Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability

Table 1 Clinicopathologic characteristics of 207 pancreatic ductal adenocarcinoma patients undergoing surgery

Parameter	No. of patients
	Simultaneous resections (Group A)	Palliative surgical bypass (Group B)	Total (Group A + Group B)	Pancreatectomy alone (Group C)
	n = 30	n = 39	n = 69	n = 138
Mean age ± SD, yr	62.2 ± 10.0	63.0 ± 10.4	62.6 ± 10.1	58.8 ± 10.6
Sex (Female)	10	12	22	45
ASA
I	11	10	21	37
II	19	27	46	97
III	0	2	2	4
IV	0	0	0	0
Primary tumor location
Head/neck	15	38	53	106
Body/tail	15	1	16	32
Median primary tumor size [IQR], cm	4.0 (2.5-5.0)	-	-	3.0 (2.0-3.5)
Pathology (PDAC)	30	39	69	138
TNM stage
I	0	0	0	22
IIA	0	0	0	22
IIB	0	0	0	94
III	0	0	0	0
IV	30	39	69	0
Primary tumor differentiation
Well/moderate	13	-	-	71
Poor	17	-	-	67
Ki67 [IQR], %	20 (8-30)	-	-	30 (15-50)
Venous invasion	3	19	22	37
Lymph node invasion	14	-	-	82
Hepatic metastasis	30	39	69	0
Surgery for primary tumor
Total pancreatectomy	1	0	1	5
Pancreaticoduodenectomy	11	0	11	95
Distal pancreatectomy	18	0	18	38
Palliative bypass	0	39	39	0

Table 2 Predictors of synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma

Parameter	Total (Group A + Group B)	Pancreatectomy alone (Group C)	P value (univariate)
	n = 69	n = 138
Age, yr
≤ 62	32	80
> 62	37	58	0.116
Sex
Male	47	93
Female	22	45	0.916
BMI
< 18 kg/m2	6	11	0.196
18-25 kg/m2	54	101
> 25 kg/m2	9	26	0.965
Smoke
No	50	97
Yes	19	41	0.745
ASA
I	21	37
II-III	48	101	0.584
CA19-9
≤ 400 U/mL	40	116
> 400 U/mL	29	22	< 0.001
CA125
≤ 38 U/mL	20	121
> 38 U/mL	49	26	< 0.001
CEA
≤ 5 U/mL	42	112
> 5 U/mL	27	26	0.002
Fibrinogen
≤ 4.0 g/L	50	101
> 4.0 g/L	19	37	0.912
NLR
≤ 5	59	131
> 5	10	7	0.026
PLR
≤ 150	36	78
> 150	33	60	0.553
PNI
> 45	42	101
≤ 45	27	37	0.072
Platelet
≤ 250 × 109/L	53	108
> 250 × 109/L	16	30	0.813
Jaundice
No	34	78
Yes	35	60	0.431
Albumin
> 35 g/L	42	82
≤ 35 g/L	27	56	0.841
Diabetes mellitus
No	39	101
Yes	30	37	0.017
Pancreatitis
No	42	93
Yes	27	45	0.354

Table 3 Multivariate analysis of predictors of synchronous liver metastasis

Parameter	Odds ratio	95%CI	P value
CA19-9
≤ 400 U/mL
> 400 U/mL	2.398	0.909-6.327	0.077
CA125
≤ 38 U/mL
> 38 U/mL	12.397	5.468-28.105	< 0.001
CEA
≤ 5 U/mL
> 5 U/mL	0.672	0.249-1.817	0.434
NLR
≤ 5
> 5	0.934	0.283-3.083	0.911
Diabetes mellitus
No
Yes	3.343	1.539-7.262	0.002

Table 4 Risk factors for unresectability of synchronous liver metastasis from pancreatic ductal adenocarcinoma

Parameter	Simultaneous resections (Group A)	Palliative surgical bypass (Group B)	P value (univariate)
	n = 30	n = 39
Age, yr
≤ 62	20	12
> 62	10	27	0.004
Sex
Male	20	27
Female	10	12	0.821
BMI
< 18 kg/m2	2	4	0.664
18-25 kg/m2	23	31
> 25 kg/m2	5	4	0.472
Smoke
No	23	27
Yes	7	12	0.494
ASA
I	11	10
II-III	19	29	0.326
CA19-9
≤ 400 U/mL	22	18
> 400 U/mL	8	21	0.026
CA125
≤ 38 U/mL	11	9
> 38 U/mL	19	30	0.221
CA125
≤ 62 U/mL	21	11
> 62 U/mL	9	28	0.001
CEA
≤ 5 U/mL	22	20
> 5 U/mL	8	19	0.066
Fibrinogen
≤ 4.0 g/L	21	29
> 4.0 g/L	9	10	0.688
NLR
≤ 5	26	33
> 5	4	6	0.811
PLR
≤ 150	17	19
> 150	13	20	0.513
PNI
> 45	22	20
≤ 45	8	19	0.066
Platelet
≤ 250 × 109/L	26	27
> 250 × 109/L	4	12	0.097
Albumin
> 35 g/L	23	19
≤ 35 g/L	7	20	0.021
Diabetes mellitus
No	17	22
Yes	13	17	0.983
Pancreatitis
No	22	20
Yes	8	19	0.066

Table 5 Multivariate analysis of risk factors for unresectability of synchronous liver metastasis from pancreatic ductal adenocarcinoma

