Assessment for the minimal invasiveness of laparoscopic liver resection by interleukin-6 and thrombospondin-1

Table 1 Clinical characteristics of study patients

Factors	LLR	OLR	P
	n = 10	n = 20
Age, years	74 (31-94)	71 (35-83)	0.91
Sex (male/female)	6/4	12/8	1.0
HBs-Ag (positive/negative)	0/10	2/18	0.20
HCV-Ab (positive/negative)	4/6	8/12	1.0
White blood cell, × 103 /uL	5.5 (3.1-6.0)	6.8 (2.5-10.6)	0.23
Platelet, × 104 /uL	16.4 (11.2-21.2)	17.5 (8.3-88.0)	0.36
Prothrombin time, %	102 (69-122)	105 (65-126)	0.86
AST, U/L	23 (14-48)	27 (13-175)	0.52
ALT, U/L	23 (10-46)	26 (6-103)	0.31
ALP, U/L	221 (138-375)	243 (134-676)	0.36
ChE, U/L	263 (154-327)	231 (121-357)	0.39
ICG R15, %	10.4 (4.5-24.7)	10.6 (0.9-65.4)	0.84
Child-Pugh classification (A/B)	10/0	18/2	0.20
Difficulty scoring system	4 (2-5)	4 (2-6)	0.44
Operative time, min	290 (126-660)	385 (82-633)	0.88
Bleeding volume, mL	57 (5-750)	528 (116-9527)	0.003
Resected liver volume, g	66.5 (4-206)	77.5 (2-220)	0.76
Longest diameter of the tumor, mm	17 (6-53)	25 (7-55)	0.27
Number of resected lesion	1 (1-2)	2 (1-7)	0.1
Surgical margin, mm	5 (0-55)	1 (0-22)	0.24
Diagnosis(primary/metastasis/benign)	7/2/1	13/6/1	0.77
Postoperative hospital stay, d	10 (6-14)	14 (8-26)	0.003
Complications (no/yes)	10/0	17/3	0.1

No complication means less than IIIa at clavien-dindo classification. LLR: Laparoscopic liver resection; OLR: Open liver resection; HBs-Ag: hepatitis B surface antigen; HCV-Ab: hepatitis C antibody; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; ChE: Cholinesterase; ICG-R15: Retention of indocyanine green at 15 min.

Table 2 Time course of circulating serum level of interleukin-6 and plasma level of thrombospondin-1 before and after laparoscopic and open liver resection

Factors	LLR	OLR	P
	n = 10	n = 20
IL-6, pg/mL
Preoperatively	3.9 (2.6-43.6)	3.7 (2.0-68.8)	0.50
Postoperatively	30.8 (4.9-189.8)	73.6 (4.7-348.8)	0.14
POD1	8.7 (4.8-359.3)	30.3 (10.8-376.3)	0.003
POD3	9.3 (4.1-99.7)	31.7 (7.0-212.3)	0.03
TSP-1, ng/mL
Preoperatively	1817.1 (141.7-2985.7)	2025.1 (124.6-3815.0)	0.98
Postoperatively	1364.7 (84.1-2459.3)	684.4 (42.5-3580.3)	0.52
POD1	589.1 (139.3-3186.4)	233.6 (36.6-4058.3)	0.12
POD3	1704.0 (665.4-3399.2)	548.3 (30.4-2239.2)	0.009

TSP-1: Thrombospondin-1; IL-6: Interleukin-6; LLR: Laparoscopic liver resection; OLR: Open liver resection; POD: Postoperative days.

Table 3 Comparison between changes in inflammatory and liver functional markers before and after laparoscopic and open liver resection

