Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer.

BACKGROUND: Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer. METHODS: Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR. RESULTS: Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52). CONCLUSIONS: Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Influences of dietary uptake and reactive sulfides on metal bioavailability from aquatic sediments.

Understanding how animals are exposed to the large repository of metal pollutants in aquatic sediments is complicated and is important in regulatory decisions. Experiments with four types of invertebrates showed that feeding behavior and dietary uptake control bioaccumulation of cadmium, silver, nickel, and zinc. Metal concentrations in animal tissue correlated with metal concentrations extracted from sediments, but not with metal in porewater, across a range of reactive sulfide concentrations, from 0.5 to 30 micromoles per gram. These results contradict the notion that metal bioavailability in sediments is controlled by geochemical equilibration of metals between porewater and reactive sulfides, a proposed basis for regulatory criteria for metals.

Congenital Partial Absence of Pericardium: A Mimic of Arrhythmogenic Right Ventricular Cardiomyopathy.

Congenital absence of pericardium is a rare condition with electrocardiogram, chest X-ray, and echocardiographic findings which may mimic those of other cardiac conditions. We present a case of a 19-year-old asymptomatic female with incidental cardiomegaly on chest X-ray and electrocardiographic and echocardiographic changes, which meet the revised task force criteria for definite arrhythmogenic right ventricular cardiomyopathy but subsequently confirmed to have congenital partial absence of pericardium on cardiac magnetic resonance imaging.

Vinorelbine induces apoptosis and caspase-3 (CPP32) expression in leukemia and lymphoma cells: a comparison with vincristine.

Vinorelbine (NVB) is a novel vinca alkaloid FDA approved for use in some advanced carcinomas. However, its role in non-Hodgkin's lymphoma (NHL) is still not well defined. NVB is an antimicrotubule agent, but as yet, it is not known whether it induces apoptosis. By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrated that NVB and vincristine (VCR) induced both mitotic arrest and apoptosis in leukemia and lymphoma cells, in a drug exposure time dependent manner. Cell cycle kinetics in 3 different cell lines varied during vinca alkaloid treatment. The annexin V method showed that apoptosis, as opposed to necrosis, was the dominant mode of cell kill of chemosensitive leukemia and lymphoma cells. Phosphatidylserine expression on the cell surface was detectable as a hallmark of apoptosis at earlier drug exposure when compared to conventional flow cytometry with PI staining. By Western blot analysis, we demonstrated that CPP32 or caspase-3, a critical apoptosis inducer, and its active subunits p20 and p11 were upregulated in chemo- and apoptosis-sensitive lymphoma and leukemia cells treated with NVB. Our data contributes to the emerging hypothesis suggesting that widely divergent exogenous stimuli and chemotherapeutic agents can effect apoptosis in cancer cells via different pathways involving the caspases. We believe that vinorelbine may be a potentially important drug in the treatment of NHL in the future.

Laparoscopic microsurgical tubal anastomosis.

The authors explored the feasibility of performing true microsurgery through the laparoscope in 1990. The first laparoscopic microsurgical tubal anastomosis was performed in February 1992. Operative laparoscopy will continue to expand as technical feasibility continues to improve, driven by both hardware advances and increased surgical dexterity. Laparoscopic microsurgery will introduce a new dimension to reproductive surgery and over time, will replace laparotomy for microsurgery.

Distribution of organochlorine pesticides in sediments from Kyeonggi Bay and nearby areas, Korea.

The residues of oragnochlorine pesticides (OCPs) in 62 sediments from Kyeonggi Bay and nearby areas in the west coast of Korea were determined. The concentrations of chlordanes (CHLs) and DDTs showed a distinctive gradient of contamination between inner and outer sites of Incheon North Harbor (INH), whereas hexachlorocyclohexanes (HCHs) were uniformly distributed at most sites studied. The distribution of CHLs and DDTs was strongly correlated with total organic carbon contents in sediments while HCH residue levels were independent. Relationship between contaminant's concentration and environmental factors was analyzed by principal component analysis. Distribution patterns of T-CHLs, T-DDTs, and TOC were similar while those of T-HCHs, mud content, and grain size were similar. The notable contamination by CHLs and DDTs was found in INH where these levels were one or two orders of magnitude higher than other sites. The dominant OCPs in sediments were beta-HCH among HCH compounds, trans-chlordane among CHL compounds, and p,p'-DDD among DDT compounds. The higher concentrations and compositional pattern of OCPs in INH sediments indicate that INH is in the vicinity of the source.

