Biomedical subjects

Raymond Sawaya

Publications and source records attributed to Raymond Sawaya.

46 records · Page 3Linked to original sources

PubMed2003

Neuropsychological effects of third ventricle tumor surgery.

OBJECTIVE: This study assessed the neuropsychological outcome of patients after surgical treatment for third ventricle brain tumors. Neuropsychological consequences of surgical intervention can have a major impact on patients' quality of life and therefore have important implications for treatment planning. METHODS: A retrospective analysis of 33 patients' neuropsychological data was performed. All patients received a comprehensive neuropsychological evaluation after treatment for a primary brain tumor in the third ventricular region. Twenty-six patients underwent surgery, 14 via the transcallosal approach and 12 via a subfrontal, left transcortical, right pterional, or infratentorial supracerebellar approach. Seven patients were not treated by surgical intervention. RESULTS: There was a significantly elevated frequency of cognitive impairment relative to normative values in memory, executive functioning, and fine manual speed and dexterity. There were no differences in mean neuropsychological scores between patients who underwent surgery and those who did not. There were no differences in mean performance on the basis of surgical approach, tumor infiltration, or history of cranial irradiation. Repeated measures data available for two patients revealed memory impairment before and after surgery, and one patient experienced major improvement after surgery on a measure of mental flexibility and problem solving. CONCLUSION: Patients with third ventricle tumors are at risk for developing impairments in memory, executive function, and fine manual speed and dexterity, which are domains associated with frontal subcortical functions. In the current study, different types of treatment were not associated with differential cognitive sequelae, and surgical intervention did not account for cognitive deficits.

Adolescent↗

PubMed2003

The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases.

OBJECTIVE: To identify a size cutoff below which it is safe to observe obscure brain lesions suspected of being metastases so that treatment of nonmetastases can be avoided. METHODS: Medical records from patients who underwent linear accelerator-based radiosurgery from August 1991 to October 2001 were reviewed. Inclusion criteria were defined as brain metastasis tumor volume less than 5 cm(3) (diameter, thick similar 2.1 cm) treated with a dose of 20 Gy or more. One hundred thirty-five patients had 153 evaluable brain metastases with follow-up imaging that met inclusion criteria. Median age was 54 years (range, 18-79 yr). Lesion primaries were non-small-cell lung (n = 39), melanoma (n = 44), renal (n = 37), breast (n = 18), colon (n = 3), sarcoma (n = 5), other (n = 5), and unknown primary (n = 2). Median tumor volume was 0.67 cm(3) (range, 0.06-4.58 cm(3)). The minimum peripheral dose was 20 Gy (n = 132) or 21 to 24 Gy (n = 21). At the time of analysis, the median follow-up for all patients was 10 months (range, 0.2-99 mo). RESULTS: The 1- and 2-year actuarial local control rates for all of the lesions were 69 and 46%, respectively. For lesions of 1 cm (0.5 cm(3)) or less, the corresponding local control rates were 86 and 78%, respectively, which was significantly higher than the corresponding rates of 56 and 24%, respectively, for lesions larger than 1 cm (0.5 cm(3)) (P = 0.0016). CONCLUSION: A convincing brain metastasis measuring less than 1 cm should be pursued aggressively. If the suspected brain metastasis is ambiguous, observation is proposed up to a diameter of 1 cm. This is the first study in the literature to identify a 1-cm cutoff for radiosurgical control of small brain metastases, and validation by additional studies is required.

Actuarial Analysis↗

PubMed2003

A role for curative surgery in the treatment of selected patients with metastatic breast cancer.

