J R Soc Med 2001;94:567-572
© 2001 Royal Society of Medicine
The causes of dysphagia in carcinoma of the lung
D R Camidge PhD MRCP
Department of Oncology, Western General Hospital, Edinburgh EH4 2XU,
Scotland, UK
E-mail:
drcamidge{at}talk21.com
 |
SUMMARY
|
|---|
Dysphagia occurs in only a small percentage of patients with
lung cancer,
but the frequency of this cancer means that large
numbers are affected.
Non-quantitative analysis of a large Scottish
series of lung cancer cases
indicates the following eight broad
categories of dysphagia according to
underlying mechanisms:
mediastinal disease; cervical lymphadenopathy;
brainstem lesions;
gastrointestinal tract metastases; associated systemic
disorders;
second primaries; oropharyngeal and oesophageal infections;
and
radiation-induced oesophageal toxicity.
|
INTRODUCTION
|
|---|
Carcinoma of the lung affects 125 men per 100 000 and 33 women
per 100 000
of the UK
population
1. About
80% of cases are non-small-cell
and 20% small-cell
carcinomas
2.
Although respiratory symptoms
predominate, substantial numbers of patients
experience difficulty
in swallowing.
LeRoux
3 reported
that 1-2% of lung cancer patients
had dysphagia at presentation—about
the same proportion
as those with wheeze or stridor. When the full clinical
course
of the disease is considered the percentage experiencing dysphagia
rises
to
6-7%
4,5.
According to Stankey et
al.6 in 1969,
the dysphagia associated with lung cancer could be accounted for in all cases
by three possible mechanisms—first and most commonly, extrinsic
compression of the oesophagus within the mediastinum; second, compression of
the pharynx and upper oesophagus by lymph-node deposits within the neck; and
third and most infrequently, oesophageal stenosis secondary to antecedent
mediastinal radiotherapy. To these three causes Makker et
al.7, in 1995,
added secondary achalasia. The present communication aims to expand this list
further towards completeness.
In a prospective study from September 1999 to April 2001 in the Edinburgh
Cancer Centre, cases of lung cancer associated with different causes of
dysphagia were collected. In addition, both a literature search and a survey
of the department's consultants (covering a cumulative oncological experience
of 153 years) were undertaken to identify rarer causes. Six separate
condition-related causes and two treatment-related causes of dysphagia were
identified. The eight causes, with illustrative case histories, are discussed
in detail below.
|
MEDIASTINAL DISEASE
|
|---|
Case history
A man of 53 had experienced dizziness and increasing dysphagia
to solids
for the previous month. CT scans revealed multiple
cerebral metastases in
addition to massive mediastinal lymphadenopathy
almost completely obliterating
the lumen of his oesophagus (
Figure
1).
Small-cell carcinoma was diagnosed on transoesophageal biopsy.
A
nasogastric tube was inserted endoscopically to allow enteral
nutrition.
After treatment with dexamethasone his dizziness
improved and he received two
cycles of cisplatin and etoposide
chemotherapy. Within a few days of the first
cycle his swallowing
improved subjectively and the nasogastric tube was
removed,
but soon after the second cycle he became confused. Palliative
whole-brain
radiotherapy was given without apparent benefit and he died
12
days later.
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Figure 1. CT scan of chest showing massive mediastinal lymphadenopathy (secondary
to small-cell carcinoma) obliterating the oesophageal lumen
|
|
Comment
In both the prospective data collection and the consultant survey the most
commonly reported cause of lung-cancer-associated dysphagia was mediastinal
disease (92% of all cases).
Direct invasion may occur with lesions in the left main bronchus but
perioesophageal or subcarinal lymphnode deposits are more often
responsible6.
Anatomically, the subcarinal lymph nodes, limited in their potential for
lateral growth and therefore tending to expand posteriorly, are the group most
likely to intrude on the adjacent
oesophagus6. In
addition to a direct physical effect on the passage of food, both small-cell
and non-small-cell carcinomas have been reported to produce secondary
achalasia by interfering with oesophageal
motility7,8.
Whether this phenomenon reflects direct invasion of the nerve supply of the
oesophagus is unclear. Changes in oesophageal motility have been observed
after
pneumonectomy9,
suggesting that nerve damage within the mediastinum might sometimes be the
mechanism in lung cancer, but another possibility is a paraneoplastic effect
on gastrointestinal
motility10,11.
|
CERVICAL LYMPHADENOPATHY
|
|---|
Case history
A woman aged 49 reported a dragging feeling in her chest and
right-sided
cervical lymphadenopathy. Lymph-node biopsy revealed
adenocarcinoma. A 15 mm
right midzone peripheral nodule with
right hilar, right pretracheal,
subcarinal and left para-aortic
lymphadenopathy was apparent on a CT scan of
the chest. In a
clinical trial she received chemotherapy with gemcitabine and
cisplatin.
