The n e w e ng l a n d j o u r na l of m e dic i n e

be applicable to syndromes produced by other Since publication of their article, the authors report no fur
ther potential conflict of interest.
new psychoactive substances.
Roy Gerona, Ph.D. 1. Trecki J, Gerona RR, Schwartz MD. Synthetic cannabinoid
related illnesses and deaths. N Engl J Med 2015;373:103-7.
Axel Adams, B.S. 2. Weiss LA, Abney M, Cook EH Jr, Ober C. Sex-specific ge
University of California, San Francisco netic architecture of whole blood serotonin levels. Am J Hum
San Francisco, CA Genet 2005;76:33-41.
roy.gerona@ucsf.edu 3. Schwartz MD, Trecki J, Edison LA, Steck AR, Arnold JK,
Gerona RR. A common source outbreak of severe delirium
SamuelD. Banister, Ph.D. associated with exposure to the novel synthetic cannabinoid
Stanford University ADB-PINACA. J Emerg Med 2015;48:573-80.
Stanford, CA DOI: 10.1056/NEJMc1701936

Screening for Colorectal Neoplasia

To the Editor: The Clinical Practice article by
Inadomi (Jan. 12 issue)1 did not mention the
potential role of double-contrast barium enema.
Double-contrast barium enema, sometimes re
ferred to as air-contrast barium enema, involves
the study of the whole colon and rectum after air
and barium have been injected transrectally. Mul
tiple radiographs are obtained with the use of
conventional radiographic equipment. Double-
contrast barium enema can detect most cancers
and clinically significant polyps.2
When double-contrast barium enema is com
bined with flexible sigmoidoscopy, the procedure
has a sensitivity similar to that of colonoscopy
for colorectal cancer screening, although the
detection rate of small polyps is lower.3 Flexible
sigmoidoscopy with double-contrast barium
enema should remain an option for colorectal
cancer screening in patients who are at average
risk for colorectal cancer, particularly in third-
world countries where colonoscopy or computed
tomographic colonography is rarely available for
the general population. It is better than doing
nothing.
Jacobo Dib, Jr., M.D.
Hospital de Lidice
Caracas, Venezuela
dib.j@hotmail.com DNA test (FIT combined with a stool DNA test,
No potential conflict of interest relevant to this letter was re
ported.
1. Inadomi JM. Screening for colorectal neoplasia. N Engl J
Med 2017;376:149-56.
2. Levin B, Lieberman DA, McFarland B, et al. Screening and
surveillance for the early detection of colorectal cancer and ad
enomatous polyps, 2008: a joint guideline from the American
Cancer Society, the US Multi-Society Task Force on Colorectal
Cancer, and the American College of Radiology. CA Cancer J Clin
2008;58:130-60.
3. Leung WC, Foo DC, Chan TT, et al. Alternatives to colonos
copy for population-wide colorectal cancer screening. Hong Kong
Med J 2016;22:70-7.
DOI: 10.1056/NEJMc1702535
To the Editor: The article by Inadomi on
colorectal cancer screening considers a healthy,
previously unscreened, 79-year-old woman. For
persons 76 to 85 years of age, the U.S. Preventive
Services Task Force recommends individualized
screening on the basis of the patients health and
screening history. Inadomi appropriately recom
mends shared decision making; however, the mul
tiple screening options could lead to a lengthy
and complex discussion between the patient and
clinician and prompt the clinician to focus on
tests that are the most appropriate for the pa
tient, particularly ones with high sensitivity that,
if negative, could rule out cancer or advanced pre
cancerous lesions. The options of colonoscopy
and annual fecal immunochemical test (FIT) were
suggested, but an elderly person who has previ
ously avoided screening altogether is unlikely to
adhere to annual testing. The multitarget stool
or FIT-DNA) would seem to be a better option
than FIT, because in a single application it is much
more sensitive for colorectal cancer (92% with
FIT-DNA vs. 73.8% with FIT) and advanced pre
cancerous polyps (42% vs. 23.8%)1 and because
this may be the only opportunity for this patient
to benefit from screening.

