Patients with osteosarcoma with a single pulmonary nodule on computed tomography: a single-institution experience

Background/PurposeThe purpose of this study is to determine if patients with osteosarcoma (OS) with metachronous metastatic pulmonary disease presenting with a single pulmonary nodule (SPN) on computed tomography (CT) were found to have other lesions at the time of thoracotomy.MethodsData were collected retrospectively on consecutive patients with OS treated at our institution from 1982 to 2007. Patients with no evidence of disease at the end of initial therapy who subsequently relapsed in the lung were identified.ResultsIn our study, 16 (8%) of 198 patients with OS with metachronous metastatic pulmonary disease presented with a SPN on CT scan. In all patients, only 1 metastatic nodule for OS was found at the time of thoracotomy. The median time between diagnosis and first lung relapse was 23.8 months (range, 4-80 months). Eleven patients (68.7%) subsequently had a second lung relapse, but only 3 patients had involvement of the ipsilateral lung (mean time interval between first and second pulmonary relapses of 17 months; range, 2-44 months). Five-year overall survival from diagnosis was 56.2%. Seven patients (43.8%) died of disease progression.ConclusionsIn our experience, patients with OS with metachronous metastatic pulmonary disease presenting with a SPN on CT were not found to have additional malignant lesions at the time of thoracotomy. Consideration should be given in this group of selected patients to use a minimally invasive approach to nodule removal with image-guided localization, if needed, rather than open thoracotomy because ipsilateral metastases are not likely to be found.     

Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients

Gefitinib (ZD1839, Iressa), a member of the 4-anilinoquinazoline class of compounds, has the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib often is referred to as a "specific" or "selective" inhibitor of epidermal growth factor receptor (EGFR). EGFR expression has been noted in neuroblastoma and rhabdomyosarcoma cell lines and in tumor specimens from children with Wilms tumor, osteosarcoma, and glioma. Thus, gefitinib, the first marketed EGFR tyrosine kinase inhibitor, was chosen for study in children with refractory solid tumors and central nervous system (CNS) malignancies. This review discusses findings from 3 clinical trials of gefitinib in children with refractory solid tumors and CNS malignancies, focusing on the clinical pharmacology of the compound. To date, gefitinib has been studied in children as a single agent and in combination with irinotecan. Overall, the compound has been well tolerated in children and has a safety profile similar to that observed in adults. The clinical pharmacokinetics of gefitinib in children are similar to those observed in adults. Finally, the future for the use of gefitinib in pediatrics is similar to that of other molecularly targeted agents and awaits definition of tumors and patient populations in which it will be most advantageous.     

Implication of MYH in colorectal polyposis

OBJECTIVE: The aim of this study was to determine the frequency of MYH mutations in one large population of polyposis patients without APC mutation identified. SUMMARY BACKGROUND DATA: Familial adenomatous polyposis (FAP) is the most known inherited colorectal cancer syndrome. In 70% to 80% of polyposis patients, an APC mutation is found. Patients with polyposis but no APC mutation are considered as APC-muted patients and followed as their relatives accordingly. Biallelic mutation of MYH has been found to responsible of colorectal polyposis and cancer in an autosomal recessive pattern of inheritance. METHODS: Between 1978 and 2004, 433 patients were operated for polyposis. A mutation on APC was identified in 322 patients. Among the remaining patients, 44 were identified as possible MYH-muted patients and contacted, and 31 signed informed consent. Clinical data were obtained from the patients' medical notes. Germline mutation of MYH was searched by sequencing the whole gene. To confirm the deleterious effects of biallelic MYH mutation, transversions on K-ras and APC were searched. RESULTS: There were 9 women and 22 men with a mean age of 53.9 years (range, 22-68 years) at the time of diagnosis. The mean number of polyps was 62.8 (range, 11-266). Eighteen patients (58.1%) had a colorectal cancer. We found biallelic MYH mutation in 6 patients (19.3%; 95% confidence interval, 5.2%-33.5%) and 5 (83.3%) had transversions in K-ras and/or APC. CONCLUSION: MYH is a new gene responsible for about 1.4% of all adenomatous polyposis and about 20% of adenomatous polyposis without APC mutation identified. Search for MYH biallelic mutation in these patients should be systematic as it changes their and relatives'surveillance.     