After two cycles of treatment the cervical lymphadenopathy had
progressed.
Over the next 6 weeks she reported worsening dysphagia, as the
lymph-nodes
on both sides of her neck enlarged into masses approximately
7 cm
across (
Figure 2). She became
unable to swallow solids
or liquids and was admitted for intravenous hydration
and nasogastric
feeding. Barium swallow showed extrinsic compression of the
oesophagus
at the level of the thoracic inlet but good flow throughout
the
rest of the oesophagus. Palliative radiotherapy to the neck
and mediastinum
produced little improvement in her dysphagia.
She continued to be fed
nasogastrically at home until her death
10 weeks later.
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Figure 2. Chest X-ray of patient with cervical lymphadenopathy showing extent of
bilateral soft-tissue masses in cervical region
|
|
Comment
Cervical lymph nodes are involved in 15-20% of patients with lung
cancer4.
|
BRAINSTEM LESIONS
|
|---|
Case history
A woman of 64 reported cough and intermittent hoarseness, and
a CT scan
showed a large left hilar mass encasing the left pulmonary
artery with
multiple enlarged mediastinal lymph-nodes. Small-cell
carcinoma was found on
bronchoscopic biopsy, and she had a complete
radiological response to four
cycles of cisplatin and etoposide.
The chemotherapy was followed by
consolidation radiotherapy
(40 Gray in fifteen fractions over 22 days) to the
mediastinum
with prophylactic cranial irradiation (30 Gray in ten fractions
over
12 days). 22 months later she developed progressive dysphagia
over 2
weeks. A chest X-ray revealed complete collapse of the
left lung. She received
palliative radiotherapy to the mediastinum
(20 Gray in five fractions over 5
days). Two weeks from the
end of radiotherapy she was admitted because of the
sensation
of food sticking in her throat, reduced oral intake and dehydration.
The
presumptive diagnosis was radiation oesophagitis, and she improved
over 7
days with parenteral fluid support. 12 days later, although
tolerating
semisolid food, she became unable to swallow liquids.
A barium swallow showed
no obstructive lesion but there was
considerable aspiration into the lungs. On
neurological assessment
her speech was nasal and movement was reduced on the
left side
of the soft palate. The patient was intolerant of MRI scanning
but a
contrast CT scan of the brain revealed a 1 cm metastasis
in the right side of
the brainstem (
Figure 3).
Despite intravenous
dexamethasone her level of consciousness deteriorated and
she
died 6 days later.
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Figure 3. Contrast enhanced CT scan of brain showing solitary right brainstem
metastasis from small-cell carcinoma
|
|
Comment
Damage to the nucleus ambiguus in the ventral medulla, comprising the motor
nuclei of the IXth, Xth and XIth cranial nerves, may affect both phonation and
swallowing (bulbar
palsy)12. A similar
clinical appearance (but with more prominent upper-motor-neuron signs
including an exaggerated jaw jerk) may be seen with lesions within the
internal capsule affecting the supranuclear control of this region
(pseudobulbar palsy). Either syndrome may be caused by metastatic disease.
From a large study based in South East Scotland, 50% of intracranial tumours
are secondaries and by far the most common source of these (53%) is lung
cancer13. In
necropsy series cerebral metastases can be documented in about 20% of lung
cancer cases4. In
LeRoux's series 3.3% of lung cancer patients presented with intracranial
lesions3: the
commonest manifestation is hemiplegia, but about 5% have isolated cranial
nerve palsies.
Occasionally, brainstem dysfunction can also be treatment-related. In a
phase I study of diethylnorspermine the dose-limiting toxicity of the drug was
a central nervous system syndrome characterized by ataxia, dysarthria and
dysphagia14.
|
GASTROINTESTINAL TRACT METASTASES
|
|---|
Case history
A woman aged 62 reported pain in the left side of her tongue.
On
examination the tongue was fixed: no ulceration was present
but a mass was
palpable at the base which on biopsy contained
metastatic adenocarcinoma. A CT
scan of the chest and abdomen
revealed a left lower lobe mass and multiple
liver metastases.
Histology of the lung mass was the same as that of the
tongue
lesion. She received combination chemotherapy with mitomycin
C,
ifosfamide and cisplatin. After two cycles her tongue was
less uncomfortable
but after four it was worse again and her
oral intake declined. She was
admitted for pain control and
died 6 weeks later.