Parameter	Odds ratio	95%CI	P value
Age, yr
≤ 62
> 62	3.921	1.217-12.632	0.022
CA19-9, U/mL
≤ 400 L
> 400	1.760	0.517-5992	0.366
CA125, U/mL
≤ 62
> 62	5.181	1.612-16.665	0.006
Albumin
> 35 g/L
≤ 35 g/L	1.796	0.516-6.253	0.357

Table 6 Cox regression analysis of prognostic factors in pancreatic ductal adenocarcinoma patients with synchronous liver metastasis undergoing surgery

Parameter	n	Median OS (95%CI) (mo)	Univariate analysis	Multivariate analysis
			P value	Hazard ratio	95%CI	P value
Age, yr
≤ 62	32	9.988 (5.215-14.760)
> 62	37	4.534 (3.294-5.774)	0.006	2.191	1.182-4.060	0.013
Sex
Male	47	5.388 (2.454-8.322)
Female	22	7.129 (5.820-8.439)	0.428
BMI, kg/m2
< 18	6	4.008 (0.000-8.701)	0.939
18-25	54	6.998 (5.147-8.849)
> 25	9	7.721 (1.548-13.894)	0.548
Smoke
No	50	7.031 (4.606-9.455)
Yes	19	5.979 (0.607-11.352)	0.317
ASA
I	21	9.988 (3.524-16.452)
II-III	48	6.998 (3.803-10.193)	0.273
Primary tumor location
Head/neck	53	6.998 (4.910-9.086)
Body/tail	16	7.129 (3.438-10.820)	0.762
CA19-9, U/mL
≤ 400	40	7.984 (6.454-9.513)
> 400	29	4.008 (2.832-5.185)	0.042	1.398	0.773-2.527	0.267
CA125, U/mL
≤ 62	32	9.035 (7.052-11.017)
> 62	37	4.008 (2.801-5.215)	0.003	2.601	1.403-4.823	0.002
CEA, U/mL
≤ 5	42	7.721 (6.340-9.102)
> 5	27	5.191 (1.847-8.535)	0.320
Fibrinogen, g/L
≤ 4.0	50	7.129 (5.373-8.886)
> 4.0	19	5.191 (2.575-7.807)	0.533
NLR
≤ 5	59	7.031 (5.123-8.939)
> 5	10	4.008 (0.000-9.812)	0.495
PLR
≤ 150	36	7.031 (4.545-9.517)
> 150	33	5.979 (3.287-8.672)	0.851
PNI
> 45	42	7.129 (6.237-8.022)
≤ 45	27	5.848 (3.396-8.300)	0.890
Platelet
≤ 250 × 109/L	53	6.998 (5.018-8.978)
> 250 × 109/L	16	7.097 (0.957-13.236)	0.993
Jaundice
No	34	7.721 (4.540-10.901)
Yes	35	6.998 (3.593-10.403)	0.446
Biliary drainage
No	45	7.129 (5.245-9.014)
Yes	24	5.027 (1.872-8.181)	0.878
Bilirubin, μmol/L
≤ 50	58	6.998 (4.918-9.078)
> 50	11	7.031 (1.408-12.651)	0.448
Albumin, g/L
> 35	42	7.097 (4.893-9.300)
≤ 35	27	5.027 (2.171-7.882)	0.799
Diabetes mellitus
No	39	6.998 (4.177-9.819)
Yes	30	6.998 (4.424-9.572)	0.300
Pancreatitis
No	42	5.979 (4.876-9.186)
Yes	27	6.998 (2.516-11.480)	0.789

Table 7 Comparison of perioperative parameters in different cohorts of patients undergoing surgery

Parameter	No. of patients		P value
	Simultaneous resections (Group A)n = 30	Pancreatectomy alone (Group C) n = 138
Mean operative time, min	344.3	380.5	0.494
Median blood loss, mL	400	400	0.780
Intra-operative RBC transfusion	12	61	0.691
Complication
Pancreatic fistula	9	22	0.072
Any other	13	44	0.230
Biliary fistula	0	0
Chylous fistula	1	3
Delayed gastric emptying	4	10
Intra-abdominal infection	6	28
Gastrointestinal hemorrhage	0	1
Cerebral infarction	1	0
Pneumonia	1	2
Post-operative diabetes mellitus			0.602
Dissolved	7	15
New-onset	6	12
Persistent	6	22
Re-admission	2	4
In-hospital mortality	0	0
Hospital stay, d	18	19	0.479

Table 8 Survival data from published studies with simultaneous resections of primary pancreatic ductal adenocarcinoma and synchronous liver metastasis

	Simultaneous resections		Palliative surgical bypass or chemotherapy		Pancreatectomy alone		P value
	Median (mo)	n	Median (mo)	n	Median (mo)	n
Adam et al[57] (2006)	NA1	41	-	-	-	-	-
Yamada et al[58] (2006)	15.0	6	-	-	-	-	-
Gleisner et al[59] (2007)	5.9	17	-	-	-	-	-
Shrikhande et al[60] (2007)	7.9	10	-	-	-	-	-
De Jong et al[51] (2010)	17.7	NA	-	-	17.9	NA	0.730
De Jong et al[61] (2010)	13.02	14	-	-	-	-	-
Dünschede et al[49] (2010)	8.0	9	11	5	-	-	-
Seelig et al[62] (2010)	11.8	4	-	-	-	-	-
Klein et al[50] (2012)	13.0	7	-	-	26.5	13	NA
Tachezy et al[63] (2016)	14.5	69	7.5	69	-	-	< 0.001

¹Five-year survival of 20% was provided;

²The median survival of 25 patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma.