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Biomedical subjects

J R Perry

Publications and source records attributed to J R Perry.

At least 19 recordsLinked to original sources
PubMed2001

Oligodendrogliomas: clinical and genetic correlations.

Oligodendrogliomas, once obscure, are now recognized as a relatively common form of primary brain tumour, and are among the most chemosensitive of all solid human malignancies. New histopathological, molecular, and genetic information has, for the first time, allowed the distinction of several subtypes of human glioma with predictable biological and clinical behaviour. Genetic markers are emerging as useful not only for the diagnosis of oligodendroglioma, but also as specific predictors of both the response to treatment and prolonged survival. This review will focus upon the past year of advances in the area of clinical-molecular genetic predictors of glioma behaviour and highlight the importance of these advances in everyday clinical practice.

Antineoplastic Agents↗
PubMed2000

The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review.

BACKGROUND: Venous thromboembolism (VTE) frequently complicates the course of patients with cancer, and there is evidence to suggest that patients with brain tumors are at particularly high risk. The objective of this methodology-based literature review was to quantify the rate of incidence of VTE in patients with malignant glioma and to determine the factors that predict an increased risk of this complication. METHODS: Studies meeting predefined inclusion criteria were evaluated independently on an eight-item methodology index by three raters. Authors were contacted to resolve ambiguities. The results of the studies were summarized and the incidence rate of VTE within the early postoperative phase and during extended follow-up were reported separately. RESULTS: Within 6 weeks after surgery the incidence rate of deep venous thrombosis (DVT) ranged from 3% to 60%, varying with the prophylaxis regimen used, the method of diagnosis, and the study design. Beyond 6 weeks postoperatively, the rates of DVT ranged from 0.013 to 0.023 per patient-month of follow-up. The single study with no significant methodologic deficiencies found a 24% rate of incidence of symptomatic DVT over the 17 months of follow-up beyond the first 6 postoperative weeks. In 6 studies the presence of leg paresis, histologic diagnosis of glioblastoma multiform, age >/= 60 years, large tumor size, use of chemotherapy, and length of surgery > 4 hours were identified as possible risk factors. CONCLUSIONS: The incidence of VTE is high throughout the course of malignant glioma. A randomized, controlled trial is needed to clarify whether the benefits of long term anticoagulant prophylaxis outweigh the risks and costs of such therapy.

Anticoagulants↗
PubMed1998

Bias, benefit, or both: evaluating new glioma therapies.

Despite the development of many new promising therapies for malignant glioma, virtually all randomized controlled trials testing them have proven negative. These disappointing results are largely due to complex mechanisms of treatment resistance, but increasingly there is evidence that experimental bias rather than benefit accounts for both the promising early phase I/II trial results and later phase III failures. This paper highlights the aspects of clinical trial design and outcome analysis that specifically affect interpretation of results from therapeutic trials for malignant glioma. Phase II trials of both tumor response and tumor control are subject to selection bias; the early promising results seen with interstitial brachytherapy and intraarterial chemotherapy and yet negative phase III results are examples of this. Methods for detecting selection bias include modeling techniques in which databases of patients with known outcomes are used to emulate phase III outcomes. Modeling may assist in the determination of whether a given phase II result appears to exceed that expected by selection bias alone. Such an experiment on paper is quite unlikely to replace a well-designed randomized trial; however, in this time of increasing numbers of novel therapies but shrinking resources, these techniques should find utility in selecting those therapies most suitable for testing in cooperative group randomized trials.

Journal Article↗
PubMed1998

Acute leukemia following treatment of malignant glioma.

