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The optimal approach towards IMA in rectal cancer surgery has been debated among the low tie and high tie performers. The debate among them is primarily based on three factors viz) Oncologic outcome b) Vascular factor (evidenced by leak rate) and c) Injury to hypogastric nerves. The most important advantage of high tie is its clearance of Inferior Mesenteric Artery (IMA) root or apical lymph node (LN) i.e. D3 or central Lymphadenectomy. But the reported incidence of IMA root LN metastasis is 0.3 to 8.6%^1,2. The concept of avoiding routine dissection of IMA root LN unless clinically indicated and avoiding routine splenic flexure mobilisation in low tie approach has gained wide spread interest. Thus, in low tie there is less dissection, better blood supply to the proximal anastomotic limb with less chance of injury to hypogastric nerves and adequate LN clearance following rectal cancer surgery. 

In our centre we do Low tie resections in rectal and rectosigmoid cancer surgery without routine mobilisation of splenic flexure (unless there is tension on mesocolic vasculature or proximal limb) and IMA root LN clearance unless clinically indicated. This study intends to explore the effectiveness and safety of low-tie of IMA for rectal cancer surgery by evaluating the oncologic outcome in the form of 3-year Disease Free Survival (DFS) rates; with LN yield and clinical leak rates as the secondary endpoints.

This study included all consecutive patients in this Department who underwent Rectal/rectosigmoid cancer surgery with curative intent (R0) by low tie of IMA from 01/01/2009 to 31/12/2016. Patients associated with familial syndromes or history of other malignancies in the past were excluded. Data was obtained from the prospectively held computerized operation register which holds the demographic details as well as the intraoperative details and 30-day postoperative outcomes. Follow up data was collected from patients directly as per the departmental protocol for follow up as well as from the tumour board register maintained prospectively in the Department. Follow up was done by clinical examination, Carcinoembryonic antigen (CEA), colonoscopy and Contrast enhanced Computerised Tomography (CECT) / Magnetic Resonance Imaging (MRI) Abdomen and Pelvis to look for recurrence as per National Comprehensive Cancer Network (NCCN) guidelines. 

Disease free Survival (DFS) was defined as time from the date of operation to date of first recurrence.

Rectal Cancer: Tumours within 15cm from the anal Verge 

Recto-sigmoid Cancer: Tumour between 16 and 20 cm from the anal Verge.

Low tie was defined as ligation of the IMA distal to the take-off of Left Colic artery (LCA).

Clinical leak was defined as the presence of intestinal content in pelvic drain or wound; or Systemic Inflammatory Response Syndrome (SIRS) with either contrast extravasation on imaging or radiologic evidence of pelvic collection requiring percutaneous drainage / laparotomy (with or without diverting stoma / Hartmann’s procedure). 

Neoadjuvant Chemoradiotherapy (NACRT) protocol: All patients with mid and lower rectal T3 and higher stage, mesocolic nodules and/or lymphadenopathy on CECT/MRI or restricted mobility on rectal examination were subjected to NACRT. 5-Fluorouracil (FU) infusional / capecitabine based radiosensitizer dose with long course 5040cGy in 28 fractions was the protocol followed for NACRT. Rectal tumours above peritoneal reflection and rectosigmoid tumours were taken up for upfront surgery.

Mechanical bowel preparation was not used in any of the patients. The Department protocol being followed is to keep the patient on low residue diet for three days prior to surgery. Low residue diet schedule was defined as semisolid diet without leafy vegetables or coarse grains.

The primary objective was to assess the 3-year Disease Free Survival (DFS) following Low Tie in Rectal Cancer surgery. The secondary objectives were to evaluate the Lymph Node (LN) yield in histopathology specimens and the clinical anastomotic leak rates following low tie without mechanical bowel preparation.

The results were analysed using Statistical Package for Social Sciences (SPSS) version 16.0. Data are expressed in its frequency and percentage. Quantitative variables were summarized as mean and standard deviation; and qualitative variables as proportions. Three-year Disease-free Survival and overall median survival rates among rectal cancer patients were assessed using Kaplan–Meier survival analysis. For all statistical evaluations, a two-tailed probability of value, <0.05 was considered significant.

It was ensured that participants were fully informed and gave their written consent to participate in the study. Institutional ethics committee clearance was obtained before starting the study. No expenses were incurred from the participants. 

There were 254 patients during the study period, of which 53 patients were lost to follow up and 29 patients expired while on follow up due to other causes (14-Cardiac cause, 6-chemotherapy associated toxicity, 5-Renal co-morbidities and 4-unknown cause). The remaining 172 patients were included for analysis (Figure 1).

In this study, 131 (76.2%) patients were more than 50 years. Pathologic complete response was seen in 5/82 (6.1%). The median LN yield in those patients who underwent upfront surgery and those following NACRT was 14 (8-24) and 5 (0-20) respectively (Table 1). 

Open surgery was done in 140 (81.4%) patients and Laparoscopic surgery in 32 (18.6%). Though we started doing Laparoscopic Colorectal resections from 2010, as the numbers were small compared to open surgeries no comparison between open and laparoscopic resection was done. In 5 (2.9%) patients Hartmann procedure was done. In two patients it was done due to failure of stapling device with wide defect at anastomosis and the remaining were done in obstructing tumours. There was no anastomosis in 51 (29.7%) patients (APR-46 and Hartmann procedure -5). 