Although metastatic breast cancer is widely believed to carry a grim prognosis, treatment developments over the past 25 years have greatly improved survival outcomes in these patients. In selected cases, aggressive treatment approaches may occasionally result in long-term survival of 15 years or more. This review considers the role of surgery in the treatment of single or multiple metastatic lesions restricted to one site. For each site, available literature from 1992-2002 was assessed to determine the role of surgery on survival outcomes and to determine appropriate criteria for selecting the best candidates for surgery. For lung, liver, brain, and sternum metastases, the use of surgery with or without adjuvant therapy resulted in greater median survival times and 5-year survival rates. The best candidate for surgery had no evidence of additional metastatic disease, good performance status, and a long disease-free interval after treatment of the primary tumor. Current treatment standards for breast cancer follow-up do not include imaging studies other than mammography. The addition of chest x-rays as part of routine follow-up should be considered as a cost-effective approach for early assessment of metastases to the lung or sternum that may be appropriate for surgical excision.

Bone Neoplasms↗

PubMed2003

Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases.

PURPOSE: The purpose is to identify biological markers that predict brain metastasis and treatment outcome in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Samples were obtained from the primary tumors, lymph nodes, and brain metastases of 29 patients with NSCLC who had undergone resection of both the pulmonary tumors and the brain lesions. Samples from 29 patients matched for age, sex, and histology whose pulmonary tumors were resected served as controls. Samples were stained with H&E as well as immunohistochemical stains for epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX-2), and BAX. Comparisons were made between patients with and without brain metastasis. Independent investigators determined the percentage of positive cells. RESULTS: There was positive correlation in expression of all three biomarkers between primary lung tumors and lymph node metastases. Significantly higher levels of EGFR were found in lymph node metastases in the control group (P = 0.0147). COX-2 expression in brain lesions correlated with expression in primary tumors (P = 0.023). BAX levels were lower in poorly differentiated tumors in lymph node metastases in the control group (P = 0.01) and in brain metastases (P = 0.045). Low EGFR expression and high COX-2 expression in lymph node metastasis were associated with poorer treatment outcome. CONCLUSIONS: Expression of EGFR, COX-2, and BAX in primary lung tumors did not differ between patients with brain metastases from NSCLC and those without brain metastases. These three biomarkers cannot be used to predict brain metastasis. Studies of other biomarkers are under way in an effort to predict brain metastasis among patients with NSCLC.

Adult↗

PubMed2002

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion.

PURPOSE: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar. METHODS AND MATERIALS: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis. RESULTS: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p = 0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p = 0.04), and these patients had a higher rate of nonbrain distant metastases (p = 0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p = 0.01). There was a positive correlation in the expression of Ki-67 (p = 0.02)(r(2) = 0.1608), as well as p53 (p < 0.001) (r(2) = 0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive. CONCLUSION: Differences in biomarker expression between the case and control groups did not serve as significant predictors of brain metastasis or patient survival. There was a strong correlation between lung primary biomarker expression and brain metastasis expression for Ki-67 and p53. Univariate analysis showed that low p53 and high Ki-67 expression predicted poor prognosis. This study shows that there may be a strong correlation between biomarker expression in non-small-cell lung cancer primary tumors and their brain metastases.

Adult↗

PubMed2002

Toward better early-phase brain tumor clinical trials: a reappraisal of current methods and proposals for future strategies.

Although no optimal treatment is currently available for malignant brain tumors, as the molecular mechanisms underlying brain tumor development have been delineated, new chemotherapeutic agents that act directly on specific molecular targets have become available. Defining a specific molecular target raises the possibility that the molecular effects of a given agent can be analyzed in patients in a clinical trial. Specifically, whereas standard phase I and II clinical trials classically determine the safety and efficacy of agents by using indirect global end points, these new biological agents afford the opportunity to incorporate molecular end points into phase I and II clinical trials to determine whether the agent under investigation is actually doing what it was intended to do. This work presents avenues for improving current brain tumor clinical trial designs based on the molecular specificity of new agents and the unique features of brain tumors. Specifically, the authors recommend brain-applicable phase I and II clinical trial strategies that take advantage of the targeted nature of new agents to maximize information about their efficacy, toxicity, and molecular effects.

Brain Neoplasms↗

PubMed2002

Necrosis and glioblastoma: a friend or a foe? A review and a hypothesis.

