Asbestos Related Diseases

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Asbestos related pleural diseases is known to consist of pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and Malignant Pleural Mesothelioma. Advances in this area remain limited but there have been several studies made on this topic.

Pleural Plaques

Pleural plaques, either localized or diffused are the most frequent manifestation of asbestos exposure. They are considered the hallmark of asbestos exposure. They rarely occur within less than 20 years from exposure and are often calcified (Figures. 1 and 2).

Figure 1: Anterior pleural plaques identified on computed tomography scan.

Figure 2: Posterior pleural plaques identified on computed tomography scan

Although the plaques themselves are not precursors of malignant pleural disease they do indicate significant exposure, and therefore the patient is at increased risk of mesothelioma and lung cancer. This raises the question of “how to follow the patient once pleural plaques are identified?”. There are no evidence-based recommendations on how to follow these plaques with respect to the interval or diagnostic imaging modality. Slow progression of the plaques is normal. The only screening study of prior asbestos-exposed individuals targeted the early diagnosis of Malignant Pleural Mesothelioma. It focused on the morphology of pleural plaques for early diagnosis and was completed in 2009. It found that screening asbestos-exposed workers did detect advanced Malignant Pleural Mesothelioma and early as well as late-stage lung cancer.

A successful screening program must include an effective treatment to improve the prognosis of the early detected disease. Unfortunately, treatment options for Malignant Pleural Mesothelioma are limited and prognosis remains poor despite earlier detection. The study concluded that further screening may give more insight to plaque morphology and progression gression. Pleural plaques are often incidental findings on chest radiographs (CXR) and although it has been thought pleural plaques are under-appreciated on chest X-ray (CXR) when compared with computed tomography (CT) scan, most pleural plaques are in fact identified via CXR. A recent study compared chest radiograph with CT scan in 140 asbestos exposed construction workers shows that using CT scan is the gold standard. They found that CXR failed to detect pleural plaques only %3.7 of the time. This occurred when the pleural plaques were located in the paravertebral area. CXR detection in this study was improved by classifications of plaques that included morphology with anatomical location. CXR should continue to be used as first for detection, as it remains the most costeffective and widely available.

Traditionally, pleural plaques were thought not to have any impact on lung function. There is evidence, however, suggesting that isolated parietal and or diaphragmatic plaques are associated with a significant decrease in total lung capacity (TLC), forced expiratory volume in 1 s (FEV1), and forced vital capacity (FVC) consistent with a restrictive pattern. This particular study also demonstrated that direct relationship between the extent of pleural plaques on high-resolution computed tomography (HRCT) and the decrease in lung volume. By using HRCT, interstitial lung disease could be controlled. It should be noted, however, that the decrease in lung function, although statistically significant when compared to controls, is minimal and the clinical significance is unknown. Interestingly, patients often complain of dyspnea and are found to have increased ventilation on cardiopulmonary exercise testing which is postulated to be secondary to a restrictive process from the pleural plaques.

Asbestos Related Diffuse: Pleural Thickening

Asbestos related diffuse pleural thickening (DPT) or extensive fibrosis of the visceral pleura is another disease manifestation of asbestos exposure. It may coexist with asbestos related pleural plaques. The prevalence of DPT is difficult to adequately document as this disorder is asymptomatic in its earliest stages but in advanced stages can cause a restrictive lung pattern and increased dyspnea. The differential for diffuse pleural thickening is wide and includes tuberculosis. It is reasonable to assume that asbestos is responsible for the majority of the cases when there is a history of asbestos exposure and the characteristic radiologic appearances are seen.

Asbestos Related Benign Pleural Effusions

Asbestos related benign pleural effusions generally occur 15–20 years from post-exposure of asbestos and are more common in younger patients aged 20–40 years. The diagnosis requires an appropriate exposure history, the absence of other causes, and the absence of tumor in a 3-year follow-up. The effusion is exudative and can be hemorrhagic, as well as eosinophilic predominant. It is generally transient in nature. It can reoccur on either the ipsilateral or contralateral side. The effusion may be found incidentally or may present with an episode of pleuritic chest pain and fevers. Because mesothelioma often presents with a pleural effusion, exclusion of malignancy is imperative and this usually requires thoracoscopy and biopsy. If a malignancy has not manifested itself in 3 years, the effusion is determined to be benign (Benign is meant to refer to a nonmalignant process but these effusions can be associated with significant morbidity) The effusion may occur on the background of pleural plaques or without evidence of previous asbestos exposure (Figure 3). The effusions generally take a long period of time to resolve.

Figure 3: Small right pleural effusion, determined to be asbestosrelated benign pleural effusion.

