Most colon cancers arise from conventional adenomatous polyps (conventional adenoma-to-carcinoma sequence), while some colon cancers appear to arise from the recently recognized serrated adenomatous polyp (serrated adenoma-to-carcinoma theory). Because conventional adenomas and serrated adenomas are usually asymptomatic, mass screening of asymptomatic patients has become the cornerstone for detecting and eliminating these precursor lesions to reduce the risk of colon cancer. Colonoscopy has become the primary screening test because of its high sensitivity and specificity, and the ability to perform polypectomy. Other screening tests include guaiac tests or fecal immunochemical tests (FIT) for fecal occult blood, and flexible sigmoidoscopy. A minimal colonoscopic withdrawal time of 6 minutes is important to maximize polyp detection at colonoscopy. Chromoendoscopy is an experimental technique used to highlight abnormal colonic areas to identify neoplastic tissue and to potentially determine the histology of colonic polyps at colonoscopy based on superficial pit anatomy.
Colorectal cancer afflicts about 150,000 Americans annually, about 50,000 of whom die from the disease . Established screening and surveillance colonoscopy regimens, as recommended by American and international medical societies , largely can prevent this mortality by detecting and removing premalignant colonic polyps and by detecting colon cancer at an early and curable stage . Yet, nearly half of eligible United States patients have not undergone any form of screening for colon cancer . Patients refuse screening because of embarrassment, fear of potential complications, reluctance to undergo invasive tests when asymptomatic, denial, and potential economic costs. Patients will become progressively harder to recruit for colon cancer screening tests as the more compliant patients have already undergone screening. The residual unscreened patients tend to be poor or ethnic minorities who have limited access to health care .
Although mostly because of patient factors, noncompliance also stems from physician factors. For example, most United States primary care physicians do not offer any form of colon cancer screening to eligible indigent patients . This problem is not confined to America, but occurs throughout the world . In a recent survey, only about one-quarter of 700 Italian general practitioners properly referred their patients for colon cancer screening, with both frequent over-referral and under-referral . Under-referral results in thousands of preventable deaths in Italy per year . Over-referral, such as referral for colonoscopy of average-risk patients less than 5 years after a negative screening colonoscopy, results in excessive costs without demonstrable benefits. To save patient lives and minimize costs, physicians in the United States and throughout the world must educate themselves to appropriately advocate screening colonoscopy, to answer patient misgivings about undergoing colonoscopy , and to follow practice guidelines . Patient education by educated physicians moreover, should help eliminate patient barriers to mass screening .
A review of the natural history of premalignant colonic polyps and the benefits of colorectal cancer screening is important and timely. This field is changing rapidly because of breakthroughs in the pathophysiology of colon cancer and in the technology for colon cancer screening and therapy. This article reviews colon cancer with a focus on the natural history, detection, and therapy of colonic polyps, the precursor lesions of colon cancer, to help the clinician and the gastroenterologist appropriately screen and treat patients to reduce colon cancer mortality.
Pathophysiology
Histopathogenesis
Colon cancer arises from mucosal colonic polyps. Polyp histology is critical for determining malignant potential. The two common histologic types are hyperplastic and adenomatous. Histologically, hyperplastic polyps contain an increased number of glandular cells with decreased cytoplasmic mucus, but lack nuclear hyperchromatism, stratification, or atypia . Adenomatous nuclei are usually hyperchromatic, enlarged, cigar-shaped, and crowded together in a palisade pattern. Adenomas are classified as tubular or villous. Histologically, tubular adenomas are composed of branched tubules, whereas villous adenomas contain digitiform villi arranged in a frond. Tubulovillous adenomas contain both elements.
Most colon cancers arise from conventional adenomas (conventional adenoma-to-carcinoma sequence) as demonstrated by epidemiologic, clinical, pathologic, and molecular genetic findings . Although many hyperplastic polyps have little or no association with colon cancer , some hyperplastic polyps are associated with colon cancer . Hyperplastic polyps appear to be linked to colon cancer by means of the recently reclassified (sessile) serrated adenoma (serrated adenoma-to-carcinoma theory), which previously was characterized as a hyperplastic polyp . The pathophysiology of colon cancer, including its pathogenesis from conventional adenomas and serrated adenomas, is considered in detail in accompanying articles by Cappell, and East and Jass.
Epidemiology of Conventional Adenomas
Adenomas are somewhat more common in men than in women. Their incidence increases with patient age. They are rare in patients younger than 40 years old, except in patients who have genetic syndromes. Classically, about 15% to 25% of asymptomatic patients age 50 or older have adenomas detected at screening colonoscopy. A higher rate is, however, found at autopsy. For example, in a prospective necropsy study of 365 patients, 121 (33%) had colonic polyps . The incidence rose to 50% in patients more than 70 years old.
