Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors.

UNLABELLED: Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood. BACKGROUND: Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.) MATERIALS AND METHODS: The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained. RESULTS: Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical significance for disease free survival. CONCLUSION: Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.

Preliminary experience in the treatment of choroidal melanoma with gamma knife radiosurgery.

OBJECT: The authors report their early results from an ongoing experience treating patients with choroidal melanoma by using gamma knife radiosurgery (GKS). METHODS: Between September 1998 and March 2000, 11 patients were treated for choroidal melanoma. Treatment was facilitated with specialized frame placement. Eye immobilization was accomplished with supra- and infraorbital nerve block and tethering sutures to the periorbital tissue. Magnetic resonance imaging was performed to localize the tumor for treatment planning. Plugging patterns were used to steer fall-off radiation away from the fovea, optic nerve, or lens. Tumor volume, tumor location relative to critical structures, and dose to critical structures were determined using GammaPlan. Tumor response was determined using ultrasonography. Toxicity was determined by clinical assessment, visual acuity testing, and ophthalmoscopy. All 11 patients successfully completed the treatment. In every case, 40 Gy was prescribed to the 50% isodose, which completely encompassed all visible tumor. Tumor height ranged from 2.9 to 7 mm. The tumor diameter ranged from 6 to 13 mm. The range of follow up was 2 to 19 months. No tumor has progressed. One patient had improvement in vision because of improvement in retinal detachment. Two patients experienced visual decline. One patient's visual decline was due to a vitreous hemorrhage, and the other's was due to hard exudates encroaching on the macula. One patient has developed a dry eye that is managed effectively with topical eye lubricants. CONCLUSIONS: This preliminary experience demonstrates that GKS is a feasible treatment option for small- to medium-sized choroidal melanomas. Longer follow up and additional patients will be required to improve the assessment and the ultimate tumor control and toxicity in this ongoing series.

New techniques in the radiotherapeutic treatment of gynecological malignancies.

The management of patients with gynecological malignancies serves as a prominent example of the importance of multi-modality oncologic therapy. Optimal treatment of these patients requires the skillful implementation of surgery, radiation therapy and chemotherapy. The decision to use simple versus combined modality therapy is crucial and best carried out in centers in which an experienced and coordinated multidisciplinary team is available. In this article, we have reviewed the most recent data regarding the role of radiation therapy in gynecological malignancies and have pointed out those areas where additional confirmatory studies are needed.

Advances in gynecologic radiation oncology.

Radiation therapy is an important modality in the curative and palliative management of patients with gynecologic malignancies. However, the specific roles of radiation therapy continue to evolve in terms of specific indications, volumes treated, techniques, and integration with other modalities. Retrospective assessments of outcome and prospective clinical trials are necessary to answer questions, generate additional hypotheses, and guide further refinements in the application of radiation therapy. This article focuses on recent literature and ongoing clinical trials in this disease group.

The prospects for analogue neural VLSI.

In recent years, the efforts of analogue, neural-hardware designers have shifted from generic analogue neurocomputers to "niche" markets in sensor fusion and robotics, and we explain why this is so. We describe the main differences between digital and analogue computation, and consider the advantages of pure analogue and pulsed methods of design. We then investigate some important issues in analogue design of neural machines, namely weight storage (volatile and non-volatile), on-chip learning, and arithmetic accuracy and its relationship to noise. Finally, we outline those areas in which analogue techniques are likely to prove most useful, and speculate as to their likely long-term utility.

The A-1 antigen: a novel marker in experimental peripheral nerve injury.

Expression of the Schwann cell phenotype is regulated by signals from the adjoining axon. After axotomy, the Schwann cell ceases the production and maintenance of the myelin sheath and assumes phagocytic properties necessary to digest its own myelin. The molecular mechanisms responsible for this behavior remain unclear. A monoclonal antibody termed BIKS was produced after the immunization of mice with guinea pig lymphoid tissue. This antibody recognizes a cytoplasmic vesicle-associated molecule (A-1 antigen) which is abundant in all tissue macrophages but is also expressed in small amounts in normal Schwann cells. Following axotomy, the A-1 antigen appears to be translocated from a perinuclear site to accumulate in large quantities around myelin ovoids in Schwann cells, as well at the nodes of Ranvier-sites where Wallerian degeneration is known to commence. The level of the antigen remains high when axons are prevented from regeneration. During repair of crush injury, however, the level of antigen drops concomitant with the ingrowth of regenerating axons, suggesting axonal control of A-1 antigen expression.

A prospective randomized trial of fluorouracil versus fluorouracil plus cisplatin in the treatment of metastatic colorectal cancer: a Hoosier Oncology Group trial.

From May 1984 through December 1986, 141 patients with metastatic adenocarcinoma of the colon or rectum were entered on this Hoosier Oncology Group (HOG) trial evaluating the role of cisplatin in systemic therapy. Patients were stratified by the presence or absence of hepatic metastases and by performance status, and were subsequently randomized to receive fluorouracil (5-FU) (15 mg/kg/wk) alone or the same dose of 5-FU plus cisplatin (60 mg/m2 every 3 weeks). The total duration of treatment was six cycles (18 weeks). In 132 fully evaluable patients the objective response rates were 19% for 5-FU and 22% for 5-FU plus cisplatin. Statistically, the median survival times of 40 and 39 weeks were not significantly different (P = .62). However, the median duration of remission (MDR) was superior (P = .05) for 5-FU alone. This study fails to confirm clinically significant synergy of 5-FU plus cisplatin in the treatment of metastatic colorectal cancer.

Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer.

In this phase III randomized study, 124 evaluable patients with unresectable non-small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens.

Induction of myeloperoxidase deficiency in granulocytes in lead-intoxicated dogs.

Lead interferes with heme synthesis in erythrocytes and has a deleterious effect on red cell membranes. We measured myeloperoxidase (MPO) enzyme activity in the granulocytes of dogs fed increasing quantities of lead. Concurrently, iodination capability and in vitro bactericidal activity were measured. Blood lead levels were monitored. Three of 4 dogs poisoned with lead developed significant decreases in MPO enzyme activity in their granulocytes. The decline in MPO activity correlated with cumulative lead toxicity as judged by blood lead levels and clinical signs of lead poisoning. Iodination ability in all 4 dogs decreased with cumulative lead toxicity. After discontinuation of lead administration, recovery of granulocyte MPO activity preceded recovery of iodination ability. This observation suggests the possibility of separate effects of lead on iodination ability and MPO activity. Moderate impairment of bactericidal capacity developed in 3 of 4 dogs with severe lead poisoning. Clinical infections were not observed during the course of the study.