Update on malignant mesothelioma

Mesotheliomas are uncommon in the United States, with an incidence of about 3,000 new cases per year (or a risk of about 11 per million Americans per year). Incidence and mortality, however, are probably underestimated. Most are associated with asbestos, although some have arisen in ports of prior radiation, and a reported association with simian virus (SV)40 remains controversial. About 85% of mesotheliomas arise in the pleura, about 91% in the peritoneum, and a small percentage in the pericardium or tunica vaginalis testis. The histology of about half of mesotheliomas is epithelial (tubular papillary), with the remainder sarcomatous or mixed. Multicystic mesotheliomas and well-differentiated papillary mesotheliomas are associated with long survival in the absence of treatment and should be excluded from clinical trials intended for the usual rapidly lethal histologic variants of the disease. The median survival is under a year, although longer median survivals for selected patients, particularly those with epithelial histology, have been reported in some combined-modality studies. Recent randomized trials have shown significant improvement in time to progression and survival for the addition of new antifolates to platinum-based chemotherapy.     

A national framework for cancer surveillance in the United States

Enhancements to cancer surveillance systems are needed for meeting increased demands for data and for developing effective program planning, evaluation, and research on cancer prevention and control. Representatives from the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, National Cancer Registrars Association, and North American Association of Central Cancer Registries have worked together on the National Coordinating Council for Cancer Surveillance to develop a national framework for cancer surveillance in the United States. The framework addresses a continuum of disease progression from a healthy state to the end of life and includes primary prevention (factors that increase or decrease cancer occurrence in healthy populations), secondary prevention (screening and diagnosis), and tertiary prevention (factors that affect treatment, survival, quality of life, and palliative care). The framework also addresses cross-cutting information needs, including better data to monitor disparities by measures of socioeconomic status, to assess economic costs and benefits of specific interventions for individuals and for society, and to study the relationship between disease and individual biologic factors, social policies, and the environment. Implementation of the framework will require long-term, extensive coordination and cooperation among these major cancer surveillance organizations. We acknowledge the contributions of Ronda Starr, who assisted in the preparation of the tables, the web addresses for the data sources, and the references.     

The validity of the family relationships index as a screening tool for psychological risk in families of cancer patients

The Family Relationships Inventory (FRI) has been proposed as a measure of psychological risk however its validity has only been tested in one cross-sectional study against another measure of family functioning where patients had less than six months to live. The current study presented longitudinal data on the validity of the FRI in identifying family dysfunction, and clinical levels of depression and anxiety in 48 families where the patient had been recently diagnosed. Over the three phases, the FRI identified all families at risk of family dysfunction, 88% or more families with one or more members with clinical depression and 78% or more with a member with clinical levels of anxiety. The FRI was also far more sensitive in identifying families with a member with clinical levels of depression and anxiety than the General Functioning (FAD-GF) scale of the Family Assessment Device. Although other measures of screening adequacy (such as specificity), suggested that the FRI identified too many false positives, the higher sensitivity of the FRI makes it preferable to the FAD-GF as a screening measure for families at risk of a poor psychological outcome in the oncology setting. However, because of the FRI's poor specificity, further follow-up of those families that are identified as being at some risk of a poor psychological outcome should be undertaken before referral to a mental health professional is warranted.     

Ecstasy use among Hispanic and black substance users in New York City

Surveillance data suggests that use of ecstasy in the U.S. is predominantly among white adolescent and young adults. To investigate ecstasy use among substance users in New York City we added questions to ongoing efforts to recruit heroin and cocaine users. Of 715 participants recruited, 58.3% were injection drug users (IDUs). The median age was 32 (range 17-64), 76.4% were male, 49.0% were currently homeless, 62.4% were Hispanic, 27.3% were black, and 34.5% were born outside the United States. Overall, 23.4% used ecstasy in their lifetime and 11.9% had used in the last-6 months. In multivariate logistic regression, correlates of lifetime ecstasy use included younger age, being born in the U.S., and current homelessness. We observed a significant interaction between injection drug use and race where, compared to black non-IDUs, Hispanic non-IDUs, and white IDUs were significantly more likely to have a history of lifetime ecstasy use while black IDUs were significantly less likely. These findings are limited to persons who use other drugs, but suggest that further investigation of ecstasy use in minority populations is warranted.     