Clinical Presentation of Conventional Adenomas
Symptoms and signs are common when colon cancer is advanced and most likely incurable. They are less common when colon cancer is early and highly curable, and they are relatively uncommon with adenomatous polyps. This phenomenon renders adenomas or early colon cancer difficult to detect by clinical presentation and provides the rationale for mass screening of the general population before symptoms or signs occur to detect colon cancer at an early stage and to detect and remove premalignant colonic polyps to prevent their malignant transformation.
In a review of 800 patients who had colorectal polyps, about two-thirds were asymptomatic, and many of the others had symptoms that were likely coincidental and not caused by the polyps . For example, rectal bleeding in a patient who has a small colonic polyp is more likely caused by other conditions, especially hemorrhoids . Polyps more than 1 cm in diameter are more likely to produce symptoms, and polyps less than 0.5 cm rarely produce symptoms . The most common symptoms attributable to polyps are rectal bleeding, abdominal pain, and change in bowel habits. A large polyp rarely forms the leading edge of a colonic intussusception.
Physical findings and laboratory abnormalities are uncommon with adenomatous polyps. A rectal polyp may be palpable by digital rectal examination. Much less than half of adenomas cause fecal occult blood . Large adenomas are much more likely than small adenomas to cause fecal occult blood . A benign colonic polyp rarely causes iron deficiency anemia; iron deficiency anemia is much more common with a malignant polyp because of greater chronic blood loss.
Small adenomas are believed to grow very slowly, unless they undergo malignant transformation. Perhaps, only 1 in 20 adenomas progresses to colon cancer. Advanced adenomas with significant dysplasia, diameter greater than 1 cm, or villous features, are more likely to progress to colon cancer.
Epidemiology of Conventional Adenomas
Adenomas are somewhat more common in men than in women. Their incidence increases with patient age. They are rare in patients younger than 40 years old, except in patients who have genetic syndromes. Classically, about 15% to 25% of asymptomatic patients age 50 or older have adenomas detected at screening colonoscopy. A higher rate is, however, found at autopsy. For example, in a prospective necropsy study of 365 patients, 121 (33%) had colonic polyps . The incidence rose to 50% in patients more than 70 years old.
Clinical Presentation of Conventional Adenomas
Symptoms and signs are common when colon cancer is advanced and most likely incurable. They are less common when colon cancer is early and highly curable, and they are relatively uncommon with adenomatous polyps. This phenomenon renders adenomas or early colon cancer difficult to detect by clinical presentation and provides the rationale for mass screening of the general population before symptoms or signs occur to detect colon cancer at an early stage and to detect and remove premalignant colonic polyps to prevent their malignant transformation.
In a review of 800 patients who had colorectal polyps, about two-thirds were asymptomatic, and many of the others had symptoms that were likely coincidental and not caused by the polyps . For example, rectal bleeding in a patient who has a small colonic polyp is more likely caused by other conditions, especially hemorrhoids . Polyps more than 1 cm in diameter are more likely to produce symptoms, and polyps less than 0.5 cm rarely produce symptoms . The most common symptoms attributable to polyps are rectal bleeding, abdominal pain, and change in bowel habits. A large polyp rarely forms the leading edge of a colonic intussusception.
Physical findings and laboratory abnormalities are uncommon with adenomatous polyps. A rectal polyp may be palpable by digital rectal examination. Much less than half of adenomas cause fecal occult blood . Large adenomas are much more likely than small adenomas to cause fecal occult blood . A benign colonic polyp rarely causes iron deficiency anemia; iron deficiency anemia is much more common with a malignant polyp because of greater chronic blood loss.
Small adenomas are believed to grow very slowly, unless they undergo malignant transformation. Perhaps, only 1 in 20 adenomas progresses to colon cancer. Advanced adenomas with significant dysplasia, diameter greater than 1 cm, or villous features, are more likely to progress to colon cancer.
Clinical Presentation of Serrated Adenomas
Serrated adenomas are relatively uncommon. In a pioneering pathologic study of 18,000 colonic polyps published in 1990, only 0.6% were serrated adenomas . In another study, about 18% of removed polyps originally classified as hyperplastic were reclassified as serrated adenomas using the revised histologic criteria . Serrated adenomas frequently are right-sided and sessile. They may be flat and therefore difficult to identify at conventional colonoscopy using white light. The clinical presentation of serrated adenomas is largely unstudied and unknown. It is likely that most serrated adenomas are asymptomatic and do not produce fecal occult blood. For example, in a prospective study, only 10 of 276 hyperplastic polyps identified by colonoscopy and characterized pathologically after colonoscopic polypectomy had produced guaiac positive stool . This study, and other studies, however, did not stratify and differentiate serrated adenomas from ordinary hyperplastic polyps. Large clinical studies are needed with sufficient follow-up to ascertain the clinical presentation and natural history of serrated adenomas.
