Diagnostic strategy

The first point to emphasise is the importance of the history, particularly occupational aspects. A detailed occupational history should alert the clinician to the possibility of mesothelioma as a cause of the patient's symptoms. Obtaining an accurate occupational history at the first consultation may have medicolegal importance since it may carry more weight than a history which is elicited after a diagnosis of mesothelioma has been made. A detailed history will include identification of employer and dates of employment, together with enquiry about direct and indirect exposure. An accompanying environmental history including questions about employment of parents may be important where no clearcut exposure can be identified. It is important to obtain this history promptly because such details may not be possible to elicit as the patient's condition deteriorates.

A history of direct asbestos exposure may not be obvious. Many cases may occur in patients working in occupations not traditionally recognised as being associated with asbestos exposure, particularly the construction industry. It is recommended that prompt referral to a respiratory physician should occur for any patient in whom early assessment raises the possibility of mesothelioma.

A diagnostic strategy algorithm, based on the clinical presentation which has raised the possibility, is shown in fig 1. The algorithm emphasises the key role of computed tomographic (CT) scanning and the techniques available to confirm the diagnosis. In a small proportion of patients the diagnosis may not be made even after thoracic surgery. In such individuals clinical follow up may clarify the situation. Benign disease is likely to remain stable while, in patients with mesothelioma, follow up radiology will reveal a progressive pleural mass. If thoracoscopy fails or is not technically possible, open pleural biopsy may ultimately be needed.

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Figure 1

Diagnostic strategy for suspected pleural mesothelioma.

In most cases it is preferable to obtain pathological confirmation and the clinician should be aware that negative pleural biopsy and pleural fluid cytological results do not exclude mesothelioma and should lead to further investigation. However, if the diagnosis is reasonably certain on the basis of typical clinical and radiological features, it is appropriate to accept it without taking biopsy specimens in a frail patient or in those in whom there is some contraindication to biopsy techniques.

The initial approach to diagnosis depends on the presenting feature. For instance, chest wall pain, unilateral pleural thickening, and undiagnosed pleural effusion all raise the possibility of mesothelioma but are investigated in different ways.

Incorrect diagnosis of mesothelioma leads to missed opportunities for treatment of a disease more responsive to treatment. Furthermore, an erroneous diagnosis of an incurable malignant disease when, in fact, the patient has benign asbestos related pleural thickening may cause unnecessary distress and may prompt irreversible decisions—for example, about employment—before time disproves the diagnosis. Although some authors state that pathological confirmation is not necessary for the prescribed disease of mesothelioma to be diagnosed, in practice lack of confirmation may make it more difficult for the patient to obtain disablement benefits from the Benefits Agency and damages at common law. If a patient is to be included in a clinical trial of treatment, pathological confirmation of the diagnosis is essential.

Key points

• The importance of a detailed occupational history cannot be overemphasised.

• Any patient in whom mesothelioma is suspected should be promptly referred to a respiratory physician for further assessment.

• Pathological confirmation of the diagnosis is recommended, unless the patient is frail or has extremely advanced disease.

• Negative pleural biopsy and cytological results do not exclude mesothelioma and should lead to further investigation.

• CT scanning plays a key role in the diagnosis of mesothelioma.

Diagnostic imaging

Imaging at presentation— Mesothelioma is usually suspected because of pleural opacification detected on a standard plain chest radiograph. Lateral and plain decubitus views may aid initial assessment. Ultrasound and CT scans may be helpful at presentation, particularly in the differentiation between fluid and solid pleural thickening. CT scanning is also very useful in demonstrating a solid component in association with apparently simple effusions and should be undertaken in all patients with undiagnosed pleural disease.14

Frequently, the radiological changes may be associated with pleural plaques from exposure to asbestos, but there are many patients in whom coincidental pleural plaques are not found. A nodular or irregular pleural shadow or pleural thickening extending onto the mediastinal surfaces are pointers to mesothelioma.

Imaging in differential diagnosis—In practice, the main differential diagnosis is between benign pleural thickening and adenocarcinoma involving the pleura. Occasionally empyema, fibrothorax, and apparently idiopathic pleural exudates may cause confusion. Benign pleural thickening can sometimes be distinguished from mesothelioma on the CT scan by the presence of a fat line between the pleural thickening and the chest wall. Absence of this line raises the likelihood that the abnormality under assessment is malignant.

