Editors: Jerome Waye, Christopher Williams & Douglas Rex
3. Screening colonoscopy: rationale and performance
Colorectal cancer (CRC) is the second leading cause of cancer death in North America and Western Europe . As populations live longer due to advances in medicine and public health, rates of CRC are likely to increase. The biology
of CRC offers an opportunity for both early detection and prevention. Most cancers evolve from premalignant adenomas over
a period of many years; spread of malignancy from the colon to sites outside the colon likewise occurs over years. Screening
of asymptomatic populations has demonstrated that cancers can be detected at early, more curable stages, compared to unscreened
controls. Furthermore, studies have demonstrated that detection and removal of premalignant adenomas can prevent incident
cancers [2,3]. Therefore, if screening tests could identify patients with high-risk adenomas, many cancers could be prevented, mortality
reduced, and the burden of caring for patients with cancer diminished. If the target of screening is the advanced adenoma,
we should ask: how effectively do screening tests identify patients with advanced adenomas?
Higher risk subjects
There is consensus that colonoscopy should be the preferred screening test for individuals known to have higher than average
risk . Higher risk categories include individuals with familial hereditary syndromes (familial polyposis, hereditary nonpolyposis
colorectal cancer syndrome), chronic colitis due to ulcerative colitis or Crohns disease, and a family history of colorectal
cancer in a first degree relative. Patients with a personal history of adenoma or cancer should receive colonoscopic surveillance,
and are not considered part of a screening cohort.
Recent studies [5,6] have raised questions about whether colonoscopy should also be a preferred screening test in average-risk individuals. The
performance characteristics of several screening modalities in average-risk populations have been scrutinized by the United
States Preventive Services Task Force (USPSTF) and by expert multidisciplinary panels [4,710]. All of the expert panels strongly recommend that population screening should begin for average-risk individuals at age 50
years. They have noted that colonoscopy is more effective than other screening tests for polyp detection. Although some experts
have argued that colonoscopy itself should be the preferred screening test , others have argued that it should be one of several screening options [4,7,9].
This chapter will review the rationale for considering colonoscopy as a primary screening test in average-risk populations
and discuss implementation issues including compliance, resources, and cost.
Rationale for screening
Screening with colonoscopy should be considered in the context of other screening tests. For each test we should ask:
- What is the likelihood that the test will detect the target lesion (advanced adenoma or early cancer)? (2) Are there programmatic
issues, such as need for repeat testing, which impact effectiveness?
- What are the potential harms?
Fecal occult blood test (FOBT)
Three randomized, controlled trials have compared population screening with FOBT to no screening . Although there were differences in study methods, the findings are consistent across all of the studies. Cancers are detected
at earlier stages in screened compared to unscreened subjects, and this translates into significant mortality reduction of
1533% over time . Rehydration of FOBT slides increases sensitivity, but reduces specificity, so that many more patients will receive colonoscopy
for false positive results over time. In the Minnesota study , 38% of subjects in the FOBT arm received colonoscopy during the first 13 years of the study. One analysis has suggested
that some of the benefit of the FOBT test could be explained by random assignment to screening colonoscopy .
In the Veterans Affairs (VA) Cooperative Study , average-risk subjects (n = 2885) had both one-time rehydrated FOBT and screening colonoscopy. FOBT was positive in 50% of patients with cancer, consistent
with other studies [16,17]. However, among patients with advanced neoplasia without invasive cancer (defined as adenoma with high-grade dysplasia or
villous histology, or tubular adenoma >= 1 cm), the FOBT was positive in only 21.6%. Moreover, it is likely that if rehydration had not been used, the positive rate
would have been lower. These results suggest that one-time FOBT has serious limitations for detection of high-risk adenomas. If FOBT is to be used for screening, a program of repeat
screening must be developed. Compliance with repeat screening is poor. There is some concern that patients may be falsely
reassured after a negative test, and not return for repeat testing . If the FOBT is positive, there is consensus that patients should undergo complete colonoscopy. This represents a second
step in which compliance can break down.
These studies support the hypothesis that population screening of average-risk subjects could reduce CRC mortality. FOBT is
a poor test for detection of advanced adenomas. Although there is some evidence  that screening with FOBT can lead to reduction in cancer incidence (due to polyp detection and removal), this incidence reduction
is modest. The need for frequent repeat testing, and appropriate follow-up of positive tests with colonoscopy, represent important
There is evidence from two case control studies [18,19] that exposure to sigmoidoscopy is associated with a reduction in colon cancer mortality, in that portion of the colon examined.
