Colon Cancer: a Review

1. General Background
2. General Anatomy
3. Epidemiology/Etiology
4. Relevant Physiology
5. Diagnosis
6. Surgical Management
7. Medical Therapy
8. Screening
9. Prognosis and Complications
10. Conclusion
11. References

1. General Background
Colorectal cancer (CRC) is unfortunately an all-too common lethal disease and is a major
health concern that affects men and women equally. Worldwide it accounts for
approximately 1 million new cancers and one-half million deaths, equating 10 percent of
all cancer deaths annually1. Although both colon and rectal cancer are similar in many
respects, there are significant differences due, in part, to there anatomic locations. This
review focuses on colon cancer; please refer to a subsequent review for more details on
rectal cancer.

2. General Anatomy
The colon is a muscular organ of approximately 150 cm in length. It extends from the
cecum and terminal ileal junction at the ileocecal valve to the rectosigmoid junction.
From inside out the bowel layers include mucosa, submucosa, muscularis propria
(longitudinal externally and circular internally), and serosa. The organ is divided into four
parts: the ascending, transverse, descending and sigmoid regions. The ascending colon
lies in the retroperitoneum, on average 15 cm in length. It is continuous with the cecum,
a blind-ending loop, considered the beginning of the colon but smaller in diameter, and
ends at the hepatic flexure. The transverse colon is the longest segment, about 45cm, and
stretches from the hepatic to the splenic flexure. Its course is convex and is located
intraperitoneally based on a long mesentery. At its superior aspect the transverse colon is
adherent to the greater omentum, while along the inferior border lies its blood supply via
the transverse mesocolon extending upward from the retroperitoneum adjacent to the
pancreas. The descending colon is 25cm in length and runs from the splenic flexure,
where it is attached to the 11th rib by the phrenocolic ligament, and ends at the sigmoid
junction. While the descending colon, like the ascending, is secondarily
retroperitonealized, the sigmoid colon, akin to the transverse colon lies intraperitoneal.
The sigmoid colon forms a loop of about 30-40cm within the hypogastrium and ends at
rectum. Nearby, the iliac vessels, ureter, and sacral plexus lie posteriorly, while the
bladder (and in females, the uterus) are adjacent anteriorly.
Arterial supply comes from the superior (SMA) and inferior (IMA) mesenteric arteries,
with the superior supplying up to the distal one third of the transverse colon and the
inferior supplying distal portion, including the proximal rectum. A marginal artery
connects the two and forms an arcade along the mesenteric border, also named the artery
of Drummond. Named branches include the ileocolic (supplying the ileum, cecum and
appendix), the right colic (supplying the ascending and proximal transverse colon), the
middle colic (supplying the transverse colon), the left colic (supplying the distal
transverse and descending colon) and the sigmoid artery (supplying the sigmoid colon
and proximal rectum). A direct connection between the SMA and IMA is often seen
known as the arc of Riolan or meandering mesenteric artery. An increased diameter of
this arc suggests obstruction of one of the major vessels. Anatomical variations are not
uncommon. Although collateral circulation is significant, inconsistent watershed areas
do occur at the splenic and hepatic flexures, along with the rectosigmoid junction. The
venous drainage mirrors the arterial supply with the inferior mesenteric vein emptying
into the splenic vein and then forming the portal vein together with the superior
mesenteric vein.
Lymphatic drainage also follows the arterial anatomy. Epicolic nodes lie adjacent to the
colon, draining proximally into the paracolic nodes, and subsequently into intermediate
nodes located along the above named vessels. Ultimately lymph drainage reaches the
primary nodes located at the SMA and IMA level before going into the para-aortic nodal
chain.
Innervation of the colon comes from both sympathetic and parasympathetic systems. The
sympathetic nerves arise from the sympathetic plexuses of spinal levels T1 to L3 located
at pre-aortic ganglia and mesenteric vessels. The parasympathetic nerves arise from the
vagus, supplying the colon up to the splenic flexure, and sacral nerves S2-S4 which
supply the descending colon and rectum.In broad terms, the main functions of the colon
include concentrating the fecal fluid by absorption, storing fecal material, and minimal
digestion of nutrients. The absorption of these nutrients depends mostly on their digestion
by microflora. They include but are not limited to starches and nonstarch
polysaccharides, bile acids not absorbed by the terminal ileum and short chain fatty acids
(SCFA). These SCFA are the primary substrate for colonocytes, especially butyrate, but
also include acetate and proprionate. Fecal fluid absorption and concentration is mostly
done in the ascending colon, while the descending and sigmoid are responsible for
storage.

