Breathlessness and weight loss in a 58-year-old man

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Problem 34 Breathlessness and weight loss in a 58-year-old man

Hubertus P.A. Jersmann

A 58-year-old accountant presents with 3 months of progressive breathlessness on exertion. He has no associated chest pain or wheeze but has had a smoker’s cough for years. He has lost 5 kg over the last 3 months but says that his appetite is normal. He complains of a ‘frog in his throat’ for the last 6 weeks, which he has put down to his smoking. His breathlessness has progressed to such an extent that he has been unable to work for the last few days and was only able to walk up the one flight of stairs to your clinic with difficulty. Apart from feeling generally lethargic, he reports no other symptoms.
He has a history of hypertension for which he takes ramipril. He smokes 20–30 cigarettes a day; his alcohol consumption is regular and has never exceeded an average of 20 g a day. He is in his second marriage and has two young children aged 9 and 14.

Q.1

What other information would you like from the history? What will you look for on examination?

On examination he is slightly plethoric and has signs of recent weight loss. He has a hoarse voice. His pulse is 80 bpm, his blood pressure is 155/95 mmHg and he is afebrile. He is tachypnoeic with a respiratory rate of 25 breaths per minute and appears to be centrally cyanosed. Cardiovascular examination is normal.

His trachea is in the midline and the chest is not obviously over-inflated. The percussion note is dull in the lower zone of the right chest. The breath sounds are reduced in this area and there is an associated increased vocal resonance. There is a widespread polyphonic wheeze throughout both lung fields. There are no other clinical signs on full examination.

Q.2

What are the possible diagnoses?

The man looks unwell and dyspnoeic and you decide to admit him to hospital for further management.

Q.3

What investigations will you order?

You receive the results shown in Investigation 34.1.

Investigation 34.1 Summary of results

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Q.4

What do these results tell you?

A chest X-ray is shown in Figure 34.1.

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Figure 34.1

Q.5

What does the chest X-ray show? How are you going to manage this patient?

Q.6

What further investigations should now be considered?

A further radiological investigation is performed. Two representative films are shown (Figures 34.2 and 34.3).

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Figure 34.2

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Figure 34.3

Q.7

What do these CT scans show?

A bronchoscopy is performed. The right vocal cord is adducted and does not move. A tumour is found obstructing the right main bronchus. The right middle lobe and the right lower lobe bronchi could not be entered. Biopsy of this tumour reveals a poorly differentiated adenocarcinoma.

Q.8

What treatment options are open to you at this stage? What will you tell the patient?

Five days after admission you are called to see him on the ward. He has become confused over the past 24 hours. A decision has been made not to proceed with chemotherapy or radiotherapy. The nurses report that he has not opened his bowels for 4 days.

On examination he is mildly confused with a GCS of 13. Despite his humidified oxygen he has dry mucous membranes and has decreased skin turgor. He is afebrile. The examination is otherwise unchanged since admission.

Q.9

What are the possible causes for his confusion? What would you like to do?

Some serum biochemistry had been performed earlier that day. The results are shown in Investigation 34.2.

Investigation 34.2 Summary of results

image

Q.10

What is the problem and what would you like to do now?

He received rehydration and a single dose of pamidronate. This was associated with clearing of his confusion and after discussion with his wife he elected to be transferred to inpatient hospice care. His hypercalcaemia rapidly recurred and he died peacefully surrounded by his family 3 weeks after his initial presentation.

Answers

A.1 Find out the following:

• The nature and severity of his shortness of breath. After how much exertion does he get short of breath? How rapidly did this develop? Does it occur at rest, during the night or when he lies flat? How many pillows does he sleep with?
• The nature of his cough. Has it changed? Is it productive and if so is it purulent? Has he coughed up any blood?
• Has he had any other symptoms to explain his weight loss? Has he had fevers or night sweats?
• Enquire further about his smoking history. How long has he smoked? Express the smoking history in ‘pack-years’ where 20 cigarettes a day for 1 year is 1 pack-year. Thus a comparative figure can be derived for overall consumption of tobacco measured in terms of the total number of pack-years.
• Are there any other risk factors for lung disease such as industrial exposure to asbestos in the past? Does he keep birds? Has he had any recent foreign travel? Is there a family history of pulmonary disease? Has he had previous cancers or is there a family history of cancers such as colon cancer? Has he had any previous blood clots?

