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380 R.K.S. Phillips and S.K. Clark
chemotherapy is considered. Treatment of desmoids preferably should take place in the setting of an international study.
Peutz-Jeghers Syndrome
This syndrome, which has an incidence in the region of 1 in
200,000, consists of perioral, buccal, and occasionally genital melanin pigmentation together with gastrointestinal
hamartomatous polyposis. Pigmentation can also be seen
on the lips and sometimes on the eyelids, hands and feet, or
be absent altogether. It usually appears in early childhood
and tends to fade in the late twenties. The polyps occur predominantly in the small intestine (78%), but are also found
in the stomach (38%), colon (42%), and rectum (28%).
They are hamartomas with a characteristic branching morphology, containing smooth muscle. Adenomatous change
with dysplasia and progression to invasive adenocarcinoma
has been observed.
77
Inheritance
Peutz-Jeghers is autosomal dominantly inherited with high
penetrance, and is caused by mutation of LKB1 (also known
as STK11) on chromosome 19p13.3,
threonine kinase of unknown function. Mutation of LKB1 is
only found in about 50% of cases, and has been formally
excluded in some,
79
suggesting that other genes are responsible in a proportion of cases. Although a family history is frequently evident, new mutations are responsible for a
significant number of cases.
78
which encodes a serine-
76
cell testicular tumors in prepubertal boys, and cervical malignancies.
Management
Gastrointestinal Surveillance
Two or three yearly gastroduodenoscopy and colonoscopy
with polypectomy are recommended, with barium study (and
increasingly capsule endoscopy) of the small intestine at the
same interval. Hemoglobin should be checked annually.
Small bowel polyps causing symptoms or anemia, or measuring more than 1.5 cm, should be removed at laparotomy with
intraoperative enteroscopy.
Laparotomy in Peutz-Jeghers Syndrome
The technique of laparotomy with intraoperative enteroscopy
was introduced to reduce the repeated emergency laparotomies and small bowel resections undertaken on these
patients. At laparotomy an enterotomy is made, usually at the
site of the largest polyp, and a flexible endoscope is passed
through a sterile laparoscope sheath to the proximal and distal ends of the small bowel. During scope withdrawal, polyps
are excised using a snare or electrocautery biopsy forceps,
and then retrieved via the enterotomy. This approach identifies many more polyps than conventional palpation and transillumination of the bowel, permitting removal without
multiple enterotomies and increasing obstruction-free inter-
82
val.
This procedure may be amenable to performance in a
laparoscopically assisted method.
Extraintestinal Surveillance
Clinical Issues
Polyp-related Complications
The most common clinical problems in Peutz-Jeghers syndrome are anemia caused by chronic blood loss from large
polyps and small bowel obstruction, caused by intussusception with a polyp at the apex. Repeated emergency bowel
resections can lead to increasing operative difficulty and even
short-bowel syndrome.
Risk of Malignancy
Follow-up studies have shown that individuals with this syndrome are at increased risk of developing a range of malignancies at a particularly young age.
years, approximately half of all patients in one series had died
of cancer, of which about half were gastrointestinal.
estimated that there is a 50-fold excess of gastrointestinal cancer in Peutz-Jeghers syndrome, resulting in a lifetime risk of
approximately 20% of colorectal cancer and about 5% of gastric cancer, as well as breast, pancreatic (30% lifetime risk),
ovarian sex-cord tumors (10% of females), feminizing Sertoli
80
Indeed, by the age of 57
81
It is
Mammography in premenopausal woman lacks sensitivity,
but there is little evidence to support ultrasound or MRI as
alternatives. Testicular tumors tend to occur in prepubertal
boys, and it would seem sensible to encourage regular examination. Women should undergo standard cervical and breast
screening according to nationally agreed protocols. Although
in some centers regular ultrasound scanning of the pancreas
and ovaries is performed, there is no evidence that such measures have any impact on prognosis. Indeed, even in rare cases
of familial pancreatic cancer, an appropriate screening
method remains controversial. It is important that clinicians
caring for these patients are aware of the high cancer risk, and
maintain a high index of suspicion.
