Patients characteristics
The clinicopathological characteristics of the study cohort were summarized in Table 1. In brief, the median age at diagnosis was 71 years (range, 44–91). The patients comprised 59.7% male and 40.3% female. 56.2% of tumor were larger than 5 cm in maximum diameter. By anatomic site, 24.4% of tumor were in the rectum, 37.8% in the left colon, and 37.8% in the right colon. The majority of tumor were adenocarcinoma (69.7%), with well or moderate differentiation (82.6%). 34.3% and 40.8% of tumor presented with lymphovascular invasion and perineural invasion, respectively. According to the AJCC staging system (8th edition), 54.7% of patients had stage I-II disease and 45.3% had stage III-IV disease. Hepatic schistosomiasis was found in 28.9% of patients.
Table 1
Characteristics of 201 patients with SCRC
Characteristics | All patients(n = 201) |
| No. | % |
Age | | |
< 60 | 13 | 6.5 |
≥ 60 | 188 | 93.5 |
Gender | | |
Male | 120 | 59.7 |
Female | 81 | 40.3 |
Tumor size | | |
< 5cm | 113 | 56.2 |
≥ 5cm | 88 | 43.8 |
Tumor location | | |
Rectum | 49 | 24.4 |
Left colon | 76 | 37.8 |
Right colon | 76 | 37.8 |
Histology subtypes | | |
Adenocarcinoma | 140 | 69.7 |
Mucinous/SRCC | 61 | 30.3 |
Histology grade | | |
Well/moderate | 166 | 82.6 |
Poor | 35 | 17.4 |
Lymphovascular invasion | |
Absent | 132 | 65.7 |
Present | 69 | 34.3 |
Perineural invasion | | |
Absent | 119 | 59.2 |
Present | 82 | 40.8 |
pT stage | | |
1–2 | 37 | 18.4 |
3–4 | 164 | 81.6 |
pN stage | | |
0 | 116 | 57.7 |
1–2 | 85 | 42.3 |
TNM stage | | |
I-II | 110 | 54.7 |
III-IV | 91 | 45.3 |
Hepatic schistosomiasis | | |
Absent | 143 | 71.1 |
Present | 58 | 28.9 |
Abbreviations: pT stage = pathological T stage;pN stage = pathological N stage |
The median follow-up was 3.85 years (range, 0.08–6.30). Forty-eight patients died of diseases, and 41 patients had recurrence or metastasis.
The Correlation Of Schistosome Eggs With Clinicopathological Characteristics
According to the deepest position of eggs deposited, we divided patients into PS1 group (presence site 1, eggs deposited in the mucosa, Fig. 1A), PS2 group (presence site 2, eggs deposited in the muscularis propria or throughout the full thickness of the intestinal wall, Fig. 1B). It was regarded as positive when eggs were present in the distal or proximal cutting edge (Fig. 1C), in one or more LNs (Fig. 1D). In this study, there were 104 patients with PS1 and 97 patients with PS2, 184 patients had positive cutting edge and 98 patients had positive LNs by pathological examination.
As shown in Table 2, patients with PS2 were more likely to be mucinous adenocarcinoma or signet-ring cell carcinoma (SRCC) subtype (37.1% vs. 24.0%, P = 0.044) compared with patients with PS1. Patients with PS2 were more likely to combined hepatic schistosomiasis (41.2% vs 17.3%, P < 0.001) than patients with PS1. The correlation analysis between positive cutting edge and clinicopathologic characteristics showed that the majority of male patients had positive cutting edge compared with female patients (62.5% vs 37.5%, P = 0.008). LNs-positive patients were more likely to combine hepatic schistosomiasis (42.9% vs 15.5%, P < 0.001) than LNs-negative patients.
Table 2
Association of schistosome eggs with clinicopathologic characteristics
| Presence site of schistosome eggs | P-values | Schistosome eggs in cutting edges | P-values | Schistosome eggs in LNs | P-values |
| PS1, n (%) | PS2, n (%) | Neg, n (%) | Pos, n (%) | Neg, n (%) | Pos, n (%) |
Gender | | | 0.143 | | | 0.008 | | | 0.668 |
Male | 57(54.8) | 63(64.9) | | 5(29.4) | 115(62.5) | | 60(58.3) | 60(61.2) | |
Female | 47(45.2) | 34(35.1) | | 12(70.6) | 69(37.5) | | 43(41.7) | 38(38.8) | |
Histology subtypes | | | 0.044 | | | 0.31 | | | 0.191 |
Adenocarcinoma | 79(76.0) | 61(62.9) | | 10(58.8) | 130(70.7) | | 76(73.8) | 64(65.3) | |
Mucinous/SRCC | 25(24.0) | 36(37.1) | | 7(41.2) | 54(29.3) | | 27(26.2) | 34(34.7) | |
Hepatic schistosomiasis | | | < 0.001 | | | 0.612 | | | < 0.001 |
Absent | 86(82.7) | 57(58.8) | | 13(76.5) | 130(70.7) | | 87(84.5) | 56(57.1) | |
Present | 18(17.3) | 40(41.2) | | 4(23.5) | 54(29.3) | | 16(15.5) | 42(42.9) | |
Survival Analyses Based On The Depositional Site Of Schistosome Eggs
The Kaplan-Meier survival analysis showed that DFS was not significantly different between PS1 group and PS2 group (P = 0.184, Fig. 2A). Further analysis based on the clinical stage found that patients with PS2 tended to show worse DFS in stage III-IV, but did not achieve statistical significance (P = 0.148, Fig. 2C). OS was not significantly different between PS1 group and PS2 group (P = 0.435, Fig. 2D). Further analysis based on the clinical stage found no significant difference in OS between the two groups (Fig. 2E-F).
