Propensity score-matched comparison of non-anatomical resection and radiofrequency ablation for hepatocellular carcinoma in patients with up to three tumours, each measuring up to 3 cm in diameter.

BACKGROUND: Non-anatomical liver resection (NAR) and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). The aim was to compare the outcomes of NAR and RFA for HCC in patients with three or fewer tumour nodules, each measuring not more than 3 cm in maximum diameter. METHODS: Eligible patients undergoing NAR or RFA with curative intent between September 2002 and December 2014 were identified. A propensity score-matching analysis was performed to reduce bias, and outcomes in these patients were analysed. RESULTS: From a total of 199 patients, 1:1 propensity score matching identified 70 matched pairs. Patients having NAR had a longer hospital stay (median 10 days versus 4 days for those who had RFA; P < 0·001) and a higher morbidity rate (24 versus 10 per cent respectively; P = 0·042). Patients who had NAR had slightly better recurrence-free survival but this failed to reach statistical significance in univariable analysis (P = 0·064). There was no significant difference in overall survival between the two groups (P = 0·475). RFA was identified as an independent risk factor for recurrence-free survival (hazard ratio (HR) 1·57; P = 0·041) in multivariable analysis. Local recurrence was significantly more common in patients receiving RFA (23 versus 1 per cent; P < 0·001). CONCLUSION: RFA was an independent risk factor for shorter recurrence-free survival, with a significantly higher local recurrence rate than NAR. Despite these differences, overall survival was not affected.

Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage.

OBJECTIVES: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. METHODS: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. RESULTS: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. CONCLUSIONS: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.

Interstitial pulmonary disorders in indium-processing workers.

The production of indium-tin oxide has increased, owing to the increased manufacture of liquid-crystal panels. It has been reported that interstitial pneumonia occurred in two indium-processing workers; therefore, the present study aimed to evaluate whether interstitial pulmonary disorders were prevalent among indium workers. The study was carried out in 108 male workers in the indium plant where the two interstitial pneumonia patients mentioned above were employed, and included high-resolution computed tomography (HRCT) of the lungs, pulmonary function tests and analysis of serum sialylated carbohydrate antigen KL-6 and the serum indium concentration. Significant interstitial changes were observed in 23 indium workers on HRCT and serum KL-6 was abnormally high (>500 U x mL(-1)) in 40 workers. Workers with serum indium concentrations in the highest quartile had significantly longer exposure periods, greater HRCT changes, lower diffusing capacity of the lung for carbon monoxide and higher KL-6 levels compared with those in the lowest quartile. The serum indium concentration was positively correlated with the KL-6 level and with the degree of HRCT changes. In conclusion, the results of the present study indicated that serum KL-6 and high-resolution computed tomography abnormalities were prevalent among indium workers and that these abnormalities increased with the indium burden, suggesting that inhaled indium could be a potential cause of occupational lung disease.

Difference by instructional set in stabilometry.

There is no standard for the awareness of standing posture in stabilometry, yet little research addressing the matter has been carried out. In the present study, we evaluated the influence of different instructional sets during a test on stabilometry. Stabilometry was performed on 349 male subjects. Two different instructions were prepared for the subjects regarding the awareness of their standing posture. These instructions were a) "Please relax when you stand" (R-standing), and b) "Please make an effort to minimize your body sway" (E-standing). Subjects were classified into four groups according to the combination of these instructions they received. For the five body sway parameters, a comparison between R-standing and E-standing was performed, controlling for possible confounders such as age, height, body weight, educational history, alcohol consumption, and smoking status. The sway length in E-standing was larger than that in R-standing, even after the adjustment for possible confounders. Our results indicate that the difference in the instructional set caused a significant measurement bias. Thorough-going unification of instructions for the stabilometry should be recommended when stabilometry is performed in an epidemiological investigation.

Factors influencing arterial oxygenation early after bidirectional cavopulmonary shunt without additional sources of pulmonary blood flow.

OBJECTIVES: Although the arterial oxygen saturation after bidirectional cavopulmonary shunting should theoretically be homogeneous if additional pulmonary flow is obliterated, the arterial oxygen saturation has been found to vary in clinical practice. Knowledge of the preoperative and operative determinants of arterial oxygen saturation early after bidirectional cavopulmonary shunting may lead to a better understanding of this unique physiology. METHODS: Thirty-five patients who underwent bidirectional cavopulmonary shunting with obliteration of additional pulmonary flow were included in this study. The arterial oxygen saturation was determined at the 5 time points over a 48-hour period. Multivariable regression analysis was used to identify the independent predictors of the arterial oxygen saturation. RESULTS: No significant interval changes occurred in the arterial oxygen saturation during the 48 hours after bidirectional cavopulmonary shunting, which ranged from 61.6% to 95.6%. There was a significant inverse correlation between the postoperative superior vena cava pressure and the arterial oxygen saturation (P =.003). A low arterial oxygen saturation early after bidirectional cavopulmonary shunting was a predictor of mortality or exclusion from univentricular repair within 24 months (P =.012, odds ratio = 1.14). Of 11 factors identified by univariable analysis, multiple regression analysis indicated that age less than 8 months at the time of shunting (P <.0001) and ventricular volume overload (P =. 002) predicted a lower arterial oxygen saturation after bidirectional cavopulmonary shunting. CONCLUSIONS: Even without additional sources of pulmonary blood flow, several preoperative factors, including younger age and severe ventricular volume overload, predicted a decrease in the arterial oxygen saturation early after bidirectional cavopulmonary shunting. This, in turn, predicted poor outcome during 2 years of follow-up.

Increased formation of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, in human breast cancer tissue and its relationship to GSTP1 and COMT genotypes.

Reactive oxygen species (ROS) induced damage to DNA plays a major role in carcinogenesis. In order to estimate the level of oxidative damage and its role in breast cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined in DNA isolated from human breast tissue. Furthermore, we investigated whether polymorphisms in genes for enzymes involved in generation and elimination of ROS had any association with the level of 8-OHdG in breast tissue. In this study, the level of 8-OHdG in DNA was measured by the high performance liquid chromatography-electrochemical detector (HPLC-ECD) method. Genotypes of cytochrome P450 (CYP)1A1, glutathione S-transferase (GST)M 1, GSTP1 and catechol O-methyltransferase (COMT) were determined by PCR-based restriction fragment length polymorphism analysis. A total of 61 Japanese patients were included in the study. The mean level of 8-OHdG in DNA of breast cancer tissues was 2.07 +/- 0.95 per 10(5) dG residues, while the mean level of 8-OHdG in DNA of non-cancerous breast tissues was 1.34 +/- 0.46 per 10(5) dG residues. The 8-OHdG levels in DNA of breast cancer tissues were significantly higher than those of their corresponding non-cancerous breast tissues (P < 0.0001). There was negative correlation between the clinical stage and the mean level of 8-OHdG in DNA of breast cancer tissues. Furthermore, patients with genotype of high GSTP1 activity had lower level of 8-OHdG in DNA of breast cancer tissues than others. On the contrary, the mean level of 8-OHdG in DNA of breast cancer tissues was higher among patients with genotype of high COMT activity. Our findings support the assumption that cancer cells are more exposed to oxidative stress than adjacent non-cancerous tissue. Genetic polymorphisms in enzymes involved in ROS metabolism may have a role in individual susceptibility to oxidant-related breast disease. At the same time, reduction of oxidative stress is thought to be a very important measure for primary prevention of breast cancer.

Progression of human breast cancers to the metastatic state is linked to genotypes of catechol-O-methyltransferase.

