In a previous study, we reported a fascial space priority approach for lateral lymph node dissection in patients with rectal cancer.  Using this approach, we found in the current study that 5 out of a total of 42 patients (11.9%) with low rectal cancer had metastasis to lateral lymph nodes but not to mesenteric lymph nodes. This finding supports managing lateral lymph node involvement as local metastasis, [6-8] and suggests the possibility that lateral lymph nodes may be sentinel lymph nodes in some patients.
Lymphatic drainage of the lower rectum passes to external pelvic (inguinal area) or pelvic (iliac vessels and anterior sacral) lymph nodes, or to the root of inferior mesenteric artery along the superior rectal artery. In a study by Akiyoshi and colleagues, prognosis did not differ significantly between patients with N2a vs those with either lymph node metastasis in the external iliac artery region (5-year overall survival:45%vs45%,P=0.9585;5-year cancer-specific survival:51%vs49%,P=0.5742) or in the internal iliac artery region 5-year overall survival: 32% vs 29%, P = 0.3342). 5-year cancer-specific survival: 37% vs 34%, P = 0.4347) , suggesting that the lateral lymph node involvement should be regarded as local metastasis. The findings from the current study supported such a notion. Lymphatic mapping technology can be adopted to study drainage pattern of low rectal cancer. 
Few studies have examined the prognosis of patients with lateral lymph node metastasis but no mesenteric lymph nodes metastasis. Based on a study by Takahashi,  the 5-year survival rate was 90.1% in patients with no metastasis to either mesenteric or lateral lymph nodes, 75% in patients with metastasis to lateral but not mesenteric lymph nodes, 67.7% in patients with metastasis to mesenteric but not lateral lymph nodes, and 32% in patients with metastasis to both lateral and mesenteric lymph nodes. Akiyoshi and colleagues argued that metastasis to lymph nodes located in the area medial to internal iliac artery should be classified as N2a and those located in the area lateral to internal iliac artery should be classified as N2b . Despite of such detailed differences, the prognosis of patients with metastasis to lateral but not mesenteric lymph nodes is clearly better than in patients with metastasis to both lateral and mesenteric lymph nodes. Studies with larger sample size and with a focus on the long-term survival in patients with distinct lymph node metastasis (lateral vs mesenteric) are needed to examine the clinical significance.
Lateral lymph node dissection could influence pathologic staging and hence postoperative management of the patients. In the current study, the 5 patients with metastasis to lateral but not mesenteric lymph nodes would have been classified as pN0 and stage II if lateral lymph nodes were not dissected. With erroneous staging, adjuvant chemotherapy after surgery would not be recommended. In low rectal cancer patients with MRI evidence for lateral lymph node involvement but no metastasis to mesenteric lymph node, CRT should be initiated; in patients who does not respond to CRT, LLND should be conducted. For patients with no mesenteric lymph node metastasis upon pathologic examination (regardless of the lateral lymph node status), the 2020 NCCN Guideline recommends the “watch and wait” approach. The results from the current study suggest that more attention should be given to lateral lymph node metastasis after neoadjuvant chemoradiation.
The AJCC colorectal cancer staging Guideline  classifies lymph nodes in the iliac artery region as regional, but considers metastasis to lymph nodes in obturator artery region as distant metastasis. Two patients in the current study had metastasis to lymph nodes in the obturator but not iliac artery lymph nodes or mesenteric lymph nodes. Based on this finding, we speculate that obturator lymph nodes should also be regarded as regional. Cirocchi et al reported that the pooled prevalence estimate of LCA absence was 1.2% (95% CI 0.0–3.6%).This rare absence of the left colonic artery/superior rectal artery or variation in lymphatic drainage may also contribute to this phenomenon. Due to very small number of the cases, this speculation must be examined in future studies.
There are several important limitations in the current study. First, this is a retrospective analysis of the patients receiving TME plus LLND for low rectal cancer. Due to the retrospective nature, there was no strict criteria for LLND. Nevertheless, we adopted a general set of indications for LLND. Another important limitation is the use of neoadjuvant CRT in some but not all patients, which may have influenced the pathologic staging. Third, we did not conduct systematic follow-up. As a result, the clinical significance of metastasis to lateral but not mesenteric lymph nodes remains ambiguous. The sample size is also relatively small, and wo could not compare the baseline features across patients with different pattern of lymph node metastasis.