Invasion of the chest wall demonstrated by either CT scanning or magnetic resonance imaging (MRI) suggests a malignant lesion as does spread to the mediastinum or the presence of mediastinal lymph nodes. However, it should be remembered that infections such as actinomycosis and tuberculosis can occasionally invade soft tissues.

Imaging of the pleura after drainage of pleural fluid may also provide useful information but radiology can neither make a firm diagnosis of mesothelioma nor reliably distinguish the disease from other forms of malignancy.

Imaging in management—CT scanning can be used to assist diagnosis by a guiding percutaneous needle biopsy. MRI may be of value in determining local spread of tumour, particularly where there is a suspicion about chest wall invasion and assessment of disease in specific areas such as lung apex, diaphragm, heart, and spine.15 However, CT and MRI scans provide similar information about resectability in most cases. Sensitivity for detection of involvement of the diaphragm and chest wall is high for both techniques, and both are valuable in appropriate patients when planning radiotherapy and surgery.16 ,17 CT scanning is likely to be the initial study for determining resectability in most cases because it is more widely available. Important complementary information is occasionally obtained by MRI in difficult cases because of its ability to provide different views of the pleura.18

Routine clinical follow up is usually undertaken with plain radiographs. CT scanning is not generally necessary but may be helpful either when the diagnosis has not been firmly established after initial work up or for assessing a patient's response to chemotherapy.

Key points

• CT scanning should be performed on all patients with undiagnosed pleural exudates.

• Pleural plaques are indicators of asbestos exposure but are absent in many proven cases of mesothelioma attributable to asbestos fibre.

• Demonstration of chest wall invasion by either CT scanning or MRI is highly suggestive of malignant rather than benign pleural disease.

Pathological diagnosis

Routine cytological examination of pleural fluid has a sensitivity of only 32% in the diagnosis of mesothelioma,19 although immunocytochemistry may assist in distinguishing mesothelioma from adenocarcinoma and from reactive mesothelial cells.

Samples for histological analysis are more useful. It is important that the pathologist is provided with full thickness biopsy specimens since superficial tissue may include only reactive change associated with the malignant process. Blind percutaneous needle biopsy specimens taken by Abrams' needle, for example, gives a diagnosis in less than 50% of cases.20 Ultrasound or CT guided cutting needle biopsy specimens give much better results and thoracoscopic biopsy under direct vision will yield a diagnosis in most cases.21 Open biopsy is occasionally necessary, but even then the diagnosis may remain elusive and may only be confirmed at necropsy. This is because the tumour often evokes a marked fibrous response and the malignant tissue may be missed by the biopsy.

The main pathological types are epithelioid, sarcomatoid (or fibrous), and biphasic (or mixed). The biphasic type combining epithelioid and sarcomatoid features is easiest to diagnose. The epithelioid type is most common and is easily confused with adenocarcinoma. Pathologists should attempt to specify the histological subtype because it affords prognostic information to the clinician which is helpful in clinical management and important to take into account if the patient is being considered for surgery or a clinical trial. Table 2 is given to guide clinicians to the approach pathologists might take in differentiating malignant epithelioid mesothelioma from pleural adenocarcinoma using special stains.

Histochemical and immunohistochemical stains assist in differentiating epithelioid mesothelioma from adenocarcinoma. The most useful are shown in table 2. Additionally, epithelial membrane antigen (EMA) staining is generally positive if the process is malignant in both mesothelioma and adenocarcinoma, but not if the process represents mesothelial hyperplasia. EMA is therefore helpful if the proliferation is suspicious of malignancy but there is no evidence of invasive activity.

It is not appropriate to report a tumour as “consistent with either adenocarcinoma or mesothelioma” without using a selection of these stains to attempt differentiation, providing that sufficient tissue is available. Any stain may give an atypical result and a conclusion should be reached on the basis of the results of several stains.

In the sarcomatoid variety spindle shaped cells are set in a varying amount of collagenised stroma. When bland spindle cells are set in much stroma, differentiation from scar tissue may be very difficult while, at the other end of the spectrum, markedly pleomorphic cellular foci showing mitotic activity are indistinguishable from other forms of undifferentiated sarcoma and cartilaginous, osseous, muscular, or fatty differentiation may occasionally occur. Immunostains for broad spectrum cytokeratins may assist in differentiating sarcomatoid mesotheliomas, which react positively, from sarcomas, which react negatively. The adoption of nomenclature such as “osteosarcoma of the pleura” for an otherwise typical mesothelioma in an asbestos worker is inappropriate.

