Negative oncologic impact of poor postoperative pain control in left-sided pancreatic cancer

Table 1 Clinicopathologic characteristics of the patients n (%)

Characteristic (n = 212)	Frequency, mean ± SD
Age (yr)	62.8 ± 9.5
Male gender	125 (59.0)
BMI (kg/m2)	22.8 ± 2.9
Diabetes	73 (34.4)
ASA
1	66 (31.1)
2	92 (43.4)
3	49 (23.1)
4	2 (0.9)
Operative time (min)	402.2 ± 129.3
Intraoperative bleeding (mL)	626.0 ± 482.8
Intraoperative transfusion	47 (22.2)
pT stage
T0	9 (4.2)
T1	16 (7.5)
T2	3 (1.4)
T3	182 (85.8)
T4	2 (0.9)
pN stage
N0	106 (50.0)
N1	106 (50.0)
pTNM staging
I	18 (8.5)
II	182 (85.8)
III	2 (0.9)
IV	1 (0.5)
R status
R0	187 (88.2)
R1	23 (10.8)
R2	2 (0.9)
Cell differentiation
Well	24 (11.3)
Moderate	152 (71.7)
Poor	17 (8.0)
Undifferentiated	1 (0.5)
Retrieved lymph nodes	17.3 ± 9.9
Vascular resection	55 (25.9)
Mutivisceral resection	36 (17.5)
Combined resection	71 (33.5)
Lymphovascular invasion	71 (33.5)
Perineural invasion	146 (68.9)
Neoadjuvant CCRT	66 (31.3)
Adjuvant treatment	154 (72.6)
Complications
Minor	112 (52.8)
Major(≥ G3)	20 (9.4)
Length of hospital stay (d)	21.1 ± 15.0
Recurrence	137 (64.6)

ASA: American Society of Anesthesiologists; CCRT: Concurrent chemoradiotherapy.

Table 2 Clinicopathologic differences between the good pain control group and poor pain control group undergoing distal pancreatectomy n (%)

	Pain control group		P value
	Good(n = 53)	Poor(n = 13)
Age (yr)	65.6 ± 8.2	63.2 ± 11.3	0.378
Male gender	30 (56.6)	7 (53.8)	0.858
BMI (kg/m2)	23.1 ± 2.7	23.1 ± 2.4	0.993
Diabetes	17 (32.1)	3 (23.1)	0.739
ASA
1	16 (30.2)	5 (41.7)	0.342
2	22 (41.5)	6 (50.0)
3	15 (28.3)	1 (8.3)
Surgical approach
Open	35 (66.0)	7 (53.8)	0.523
MIS	18 (34.0%)	6 (46.2)
Spleen preservation	7 (13.2)	2 (15.4)	> 0.999
Operation time (min)	254.1 ± 95.3	304.6 ± 89.0	0.088
Intraoperative bleeding (mL)	364.2 ± 296.0	470.38 ± 624.8	0.373
Intraoperative transfusion	5 (9.4)	3 (23.1)	0.185
Tumor size (cm)			0.407
< 3	30 (56.6)	9 (69.2)
≥ 3	23 (43.4)	4 (30.8)
pT stage			0.148
T0	3 (5.7)	0 (0)
T1	3 (5.7)	2 (15.4)
T2	2 (3.8)	1 (7.7)
T3	45 (84.9)	9 (69.2)
T4	0 (0.0)	1 (7.7)
pN stage			0.851
N0	27 (50.9)	7 (53.8)
N1	26 (49.1)	6 (46.2)
pTNM staging			0.429
I	5 (9.5)	2 (15.4)
II	44 (83.0)	10 (77.0)
III	0 (0.0)	1 (7.7)
IV	1 (1.9)	0 (0.0)
R status			0.121
R0	47 (88.7)	11 (84.6)
R1	6 (11.3 )	1 (7.7)
R2	0 (0.0 )	1 (7.7)
Retrieved lymph nodes	14.8 ± 11.0	14.2 ± 6.6	0.735
Multivisceral resection	12 (22.6)	2 (15.4)	0.718
Combined resection	14 (26.4)	2 (15.4)	0.496
Lymphovascular invasion	14 (27.5)	4 (33.3)	0.729
Perineural invasion	34 (66.7)	5 (41.7)	0.185
Grade			0.499
Well	3 (6.4)	2 (16.7)
Moderate	38 (80.9)	9 (75.0)
Poor	6 (12.8)	1 (8.3)
Neoadjuvant CCRT	12 (22.6)	4 (30.8)	0.719
Preoperative CA19-9			0.154
< 300	34 (69.4)	12 (92.3)
≥ 300	15 (30.6)	1 (7.7)
Adjuvant treatment	39 (73.6)	9 (69.2)	0.739
Time to adjuvant treatment (d)	53.7 ± 36.8	63.0 ± 47.0	0.520
Complications
Minor	33 (62.3)	7 (53.8)	0.578
Major(≥ G3)	3 (7.3)	2 (28.6)	0.148
Use of PCA			0.445
IV PCA	34 (64.2)	10 (76.9)
Epidural PCA	17 (32.1)	2 (15.4)
None	2 (3.8)	1 (7.7)
Length of hospital stay (d)	17.1 ± 11.0	27.2 ± 45.9	0.446

ASA: American Society of Anesthesiologists; CCRT: Concurrent chemoradiotherapy; MIS: Minimal invasive surgery; PCA: Patient-controlled analgesia.