In these studies, patients with death due to CRC were ascertained, and an age-matched control group without CRC was used for
comparison. Selby et al.  compared 261 patients with fatal rectosigmoid cancers (within reach of the sigmoidoscope) to 868 age and sex matched controls:
8.8% of cases had sigmoidoscopy compared to 24.2% of controls, suggesting that endoscopic sigmoid screening could reduce the
risk of fatal cancers within the range of the sigmoidoscope (odds ratio 0.41). Moreover, the benefit remained strong even
when the most recent exam was 910 years earlier. Newcomb et al.  had similar results.
Both studies did not find that sigmoidoscopy reduced the likelihood of fatal cancers of the right colon, perhaps because such
tumors would not be readily detected with sigmoidoscopy. Muller and Sonnenberg  reported another case control study in a VA population to determine the impact of either sigmoidoscopy or colonoscopy on
CRC risk. Compared to controls, patients with CRC were less likely to have had prior endoscopic exams of the colon (odds ratio
0.51 for colon cancer; 0.55 for rectal cancer). Two ongoing, randomized trials using flexible sigmoidoscopy will report findings
in the next few years [21,22].
Limitations of screening by flexible sigmoidoscopy
These case control data provide compelling evidence that screening sigmoidoscopy could substantially reduce CRC mortality,
particularly from tumors in the distal colon. An important limitation is that a large portion of the colon is not examined
at sigmoidoscopy. If most patients with advanced neoplasia in the proximal colon, had index adenomas in the distal colon,
which would lead to complete colonoscopy, then sigmoidoscopy would be a sensitive screening test.
Two screening colonoscopy studies reported the findings of complete colonoscopy, and estimated the potential findings of screening
sigmoidoscopy in average-risk subjects [5,6]. Advanced neoplasia was more likely to be found in the distal colon (55% in Indiana study; 53% in the VA study). Both studies
found that more than 50% of patients with advanced proximal neoplasia (beyond the reach of the sigmoidoscope) would not have
been identified with sigmoidoscopy, even assuming that any index adenoma would lead to colonoscopy. In addition, both studies
found that as average-risk subjects get older, they are more likely to harbour advanced proximal neoplasia, and that these
are less likely to be identified with sigmoidoscopy alone.
Sigmoidoscopy is able to detect advanced adenomas and early cancers in the area examined. The key limitation of sigmoidoscopy
is that a large portion of the colon is not examined; some patients with advanced proximal neoplasia would go undetected.
There is also concern that with increasing age, sigmoidoscopy may be less effective.
Combined flexible sigmoidoscopy and FOBT
The American Cancer Society has long recommended screening with both FOBT and FS beginning at age 50 , among other options. Intuitively, this combined approach should have a greater impact on CRC mortality than either test
alone. In one study , patients were offered sigmoidoscopy with or without FOBT. Although the patients were not randomly assigned to groups, the
groups were comparable. Follow-up was irregular and compliance with follow-up testing poor. During the 9-year follow-up, 144
cases of CRC were found, but only 28 were actually detected through screening. The major finding was that patients screened
with both FOBT and sigmoidoscopy had better long-term survival after detection of cancer compared with controls suggesting
a benefit from evaluation of positive screening tests. The overall mortality rate of the two groups was similar.
In the VA Cooperative Study , combined screening with one-time FOBT and sigmoidoscopy would have identified 76% of patients with advanced neoplasia, only
slightly better than sigmoidoscopy alone (70%). With increasing age, there was a trend for decreasing efficacy of the combined
screening approach. Modelling  has suggested that the combined approach could be more effective and less costly than other screening approaches, if tests
are performed programmatically, on a regular basis as is recommended (annual FOBT and sigmoidoscopy every 5 years). However,
the models require assumptions about compliance with initial testing and follow-up colonoscopy after positive tests, which
may not be realistic in clinical practice.
Radiographic colon imaging with barium, CT, or MRI
No large studies have evaluated colon imaging with barium in an average-risk population. The USPSTF rates barium as 'unknown' with regard to effectiveness in reducing incidence and mortality from CRC, and only 'fair' with regard to ability to detect cancer and advanced neoplasia. The National Polyp Study found that the sensitivity of barium
studies for detection of polyps larger than 1 cm was 48% .