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-TCDD equivalents (TEQs) in sediment from the Hyeongsan River, Korea.

Sediment, pore water and water samples from the Hyeongsan River, Korea were analyzed for several classes of halogenated aromatic hydrocarbons (HAHs) and their dioxin-like activities were evaluated using the in vitro H4IIE-luc bioassay. Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) were detected in sediments from all six sampling locations with mean concentrations of 2.8 x 10(2) pg/g, 190 pg/g, and 61.4 ng/g, dw, respectively. Polycyclic aromatic hydrocarbons (PAHs) were predominated by 4-6 ring compounds with concentrations in the range of 5.30-7680 ng/g, dw. Chemical profiles of target analytes in sediment and water samples revealed that there was a gradient of concentrations along the river from upstream to downstream, which suggested that the primary source was a wastewater reservoir adjacent to a sewage treatment plant (STP). TEQs derived by summing the product of concentrations of individual congeners by their respective relative potencies (REPs or TEFs) ranged from 4.3 x 10(-1) to 1.1 x 10(3) pg/g, dw. Raw Soxhlet extracts from all six sampling locations induced significant dioxin-like responses in the H4IIE-luc bioassay. TCDD-EQs derived from H4IIE bioassay ranged from 7 x 10(-3) to 1.5 x 10(3) pg/g, dw, which were significantly correlated with TEQs (r2 = 0.994, p < 0.05). Among the three Florisil fractions tested, PCDD/Fs in fraction (F2) induced the greatest magnitude of response (range: 24-83%-TCDD-max.) in the H4IIE-luc assay. Comparison of the TEQ and TCDD-EQ suggested little non-additive interaction between fractions and AhR-active and inactive compounds. Concentrations of individual congeners as well as TEQs and TCDD-EQs suggest inputs from the industrial center waste stream in the Hyeongsan River.

Assessment of metal pollution in Onsan Bay, Korea using Asian periwinkle Littorina brevicula as a biomonitor.

Cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn) concentrations in the marine gastropod, Littorina brevicula Philippi, were determined to assess the metal pollution in Onsan Bay, Korea. Samples of L. brevicula employed as a biomonitor and seawater were collected from 12 to 20 stations of Onsan Bay in November 1997, respectively. Dissolved metal concentrations in surface seawater were highest at the station near Onsan Non-ferrous Industrial Complex: 1.15 micrograms l-1 for Cd, 2.49 micrograms l-1 for Pb, 3.75 micrograms l-1 for Cu and 23.98 micrograms l-1 for Zn. These values were 1-2 orders higher than those shown at outer regions of the Bay. Metal concentrations in the soft body of periwinkles were highly variable at different sampling locations: 0.48-27.11 micrograms g-1 for Cd, 1.41-24.91 micrograms g-1 for Pb, 57-664 micrograms g-1 for Cu and 83-246 micrograms g-1 for Zn. The values from stations near the industrial complex were higher than those expected from relationships between body sizes and metal body burdens in periwinkles collected from the whole Korean coast. Spatial distribution of metal concentrations in the periwinkle and seawater indicated that Onsan industrial complex near the Bay is the input source of these metals. Especially, Cd and Pb concentrations in the periwinkle and seawater were distinctly decreased with distance from the Onsan industrial complex. Non-essential metals such as Cd and Pb in the periwinkle showed a strong correlation with dissolved metal concentrations in seawater. Conversely, essential Cu and Zn in the periwinkle were hardly explained by those in seawater, except at the most contaminated sites.

