Ann Surg Oncol (2012) 19:25002505
DOI 10.1245/s10434-012-2292-8
ORIGINAL ARTICLE COLORECTAL CANCER
T4N0 Colon Cancer Has Oncologic Outcomes Comparable
to Stage III in a Specialized Center
Matteo Rottoli, MD, Luca Stocchi, MD, and David W. Dietz, MD
Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH
ABSTRACT
Background. National data indicate that patients with
T4N0 colon carcinoma have worse oncologic outcomes
than other stage II cases. Our hypothesis was that opti-
mized surgical resection and lymph node staging in a
specialized center could eliminate discrepancies in onco-
logic outcomes within stage II colon carcinomas.
Methods. Patient characteristics and outcomes after on-
cologically radical colectomy for pT4N0 were compared to
control groups of T12N1, T3N1, and T3N0 cases. Group
comparisons were adjusted for age, American Society of
Anesthesiologists score, tumor location, year of surgery,
and duration of follow-up. Cases with at least 12 collected
lymph nodes and uninvolved resection margins (R0) were
analyzed separately. In addition, the T4a subgroup was
compared to both T4b cases with involvement of bowel
loops and with infiltration of other organs or structures.
Results. T4N0 patients had worse oncologic outcomes
than T12N1 patients and were comparable to T3N1
patients, regardless of margins status or lymph node col-
lection. When a T4b tumor infiltrated bowel, survival and
recurrence rates were similar to T4a cases, while T4b
tumors involving other organs were associated with
increased recurrence rate and reduced survival.
Conclusions. T4N0 colon carcinoma remains associated
with poor oncologic outcomes, regardless of treatment in a
specialized center. The biologic aggressiveness of T4N0
colon cancers and the different oncologic outcomes
Poster presentation at the Annual Meeting of the American Society of
Colon and Rectal Surgeons, May 1519, 2010, Minneapolis, MN.
Society of Surgical Oncology 2012
First Received: 10 February 2011;
Published Online: 7 March 2012
L. Stocchi, MD
e-mail: stocchl@ccf.org
according to specific organ infiltration should be taken into
consideration in the choice of adjuvant therapies.
Despite increased awareness and emphasis on screening,
the incidence of colon cancer remains approximately 100,000
new cases per year, with a cumulative estimated mortality of
50,000 cases per year in the United States.1 Evaluations of
national administrative databases indicate that T4N0 colon
carcinoma is associated with worse oncologic outcomes when
compared with the other patients with stage II disease.2 These
findings have been previously described by other single-
institution series, where stage IIb disease was associated with
decreased survival when compared to stage IIIa (T12N1)
disease.35 However, other studies have reported that T4
stage, contiguous tumor invasion, and multivisceral resection
do not adversely affect long-term survival.69
A worse outcome for T4N0 patients might be caused by
a more inherently aggressive biologic behavior, under-
staging of node-positive tumors, or incomplete surgical
resection for these often challenging cases. If the main
reasons for worse oncologic outcomes after resection of
T4N0 carcinomas reside in technical difficulty or inaccu-
rate staging, it is possible that surgical treatment and
pathologic staging in a specialized center might result in
improved oncologic outcomes than what is reported in the
national administrative database.
The aims of this study were therefore to analyze peri-
operative and oncologic outcomes of T4N0 colon cancer in
a single institution specializing in the surgical treatment of
colorectal disease, to identify possible variables predictive
of outcomes, and to compare results with control groups
from patients with other stages of colon carcinoma.
MATERIALS AND METHODS
All patients who underwent colectomy for colonic car-
cinoma in our institution from 1978 to May 2008 were
Oncologic Outcomes of T4N0 Colon Cancer
identified through a departmental colorectal cancer data-
base, approved by our institutional review board. Data
were collected prospectively. If patients underwent onco-
logic follow-up elsewhere, clinical information was
obtained by phone and through the request of clinical
documentation. On the other hand, follow-up performed in
our institution was based on a combination of physical
examination, serial evaluation of biochemical tumor
markers, colonoscopy, and computed tomographic scans,
which varied slightly among individual surgeons but were
all within accepted standards.10
Exclusion criteria were location of tumor distally to
rectosigmoid junction, palliative surgery inclusive of gross
positive resection margins (R2 disease), presence of syn-
