Colorectal Anastomosis: The Critical Aspect of Any Colorectal Surgery

Abstract

Colorectal surgery has undergone an enormous technical evolution with the advent of laparoscopy and, more recently, the robotics approach. Technology, combined with the use of more advanced materials and the implementation of pre-habilitation and enhanced recovery after multimodal surgery programs, has allowed the performance of complex surgeries with excellent results. As a result, reaching optimal oncological, physiological, and cosmetic results associated with the patient’s better and shorter postoperative stay is possible. However, colorectal anastomosis is still a critical aspect of this process that always affects the final result of the surgery. Therefore, it has profound implications in the short, medium, and long term. When an anastomotic leak occurs, it is usually the surgeon’s biggest nightmare and can have devastating consequences for both the patient and the surgeon. This chapter’s aim pretended to reflect on how to avoid colorectal anastomotic leakage and, if it happens, how to detect and treat it early, trying to minimize the number and the consequence.

1. Introduction

1.1 Importance of colorectal anastomosis in colorectal surgery and anastomotic leakage implications

Most colorectal surgery implies intestinal resection and, if possible, bowel continuity restoration. Conceptually, colorectal resection surgery without reconstitution of intestinal continuity is a functional surgery not entirely achieved. The patient and the surgeon aim to avoid a permanent stoma after any bowel resection surgery. The reconstitution step is, therefore, the critical point for any colorectal surgery. The surgery may have been perfect from the point of view of surgical technique. However, if any problems arise at the level of the anastomosis, the surgical results obtained will be compromised temporarily or permanently, with a spectrum of variable severity. In fact, the presence of some leak in the anastomosis may have, in addition to short- and medium-term infectious implications, functional and survival implications, in the latter case in oncological patients.

In this perspective, it is essential to define and standardize the concept of colorectal anastomotic leakage (CAL), as well as know its etiopathogenesis, the possible occurrence promotor factors, how to detect it early and, if present, how to manage and reduce its consequences.

This chapter intends to analyze and reflect on these aspects and, in this way, prevent and reduce the occurrence of anastomotic leaks and, if it happens, minimize their consequences and settle the issue.

2. Definition and grading severity of colorectal anastomotic leakage (CAL)

Colorectal anastomotic leakage (CAL) is one of the most serious and feared complications in coloproctology, as said before. Generically, it is a break in the anastomosis between the two intestinal segments performed during colorectal surgery, which means communication between in- and extra-luminal spaces due to a defect in the integrity of the surgical anastomose performed. Therefore, in practical terms, anastomosis’s failure must be classified in dimensions, severity, and consequences. However, its precise definition and diagnosis are still the subject of some controversy.

Many CAL definitions have been proposed for decades, but consensus has been proven hard to find. The finding of the lack of consensus on the definition and the subsequent concern to standardize the definition and severity scale common to colorectal surgeons has become more evident in the last decade, with a particular incidence in the last 5 years [1, 2, 3, 4, 5]. The use of a CAL consensus survey in some countries [3, 4] and a modified Delphi study that included colorectal surgeons and researchers who had published three or more articles about CAL [5] are evident attempts to use a common language to compare results and define strategies.

According to Helsdingen et al., CAL definition can be standardized into four categories: clinical, laboratory, imaging, and operative findings. Consensual clinical parameters included tachycardia, clinical deterioration, abdominal pain, discharge from the abdominal drain, discharge from the rectum, rectovaginal fistula, and anastomotic defect detected by digital rectal examination. The main laboratory parameters for CAL suspicion are increased plasma CRP or its combination with leukocytosis. The imaging findings valorizing signs of CAL are extravasation of endoluminal water-soluble contrast, collection around the anastomosis, presacral abscess near the anastomosis, perianastomotic air, and intra-abdominal free air on CT scan. Furthermore, indicative re-operative findings of CAL were evidence of necrosis of anastomosis or blind loop, signs of peritonitis, and dehiscence of anastomosis [5].

On the other hand, CAL is an anastomotic failure and must be classified in terms of severity as it has management implications and different outcomes. Rahbari et al. proposed a three-degree (A, B, and C) clinical severity classification, impacting the treatment and consequences. For example, an anastomotic failure type “A” was considered generally sub-clinical and would not require any active therapeutic intervention; type “B” required active management (antibiotic therapy, image-guided drainage, or transanal drainage) with no need for further re-operations; type “C” required further re-operations [1]. This severity classification correlates with the Clavien-Dindo classification [6] and allows us to measure and grade CAL short-term consequences.