We report two patients with acute myeloid leukemia (AML) following therapy for malignant glioma; one was a young women treated heavily with alkylating agents for glioblastoma and the other a young man treated with high doses of procarbazine, lomustine, and vincristine (PCV) for anaplastic astrocytoma. We found 26 other examples of therapy related leukemia in adult and pediatric brain tumor patients. Including our two, there were 12 patients with malignant glioma; median interval from treatment to diagnosis of AML was 31 months. Nine adult malignant glioma patients all received nitrosoureas, some as the sole form of chemotherapy. No definite cases occurred after radiotherapy alone. Based upon analogy with other cancers, the cumulative dose of chemotherapy, especially alkylating agents, is the major risk factor for development of secondary AML. Agents implicated include carmustine (BCNU), lomustine (CCNU), and procarbazine. Conventional radiotherapy appears not to confer additional risk. Progressive macrocytosis, early dose reductions for thrombocytopenia, and refractory anemia may provide early diagnostic clues. Current glioma therapy is leukemogenic but the number of patients who survive the interval required to induce AML is small; nevertheless, the identification of chemosensitive types of glioma, and subgroups of patients who derive the most benefit from chemotherapy, may result in increasing numbers of patients at risk of long term complications. If regimens such as PCV continue to prove valuable in neurooncology the risk of leukemia will require integration into the clinical decision process. A search for more effective therapy with minimal mutagenicity remains critical.

Acute Disease↗
PubMed1998

Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management.

BACKGROUND: Postpartum cerebral angiopathy as a cause of hemorrhagic stroke in young women is not well recognized. It is unknown whether this disorder represents a true inflammatory vasculitis or transient vasoconstriction related to the hormonal events of pregnancy and the postpartum period. CASE DESCRIPTION: A 39-year-old woman presented with postpartum intracranial hemorrhage and, 32 months later, with subarachnoid hemorrhage, following normal pregnancies. Cerebral angiography obtained after each stroke demonstrated diffuse irregularity of branches of the middle cerebral arteries consistent with a diffuse vasospastic process or classic vasculitis. Neurological deficits resolved and results of a transcranial Doppler study normalized after a short course of high-dose corticosteroids following the second stroke. CONCLUSIONS: Postpartum cerebral angiopathy should be considered in the differential diagnosis of recurrent intracranial hemorrhagic stroke in young women. Recognition of this condition may preclude treatment with potentially toxic therapies for vasculitis and will have important implications for counseling women on subsequent pregnancies.

Adult↗
PubMed1997

Consensus against both endarterectomy and routine screening for asymptomatic carotid artery stenosis. Canadian Stroke Consortium.

BACKGROUND: Despite several randomized controlled trials, the role of carotid endarterectomy for asymptomatic patients is controversial. Validated evidence-based guidelines are needed. METHODS: Thirty-five members of the Canadian Stroke Consortium, an independent body of cerebrovascular disease experts, reviewed evidence-based guidelines developed by the Canadian Task Force on the Periodic Health Examination. We held 3 rounds of Delphi consensus to solicit opinion and agreement. RESULTS: We found a high level of interrater agreement for all guidelines using multiple statistical measures. Members agreed that evidence is insufficient to endorse carotid endarterectomy for asymptomatic patients with angiographically proven stenosis of more than 60% (kappa = 0.70, P < .01). Reasons cited included concern over the reproducibility of low surgical morbidity rates in the community at large, the questionable clinical benefit conferred by surgery, and the lack of proven reduction in the risk of major disabling stroke. Screening the general population for asymptomatic stenosis was unanimously rejected. Also, screening even patients with risk factors or proven atherosclerosis at other sites was not endorsed (kappa = 0.91 and kappa = 0.79, respectively, both P < .01). CONCLUSIONS: There is insufficient evidence to recommend carotid endarterectomy for asymptomatic patients. Evidence is also insufficient to endorse a screening strategy even for patients with risk factors for carotid disease. While stroke prevention remains a critical goal, we do not recommend that it be accomplished by screening or by performing carotid surgery in asymptomatic patients.

Canada↗
PubMed1996

Postirradiated and nonirradiated gliosarcoma: immunophenotypical profile.