Antibodies that react with mesotheliomas but not carcinomas are described but many of them require fresh tissue and are of dubious specificity. Further progress in this field can be expected.

Localised fibrous tumour of the pleura—In the past this tumour has been known as benign or localised mesothelioma. It differs from mesothelioma in being unrelated to asbestos exposure and having a much better prognosis. The tumour is well circumscribed and covered by serosa. Microscopically, the appearances are of a low grade spindle cell neoplasm. Immunocytochemistry shows positive reactions for vimentin and actin but, unlike mesothelioma, negative reactions for cytokeratin and epithelial membrane antigen. In 80% of cases there is positive staining for CD34 which is also useful in distinguishing it from mesothelioma in which CD34 reactivity is limited to blood vessels.

Multicystic mesothelial proliferation and well differentiated papillary mesothelioma—Multicystic mesothelial proliferation is a rare condition affecting the peritoneum. It has been known by various names, including multicystic mesothelioma, but it is now recognised to be a reactive rather than a neoplastic lesion, unrelated to asbestos exposure. The prognosis is good but the condition tends to recur. Patients are typically young women with a history of pelvic inflammation or surgery who have a multicystic pelvic mass. Microscopically, the cysts are lined by mesothelial cells. Immunocytochemistry and electron microscopy assist differentiation from lymphangioma. Well differentiated papillary mesothelioma is another uncommon benign condition which occurs in the peritoneum of woman of reproductive age.

Key points

• Pleural fluid cytology and histology of blind biopsy specimens have low diagnostic yield for mesothelioma but are important initial steps in differential diagnosis.

• Ultrasound and CT guided biopsy and thoracoscopic and surgical biopsy techniques should be used to increase the likelihood of accurate diagnosis.

• Pathologists should attempt to specify the histological type of mesothelioma.

• A selection of special stains should be used to help differentiation of mesothelioma and pleural adenocarcinoma.

Treatment strategy

The management of all patients with mesothelioma should be discussed by a multidisciplinary team, as with lung cancer. Essential management points to be considered on diagnosis are:

(1)

Is the patient one of the few who will have operable disease?

(2)

How should a pleural effusion, if present, be managed?

(3)

Do any biopsy sites require prompt radiotherapy?

(4)

Should the patient be considered for entry into a trial of chemotherapy?

(5)

What are the palliative care requirements?

(6)

What are the compensation issues?

 Patients potentially suitable for radical surgery have epithelioid tumours of low volume and are otherwise fit for a major operation. These are likely to be few, we estimate 1–5%. Accurate staging (see below) by CT scanning and, in selected cases, MRI scans identifies those potentially suitable for surgery. Staging also provides prognostic information for those unsuitable for surgery.

Those with early epithelioid disease without radiological evidence of lymph node involvement are the best candidates and radical surgery is otherwise seldom appropriate. In such cases early chemical pleurodesis should be avoided as it makes subsequent surgical exploration of the chest to define the extent of the tumour before radical resection virtually impossible. Patients submitted for radical surgery should be given realistic information about the outcome of surgery and should give fully informed consent.

Patients with pain or a chest wall mass should be considered for palliative radiotherapy; prophylactic radiotherapy to biopsy sites should be offered. For many patients it will be sufficient to explain that no form of active treatment offers proven survival benefit but that all possible measures to alleviate symptoms will be employed. However, some patients find it very difficult to accept a treatment policy which does not include any specific anti-tumour therapy and they should be given the opportunity to discuss what may realistically be expected from chemotherapy with an oncologist or respiratory physician interested in chemotherapy for mesothelioma. If the patient opts for chemotherapy to be given, it is reasonable that it should be offered preferably within the context of a clinical trial such as the forthcoming BTS trial which compares active symptom control (ASC) with either ASC plus combination therapy of mitomycin, vinblastine and cisplatin or ASC with the single agent vinorelbine. If no trials are available locally, chemotherapy using one of the regimens which has been reported to have some activity in mesothelioma is an option.

Staging

The goals of staging are to assess operability and, in patients subsequently deemed to be inoperable, to offer prognostic information.

Traditionally a system based on that first proposed by Butchart22 is used. This involves classification of the tumour into four stages: stage I (tumour simply confined to the ipsilateral pleura, pericardium, and diaphragm); stage II (tumour invades the chest wall, mediastinal structures, and/or intrathoracic lymph nodes); stage III (penetration of the diaphragm, with or without lymph node involvement outside the chest); and stage IV (distant metastases).