Factors	LLR	OLR	P
	n = 10	n = 20
Total bilirubin, mg/dL
Preoperatively	0.8 (0.4-1.4)	0.8 (0.4-2.6)	0.69
POD5	0.7 (0.5-0.9)	0.9 (0.3-5.2)	0.11
POD30	0.7 (0.3-1.1)	0.7 (0.4-2.5)	0.95
Bile acid, μmol/L
Preoperatively	7.4 (0.8-16.8)	12.4 (0.7-82.1)	0.21
POD3	4.9 (0.6-20.8)	9.9 (1.6-56.7)	0.13
Albumin, g/dL
Preoperatively	3.8 (3.5-4.5)	3.6 (2.9-4.4)	0.08
POD5	3.0 (2.4-3.3)	3.0 (2.3-3.5)	0.77
POD30	3.9 (3.4-4.6)	3.6 (2.2-4.4)	0.16
Neutrophil, %
Preoperatively	62.1 (46.7-74.3)	67.3 (28.8-85.2)	0.17
POD1	82.5 (68.1-92.7)	83.1 (70.7 – 92.2)	0.86
POD3	70.9 (58.7-83.7)	76.3 (52.9-86.6)	0.20
POD5	69.2 (46.3-80.4)	67.6 (45.1-80.9)	0.95
POD7	67.3 (49.8-76.7)	69.3 (38.3-77.5)	0.42
CRP, mg/dL
Preoperatively	0.07 (0.01-2.67)	0.07 (0.01-3.50)	0.57
POD1	0.96 (0.24-6.32)	1.48 (0.38-4.94)	0.28
POD3	2.04 (0.62-9.16)	5.93 (1.12-16.48)	0.01
POD5	1.18 (0.20-5.83)	4.36 (0.44-14.3)	0.01
POD7	0.65 (0.11-1.52)	2.77 (0.31-9.97)	0.01

LLR: Laparoscopic liver resection; OLR: Open liver resection; POD: Postoperative days; CRP: C-reactive protein.

Table 4 Univariate and multivariate analysis of factors that related with higher level of interleukin-6 on postoperative day 1 in 30 patients who has undergone hepatectomy

Factors	Univariate analysis			Multivariate analysis
	OR	95%CI	P	OR	95%CI	P
Sex (male/female)	0.80	0.18-3.50	0.77
Age (≥ 75/< 75, yr)	1.289	0.30-5.57	0.73
Operative method (OLR/LLR)	9.33	1.74-75.7	0.008	7,48	1.28-63.3	0.02
Number of tumors (single/multiple)	0.21	0.04-0.99	0.048	0.29	0.04-1.64	0.16
Operative time (< 369/≥ 369, min)	2.31	0.54-10.7	0.29
Bleeding loss (< 443/≥ 443, mL)	3.00	0.70-14.3	0.14
Complication (yes/no)	0.74	0.20-11.9	0.74
Skin incision (reverse L-sharp/others)	1.94	0.43-9.62	0.39
Liver mobilization (yes/no)	1.73	0.31-10.6	0.53

IL-6: Interleukin-6; OR: Odds ratio; CI: Confidence interval; OLR: Open liver resection; LLR: Laparoscopic liver resection.

Table 5 Univariate and multivariate analysis of factors that related with lower level of thrombospondin-1 on postoperative day 1 in 30 patients who has undergone hepatectomy

Factors	Univariate analysis			Multivariate analysis
	OR	95% CI	P	OR	95% CI	P
Sex (male/female)	0.57	0.12-2.48	0.46
Age (≥ 75/< 75, yr)	1.00	0.23-4.26	1.00
Higher level of IL-6 on POD1 (≥ 17.0/< 17.0, pg/mL)	5.50	1.22-29.4	0.03	5.32	1.08-32.2	0.04
Operative method (OLR/LLR)	3.50	0.73-20.3	0.29
Number of tumor (single/multiple)	1.00	0.23-4.39	1.00
Operative time (< 369/≥ 369, min)	0.33	0.07-1.43	0.14
Bleeding loss (< 443/≥ 443, ml)	0.44	0.10-1.88	0.27
Complication (yes/no)	1.63	0.23-14.0	0.62
Skin incision (reverse L-sharp/others)	4.57	0.97-26.7	0.05	4.38	0.82-29.9	0.09
Liver mobilization (yes/no)	3.24	0.56-26.2	0.19

TSP-1: Thrombospondin-1; IL-6: Interleukin-6; OR: Odds ratio; CI: Confidence interval; OLR: Open liver resection; LLR: Laparoscopic liver resection.

Table 6 Time course of circulating plasma thrombospondin-1 levels according to serum interleukin-6 levels on postoperative day 1

Factors	Lower IL-6	Higher IL-6	P
	n = 14	n = 16
TSP-1, ng/mL
Preoperatively	2420.6 (223.0-3121.1)	893.9 (124.6-3815.0)	0.088
Postoperatively	1672.7 (42.5-2674.4)	504.8 (53.9-3580.3)	0.067
POD1	447.9 (101.7-3186.4)	246.2 (36.6-4058.3)	0.24
POD3	1432.4 (30.4-3399.2)	548.3 (53.3-3153.2)	0.026

TSP-1: Thrombospondin-1; IL-6: Interleukin-6; POD: Postoperative days.