3. Consequences of short- and long-term colorectal anastomotic leakage (CAL)

The most feared complication following intestinal resection is anastomotic leakage. The short consequences of CAL are variables. This spectrum ranges from a small-contained leak without sepsis to a patient with peritonitis and septic shock and patient’s death. Once the leak is established, its consequences depend on the presence and interaction of multiple factors. Among them are the size of the leak, the level of the anastomosis, the pathology that led to the surgery, the speed and ability to control the source of contamination, the patient’s co-morbidities, the presence of sepsis, and the patient’s immune response to sepsis. Thus, we may be facing a small leak controllable with antibiotics/percutaneous drainage, only with prolonged hospitalization or readmission, up to four-quadrant peritonitis with septic shock that implies not only surgery but also the support of various organs and systems in an environment of intensive care.

When we speak about the long-term consequences of CAL, we are referring to the possible reduction in oncological survival [7, 8] or implications in anastomosis functionality, which may be partially or entirely compromised depending on the severity of the CAL, and anastomosis location [9]. Ishizuka meta-analysis demonstrates a significantly decreased 5-year OS in patients with CRC who had CAL compared with patients with CRC who did not have CAL [7].

4. Economic and social burden of CAL

A CAL almost always implies a considerable increase in direct and indirect surgical procedure costs, which can reach thousands of euros and impact the patient and society [10]. These direct costs are associated with unforeseen medical therapies, the need for re-interventions, the increase in hospital stay, readmission needs [10, 11], and indirect costs usually not accounted for as absenteeism from work and patient loss of quality of life [12].

5. CAL incidence

The incidence of CAL in colorectal surgery continues to be under-evaluated and under-reported. It is a much more frequent situation than in the public domain. It is more frequent in more distal anastomoses, and a recent multicenter European work was carried out only with ileocolic anastomoses that confirms this under-evaluated frequency. The repercussions it causes are minor and can be interpreted as other causes. On the other hand, there may be caused a certain embarrassment in the surgical environment in admitting its existence and the interpretation of its existence as a technical failure, a wrong surgical indication, or a deficient surgical plan. CAL are frequent and only do not happen to those who do not operate or work in a parallel reality. CAL is typically diagnosed 5–8 days post-surgery, although some case reports have demonstrated that a delayed presentation beyond 30 days is possible [13]. Gessler et al. debated the question of two different types of leakages (earliest and latest), confirming that 20% of patients had their leakage diagnosed after discharge and at readmission [14]. While AL can occur in up to 24% of patients undergoing distal rectal surgery, combined rates for surgery performed at any level of the intestinal tract are accepted to be 6–7% [15, 16]. One systematic review of preoperative, intraoperative, and postoperative risk factors for colorectal anastomotic leaks shows the prevalence of anastomotic leaks varies from 1 to 19% according to anatomical site. The highest leak rates occur with extraperitoneal anastomoses. The highest rate of AL occurred in coloanal and colorectal anastomoses (5–19%). This rate was significantly greater than that seen in enteroentero (1–2%), ileorectal (3–7%), ileocolic (1–4%), and colocolic (2–3%) anastomoses [17]. Degiuli et al. published a retrospective multicenter study that used data from 24 Italian referral centers of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. The overall incidence of leaks in anterior low resection for rectal cancer was 10.2% and the 30-day leak-related mortality was 2.6% [18]. Goshen-Gottstein et al. analyzed CAL in colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center in 2012. The overall leak rate was 8.4% [19]. Data were retrieved from the Dutch Surgical Colorectal Audit by Bakker et al. CAL in patients undergoing colonic cancer resection with the creation of an anastomosis occurred in 7.5% of 15,667 patients [20]. Unexpectedly, Frasson et al. reported in a prospective multicentric study of 1102 patients a rate leak in right colectomy of 8.4%, a higher value than most equivalent studies [21].

6. Concept of infection in anastomosis site promote anastomotic leak

According to John C. Alverdy (from Chicago American College of Surgeons, San Francisco, 2019), there is uncontestable and unambiguous evidence that bacteria at the site of anastomosis promote anastomotic leak, and surgeons should consider anastomosis as a wound and therefore put one focus on wound healing. This concept that the bacteria at the site of anastomosis play a causative role in anastomotic leak infection is a seductive hypothesis [22]. It can change CAL prevention and management paradigm.