Screening and Diagnostic Tests for Colonic Lesions
Screening of Average-risk Patients
Fecal occult blood: guaiac testing
Fecal occult blood testing (FOBT) was the traditional mainstay of screening for colon cancer and colonic polyps. It is tested most commonly by a colorimetric assay of a guaiac-based reaction catalyzed by the pseudoperoxidase present in blood. It is based on increased microscopic rectal bleeding in patients who have colon cancer compared with patients without colonic disease. Patients who have colon cancer, however, have a range of microscopic bleeding with considerable overlap with normal controls . This overlap results in moderate test specificity. Specificity is increased by avoiding ingestion of broccoli, cauliflower, or red meats and by discontinuing aspirin therapy for 3 days before the test. Whether iron causes a falsely positive FOBT is controversial, but withholding iron therapy for several days before the test is prudent because of possible test interference. Even in ideal research studies, only 5% to 10% of patients who have fecal occult blood have colon cancer, and another 20% to 30% have colonic adenomatous polyps . Although true- positive tests can lead to early colon cancer detection and cure, false-positive tests result in a large number of expensive and unnecessary colonoscopies.
FOBT is, moreover, only moderately sensitive. Sensitivity is improved by:
Performing stool tests on three different occasions, because colon cancer typically bleeds intermittently
Avoiding ascorbic acid for several days before the test, because ascorbic acid inhibits the guaiac reaction
Performing the test on fresh stool
Nevertheless, the sensitivity of FOBT for colon cancer using ideal techniques under the ideal circumstances of a research study is only about 85% . The sensitivity for detecting adenomas is much less than 50%, because colonic adenomas bleed less frequently than colon cancer . The sensitivity is particularly low for adenomas that are small or are located in the proximal colon.
Despite these flaws, FOBT was a traditional screening test because of test safety, simplicity, noninvasiveness, and low cost. Mandel and colleagues demonstrated that annual screening by FOBT, with referral for colonoscopy if the test was positive, reduced mortality from colon cancer in a study of 46,551 patients. Study patients who had annual screening by FOBT had a 5.88 per 1000 cumulative mortality from colon cancer compared with an 8.83 per 1000 cumulative mortality in control subjects not undergoing such screening. Unexplained fecal occult blood mandates further evaluation of the colon to exclude colon cancer or polyps in any patient more than 40 years old .
Fecal occult blood: immunochemical testing
The Japanese have developed and extensively tested the fecal immunochemical test (FIT), in which antibodies are used to detect the globin protein within human hemoglobin in stool. These tests are more specific than guaiac tests, because they:
Do not react with food that contains peroxidase activity, such as broccoli
Do not react with food that contains nonhuman hemoglobin, such as (cow) steak
Do not register a positive result with upper gastrointestinal bleeding, because the globin protein in blood is degraded during intestinal transit by intestinal enzymes
Patient participation in FIT is simple because of the absence of dietary restrictions and the ease of procuring a sample by merely swishing a brush within the toilet bowl after defection.
FIT is significantly more sensitive than guaiac testing . For example, in a colonoscopic study of 2512 patients, the FIT detected 87.5% of cancers versus 54.2% for guaiac testing, and detected 42.6% of advanced adenomas versus 23.0% for guaiac testing . FIT has been used to screen more than six million people for colon cancer in Japan . Screening with FIT, followed by colonoscopy if the screening test is positive, substantially reduces colon cancer mortality. In a study of 42,150 Japanese patients followed for 13 years, the mortality from colon cancer decreased by nearly 70% in patients screened by FIT compared with unscreened controls . Other studies have confirmed this finding . FIT, however, requires processing by a centralized laboratory and costs substantially more than guaiac tests.
Screening colonoscopy is superceding FIT . Although the 42.6% sensitivity of FIT for advanced adenomas is superior to that for guaiac testing, this rate is much lower than the 90% or higher sensitivity of screening colonoscopy. FIT may, however, play a subsidiary role for targeted screening of certain populations at mildly increased risk of colon cancer, such as asymptomatic African Americans aged 45 to 50 years.
Barium enema
Barium enema was a historically important alternative to colonoscopy, but its role is being superceded by virtual colonoscopy (CT colonography). It is only about 80% sensitive at detecting colon cancer and is much less sensitive at detecting colonic polyps . In a study of 580 patients undergoing both barium enema and colonoscopy, barium enema detected only 32% of colonic polyps less than 6 mm in diameter, and only about 50% of larger (at least 6 mm) colonic polyps . Barium enema also does not permit histologic characterization of an identified lesion because of an inability to perform biopsies, and it does not permit therapeutic removal of polyps. Thus detection of a moderate or large polyp at barium enema necessitates follow-up colonoscopy for polypectomy.
