Document pBmzgw05zLL646y7nM2onbvoD

Wednesday, March 29, 2000 Chest Volume 117 Number 2 February 2000 Copyright 2000 The American College of Chest Physicians MISCELLANEOUS Asbestos in Extrapulmonary Sites* Omentum and Mesentery MD Consult - Journal Article 486 Ronald F. Dodson i PhD, FCCP Michael F. O'Sullivan i BS Ju Huang 1 MS David B. Holiday * PhD Samuel P. Hammar - MD, FCCP 1 Department of Cell Biology and Environmental Sciences (Dr. Dodson, Messrs. O'Sullivan, and Huang) jpartment of Epidemiology and Biomathematics (Dr. Holiday), The University of Texas Health Center at Tyler, Tyler, TX Diagnostic Specialties Laboratory (Dr. Hammar), Bremerton, WA. Manuscript received April 22, 1999 revision accepted August 20, 1999. Correspondence to: Ronald F. Dodson, PhD, FCCP, Professor of Cell Biology and Environmental Sciences, The University of Texas Health Center at Tyler, 11937 U.S. Highway 271, Tyler, TX 75708 " Study objectives: Asbestos fibers have not been reported in tissues from the peritoneal cavity. Therefore, omentum, -senterv, and lung tissues from 20 individuals in whom mesothelioma was diagnosed were analyzed for asbestos bodies asbestos fibers. Design: Tissue was digested and prepared filters were analyzed by light microscopy and analytical transmission electron microscopy. Results: Asbestos bodies were found in the lungs of 18 individuals, mesentery samples from 5, and omentum samples from 2. Uncoated asbestos fibers were found in lungs of 19 patients, 17 of whom had fibers in at least one extrapulmonary site. The most common asbestos in the omentum and mesentery was amosite. Several features of asbestos found in lung influenced the likelihood of amphibole fibers being found in the omentum or mesentery. Lung features included total amphibole fiber burden, length, aspect ratio, and ferruginous body burden. An increased total ferruginous body burden was strongly associated with increased likelihood of detecting amphiboles in the omentum (p < 0.05). nclusion: Asbestos fibers reach areas in the peritoneal cavity where some mesotheliomas develop. This study suggests -ir presence can be predicted based on concentrations and characteristics of fiber burdens in lung tissue. Key words: asbestos extrapulmonary mesothelioma Abbreviations: AB asbestos body ATEM analytical transmission electron microscopy FB ferruginous body Inhaled articles are removed by several mechanisms, including the mucociliary escalator of larger airways and additional mechanisms at the alveolar Wei. til 121121 . ,ie lymphatics relocate particles from the lung to pleura and to hilar and more distant lymph nodes, tit Becklake til and Hillerdal 121 suggested the lymphatic route for asbestos relocation from the lung (the original site of deposition) to other parts of the body. A limited number of studies have reported asbestos bodies in the hilar and mediastinal lymph nodes. 121 til 121 Our laboratory has compared the burden of uncoated fibers and asbestos bodies from thoracic nodes to the concentration of asbestos fibers in h1tp://home.mdconsult.com/daa/article/body/jorg=journal&sourcesMI&sp=11210010&sid = 12041775/N/ 1694S6/1 .html Page: Wednesday, March 29, 2000 MD Consult - Journal Article pleural plaques and lung tissue. Although we have shown asbestos fibers in thoracic loci where mesotheliomas develop, few or no data exist concerning the presence or absence of bestos fibers in the linings of the peritoneal cavity, where 10 to 15% of mesotheliomas occur. It is reasonable to assume that asbestos fibers ocate to these sites and, through their physical and chemical properties, stimulate tissue reactions that favor the development of mesothelioma, uased on our previous findings, it is assumed that fibers reaching the peritoneal cavity will require transmission electron microscopy to be detected. In this study, tissue from 20 individuals with mesotheliomas, most with a history of asbestos exposure, were evaluated. The questions to be answered included whether asbestos fibers would be found in the omentum and mesentery, and, if so, would their presence be predicted by various qualitative and quantitative features of asbestos bodies (ABs) and asbestos fibers in the lung from the same individuals. Materials and Methods Description of Cohort In 20 individuals, malignant mesothelioma was diagnosed at autopsy examination by one author (S.P.H.). The diagnosis was based on macroscopic, histologic, immunohistochemical, and 487 occasionally ultrastructural features. All individuals were male, and the majority had worked in professions where contact with asbestos in the workplace would be expected (Table 11. The mean age was 69.8 8.3 years. Seventeen cases were pleural mesotheliomas (85%), and three (cases 6, 7, and 9) were peritoneal mesotheliomas (15%). Tissue Analysis sue analyzed at the Tyler, TX, laboratory included right and left lung, omentum, and mesentery from each patient. Multiple sites of tumor-free, .itnalin-fixed lung parenchyma were dissected from each lung. An area adjacent to each site was taken to determine the TABLE 1 - Historical Data for Mesothelioma Cases- Assay No. ID No. Age/Sex Occupational History Mesothelioma Years of Location Histologic CS Exposure Type Pleural Plaque Pathologic Asbestosis DOD 1 L-68-90 74/M NS Shipyard insulator > 1941-44 Right pleura Yes Yes Mar-90 Sarcomatoid 2 L-132-93 72/M nd Brakeworker > 1945-70 Boilermaker > Parietal pleura 1939-72 Parietal pleura Yes Grade 1-3 Yes Jul-93 Epithelial with focal variable differentiation Pericardium Grade 1 3 L-235-92 64/M nd Shipfitter and insulator > 1956-75 Left pleura Yes Yes Nov-92 4 L-67-93 60/M 50+ Epithelial US Coast Guard and contractor > 1938-88 Right pleura Parietal pleura No Grade 1 No Apr-93 5 L-228-93 73/M 15 Brickmason > 1946-77 Sarcomatoid with osseous differentiation Left pleura Yes Yes Oct-93 6 L-450-97 75/M 25 Sarcomatoid/desmoplasuc Parietal pleura Shipyard Peritoneal insulator and machinist > nd Yes Grade 1-2 Yes Oct-97 7 L-241-92 58/M 50+ Shipyard insulator > 1954-62 Biphasic Peritoneal Parietal pleura Yes Grade 1-2 Yes Nov-92 Epithelial Parietal pleura Grade 1-2 http://home. mdconsult.com/das/artic le/body/jorg=|ournal&source=MI&sp= 1121 00104sid= 12041 775/N/ 169456/1 hlml Page Wednesday, March 29. 2000 8 L-93-93 9 L-37-93 10 L-l-93 11 nd 12 L-101-92 13 L-140-93 14 L-278-91 15 L-259-92 16 L-448-97 17 L-227-93 18 L-239-93 19 L-233-94 20 L-296-93 MD Consult - Journal Article 52/M 34 Shipyard rigger > nd Right pleura Yes Yes Sarcomatoid/desmoplastic Parietal pleura Grade 1 67/M 43 Pipefitter and marine insulator > 1951-53 Peritonea] Yes Yes Epithelial Parietal pleura Grade 1 73/M 40+ Laborer > 1940-44 Right pleura Yes Yes Shipyard electrician > 1947-70 Sarcomatoid/desmoplastic Parietal pleura Grade 1 75 /M 38 Shipyard painter > 1941-46 Left pleura Yes Yes Painter > 1946-76 Variable differentiation Parietal pleura Grade 1 82/M 49 Shipyard electrical engineer and technician > 1942-73 Left pleura No Yes Biphasic Grade 1 80 /M 10 Shipyard sheet Right pleura metal worker > 1942-47 Yes Yes Predominantly sarcomatoid with focal variable differentiation Parietal pleura Grade 1 85 M 13 Railroad worker > 1921-46 Right pleura Yes Yes Construction > Epithelial 1947-64 Parietal pleura Grade 1 Shipyard painter > 1965-71 69 M nd Merchant Marine > 1945-75 Right pleura Yes No Biphasic predominantly Parietal sarcomatoid pleura 73/M 38 Plant machinist Right pleura and foreman > 20-25 yrs ago Yes Yes Sarcomatoid Parietal pleura Grade 1 64/M 20 US Naval machinist > 1947-67 Right pleura Yes Yes Variable differentiation Parietal pleura Grade 1 62 /M 38 Heavy equipment operator > 1957-88 Right pleura Yes No Biphasic predominantly Parietal epithelial pleura 66/M