Tumor Characteristics and their Relationship to Colorectal

Cancer Relapse
Makkai-Popa, S.-T.1,2, Zugun, F.3, Georgescu, St.-O.1,2, Popa, Paula2, Carasevici, E.1,3, Tarcoveanu, E.1,2

1Gr.

T. Popa University of Medicine and Pharmacy Iasi, 2Sf. Spiridon University Hospital First Surgical Clinic, 3Sf. Spiridon University Hospital
Genetics and Immunology Laboratory

Introduction
Colorectal cancer incidence in Romania 23,57 cases
/ 100000 people. (Trifan et al, 2006)
Most commonly used prognostic classification TNM
staging correlated with the tumor grading;
New prognostic markers:
Lymph node based ratios:
Ratio between lymph nodes containing
metastases and the total number of resected
lymph nodes Sun et al, 2010, Jung Wook Huh
et al, 2012;
Logodds ratio Wang et al, 2008; Persiani et al,
2012;

Pathology based markers:

Abundance of peritumoral inflammatory infiltrate
Jass and Klintrup criteria Jass et al, 2005;
Klintrup et al, 2009;
Type of inflammatory infiltrate Treg cells,
cytotoxic T-cells Katsuhiko et al, 2010;
The abundance of necrosis - Richards et al,
2011;

Systemic markers:
Systemic inflammation Glasgow prognostic
score -McMillan et al, 2007; Roxburgh et al, 2009;
Serum level of tumor markers - CEA Jung
Wook Huh et al, 2012;

Materials and methods

Retrospective study 2007 to 2011 39 patients - 14
metastases and 25 loco-regional relapses after
curative surgical procedure for colorectal cancer;
Aim to explore various clinical and pathological
parameters that could be used to predict if a tumor is
more aggressive (defined by how fast it relapses) and
what kind of relapse is more likely to appear(local vs.
distant);
Exclusion criteria:
Previous radiotherapy or chemotherapy;
Previous neoplasia;
Synchronous neoplastic lesions;
Autoimmune disease;
Inflammatory bovel disease;
Infectious disease present at the time of the first
surgical procedure;
Patients who underwent the first procedure in
another clinic;

Comparison between different prognostic factors was

possible in only 25 out of 39 patients because of
missing data;
Statistical analysis SPSS (20th edition) for Windows:
correlations between variables Spearman`s rank
correlation;
multivariate analysis Cox proportional hazard
model variabiles were simultaneously introduced in
the model (enter method) significance level for
exclusion of variables 0,2;
p0,05 statistically significant;

Results
39 patients 14 metastases (35,9%), 25 loco-regional
relapses (64,1%);
Gender distribution 17 (43,6%) males and 22
(56,4%) females, respectively 12 (48%) males and 13
(52%) females in the group of patients selected for
multivariate analysis;
Age distribution between 31 and 83 years old, with a
mean of 62,28 years, a standard deviation of 14,45
years and a median of 66 years;
Site of primary tumor 9(23,07%) right colon tumors
(caecum, ascending and transverse colon) 17(43,6%)
left colon tumors (descending colon and sigma)
13(33,3%) rectal tumors (including recto-sigmoid
tumors);
12(30,76%) cases presented as emergencies;
Poster template by ResearchPosters.co.za

Clinical characteristics
and theirLayout
correlation with
Altering The Column
the relapse prognosis

Number Number
of
of
invaded harvested
lymph
lymph
nodes
nodes

Type of relapse
Locoregional
relapse

Metastasis

Gender
Age
Location of primary
tumor
Emergency character
of first admission

Male

6 (54,5%)

5 (35,7%)

Female

5(45,5%)

9(64,3%)

<66

5(45,5%)

7(50%)

66

6(54,5%)

7(50%)

Right colon

1(9,1%)

5(35,7%)

Left colon

7(63,6%)

4(28,6%)

Rectum

3(27,3%)

5(35,7%)

Emergency

4(36,4%)

4(28,6%)

Elective

7(63,6%)

10(71,4%)

Chipsquare value

0,887

0,346

0,051

0.821

3,678

0,159

0,172

0,678

Table 1. Relationship between clinical characteristics and type of relapse.

Longer ICU stay was positively correlated with

advanced age (p = 0,024);
Hospital stay was longer for patients presenting as
emergency (p = 0,002) and was inversely correlated to
the disease free interval (p = 0,024);

Pathology findings and their correlation with the

relapse prognosis

Tumor size
Resection margins
Presence of a
perforated tumor
Infiltration of serosal
layer

< 50 mm
50 mm
30 mm
> 30 mm
Yes
No
Not infiltrated

Type of relapse
LocoMetastasis
regional
relapse
2 (18,2%)
5 (35,7%)
9(81,8%)
9(64,3%)
4(36,4%)
6(42,9%)
7(63,6%)
8(57,1%)
2(18,2%)
2(14,3%)
9(81,8%)
7(85,7%)
3(27,3%)
2(14,3%)

Infiltrated

8(72,7%)

12(85,7%)

Well differentiated
Moderately
differentiated

1(9,1%)

4(28,6%)

9(81,8%)

8(57,1%)

Poorly differentiated

1(9,1%)

2(14,3%)

Yes

4(36,4%)

4(28,6%)

No

7(63,6%)

10(71,4%)