OBJECTIVE: Two main forms of cell death are encountered in biology: apoptosis (i.e., programmed cell death) and necrosis (i.e., accidental cell death). Because necrosis and apoptosis can lead to cell removal, one might intuit that they are both desirable in cancer treatment. However, in the setting of glioblastoma multiforme, a malignant brain tumor for which the presence of necrosis is an important diagnostic feature, clinical studies indicate that as the degree of necrosis advances, the patient's prognosis worsens. Despite the apparent importance of this form of cell death, the mechanism of development of necrosis in glioblastomas remains unelucidated. The purpose of this article is to try to resolve this dilemma by hypothesizing the mechanism of necrosis formation in these tumors. METHODS: On the basis of an extensive review of the literature, we present a hypothesis for the mechanism of necrosis formation in glioblastoma multiforme. RESULTS: One of the many possible pathways leading to necrosis formation may involve increased tumor cell secretion of tumor necrosis factor. Procoagulation and antiapoptotic mechanisms resulting from certain pathways could prevent the completion of tumor necrosis factor-induced apoptosis and could promote necrosis as the final mode of cell death. Such a hypothesis would explain the inverse correlation that exists between tumor necrosis and the survival of patients with glioblastomas, because the hypoxia that results from procoagulation selects for tumor cells that are more aggressive and more resistant to apoptosis-inducing therapies. CONCLUSION: A complete understanding of the series of events surrounding necrosis development in glioblastomas that is evidence-based is likely to provide targets for future therapies. On the basis of the potential mechanisms of development of necrosis described in this article, we postulate that effective therapies may have to be directed against the pathways that result in the formation of necrosis.

Apoptosis↗

PubMed2002

Unusual small choroid plexus cyst obstructing the foramen of monroe: case report.

This is a case report of unusual case of choroid plexus cyst at the right foramen of Monro in the anterior third ventricle that caused unilateral obstructive hydrocephalus. The value of small-FOV thin-section MR imaging in the diagnosis of small lesions of the foramen of Monroe is demonstrated. The immunohistochemical findings in choroid epithelial cysts in comparison with those of other types of cysts at this location are discussed.

Brain Diseases↗

PubMedDate not supplied

Chairman's reflection on the past, present and future of neurosurgical oncology.

The development of neurosurgical oncology as a subspecialty is closely tied to the development of neurosurgery as a whole. Therefore, the progress that has taken place in the diagnosis and the surgical management of neurosurgical disorders has been widely applied to oncologic disorders affecting the nervous system. The challenges and opportunities that characterize the specialty are grouped into five general categories. These are issues that are related to (1) the management of a large and diverse patient population, (2) the proper training of neurosurgeons to develop the set of required technical skills, (3) the lack of disease curability and its associated opportunity for research endeavors, (4) the importance of the multidisciplinary coordination of care in a horizontal matrix model, and (5) the psychosocial dimensions that are a part of the complexity of human nature. Based on a current assessment of the subspecialty, a perspective on the unfolding future is obtained. This future can be characterized by a stronger workforce, a broader connectivity and representations, and an improved scientific inquiry.

Brain Neoplasms↗

PubMedDate not supplied

Optimizing outcomes with maximal surgical resection of malignant gliomas.

BACKGROUND: Aggressive surgical resection of malignant gliomas is a controversial issue in neurosurgery. Studies with rigorous methodology that fully address this issue have only recently become available. METHODS: The controversy regarding the role of maximal surgical resection of malignant gliomas is reviewed. The authors discuss surgical techniques and adjunctive technologies that can be utilized to assist in resection of these lesions. RESULTS: Using current microneurosurgical techniques, it is possible to resect malignant gliomas in gross total fashion. An aggressive approach in which 98% or more of the tumor mass is resected results in a statistically significant survival advantage. CONCLUSIONS: An aggressive surgical procedure for malignant gliomas can result in increased survival duration for selected groups of patients.

Brain Neoplasms↗