A more detailed staging system based on a TNM system has been suggested by the International Mesothelioma Interest Group (IMIG) (Appendix).23 In practice, full IMIG staging will require surgical intervention, although CT scanning offers a useful proximation. This is relevant because of increasing evidence that disease extent and nodal status affect prognosis in surgically resected tumours.24 ,25 Staging is essential if the possibility of including the patient in a clinical trial of treatment is contemplated.

Fuller details of these staging systems are given in Appendix .

Key points

• Staging is essential for correct selection of patients for surgery.

• Staging provides important prognostic information.

• Staging should be undertaken before clinical trials.

Radical surgery

There are no randomised controlled trials to establish the role of surgery. Historical evidence is based on centres reporting large series and recently these centres have included multimodality therapy, which follows radical surgery with chemotherapy and radiotherapy.26

Early surgical series of aggressive local control with extrapleuropneumonectomy (EPP) were reported by Butchart.22 This extensive operation, which typically involves removal of the pleura, mediastinal lymph nodes, ipsilateral pericardium and diaphragm, reported a high operative mortality and a significant number of early recurrences. This experience emphasised the need for careful and improved patient selection. More recent and larger series from specialist centres of patients treated with aggressive local surgical control, including EPP, have reported much lower operative mortality which approaches that of standard pneumonectomy for lung cancer. However, in centres where few cases have been operated on, this experience may not be repeated and the operative mortality remains high in inexperienced hands, perhaps in excess of 30%.

Virtually all long term survivors after radical treatment have had epithelioid tumours at an early stage. The diagnosis of epithelioid malignant mesothelioma must be secure before surgery. Frozen section at the time of exploratory thoracotomy is to be avoided as the disease is difficult to diagnose under these circumstances, requiring formal histological examination including immunohistochemistry and occasionally electron microscopy.

Patients with stage I or II tumours on the IMIG staging system seem to have the potential for prolonged survival following surgery. Recent series26 reporting results of trimodality therapy including EPP in 183 carefully selected patients have reported a 5 year survival of 15%.

The finding of a higher than expected incidence of N2 nodal involvement in resected specimens (approximately 40%) and the associated poor survival has led to suggestions from some experienced surgeons that mediastinoscopy should be performed on all patients considered to be surgical candidates. However, mediastinoscopy has its shortcomings and cannot be expected to detect all N2 disease.

Patients must be fit to undergo major thoracic surgery of any kind and are thus unlikely to be elderly and have associated general medical conditions; this is discussed in another BTS guideline.27Age, however, has not been an exclusion factor in larger reported series where up to 27% of patients were over 65 years of age.

Key points

• There are no randomised control trials to establish the role of radical surgery.

• Radical surgery should only be considered when there is a positive diagnosis of epithelioid mesothelioma.

• Surgery should only be performed in centres where there is an interest and experience in performing extrapleuropneumonectomies.

• The limited evidence available has reported surgical results only as part of a multimodality treatment strategy.

Management of pleural effusions

There are a number of problems associated with management of pleural effusions associated with mesothelioma. On the one hand, the clinician would like to avoid invasive measures for inoperable disease wherever possible but, equally, the prospect of recurrent pleural aspiration with the attendant risk of needle track spread of the disease is best avoided.

An early problem is to decide how aggressive to be when the patient first presents with an undiagnosed pleural effusion in whom mesothelioma is strongly suspected. Early thoracoscopic intervention may be important, given the low diagnostic yield of closed procedures. Thoracoscopic intervention allows not only safe removal of all the pleural fluid but also biopsy specimens can be taken to facilitate histological diagnosis and pleurodesis can be performed at the same time.

There are no clinical trials to suggest whether the outcome of patients with effusions referred early for thoracoscopy is better than those treated medically, and it is likely that each patient has to be managed according to the particular circumstances, including access to a thoracic surgical unit. Generally, early pleurodesis—either medical or surgical—is preferable to repeated pleural aspirations for inoperable patients, although pleural aspirations may be appropriate for frail patients with advanced disease. In many centres medical pleurodesis may be the most rapidly available option for logistical reasons.

Thoracic surgery is valuable for the control and prevention of recurrence of pleural effusion in patients with histologically proven disease who are unsuitable for radical treatment. Thoracoscopy with talc poudrage has a high success rate28 which is enhanced when there is complete drainage of pleural fluid and apposition of the parietal and visceral pleurae.29 Success is increased if suction is applied to the intercostal drain postoperatively. Drains are usually removed after 24 hours or once the intercostal drainage is less than 150 ml in 24 hours.

