Peritoneal recurrence are associated with prognosis of gastric cancer [13, 14]. Previous researches have reported that EIPL combined with intraperitoneal treatment is effective treatment for gastric cancer patients [15], which can reduce the recurrence rate of advanced patients. However, the safety and effect of EIPL alone remain unclear, so this study explore the clinical value of EIPL.
Our results indicated that the overall survival curve and recurrence free survival curve of EIPL group were better than the non-EIPL group, and technique of EIPL was a significant factor of OS and RFS with advanced gastric cancer patients. So EIPL may reduce the recurrence rate of tumor and improve the outcome of patients. Yamamoto K also conducted an RCT of EIPL with pancreatic cancer patients and got the same conclusion [16]. Based on these researches, technique of EIPL need to be applied in abdominal cancers.
The intraoperative bleeding and surgery itself can lead to the residual tumor cell in the abdominal cavities, and this may increase the risk of peritoneal metastasis. In the non-EIPL group, intraperitoneal lavage does not exceed 3 liters of saline, which may be difficult to remove free peritoneal cancer cells. Technique of EIPL can remove free cancer cells and blood in the abdominal cavity by plenty of washing (10 L or more of saline), which can prevent free cancer cells attaching to the peritoneum [17].
In recent years, there have been several reports [18–20] showing that inflammation was linked to poor survival. Inflammation can stimulate the proliferation of malignant tumors cells, promote metastasis and destroy adaptive immunity response [21]. In this study, we found that the preoperative inflammatory index of NLR in the non-EIPL group was lower than the EIPL group. However, the level of postoperative NLR in the non-EIPL group was higher than the EIPL group. As for the patients with high level of NLR, the anti-tumor immune response of T cells and natural killer cells in the system may be surrounded by a number of neutrophils, which may decrease the opportunity to contact with tumor cells [22, 23], so the free peritoneal cancer cells may survive in this course.
This study concluded that the symptoms of ileus appeared more in the non EIPL group than the EIPL group. Besides, EIPL can also reduce the possibility of abdominal abscess, but the complications of bleeding and leakage have no significant difference. Indeed, EIPL is similar to the so-called limiting dilution method [24], this technique can clean up the peritoneal effusion and reduce the risk of infection. The 10 times of regular warm saline can promote intestinal motility and functional recovery, and this may also be helpful for surgeons to find the bleeding place. Besides, the level of NLR in the EIPL group was low after surgery, technique of EIPL can reduce the inflammatory cell and cytokines which play an important role in the development of inflammatory response and tissue damage. So technique of EIPL may be beneficial for the perioperative complications and make patients more comfortable after operation.
Although EIPL could not reduce the recurrence rate of lymph node, node and other organs, the overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group, besides, the overall survival curve and recurrence free survival curve are better in the EIPL group. Currently, only three RCTs are ongoing to explore the long-term efficacy of EIPL of advance gastric cancer. Kuramoto et al[8] concluded that the peritoneal recurrence rate of the EIPL group was significantly lower than that of the non-EIPL (6.7% vs. 45.8%, P = 0.013), there is no difference in recurrence rate for liver transfer, lymph node, and other organ transfer cases between the two groups, which is similar to our study. Another advantage is that IPC is not taken in our study, it may remove side effects associated with chemotherapy and confound the effect of EIPL. Misawa K [25] conducted an RCT indicating that peritoneal recurrence-free survival was not significantly different between the EIPL group and non-EIPL group. The 3-year overall survival rate and RFS rate was better than our study, and the reason is that the proportion of T4 (49.5%) and N3 (28.1%) is smaller than our study population (T4:96.0%, N3:34.7%). The value of EIPL may be related to the stage of T status and N status. The patients of our study (more cases of T4 and N3) have higher risk of recurrence, and the reduction of recurrence rate is significant in the EIPL group. One RCT is still ongoing based in Singapore [26], eligible patients having cT3 or cT4 with M0 disease are also in their criteria, but our study collected more clinical information and explored the safety and efficacy of EIPL group. Our study showed that technique of EIPL can reduce the perioperative complications of patients.
Our study has several limitations. First, we analyze only advanced gastric cancer patients, they may not on behalf of all patients. Second, more cases need to verify our results.
In conclusion, EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. Besides, the overall survival curve and recurrence free survival curve are better in the EIPL group. This technique is easy and not-expensive. Therefore, EIPL can benefit advanced gastric cancer patients a lot and would be a promising therapeutic strategy in the future.