Introduction
Despite advancements in treatment and the establishment of a comprehensive nationwide screening program, the mortality rate from colorectal cancer (CRC) continues to be a significant concern in Korea [1]. Furthermore, the expenses related to the treatment of CRC and the management of its associated side effects pose a considerable societal burden.
Currently, the primary treatments for CRC include surgical procedures, radiotherapy, and chemotherapy [2,3]. Encouraging outcomes are being seen in a specific subgroup of patients through targeted therapy and immunotherapy [4,5]. Surgery is typically the first line of treatment for CRC. Significant advancements in the comprehensive management of CRC have been made due to improvements in surgical resection and anastomosis techniques, as well as the use of innovative instruments.
Nonetheless, surgical complications are an inherent part of the procedure, and among these, anastomotic leakage (AL) stands out as a particularly concerning complication following surgery for CRC. Studies have shown that AL can negatively impact functional outcomes and may potentially contribute to cancer recurrence [6–8].
Over the past few decades, there has been a notable expansion in the use of minimally invasive procedures, including laparoscopic surgery, robotic approaches, and trans-anal mesorectal excision. These advancements have increased the likelihood of sphincter preservation [9–12]. Importantly, as the use of sphincter-preserving techniques continues to rise, so does the population of patients potentially at risk for AL. Consequently, efforts to predict, prevent, and appropriately treat AL following rectal cancer surgery have become increasingly critical.
In this descriptive review, we aim to explore the risk factors associated with AL following rectal cancer surgery and provide an overview of recent surgical techniques applied during and after surgery for prevention, as well as insights into treatment approaches.
Intraoperative Approach to Reduce Anastomotic Leakage
Hand-sewn and stapled anastomoses are still widely performed, with the choice between the two largely dependent on individual surgeons' preferences. This is due to the ongoing debate regarding which method is safer. The essential points for ensuring safe bowel anastomosis, whether hand-sewn or stapled, include meticulous technique, adequate blood supply, and the absence of tension [13]. The choice of anastomosis method and configuration is influenced by various factors, such as the surgical approach, intestinal tension, and the surgeon's level of experience.
There is no conclusive evidence supporting the superiority of any specific method of constructing colorectal anastomoses, including the side-to-side, end-to-side, side-to-end, or end-to-end techniques. At present, the double-staple technique is the most commonly employed method for colorectal anastomoses [14–16], especially given the widespread adoption of minimally invasive surgery. With regard to the double-staple technique, it has been suggested that the number of staple cartridges used for rectal division may be linked to AL, although the findings have not been consistently conclusive [17–19].
Some colorectal surgeons aim to minimize the number of cartridges used during rectal surgery by delicately trimming the rectum to allow for a single stapler firing to transect it. However, inserting a staple to transect the rectum can be particularly challenging in obese male patients with low, bulky tumors and narrow pelvises. It has been suggested that two cartridges be intentionally used for rectal transection, followed by the removal of the intersection of staple lines using a circular stapler. The use of a suprapubic port might be beneficial in reducing multiple stapler firings by facilitating vertical rectal division [20].
The "dog-ear" deformities created at both edges of the rectal stump after rectal division are considered a risk factor for AL in the double stapling technique. Some have demonstrated a technique that involves centrally invaginating the bilateral dog-ears using sutures to eliminate the dog-ears. Subsequently, both the staple line and the dog-ears are excised using a circular stapler [21,22]. In instances of proximal bowel dilation, to reduce the risk associated with anvil application, De Robles proposed a triple stapling technique [23]. This method involves using a linear stapler with an internal anvil to cut the proximal end, followed by creating an opening to remove the anvil spike prior to forming the anastomosis.
Intraoperative reinforcement of the anastomosis with sutures may be associated with a reduced occurrence of AL. However, the existing research evidence is somewhat constrained, as many of the studies analyzed did not include patients with factors like neoadjuvant therapy or prophylactic stomas [24–28]. Recently, the use of intracorporeal circular reinforcing sutures has been introduced, utilizing barbed sutures for minimally invasive rectal surgery (Fig. 1). Although this technique could potentially be more easily implemented with a robotic approach, additional research is necessary to confirm its effectiveness in reducing AL.
Maintaining optimal blood flow is crucial for ensuring a safe anastomosis. Traditionally, surgeons have evaluated bowel perfusion during an anastomosis procedure by observing the bowel's color or the presence of pulsatile flow at the cut surface of the bowel or marginal vessel. However, these methods can be subjective and occasionally insufficient.
