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©The Author(s) 2018.
World J Gastroenterol. Dec 7, 2018; 24(45): 5154-5166
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5154
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5154
Table 1 Summary of clinical, endoscopic, and histopathological characteristics of the 199 pT1N0 esophageal squamous cell carcinoma patients n (%)
Characteristic | Patients | |
Clinical variable | ||
Sex | Male | 142 (71) |
Female | 57 (29) | |
Age (yr) | < 60 | 121 (61) |
≥ 60 | 78 (39) | |
Symptoms | No | 13 (7) |
Yes | 186 (93) | |
Endoscopic variable | ||
Tumor location | Upper thoracic | 31 (16) |
Middle thoracic | 143 (72) | |
Lower thoracic | 25 (13) | |
Tumor size (measured endoscopically) | < 2 cm | 59 (30) |
≥ 2 cm | 140 (70) | |
Macroscopic tumor type | Erosive | 73 (37) |
Papillary | 26 (13) | |
Plaque-like | 79 (40) | |
Ulcerative | 9 (5) | |
Intraluminal mass | 12 (6) | |
Standard histopathological variable | ||
Tumor invasion depth level | m2 | 21 (11) |
m3 | 26 (13) | |
sm1 | 18 (9) | |
sm2 | 45 (23) | |
sm3 | 89 (45) | |
Degree of differentiation | Well | 39 (20) |
Moderate | 76 (38) | |
Poor | 56 (28) | |
Basaloid | 19 (10) | |
Spindle cell/sarcomatoid | 9 (5) | |
Angiolymphatic invasion | No | 172 (86) |
Yes | 27 (14) | |
Multicentric invasive lesions | No | 183 (92) |
Yes | 16 (8) | |
Number of lymph nodes dissected | < 14 | 90 (45) |
≥ 14 | 109 (55) | |
Measured histopathological variables | ||
Tumor thickness | < 3000 μm | 85 (43) |
≥ 3000 μm | 114 (57) | |
Submucosal invasion thickness | 0 | 47 (24) |
0-2000 μm | 85 (43) | |
≥ 2000 μm | 67 (34) | |
Diameter of the largest single tongue of invasion | < 2 cm | 134 (67) |
≥ 2 cm | 65 (33) | |
Immunohistochemical staining1 | ||
P53 | Complete loss | 50 (39) |
Weak, patchy | 41 (32) | |
Diffuse, strong | 37 (29) | |
Cyclin D1 | - | 38 (30) |
1+ | 39 (31) | |
2+ | 49 (39) | |
EGFR | - | 52 (41) |
1+ | 44 (34) | |
2+ | 32 (25) | |
VEGF | - | 54 (44) |
1+ | 34 (28) | |
2+ | 35 (28) |
Table 2 Sites of recurrence in the 199 pT1N0 esophageal squamous cell carcinoma patients n (%)
Site of recurrence | Total patients with recurrence | Patients by tumor location | Patients by macroscopic tumor type | |||
Upper thoracic (n = 31) | Middle thoracic (n = 143) | Lower thoracic (n = 25) | Ulcerative or intraluminal (n = 21) | Erosive, papillary, or plaque-like (n = 178) | ||
Local-regional recurrences1 | 33 (17) | 15 (48) | 14 (10) | 4 (16) | 8 (38) | 25 (14) |
Anastomosis | 3 (2) | 3 (10) | 0 | 0 | 2 (10) | 1 (1) |
