Background
Methods
Ethics
General information
Biochemical assays
Surgical strategy and patient follow-up
Cell lines and culture
Cell migration and invasion assays
Western blot analysis
Quantitative real-time PCR (qRT-PCR)
Statistical analysis
Results
Comparison of coagulation tests between GBC patients and cholecystitis controls
Coagulation tests | Patients (n = 115) | Controls (n = 50) | p |
---|---|---|---|
Mean (standard deviation) | Mean (standard deviation) | ||
PT (sec) |
11.6 (1.3)
|
10.5 (1.1)
|
<0.001
|
aPTT (sec) |
27.8 (4.7)
|
32.2 (4.3)
|
<0.001
|
TT (sec) |
15.4 (3.4)
|
13.8 (1.5)
|
0.002
|
INR | 1.1 (0.9) | 1.0 (0.1) | 0.325 |
Fibrinogen (mg/dL) |
407 (121)
|
311 (67)
|
<0.001
|
Platelets (×104/mm3) |
221.7 (73.4)
|
188.2 (55.3)
|
0.013
|
Correlations between coagulation tests and clinical variables
Variable | N | Coagulation tests | |||||
---|---|---|---|---|---|---|---|
PT (s) | aPTT (s) | TT (s) | INR | Fibrinogen (mg/dL) | PLT (×104/mm3) | ||
Gender | |||||||
Male | 37 (32.2%) | 11.7 (1.6) |
29.2 (5.1)
| 14.5 (3.0) | 1.3 (1.5) | 423.7 (127.3) | 212.0 (79.6) |
Female | 78 (67.8%) | 11.6 (1.2) |
27.2 (4.4)
| 15.8 (3.6) | 1.0 (0.1) | 398.2 (118.0) | 226.3 (69.6) |
(p = 0.642) |
(p = 0.028)
| (p = 0.126) | (p = 0.323) | (p = 0.293) | (p = 0.330) | ||
Age (years) | |||||||
<60 | 29 (25.2%) | 11.3 (1.2) | 28.2 (5.0) | 14.2 (2.9) | 1.0 (1.0) | 373.7 (136.2) | 223.6 (72.9) |
≥60 | 86 (74.8%) | 11.7 (1.4) | 27.7 (4.6) | 15.8 (3.5) | 1.1 (1.0) | 417.5 (114.3) | 221.1 (73.4) |
(p = 0.123) | (p = 0.650) | (p = 0.651) | (p = 0.490) | (p = 0.653) | (p = 0.874) | ||
Histologic differentiation | |||||||
Well | 15 (13.0%) | 11.4 (1.0) | 28.0 (4.6) | 16.4 (3.3) | 1.6 (0.9) |
357.1 (86.4)
| 214.7 (61.6) |
Moderate | 59 (51.3%) | 11.5 (1.3) | 27.5 (5.1) | 15.0 (2.7) | 1.0 (0.1) |
381.5 (116.3)
| 214.9 (74.1) |
Poor | 40 (34.8%) | 11.7 (1.4) | 28.0 (4.1) | 15.3 (4.2) | 1.1 (0.1) |
454.3 (116.6)
| 231.0 (73.5) |
Undifferentiated | 1 (0.9%) | ||||||
(p = 0.593) | (p = 0.842) | (p = 0.480) | (p = 0.060)* |
(p = 0.002)
**
| (p = 0.526) | ||
Tumor invasion | |||||||
Tis-T1
| 18 (0.2%) | 11.9 (1.5) | 28.7 (5.1) |
17.0 (3.2)
| 1.0 (0.1) |
349.9 (68.7)
| 210.6 (63.9) |
T2-T4
| 95 (0.8%) | 11.5 (1.3) | 27.8 (4.7) |
14.9 (3.4)
| 1.1 (1.0) |
421.9 (127.1)
| 223.1 (75.0) |
Not available | 2 (0.0%) | ||||||
(p = 0.262) | (p = 0.423) |
(p = 0.038)
| (p = 0.643) |
(p = 0.016)