On examination you should look for signs or evidence of the following:

• Respiratory distress, e.g. tachypnoea, cyanosis and the use of accessory respiratory muscles.
• Chronic lung disease, wheeze and hyperinflated lungs.
• Pneumonia, e.g. fever and lobar consolidation.
• Malignant lung disease, e.g. clubbing, pleural effusions, lymphadenopathy, hepatomegaly and ascites.
• Anaemia.
• Cardiac disease, e.g. cardiomegaly, raised jugular venous pressure, atrial fibrillation or peripheral oedema.

In addition you should measure oxygen saturation via pulse oximetry and perform spirometry.

A.2 His smoking history makes it likely that he is suffering from a degree of chronic obstructive pulmonary disease (COPD). Patients with severe COPD often suffer from weight loss and become cachectic but this is usually in the context of a reduced intake due to severe dyspnoea at rest.

He may be suffering from an infective process but the length of the history makes it unlikely that this is bacterial in nature. The presence of weight loss raises the possibility of tuberculosis and you should ask about risk factors.

Other intrinsic lung diseases such as fibrosing alveolitis are possibilities but the presence of weight loss, the problems with his voice and his smoking history all make this a less likely diagnosis.

Cardiac failure leading to weight loss (cardiac cachexia) is unlikely in the absence of paroxysmal nocturnal dyspnoea or orthopnoea.

Anaemia may explain his shortness of breath, lethargy and, depending on the cause, his weight loss.

By far the most likely diagnosis in this man, who is a heavy smoker, has experienced recent weight loss and shortness of breath and has localizing pulmonary signs, is lung cancer. The hoarseness of his voice is an extremely sinister symptom and may be due to malignant infiltration of the recurrent laryngeal nerve by a hilar tumour causing a vocal cord paralysis.

A.3 Perform these investigations:

• Complete blood picture: look for evidence of anaemia or infection (leucocytosis).
• Urea, electrolytes, creatinine, calcium, liver function tests.
• Chest X-ray.
• Arterial blood gases, looking for evidence of respiratory failure.
• Sputum collection for microscopy, culture, AFB and cytology.

A.4 He is likely to have polycythaemia secondary to his long history of smoking (you would like to see his haematocrit). He has a neutrophilia which raises the possibility of an underlying infective process but this may be a nonspecific finding in any inflammatory condition. His mild thrombocytosis also supports an inflammatory process.

He has a moderately severe hyponatraemia in the context of otherwise normal renal function and in the absence of any culpable drugs. This may well be the syndrome of inappropriate ADH (SIADH) seen in many pulmonary conditions and particularly in bronchogenic adenocarcinoma. Paired serum and urine osmolalities would help to confirm this. If SIADH is present you would expect to see inappropriately concentrated urine in the presence of dilute or normal serum.

He has a raised alkaline phosphatase which may be due to liver infiltration with metastatic carcinoma (expect to see a raised GGT in addition) or due to bony involvement. The mild hypoalbuminaemia is likely to be due to his chronic illness or, if there is liver involvement, synthetic liver dysfunction. It is highly unlikely to be due to nutritional deficiency despite his recent weight loss.

He has a mild hypercalcaemia. This may be due to production of a parathormone-like peptide by a lung adenocarcinoma. Alternatively, in conjunction with the raised ALP, bony involvement is a distinct possibility.

His blood gases show that he has type 2 respiratory failure with both hypoxia and hypercapnia. The normal pH implies that this is a relatively well compensated and, therefore, a chronic process.

A.5 The “chest X-ray” is reported as follows:

There is partial collapse and consolidation in the right middle lobe. There is also an abnormal convexity to the posterior aspect of the right hilum and the appearances are suspicious of a right hilar mass resulting in the collapse and consolidation of the right middle lobe. There is some increased opacity in the subcarinal region and lymphadenopathy in this region is suspected. The left lung and pleural reflection appear clear.

He is in respiratory failure. You should administer oxygen by Venturi mask to correct his hypoxia. Repeat his blood gas analysis in 30 minutes to ensure he does not decompensate due to carbon dioxide retention.

In view of the X-ray appearances and the leucocytosis, the administration of antibiotics would be appropriate. An intravenous penicillin and oral macrolide would be suitable until the results of microbiological culture are known.