NS Truck driver and terrazzo helper and mechanic > 1959-72 Left pleura No No evaluation Epithelial 73/M nd Retired Right pleura Yes nd h tip ://ho me. mdconsult.com/das/article/body/jorgsjournal&sourcesMI&spa 1121 0010&sids12041775/N/ 169456/1 .him! May-93 Mar-93 Jan-93 Apr-91 May-92 May-93 Nov-91 Dec-92 Oct-97 After May-93 7 After May-94 nd Page: 3 Wednesday, March 29, 2000 MO Consult Journal Article Predominantly sarcomatoid but showing variable differentiation "S = cigarette smoking in pack years; DOD = date of death; nd = no data; NS = nonsmoker. Parietal pleura Page 488 wet/dry ratio. Omentum and mesentery tissue was processed through the modified bleach digestion procedure of Williams et al. Tissue from lungs was pooled into right and left samples. The right digest pool contained an average of 0.3588 g dry weight of lung tissue (range, 0.1295 to 0.9745 g), and the left digest pool contained an average of 0.3700 g of dry weight (range, 0.1544 to 0.7738 g). The number of asbestos fibers and ferruginous bodies (FBs) consistent with ABs was averaged from the left and right lung digests. The average omentum sample contained 1.7308 g dry tissue (range, 1.008 to 2.9382 g), and the average mesentery sample had 1.7787 g dry tissue (range, 0.3928 to 2.8621 g). All solutions used in the procedures were prefiltered through a 0.2-mum Nuclepore filter (Nucleopor Coip; Pleasanton, CA). Dry weights were calculated based on a wet/dry ratio obtained for each digest pool. Aliquots of the pools were collected on 0.2-mum pore polycarbonate filters for analytical transmission electron microscopy (ATEM) and on 0.22-mum pore mixed cellulose ester filters for quantitation of ABs by light microscopy. The mixed cellulose ester filters contained an average tissue weight of 0.0331 g dry weight (range. 0.0211 to 0.0671 g) for lung samples. The method for screening the filters by light microscopy has been previously described by Dodson et al. ^ ''e polycarbonate filters contained an average of 0.0066 g dry weight of lung (range, 0.0027 to 0.0134 g), 1.3429 g dry weight of mesentery nge, 0.3928 to 1.6910 g), and 1.3174 g dry weight of omentum (range. 0.8093 to 1.6913 g). The quality assurance issues, as well as the analytical counting scheme used for the ATEM facet of the study, have previously been reported. ^ Data for lung samples were reported as a weighted average obtained from the two sides. The quantity and quality of asbestos fibers from the lung, omentum, and mesentery are described in Table 2 Statistical Analysis Computations were done on a Digital Alpha 8200 mainframe computer (DEC; Compaq; Houston, TX) running a Digital Unix (Release 4.0) operating svstem. The Statistical Analysis System (SAS, Version 6.12; Cary, NC) was used (PROC MEANS, PROC CORR, PROC LOGISTIC). jgistic regression was used to model the probability of the occurrence (presence) of certain fiber types in the omentum and mesentery, as a function of the burden and other aspects of these fibers, as described in Table 2 . These values should be interpreted in terms of the given sampling procedure used in the present study. Independent variables were simple transformations of lung indexes, including total asbestos (fibers/g dry weight), total asbestos amphibole (fibers/g dry weight), median fiber length (mum), median fiber width (mum), median fiber aspect ratio (length/width), and total ABs (ABs/g dry weight) from light microscopy. Width was not used in some analyses because it is essentially redundant once the length and aspect ratio are known. Up to four response indicator variables were used in PROC LOGISTIC: Y {indicated presence of any asbestos in the omentum; Y 2 indicated any amphiboles in the omentum; Y 3 indicated any asbestos in the mesentery; and Y 4 indicated any amphiboles in the mesentery. Separate models were used for each of four independent