Sexual orientation, gender, and alcohol use in a cohort study of U.S. adolescent girls and boys

BACKGROUND: Sexual minority youth may be at elevated risk for alcohol use relative to heterosexual youth, but the reasons underlying higher rates and whether there may be gender differences in risk are not known. METHODS: Cross-sectional survey data from 9731 early and middle adolescent girls and boys in the Growing Up Today Study in 1999 were examined to assess sexual orientation and gender patterns in alcohol use. Multivariable regression models estimated associations between sexual orientation and alcohol-related behaviors, such as binge drinking and drinking before age 12 years. Models controlled for sociodemographic and psychosocial factors, with heterosexuals as the reference. RESULTS: Girls who described themselves as "mostly heterosexual" and lesbian/bisexual girls were at elevated risk compared to heterosexual girls on almost all alcohol-related behaviors and exposures. "Mostly heterosexual" boys were also at elevated risk. No significant differences in alcohol-related behaviors were observed between gay/bisexual and heterosexual boys. Gender-by-sexual orientation interactions were statistically significant for LGB but not other orientations, indicating that lesbian/bisexual girls experienced elevated risk above and beyond that of gay/bisexual boys relative to same-gender heterosexual peers. CONCLUSIONS: In early and middle adolescence, sexual minority girls and "mostly heterosexual" boys experienced consistent patterns of elevated risk for alcohol use.     

Carcinogenic PAH in waterpipe charcoal products

Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafés. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content.     

An Examination of the Fagerström Test for Nicotine Dependence Among Concurrent Tobacco and Khat Users

Abstract

The current study examined the psychometric properties of the Fagerström Test for Nicotine Dependence (FTND) among tobacco smokers who use khat (Catha edulis), a widely used substance in East Africa and Arabian Peninsula. We also explored gender differences in response to FTND items because little attention has been paid to women's smoking behavior in Middle Eastern societies. A total of 103 (38 women) concurrent users (mean age ± SD: 24.4 ± 5.2) were recruited from two universities in Yemen. An Arabic version of FTND was developed using back-translation method. Chronbach's alpha was used to examine the reliability and principal component analysis was conducted to test the factor structure of the scale. The scale was found to have low internal consistency reliability (Chronbach's α = .58). Two factors were identified, accounting for 57% of the total variance. A series of chi-square analyses found that men indicated more symptoms associated with nicotine dependence than women (ps < .05). Although the poor reliability observed in the present sample argues for a cautious approach when assessing nicotine dependence among khat users, the findings on factor structure and gender differences may provide support for the validity of the scale. Taking into account sociocultural factors associated with patterns of smoking behavior among this population should improve the psychometric properties of FTND.     

Severity of khat dependence among adult khat chewers: The moderating influence of gender and age

Ethnopharmacological relevance: The escalating use of khat (Catha edulis) in East Africa and Arabia is a major concern for public health. Yet little is known about the impact of khat on behavior. There has been no study in the region to assess the extent to which dependence syndrome is associated with khat use in this population. Aim of the study: To examine psychometric properties of the Severity of Dependence Scale-Khat (SDS-khat), gender differences in patterns of khat use and dependence, and the extent to which age moderated the link between gender and khat dependence. Materials and methods: Two-hundred and seventy khat chewers recruited in two Yemeni cities completed face-to-face interviews asking about demographics and patterns of khat use. Validity of SDS-khat was examined by the principle component analysis and reliability of the scale was tested by Cronbach?s alpha. A series of chi-square tests and analysis of variances (ANOVAs) were conducted to examine gender differences in khat use variables. Results: The results indicated that the mean age of khat chewers was 30.52 years (95% CI: 29.34, 31.70) and 52% of them were males. The SDS-khat was found to have two factors with moderate reliability. This pattern was consistent when the analysis was conducted in the entire sample and in each gender. Male khat chewers reported more symptoms related to khat dependence than female chewers. A significant gender by age interaction in SDS-khat levels (p=0.013) revealed a positive association between age and khat dependence in women only. Conclusion: These results provide initial support for the use of SDS-khat in the assessment of khat dependence in Yemen. Gender differences in khat use patterns and dependence observed in this study call the need for more studies carefully examining the role of gender in khat research.     

High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma

Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular‐genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray‐based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular‐genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment. © 2012 Wiley Periodicals, Inc.