Pleural Malignancies Research Articles

Cohort mortality study of women compensated for asbestosis in Italy

Background The carcinogenic effect of asbestos is accepted for lung cancer and mesothelioma, while conflicting opinions exist for other cancer sites. The aim of the present investigation is to study cause-specific mortality of women compensated for asbestosis who had certainly been exposed to high levels of asbestos fibers. Methods The cause-specific mortality of all Italian women compensated for asbestosis and alive December 31, 1979, was investigated through October 30, 1997. In the total cohort, which included 631 subjects, 277 deaths occurred. Cause-specific SMRs (Standardized Mortality Ratio) were computed using the national rates for comparison. Results A significantly increased mortality for all diseases related to asbestos exposure was observed. Mortality for all causes, all neoplasms, lung cancer, uterine cancer, ovarian cancer, and non-neoplastic respiratory diseases was significantly increased. Separate analyses for textile (n = 276) and asbestos-cement (n = 278) workers were performed. Women employed in the textile industry, mainly exposed to chrysotile, who are compensated at a younger age, showed higher SMRs for lung cancer and asbestosis. Women in the asbestos-cement industry, mainly exposed to crocidolite containing asbestos mixtures, experienced higher mortality for pleural malignancies. Conclusions The role of asbestos exposure in the development of gastrointestinal and genital neoplasms is discussed. Am. J. Ind. Med. 36:129–134, 1999. © 1999 Wiley-Liss, Inc.

Laser Therapy in Pulmonary Medicine

In this review, the different laser applications for diseases in the thoracic cavity are presented. The different laser types, Nd-YAG, CO2, diode lasers and photodynamic therapy (PDT) and their indications are presented. The indications for endobronchial laser vary from benign disorders like granuloma to the more frequent ablation of endobronchial tumours. The promising use of treatment with PDT in early stage lung cancer and its adjuvant role in surgical resection of pleural malignancies is discussed. Emphasis is given to the data obtained so far for the different laser applications.

SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases.

Pleural and pulmonary malignancies are usually associated with well-known carcinogen exposure. Recently, the presence of simian virus 40 (SV40)-like DNA sequences has been detected in brain and bone-related human cancers and in pleural mesothelioma. In order to determine whether SV40-like DNA sequences are also present in bronchopulmonary carcinoma and non-malignant lung samples, 125 frozen pleural and pulmonary samples (including 21 mesotheliomas, 63 bronchopulmonary carcinomas, 8 other tumours, and 33 non-malignant samples) and 38 additional samples distant from tumours were studied for the occurrence of SV40-like DNA sequences by polymerase chain reaction (PCR) amplification followed by hybridization with specific probes. Sequences related to SV40 large T antigen (Tag) were present in 28.6 per cent of bronchopulmonary carcinomas, 47.6 per cent of mesotheliomas, and 16.0 per cent of cases with non-neoplastic pleural and pulmonary disease. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma, but a significantly higher number of mesothelioma cases exhibited SV40-like DNA sequences in comparison with cases of non-malignant pleural or pulmonary disease (P < 0.04). Among cases positive for SV40-like DNA sequences, a history of asbestos exposure was found in 3 out of 12 bronchopulmonary carcinomas and 8 out of 10 mesotheliomas. Immunohistochemistry using monoclonal antibodies directed against Tag did not demonstrate nuclear staining. The DNA sequences were not related to BK virus sequences, but three samples were positive with probes hybridizing with JC virus DNA sequences. In conclusion, this study demonstrates the presence of SV40-like DNA sequences in pulmonary neoplasms and in non-malignant lung tissues. It appears that the presence of SV40-like DNA is not unique to cancer.

Pathology of Pulmonary, Pleural, and Mediastinal Malignancies Other than Lung Carcinoma

Pathology of Pulmonary, Pleural, and Mediastinal Malignancies Other than Lung Carcinoma

A Proposed Control Limit for Exposure to Airborne Erionite Fibers

Abstract The unique physical and chemical properties of the zeolite minerals have resulted in their use in many industrial processes. Environmental exposures to erionite, a commonly fibrous zeolite, have been linked to elevated incidence of malignant pleural mesotheliomas and associated pleural disorders through epidemiological investigations. The presence of erionite in the workplace, with its documented relationship to elevated rates of pleural malignancies in environmentally exposed populations, requires that individuals exposed to the mineral during the course of their work take precautions to avoid excessive airborne exposures to the mineral. A review of relevant environmental, toxicological, and epidemiological literature was undertaken to quantify the effects of erionite exposure. This review identified erionite as a potent mesothelioma risk agent. The risks were compared to those accepted by the U.S. Department of Labor Occupational Safety and Health Administration in the promulgation of the current asbestos permissible exposure limit. We recommend an 8-hour exposure limit of 0.0007 fibers of erionite per cubic centimeter of air based on comparison of the mortality data from an environmentally exposed population with the excess mortality risk accepted by the Occupational Safety and Health Administration in the 1994 asbestos permissible exposure limit. The proposed control limit is readily measured by current analytical techniques and may be used to assess the adequacy of respiratory protective equipment and other control measures supplied to exposed worker populations.