Cervical node | 19 (10) | 10 (32) | 7 (5) | 2 (8) | 4 (19) | 15 (8) |
Mediastinal node | 21 (11) | 9 (29) | 9 (6) | 3 (12) | 8 (38) | 13 (7) |
Abdominal node | 0 | 0 | 0 | 0 | 0 | 0 |
Distant recurrences1 | 16 (8) | 5 (16) | 8 (6) | 3 (12) | 4 (19) | 12 (7) |
Lung | 7 (4) | 2 (6) | 5 (3) | 0 | 1 (5) | 6 (3) |
Liver | 2 (1) | 1 (3) | 0 | 1 (4) | 0 | 2 (1) |
Bone | 6 (3) | 0 | 4 (3) | 2 (8) | 2 (10) | 4 (2) |
Brain | 1 (0) | 1 (3) | 0 | 0 | 0 | 1 (1) |
Pleura | 3 (2) | 2 (6) | 1 (1) | 0 | 1 (5) | 2 (1) |
Distant node | 0 | 0 | 0 | 0 | 0 | 0 |
Multiple site recurrences | 15 (8) | 7 (23) | 6 (4) | 2 (8) | 5 (24) | 10 (6) |
Mediastinal node and bone | 2 (1) | 0 | 1 (1) | 1 (4) | 1 (5) | 1 (1) |
Mediastinal node, cervical node, and bone | 1 (1) | 0 | 0 | 1 (4) | 0 | 1 (1) |
Mediastinal node, pleura, and bone | 1 (1) | 0 | 1 (1) | 0 | 0 | 1 (1) |
Mediastinal node and cervical node | 3 (1) | 2 (6) | 1 (1) | 0 | 1 (5) | 2 (1) |
Cervical node and lung | 1 (1) | 0 | 1 (1) | 0 | 0 | 1 (1) |
Mediastinal node, cervical node, and anastomosis | 1 (1) | 1 (3) | 0 | 0 | 1 (5) | 0 |
Mediastinal node, cervical node, anastomosis, and pleura | 1 (1) | 1 (3) | 0 | 0 | 1 (5) | 0 |
Mediastinal node, cervical node, and lung | 2 (1) | 1 (3) | 1 (1) | 0 | 1 (5) | 1 (1) |
Cervical node, bone, and lung | 1 (1) | 0 | 1 (1) | 0 | 0 | 1 (1) |
Mediastinal node, liver, and lung | 1 (1) | 1 (3) | 0 | 0 | 0 | 1 (1) |
Mediastinal node and brain | 1 (1) | 1 (3) | 0 | 0 | 0 | 1 (1) |
Unknown sites | 10 (5) | 1 (3) | 8 (6) | 1 (4) | 1 (5) | 9 (5) |
Total recurrences | 47 (24) | 16 (52) | 25 (17) | 6 (24) | 10 (48) | 37 (21) |
Table 3 Relationship of clinicopathological parameters with recurrence-free survival and tumor recurrence in the 199 pT1N0 esophageal squamous cell carcinoma patients n (%)
Parameter | Total | Recurrences | Kaplan-Meier analysis | Univariate Cox proportional hazards analysis | ||||||
5-yr RFS (%) | 10-yr RFS (%) | P-value | HR | 95%CI | Global P | P-for-trend | ||||
Clinical variable | ||||||||||
Sex | Male | 142 | 33 (23) | 81 | 71.6 | 0.97 | 1 | |||
Female | 57 | 14 (25) | 80 | 72.7 | 1.011 | 0.54-1.89 | 0.97 | |||
Age (yr) | < 60 | 121 | 28 (23) | 79.2 | 74.1 | 0.6 | 1 | |||
≥ 60 | 78 | 19 (24) | 82.9 | 66.4 | 1.17 | 0.65-2.10 | 0.6 | |||
Symptoms | No | 13 | 0 | 100 | 100 | 0.03 | 1 | |||
Yes | 186 | 47 (25) | 79.2 | 69.8 | 23.54 | 0.28-2017 | 0.16 | |||
Endoscopic variable | ||||||||||
Tumor location | Upper thoracic | 31 | 15 (48) | 55.9 | 44.7 | < 0.001 | 3.46 | 1.83-6.54 | < 0.001 | |
Middle thoracic | 143 | 26 (18) | 85.2 | 78.5 | 1 | |||||