Comment
Gastrointestinal metastases are found at necropsy in 2-10% of patients with
lung cancer15,
16. Lung cancer is the
commonest source of oropharyngeal
metastases17, and
in the rest of the upper gastrointestinal tract only malignant melanoma and
breast cancer are more frequent sources of
metastasis18. The
most common gastrointestinal site for lung-cancer metastasis is the
oesophagus, particularly the middle
third16. Often the
metastatic spread is clinically unsuspected. In one necropsy series only 15%
of patients with lung cancer directly involving the oesophagus had a history
of dysphagia16.
|
ASSOCIATED SYSTEMIC DISORDERS
|
|---|
Case history
A man aged 76 reported weight loss and waterbrash but nothing
abnormal was
seen on oesophagogastroscopy. Within 2 months he
developed progressive
dysphagia, periorbital oedema and weakness
and discomfort in his shoulders and
thighs. His creatine kinase
was 1205 U/L (normal range 24-161) and muscle
biopsies and electromyography
indicated dermatomyositis. A screening CT scan
of his chest
revealed a right apical mass which on biopsy proved to be
squamous
cell carcinoma. The muscle tenderness and swallowing improved
with
prednisolone. He was given palliative radiotherapy to the
mediastinum and
right apex and died 4 months later.
Comment
Dermatomyositis is associated with an underlying visceral malignancy in
15-35% of cases19.
The most common underlying malignancies are lung, breast, female genital
tract, stomach, rectum, kidney and
testis20. Symptoms
and signs characteristically include a heliotrope rash, Gottron's papules in
the hands and proximal limb myalgia and weakness. If the musculature of the
upper gastrointestinal tract is involved the consequences can include nasal
speech, regurgitation and
dysphagia20.
Clinical dysphagia is seen in 40-60% of patients with dermatomyositis or
polymyositis, although manometric abnormalities are found in
69-80%21. The
management consists of steroids with or without steroid-sparing agents such as
azathioprine; upper oesophageal dysfunction responds better than
lower21. Effective
antitumour therapy sometimes lessens the inflammation.
What other paraneoplastic conditions cause dysphagia? Systemic sclerosis,
in which the oesophagus is commonly involved, has been associated with lung
cancer though the association is not as strong as for
dermatomyositis22.
Tomkin suggests that haemoptysis in the context of systemic sclerosis should
always stimulate a search for underlying lung
malignancy22. The
Eaton—Lambert syndrome develops in 3% of patients with small-cell lung
carcinoma23.
Although this autoimmune condition is principally characterized by proximal
muscle fatiguability, dysphonia and dysphagia can
occur23.
|
SECOND PRIMARY
|
|---|
Case history
A woman of 56 had a right upper lobectomy for poorly differentiated
adenocarcinoma
of the lung. 7 years later she began to have dysphagia and
odynophagia.
Endoscopic biopsies of an obstructing mucosal lesion revealed
a
squamous carcinoma of the upper oesophagus 20-26 cm from the
incisors.
Dilatation was followed by palliative radiotherapy
to the upper oesophagus.
She remained well until her death 18
months later.
Comment
The ‘association’ of cancers may reflect nothing more than the
chance occurrence of two common conditions within an individual. Indeed, the
fact that several different histological types of lung cancer, including both
adenocarcinoma and small-cell carcinoma, have been reported in association
with squamous carcinoma of the oesophagus does support such a
‘coincidence
theory’24,25.
However, the fact that lung and oesophageal cancers have been reported
synchronously26 as
well as metachronously (as in this case) does raise the possibility that
lifestyle or genetic factors could converge within individuals to increase the
risk of malignant transformations at several sites at the same time. The most
notable example concerns patients with squamous cell carcinomas of the head
and neck, 16% of whom go on to develop second neoplasms (nearly one-third of
which will be primary lung
cancers)27.
Therefore a malignancy distinct from the original lung primary should always
be borne in mind as the possible cause of a patient's dysphagia.
|
OROPHARYNGEAL AND OESOPHAGEAL INFECTIONS
|
|---|
Case history
A man aged 56 who had smoked 30 cigarettes a day for 40 years
was referred
to the ear, nose and throat clinic with increasing
hoarseness of voice. A left
vocal cord palsy was noted in addition
to poor short-term memory and multiple
skin nodules. An excision
biopsy of one of the skin nodules revealed
neoplastic cells
with scanty mucin production consistent with metastatic
spread
from a lung primary. On CT scanning a large peripheral lung
mass was
seen abutting the pleural surface in the left upper
lobe with hilar,
aortopulmonary and subcarinal lymphadenopathy.
