[Association between cord blood BPDE-DNA and neurodevelopment of children aged 0 and 2 years: A birth cohort study].

Objective: To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development. Methods: In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old. Results: The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points. Conclusion: Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Carcinoma showing thymus-like element (CASTLE) of thyroid: combined modality treatment in 3 patients with locally advanced disease.

OBJECTIVES: To examine the value of chemotherapy, radiotherapy and surgery for treatment of locally advanced carcinoma showing thymus-like element (CASTLE) of the thyroid. METHODS: Retrospective analysis of 3 Chinese patients in a tertiary referral center in Hong Kong. RESULTS: CASTLE is a rare thyroid malignancy with a frequency of only 0.15% (3/2033 patients) in our center. Three patients (M:F=2:1) aged 43, 49 and 62 years were studied. All 3 patients had advanced T4 disease with extensive tracheal infiltration and airway compression. None had lymph node or distant metastasis. Total thyroidectomy, combined with chemotherapy and radiotherapy, was effective in local control and symptom relief. Etoposide and carboplatin were tried in 2 patients with positive response. Neoadjuvant chemotherapy shrank the tumor rapidly and relieved symptoms of airway compression. All 3 patients had external radiotherapy resulting in good local control. In a patient with inoperable disease, chemotherapy and radiotherapy rendered the disease operable. All 3 patients were symptom-free and alive at 6, 2.5 and 1.8 years after diagnosis. CONCLUSIONS: CASTLE is locally infiltrative and presents at advanced T stage in this small series. Chemotherapy and radiotherapy, apart from surgery, are effective treatment modalities. In cases of inoperable disease or advanced local disease, they can be employed in combination with surgery. Organ preservation of larynx and trachea may be achieved. Chemotherapy can be very useful for rapid relief of symptoms, especially in shrinking tumor to prevent airway obstruction.

Curative radiotherapy for early cancers of the lip, buccal mucosa, and nose--a simple interstitial brachytherapy technique employing angiocatheters as carriers for Iridium-192 wire implants.

OBJECTIVES: To evaluate treatment outcomes following interstitial brachytherapy for cancers of the lip, buccal mucosa, or nose. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 13 patients treated uniformly by a simple interstitial brachytherapy technique employing plastic angiocatheters as carriers for Iridium-192 wires: all but one patient had T1 or T2 tumours and all but one had N0 disease. MAIN OUTCOME MEASURES: Local and loco-regional control rates. RESULTS: Six of the 13 patients received external radiotherapy prior to interstitial brachytherapy. A median brachytherapy dose of 70 Gy was delivered to those treated with brachytherapy alone, while 35 Gy was delivered after a median external radiotherapy dose of 50 Gy to those receiving combined treatment. The 3-year actuarial local control rate was 75%. No significant late complications were observed. CONCLUSIONS: Employing a simple brachytherapy technique using angiocatheters and Iridium-192 wires, in conjunction with external radiotherapy when appropriate, produces good outcomes for patients with early lip, nasal vestibule, and buccal mucosa cancers.

Medullary thyroid carcinoma in Hong Kong Chinese patients.

OBJECTIVE: To study the clinical parameters and treatment outcome of medullary thyroid carcinoma in Hong Kong Chinese patients. DESIGN: Retrospective study. SETTING: Regional oncology unit, Hong Kong. PATIENTS: Patients with medullary thyroid carcinoma who were identified among 1656 patients with thyroid malignancies seen in a single institute in Hong Kong from January 1960 to June 2003. MAIN OUTCOME MEASURES: Ten-year cause-specific survival, locoregional failure-free survival, and distant metastasis failure-free survival. RESULTS: Twenty-two (1.3%) patients with medullary thyroid carcinoma were identified. The mean age at diagnosis was 43.7 (standard deviation, 16.5) years. The sex ratio was 1:1. The 10-year cause-specific survival, locoregional failure-free survival, and distant metastasis failure-free survival were 75.4%, 82.0%, and 62.4%, respectively. Lymph node metastasis was present in seven (31.8%) patients at diagnosis. Distant metastasis developed in nine (40.9%) patients: lung, 3 (13.6%); bone, 5 (22.7%); liver, 2 (9.1%); mediastinum, 4 (18.2%). Seven (31.8%) patients died of distant metastasis. Mediastinal (n=3) and bone metastases (n=3) were important causes of death. Genetic study confirmed multiple endocrine neoplasia type 2A in 3 (25.0%) of 12 patients who all had bilateral and multifocal diseases. Younger age (<45 years) was associated with better survival, better locoregional control, and less distant metastasis. Patients with pT1N0 disease (n=3) had an excellent prognosis: all were disease-free following total thyroidectomy. Among eight patients who received external radiation therapy, seven achieved good locoregional control. In seven patients with lymph node metastasis, external radiation therapy gave 100% (4/4) locoregional control compared with 33.3% (1/3) in those without external radiation therapy. Chemotherapy using dacarbazine and 5-fluorouracil was tried in three patients with poor response. CONCLUSIONS: Early stage (T1N0) medullary thyroid carcinoma is associated with a very good prognosis. Postoperative external radiation therapy can achieve good locoregional control in patients with lymph node metastasis or locally advanced disease.