We cannot forget that many factors can be present and act in microbiota patient with colorectal pathology with the collapse of the core microbiome: radiation, NSAIDS, cancer, tissue trauma, opioids, ischemia, blood loss, obesity, and smoking. It can lead to a predominance of collagenolytic microbe (P. aeruginosa, Enterococcus faecalis). These bacteria have in vivo virulence activation, adherence to tissues, immune escape, and cleavage of gelatinase B (MMP-9). This sequence promotes amplification of tissue inflammation and may lead to a clinical manifestation of a leak. Intestinal tissues induce a single nucleotide polymorphism (SNP) mutation in Pseudomonas aeruginosa. That enhances its virulence with a possible role in the anastomotic leak. About this issue, a study was realized in 2021 in rats where Olivas demonstrated a direct relation between leak anastomosis probability plus irradiation plus P. aeruginosa presence [23]. Furthermore, the phenotypic change from P1 to P2 at anastomosis is associated with increased collagenase activity, high swarming motility, and destructive phenotype [23].

On the other hand, E. faecalis can promote virulent activation of human plasminogen [24]. It happens because collagenase-producing bacteria, particularly E. faecalis, promotes anastomotic leak by degrading healing anastomotic tissue [25]. Furthermore, Clostridium difficile infection can also increase anastomotic leak after colectomy [26].

Based on the premises previously mentioned, it makes sense that an anastomotic leak should be thought of and treated as an infected wound.

In intestinal surgery, the sutures approximate tissue until the collagen is laid down. It requires meticulous attention to detail: minimize tissue trauma, ensure good blood supply, avoid tension, and beware of local sepsis.

At this point, beware of local sepsis; we must be concerned about changes in the local environment that results in a significant alteration in anastomotic tissue-associated microbiota. There are no modifiable factors such as inflammation surrounding anastomotic tissue due to infection, radiation, ischemia, or the presence of cytokines pro-inflammatory. Nevertheless, modifiable factors such as the colorectal bacterial community are present in the intestinal lumen. This presence can have either detrimental or beneficial effects depending on how the bacterial community composition is affected [27]. For that reason, a lot has been discussed about the benefits of bowel preparation before colorectal surgery with oral antibiotics and mechanical preparation. In addition, it seems appealing to implement pre-habilitation nutrition weeks before surgery to modify the patient’s intestinal microbiota quality [28]. Moreover, in an unfavorable environment, the utilization of tranexamic acid can also inhibit the virulent activation of human plasminogen by E. faecalis [29].

7. Possible promotors and factors to CAL

Relatively little is known about CAL pathophysiology. Studies, however, have identified several surgical and patient-related risk factors that can influence CAL development. Many factors that can increase the risk of CAL have been analyzed over the years. Among those considered the most important and influential are described: male gender, comorbidities (diabetes, chronic kidney failure, ischemic heart disease, ischemic stroke), type approach, protective ostomy, multiple linear staplers use, blood transfusion, surgery for cancer, and distal colorectal anastomosis was associated with the higher odds of CAL and were identified as independent risk factors [18]. Some are not modifiable, but others can and should be changed to reduce the risk of CAL. The knowledge and identification of independent risk factors for CAL allowed the creation of nomograms for the prediction of anastomotic leakage after anterior colorectal resection [30].

7.1 Non-modifiable factors that may contribute to anastomotic leak

7.1.1 Male gender and patient age

Male gender as a risk factor of CAL is consensual and is named on meta-analyses and several studies with multivariate analysis [19, 31]. It is usually related to surgery for distal rectal cancer due to narrow male pelvic that implies major complex surgery dissection and need of multiple stapling lines rectal stump section. According to some authors, this risk factor associated with distal rectal cancer and neoadjuvant radiotherapy is an indication to make a stoma diversion.

Patient age (>65 years old) is rarely considered an independent risk factor [32]—more than age, the patient’s comorbidities influence the risk of CAL.

7.1.2 Patient co-morbidities

Several patient co-morbidities are associated with higher CAL risk. Multiple studies have also shown that the American Society of Anaesthesiologists (ASA) fitness score is also an independent CAL risk factor. Patient scores III are associated with a 2.5-fold increased [20].