Lower thoracic | 25 | 6 (24) | 86.5 | 65.4 | 1.49 | 0.61-3.63 | 0.38 | |||
Tumor size (endoscopically) | < 2 cm | 59 | 16 (27) | 79.3 | 69.7 | 0.53 | 1 | |||
≥ 2 cm | 140 | 31 (22) | 81.2 | 73 | 0.82 | 0.45-1.51 | 0.53 | |||
Macroscopic | Erosive | 73 | 12 (16) | 87.2 | 78 | 0.001 | 1 | |||
tumor type | Papillary | 26 | 4 (15) | 90.2 | 90.2 | 0.98 | 0.32-3.06 | 0.98 | ||
Plaque-like | 79 | 21 (27) | 75.8 | 68.6 | 1.64 | 0.81-3.25 | 0.13 | |||
Ulcerative | 9 | 6 (67) | 53.3 | 26.7 | 6.06 | 2.26-16.26 | < 0.001 | |||
Intraluminal mass | 12 | 4 (33) | 74.1 | 49.4 | 3.94 | 1.26-12.32 | 0.02 | |||
Standard histopathological variable | ||||||||||
Tumor invasion depth level | m2 | 21 | 1 (5) | 94.1 | 94.1 | 0.04 | 1.52 | 1.14-1.97 | 0.004 | |
m3 | 26 | 3 (12) | 96.2 | 88.1 | ||||||
sm1 | 18 | 4 (22) | 81.4 | 81.4 | ||||||
sm2 | 45 | 11 (25) | 83.8 | 74.8 | ||||||
sm3 | 89 | 28 (31) | 70.6 | 58.6 | ||||||
Degree of differentiation | Well | 39 | 10 (26) | 79.5 | 65 | 0.02 | 1 | |||
Moderate | 76 | 15 (20) | 84.7 | 82 | 0.73 | 0.33-1.63 | 0.44 | |||
Poor | 56 | 13 (23) | 80.7 | 67.8 | 0.92 | 0.40-2.11 | 0.92 | |||
Basaloid | 19 | 8 (42) | 58.3 | 35 | 2.88 | 1.13-7.38 | 0.03 | |||
Spindle cell/sarcomatoid | 9 | 1 (11) | 88.9 | 88.9 | 0.54 | 0.07-4.21 | 0.55 | |||
Angiolymphatic invasion | No | 172 | 33 (19) | 84.6 | 75.3 | < 0.001 | 1 | |||
Yes | 27 | 14 (52) | 55.4 | 49.9 | 3.48 | 1.85-6.52 | < 0.001 | |||
Multicentric invasive lesions | No | 183 | 45 (25) | 80.2 | 70.9 | 0.42 | 1 | |||
Yes | 16 | 2 (13) | 86.5 | 86.5 | 0.56 | 0.14-2.32 | 0.42 | |||
Number of lymph nodes dissected | < 14 | 90 | 24 (27) | 72.7 | 70.2 | 0.25 | 1 | |||
≥ 14 | 109 | 23 (21) | 87.2 | 73.8 | 0.72 | 0.41-1.27 | 0.26 | |||
Measured histopathological variable | ||||||||||
Tumor thickness | < 3000 μm | 85 | 13 (15) | 90 | 79.3 | 0.005 | 1 | |||
≥ 3000 μm | 114 | 34 (30) | 73.2 | 65.7 | 2.41 | 1.27-4.56 | 0.007 | |||
Submucosal | 0 | 47 | 4 (9) | 95.5 | 90.5 | 0.001 | 2.24 | 1.44-3.46 | < 0.001 | |
invasion thickness | 1-2000 μm | 85 | 19 (22) | 82.8 | 74.4 | |||||
≥ 2000 μm | 67 | 24 (36) | 67.4 | 56.4 | ||||||
Diameter of the | < 2 cm | 134 | 27 (20) | 85.5 | 75.7 | 0.008 | 1 | |||
largest single tongue of invasion | ≥ 2 cm | 65 | 20 (31) | 70.1 | 64.1 | 2.15 | 1.20-3.85 | 0.01 | ||
Immunohistochemical staining1 | ||||||||||
P53 | Complete loss | 50 | 19 (38) | 64.8 | 59.5 | 0.33 | 2.43 | 1.02-5.79 | 0.045 | |
Weak, patchy | 41 | 7 (17) | 81.8 | 81.8 | 1 | |||||
Diffuse, strong | 37 | 12 (33) | 88.6 | 78.2 | 1.88 | 0.74-4.77 | 0.19 | |||
Cyclin D1 | - | 38 | 14 (37) | 71.3 | 56.4 | 0.88 | 0.93 | 0.64-1.36 | 0.72 | |