Flexible sigmoidoscopy
Flexible sigmoidoscopy every 3 to 5 years with annual FOBT has been recommended for screening . Sigmoidoscopy decreases mortality from rectosigmoid colon cancer. Selby and colleagues reported a 59% reduction of rectosigmoid cancer in patients undergoing one or more rigid sigmoidoscopies in the prior decade compared with unscreened controls matched for age and sex. In a retrospective case-controlled study by Newcomb and colleagues , 66 patients who died from colon cancer had a much lower frequency of having undergone screening flexible sigmoidoscopy than age- and sex-matched controls without colon cancer during a 13-year study period (10% versus 30% rate, P <.05).
Flexible sigmoidoscopy is, however, playing an increasingly limited role in screening. It is relatively insensitive at colon cancer and colon polyp detection, because the proximal half of the colon, where up to one-half of lesions are located, is not visualized endoscopically . Even a screening strategy that calls for colonoscopy when a patient has a distal colonic polyp detected by sigmoidoscopy misses most proximal lesions, because proximal lesions usually do not have synchronous distal lesions . Flexible sigmoidoscopy results in negligible prevention of right-sided colon cancer. For example, in the study by Newcomb and colleagues cited previously, the observed reduction in colon cancer mortality was limited to left-sided cancers. Sigmoidoscopy is also an inadequate test for patients who have distal colon cancer, because 3% to 5% of these patients have a synchronous proximal cancer .
Diagnostic colonoscopy
Colonoscopy is recommended for screening of patients more than 50 years old at average risk for colon cancer or colonic polyps . Colonoscopy is highly sensitive at detecting large (greater than 1 cm) colonic polyps, with a miss rate of only 6%, and it is moderately sensitive at detecting diminutive (less than 0.6 cm) polyps, with a miss rate of about 27% as reported in a study published in 1997 . Recent data, however, suggest that the miss rate may be higher than previously appreciated. Colon cancers rarely are missed at colonoscopy, because they tend to be larger than adenomatous polyps. Colonoscopy is a highly specific test. At colonoscopy, polyps are removed and masses biopsied for a pathologic diagnosis.
The adenoma-to-carcinoma sequence strongly suggests that screening colonoscopy with polypectomy of adenomas should prevent colon cancer substantially. This is supported strongly by clinical trials. For example, in the National Polyp Study, 699 patients underwent surveillance colonoscopy at 1, 3, and every 2 subsequent years after detecting at least one adenomatous polyp at an index colonoscopy . The 699 patients had a 76% to 90% decline in the incidence of colon cancer compared with historical reference groups. All the cancers were detected early. More recent studies have suggested a somewhat smaller reduction in colon cancer mortality.
Colonoscopy, however, has disadvantages as a screening test, because it is resource intensive, expensive, somewhat invasive, and uncomfortable, and entails a small, but significant, risk of serious complications. It requires a team, including a technician, nurse, and highly trained colonoscopist. Colonic preparation and dietary restrictions are necessary for 24 hours before the test. Diagnostic colonoscopy has about a 0.4% complication rate . The most common major complications are gastrointestinal (GI) bleeding and colonic perforation.
Current Screening Guidelines
The relative benefits of the various screening tests are summarized in Table 1 . Because of the importance of high sensitivity and relative specificity of a screening test to prevent cancer, colonoscopy has emerged as the screening test of choice . Ironically, colonoscopy is both the screening test for polyp detection, the diagnostic test (gold standard) for polyp detection, and the therapeutic technique for polyp removal. Because of the several disadvantages of colonoscopy as a screening test (see Table 1 ), alternative screening tests have been approved by multiple professional organizations ( Table 2 ) . Professional organizations generally have not endorsed virtual colonoscopy (CT colonography) for colon cancer screening because of highly variable and conflicting data about test sensitivity .
| Beneficial screening characteristics | Fecal guaiac test | Fecal immunochemical Test | Flexible sigmoidoscopy | Barium enema | Colonoscopy | Virtual colonoscopy |
|---|---|---|---|---|---|---|
| Low cost | ++++ | + ++ | ++ | ++ | + | + |
| Convenient | ++++ | ++ | ++ | + | + | + |
| Easily accessible | ++++ | ++ + a | +++ | ++ | ++ | + |
| Noninvasive | ++++ | ++++ | ++ | ++ | + | ++ |
| Safe | ++++ | ++++ | ++ | ++ | + | ++ b |
| High sensitivity | + | ++ | ++ | ++ | ++++ | +++ |
| Relatively specific | + | ++ | +++ | ++ | ++++ | ++ |
| Beneficial diagnostic or therapeutic characteristics | ||||||
| Does not require a second (diagnostic) test if positive | + | + | ++ | + | ++++ | + |
| Therapeutic | + | + | ++ | + | ++++ | + |
a Accessibility varies among countries depending upon commercial availability. The fecal immunochemical test is used routinely and is widely available in Japan, but is used rarely and is not readily available in America.
b Serious concerns have been raised about radiation risks to asymptomatic patients from mass screening of the general population.
