We performed a retrospective study using the prospective electronic records of 1,213 patients with rectal cancer treated with elective LAR with double-stapling colorectal anastomosis at Severance Hosptial, Yonsei University Health System, from January 2007 to March 2013. The study protocol was approved by the Institutional Review Board (IRB) of Yonsei University (IRB No 2019-1183-001). Written informed consents were waived because of being a retrospective study. We included patients with stage I–III, histologically proven, invasive adenocarcinoma of the rectum, located 6–15 cm from the anal verge. We excluded patients with stage IV rectal cancer; those with multiple, histologically distinct primary tumors; and those who underwent procedures other than double-stapling anastomosis, including abdominoperineal resection, LAR with coloanal anastomosis, or intersphincteric resection. We divided the participants into 2 groups for analysis. The first group included 835 patients who underwent high IMA ligation at the root of the IMA (high tie). The second group included 378 patients who underwent low IMA ligation directly distal to the origin of the left colic artery (LCA) along with dissection of the LNs around the root of the IMA (low tie). The selection of the level of IMA ligation was decided by the surgeons.

The primary outcome of this study was the AL rate. The secondary outcomes were long-term oncologic outcomes, including local recurrence-free survival rate, metastasis-free survival rate, overall survival, and cancer-specific survival, of the high-tie and low-tie groups. We defined AL as the breakdown of the colorectal anastomosis with an infected fluid collection in the pelvic cavity within 60 days after the index operation. AL was diagnosed using CT or on the basis of clinical symptoms and signs including change of drain color and/or fever with peritonitis. Overall survival was defined as the duration from the date of surgery to the date of death. Cancer specific survival was defined as the time between surgery and cancerrelated death. Local recurrence was defined as recurrence at the primary tumor site confirmed on radiologic or histologic examination. Recurrence beyond the primary site was considered distant metastasis.

The variables that were analyzed and compared between patients with high and low IMA ligation were as follows: age, sex, American Society of Anesthesiologists physical status classification grade, preoperative CEA level, surgical approach (open surgery or minimal invasive surgery), neoadjuvant chemoradiotherapy, and operative outcomes (e.g., operative time and intraoperative blood loss). Pathologic staging was based on the 7th edition of the American Joint Commission on Cancer TNM system [11]. Surgical specimens were analyzed to determine the number of harvested LNs and the circumferential resection margin (CRM). CRM involvement was defined as the presence of tumor cells within 1 mm of the CRM [12]. The tumor size, proximal resection margin, and distal resection margin were determined in the operating room, and pathologic reports were reviewed to obtain additional information.

The preoperative staging workup included colonoscopy with biopsy; CEA testing; chest, abdominal, and pelvic CT; and rectal MRI. Neoadjuvant chemoradiotherapy was administered in patients with T3/4 midrectal cancer or positive LNs. We used a standard, long-course, neoadjuvant regimen of 5-fluorouracilbased chemotherapy and a total dose of 50.4 Gy of externalbeam radiation. The follow-up strategies for patients were identical between the groups. The patients were followed up every 6 months for the first 3 years after surgery and yearly thereafter. Each follow-up evaluation included medical history taking, physical examination, and measurement of serum CEA level. Routine imaging studies consisted of chest radiography and CT of the chest, abdomen, and pelvis. Chest radiography and abdominopelvic CT were performed 6 months after surgery for 3 years and annually thereafter. Colonoscopy was performed annually after surgery. Ultrasonography, whole-body bone scintigraphy, and PET were performed when there was suspicion of recurrence on routine imaging studies.