The data on CT or MRI imaging of the colon are preliminary, and the technology is still evolving. The range of sensitivity
for large polyps is 4096%, suggesting wide variation in either skill or technique. Currently, no review panel has recommended screening with these
modalities, although they have captured the attention of the public.
The potential for genetic testing
There are other screening modalities which show promise. When specific gene mutations were identified in patients with familial
polyposis (adenomatous polyposis coli gene on chromosome 5) and hereditary nonpolyposis colorectal cancer syndrome (mismatch
repair gene mutations), there was great hope that molecular genetics would provide a simple blood test to risk-stratify otherwise
average-risk subjects. Such screening was touted to the public in the New York Times in the 1990s.
The reality of genetic testing to date has been sobering, but there has been recent progress. Several groups have identified
genetic mutations in stool samples. If tumors slough cells with genetic mutations into the bowel lumen, and if these mutations
can be identified, it may be possible to select individuals for colonoscopy based on the stool profile. This 'needle in a haystack' approach is complicated by the fact that there is no single mutation which identifies all high-risk patient.
New tests which search for several of the most common genetic alterations associated with CRC are under study . With the development of the human genome project, has come the science of proteomicsand understanding of the relationship of a gene mutation to specific protein product. If altered protein products are circulating
in the blood, it may be possible to screen patients with blood tests.
The case for screening with colonoscopy
Colonoscopy can examine the entire colon in more than 9095% of procedures, if performed by a fully trained endoscopist. Polypectomy can be performed at the same time. Given these
obvious advantages, we should ask: why not perform screening colonoscopy?
Arguments against screening with colonoscopy
General criteria for screening tests applied to the population are summarized in Fig. 1.
Colonoscopy is an invasive and expensive test. The risk of perforation, serious bleeding, and cardiopulmonary events is low
when performed by experienced endoscopists (0.30.5%), but if applied to the general population, could account for considerable morbidity . If only 56% of the adult population will develop colorectal cancer during life, most patients will not benefit from colonoscopy. Ideal
screening would target colonoscopy at the patients most likely to have advanced neoplasia or cancer, and would not employ
an expensive, invasive test to populations with a relatively low pretest probability of disease. However, the ideal simple
test has been elusive. Lacking the perfectly sensitive, and adequately specific non-invasive screening test, screening with
colonoscopy is now recommended as a screening option by all expert panels in the United States, though not in Canada, Europe,
Arguments for screening with colonoscopy
Relative to other screening tests, there is substantial evidence that colonoscopy is very accurate for detection of significant
neoplasia. In two tandem colonoscopy studies, in which patients had two colonoscopies performed. During the same session,
the miss rate for polyps greater than 1 cm was less than 10% [30,31]. Since these studies were performed by experts, it is possible that in clinical practice, more lesions are missed by less
expert endoscopists. Specificity for detection of neoplasia approaches 100%, because biopsies are usually obtained which confirm
the histologic presence of neoplasia.
Does screening colonoscopy reduce mortality?
The ability to prevent incident cancers or reduce mortality with primary screening colonoscopy has never been tested in a
clinical trial. However, there are several lines of indirect evidence which endorse the potential effectiveness of colonoscopy.
First, the FOBT trials all recommended colonoscopy as the followup test after a positive FOBT. It was colonoscopy which identified
the early cancers that led to a survival advantage in screened populations. Ransohoff and Lang  performed a posthoc analysis of the Minnesota FOBT study, in which 38% of subjects in the screened group received colonoscopy
over 13 years of study. They attributed much of the mortality reduction to high rates of colonoscopy, with only a portion
of benefit derived from performance of the FOBT. In the follow-up of the Minnesota study, the subsequent incidence of CRC
was reduced in patients who had been screeneda benefit attributed to colonoscopy with polypectomy by the authors .