Remember that although the history and investigations so far point towards an advanced lung cancer, this has not yet been proven. He should be managed in a respiratory unit and intensive care support requested should he deteriorate.

If he is suffering from SIADH then fluid restriction may be appropriate. However, in the presence of hypercalcaemia, fluid restriction may lead to profound dehydration. It would be wise not to restrict his fluid intake and, if he is unable to drink, to provide the patient with maintenance intravenous fluids using isotonic saline. Daily checks on his electrolytes and calcium will help you adapt his fluid and electrolyte regimens accordingly.

A.6 Once he is stabilized he will need:

• A CT scan of his chest to further define the hilar and mediastinal abnormalities.
• A fibreoptic bronchoscopy to look for a bronchial tumour and to obtain histological samples for diagnosis. The lymph nodes should be sampled via transbronchial needle aspiration (TBNA) or with endobronchial ultrasound (EBUS) guidance. These techniques are safe and not only enhance the chance of securing tissue diagnosis in one procedure but often also deliver important staging information at the same time as initial diagnosis. This saves time and unnecessary mediastinoscopies.
• If the bronchoscopy is inconclusive, a slightly more risky CT-guided fine needle biopsy may be necessary. (This particular patient would be too unwell for a mediastinoscopy.)

A.7 The “CT scans” are reported as follows:

There is a large soft tissue mass in the subcarinal region of the mediastinum consistent with lymphadenopathy. This is associated with soft tissue enlargement with surrounding of the right pulmonary artery by the soft tissue mass lesion. The appearances are consistent with bronchogenic carcinoma with involvement of the mediastinum. There is distal consolidation and partial collapse of the lung within the right middle and lower lobes. The left lung shows no evidence of any sinister parenchymal lesion. There is a right pleural effusion. The appearances are consistent with a bronchogenic carcinoma involving the right hilum.

A.8 This man is highly likely to have advanced (stage IV) lung cancer with respiratory failure, hypercalcaemia, SIADH and probable liver and/or bone involvement. Any treatments that you offer him at this stage are palliative.

The presence of mediastinal involvement, respiratory failure and probable metastatic disease rule out the possibility of surgery. Surgery remains the only real option for cure in non-small cell lung carcinoma but is only effective in stage I and II disease and in patients with good lung function and performance status. Surgery is now being performed in some centres for more advanced disease (IIIA), often in conjunction with either chemotherapy or radiotherapy.

Radiotherapy alone has resulted in ‘cure’ in a small number of reported cases with lower-stage disease but inoperable on general grounds, but it is largely used for palliation.

Chemotherapy for non-small cell tumours has also produced disappointing results. Aggressive regimens involving the taxanes and platinum-based drugs have been shown to be useful as palliation in selected patients. This man’s respiratory failure and metabolic upset make him poorly suited for any such treatment.

His outlook is poor. When breaking bad news it is important to be in possession of all the facts and prepared for questions. If possible, the most senior member of your team should be present when bad news is broken. It is important that you speak to him in a quiet, private environment in the presence, if he wishes, of friends and family. Allow good time, as he is likely to have many questions. Be honest and frank but avoid medical jargon and do not remove all hope. It is important to avoid phrases such as ‘there is nothing we can do’ as, although there is no chance of a cure, there are many interventions which can relieve symptoms and improve his quality of life in his final days. The main fear of many patients told they have a terminal disease is that they will die in pain or without dignity. With modern palliative care, this should not be the case. He has a young family and the devastating effects of his diagnosis on them must not be forgotten. The involvement of palliative care professionals at an early stage is important.

A.9 There are several possible causes for confusion in this man:

• Hyponatraemia: his sodium was low on presentation; this may have worsened.
• Hypercalcaemia: he may have worsening hypercalcaemia.
• Respiratory failure: he may have become more hypoxic or/and have increasing hypercapnia.
• Sepsis: keep in mind common causes of confusion. Is there any sign of sepsis?
• Cerebral metastases: he has widespread disease. The presence of cerebral metastases with attendant cerebral oedema needs to be considered.
• Alcohol withdrawal: the patient stated when first seen that he ‘drinks regularly’, and you must remember that most patients will underestimate their alcohol consumption.
• You should check his electrolytes, calcium and blood gases. If it looks likely that there are no metabolic causes for his symptoms then you could consider a CT scan to identify metastases.