3. Epidemiology/Etiology
The incidence of CRC varies tremendously worldwide with the highest rates occurring in
North America and Western Europe. Developing countries like Africa and Asia despite
having a lower incidence2 unfortunately also have lower five-year survival rates. In the
United States, the incidence of colorectal carcinoma in whites has been steadily
decreasing, while the rates in blacks continue to rise. There has also been a gradual shift
toward right-sided or proximal colon cancers observed worldwide, 3 which may, in part,
be due to increased screening rates with colonoscopy, thus identifying these lesions more
often.
Several different mechanisms have been identified to explain the development of CRC.
The most common involves the initial growth and subsequent transformation of
adenomatous polyps, which are abnormal cells located in intramural glands. These
adenomas grow over time and invade locally to become adenocarcinomas--although the
overall conversion rate remains relatively low. The risk does increase with polyp size and
the percentage of villous component within the adenomas4. In addition, other risk factors
have been linked to the development of CRC from an epidemiological stand-point. These
include age, diet, certain diseases like inflammatory bowel disease and, and a genetic
predisposition. Gender, though controversial, does not appear to be a risk factor. Age
remains a major one, with a rare diagnosis before the age of 40 outside of a familial
genetic predisposition. The age-specific incidence of adenomatous polyps and CRC is 1
in 5000 for 40 to 50 year olds and 1 in 250 for individuals greater than 80 years of age5.
Diet has been suggested as a risk factor, with a diet low in fiber and high in fat as a
suggestive cause, although exceptions have been noted. For example, Eskimos have a
low incidence of CRC, despite partaking in a diet low in fiber and high in animal fat.
While some authors suggest a diet high in fiber may decrease the contact time between
carcinogens in the bowel lumen with the mucosa, other studies demonstrate that fiber
supplementation has no significant protective effect6. The majority of studies, however,
suggest that fiber in the diet has a protective effect by decreasing the time it takes for
fecal matter to transit through the bowel and by binding carcinogens through increasing
stool bulk7. Other hypotheses regarding changes in diet and the development of CRC
involve alterations in stool bacterial flora leading to increased bile salts which are a
known risk factor8. This is the groundwork behind the research and use of pro and pre-
biotics9. Other dietary components that have been proposed as protective factor include
vitamin B6, calcium, and folate10-12. Medications that have been proposed to decrease the
risk include NSAIDS, hormone replacement therapies in women, and statins13-15,
although the degree to which these are protective has not been completely elucidated.
Diseases that are associated with an increased rate of development of CRC include
inflammatory bowel disease with ulcerative colitis, for example, having a 30% risk after
25 years if pancolitis is present16 and previous diagnosis of other cancers--especially
breast, uterine, ovarian, and other gastrointestinal tract cancers. Finally, other risk factors
include smoking, obesity, exposure to certain viruses, alcohol, and some studies even
suggesting diabetes to be a risk factor17.
Family history is also important, with the risk of colon cancer increasing 3-fold with
CRC occurring in a first-degree relative. The majority, however, are sporadic rather than
familial, which only account for 5% of cases18. All of the familial syndromes are
inherited in autosomal fashion and can broadly be divided into familial adenomatous
polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). FAP,
accounting for approximately 1% of all CRC, is a syndrome where hundreds to thousands
of polyps develop in the colon and other parts of the GI tract early in life. Individuals
have a close to 100% risk of developing colorectal cancer by the age or 40 if untreated19.
Associated syndromes are Gardner’s and Turcot’s syndrome, which are include
osteomas/desmoids and central nervous system tumors, respectively. HNPCC, accounting
for ~4-6% of all CRC, is associated with a 75% chance of having cancer by the age of 65.
Patients have fewer polyps than FAP, that are often located in the ascending colon and
sessile in nature 20. The syndrome can be subdivided into Lynch I and II, with Lynch I
being sited specific to the colon and Lynch II associated with adenocarcinomas in the
uterus, ovary, stomach and pancreas. The Amsterdam Criteria is used to help diagnose
patients with HNPCC. To fulfill these criteria, patients must have 3 or more relatives
with colorectal cancer, one of whom is a first degree relative of the other two, two or
more generations need to be affected, and at least one of the relatives diagnosed before
the age of 50. Since then these criteria have been modified to include HNPCC-associated
tumors (Amsterdam II), and the Bethesda and revised Bethesda criteria were developed
with even broader inclusion criteria including some characteristics regarding the tumor or
adenomas themselves21.