chronous distant metastases (M1), concurrent inflammatory
bowel diseases, familial adenomatous polyposis, and
hereditary nonpolyposis colorectal cancer. Disease were
classified according to the 7th edition of the American Joint
Committee on Cancer(AJCC) manual.2
All patients with a pathologically proven T4N0 cancer
(stage IIb or IIc) were considered. Patients undergoing
multivisceral resections for node-positive disease or clinical
T4 disease not confirmed pathologically were excluded from
the study. Patients with T4N0 disease were compared with
control groups composed of consecutive patients with stages
T12N1 (stage IIIa), T3N1, and T3N0 (stage IIa) undergoing
surgery with curative intent during the same period. Ana-
lyzed variables included demographics, perioperative
outcomes and mortality, postoperative recovery parameters,
use of chemotherapy, overall and cancer-specific survival,
and overall and local recurrence rates. Demographic and
perioperative outcome variables were analyzed by compar-
ing patients with T4N0 disease with all other disease
stages combined into a single group. Recorded patient
comorbidities included diabetes, hypertension, coagulation
disorders, and cardiovascular, respiratory, renal, and hepa-
tobiliary disease. Thirty-day postoperative complications
included bowel obstruction, enteric fistula, anastomotic leak,
intra-abdominal abscess or peritonitis, deep venous throm-
bosis, pulmonary embolism, wound infection or dehiscence,
urinary (retention, infection or incontinence), and cardio-
vascular and respiratory morbidity.
When evaluating pathologic results and oncologic out-
comes, each individual control group was compared to
T4N0 patients. The incidence of microscopically positive
resection margins (R1) in all groups was also assessed. We
also performed a subgroup analysis comparing oncologic
outcomes of patients who had pathologic infiltration of
different surrounding organs or structures. In addition, we
assessed cancer outcomes in the subgroup of patients who
received adjuvant chemotherapy either for T4N0 stage as
well as in the control groups. Most treated patients received
5-fluorouracil-based chemotherapy.
2501
Local recurrence was defined as clinical and/or radio-
logic evidence of locoregional relapse of the tumor. Distant
recurrence was defined as a clinical and/or radiologic evi-
dence of tumor spread to distant organs. Tumor location
was divided into right (ascending colon, hepatic flexure,
and transverse colon) and left (splenic flexure, and
descending and sigmoid colon).
Univariable comparisons of the staging groups were
performed by chi-square or Fishers exact tests with respect
to categorical variables, and by the Wilcoxon rank sum test
with respect to quantitative and ordinal variables. Com-
parisons with respect to long-term outcomes were
performed by the log rank test, with the KaplanMeier
method used to estimate likelihood of outcome at indi-
vidual time points. Logistic, linear, and Cox regression
models were used to extend these analyses to group com-
parisons that adjusted for covariates including, American
Society of Anesthesiologists (ASA) score, tumor location,
year of surgery (3 years), and follow-up time. These
analyses were performed by R version 2.4.1. A P value
of \ 0.05 was considered significant.
RESULTS
During the study period, a total of 1,389 patients
underwent colectomy with curative intent for T4N0
(n = 158), T12N1 (n = 122), T3N1 (n = 340), or T3N0
(n = 769) colon cancer.
Demographic and preoperative data are listed in
Table 1. No differences were observed between T4N0 and
control groups regarding mean age, gender, body mass
index, and tumor location. Patients with T4N0 had a lower
proportion of ASA III classification and a decreased
cumulative comorbidity rate.
Patients with T4N0 colon carcinomas were more likely
to receive perioperative blood transfusions when compared
to control groups and had an increased mortality rate,
although this was not statistically significant (4.4 vs. 2.7%,
P = 0.2). Overall morbidity (22.2 vs. 25.1%, P = 0.4),
including cardiopulmonary complications, postoperative
anastomotic leak rate, reoperation, and readmission rates,
were comparable.
Pathologic data are shown in Table 2. The median
number of collected lymph nodes was comparable between
T4N0 and T12N1, while it was significantly higher in
T3N1 and T3N0. Similarly, the rate of patients with fewer
than 12 collected lymph nodes was similar between T4N0
and T12N1 groups, and lower in T3N1 and T3N0 cases.
However, when the number of examined lymph nodes was
adjusted for the year of surgery as a covariate, the rate of
patients with suboptimal node sampling was similar among
groups.
2502 M. Rottoli et al.