The second line of evidence is extrapolated from the case-control studies of sigmoidoscopy. These studies found a significant
reduction in fatal colon cancers in that portion of the colon examined. There was no reduction in mortality from proximal
colon cancers . It is logical to assume that if more colon is examined, the benefit could be extended to as much of the colon as can be
examined. The third line of evidence comes from the National Polyp Study , in which patients underwent complete colonoscopy with polypectomy and were followed over the next 5 years. When compared
to reference populations, the incident rates of CRC were reduced by 7690% in the study subjects. Although the comparison groups differed from the study subjects, the marked reduction in expected
incidence is compelling. Finally, a case-control study in the VA population found that patients diagnosed with CRC were less
likely to have had prior colonoscopy, compared to patients without CRC . The risk reduction of 53% for colon cancer, and 39% for rectal cancer was significant. These studies provide compelling
indirect evidence that screening colonoscopy could be effective:, i.e. reduce colon cancer mortality and incidence.
Several investigators have modelled colon cancer screening, and evaluated a broad range of assumptions regarding accuracy,
compliance, and harms. The conclusion of the most recent analyses is that colon cancer incidence could be reduced by 5886%, and that CRC mortality could be reduced by 6490% .
Patient acceptance of colonoscopy screening
Patient acceptance of colonoscopy as a screening test is unknown. Colonoscopy is well-accepted when recommended for evaluation
of other positive screening tests and other gastrointestinal symptoms. In the VA Cooperative Study, nearly two-thirds of eligible
subjects who were offered colonoscopy, completed the examination. The VA population may not be generalizable, but this study
does demonstrate that good compliance can be obtained when procedures are fully explained. Acceptance of sigmoidoscopy is
estimated to be 2550% . Although acceptance of one-time FOBT may exceed 75%, compliance with repeat FOBT testing is poor. A colonoscopy screening
program may require only one or two exams in a lifetimea factor which may enhance program performance compared to other programs requiring frequent repeat testing and colonosocopic
follow-up of positive screening tests.
Potential harm from colonoscopy
The largest study to report complications of colonoscopy is the VA Cooperative Study # 380 . Serious complications, definitely attributed to colonoscopy, occurred in 0.3% of patients receiving screening colonoscopy.
The most common serious complications were serious bleeding and myocardial infarction or serious arrhythmia. Most of the serious
complications occurred in association with polypectomy. The serious complication rate of a diagnostic colonoscopy was 0.1%.
Less serious complications were commonincluding vasovagal events (5.4%), transient oxygen desaturation (4.4%), abdominal pain requiring termination of the procedure
(0.9%), and minor GI bleeding which did not require hospitalization or intervention (0.2%). Since these procedures were performed
by experts, it is not known if complications would be more common in community practice. Studies are currently underway to
measure 30 day complication rates in diverse clinical practice settings.
Resources for screening colonoscopy
The algorithm of every CRC screening program eventually leads to colonoscopy to evaluate positive tests. Public and provider
awareness of the benefits of colon screening has increased over the past few years.
A Gallup poll in 1998, indicated that nearly 90% of the public was aware of potential benefits of colon screening. In March,
2000, a prominent television personality, had a screening colonoscopy performed on her program, with the goal of diminishing
public fear of the test. An aggressive public education campaign followed the program. Despite this increased public awareness,
compliance with screening has been pooronly 3040% of the age-eligible population have had the recommended screening. However, there are indications that this may improve
over the next few years.
In 1998, the Department of Health and Human Services added colon screening with FOBT or sigmoidoscopy as a Medicare benefit
for average-risk individuals, and colonoscopy for individuals with a positive family history.
In July, 2001, the federal government extended the benefit to include colonoscopy screening for all. Health care systems such
as the Department of Veterans Affairs have initiated annual reminders to primary providers to encourage fecal occult blood
testing. Health maintenance organizations like Kaiser have enrolled all age-eligible patients into flexible sigmoidoscopy
screening programs. The National Cancer Institute and the Centers for Disease Control are dedicating resources to study strategies
which will improve compliance.
By 2000, most GI practices in the United States were confronted with increased demand for colonoscopy services. During this
same time period of the late 1990s, there was a decline in the number of GI fellowship positions in the United States. The
shifting demand for colonoscopy and the decline in newly trained endoscopists, has raised concerns about whether there are
sufficient resources to provide colonoscopy screening to the general population.
