ANTICANCER RESEARCH 29: 1681-1684 (2009)
Clinicopathological Features of Perforated Colorectal Cancer
MASAICHI OGAWA, MICHIAKI WATANABE, KEN ETO, TAKAHIRO OMACHI, MAKOTO KOSUGE,
KEN HANYU, LOHTA NOAKI, TETSUJI FUJITA and KATSUHIKO YANAGA
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
Abstract. Τhe aim of this retrospective study was to
determine clinicopathological factors pertinent to the
prognosis of perforated colorectal cancer (PCRC). Patients
and Methods: A retrospective review of clinical records of 17
cases of emergency primary resection for PCRC (stage IIIa
in 2, stage IIIb in 6 and stage IV in 9) was perfomed. Result:
The 5-year survival rate was 31% (31% for stage III and
12% for stage IV). When compared with non-PCRC (533
cases) in stage III (78.8% ) or stage IV (14.8% ), the 5-year
survival rate of stage III perforated colorectal cancer was
clearly worse (p<0.01) than the non-perforated counterpart.
For stage IV, however, the two groups had a similar
prognosis. MST of the PCRC was 31 months for stage III and
12 months for stage IV. Approximately half of the recurrence
pattern of stage III (75% ), or stage IV (44% ) PCRC was
peritoneal carcinomatosis. As for the type of operations
performed, Hartmann’s procedure was the preferred
technique (71% ), for which mortality and morbidity rate
were both low. Conclusion: Because of the high incidence of
peritoneal carcinomatosis and low 5-year survival rate, stage
III PCRC should be regarded as a stage IV disease, for which
postoperative chemotherapy seems essential.
The treatment for perforated colorectal cancer (PCRC) is not
an easy task because most cases are already stage IV at the
onset of the disease and not eligible for curative surgery (1-
10). For colorectal cancer, the reported incidence of
perforation ranges from 3% to 10% (1-3). It has been
accepted that the emergency surgery for perforated colorectal
cancer has a worse progress than those treated by elective
surgery (4-6). As to the survival rate of PCRC, Badia et al.
observed 1-year survival rate of 52% and 2-year survival
rate of 40% (1). The 5-year survival rate varies from 32% to
Correspondence to: Masaichi Ogawa, MD, Department of Surgery,
The Jikei University School of Medicine, Tokyo 105-8461, Japan.
Tel: +81 3 3433 1111 (Ext.3401), Fax: +81 3 5472 4140, e-mail:
masatchmo@k5.dion.ne.jp
Key Words: Clinico-pathological features, colorectal cancer,
perforation, Hartmann’s procedure.
0250-7005/2009 $2.00+.40
52.8% (2, 3, 7). In 1986, Steinberg et al. found that
neoplastic perforation was only a significant indicator for
disease-free survival (8). This retrospective study sought to
determine clinicopathological factors pertinent to the
prognosis of PCRC.
Patients and Methods
A total of 535 patients underwent resection of colorectal cancer at
Jikei University Hospital between January 1998 and December
2000. Of these, 17 patients were PCRC, consisting of 13 men and 4
women, with an age between 25 and 87 [71±8.4 (mean±SD)] years.
The definition of PCRC is perforation at the site of the cancer and
proximally to the tumor in case of obstruction. The follow-up data
of the patients were updated in January 2006. In this series, the
cancer was located in the right colon in 2 (12% ), cecum in 1 (6% ),
ascending colon in 1 (6% ), left colon in 15 (88% ), descending
colon in 2 (12% ), sigmoid colon in 6 (35% ), and rectum in 7 cases
(41% ). In terms of TNM classification, stage IIIa in 2 (12% ), stage
IIIb in 6 (35% ), and stage IV in 9 cases (53% ). All patients
received fluorouracil- and leucovorin-based chemotherapy and same
mode of follow-up.
Patients information collected from the medical records included
the age, gender, location, size and histological grade of the primary
tumor. The histological depth of invasion, lymphatic or venous
invasion, TNM classification (11), and prognosis were also
recorded. Patients who underwent emergency surgery of PCRC were
compared with non-PCRC patients who underwent elective surgery.
Statistical analysis. Survival time was calculated from the date of
resection, to the date of death or date of the latest follow-up.
Survival curves were plotted according to the Kaplan-Meier method;
statistical differences were analyzed by the log-rank test. The
statistical analyses were performed with Stat View software version
5.0 (Abacus Concepts, Berkeley, CA, USA) and SPSS software
version 11.0 (SPSS Inc, Chicago, IL, USA). A p-value less than
0.05 was regarded as statistically significant.
Results
Histopathological factors. Macroscopic findings resulted in a
broad range of types; type 2 in 8 (47% ), type 3 in 6 (35% ), and
type 4 in 3 cases (18% ). The maximal diameter of the tumor
was 61±13 mm. Tumor histology was poorly differentiated
adenocarcinoma in 1 (6% ), moderate differentiated adeno-
carcinoma in 9 (53% ), and well differentiated adenocarcinoma
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 ANTICANCER RESEARCH 29: 1681-1684 (2009)
in 7 cases (41% ). All cases were lymphatic invasion, and venous
invasion showed in 12 cases (72% ).
