2.1 Clinicopathological parameters (Table 1)
Table 1
Univariate analysis of risk factors and occurrence of lymph node metastasis
Factors | N | LNM(-),n(%) | LNM(+),n(%) | P-value |
N | 288 | 271 | 17 | |
Gender | | | | 0.431 |
Male | 162 | 154(53.47) | 8(47.06) | |
Female | 126 | 117(46.53) | 9(52.94) | |
Age,χ ± SD(years old) | 59.5 + 11.6 | 59.7 + 11.7 | 56.8 + 11.2 | 0.316 |
Smoking | | | | 0.084 |
Positive | 68 | 67(23.26) | 1(5.88) | |
Negative | 220 | 204(76.74) | 16(94.12) | |
Alcohol | | | | 0.520 |
Positive | 43 | 41(15.13) | 2(11.76) | |
Negative | 245 | 230(84.87) | 15(88.24) | |
Family history | | | | 0.557 |
Positive | 10 | 10(3.69) | (0.00) | |
Negative | 278 | 261(96.31) | 17(100.00) | |
Tumor size, χ ± SD(mm) | 30.0 ± 15.6 | 29.2 ± 15.4 | 38.3 ± 17.3 | 0.026* |
Tumor location | | | | 0.115 |
Rectum | 186 | 171(63.10) | 15(88.24) | |
Sigmoid colon | 68 | 68(25.09) | 0 | |
Ascending colon | 19 | 17(6.27) | 2(11.76) | |
Descending colon | 10 | 10(3.69) | 0 | |
Transverse colon | 5 | 5(1.85) | 0 | |
Endoscopic morphology | | | | 0.703 |
I (the uplift type) | 248 | 232(85.61) | 16(94.12) | |
II (the flat type) | 7 | 7(2.58) | 0(0.00) | |
III (the concave type) | 25 | 24(8.86) | 1(5.88) | |
Uncertain | 8 | 8(2.95) | 0(0.00) | |
Pathology | | | | <0.001** |
Highly differentiated | 78 | 78(28.78) | 0(0.00) | |
Moderately differentiated | 202 | 189(69.74) | 13(76.47) | |
Poorly differentiated | 8 | 4(1.48) | 4(23.53) | |
Depth of invasion | | | | 0.255 |
Mucosal layer | 76 | 74(27.31) | 2(11.76) | |
Submucosal layer | 212 | 197(72.69) | 15(88.24) | |
Lympho-vascular invasion | | | | <0.001** |
Positive | 6 | 2(0.74) | 4(23.53) | |
Negative | 282 | 269(99.26) | 13(76.47) | |
Tumor budding | | | | 0.833 |
Positive | 3 | 3(1.11) | 0(0.00) | |
Negative | 285 | 268(98.89) | 17(100.00) | |
Note: * P < 0.05, ** P < 0.01. LNM(-):No lymph node metastasis, LNM(+):Lymph node metastasis. |
Two hundred and eighty-eight patients who underwent surgery and lymph node dissection were enrolled (male: female = 162 :126). The age of the patients ranged from 27 to 82 years old. The cancer was located in the rectum in 186 patients, sigmoid colon in 68 patients, in the ascending colon in 16 patients, in the descending colon in 10 cases, and in the transverse colon in 4 cases. In the endoscopic morphological classification, there were 248 cases of the type I (including the uplift type, Ip, Isp, Is), 7 cases of type II (including the flat type, IIa, IIb, IIa + dep, non-granular type LST, granular LST), and 25 cases of type III(including the concave type, IIc, IIc + IIa, Is + IIc). The diameter of the mass ranged from 7-120 mm (30.0 ± 15.6 mm). For pathological grading, 78 cases were highly differentiated, 202 cases were moderately differentiated, 8 cases were poorly differentiated. With regard to the depth of invasion, 76 cases infiltrated the mucosal layer, while 212 cases infiltrated the submucosal layer. A total of 6 patients patients had lymphovascular invasion, and 3 cases had tumor budding.
2.2 Univariate analysis of factors associated with LNM in ECC
LNM was more prevalent in patients with larger tumor size (P = 0.026 < 0.05). Further, the rate of LNM was also highest for the uplift type than for other endoscopic types in all the patients. For the LNM group, there were 4 cases with poorly differentiated type (23.53% VS 1.48%, LNM VS no LNM group), the others presented with moderately differentiated type (76.47% VS 69.74%, LNM VS no LNM group) (P < 0.01).With respect to the depth of invasion, there were no significant difference (P > 0.05) between LNM and no LNM group(88.24% vs 72.69%). Furthermore, the rate of lympho-vascular invasion was higher in cases with LNM than in those without LNM (23.53% vs 0.74%, P < 0.001). Details of the comparisons with P-values were shown in Table 1.