There is increasing evidence that catecholestrogens may contribute to the development of breast cancer. Specifically, inactivation of catecholestrogens may prevent the genesis and arrest the progression of the disease. Catechol-O-methyltransferase (COMT), Glutathione S-transferase (GST) M1 and GSTP1 are responsible for the detoxification of catecholestrogens, and are polymorphic in the human population. In this study, a PCR-based restriction fragment length polymorphism analysis was performed to determine genotypes of the COMT, GSTM1 and GSTP1 genes. We investigated the relationship between the germline polymorphism of these genes and clinico-pathological characteristics in 140 patients with breast cancer. Among 73 patients with the low activity COMT allele, 49 (67%) had regional lymph node metastasis. On the other hand, only 27 (40%) of 67 patients without the low activity allele had lymph node metastasis. The COMT genotype was significantly associated with clinical stage and the extent of regional lymph node metastasis of breast cancer (P<0.05). However, polymorphisms of the GSTM1 and GSTP1 gene were not associated with clinico-pathological factors. Our findings suggest that the allele encoding for low activity COMT may contribute to the progression of breast cancer.

Occupational exposure limits based on biological monitoring: the Japan Society for Occupational Health.

The Japan Society for Occupational Health started to recommend an occupational exposure limit based on biological monitoring (OEL-B) in 1993. Up to 1998, OEL-Bs for mercury, lead, hexane and 3,3'-dichloro-4,4'-diaminodiphenylmethane had been adopted and those for 17 chemical substances (arsenic, cadmium, chromium, nickel, acetone, methanol, benzene, toluene, xylene, styrene, tetrachloroethylene, trichloroethylene, N,N-dimethylacetoamide, N,N-dimethylformamide, carbon disulfide, carbon monoxide, and organophospate insecticides) are in preparation.

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice.

Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS.

Acute and subacute inhalation toxicity of diborane in male ICR mice.

To clarify the toxicity of diborane, we conducted acute (15 ppm for 1, 2, 4 or 8 h) and subacute (5 ppm for 2 or 4 weeks) inhalation studies on ICR mice. The concentration resulting in a 50% kill after 4 h exposure was 31.5 ppm. Body weight gain was suppressed and the lung weight was increased in diborane-exposed mice in both acute and subacute studies. In the acute study, diffuse pan bronchiolitis-like lesions developed in the lung in various degrees depending on exposure time, which can be pathologically characterized as infiltration of inflammatory cells into the terminal bronchioles and surrounding alveoli, pulmonary congestion and bleeding and/or edema. In the subacute study, we observed lymphoid hyperplasia in the perivascular and peribronchial areas, and infiltration of macrophage and plasma cells into the alveoli. In the mice exposed for 4 weeks, the lesions were more severe than in those exposed for 2 weeks, consisting of hyperplasia and desquamation of Clara cells. In the nasal cavity, we saw mucous exudate and inflammatory cells, suggesting irritation caused by diborane. The histopathological findings, except for the respiratory organs, did not reveal any exposure-related changes. No significant changes were seen in hematological and serum biochemical examinations either. In conclusion, the target organ of diborane inhalation is the respiratory organs, particularly the lung. Further inhalation experiments are essential to investigate the safety exposure levels of diborane.

Work environment of plants manufacturing asbestos-containing products in Japan.

In 1985, a comprehensive study of asbestos-containing product plants (A/C, friction, textile) was performed. The data presented were based not on personal but on area sampling. A conversion equation from area sampling data to personal exposure values was developed. Exposure concentrations were 0.07-0.66 f ml-1. In workplaces which belonged to member companies of the Japan Asbestos Association, the percentage of workplaces whose exposure concentrations was less than 0.3 f ml-1 was 70% in 1985 (N = 510), but 98% in 1992 (N = 430). Concentrations in a new, well-controlled A/C plant were less than 0.1 f ml-1.

Health profiles of workers exposed to acrylonitrile.