Cumulative survival rate. The overall 5-year survival rate of
PCRC was 31% , consisting of 31% in stage III and 12% in
stage IV (Figure 1).The 5-year survival rate of 533 patients
who underwent surgery for non-perforated colorectal cancer
(non-PCRC) was 78.8% for stage III and 14.8% for stage
IV. In stage III, PCRC had a significantly worse prognosis
(p<0.01) as compared with the non-PCRC. For stage IV,
however, the 5-year survival rate was not significantly
different between those two groups. For PCRC, the mean
survival time (MST) of stage III was 31 months as compared
to 12 months for stage IV. In this study, perforation of the
colorectal cancer in stage III was an independent factor for
short survival (13% for PCRC and 78.8% for non-PCRC;
p<0.01).
Clinical feature. For stage III PCRC, 75% of the recurrence
pattern was peritoneal carcinomatosis, as composed to 44%
for stage IV PCRC (Figure 2). In these 17 cases, the
following operations were performed: right hemicolectomy
and primary ileo-transverse anastomosis in 2 (12% ), a
Hartmann’s procedure in 14 (82% ) and sigmoid-colostomy
in 1 case (4% ). All cases underwent peritoneal lavage and
drainage. As for the type of operations performed,
Hartmann’s procedure was the preferred technique (71% ),
for which mortality and morbidity rate were both low (Table
I). In 2 cases, there was respiratory infection.
Discussion
In the literature, neoplastic perforation has been reported to
be the only significant indicator for survival because the
spillage of tumor cells into the peritoneal cavity would lead
to wide-spread interperitoneal tumor dissemination (8, 9),
while one report describes the absence of negative impact of
perforation on survival (10, 11). Concerning the effect of
spillage of tumor cells, Lehnert et al. have reported that
viability-free cancer cells were not demonstrated in the
peritoneal cavity of patients with perforated GI cancer, and
the metastatic efficacy of cancer cells that are possibly shed
during perforation is uncertain in the presence of peritonitis
(12). Chen and Sheen-Chen found that the 5-year survival
rate of patients with perforation at the site of the cancer was
similar to that of uncomplicated cancer, and that spillage of
tumor cells into the peritoneal cavity through a perforation
at the site of the tumor was not an indicator of a poor
prognosis (9). However in the present study, for stage III
PCRC, 75% of the recurrence pattern was peritoneal
carcinomatosis, as opposed to 44% for stage IV PCRC.
Therefore, with respect to the long-term prognosis,
perforation of the colorectal cancer in stage III is an
1682
Table I. Operation techniques and mortality and morbidity.
Operation methods Stage III Stage IV
(n=8) (n=9)
Hartman’s procedure 8 6
colostomy 0 1
colectomy+primary anastomosis 0 2
Morbidity 0 2*
Mortality 0 0
*Respiratory infection.
independent factor (13% for PCRC and 78.8% for non-
PCRC; p<0.01).
The operative mortality of elective surgery for colorectal
cancer is 3% , whereas that for perforated (including
obstructive) colorectal cancer is increased 2 to 4 folds (13) . It
is well-established that primary resection of the diseased
segment is chosen in most colorectal emergency operations
(14-16). In the present study, primary resection was performed
in 94% (16/17) of patients. Left-sided resection with
immediate anastomosis in the presence of peritoneal sepsis is
still debated in the literature (15-17). Biondo et al. had
reported that immediate anastomosis can be performed safely
after the use of intraoperative antegrade colonic irrigation, and
perforated primary anastomosis in 61 (48% ) of 127 patients
with peritonitis. In their report, 2 patients (8.7% ) with diffuse
peritonitis died, and anastomostic leakage developed in only
1 patient. For generalized peritonitis due to large bowel
perforation, especially for left-side one, appropriate treatment
remains controversial, but Hartman’s operation has become
popular during the last decades (14, 18). Bielecki et al.
reviewed the Mannheim peritonitis index (MPI) of large
bowel perforation. In their conclusion, no patient with MPI
less than 25, even with primary anastomosis died, while
38.5% of the patients with MPI between 26 and 36 died (19).
Minopoulos et al. described for the treatment of emergency
surgery to CRC that the choice of operative procedures
depends on the conditions of the patient, the experience of
surgeon, and the means that the hospital provides (20). The
presented results suggest that Hartman’s procedure was the
preferred technique for the left-sided PCRC, and such a
surgical strategy seems to account for the low morbidity.
In recent years FOLFOX/ FOLFIRI regimens have been
reported to improve survival rate of metastatic colorectal
cancer (21-23). On the other hand, Koppe et al. suggested
that the adjuvant hyperthermic intraperitoneal chemotherapy
has shown efficacy in selected patients with resectable
peritoneal carcinomatosis of colorectal origin (24).
In conclusion, the prognosis of stage III perforated
colorectal cancer is poor, and the recurrence pattern of PCRC
is mainly by peritoneal seeding, for which intensive adjuvant
chemotherapy should be conducted.
