Materials and Methods
Patients
Blood Count Parameters
Identification of Lymphatic Cells in Peripheral Blood
Statistical Analysis
Results
Patient Characteristics
Parameter | Cohort | |
---|---|---|
Retrospective (n = 442) | Prospective (n = 54) | |
Age, years (median, IQR) | 60 (55–66) | 59 (50–68) |
Female/male (n, %) | 182 (41)/260 (59) | 25 (46)/29 (54) |
Body mass index (median, IQR) | 23.3 (21.3–26.1) | 22.6 (20.4–26.9) |
WBC, 109/L (median, IQR) | 6.915 (5.745–8.560) | 7.725 (5.930–8.430) |
Neutrophils, 109/L (median, IQR) | 4.25 (3.36–5.67) | 5.20 (3.30–6.40) |
Lymphocytes, 109/L (median, IQR) | 1.75 (1.28–2.22) | 1.64 (1.20–2.07) |
Monocytes, 109/L (median, IQR) | 0.590 (0.480–0.850) | 0.700 (0.500–0.900) |
Platelets, 109/L (median, IQR) | 249 (200–326) | 248 (198–319) |
Neutrophil-lymphocyte ratio (median, IQR) | 3.0 (2.0–4.1) | 2.9 (2.2–3.7) |
Lymphocyte-monocyte ratio (median, IQR) | 3.3 (2.3–5.0) | 2.7 (1.7–3.5) |
Platelet-lymphocyte ratio (median, IQR) | 149 (105–208) | 156 (129–247) |
Preoperative endoscopic biliary drainage, n (%) | 121 (27) | 17 (31) |
Procedure (n, %) | ||
Pancreaticoduodenectomy (PD) | 146 (33) | 18 (33) |
Pylorus preserving PD | 107 (24) | 21 (39) |
Distal pancreatectomy | 101 (23) | 12 (22) |
Total pancreatectomy | 88 (20) | 3 (6) |
Tumor size, mm (median, IQR) | 30 (25–40) | 28 (22–44) |
Perineural invasion, n (%) | 292 (66) | 34 (62) |
Lymphovascular invasion, n (%) | 339 (77) | 39 (72) |
Tumor differentiation, n (%) | ||
Well-differentiated | 43 (10) | 6 (11) |
Moderately/poorly differentiated | 399 (90) | 48 (89) |
AJCC stage (n, %) | ||
IA | 18 (4) | 3 (6) |
IB | 29 (7) | 5 (9) |
IIA | 103 (23) | 12 (22) |
IIB | 283 (64) | 33 (61) |
III | 9 (2) | 1 (2) |
Resection margin, n (%) | ||
R0 | 226 (51) | 29 (54) |
R1/R2 | 210 (48)/6 (1) | 24 (44)/1 (2) |
Postoperative chemotherapy, n (%) | 235 (53) | 42 (78) |
Blood Count Parameters
Predictive Factors for Survival
Parameter | Categoriesa
| Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|---|
HR (95 % CI) |
P
b
| HR (95 % CI) |
P
c
| ||
Age | <65/≥65 years | 1.45 (1.07–1.96) | 0.016 | 1.74 (1.19–2.55) | 0.004 |
Gender | Female/male | 1.07 (0.80–1.43) | 0.662 | – | |
NLR | <5, ≥5 | 1.58 (1.12–2.72) | 0.001 | 1.66 (1.12–2.46) | 0.012 |
LMR | ≥3, <3 | 1.93 (1.19–3.11) | 0.001 | 1.65 (1.06–2.58) | 0.026 |
CA 19-9 level | <180/> 180 U/mL | 1.04 (0.68–1.41) | 0.623 | – | |
Tumor location | Head/other | 1.09 (0.77–1.54) | 0.599 | – | |
Tumor size | <20/≥20 mm | 1.08 (0.74–1.58) | 0.675 | – | |
Perineural invasion | No/yes | 1.41 (1.06–1.89) | 0.018 | 1.32 (0.75–2.31) | 0.332 |
Lymphovascular invasion | No/yes | 0.98 (0.59–1.60) | 0.935 | – | |
Tumor differentiation | Well/other | 1.36 (0.81–2.28) | 0.237 | – | |
AJCC T category | T1–2/T3–T4 | 2.25 (1.23–4.09) | 0.008 | 2.90 (0.73–11.42) | 0.127 |
AJCC N category | N0/N1 | 1.57 (1.13–2.17) | 0.007 | 1.75 (1.090–2.79) | 0.019 |
Metastatic lymph node ratio | <0.2; ≥0.2 | 1.92 (1.39–2.65) | <0.001 | 1.69 (1.10–2.60) | 0.016 |
AJCC stage | I/II and III | 1.86 (1.01–3.45) | 0.049 | 2.96 (0.79–13.94) | 0.337 |
