In our study, we evaluated the effectiveness of tumor size on MDCT as a tool for the initial prediction of LNM in colon cancer. Our preliminary results showed that Tvol was an independent risk factor for LNM. Tumor size including Tlen, Tdia, Tare, and Tvol could distinguish between N0 and N1 stage, N0 and N2, N0 and N1-2, and N0-1 and N2 disease. Tvol had the best diagnostic efficacy in identifying LNM and differentiating N stage.
Previous study reported that tumor length is an independent predictor of mortality in patients with esophageal carcinoma and a risk factor for LNM to predict survival in patients with ESCC (21–22). In this study, we indicated that tumor length could predict LNM in patients with colon cancer. This was because increasing longitudinal growth in the lymphatic-rich submucosa was a predictor of regional LNM. The longer the tumor length, the deeper the tumor invading the colonic wall and the more frequent the incidence of LNM. Tumor thickness was an independent adverse factor for LNM in oral carcinoma (23) and could be associated with LNM in ESCC (21). The larger the tumor diameter, the deeper tumor invading the colon wall, more likely invading adjacent structures, and the higher risk of LNM. In our study, Tdia could help identify LNM but the diagnostic efficacy of Tdia is the worst in colon cancer. We thought that the inflatable dilatation of the colon and blur margin caused by tumor inflammation and invasion could affect tumor diameter measurement. For Tare, we found that Tare could predict LNM. Tare is the maximum cross-sectional area of colon cancer and is used for delineating the whole circumference of the tumor. Compared with Tdia, it contains a much broader margin and could reflect tumor geometry and growth.
Although a recent article showed that CT tumor volumetry indicated no significant differences according to N stage, it serves as a useful prediction of prognosis in pT4b and M1b stages using CT colonography (24). Our result was different from that study. In this study, we confirmed that tumor volume had the best repeatability measurement, it could predict LNM and was the only risk factor for LNM in the patients with colon cancer by multivariate analysis compared with Tlen, Tdia and Tare. We demonstrated that Tvol could help differentiate N0 from N1-2, N0 from N1, N0 from N2, and N0-1 from N2 with moderately sensitivity (69.2%, 88.6%, 94.1%, 94.1%), specificity (83.3%, 57.4%, 83.3%, 68.5%) and accuracy (77.4%, 69.7%, 88.7%, 83.0%). CT tumor volumetry for discriminating N staging and is an independent risk factor for LNM had been confirmed by most of the previous articles (19–21). Tumor volume was moderately accurate in predicting N1, N2 and N3 stage in gastric carcinoma (19). Li et al. showed that tumor volume could predict regional LNM and differentiate various N stages with an accuracy of 70% in adenocarcinoma of the esophagogastric Junction (20). Tumor volume measured on MDCT could differentiate N0 and N1-3 stages, N0-1 and N2-3, and N0-2 and N3 with sensitivity values of 76%, 63% and 75% and specificity values of 75%, 61% and 81%, respectively, in resectable esophageal squamous cell carcinoma (21). Chen et al reported that tumor volume data had better correlation with LNM than tumor length and tumor diameters (25). We also demonstrated that Tvol had the highest AUC than Tlen, Tdia and Tare in distinguishing N stage. This may be because that Tvol contains more morpholoy information to reflect tumor growth pattern and infiltration based on Tlen, Tdia and Tare. The larger the tumor volume, the deeper the tumor invading the colonic wall and the more frequent the incidence of LNM. We can conclude that Tvol may be the best predictor to predict N stage in colon cancer.
Previous studies have applied different criteria based on either size and/or morphology for identifying LNM (26). Audrey et al. used the radiographic criteria of lymph node diameter (> 1.0 cm) or round shape, heterogeneity, eccentricity, hilar thinning, calcification, central necrosis, and perinodal infiltration to evaluate lymph node involvement with sensitivity of 54%-88%, specificity of 55%-66%, accuracy of 61%-70%, positive predictive value of 52%-59% and negative predictive value of 68%-88% (13). Sibileau et al. reported a method for identifying LNM using a long-axis diameter of 5 mm or more, clustering of three or more lymph nodes regardless of size, and a density of 100 HU or more, with high sensitivity (91%) and low specificity (68%) (27). However, metastatic lymph node smaller than 2 mm are difficult to depict with MR imaging and CT imaging and can easily be misinterpreted as small blood vessels and, most important, that some of nodes larger than 1 cm seen on CT images may be the benign. Therefore, the node seen on CT images that could not be matched with histopathologic findings all were judged to be benign on CT images. This limitation made morphological method not accurate to assess lymph node status. It is hard to ensure the metastatic lymph node we diagnosed on CT images is the one confirmed by pathology eventually. In our study, Tvol showed good diagnostic efficacy for differentiating N0 from N1-2 with sensitivity values of 69.2%, specificity values of 83.3%, and accuracy values of 77.4%.
Our study had several limitations. First, the collected sample number for LNM is too small compared with a previous study (19, 20). Lymphovascular invasion and perineural invasion have a high risk for LNM and a poor prognostic factor in colon diseases (25, 28, 29). In our study, we did not find these correlations because of small sample size of positive lymphovascular or perineural invasion. Second, Tumor volume measurements on CT images can be time-consuming. However, in this study, the time required for well-trained radiologists to draw the whole tumor area was controlled to 10 minutes. In future study, semiautomatic measurement method may be used to reduce the time of measurement. Third, the measurement of Tlen, Tdia and Tare might be affected by the distention of the contents in the intestinal canal. To minimize this effect, all patients were asked to perform bowel preparation with butylscopolamine bromide and drink 1000 mL of water before CT scanning.