Based on the synthetic evaluation of predicting ability of hemodynamic parameters, particularly considering the optimal sensitivity, specificity, and accuracy, the predictive model reflecting anastomotic blood supply consisted of PSV60 and PI60 [Table 3]. Insufficient blood supply was defined as PSV%R or PI%R <60 (56/163, 34.3%), while both PSV%R and PI%R ≥60 were classified as sufficient blood supply (107/163, 65.7%) [Table 4].
The results showed that patients with insufficient blood supply had a considerably higher hazard of AL than those with sufficient blood supply [Table 4]. To obtain additional information for identifying the patients at a high risk of AL, we analyzed the relationship between blood supply and AL (strong or weak) in different patient groups stratified according to the presence of prophylactic ileostoma, the receipt of neoadjuvant therapy, and tumor location. The analysis revealed that the patients with low rectal cancer and those receiving neoadjuvant therapy were more vulnerable to insufficient anastomotic blood supply because the patients with insufficient blood supply in these groups exhibited a higher incidence rate of AL than did those with a sufficient blood supply (25.9% vs. 3.9%, P = 0.007; 32.1% vs. 3.7%, P = 0.001, respectively); however, ileostoma did not evidently reduce the risk of AL in the patients with insufficient blood supply [Table 4]. Therefore, the predictive model was relatively accurate for the patients with low rectal cancer and those receiving neoadjuvant chemoradiotherapy.
To identify the independent risk factors for AL, we used both univariate and multivariate analyses. Only a variable with statistical significance in both analyses could be considered an independent clinical risk factor for AL.
Apart from blood supply, other potential clinical factors affecting AL, such as sex, body mass index, tumor location, neoadjuvant chemoradiotherapy, and ileostoma, were analyzed; however, none of these factors, except blood supply, was significantly related to AL in univariate analysis [Supplementary Table S4, http://links.lww.com/CM9/A83].
To investigate whether blood supply is an independent risk factor of AL, we verified blood supply as well as other variables using logistic regression model. The result showed that blood supply and neoadjuvant chemoradiotherapy were left in the equation, while tumor location, bowel resection length, distance of lengthening, and ileostoma were excluded, suggesting that blood supply and neoadjuvant chemoradiotherapy were independent risk factors of AL [Table 5].
A tension-free anastomosis with sufficient blood supply is generally considered crucial for sphincter-preservation surgery.[13,16] Although high-ligation surgery has not been definitely linked to anastomotic ischemia and leakage[21–23]; the low-ligation procedure is theoretically superior to the high-ligation procedure for improving proximal colonic blood supply by preserving the IMA and the LCA branches.[15,24] The oncological safety of low-ligation may be an issue to limit its use. However, a new coming result of a randomized clinical trial demonstrated that the low-ligation had the same lymph node harvest and long-term survival condition comparing to high-ligation. Thus low-ligation is also an option for rectal cancer surgery.
From a surgical viewpoint, the high-ligation procedure maximized colonic mobility, which could provide a sufficient colon length, thereby facilitating a favorable tension-free anastomosis. Whereas the low-ligation procedure limited the mobility of the proximal limb because of tethering by the SA or LCA. Thus, ligation of 1 or 2 branches of the SA or LCA is effective for acquiring a favorable tension-free anastomosis in most situations of low ligation. Although a series of studies have investigated the effects of ligating IMA on blood perfusion of the anastomotic bowel in a high-ligation procedure,[15,27] studies investigating the alterations in blood supply during the low-ligation procedure are not currently available. Our data revealed that vascular ligation during the mobilization of the proximal limb evidently reduced the blood perfusion of the anastomosis in one-third of the patients; these findings were significantly different from the hypothesis that the low-ligation procedure had a relatively weak influence on the anastomotic blood supply. The reasons behind why some patients had significantly lower blood supply after the ligation of the SA or LCA branches remain unclear; the absence or malfunction of the marginal arcade may cause the reduction in blood supply. The high-risk of AL is well established in these patients; particularly in those with low rectal cancer and receiving neoadjuvant therapy. Because TME surgery severely damages the vascularization surrounding the rectum in low rectal cancer and radiation reduces the healing ability of the colorectal tissue, we hypothesized that the patients with low cancer and those receiving neoadjuvant chemoradiotherapy were more vulnerable than the other patients to colonic ischemia. Therefore, the predictive model based on hemodynamic measurements could be considered a determinant factor in deciding whether to construct a defunctioning ileostomy during surgery, particularly if the patients had undergone neoadjuvant therapy or had a tumor at a low location. A defunctioning stoma significantly mitigates the consequences of a leakage; however, whether it can reduce AL remains debatable. For the cases with severely reduced blood supply, even Hartmann's procedure could be considered as an option; whereas for those with good blood supply, the rectal tube may be enough instead of routine ileostomy.
Conventionally, senior colorectal surgeons assess the blood supply of the proximal anastomotic segment by observing visible pulsation. However, this observation is highly subjective; moreover, observing vascular pulsation is difficult in patients with obesity. Karliczek et al reported that the surgeons’ clinical judgment had quite a low accuracy (<50%) in predicting AL. Doppler sonography is an effective and convenient tool for measuring colonic blood perfusion, which provides sufficient hemodynamic data, thus enabling the quantitative evaluation of blood supply. According to our experience, Doppler sonographic measurement requires a total time of only 15 to 20 min for all data collection. Furthermore, this technique does not cause an additional hazard to the patients. Nevertheless, it requires surgeons to modify their operating steps. They have to identify the proximal anastomotic location and measure its blood supply before ligation of the SA and mobilization of the proximal colonic limb to allow the collection of hemodynamic parameters before and after vascular ligation. We demonstrated that the predictive model based on hemodynamic analysis was an effective method for reflecting the degree of ischemia in an anastomotic bowel, which was predictive of AL. Although other methods for detecting blood signal such as laser Doppler flowmetry (LDF) are available, LDF only provides limited information about blood perfusion, and it is not a favorable assay to predict AL based on its low accuracy. Compared with LDF, Doppler sonography provides more detailed hemodynamic information and sonographic images, and its high predictive efficiency makes it a promising application prospect. Moreover, the convenience of this method expands the use of Doppler sonography during surgery. However, a limitation of the current technique was that evaluating the blood supply of the rectal stump by the routine probes was not available; thus, the alteration in blood perfusion of the rectal stump was unknown in this study. Some reports have pointed out that TME would decrease the blood supply of the rectal stump.[13,32] If the blood flow change of the distal rectal stump could also be counted into the model, the predictive efficacy of the model might be further improved.
Another notable point of this study was that it was an explorative study; the cut-off values here come from the single cohort which needed to be validated in other data sets. In addition, this study was a single-center study, with a relatively small population size. All the surgery and measurement were performed by a group of specialists, thus, compromising its persuasion on the repeatability between different manipulators.
The author like to appreciate the following staff for their contribution to this work: Dr. Yi-Fan Peng, Dr. Ming Li, Dr. Yun-Feng Yao, Dr. Jun Zhao, Dr. Tian-Cheng Zhan, Dr. Lin Wang, Dr. Nan Chen, and Dr. Peng-Ju Chen in Peking University Cancer Hospital.
This study was supported by a grant from the Beijing Municipal Commission of Science and Technology Funding (No. Z141107002514076).
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