It is important to identify easily treatable causes of his deterioration if such treatment will result in improved symptomatology and quality of life. However, in the setting of palliative care, investigations and interventions should only be carried out if they are likely to lead to such improvements. If not then treatments should aim for symptom control and comfort. Always involve his relatives, particularly his next of kin. Palliative care professionals can also be very helpful.

A.10 He has hypercalcaemia with associated dehydration and renal failure. Fluid restriction instituted at first for his hyponatraemia may have exacerbated this situation.

Hypercalcaemia of malignancy often occurs in the presence of bone metastases but may also be mediated by the production of a parathormone-like peptide from malignant cells; a so-called paraneoplastic syndrome. It often produces a dramatic clinical picture and should be treated in all but the most terminal of cases.

Treatment involves initial rehydration with isotonic saline. This man is likely to need 3–4 litres over the next 24 hours. Bear in mind that this may exacerbate his hyponatraemia.

A bisphosphonate such as pamidronate can be added to palliate the hypercalcaemia if this were thought appropriate. These drugs work by inhibiting the mobilization of calcium from the skeleton.

Revision Points

Lung Cancer

Epidemiology

• The most common form of cancer in men and now, in most developed countries, in women.
• Causes more deaths in the USA than breast, prostate and bowel cancer combined.
• On the increase, especially in women due to a dramatic rise in female smoking. Also increasing in developing societies.
• Almost all forms of lung cancer are a direct result of tobacco smoking, making it one the West’s biggest preventable health problems.

Presentation

• Always suspect in smokers with unexplained deterioration in health and/or weight loss.
• May have no pulmonary symptoms. The presence of shortness of breath, pain and haemoptysis often imply advanced disease. Hoarseness of voice if recurrent laryngeal nerve involvement.
• Sometimes picked up incidentally in medical assessments.

Types

Two major groups

• Small cell lung cancer

– accounts for 10–15% of total number of cases
– tumours tend to be rapidly progressive
– responds to high-dose chemotherapy regimens ± radiotherapy but have a very high recurrence rate following treatment. Metastatic disease is common.

• Non-small cell lung cancer (NSCLC).

Three subtypes:

– adenocarcinoma
– squamous cell carcinoma
– large cell carcinoma.

Diagnosis

New bronchoscopic techniques, in particular transbronchial needle aspiration with endobronchial ultrasound (EBUS), often allow not only tissue diagnosis but also hilar and mediastinal staging with a single procedure. This often saves valuable time and resources by avoiding readmission and mediastinoscopy. The state-of-the-art method for staging for distal disease is positron emission tomography (PET) using radioactive 18F-fluorodeoxyglucose. An additional CT brain is required because of the inability of PET to detect brain metastases due to the high glucose utilization of the cerebrum.

Treatment

Treatment depends on stage.

• Surgical resection ± adjuvant therapy are options for early-stage tumours (IA–IIB).
• For later-stage tumours, treatment is largely palliative. New high-dose chemotherapeutic regimens may improve quality and prolong length of life.
• Current research involves a variety of approaches, e.g. novel chemotherapy agents, photodynamic therapy and vaccine therapy.
• Palliative care measures and psychological support especially important in patients with advanced disease.

Prognosis

• Prognosis of NSCLC depends on stage at presentation. IA (small volume local disease with no nodes or metastases) has a 5-year survival of up to 70%. Only 1% of patients with stage IV disease (presence of metastases) will be alive at 5 years.
• Overall, prevention by not smoking is the most important approach for this disease. Advising patients and their relatives not to smoke should be the responsibility of all healthcare professionals.

Issues to Consider

• What are the factors that influence the incidence of smoking in various countries? Are there any effective measures that might be used to treat nicotine addiction and thus reduce the incidence of cigarette smoking?
• What other paraneoplastic phenomena occur in advanced lung cancer? How can they best be treated?
• What palliative care options exist for the treatment of respiratory distress in this situation?

Further Information

, http://en.wikipedia.org/wiki/Non-small_cell_lung_carcinoma_staging. Summarizes the latest revision to the NSCLC staging system (January 2009)

, www.cancerresearchuk.org. Website of the Cancer Research Campaign in the UK with lots of information and links for lung and other tumours

, www.lungcancer.org. Excellent website with links and information for patients and healthcare professionals alike

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