Pre-existing atrial fibrillation or chronic obstructive pulmonary disease (COPD) are independent factors of high-grade risk of colorectal complications [33]. According to Goshen-Gottstein in a multivariate analysis, pulmonary disease (OR 4.37, 95%CI 1.58–12.10) was associated with a greater risk of CAL [19].

Metabolic diseases, such as diabetes mellitus, can increase AL risk through impaired wound healing [34]. Some studies show the presence of diabetes mellitus as an independent risk factor for CAL. On the other hand, patients with pre-existing renal disease, have been identified as high-risk for CAL development [35, 36].

A meta-analysis realized by Cheng et al. shows that preexisting liver cirrhosis was associated with an increased postoperative major complication rate, a higher rate of re-operation, a higher short-term mortality rate, and poor overall survival following CRC surgery [37]. Kaser et al. demonstrated in a retrospective study that patients with liver cirrhosis/severe fibrosis have a significant increased risk of leakage after colonic anastomosis (12.5% (3/24) in patients with liver cirrhosis, while it was only 2.5% (47/1851) of CAL in patients without liver cirrhosis. The difference remained statistically significant after correction for confounding factors by multivariate analysis [38].

The association of more than one comorbidity results in a higher Charlson Comorbidity Index (CCI) score that can be used as a tool to predict risk CAL [39]. Tian et al. found that patients with a CCI score > 3 had 1.82 times higher risk of anastomotic leakage compared to patients with a CCI score of zero [40].

7.1.3 Underlying pathology and its characteristics

In surgery for rectal cancer, advanced tumor, tumors >5 cm, and distal rectal cancer have also been identified as CAL risk factors [41, 42].

Patients with autoimmune disease or related autoimmune diseases such as Crohn’s disease can have a higher risk of CAL when submitted to colorectal surgery. This aspect can be related to underlying pathology and its characteristics, but generally is associated with chronic immunosuppressive therapies, mainly if medicated with corticosteroids in high doses treatment with corticosteroids before surgery (within 4 weeks before surgery).

7.2 Potentially modifiable factors in the prevention of anastomotic leak

7.2.1 Patient-specific characteristics

Adequate nutrition is an important factor for intestinal healing as it contributes to collagen synthesis and immune responses. Several studies have shown obesity to independently increase the risk of CAL [18, 43]. While obesity [44] has often been poorly defined in these studies and the degree of obesity and an associated increase in risk may consequently be open to interpretation [45]. Recently it was published in an article where the authors used three different computed tomography obesity indices, two standard methods, and one novel measurement, and their association with outcomes after colorectal cancer surgery [44]. Nevertheless, measures of central obesity, such as waist circumference and waist-hip ratios may be more sensitive than BMI in predicting CAL [46]. Visceral obesity is probably the main parameter to quantify risk for CAL [47]. The findings of this analysis confirm that obesity is a significant risk factor for anastomotic leak, particularly in rectal anastomoses. This effect is thought to be primarily mediated via technical difficulties of surgery although metabolic and immunological factors may also play a role. Obesity in patients undergoing restorative CRC resection should be discussed and considered as part of the pre-operative counseling [48].

Malnutrition, weight loss, or sarcopenia are all factors related to the difficulty of healing and an insufficient plastic capacity for tissue reconstitution. All of them increase CAL risk. Weight loss and nutrition status are important factors when evaluating patients for colorectal anastomosis. Weight loss and malnutrition before surgery can result in anastomotic dehiscence, and some studies support this association [49, 50]. Usually, malnutrition is associated with other factors influencing the healing process, such as hypoalbuminemia and alcohol abuse consumption. The presence of severe malnutrition is an indication of parenteral nutrition at least 15 days before surgery. One of the factors for colorectal surgery complications in multivariate analysis by Cheng was sarcopenia [47]. Herrod et al. confirmed this fact and stated that measuring psoas density on a preoperative CT scan is a quick and easy radiological assessment of sarcopenia [51].