4. Relevant Physiology
As stated above, over 70% of colorectal cancers, regardless of etiology, arise from
adenomatous polyps. A polyp is a mass that arises from the intestinal mucosa and often
projects into the lumen of the bowel. Recent evidence also suggests that depressed
polyps carry an increased risk of malignancy as well. Unfortunately, most are
asymptomatic, highlighting the need for adequate screening and surveillance. They can
be classified as hamartomas (juvenile polyps), hyperplastic polyps and adenomatous
polyps. Although only adenomatous polyps are felt to be premalignant, large or extensive
polyps of the other varieties have been associated with an increase risk of cancer22.
Despite this, only a minority of these lesions eventually develop into cancer.
Adenomatous polyps are classified by gross appearance (pedunculated or sessile),
histological appearance (tubular, villous or tubulovillous), size and degree of cellular
atypia23. Hereditary and somatic molecular changes have been noted in adenomatous
polyps, which are thought to lead via a multistep process into invasive carcinoma24. The
mutations that occur can be divided into three categories: mutations of tumor suppressor
genes, oncogenes, or DNA repair genes25. Tumor suppressor genes normally suppress or
control cell growth, thus when this function is lost, cell growth becomes uncontrolled.
As this works via an autosomal recessive trait, both alleles need to be damaged to lose
control. On the other hand, oncogenes are mutated proto-oncogenes and stimulate cell
growth, and require only one allele to be mutated to cause dysfunction. DNA repair genes
correct DNA errors that occur either during replication or mutational change.
Dysfunction of these genes leads to the overall accumulation of mutations and increased
possibility of uncontrolled growth.
This adenoma-carcinoma sequence takes place over 10 to 15 years. It includes
characteristic changes like point mutations in the K-ras proto-oncogene; hypomethylation
of DNA, leading to gene activation; loss of tumor-suppressor gene (the adenomatous
polyposis coli (APC) gene on 5q21 and colorectal cancer (DCC) gene on 18q) and
mutations in the p53 tumor-suppressor gene. These alterations then result in mucosal
proliferation forming a polyp and finally carcinoma. Since the discovery of the APC
mutation, it is seen as the major etiology of FAP26. APC mutations are also very common
in sporadic colorectal cancers. Mutations associated with the cause of HNPCC include
MLH1 and MSH2 germline mutations27. All these changes have been associated with
increased risk of recurrence following surgery. Although molecular markers are being
investigated28, the most important prognostic factor remains surgical pathologic staging
of the resected primary tumor, which is discussed later in this review.
Although most patients harboring a malignancy will have an isolated lesion on
presentation, approximately 3-10% of patients will present with cancer in multiple
locations. In addition, the presence of multiple adenomas has been shown to significantly
increase the risk of both subsequent colorectal adenomas and carcinomas29. Thus it is
imperative to ensure an evaluation of the entire colon is performed to exclude more
proximal or distant disease. Local and distant metastases, when present, occur following
tumor cell migration through lymphatic channels to mesenteric or para-aortic lymph
nodes and hematogenous spread to distant organs such as the liver, lung, and brain.
Lastly the degree of local invasion is critically important to accurate staging,
management, and prognosis. Once an invasive component is present, lymph node
metastasis and local recurrence are increased and often a more extensive resection than
just polypectomy is required. Haggitt and colleagues proposed a classification system
according to the depth of invasion seen on pathology following a polypectomy: Level 0
(no invasion muscularis mucosa), Level 1 (invasion through muscularis mucosa limited
to head of polyp), Level 2 (invasion through muscularis mucosa limited to neck of
polyp), Level 3 (invasion through muscularis mucosa in any part of the stalk), and Level
4 (invasion into the submucosa of the bowel wall below the polyp). These levels correlate
with degree of lymph node metastases with level 0-3 being associated with less than 5%
risk and level 4 has a 10-25% risk of associated metastases30.