TABLE 1 Patient demographic data and preoperative variablesa cancer-specific mortality, overall recurrence, and local
Variable T4N0 stage Control group b
P
recurrence rate to those of T3N1 group.
A subsequent survival analysis, performed after exclu-
No. of patients 158 1228 sion of patients with fewer than 12 collected lymph nodes
Male gender 86 (54.4%) 685 (55.8%) 0.7 and R1 resections, confirmed a higher incidence of local
Age (year) 65 12 68 13 0.9 recurrence in T4N0 than in T12N1 patients (6.3 vs. 1.5%,
ASA class \0.001 P = 0.04). Moreover, the difference in overall recurrence
I 30 (19%) 88 (7.2%) rate between the two groups showed an absolute difference
II 73 (46.2%) 460 (37.7%) of almost 10%, although this did not reach statistical sig-
III 52 (32.9%) 578 (47.4%) nificance (24.2 vs. 14.9%, P = 0.07; Table 4).
IV 3 (1.9%) 94 (7.7%) Additional analyses performed only for patients under-
Comorbidity going adjuvant chemotherapy also confirmed that patients
Overall 52 (32.9%) 554 (45.1%) 0.003 with stage T4N0 were associated with worse cancer out-
Cardiovascular 23 (14.6%) 268 (21.8%) 0.03 comes when compared with control groups (Table 5). In
Diabetes 11 (7.0%) 105 (8.5%) 0.5 assessing the possible effect of chemotherapy limited to
Pulmonary 3 (1.9%) 121 (9.9%) 0.001 T4N0 patients, we noted a significantly increased per-
BMI, kg/m2 27 7 27.4 6 0.7 centage of T4b cases selectively treated with chemotherapy
Tumor location \0.001 when compared to T4a patients (45 vs. 15.2%, P = 0.04).
Left colon 89 (56.3%) 515 (41.9%) With respect to cancer outcomes, patients receiving che-
Right colon 69 (43.7%) 714 (58.1%) motherapy had a significantly increased local recurrence
rate when compared with patients who did not undergo
ASA American Society of Anesthesiologists, BMI body mass index
a
chemotherapy (26.4 vs. 4.1%, P = 0.008). A similar
Data are presented as numbers (%) or as means standard deviation
b
numerical difference, although not statistically significant,
Combined patients with stages T12N1, T3N1, and T3N0 disease
was noted after exclusion of cases with margin involve-
ment or fewer than 12 collected lymph nodes (21.2 vs.
The incidence of R1 resections was significantly 3.6%, P = 0.06). The remaining cancer outcomes were
increased in T4N0 group (7.6%) when compared to all statistically similar between the 2 subgroups (overall sur-
control stages (T12N1 1.6%, P = 0.01; T3N1 3.2%, vival 70 vs. 71%, P = 0.4; overall recurrence rate 41.3 vs.
P = 0.03; T3N0 2.6%, P = 0.001). With respect to use of 24.1%, P = 0.2; cancer-specific mortality 26.1 vs. 20.3%,
adjuvant treatments, 12.7% of T4N0 patients received P = 0.2 for patients receiving chemotherapy vs. untreated
chemotherapy compared with 40.2% of T12N1, 42.4% of patients, respectively).
T3N1, and 6.5% of T3N0 counterparts. Among 146 R0 pT4N0 patients, 118 had a pathologi-
Oncologic outcome analysis revealed an increased cally confirmed T4a tumor. Of these, 95 patients (65%)
5-year local recurrence rate in T4N0 cases when compared underwent colectomy for pT4 carcinoma extending into the
to stage T12N1 (7.3 vs. 2.1%, P = 0.02). As shown in free peritoneal serosa, and 23 patients (15.8%) required
Table 3, T4N0 patients had similar 5-year overall survival, multivisceral resection for a clinical adhesion of the tumor

