Symptomatic anastomotic leakage and most 12-month patient-reported outcomes did not differ significantly between low and high inferior mesenteric artery ligation in a randomized trial of minimally invasive rectal cancer surgery.
Symptomatic anastomotic leakage occurred in 5% of patients assigned to low ligation and 6% assigned to high ligation, a difference that was not statistically significant. The trial also found no statistically significant differences in overall 30-day morbidity or most bowel, urinary, sexual, and quality-of-life outcomes at 12 months.
Researchers conducted the multicenter, prospective, randomized clinical trial at 7 tertiary hospitals in South Korea from July 2019 through August 2024. Eligible patients were aged 18 to 80 years, had histologically confirmed clinical stage I to III primary rectal adenocarcinoma within 15 cm of the anal verge, and were scheduled for minimally invasive anterior resection.
Patients were randomly assigned to low ligation, in which the inferior mesenteric artery was divided distal to the origin of the left colic artery, or high ligation within 2 cm of the artery’s origin. Randomization was stratified according to sex and preoperative chemoradiotherapy. Surgeons were aware of treatment assignment, while patients and data analysts were blinded.
All participating surgeons had performed more than 50 minimally invasive rectal cancer resections prior to the trial. Patients scheduled for intersphincteric or abdominoperineal resection were excluded.
Of 314 randomized patients, 293 underwent anterior resection with primary anastomosis and were included in the modified intention-to-treat analysis. This population included 143 patients assigned to low ligation and 150 assigned to high ligation.
Seven patients assigned to low ligation were converted to high ligation during surgery. Six conversions followed vascular injury, and one followed suspected lymph-node metastasis. These patients remained in their originally assigned group for the primary analysis and were classified according to the procedure received in an as-treated sensitivity analysis.
The primary endpoint was symptomatic grade B or C anastomotic leakage within 30 days following surgery. Asymptomatic leaks identified only on imaging were excluded from the primary endpoint.
The adjusted analysis, which accounted for study site, sex, and neoadjuvant chemoradiotherapy, also found no statistically significant difference in leakage between the groups. The as-treated sensitivity analysis yielded a consistent result.
The trial was designed on the assumption that leakage would occur in 15% of patients undergoing high ligation and 5% undergoing low ligation. Because the observed rates were substantially lower, the researchers acknowledged that the study may have been underpowered to detect smaller differences between the procedures.
Overall 30-day postoperative morbidity occurred in 14% of the low-ligation group and 22% of the high-ligation group, a difference that was not statistically significant. Intraoperative complication rates also did not differ significantly.
Splenic flexure mobilization was performed more frequently in the low-ligation group, including complete mobilization in 57% of patients assigned to low ligation and 35% assigned to high ligation. Splenic flexure mobilization and diverting ileostomy were performed at the surgeon’s discretion. The researchers reported that mobilization was used more frequently with low ligation to achieve a tension-free anastomosis.
Exploratory analyses according to splenic flexure mobilization and diverting stoma status did not identify statistically significant differences in leakage. Because these adjunctive procedures were surgeon-directed rather than randomized, the researchers cautioned that the findings should be interpreted carefully.
Total and apical lymph-node yields and recorded completeness of mesorectal excision were similar between groups. Long-term cancer recurrence and survival were not assessed in the trial.
At 12 months, patient-reported questionnaires were completed by 85% of patients assigned to low ligation and 87% assigned to high ligation. Missing responses were not imputed.
Mean Low Anterior Resection Syndrome scores and the proportion of patients with major syndrome did not differ statistically. Urinary function, male sexual-function measures, retrograde ejaculation, and quality-of-life measures also did not differ significantly.
Among available female respondents, the mean Female Sexual Function Index score at 12 months was higher in the high-ligation group, although the proportion meeting the study threshold for female sexual dysfunction did not differ significantly.
The researchers noted that the proportion of patients receiving neoadjuvant chemoradiotherapy was lower than is typical in Western practice, warranting caution when generalizing the findings because of radiation’s effects on anastomotic healing. They described intersphincteric resection as a procedure associated with particularly high leakage risk and anastomotic tension. Because these patients were excluded, the trial could not evaluate a subgroup that might theoretically benefit from vascular preservation.
In an invited commentary, David R. Rosen, MD, and David Liska, MD, of Cleveland Clinic, wrote that the trial did not definitively endorse one ligation strategy. Instead, they noted that colonic reach, vascular anatomy, lymphadenectomy requirements, perfusion, and anastomotic tension should inform individualized decision-making.
Lead study author Chang Hyun Kim, MD, of Chonnam National University Hwasun Hospital and Medical School, and colleagues concluded that because low ligation was accompanied by more frequent splenic flexure mobilization, surgeons should consider both perfusion and the need to achieve a tension-free anastomosis when selecting the ligation level.
Disclosures: The study researchers reported no conflicts of interest.
Source: JAMA Surgery