Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib.

AIM: To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S). METHODS: We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival. RESULTS: Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses. CONCLUSION: The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.

[Effect of occupational combined exposure of chromium and iron on erythrocyte metabolism].

OBJECTIVE: To investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism. METHODS: A total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B12 in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted. RESULTS: The median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B12 ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B12 were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B12 and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01). CONCLUSION: Combined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B12 metabolism, while iron may via copper metabolism.

Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study.

The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs-CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate.

OBJECTIVES: Chronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not been fully investigated. This study was designed to examine vitamin B12, folate and homocysteine metabolic changes in workers chronically exposed to chromate. The potential association between metabolic alteration and renal impairment induced by chromate exposure was also assessed. METHODS: The level of chromium exposure was evaluated by measuring chromium concentrations in red blood cells (RBC-Cr) and urine (U-Cr). Renal impairment was assessed with serum cystatin C (Cys-C) and urinary ß2-microglobulin (ß2M). Serum vitamin B(12), folate and plasma total homocysteine (tHcy) were measured and correlations analysed. RESULTS: Significant increases in RBC-Cr, U-Cr, serum Cys-C, plasma tHcy and urinary ß2M concentrations were observed in workers chronically exposed to chromate compared to controls. In the exposed workers, serum vitamin B12 and folate levels were decreased and significantly inversely correlated with RBC-Cr concentrations, and increased plasma tHcy concentrations were mirrored by decreased serum vitamin B12 and folate levels. Elevated plasma tHcy concentrations were positively related to serum Cys-C concentrations. CONCLUSIONS: Hyperhomocysteinemia in chronically exposed workers was primarily induced by vitamin B12 and folate deficiency. This metabolic change might be associated with renal dysfunction in chromate processing workers after long term exposure.

[The effect of inhalable titanium dioxide on the oxidative stress among occupational population].

OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make an assessment of its oxidative effect on occupational exposed population. METHODS: A total of 7 workers occupationally exposing to inhalable titanium dioxide were recruited into the study. The basic information and occupational history were collected by interview, while their blood sample (10 ml for each subject) were collected before and after the investigation, respectively. Pre- and post-work shift urine samples (60 ml for each subject) were collected for 29 days consecutively. The daily personal titanium dioxide exposure level, temperature and relative humidity were detected too. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were detected by ELISA and latex immunoturbidimetric assay, respectively. RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 ± 1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13 ± 1.08), (1.33 ± 1.01) mg/L, respectively. No statistical significance was observed between hs-CRP level before and after the investigation (t = -0.848, P = 0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 ± 1.39), (3.65 ± 1.06) µmol/mol Cr, respectively. A positive correlation was found between the concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r = 0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift, years of employment, age, body mass index, smoking status, temperature and relative humidity, showed no significant exposure-respond trend between the inhalable titanium dioxide concentration and 8-OHdG level (ß = 0.288, t = 1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link between occupationally exposure to inhalable titanium dioxide and high induction of DNA oxidative stress.

[The effects of occupational soluble chromate exposure on immunological function of T-cell].

OBJECTIVE: To investigate the early changes of some immunological function of T-cell in chromate workers. METHODS: A total of 115 workers exposed to different levels of soluble chromate were enrolled in exposed group; while 90 non-exposure workers who lived far away from the chromate plant were enrolled as control. The air concentration of soluble chromate was determined by atomic absorption spectrometry. CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+) of T-cell were determined by flow cytometry analysis. RESULTS: The individual air chromate concentration in the exposed group was (27.51 +/- 33.25) microg/m(3), and the control group was (0.16 +/- 0.15) microg/m(3). The significant difference between the two groups was observed (z = 8.045, P < 0.01). The levels of the lymphocyte subsets (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+)) in exposed group were (30.08 +/- 17.75)%, (1.04 +/- 1.73)%, (11.94 +/- 9.78)%, 0.10 +/- 0.14. While, those of control group were (63.00 +/- 13.57)%, (30.51 +/- 5.16)%, (14.82 +/- 4.59)%, 2.17 +/- 0.53, higher than that of the exposed group (z values were 4.484, 5.227, 1.976, -5.218, respectively, P < 0.05). CONCLUSION: On the basis of individual air monitoring, the cellular immune function affected by soluble chromate is mainly based on T lymphocyte inhibition. The indicators CD3(+)CD4(+) mentioned above may be considered as efficient biomarkers in further research.