| Recommended tests or procedures | Frequency |
|---|---|
| 1. Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) a | Annually |
| Annually | |
| 2. Flexible sigmoidoscopy a | Every five years |
| 3. Fecal occult blood test (FOBT) and flexible sigmoidoscopy | Annual FOBT and flexible sigmoidoscopy every five years |
| 4. Double contrast barium enema | Every five years |
| 5. Colonoscopy | Every 10 years |
a The American Cancer Society recommends “Flexible sigmoidoscopy together with FOBT is preferred compared with FOBT or flexible sigmoidoscopy alone.” The author feels strongly that only FOBT (option 1) or only flexible sigmoidoscopy (option 2) should be eliminated as acceptable screening tests because of insufficient sensitivity of these tests, and that these tests only should be used in combination (option 3). For example, FOBT may fail to detect up to 87% of colonic adenomas .
Surveillance of High-risk Patients and Diagnostic Testing of Patients Who Have Strong Clinical Indications
Patients at average risk for colonic adenomatous polyps or cancer undergo screening colonoscopy every 10 years, or alternative screening tests at periodic intervals. Patients who are members of high-risk groups undergo periodic surveillance more frequently, with colonoscopy as the recommended test. The age of beginning surveillance and the frequency of surveillance depend upon the age of onset of the increased cancer risk and the quantitative risk of cancer . This topic is reviewed in detail in accompanying articles by Konda and Duffy for nonsyndromic colon cancer, and by Desai and Barkel for syndromic colon cancer. Aside from periodic screening or surveillance, patients require colonoscopy to exclude colon cancer, adenomatous polyps, or other colonic diseases for specific indications, as listed in Boxes 1 and 2 .
Personal history
Prior colonic adenomatous polyps
Prior colon cancer
Peutz-Jeghers syndrome
Hereditary nonpolyposis colon cancer (Lynch syndrome)
Juvenile polyposis syndrome
Chronic ulcerative colitis
Chronic Crohn’s colitis
Family history
Colon cancer
Colonic adenomatous polyps
Hereditary nonpolyposis colon cancer (Lynch syndrome)
Familial adenomatous polyposis
Fecal occult blood
Iron deficiency anemia
Hematochezia
Melena with a nondiagnostic esophagogastroduodenoscopy (EGD)
Streptococcus bovis bacteremia
Finding of colonic polyps at sigmoidoscopy
Adenocarcinoma metastatic to the liver with an unknown primary
Change in bowel habits in the elderly
Follow-up after colonoscopic removal of a large sessile proximal colonic polyp
Abnormal radiologic study (barium enema, virtual colonoscopy) suggestive of colon cancer
Colonic stricture
Dye injection to label a malignant polyp for subsequent surgical removal
Intraoperative colonoscopy to localize a lesion for surgical removal
Improving Polyp Detection at Colonoscopy: Conventional Techniques
The primary benefit of screening colonoscopy in preventing colon cancer lies in the removal of premalignant polyps, which is predicated upon polyp identification. Identification of premalignant or potentially malignant polyps has become more complicated recently with the realization that serrated adenomas, which are often flat and inconspicuous, have a risk of malignant transformation equivalent to, or potentially greater than, that of conventional adenomas , and the realization that conventional colonoscopy frequently misses colonic polyps. In a study of 26 colonoscopists, the miss rates of adenomas ranged from 17% to 28%, as determined by a second tandem colonoscopy performed immediately after the index colonoscopy . Moreover, the detection rate of adenomas varies greatly among experienced colonoscopists. For example, the rate of adenoma detection varied tenfold among 12 experienced colonoscopists in private practice in Rockford, Illinois , and varied threefold among academic colonoscopists at the Mayo Clinic . Although colonoscopy tends to be quite sensitive at detecting large polyps, which are more likely to be malignant or advanced adenomas, colonoscopy occasionally can miss even these polyps . Furthermore, small polyps, which are missed frequently, occasionally exhibit advanced histology or even harbor frank cancer. For example, in a study of 1933 small (5 to 10 mm) or diminutive (1 to 4 mm) adenomatous polyps detected in 3291 consecutive colonoscopies, 10.1% of small polyps exhibited cancer or advanced adenomatous histology, and 1.7% of diminutive polyps exhibited these histologic findings . In another study of 5047 consecutive small or diminutive polyps, 15.6% of small polyps and 4.4% of diminutive polyps exhibited advanced histology . Even small, flat serrated adenomas have a malignant potential .