variables, as previously described. e zero logit solutions were back-transformed to the original scales. These are interpreted as the value of the predictor for which the probability of lecting asbestos at an extrapulmonary site is "more likely than not" as a function of the magnitude of the lung predictor. The exact p values were reported to enable readers to make a judgment for significance of the curvature in the logistic model. Results AB Burden Eighteen individuals (90%) had ABs in their lung tissue (Table 21. No ABs were found in lung samples from two cases (10%). The average AB concentration in the 18 positive samples was 183,638 ABs/g dry weight (range, 229 to 1,337,948 AB/g dry weight). The subject (case 1) with the highest number of ABs had pleural mesothelioma. The second highest number was found in a case of peritoneal mesothelioma (case 7). In the ATEM scan, ABs were found in lung digests from 12 cases (60%). The cores of 172 ABs were analyzed, and all were found to contain amosite cores with one exception, a tremolite asbestos core. ABs were found in the mesentery in five patients (25%; Table 2). Two of the five cases positive for ABs in the mesentery (cases 6 and 7) were peritoneal mesotheliomas. The concentration of ABs in the positive samples ranged from 1 to 38/g dry tissue. The highest number occurred for the case with highest number of ABs in lung tissue (case 1). Only two cases (10%) were found to have ABs in their digest from the omentum (cases 1 and 10; Table 2). The range was from 1 AB/g dry weight of tissue (case 10) to 37/g dry weight (case 1). As in the mesentery, the highest number of ABs in the omentum was found in the individual with the highest number of ABs in lung tissue (case 1). Core analysis by ATEM of ABs from the omentum and mesentery of case 1 confirmed that all were formed on amosite cores. All FBs counted by light microscopy of samples from lung, omentum, and mesentery were considered to be ABs if they had features consistent with such structures. '.coated Asbestos Fibers Uncoated asbestos fibers were found in the lungs of 19 of 20 individuals (95%). Only in case 19 were asbestos fibers not found, as based on the detectable limits within the study. The range of uncoated asbestos fibers in lung tissue was from 13,601,236/g dry weight in an individual with a peritoneal mesothelioma (case 7) to nondetectable (Tattle 2 , Fig 1) . The second highest lung burden of uncoated fibers (12,908,314 fibers/g dry weight) occurred in an individual with pleural mesothelioma (case 1). Ten cases (50%) had an uncoated asbestos burden of > 1.4 million asbestos h tip ://ho me. mdconsull .com/das/arlicle/body/jorgsjourna I & source = MI&sps1121001 0&sid=12041775/N/ 169458/1 hlml Wednesday, March 29. 2000 MO Consult - Journal Article fibers/g dry weight, with all peritoneal mesothelioma cases (cases 6, 7. and 9) having > 1 million asbestos fibers/g dry weight. Two cases of peritoneal mesothelioma (cases 7 and 9) were in the top five for total uncoated asbestos burden. Seventeen cases (85%) were found to have uncoated Page: 5 439 TABLE 2 -- Ferruginous Body and Uncoated Fiber Burden of Lung, Omentum, Mesentery per Case (FBs/g dry or fibers/g dry) Assay No. Tissue FB/g dry Total Asbestos Fibers Total Asbestos Fibers/FB's Ratio Chrysotile Amosite Non-Asbestos Tremolite Crocidolite Anthophyllite Actinolite Fibers 1 Lung 1,337,948 12,908,314 10 105,806 12,802,509 0 687.738 Omentum 37 6,553 177 0 6,208 345 517 Mesentery 2 Lung Omentum Mesentery 3 Lung Omentum 38 4,311 102,688 4,008,137 0 6,077 1 5,445 106,906 696,395 0 1,544 113 39 5.445 7 172 124,476 868 0 81,929 1,029 3,966 3,659,603 4.630 5,445 491,573 258 172 61,447 224,058 289 20,482 1,380 597,487 289 2,604 573 20,482 245,787 258 2,573 Mesentery 4 Lung 0 4,178 0 223,119 0 99,164 3,969 49,582 209 74,373 6,058 570,194 Omentum 0 799 799 