Open pleurectomy and decortication is effective in controlling pleural effusions, but it is invasive and is likely to have high operative mortality (about 30%) and morbidity and should only be considered in difficult situations. However, video-assisted thoracic surgery (VATS) is now available in most thoracic surgical centres. This technique allows for partial pleurectomy extending up to cytoreductive surgery to be performed with a low morbidity and mortality (about 1.5% for all VATS procedures); there are low recurrence rates in patients whose effusions have been resistant to other forms of treatment.30 This treatment, which may prove to be the technique of choice, requires further evaluation and should be subjected to a randomised trial.

The risk of tumour seeding at drain and port sites following surgical interventions for malignant mesothelioma is considered to be high. This risk can be significantly reduced by early local radiotherapy.

Pleuroperitoneal shunts can be considered for the small number of patients in whom it is not possible to achieve apposition of the pleural surfaces due to trapped lung and persistence of pleural fluid. These shunts can be inserted at mini-thoracotomy and laparotomy or by minimally invasive techniques. There is, however, a high failure and complication rate including blockage of the shunt and peritoneal seedings.

Key points

• Talc pleurodesis is probably the treatment of choice for the control of pleural fluid.

• VATS pleurectomy is an effective treatment to control pleural fluid in mesothelioma and is much safer than open pleurectomy and decortication.

• The value of pleuroperitoneal shunts remains uncertain.

Radiotherapy

Irradiation of large volumes of the thorax can result in a high incidence of lung damage. Elegant techniques are available which aim to deliver a high dose to the pleura, minimising the dose to the underlying lung. These techniques remain under investigation and there is no evidence to support the use of radical radiotherapy as a single modality therapy. Radical radiotherapy in combination with surgery and chemotherapy is under investigation as part of multimodality therapy and is subject to ongoing studies. Palliative radiotherapy may be effective in relieving pain while prophylactic radiotherapy to drain and biopsy sites and chest wall masses is indicated.

Prophylactic radiotherapy following any invasive procedures (whether drainage or biopsy)—There is a risk of seeding along the track and this may result in a painful mass, although the risk of clinically important disease is unknown. Radiotherapy to the drain site with 21 Gy in three daily fractions in a randomised study of 40 patients reduced the risk of seeding from 40% to zero.31 A non-randomised study published at around the same time with the same fractionation scheme and 250 kVx rays reported no recurrences in 38 sites irradiated in 20 patients.32 It is noteworthy that, in an earlier non-randomised study, Boutin et al 33 had observed recurrences when the radiotherapy was delayed for 2 months. The recommendation is that radiotherapy should be given within 4 weeks. Depending on local arrangements, it may help to book the radiotherapy before the procedure is carried out.

Palliative radiotherapy for pain or chest wall masses—In two retrospective series pain improved in 23 of 37 patients (62%).34 ,35 Davis et al,36 incorporating Ball and Cruickshank,37 found that first courses of palliative radiotherapy resulted in improved symptoms in at least 43 of 87 patients (49%). This is probably an underestimate as the response was unknown in 15 of the patients. These series also included patients with superior vena caval obstruction (SVCO) and metastatic disease. Objective response of chest wall masses was seen in five out of nine patients.35 In these series a variety of radiotherapy regimens was used. Most UK clinical oncologists would use a short course of treatment of generally no longer than 2 weeks' duration with the actual regimen being determined by performance status and the size of the treatment field.

Breathlessness is rarely improved by radiotherapy. Pain relief may be disappointingly short lived and there is no evidence for a dose response relationship to radiotherapy under these circumstances.

Palliative radiotherapy to other sites—None of the nine patients with SVCO had relief of symptoms.34 ,36 Stenting is therefore recommended as first line treatment for SVCO when it occurs.

Future directions—An additional BTS/MRC trial has been proposed comparing two radiotherapy regimens for prophylactic radiotherapy (21 Gy in three fractions and a single fraction of 14 Gy). Randomised trials of palliative radiotherapy are required. A non-randomised study with prospective recording of symptoms and quality of life is in progress and should pave the way for future randomised studies.

Key points

• Prophylactic radiotherapy reduces chest wall implantation following invasive procedures.

• Palliative radiotherapy provides pain relief in about half of all patients.

• Palpable masses respond to radiotherapy in about half of all patients.

• Breathlessness and superior vena caval obstruction rarely respond to radiotherapy.