Several colonoscopic techniques are recommended to increase the detection of colonic polyps. First, a properly prepared colon is essential for colonoscopy. Polyps can and are missed in areas containing stool. An unclean colon also renders colonoscopic intubation and colonoscopic polypectomy technically more difficult and potentially more dangerous. A dirty colon usually is caused by failure of the patient to follow the proper directions for colonic preparation. When scheduling a colonoscopy, the colonoscopist should review the colonic preparation with the patient and stress the importance of the patient taking the whole colonic preparation and drinking only clear liquids the day before the procedure. The polyethylene glycol (PEG) electrolyte solution requires drinking 4 L of liquid in about 4 hours. Some patients fail to drink the entire amount. Administration of a PEG electrolyte solution on the day of colonoscopy or in divided doses, with one half the night before and one half on the day of the procedure, may improve the quality of the colonic preparation . Fleet’s phospho-soda is a useful alternative preparation, but the patient must drink plenty of fluids when taking this preparation. It should be used with extreme caution in patients who have even mild renal insufficiency. This preparation can precipitate renal failure or electrolyte disturbances .
Second, adequate sedation is a prerequisite for colonoscopy. Highly anxious patients, patients who failed a prior attempt at colonoscopy because of pain or anxiety, and uncooperative patients may require the assistance of an anesthesiologist for adequate sedation. Propofol provides deeper sedation and a faster recovery time than conventional sedation with benzodiazepines and opiates, highly attractive attributes for outpatient screening colonoscopy . In many endoscopy units, propofol is administered exclusively by anesthesiologists because of concerns about its toxicity, mostly hypoventilation, caused by a low therapeutic index. This practice is controversial, however. Participation of an anesthesiologist at colonoscopy substantially increases the procedural costs. A very large colonoscopic study has shown gastroenterologists and nurses can administer propofol safely .
Third, confirmation of cecal intubation is essential at colonoscopy. Mischaracterization of an incomplete colonoscopy as complete because of mistaken identification of the cecum can result in missing clinically significant right-sided colonic lesions, including cancers. Missed polyps that are not removed at an index incomplete screening colonoscopy may continue to grow without colonoscopic intervention for 10 years until the next recommended screening colonoscopy. This phenomenon may be a common reason for early interval cancers after an index colonoscopy purportedly devoid of polyps . For example, in a retrospective analysis of 35,975 colonoscopies in Manitoba, Canada, the rate of colon cancer was reduced markedly for the first 5 years after an index colonoscopy, but an unusually large proportion of the early cancers detected during these 5 years were right-sided, presumably because of right-sided lesions missed at the index colonoscopy .
Deep colonoscopic intubation, as indicated by the centimeter ruler markings on the colonoscope shaft, does not indicate cecal intubation reliably, because the colonoscope could be looped within the colon. Several cecal landmarks reliably confirm cecal intubation. The appendix is visualized as a slit-like, semilunar, or ovoid opening near the caput of the cecum on the (medial) colonic wall closest to the middle of the ileocecal valve. The ileocecal valve is a characteristic round, smooth, soft, homogeneous mound lying on a prominent fold on the medial colonic wall just distal to the caput of the cecum. Occasionally, air or stool is seen exiting by means of the ileocecal valve into the colon. The ileocecal valve may contain a central dimple above its opening, and may appear yellowish due to fatty infiltration. The valve opening is not seen directly, because it is perpendicular to the colon, but may be intubated blindly. Such intubation also confirms ileocecal valve identification. Documentation of cecal landmarks by a videophotograph during colonoscopy may help avoid malpractice litigation concerning missed colonic lesions because of incomplete colonoscopy .
Other colonic landmarks suggest but do not prove cecal intubation. A combination of landmarks may be convincing. The cecum is a wide saccular organ that ends blindly. Other colonic regions, particularly the hepatic flexure, may be confused with the cecum, because the lumen may appear to end blindly at a sharp colonic turn. The merger of the three teniae coli at the cecal base produces a characteristic appearance resembling a crow’s foot or the “Mercedes Benz” car symbol. Transillumination with the colonoscopic light source during cecal intubation may demonstrate light visible in the deep right lower quadrant of the abdomen. External manual compression in the same abdominal region may reveal discrete one-for-one indentation of the colonic lumen in the cecum. Colonoscopic passage through the hepatic flexure usually is indicated by visualization of a purplish-blue macular patch on one side of the colonic wall at an acute colonic turn due to the adjacent liver. A similar finding occasionally can be seen at the splenic flexure caused by the adjacent spleen.
Fourth, if a screening colonoscopy is incomplete, another colonic examination is indicated. If it was incomplete because of poor colonic preparation, the colonoscopy should be repeated after a more vigorous colonic preparation. Repeating the colonoscopy on the next day is advantageous, because the patient can be prepared further to supplement the prior partial, but inadequate, preparation. If the colonoscopy was incomplete because the patient was uncooperative or experienced too much pain, it should be repeated with an anesthesiologist in attendance. If it was incomplete because of technical difficulty, such as diverticular disease or excessive colonic looping, virtual colonoscopy should be considered instead of colonoscopy. The previous recommendations pertain when the ileocecal valve was not visualized at the initial colonoscopy. In this situation, the colonoscopist does not know how much of the colon was not intubated and not visualized. If the colonoscopy was complete except for visualization of the last few centimeters beyond the ileocecal valve—whether because of stool in the caput of the cecum, spasm of the caput, or excessive looping—and the colonoscopy was otherwise free of polyps, the situation should be explained to the patient. The patient may in this situation elect to forgo the rigors of another colonoscopy because of the small likelihood of missing a polyp in the cecum.