0 16,782 Mesentery 0 3,713 743 743 2,228 5,198 5 Lung Omentum Mesentery 6 Lung 357,551 0 2 218,578 3,836,779 2,889 1,303 1,744,106 11 47,662 3,669.962 47,662 0 2,889 652 0 1,303 8 0 1,724,059 47,662 23,831 20,047 1,263,039 667 217 140,330 Omentum 0 2,555 0 2,555 547 Mesentery 2 3,009 1.505 0 3,009 401 7 Lung 1.008,797 13,601,236 13 212,519 13,388.717 566,718 Omentum 0 852 0 852 3,410 Mesentery 8 Lung 1 1,937 14,434 1.468.028 1.937 102 0 1.660 110,795 1,357,233 277 2,213 249,288 Omentum 0 1,644 0 1,644 411 Mesentery 9 Lung Omentum Mesentery 10 Lung 0 32,091 0 0 80,714 761 3,988.091 1,180 447 1,893,778 381 0 124 33,514 3.451,875 134,054 134,054 0 1,180 0 447 23 49,836 1,345.579 348,854 381 234,594 49,836 99,673 9,135 804,320 295 15,427 697,708 Omentum 1 443 443 0 443 664 Mesentery 11 Lung 0 14,448 525 292,643 0 175 175 20 73,161 97,547 175 121,935 2,625 146,321 Omentum 0 0 4,625 Mesentery 0 707 707 2,121 12 Lung 3,661 239,055 65 19.921 19,921 19,921 737,085 Omentum 0 0 1,820 Mesentery 13 Lung Omentum Mesentery 14 Lung Omentum Mesentery 0 1,132 0 0 14,088 0 0 581 898,183 193 447 1,435,107 184 189 581 794 752,532 24,275 193 224 224 102 18,883 1,057.447 321,011 184 189 97,101 37,766 5,812 388,403 579 2,014 1,208,511 1,286 567 http //home.mdconsult.com/das/articla/body/jorg=)ournal&sourca=MI43p = 1121001 0Ssid = 12041775/N/ 169456/1 html Wednesday, March 29, 2000 15 Lung Omentum Mesentery 16 Lung Omentum Mesentery 17 Lung Omentum Mesentery 18 Lung Omentum Mesentery 19 Lung Omentum Mesentery 20 Lung Omentum Mesentery 8,292 0 0 1,934 0 0 229 0 0 277 0 0 0 0 0 1,721 0 0 62,118 215 0 15,141 174 173 277,857 224 185 20,208 0 0 0 0 0 1,520,103 0 0 7 8 1,215 73 883 MO Consult - Journal Article 62,118 215 174 250.071 224 185 15,141 173 20,208 1,447,717 24,129 490 Figure 1. Logarithm ot~ uncoated asbestos fiber burden in lung, omentum, attd mesentery, by case. 27,786 48,257 393,417 2,149 827 969,019 2,085 2,428 138,929 4,927 739 303,125 5,045 747 968,473 2.645 593 120,643 189 7,033 -ihestus fibers in at least one extrapulmonary site. Fourteen individuals (70%) had uncoated asbestos fibers in the mesentery and omentum (Table 2 . Fig 21 . The most prevalent type of asbestos in the mesentery and omentum was amosite (Fig 21. Thirteen mesentery samples (65%) and 14 omentum samples (70%) contained amosite. The range of amosite fibers among 13 positive mesentery samples was 175 to 5,445 fibers/g dry weight, while in the 14 positive omentum samples, amosite concentrations ranged from 174 to 6,208 fibers/g dry weight. Amosite was found in all three sites (lung, mesentery, and omentum) in 11 cases (55%; Table 2). The longest uncoated amosite fiber found in the lung was 100 mum (case 2) and the Figure 2. Percentage of cases wiih coated and uncoated asbestos fibers by tissue site. 49 1 shortest amosite fiber was 0.5 mum (case 7). The average length of uncoated amosite fibers in lung from all 20 cases was 11.23 mum. The width of uncoated amosite fibers found in lung ranged from 0.03 mum (case 7) to 1.6 mum (case 7). The longest amosite fiber in the omentum was 70.0 mum (case 2); the longest in the mesentery was 40.0 mum (case 11). The width of amosite in the mesentery ranged from 0.06 to 1.1 mum; and in the omentum, 0.06 to 0.8 mum. Other results showed that 74.1% of amosite in the lung sampled was -- 5.0 mum long. The percentage of those in the omentum that were -- 5.0 mum long was 73.3%, and in the mesentery, 72.4%. The evidence that both long chrysotile and amosite fibers reach these extrapulmonary sites is presented in Table 3 . The second most common type of asbestos found in the extrapulmonary samples, chrysotile, was found in 10 lungs (50% of cases). There were five positive mesentery samples (25% of the sites) and three positive omentum samples (15% of the sites; Fig 21. "Hie amount of chrysotile ranged from 172 to 743 