High ligation of the inferior mesenteric artery during sigmoid colon and rectal cancer surgery increases the risk of anastomotic leakage: a meta-analysis

Colorectal cancer (CRC) is the third most common cancer in the world and the fourth most common cause of cancer-related death [1]. The standard operative procedure for curative resection of rectal cancer and sigmoid colon cancer includes removal of the tumor, wide resection of the colonic mesentery, and ligation of inferior mesenteric vessels [2]. There are two options for ligation of the inferior mesenteric artery (IMA): (1) high ligation, with ligation of the left colic artery (LCA), and (2) low ligation, with preservation of the LCA [3]. Ever since 1908, when Miles et al. recommended low ligation of the IMA [4] and Moynihan et al. recommended high ligation of the IMA [5], the controversy over the level of ligation of the IMA has persisted.

Lymph node metastasis is a crucial factor affecting the outcome of sigmoid colon and rectal cancer surgery [6], and ligation of the IMA root can facilitate removal of the surrounding lymph nodes during curative resection of sigmoid colon and rectal cancer. Thus, the high ligation of the IMA can improve lymph node retrieval rates and enable accurate tumor staging [7]. However, it is uncertain whether there are long-term survival benefits to be had with high ligation [8‐10]. Seike et al. reported significant reduction in blood flow to the anastomosis after high ligation of the IMA [11]. Others have argued that high ligation is associated with higher risk of hypogastric plexus injury, whereas low ligation avoids damage to the pre-aortic nerves and preserves the blood supply to the anastomosis [12, 13]. Meanwhile, several clinical studies have demonstrated that high ligation allows complete mobilization of the proximal colonic limb and thus helps reduce anastomotic tension [14]. Interestingly, previous meta-analyses have arrived at different conclusions about the incidence of anastomotic leakage (AL) with the two approaches. Fan et al. reported that low ligation of the IMA may lower the risk of AL, whereas pooled data from the studies of Cirocchi et al. and Yang et al. showed that there was no significant difference in the incidence of AL with the two approaches [5, 8, 9].

This meta-analysis was performed to compare the effect of high versus low ligation of the IMA during curative resection of sigmoid colon and rectal cancer on outcomes such as AL, overall morbidity, postoperative mortality, recurrence, and survival.

In CRC surgery, AL is the most common serious postoperative complication and an important cause of mortality. It is still not certain whether high or low ligation of the IMA is better for reducing the risk of AL. The primary aim of this meta-analysis was to examine how the level of IMA ligation was associated with the risk of AL. Factors reported to be associated with AL [40] include anastomosis tension, hemorrhage, hypoalbuminemia, blood transfusion, operative field infection, longer operation time, and corticosteroid use.

Anastomotic ischemia and increased anastomosis tension are believed to be the major reasons for the development of AL [14, 41]. High ligation of the IMA is often indispensable to achieve a tension-free anastomosis during low anterior resection, and undoubtedly, blood supply is a crucial factor for the healing of colorectal anastomoses. Some surgeons believe that the marginal arteries are sufficient to guarantee adequate blood supply to the anastomosis in patients receiving high ligation of the IMA [42, 43], whereas others argue that LCA ligation would reduce blood supply to the proximal limb [11, 23, 24, 44]. In 2012, Bonnet et al. performed an anatomical study to examine how high and low ligation of the IMA affected colon length in CRC surgery and concluded that the remnant colon was 10 cm longer when high ligation was performed [45]. However, in another anatomical study, Buunen et al. found that low ligation provided sufficient remnant colon length to guarantee a tension-free anastomosis in 80% of their specimens [46]. Komen et al. [24] used laser Doppler flowmetry to compare colonic perfusion after high or low ligation of the IMA in rectal surgery and reported that the blood flow ratio was higher when patients received low ligation, suggesting that the anastomosis might benefit from low ligation of the IMA. A prospective cohort study conducted by Hinoi et al. [27] in 2013 showed that LCA preservation (i.e., low ligation of the IMA) in laparoscopic anterior resection for middle and low rectal cancer was associated with a lower AL rate.

Some recently published meta-analyses [5, 8‐10] that compared outcomes after CRC surgery found no statistically significant differences between high ligation patients and low ligation patients in 5-year survival rate, lymph node yield, postoperative morbidity, postoperative mortality, overall recurrence rate, incidence of bowel obstruction, intraoperative blood loss, operation time, surgical site infection, postoperative bleeding, and so on. However, the AL rate differed between the two sets of patients. Fan et al. [9] analyzed the division branches of the IMA in sigmoid colon and rectal cancer surgery and concluded that low ligation of the IMA may be less likely to cause AL. Cirocchi et al. and Yang et al. [5, 8] analyzed high tie and low tie of the IMA in CRC surgery and showed that there was no significant difference between the two approaches. It should be noted that Cirocchi et al. and Yang et al. had a fewer number of studies with data on AL than did Fan et al., and so their results may be less reliable. We included both randomized and non-randomized studies in our meta-analysis and found that low ligation of the IMA in sigmoid colon and rectal cancer surgery could significantly reduce the AL rate (P = 0.004). Analysis of data from non-randomized studies and RCTs separately also showed that high ligation was associated with higher risk of AL (P = 0.01 and P = 0.04, respectively). Unfortunately, the number of RCTs in our meta-analysis was small and a lack of the data on the incidence of anastomotic leakage in the RCTs. Furthermore, there were obvious limitations in the data available. Most of the data were from non-randomized clinical studies performed over a decade ago, and it is likely that there were many differences in the management of sigmoid colon and rectal cancer over this period.

We found no significant differences between high ligation and low ligation patients in postoperative mortality, number of harvested lymph nodes, overall recurrence rate, and 5-year survival rate. This is consistent with previous meta-analyses. We found higher incidence of overall morbidity in high ligation patients; higher incidence of AL is probably the major reason. Although it is to be expected that higher incidence of AL will also increase postoperative mortality, we did not find any significant increase in this outcome in the high ligation group. This may have been because of the small number of studies and incomplete reporting of this outcome. Several authors have reported that low ligation of the IMA in CRC surgery is associated with decrease in the number of harvested lymph nodes [47, 48]. However, we did not find a statistically significant difference between the two groups in the number of lymph nodes harvested. Furthermore, in both groups, the number of lymph nodes harvested was > 12, which meets the recommendation in the National Comprehensive Cancer Network guidelines [49]. Some authors have reported that AL after CRC surgery is associated with cancer recurrence and poor prognosis [50]. We did not find any association between level of ligation and survival or recurrence after CRC, but this too may have been because of the small number of included studies and the lack of relevant data in the four RCTs in this meta-analysis.

Low IMA ligation during curative resection of sigmoid colon and rectal cancer appears to be associated with relatively higher risk of AL and overall morbidity. However, postoperative mortality, number of harvested lymph nodes, overall recurrence rate, and 5-year survival rate do not seem to be affected by the level of ligation. Large well-designed multicenter randomized clinical trials are necessary to confirm these findings and throw more light on this topic.