Ryu et al. [29] attempted to determine the perfusion status by grading the bleeding of marginal vessels during left colon cancer surgery. They proposed a visual grading system that categorizes the bleeding from the marginal vessel into four groups. Despite not observing a difference in the AL rate among the groups due to the absence of AL occurrences during the study period, they discovered a correlation between age and the perfusion status of the proximal bowel, as determined by the visual grading system.
The use of indocyanine green (ICG) to assess bowel perfusion during surgery has recently garnered increasing interest [30]. Fluorescence imaging with ICG facilitates the clear delineation of vascular and avascular segments. This assists in establishing a well-perfused anastomosis, which may help prevent AL. There is a growing body of evidence supporting its effectiveness in reducing AL following colorectal surgery [30–33].
The PILLAR study demonstrated a reduced incidence of AL when intraoperative angiography was utilized. Specifically, the study reported a 1.2% incidence rate for low-risk left-sided anastomoses, and a 1.9% rate for high-risk cases. High-risk cases were defined as those involving anastomoses located less than 10 cm from the anal verge and/or in patients who had undergone pelvic radiation [32]. Shen et al. performed an analysis of four studies, which included a total of 1,177 patients. Their results indicated a combined OR of 0.27 (95% CI, 0.13–0.53) favoring intraoperative angiography (P<0.001) [33].
However, it should be noted that ICG imaging, while useful, has the limitation of not being able to objectively quantify the degree of perfusion. As a result, there have been studies conducted with the aim of establishing a grading system for perfusion assessment. A study by Kim et al. [34] proposed a five-tier grading system for this purpose, considering both perfusion time and intensity. This study involved 657 patients who underwent curative robot-assisted sphincter-saving surgery for rectal cancer. The findings revealed that delayed perfusion (>60 s) and low perfusion intensity (rated 1−2) were significantly more common in patients with anastomotic strictures and marginal artery defects, compared to those without these factors (P≤0.001).
These findings suggest that integrating ICG fluorescence angiography into colorectal surgery could potentially be beneficial for preventing AL. However, it is essential to establish standardized protocols and develop objective evaluation methods for its practical implementation.
Surgeons have employed various mechanical intraoperative techniques to evaluate the integrity of anastomoses to reduce AL in colorectal surgery. The air leak test has traditionally been used during surgery as a method to evaluate the integrity of anastomosis. This test involves insufflating the bowel at the anastomotic site to identify any defects in the anastomosis, allowing for immediate repair if necessary. While this test can effectively detect mechanical faults intraoperatively, it has limitations in identifying anastomotic leaks caused by poor perfusion and its use in low colorectal or coloanal anastomosis. A modified method to address the limitations of the conventional air leak test has been suggested [35]. Crafa et al. [35] proposed the direct observation of air leaks within the anastomosis using a circular anal dilator under pneumoperitoneum (Fig. 2). However, as they also utilized ICG imaging, it is difficult to conclude that the modified air leak test alone was effective in reducing AL.
Intraoperative endoscopy has been used to evaluate the integrity of anastomoses, enabling the identification of bleeding at the anastomotic level or disruption of the anastomosis during surgery [36]. Endoscopy may also manage anastomotic bleeding, as it can be employed in a postoperative setting [37]. A systematic review and meta-analysis of six studies revealed that intraoperative endoscopy was linked with a decrease in postoperative AL (from 6.9% to 3.5%; OR=0.37; 95% CI, 0.21−0.68; P=0.001) and anastomotic bleeding (from 5.8% to 2.4%; OR=0.35; 95% CI, 0.15−0.82; P=0.02) in left-sided colon resection [36]. However, the air leak test using endoscopy requires endoscopic skills, additional materials, and is time-consuming. Furthermore, its effectiveness in preventing AL in colorectal surgery requires further scientific validation.
While there may be debates about the effectiveness of mechanical intraoperative methods in reducing AL, they can still be valuable for identifying immediate technical issues.