TABLE 2 Pathologic data and adjuvant therapy

Variable T4N0 T12N1 P T3N1 P T3N0 P

Differentiation 0.7 0.001 0.4

Moderate/well 131 (83.4%) 96 (81.4%) 232 (68.8%) 615 (80.3%)
Poor 26 (16.6%) 22 (18.6%) 105 (31.2%) 151 (19.7%)
Examined lymph nodes
Total no. examined 18 (398) 19.5 (2241) 0.2 22 (2333) 0.001 21 (0199) 0.006
\12 examined 43 (27.2%) 25 (20.5%) 0.7 40 (11.8%) 0.2 145 (18.9%) 0.5
Tumor size, cm 6.6 3.6 3.5 3 \0.001 5.1 3.4 \0.001 5.4 8.8 \0.001
Margin involvement (R1) 12 (7.6%) 2 (1.6%) 0.01 11 (3.2%) 0.03 20 (2.6%) 0.001
Postoperative chemotherapy 20 (12.7%) 49 (40.2%) \0.001 144 (42.4%) \0.001 50 (6.5%) 0.009
a
Data are presented as numbers (%), means standard deviation, or medians (range)
b
P value refers to comparison between each control group to T4N0 group and was calculated by a regression model with the year of surgery as a
covariate
Oncologic Outcomes of T4N0 Colon Cancer 2503

TABLE 3 Five-year oncologic outcomes in all patients

Variable T4N0 T12N1 P T3N1 P T3N0 P

Total no. of patients 158 122 329 749

Follow-up time (years) 8.8 (028.4) 5.7 (026.9) 0.03 6.1 (027.8) 0.001 6.9 (028.2) 0.03
Overall survival 70% (3.7) 76.1% (4.2) 0.6 65% (2.6) 0.6 74% (1.6) 0.02
Overall recurrence rate 26.5% (3.8) 17.1% (3.7) 0.1 31.2% (2.6) 0.1 16.4% (1.4) 0.02
Local recurrence rate 7.3% (2.2) 2.1% (1.5) 0.02 6.2% (1.4) 0.4 2.5% (0.6) 0.01
Cancer-specific mortality 21.1% (3.4) 14.7% (3.6) 0.08 26.5 % (2.5) 0.3 9.8 % (1.2) \0.001
Data are presented as percentages (standard error) and medians (range). P values refer to comparison between each control group to T4N0 group
and were adjusted for age, American Society of Anesthesiology class, tumor location, surgery period, and follow-up time as covariates

TABLE 4 Five-year oncologic outcomes in R0 patients with C12 collected lymph nodesa
Variable T4N0 T12N1 P T3N1 P T3N0 P

Total no. of patients 106 95 292 605

Overall survival 76.2% (4.2) 77.9% (4.7) 0.8 68.5% (2.8) 0.2 76.5% (1.8) 0.2
Overall recurrence rate 24.2% (4.3) 14.9% (4) 0.07 29% (2.8) 0.09 14.4% (1.5) 0.05
Local recurrence rate 6.3%(2.5) 1.5% (1.5) 0.04 5.7% (1.5) 0.5 2.5% (0.7) 0.12
Cancer-specific mortality 18.2% (3.9) 12.6% (3.8) 0.09 24.1% (2.7) 0.2 8.5% (1.2) 0.002
a
Data are presented as percentages (standard error). P value refers to comparison between each control group to T4N0 group, and was adjusted
for age, American Society of Anesthesiology class, tumor location, surgery period, and follow-up time as covariates

TABLE 5 Five-year oncologic outcomes in patients receiving adjuvant chemotherapya

