Determination of HER-2/neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors.

INTRODUCTION: HER-2/neu overexpression has been associated with poor prognosis in a variety of malignancies. The extent and relevance of HER-2/neu overexpression in human central nervous system (CNS) malignancies is unclear. We retrospectively analyzed a large cohort of patients with primary malignant brain tumors to evaluate the role of HER-2/neu overexpression, clinical characteristics at presentation, and other predisposing factors as predictors of survival. MATERIALS AND METHODS: Records of 347 adult patients (193 males, 154 females) diagnosed and followed between 1986 and 2001 with a biopsy-proven diagnosis of a primary malignant brain tumor at a tertiary care oncology center were reviewed. Archival pathologic samples were analyzed for HER-2/neu overexpression using the Hercep immunohistochemical (IHC) assay (DAKO). A score of 2+ or greater on the assay was considered positive for HER-2/neu overexpression. Mortality and its predictors were evaluated using multiple logistic regression. (This study was approved and reviewed by the Institutional Review Board Committee [IRB] of University of North Dakota School of Medicine and Health Sciences.) RESULTS: Among the 347 adult patients with a mean age of 53 years (range; 41-73 years), overall mean survival was 23 months (range; 0-151 months). It was found that 10.4% of the archival pathologic samples showed presence of HER-2/neu overexpression by IHC. The HER-2/neu overexpression predicted significantly increased mortality [p = 0.01, analysis of variance (ANOVA)]. Other clinical predictors associated with increased mortality included site of tumor (occipital and parietal lobes) (p = 0.02, ANOVA), tumor histology (glioblastoma) (p < 0.01, ANOVA), and presenting symptom (nausea/vomiting) (p < 0.01, ANOVA). Also, there was a higher incidence of associated primary malignancies (outside the CNS) in the HER-2/neu overexpression group (30% vs. 7%). CONCLUSIONS: HER-2/neu overexpression seen in 10.4% appears to predict a slight increased mortality in patients with primary malignant brain tumors, especially glioblastoma multiforme, and is associated with a high incidence of a second primary malignancy outside the CNS. Additionally, our data suggests that other clinical variables were predictive of increased mortality, including tumor location (occipital), histology (glioblastoma), and presenting symptoms (nausea/vomiting). The large, heterogeneous sample employed in our study allows more definitive conclusions to be made with regard to the usefulness of HER-2/neu and other clinical predictors of survival in patients with primary brain tumors.

An epidemiological study evaluating the relationship of distance from a tertiary care cancer center to early detection of colorectal carcinoma.

OBJECTIVE: AJCC stage at diagnosis determines the treatment approach and indirectly predicts outcome in patients with colorectal carcinoma. The purpose of our study was to investigate whether there was a delay in diagnosis leading to a more advanced stage at diagnosis (which affects outcome) of patients with colorectal cancers because of distance from a referral center, after positive fecal occult blood testing (FOBT). DESIGN: Our retrospective observational study involved all cases of colonic and rectosigmoid cancers that were referred for an endoscopic procedure after an initial positive FOBT done as a part of routine screening in asymptomatic patients. PARTICIPANTS: Roger Maris Cancer Center and University of North Dakota School of Medicine and Health Sciences. RESULTS: Between the years 1996-2001, 178 subjects with biopsy-proven colon cancer and 80 patients with rectosigmoid cancer were included in our study. Pearson's correlation coefficients were constructed to look at the relationship between distance from a referral center (place where the diagnosis was made) and stage at diagnosis in patients with colonic and rectosigmoid malignancies. For the colon cancer group, the regression coefficient between AJCC stage at diagnosis and distance from the referral center was 0.013 and for rectosigmoid cancers it was 0.12. Even after stratifying distances into tertiles, the correlation coefficients did not show a significant relationship (0.04 for colon and 0.16 for rectosigmoid cancers). CONCLUSION: Distance (of residence) from a tertiary care center does not seem to be a barrier to early diagnosis of colorectal carcinoma and primary care providers in rural settings are referring patients appropriately leading to optimal outcomes.

Spinal epidural abscess after corticosteroid injections.

Although spinal epidural abscess is uncommon, its incidence is likely to rise with increasing use of epidural injections for the control of lower back pain. We report a case of spinal epidural abscess after epidural steroid injection. The abscess resolved with conservative medical management.

Hyperhomocysteinemia and the risk of thromboembolic phenomenon in patients with chronic renal failure.

Thromboembolic phenomena are a major cause of morbidity and mortality in patients with end-stage renal disease. Studies in patients with chronic renal failure (CRF) have demonstrated an increased relative risk of coronary artery disease (CAD) in association with hyperhomocysteinemia (HHe). However, very little data exist about the causal relationship between HHe and cerebrovascular diseases (CVA) in patients with CRF. We report the results of our observational retrospective study to determine the effect of HHe on CVA and CAD in patients with CRF (defined as creatinine clearance <50 ml/min). One hundred ten male patients were eligible for our study performed at a Veterans Affairs Medical Center. Age range was 36-86 years (median age 67 years). A fasting plasma HC level >15 micromol/l was considered as HHe. Thirty-four patients were on dialysis. Eight patients were postrenal transplantation. Our study results showed that a homocysteine (HC) level greater than 15 micromol/l was an independent predictor of CVA, after adjusting for potential confounders. Adjusted odds ratio (OR) for CVA was 10.9 (CI: 1.8-67.2, p=.01). Although our study results suggest a strong relationship between HHe and CVA, they failed to demonstrate an association between HHe and CAD. There exists a need for larger prospective randomized clinical trials to evaluate the effect of HHe on the incidence of CVA and CAD in patients with CRF.