5. Diagnosis
Colon cancer often causes no symptoms until it reaches an advanced stage, especially
with right sided lesions in a capacious cecum. Screening is therefore the primary
modality of diagnosis31. Symptoms may be present, but difficult to elucidate, as they are
often very general and not very specific. Thus in addition to hematochezia, melena,
abdominal pain, and change in bowel habits, patients should be questioned regarding
fatigue and weakness that may be due to iron deficiency anemia seen especially with
right-sided cancers. Iron deficiency is also seen more commonly in developing countries
due increased prevalence of parasitic infections. Weight loss may be present, but most
commonly seen in more advanced stages and metastatic disease. The abdominal pain can
be secondary to a number of conditions, including obstruction, peritoneal dissemination,
or perforation. A change in bowel habits is mostly seen in left-sided cancers as right-
sided cancers tend to grow outwards and, as such, very rarely cause obstruction outside of
obstructing the ileocecal valve. Tenesmus can be associated with colon cancer, although
again mostly with rectal cancer. Importantly, symptomatic patients tend to have a worse
prognosis as they often present in later stages32.
The initial diagnostic workup for patients either symptomatic or in need of screening is
similar with the exception of regular computed tomography (CT) scanning which has no
role in screening. A digital rectal exam (DRE) is needed to evaluate the rectum and
sphincter tone. It only detects tumors low enough to be felt in the distal part of the rectum
but is useful as an initial screening test. Fecal occult blood testing (FOBT) is used to test
for blood in the stool. It has the advantage of being inexpensive, and having good
compliance. A major disadvantage is that most colon cancers do not bleed till later stages
and many false positives are found. Yet in many large scale series, annual or biennial
testing with fecal occult blood has been shown to significantly reduce the incidence of
colorectal cancer. This is especially important in those areas where other screening
methods are limited. Sigmoidoscopy can be used for evaluation of the rectum and distal
part of the colon up to 60cm. The procedure can be performed in the office without
sedation. It is inexpensive and cost-effective; however, it can only evaluate the colon to
approximately the splenic flexure and, as such, could miss more proximal lesions: up to
40% of cancers are proximal to the splenic flexure. In general, colonoscopy is favored as
it not only can biopsy or remove a lesion as with sigmoidoscopy; it can also evaluate the
entire colon Double contrast barium enema (DCBE) can be used if scopes are
unavailable, but can miss sessile polyps. Accuracy of DCBE and colonoscopy are 67%
and 94%, respectively33. The sensitivity of DCBE for adenomas less than 0.5 cm is 32%;
for adenomas of 0.6-1cm is 53%; and larger than 1cm is 48% 34. With this procedure an
enema of barium sulfate is administered. Air is then insufflated into the colon, distending
it, resulting in a thin layer of barium over the inner mucosal lining. Plain film is used for
evaluation. For scopes and DCBE the colon needs to be prepped with bowel preparations
including polyetheleneglycol (PEG) and Magnesium Citrate. If these preparations are not
available, a clear liquid diet for 1-2 days may be used. Although still only available in
select institutions, virtual colonoscopy in which a CT scan is used to reconstruct a three-
dimensional image of the inner surface of the colon, has been recently added as a
recommended screening tool54. Here the CT replaces the plain film used in DCBE.
Polyps found, however, still need to be removed by standard colonoscopy. Standard
abdominopelvic and chest CT, while not used in routine screening, is essential in pre-
surgical evaluation. It can demonstrate regional tumor extension, lymphatic and distant
metastases, and potential complications like perforation and fistula formation. Other
modalities include plain chest radiograph for lung metastases and intra-operative
ultrasound for hepatic metastases.
Positron emission tomography (PET) is a 3-dimensional scanning technology in which a
radioactive sugar is injected intravenously and collects in tissues with high metabolic
activity, including cancer cells. Areas with high emission are suggestive of malignancy
and this test can be useful in localizing metastases or recurrence. Currently it is not used
for screening or for routine workup.
Other pre-operative tests that are suggested include a cell blood count (CBC), chemistry
panel, carcinoembryonic antigen (CEA), CA19-9, and liver function tests (LFTs). One
needs to be aware that CEA can be related to tumor load, but is not very reliable as it is
also elevated in pancreatic and hepatobiliary disease35. Its levels are often used for
monitoring response to medical treatment, especially in treatment of recurrence. A more
recent approach uses radioactively labeled antibodies directed against CEA36. Regarding
LFTs, they can be normal even with hepatic metastases and are thus not a reliable marker
for liver involvement, but allow some evaluation of liver synthetic function, and when
abnormal may lead to further evaluation for disease. Lastly genetic counseling and DNA
testing should be performed if available, especially in those patients with a known genetic
disposition or familial syndrome.
The most common colon cancer cell type is adenocarcinoma arising from the glandular
columnar epithelium, accounting for 95% of cases. Other types of malignancy include
lymphoma, sarcoma, melenoma and squamous cell carcinoma. The differential
diagnoses remains large and includes diverticulitis, colitis, inflammatory bowel disease,
ischemia, or foreign bodies.
As stated, accurate staging leads to both proper management and prognostic significance
for the patient. Therefore, depth of tumor penetration, presence of lymph node
involvement and distant metastases guide the preoperative clinical and postoperative
pathological staging process. Although radiographic and endoscopic findings can be used
to assign a clinical stage, surgical assessment and histopathologic examination are often
necessary outside of the end stage patient37. Currently two staging classification systems
are used: Dukes38 and TNM39 (Tumor, lymph Node and Metastases) (Table 1 and 2)
Approximately 15 to 20 percent of patients have distant metastatic disease at the time of
presentation. Spread occurs to regional lymph nodes or to the liver via the portal venous
circulation. The liver represents the most frequent visceral site of metastatic spread with
one third of recurrent disease being associated with hepatic lesions. Rarely CRC
metastasizes to the lungs, supraclavicular lymph nodes, bone, or brain without a liver
lesion being present through systemic hematogenous spread. The median survival after
the detection of such distant metastases is 6 to 9 months.
Most recurrences after a surgical resection occur within the first 4 years with one third to
one half occurring in the first 2 years. For this reason the 5-year survival rate remains
important for prognosis and predicting local and distant recurrence. (See below)