Variable T4N0 T3N0 P T12N1 P T3N1 P

Total no. of patients 20 50 49 144

Overall survival 70% (10.2) 84.6% (5.4) 0.03 83.6% (5.7) 0.2 75.1% (3.7) 0.3
Overall recurrence rate 41.3% (11.2) 16.1% (5.6) 0.05 13.7% (5.2) 0.03 27.6% (3.8) 0.5
Local recurrence rate 26.4% (10.2) 2.9% (2.8) 0.02 2.6% (2.6) 0.03 6.6 (2.1) 0.06
Cancer-specific mortality 26.1% (10.1) 7.1 (4) 0.009 14% (5.3) 0.04 20.3 (3.5) 0.1
a
Data are presented as percentages (standard error). P value refers to comparison between each control group to T4N0 group, and was adjusted
for age, American Society of Anesthesiology class, tumor location, surgery period, and follow-up time as covariates

to other organs, although the pathologic examination did
not detect any microscopical infiltration. A T4b cancer was
pathologically confirmed in 28 patients (19.2%) who
required multivisceral resection. Five-year cancer out-
comes were worse for T4b than T4a patients, including
decreased overall survival (48.9 vs. 68.4%, P = 0.2),
decreased cancer-specific survival (54.4 vs. 83.6%,
P = 0.01), increased 5-year overall recurrence rate (48.8
vs. 23%, P = 0.01), and increased local recurrence rate
(15.1 vs. 5%, P = 0.06).
To evaluate whether the infiltration of different organs
corresponded to different oncologic outcomes, two sub-
groups were arbitrarily created among T4b patients, each of
which was individually compared to the T4a group. The
first subgroup included 11 cases of pathologic involvement
of adjacent bowel (small bowel in eight patients and colon
in three patients).The second subgroup included 17 cases of
involvement of other organs or structures (abdominal wall
in five patients, retroperitoneum in 2, pancreas in 2,
stomach in 3, bladder in 4, and uterus in 1). The analysis
revealed that bowel involvement was associated with
improved oncologic outcomes, which were comparable to
those of T4a patients. On the other hand, tumor infiltration
of retroperitoneum, abdominal wall, or other organs
resulted in a significantly increased incidence of 5-year
local and overall recurrence rate and reduced overall and
cancer-specific survival (Table 6).
DISCUSSION
Our study confirms the challenges posed by T4 carci-
nomas to the operating surgeon. Despite a selection in
favor of patients with reduced comorbidities, postoperative
morbidity after surgical resection of T4N0 colon carcino-
mas was comparable to the control stages, and mortality
was increased, albeit not significantly. The rate of R1
2504
TABLE 6 Five-year oncologic outcome in R0 T4N0 patients according to pathologic infiltration into different surrounding organs or structuresa
Variable T4a (n = 118) pT4b invading into small
bowel or colon (n = 11)
Overall survival 68.4% (0.04) 63.6% (0.1)
Overall recurrence rate 23% (0.04) 21.3% (0.1)
Local recurrence rate 5% (0.02) 0%
Cancer-specific mortality 16.4% (0.03) 21.3% (0.1)
a
Data are presented as percentages (standard error)
resections was also significantly increased, as was the rate
of perioperative blood transfusion, which confirms what
other studies have indicated, especially in case of multi-
visceral resections.68,1114
Our results also confirm the adverse oncologic outcomes
associated with T4N0 colon carcinomas, with survival rates
worse than in patients with both stage IIa and stage IIIa
disease and more similar to the outcomes of T3N1
tumors.3,1519 This reflects the analysis based on the Sur-
vival Epidemiologic End Results data based on almost
120,000 patients from all over the United States and the
latest results published in the 7th edition of the AJCC
cancer staging manual.2
We hypothesized that surgical treatment and pathologic
staging in a large center with substantial experience in the
treatment of colon cancer might be associated with
improved outcomes compared to national data. Although
we believe that our data reflect appropriate surgical care
and pathologic staging, our hypothesis was proven wrong;
our oncologic outcomes were indeed similar to the national
data.2,20 Assuming that an increased rate of incomplete
surgical resection and/or inadequate node sampling might
be the major determinants of cancer outcomes in our
patient population, we also decided to perform a subgroup
analysis limited to patients undergoing R0 resections with
at least 12 examined lymph nodes.
