For resectable colorectal cancer, when acute intestinal obstruction occurs, there are currently three main treatment: (1) emergency surgical resection of the tumor, and stoma should be decided according to the patient's condition; (2) elective surgical resection of the tumor after emergency stoma to relieve the intestinal obstruction; (3) elective surgical resection of the tumor after the placement of SEMS. Once intestinal obstruction occurs, there is a high risk of emergency surgery due to various factors such as water-electrolyte balance disorder, acid-base balance disorder, and bacterial translocation, and the mortality rate can be up to 15%(30). Since the first reported use of SEMS in 1991, SEMS as a bridge of surgery has been widely developed because of its good short-term results, but its long-term oncology results are worrying(4). Several studies(31-34) have found that SEMS implantation can cause tumor cells to release into the circulatory system, but Ishibashi(31) believes that these tumor cells are not cancer stem-like cells, which can be quickly removed by the body, so they will not cause distant metastasis of the tumor. Some scholars(5-6) also observed many adverse histopathological changes after SEMS implantation, including tumor ulceration, perineural invasion, and lymph node metastasis. However, Matsuda(35) found that the increase of tumor p27kip1 expression level and the decrease of Ki-67 expression level after SEMS insertion, suggesting that the increase of mechanical pressure caused by SEMS may inhibit the proliferation of tumor. In the study of cancer recurrence and disease-free survival rate, etc., the results were also contradictory. Most scholars(20, 36-37) have not observed the difference between the SEMS group and the ES group, while Gorissen(11) believed that SEMS can increase the local recurrence rate of cancer. Sabbagh(27) found the SEMS group was inferior to the ES group in long-term outcomes such as overall survival and cancer-specific mortality apparently. In this meta-analysis, we compared the pathological characteristics of neoplasm between the two treatments to explore the potential oncological results of SEMS as a bridge to surgery.
Perineural invasion is a special pathological feature of many malignant tumors, and the current mainstream view is that PNI refers to the discovery of tumor cells in any of the three layers of nerve structure(38-39). In colorectal cancer, many scholars believe that PNI positive is an independent prognostic factor for poor prognosis, such as less survival time, shorter recurrence time, and increased local recurrence rate(40-44). Liebig's(45) research showed that the 5-year disease-free survival rate of PNI negative patients was 4 times higher than that of PNI positive patients, and a previous meta-analysis(46) showed that PNI positive patients with stage II colorectal cancer had a similar postoperative survival to stage III patients. Nozawa(42) found that the increase of mechanical pressure may lead to the development of PNI, and that the SEMS can relieve the intestinal obstruction by expanding the part of the intestine that contains the tumor, no doubt increasing the pressure in that part of the intestine. Many studies have observed a higher PNI positive rate in patients with SEMS(6-7). The results of this meta-analysis also showed that the PNI positive rate in the SEMS group was significantly higher than that in the ES group. At present, there is no sufficient explanation for the higher PNI positive rate after SEMS implantation, and the increase of mechanical pressure may be one reason. Theoretically, as a recognized independent prognostic factor for colorectal cancer, a higher PNI positive rate would result in a worse prognosis. However, no significant difference was found between the two groups in most studies, which may be due to the following reasons. Firstly, the proportion of postoperative adjuvant chemotherapy is greatly increased due to the acute intestinal obstruction. Previous studies suggested that PNI positive patients could achieve similar survival outcomes as PNI negative patients through adjuvant chemotherapy(43, 46). Perhaps benefiting from adjuvant chemotherapy, the SEMS group and the ES group achieved similar long-term oncology outcomes. Secondly, the time interval between the placement of SEMS and elective surgery is usually between 5-10 days(47), SEMS may lead to more PNI, but the time interval is too short, and the tumor has been radical resected before it can be converted into the effect on long-term oncology results. Besides, since these invaded cells may not be cancer stem cells, have a low malignant potential and maybe quickly recognized and cleared by the body, and therefore do not affect the prognosis of patients. Finally, previous studies have found that mechanical pressure can inhibit the proliferation of tumor cells, while similar phenomena have been observed after SMES implantation(35), and patients may benefit from this to a certain extent.
Lymphovascular invasion refers to the structure of lymphatic or blood vessels invaded by tumor cells, so it can be divided into lymphatic invasion and vascular invasion. Due to the high difficulty in accurately distinguishing lymphatic and vascular in pathological specimens, lymphovascular invasion is generally reported uniformly. In colorectal cancer, lymphovascular invasion is considered to be an independent predictor of poor prognosis(48-49). It is not only associated with higher T stage and poor differentiation, but also a key link of distant metastasis, and an important risk factor for cancer recurrence and shortened survival(50-52). In this meta-analysis, we observed a higher rate of lymphovascular invasion in the SEMS group. Some studies suggested that lymphatic invasion and vascular invasion may have different effects on tumors. Compared with lymphatic invasion, vascular invasion is more likely to lead to viscera metastasis(53-54). The survival time of patients with positive vascular invasion is much lower than that of negative patients, and the number of vascular invasion is positively correlated with recurrence(55-56). In our meta-analysis, 5 studies reported lymphatic invasion and 4 studies reported vascular invasion respectively, and the results showed that no significant difference was found in lymphatic invasion, while the positive rate of vascular invasion in the SEMS group was significantly higher than that in the ES group. In theory, the prognosis of SEMS group with more lymphovascular invasion or vascular invasion should be worse, but perhaps as with PNI, there is no significant difference in the long-term outcomes between the two groups due to adjuvant chemotherapy, short time interval, non-cancer stem cells invaded and other reasons, but considering the potential adverse effects, SEMS should not be considered as the preferred treatment.
