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BO
X 53-1:
Syndr
ardiovascular
C
M
Congestive heart failure
Peripheral vascular disease
Cardiovascular surgery
Aortic aneurysm
lmonary
Pu
P
neumonia
Mechanical ventilation
Pulmonary embolus
Chronic obstructive
oracic surgery
eurologic
N
C
Nerve root compression
Multiple sclerosis
Subarachnoid hemorrhage
Parkinson disease
Dementia
rauma
T
A
Pelvic fracture
Spinal trauma
Femoral fracture
Burns
urgery
S
A
Pelvic/gynecologic
Cardiovascular surgery
oracic surgery
Hip surgery
Craniotomy
Spinal surgery
Cesarean section
Renal transplantation
Liver transplantation
Underl
ome
yocardial infarction
pulmonary disease
erebrovascular accident
bdominal trauma
bdominal surgery
surgery
ying Conditions Associated with Ogilvie
alignancy
M
sseminated metastases
Di
Leukemia
Pelvic radiotherapy
Retroperitoneal cancer
Small cell lung cancer
nfection/inammation
I
S
epsis
Abdominal/pelvic abscess
Appendicitis
Cholecystitis
Pancreatitis
Herpes zoster
Pseudomembranous colitis
etabolic
M
E
lectrolyte abnormalities
Liver failure
Uremia
Diabetes mellitus
Alcoholism
Hypothyroidism
Lead toxicity
ugs
Dr
ntidepressants
A
Phenothiazines
Opiates
Antiparkinsonian drugs
Laxative abuse
Anticholinergics
Benzodiazepines
Vincristine
Interleukin
Amphetamines
Calcium-channel blockers
Clonidine
tetric
Obs
P
ostpartum
Cesarean section
COLON
t
omography (CT) scan can be used to exclude a mechanical obstruction. A contrast enema has a sensitivity and specicity of 80% and
100%, respectively, in the diagnosis of large bowel obstruction. Watersoluble contrast enemas may help decompress the colon through
their osmotic eect, but despite this benet, CT has largely replaced
contrast enema for the diagnosis of a large bowel obstruction. e
scanning protocol for bowel obstruction requires use of intravenous
contrast material, and the patient should be in the supine position.
e sensitivity and specicity of CT is 96% and 93%, respectively, to
diagnose obstruction. CT also can help identify bowel ischemia or a
contained perforation, as well as the condition of pericolic structures.
Typical CT ndings for acute pseudo-obstruction of the colon are
proximal colonic dilatation with an intermediate transitional zone at
or adjacent to the splenic exure.
Electrolyte disturbances are common with acute colonic pseudoobstruction; hypocalcemia, hyponatremia, and hypokalemia are
most oen found. Leukocytosis is a more variable nding but can be
a sign of associated signicant ischemia and/or necrosis.
TREA
TMENT OPTIONS
261
Initial Management
imely recognition and close monitoring are crucial in the man-
T
agement of an acute colonic pseudo-obstruction. Signs of perforation, ischemia, and peritonitis are indications for urgent surgery. In
uncomplicated cases, medical management must be started immediately. Deterioration or nonresolution despite maximal medical
therapy within 48 to 72 hours should prompt reconsideration of the
management plan.
Patients should take nothing by mouth, a nasogastric tube should
be inserted, and aggressive uid and electrolyte resuscitation should
be initiated. Administration of any oending medications should be
stopped. Serial abdominal physical examinations and radiographs
should be obtained every 12 to 24 hours to determine the response
to these measures. Wegener etal reviewed 1027 cases of Ogilvie syndrome and presented the ecacy of various therapeutic modalities.
In this review, 70% of patients responded to supportive management
alone with a complication rate of 6% and mortality approximating
10%.
Pharmacologic Management
s
uggested as a sign of impending perforation. Along with absolute
diameter, the duration of distension and the rapidity with which the
distension occurred may be predictive of perforation. Saunders etal
found higher risk of perforation if distension had been present for
more than 6 days. However, a chronically dilated colon is less likely
to perforate than bowel that becomes acutely dilated to the same
diameter.
GNOSIS
DIA
atients present with a largely distended abdomen, and the diagno-
P
sis may be suspected upon review of a plain abdominal radiograph.
e lm typically demonstrates a dilated proximal colon with small
bowel of normal caliber unless an incompetent ileocecal valve permits reux of air into the ileum. Typically the dilated colon is lled
with gas, haustral markings are maintained, and a transition from
proximal dilatation to decompressed distal colon is seen at the splenic
exure. is transition point also can be seen at the hepatic exure
or rectosigmoid junction. Making a distinction between a mechanical and functional obstruction on plain lm alone may be dicult.
In the absence of signs of peritonitis, a contrast enema or computed
H
istorically, patients who did not respond to supportive management
were oered endoscopic decompression or surgery. However, based
on the presumed pathophysiology of acute colonic pseudo-obstruction, Hutchinson and Griths used neostigmine and guanethidine
to treat this condition. Neostigmine acts as a reversible acetyl-cholinesterase inhibitor, thereby increasing acetylcholine and promoting
colonic motor activity. Ponec at al performed a prospective randomized trial proving the ecacy of intravenous neostigmine compared
with nonpharmacologic management. In this trial, 10 of 11 patients
(91%) responded to a single dose of 2 mg of neostigmine administered intravenously over 3 to 5 minutes. e placebo group receiving
supportive management alone experienced no resolution. e dose
commonly used is a 2- or 2.5-mg bolus, with success greater than
80% aer the rst dose. A repeat dose can be administered up to a
suggested limit of two to three doses. Oral administration of neostigmine is not recommended in persons with acute colonic pseudoobstruction because of its erratic absorption in the gastrointestinal
tract. Patients can experience eects of parasympathetic overactivity
such as bradycardia, hypotension, seizures, restlessness, tremor, and
bronchoconstriction. Because of the relatively common occurrence
of bradycardia, atropine should be available when administering neostigmine, and patients should be monitored.
262
ColoniC Pseudo-obstruCtion (ogil
vie
syndr
ome)
R
ecently, several studies have been performed to explore other
pharmacologic treatments for this syndrome. O’Dea etal described
success with oral pyridostigmine, a long-acting acetylcholinesterase inhibitor. In a prospective nonrandomized study, all seven
patients who had not responded to previous treatment with neostigmine and endoscopic decompression received 10 to 30 mg of
pyridostigmine two times a day, and they responded to this treatment. Adverse eects of this drug also tend to be less severe than
with neostigmine.
Interest in opioid receptor antagonists for treatment of acute
colonic pseudo-obstructions has also increased. Weinstock et al
reported a case of Ogilvie syndrome in which the patient had a successful response to methylnaltrexone aer failed treatment attempts
with neostigmine. Another opioid receptor antagonist, alvimopan,
has shown promise in postoperative ileus but has yet to be tested in
pseudo-obstruction of the colon.
Endoscopic Thera
C
olonoscopy is the quickest way to achieve decompression, but air
py
should be insuated in small amounts (or carbon dioxide should be
used as the insuating gas) to prevent further increases in pressure.
If any signs of mucosal ischemia are noted, the procedure should
be stopped and the patient should be taken urgently to the operating room. Sedation should be provided with benzodiazepines alone
because narcotics can inhibit colonic motility and the combination of
a narcotic and benzodiazepine can lower blood pressure.
Recurrences aer colonoscopic decompression are common, and
thus insertion of a decompression tube may be benecial. is procedure is typically performed under uoroscopic control using a guide
wire. e tube should be placed to gravity drainage and ushed frequently to prevent clogging. In a retrospective review of 56 patients,
Geller etal reported a success rate of 60% to 90% aer colonoscopy
and decompression tube placement and 25% when a decompression
tube was not used.
Another relatively advanced endoscopic treatment is percutaneous endoscopic colostomy (PEC) of the cecum. is procedure can
be performed using a combination of endoscopy and radiology or in
a manner similar to placement of a percutaneous endoscopic gastrostomy tube. e PEC tube is usually removed once symptoms have
resolved. is method is safe and eective if it is performed by an
experienced endoscopist. A complication rate of PEC tube placement of up to 42% has been reported, including but not limited to
wound infection, bleeding, and free perforation of the colon with
contamination.
Decompression of the colon has been shown to be eective in
approximately 80% of cases. Unfortunately, 20% of these patients
will experience recurrent pseudo-obstruction. In most of these
recurrent cases, repeat decompressive colonoscopy is successful.
Passage of the colonoscope to the cecum is more likely to succeed
in decompressing the colon. In a series of 60 patients, Jetmore etal
reported a 71% success rate with full advancement of the colonoscope to the level of the ascending colon and cecum, compared with
a 37% success rate when the colonoscope was passed to the hepatic
exure or just distally to it. e colonic perforation rate is 2% with
endoscopic decompressions.
in
dicated. The approach can be laparoscopic or open. Laparoscopy has the potential additional benefit of visualizing the entire
colon to identify missed ischemia or bowel perforation. However,
it also can be challenging with a massively dilated colon. Typically, the camera is placed below the umbilicus and a port is placed
in the right anterior axillary line at the umbilical level to enable
a grasper to move the colon. Four T-fasteners are then placed
into the cecum through the abdominal wall in a diamond configuration. The T-fasteners are used to hold the cecum against the
abdominal wall, and an 18-gauge needle is placed into the cecum.
A flexible J-tipped wire is placed into the cecum, and serial dilators are passed over the wire until a tract is created. A Foley catheter is then placed over the wire, into the cecum, and fastened into
place. This placement is confirmed radiographically. The T-fasteners are then secured to keep the cecum at the abdominal wall
and are cut 2 weeks later.
Regardless of the technique used, a cecostomy is associated with
postoperative management challenges, including tube and appliance
management, the corrosive nature of the euent, and catheter displacement. Patients also may experience wound infections and incisional hernias and have problems with the patency of the tube. e
perioperative mortality of a cecostomy can be high, but this outcome
typically reects the medical condition of the patient and is usually
not attributable to the cecostomy procedure itself.
Laparotomy is indicated for ischemia or perforation or if the
diagnosis is not clear. Typically, diagnosis of colonic ischemia is clinical and is suggested by tenderness on physical examination, leukocytosis, fever, and a rising lactic acidosis level. Plain lms can show
thumb printing, which results from mucosal edema and submucosa hemorrhage. A CT scan oen shows nonspecic colonic wall
thickening and pericolic fat stranding. Pneumatosis on a CT scan
is an ominous nding when dealing with an acute colonic pseudoobstruction. If a cecal perforation is found at laparotomy and the
cecum appears ischemic, a right hemicolectomy is performed and
either a primary anastomosis or an ileostomy with a mucus stula
is carried out.
SUMMAR
cute colonic pseudo-obstruction, also known as Ogilvie syndrome,
A
Y
continues to be a serious problem in acutely ill medical and surgical patients. It oen carries a poor prognosis if diagnosed late in its
course. High clinical suspicion and appropriate use of diagnostic
imaging will help dierentiate mechanical obstruction and pseudoobstruction. Signicant advances in pharmacologic and endoscopic
interventions for persons with Ogilvie syndrome have been achieved.
With continued research into mu-opioid antagonists, the potential
exists for a new horizon for patients refractory to other medical
management. When pharmacologic treatment fails, decompressive
colonoscopy remains the treatment of choice prior to taking a patient
to the operating room. It is hoped that with the recent advances in
conservative and endoscopic management of patients with Ogilvie syndrome, the role of emergency surgery will decrease, which
could reduce the morbidity and mortality associated with colonic
pseudo-obstruction.
Surger
S
y
urgery is rarely necessary and should be reserved for patients with
ischemia, peritonitis, or pseudo-obstruction refractory to pharmacologic or endoscopic therapy. Nonoperative management should be
oered to patients for whom peritonitis is not a clinical concern. At
times, up to 3 to 5 days can pass before resolution of symptoms.
Surgical options include a cecostomy or colectomy. Ogilvie
syndrome is one of the few conditions for which a cecostomy is
g g e
u
S
B
eattle GC, Peters RT, Guy S, Mendelson RM. Computed tomography
in the assessment of suspected large bowel obstruction. ANZ J Surg.
2007;77(3):160–165.
De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. Br J Surg.
2009;96(3):229–239.