6. Surgical Management
Surgery is the only potentially curative modality for localized colon cancer. In addition, it
is often required for diagnosis, staging or palliation of tumor-related obstruction or
bleeding. Goals for surgery are exploration of abdomen, resection of involved segment,
and wide lymphadenectomy—all with minimal complications. Total colectomy is
necessary in patients with familial syndromes, multiple lesions, or those at high risk for
further development of a malignancy. Pre-operative bowel prep is often recommended to
reduce microbial load40 although the utility of bowel preparation in elective surgery has
been questioned, with some evidence suggesting it actually increases postoperative
complications41.
The vast majority of polyps can be removed at the time of diagnosis via the endoscope.
Solitary tubular adenomas can be removed by either ligation or snaring of the pedicle for
those pedunculated lesions or piecemeal polypectomy. Sessile lesions may need removal
by submucosal dissection, but depending on size location (i.e., >4cm or right sided in the
thin-walled cecum) surgical excision is often indicated. Complete excision is always
desirable for good pathologic assessment. If carcinoma is discovered in the polyp without
invasion of the line of resection, no further workup is necessary. If it is, surgery is
indicated. As discussed previously, level of invasion is important in risk of lymphatic
metastases and plan of surgery. Criteria needed for endoscopic management include:
Haggitt level 1, 2 and 3; polyp is complete at pathologic examination and can completely
be evaluated; no vascular or lymphatic invasion is present; no poor histological
differentiation; and the margin of excision is not involved46.
After resection, the remaining colon segments are primarily anastomosed to create a
functioning colon, if possible. If this is not possible or in those patients with distal lesions
and poor sphincter control a stoma is created. The extent of resection should include at
least a 5 cm segment of normal bowel on either side42. Excision of accompanying
vascular arcades and associated mesentery is needed to completely excise the associated
lymphatics. Recommendations are that at least 12 lymph nodes should be assessed for
accurate staging and prognosis43. Sentinel node biopsy at the time of colon resection can
be used and is under investigation44. A no touch technique has been advocated by some
authors with the goal of avoiding intraoperative tumor manipulation to decrease shedding
of tumor cells45. This involves early division and ligation of the vascular supply, and
occlusion of the proximal and distal bowel lumen around the area of the tumor prior to
resection of the tumor bearing colon.
Patient positioning can be either supine or low lithotomy position. Before the skin
incision patients should have preoperative antibiotics and deep venous thrombosis
prophylaxis. Although not mandatory, ureteral catheters can be considered for help in
ureteral identification during surgery. Skin incision can be midline or lower transverse.
Resection of right-sided colon cancer is done via a right hemicolectomy. Overall care
must be taken to visualize and protect the duodenum, right ureter, and right gonadal
vessels as the right colon is mobilized. Visualization of these structures is mandatory to
prevent injury. Mobilization begins at the ileocecal junction and continues along the
lateral peritoneal attachments up to the hepatic flexure. This allows medial mobility of
the colon away from the retroperitoneal tissue to give exposure to the ureter, spermatic
vein and ovary if present. Some surgeons prefer a medial approach in which the ileocolic
artery is initially divided and dissection proceeds in a medial to lateral fashion between
the retroperitoneum and mesentery. With either method, when local invasion is present,
multivisceral enbloc resection is necessary to obtain negative margins47. Tissue planes
between tumor and invaded organ should never be disrupted as this may decrease the
cure rate by more than 50 percent48. In general, the right colon is resected up to the right
of the middle colic vessels with ligation and resection of the right branch of the middle
colic artery. Lesions located at the hepatic flexure may require an extended right
hemicolectomy with division of the middle colic artery at its base and extended resection
of the associated bowel and mesentery. During this procedure, the lesser sac is entered
via detachment of the omentum from the greater curvature of the stomach. If the cecum
is involved, the specimen should include approximately 30cm of the terminal ileum in the
resection. Control the ileocolic and right colic vessels as they are encountered during
dissection can be performed with clamps or tissue sealant devices. In general dividing
vessels about 1cm from the branch divisions is often preferred to prevent narrowing of
the remaining vessels, though major branches should be taken proximally to ensure
adequate lymph node retrieval. After ligation of all necessary vessels and mesentery, the
specimen can be transected and delivered. Once adequate hemostasis and integrity of
remaining structures such as the ureter has been confirmed, the bowel anastomosis can be
performed with a one or two layer suture closure or stapling technique. Rotation of the
ileum may be necessary and closure of exposed mesentery may be performed.
Left colon cancers require a left hemicolectomy with associated draining lymphatics or a
sigmoid colectomy49. After thorough abdominal exploration, the inferior mesenteric
artery is identified and ligated after the takeoff of the left colic branch for more distal
