Recently, a technique involving LL and lymph nodes dissection around the root of the IMA to achieve D3 lymph nodes dissection has been widely used clinically, especially in Asian countries. To compare the efficacy and safety of LL and HL, A total of 5947 patients (2519 patients in LL group and 3428 patients in HL group) were involved in this meta-analysis. The first objective of this meta-analysis was to understand whether the two ligation methods of IMA had a certain impact on the incidence of anastomotic leakage. It has been reported that the incidence of anastomotic leakage is 2.2%~12%. There are many risk factors for anastomotic leakage, however, blood perfusion and anastomotic tension are of primary concern to surgeons because good blood supply and tension-free anastomosis are critical in radical resection of colorectal cancer[8, 39, 40]. The colon below the root of IMA is perfused by IMA and the limbic artery from the middle colon artery(MCA)[8, 41]. Some studies have shown that in patients receiving HL treatment, since the LCA and its ascending branches are ligated, the perfusion of the distal colon is completely dependent on the limbic artery from the MCA, leading to a significant impact on the perfusion of the distal colon. Dworkin et al. used Doppler flowmeter to make measurements and found that HL significantly reduced blood perfusion in the distal colon[42, 43]. This undoubtedly increases the incidence of anastomotic leakage in HL patients. However, other studies suggest that HL can provide enough colon length for tension-free anastomosis, and the limbic artery can provide sufficient blood supply to the remaining colon[44, 45].
In some previously published meta-analyses, Fan et al. reported that low ligation significantly reduced the risk of anastomotic leakage, whereas Yang et al. reported that there was no significant difference in the incidence of anastomotic leakage with the two approaches[5, 14]. However, there are significant limitations to their findings. In the meta-analysis published by Yang Y et al., not enough studies on anastomotic leakage were included. In the meta-analysis published by Fan et al., the included studies were basically retrospective studies, lacking RCT data, and the results lacked stability and reliability. In our meta-analysis, we included the latest high-quality literature from Asian countries, including 8 RCTs and 13 non-RCTs, to evaluate the technical feasibility and oncological safety of low and high ligation of the inferior mesenteric artery in colorectal cancer surgery for Asian populations. The pooled anastomotic leakage rate was 5.5% (132/2411) in the low ligation group and 9.5% (316/3321) in the high ligation group. The meta-analysis of 20 trials reporting this data indicated that there was a significant difference between the two groups(p < 0.05). The results showed LL-treated patients had a lower incidence of anastomotic leakage compared to HL-treated patients. This finding is consistent with a meta-analysis recently published by Si et al. From an anatomical point of view, the left branch of the MCA and the ascending branch of the LCA form anastomotic branches near the splenic flexion through the Riolan arch. However, this region is usually relatively thin and is absent in 5% of the cases. Furthermore, postoperative systemic blood perfusion decline, elderly patients or patients with metabolic diseases and especially the increasing number of patients with vascular lesions, may become risk factors for anastomotic blood supply deficiency. Thus, low ligation is of great advantage in improving anastomotic blood supply and reducing anastomotic leakage.
Our meta-analysis confirmed that there were no significant differences between LL group and HL group in terms of operation time, blood loss, and early complications. This is consistent with the previously published meta-analysis[13, 46]. However, we found that regarding postoperative first anal exhaust time, LL group was earlier than HL group, which was rarely reported in previous studies. It may be because LL retains the LCA and provides better blood perfusion at the anastomosis, thus promoting the recovery time of bowel function.
Lymph node yield and involvement state, especially around the root of IMA, is a key prognostic factor for colorectal cancer[47, 48]. Some studies suggest that high ligation can more thoroughly remove lymph nodes and improve lymph nodes harvest rate, thus contributing to more accurate tumor stage and better disease prognosis[6, 7]. This may be because in those studies, LL group did not undergo IMA root lymph node dissection. Moreover, with the development of laparoscopic-assisted radical resection of colorectal cancer, the techniques of low ligation and IMA root lymph node dissection to achieve D3 lymph node dissection are increasingly mature. This meta-analysis shows that, the pooled rate of total lymph node involvement was 39.8% (257/645) in the low ligation group and 38.8% (244/629) in the high ligation group, and the pooled rate of lymph node involvement around the root of the IMA was 5.9% (36/608) in the low ligation group and 6.1% (38/662) in the high ligation group. We observed that there was no statistical difference between LL group and the HL group either in terms of the harvested number of lymph nodes or the involvement state of lymph node(p > 0.05). And, the metastasis rate of the IMA root lymph nodes is stable and low. This indicated that the number of lymph nodes dissected by low ligation was similar to that by high ligation, and the oncological safety was comparable. It is not surprising, therefore, that we observed similarities in 5-year OS and 5-year DFS between the two groups(p > 0.05). Because of the differences in physical fitness and dietary culture between Eastern and Western people, we only included Asian patients to assess the long-term prognosis of tumors. Our meta-analysis confirmed that HL did not significantly improve the long-term prognosis of tumors in patients with radical resection of colorectal cancer compared with LL, which was consistent with previous studies[6, 12, 49]. However, the meta-analysis published by Singh et al. showed no significant difference in OS among all case groups, while HL over LL had a significant OS benefit in the IMA positive lymph nodes group. Si et al. recently published a meta-analysis that compared stage II and III patients in greater depth and found no difference in survival between the two IMA ligation techniques. Therefore, based on the available evidence, LL of IMA is recommended in colorectal cancer surgery for Asian populations regardless of tumor stage.
Some limitations exist that should not be neglected for this meta-analysis. First, many studies related with the theme are non-randomized retrospective trials. Therefore, we have analyzed both the RCTs and non-RCTs to avoid lack of samples. Second, the data including postoperative defecation, urinary and sexual function are obviously insufficient in the literatures, so the functional results are not analyzed. Third, Individual differences in patient anatomy and the skill of surgeon, as well as differences in measurement methods, led to a high degree of heterogeneity in some of the results, which may affect the quality of evidence to some extent. Finally, the meta-analysis was limited to literature in English and the studies from China accounting for a larger proportion, which is a potential source of bias.