Mesothelioma

Malignant pleural mesothelioma is an aggressive neoplasm that arises from mesothelial cells on the serosal surfaces of the pleura. Patients frequently present symptomatic and the prognosis is very poor. Several retrospective studies have determined the 5-year survival rates to be as low as %1. It usually grows as a rind around the pleural surface (Figure 4) and can progress into the fissures (Figure 5). Symptoms are nonspecific and include chest pain, cough and dyspnea. Diagnosis usually relies on pleural biopsy via video-assisted thoracoscopy (VATS). This allows a large pleural biopsy as well as drainage of any existing effusion and the option to perform talc pleurodesis for long-term management if the lung is not entrapped.

Figure 4: Mesothelioma of the right lung forming a rind around the lung.

Figure 5: Mesothelioma lining the fissure in advanced disease

The majority of patients present with a pleural effusion. There have been several studies looking at cell markers to diagnose mesothelioma via pleural fluid analysis which would allow an earlier diagnosis and perhaps a better chance. Making the distinction between malignant proliferation and benign proliferations remains challenging on cytology samples. Mesothelin and calretinin are useful as positive markers to determine mesothlial cell nature and indicate carcinoma; however, they are not diagnostic. Mesothelin in the serum has greater than %90 specificity but with only %50 sensitivity. Pleural biopsy remains the most definitive method for diagnosis as it allows larger tissue sampling.

Although CT remains the initial imaging modality of choice, MRI and PET scanning have been increasingly useful in further delineating the extent of the disease. MRI is particularly useful in revealing invasion of the diaphragm or endothoracic fascia. PET scan is very useful in staging Malignant Pleural Mesothelioma and also guiding the biopsy. Malignant Pleural Mesothelioma can be classified into three subtypes, which has implications for prognosis.

The epithelioid variant is the most common, comprising about %60 of all mesotheliomas and has the best prognosis.

Sarcomatoid mesotheliomas have the worst prognosis and mixed mesotheliomas – which have both epithelioid and sarcomatoid features – fall between the other two types. Advances in therapy are limited.

Surgical resection options include extrapleural pneumonectomy and pleurectomy/decortication. These surgeries incur a high morbidity and the question remains whether surgery offers a survival benefit with the introduction of cisplatin–antifolate chemotherapy combinations.

A prospective study of 174 patients with epithelial Malignant Pleural Mesothelioma received a multimodal treatment protocol involving surgical resection. In this study, early-stage Malignant Pleural Mesothelioma was confirmed in 77 patients, of which 40 under went extrapleural pneumonectomy and 37 received pleurectomy/decortication. The pleurectomy/decortication group had a lower morbidity and mortality and better quality of life scores until disease recurrence and a longer survival after recurrence when compared with extrapleural pneumonectomy . The overall survival after surgical resection for epithelial Malignant Pleural Mesothelioma did not significantly differ when comparing extrapleural pneumonectomy and pleurectomy/decortication. Therefore a lung-sparing procedure is superior for disease control in symptomatic patients for this incurable malignancy.

There are no randomized trials comparing best supportive care to palliative chemotherapy but when comparing single agent to combination therapy with cisplatin–antifolate.

Several guidelines recommend palliative chemotherapy is reasonable to offer in patients with a good performance status. First line combination chemotherapy includes a platinum agent and pemetrexed or raltitrexed. Alternatively, patients can be offered enrollment in first and second line clinical trials.

It is unclear whether surgery offers a survival advantage compared with palliative cisplatin–antifolate chemotherapy.

Key Points

 Pleural plaques are the most common manifestation of asbestos exposure.
 Chest X-ray is comparable with high-resolution computed tomography for plaque detection.
 Pleural plaques, although benign, can be associated with neuropathic pain, and when compared to normal controls cause alteration in pulmonary function tests, although the clinical significance is unknown.
 MRI and PET scanning can provide additional staging and diagnostic information in Malignant Pleural Mesothelioma.
 It is unclear whether debulking surgery offers a survival advantage in the treatment of Malignant Pleural Mesothelioma when compared to palliative chemotherapy. Of the two surgical options, it appears lung-sparing procedures offer comparable disease control but improved quality of life over extrapleural pneumonectomy.

Conclusion

Asbestos related pleural disease is the most common manifestation of asbestos exposure. Although pleural plaques are benign, they are a marker of significant asbestos exposure which is a risk for lung cancer. In this case an appropriate screening protocol is necessary. Pleural plaques are shown to be associated with increased neuropathic pain and demonstrate a trend towards a restrictive pattern on PFTS, although the clinical significance unknown. Greater awareness and further studies of this relatively common problem are required to better treat and screen these patients.

Malignant pleural mesothelioma, although relatively rare and it is an incurable. Further studies comparing standard cisplatin–antifolate chemotherapy to surgical debulking procedures are required to implement an effective treatment protocol.

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