Presence of perineural
invasion

Yes

2(18,2%)

3(21,4%)

No

9(81,8%)

11(78,6%)

Presence of
intravascular tumor
emboli

Yes

6(54,5%)

3(21,4%)

Degree of tumor
differentiation

Presence of a mucinous
component

Degree of necrosis

No

5(45,5%)

11(78,6%)

Abundant

5(45,5%)

10(71,4%)

Rare

6(54,5%)

4(28,6%)

Lymph node
ratio (LNR)
Logodds
ratio
(LODDS)
Logodds
ratio for
patients
with 12
harvested
lymph
nodes
(LODDS12)
LNR
categories
defined by
quartiles
(LNR
quartiles)
Logodds
ratio
categories
defined by
quartiles
(LODDS
quartiles)

LNR

LODDS LODDS12

LNR
quartiles

LODDS
quartiles

rho

,945

-0,247

,938

,990

,949

,899

p-value

<0,001

0,235

<0,001

<0,001

<0,001

<0,001

rho

,872

-,498*

,938

,898

,961

p-value

<0,001

0,011

<0,001

<0,001

<0,001

rho

,951

-0,517

,990

,847

,917

p-value

<0,001

0,07

<0,001

<0,001

<0,001

rho

,848

-0,315

,949

,898

,847

,892

p-value

<0,001

0,126

<0,001

<0,001

<0,001

<0,001

rho

,785

-,579

,899

,961

,917

,892

p-value

<0,001

0,002

<0,001

<0,001

<0,001

<0,001

Table 4. Correlation of different lymph node ratios with the number of invaded lymph
nodes, with the number of harvested lymph nodes and between different coefficients .

pvalue

p-value = 0,021.

0,332
0,742
0,792
0,623

p-value = 0,049.
0,395

0,678

0,840

0,087

0,188

Table 2. Relationship between pathology findings and type of relapse.

Correlation of pathology findings with the disease free
interval

Spearman`s
rho

pvalue

Size of the tumor

-0,197

0,346

Vegetant character of the tumor

0,514

0,009

Perforated tumor

0,136

0,516

Stenotic tumor

0,055

0,792

Circumferential growth of the tumor

0,023

0,914

Resection margin

-0,111

0,599

Infiltrated serosa

0,069

0,742

Inflammation

0,044

0,833

Acute inflammation

0,123

0,558

Chronic inflammation

-0,085

0,685

Presence of a peritumoral abcess

-0,104

0,621

Tumor differentiation

0,309

0,133

Tumor grading

0,208

0,318

Presence of a mucinous component

0,166

0,426

Presence of perineural invasion

0,305

0,138

Presence of intravascular tumor emboli

0,035

0,869

Presence of extensive necrosis

0,238

0,252

Table 3. Correlation of pathology findings with the disease free interval.

Lymph node based ratios and their correlation with

the relapse prognosis

Figure 1. Kaplan-Meier survival curves when clasifying the patients according to pN

categories and Logdds categories and the p-values resulted from comparing the groups
by using the log-rank test.
Gender
Onset age category
Necrosis
Intravascular tumor
emboli
Perineural invasion
Mucinous component
Resection margin
Tumor size
Logodds ratio
Logodds ratio
category quartiles
Logodds ratio
category quartiles(1)
Logodds ratio
category quartiles(2)
Logodds ratio
category quartiles(3)

SE

Wald

df

p-value

Exp(B)

0,906
-2,235
-0,898

0,73
0,82
1,1

1,53
7,32
0,62

1
1
1

0,216
0,007
0,431

2,47
0,10
0,40

95,0% CI for Exp(B)

Lower
Upper
0,59
10,375
0,021
0,54
0,044
3,808

-0,903

1,05

0,73

0,391

0,40

0,052

3,187

-0,006
-2,196
0,002
-0,087
5,526

1,01
0,82
0,01
0,04
1,80

0
7,13
0,03
4,71
9,33

1
1
1
1
1

0,995
0,008
0,856
0,03
0,002

0,99
0,11
1,00
0,91
251,11

0,137
0,022
0,982
0,847
7,257

7,204
0,557
1,022
0,992
8689,516

14,55

0,002

12,444 3,76 10,95

0,001

253824,5

5,252

2,17

5,85

0,016

190,97

2,715

13432,481

3,563

1,67

4,54

0,033

35,26

1,332

933,749

159,93 402836977,7

Table 5. Cox regression model for Logodds ratio and Logodds ratio categories after
allowing for the effects of other significant variables.

Conclusions
Small number of patients short time interval and
selection criteria further large scale studies are
necessary;
None of the pathology related factors could be
correlated to the type of relapse at a statistical
significance level of 0,05 or under;
Logodds ratio correlates well with all other lymph node
based scores, with the number of positive lymph nodes
(p<0,001) and with the number of harvested lymph
nodes (p=0,011, when Logodds is treated as a
continuous variable), whereas LNR only correlates
with the number of positive nodes (p<0,001), but not
with the total number of harvested nodes (p= 0,235);
Logodds could be used to stratify patients in terms of
relapse free survival time as shown by the KaplanMeier survival analysis;
In a Cox proportional hazard model we show that
Logodds ratio (p=0,002) togheter with the presence of
a mucionous component (p=0,008) can be used to
asses the aggressivness of the tumor in terms of how
fast a relapse can occur;