| (p = 0.509) | ||
Lymph node metastasis | |||||||
Absent | 73 (63.5%) | 11.6 (1.3) | 27.8 (4.8) | 15.7 (3.2) | 1.2 (1.1) |
382.7 (116.0)
|
208.5 (64.5)
|
Present | 42 (36.5%) | 11.5 (1.5) | 27.9 (4.6) | 14.7 (3.8) | 1.0 (0.1) |
447.7 (120.0)
|
244.7 (81.4)
|
(p = 0.759) | (p = 0.917) | (p = 0.223) | (p = 0.524) |
(p = 0.005)
|
(p = 0.010)
| ||
TNM stage | |||||||
0-I | 22 (19.1%) | 11.9 (1.3) | 27.7 (5.1) | 16.9 (3.2) | 1.0 (0.1) |
331.4 (86.3)
| 208.6 (67.0) |
II-IV | 93 (80.9%) | 11.5 (1.3) | 27.9 (4.6) | 14.9 (3.4) | 1.1 (1.0) |
432.9 (120.9)
| 224.8 (74.3) |
(p = 0.260) | (p = 0.891) | (p = 0.057) | (p = 0.616) |
(p < 0.001)
| (p = 0.353) |
Diagnostic performance of preoperative plasma fibrinogen levels for tumor staging in GBC patients
Correlations between preoperative hyperfibrinogenemia and clinicopathological characteristics
Variables | Plasma fibrinogen levels (mg/dL) | pa
| |
---|---|---|---|
≤402 (n = 60 52.2%) | >402 (n = 55 47.8%) | ||
Gender | |||
Male |
14 (12.2%)
|
23 (20%)
|
0.034
|
Female |
46 (40%)
|
32 (27.8%)
| |
Age | |||
<60 years | 19 (16.5%) | 10 (8.7%) | 0.096 |
≥60 years | 41 (35.7%) | 45 (39.1%) | |
Incidental GBC | 16 (13.9%) | 9 (7.8%) | 0.181 |
Associated gallstone | |||
Absent | 18 (15.7%) | 21 (18.3%) | 0.355 |
Present | 42 (36.5%) | 34 (29.6%) | |
Liver function | |||
ALT | 63.9 ± 160.8 | 89.0 ± 148.5 | 0.439 |
AST | 48.3 ± 99.8 | 63.9 ± 106.0 | 0.471 |
Serum total bilirubin (mg/dL) | 23.7 ± 44.4 | 54.3 ± 95.1 | 0.056 |
Albumin (g/dL) |
39.5 ± 4.6
|
37.4 ± 4.9
|
0.04
|
Hemoglobin (g/dL) | 128.7 ± 15.3 | 122.7 ± 19.5 | 0.087 |
Platelet count (×104/mm3) | 209.3 ± 63.1 | 235.3 ± 80.7 | 0.056 |
WBC count (×109/mm3) |
6.85 ± 3.84
|
8.30 ± 3.45
|
0.048
|
CA19-9 (U/mL) | 131.6 ± 263.7 | 474.1 ± 370.9 | 0.132 |
CEA (ng/mL) | 6.3 ± 21.7 | 13.4 ± 47.6 | 0.358 |
CA125 (U/mL) |
35.3 ± 55.8
|
95.1 ± 141.6
|
0.025
|
Histologic differentiation |
<0.001
| ||
Well |
11 (9.6%)
|
4 (3.5%)
| |
Moderate |
38 (33.0%)
|
21 (18.3%)
| |
Poor |
11 (9.6%)
|
29 (25.2%)
| |
Undifferentiated |
1 (0.9%)
| ||
Tumor invasion | |||
Tis-T1
|
15 (13.0%)
|
5 (4.4%)
|
0.019
|
T2-T4
|
42 (36.5%)
|
49 (42.6%)
| |
Not available |
3 (2.6%)
|
1 (0.9%)
| |
Lymph node metastasis | |||
Absent |
48 (41.7%)
|
25 (21.7%)
|
<0.001
|
Present |
12 (10.4%)
|
30 (26.1%)
| |
TNM stage | |||
0-I |
25 (21.7%)
|
4 (3.5%)
|
<0.001
|
II-IV |
35 (30.4%)
|
51 (44.4%)
|
Survival analysis