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse sclerosing variant of papillary thyroid carcinoma--clinical features and outcome.

AIM: Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is rare and occurs in young patients. This is a single institute retrospective analysis to report the clinical features and outcome of DSPC. METHOD: DSPC constituted 8 (0.74%) of 1086 papillary thyroid carcinomas (PTC) referred to the department of Clinical Oncology, Queen Elizabeth Hospital Hong Kong from 1960 to 2000. RESULTS: The mean follow-up was 8 years (range: 1.4 to 15.2 years). Six were females and two were males, with age ranging from 11 to 48 years. All were ethnic Chinese. Compared with the whole cohort of PTC followed in the same period, these patients showed younger age at presentation (mean 27.4 vs 45.3 years), larger tumor size (mean 6.9 cm vs 2.4 cm), higher incidence of lymph node metastasis (100% vs 32.4%), and more frequent presence of serum anti-thyroglobulin autoantibody (75% vs 11.3%). The patients were managed as for differentiated thyroid carcinoma according to the institute's protocol, including total thyroidectomy followed by radioiodine (RAI) treatment. External radiotherapy was given to two patients as primary treatment and one patient after regional relapse. One patient had distant metastases at presentation and she was successfully treated by surgery followed by RAI, remaining in complete remission at 12.1 years. One patient had lymph node recurrence after primary total thyroidectomy and RAI treatment and was successfully salvaged by surgery and external radiotherapy. At last follow-up, all eight patients were alive with no evidence of disease. CONCLUSIONS: Although DSPC is associated with some unfavourable features at presentation (such as large tumor size, extensive lymph node metastasis), the prognosis appears to be as good as classical PTC. After aggressive treatment by radical surgery, RAI ablation and/or external radiotherapy, the outcome and survival was excellent.

Photoluminescence from C60-coupled porous structures formed on Fe+-implanted silicon.

111-oriented p-type Si wafer with a resistivity of 1-5 Omega cm was implanted with Fe+ and then annealed at 1100 degrees C in N2 for 60 min, followed by anodization in a solution of HF to form porous structure with beta-FeSi2 nanocrystallites. Photoluminescence (PL) spectral measurements show that a strong PL peak appears in the range of 610-670 nm. The position of the PL peak remains unchanged, but its intensity increases with the storage time in air until about three months and then saturates. C60 molecules were chemically coupled on the porous structure through a kind of silane coupling agent to form a nanocomposite. It is revealed that the stable PL peak monotonically shifts to a pinning wavelength at 570 nm. Experimental results from PL, PL excitation, Raman scattering, and x-ray diffraction measurements clearly show that the pinned PL originates from optical transition in C60-related defect states, whereas the photoexcited carriers occur in the beta-FeSi2 nanocrystallites formed during anodization. This work opens a new way to tailor nanometer environment for seeking optimal luminescent properties.

The role of molecular epidemiology in cancer prevention.

Risk of cancer is determined by the complex interaction between "environmental" exposures and genetic and nutritional factors that modulate response to carcinogenic insults. Here, the term "environmental" encompasses lifestyle, occupation, and the ambient environment. As a promising approach in cancer prevention, a number of biologic markers are currently being evaluated in terms of their ability to identify harmful exposures and populations at risk in time to effectively intervene. These biomarkers are reflective of the molecular dose or early effect of carcinogens (such as DNA or protein adducts, gene or chromosomal alterations and oncogene activation) or they provide information on potential susceptibility (such as the genetically or nutritionally determined handling of carcinogens). Techniques as diverse as immunoassays, 32P-postlabelling and gas chromatography-mass spectroscopy (GC/MS) are being deployed to measure DNA and protein adducts in cells and tissues from persons with occupational, community or lifestyle-related exposure to chemical carcinogens. Signal changes in target oncogenes and tumor suppressor genes are also being investigated in heavily exposed, "healthy" populations and in lung cancer cases and controls using current molecular biologic techniques. Inherited predisposition to lung cancer is being evaluated through such assays as aryl hydrocarbon hydroxylase (AHH), glutathione activity and restriction fragment length polymorphism. A review of recent studies using a panoply of biomarkers provides a departure point for recommendations for future, integrated molecular epidemiologic studies of cancer.

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.