Geller A, Petersen BT, Gostout CJ. Endoscopic decompression for acute co-
lonic pseudo-obstruction. Gastrointest Endosc. 1996;44(2):144–150.
Hutchinson R, Griths C. Acute colonic pseudo-obstruction: a pharmaco-
logical approach. Ann R Coll Surg Engl. 1992;74(5):364–367.
S t
e d
e
R
a d i n g
COLON
263
Jacob SE, Lee SH, Hill J. e demise of the instant/unprepared contrast enema
in large bowel obstruction. Colorectal Dis. 2008;10(7):729–731.
O’Dea CJ, Brookes JH, Wattchow DA. e ecacy of treatment of patients
with severe constipation or recurrent pseudo-obstruction with pyridostigmine. Colorectal Dis. 2010;12(6):540–548.
Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute
colonic pseudo-obstruction. N Engl J Med. 1999;341(3):137–141.
Saunders MD, Kimmey MB. Systemic review: acute colonic pseudo-obstruc-
tion. Aliment Pharmacol er. 2005;22(10):917–925.
Wegener M, Bursch G. Acute colonic pseudo-obstruction (Ogilvie’s syn-
drome). Presentation of 14 of our own cases and analysis of 1027 cases
report in the literature. Surg Endosc. 1987;1(3):169–174.
Weinstock LB, Chang AC. Methylnaltrexone for treatment of opioid-induced
gastrointestinal eects. Curr Opin Anesthesiol. 2010;23(5):616–622.
M
M P
Skandan Shanm
INTR
ODUCTION
M
alignant polyps of the large intestine can be divided into polypoid
cancers, which are largely cancerous lesions with a polypoid shape,
and polyps that are mostly benign but have a focus of cancer. Polypoid cancers are generally unsuited to endoscopic treatment and are
resected along with the segment of bowel in which they lie. Malignant polyps that are mostly benign but have a focus of cancer. ey
can sometimes be managed endoscopically, but in some cases, formal
bowel resection is required. e way to make this oen-dicult decision is discussed in this chapter.
ugan and Cary B.
Aar
ons
BIOLOGY
alignant neoplasms of the colon and rectum arise from a pre-
M
existing benign polyp by the “adenoma-carcinoma” or “serrated
polyp-carcinoma” sequence. ese stepwise progressions of normal
epithelium to dysplastic adenoma or of a normal to serrated polyp to
carcinoma occur as a result of an accumulation of multiple genetic
and epigenetic abnormalities; thus all colorectal polyps are “genetic.”
e process of carcinogenesis is oen indolent, taking many years,
during which time a benign polyp gradually acquires the characteristics of malignancy. Family history, gender, smoking, inammatory
bowel disease, inherited syndromes, and obesity are all risk factors
for colorectal carcinogenesis, but age and family history are the basis
of current screening guidelines. Eective screening programs have
contributed to the declining incidence of colon cancer by identifying and removing precancerous lesions. However, there comes a time
in the history of a neoplasm when it transforms from being benign
to malignant, dened as the passage of neoplastic cells through the
muscularis mucosae into the submucosa. Here the cells gain access to
blood vessels and lymphatics, acquiring the ability to spread outside
severely dysplastic cells by generating a desmoplastic reaction, which
is a clue to the presence of invasive neoplasia.
ASSESSMENT OF POL
When a polyp is seen during a colonoscopy, an assessment is made
of the likelihood that malignancy is present. e risk of malignancy
varies with polyp size, shape, mobility, and appearance. e larger the
polyp, the higher the risk. Up to 46% of polyps greater than 2 cm in
diameter may contain microscopic cancer, but other characteristics
can rene the risk. Asymmetrical polyps, fragile polyps, hard polyps,
and polyps that are not mobile on the submucosa are very likely to
contain a cancer and thus should either be resected formally or at
least marked with an endoscopic tattoo. e shape of the polyp dictates treatment because the stalk of pedunculated polyps oers the
opportunity of snare excision in one piece with a good margin. Large
264
YPS
s
essile polyps may require piecemeal excision or treatment with an
advanced technique such as endoscopic submucosal resection. Endoscopic polypectomy should be complete and ideally performed in a
fashion that allows complete histologic evaluation. If a large polyp
cannot be removed endoscopically, a segmental colectomy is necessary because the presence of a malignancy cannot be assessed without removal of the entire polyp. A biopsy alone is not sucient.
POL
YPECTOMY
En
doscopic polypectomy techniques include snare polypectomy,
endoscopic mucosal resection, endoscopic submucosal dissection,
and laparoscopic-assisted endoscopic resection. An appropriate polypectomy should include some submucosa to allow optimal histologic evaluation of the deep margin. Piecemeal removal of a polyp
complicates the histologic interpretation of the margin and should
be avoided if possible. If a piecemeal technique is used, all the polyp
tissue should be recovered for pathologic examination. Other techniques such as coagulation of the polyp bed with argon plasma coagulation/electrocautery, although possibly eective in achieving clear
margins, does not provide any direct evidence that clear margins
have been achieved. erefore, recent guidelines recommend early
follow-up colonoscopy in 1 to 3 months.
When a polypectomy is performed for a suspicious polyp, the site of
the polypectomy should be tattooed on three sides of the colon wall to
identify the site for close follow-up and for surgical resection if necessary.
HIST
OLOGY
denomatous polyps are noninvasive glandular neoplasms with dys-
A
plastic epithelial cells that have variable malignant potential. ey
can be viewed as a continuum of carcinogenesis, and those with villous histologic features or high-grade dysplasia are closer to cancer
than are those without these characteristics. High-grade dysplasia
(carcinoma in situ) is dened as severely dysplastic cells in the epithelium, bounded by the basement membrane. When these cells traverse
the basement membrane and enter the lamina propria, the denition
is intramucosal carcinoma, which is an unfortunate term, because it
implies that cancer is present when in fact the chance of these cells
metastasizing is extremely low. Such polyps should not be treated
radically, but such reports should be checked by a review of slides.
Malignant polyps are dened by the presence of severely dysplastic
cells invading through the muscularis mucosa into the submucosa.
ey sometimes appear benign endoscopically, and if invasive malignant cells are recognized only aer pathologic evaluation, management may be dicult and controversial. If the chances of residual
or metastatic cancer are small, then polypectomy alone is adequate
treatment. If the chances are high, then formal resection of the bowel
s necessary. e decision represents a balance of the chance of resid-
i
ual cancer versus the complications of treatment.
e chance of residual cancer focuses on two issues: whether
the neoplasm has been completely removed via a polypectomy, and
whether lymph node metastases are present.
