Gastric cancer (GC) has been a critical health burden due to its high morbidity and mortality worldwide, with approximately 1,033,701 new cases and 782,654 deaths in 2018[2]. Gastric cancer can be divided into early gastric cancer (EGC) and advanced gastric cancer, with significant differences in prognosis. Moreover, despite the declining incidence of GC and due to the advancement of early diagnostic techniques and health examinations, the incidence of EGC seems to have steadily increased since the late 1980s[10–11]. Many studies have indicated clinicopathologic features, multiple genes and molecules in advanced gastric cancer; however, there are limited studies focusing on the clinicopathologic and prognostic features of EGC.
Our retrospective analysis of 244 patients with EGC found that the male-to-female ratio was 1.6:1, indicated that gastric cancer is a sex-related carcinoma regardless of whether early gastric cancer or overall gastric cancer patients were included, similar results were indicated by McGuire, S [8]. We further investigated the prognostic features in EGC and found no significant differences in age, sex, surgical methods, reconstruction methods, tumor location, tumor differentiation, perineurium invasion or immunohistochemistry score for HER2. As our previous study indicated that laparoscopic distal gastrectomy achieves the same degree of radicality and short-term prognosis as open distal gastrectomy[12], we now verified no significant difference between laparoscopic and open surgical methods in terms of long-term survival of GC patients. Additionally, we found that HER2 expression had no prognostic influence in EGC. However, some retrospective studies have suggested that HER2 positivity is the second worst prognostic factor[13, 14], whereas other studies have suggested that HER2 status has no relationship with short- and long-term survival according to univariate and multivariate analyses[15].
We found that the longest diameter of the tumor = 2 cm were the best cutoff points for the prognosis factor in our large-scale group of EGC patients. Furthermore, the longest diameter of the tumor (≤ 2/༞2 cm) and total number of dissected LNs(≤ 13/༞13) were independent risk factors for EGC patients according to multivariate analysis, with RRs of 7.404 (P = 0.001) and 0.289 (P = 0.015), respectively. Li Y reported that lesions of over 2 cm might be more likely to have lymph node metastasis in EGC[17]. Similar results have been verified by Li H et al.[18]. Our research is the first to identify the relationship between the longest diameter of the tumor and disease-free survival rate by using X-tile software and ROC curves.
The radical dissection of lymph nodes is a highly effective procedure in gastric cancer to improve the prognosis of GC and limit LN metastasis. Our study found that LN metastasis was 13.9% in EGC, which is higher than the LN metastasis rate of 2.5–8.6% in Japan[19]. In addition, NCCN guidelines indicated that the number of dissected LNs in GC should be greater than 15; due to the lower incidence of LN metastasis in EGC, lymphadenectomy is always applied with D1+, modified D2 or D2. However, Wu H et al, indicated that in EGC patients with unknown LN status, D2 dissection was the first choice, which could prolong the survival time for those patients[20]; a similar suggestion was given by Korean and Japanese investigators[21, 22]. Our research also showed that the number of dissected LNs lower than 13 was associated with a poor prognosis of EGC patients, and this might be because limited LN dissection might lead to residual cancer, increasing the risk of recurrence or metastasis.
Since lymph node metastasis remains a critical role in the therapeutic approach (EMR/ESD vs surgery) for EGC patients, it is important to identify the risk factors for EGC patients[23]. Our study demonstrated that longest diameter of the tumor (≤ 1.9/༞1.9 cm), T stage (Tis + T1a/T1b), vascular invasion (yes/no), and NLRc (≤ 5.29/༞5.29) were the independent risk factors for LN metastasis. Similarly, Japanese Gastric Cancer Association (JGCA) points that nonulcerated, well-differentiated and lesions diameter less than 2 cm are the indications for EMR/EDS approach in EGC patients[24]. Additionally, our study also found that the invasive depth of EGC(T stage) and vascular invasion were also associated with lymph node metastasis, Chu YN et al also found that submucosal invasion depth and LVI were the predictive factors for lymph node metastasis[25], hence, it is truely for the application of ultrasound gastroscope to identify the invasive depths in EGC patients, which could not only measured the lesion size, but also measured the invasive depths of EGC tumors[26]. In collaboration with previous studies, our research indicated that tumor size ≤ 1.9 cm, ultrasound gastroscope presents the non-submucosa invasion and non-vascular invasion might be the indications for ESD/EMR in EGC patients.
There are several limitations in our study. Due to the retrospective nature of the study, some information(such as H.pylori infection, E.B virus infection et, al.) could not be collected; therefore, the analysable risk factors for those patients are still limited, and more data should be considered and collected. In addition, our findings should be verified by large-scale, multiple-center corhort. Moreover, our research retrospected from 2013 to 2018, which might be affected by the developments of practices and surgical expertise in different surgeons. Furthermore, adequate interventions should be applied to improve the EGC prognosis as patients have such poor prognostic factors.