Use of photodynamic therapy for the management of pleural malignancies.

Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequently involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations have been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details evolution of the methodology, toxicity, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant chest neoplasms, with an emphasis on malignant pleural mesothelioma. These investigations have culminated in an ongoing Phase III trial to define the efficacy of intrapleural PDT.

Pleural mesothelioma: A descriptive analysis based on a case‐control study and mortality data in Ile de France, 1987–1990

Incidence rates of pleural mesothelioma in Ile de France were examined for the period 1987-1990, on the basis of information collected in a case-control study. This study was designed to include all new cases of pleural mesothelioma occurring in the region. On the other hand, mortality rates from pleural malignancies in the same region were examined on the basis of death certificates recorded by INSERM for the same period. A large difference was found between the two types of data. Average annual incidence rates were 7.5 per million among men and 1.6 per million among women. Average annual mortality rates due to primary pleural malignancies were 25.2 per million in males and 8.9 per million in females. This study confirms discordances between incidence and mortality data for pleural malignancies already reported in several countries. However, contrasting with some previous reports, the annual mortality rate from pleural malignancies was higher than the incidence rate of mesothelioma in this study. This emphasizes the usefulness of a specific investigation to explain such discordances, prior to comparison of data from one country to another.

Intrapleural photodynamic therapy: Results of a phase I trial

The management of pleural neoplasms, specifically mesothelioma, remains difficult. We performed a phase I trial in 54 patients with isolated hemithorax pleural malignancy to determine (a) the feasibility of intraoperative, intrapleural photodynamic therapy after debulking surgery; (b) the influence of light dose/sensitizer interval on postoperative morbidity in order to define the photodynamic therapy (PDT) maximal tolerated dose (MTD); and (c) whether first order dosimetry could be applied to this complex geometry. Cohorts of three patients were given escalating intraoperative light doses of 15-35 J/cm2 48 h after i.v. delivery of 2.0 mg/kg Photofrin II (Quadra Logic Technologies, Vancouver, British Columbia, Canada), and then escalating light doses of 30-32.5 J/cm2 after a 24-h sensitizer/operation interval. Twelve patients could not be debulked to the prerequisite 5 mm residual tumor thickness. The remaining 42 patients underwent 19 modified pleuropneumonectomies, five lobectomy-pleurectomies, and 18 pleurectomies. Intrapleural PDT was delivered using 630 nm light from two argon pump-dye lasers, and real-time and cumulative light doses were monitored using seven uniquely designed, computer-interfaced photodiodes. There was one 30-day mortality from intraoperative hemorrhage. In the 48-h sensitizer/operation group (n = 33), possible PDT-related complications included an empyema with late hemorrhage in one of three patients at 17.5 J/cm2 and a bronchopleural fistula at 35 J/cm2. At each of these light doses, three additional patients were treated without complication. Two patients subjected to 24-h sensitizer dosing and 32.5 J/cm2 developed esophageal perforations after pleuropneumonectomy at identical sites. The MTD was declared as 30 J/cm2 light with a 24-h dosing interval when none of the six patients (three original, three repeat) at that level developed toxicity. These data demonstrate that resection and intrapleural PDT can be performed safely with currently available sensitizers and lasers. Phase II and III trials are now warranted at this MTD in a homogeneous population of patients with pleural malignancies.

Intrathoracic photodynamic therapy: A canine normal tissue tolerance study and early clinical experience

Surgery with intraoperative photodynamic therapy (PDT) has the potential to improve the treatment of pleural malignancies. Before embarking on such treatment in humans, however, thoracic tissue tolerance to PDT was studied. For each of three (1 week, 1 month, and 6 month) study end-points, one control (no Photofrin II [PII]) and four treated animals underwent thoracotomy 72 hours after I.V. injection (6 mg/kg) PII. Red light (630 nm) was delivered (5-40 J/cm2) to the pleural surface (1 cm diameter) of selected thoracic organs. No clinical differences were observed between PDT and control dogs. The control showed no histological changes; however, in the treated animals focal areas of coagulation necrosis were found at 1 week which progressed to fibrosis at 1 month. The extent and depth of injury was proportional to light dose. The lung was the most sensitive; the chest wall was the most resistant. Myocardium had superficial damage, whereas coronary arteries appeared normal. The results provide the basis for proceeding to phase I human trials in the evaluation of PDT as an intraoperative adjuvant treatment in the management of pleural malignancies.

Video-Assisted Minimal Invasive Thoracic Surgery: A Review of 81 Surgical Procedure

Video-assisted minima11y invasive thoracic surgery (VAMIS) is a new procedure that allows visualisation of and access to the intrathoracic organs without a thoracotomy incision. 81 consecutive patients are operated with this technique (group I n=66; group il n=15). We recently performed 54 pulmonary wedge and bulla excision using videothoracoscopic techniques. Average age 30.5 years (range 15 to 67 years). Indications were pneumothorax in 54 patients, small peripheral solitary nodule in 1, diffuse pulmonary infiltrate in 1, neurinoms in 3, pleural malignancies in 2, pulmonary cyst in 1, pleural thickening in 1, mediastinaly masses in 2, pleural fibrom in 1, pleural metastases in 1, pulmonary metastases in 13. There were no operative death. Intraoperative complications were 8 intercostal vessels bleeding, one patient required blood transfusion. Average hospitalisation was 7.2 days. Patients undergoing videoassisted thoracic operations seem to have reduced postoperative pain, shorter hospitalisation, and quicker recovery times. This new modality appears to have beneficial value for patients, but further evaluation and prospective studies are indicated.