A CT scan of his head showed
multiple cerebral metastases. He
was started on oral dexamethasone 16 mg
daily, with some improvement
in his short-term memory, and palliative
radiotherapy to the
whole brain was initiated; after 7 days the daily dose of
dexamethasone
was reduced to 8 mg. 5 days later he began to feel nauseated,
and
after another 48 hours he developed dysphagia and started to
regurgitate
food soon after eating. A barium swallow showed
free flow of contrast but with
widespread mucosal ulceration
throughout the length of the oesophagus highly
suggestive of
oesophageal candidiasis. His swallowing improved after 7 days
of
oral fluconazole 100 mg. He was transferred to a hospice
three weeks after
admission, where he died 10 days later.
Comment
Oropharyngeal candidal infections are common in cancer
patients28. They
are usually obvious clinically but seldom cause enough oropharyngeal
discomfort to limit
intake29. Candidal
infections of the oesophagus are, in contrast, commonly associated with both
severe dysphagia and odynophagia. Although a well recognized complication of
leukaemias and lymphomas (or their treatment), oesophageal candidiasis is less
often associated with lung
cancer28. Abnormal
oesophageal motility (due to obstruction or achalasia) may be a predisposing
factor28, as may be
use of corticosteroids, antibiotics or
radiotherapy29. The
definitive diagnosis of oesophageal candida rests on oesophagoscopy and
biopsy30, but in
practice antifungal agents such as fluconazole are often used empirically. The
presence or absence of oropharyngeal candida is not predictive of oesophageal
disease30.
Viral and bacterial stomatitis and oesophagitis can occur in the lung
cancer population but they are sufficiently rare that additional risk factors,
such as underlying HIV infection, should probably be
sought28.
|
RADIATION-INDUCED OESOPHAGEAL TOXICITY
|
|---|
Case history
A man aged 55 sought advice for hoarseness and left anterior
chest pain. A
CT scan revealed a 4.7
x 4 cm left hilar mass
extending anterior to the
left main bronchus with right paratracheal
lymphadenopathy. A biopsy specimen
obtained at video-assisted
thoracoscopy showed adenocarcinoma of the lung. In
a clinical
trial he received weekly gemcitabine and concomitant radical
radiotherapy
(60 Gray in thirty fractions over 46 days) to the left lung
mass
and mediastinum. Odynophagia gradually developed two weeks
into his
radiotherapy. The discomfort progressed, limiting his
intake of solid food and
hot liquids. Soluble aspirin and Mucaine
(aluminium and magnesium hydroxide
and oxetacaine) were ineffective
but some symptomatic relief was achieved with
dihydrocodeine.
There was no response to a trial of fluconazole. His
swallowing
difficulties disappeared 6 weeks after the end of his radiotherapy.
He
remained well, without dysphagia or evidence of progression,
8 months
later.
Comment
Symptomatic acute radiation oesophagitis usually develops 2 or 3 weeks
after the beginning of treatment and may last for several months. Kaasa et
al.31 followed
the subjective reporting of dysphagia in 51 patients with inoperable
non-small-cell lung cancer treated with 42 Gray in fifteen fractions over 3
weeks. After 2 weeks of treatment 75% reported dysphagia. Three weeks after
the end of treatment this had fallen to 64% and 8 weeks later to 22%. Maguire
et al.5
similarly found that 75% of their patients receiving high-dose conformal
radiotherapy for lung cancer (64.2-85.6 Gray) experienced dysphagia. However,
the degree of dysphagia was very variable. On a well-recognized morbidity
scale (RTOG), only 11% had grade 3 acute oesophageal toxicity (requiring
parenteral fluid support). Factors that seemed to predispose to severe acute
toxicity were the existence of dysphagia before treatment and the use of
hyperfractionated treatment regimens. Chronic oesophageal toxicity was much
rarer than acute toxicity in the series of Maguire et al. (18%), with
grade 3 toxicity (requiring dilatation) developing in only 3% of patients.
Again pretreatment dysphagia was a risk factor. The incidence of severe late
toxicity seems to be increased when chemotherapy and
radiotherapy32 are
used together.
|
CONCLUSION
|
|---|
In lung cancer life expectancy is often short, and rapid palliation
of
symptoms is of paramount importance. Many different mechanisms
can underlie
dysphagia in lung cancer. By considering the eight
broad categories discussed
above the clinician should aim to
reach the correct diagnosis and start
appropriate treatment
promptly.
|
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SUMMARY
INTRODUCTION