1+ | 39 | 11 (28) | 80.7 | 73.7 | ||||||
2+ | 49 | 14 (29) | 68.7 | 68.7 | ||||||
EGFR | - | 52 | 13 (25) | 82.9 | 75.6 | 0.27 | 1.15 | 0.78-1.69 | 0.49 | |
1+ | 44 | 17 (39) | 65.6 | 51.3 | ||||||
2+ | 32 | 9 (28) | 70.2 | 68 | ||||||
VEGF | - | 54 | 15 (28) | 76 | 67.3 | 0.59 | 1.05 | 0.72-1.54 | 0.79 | |
1+ | 34 | 12 (35) | 74.1 | 59.6 | ||||||
2+ | 35 | 10 (29) | 72.2 | 72.2 |
Table 4 Multivariate Cox proportional hazard models for tumor recurrence in the 199 pT1N0 esophageal squamous cell carcinoma patients
Parameter | HR | 95%CI | Global P | P-for-trend | |
Tumor location | Upper thoracic | 3.26 | 1.70-6.27 | < 0.001 | |
Middle thoracic | 1 | ||||
Lower thoracic | 1.05 | 0.43-2.59 | 0.91 | ||
Angiolymphatic invasion | 3.42 | 1.80-6.52 | < 0.001 | ||
Submucosal invasion thickness | 2.06 | 1.30-3.27 | 0.002 |
Table 5 Relationship between clinicopathological parameters and distant tumor recurrence in the 189 informative patients1
Univariate Cox proportional hazards analysis | |||||||
Parameter | Total | Distant recurrences (%) | HR | 95%CI | Global P | P-for-trend | |
Clinical variables | |||||||
Sex | Male | 136 | 14 (10) | 1 | |||
Female | 53 | 2 (4) | 0.33 | 0.07-1.44 | 0.14 | ||
Age (yr) | < 60 | 118 | 8 (7) | 1 | |||
≥ 60 | 71 | 8 (11) | 2.18 | 0.79-6.02 | 0.13 | ||
Symptoms | No | 13 | 0 | 1 | |||
Yes | 176 | 16 (9) | 23.59 | 0.01-40030 | 0.41 | ||
Endoscopic variables | |||||||
Tumor location | Upper thoracic | 30 | 5 (17) | 3.56 | 1.15-11.07 | 0.03 | |
Middle thoracic | 135 | 8 (6) | 1 | ||||
Lower thoracic | 24 | 3 (13) | 2.37 | 0.63-8.94 | 0.2 | ||
Tumor size (measured endoscopically) | < 2 cm | 55 | 6 (11) | 1 | |||
≥ 2 cm | 134 | 10 (8) | 0.76 | 0.27-2.09 | 0.59 | ||
Macroscopic type | Erosive | 71 | 5 (7) | 1 | |||
Papillary | 26 | 2 (8) | 1.11 | 0.21-5.75 | 0.9 | ||
Plaque-like | 72 | 5 (7) | 0.95 | 0.27-3.31 | 0.94 | ||
Ulcerative | 8 | 2 (25) | 5.58 | 1.06-29.32 | 0.04 | ||
Intraluminal mass | 12 | 2 (17) | 5.41 | 1.02-28.68 | 0.047 | ||
Standard histopathological variable | |||||||
Tumor invasion depth level | m2 | 21 | 0 | 1.42 | 0.91-2.21 | 0.13 | |
m3 | 26 | 2 (8) | |||||
sm1 | 16 | 1 (6) | |||||
sm2 | 43 | 4 (9) | |||||
sm3 | 83 | 9 (11) | |||||
Degree of differentiation | Well | 36 | 1 (3) | 1 | |||
Moderate | 73 | 5 (7) | 2.19 | 0.25-18.98 | 0.48 | ||
Poor | 54 | 6 (11) | 3.93 | 0.47-32.89 | 0.21 | ||
Basaloid | 17 | 3 (18) | 12.4 | 1.27-121.08 | 0.03 | ||
Spindle cell/sarcomatoid | 9 | 1 (11) | 5.73 | 0.35 -92.90 | 0.22 | ||
Angiolymphatic invasion | No | 166 | 11 (7) | 1 | |||
