煤矽肺并发肺癌16例的尸检病理分析

目的 探讨煤矽肺并发肺癌的临床病理特点.方法 对16例生前诊断为尘肺0＋的煤尘接触工人并发肺癌者的尸检资料采用HE、组织化学、免疫组化染色进行回顾性分析.结果 16例患者均为男性,年龄46～57岁（平均52.8岁）,尸检肺内可见不同程度的煤尘沉积和煤尘纤维灶,煤矽结节检出率为93.75%（15/16）,15例病理诊断为Ⅰ期煤矽肺,1例为煤矽尘性反应;16例肺癌中鳞状细胞癌5例、小细胞未分化癌5例、肺泡细胞癌3例、腺癌2例、腺鳞癌1例.煤矽肺并发肺癌最明显的特点是癌组织位于煤尘纤维灶和纤维化病变旁或与尘肺病变混合存在.免疫组化结果除2例未分化癌表达神经源性标记外,余均表达上皮性标记物.波形蛋白可显示纤维成分.结论 部分肺癌的发生可能与纤维化病变有关.接尘工人可患与普通人群组织学类型相同的癌.PCNA和Ki67可作为预测患者预后的指标,波形蛋白可作为煤尘纤维灶中纤维成分的标记物.     

Dust and Fibrosis in the Lungs of Coal-Workers from the Wigan Area of Lancashire

During the years 1953 to 1957 more than 1,000 lungs of coal-workers in the Wigan area were examined and compared with lungs from workers in South Wales. The Wigan lungs in general appeared to be less dusty and progressive massive fibrosis less frequent than in the South Wales lungs. Also, the more advanced cases of progressive massive fibrosis appeared to be of a silicotic type.

Of these lungs, 100 were selected for study of the relation of the type and severity of pneumoconiosis to right ventricular hypertrophy, using Gough-Wentworth sections. The remaining tissues from 47 of these lungs were used for an analysis of the content and composition of the dust and its relation to the grade of fibrosis. The average coal and quartz percentages of the dust from the lungs in the Wigan area were similar to previous findings in lungs from the Cumberland coalfield but differed from those in South Wales where the lung dust has a higher coal and a lower quartz percentage. Two possible explanations for this finding are discussed.

     

铝矾土矿粉尘作业工人五例尸检的病理研究

目的 研究铝矾土尘肺病理学特点和尘性病变组织形态的发生过程。方法 对5例死亡的铝矾土矿接尘工人尸检肺脏进行病理学观察分析。结果 粉尘沉积性尘斑是铝矾土尘肺最常见的尘性病变。尘性纤维化有两种表现：一种是非灶性间质纤维组织增生，另一种是尘斑内纤维组织增生，进一步发展可以形成非典型尘肺结节。结论 铝矾土尘肺的病理特点不完全同于金属铝和氧化铝尘肺，铝矾土尘肺属混合性尘肺，特征性病变是尘斑气肿伴尘性间质纤维化。尘肺患者肺内感染和并发肺肿瘤，特别是并发肺结核，能促进尘性纤维化过程加快。胸膜增厚、肺癌与接触铝矾土粉尘的关系应引起重视。     

Clinical, pathological and mineralogical features in two autopsy cases of workers exposed to agalmatolite dust.

An agalmatolite miner and processor showed large shadows at the bilateral hila accompanied by surrounding emphysematous changes and irregular shadows on chest X-ray films. Chest CT scans were characterized by a mixture of tiny irregular structures and small round opacities. Histopathological examination revealed massive fibrosis, which corresponded to large shadows, but only a small number of typical silicotic nodules, indicating mixed dust pneumoconiosis. Mineralogical examination of the autopsy lungs showed quartz, pyrophyllite, mica, and kaolinite. Quartz accounted for 70% of the amount of all mineral dust in both patients, but pyrophyllite accounted for 10.8% and 14.4%. The pulmonary mineral dust composition in the two patients was well consistent with the mineral composition of the raw clays in the agalmatolite mine. In the two patients, chest X-ray findings and histopathological findings of the lungs also suggested agalmatolite pneumoconiosis, which was confirmed by mineral analysis of the lungs.     