Rex and Lieberman  examined some of the assumptions which underlie the demand for services. They assumed that some patients would have comorbid
conditions which would preclude screening, some would have examinations to evaluate symptoms, and a large number would be
non-compliant. In a 'best-case' scenario, 60% of the population would be compliant with screening. Therefore, rather than a stampede to screening colonoscopy,
the demand may more closely resemble a traffic jam. If traffic patterns are understood, most traffic jams have engineering
solutions. To offer colonoscopy services with existing resources, Rex and Lieberman have several recommendations:
1. Improve the efficiency of delivering colonoscopy. Most endoscopy units are not efficient with regard to room scheduling and turnover. Endoscopists could develop open access
systems for screening of otherwise healthy individuals, and use physician extenders to obtain consent and perform initial
history and physical examinations. Support personnel could handle much of the postprocedure follow-up with patients who do
not have complex pathology.
2. Shift current colonoscopy resources: 2025% of colonoscopy procedures in the United States are performed for surveillance of prior adenomas (Lieberman, unpublished
data from the Clinical Outcomes Research Initiative [CORI] database). Based on the VA Cooperative Study , more than 70% of patients found to have adenomas at screening will have only small (< 1 cm) tubular adenomas. The Indiana colonoscopy study found that 65% of patients with neoplasia had only small tubular adenomas
. Data from the National Polyp Study  suggest that these patients may have a low risk of serious pathology at surveillance examinations. Extending the interval
for surveillance of patients with low risk lesions could shift considerable resources towards screening. Rex  estimated that screening will have a greater yield than surveillance (64 colonoscopies to detect one cancer for screening
average-risk male, vs. 317 colonoscopies to detect one cancer in postpolypectomy surveillance). If specialists in gastroenterology
spend more time performing colonoscopy, and less with flexible sigmoidoscopy, this will allow some resource shifting. This
trend is currently observed in the CORI database which shows a significant decline in sigmoidoscopy as a fraction of endoscopic
practice by GI specialists (Lieberman, unpublished data).
In summary, existing resources can be provided more efficiently and selectively to increase the capacity for screening colonoscopy
(or colonoscopy to evaluate other positive screening tests).
Costs of screening for colon cancer
Several recent analyses of colon screening costs have reached similar conclusions: screening with any of the recommended tests
is cost-effective relative to other medical interventions, and could even be cost-saving if large numbers of cancers can be
prevented [2426,3741]. The analyses show that various screening tests are quite similar in programmatic costs over liferoughly $20 000 per life-year saved. The analysis of these studies by the United States Preventive Services Task Force stated that the
current evidence is insufficient to determine the most effective or cost-effective strategy for screening .
Important assumptions in these analyses include the rate of cancer prevention, and the cost of cancer care. The cost of care
for patients with CRC in the United States probably exceeds $50 000 . This cost includes diagnostic studies, cancer surgery, chemotherapy or radiation therapy, postcancer surveillance, and end-of-life
care if detection is late. As the cost of cancer care increases, averting this cost by detection and removal of advanced adenomas
will probably result in cost-saving. In each model, colonoscopy results in the greatest potential for cancer prevention because
of the highly accurate detection and removal of adenomas.
If cost differences between the screening tests are small, why are many insurers reluctant to include colonoscopy screening
as a benefit to their clients? From the standpoint of the insurer, screening is a large investment, with potential downstream
benefit. If cancers are averted, then the cost of cancer care can be reducedbut this benefit may not be realized for many years. If individuals change insurance coverage frequently, the insurer may
not wish to make a large 'up-front' investment for a downstream benefit that may occur after the individual is no longer covered by the insurer. Among the screening
test options, colonoscopy would represent the largest up-front investment. If we approach the screening from a societal point
of view (a lifetime, single-payer system), an effective cancer prevention program would be a worthwhile investment.
Screening colonoscopy: areas of uncertainty
Colonoscopy screening has not been studied in a clinical trial. Therefore, the balance of benefits and harms remains uncertain.
Although there is little doubt that colonoscopy is beneficial in the evaluation of other positive screening tests (FOBT, sigmoidoscopy,
imaging), it is uncertain if whole population colonoscopy screening would necessarily confer the degree of benefit that would
justify the risk and resource utilization. For colonoscopy to be effective, the examinations will need to be accurate and
complete, and performed with minimal risk. The overall success rate and risk of colonoscopy in community practice is unknown,
and requires study. Future advances in colonoscopy technology may improve success rates and reduce risk.
Reducing overall mortality?