Even after statistical adjustment for R0 resection, age,
ASA score, year of surgery, follow-up time, and sampling
of at least 12 lymph nodes, cancer outcomes of T4N0
patients remained statistically comparable to T3N1 stage.
Although the differences with stage IIa disease were less
pronounced, a significant increase in 5-year local recur-
rence rate became apparent when comparing our T4N0
sample to stage IIIa control cases. These results would
therefore suggest an inherently aggressive biologic
behavior of T4N0 carcinomas. The American Society of
Clinical Oncology guidelines also recommended consid-
eration for postoperative chemotherapy in high-risk stage II
colon cancer including T4 tumors.21
Despite this, postoperative chemotherapy was rarely
utilized in our patient population. The chemotherapy uti-
lization rate reported in our study refers to a patient
M. Rottoli et al.
P pT4b invading into retroperitoneum, P
abdominal wall, or other organs (n = 17)
0.5 45.3% (0.1) 0.03
0.7 64.7% (0.1) \0.001
0.5 24.4% (0.1) 0.003
0.9 58.9% (0.1) \0.001
population with often significant comorbidities evaluated
during a long study period. However, even considering
these limitations, our patient population with T4N0 carci-
noma received chemotherapy much less frequently than
our control groups during the same period. This confirms
the results of at least one report from a specialized cancer
center.22 Beside underutilization in stage T4N0 disease,
chemotherapy was also selectively administered to those
patients at higher risk of recurrence (multivisceral resection
with infiltration of surrounding organs). This treatment
selection bias does not allow drawing meaningful conclu-
sions regarding the lack of benefits noted in T4N0 patients
undergoing adjuvant chemotherapy, who instead experi-
enced generally worse cancer outcomes.
With respect to subsets of T4N0 carcinomas, patients
treated for T4 disease extended only to serosa were asso-
ciated with improved oncologic outcomes when compared
to T4b cases, confirming the results of national data.2
Among patients with stage IIc disease, cancer outcomes
were significantly worse when tumor involved the retro-
peritoneum or abdominal wall or other abdominal organs
when compared with other bowel segments. Although our
numbers for this subset of patients are small and our
division into subgroups based on bowel involvement is
somewhat arbitrary, it seems intuitive that an en bloc
resection of a discrete segment of additional intraperitoneal
bowel is more likely to achieve cure. The absence of any
cases of local recurrence in this group would seem to
confirm this hypothesis.
The limitations of our study include its retrospective
nature and its long time span, which also includes patients
who underwent surgery decades ago. On the other hand,
our prospectively maintained departmental database
allowed us to collect and analyze more detailed informa-
tion regarding demographics, perioperative variables, and
follow-up data, such as R1 resections, than what is gen-
erally reported in administrative databases.
An additional strength of our study was that rectal
cancers were excluded from our analysis, thus making our
study design more rigorous.6,7 We believe that this is an
important consideration because the use of neoadjuvant
chemoradiation in rectal carcinoma confuses the pathologic
Oncologic Outcomes of T4N0 Colon Cancer
assessment of clinical T4 disease. In addition, outcomes of
patients whose disease does not respond to neoadjuvant
treatment are significantly worse, and T4 rectal carcinoma
is associated with worse oncologic outcomes when com-
pared to T4 colonic disease.8,23
These results suggest that use of adjuvant treatments
could be tailored depending on the organ or structure
involved by the tumor. Future introduction of molecular
and genetic markers for colon cancer staging could allow a
more precise selection of patient populations at high risk of
recurrence.2426
In conclusion, T4N0 colon cancer has a worse oncologic
outcome than other stage II tumors and is more similar to
more advanced stage III cancers, regardless of possible
technical difficulties and staging limitations. Therefore,
aggressive multimodal treatment should be used in most of
these cases to optimize outcomes.