Several colonoscopic maneuvers aid in colonoscopic intubation beyond the ileocecal valve into the cecum, including:
Colonic decompression by aspiration of air
Manual external compression of the abdomen by the endoscopic assistant to prevent colonic looping during colonic intubation
Colonic aspiration to hold the colonoscope against the cecal wall while withdrawing the colonoscope a few centimeters
Jiggling the colonoscope back and forth over a short distance to reduce colonic loops
Turning the patient
Partial withdrawal of the colonoscope shaft to reduce colonic loops before attempting cecal intubation
In a variable stiffness colonoscope, the colonoscope should be set on maximal stiffness to minimize colonic looping during cecal intubation.
Fifth, a withdrawal time of at least 6 min is recommended to ensure adequate colonic examination and to maximize the detection of adenomas . In an initial study of 10,159 diagnostic colonoscopies among 31 colonoscopists, the detection rate of polyps was correlated directly with the mean time of colonoscopy . In a subsequent study, these data were refined by analyzing only colonoscopic withdrawal time to more accurately measure the time spent searching for colonic polyps. Colonoscopists generally search for polyps during colonoscopic withdrawal as they focus on finding the colonic lumen for safe colonoscopic advancement during colonic intubation. The author’s practice is to examine for colonic polyps during colonoscopic withdrawal by holding the colonoscope in the center of the colonic lumen and circling around toward the periphery as necessary. In a prospective study of 7882 colonoscopies among 12 colonoscopists, colonoscopists who had a mean withdrawal time greater than 6 min had, compared with colonoscopists who had a shorter withdrawal time, a significantly higher detection rate of neoplastic polyps (28.3% versus 11.8%, P <.001), and of advanced neoplasia (6.4% versus 2.6%, P <.005; ).
Sixth, colonoscopic maneuvers can improve polyp detection. Colonic polyps may be missed around sharp turns, especially the hepatic and sigmoid flexures; at areas of colonic spasm, especially in the sigmoid colon or with severe diverticulosis; and behind large folds. During withdrawal, the colonoscope may fly rapidly around a turn so that one side or that entire area is not visualized. If this occurs, the colon should be reintubated beyond the poorly visualized area. The missed area around the turn should be inspected during the second intubation and the second withdrawal. This maneuver may be repeated until this area is inspected satisfactorily. The colonoscope also can rapidly fly around colonic areas occasionally because of reduction of a loop during extubation. This phenomenon is best prevented by avoiding colonic loops.
Colonic spasm is avoided by not irritating the colon by meticulous colonoscopic technique that avoids excessive colonic air insufflation, colonic loops, and traumatic intubation. Trauma is avoided by identifying proximal lumen before colonoscope advancement, with minimal, judicious use of the slide-by technique. Colonic spasm is usually more apparent during colonic intubation than extubation. Colonic spasm is often troublesome in areas of severe colonic diverticulosis, particularly in the sigmoid colon where the lumen is relatively narrow even without diverticulosis. Colonic spasm may be addressed by gentle air insufflation to distend the spastic area. Paradoxically, withdrawal of air from other colonic areas not suffering from spasm may decrease colonic irritability and decrease the spasm in the area being examined. Instillation of warm water may be more effective than insufflation of air to address colonic spasm, because water is less irritating to the colon than air . The author suspects that the conscious sensation of pain during colonoscopy may increase colonic spasm, and that adequate sedation and analgesia may reduce colonic spasm. Although intravenous glucagon can help reverse colonic spasm, this agent should be used rarely and sparingly. If colonic visualization is limited in a small colonic segment because of the presence of liquid stool, the area can be irrigated and aspirated to remove the stool and to improve visibility. This approach is not feasible if most of the colon is contaminated heavily with stool, particularly if the stool is solid.
Areas behind a fold not visualized with the colonoscope in the orthograde (unretroflexed) position can be viewed by retroflexing the colonoscope. A colonoscope with variable shaft stiffness should be set on minimal shaft stiffness during colonic retroflexion. Retroflexion can be performed safely by an experienced colonoscopist in the ascending colon, where the colonic lumen is sufficiently wide to permit this maneuver. This maneuver:
Should not be attempted by inexperienced colonoscopists
Should be avoided in areas where the colon is narrow, such as the sigmoid
Should be avoided in areas of diverticulosis
Should be avoided in areas where the colon is weakened by disease
The author is aware of two cases of colonic perforation due to colonoscopic retroflexion, one performed in an area of ischemic colitis, where the colonic wall integrity was weakened by the colonic ischemia, and one performed in an area of colonic diverticulosis, in which a diverticulum was intubated inadvertently during colonoscopic retroflexion.
