The treatment of GC, one of the most commonly malignancies, is remain a long-term and difficult challenge worldwide. The prognosis of EGC has improved obviously with the technical advances of diagnosis and endoscopic dissection in past decade. Due to the increased morbidity of SMGC which resulted from improvement of endoscopic technology recent years, more studies about SMGC patients are needed to enhance the understanding of SMGC.
As previous studies reported, elderly, male sex, tumor size ≤ 2 cm and atrophic gastritis were the independent risk factors of occurrence of early SMGC, and a family history of GC, smoking and alcohol consumption might be the risk factors of morbidity of patients with early SMGC[2,3]. Therefore, we also chose 2cm as the cutoff value for grouping of tumor size. Nitta et al and Eom et al demonstrated that age≥65 years, male, a family history of cancer, tumor in the upper third of stomach, early T stage and severe intestinal metaplasia were the independent risk factors of developing SMGC[5,11]. Compared to youngsters, atrophic change and intestinal metaplasia were more common in the gastric mucosa of elderly people, which might result in the higher morbidity of SMGC in elderly. In present study, similar to the outcomes of previous studies, most (78.9%, 45/57) of all patients with SMGC were male. However, only 43.9% (25/57) of the patients were with age≥65 year-old, and just 7.0% (4/57) of the patients were with tumor size <2 cm, which were differ from previous studies. Furthermore, the data of atrophic gastritis and intestinal metaplasia were partly lacking in our study. Insufficient sample size is the main limitation of this study.
As a special cohort of GC, SMGC is more common in EGC patients compared to advanced GC patients[2,12]. Differently, in this study, only 35.1% of the patients were early SMGC, and most patients presented the advanced cancer lesions. In regard to the number of primary lesions, Zhao et al reported that most patients presented two lesions, and three or more lesions existed in a few patients with SMGC. Similar to previous study, 52 patients had two lesions, 3 patients presented three lesions, and only 2 patients were with four lesions in our study. And the number of primary lesions was not significantly associated with risk of LNM and tumor recurrence of SMGC. What’s more, there was no significant difference of number of primary lesions between early and advanced SMGC patients.
As previous study confirmed, most main and minor lesions in SMGC patients were confined to the same third of stomach, and the lower third of stomach was the most common tumor location. In patients with early SMGC, the clinicopathologic features were similar between main and minor lesions, including tumor location, macroscopic appearance, histological type, invasion depth, et al[12,13]. However, we found that 42.1% (24/57) and 52.6% (30/57) of all patients with SMGC had inconsistent histological type and tumor pT staging, respectively, between the main and minor lesions. But the inconsistency of histological type or tumor pT staging was not significantly associated with LNM and recurrence of SMGC, and no significant difference of them existed between early and advanced SMGCs.
Previous study showed that the clinicopathologic characteristics and risk of LNM of early SMGC patients were not significantly different from that of early SGC patients. Furthermore, there was no significant difference of long-term survival outcomes between patients with early SMGC and early SGC[2,3,15]. However, few previous studies have evaluated the correlationship between early and advanced SMGCs, and the independent risk factors of LNM and long-term prognosis in SMGC patients.
The rate of LNM, about 35.6% (67/188) in patients with SMGC, was reported to be significantly lower than that of patients with SGC. Similarly, in our study, the incidence of LNM in SMGC patients was 42.1% (24/57). Tumor size ≥3 cm and lymphovascular invasion were confirmed to be the independent risk factors of LNM in patients with early SMGC. Furthermore, lymphatic tumor invasion was regarded as the strongest predictor for LNM in EGC patients. However, few studies were found to investigate the risk factors of LNM in SMGC patients. Similar to previous studies, lymphovascular cancer plug was proved to be the independent risk factors of LNM for SMGC patients in this study. No previous study reported the correlation between CA125 level and LNM of SMGC. Innovatively, we found that preoperative CA125 was significantly positively correlated with LNM in SMGC patients. Our results may will be significant in preoperative assess of LNM of SMGCs, but need further validation by a prospective study with larger sample size. Furthermore, histological type, tumor pT staging and nerve invasion might be the influence factors of LNM, but with no significant difference.
With regard to the long-term prognosis, previous study indicated that the 5-year survival rate in patients with SMGC was significantly higher than that in patients with SGC. Furthermore, LNM, serosal invasion and curative resection were the independent prognostic factors of survival in SMGC patients. Differently, there was a trend that LNM, nerve invasion and preoperative AFP level might be the independent risk factors of tumor recurrence of patients with SMGC in present study, but with no statistically significant difference.
In conclusion, there were several factors with significant difference between early and advanced SMGC patients. In patients with SMGC, the presence of tumor size ≥2 cm, poorly-differentiated type, LNM, ulcer, nerve invasion and relatively high preoperative CEA level might make them more likely to be advanced SMGC, which should be paid more attention by surgeons. Furthermore, the appearance of lymphovascular cancer plug and high preoperative CA125 level indicated the increased risk of LNM in SMGC patients. Although with no significant difference, LNM, nerve invasion and preoperative AFP level might be the predictive factors of recurrence of SMGC. A larger sample prospective study is needed to validate or improve the present outcomes because of the limitation of insufficient sample size in this study.