Resection margin | R0/R1 and 2 | 2.17 (1.51–3.11) | <0.001 | 2.16 (1.16–4.02) | 0.015 |
Chemotherapy | Yes/no | 0.94 (0.61–1.45) | 0.794 | – |
Correlation of NLR and LMR with Changes in Lymphocyte and Monocyte Sub-populations
Cell phenotype | Population | NLR | LMR | ||
---|---|---|---|---|---|
<5 | ≥5 | <3 | ≥3 | ||
Neutrophils | Neutrophils | 4250 (3257–6140) | 6090 (4700–7570)* | 4900 (3250–6200) | 5300 (4000–7900) |
Lymphocytes overall | Lymphocytes | 1839 (1462–2550) | 928 (484–1156)* | 1316 (1026–1760) | 2360 (1787–3948)* |
CD3+ | T cells | 1384 (1007–1833) | 761 (371–966)* | 985 (788–1308) | 1655 (1384–3055)* |
CD3 +/CD4+ | Helper T cells | 797 (654–1252) | 466 (271–581)* | 589 (466–981) | 808 (716–1811)* |
CD3 +/CD8+ | Cytotoxic T cells | 421 (299–717) | 244 (158–319)* | 306 (223–373) | 717 (485–1071)* |
CD19+ | B cells | 164 (137–211) | 66 (37–96)* | 128 (66–180) | 170 (137–211)* |
CD16 + 56 | NK cells | 266 (148–314) | 75 (40–143)* | 174 (103–264) | 314 (117–576)* |
CD14 ++ CD16− | Monocytes, classical | 669 (371–945) | 512 (370–649) | 659 (520–929) | 395 (275–566)* |
CD14 ++ CD16+ | Monocytes, intermediate | 26 (15–34) | 22 (11–34) | 29 (18–42) | 23 (11–29)* |
CD14 + CD16 ++ | Monocytes, non-classical | 43 (30–56) | 35 (25–55) | 49 (35–59) | 34 (24–45)* |
Discussion
Author, year | No. of patients | Cut-off values* | Median survival (months) | Multivariate survival analysis HR (95 % CI) |
---|---|---|---|---|
Neutrophil-lymphocyte ratio (NLR) | ||||
Clark, 200723
| 44 | <5, ≥5 | 10.5/8.9 | No effects on survival |
Smith, 20094
| 110 | Continuous | Not applicable | No effects on survival |
Bhatti, 20105
| 84 | Continuous | Not applicable | 1.21 (1.01–1.45), P = 0.039 |
Jamieson, 201137
| 135 | <5, ≥5 | 20.9/25.7 | No effects on survival |
Garcea, 201138
| 74 | <5, ≥5 | 52.0/12.0 | No effects on survival |
Sanjay, 201239
| 51 | <5, ≥5 | 16.2/9.2 | No effects on survival |
Stotz, 201340
| 110 | <5, ≥5 | Not reported | 1.61 (1.02–2.53), P = 0.039 |
Hamed, 201341
| 85 | <5, ≥5 | 20.6/11.3 | No effects on survival |
Ben, 201542
| 381 | <2, ≥2 | 19.4/12.4 | 1.51 (1.15–1.99), P = 0.003 |
Watanabe, 201635
| 46 | <2.5, ≥2.5 | Not reported | No effects on survival |
Current study | 442 | <5, ≥5 | 25.7/12.6 | 1.66 (1.12–2.46), P = 0.012 |
Lymphocyte-monocyte ratio (LMR) | ||||
Li, 201631
| 144 | <2.86, ≥2.86 | 12.0/19.0 | 0.15 (0.09–0.25), P < 0.001 |
Current study | 442 | ≥3, <3 | 29.2/13.1 | 1.65 (1.06–2.58), P = 0.026 |
Platelet-lymphocyte ratio (PLR) | ||||
Smith, 20094
| 110 | Continuous | Not applicable | 1.004 (1.002–1.006), P < 0.001 |
Bhatti, 20105
| 84 | Continuous | Not applicable | No effects on survival |
Jamieson, 201137
| 135 | <150, ≥150 | 26.7/20.7 | No effects on survival |
Sanjay, 201239
| 51 | 150, 150–300, 300 | 15.9/15.0/4.1 | No effects on survival |
Stotz, 201340
| 110 | <150, ≥150 | Not reported | No effects on survival |
Watanabe, 201635
| 46 | <200, ≥200 | Not reported | 4.55, P = 0.002 |
Current study | 442 | No effects on survival | No effects on survival |