Juvenile Polyposis
Juvenile polyps are hamartomas that lack smooth muscle histologically, having poor anchorage to the bowel wall, and not
infrequently becoming detached and being passed anally.
Solitary juvenile polyps may affect up to 2% of children and
adolescents, but have little or no malignant potential.
83
26. Polyposis Syndromes 381
Juvenile polyposis is characterized by the finding of multiple
juvenile polyps in the large bowel, although the stomach (and
perhaps small intestine) is affected as well in about 50%.
The precise number of juvenile polyps needed to make the
diagnosis varies among authors, with numbers between three
and five being suggested. Most affected individuals develop
50–200 polyps, but some have very few. One juvenile polyp
in a patient with a family history of juvenile polyposis is sufficient to diagnose juvenile polyposis.
It is a rare condition, with a frequency of about 1 per
100,000, and presents with rectal bleeding, anemia, or polyp
prolapse, at an average age of approximately 9 years. The
polyps are hamartomas, with a characteristic hyperplastic
stroma, abundant lamina propria, cystic glands, and inflammation. Adenomatous dysplasia occurs in up to half of these,
which may then progress to invasive adenocarcinoma.
Other morphologic abnormalities including macrocephaly,
mental retardation, cleft lip or palate, congenital heart disease, genitourinary malformations, and malrotations are
found in 10%–20%.
85
Genetics
This syndrome is genetically heterogeneous, with three separate genes currently implicated. Mutations have been identified in affected individuals in SMAD4 which lies on
chromosome 18q21 and is a known tumor suppressor gene,
implicated in sporadic colorectal carcinogenesis. It codes for a
protein involved in the transforming growth factor-β signaling
pathway, and germline mutations have been found in
35%–60% of juvenile polyposis patients in the United States,
but rather fewer (3%–28%) in Europe.
86
Recently, germline
mutations of BMPR1A on 10q22, which encodes a protein
involved in the same signaling pathway, have been found in a
further 15%.
called “juvenile polyposis,”
87
PTEN mutations have also been reported in so-
85
but it is as yet unclear whether
these are genuine cases, or in fact Cowden syndrome, or even
whether this syndrome is simply a clinical variant of juvenile
polyposis.
88
Cancer Risk and Management
The cumulative risk of colorectal cancer has been estimated at
30%–50%, and 10%–20% in the upper gastrointestinal tract.
First-degree relatives of affected individuals should be
screened by colonoscopy from around the age of 12 years if
asymptomatic
polyps can be controlled by regular endoscopic polypectomy,
with both upper gastrointestinal endoscopy and colonoscopy
recommended at least every 2 years. In cases in which polyps
are either too numerous or too large to be managed in this
way, colectomy and IRA or restorative proctocolectomy is
advised.
polypectomy are adequate to prevent malignancy, but there
are insufficient data to justify purely prophylactic colectomy.
89
and five yearly thereafter. In most cases, the
90
It is not clear whether endoscopic surveillance and
Affected individuals should also undergo upper gastrointestinal
surveillance from the age of 25 years.
84
Other Juvenile Polyposes
Several very rare dominantly inherited conditions have been
described in which juvenile-type hamartomatous colorectal
polyps occur together with other features. In these syndromes,
the juvenile polyps seem to be of low malignant potential.
Cowden Syndrome
This is autosomal dominantly inherited and attributable to
mutation of the PTEN gene,
sine phosphatase involved in inhibiting cell growth. It is characterized by macrocephaly (30%), trichilemmomas (which
are considered pathognomonic), and both benign and malignant neoplasms of the thyroid, breast, uterus, and skin. The
hamartomas occur in the mouth as well as other parts of the
gastrointestinal tract, resulting in a nodular appearance of the
buccal mucosa.