lesions or just at the takeoff of the left colic branch for a standard left hemicolectomy.
Although high ligation near the aorta has been advocated by some authors, others have
failed to demonstrate any survival advantage from this practice, even in those with stage
III lymph node positive disease. The inferior mesenteric vein is ligated at the point of the
duodenojejunal recess. Mobilization begins with the colon by dividing the arcade vessels
and peritoneum at the left colic gutter from the base of the peritoneal reflection from the
rectum to the splenic flexure. The mobilization proceeds again with lateral to medial or
medial to lateral fashion and again identification of the ureter should take place early.
The rectum may be mobilized for a small distance by separating the mesentery from the
sacrum and ligating the mesenteric vessels at the rectosigmoid colon, although these
planes should normally be relatively preserved with colon cancers. For an extended left
hemicolectomy, full splenic flexure mobilization should be performed with division of
the splenocolic ligament prior to mobilizing the transverse colon to the base of the middle
colic artery. This vessel is dividing either near its base at the pancreas or division of the
left branch for a standard left hemicolectomy. Once the remainder of the colon is
mobilized, it is divided at the proximal and distal ends, and an anastomosis is performed.
Additional length can be obtained by further mobilization of the rectum or more proximal
mobilization (including ligation of the middle colic near its base if that was not
performed). Excess tension should be avoided at all costs to avoid an ischemic
anastomosis. Care must be taken to not damage the left ureter, left gonadal vessels, and
tail of the pancreas during resection. Also small tears might occur in the spleen by
excessive retraction and should be avoided.
Tumors in the transverse colon are usually resected from the hepatic flexure to the splenic
flexure, extended right hemicolectomy (the authors’ preference) or extended left
hemicolectomy, with removal of the contiguous mesentery of the middle colic vessels
and techniques described above. If a total colectomy is indicated, for example with FAP,
primary anastomosis is still possible with an ileorectal anastomosis.
In general, metastases are associated with poor prognosis. However colon resection is
indicated unless there is carcinomatosis to prevent local complications of obstruction and
perforation. Patients with isolated liver or pulmonary metastases may be resectable for
cure. Resectability of a liver metastasis is determined using preoperative imaging,
intraoperative ultrasound, and by direct palpation and visualization during resection.
Lesions in the right lobe are amenable to right hepatectomy while small lesions of the
central or left liver lobe can be resected through anatomic "segments.” Lesions that
initially are not amenable to surgical resection may become so after preoperative
chemotherapy or immunotherapy regimens. Lesions that are still not amenable to surgical
resection can be treated with modalities including radio-frequency ablation, cryoablation,
and chemoembolization.
Unresectable or metastatic disease can benefit from palliative surgery for relief of
obstruction or control of bleeding via resection, stoma construction, or, in severe cases,
side-to-side bypass. Ostomies can be divided into loop colostomy or end colostomy with
or without creation of a mucous fistula. With the first method stool is diverted through
the ostomy. A mucous fistula serves to decompress the secretions from the distal bowel.
End colostomy without mucous fistula diverts the stool with the distal bowel ending in a
blind loop, also referred to as a Hartmann’s pouch.
Colorectal cancer is the most common reason for colonic obstruction in the United States,
whereas volvulus is the more common cause in developed countries. In general
management of malignant obstruction should be considered for immediate resection if
possible as it is a surgical emergency. Distention due to gas buildup from swallowed air
and bacterial fermentation and accumulation of stool and liquid occurs rapidly. Also
vascular compromise is a risk due to increased intramural pressure and can result in
ischemic necrosis. A closed loop obstruction occurs when both the proximal and distal
ends of the colon are occluded. Obstruction due to cancer in the rectum is often relieved
by colostomy followed by neoadjuvant chemoradiation with later resection. Colon cancer
on the other hand can be surgically treated with primary anastomosis if healthy ends of
resection are present, or by colostomy if deemed necessary60. Where available, colonic
stenting is an option for resolution of the obstruction itself without treatment of the
cancer. Always keep in mind that pseudo-obstruction or Ogilvie’s Syndrome needs to be
ruled out before committing to mechanical obstruction.
Lastly, laparoscopic approaches have been increasingly applied and are evolving.
Though the technology is often not available in developing countries, or rural areas, it is
gaining foothold as a preferred approach in many centers. Yet, technical experience is
required to ensure adequate and equivalent outcomes as its open predecessor. Several
series have demonstrated advantages including reduced postoperative pain, earlier
recovery of bowel function, and shorter length of hospital sta50. A unique complication is
tumor spread in port sites, though this has not been borne out in larger studies apart from
the initial reports following the early use of this modality. Overall, the laparoscopic
approach provides oncologic outcomes that are comparable to those achieved using open
approaches51.