COLON
265
TABLE 54-1: Risk of Lymph Node Metastasis Based
on Haggitt Level
Haggitt Le
0 <1
vel Risk of Lymph Node Metastasis, %
MARGIN
e risk of residual primary neoplasm depends on the margin of
excision. Although various acceptable margins have been published,
a 2-mm margin between the deepest cancer cells and the level of excision is safe. Margins can be most accurately determined for pedunculated polyps, where the stalk provides the margin; this is the basis
of the Haggitt classication, in which Haggitt levels 1 and 2 represent
safety. Sometimes the stalk of a malignant pedunculated polyp that
was originally resected with close margins can be resnared to provide
acceptable margins and prevent radical resection. It may be worth a
look. However, pedunculated polyps are relatively uncommon, and
management of sessile malignant polyps is relatively unstudied and
poses more dicult problems. Because snare excision of sessile polyps should not be performed with pieces larger than 2 cm because
of risks of perforation or hemorrhage, many snare excisions of very
large polyps are piecemeal. When resection is piecemeal, margins
oen cannot be determined, and in this case the safest option is
formal resection. However, recent data suggest that malignant sessile polyps can be treated endoscopically, using the same rules as for
pedunculated polyps.
NODES
e extent that the cancer has extended into the polyp, or the depth
of invasion, correlates with the risk of lymph node metastasis. Haggitt etal described a classication system for assessing this risk in
pedunculated polyps, and Kitajima etal classied the risk for sessile
polyps (Table 54-1).
e risk of positive nodes is increased in poorly dierentiated
cancers, and some studies have shown that cancers with lymphovascular invasion are also at high risk, although these two factors usually
go together (Box 54-1).
Haggitt level 3 and 4 cancers in at or sessile adenomas and sessile
serrated adenomas/polyps may also be treated with endoscopic polypectomy alone if they are snared in one piece with 2-mm margins and as
long as they do not harbor any unfavorable features (Box 54-1). However, if a polyp exhibits lymphovascular invasion, poor dierentiation,
or inadequate margins, an oncologic surgical colectomy is indicated.
e proper assessment of polyps to determine the risks of residual
malignancy relies not only on the proper retrieval of the specimen but
also on the precision of pathologic reporting. However, until recently
many pathologists were not adequately reporting histologic criteria of
the specimen. A study from the University of Minnesota showed that
the pathologic assessment of malignant polyps varies between observers.
ere was a high degree of interobserver variability in the assessment of
lymphovascular invasion that limited the value of this feature for clinical decision making. In every case there should be close communication
between the pathologist and surgeon to minimize the chance of misinterpretation of the true malignant potential of a polyp. A review of the
original slides by an experienced local pathologist may make a big dierence in the diagnosis and the treatment to be recommended.
SURGIC
urgical resection is usually indicated if a polyp cannot be excised
S
with the colonoscope or if the excised polyp is found to contain an
invasive cancer with a signicant potential for local recurrence or
AL CONSIDERATIONS
1 <1
2 <1
3 2-5
4 12-25
BO
X 54-1: Prognostic Factors of a Malignant Polyp
avorable Criteria
F
omplete endoscopic resection
C
Negative 2-mm margins
Well- or moderately dierentiated histologic features
No lymphatic or vascular invasion
nfavorable Criteria
U
Incomplete or piecemeal resection
Positive 2-mm margins or unknown margins
Poorly dierentiated, mucinous, or signet cell histologic
features
Lymphatic or vascular invasion
lymph node metastasis. In such circumstances, the therapeutic goal
is to resect the appropriate segment of colon and its mesentery. e
nature of the operation obviously depends on the location of the
unresectable polyp or cancer, bearing in mind that malignant polyps
of the rectum are treated dierently from those of the colon and are
discussed elsewhere in this textbook. For colonic malignant polyps,
laparoscopic colectomy using an oncologic technique is the optimal
approach.
A problem arises when the surgeon cannot identify the previous
polypectomy site, which emphasizes the importance of tattooing the
location of a suspicious polyp. e length of scope insertion is unreliable for determining the site of a lesion, because a depth of 50 cm
from the anal verge could represent either the sigmoid or transverse
colon. e surgeon can condently proceed with an appropriate
oncologic resection if the site of the cancer has been identied with a
tattoo. In a case in which the previous polypectomy site has not been
tattooed, a repeat colonoscopy is useful in an attempt to identify and
tattoo the site. Time may be of the essence because polypectomy
sites that have been healed for several weeks may be inconspicuous.
Referrals for a malignant polyp should be timely, and a repeat colonoscopy should be performed quickly if no tattoo was applied at the
original examination. If the polyp site cannot be dened preoperatively, a discussion with the referring colonoscopist is required to try
to narrow down the location so the colectomy can be as limited as
possible, while still resecting the polyp site. An intraoperative colonoscopy also can be performed to conrm the polypectomy site, and
the resected colonic specimen should be opened on the back table
for conrmation. e alternatives of blindly resecting more colon,
the possibility of missing the site, and the risks of observation alone
should be discussed with the patient preoperatively. In all cases that
proceed to surgery, the patient should be alerted of the possibility
that no cancer may be found in the resected specimen. Not nding cancer is good news, because the procedure is being performed
as much for assessment of potential metastatic lymph nodes as for
removal of the primary lesion.
266
ManageMent of
the Malignant Poly
P
COMORBIDITIES
W
hereas an unfavorable malignant polyp is an indication for radical
resection, high comorbidity is a relative contraindication. Each case
represents a balance of indications and contraindications, in which
the danger represented by the malignant polyp and the danger represented by comorbidities are on sliding scales. However, the use of
laparoscopic technique and endoscopic resections allows the denition of restrictive comorbidity to be eased in many patients.
