Esophageal cancer is a relatively rare but deadly cancer in the
United States. Even in patients with limited locoregional disease at
the time of diagnosis, who have received aggressive multimodality
therapies as part of clinical protocols, median survival is only 17
months and 3-year survival, only 30%.[1,2] Patients with metastatic
disease have a 6-month median survival, which is not improved by the
administration of chemotherapy.
Given these statistics, the identification of risk factors and
preventive strategies for esophageal cancer represents a promising
alternative approach to a disease that has been relatively resistant
to treatment. Dr. Forastiere and colleagues have prepared an
excellent, comprehensive review of current data regarding the
potential identification of individuals at risk for developing
esophageal cancer and the few preventive measures that may be taken
in such persons.
As the authors point out, Barretts esophagus is the risk factor
that has the strongest association with esophageal adenocarcinoma,
and patients with Barretts warrant scheduled surveillance
endoscopies at recommended intervals. Identification of high-grade
dysplasia in these patients requires either frequent endoscopic
follow-up or surgery.
At the University of Michigan, we recommend surgical resection for
patients with high-grade dysplasia, and have found cancer in more
than 50% of these surgical specimens. However, surgeons at our
medical center perform a very high volume of esophageal surgeries,
and such surgeries are associated with very low operative morbidity
and mortality. As Forastiere et al point out, other centers may opt
to perform endoscopy every 3 months and initiate rigorous use of
histamine blockers and proton-pump inhibitors in patients with
Ongoing research is attempting to identify biomarkers that may help
assess cancer risk in patients with Barretts esophagus, which
will allow more frequent surveillance of patients at higher risk.
Possible biomarkers include Ki-67, p53 abnormalities, and ornithine
decarboxylase activity. These markers can be abnormal in patients
with squamous metaplasia and normal in those with completely reversed
metaplasia, as well as normal squamous epithelium.
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is another clinical problem
that predates esophageal adenocarcinoma in a large number of
patients. Of interest, the authors point out that GERD, in addition
to its relationship to the evolution of Barretts esophagus, has
been identified as an independent risk factor.
Lagergren et al reported that the association between the risk of
esophageal cancer and severe, longstanding symptoms of reflux was of
the same magnitude in patients with or without Barretts
esophagus. However, it is possible that Barretts may not have
been diagnosed in some specimens because of tumor overgrowth or
sampling error. Letters to the editor in response to that
manuscript noted that other factors may be associated with GERD, such
as long-term acid suppression secondary to therapy with histamine
blockers and proton-pump inhibitors (although this hypothesis is
currently unsubstantiated). Other letters suggested that
undiagnosed short-segment Barretts esophagus may be an
intermediary step between GERD and cancer.
The implications of the possible association between GERD and
adenocarcinoma cause one to consider whether patients with GERD
should undergo endoscopic screening, rather than limiting
surveillance to patients with Barretts esophagus. Forastiere et
al correctly point out that a rigorous evaluation of the
benefits and risks of such an approach is needed, because of the
tremendous implications for medical costs and resource utilization.
Avoidable Risk Factors
Patients can be educated to avoid or control some of the most
important risk factors for esophageal cancer identified in the
article, such as tobacco, alcohol, and obesity, and these efforts may
result in an eventual decline in the incidence of the disease.
Avoidance of excessive alcohol and tobacco can lead to a decrease in
squamous cell cancer, and a decrease in smoking and control of
obesity may diminish the incidence of adenocarcinoma. Of course, the
issue of obesity is complicated because of the possible risks and
benefits contributed by such foods as vegetables, nitrates, fiber,
and fats, as well as the increased incidence of GERD with obesity.
Education regarding these risks must start at a very early age, since
the length of time between exposure to a carcinogen and the
development of esophageal cancer itself may be quite a few years.
Although it is laudable for any patient to stop smoking or drinking
or to lose weight, the greatest impact on the disease will occur only
if young people can be convinced to avoid or limit their use of
risky foods or substances.
Forastiere and colleagues have done an extraordinary job of
summarizing a difficult topic. Because risk and prevention are harder
to quantify than the results of treatments, interpretation of the
available data regarding these issues requires judgment and experience.
The authors include a discussion of factors that confer minimal or no
risk (eg, breast cancer, prostate cancer, calcium channel blockers,
histamine-2-blockers, asbestos, silica, and dusts) to clarify some of
the more commonly asked questions about possible risk factors.
However, they appropriately concentrate their discussion on the more
pertinent issues influencing esophageal cancer: Barretts
esophagus, GERD, tobacco, alcohol, obesity, and diet. It is exciting
to learn from the research in these areas, so that we may continually
refine our ability to predict who is at risk for this deadly disease
and how we can possibly prevent its development.
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2. Urba S, Orringer M, Turrisi A, et al: A randomized trial comparing
surgery to preoperative concomitant chemoradiation plus surgery in
patients with respectable esophageal cancer: Updated analysis
(abstract). Proc Am Soc Clin Oncol 16:983, 1997.
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4. Lagergren J, Bergstrom R, Lindgren A, et al: Symptomatic
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