7. Medical Therapy
Although an extensive review of the medical therapy for colon cancer is beyond the
scope of this article, a few generalizations should be noted. Adjuvant therapies for colon
cancers are very distinct from those for rectal cancers. Whereas in rectal cancer,
chemoradiation therapy is extensively used, often in an upfront role, in colon cancer,
chemotherapy remains the principal adjuvant treatment, with the addition of radiotherapy
not showing improved outcome52. In this setting chemotherapy is used to reduce the
likelihood of metastasis developing, shrink tumor size, or slow tumor growth.
Chemotherapy is often applied after surgery for cure (adjuvant) or as the primary therapy
if surgery is not indicated (palliative). Very rarely with colon cancer will chemotherapy
be used in a neoadjuvant (initial) setting. In general, adjuvant treatment should be started
within 6-7 weeks of surgery, following healing of the surgical wounds. Although this has
been well established in stage III disease, use in stage II disease is less clearly defined.53
Regimens include the combination of 5-fluorouracil, leucovorin, and oxaliplatin,
Irinotecan has also been used with more recently bevacizumab, a monoclonal antibody to
VEG-F, being used in the recurrent and resistant disease. It is often given IV over a 4-6
week time frame on a weekly basis. Intrahepatic lesions if not treated with surgery can be
treated with chemotherapy as well, either systemically with the above regimens or
intraarterial with Floxuridine. If progression of disease occurs during adjuvant therapy,
options are limited. Repeat surgical resection may necessary or other second line
chemotherapeutic agents could be used.
Other therapies are being investigated like Bacillus Calmette-Guérin (BCG) as an
adjuvant mixed with autologous tumor cells in immunotherapy54 and introduction of
exogenous genes. All these hold enormous potential, although considerable practical
difficulties remain.