SUMMARY
C
olonoscopy with an endoscopic polypectomy is the preferred
approach to the diagnosis and treatment of most colorectal polyps.
e management of malignant polyps can be challenging and oen
requires consideration of the risk of residual cancer aer a polypectomy versus the risk of the possible complications associated with
surgical resection of the colon. Careful pathologic review of the slides
determines whether unfavorable features are present. Polyps with
unfavorable features or unclear margins of resection that may potentially increase the risk of lymph node metastasis warrant a laparoscopic or open oncologic surgical resection.
g g e
u
S
dler A, etal. Narrow-band versus white-light high denition television en-
A
Boenicke L, Fein M, Sailer M, etal. e concurrence of histologically positive
S t
doscopic imaging for screening colonoscopy: a prospective randomized
trial. Gastroenterology. 2009;135:410–416.
resection margins and sessile morphology is an important risk factor for
lymph node metastasis aer complete endoscopic removal of malignant
colorectal polyps. Int J Colorectal Dis. 2010;25:433–438.
e d
R
e
a d i n g
Haggitt RC, et al. Prognostic factors in colorectal carcinoma arising in
adenomas: implications for lesions removed by endoscopic polypectomy.
Gastroenterology. 1985;89:328.
Kitajima K, etal. Correlations between lymph node metastasis and depth of
submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004;39:534–543.
Komuta K, et al. Interobserver variability in the pathological assessment of
malignant colorectal polyps. Br J Surg. 2004;91(11):1479–1484.
Kudo S, etal. Colorectal tumours and pit pattern. J Clin Pathol. 1994;47:
880–885.
Muto T, et al. e evolution of cancer of the colon and rectum. Cancer.
1975;36:2251–2270.
Seitz U, Bohnacker S, Seewald S, etal. Is endoscopic polypectomy an adequate
therapy for malignant colorectal adenomas? Presentation of 114 patients
and review of the literature. Dis Colon Rectum. 2004;47:1789–1796.
Winawer S, etal. Colorectal cancer screening and surveillance: clinical guide-
lines and rationale-update based on new evidence. Gastroenterology.
2003;124:544–560.
Winawer SJ, etal. e National Polyp Study: design, methods, and characteris-
tics of patients with newly diagnosed polyps. Cancer. 1992;70:1236–1245.
Wu XR, Liang J, Church JM. Management of sessile malignant polyps: is colo-
noscopic polypectomy enough? Surg Endosc. 2015;29:2947–2952.
C
C
SCREENING FOR COLORECTAL CANCER
I
n the United States, colorectal cancer (CRC) is the second most
commonly diagnosed cancer in males and females. e age-adjusted
incidence rate during the period 2006-2010 was 52.2 per 100,000
men and 39.3 per 100,000 women per year, according to data from
the Surveillance, Epidemiology, and End Results (SEER) populationbased cancer registries. e projected number of new cases in 2014
is 136,830, with 50,310 anticipated deaths, accounting for 8% of estimated new cancer cases and deaths in men and women.
CRC incidence rates established from the most recent data
(2005-2009) decreased in males by 2.6% per year and in females by
2.1% per year. Mortality from CRC has also been steadily declining
in the United States by 2.5% to 3% per year. ese reductions have
been largely attributed to increases in the use of CRC screening and
removal of colorectal polyps.
Although an overall decline in CRC incidence and mortality has
occurred, racial disparity is growing. African American males have
the highest incidence (65.1 vs. 52.8 per 100,000) and stage-adjusted
mortality (29.8 vs. 19.8 per 100,000) compared with white males.
Racial dierences in access to or utilization of CRC screening, a
higher prevalence of comorbidities such as obesity, diabetes, and
hyperlipidemia, and the early age at diagnosis in African Americans
may explain some of the dierences.
A variety of modalities may be used for CRC screening in the
average-risk population. ey include stool tests (fecal occult blood
tests or stool DNA testing), radiologic tests (computed tomography [CT] colonography), and endoscopy (exible sigmoidoscopy
or colonoscopy). ese tests have dierent rates of sensitivity, specicity, cost, potential harm, and adherence. Patients should have an
opportunity to make an informed decision when choosing one of the
screening modalities.
Multiple organizations have issued guidelines for CRC screening,
most notably the American College of Gastroenterology (ACG), the
U.S. Preventive Services Task Force (USPSTF), and the U.S. MultiSociety Task Force on Colorectal Cancer (USMSTF). However,
adherence to guidelines remains a challenge, with signicant overutilization of screening in average-risk persons and underutilization of
surveillance in high-risk patients who are prone to CRC.
Who Should Be Scr
e age to begin screening, the modality chosen for screening, and
the interval between examinations depends on the presence or
absence of known risk factors for CRC. Persons with no risk factors
are considered to be at average risk of CRC with a cumulative lifetime
risk of approximately 5% in both men and women. Patients at higher
than average risk of CRC include patients with a personal or family
eened? Determining Risk
S
S
Car
ole Macaron and Carol A. Burke
story of CRC or polyps and patients with Crohn disease or ulcer-
hi
ative colitis. Patients with a genetic predisposition to CRC are at the
highest lifetime risk of CRC. Hereditary CRC syndromes account for
5% of all CRC cases and warrant the most aggressive screening and
surveillance.
e USMSTF, USPSTF, and ACG recommend that screening for
CRC begin at age 50 years in average-risk, asymptomatic men and
women. e ACG further suggests that African Americans start
screening at age 45 years because of the increased incidence of CRC
before age 50 years in this population.
eening Average-Risk Persons
Scr
CRC screening tests can be divided into cancer prevention tests with
the potential to identify both cancer and polyps and cancer detection
tests that are primarily eective in diagnosing CRC (Table 55-1).
Colonoscopy every 10 years is the preferred CRC prevention test,
and annual fecal occult blood testing with high-sensitivity guaiacbased testing or the fecal immunochemical test (FIT) is the preferred
cancer detection test. Table 55-2 summarizes the current screening
guidelines for average-risk individuals issued by the ACG, USPSTF,
and USMSTF.
ANCER PREVENTION TESTS
C
Colonoscop
C
olonoscopy is frequently cited as the gold standard CRC screening
test because it has both diagnostic and therapeutic capabilities. Additionally, abnormalities detected on other CRC screening tests lead to
a colonoscopy.