REFERENCES
1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA
Cancer J Clin. 2010;60:277300.
2. Edge SB, Byrd DR, Compton CC et al.,(eds). AJCC cancer
staging manual. 7th ed. (Springer, New York, 2009), pp. 11726.
3. Morris M, Platell C, de Boer B, et al. Population-based study of
prognostic factors in stage II colonic cancer. Br J Surg. 2006;
93:86671.
4. Merkel S, Wein A, Gunther K, et al. High-risk groups of patients
with stage II colon carcinoma. Cancer. 2001;92:143543.
5. OConnell JB, Maggard MA, Ko CY. Colon cancer survival rates
with the new American Joint Committee on Cancer sixth edition
staging. J Natl Cancer Inst. 2004;96:14205.
6. Lehnert T, Methner M, Pollok A, et al. Multivisceral resection for
locally advanced primary colon and rectal cancer: an analysis of
prognostic factors in 201 patients. Ann Surg. 2002;235:21725.
7. Nakafusa Y, Tanaka T, Tanaka M, et al. Comparison of multi-
visceral resection and standard operation for locally advanced
colorectal cancer: analysis of prognostic factors for short-term
and long-term outcome. Dis Colon Rectum. 2004;47:205563.
8. Darakhshan A, Lin BP, Chan C, et al. Correlates and outcomes of
tumor adherence in resected colonic and rectal cancers. Ann Surg.
2008;247:6508.
9. Oh SY, Kim YB, Paek OJ, et al. Contiguous invasion per se does
not affect prognosis in colon cancer. J Surg Oncol. 2009;99:714.
10. Rex DK, Kahi CJ, Levin B, et al. Guidelines for colonoscopy
surveillance after cancer resection: a consensus update by the
American Cancer Society and the U.S. Multi-Society Task Force
on Colorectal Cancer. Gastroenterology. 2006;130:186571.
2505
11. Hakimi AN, Rosing DK, Stabile BE, et al. En bloc resection of
the duodenum for locally advanced right colon adenocarcinoma.
Am Surg. 2007;73:10636.
12. Fuks D, Pessaux P, Tuech JJ, et al. Management of patients with
carcinoma of the right colon invading the duodenum or pancre-
atic head. Int J Colorectal Dis. 2008;23:47781.
13. Curley SA, Evans DB, Ames FC. Resection for cure of carcinoma
of the colon directly invading the duodenum or pancreatic head.
J Am Coll Surg. 1994;179:58792.
14. Yun SH, Yun HR, Lee WS, et al. The clinical outcome and
prognostic factors after multi-visceral resection for advanced
colon cancer. Eur J Surg Oncol. 2009;35:7217.
15. Quah HM, Chou JF, Gonen M, et al. Identification of patients
with high-risk stage II colon cancer for adjuvant therapy. Dis
Colon Rectum. 2008;51:5037.
16. Sobrero A. Should adjuvant chemotherapy become standard
treatment for patients with stage II colon cancer? For the pro-
posal. Lancet Oncol. 2006;7:5156.
17. Burdy G, Panis Y, Alves A, et al. Identifying patients with T3-T4
node-negative colon cancer at high risk of recurrence. Dis Colon
Rectum. 2001;44:16828.
18. Olson RM, Perencevich NP, Malcolm AW, et al. Patterns of
recurrence following curative resection of adenocarcinoma of the
colon and rectum. Cancer. 1980;45:296974.
19. Willett CG, Tepper JE, Cohen AM, et al. Failure patterns fol-
lowing curative resection of colonic carcinoma. Ann Surg.
1984;200:68590.
20. Greene FL, Stewart AK, Norton HJ. A new TNM staging strategy
for node-positive (stage III) colon cancer: an analysis of 50,042
patients. Ann Surg. 2002;236:41621.
21. Benson AB 3rd, Schrag D, Somerfield MR, et al. American
Society of Clinical Oncology recommendations on adjuvant
chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:
340819.
22. Jeong SY, Chessin DB, Schrag D, et al. Re: Colon cancer survival
rates with the new American Joint Committee on Cancer sixth
edition staging. J Natl Cancer Inst. 2005;97:17056.
23. Castaldo ET, Parikh AA, Pinson CW, et al. Improvement of
survival with response to neoadjuvant radiation therapy for rectal
cancer. Arch Surg. 2009;144:12934.
24. Uen YH, Lin SR, Wu DC, et al. Prognostic significance of
multiple molecular markers for patients with stage II colorectal
cancer undergoing curative resection. Ann Surg. 2007;246:
10406.
25. Strzelczyk B, Szulc A, Rzepko R, et al. Identification of high-risk
stage II colorectal tumors by combined analysis of the NDRG1
gene expression and the depth of tumor invasion. Ann Surg
Oncol. 2009;16:128794.
26. Meyer A, Merkel S, Bruckl W, et al. Cdc2 as prognostic marker
in stage UICC II colon carcinomas. Eur J Cancer. 2009;45:
146673.