Effects of anesthetic methods on preserving anti-tumor T-helper polarization following hepatectomy

Table 1 Patient characteristics

Characteristics	G + E group (n = 31)	G group (n = 30)	P
Age (yr)	50.7 ± 1.8	46.9 ± 1.5	0.4161
Gender (male/female)	4/27	8/22	0.2112
Hepatitis history (yes/no)	5/26	6/24	0.7492
AFP ( ≤ 20 ng/mL/> 20 ng/mL)	13/18	14/16	0.7992
Liver cirrhosis (Yes/no)	10/21	7/23	0.5702
ALT ( ≤ 40 U/L/> 40 U/L)	18/13	11/19	0.7952
Child-Pugh Score (A/B)	2/29	2/28	1.0002
Tumor differentiation (I-II/III-IV)	7/24	9/21	0.5702
Tumor size ( ≤ 5 cm/> 5 cm)	8/23	7/23	1.0002
Tumor number (single/multiple)	8/23	5/25	0.5342
Tumor encapsulation (complete/none)	12/19	15/15	0.4442
Vascular invasion (no/yes)	6/25	8/22	0.5542
Blood loss ( ≤ 200 mL/> 200 mL)	1/30	4/26	0.1952
Anesthesia time ( ≤ 3 h/> 3 h)	18/13	9/21	0.4262
VAS score	3.58 ± 0.32	3.67 ± 0.38	0.8631
Dose of fentanyl (μg)	0.30 ± 0.01	0.51 ± 0.01	< 0.0011
Dose of morphine (mg)	2.26 ± 0.08	95.30 ± 1.17	< 0.0011
Dose of sevoflurane (mL)	21.74 ± 0.70	37.90 ± 1.60	< 0.0011

¹Student’s t test;

²Fisher’s exact test. G: General anesthesia; E: Epidural block; AFP: Alpha-fetoprotein; ALT: Alanine transaminase; VAS: Visual analogue scale.

Table 2 T-helper 1, T-helper 2, T-helper 17 and regulatory T cell frequencies in patients

Variables	d0 (%)	d2 (%)	d7 (%)	P (d0/d2)	P (d0/d7)	P (d2/d7)
Th1	7.21 ± 1.01	18.82 ± 1.93	13.40 ± 0.79	< 0.001	< 0.001	0.015
Th2	1.12 ± 0.09	3.32 ± 0.31	0.93 ± 0.10	< 0.001	0.180	< 0.001
Th17	2.57 ± 0.22	2.95 ± 0.26	1.23 ± 0.10	0.269	< 0.001	< 0.001
Treg	6.02 ± 0.27	6.93 ± 0.38	5.45 ± 0.52	0.160	0.329	0.021
Th1/Th2	8.12 ± 1.24	8.50 ± 1.14	14.87 ± 1.26	0.823	< 0.001	< 0.001

Paired student’s t test. Th: T-helper; Treg: Regulatory T cell.

Table 3 Comparison of T-helper 1, T-helper 2, T-helper 17, regulatory T cell frequencies and T-helper 1/T-helper 2 cell ratio between G + E and G anesthesia groups

Variables	G + E group (%)	G group (%)	P
Th1
d0	7.44 ± 1.54	7.38 ± 1.35	0.87
d2	14.66 ± 1.96	20.42 ± 2.77	0.098
d7	16.57 ± 0.96	10.37 ± 0.84	< 0.001
Th2
d0	1.08 ± 0.14	1.14 ± 0.12	0.745
d2	2.64 ± 0.30	3.98 ± 0.49	0.028
d7	0.73 ± 0.07	1.14 ± 0.17	0.231
Th17
d0	2.80 ± 0.26	2.65 ± 0.36	0.424
d2	2.56 ± 0.30	3.01 ± 0.38	0.374
d7	1.08 ± 0.10	1.45 ± 0.15	0.047
Treg
d0	5.44 ± 0.26	6.62 ± 0.45	0.372
d2	7.42 ± 0.60	6.43 ± 0.46	0.194
d7	4.51 ± 0.56	6.19 ± 0.80	0.003
Th1/Th2 ratio
d0	8.63 ± 1.76	7.62 ± 1.32	0.688
d2	9.67 ± 1.94	7.40 ± 1.26	0.253
d7	14.64 ± 0.56	6.03 ± 0.83	< 0.001

Student’s t test. G: General anesthesia; E: Epidural block; Th: T-helper; Treg: Regulatory T cell.