A trans-anal drain can potentially alleviate endo-luminal pressure at the anastomotic site and facilitate drainage on the proximal side of the anastomosis. It may also offer protection against watery stool or gas, and theoretically decrease bacterial contamination in the area, thus potentially preventing AL following rectal surgery. However, the outcomes of various studies have been inconsistent, casting doubt on the effectiveness and validity of trans-anal drainage [38,39]. A meta-analysis involving 909 participants (401 with trans-anal tubes and 508 without) from four trials concluded that the use of a trans-anal tube is an effective and safe procedure that can reduce the incidence of AL [38]. The group with the trans-anal drain exhibited a significantly reduced risk of AL compared to the group without the drain (OR=0.30; 95% CI, 0.16–0.55; P=0.0001). Additionally, there were notable differences between the two groups in terms of the reoperation rate (OR=0.18; 95% CI, 0.07–0.44; P=0.0002) in this meta-analysis. However, more recent analyses have presented contradictory findings [39]. These included three randomized controlled trials (RCTs) and 16 observational studies (both prospective and retrospective), involving a total of 4,560 patients. Interestingly, the impact of the trans-anal drain varied depending on the type of study. In the RCTs, the use of a trans-anal drain was not significantly associated with differences in AL (OR=0.67; 95% CI, 0.42–1.05; P=0.08). However, it was linked to a significant reduction in reoperation (OR=0.11; 95% CI, 0.03–0.51, P=0.004) and an increased rate of anastomotic bleeding (OR=2.36; 95% CI, 1.11–5.01; P=0.03). In observational studies, the use of a trans-anal drain was associated with a significant reduction in both AL (OR=0.44; 95% CI, 0.30–0.64; P<0.0001) and reoperation (OR=0.47; 95% CI, 0.33–0.69; P<0.0001). The conclusion drawn from these studies suggests that trans-anal drainage tubes may not clearly demonstrate superiority in reducing AL. Therefore, the use of trans-anal drainage to prevent AL is not currently recommended with a high level of evidence. However, well-designed future studies are warranted to evaluate its potential role.
The practice of prophylactic intra-abdominal drainage during elective colorectal surgery was once thought to be beneficial for the early detection of AL. However, recent studies have reported that this prophylactic measure does not reduce the incidence of AL [40,41]. The GRECCAR 5 trial, which compared 236 patients in the intra-abdominal drain group to 233 patients without drainage undergoing rectal cancer surgery, found that the use of intra-abdominal drainage did not result in a decrease in the rates of pelvic sepsis, postoperative morbidity, reoperation, length of hospital stay, or the rate of stoma closure [40]. A meta-analysis of a systematic review of four RCTs, including the GRECCAR 5 trial, compared patients undergoing colorectal resections with and without drainage. The results showed no significant differences between the groups in terms of clinical AL (8.5% vs. 7.6%; P=0.57), radiologic AL (4.2% vs. 5.6%; P=0.42), and pelvic sepsis (9.7% vs.10.5%, P=0.75) [41]. Therefore, the routine use of intra-abdominal drainage is currently not recommended.
While diverting stomas were initially intended to prevent AL and mitigate the severe morbidity associated with AL, their effectiveness in preventing AL remains unconfirmed. Furthermore, the use of diverting stomas comes with the potential risks of dehydration and complications related to stoma closure [42,43].
A systematic review and meta-analysis, which solely focused on RCTs and included four RCTs with a total of 358 patients, found that the use of diverting stomas significantly diminished the risk of AL (OR=0.32) [44]. A more recent meta-analysis revealed that patients without diverting ileostomies experienced a significantly higher incidence of AL than those with a diversion (OR=0.292; 95% CI, 0.177−0.481) [45]. However, this study also discovered that the rate of complications other than AL was significantly higher in patients with diverting ileostomies than in those without (OR=3.337; 95% CI, 1.570−7.093).
A blow-hole type stoma was proposed as a method to reduce stoma-related complications in certain clinical settings [46]. However, it is not expected to prevent AL or reduce the morbidity associated with AL.
Therefore, in clinical practice, careful consideration of both the benefits and risks associated with diverting stomas is essential.
Conclusion
AL remains a significant concern in colorectal surgery. The method of anastomosis does not appear to be associated with AL, but the use of multiple cartridges in transecting the rectum during rectal surgery could be linked to AL. Several new techniques aimed at reducing cartridge use have been introduced and have shown promising results in small-scale studies. Intraoperative reinforcing sutures have also been effectively utilized to mitigate AL. The application of fluorescence angiography has demonstrated the potential to decrease AL. However, the use of intra-abdominal drains has proven ineffective in preventing AL and thus cannot be recommended. A recent meta-analysis has shown that trans-anal drains can have a positive effect in reducing AL, although the results have been inconsistent. The use of diverting stomas could potentially reduce AL-associated morbidity, but complications related to the stoma must also be considered.
Numerous efforts have been made to reduce AL in colorectal surgery. However, some of these approaches lack high-level evidence to support their effectiveness. To address this, well-designed studies should be conducted to determine the impact of both traditionally used and newly developed techniques in preventing AL. Moreover, the adoption of these techniques should be individualized, taking into account patient-specific risk factors and the clinical settings.