1598 n engl j med 376;16nejm.org April 20, 2017

The New England Journal of Medicine

Downloaded from nejm.org on April 23, 2017. For personal use only. No other uses without permission.
Copyright 2017 Massachusetts Medical Society. All rights reserved.
 Correspondence
ThomasF. Imperiale, M.D.
Indiana University Medical Center
Indianapolis, IN
DavidF. Ransohoff, M.D.
University of North Carolina
Chapel Hill, NC
Dr. Imperiale reports funding from Exact Sciences to his uni
versity, Indiana University. No other potential conflict of inter
est relevant to this letter was reported.
1. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget
stool DNA testing for colorectal-cancer screening. N Engl J Med
2014;370:1287-97.
DOI: 10.1056/NEJMc1702535
To the Editor: The article by Inadomi did not
make clear that although screening for colorectal
neoplasia has been reported to reduce colorectal
cancer mortality, it has not been reported to re
duce overall mortality. In addition, the patient
described in the vignette is unlikely to be repre
sentative of patients seen commonly in clinical
practice. Both factors may lead to overestimates
of the benefits of screening and to possible over
screening.
Conclusions that screening results in a small
net benefit for patients 75 to 84 years of age are
based on modeling studies of estimated life-
years gained, on a presumption that preventing
disease-specific mortality would increase overall
survival.1 This is an optimistic presumption, con
sidering that in multiple large trials investigators
have not found reductions in all-cause mortality,
even with long-term follow-up.2 Furthermore, if
the patient described in the vignette has not
undergone screening, it probably reflects her
personal values about the balance between the
benefits and harms of screening. Physicians
should discuss with patients, such as the one in
the vignette, that screening is unlikely to lengthen
ones life and has important risks. On average,
the potential benefit a patient may derive from
screening is from a change in the cause of death
rather than in the time of death.
Aasma Shaukat, M.D., M.P.H.
KyleP. Lehenbauer, M.D.
Minneapolis Veterans Affairs Health Care System
Minneapolis, MN
shaukat@umn.edu
No potential conflict of interest relevant to this letter was re
ported.
1. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screen
n engl j med 376;16nejm.org April 20, 2017
The New England Journal of Medicine
Downloaded from nejm.org on April 23, 2017. For personal use only. No other uses without permission.
Copyright 2017 Massachusetts Medical Society. All rights reserved.
ing for colorectal cancer: US Preventive Services Task Force rec
ommendation statement. JAMA 2016;315:2564-75.
2. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortal
ity after screening for colorectal cancer. N Engl J Med 2013;369:
1106-14.
DOI: 10.1056/NEJMc1702535
The author replies: I appreciate the interna
tional perspective provided by Dib regarding the
role of double-contrast barium enema for colorec
tal neoplasia screening. Double-contrast barium
enema at 5-year intervals was recommended as a
strategy for colorectal cancer screening by the
American Cancer Society, the U.S. Multi-Society
Task Force on Colorectal Cancer, and the Ameri
can College of Radiology in 2008,1 but not by the
National Comprehensive Cancer Network in 20152
or the U.S. Preventive Services Task Force in
2016.3 Data from randomized trials or casecon
trol studies on the efficacy of double-contrast
barium enema in reducing mortality from colorec
tal cancer are lacking; however, in regions where
other tests may not be available but experienced
radiologists have the capacity to perform testing
with high-quality double-contrast barium enema,
it seems reasonable to use this strategy of testing
at 5-year intervals, with colonoscopy as follow-up
if polyps are detected.
Imperiale and Ransohoff refocus our attention
on adherence to screening tests. Adherence is a
key aspect to any screening strategy, and the
patient navigation program that mails screening
kits and calls patients to increase sample collec
tion and return (included in the cost of FIT-DNA)
should increase participation in screening, which
is made easier if a 3-year screening interval is