Chemotherapy

Most of the available chemotherapeutic agents have been tried in mesothelioma but none has consistently produced a response rate above 20%.38 ,39 Agents which have consistently been reported to produce response rates of 10–20% include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, carboplatin, and antifolates. Combination chemotherapy trials have not demonstrated consistently greater response rates than single agent trials. There are no published randomised studies which show improved survival in patients treated with chemotherapy compared with supportive care. Symptomatic improvement has been reported following chemotherapy, both in patients with and those without demonstrable tumour regression.40 However, no randomised studies have compared the effects of chemotherapy and best supportive care on symptoms and quality of life.

There is a need to continue to explore new agents and new approaches in phase I and II trials and to evaluate regimes which appear to show activity in larger randomised trials. Comparison of different chemotherapy regimens and comparison of chemotherapy with best supportive care would be appropriate, particularly in patients with few symptoms. End points should include tumour response as assessed by serial CT scans, quality of life, and survival.

The proposed BTS/MRC trial compares active symptom control (ASC) with ASC and either three agents (mitomycin, vinblastine and cisplatin) or a single agent (navelbine). All patients should be offered the opportunity to discuss what chemotherapy may offer with an oncologist or respiratory specialist with an interest in management of mesothelioma as part of their multidisciplinary care. For those who wish to have chemotherapy it is reasonable that it should be offered, preferably within the context of a clinical trial.

Key points

• All patients with mesothelioma should have the opportunity to discuss the pros and cons of chemotherapy with either an oncologist or a respiratory specialist.

• There are no published randomised trials comparing either survival or symptom control in patients treated with chemotherapy or best supportive care.

• Chemotherapy, where used, should be given as part of a clinical trial.

• Clinicians should be encouraged to enter patients into suitable trials.

New approaches to treatment

New approaches to treatment are under investigation. Some patients are well informed about these, increasingly frequently as a result of searching the internet.

Various types of gene therapy have been proposed. These include introduction of “suicide genes” which make the tumour cells susceptible to antiviral agents, and genes to stimulate natural defence mechanisms against tumours (such as cytokine genes to stimulate natural killer cell activity and the heat shock protein gene to increase presentation of tumour antigens).41 These studies are all at a very early stage and are not yet realistic options for treatment.

Photodynamic therapy employs a red laser light to activate drugs which have a cytotoxic effect. A randomised trial found no benefit from this mode of therapy added to debulking surgery.42

Various types of immunotherapy have been tried, including intrapleural and systemic interleukin 2 and interferon.43 Occasional responses have been observed but there is no evidence that these treatments are superior to chemotherapy.

Key point

• Gene therapy, photodynamic therapy, and immunotherapy do not yet have an established role.

Palliative care

Palliative care of the patient with mesothelioma and the family has an important part to play, given that the disease has a uniformly poor—although relatively well defined—prognosis. Most patients need symptom palliation from the time of diagnosis onwards. It needs to be recognised that all symptoms have a context which is physical, psychological, and social. If the context is not heeded, symptom relief may be suboptimal. Palliative care aims to provide relief from pain and other physical symptoms and to respond to psychological, social, and spiritual needs.

The patient, the family, and the general practitioner may often have difficulty in accepting that palliative care is the only available treatment for the great majority of cases. Anger and frustration are common, and there are particular issues in mesothelioma concerning blame for the disease, obtaining pensions, and litigation.

This document does not present a comprehensive account of palliative care and symptom relief and more details can be found in standard references.44 ,45

Key points

• Most patients need symptom palliation from the time of diagnosis onwards.

• Palliative care should aim to provide relief from pain and other physical symptoms and to respond to emotional, psychological, social, and spiritual needs.

General management—Patients with mesothelioma should be under the care of a specialist, usually a respiratory physician who should be able to liaise with a cardiothoracic surgeon, an oncologist with a special interest in thoracic oncology, a specialist palliative care team, and a pain relief service.

The specialist should ensure that the diagnosis is communicated skilfully and sympathetically. A clear picture of the disease and what to expect, including a realistic prognosis, should be given to the patient and, if appropriate, to families and carers. However, it is important never to imply that “nothing can be done”.

Immediate communication with the general practitioner should include the known extent of the disease, what was said to the patient, and the management plan.46

Physicians should ensure that relatives or carers and the general practitioner are warned, at an appropriate stage, that a Coroner's post mortem will nearly always be required after the death of a patient with mesothelioma, and all deaths have to be reported to the Coroner (in Scotland the Procurator Fiscal).