Yes | 23 | 5 (22) | 3.38 | 1.15-9.93 | 0.03 | ||
Multicentric invasive lesions | No | 173 | 15 (9) | 1 | |||
Yes | 16 | 1 (6) | 0.92 | 0.12-7.00 | 0.93 | ||
Number of lymph nodes dissected | < 14 | 85 | 7 (8) | 1 | |||
≥ 14 | 104 | 9 (9) | 0.95 | 0.36-2.57 | 0.93 | ||
Measured histopathological variable | |||||||
Tumor thickness | < 3000 μm | 82 | 6 (7) | 1 | |||
≥ 3000 μm | 107 | 10 (9) | 1.53 | 0.56-4.21 | 0.42 | ||
Submucosal | 0 | 47 | 2 (4) | 1.88 | 0.91-3.90 | 0.09 | |
invasion thickness | < 2000 μm | 80 | 7 (9) | ||||
≥ 2000 μm | 62 | 7 (11) | |||||
Diameter of the | < 2 cm | 126 | 9 (7) | 1 | |||
largest invasive lesion | ≥ 2 cm | 63 | 7 (11) | 2.56 | 0.92-7.15 | 0.07 | |
Immunohistochemical staining2 | |||||||
P53 | Complete loss | 47 | 6 (13) | 1.78 | 0.44-7.16 | 0.42 | |
Weak, patchy | 40 | 3 (8) | 1 | ||||
Diffuse, strong | 34 | 6 (18) | 2.31 | 0.58-9.25 | 0.24 | ||
Cyclin D1 | - | 35 | 5 (14) | 0.94 | 0.51-1.74 | 0.84 | |
+ | 37 | 5 (14) | |||||
++ | 47 | 5 (11) | |||||
EGFR | - | 52 | 9 (17) | 0.63 | 0.31-1.28 | 0.2 | |
+ | 40 | 4 (10) | |||||
++ | 29 | 2 (7) | |||||
VEGF | - | 50 | 6 (12) | 0.95 | 0.50-1.81 | 0.88 | |
+ | 33 | 3 (9) | |||||
++ | 33 | 4 (12) | |||||
Multivariate Cox proportional hazards analysis | |||||||
Parameter | |||||||
Tumor location | Upper thoracic | 3.83 | 1.23-11.96 | 0.02 | |||
Middle thoracic | 1 | ||||||
Lower thoracic | 1.95 | 0.50-7.54 | 0.34 | ||||
Angiolymphatic invasion | 3.55 | 1.17-10.77 | 0.03 |
Table 6 Relationship between clinicopathological parameters and the likelihood of having early recurrence (≤ 24 mo) in the 199 pT1N0 esophageal squamous cell carcinoma patients n (%)
Univariate logistic regression | |||||||
Parameter | Total | Early recurrence | Odds ratio | 95%CI | Global P | P-for-trend | |
Clinical variable | |||||||
Sex | Male | 142 | 12 (9) | 1 | |||
Female | 57 | 6 (11) | 1.28 | 0.45-3.58 | 0.65 | ||
Age (yr) | < 60 | 121 | 15 (12) | 1 | |||
≥ 60 | 78 | 3 (4) | 0.28 | 0.08-1.01 | 0.052 | ||
Endoscopic variable | |||||||
Tumor location | Upper thoracic | 31 | 9 (29) | 7.95 | 2.68-23.54 | < 0.001 | |
Middle thoracic | 143 | 7 (5) | 1 | ||||
Lower thoracic | 25 | 2 (8) | 1.69 | 0.33-8.64 | 0.53 | ||
Tumor size (endoscopically) | < 2 cm | 59 | 4 (7) | 1 | |||
≥ 2 cm | 140 | 14 (10) | 1.53 | 0.48-4.85 | 0.47 | ||
Macroscopic | Erosive | 73 | 4 (6) | 1 | |||
tumor types | Papillary | 26 | 1 (4) | 0.69 | 0.07-6.47 | 0.75 | |
Plaque-like | 79 | 7 (9) | 1.68 | 0.47-5.98 | 0.43 | ||
Ulcerative | 9 | 3 (33) | 8.63 | 1.55-47.86 | 0.01 | ||
Intraluminal mass | 12 | 3 (25) | 5.75 | 1.10-29.95 | 0.04 | ||