92
which encodes a protein tyro-
Bannayan-Riley-Ruvalcaba Syndrome
Here the juvenile polyps (50%) are associated with characteristic pigmented penile macules, macrocephaly, mental retardation (50%), lipomatosis, and hemangiomas. PTEN
mutations have also been identified in this syndrome.
seems likely as Cowden and Bannayan-Riley-Ruvalcaba syndromes are caused by mutation of the same gene that they are
slightly different forms of the same disorder,
have been identified in which both phenotypes are evident.
The risk of colorectal cancer is not clear.
87
and families
Metaplastic Polyposis
Metaplastic (hyperplastic) polyps are the most common
lesions observed in the large bowel, being found in 40% at the
age of 50 years. Their significance is unclear and there is
much controversy surrounding their potential as precursors of
adenomas and carcinoma. There is increasing evidence of
correlation between numbers of metaplastic polyps and adenomas and cancer risk.
86
loosely defined entity in which multiple hyperplastic polyps
95
In addition, metaplastic polyposis, a
are seen, does appear to be associated with an increased risk
of colorectal cancer, often with microsatellite instability.
There are at present, however, insufficient data to allow clear
guidance on clinical management.
Cronkhite-Canada Syndrome
This is a very rare condition with onset in adulthood and
no evidence of an inherited predisposition. The disease is
characterized by gastrointestinal hamartomatous polyposis
91
93
It
94
96
382 R.K.S. Phillips and S.K. Clark
together with ectodermal abnormalities including alopecia,
onychodystrophy, and hyperpigmentation of the skin of the
face and eyelids. The gastric mucosa resembles Ménétrier’s
disease, and malabsorption and protein loss can lead to anemia, diarrhea, weight loss, edema, and tetany. Hypokalemia
can also be a feature.
Multiple juvenile-type polyps, with marked inflammatory
features, are found in the duodenum in 75% of cases, the
small intestine in 50%, and occasionally in the stomach and
large bowel. Adenomatous change is seen and gastrointestinal
cancer has been reported in about 10%.
The pathogenesis of this condition is unknown, and there
is no established treatment. Management is essentially supportive, with aggressive fluid resuscitation and nutrition.
Tetracycline can help, and corticosteroids have also been
97
used.
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27
Colon Cancer Evaluation and Staging
Eric G. Weiss and Ian Lavery
Colorectal cancer is the third most common cancer affecting
persons in the United States. In 2004, there were an estimated
146,940 new cases of colon and rectal cancer with colon cancer making up the majority of new cases at 106,370.
approximately 38% of newly diagnosed patients with colorectal cancer in the United States will die of their disease.
1
Overall,
Clinical Presentation
Most importantly, colon cancers are diagnosed in patients
who are asymptomatic, who undergo surveillance, or who are
investigated for other problems such as amenia. In symptomatic patients, the most common presenting symptoms are
abdominal pain, change in bowel habits, rectal bleeding, and
occult blood in the stool.
that the tumor is more advanced than in asymptomatic
patients.
Abdominal pain is the most common presenting symptom
of colon cancer. The pain can vary in type, location, and
intensity. In the early phases or stages of colon cancer without evidence of obstructive symptoms, the pain can be vague,
dull, and poorly localized. With progression of the disease
with a larger growing mass or a mass causing obstruction,
symptoms of intestinal obstruction will eventually occur. This
type of pain is characterized by crampy, colicky pain, often
associated with meals, and occurring after meals. The location of the pain is often periumbilical or midabdominal but
can be located at the site of obstruction.
A change in bowel habits is the second most common
symptom of colon cancer. The changes seen can be very subtle or very significant. In early lesions the change may be
minor, with only a change in stool frequency. There can be
changes in size, shape, and/or consistency of bowel movements. Characteristic changes include narrowing of the stool,
irregular shape, and typically looser or diarrheal stool. The
symptoms will depend on the location of the tumor. Rightsided tumors occur where the bowel lumen is larger and the
2
These symptoms frequently mean
stool is liquid. Symptoms occur later, but on the left side
where the stool is more solid and the lumen narrower, symptoms occur at an earlier stage.