Little has been investigated about alcohol and tobacco consumption and CAL in recent years. It seems that alcohol consumption over recommended levels (>105 g alcohol per week) is associated with an increased risk of CAL [52, 53]. The risk associated with cigarette smoking and CAL is more consistent than with alcohol. Smoking consumption increases the risk of postoperative complications nearly 2-fold [54]. The relationship between the two might be secondary to ischemia caused by smoking-related microvascular disease. It seems that vascular ischemia from nicotine-induced vasoconstriction and microthromboses, together with carbon monoxide-induced cellular hypoxia, inhibits anastomotic circulation in smokers. There is a recent study that suggests the implementation of preoperative smoking cessation programs may reduce complications as well as overall postoperative costs [55].

7.2.2 Other patient aspects in the preoperative phase

Anemia and low albumin levels are an increased risk of CAL [56, 57]. Authors were reporting the preoperative albumin level less than 3.5 g/dl as being a significant factor for leakage [58, 59]. Preoperative hypoalbuminemia increases the risk of CAL rate level and the delay of surgical procedures to allow correction of preoperative albumin level has been shown to improve the morbidity and mortality in patients with severe nutritional risk [60].

Pre-operative blood transfusions have also been identified as AL risk factors [42, 61]. For this reason, patients with anemia and low ferrum are an indication for ferrum IV administration ideally one month before surgery.

Radiotherapy causes poor intestinal healing and increased fibrosis by damaging the local intestinal vascular system and impairing fibroblast function. Neoadjuvant chemoradiotherapy (CRT) is part of multimodal treatment and is generally recommended for patients with locally advanced rectal cancer, followed by (total mesorectum excision) TME surgery. This therapeutic modality is used to reduce the local recurrence rate. Furthermore, neoadjuvant chemoradiotherapy has also been an independent risk factor for CAL [57, 61, 62]. Nonetheless, conflicting data have emerged over the last decade regarding the effect of preoperative CRT on CAL. For example, a systematic review and meta-analyses published in 2017 could not prove a higher risk of CAL in patients treated with preoperative CRT [63]. Even though, usually in clinical practice, in most of the centers, male patients with distal rectal cancer and neoadjuvant CRT, the TME surgery is realized with a protecting stoma due to the high risk of CAL.

Steroid therapy is associated with an increased risk of CAL [64]. On the contrary, preoperative biologic therapy and immunomodulator use appear not to confer increased anastomotic-related complications [65]. Whenever possible, corticosteroid administration should be suspended, or at least reduced. Slieker et al. found a significantly increased incidence of AL in patients treated with long-term corticosteroids and perioperative corticosteroids for pulmonary comorbidity. In those cases, they recommend that anastomoses should be protected by a diverting stoma or a Hartmann procedure should be considered to avoid CAL [66].

Asymptomatic patients infected with COVID-19 submitted to elective surgery could be at higher risk, sometimes resulting in postoperative mortality. This subject is not consensual. The COVIDSurg collaborative et al. publish the results of an international cohort study of patients undergoing elective resection of the colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centers entered data from their first recorded case of COVID-19 until 19 April 2020. Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%), but they did not find a higher rate of CAL. These results must be analyzed with concern due probably bias, namely patient selection, surgeon experience, and confection of defunctioning stoma or end stoma instead of an anastomosis only [67].

7.2.3 Surgical planning

Patients that require an emergency resection and anastomosis at any level of the gastrointestinal tract are also at higher risk of CAL than patients submitted to elective surgery [20, 68]. This difference is mainly due to intestinal obstruction or sepsis requiring emergency surgery. In other circumstances, surgery must be deferred and the patient’s condition optimized before surgery.

In elective colorectal surgery, it is always possible that an effort must be made to prehabilitation and functional recovery program implementation [69]. Since this kind of program can reduce surgery complications, promote a fast recovery and probably help to increase patient survival, especially in aging patients with several comorbidities.

In high-risk patients with Crohn’s disease before ileocolic resection, a personalized prehabilitation (PP) program reduces the number of preoperative risk factors. This way, a PP program allows primary anastomosis with a lower complication rate than in upfront operated patients [70].

A combination of a high-fat/low-fiber Western diet, antibiotics, and surgery promotes the development of lethal sepsis. Future studies may inform the use of microbiota analysis and personalized diets to protect patients from infection and sepsis following surgery [28].

Although it has differences in intravenous antibiotics selection, it is consensual that intravenous prophylactic antibiotic preoperative used in elective surgery, administrated between anesthesia induction and the beginning of surgery procedure with subsequent intravenous antibiotic doses two hours of surgery time (to achieve steady-state pharmacokinetics), is essential for reducing perioperative infection.