Standard histopathological variable | |||||||
Tumor invasion depth level | m2 | 21 | 0 | 1.78 | 1.05-3.01 | 0.03 | |
m3 | 26 | 1 (4) | |||||
sm1 | 18 | 2 (11) | |||||
sm2 | 45 | 2 (4) | |||||
sm3 | 89 | 13 (15) | |||||
Degree of differentiation | Well | 39 | 3 (8) | 1 | |||
Moderate | 76 | 6 (8) | 1.03 | 0.24-4.35 | 0.97 | ||
Poor | 56 | 4 (7) | 0.92 | 0.20-4.38 | 0.92 | ||
Basaloid | 19 | 4 (21) | 3.2 | 0.64-16.07 | 0.16 | ||
Spindle cell/sarcomatoid | 9 | 1 (11) | 1.5 | 0.14-16.36 | 0.74 | ||
Angiolymphatic invasion | No | 172 | 10 (6) | 1 | |||
Yes | 27 | 8 (30) | 6.82 | 2.40-19.38 | < 0.001 | ||
Multicentric invasive lesions | No | 183 | 17 (9) | 1 | |||
Yes | 16 | 2 (13) | 0.65 | 0.08-5.24 | 0.69 | ||
Number of lymph nodes dissected | < 14 | 90 | 11 (12) | 1 | |||
≥ 14 | 109 | 0.49 | 0.18-1.33 | 0.16 | |||
Measured histopathological variable | |||||||
Tumor thickness | < 3000 μm | 85 | 2(2) | 1 | |||
≥ 3000 μm | 114 | 16(14) | 6.78 | 1.51-30.33 | 0.01 | ||
Submucosal invasion thickness | 0 | 47 | 1(2) | 4.02 | 1.66 -9.73 | 0.001 | |
0-2000 μm | 85 | 4(5) | |||||
≥ 2000 μm | 67 | 13(19) | |||||
Diameter of the largest single tongue of invasion | < 2 cm | 134 | 5(4) | 1 | |||
≥ 2 cm | 65 | 13(20) | 6.45 | 2.19-19.00 | 0.001 | ||
Immunohistochemical staining1 | |||||||
P53 | Complete loss | 50 | 7 (14) | 1.34 | 0.36-4.98 | 0.66 | |
Weak, patchy | 41 | 5 (12) | 1 | ||||
Diffuse, strong | 37 | 4 (11) | 1.15 | 0.28-4.63 | 0.85 | ||
Cyclin D1 | - | 38 | 4 (11) | 1.32 | 0.69-2.54 | 0.4 | |
1+ | 39 | 4 (10) | |||||
2+ | 49 | 8 (16) | |||||
EGFR | - | 52 | 4 (8) | 1.32 | 0.69-2.54 | 0.4 | |
1+ | 44 | 8 (18) | |||||
2+ | 32 | 4 (13) | |||||
VEGF | - | 54 | 4 (7) | 1.59 | 0.83-3.04 | 0.16 | |
1+ | 34 | 5 (15) | |||||
2+ | 35 | 6 (17) | |||||
Multivariate logistic regression | |||||||
Tumor location | Upper thoracic | 7.73 | 2.15-27.78 | 0.002 | |||
Middle thoracic | 1 | ||||||
Lower thoracic | 1.18 | 0.20-6.86 | 0.85 | ||||
Angiolymphatic invasion | 5.75 | 1.63-20.24 | 0.006 | ||||
Submucosal invasion thickness | 2.64 | 0.92-7.60 | 0.07 | ||||
Diameter of the largest single tongue of invasion | 4.13 | 1.17-14.56 | 0.03 |
- Citation: Xue LY, Qin XM, Liu Y, Liang J, Lin H, Xue XM, Zou SM, Zhang MY, Zhang BH, Hui ZG, Zhao ZT, Ren LQ, Zhang YM, Liu XY, Yuan YL, Ying JM, Gao SG, Song YM, Wang GQ, Dawsey SM, Lu N. Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma. World J Gastroenterol 2018; 24(45): 5154-5166
- URL: https://www.wjgnet.com/1007-9327/full/v24/i45/5154.htm
- DOI: https://dx.doi.org/10.3748/wjg.v24.i45.5154