Variables | Characteristics | n | Median OS (months) | HR (95% CI) | p value |
---|---|---|---|---|---|
Gender | Male | 37 | 14 | 1.23 (0.76, 2.01) | 0.392 |
Female | 78 | 11 | |||
Age | ≤60 years | 29 | 16 | 0.66 (0.38, 1.13) | 0.122 |
>60 years | 86 | 11 | |||
Associated gallstone | Absent | 39 | 13 | 0.68 (0.43, 1.09) | 0.105 |
Present | 76 | 12 | |||
ALT | ≤75 U/L | 85 | 12 | 1.35 (0.75, 2.41) | 0.315 |
>75 U/L | 32 | 10 | |||
AST | ≤38 U/L | 78 | 13 | 1.24 (0.72, 2.13) | 0.437 |
>38 U/L | 37 | 11 | |||
Serum total bilirubin | ≤12 mg/dL | 60 | 14 | 1.50 (0.91, 2.45) | 0.107 |
>12 mg/dL | 55 | 10 | |||
Albumin | <35 g/dL | 29 | 11 | 0.82 (0.45, 1.48) | 0.506 |
≥35 g/dL | 86 | 12 | |||
Hemoglobin | ≤125 g/dL |
53
|
10
|
0.54 (0.34, 0.88)
|
0.012
|
>125 g/dL |
49
|
15
| |||
WBC count | ≤6.8 × 103/mm3
|
57
|
15
|
1.65 (1.03, 2.64)
|
0.035
|
>6.8 × 103/mm3
|
45
|
9
| |||
Fibrinogen | ≤402 mg/dL |
60
|
17
|
0.48 (0.31, 0.75)
|
0.001
|
>402 mg/dL |
55
|
8
| |||
Platelet count | ≤215 × 104/mm3
| 58 | 13 | 1.44 (0.92, 2.24) | 0.108 |
>215 × 104/mm3
| 57 | 11 | |||
CA19-9 | ≤35 U/mL | 54 | 13 | 1.36 (0.82, 2.25) | 0.239 |
>35 U/mL | 61 | 10 | |||
CEA | ≤10 ng/mL | 62 | 13 | 1.61 (0.94, 2.76) | 0.078 |
>10 ng/mL | 53 | 11 | |||
CA125 | ≤35 U/mL | 66 | 12 | 1.60 (0.89, 2.88) | 0.11 |
>35 U/mL | 49 | 11 | |||
Histologic differentiation | Well |
15
|
32
|
0.51 (0.36, 0.72)
|
<0.001
|
Moderate |
59
|
13
| |||
Poor and undifferentiated |
41
|
8
| |||
Tumor invasion | Tis and T1
|
20
|
32
|
4.58 (2.15, 9.76)
|
<0.001
|
T2, T3 and T4
|
91
|
11
| |||
Lymph node metastasis | Absent |
73
|
17
|
4.08 (2.49, 6.67)
|
<0.001
|
Present |
42
|
7
| |||
TNM stage | 0 and I |
29
|
33
|
5.97 (2.78, 12.82)
|
<0.001
|
II and IV |
86
|
11
| |||
Margin status | R0 |
69
|
20
|
0.14 (0.09, 0.24)
|
<0.001
|
R1 |
46
|
6
| |||
Combined hepatectomy | No | 51 | 11 | 0.94 (0.59, 1.49) | 0.792 |
Yes | 54 | 12 | |||
Combined CBD resection | No |
87
|
14
|
2.06 (1.15, 3.69)
|
0.013
|
Yes |
18
|
9
| |||
Lymphadenectomy | No | 15 | 8 |
1.89 (1.01, 3.56)
|
0.044
|
Yes | 83 | 12 |
Variables | OS HR (95% CI) | p value |
---|---|---|
TNM stage | 17.42 (1.71, 177.56) | 0.016 |
0-I vs. II-IV | ||
Lymph node metastasis | 2.15 (1.06, 4.40) | 0.035 |
Absent and not available vs. Present | ||
Fibrinogen | 0.52 (0.29, 0.94) | 0.031 |
≤402 mg/dL vs. >402 mg/dL | ||
Margin status | 0.15 (0.07, 0.31) | <0.001 |
R0 vs. R1 |