Patients and families should have access to written information about both the disease and organisations with a specific interest in asbestos related disorders, cancer, and life threatening illness. A list of available organisations is given in Appendix .

There should be involvement of an appropriately trained specialist nurse who can facilitate the pathway of care of the patient and the family throughout the illness, and ensure good liaison between hospital services and primary care, and access to specialist palliative care services as required. Patients should be made aware of whom to contact in case of need.

Appropriate regular outpatient follow up is recommended, even if there is no change in treatment, as it provides an opportunity for further discussion including issues of compensation and benefits. There should be continuing close liaison with the general practitioner and primary health care team.

Key points

• Patients with mesothelioma should be under the care of a specialist.

• The specialist should ensure that the diagnosis is communicated skilfully and sympathetically with a clear picture of the disease and the management plan.

• This information should be communicated immediately to the general practitioner.

• Written information about the disease and relevant organisations should be available to the patient and family.

• An appropriately trained specialist nurse should be involved from the outset to support the care of the patient and liaise between hospital services, primary care, and specialist palliative care services.

• The general practitioner should be reminded that all deaths have to be reported to the Coroner (in Scotland the Procurator Fiscal); a post mortem is usually required.

Symptom control—All symptoms need a working diagnosis. Some may be caused by intercurrent non-cancer related problems. It is often helpful to record symptom severity on a simple scale to assess progress and response to treatment.

(1)

Pain relief. Analgesic use should follow the standard WHO “analgesic ladder” with the use of appropriate laxatives. Analgesics, especially opiates, should be given regularly with adequate escape medication for intermittent breakthrough pain. In pain from chest wall involvement the response to opiates is variable because of added inflammatory and neuropathic components. In such cases adjuvant analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), amitriptyline, anticonvulsants, and steroids should be considered early. If the pain is not easily and well controlled by these drugs, then referral to a pain relief service is advised, because other pain relief techniques can be useful. These will depend on local expertise and availability and include TENS machines, intercostal or paravertebral nerve blocks, interpleural,47 epidural or intrathecal analgesic infusions, local thoracic spine neurolytic blocks, or percutaneous cervical cordotomy.48 Localised pain associated with tumour invasion of the chest wall may respond to radiotherapy.36 The role of chemotherapy in pain relief is as yet uncertain. Pain control may be improved by attention to emotional, psychosocial, and spiritual problems.

(2)

Breathlessness. The common causes of breathlessness in mesothelioma are pleural effusion, lung compression, and chest wall stiffness. Weakness and malaise, and anxiety or panic, may contribute. If dyspnoea worsens acutely, additional problems to consider include increasing pain, pulmonary embolism, pulmonary vessel invasion by tumour, chest infections, and contralateral pleural or pericardial spread. The treatment of breathlessness due to progressive disease and lung compression is difficult. Breathing exercises and relaxation training combined with re-adaptation (as in pulmonary rehabilitation programmes) and relief of anxieties, fears, and psychosocial problems can reduce the impact of breathlessness, particularly when associated with panic.49 Drug therapy for severe breathlessness includes the use of opiates and benzodiazepines. The use of oxygen is discussed fully elsewhere.50 In the terminal phase it is often appropriate to use a combination of diamorphine and midazolam in a subcutaneous infusion via syringe driver.

(3)

Cough. A persistent cough is probably due to lung compression and is common in patients with mesothelioma. Symptomatic trials of opiate linctuses, oral steroids, and nebulised local anaesthetics can be considered.51

(4)

Anorexia, weight loss, and fatigue syndrome. This is common in the later stages of mesothelioma. Treatment is unsatisfactory but gastric prokinetic agents, steroids, and megestrol acetate have been tried.52 Dietary advice and experimentation can be helpful. Depression may mimic this syndrome and respond to appropriate treatment.

(5)

Other problems. Generalised troublesome sweating can occur. This sometimes responds to paracetamol, NSAIDs, cimetidine, or thioridazine (10–30 mg nightly).53 Occasionally, patients have lymphatic or local spread resulting in dysphagia or SVCO (for both of which stents can be considered) or leg oedema (for which referral to a lymphoedema therapist is advised). Metastases commonly occur late in the disease and are rarely symptomatic. Their management is as for metastases due to other cancers. Confusion can be a problem in the later stages of the disease and underlying causes should be identified and treated before symptomatic drugs are prescribed. Possible causes include drug toxicity (particularly opiates), infection, hypoxia, uncontrolled pain, and fear. Haloperidol is the drug of choice.54

Key points

• Early involvement of a pain relief service is often needed.