fibers/g dry weight in mesentery samples and from 799 to 1,029 fibers/g dry weight in the nentum. Chrysotile was found in the lung tissue from each of the individuals with positive omentum samples and in three of five individuals with positive mesentery samples (Table 21. The length of the uncoated chrysotile fibers in lung tissue ranged from 0.50 mum (case 1) to 23.0 mum (case 4). In samples of mesentery, chrysotile fibers ranged from 1.2 to 17.0 mum long. In the omentum, chrysotile length ranged from 1.0 to 14.5 mum. The width of chrysotile fibers ranged from 0.04 to 0.4 mum in lung, from 0.04 to 0.34 mum in the mesentery, and from 0.04 to 0.2 mum in the omentum. The percentage of chrysotile htlp://home.mdconault.cofn/das/afticle/body/jofg*journal4aource=MI4sp*1 1210010&sid= 12041775/N/ 169456/1 html Wednesday, March 29. 2000 MD Consult Journal Article -- 5.0 mum long in each site was 57.1% in the lung, 42.9% in mesentery samples, and 10.0% in the omentum (Table 31. Crocidolite was found in five lung samples (25%; range, 20,482 to 224,058/g dry weight), in three mesentery samples (15%; range, 209 to 2,228/g y weight), and in one omentum sample (5%; 289/g dry weight), as shown in Table 2 and Figure 2 . The individual with a positive omental sample for crocidolite was positive for crocidolite in the lung sample (Table 2). One of three positive mesentery samples was from a patient (case 3) found to have crocidolite in his lung sample (Table 2). The length of crocidolite fibers in the lung ranged from 2.0 mum (case 2) to 35.0 mum (case 2), and the length of uncoated crocidolite in the mesentery ranged from 1.0 mum (case 4) to 26.0 mum (case 3). In the omentum, the crocidolite fiber was 9.0 mum long; 74.1% of the crocidolite fibers in the lung were -- 5.0 mum. In the mesentery, 40% of crocidolite fibers were -- 5.0 mum, and in the omentum, 100% were that length. One omentum sample contained an anthophyllite fiber, and another sample was positive for tremolite (Table 2). Two samples of the mesentery were positive for anthophyllite (Table 2) Two of three mesentery samples positive for tremolite (cases 10 and 16) were from individuals who had tremolite in their lung tissue, while only one sample of omentum was positive for tremolite (case 1). Although this subject had the second highest level of total uncoated asbestos fibers, no tremolite was detected in his lung tissue. Tremolite fibers ranged from 1.6 mum (case 14) to 23.5 mum long (case 14) in lung tissue, from 3.0 mum (case 16) to 10.5 mum long (case 10) in the mesentery, and 18.0 mum to 30.0 mum long (case 1) in the omentum. The percentage of tremolite fibers -- 5.0 mum was 34.1% in lung, 100% in the omentum, and 66.6% in the mesentery. In the one subject (case 10) whose lung tissue was negative for ABs and uncoated asbestos fibers, the omentum and mesentery also were negative. Logistic Modeling ie features used to model the likelihood of amphibole presence in the omentum or mesentery (total asbestos burden in lung, median fiber length, rdian aspect ratio, and AB burden in lung) are described in Table 4 . The logistic model using the median light microscopy AB burden (in the lung) had the most significant curvature within the range TABLE 3 - Fiber Length Characteristics 72.2% 3.8% 74.2% Length -- 5.0 Lung Mesentery Omentum Asbestos 170.8% 167.2% | Within site Chrysotile j 42.9% 110.0% | Type Amosite 172.4% |73.3% | Type Length -- 8.0 Lung Mesentery Omentum Asbestos 47.1% 44.2% 154.3% | Within site Chrysotile 42.3% 14.3% 110.0% | Type Amosite 48.7% 46.9% j 58.4% | Type 49 2 TABLE 4 -- Estimated Values of Lung Predictors for Which the Probability of Detecting Any Amphibole Fibers in the Omentum and Mesentery Exceeds a 50% Level in Similar Mesothelioma Populations - m Univariate Predictor *--1: Lung Burden/Attribute Total amphibole asbestos fibers/g dry weight