Objective Patient age, hemorrhagic presentation, nidal diffuseness, and deep perforating artery supply are important factors when selecting patients with brain arteriovenous malformations for surgery. We hypothesized that these factors outside of the Spetzler-Martin grading system could be combined into a simple, supplementary grading system that would accurately predict neurological outcome and refine patient selection. Methods A consecutive, single-surgeon series of 300 patients with AVMs treated microsurgically was analyzed in terms of change between preoperative and final postoperative Modified Rankin Scale scores. Three different multivariable logistic models (full, Spetzler-Martin, and supplementary models) were constructed to test the association of combined predictor variables with the change in MRS score. A simplified supplementary grading system was developed from the data which combined age, hemorrhagic presentation, and diffuseness in a manner analogous to the Spetzler-Martin grading system, with points assigned according to each variable and added together for a supplementary AVM grade. Results Predictive accuracy was highest for the full multivariable model (receiver operating characteristic curve area, 0.78), followed by the supplementary model (0.73), and least for the Spetzler-Martin model (0.66). Predictive accuracy of the simplified supplementary grade was significantly better than that of the Spetzler-Martin grade (P=0.042), with ROC curve areas of 0.73 and 0.65, respectively. The predictive accuracy of the supplementary grade was only slightly less than a full point score with all 7 weighted variables (P=0.364), with areas under the ROC curve of 0.73 and 0.75, respectively. Conclusions This new AVM grading system supplements rather than replaces the well established Spetzler-Martin grading system, and is a better predictor of neurological outcomes after AVM surgery. The supplementary grading scale has high predictive accuracy on its own and stratifies surgical risk more evenly. Supplementary grades can confirm risk predicted by the Spetzler-Martin grade, or in cases of mismatched grades, may alter management decisions. The supplementary grading system is easily applicable at the bedside, where it is intended to improve preoperative risk prediction and patient selection for surgery.
In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC.
Purpose: To determine the toxicity, immunologic, and clinical activity of immunotherapy with irradiated, allogeneic, prostate cancer cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with recurrent prostate cancer. Patients and Methods: A single-institution phase I/II trial was done in hormone therapy^naI« ve patients with prostate-specific antigen (PSA) relapse following radical prostatectomy and absence of radiologic metastases.Treatments were administered weekly via intradermal injections of1.2 Â 10 8 GM-CSF gene^transduced, irradiated, cancer cells (6 Â 10 7 LNCaP cells and 6 Â 10 7 PC-3 cells) for 8 weeks.Results: Twenty-one patients were enrolled and treated. Toxicities included local injection-site reactions, pruritus, and flu-like symptoms. One patient had a partial PSA response of 7-month duration. At 20 weeks post first treatment, 16 of 21 (76%) patients showed a statistically significant decrease in PSA velocity (slope) compared with prevaccination (P < 0.001). Injection site biopsies showed intradermal infiltrates consisting of CD1a + dendritic cells and CD68 + macrophages, similar to previous clinical trials using autologous GM-CSF-transduced cancer cells. Posttreatment, patients developed new oligoclonal antibodies reactive against at least five identified antigens present in LNCaP or PC-3 cells. A high-titer antibody response against a 250-kDa antigen expressed on normal prostate epithelial cells was induced in a patient with partial PSA remission; titers of this antibody decreased when treatment ended, and subsequent PSA relapse occurred. Conclusions: This non-patient-specific prostate cancer immunotherapy has a favorable safety profile and is immunologically active. Continued clinical investigation at higher doses and with longer boosting schedules is warranted.
In this cohort of mainly white men, the MnSOD gene Ala16Val polymorphism was not associated with total or aggressive prostate cancer risk. However, men with the MnSOD Ala/Ala genotype who had low long-term lycopene status had a higher risk of aggressive prostate cancer compared with individuals with the other genotypes. These results are consistent with findings from earlier studies that reported when antioxidant status is low, the MnSOD Ala/Ala genotype may be associated with an increased risk of aggressive prostate cancer.
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