All surgeries were performed by five surgeons of the Division of Colorectal Surgery of Severance Hosptial, Yonsei University Health System. All procedures started from a medial to a lateral approach according to the oncologic concept. The level of ligation of the IMA was at the origin of the aorta among patients allocated to high ligation, and below the origin of the LCA among those allocated to low ligation (Fig. 1). Before 2010, high IMA ligation was the standard practice used by all surgeons involved in this study. Starting in 2010, three of the surgeons began performing low IMA ligation with concurrent dissection of the LNs around the root of the IMA for rectal cancer surgeries, whereas the other 2 surgeons continued to perform high ligation for all rectal cancer surgeries. However, these 3 surgeons selectively performed high ligation when preoperative APCT showed suspicious metastatic LNs at the root of the IMA or when metastasis LNs were diagnosed by frozen biopsy at the root of IMA. The peritoneum was incised at the level of the sacral promontory below the aortic bifurcation. Medial-to-lateral dissection of the sigmoid and descending colon along the avascular plane with autonomic nerve preservation and dissection of the LNs around the root of the IMA were performed. For low ligation, after identifying the LCA around the origin of the IMA, the IMA was resected below the origin of the LCA. Then, the inferior mesenteric vein was ligated with careful skeletonization on the level of its origin after assessing the collateral artery near the inferior mesenteric vein and pancreas. The left paracolic gutter was dissected, and the greater omentum of the transverse colon was detached. Complete splenic flexure mobilization was performed for a tension-free anastomosis for mid-rectal cancer, regardless if low or high IMA ligation was done, and the descending colon was used for the anastomosis. Patients with midrectal cancer underwent total mesorectal excision, whereas those with upper rectal cancer underwent tumor-specific mesorectal excision. After specimen extraction, end-to-end intracorporeal anastomosis was done with a double stapling technique. A suction drain was placed in the pelvic cavity. The anastomosis was then tested using an air-leak test. Protective ileostomy was performed in patients with two or more of the following indications: male sex, low anastomosis, neoadjuvant chemoradiotherapy, use of multiple staplers, and positive air-leak test. The operative details were as described in our previous studies [1314].

All statistical analyses were performed using IBM SPSS Statistics ver. 23.0 (IBM Co., Armonk, NY, USA). Categorical variables were analyzed using the χ² test, and continuous variables were analyzed using Student t-test. Differences in survival between groups were compared using the Kaplan-Meier method and tested with the log-rank test. A P-value of <0.05 was considered statistically significant.

There were no significant differences between patients who underwent high IMA ligation and those who underwent low IMA ligation with respect to age, sex, body mass index, American Society of Anesthesiologists physical status classification grade, preoperative CEA level, neoadjuvant chemoradiotherapy, tumor location from the anal verge, and diverting ileostomy. Patients who underwent high IMA ligation were more likely to have undergone an open operation than those who underwent low IMA ligation (15.9% vs. 5.6%, P < 0.001) (Table 1).

The pathologic and surgical outcomes of patients who underwent LAR for rectal cancer are summarized in Table 2. The total numbers of harvested LNs and metastatic IMA LNs were not significantly different between the groups. However, more metastatic LNs were harvested in the high-tie group than in the low-tie group (1.3 ± 2.9 vs. 0.8 ± 1.9, P = 0.002), and the incidence of positive pathologic N status was higher in the high-tie group (37.9% vs. 28.6%, P = 0.001). The other pathologic outcomes, such as pathologic T stage and CRM involvement, showed no difference between the 2 groups. Factors related to surgical outcomes were compared between the groups. The 2 groups had similar incidences of AL (the primary end point of this study), which occurred in 94 patients (11.3%) who underwent high IMA ligation and in 41 patients (10.8%) who underwent low IMA ligation (P = 0.85). Postoperative complications occurred in 40 patients (4.8%) who underwent high IMA ligation and in 12 patients (3.2%) who underwent low IMA ligation (P = 0.22). In both groups, the most common complication was paralytic ileus (38% and 42%), followed by wound infection (25% and 30%), bleeding (27% and 25%), and urinary infection (10% and 3%). As expected, the operative time was significantly longer in the low-tie group (248.1 ± 110 minutes vs. 281.8 ± 181.4 minutes, P < 0.001), whereas there was no significant difference in estimated blood loss.

The oncologic outcomes of the 2 groups are summarized in Table 3. With a median follow-up of 44 months (interquartile range, 27–59 months), the local recurrence-free survival rate was comparable between groups (92.1% vs. 96.1%, P = 0.197) (Fig. 2A). In addition, there was no significant difference in the metastatic recurrence-free survival rate between high-tie and low-tie groups (Fig. 2B). As shown in Fig. 2C and D, there were no significant differences between groups in the 5-year overall survival and 5-year cancer-specific survival rates.