Extrapulmonary Site E' Omentum p Value 4 0.0866 QD Antilog "1 >72,515 Median fiber length, mum Mesentery Omentum 0.0809 0.1384 >45,801 >5.41 Mesentery 0.9973 >2.55 31 Median fiber aspect ratio Omentum 0.1163 >17.3 Mesentery 0.8266 >8.53 Light microscopy FB/g dry weight Omentum 0.0473 >778 Mesentery 0.0938 >48.1 ^Estimated by a univariate logistic regression model with response 1 = any amphibole detected at the given site (omentum or mesentery), 0 - otherwise; the 50th percentile was selected to reflect a level for which a preponderance of evidence exists. * These independent variables, calculated from the lung sites, were allowed in the logistic model, while limiting the model to only one predictor at a time. The variable was first log-transformed to eliminate the skewed nature of their distributions. Dependent response variables indicating the presence of any amphiboles at each of these two extrapulmonary sites were separately considered, li" test for significance of logistic model within the range of the observed data; a small p value suggests statistically significant curvature in the logistic model, which means me lung attribute predicts the probability (likelihood) of the extrapulmonary event. The 50th percentile of the log-transformed attribute was first estimated from the logistic model. This is the antilog in terms of the original unit of measurement that defines the 50th percentile. The attached signs (> or <) indicate whether the probability increases or decreases (from 0.50), respectively, for larger values of this cutoff point. As the p value approaches 1.0, the estimate of this percentile becomes unstable and less accurate because the probability tends to flatten out within the range of the observed attribute. fThis estimated cutoff value may be unstable due to the flatness in the model as indicated by the high p value. httpV/home.mdconsult.com/das/arlicle/body/iorgajournal&sourceaMI&sps1121001 O&sid = 12041775/N/ 189456/1. html Page Wednesday, March 29, 2000 MD Consult - Journal Article "the observed data (p = 0.0473 < 0.05, modeling frequency of amphiboles in the omentum; Table 41. The curvature in the models approached nificance (p < 0.10) for total asbestos (p = 0.0866) when used to predict the probability of any amphibole in the omentum. The same predictors approached significant curvature for modeling the probability of detecting any amphiboles in the mesentery (p = 0.0809, p = 0.0938; Table 4). Although the values were not statistically significant, Table 4 suggests that the median length and median aspect ratio of amphiboles are perhaps more significant predictors of the presence of amphiboles in the omentum (p = 0.1384, p = 0.1163) than the mesentery (p = 0.9973, p = 0.8266). (Note: A p value of 1.0 would indicate a flat estimate of the probability for all values of the predictor.) In this study group, allowing marginal significance (p < 0.10), an amphibole burden of > 72,515 fibers/g dry lung tissue resulted in a > 50% probability (preponderance) of there being an amphibole asbestos fiber found in the omentum (Table 4). Similarly, whenever the AB burdeti/g dry lung tissue as assessed by light microscopy was > 778, it is estimated that amphiboles will be seen in the omentum in a majority of mesothelioma cases in similar populations. The relationships between lung variables and the probability of finding asbestos fibers in the mesentery were also determined. A total amphibole burden in lung of > 45,801 fibers/g dry lung, or an AB burden of > 48.1/g dry lung, resulted in a preponderance for asbestos fibers being found in the mesentery (p < 0.10; Table 41. Similar percentiles can be estimated from the model for any chosen level of probability. Discussion We demonstrated that asbestos fibers were found in the omentum and mesentery, and that the likelihood of this occurrence could be