Univariate analysis of the clinicopathological factors assessed in patients with LNM and without LNM revealed a significant relationship between LNM and Tumor size (t=-2.234, P = 0.026 < 0.05), Pathology differentiation, lymphovascular invasion (X2 = 23.593, 40.734, both P < 0.001). LNM rates were higher in patients with poorly differentiated carcinomas, tumor in large diameter, lympho-vascular invasion. However, gender, age, tumor location, endoscopic morphology, depth of invasion and tumor budding did not have a statistically significant association with LNM (P = 0.431, 0.316, 0.115, 0.703, 0.255 and 0.833 respectively; Table 1).
2.3 Multivariate logistic regression analysis of factors associated with LNM in ECC
Multivariate logistic regression analysis was used for multivariate analysis of the following factors that were identified as significant during univariate analysis: tumor size, pathology differentiation and lympho-vascular invasion. The analysis showed that tumor size, pathology differentiation and lympho-vascular invasion were the risk factors for LNM in ECC (OR = 1.036, and P = 0.021; OR = 8.877, and P = 0.023; OR = 0.039, and P = 0.001; Table 2).
Table 2
Multivariate logistic regression analysis of ECC lymph node metastasis
Factors | OR | P-value | 95% CI |
Tumor size | 1.036 | 0.021 * | 1.005–1.068 |
Pathology differentiation | 8.877 | 0.023 * | 1.357–58.050 |
Lympho-vascular invasion | 0.039 | 0.001 * | 0.005–0.285 |
Note: * P < 0.05 | | | |
2.4 Kaplan-Meier estimates of overall survivals and recurrence rates associated with chemotherapy in no-LNM ECC patients
The overall survival and recurrence rate of no-LNM ECC patients was determined by Kaplan–Meier analysis between chemotherapy (20 cases included) and no- chemotherapy (251 cases included) groups. The 11-year overall survival rates and recurrence rates were 95.94% (260/271) and 3.32% (9/271) individually in all 271 followed up no-LNM ECC patients after surgery. Furtherly, 20 patients received chemo-therapy after resection of the tumor, and 2 of those patients had recurrences, including 1 death. The main chemotherapy regimen included CapeOX (L-OHP + Cap) and FLOX (L-OHP + CF + 5-FU), and periods of treatment ranged from 4 to 12 weeks. In this study, the patients treated with chemotherapy after surgery had no difference in overall survival rates (95.0% vs. 96.02%, P = 0.729 > 0.05). For the ECC patients without LNM, there were no significant differences between the chemotherapy and non-chemotherapy groups in overall survivals and recurrence rates (Fig. 2).
2.5 Kaplan-Meier estimates of overall survivals and recurrence rates in matched LNM and no-LNM ECC patients according to the base-line
Seventeen ECC patients with LNM were matched with no LNM patients. The base line was showed in the Table 3. But more patients in the LNM group received chemotherapy therapy (P = 0.034 < 0.05) and got lymphovascular invasion (P = 0.033 < 0.05) than the ECC patients with negative LNM. Kaplan-Meier analysis showed that there were no significant differences of overall survivals and recurrence rates between the ECC patients with LNM and without LNM (Fig. 3).
Table 3
Base-line of the ECC patients with and without LNM after matching
Factors | N n = 34 | LNM(-) n = 17 | LNM(+) N = 17 | P-value |
Gender | | | | 0.730 |
Male | 15 | 7 | 8 | |
Female | 19 | 10 | 9 | |
Age (years old) | 57.1 ± 11.4 | 57.5 ± 12.3 | 56.8 ± 11.2 | 0.851 |
Chemotherapy | | | | 0.034* |
Negative | 27 | 16 | 11 | |
Positive | 7 | 1 | 6 | |
Smoking | | | | 0.287 |
Negative | 30 | 14 | 16 | |
Positive | 4 | 3 | 1 | |
Alcohol | | | | 0.628 |
Negative | 29 | 14 | 15 | |
Positive | 5 | 3 | 2 | |
Family history | | | | 0.628 |
Negative | 31 | 15 | 16 | |
Positive | 3 | 2 | 1 | |
Tumor size | 38.3 ± 17.3 | 38.3 ± 17.3 | 38.3 ± 17.3 | 1.000 |
Tumor location | | | | 1.000 |
Rectum | 30 | 15 | 15 | |
Colon | 4 | 2 | 2 | |
Endoscopic morphology | | | | 0.480 |
I (the uplift type) | 30 | 14 | 16 | |
II (the flat type) | 1 | 1 | 0 | |
III (the concave type) | 3 | 2 | 1 | |
Pathology | | | | 0.504 |
Highly differentiated | 3 | 2 | 1 | |
Medium differentiated | 27 | 14 | 13 | |
Poorly differentiated | 4 | 1 | 3 | |
Depth of invasion | | | | 1.000 |
Mucosal layer | 4 | 2 | 2 | |
Submucosal layer | 30 | 15 | 15 | |
Negative | 30 | 17 | 13 | |
Positive | 4 | 0 | 4 | |
Note: * P < 0.05, LNM(-):No lymph node metastasis, LNM(+):Lymph node metastasis. |