The Third Eye Retroscope (Avantis Medical Systems, Sunnyvale, California) is an auxiliary viewing lens that is passed through the instrument channel and positioned several centimeters beyond the tip of a standard colonoscope to provide a retrograde view behind colonic folds. The Third Eye Retroscope permitted identification of significantly more simulated colonic polyps, placed behind a fold, than a standard colonoscope (81% versus 12%, P <.0001) in a commercially available anatomic model of the colon . This device has not been tested in people and is currently experimental. Conventional colonoscopes with a 140° angle of view are being replaced with new-generation colonoscopes with a 170° angle of view. These wide-angle colonoscopes may render colonic intubation more efficient, as measured by a shorter intubation time, because of better visualization of colonic lumen around sharp turns, but they have not resulted in a greater detection rate of colonic polyps by visualizing polyps behind folds . A small area not visualized behind a single large fold usually can be visualized by pressing a closed biopsy forceps against the fold to efface it. This technique is useful to visualize a polyp behind a fold for forceps biopsy or snare polypectomy, but it is time-consuming and impractical to apply to the entire colon or even a large colonic segment.
Improving Colonic Polyp Detection at Colonoscopy: Advanced Techniques
New technologies can enhance the detection rate of colonic polyps, particularly chromoendoscopy and narrow band imaging. In chromoendoscopy a vital dye, either methylene blue or indigo carmine, is sprayed on the colon to highlight areas of abnormal mucosa before the area of the colon is examined. This technique requires insertion of a special catheter through the instrument channel to completely spray and uniformly cover colonic mucosa. In a colonoscopic study of 259 patients randomly assigned to chromoendoscopy versus standard colonoscopy, chromoendoscopy was associated with a trend toward greater detection of adenomas, which was statistically significant only for diminutive (less than 5 mm) adenomas (89 versus 37 P =.026; ). In another colonoscopic study, 260 patients were randomized to receive either panchromoendoscopy, performed throughout the colon, versus targeted chromoendoscopy, performed only at the site of potential lesions . Panchromoendoscopy detected significantly more adenomas than targeted chromoendoscopy (66% versus 33%, P <.05), including detection of significantly more diminutive (less than 5 mm wide) adenomas. Flat adenomas are important because of a potentially significant risk of high-grade dysplasia. They are difficult to detect and often missed at conventional colonoscopy. These lesions are identified better by high magnification colonoscopy with either chromoendoscopy or narrow-band imaging .
Although chromoendoscopy increases the detection of small polyps and flat adenomas, the clinical significance of this improved detection is uncertain. Chromoendoscopy is not indicated for routine screening colonoscopy in average-risk patients, because it greatly prolongs procedure time, leading to significantly greater costs . A recent study suggests that an expert colonoscopist may detect as many colonic polyps using ordinary white light, with a new-generation high-definition colonoscope, as when using expensive, advanced technology, such as narrow band imaging. In this colonoscopic study of 434 patients, the colonoscopist detected 1 or more adenomas in 67% of patients with white light versus 65% of patients with narrow band imaging ( P =.61; ). This study suggests that advanced, expensive colonoscopic technologies may be unnecessary, and may be replaced by introduction of the new-generation high-definition colonoscopes and by further education of colonoscopists to recognize subtle colonoscopic features of small or inconspicuous adenomas. Methylene blue use for chromoendoscopy recently has been associated with DNA damage to colonocytes .
The enhanced detection rate of advanced technologies, such as chromoendoscopy, however, may be beneficial for high-risk patients, such as patients who have the Lynch syndrome . It also may permit targeted biopsies of suspicious areas in patients who have ulcerative colitis, as opposed to the standard clinical practice of random nontargeted biopsies .
Finally, even under ideal circumstances and even with excellent colonoscopic technique, significant colonic lesions are missed. In one colonoscopic study of 5055 colonoscopies, 17 (5.9%) of 286 cancers were missed by an initial colonoscopy . Missed lesions at colonoscopy are a potential source of medical malpractice litigation . It is recommended that the colonoscopist inform the patient of this potential complication of colonoscopy when obtaining informed consent for the procedure. Also, if a patient presents with symptoms or signs highly suggestive of colon cancer after a recent negative colonoscopy, the colonoscopist should consider repeating the colonoscopy .
Related posts:
Syndromic Colon Cancer: Lynch Syndrome and Familial Adenomatous Polyposis
Prevention of Colorectal Cancer: Diet, Chemoprevention, and Lifestyle
Implementation of Colon Cancer Screening: Techniques, Costs, and Barriers
Surveillance of Patients at Increased Risk of Colon Cancer: Inflammatory Bowel Disease and Other Conditions
Surgical Therapy for Colorectal Adenocarcinoma
Colonoscopic Polypectomy
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