Mesothelioma, peritoneal

In an animal study of rats exposed by inhalation to ethylene oxide at 10, 33, or 100 ppm for approximately two years (245), and in a separate chronic rat study in which rats were exposed to 50 or 100 ppm of ethylene oxide (240), increased incidences of mononuclear cell leukemia, peritoneal mesothelioma, and various brain tumors have been reported. In an NTP (246) two-year inhalation study of mice at 50 and 100 ppm, alveolar/bronchiolar carcinomas and adenomas, papillary cystadenomas of the harderian gland, and malignant lymphomas, uterine adenocarcinomas, and mammary gland tumors were increased in one or both exposure groups. 

Malignant mesothelioma, described more than 100 years ago, is a comparatively rare tumor that occurs in the pleura and peritoneum, membranes that surround the lungs, line the thoracic cavity, surround the gut, and line the abdominal cavity. The survival time of mesothelioma patients is often less than a year, in spite of chemotherapy and radiotherapy. Combined therapy and surgical resection in cases of early diagnosis, a treatment currently being tested, has produced a few long-term (more than five years) survivors (Ant-man, et ah, 1980 Antman et ah, 1983), usually in cases with peritoneal rather than pleural involvement. 

The initial connection between asbestos and mesothelioma was made by Wagner et al. (1960), when all but one patient in a study of mesothelioma-related deaths were found to be miners, workers, members of their families, or others living in the area of South Africa where the amphibole-asbestos crocidolite was mined. A comparable occupational exposure to crocidolite has been documented in Australia, with similar results (Armstrong et al., 1984). Mann and his associates (1966) documented three cases of mesothelioma among fifty-four patients dying of pulmonary asbestosis, and in two of the patients the mesotheliomas were peritoneal rather than pleural. 

Effects of three commercially produced calcium silicate insulation materials were examined in rats by inhalation and intraperitoneal injection. Exposure to lOmg/m of respirable dust for 7 bours/day, 5 days/week for 12 months bad no effect on tbe survival of treated animals compared with controls. Although two pulmonary neoplasms, one malignant and one benign, were found in exposed animals, neither was the cause of death, and the incidence was not significantly different from the control group, where no mmors were found. One peritoneal mesothelioma was found in an animal from one of the inhalation groups, but tbis was considered to be a spontaneous tumor as none of over 100 animals injected intraperitoneally with 25 mg of calcium silicate developed these tumors. 

In a chronic inhalation bioassay in rats exposed for 6 hours/day, 5 days/week for 2 years to 100, 33, or 10ppm ethylene oxide, there was a dose-related increased occurrence of mononuclear cell leukemia in both sexes at all concentrations. There was also an increased occurrence of primary brain tumors at 100 and 33 ppm in both sexes and peritoneal mesotheliomas arising from the testicular serosa at 100 and 33 ppm in male rats. ... 

In November 2005, a phase II/III study in NSCLC patients started in Australia and Canada, hi February 2006, Cediranib was undergoing a UK phase II/III trials in colorectal cancer. At that time, US phase II trials were underway in patients with advanced solid tumors, mesothelioma, melanoma, fiver, ovarian, peritoneal, fallopian tube, kidney, and breast cancers, hi May 2006, a US phase II trial began for neurofibromatosis type I and plexiform neurofibroma. 

Feng M, Zhang J, Anver M et al (2011) In vivo imaging of hmnan malignant mesothelioma grown orthotopicaUy in the peritoneal cavity of nude mice. J Cancer 2 123-131... 

Based largely on an industry-sponsored study showing that ETO is carcinogenic to animals, NI0SH recommends that it be treated as a potential occupational carcinogen. The study showed dose-related increased leukemia in female rats and treatment-related (33 and 100 ppm) peritoneal mesotheliomas in male rats (ref. 77a). Limited epidemiologic investigation at two work sites revealed excess cancer mortality in the cohort studied (refs. 77b,c). There is widespread... 

As discussed in Section 3.2 and Chapter 2, numerous studies of occupationally-exposed adult workers identify respiratory effects including interstitial fibrosis, lung cancer, and pleural and/or peritoneal mesotheliomas, as critical health effects, of concern from exposure to airborne asbestos. T ically, these health effects follow chronic exposures and exhibit latencies of 10-40 years, although some cases of asbestosis and pleural plaques have been reported following subchronic exposure. 

Andrion A, Bosia S, Paoletti L, et al. 1994. Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos. Hum Pathol 25(6) 617-622. 

Fischbein A, Luo J-C, Pinkston GR. 1991a. Asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma in an insulation worker. Br J Ind Med 48(5) 338-341. 

Heler DS, Gordon RE, Tumnir R, et al. 1998. Presence of asbestos in peritoneal mesothelioma [Abstract]. Lab Invest 78 104A. 

Manavoglu O, Orhan B, Evrensel T, et al. 1996. Malignant peritoneal mesothelioma following asbestos exposure. J Environ Pathol Toxicol Oncol 15 191-194. 

Miller BG, Searl A, Davis JMG, et al. 1999b. Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity. Aim Occup Hyg 43(3) 155-166. 

Ribak J, Lilis R, Suzuki Y, et al. 1991. Death certificate categorization of malignant pleural and peritoneal mesothelioma in a cohort of asbestos insulation workers. J Soc Occup Med 41(3) 137-139. 

Erionite induced peritoneal mesotheliomas in male rats when administered by intraperitoneal injection, induced pleural mesotheliomas in rats of both sexes when administered by intrapleural injection or inhalation. 

Cancer is generally considered the critical endpoint for chronic exposures. In lifetime studies, rats exposed to airborne concentrations of 10, 33, or 100 ppm for 6hday , 5 days week exhibited several treatment-related tumors including mononuclear cell leukemia, peritoneal mesothelioma, and... 

Azumi and associates used immunohistochemistry to study 33 mesotheliomas (32 pleural, 1 peritoneal, 18 epithelial, 10 biphasic, 4 sarcomatoid, 1 desmoplastic) and 37 adenocarcinomas for hyaluronate. Three of 37 (8.1%) adenocarcinomas and all mesotheliomas immunostained for hyaluronate. The location of the staining reaction in the mesotheliomas was membranous in 30 cases, cytoplasmic in 21 cases, and membranous and cytoplasmic in 19 cases. The staining reaction in mesotheliomas was classified as moderate or greater in 27 of 33 (81.8%) cases. The authors concluded that the demonstration of hyaluronate should be considered an important adjunct to other immunohistochemical tests and electron microscopy in diagnosing epithelial mesotheliomas. 

Bollinger DJ, Wick MR, Dehner LP, et al. Peritoneal malignant mesothelioma versus serous papillary adenocarcinoma A his-tochemical and immunohistochemical comparison. Am J Surg Pathol. 1989 13 659-670. 

Ordonez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol. 1998 22 1203-1214. 

Attanoos RL, Webb R, Dojcinov SD, et al. Value of mesothe-lial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. Histopathology. 2002 40 237-244. 

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