Anastomotic leakage (AL) is the most common complication after rectal cancer surgery and can result in not only increased morbidity and mortality but also increased local recurrence and poorer prognosis [
8‐
10]. The double-stapling technique (DST) has greatly facilitated intestinal reconstruction especially for anastomosis after LAR. Despite technical improvements and instrumental developments, recent studies have reported that the AL rate remains at 6.3–13.7 %; the most commonly reported rate is approximately 10 % [
7,
9,
11‐
14]. Risk factor analyses for AL after open LAR have been widely reported. However, a few studies have analyzed the risk factors for AL after laparoscopic LAR [
14‐
18]. In addition, the rates of protective diverting stoma, preoperative chemoradiotherapy, and TME in each study were not consistent, which might produce different results. In the present study, cases with protective diverting stoma or preoperative chemoradiotherapy were excluded from the analysis to investigate the pure risk factor for AL.
Discussion
AL is a major problem in patients who undergo operations for rectal cancers. It is associated with not only postoperative morbidity and mortality, but also local recurrence and patient’s survival [
8‐
10]. Several risk factors, including age, sex, intraoperative bleeding, obesity, preoperative chemoradiotherapy, protective diverting stoma, pelvic drainage, tumor size, tumor location, and the level of anastomosis, have been reported to be associated with AL after open LAR [
11,
26‐
29]. In contrast, only a few studies have examined risk factors for AL after laparoscopic LAR [
14‐
18]. Several studies reported that laparoscopic surgery and open surgery for rectal cancer did not differ in terms of the AL rate [
2,
3,
5,
30]. Laparoscopic rectal surgery provides an excellent operative field in a narrow pelvic space, and enables the preservation of autonomic nervous system more precisely. However, rectal transection using a laparoscopic linear stapler is relatively difficult when compared with open surgery because of the width and limited performance of the linear stapler. The devices and techniques used for laparoscopic LAR are different from those used for open LAR, which suggests that the risk factors for AL after laparoscopic LAR may also differ from those after open LAR. In the present study, multivariate analysis identified tumor size (≥5.0 cm) and precompression before stapler firings as independent risk factors of symptomatic AL after laparoscopic LAR with DST anastomosis (Table
5;
P = 0.02 and 0.024, respectively). Tumor size is well known to be a risk factor for AL after LAR [
29]. Pelvic space is limited, and so tumor size could adversely affect the ease of rectal transection and anastomosis. We previously reported that a sufficient amount of precompression time before stapler firings resulted in reduced intestinal wall thickness and proper staple formation in an animal model [
19], which was in agreement with the result of this clinical study. This study provided the first evidence that precompression before stapler firings was associated with AL in a clinical setting. We assume that precompression time and proper cartridge selection according to the wall thickness were critical to achieve secure staple formation.
Previous studies reported that the use of more than three cartridges for rectal transection was a risk factor for AL after laparoscopic LAR [
14,
15,
17]. When the number of stapler cartridges increases, there is a concern that an increased number of stapler firings may lead to small defects between the staple lines and, in turn, cause AL. In the present study, AL occurred in 26.0 % (6/23) of the cases in which more than three cartridges were used, whereas in only 9.9 % (13/131) of the cases in which one or two cartridges were used (Table
4;
P = 0.041). In addition, the AL rate in cases with two cartridges was 10.9 % (11/101), whereas that in cases with one cartridge was 6.7 % (2/30). Although there was no statistical significance in multivariate analysis (Table
5), we assume that the efforts to reduce the number of linear stapler seem to be recommended.
Several surgical techniques for laparoscopic LAR have been proposed to decrease AL. Ito et al. [
15] reported that vertical rectal transection through an additional suprapubic site was useful for avoiding multiple stapler firings and decreasing the AL rate. Kuroyanagi et al. [
23] reported that rectal transection was performed using two cartridges in most cases, with harmonious operator-assistant movement. They insisted the technical efforts to remove the crossing point of staple lines, which might otherwise be the cause of AL. In the present study, we analyzed whether the remnant crossing point could increase the AL rate, and found that it was not significantly associated with AL (Table
4); AL occurred in 17.4 % (8/46) of cases with remnant crossing point, whereas in 10.4 % (11/106) of cases without remnant crossing point (
P = 0.29). We assume that surgeons do not have to persist to remove the crossing point, especially when the crossing point is placed near the edge of the rectal stump and so removal of the crossing point is technically difficult. To our knowledge, this is the first study to investigate the effect of the remnant crossing point in a clinical setting.
Some studies recently reported that a transanal tube was important to prevent AL after LAR [
31,
32], although other study reported that a transanal stent did not reduce AL [
33]. In theory, a transanal tube decreases the intraluminal pressure around the anastomotic site, and protects the anastomosis from watery stool and flatus when gastrointestinal motility improves. In the present study, AL occurred in 10.2 % (13/128) of cases with a transanal tube, whereas in 23.1 % (6/26) of cases without a transanal tube (Table
4;
P = 0.096). Although there was no statistical significance, we assume that a transanal tube seems to be useful to reduce the AL rate. We usually remove a transanal tube at 5–7 days after surgery.
A number of studies have reported that lower anastomosis level is an important risk factor for AL after LAR [
27,
28]. However, the correlation between anastomosis level and AL was not statistically significant in the present study: AL rates for low anastomosis (height of the anastomosis from the anal verge was less than 3 cm) and high anastomosis (height of the anastomosis from the anal verge was 3 cm or more) were 16.0 % (4/25) and 8.4 % (9/107), respectively (Table
4;
P = 0.27). In addition, the correlation between tumor location and AL was not significant (Table
3;
P = 0.80). Although there was no statistical significance, the height of the anastomosis or the tumor location can reflect technical difficulties of laparoscopic LAR. All surgeries in the present study were conducted by well-experienced, board-certified laparoscopic colorectal surgeons. This minimized the risk of bias potentially associated with the early phase of the learning curve of surgeons, and with any inter-institutional variability in a multi-institutional trial.
There is still debate as to whether the creation of diverting stoma reduces AL. A recent randomized controlled study showed that the creation of diverting stoma reduced the incidence and clinical significance of AL [
34]. A considerable amount of retrospective studies have also described the beneficial effect of a diverting stoma on AL [
11,
35,
36]. On the other hand, there are some studies that the creation of a diverting stoma did not reduce the AL rate [
37,
38]. However, it is generally agreed that the creation of a diverting stoma can reduce the incidence of the severe complications that AL can cause. In the present study, cases with a diverting stoma were excluded from the analysis, because the creation of a diverting stoma seems to effectively reduce the clinical significance of AL and could be considered in high-risk patients.
In conclusion, we demonstrated that tumor size and precompression before stapler firings were independent risk factors for AL after laparoscopic LAR with DST anastomosis. In addition, precompression before stapler firings and multiple firings of the linear stapler tended to be associated with the AL occurring in early postoperative period. This study provides interesting data in the effort to reduce AL. However, because of the retrospective nature, the limited number of patients, and the likely multifactorial nature of AL, it is hard to draw robust conclusions. The outcomes of this study could not be corrected in a case-mix adjusted comparison, since this requires a large amount of cases to prevent over-fitting. Further studies including a large multi-institutional randomized controlled study are required to identify risk factors of AL and to develop the approaches to reduce this risk for patients with rectal cancers who undergo laparoscopic LAR.