Dust and Collagen Content of Lungs of Coal-Workers with Progressive Massive Fibrosis

In order to test the silica theory of the origin of progressive massive fibrosis (P.M.F.) in coal-miners' pneumoconiosis, separate dust analyses have been made of the massive lesions and of the rest of the lung from 18 coal-workers with P.M.F. who had been employed in several coalfields. The dry weight of the massive lesions ranged from 5 to over 100 g. and the dust concentration in the P.M.F. lesions was on an average twice as high as in the rest of the lung. It was found that the quartz percentage of the lung dust was almost identical in the two samples from each lung (Table 3). The quartz content of the average lung dust (P.M.F. and “rest of lung”) of 32 cases of P.M.F. was compared with that of 58 cases of simple pneumoconiosis. The quartz content of the P.M.F. dust was slightly higher but, allowing for variable dust composition in different coalfields, the difference was not significant (Table 8). The silica theory of P.M.F. cannot be supported by this study.

Comparisons of the collagen content of the P.M.F. lesions and of the rest of the lung in 17 lungs and of lesions of P.M.F. and of simple pneumoconiosis in 31 and 27 lungs, respectively, showed no clear difference between any of the groups and surprisingly low values for the massive lesions. A possible way in which this result could be reconciled with the histopathological observations is suggested. One gram of coal-mine dust produced, on an average, 0·4 g. of dust produced between 2 and 7 g. of extra collagen.

extra collagen. In five silicotic lungs, where the lung dust contained 15 to 50% of free silica, 1 g. of dust produced between 2 and 7 g. of extra collagen.

     

Pneumoconiosis and Associated Medical Conditions

Hospital discharge data from Michigan for the years 1990 and 1991 were used to examine potential associations between pneumoconiosis and pulmonary hypertension, lung cancer, obstructive lung disease, and connective tissue disease among both men and women. Lung cancer, pulmonary hypertension, and obstructive lung disease were associated with coal workers' pneumoconiosis. Pulmonary hypertension and obstructive lung disease were associated with asbestosis and silicosis. Rheumatoid arthritis was associated with silicosis. The potential is suggested that misdiagnosis is the cause of the association between lung cancer and coal workers' pneumoconiosis.     

Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up

OBJECTIVES—To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997.METHODS—Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society''s criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates.RESULTS—The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox''s proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates.CONCLUSIONS—The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors—such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines—rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.     

Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.

OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.     

Presence of stable coal radicals in autopsied coal miners' lungs and its possible correlation to coal workers' pneumoconiosis.

Stable coal radicals (SCRs) were detected by electron spin resonance (ESR) spectroscopy in the lung tissue of autopsied coal miners. The SCR concentrations were measured in the lung tissues from 98 coal miners with and without (a) coal workers' pneumoconiosis (CWP), (b) cancer, and (c) a history of cigarette smoking. Concentrations of SCRs were also determined in the lungs of nonminer controls. The SCR concentration was related to longer mining tenure, CWP disease severity, lung cancer, and cigarette smoking. The mean concentration of SCRs in the lung tissues of miners with 30 +/- 1.4 y of coal mining exposure was 5.3 +/- 1.3 x 10(17) spins/g versus controls who had a nondetectable level (less than 10(15) spins/g). An increase in disease severity was accompanied by a progressive increase in SCR concentration. A SCR concentration of 4.8 +/- 0.7 x 10(17) spins/g was found for simple CWP (with moderate coal macules) versus 7.8 +/- 4.6 spins/g lung tissue for complicated CWP (with progressive massive fibrosis). Significantly higher (i.e., 10 x 10(17] concentrations of SCR in the coal miners' lung tissues were associated with an exposure history in the anthracite regions of northeastern Pennsylvania. These results indicate a possible role for SCRs in the disease process. Furthermore, ESR appears to be an adequate methodology for the quantitation of coal dust retained in the lung and for distinguishing exposures to anthracite and/or bituminous coal.     

Comparison of radiographic appearances with associated pathology and lung dust content in a group of coalworkers

The pathology and dust content of lungs from 261 coalminers in relation to the appearances of their chest radiographs taken within four years of death were examined. Radiological opacities of coalworkers' pneumoconiosis were more profuse the more dust was retained in lungs. Among the men who had mined low rank coal--that is, with a relatively high proportion of ash--the increase in profusion was most closely related to the ash component of the dust, whereas in men who had mined high rank coal both coal and ash increased in the lungs in relation to radiological profusion. The fine p type of opacity was found to be associated with more dust and a higher proportion of coal and less ash than the nodular r opacity, and was also more likely to be associated with emphysema. The pathological basis of the different types of opacity found on the radiographs of coalminers related to the number, size, and nodularity of the dust lesions. Larger fibrotic lesions were likely to appear as r opacities, whereas fine reticular dust deposition was most likely to present as p opacities, q opacities showing a mixture of appearances. The study has shown that the composition of dust retained in the lung, as well as its amount, makes an important contribution to the radiographic appearances of pneumoconiosis. In particular, the r type of lesion on the radiograph of a low rank coalminer indicates the possibility of a silicotic like lesion.     