 Ogawa et al: Clinicopathological Features of Perforated Colorectal Cancer

Figure 1. The five-year survival rate of PCRC. The overall five-year survival rate of PCRC was 31% , consisting of 31% in stage III and 12 % in stage
IV.

Figure 2. Recurrence pattern of PCRC. For stage III, 75% of the recurrence pattern was peritonitis carcinomatosa, as opposed to 44% for stage

1683
 ANTICANCER RESEARCH 29: 1681-1684 (2009)
References
1 Badia JM, Sitges-Serra A, Pla J et al: Perforation of colonic
neoplasms: a review of 36 cases. Int J Colorectal Dis 2(4): 187-
189, 1987.
2 Mandava N, Kumar S, Pizzi S et al: Perforated colorectal
carcinomas. Am J Surg 172(3): 236-238, 1996.
3 Lee IK, Sung NY, Lee SC et al: The survival rate and prognostic
factors in 26 perforated colorectal patients. Int J Colorectal Dis
22(5): 467-473, 2007.
4 Corman ML: Principles of surgical technique in the treatment of
carcinoma of large bowel. World J Surg 15: 592-586, 1991.
5 Phillips RKS: Clinical factors which influence outcome after
colorectal cancer surgery. Modern Coloproctol 4: 69-79, 1993.
6 Korenaga D, Ueno H, Mochida K et al: Prognosis factors in
Japanese patients with colorectal cancer: the significant of the
large bowel obstruction: univariate and multivariate analysis. J
Surg Oncol 47(3): 188-192, 1991.
7 Gullino D, Giordano O, Masella M et al: The single-stage
surgery of perforated colon carcinoma: our experience of 46
cases. Mineva Chir 54(3): 127-137, 1999.
8 Steinberg SM, Barkin JS, Kaplan RS et al: Prognostic indicators
of colon tumors: the gastrointestinal tumor study group
experience. Cancer 57: 1866-1870, 1986.
9 Chen HS and Sheen-Chen SM: Obstruction and perforation in
colorectal adenocarcinoma: an analysis of prognosis and current
trends. Surgery 127: 370-376, 2000.
10 Moertel CG, Fleming TR, MacDonald JS et al: Levamisole and
fluoruracil for adjuvant therapy for resected colon carcinoma. N
Eng J Med 6: 352-358, 1990.
11 Moertel CG, Fleming TR, MacDonald JS et al: Intergroup study
of fluoruracil plus levamisole as adjuvant therapy for stage II/
Dukes B2 colon cancer. J Clin Oncol 12: 2936-2943, 1995.
12 Lahnert T, Buhl K, Dueck M et al: Two-stage radical gastrectomy
for perforated gastric cancer. Eur J Surg Oncol 26: 780-784, 2000.
13 Alcobendas F, Jorba R, Poves I et al: Perforated colonic cancer:
evolution and prognosis. Rev Esp Enferm Dig 92(5): 326-333,
2000.
14 Gracia-Peche P: Factors of prognostic value in long term survival
of colorectal cancer patients. Hepatogastroenterolo 38: 438-443,
1991.
1684
15 Biondo S, Jaurrieta E, Rague JM et al: Role of resection and
primary anastomosis of the left colon in the presence of
peritonitis. Br J Surg 87: 80-84, 2000.
16 Gooszen AW, Tollenar RAEM, Geelkerken RH et al: Prospective
study of primary anastomosis following sigmoid resection for
suspected acute complicated diverticular disease. Br J Surg 88:
693-697, 2001.
17 Hoemke M, Treckman J, Schmitz R et al: Complicated
diverticulitis of the sigmoid: a prospective study concerning
primary resection with secure primary anastomosis. Dig Surg 16:
420-424, 1999.
18 Krivanek S, Armbruster C, Dittrich K et al: Perforated colorectal
cancer. Dis Colon Rectum 39: 1409-1414, 1996.
19 Bielecki K, Kaminski P and Klukowski M: Large bowel
perforation: morbidity and mortality. Tech Coloproctol 6: 177-
182, 2002.
20 Minopoulos GI, Lyratzopoulas N, Efremidou HI et al: Emergency
operations for carcinoma of the colon. Tech Coloproctol 8: S235-
S237, 2004.
21 Saltz IB, Cox JV, Blanke C et al: Irinotecan plus fluorouracil and
leucovorin for metastatic colorectal cancer: Irinotecan Study
Group. N Eng J Med 343: 905-914, 2000.
22 Goldberg RM, Sargent DJ, Morton RF et al: A randomized
controlled trial of fluorouracil plus leucovorin, irinotecan, and
oxaliplatin combinations in patients with previously untreated
metastatic colorectal cancer. J Clin Oncol 22: 23-30, 2004.
23 Tournigand C, Andre T, Achille E et al: FOLFIRI followed by
FOLFOX6 or the reverse sequence in sdvanced colorectal cancer:
a randomized GERCOR study. J Clin Oncol 22: 229-237, 2004.
24 Koppe MJ, Boerman OC, Oyen WJG et al: Peritoneal
carcimatosis of colorectal origin incidence and current treatment
strategies. Ann Surg 243(2): 212-222, 2006.
Received July 3, 2008
Revised January 8, 2009
Accepted January 27, 2009