Table 3 Univariate analysis of factors affecting disease-free survival and overall survival after distal pancreatectomy

	n	DFS		OS
		Median survival (mo)	P value1	Median survival (mo)	P value1
Age
< 65	30	15	0.216	42	0.150
≥ 65	36	11		23
Sex
Female	29	11	0.136	27	0.829
Male	37	18		33
BMI (kg/m2)
< 25	52	11	0.209	30	0.384
≥ 25	14			27
Diabetes
No	46	13	0.674	27	0.654
Yes	20	15
ASA
1/2	49	13	0.569	30	0.903
3/4	16	15
Surgical approach
Open	42	14	0.971	30	0.645
MIS	24	11		41
Spleen preservation
Yes	9	15	0.931	27	0.619
No	57	13		33
Operation time (min)
< 300	39	17	0.254	41	0.035
≥ 300	27	13		15
Bleeding (mL)
< 500	42	11	0.632	30	0.881
≥ 500	23	15		33
Intraoperative transfusion
No	58	15	0.005	33	0.056
Yes	8	4		13
Resection status
R0	58	13	0.689	30	0.382
R1/R2	8	13		21
Lymph node status
N0	34		0.011	41	0.020
N1	32	9		17
Tumor size (cm)
< 3	39	18	0.028	42	0.023
≥ 3	27	8		15
pT stage
≤ 2	11		0.293	21	0.949
≥ 3	55	13		33
Multivisceral resection
No	52	15	0.111	33	0.043
Yes	14	10		13
Combined resection
No	50	15	0.474	33	0.303
Yes	16	10		15
Lymphovascular invasion
No	45	11	0.259	23	0.762
Yes	18	18		30
Perineural invasion
No	24	11	0.947	21	0.621
Yes	39	15		27
Neoadjuvant CCRT
Yes	16	15	0.351	33	0.433
No	50	11		21
Preop CA19-9 (U/mL)
< 300	46	15	0.782	27	0.540
≥ 300	16	13		42
Adjuvant treatment
Yes	48	15	0.094	41	0.017
No	18	4		8
Major complications (≥ G3)
No	43	15	0.813	42	0.916
Yes	5	4		21
Use of PCA
Epidural	19	13	0.757	27	0.943
IV	44	15		33
Pain control
Good	53	18	0.001	42	0.001
Poor	13	8		15

¹P values were obtained using a log-rank test. DFS: Disease-free survival; OS: Overall survival; ASA: American Society of Anesthesiologists; MIS: Minimal invasive surgery; CCRT: Concurrent chemoradiotherapy; PCA: Patient-controlled analgesia.

Table 4 Univariate and multivariate Cox regression analysis of factors affecting disease-free survival and overall survival after distal pancreatectomy

Variables	Disease-free survival						Overall survival
	Univariate analysis			Multivariate analysis			Univariate analysis			Multivariate analysis
	Exp (β)	95%CI	P value	Exp (β)	95%CI	P value	Exp (β)	95%CI	P value	Exp (β)	95%CI	P value
Positive lymph node status	2.183	1.162-4.101	0.011	2.259	1.150-4.437	0.018	2.105	1.094-4.053	0.02	2.501	1.218-5.134	0.012
Tumor size (≥ 3 cm)	1.943	0.999-3.781	0.028	2.215	1.130-4.341	0.021	2.030	1.016-4.055	0.023	2.662	1.282-5.529	0.009
No adjuvant treatment	1.742	0.800-3.794	0.094	2.468	1.196-5.093	0.015	2.205	0.981-4.955	0.017	4.649	2.124-10.172	< 0.001
Poor pain control	2.934	1.158-7.430	0.001	4.157	1.938-8.915	< 0.001	2.915	1.156-7.350	0.001	4.741	2.214-10.153	< 0.001
Age (≥ 65 yr)	ND			ND			1.608	0.844-3.064	0.150	1.706	0.799-3.640	0.167
Sex (Male)	0.632	0.338-1.181	0.136	0.614	0.318-1.186	0.146	ND			ND
Operation time (≥ 300 min)	ND			ND			1.949	0.981-3.873	0.035	1.890	0.923-3.868	0.082
Intraoperative transfusion	2.788	0.903-8.612	0.005	1.745	0.688-4.425	0.241	2.159	0.729-6.396	0.056	1.986	0.750-5.257	0.167
Multivisceral resection	1.720	0.769-3.849	0.111	1.166	0.532-2.557	0.701	2.046	0.837-5.006	0.043	1.273	0.563-2.876	0.562

ND: Not determined due to lack of significance.