No randomized clinical trials of the eect of screening colonoscopy on CRC mortality have been performed, but epidemiologic and
cohort studies have shown that exposure to colonoscopy is associated
with up to a 75% decrease in CRC incidence, which includes a durable protective eect up to and greater than 10 years. is protective
eect extends to patients who have no polyps detected on colonoscopy, in addition to those who have had a polyp removed. A recent
follow-up on the National Polyp Study evaluating the long-term benet of colonoscopy with polypectomy found a 53% reduction in CRC
mortality when compared with the expected deaths from CRC in the
general population. An inverse relationship between colonoscopy
screening and death from CRC was found in a recent large Canadian
population–based study. ese investigators found that for every 1%
increase in colonoscopy screening, a 3% decrease in CRC occurs.
e reduction in colorectal cancer mortality aer colonoscopy varies by the site of the cancer, with less protection in the
y
267
268
ColoreCt
al Can
Cer SCreening
and Surveillan
Ce
TABLE 55-1: Cancer Prevention and Cancer
Detection Tests
Prevention Tests Cancer Detection Tests
Cancer
olonoscopy High-sensitivity guaiac-based
C
fecal occult blood test or fecal
immunochemical testing
Flexible sigmoidoscopy
Computed tomography colonog-
Stool DNA
raphy (requires optical colonoscopy to achieve prevention)
TABLE 55-2: Colorectal Cancer Screening
Guidelines for Average-Risk Persons
.S. Multi-
U
Society
Method Interval for Screening
ecal occult
F
Task Force
Annual Annual Annual
blood test
Flexible sigmoi-
5 yr 5 yr 5 yr
doscopy
Colonoscopy 10 yr 10 yr 10 yr
Computed
5 yr Insucient
tomography
colonography
Stool DNA Unknown Insucient
p
roximal than in the distal colon. In a Canadian case-control study
that matched more than 10,000 patients who died with CRC to 5 control subjects each, colonoscopy was associated with lower mortality
from le-sided colon cancer (adjusted odds ratio [OR], 0.33; 95%
condence interval [CI], 0.28 to 0.39) but not right-sided CRC (OR,
0.99; 95% CI, 0.86 to 1.14). It is suggested that the biologic dierences between proximal and distal CRC (a higher proportion of CpG
island methylation phenotype, DNA microsatellite instability, and
BRAF mutations in proximal tumors and sessile serrated adenomas/
polyps), the higher proportion of at polyps in the proximal colon,
and the technical skill of the endoscopist aect the miss rate of premalignant lesions and the development of interval CRC.
Quality indicators have been established to standardize colonoscopy and aid in determining areas for continuous quality improvement. e minimum quality standards include but are not limited
to the cecal intubation rate (>90% for diagnostic cases and >95% for
screening examinations), high quality of bowel preparation, colonoscopy withdrawal time (>6 minutes in screening examination), and
adenoma detection rate (ADR; >25% in a mixed gender population
aged ≥50 years or >30% for men and >20% for female patients older
than 50 years). e ADR is dened as the proportion of screened subjects in whom at least one adenoma is detected. Endoscopists who
meet these standards have decreased interval cancer rates. Compared
with physicians who have an ADR greater than 20%, the hazard ratios
for interval CRC based on ADRs of less than 11%, 11% to 14.9%, and
15% to 19.9%, were 10.94, 10.75, and 12.50, respectively (P = .02 for
all comparisons). In a recent study published, Corley and colleagues
U.S. Preventive
Services Task
Force
evidence to
recommend
evidence to
recommend
American
College of Gastroenterology
5 yr
3 yr
found a continued protection against CRC with an ADR above 32%.
Each 1% increase in the ADR was associated with a 3 % decrease in
the risk of CRC.
One major factor aecting the quality of mucosal inspection and
subsequently ADR is the quality of bowel preparation. e American Society of Gastrointestinal Endoscopy/ACG Task Force recommends that the examination be considered adequate if it allows
detection of polyps greater than 5 mm. Inadequate (poor or fair)
bowel preparation is associated with an adenoma miss rate as high
as 42% when a repeat colonoscopy is performed within 3 years of
the initial suboptimal examination. e quality of bowel preparation worsens with a longer time interval between completion of the
preparation and the start of colonoscopy. A meta-analysis of nine
studies concluded that receiving at least half of the bowel preparation on the day of the examination, also known as “split-dose”
bowel preparation, resulted in more excellent and good results
(OR, 3.46; 95% CI, 2.45 to 4.89) compared with night-before dosing. erefore, to maximize bowel preparation quality, it is recommended that the colonoscopy be started within 3 to 5 hours of the
last dose of preparation.
Flexible Sigmoidoscop
r
ee of four randomized controlled trials have shown that exible
y
sigmoidoscopy decreases CRC incidence up to 25%. Two of the three
trials found up to a 30% reduction in mortality from CRC.
Flexible sigmoidoscopy is oen performed without sedation and
does not usually require an oral bowel preparation, which is one barrier to colonoscopy. However, the examination is limited to the le
colon, and about 37% of lesions are beyond the reach of the exible
sigmoidoscope. Patients for whom precancerous lesions are detected
with sigmoidoscopy should be referred for a colonoscopy.
Computed T
lso known as virtual colonoscopy, CT colonography (CTC), a
A
omographic Colonography
promising CRC screening modality, does not require sedation and
has very low immediate test-related complications. However, CTC
currently is not covered by Medicare or by many commercial payers, it requires an extensive bowel preparation, and it has poor
discrimination for colorectal lesions less than 6 mm, flat lesions,
and serrated lesions. A meta-analysis by Mulhall and colleagues
showed that the sensitivity of CTC improved as the polyp size
increased, with a sensitivity ranging from 48% for polyps less than
6 mm to 85% to 93% for polyps larger than 9 mm. Similar findings were reported in a more recent randomized controlled trial.
The American College of Radiology Imaging Network National
CT Colonography Trial assessed the accuracy of CTC for detecting histologically confirmed colorectal neoplasms (adenomas and
cancers), using colonoscopy as the reference standard. Although
CTC had a sensitivity of 90% for the detection of large lesions, its
sensitivity for the detection of adenoma or cancers was 65% for
lesions larger than 5 mm, 78% for lesions 6 mm or larger, and 84%
for lesions 7 mm or larger.
Nonrandomized controlled studies show that the detection rate
for advanced neoplasia was similar between screening patients
undergoing CTC (3.2%) or colonoscopy (3.4%), with a 7.9% referral
rate for follow-up colonoscopy aer CTC. e Special Interest Group
in Gastrointestinal and Abdominal Radiology (SIGGAR) study, a
recent large randomized study of symptomatic patients, showed that
the yield for colorectal cancer or large polyps was identical with CTC
and colonoscopy with a very low miss rate (1 of 29 in the CTC group).
However, the referral rate for colonoscopy aer CTC was unexpectedly high (30%), a fact that has major cost implications.
Adherence to CTC has been shown to be higher than adherence
to colonoscopy in some studies. In one analysis, signicantly more
COLON
269
p
atients accepted the invitation to have a CTC than to undergo colo-
noscopy (34% vs. 22%).
Radiation exposure and radiation-related cancer risk should be
considered, especially with repeated scanning. Other limitations of
CTC include the need for a standardized technique, a consensus in
reporting the ndings, and the dilemma posed by the number of incidental extracolonic ndings identied on imaging, which are present
in up to 16% of patients.
e USMSTF recommends that CTC screening begin at age 50
years; however, the interval for repeat examination aer a negative
CTC is uncertain. e authors state that it is “reasonable to repeat
exams every 5 years if the initial CTC is negative for signicant polyps until further studies are completed and are able to provide additional guidance.” e USMSTF guidelines recommend surveillance
colonoscopy as opposed to CTC for patients with polyps 6 mm or
larger detected with CTC.
ANCER DETECTION TESTS
C
ecal Occult Blood Tests
F
ecal occult blood tests (FOBTs) are stool-based tests designed to
F
detect occult blood loss from colorectal neoplasms. ey are based
on the concept that large adenomatous polyps and early-stage colon
cancer intermittently bleed, and this blood may be detected with
occult blood tests. Two major types of FOBTs exist: the guaiac-based
test (gFOBT) and the FIT. e gFOBT detects blood through the peroxidase activity of heme or hemoglobin, which converts the colorless guaiac to a blue color. e FIT uses an antibody that reacts with
human globin.
e gFOBT protocol requires the collection of two stool samples
from each of three consecutive bowel movements at home. Multiple
stool samples increase the yield because colorectal neoplasms tend
to bleed intermittently. Prior to testing with a sensitive guaiac-based
test, persons should be instructed to avoid eating red meat, some
fruits, and some raw vegetables because of a false-positive reaction
due to the presence of peroxidase or pseudoperoxidase in these
foods. Medications such as high-dose aspirin and nonsteroidal antiinammatory drugs may cause occult bleeding and therefore should
be avoided for 7 days prior to testing. Vitamin C and antioxidants
may interfere with the reaction and cause false-negative results by
blocking the peroxidase reaction.
e sensitivity of gFOBT for CRC varies among the available tests,
from the low test sensitivity gFOBT (such as Hemoccult II, Beckman
Coulter, Brea, Calif.), with a sensitivity of 37.1%, and the high test
sensitivity gFOBT (such as Hemoccult SENSA, Beckman Coulter),
with a sensitivity of 79.4%. Five large randomized controlled trials
with gFOBT have demonstrated a signicant reduction in CRC mortality of 15% to 33%.
Because FIT detects human globin, it is more specic for human
blood than guaiac-based tests. It is not subject to interactions with
diet and is more specic for lower gastrointestinal bleeding, because
globin is degraded by digestive enzymes in the upper intestinal tract.
Although no randomized controlled trials are available for FIT,
cohort studies report a one-time sensitivity for CRC of 60% to 85%
and a sensitivity for advanced adenoma of 20% to 50%.
Multiple studies have compared dierent types of FIT with
Hemoccult SENSA (high-sensitivity gFOBT). ere is no clear superiority in overall test performance between highly sensitive gFOBT
and FIT. e sensitivity of FIT and gFOBT was 81.8% and 64.3%,
respectively, in a recent study by Allison and colleagues. In terms of
specicity, FIT tends to be superior to gFOBT, with a specicity of
97% for distal cancer.
Annual screening with high-sensitivity gFOBT (such as Hemoccult SENSA) or with FIT has been shown to detect a majority of
prevalent CRC in an asymptomatic population and is an acceptable
o
ption for colorectal screening in average-risk adults aged 50 years
and older who refuse to undergo a colonoscopy. Patients should be
advised that any positive FOBT test should be followed up with a
colonoscopy.
Stool DNA
tool DNA testing relies on the fact that adenomas and carcinomas
S
continuously shed cells that contain altered DNA into the bowel
lumen. Because no single gene mutation is shed by all cells in all
tumors, a multitarget stool DNA test is needed to improve sensitivity. e currently available stool DNA assay requires the entire stool
specimen (30 g minimum) to ensure an adequate stool sample for
evaluation. e sensitivity of fecal DNA testing varies from 52% to
93%, with the lower performance attributed to inadequate stability of
the stool DNA, as well as imperfect extraction.
e most recent version of the test (Cologuard, Exact Sciences,
Madison, Wis.) has a sensitivity of 93% for CRC, 43% for advanced
adenoma, and 42% for sessile serrated adenomas/polyps. It has
recently been approved by the Food and Drug Administration, and
the cost of the test is reimbursed by Medicare for average-risk patients
older than 50 years every 3 years.
Although the USMSTF recommends stool DNA as an acceptable
option for CRC screening, further research is needed to determine
the interval between negative stool DNA tests. At this time, the appropriate interval is unknown. Cologuard is currently recommended for
average-risk patients who refuse to undergo a colonoscopy or who for
some reason cannot have a colonoscopy.
SCREENING IN PERSONS
AT
AN ABOVE-AVERAGE RISK FOR
COLORECTAL CANCER
P
ersons with a personal or family history of CRC, precancerous
colorectal polyps, or inammatory bowel disease are at a moderately
increased risk for CRC. Approximately 80% of CRC arises from conventional adenomas through the adenoma-carcinoma pathway as a
result of chromosomal instability. Observational data suggest that the
adenoma-carcinoma sequence takes approximately 10 years. Adenomas are dysplastic lesions histologically characterized as tubular, villous, or a mixture of the two (tubulovillous), based on the percentage
of villous component in their glandular architecture. An advanced
adenoma is an adenoma with high-grade dysplasia, an adenoma
10 mm or greater, or an adenoma with a greater than 25% villous
component.
veillance Colonoscopy in Patients with
Sur
Adenomatous Lesions at Baseline
trong evidence has shown that baseline polyp characteristics predict
S
the recurrence of advanced neoplasia. Lower risk adenoma-bearing
persons have one to two tubular adenomas measuring less than 10
mm. Higher risk persons have more than 2 adenomas or one or more
advanced adenomas. e National Cancer Institute pooling project
found that with each additional polyp, there is a linear increase in the
risk of advanced neoplasia on follow-up. Patients with three or more
adenomas have a risk of metachronous advanced neoplasia (OR,
1.32) comparable with that of patients who have an advanced adenoma (OR, 1.4). Recurrence of advanced neoplasms has been shown
to be nearly twofold higher in the higher versus low-risk cohorts.
In its 2012 guideline, the USMSTF risk straties patients based on
the ndings at the baseline colonoscopy and alters the colonoscopy
interval accordingly (Table 55-3). It is recommended that low-risk
patients with an adenoma have their next colonoscopy in 5 to 10 years
and that higher risk patients have their next colonoscopy in 3 years.
270
ColoreCt
al Can
Cer SCreening
and Surveillan
Ce
TABLE 55-3: 2012 U.S. Multi-Society Task Force Recommendations for Surveillance and Screening Intervals
in Patients with Adenomatous Lesions
Adenomatous Lesions Sur
Low-Risk Patient
ubular adenoma(s) measuring <10 mm 5-10 Moderate
1-2 t
Higher Risk Patient
3-10 t
ubular adenomas, or
≥10 mm in size, or
high-grade dysplasia, or
presence of villous component
veillance Interval (Yr) Quality of Evidence
3 Moderate
High
Moderate
Moderate
Patients with colorectal cancer Colonoscopy at 1 yr; if normal, repeat colonoscopy at 3 yr, and if
Moderate
that is normal, then repeat in 5 yr
Every 3-6 mo, exible sigmoidoscopy or endoscopic ultrasound for
the rst 2 yr aer low anterior resection of rectal cancer
Highest-Risk Patient
>10 t
ubular adenomas <3
Moderate
Consider genetic syndrome and counseling
M
odied from Lieberman DA, Rex DK, Winawer SJ, etal. Guidelines for colonoscopy surveillance aer screening and polypectomy: a consensus update by the
US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143(3):844-857.
veillance Colonoscopy in Patients with Serrated
Sur
Lesions at Baseline
pproximately 20% of CRCs arise from a distinct molecular pathway
A
characterized by hypermethylation of genes, known as the CpG Island
Methylator Phenotype pathway. e precursor lesions of this pathway
are serrated polyps, predominantly the sessile serrated adenoma/polyp
(SSA/P), which is also known as a sessile serrated adenoma.
TABLE 55-4: 2012 U.S. Multi-Society Task Force
Recommendations for Surveillance and Screening
Intervals in Patients with Serrated Lesions
Surveillance
rated Lesions
Ser
S
mall rectosigmoid
HP <10 mm
Interval (yr) Quality of Evidence
10 Moderate
Small rectosigmoid hyperplastic polyps are a common nding at
screening colonoscopy and are non-neoplastic. ese lesions are not
a marker of advanced neoplasia elsewhere in the colon, and Polyp
SSP <10 mm with
no dysplasia
5 Low
Prevention Trial investigators found that neither proximal nor distal
hyperplastic polyps were associated with an increased risk of adenoma
aer 3 years from the baseline colonoscopy. e clinical implication of
a sessile serrated polyp (SSP) is still undened. Recent studies observed
SSP >10 mm
SSP with dysplasia
TSA
3 Low
a signicant association between specic characteristics of SSPs,
including their size (>10 mm) and location in the colon (proximal) and
synchronous advanced adenomas elsewhere in the colon. Only a few
studies assessed the risk of serrated polyps for metachronous neoplasia. Schreiner and colleagues found that persons with small proximal
serrated polyps at baseline have a similar risk of advanced adenoma
on follow-up colonoscopy as patients with a nonadvanced adenoma
at baseline (5.1% vs. 6.3%). e same study showed that patients with
coexisting serrated polyps and advanced adenomas at baseline had a
28.9% risk of advanced adenoma on follow-up compared with 14.7%
Serrated polyposis
syndrome
P, Hyperplastic polyp; S SP, sessile serrated polyp; TSA, traditional serrated
H
adenoma.
Modied from Lieberman DA, Rex DK, Winawer SJ, etal. Guidelines for
lonoscopy surveillance aer screening and polypectomy: a consensus update
co
y the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology.
b
2012;143(3):844-857.
1 Moderate
in patients with only an advanced adenoma at baseline.
With the current evidence suggesting that size greater than 10 mm,
histologic features, and proximal location may be associated with an
increased risk of CRC, the USMSTF recommends that an SSP greater
than 10 mm, an SSP with dysplasia, or traditional serrated adenoma
(TSA) be managed like an advanced adenoma, whereas small SSPs
(<10 mm) and SSPs without dysplasia be managed as nonadvanced
adenomas (Table 55-4).
Resection (CARE) study, Pohl and colleagues reported an overall
incomplete polyp resection rate of 10.1%. e incomplete resection
rate increased with polyp size (large [>10 mm], 17.3%, vs. small,
6.8%; relative risk [RR], 2.1) and with polyp histology (SSP, 31%,
vs. adenoma, 7.2%; RR, 3.7). e incomplete resection rate varied
among endoscopists with a 3.4-fold dierence (6.5% to 22.7%) aer
adjusting for the size and histology of the polyps. e USMSTF recommends that patients with large (>20 mm) or sessile adenomas
veillance Colonoscopy after Piecemeal
Sur
Polypectomy
t is important to mention that incomplete removal of polyps is
I
an important cause of interval CRC. In the Complete Adenoma
that are resected piecemeal return for a repeat colonoscopy in 2 to
6 months with biopsy of the scar at the polypectomy site to ensure
complete removal of the polyp. Once the resection is completed,
subsequent surveillance should be individualized based on the
endoscopist’s judgment.