The objective of this study was to reveal the health effects of acrylonitrile (AN) in seven Japanese acrylic fiber manufacturing factories. The study subjects were 157 AN-exposed male shift workers who had been exposed to AN for 17 years on the average and 537 control workers whose working conditions were similar to those of the AN-exposed workers. The seven factories were classified into two groups according to their AN exposure levels in 1987, and also into three groups on the basis of 1976 exposure levels. The most highly exposed group of subjects showed a mean AN concentration of 1.13 ppm by personal sampling. Medical examination failed to detect any health effects attributable to long-term exposure to AN, although the existence of some symptoms of acute irritation could not be completely ruled out. The results of this study may provide a "no observed effects level" for human on-the-job exposure with regard to the health effects examined here.

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system.

Fifty-seven polyurethane foam manufacturing workers (PF workers) and 24 reference workers were followed for 4 years to clarify the effects on pulmonary function of working in PF factories with exposure to toluene diisocyanate (TDI). No significant differences in the average annual losses (AALs) of pulmonary function for 4 years were observed among the 28PF workers whose TDI exposure levels were very low (mean = 0.1 ppb, group L), the remaining 29 PF workers with mean TDI exposure of 5.7 ppb (group H), and the reference workers. However, 15 PF workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concentration of 8.2 ppb showed significantly larger AALs in percentage maximal mid-expiratory flow, forced expiratory volume in 1 s ratio to vital capacity (FVC), and forced expiratory flow at 25% of FVC than expected, and significantly larger AALs in some obstructive pulmonary function indices than those of the 14 remaining PF workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average (TWA) of 1.7 ppb, group L, and the reference workers. These findings suggest that the peak exposure excursion level of TDI might be important in inducing obstructive pulmonary function changes in the PF workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable.

[Healthy worker effect on Japanese industry workers: a commentary from the viewpoint of industrial health management].

Healthy worker effect (HWE), which can be described as a lower death rate within a work force when compared to the general population, has been observed in many epidemiological mortality studies on industrial work populations free of significant life-shortening hazards. The purpose of this report is to evaluate this effect on the active work populations engaged in large scale manufacturing companies in Japan, and to appreciate the possible attributable factors to this phenomenon. Standardized mortality ratios (SMRs) were calculated for workers in the member companies of The Japan Iron and Steel Federation (JISF) and The Japan Chemical Fibers and Textile Association (JCFTA), where mortality surveillance systems have been established. SMRs for all causes of death from 1969 to 1981 were within the range of 50 to 81 in JISF, and 34 to 41 in JCFTA. These results point to the existence of strong HWE, equal to or even lower than the reported values in some industrial populations in the United States. An evident HWE for cancer was also observed in the study populations, but it was reported to be of little significance, if at all, in the United States. HWE can be considered as a composite result of factors such as: (1) selection of healthier work force, (2) risk reduction due to life style modification during employment, and (3) methodological characteristics of the SMR, which are dependent on the percentage of active workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-sectional study of pulmonary function in cadmium alloy workers.

Two groups of cadmium workers (7 and 9 men) and a group of reference workers (122 men) were studied for the purpose of determining the pulmonary effects of cadmium. Indices of pulmonary function, based on the forced expiratory flow volume curve and respiratory impedance, were measured for all the groups, and indicators of cadmium exposure and effects on renal tubular reabsorption functions were also measured in the two groups of cadmium workers. The mean blood and urinary levels of cadmium were 2.08 microgram/100 ml (185.06 nmol/l) and 32.6 microgram/l (290.04 nmol/l), respectively, and the level of inhalation exposure was estimated at about 1 mg/m3 as the 8-h average concentration for about 5 a in the high exposure group. The percentage of the predicted function values of the highly exposed workers was significantly deteriorated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), peak expiratory flow, maximum expiratory flow at 75, 50, and 25% of the FVC, percentage of FEV1.0 to FVC, and respiratory impedance, whereas those of the slightly exposed workers were reduced only for FVC and FEV1.0. A paired comparison between the highly exposed workers and matched referents disclosed the same results. It was concluded that chronic obstructive pulmonary changes had been induced by cadmium in Japanese workers without a history of acute or subacute cadmium pneumonitis.