Rectal bleeding may be present in as many as 25% of
patients with colon cancer.
intensity and color. Bright red rectal bleeding is more consistent with a more distal location of a cancer. The mistake of
attributing rectal bleeding to hemorrhoids even in a young
population can lead to serious and at times fatal delays in the
diagnosis of a colon cancer. Almost all patients regardless of
age who present with rectal bleeding should undergo colonoscopic evaluation. In a series of 570 patients, 50 years of
age or younger with rectal bleeding who underwent endoscopic evaluation, there was a 17.5% incidence of colorectal
neoplasm.
Patients undergoing stool guaiac tests for occult blood in
the stool for routine screening with a positive result have a
5.1% chance of having an invasive cancer and a 24% chance
of having a benign polyp.
As mentioned previously, some of the symptoms that occur
may be early or late based on the distribution of cancer within
the colon. There has been a more proximal shift overall of
colon cancers with more tumors being in the proximal colon.
The Lahey Clinic reported a 10-year representative anatomic
site distribution in which the cancer was located in the right
colon in 18%, the transverse colon in 9%, the descending colon
in 5%, the sigmoid colon in 25%, and the rectum in 43%.
5
3,4
The bleeding may be of varying
6
7
Staging and Prognostic Factors
Evolution of Staging Systems
The original staging system for colorectal cancer was
reported by Cuthbert Dukes in 1930 and then revised by him
in 1932.
Stage A had the cancer limited to the bowel wall, Stage B had
cancer that spread by direct extension to extrarectal tissues,
8
This classification had three stages: A, B, and C.
385
386 E.G. Weiss and I. Lavery
and Stage C had cancer with regional lymph node metastasis.
Dukes further revised the classification in 1944 to subdivide
the Stage C group into those with positive regional lymph
nodes below a ligature (C1) and at a ligature (C2). In addition a more advanced stage, Stage D was added for distant
metastases.
Others have subsequently modified the Dukes’ staging system in an attempt to further stratify, prognosticate, and treat
patients with a more useful system. The most common modification is know as the Astler Coller Modification.
9
In this
modification, the Dukes’ B and Dukes’ C tumors are subdivided into two groups, each with Dukes’ B having depth of
tumor invasion into but not through the colonic wall with (B2)
or without (B1) lymph node involvement. Similarly, Dukes’ C
tumors with full-thinness tumor invasion involving lymph
nodes, Stage C2, and when they are not C1. Although both the
Dukes’ and modified Dukes’ staging systems are still used,
the TMN staging system is the preferred method of colorectal
cancer staging.
Current Staging Systems
The TNM classification is the system developed by the
American Joint Committee on Cancer (AJCC) and the
International Union Against Cancer (UICC). It utilizes three
descriptors based on each letter in the name, T for tumor
depth, N for nodal involvement, and M for metastases. Based
on a combination of T, N, and M for any given tumor, an
overall stage from Stage I to IV can be determined. The most
recent AJCC/UICC definitions were published in 2002.
The T stage can be divided into seven possible categories
based on the depth of invasion. Tis, carcinoma in situ, represents a nonmalignant tumor, T1 has invasion into the submucosa, T2 has invasion into the muscularis propria, T3 has
invasion into the subserosa or nonperitonealized pericolonic
or rectal tissue (through the bowel wall). T4 has invasion of
other organs or structures. The T3 category can be further
subdivided by the depth of penetration into the muscularis
propria. The N stage can be divided into three categories. N0,
with no lymph node involvement, N1 with 1–3 lymph nodes
involved, and N2 with 4 or more lymph nodes involved. The
M stage is only divided into two categories, either no metastases (M0) or distant metastases (M1).
Typically, the combination of T, N, and M will lead to one
of four stages based on the combination of findings. Stage 0
is Tis, N0, and M0. Stage 1 is T1 or T2, N0, M0. Stage 2 is
T3 or T4, N0, M0. Stage 3 is Any T, N1 or N2, and M0. Stage
4 is Any T, Any N, and M1. In the most recent AJCC/UICC
Definitions, Stage II and III are subdivided into two Stage II
categories: Stage IIA (T3, N0, M0) and Stage IIB (T4, N0,
M0); and three Stage III categories: Stage IIIA (T1 or T2, N1,
M0), Stage IIIB (T3 or T4, N1, M0), and Stage IIIC (Any T,
N2, M0).