Induction of the P450 reporter gene system bioassay by polycyclic aromatic hydrocarbons in Ulsan Bay (South Korea) sediments.

Polycyclic aromatic hydrocarbons (PAHs) and induction of the P450 reporter gene system (RGS) for 6- and 16-h exposure periods were determined in organic extracts of Ulsan Bay (South Korea) sediments to assess the utility of this bioassay as a screening tool for PAH contamination. The sum of the concentrations of 23 individual PAHs in 30 sediment samples (sigma PAH) based on GC-MS analysis ranged from 0.05 to 6.1 micrograms/g dry wt. P450 RGS fold induction ranged from 4.0 to 320 micrograms/g based on benzo[a]pyrene toxic equivalents (BaPEq). P450 RGS BaPEq and the 'chemical BaPEq', defined as the sum of the products of individual PAH concentrations and pre-determined toxic equivalency factors, exhibited very strong positive correlations with sigma PAH (r2 > 0.90; P < 0.001). Fold induction did not increase (and in some cases decreased) after the optimal incubation period (6 h) for PAHs, indicating that other compounds known to induce the P450 RGS (e.g. chlorinated organics) were not present at levels effecting significant induction. This was supported by GC-ECD analysis where non-ortho and mono-ortho polychlorinated biphenyls (PCBs) known to be strong P450 RGS inducers were found to be at very low or non-detectable levels in samples with the highest P450 RGS responses. The profound difference in PAH profiles for the two most contaminated sites suggested that this assay is especially sensitive for selected PAHs with greater than four rings. Combined with previous results, the P450 RGS shows promise as a useful screening tool for predicting deleterious biological effects resulting from CYP1A1-inducing, sediment-associated chemicals, particularly high molecular weight PAHs.

Application of a sigmapolycyclic aromatic hydrocarbon model and a logistic regression model to sediment toxicity data based on a species-specific, water-only LC50 toxic unit for Hyalella azteca.

Two models, a sigmapolycyclic aromatic hydrocarbon (PAH) model based on equilibrium partitioning theory and a logistic-regression model, were developed and evaluated to predict sediment-associated PAH toxicity to Hyalella azteca. A sigmaPAH model was applied to freshwater sediments. This study is the first attempt to use a sigmaPAH model based on water-only, median lethal concentration (LC50) toxic unit (TU) values for sediment-associated PAH mixtures and its application to freshwater sediments. To predict the toxicity (i.e., mortality) from contaminated sediments to H. azteca, an interstitial water TU, calculated as the ambient interstitial water concentration divided by the water-only LC50 in which the interstitial water concentrations were predicted by equilibrium partitioning theory, was used. Assuming additive toxicity for PAH, the sum of TUs was calculated to predict the total toxicity of PAH mixtures in sediments. The sigmaPAH model was developed from 10- and 14-d H. azteca water-only LC50 values. To obtain estimates of LC50 values for a wide range of PAHs, a quantitative structure-activity relationship (QSAR) model (log LC50 - log Kow) with a constant slope was derived using the time-variable LC50 values for four PAH congeners. The logistic-regression model was derived to assess the concentration-response relationship for field sediments, which showed that 1.3 (0.6-3.9) TU were required for a 50% probability that a sediment was toxic. The logistic-regression model reflects both the effects of co-occurring contaminants (i.e., nonmeasured PAH and unknown pollutants) and the overestimation of exposure to sediment-associated PAH. An apparent site-specific bioavailability limitation of sediment-associated PAH was found for a site contaminated by creosote. At this site, no toxic samples were less than 3.9 TU. Finally, the predictability of the sigmaPAH model can be affected by species-specific responses (Hyalella vs Rhepoxynius); chemical specific (PAH vs DDT in H. azteca) biases, which are not incorporated in the equilibrium partitioning model; and the uncertainty from site-specific effects (creosote vs other sources of PAH contamination) on the bioavailability of sediment-associated PAH mixtures.