Mechanical bowel preparation (MBP) with or without prophylactic non-absorbable antibiotic therapy in colorectal surgery has been used for decades. However, over the years, trends have changed. Generally, MBP plus oral non-absorbable antibiotics are advocated despite increasing evidence challenging its benefits. For example, intestinal preparation reduces fecal bulk, clears the bowel lumen, and reduces bacterial colonization, decreasing postoperative complications risks such as anastomotic dehiscence and wound infection. In addition, oral non-absorbable antibiotics decrease intraluminal bacterial content after mechanical bowel preparation. On the other hand, MBP detractors oppose that MBP has complications, such as clinically significant dehydration and electrolyte disturbances in the preoperative period, and the process is both time-consuming and unpleasant for patients. Therefore, they said the clinical practice sustains that oral and intravenous prophylactic antibiotics are sufficient because the evidence has shown that the gut microbial flora load is not reduced grossly by bowel preparation.

These two main currents of opinion may contribute to implementing different ERAS programs: ERAS pathways in the UK and European guidelines do not include MBP/oral antibiotics. In contradiction to the UK and Europe, North American guidelines recommend incorporating combined mechanical and oral antibiotic bowel preparation into ERAS programs stated [71].

More solid and structured studies are necessary to clarify the real benefits of combined intestinal preparation in colorectal surgery. The published studies are not comparable due to different designs. For example, if MBP is recommended for all colorectal surgery or only in specific situations (left colorectal surgery, anterior rectal resection, or right laparoscopic surgery); if MBP is performed with or without prophylactic oral antibiotic therapy and in case of oral therapy what kind of antibiotics are due and which scheme. On the other hand, some meta-analyses analyzed studies with different features, such as prospective vs. retrospective and randomized vs. not randomized, which do not have the same scientific value. These aspects induce the appearance of difficult-to-interpret biases.

Despite these constraints, in summary, we can read recent papers defending reducing the risk of CAL and surgical site infections with:

• The realization of MBP alone, without oral antibiotics, according to Guenaga et al., does not have advantages over perioperative intravenous antibiotics [72].

• The use of combined MBP plus oral antibiotics for all elective colorectal surgery is a defense by Klinger et al. whenever feasible. They conclude that combined MBP/Oral antibiotics results in significantly lower rates of SSI, organ space infection, wound dehiscence, and anastomotic leak than no preparation and a lower rate of SSI than oral antibiotics alone [73]. Other authors share the same opinion for all colorectal surgery [74, 75] or left colorectal surgery [76]. Two recent meta-analyses confirmed the interest in this actuation [77, 78].

• The advantage of elective decontamination of the digestive tract only with oral antibiotics for all colorectal surgery vs. a combined intestinal preparation strategy is recognized by Garfinkle et al. [79], but not consensual, according to other authors [80].

• The only administration of prophylactic perioperative intravenous antibiotics without mechanical or oral antibiotics is advocated in a prospective study published by Koskenvuo et al. [81] and in a meta-analysis made by Slim [82]. They do not find differences in CAL rate after colectomy in patients who have to make mechanical bowel and oral preparation before surgery and patients who with not.

In current practice, at least for low anterior resection and laparoscopic right colectomy, MBP plus oral antibiotics seems defensible. Indeed, the higher risk of CAL and its consequences on distal colorectal anastomoses and the more significant contamination with enteric content during laparoscopic anastomosis if intestinal preparation is not performed are valid and essential arguments to consider.

So, this issue remains in debate. The current recommendations for mechanical bowel and oral preparation before colectomy surgery to reduce SSIs or CAL risk should be reconsidered after the realization of well-designed, prospective, and double-blind studies.

7.2.4 Anesthesia technique

With the development of ERAS protocols, epidural anesthesia is commonly used in abdominal surgery to improve pain management and early patient mobility. In addition, epidural anesthesia is essential when the approach is open instead laparoscopic. The initial studies about the utilization of this technique aroused some doubts if it can contribute to a higher risk of CAL.