In the remaining 121 (70.3%) patients (LAR- 61, AR-54, and uLAR-6) in whom anastomosis was done, 48 (39.7%) patients had proximal defunctioning stoma. In these 121 (70.3%) patients who underwent resection with anastomosis, 6/121 (4.9%) patients had clinical leak. The surgery performed in these patients were LAR-3, AR-2 and uLAR-1. Proximal defunctioning stoma was there in three patients and the anastomotic leak in these patients were managed conservatively. Among the remaining three patients, two underwent relaparotomy, lavage and proximal stoma; and the other patient underwent relaparotomy, lavage and Hartmann procedure. The median post-operative stay in these patients was 22.5 (SD-8.96) days. Over a median follow up of 61.5 months; two patients in the leak group had recurrence out of which one patient expired due to recurrence.

In this study, six patients required relaparotomy; three patients for anastomotic leak and the other three patients for post-operative adhesive obstruction (Clavein-Dindo score-3B). Overall the median hospital stay in the study was 11days (mean=11.92 +/- 3.77).

The median follow-up of the patients was 61 months (8-117 months). The mean DFS was 81.6 months [standard error (SE): 3.2; 95% Confidence Interval (CI): 75.35-87.91]. The mean OS was 90.7months (SE:2.78, 95% CI 85.2 – 96.1). The 3-year DFS and the 3-year OS was 76.9% and 83.5% respectively (Figure 2 and 3). In a subset of 69 patients who had at least 60 months follow-up, 5-year DFS and 5-year OS was 73.9% and 79.7% respectively. On comparing the DFS between rectum and rectosigmoid, the mean DFS was 81.6months (SE: 3.45, 95% CI: 74.9-88.4) and 71.8months (SE: 6.65, 95% CI: 58.8-84.9) respectively for rectum and rectosigmoid cancers (Figure 4). There was no significant difference in DFS between the two sites (p=0.947). On subgroup analysis, the stage of the tumour and the LN positivity had significant impact on DFS and OS; p= 0.006 and p <0.001 respectively (Table 2 and 3).  However, there was no statistically significant impact of the number of positive LNs on DFS (0.931) and OS (p=0.783) (Figure 5-10), (Table 2 and 3).

The Loco-regional recurrence (LRR) was seen in 11 (6.3%) patients. Distant failure was more common than locoregional recurrence with liver being the most common site of recurrence. Lung only metastasis was least common and seen in 2 (4.4%) patient (Table 4).

Miles and Moynihan respectively proposed low tie and high tie techniques for rectal cancer surgery around the same time, in 1908³,⁴. High tie has the presumed advantage of easily creating mesenteric windows in laparoscopy, gain in length of the proximal anastomotic colonic limb and hence the resultant tension free anastomosis, as well as, clearance of apical LN^5-12. However, the incidence of metastatic LNs at the origin of IMA has been reported to be relatively low in several studies, ranging from 0.3 to 8.6%^1,2. The disadvantages of high tie are the possible impaired perfusion^13-15 and impaired innervation of the proximal anastomotic limb, thereby resulting in a probable higher chance of anastomotic leak rate and bowel dysfunction respectively¹⁶. Whereas in low tie, the advantages are perfusion to the anastomotic limb is attenuated by left colic artery (LCA), there is less invasive dissection, lesser need for splenic flexure mobilisation and less chance of hypogastric nerve injury. The reported disadvantages are possibility of tension at anastomotic site and lack of apical LN clearance^12-14,17-19 (Table 5 and 6).

Several studies have reported that high IMA ligation did not improve the 5-year survival rates of patients with rectosigmoid or rectal cancers as compared to low IMA ligation^17-19,21. In this study the 3-year DFS and the 3-year OS was 76.9% and 83.5% respectively. In a subset of 69 patients who had at least 60 months follow-up, 5-year DFS and 5-year OS was 73.9% and 79.7% respectively. Various studies have reported 5-year OS of high tie ranging from 50-73.4%^14,22. In the RCT by Matsuda et al, the 5-year DFS and OS of high ligation was 74.9 and 79.3%, respectively; the 5-year DFS and OS of low ligation was 80.7 and 83.0%, respectively. Hence, there was no statistical difference in DFS and OS²³.

The median LN yield in our study of patients who underwent upfront surgery and surgery following NACRT was 14 (8-24) and 5 (0-20) respectively. There is significant decrease in the LN yield following NACRT^24-27. This has been reported in various other studies as well and the median LN yield after NACRT ranges from 4-14^24,28. According to study by Won-Suk Lee et al the absence of recovered LN in resected specimens after neoadjuvant chemoradiation was observed in 7.6% of specimens; and the absence of LN following NACRT should not be regarded as a risk factor for poor survival or as a sign of less radical surgery²⁹. The NACRT has a significant effect on the adequacy of lymph node sampling and a negative impact on the lymph nodes retrieved. This negative effect was more prominent with the long term rather than the short-term NACRT³⁰. The LN yield and status following NACRT were not significant predictors of overall survival³¹.

The anastomotic leak rate in the present study without mechanical bowel preparation was 4.9%. The reported leak rates after anterior resection with TME ranges from 3-27%32 (Table 7). Low tie rectal cancer surgery assumes significance in this era of Laparoscopic surgery where low tie without routine mobilisation of splenic flexure may decrease the operating time and make the procedure simpler yet oncologically adequate enough. 

Low tie in rectal cancer surgery provides comparable 3-year and 5-year DFS and OS with that of high tie reported in literature. Adequate LN yield can be achieved in low tie rectal cancer surgery with a low clinical anastomotic leak rate (without mechanical bowel preparation) compared to  that of other studies reported.