Profile of territrem metabolism and cytochrome P-450 3A expression in liver microsomes from Wistar rats of both genders as a function of age

This study determined territrem metabolites after incubation of territrem A, B, or C with NADPH and liver microsomes from Wistar rat of both genders aged 2 to 76 wk. The liver microsomal cytochrome P-450 content, NADPH-cytochrome P-450 reductase activity, and CYP3A1 and CYP3A2 protein and mRNA levels were also analyzed. Male rats had significantly higher liver microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase activities than females at 14 to 26 wk. Microsomal cytochrome P-450 content was decreased in senescence in both genders compared with postpubertal and adulthood stages. The activity of 6beta-testosterone hydroxylase in male rats, which was significantly higher than those in females at all ages, decreased after 52 wk. After 26 wk, the levels of CYP3A1 protein markely declined in both genders, which resulted in a large gender difference (male greater than female). The protein levels and mRNA of CYP3A2 were constitutively expressed in 2- to 52-wk-old male rats, but they decreased after 76 wk, and decreased in females after 6 wk. The expression of CYP3A1 or CYP3A2 in males are generally higher than in females. The metabolites of territrems MA1, MAX, MA2, MB2, MB4, and MC were measured by high-performance chromatography (HPLC). Formation of MA1, MAX, and MA2 decreased after 52 wk in males, and MAX and MA2 were not formed after 6 wk in females. The amount of MB2 formed in females was less than in males, but the amount of MC (TRC metabolites) formed in females was higher than in males. The gender differences in metabolism of TRA were related to the protein and mRNA expression of CYP3A2. The protein levels and mRNA expression of CYP3A2 and efficiency of territrems metabolism were decreased after 76 wk. The results suggested that the effects of age and gender on territrem metabolism are due to differences in CYP3A1 and CYP3A2 expression in the liver microsomes.     

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.     

Using Community Readiness Key Informant Assessments in a Randomized Group Prevention Trial: Impact of a Participatory Community-Media Intervention

This study examines the role of key informant community readiness assessments in a randomized group trial testing the impact of a participatory community-media intervention (which was also complemented by in-school efforts). These assessments were used to help match communities in random assignment, as a source of formative data about the community, as the basis for a coalition-building workshop, and as an evaluation tool, with a follow-up set of surveys approximately 2 years after the baseline survey. Results of the nested, random effects analysis indicated that the intervention influenced community knowledge of efforts and (at marginally significant levels) improved prevention leadership quality and community climate supportive of prevention efforts. There was evidence that the professional affiliation of informants in some cases had an effect on their assessments, which could be controlled in the analysis. The authors conclude that key informant community readiness assessments can usefully serve to supplement aggregated measures of individual attitudes and behavior (reported elsewhere for this study) in evaluating community-based interventions.     

Prospective evaluation of 6895 groin hernia repairs in women

BACKGROUND: Although 8 per cent of groin hernia repairs are performed in women, there is little published literature relating specifically to women. This study compared differences in outcome between women and men after groin hernia repair. METHODS: Data collected prospectively in the Swedish Hernia Register between 1992 and 2003 were analysed, including 6895 groin hernia repairs in women and 83 753 in men. RESULTS: A higher proportion of emergency operations was carried out in women (16.9 per cent) than men (5.0 per cent), leading to bowel resection in 16.6 and 5.6 per cent respectively. During reoperation femoral hernias were found in 41.6 per cent of the women who were diagnosed with a direct or indirect inguinal hernia at the primary operation. The corresponding proportion for men was 4.6 per cent. The hernia repair was not classified as a standard operation (e.g. Shouldice, Lichtenstein, Plug/Mesh, TAPP/TEP) in 38.2 per cent of women and 11.2 per cent of men. Women had a significantly higher risk of reoperation for recurrence than men, and techniques associated with the lowest risk for reoperation in men had the highest risk in women. CONCLUSION: A greater proportion of women than men require emergency groin hernia repair, with consequently higher rates of bowel resection, complications and death. Surgical techniques developed for use in men may put women at unnecessary risk.