The importance of staging is for treatment planning and
prognosis.
10
Clinical Prognostic Factors
Age
As with many cancers, colon cancer incidence increases with
increasing age. Most series report a mean age in the sixth
decade for nonhereditary colon cancer. Patients with familial
adenomatous polyposis (FAP) will present with colon cancer
in their mid to late 30s if colectomy is not performed before
this age. Patients with hereditary nonpolyposis colorectal cancer (HNPCC) can present at any age but tend to have colon
cancer between the ages of 40 and 60, significantly younger
than individuals with nonhereditary colon cancers.
It has been reported that younger patients present with
worse tumors being of more advanced stage and grade.
However, recent studies refute this claim. O’Connell et al.
recently reported using SEER data a comparison of two groups
of patients with colon cancer. The SEER database is a prospectively entered database of the National Cancer Institute in the
United States and stands for Surveillance, Epidemiology, and
End Results. They compared outcome in patients 20–40 years
of age to those 40–60 years of age. Although there was an
increased incidence of higher stage tumors, stage for stage
they had an equivalent or improved 5-year survival.
Symptoms
Obstruction and perforation are poor prognostic signs often
associated with advanced disease. In addition, because patients
are operated on in an urgent manner, their operative morbidity
and mortality is increased. Chen and Sheen-Chen
on outcome in patients with obstructing and/or perforated
colon cancer. Perforated cancers had a 9% operative mortality
compared with obstructed cancers of 5%. Overall 5-year survival was 33% in each group, approximately 2 times the
expected rate based on similar stages in noncomplicated cases.
Blood Transfusion
Blood transfusions can cause immunosuppression in the postoperative period which may allow for an inability to combat
tumor cells shed at the time of surgery and theoretically lead
to a worse prognosis. Sibbering et al.
13
patients with colon cancer, some of whom received blood
transfusions and others that did not. There was no difference in
survival comparing the two groups. However, Chung et al.
reviewed 20 papers, representing 5236 patients supporting the
hypothesis that perioperative blood transfusions are associated
with an increased recurrence and death from colon carcinoma.
Adjacent Organ Involvement
Local extension of colon carcinoma can involve any structure
or organ adjacent to the primary tumor. It occurs in 5%–12%
of colorectal cancers. All tumors with local extension would
12
reported
reported on 266
11
14
27. Colon Cancer Evaluation and Staging 387
be considered T4. For right colon cancers, the most frequently
involved structures are the liver, duodenum, pancreas, and
abdominal wall. Kama et al.
15
reported a 75% disease-free
survival of 14–41 months after en bloc pancreaticoduodenectomy and right colectomy. Similarly, Izbicki et al.
16
reported
on 83 patients with colorectal cancer undergoing extended en
bloc resections. Comparing extended to nonextended resections; mean survival of both groups was around 45 months
conferring the benefit of extended resections when necessary
to achieve R0 resections. These data were supported by
Kroneman et al.
17
who found 4-year survival was 33% after
en bloc resection compared with those receiving noncurable
resections of 6 months.
Histologic/Biochemical/Genetic Factors
Histologic Grade
Broders described classifying adenocarcinomas by the
degree of differentiation. He described four grades based on
how much of the tumor had differentiated cells within it.
Today three grades are used and include Grade 1 with welldifferentiated features, Grade 2 moderately differentiated,
and Grade 3 poorly differentiated. The vast majority of colon
cancers are moderately differentiated (Grade 2) with preservation of gland-forming architecture. However, the amount
of preservation of this architecture is variable and when
absent leads to sheets of invasive cells classified as poorly
differentiated. The degree of differentiation corresponds to
prognosis. Poorly differentiated tumors have a worse prognosis stage for stage compared with better differentiated
18
tumors.