Comparison of radiographic appearances with associated pathology and lung dust content in a group of coalworkers.

The pathology and dust content of lungs from 261 coalminers in relation to the appearances of their chest radiographs taken within four years of death were examined. Radiological opacities of coalworkers' pneumoconiosis were more profuse the more dust was retained in lungs. Among the men who had mined low rank coal--that is, with a relatively high proportion of ash--the increase in profusion was most closely related to the ash component of the dust, whereas in men who had mined high rank coal both coal and ash increased in the lungs in relation to radiological profusion. The fine p type of opacity was found to be associated with more dust and a higher proportion of coal and less ash than the nodular r opacity, and was also more likely to be associated with emphysema. The pathological basis of the different types of opacity found on the radiographs of coalminers related to the number, size, and nodularity of the dust lesions. Larger fibrotic lesions were likely to appear as r opacities, whereas fine reticular dust deposition was most likely to present as p opacities, q opacities showing a mixture of appearances. The study has shown that the composition of dust retained in the lung, as well as its amount, makes an important contribution to the radiographic appearances of pneumoconiosis. In particular, the r type of lesion on the radiograph of a low rank coalminer indicates the possibility of a silicotic like lesion.     

PCR-SSCP技术检测矽肺合并肺癌癌组织p53基因突变的研究

用ＰＣＲ－ＳＳＣＰ分析法对３６例矽肺患者的石蜡包埋的原发性肺癌组织ｐ５３基因第５、７、８外显子进行了检测，检出突变１５例。突变在第５、７、８外显子上都有发生，但以第８外显子上发现的阳性突变最多。对肿瘤类型和ｐ５３基因突变的关系进行了分析，发现矽肺病例肺腺癌ｐ５３基因阳性突变率最高，为５３．９％，高于普通型肺癌（３３．０％）。进一步对其中１例样本进行核苷酸序列直接测定，结果显示第５外显子非突变热点区的第１４４位密码子核苷酸由ＣＡＧ突变为ＡＡＧ，氨基酸由谷氨酰胺突变为赖氨酸，以上结果与非职业肺癌明显不同，提示ｐ５３基因突变在矽肺病例肺癌发生中起着重要作用，可能与矽尘作业环境中含有的某些化学致癌物有关。     

Mortality of a cohort of U.S. workers employed in the crushed stone industry, 1940-1980

The mortality of 3,246 males who had been employed 1 or more years during 1940-1980 at 20 crushed stone operations was evaluated for possible association between employment and death from lung cancer, pneumoconiosis, and other respiratory diseases. Four deaths were attributed to pneumoconiosis. Based on available work histories, at least two of these deaths were probably due to dust exposures in the crushed stone industry. Mortality attributed to pneumoconiosis and other nonmalignant respiratory diseases, including chronic obstructive lung disease, was significantly increased overall (SMR: 1.98; 95%CI: 1.21-3.05), and especially so for a subcohort of crushed stone workers that processed granite (SMR: 7.26; 95%CI: 1.97-18.59). With regard to lung cancer, overall SMRs were elevated (although not statistically significant). Analyzed by rock type, there was a significantly elevated lung cancer SMR among granite workers with at least 20 years latency (SMR: 3.35; 95%CI: 1.34-6.90). Although not definitive, results of this study are consistent with the hypothesis that exposure to respirable silica dust is a risk factor for lung cancer.     

