Histopathological investigation of colon liver metastases – which factors affect survival after surgery?

Figures & data

Table 1. Baseline characteristics of included patients collected from medical journals.

	n (column %)
Patients included	260
Gender
Male	150 (58)
Female	110 (42)
Missing	0
Age
<70	130 (50)
≥70	130 (50)
Missing	0
Site of primary tumor
Right	83 (32)
Left	174 (68)
Missing	3
Primary node status
Positive	164 (68)
Negative (0)	78 (32)
Missing	18
Number of liver metastases
1	118 (48)
≥1	130 (52)
Missing	12
Size of largest tumor
<50 mm	191 (77)
≥50 mm	56 (23)
Missing	13
R0
Yes	196 (87)
No	30 (13)
Missing	36
Synchronous
Yes	192 (74)
No	68 (26)
Missing	0
Extrahepatic disease
Yes	28 (11)
No	229 (89)
Missing	3
Vascular/lymphatic invasion
Yes	90 (35)
No	170 (65)
Missing	0
Perineural invasion
Yes	64 (25)
No	195 (75)
Missing	1
Preoperative CEA
<200	230 (95)
≥200	13 (5)
Missing	17
TRG
1	4 (2)
2	180 (69)
3	76 (29)
Missing	0
Pattern
A	25 (10)
B	169 (65)
C	63 (25)
Missing	3
Pseudocapsule
Yes	35 (14)
No	224 (86)
Missing	1
Acellullar mucin
<1%	215 (83)
≥1%	44 (17)
Missing	1
Neoadjuvant chemotherapy
Yes	183 (73)
No	67 (27)
Missing	10
Adjuvant chemotherapy
Yes	184 (74)
No	64 (26)
Missing	12

Note: CEA: carcinoembryonic antigen; TRG: tumor regression grade

Figure 1. Flowchart representing patient inclusion and exclusion process.

Figure 2. Tumor growth patterns. (A) Pushing growth pattern. (B) Desmoplastic growth pattern. (C) Replacement growth pattern.

Table 2. Survival data generated by using Cox proportional hazard model.

	Univariate analysis			Multivariate analysis
Variable	HR	95% CI	p	HR	95% CI	p
Right sided primary tumor	1.3	0.93–1.86	.12
Age >70	1.0	0.71–1.37	.93
Gender (man)	1.0	0.75–1.50	.80
Node positive primary tumor	1.2	0.85–1.80	.26
>1 liver metastasis	1.1	0.75–1.50	.73
Tumor size > 50 mm	1.4	0.95–2.04	.09
Preoperative CEA >200	2.2	1.24–4.07	<.01*	2.1	1.13–3.92	.02*
Lung metastases at time of liver resection	1.9	1.18–3.00	<.01*	1.7	1.06–2.81	.03*
R0 resection (radical VS non-radical)	0.7	0.42–1.12	.13
Synchronous (DFI < 12 months)	1.1	0.74–1.59	.66
Acellular mucin	1.4	0.92–2.14	.11
TRG 3 (vs 2)	0.85	0.59–1.24	.41
Pattern C (vs B)	1.3	0.90–1.92	.16
Pseudo capsule	0.95	0.59–1.55	.85
Perineural invasion	1.7	1.20–2.51	<.01*	1.3	0.88–2.01	.17
Vascular invasion	1.7	1.23–2.4	<.01*	1.6	1.07–2.25	.02*

Note: CEA: carcinoembryonic antigen; TRG: tumor regression grade; HR: hazard ratio; CI: confidence interval.

*p < .05.

Table 3. Recurrence data generated by using Cox proportional hazard model.

	Univariate analysis			Multivariate analysis
Variable	HR	95% CI	p	HR	95% CI	p
Right sided primary tumor	1.1	0.78–1.50	.62
Age >70	0.8	0.58–1.06	.12
Gender (man)	1.1	0.83–1.54	.45
Node positive primary tumor	2.0	1.35–2.86	<.001*	1.3	0.80–2.12	.28
>1 liver metastasis	1.5	1.11–2.07	<.01*	1.7	1.12–2.50	.01*
Tumor size > 50 mm	1.3	0.93–1.89	.12
Preoperative CEA >200	2.0	1.10–3.76	.02*	1.6	0.79–3.30	.19
Lung metastases at time of liver resection	3.0	2.0–4.56	<.001*	2.9	1.80–4.80	<.001*
R0 resection (radical VS non-radical)	0.6	0.47–0.88	.01*	0.7	0.42–1.11	.13
Synchronous (DFI < 12 months)	1.2	0.83–1.72	.33
Acellular mucin	1.4	0.94–2.07	.10
TRG 3 (vs 2)	0.9	0.62–1.21	.41
Pattern C (vs B)	1.2	0.84–1.72	.33
Pseudo capsule	1.0	0.65–1.56	.99
Perineural invasion	1.8	1.30–2.52	<.001*	1.3	0.88–2.03	.17
Vascular invasion	2.2	1.64–3.02	<.001*	2.0	1.30–3.00	.001*

Note: CEA: carcinoembryonic antigen; TRG: tumor regression grade; HR: hazard ratio; CI: confidence interval.

*p < .05.

Table 4. Literature overview of studied histopathological markers.

Marker	Study	Patients included	Findings
Acellular mucin	Poultsides et al. [34]	366	No evidence of association acellulcar mucin presence and disease-specific survival
Pseudocapsule	Okano et al. [35]	152	Presence of pseudocapsule was associated with superior survival
	Wiggans et al. [36]	66	Abscence of pseudocapsule was associated with shorter time to recurrence
	Fonseca et al. [23]	229	Absence of pseudo capsule was associated with poor overall survival
	Yamamoto et al. [37]	96	Absence of pseudo capsule was associated with poor overall survival
	Serrablo et al. [22]	150	No correlation between presence of pseudocapsule and disease-free survival could be found
Tumor growth pattern	Van den Eynden et al. [38]	205	Pushing pattern was associated with poor survival
	Nielsen et al. [28]	217	Replacement pattern was associated with poor survival
	Eefsen et al. [27]	224	Desmoplastic growth was associated with superior survival

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