Tumors of the Osseous Spine

Recent advances in molecular biology with the development of novel therapeutic agents, as well as fundamental understanding of the mechanisms of bone metastases have greatly altered the therapeutic options in patients with spine tumors. Improvements in spine instrumentation as well as the development of recombinant Bone Morphogenetic Protein for spine reconstruction and fusion offers promising hope for curative strategies in selected patients. A clearer application of the fundamentals of surgical oncology applied to spine tumors should result in a greater proportion of patients undergoing surgically appropriate en bloc resections for spine tumors. Finally, the superiority of surgery over external irradiation in the controlled clinical trial setting should greatly expand the pool of patients requiring surgery. In this review, we consider the recent advances in primary bone tumors including chordoma, sarcomas, multiple myeloma, as well as metastatic cancer to the spine.     

Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene

Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be specific biomarkers of exposure to benzene. We analyzed BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19 workers and 19 controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. The adducts were analyzed by gas chromatography-mass spectrometry following reaction of the protein with trifluoroacetic anhydride and methanesulfonic acid. When subjects were divided into controls (n = 42) and workers exposed to < or =31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure: Spearman r = 0.67, P < 0.0001). To our knowledge, these results represent the first observation in humans that BO-Hb levels are significantly correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting a significant correlation with exposure (Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from both Hb and Alb adducts was very similar. These results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of exposure to high levels of benzene. As part of our investigation of the background levels of BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the observed background adducts reflect an artifact of the assay, while other portions are indicative of either unknown exposures or endogenous production of adducts.      

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S- transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.      

Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene

Two of the most common cytogenetic changes in therapy- and chemical- related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.      

Prostate vascular flow: the effect of ejaculation as revealed on transrectal power Doppler sonography

OBJECTIVE. The objective of our study was to determine the effect of ejaculation on prostate vascular flow. SUBJECTS AND METHODS. Using power Doppler technology, we performed four transrectal sonographic examinations before and immediately, 6 hr, and 24 hr after ejaculation in 10 healthy volunteers. Images were assessed by three independent observers. RESULTS. Ninety-seven percent of the images ranked as having the least flow were from the baseline examination. There was a significant difference between the rankings when categorized into the four time sets (mean score for the baseline group was 1.1, whereas for the immediate, 6-, and 24-hr postejaculation groups it was 2.5, 2.9, and 2.4, respectively (p<0.0001). The only statistically significant difference was between the baseline and the three remaining groups. Interobserver agreement was high, with the chance-corrected measure of agreement of 0.78. CONCLUSION. Transrectal sonography revealed that prostate vascular flow increases dramatically after ejaculation and remains elevated for at least 24 hr. This observation should be considered when power Doppler sonography is used to assess for potential hyperemia in patients suspected of having prostate abnormalities.     

Evaluation of Safe Kids Week 2004: Age 4 to 9? It's Booster Seat Time!

OBJECTIVE: To assess the effectiveness of a national one week media campaign promoting booster seat use. DESIGN: Pre-test, post-test design based on nationally representative random digit dialing telephone survey, with control for exposure to campaign. SETTING: Canada. SUBJECTS: Parents of children aged 4-9 years. INTERVENTIONS: During a one week campaign in May 2004, information on booster seat use was distributed via a national media campaign, retail stores, medical clinics, and community events. Information included pamphlets with guidelines for booster seat use, as well as a growth chart (designed by Safe Kids Canada) to assist parents in determining if their child should be using a booster seat. Assessing seat belt fit was described in detail on the growth chart. MAIN OUTCOME MEASURES: Knowledge, attitudes, and self-reported behaviors regarding booster seat use. RESULTS: Respondents in the group exposed to the campaign were twice as likely to report using a booster seat with lap and shoulder belt for their child (47%), compared to those in the pre-test (24%) and the unexposed (23%) groups (p<0.001). However, only small differences in general knowledge regarding booster seat use were found between the groups. CONCLUSIONS: A one week national media campaign substantially increased self-reported use of booster seats. Parents did not remember details of the campaign content, but did remember implications for their own child.     

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer

Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high‐volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high‐volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.     

Ethical and Practical Considerations for Collecting Research-Related Data from Commercially Sexually Exploited Children

This article presents seven challenges of collecting primary (i.e., firsthand) data from commercially sexually exploited children (CSEC). We drew on our research team's experience collecting longitudinal data from 28 CSEC survivors with a 12-month follow-up period. We used both face-to-face and electronic group brainstorming methods to nominate a list of research-related challenges. The two main themes that were identified were challenges that can limit data quality and concerns about the impact of research on participants, researchers, and others. The three challenges related to data quality are (1) the age of the research participants; (2) questions about obtaining informed consent from parents or guardians; and (3) the over-interrogation of CSEC youth. The four challenges related to concerns about the impact of research were (4) concerns that research participation may further exploit youth; (5) staying in the role of researcher and refraining from providing advocacy; (6) secondary trauma and burnout experienced by research staff; and (7) the additional burden that research and data collection may place on the advocates and direct service providers. Because the process of collecting data from CSEC youth can be complicated, and rife with ethical and practical challenges, we have relayed our experiences with seven specific research-related challenges in order to stimulate discourse and further progress in the field.