BACKGROUND: Thirty-one gliosarcomas (25 nonirradiated and 6 postirradiated tumors) were selected based on the presence of two distinctive areas: a malignant gliomatous and a sarcomatous component. In all cases, the sarcomatous component appears like fibrosarcoma or malignant fibrous histiocytoma. Two tumors showed additional areas consisting of osteochondroid differentiation. METHODS: All tumors were examined using antibodies against Ulex europaeus agglutinin I (UEA), glial fibrillary acidic protein (GFAP), vimentin (VM), epithelial membrane antigen (EMA), desmin, collagen IV, alpha-1-antitrypsin (alpha-1-AT) and smooth muscle actin (SMA). RESULTS: While the VM highlighted the sarcomatous areas of all tumors there were only scattered spindle cells that were GFAP-positive in the same areas. The alpha-1-AT was diffusely reactive in the sarcomatous areas in 20 cases. Focal immunoreactivity was seen with SMA (20 tumors), UEA (8 tumors), EMA (5 tumors), collagen IV (5 tumors) and desmin (4 tumors) in the nonvascular sarcomatous cells. CONCLUSIONS: The range of immunophenotypical expression is likely to be a reflection of the capacity of a multipotential progenitor to undergo divergent differentiation. There is a very little morphological difference between the postirradiated and nonirradiated tumors except that a higher proportion of postirradiated tumors are immunoreactive to SMA and desmin.

Brain Neoplasms↗
PubMed1996

Add-on gabapentin for refractory seizures in patients with brain tumours.

BACKGROUND: Seizures associated with intracranial neoplasms are occasionally refractory to conventional anti-epileptic drugs. Gabapentin (GBP) is one of several novel anti-epileptic drugs effective as an add-on therapy for intractable seizures but has not been studied in patients with cerebral tumours. PATIENTS AND METHODS: We used GBP in a open-label add-on fashion to treat 14 patients with intractable seizures associated with intracranial tumours including four glioblastomas, four metastases, three recurrent glioblastomas, and one each of anaplastic and low grade astrocytoma and meningioma. GBP was added if optimization of pre-existing therapy failed and was titrated until seizures were controlled. RESULTS: One patient experienced adverse drowsiness. Follow-up ranged from 3-24 weeks during which time 7 patients died from disease progression. Concurrent therapy included dexamethasone in eight, cranial irradiation in four, and radiosurgery in one. Responder rate (number with at least 50% fewer seizures) was 100% and persisted throughout follow-up. Complete resolution of seizures occurred in 8/14 patients. CONCLUSIONS: GBP was well tolerated in patients with brain tumours. Seizure frequency was reduced in all patients and efficacy persisted over time; however, the mechanism of this improvement is unclear. Concurrent therapy, regression of frequency to the mean, and the lack of controls may account for apparent benefit. In addition, because GBP may interact with a leucine-related neuronal binding site we also speculate that this novel mechanism of action may have been enhanced in our patients due to the abnormal blood-brain barrier associated with cerebral tumours. Further investigation and a controlled trial are warranted.

Acetates↗
PubMed1996

Transient encephalopathy after paclitaxel (Taxol) infusion.

Paclitaxel (Taxol) is a novel antineoplastic agent that acts by promoting microtubule polymerization. Although myelosuppression and peripheral neurotoxicity are well known and dose limiting, there have been no reports of CNS toxicity apart from two patients with seizures. This may reflect that paclitaxel has little or no blood-brain barrier penetration. We report two women treated with paclitaxel who developed a clinical state characterized by confusion, word-finding difficulty, and behavioral changes. One had bilateral extensor plantar responses. These symptoms appeared 1 week after paclitaxel infusion and resolved spontaneously. Subsequent infusions were associated with a similar self-resolving encephalopathy in one patient and recurrent headache and ataxia in the other. Neuroimaging (including enhanced MRI), LP, and laboratory investigations did not reveal other causes. Electroencephalography showed diffuse nonspecific slowing. One MRI had prominent but nonspecific high signal intensity abnormalities in the deep white matter of the cerebral hemispheres. Based on temporal association, diagnostic exclusion, and repeated episodes with subsequent challenges, we believe these patients may have experienced CNS toxicity from paclitaxel. The mechanism for this self-resolving encephalopathic process is unclear.

Adenocarcinoma↗