The 'holy grail' of screening is mortality reduction. Some may argue that if all-cause mortality is not reduced by colon cancer screening,
then the benefit may not offset harm. For example, let us assume that a hypothetical individual would have died from consequences
of CRC at age 80. If his colon cancer is prevented by screening, but he has a myocardial infarction and dies at age 80, is
there a benefit? Although society is spared the cost of caring for a patient with cancer, would the resources spent for screening,
have been better spent on some other form of health care? These are difficult questions to answer in clinical trials. The
modelling analyses are helpful because they account for all causes of death, and consistently show that there is a benefit
from screening. A clinical trial to resolve this issue would require 1020 years, large numbers of patients, and an enormous budget. As in other areas of medicine, we may lack precise information
for medical decision making. As new information becomes available from the VA Study follow-up and the CONCeRN trial  in women, this can be incorporated into the models, and reduce areas of uncertainty.
Timing of colonoscopy screening
The appropriate timing for screening colonoscopy is uncertain, and has implications for cost, resource utilization, and benefit.
Imperiale et al.  found that detection of serious pathology is uncommon in asymptomatic persons age 4049 years, who had screening colonoscopy. Ness et al.  found that screening colonoscopy at age 5054 years would be cost-effective, in comparison to no screening. The VA Cooperative Study data showed that the prevalence
of any advanced pathology in men, age 5059, was 5.7%, and few had cancer. Only 2% had advanced proximal neoplasia, and most of these patients would have been detected
with sigmoidoscopy . In contrast, 4.9% of patients age 6069 years, and 5.9% of patients age 7074 years had advanced proximal neoplasia. Less than one half of these patients would have been detected with sigmoidoscopy.
Therefore, a strategy of screening sigmoidoscopy during the 6th decade, followed by complete colonoscopy at age 60 years might
be a cost-effective screening strategy in men.
When to repeat screening?
Expert groups have recommended that colonoscopy screening be performed at 10-year intervals, based largely on the expected
natural history of progression of colonic neoplasia. There has not been a study evaluating a 10-year interval. Rex et al.  performed follow-up colonoscopy at 5.5 years in 154 average-risk persons who had a negative baseline colonoscopyonly one patient had an adenoma greater than 1 cm. These data suggest that a 6-years interval is quite safe. Would a negative screening colonoscopy at age 60 years identify
a low-risk person who does not need further screening? These data are crucial to decision-making about when to stop screening.
The VA Cooperative Study will follow its population for 10 years, which will provide some prognostic information in men who
have had a baseline screening colonoscopy. For now, there is some uncertainty about the appropriate screening interval.
Will screening colonoscopy be superseded?
Will screening colonoscopy be replaced by new methods of screening? This is an important question because of resource utilization.
If society determines that screening colonoscopy should be offered to everyone, significant resources will need to be dedicated
to provide endoscopy services, and train endoscopists. If colonoscopy is subsequently replaced, then there will be issues
of excess capacity, and wasted resources. The ideal screening test of the future will target colonoscopy precisely at those
patients most likely to develop cancer. If a genetic or biologic marker could successfully risk-stratify patients, colonoscopy
may only need to be offered to 1020% of the population who develop high-risk lesions. For patients with sporadic colorectal cancer, this ideal test remains
in the distant future. In the best case scenario, once a marker was identified, years of testing would likely precede widespread
acceptance. Imaging studies are not likely to provide precise targeting because they will identify patients with advanced
and nonadvanced lesions. Unless clinicians are willing to ignore small polyps found on imaging studies, these tests are not
likely to reduce the need for colonoscopy services. Therefore, for the next generation, colonoscopy will be the most accurate
test for assessing risk and enhancing prevention.
Colorectal cancer screening in average-risk populations with colonoscopy could have a significant impact on colorectal cancer
incidence and mortality . Advantages over other forms of screening include the ability to examine the entire colon, and remove pathology during the
exam. Uncertainties exist about the application of the procedure in practicewould completion rates and complication rates be similar to those reported from clinical trials? Further study is needed in
community practice. Would one or two exams during a lifetime be sufficient if they are negative? Are there sufficient resources
to provide colonoscopy to large populations? Despite these questions, there is little doubt that colonoscopy screening would
have a large impact on colorectal cancer incidence and mortality. Until selective screening can be targeted at those individuals
most likely to develop colorectal cancer, colonoscopy screening may offer the most effective means to reduce mortality.
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