Accurate pathological stage is very important for guiding the postoperative treatment of colorectal cancer, and sufficient lymph nodes dissection is one of the decisive factors to judge the stage of cancer. When the number of lymph nodes in the resected surgical specimens is insufficient, the pathological stage of cancer may be misjudged and the patient cannot receive effective follow-up adjuvant therapy. Meanwhile, the lymph nodes that have been invaded may be omitted, which may lead to the recurrence of cancer and other adverse outcomes. The current study suggests that a low number of lymph nodes harvested can lead to poor prognosis of colorectal cancer. In the emergency surgery for obstructive colorectal cancer, due to severe intestinal dilatation at the upper end of the obstruction and edema of abdominal tissue, the operative field is usually poor, and the difficulty of tissue separation and exposure increases. The placement of SEMS can effectively restore the intestinal patency and make the abdominal tissue edema subside, thus providing a good surgical field of vision. Moreover, the general situation of patients after stent implantation improved significantly, which made the laparoscopy rate in the SEMS group much higher than that in the ES group. The operative field of vision under laparoscopy was broader, which can more clearly show the anatomical structures that are difficult to expose in open surgery. This may explain that in most studies, the number of harvested lymph nodes in the SEMS group was higher than that in the ES group, and our meta-analysis showed the same results. However, there is no significant difference in the number of positive lymph nodes in the meta-analysis. The current guidelines suggest that the number of lymph nodes to be harvested should be more than 12(57), and most of the included studies were significantly higher than this requirement. At this time, the difference in the number of lymph nodes harvested between the two groups may not affect the pathological stage of patients. This was also confirmed by the meta-analysis of the N stage. Therefore, although the SEMS group has a significant advantage in the number of lymph nodes harvested, this advantage may be of limited significance.
There is no doubt that SEMS, as a bridge to surgery, is superior to emergency surgery in terms of some short outcomes such as primary anastomosis, complications, and permanent stoma rate(4), but its histopathological performance is significantly inferior to emergency surgery. The complications of SEMS placement also can not be ignored. Perforation, as the most serious complication, will not only cause peritoneal dissemination of tumors, but also be the main cause of early death. According to the literature, its incidence is as high as 7.4%, while the rate of occult perforation is higher(5, 58). Overall survival (OS) and disease-free survival(DFS) are the most commonly used indicators to evaluate the prognosis of cancer patients. A recent literature review showed that only a small number of studies showed that the placement of SEMS may affect the long-term surgical outcomes, and most studies showed that SEMS did not have a negative impact on the patients’ long-term survival and prognosis(59). Two recent meta-analyses respectively summarize the data of 2508 patients and 15224 patients, the results showed no significant difference between SEMS and ES in terms of three-year OS and three-year DFS, or five-year OS and five-year DFS, which was consistent with the results of previous meta-analysis(59-61). However, given the relatively small proportion of randomized controlled studies (20.8% and 26.7% respectively), and the factors such as stent placement technology and stent type can not be standardized, and due to the possible influence of factors such as chemotherapy and surgical interval mentioned above, the absence of significant differences in long-term surgical outcomes should be interpreted with caution. In summary, there is a risk of using SEMS as the preferred treatment for patients with resectable tumors. The European Society of Gastrointestinal Endoscopy (ESGE) has not recommended the routine use of SEMS as a bridge to elective surgery for left-sided malignant intestinal obstruction,but SEMS can be considered as a bridge for elective surgery in potentially curable patients ASA ≥III and/or age >70 years (47).
This meta-analysis compared the pathological characteristics of the SEMS group and the ES group to explore the long-term oncology safety of SEMS as a surgical bridge, but many limitations of this study may affect the interpretation of the results. First, twenty-two of the 27 studies were retrospective(about 81.5%) with inherent limitations, and its’ large proportion required careful interpretation of the results. Furthermore, the 3 included RCTs also failed to achieve blind allocation between doctors and patients. Secondly, there was high heterogeneity among studies, such as different types of self-expanding metal stents, the proficiency of endoscopists, the experience of the center, different emergency surgical procedures in different hospitals, and different selection criteria for SEMS and emergency surgery, etc. Third, the definition of some pathological features is currently controversial. For example, PNI may be missed or misreported due to the inconsistent definition, and the authenticity of the results may be affected. A similar situation may also exist in LVI.