adopted. An economic analysis concluded that
annual FIT, even with the addition of an annual
$153 cost of patient navigation to improve ad
herence, is more effective and less costly than
FIT-DNA every 3 years4; however, if a person
refuses to undergo colonoscopy or FIT, FIT-DNA
is a screening option that has been approved by
the Food and Drug Administration and is reim
bursed by the Centers for Medicare and Medicaid
Services.
The insight provided by Shaukat and Lehen
bauer is sobering but true. Colorectal cancer
mortality increases with age, so any reductions
in cancer mortality are likely to affect older per
sons, who have increasing risks of death from
1599
 The n e w e ng l a n d j o u r na l
other diseases. In the study by Shaukat et al.,5 no
significant difference in all-cause mortality was
observed between the screening groups and the
usual-care group, despite reductions in cancer
mortality associated with screening with fecal
occult-blood testing annually or every other year.
However, this finding could reflect the low per
centage of participants dying of colorectal cancer
(1.8 to 2.7%, depending on the study group)
relative to the percentage of participants dying
of other malignant neoplasms (20 to 22%) or the
percentage dying of cardiovascular and cerebro
vascular events (32 to 33%). From a pragmatic
point of view, a person could decide to forgo
colorectal cancer screening altogether until a cure
is found for myocardial infarction and stroke, or a
clinician could choose to screen only persons at
low risk for death from cardiac or neurovascular
disease. In either case, this issue highlights the
need to focus on screening strategies that have
evidence to support their effectiveness at a price
that society is willing to pay.
JohnM. Inadomi, M.D.
University of Washington Schools of Medicine and Public
Health
Seattle, WA
jinadomi@uw.edu
Since publication of his article, the author reports no further
potential conflict of interest.
1. Levin B, Lieberman DA, McFarland B, et al. Screening and
surveillance for the early detection of colorectal cancer and ad
enomatous polyps, 2008: a joint guideline from the American
Cancer Society, the US Multi-Society Task Force on Colorectal
Cancer, and the American College of Radiology. Gastroenterol
ogy 2008;134:1570-95.
2. Provenzale D, Jasperson K, Ahnen DJ, et al. Colorectal can
cer screening, version 1.2015. J Natl Compr Canc Netw 2015;13:
959-68.
3. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screen
ing for colorectal cancer: US Preventive Services Task Force rec
ommendation statement. JAMA 2016;315:2564-75.
4. Ladabaum U, Mannalithara A. Comparative effectiveness and
cost effectiveness of a multitarget stool DNA test to screen for
colorectal neoplasia. Gastroenterology 2016;151(3):427-439.e6.
5. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortal
ity after screening for colorectal cancer. N Engl J Med 2013;369:
1106-14.
DOI: 10.1056/NEJMc1702535
Correspondence Copyright 2017 Massachusetts Medical Society.
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of m e dic i n e
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EUROPEAN ACADEMY OF PAEDIATRICS
The EAP 2017 Congress and MasterCourse will be held in
Ljubljana, Slovenia, Oct. 1215. Deadline for submission of
abstracts is May 5. Deadline for early registration is June 15.
Application deadline for travel grants is July 3.
Contact Paragon Group, 18 Avenue Louis-Casai, 1209 Ge
neva, Switzerland; or call (41) 22 5330 948; or fax (41) 22 5802
953; or e-mail congress@eapaediatrics.eu; or see http://2017
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8TH ADVANCES AGAINST ASPERGILLOSIS CONFERENCE
The conference will be held in Lisbon, Portugal, Feb. 13.
Contact Prof. David A. Stevens, California Institute for Med
ical Research, 2260 Clove Dr., San Jose, CA 95128; or call (408)
998-4554; or see http://www.AAA2018.org.
5TH ANNUAL MEETING OF THE INTERNATIONAL
CYTOKINE AND INTERFERON SOCIETY
The meeting, entitled Looking Beyond the Horizon of Inte
grated Cytokine Research, will be held in Kanazawa, Japan,
Oct. 29Nov. 2.
Contact the International Cytokine and Interferon Society,
297 Kinderkamack Rd., Suite 348, Oradell, NJ 07649; or call (800)
947-1960; or fax (201) 322-1818; or see http://icis2017japan.com.