• Breathlessness is often multifactorial and a variety of approaches may be necessary for palliation.

Industrial Injuries Disablement Benefit

Industrial injuries benefit is awarded under the terms of the Social Security Contributions and Benefits Act 1992. This Act specifies that the following criteria must be met to qualify for industrial injuries benefit:

(a)

The person must be suffering from a prescribed disease or personal injury which developed after 4 July 1948.

(b)

(i) The claimant must have been an employee, i.e. not self-employed; and (ii) he should have worked in a scheduled occupation—that is, one where there was exposure to asbestos.

 Mesothelioma is designated a prescribed disease (D3) under Schedule 1 of the Social Security (Industrial Injuries) (Prescribed Diseases) Regulations 1985. Under new regulations (The Social Security (Industrial Injuries) (Miscellaneous Amendment) Regulations 1997) the schedule of prescribed occupations has been broadened to includeany occupation in which there has been “exposure to asbestos, asbestos dust or any admixture of asbestos at a level above that commonly found in the environment at large”.

This alteration means that anyone, whatever their occupation, who is diagnosed as having mesothelioma should have a detailed occupational history taken to see whether they have ever been exposed to asbestos, even for a short period, while carrying out their work. Their work may not have involved the handling of asbestos but may have been carried out in its presence.

Procedure for claiming benefit—A claim for Industrial Injuries Disablement Benefit is made by contacting the local Benefits Agency (local telephone directory or enquiry line 0800 882200). Leaflets SD5 “Ill or Disabled Because of Work” and NI12 “If you have an Industrial Disease” may be useful. It may be helpful to patients if a supply of these forms is obtained by chest clinics. Occasionally the claimant may need some help with completing the form and this can usually be obtained from the trade union, a social worker, a relative, the general practitioner, or the doctor advising the patient to make a claim.

War Pensions Scheme—Mesothelioma caused by asbestos exposure during service in the defence forces is compensated under the War Pensions Scheme. A claim should be registered with the War Pensions Agency (helpline 01253 8588858).

Benefits payable for incapacity and disability— Patients should obtain Benefits Agency leaflet SD1 “Sick or Disabled” (available in tape, Braille and a number of languages) and the following benefits are available:

(a)

Income replacement: (i) For those with adequate National Insurance contributions: Statutory Sick Pay (SSP) or Occupational Sick Pay from the employer for the first 6 months of illness or Short Term Lower Rate Incapacity Benefit where there is no employer to pay; in either case then Incapacity Benefit.

(ii)

For those with inadequate National Insurance contributions: Income Support for those whose income and capital is below specified limits and/or Severe Disablement Allowance after 28 weeks of incapacity for work.

(b)

Help with excess costs of disability:

(i)

For those with an assessment for Industrial Injuries Disablement Benefit of 100%, Constant Attendance Allowance (CAA) is available.

(ii)

For those not entitled to CAA, Disability Living Allowance (DLA) is available for those whose disability began before their 65th birthday and Attendance Allowance (AA) is available for those whose disability began on or after their 65th birthday.

Common Law Compensation

We suggest that clinicians seeing any case of asbestos related lung disease should advise the patient to consider seeking legal advice promptly. This will reduce the risk of subsequent claims for mesothelioma being statute barred (see below).

Damages may be recovered from an employer by suing the employer for negligence. The claimant must show that, on the balance of probabilities, his injuries and/or disability are due to his occupational exposure to asbestos, this exposure being attributable to the employer's negligence in maintaining the standards required by the common law. It may also be possible to sue the employer for a breach of his/her statutory duty to comply with specific health and safety regulations. Claims can also be made against a former employer's insurer, even if the employer is no longer in business.

Proceedings for these claims must be started within 3 years of the claimant's “date of knowledge” of any injury caused by asbestos exposure, including pleural plaques, which is different from 3 years after first being exposed to the risk. A claim brought after the expiry of 3 years is generally “statute barred” and is unable to be pursued in the courts. The date of knowledge is based on when the claimant first becomes aware (i) that the injury is significant; (ii) that the injury is attributable in whole or in part to the act/omission alleged to constitute the negligence or breach of duty; and (iii) of the identity of the defendant. The date of knowledge is not always going to be the first time a potential claimant is examined by a doctor. The claimant is expected to make reasonable inquiries himself as to the cause of his disability. The courts also have the discretion to extend the 3 year time limit but this remains only a discretion and the claimant will have to persuade the court to do so.