A new device for the treatment of pleural malignancies: intrapleural chemohyperthermia preliminary report.

The prognosis of malignant pleural tumors remains extremely unfavorable. The aim of this study is to evaluate the combination of intrathoracic intrapleural chemotherapy and intrapleural hyperthermia (ITCH) in these diseases. Under anesthesia, 5 men were studied. After pleurectomy for mesothelioma (3/5) or adenocarcinoma (2/5), ITCH is carried out for over 60 min, either with mitomycin C (4/5) or cisplatin (1/5). No pre- or postoperative death occurred. The maximal pleural temperature is 42.6 degrees C. The blood level of mitomycin C never reached the systemic toxic level. All the patients were discharged from the surgical ward, 3 are still alive 15 months later. Therefore, ITCH appears to be a safe and reliable therapy.

Photodynamic therapy for thoracic malignancies.

Photodynamic therapy (PDT) is an experimental form of cancer therapy which employs photoactivation of a sensitizing chemical by light of a given wavelength via the production of toxic oxygen species. PDT causes local destruction of cancer, and relies on a therapeutic index between normal and malignant tissue since the latter seems to selectively retain the sensitizer. PDT has both direct tumoricidal effects as well as indirect effects on tumor vasculature causing an early hemorrhagic necrosis of tissue. The treatment has been used for the treatment of endobronchial obstruction by primary and metastatic tumors. Most recently, trials are being performed to evaluate this therapy as a surgical adjunct in the treatment of pleural malignancies such as mesothelioma.

Trends and geographical patterns of pleural mesotheliomas in the Netherlands 1970-87.

The sex and age related trends and geographical distribution of asbestos related mortality from pleural mesothelioma in the Netherlands between 1970 and 1987 were investigated. Deaths from pleural malignancies recorded by the Dutch Central Bureau of Statistics (CBS) were used and death rates were age adjusted per year by the indirect method. Standardised mortality ratios (SMRs) were computed for 43 regions over the period 1979-86. For men, total mortality increased from 10.8 per million in the period 1970-8 to 20.9 per million during 1979-87. The highest mortality occurred in the group aged between 65 and 74 with 147.7 per million in 1987. The death rate for the group aged between 55 and 64 was 96.5 per million in 1987. For women, total death rates for pleural mesothelioma showed a moderate increase from 2.5 per million in the period 1970-8 to 3.6 per million during 1979-87. The highest mortality occurred in the group aged over 65, fluctuating around 10-15 per million. For men and women under 45 mortality was very low and presented no upward trend. The geographical distribution over the country for the period 1979-86 showed a pattern with a clear concentration of deaths from mesothelioma in men, in conurbations with many harbours, shipyards, and heavy industry near the river mouths and along the North Sea Coast.

Computed tomography of pleural lesions with special reference to the mediastinal pleura.

Computed tomography (CT) and conventional chest radiography were reviewed in retrospect in 84 patients in whom pleural pathology was suggested clinically. The importance of administration of contrast medium in distinguishing between malignant lesions and other pleural diseases was given special attention. CT was found to be of value in diagnosing and establishing the extent of pleural lesions, especially in the mediastinal region. All malignancies exhibited high contrast enhancement following intravenous bolus injection of contrast medium. There were no features specific for mesotheliomas distinguishing these from other pleural malignancies. Some benign infectious lesions also showed high contrast enhancement. High contrast enhancement thus indicated malignancy only if an infectious lesion could be excluded. If contrast enhancement was absent or slight, the lesion was likely to be benign. Clinical follow-up may be regarded as justified in such cases. Indirect signs were not helpful in distinguishing between malignant and benign lesions.

The role of concurrent determinations of pleural fluid and tissue carcinoembryonic antigen in the distinction of malignant mesothelioma from metastatic pleural malignancies

A combined determination of pleural fluid and tissue carcinoembryonic antigen (PF-CEA and T-CEA) by radioimmunoassay and immunoperoxidase staining technique respectively was performed in patients with malignant mesotheliomas (12), metastatic pleural carcinomas (17) and benign pleural diseases (seven). All PF-CEA-positive (>39 ng/ml) cases were T-CEA-positive metastatic carcinomas. In contrast, 4 30 PF-CEA-negative (<39 ng/ml) cases were T-CEA-positive metastatic carcinomas (three cases) and idiopathic pleuritis (one case). These results suggest that CEA, though present in the tumour, is not always released in measurable amounts in effusions. Hence T-CEA content should be determined in the PF-CEA-negative cases when an early and definite diagnosis of tumour type is required to enable correct management of these patients. These ancillary tests aim at enhancing the level of confidence of the routine morphological diagnosis of serous surface malignancies in living patients using minimal intervention instead of resorting to open chest surgery.