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Case Study 2: Neoplasia
Kevin worked for 10 years at a uranium mine, excavating uranium for a nearby nuclear power
plant. Now, 25 years later, he has small cell lung cancer. Kevin is anorexic and has lost a
considerable amount of weight. His muscles are wasting, and he is weak. He tries to move
around the house throughout the day but tires easily. It has been difficult for him to access care,
and the treatment for his cancer is just starting.
1.
With the ongoing exposure to the ionizing radiation, DNA damage occurred. Outline the three
stages of carcinogenesis that occurred after his exposure to radiation.
The three stages of carcinogenesis are initiation, promotion, and progression. Initiation involves
the exposure of cells to appropriate doses of a carcinogenic agent (uranium in this case) that
makes them susceptible to malignant transformation. With Kevin, uranium produced irreversible
changes in the genome of previously normal cells (Porth, p. 173). Promotion involves the
induction of unregulated accelerated growth in already initiated cells by various chemicals and
growth factors. Promotion is reversible if the promoter substance is removed, but Kevin had 10
years of repeated exposure to a single carcinogenic agent, uranium, and even after 25 years of a
latency period, the cells in his body have been irreversibly initiated and promotion has occurred.
Progression is the process whereby tumor cells acquire malignant phenotypic changes that
promote invasiveness, metastatic competence, autonomous growth tendencies, and increased
karyotypic instability.
Small cell lung cancer is most common with uranium mining. Radon is the inert gas developed
from the decay of uranium A chemical carcinogen like uranium may act in concert with the
radiation to induce neoplasia. Kevin had 10 years exposure, and 25 years later, the typical time
delay, developed small cell lung cancer.
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2.
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Kevin is normally a fit and active man, and his wife often commented on how much food he
used to eat after a day at mine. Why would there be muscle wasting and weight loss now?
Explain your answer using your knowledge of the metabolic changes seen with cancer.
Fatigue, anorexia and weight loss are common symptoms of small cell lung cancer. The wasting
syndrome that Kevin is experiencing, with weight loss, wasting of body fat and muscle tissue,
weakness, and anorexia, is often referred to as the cancer-anorexia- cachexia syndrome (Porth, p.
178). It is a common manifestation of most solid tumors and is a significant cause of morbidity
and mortality in 80% of persons with advanced cancer. It becomes more pronounced with
progression of the disease, and persons with cancer cachexia respond less well to chemotherapy
and are more prone to toxic side effects.
The mechanisms of cancer cachexia appear to reside in a hypermetabolic state and altered
nutrient metabolism that are specific to the tumor-bearing state. Tumors consume large amounts
of glucose, with a resultant increase in lactate formation because the tumor oxygen levels are too
low to support the citric acid cycle and mitochondrial oxidative phosphorylation. The production
of glucose from lactate uses ATP and is very energy inefficient, contributing to the
hypermetabolic state of cachectic patients. During starvation in persons without cancer, muscle
mass is preserved, whereas in persons with cancer cachexia, amino acids are not spared and there
is depletion of lean body mass, a condition also thought to be related to decreased survival time.
3.
In some cancer patients, muscle weakness may result from the production of onconeural
antigens. Describe the effects of these antigens. What form would this process likely take in
Kevin’s situation?
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Kevin may have a paraneoplastic neurological syndrome (PNS), called Lambert-Eaton
myasthenic syndrome (LEMS), caused by an onconeural antigen. Onconeural antigens are
autoimmune processes triggered by the cancer and directed against antigens common to both the
cancer and the nervous system (Honnorat and Antoine, 2007). PNS can be defined as remote
effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or
metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer (Honnorat
and Antoine). Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in
about 1% of patients with small-cell lung cancer, the cancer that Kevin has. Lambert-Eaton
myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction
characterized by muscle weakness and autonomic dysfunction. Almost 60% of patients with
LEMS are paraneoplastic and small cell lung cancer is the main associated cancer, detected
mostly within two years after the diagnosis of LEMS. No serological marker for the
paraneoplastic etiology exists (Honnorat and Antoine).
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References
Honnorat, J. & Antoine, J., (May 2007); Paraneoplastic neurological syndromes. Orphanet
Journal of Rare Diseases: 2:22. Doi: 10.1186/1750-1172-2-22.