Table 4 Comparison of interferon-γ, interleukin-4, interleukin-17, FoxP3 mRNA levels and interferon-γ/interleukin-4 mRNA ratio between G + E and G groups

Variables	G + E group (×105)	G group (×105)	P
IFN-γ
d0	21.84 ± 2.99	16.49 ± 0.84	0.585
d2	50.91 ± 1.46	62.87 ± 2.71	0.096
d7	41.05 ± 1.05	29.36 ± 0.73	0.029
IL-4
d0	47.12 ± 28.65	59.97 ± 15.17	0.651
d2	66.63 ± 18.45	110.12 ± 24.11	< 0.001
d7	31.80 ± 14.59	58.21 ± 5.74	0.224
IL-17
d0	351.29 ± 55.29	386.64 ± 61.88	0.768
d2	406.68 ± 68.21	677.80 ± 133.07	0.171
d7	226.20 ± 18.37	429.94 ± 11.90	0.042
FoxP3
d0	430.38 ± 48.95	384.52 ± 42.19	0.408
d2	468.85 ± 89.81	432.97 ± 44.45	0.338
d7	248.68 ± 58.71	361.01 ± 46.75	0.109
IFN-γ/IL-4 ratio
d0	0.44 ± 0.03	0.39 ± 0.04	0.883
d2	0.80 ± 0.10	0.58 ± 0.03	0.198
d7	1.14 ± 0.08	0.56 ± 0.01	0.003

Student’s t test. G: General anesthesia; E: Epidural block; IFN-γ: Interferon-γ; IL: Interleukin.

Table 5 Plasma interferon-γ, interleukin-4, interleukin-17, interleukin-10, transforming growth factor-β1 concentrations between G + E and G groups

Variables	G + E group (pg/mL)	G group (pg/mL)	P
IFN-γ
d0	7.56 ± 0.44	6.67 ± 0.70	0.653
d2	11.17 ± 0.97	19.94 ± 1.37	0.018
d7	8.67 ± 0.74	5.76 ± 0.53	0.165
IL-4
d0	10.31 ± 1.78	10.53 ± 1.28	0.892
d2	21.11 ± 3.76	36.69 ± 6.97	0.013
d7	13.00 ± 1.88	25.50 ± 2.98	0.065
IL-17
d0	20.26 ± 5.82	18.83 ± 3.95	0.304
d2	27.26 ± 10.30	40.10 ± 10.56	0.239
d7	9.12 ± 1.67	16.66 ± 2.38	0.009
IL-10
d0	3.67 ± 0.35	3.37 ± 0.31	0.528
d2	7.17 ± 0.86	5.97 ± 0.48	0.218
d7	4.09 ± 0.29	5.65 ± 0.72	0.06
TGF-β1
d0	6565 ± 1667	5312 ± 1102	0.539
d2	15680 ± 4254	8375 ± 1395	0.12
d7	7555 ± 1555	10691 ± 2571	0.311
IFN-γ/ IL-4
d0	0.74 ± 0.10	0.65 ± 0.13	0.618
d2	0.67 ± 0.08	0.56 ± 0.05	0.309
d7	1.10 ± 0.14	0.35 ± 0.08	< 0.001

Student’s t test. G: General anesthesia; E: Epidural block; IFN-γ: Interferon-γ; IL: Interleukin; TGF: Transforming growth factor.