The clinical manifestations of patients with GISTs are non-specific and are related to factors such as tumor size and site. The most common clinical manifestations are abdominal pain (20%-50%), gastrointestinal bleeding (30%) and gastrointestinal obstruction (10%-30%)(2, 13, 14). GISTs with gastrointestinal bleeding as the main symptom often require emergency surgery due to uncontrolled bleeding and hypotension. Despite revolutionary changes in the prognosis of GISTs and the promotion of individualized management in treatment over the past decade (15), the prognosis and postoperative management of patients with GIST remains controversial. Although the current version of the guidelines recommends the four most important factors that currently influence prognosis: tumour size, tumour site, mitotic rate and tumor rupture, but there are still many valuable predictors being studied, including gastrointestinal bleeding, Ki67 index and the type of tumour gene mutation (16–18). Gastrointestinal bleeding has been shown to be an independent risk factor for poor prognosis in other digestive malignancies, such as colon or gastric cancer, because gastrointestinal bleeding can lead to the dissemination of tumor cells or disruption of the mucosal barrier, which ultimately leads to poor prognosis(14, 19). However, it remains controversial in the study of gastrointestinal stromal tumors. In 2013, Xiao et al. conducted a retrospective study on a small sample and revealed that rectal bleeding is an independent risk factor for prognosis of rectal stromal tumor(9). Over the next few years, several studies have also demonstrated that gastrointestinal bleeding causes poor DFS or OS in patients with GIST(20–22). Interestingly, two studies have shown that the prognosis in the group with gastrointestinal bleeding is better than that in the group without bleeding. Bleeding may be a protective factor for recurrence of GISTs(10, 23). However, Gyu Young Pih et al. from South Korea concluded in a large retrospective study that gastric bleeding leads to a poor prognosis for GISTs, while duodenal bleeding has no effect on GISTs(24, 25).
Although the risk classification criteria for gastrointestinal stromal tumors have been preliminarily established, some influencing factors, including gastrointestinal bleeding, are still controversial. Previous studies have shown that gastrointestinal bleeding caused by gastrointestinal stromal tumors can cause tumor dissemination, suggesting that this bleeding is another form of rupture and should be considered as tumor rupture(6, 8). The final conclusion of our study is that gastrointestinal bleeding had no effect on prognosis, possibly because gastrointestinal bleeding would indicate the occurrence of tumors, and medical intervention would be carried out earlier, thus changing the prognosis of patients.
In summary, we used this meta-analysis to demonstrate that there is no significant difference in prognosis between patients with gastrointestinal bleeding and patients with gastrointestinal stromal tumors without gastrointestinal bleeding, either in RFS (HR = 1.33, 95% CI 0.66–2.68, P < 0.001) or OS (HR = 1.29, 95% CI 0.43–3.87, P < 0.001). However, there was significant heterogeneity in the results (I2 = 87.7, P < 0.001; I2 = 88.9, P < 0.001), and we believed that the important reasons for such heterogeneity were the different tumor sites, genotypes, tumor stages and some pathological parameters. More importantly, due to the different years of the studies, the different perioperative treatment of these patients with stromal tumors, and the failure to classify patients for postoperative management according to the standard risk of recurrence, are important factors contributing to the higher heterogeneity. However, due to the small number of included studies or the small sample size of some articles, it is difficult to conduct further subgroup analysis, which are also the limitations of this study. But due to the current treatment guidelines about GISTs widely used, and the effectiveness of TKIs treatment, the treatment of GISTs strategy compared with before the revolutionary change, so it's hard to get a large sample of retrospective or prospective studies to confirm whether the gastrointestinal bleeding is an independent risk factors of poor prognosis for GISTs. Consequently, high-quality studies that are at large-scale are necessary for the verification of our conclusion.