Mucin Production and Microsatellite Instability
Microsatellite instability, known as MSI, is associated with
HNPCC. MSI is an alteration in mismatch repair genes which
are important to repairing errors in replication. When altered,
they can lead to colorectal cancer. Because there is loss of one
of the two alleles in HNPCC, these patients tend to present
earlier in life, with multiple colonic and extracolonic cancers.
Many HNPCC cancers are mucin producing which when
present have a better prognosis compared with non–mucinproducing tumors in these patients.
Signet-cell Histology
Signet-ring or signet-cell tumors have a worse prognosis in
many intestinal cancers. Signet-cell tumors tend to be of a
more advanced stage when discovered. In a comparison
between signet-ring and non–signet-ring colon cancers, it was
noted that patients with signet-ring cancers were younger, had
more advanced stages, and an increased incidence of liver
metastases.
19
In addition, the rate of curative resection was
lower at 35% compared with 79%. This rate was similar to
poorly differentiated tumors at 46% at 5 years. In another
study, the risk of peritoneal seeding was higher in signet-cell
tumors leading to a high incidence of palliative resections and
a mean survival of 16 months.
20
Venous Invasion
Blood vessel invasion has been linked with poor prognosis
both independently as well as with its association with lymph
node metastasis. Blood vessel invasion can occur intramurally
within the wall of the colon itself or in the surrounding tissue.
Although arterial invasion occurs, most series define and
describe vascular invasion based on venous invasion. Venous
invasion in colon cancer occurs in 42% of patients and
increases with increasing grade and stage.
21
Patients with
blood vessel invasion had a 74% survival compared with
those without it at 85%. In those patients with both intramural and extramural vascular invasion, the prognosis was even
worse at 32%.
Perineural Invasion
The growth of tumor along perineural spaces is known as perineural invasion and, similar to venous invasion, it increases
with increasing grade and stage of the tumor. It occurs in
14%–32% of colorectal cancers and can extend to as far away
as 10 cm from the primary tumor. Numerous studies have
confirmed poorer prognosis when perineural invasion is
22,23
noted.
Lymph Node Involvement
Lymph node metastasis has been long understood to be one
of, if not the most, important prognostic factors in colon cancer outcome. All currently utilized staging systems as
described above for colon cancer use and rely on the presence
or absence of lymph node metastases. It is therefore important
to adequately remove the lymph node bearing tissue associated with the underlying colon cancer. It has been reported by
Scott and Grace
25
that, if 13 lymph nodes are not recovered,
adequate staging cannot be performed. The main determinant
for an adequate lymph node harvest is surgical but a variety of
means to enhance the yield have been developed and include
fat clearance with xylene, other chemicals, and polymerase
chain reaction techniques.
26
Using these techniques, more
lymph nodes, or lymph nodes not found by standard techniques, can be discovered, improving the accuracy of staging
and allowing for better prognosis and application of adjuvant
treatment.
Carcinoembryonic Antigen
Carcinoembryonic antigen (CEA), a glycoprotein absent
in normal colonic mucosa but present in 97% of patients
388 E.G. Weiss and I. Lavery
with colon cancer, was discovered in 1965.27CEA increase
correlates with either disease that has metastasized to the liver
or with very large tumors. Patients with disease confined to
the colonic mucosa or submucosa will have increased CEA in
30%–40% of cases. It is therefore not useful for screening but
can be used to follow patients with colon cancer. In patients
with increased CEA preoperatively and localized disease that
is resectable, the CEA should decrease after surgery. If the
CEA level does not decrease, then occult metastases may be
present and may be an indication for adjuvant therapy. The
absolute level of CEA is also important. A CEA of greater
than 15 mg/mL predicts an increased risk of metastases in
otherwise apparently curable colon cancer.
28
A normal preoperative CEA may become increased with metastatic disease.
Controversy exists as to the utility of following CEA postoperatively because it may not allow any advantage to salvage or
treatment when compared with symptomatic recurrences.
Despite that, the routine periodic CEA measurement is
endorsed by the American Society of Colon and Rectal
Surgeons in their Practice Parameters.