Survival Analyses Based On The Schistosome Eggs In Cutting Edges
The Kaplan-Meier survival analysis showed that DFS of patients with positive cutting edge were not significantly different from that of patients with negative cutting edge (P = 0.794, Fig. 3A). Further analysis based on the clinical stage found no significant difference in DFS between the two groups (Fig. 3B-C). There was also no correlation between positive cutting edge and OS (Fig. 3D-F).
Survival Analyses Based On The Schistosome Eggs In Lns
The Kaplan-Meier survival analysis showed that DFS was not significantly associated with the presence of eggs in LNs (P = 0.127, Fig. 4A). But further analysis based on the clinical stage found that patients with positive LNs had worse DFS in stage III-IV (P = 0.001, Fig. 4C). Patients with positive LNs also tended to show worse OS in stage III-IV, while having only cutting marginal significance (P = 0.067, Fig. 3F).
Univariate And Multivariate Analyses
Univariate and multivariate analyses of DFS and OS were performed using prognostic factors, such as known clinicopathologic factors, the depositional site of eggs, the presence of eggs in cutting edge status, as well as in LNs. As shown in Table 3, univariate analysis revealed that the conventional clinicopathologic factors, including lymphovascular invasion, perineural invasion, pN stage, TNM stage, and positive LNs, were significant prognostic factors for DFS. In multivariate analysis, only perineural invasion was independently prognostic for DFS (P < 0.001, HR = 3.073, 95%CI, 1.809–5.221).
Table 3
Univariate and multivariate Cox proportional hazard regression analysis for DFS and OS among patients with SCRC
Variable | DFS | OS |
| P-values | Hazard Ratio | 95%CI | P-values | Hazard Ratio | 95%CI |
Univariate analysis | | | | | | |
Age (< 60 years) | 0.187 | 2.578 | 0.632–10.520 | 0.23 | 3.367 | 0.464–24.414 |
Gender (male/female) | 0.144 | 1.417 | 0.888–2.262 | 0.67 | 1.133 | 0.637–2.014 |
Tumor size (5cm) | 0.821 | 0.947 | 0.591–1.517 | 0.688 | 1.123 | 0.637–1.982 |
Tumor location | | | | | | |
Rectum | Reference | Reference |
Left colon | 0.46 | 1.226 | 0.714–2.103 | 0.724 | 1.127 | 0.580–2.188 |
Right colon | 0.506 | 1.228 | 0.670–2.252 | 0.481 | 1.297 | 0.630–2.670 |
Histology subtypes | 0.576 | 1.152 | 0.701–1.895 | 0.788 | 1.087 | 0.590–2.003 |
Histology grade | 0.14 | 1.536 | 0.868–2.717 | 0.014 | 2.233 | 1.180–4.227 |
Lymphovascular invasion | < 0.001 | 2.413 | 1.510–3.855 | 0.008 | 2.172 | 1.227–3.846 |
Perineural invasion | < 0.001 | 3.104 | 1.915–5.030 | < 0.001 | 3.103 | 1.722–5.592 |
pT stage | 0.038 | 2.282 | 1.046–4.980 | 0.016 | 5.705 | 1.385–23.506 |
pN stage | < 0.001 | 2.906 | 1.791–4.714 | < 0.001 | 3.186 | 1.746–5.813 |
TNM stage | < 0.001 | 3.866 | 2.318–6.446 | < 0.001 | 4.107 | 2.168–7.780 |
Hepatic schistosomiasis | 0.149 | 1.443 | 0.877–2.375 | 0.583 | 1.191 | 0.638–2.222 |
Presence site of schistosome eggs | 0.153 | 1.406 | 0.881–2.245 | 0.357 | 1.306 | 0.740–2.304 |
Schistosome eggs in cutting edges | 0.78 | 1.127 | 0.488–2.601 | 0.476 | 1.53 | 0.475–4.924 |
Schistosome eggs in LNs | 0.165 | 1.393 | 0.873–2.224 | 0.516 | 1.207 | 0.684–2.127 |
Multivariate analysis | | | | | | |
Histology grade | — | — | — | 0.001 | 3.019 | 1.536–5.935 |
Perineural invasion | < 0.001 | 3.073 | 1.809–5.221 | 0.027 | 2.012 | 1.081–3.747 |
Abbreviations: CI = confidence interval | | | | | |
For OS, the following factors were regarded as significant predictive by univariate analysis: histology grade, lymphovascular invasion, perineural invasion, pT stage, pN stage, TNM stage. In multivariate analysis, histology grade (P = 0.001, HR = 3.019, 95%CI, 1.536–5.935) and perineural invasion (P = 0.027, HR = 2.012, 95%CI, 1.081–3.746) were independently prognostic for OS.