煤矿矿工尘肺与肺癌死亡Poisson回归分析

目的 探讨尘肺与肺癌的关系。方法 对涟邵矿务局3140例尘肺矿工进行回顾性队列分析,计算主要死因的标化死亡比（SMR）,对尘肺与肺癌的关系进行Poisson回归分析。结果 尘肺矿工全死因与肺癌均高于对照人数,其中肺癌高于湖南省人群5倍;Poisson回归分析表明尘肺矿工肺癌与对照组的差别主要在25－44岁组。结论 支持尘肺与肺癌的相关关系。     

Mortality and lung cancer in ceramic workers in the Netherlands: Preliminary results

A retrospective cohort study in 1974 male ceramic workers in the Netherlands was carried out to analyze the lung cancer risk in relation to crystalline silica exposure and silicosis. They had all been employed for two years or longer in ceramic industries between 1972 and 1982. During a health survey, 124 cases of simple pneumoconiosis were diagnosed: after 14 years of follow-up, 161 deaths had occurred. No increased overall and cause-specific mortality was found in the total group of ceramic workers, and a statistically significant cumulative dose-response relation for silica exposure and lung cancer did not emerge. An excess lung cancer mortality appeared among workers with simple pneumoconiosis. The authors conclude that the disease process resulting in silicosis in the ceramic industry carries an increased risk of lung cancer, which is supportive of a nongenotoxic pathway. © 1996 Wiley-Liss, Inc.     

云母矿工人肺癌的流行病学调查

对内蒙古某云母矿井下男性矿工进行了肺癌回顾性队列调查。对生产环境中某些有害因素进行了测定。以全国及内蒙古男性人群肺癌死亡率作参比人群，标化死亡比（ＳＭＲ）分别为４．０５和６．６２，具有统计学意义。肺癌标化死亡率为８７．６１／１０５。有矽肺和无矽肺者肺癌发病有显著差异（Ｐ＜０．０５）。肺癌患者皆为尘肺患者。对肺癌高发原因，初步认为肺癌高发与长期高浓度接尘有关。很难排除矿尘中ＳｉＯ２和云母的作用。井下空气中存在的３，４－苯并芘，氡及其子体浓度极低，不足以构成本矿肺癌的原因。本次调查未见肺癌与吸烟有关。     

Lung cancer mortality among a cohort of men in a silicotic register

To examine any association between silicosis and lung cancer, the clinic records of a cohort of 1502 silicotic workers diagnosed after 1981 were reviewed. All of the essential data, including occupational exposure, smoking habits, radiographic extent of silicosis, and vital status of each subject, were noted. The standardized mortality ratio for various causes of death was calculated. Thirty-three patients died from lung cancer, giving a standardized mortality ratio of 1.94 (95% confidence interval, 1.35 to 2.70). However, smoking accounted for most of the excess of lung cancer deaths among the silicotic workers in the cohort, and no consistent relationship between lung cancer mortality risk and either duration of exposure to silica dust or severity of silicosis was observed. There is no conclusive evidence in our data to support the hypothesis that lung cancer may be associated with silicosis.     

矽肺大鼠和病人肺组织中Ⅰ型与Ⅲ型胶原纤维的分布及相对含量的研究

免疫酶标法用于观察肺组织中胶原的分布。显微分光光度法用于研究大鼠与矽肺病人的纤维化组织中Ⅰ型与Ⅲ型胶原的相对含量。染色中应用大鼠及人的抗Ⅰ型与Ⅲ型胶原多克隆抗体。Ⅰ型胶原分布于正常肺泡间隔及间质中。Ⅲ型胶原也在相同的部位存在。在由石英所致的大鼠纤维化肺组织中,Ⅰ型与Ⅲ型胶原在极度扩展的间质中聚集。Ⅲ型胶原是早期纤维化肺中主要增生的胶原。Ⅰ型胶原是纤维化后期主要增生的胶原。在矽肺病人肺组织中也见到同样的现象。染电焊烟尘的大鼠肺,直至180天以前,Ⅲ型胶原为主要积聚的胶原,而在180天以后,Ⅰ型胶原的增加才占优势。     

矽宁、汉防己甲素及磷酸羟基喹哌对实验性矽肺疗效的比较

对矽宁、汉防己甲素(汉甲)和磷酸羟基喹哌在等毒条件下进行了大鼠实验性矽肺的疗效研究,结果表明,治疗3个月后全肺湿、干重及肺胶原蛋白含量明显低于矽肺对照组,差别显著,但治疗组之间无明显差异;病理形态显示矽宁和汉甲组对矽肺纤维化有更明显的抑制作用,病灶间和肺泡腔内具有大量泡沫样细胞浸润。治疗组的肺巨噬细胞内均有细小的棕褐色颗粒。矽宁治疗组血清中SOD和铜蓝蛋白的含量明显低于其它治疗组。