30
Sentinel Node
The idea of a sentinel lymph node being present and if identified be able to predict lymph node metastases has become
standard of care in breast cancer and melanoma. Its application to colon cancer is in its infancy and may be less important in colon cancer than these others. The idea that the
lymphatic drainage can be mapped and the first node identified has significance in oncologic surgery. In colon cancer,
resecting the associated lymphovascular pedicle with the primary cancer is considered paramount to performing an adequate operation; this adds little to no morbidity unlike
excising level 3 nodes in breast cancer patients. In an attempt
to validate the sentinel lymph node theory in colon cancer,
Paramo et al.
who underwent intraoperative sentinel lymph node mapping
using isosulfan blue dye. Sentinel lymph nodes were identified 82% of the time and predicted regional metastases in
98% of cases, with only a single case of a false-negative sentinel lymph node. Others have agreed that its utility may be
marginal in colon cancer.
31
reported on their experience with 45 patients
32
Intramural Spread
Intramural spread is the tumor spreading along the bowel wall
either proximally or distally in one of the bowel wall layers.
Like rectal cancers, colon cancer rarely spreads this way. In a
study of 42 colorectal cancers of which 64% were colonic, the
maximum extent of intramural spread was 2 cm.
34
ports the practice of excising 5 cm or more of colon on either
side of a tumor to decrease the risk of anastomotic recurrence.
Transmural Spread
As they become more advanced, colon cancers invade the
colonic wall. Almost all colon cancers start as a mucosal
lesion and then penetrate a variable degree into deeper layers
of the colonic wall. This colonic wall invasion is the basis of
29
many of the currently used staging systems including the
Dukes’ and TNM. Transmural spread is the mechanism that
produces T4 tumors. T4 tumors penetrate full thickness into
the colonic wall and then by direct extension or adherence,
invade into other structures in proximity to the primary tumor.
When present, en bloc resection is mandatory for an R0 resection. Preoperative evaluation can sometimes predict adjacent
organ involvement but often it is an intraoperative finding.
Margins
The acceptable bowel wall margins are dictated by three
issues: first, thickness of penetration of the bowel wall margin
and the risk based on the distance of local tumor spread intramurally. As described above, colon cancer rarely invades
proximally or distally along the bowel wall for more than
2 cm. Convention has led to the recommendation that proximal and distal margins be a minimum of 5 cm. It has been
stated that the “ideal extent of a bowel resection is defined by
removing the blood supply and the lymphatics at the level of
the origin of the primary feeding arterial vessel.”
other two factors may modify the length of the proximal
and/or distal margins because further resections may be
required because of these issues.
Radial Margins
This sup-
35
These
36
DNA Ploidy
Normal cells are made up of diploid cells. Tumors can maintain normal diploid cells or can be aneuploid. Numerous studies show that nondiploid tumors have a worse prognosis and
correlate with more advanced Dukes’ stage.
33
Spreading Patterns
Colon cancer can spread via a variety of pathways. Spread
can be local or distant based on these pathways.
The circumferential margins are important to both colon and
rectal cancer, but most series and studies have been confined
to rectal cancers. It has been shown that positive circumferential margins in rectal cancer are associated with local recurrence rates as high as 85%.
36
In colon cancer, the radial
margins are less important with the exception of T4 tumors
where en bloc resection is required. Typically for colon cancer, the only radial margin that may be involved in a tumor
less than T4 are those tumors with serosal involvement. In
279 patients with colon cancer, serosal involvement was not
associated with a poorer outcome, and outcome was related
only to tumor stage.
37
27. Colon Cancer Evaluation and Staging 389
Transperitoneal/Implantation
Tumors with serosal involvement can shed viable tumor cells
which can spread throughout the peritoneal cavity and
implant on a variety of structures. Usually, tumors will
implant on the ovaries, omentum, serosal, or peritoneal surfaces. When widespread, this is known as carcinomatosis.
When localized to the ovaries which occurs in 3%–5% of
patients, bilateral oophorectomy should be performed. In a
recent series, 86% of patients with ovarian metastases had
transmural extension of the primary colon cancers.