predicted by features of the asbestos in the lung tissue. Heavier inhaled exposures, especially as evidenced by increased FB counts, and, to a lesser extent, total amphibole burden tended to favor the migration of amphibole fibers to these extrapulmonary sites. The longer and thinner amphibole fibers seemed to migrate more readily to the omentum than to the mesentery. This raises an interesting question regarding the nature of the lymphatic or other mechanisms involved for relocation to extrapulmonary sites. his cohort, there was a considerable amphibole burden in all asbestos-positive sites sampled. These primarily consisted of amosite and crocidolite, ^,oth commercial amphiboles. The presence of these types of fibers in the omentum and mesentery was less surprising than their size was. By comparison, no ABs were found in our earlier studies of pleural plaques, and only a small percentage of uncoated fibers in the plaques were > 5.0 mum long. 1511-*-*-' Unlike those extrapulmonary sites, 67.2% of* 1 2 3 4 5 6 * 8 493 the asbestos fibers in the omentum and 70.5% in the mesentery were -- 5.0 mum. Asbestos fibers in these sites were predominantly longer ohiboles, particularly amosite. While the shorter chrysotile fibers arguably may clear more readily from the lung, longer chrysotile fibers did reach .se extrapulmonary sites: 42.9% of chrysotile fibers in the mesentery and 10% in the omentum were -- 5.0 mum. These percentages exclude ABs. which are formed only on fibers that are -- 8.0 mum long. There was a match between at least one type of asbestos found in the extrapulmonary sites in this study with the type(s) of asbestos found in the lung. Animal studies have concluded that chrysotile fibers clear more rapidly from the lung than do amphiboles.^ Chrysotile has also been suggested as having a relatively rapid turnover in human lungs, whereas amphiboles have a slower rate of turnover. 1^1 Lippmann ^ has even suggested that those chrysotile fibers that do escape clearance by the mucociliary escalator may be insufficiently biopersistent because of dissolution during translocation to extrapulmonary sites, which influences the transformation or progression to mesothelioma. 'vhile we do not choose to comment on chrysotile clearance from the lung, we note that chrysotile fibers reached the omentum and/or mesentery in b of the cases. Furthermore, there was no apparent degradation of these fibers, and a portion of them were long fibers ( -- 5.0 mum). Long fibers of chrysotile reached the omentum in several cases, which indicates that chrysotile is also translocated and could be potentially important in the pathogenesis of peritoneal mesothelioma. We conclude that individuals whose exposure and lung burdens conform to the defined population parameters would reasonably be expected to have fiber relocation to the omentum and mesentery. Vulnerable individuals in such groups with sufficient exposures would have fiber burdens available for the stimulation of cells in the omentum and mesentery, which could pose additional risks for the development of peritoneal mesothelioma. References 1. Lippmann M, Yeates DB. Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med 1980; 37:337-362 abstract 2. Leak LV. Lymphatic removal of fluids and particles in the mammalian lung. Environ Health Perspect 1980; 35:55-76 abstract 3. Lauweryns JM, Baert JH. Alveolar clearance and the role of the pulmonary lymphatics. 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Effects of fiber characteristics on lung deposition, retention, and disease. Environ Health Perspect 1990; 88:311-317 abstract MD Consult L.L.C. http://www.mdconsult.com Bookmark URL: /das/iournal/view/N711210QLQ?ja=L69456&PAGE=l.html&ANCHQR=top&source=Ml Page hltp://home.mdconsult com/das/article/body/jorg*ioufnal&source=MI&sp*li21001 O&sid* 12041775/N/ 169456/1. html