The incidence of positive RM in the entire cohort was not high (1.8%), as compared with that in previous studies evaluating macroscopically positive RM in patients with gastric cancer (1.8%-8.2%) [4–7, 16]. The results suggest that our surgical procedures and methods for evaluating appropriate resection lines were at high levels. Nevertheless, surgeons misdiagnosed the resection lines of specimens as being tumor-free, despite the fact that tumor cells remained. Therefore, to prevent unexpected microscopically positive RM, resection with wider excision or IFSD should be performed in cases with a high risk of positive RM.
Our study showed that remnant gastric cancer, esophageal invasion, a tumor size of ≥ 80 mm, undifferentiated type of histopathology, macroscopic type 4, and pT4 were risk factors for positive RM in patients with gastric cancer. Moreover, the risk of positive RM increased in patients with three or more of those risk factors. In particular, owing to high-risk associated with four (21.3%) or five factors (85.7%), IFSD should be considered in patients who have four risk factors and is mandatory in patients who have five risk factors. On the other hand, patients without any risk factors do not have to undergo IFSD, because the incidence rate of positive RM is extremely low (0.1%).
Previous studies have similarly reported that advanced T category, advanced N category, total gastrectomy, larger tumor, EGJ location, diffuse histology, and linitis plastica, which is also referred to as macroscopic type 4, [3, 17, 18] are risk factors for positive RM. On the basis of these studies, we chose candidate risk factors for preoperatively predicting clinicopathological features. We did not adopt N category as one of the risk factors because it was not appropriate to substitute pN for cN owing to the low preoperative diagnostic accuracy (63.6%) [19]. Remnant gastric cancer, which remains an unknown risk factor for positive RM in previous studies, was more frequent in the PM group of our study and was therefore adopted as a risk factor for remnant gastric cancer. Finally, six clinicopathological features were identified as risk factors on multivariate analysis in our study, although the factors other than remnant cancer have been reported previously. An innovation of our study was to stratify patients who have risk factors and to show how often microscopically positive RM occurred in patients with such risk factors. To our knowledge, no previous study has reported on risk stratification of positive RM in patients with gastric cancer.
Our study had some limitations that should be taken into consideration when interpreting the results. First, we used the pathological T category, not the clinical T category, as an indicator of the invasion depth of tumor. There were no pT1 tumors with positive RM in our study. To utilize this result, accurate preoperative diagnosis is essential. The preoperative diagnosis of cT1 gastric cancer is reported to have 92.4–95.4% accuracy [20–22]. The invasion depth was underestimated in 4.6–7.6% of the patients, who actually had advanced cancer. If the tumor is diagnosed to be being somewhat shallower than the actual depth, the actual resection margin distance would be shorter than the essential margin, which suggests that the incidence rate of positive RM may increase.
A second limitation was that we could not evaluate the margin distance between the tumor and resection line, which was shown to be a risk factor in other studies [17]. Risk stratification in our study was useful for preoperatively estimating the risk of positive RM and for deciding whether IFSD should be performed. However, the estimated risk would change depending on the actual secured margin distance. A multicenter Italian study reported that a RM distance of less than 2 cm was a risk factor for T1 tumors, and a RM distance of less than 3 cm was a risk factor for T2 to T4 Lauren intestinal pattern tumors [18]. The required margin distance should be evaluated in patients who have high-risk factors for positive RM in future studies.