMT) is widely used as treatment for malignant disease. Although the major cause of treatment failure is relapse, it is unknown if this arises entirely because of residual disease in the patient or whether contaminating cells in the rescuing marrow contribute. Attempts to purge marrow of its putative residual malignant cells may delay hematopoietic reconstitution and are of uncertain efficacy. We now describe how retrovirus-mediated gene transfer may be used to elucidate the source of relapse after ABMT for acute myeloid leukemia and to evaluate the efficacy of purging. Clonogenic myeloid leukemic blast cells in patient marrow can be transduced with the NeoR gene-containing helper-free retrovirus, LNL6, with an efficacy of 0% to 23.5% (mean, 10.5%). Transduced colonies grow in selective media and the presence of the marker gene can be confirmed in individual malignant colonies by polymerase chain reaction. If such malignant cells remain in harvested "remission" marrow, they will therefore be marked after exposure to LNL6. Detection of the marker gene in the malignant cells present at any later relapse would be firm evidence that residual disease contributed to disease recurrence, and would permit rapid subsequent evaluation of purging techniques. The technique also marks normal marrow progenitors from patients with acute myeloblastic leukemia. These colony-forming cells can be detected in long-term marrow cultures at a frequency of 1% to 18% for up to 10 weeks after exposure to the vector. Animal models and analysis of probability tables both suggest that these levels of marking in vitro are sufficient to provide information about the mechanisms of relapse and the biology of marrow regeneration in vivo. These preclinical data form part of the basis for current clinical studies of gene transfer into marrow before ABMT.

Bone Marrow↗
PubMed1992

Recurrent cerebrovascular accident with L-asparaginase rechallenge.

We report a 15-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) in 1983. Induction therapy included L-asparaginase. After the second dose of L-asparaginase, he had a left sided focal seizure and computed tomography (CT) scan of the head showed a right frontal infarct. No further L-asparaginase was given. Complete remission was achieved and he successfully completed therapy in 1986. Eight months later he had an isolated bone marrow relapse. Reinduction therapy included L-asparaginase. After the fourth dose of L-asparaginase, he presented with severe headache and a CT scan showed a right temporal infarct. Repeat infarction on rechallenge with L-asparaginase has not been previously reported. Prophylactic therapy, such as fresh frozen plasma, should be considered before patients, with a previous cerebral insult, are rechallenged with L-asparaginase. However the effectiveness of such therapy has not been established.

Adolescent↗
PubMed1992

Retrovirus-mediated gene transfer as an approach to analyze neuroblastoma relapse after autologous bone marrow transplantation.

Disseminated neuroblastoma is a malignancy of children often treated by intensive chemotherapy/radiotherapy followed by autologous bone marrow transplantation (ABMT). A high proportion of those treated subsequently relapse. It is unknown if relapse is a consequence of residual disease in the patient or of contaminating malignant cells remaining in the infused marrow, which, of necessity, is harvested and stored prior to ablative chemotherapy/radiotherapy. The assumption that residual cells in the infused marrow contribute to relapse has lead to the adoption of marrow purging prior to reinfusion. However, neither the necessity nor the efficacy of the procedure have been established. We now show how retroviral-mediated gene transfer using the LNL6 vector may resolve this issue. Clonogenic neuroblastoma cells in patient marrow can be transduced and the NEOR gene detected by observing individual neuroblastoma cell colony growth in G418, and by polymerase chain reaction (PCR) of individual colonies. Efficiency of transduction is between 0 and 13.5%. If marrow is exposed to LNL6 prior to infusion and marked cells are detected at the time of relapse, this would demonstrate that infused marrow contributed to disease recurrence. The technique could then be used to analyze the efficacy of marrow purging techniques. Since normal progenitor cells from these patients are also marked, the technique can be used to study factors that modify reconstitution and transducibility of infused marrow. Clinical studies using this approach have now begun.

Base Sequence↗
PubMed1991

Percutaneous lumbar intrathecal catheter for the administration of chemotherapy.

We present a patient with Burkitt's lymphoma in whom the initial diagnostic lumbar puncture was difficult due to a recent lumbar laminectomy and residual spinal cord tumor. According to our current protocol, he was to receive intrathecal chemotherapy for three consecutive days. To avoid the need for repeated attempts at lumbar puncture and to ensure the proper instillation of therapy, a percutaneous IT catheter was placed for 48 hours and the three doses of IT chemotherapy were administered through this catheter. Due to the importance of IT chemotherapy, options must be available to deliver these medications when technical or anatomic abnormalities exist. One such option is the short term placement of a percutaneous IT catheter.

Adolescent↗