38
Lymphatic
Lymphatic invasion is the most common mechanism leading
to metastatic disease. Lymphatics exist within the colonic
wall and lymphatic invasion correlates with the depth of penetration of colon cancers. T1 tumors have a risk of lymph
node involvement up to 9%, T2 up to 25%, and T3 up to 45%.
Most currently used staging systems assign increased stage to
increasing T stage and lymph node involvement and prognosis correlates with the overall stage. The lymphatic drainage
goes along the venous drainage of the colon, ultimately coursing through the portal vein and into the liver. Metastatic liver
disease is believed to occur typically as a result of lymphatic
spread.
remainder of the colon. Six lesions greater than 1 cm were
identified with five of six being proximal cancers or advanced
adenomas.
40
Virtual colonoscopy was used in 34 patients suspected of colon cancer with incomplete colonoscopies. Virtual
colonoscopy identified all primary and three synchronous
tumors proximal to the primary tumor.
40
When a colon cancer
is diagnosed by colonoscopy, synchronous cancers occur in
6% or fewer of patients. When present, it should raise the suspicion of possibly HNPCC which is associated with synchronous colon cancer. When synchronous colon cancer is
diagnosed, the treatment should consider a subtotal colectomy.
Distant Metastatic Disease
Distant metastatic disease associated with colon cancer is
almost always either liver or lung metastases. Although bone,
brain, and other organ involvement can occur, it is rare and
therefore the search for these metastases in an asymptomatic
patient is unwarranted. The search for liver and lung metastases can be accomplished by a variety of imaging studies
including ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), chest X-ray, and positron
emission tomography (PET) scans. Each test has different
abilities, availabilities, and costs.
Liver Metastases
Hematogenous
Hematogenous spread of colon cancer is less common than
lymphatic spread. Hematogenous spread will bypass the liver
and allow tumor cells to go peripherally into the systemic circulation. This is thought to be the mechanism for the development of pulmonary metastases.
Metastatic Evaluation
Once diagnosed with colon carcinoma, a search for metastatic disease is often performed. This assessment includes a
variety of imaging studies, laboratory tests, and endoscopic
procedures.
Detection and Management of Synchronous
Lesions
Synchronous polyps and cancers occur in patients with colon
cancer. Most colon cancers are diagnosed by colonoscopy and
the remainder of the colon is evaluated at the same time by
colonoscopy. However, if an obstructing lesion is noted that
will not allow a colonoscope to pass, evaluation of the more
proximal colon may be jeopardized. Alternatives to evaluating
the remainder of the colon in these instances include contrast
enemas, virtual colonoscopy, or intraoperative colonoscopy at
the time of resection. In a series of 158 patients with incomplete colonoscopies, barium enema was used to examine the
The first available test for the evaluation of the liver for
metastases is surface ultrasound. Surface ultrasound is available in almost all institutions; however, its accuracy compared
with newer modalities is lower in comparative studies comparing it with CT and liver scans.
41,42
CT scan is the most frequently used method to preoperatively and postoperatively determine the presence or absence
of liver metastases associated with colon cancer. There are
numerous advantages to cross-sectional imaging such as CT
over ulstrasound and include the ability to find abdominal
wall or contiguous organ invasion as well as liver metastases.
Standard CT scan is 64% sensitive in identifying liver lesions
larger than 1 cm. MRI of the liver has been poorly studied and
is not typically used in the evaluation of liver metastases.
Lung Metastases
Lung metastases occur in 3.5 % of patients with colon can-
43
cer
; there are limited data on the utility of plain chest radiographs or CT scans in the initial evaluation of the lungs for
metastatic disease. CT scan clearly has advantages over plain
radiographs and can identify and characterize lung pathology
better than plain X-rays. Given that most patients will
undergo CT imaging of the abdomen before surgical intervention, the addition of imaging of the chest via CT seems
reasonable. One must be careful about the amount of intravenous contrast when simultaneously scanning multiple
regions such as chest, abdomen, and pelvis.
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