8. Screening
The rationale for colorectal cancer screening programs lies both in the fact that the earlier
detection of localized, superficial cancers in asymptomatic individuals will increase the
surgical cure rate and that the detection and resection of polyps prior to cancerous
development decreases the incidence of CRC55. Screening is recommend for CRC in
average-risk people older than 50 years as well as in people 40 years old and older that
have a family history of CRC. Modalities are discussed above. Guidelines include fecal
occult blood testing every year combined with flexible sigmoidoscopy every 5 years,
double-contrast barium enema every 5-10 years, colonoscopy every 10 years and recently
virtual colonoscopy every 5 years has been added56

9. Prognosis and Complications

The overall 5-year survival rate from colon cancer for all-comers in all stages is 60%. In
the United States nearly 60,000 patients die of the disease each year, making it the second
leading cause of death. Accurate staging allows the physician to provide prognostic
information to the patient. As a part of this, determining depth of invasion, number of
involved lymph nodes (one to four lymph nodes versus five or more lymph nodes)57 and
presence of distant disease is imperative. The survival rate depends on the stage at the
time of diagnosis. Approximate 5-year survival rates are: stage I 90%,; stage IIA 85%;
IIB 72%; IIIA 83%, IIIB 64%, stage IIIC 44% and stage IV 8%.
After an apparently curative resection, diagnostic concern should focus on the early
recognition of recurrence and the detection of metachronous carcinomas and adenomas.
In 30-50% of patients recurrent disease develops despite undergoing an initial apparently
curative resection, with the majority of these manifesting within the first 2 years. Local
recurrence alone accounts for approximately one third of recurrences, distant metastases
alone (mostly hepatic) are found in approximately 45%, and in the remainder multiple
locations are involved58. Once recurrent disease is discovered, the average survival time
is usually less than a year, although improvements in adjuvant therapy have improved
this dismal outcome.
Surgery may be necessary to obtain diagnostic tissue in patients with recurrent disease.
These patients may warrant reexploration for diagnosis and possible resection. Although
a minority of such patients may still have the potential for cure through a combination of
surgery and chemotherapy, extensive evaluation to fully elucidate the extent of disease is
imperative to ensure useful and not futile exploration.
Operative mortality in most centers is less than 5%, but increases with complicated cases
like perforation and small hospital volume of cases. The number one cause for morbidity
and mortality following surgery is cardiorespiratory complications such as myocardial
infarction and pneumonia, as most cancers occur in the elderly population. Although
anastomotic leaks following resection are a major morbidity and potential source of
mortality, these occur in only ~3-10% following colonic resection. When small, they can
be self-limiting and treated with antibiotics and/or drainage. Larger leaks may need
drainage by insertion of drains, although often re-operation and proximal diversion are
required.
Other nonfatal complications include wound infection, wound dehiscence, hernia,
fistulas, hematomas, genitourinary dysfunction like urinary retention and impotence,
adhesions and adjacent organ injury59.
Adverse effects from adjuvant therapy are common and include diarrhea, mucositis,
neutropenia, hair loss, skin hypersensitivity and sclerosing cholangitis. They can also
result in secondary complications such as dehydration with renal failure and metabolic
disorders following severe diarrhea or infectious risks due to neutropenia. To try to
prevent the likelihood of such adverse effects, initial adjuvant doses can be lowered and
increased over the next 2-3 doses.
10. Conclusion
Colon cancer is a health issue worldwide. Yet it is a potentially preventable disease,
highlighting the need for adequate mass-scale screening by whatever means available.
Primary prevention involves behavior modification and elimination of risk factors, such
as increasing physical activity, decreasing alcohol consumption and tobacco use, and
eating more fiber and other elements like calcium and folate. Secondary prevention
involves early tumor detection by screening and evaluation. Tertiary prevention includes
decreasing mortality in those patients with established tumors by proper surgical and
medical management. Colon cancer is a disease that requires multidisciplinary teamwork
from the general practitioner to the gastroenterologist, general surgeon, medical and
occasionally radiation oncologist. A well defined guideline for screening, biopsies,
surgical and medical management for both primary and recurrent disease is important to
not only screen appropriate patients and reduce its incidence, but also care for those
affected by this disease.

Lionel R. Brounts, MD*, Robert Zulu, MD+, Scott R. Steele, MD*

*Department of Surgery, Madigan Army Medical Center, Tacoma, Washington.

+
Department of Surgery, School of Medicine, Lusaka, Zambia

Corresponding author:
Scott R. Steele, MD
Department of Surgery
Madigan Army Medical Center
Fort Lewis, WA 98431
Phone: (253) 968-2200
Fax: (253) 968-0232; 968-5900
Email: harkersteele@mac.com

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