Recent studies demonstrated that intraoperative fluid management in the ERAS programs is not consensual, with limited evidence regarding fluid management protocols. A restrictive vs. liberal fluid regimen seems to benefit pulmonary complications but not the other morbidity [83]. Several studies do not report differences in CAL rate between restricted vs. liberal fluid administration [84, 85]. The National Institute for Health and Care Excellence (NICE) recommended major abdominal surgery by using esophageal Doppler monitoring for individualized fluid management to reduce complications (not necessarily the CAL rate), as shown in the meta-analysis by Walsh et al. [86].

7.2.5 Surgical technique

High surgeon experience, volume center, and operation time can influence the rate of CAL [30, 87, 88, 89]. Operative time longer than 3 hours has also been described in the literature as being associated with an increased incidence of anastomotic dehiscence [68, 90]. Blood loss greater than 300 ml with multiple blood transfusions or large fecal contamination is independent risk factors for CAL [91]. In those cases, it is unclear if they are related to a particular complex procedure or a lack of surgeon experience.

Differences between open or laparoscopic colorectal approaches in terms of CAL have not been demonstrated [92, 93]. The COLOR II trial showed statistically significant differences in blood loss, bowel recovery, and the length of hospital stay in favor of the laparoscopic approach and no difference between open and laparoscopic rectal resection in terms of postoperative anastomotic leakage or mortality [94]. Two recent meta-analyses comparing laparoscopic intersphincteric resection vs. an open approach for low rectal cancer have shown no significant difference in anastomotic leakage incidence between the two groups [95, 96]. Nevertheless, the results are contradictory. In anterior rectal resection for rectal cancer, some studies refer to laparoscopic surgery vs. open surgery as a significant factor in decreasing CAL [41].

Robotic colorectal surgery, including right and low anterior resection, is safe and feasible but has no clear advantages compared with laparoscopic surgery in terms of postoperative outcomes. The rate of anastomotic leakage was comparable between the two techniques [97, 98].

There are general rules of surgical procedures that must be fulfilled to contribute to achieving in colorectal surgery, a low rate of CAL. First, independent colorectal type procedure, the surgical technique must be standardized with careful and meticulous dissection. Avoid anastomosis tension is one of the general principles to follow during anastomosis confection. In a German expert meeting, a three-step Delphi method was used to find consensus recommendations for how to reduce anastomotic leakage in colorectal surgery. There was a strong consensus in regard to routinely mobilizing the splenic flexure and dividing the inferior mesenteric vein as the main technical aspects to avoid anastomosis tension [99]. Proper vascularization of intestinal segments involved in an anastomosis is a primordial factor that can determine healing on the digestive suture. In anterior rectal resection preservation of the left colic artery is an independent factor for anastomotic leakage in laparoscopic rectal cancer surgery according to the studies made by Yao et al. [30] and also by Trencheva et al. [39]. Intraoperative endoscopic visualization can detect anastomotic insufficiency. This procedure can be routinely performed in colorectal anastomosis reducing CAL probability. Recently, the measurement of microcirculation has gained substantial interest. Indocyanine green (ICG) fluorescence angiography is a new technique that helps surgeons to assess the blood perfusion of the colon in anastomosis. The meta-analysis and systematic review realized by Li et al. and by Liu et al. agree that ICG fluorescence angiography reduced the CAL rate after colorectal anastomoses for rectal cancer patients. However, both authors considered that more high-quality randomized controlled trials are needed to confirm this benefit [100, 101].

When considering the surgical technique in left colorectal surgery, studies have failed to show significant CAL rate differences between handsewn or stapled anastomoses [102]. The considerations about stapled vs. handsewn colorectal/coloanal anastomoses for CAL risk [103] differ from ileocolic anastomoses. In the last one making stapled anastomoses seems safer with minor CAL risk [104, 105].

In ileocolic anastomosis, stapled has less risk of leakage than hand-sewn. It seems that stapled functional end-to-end ileocolic anastomosis is associated with fewer leaks than handsewn anastomosis [105]. In colorectal anastomosis the panorama is different. In stapled anastomosis is necessaire linear stapler for transecting the rectum and a circular suturing machine for the anastomosis. A systematic review and meta-analysis realized by Balciscueta et al. confirm the impact of the number of stapler firings on anastomotic leakage in laparoscopic rectal surgery [106].

During the surgery, an effort must be made to reduce the number of linear stapler firings and try to transect the rectum with a single fire. Several studies corroborate the importance of this technical procedure step [107, 108].

The powered circular stapler device (ECPS) could have a positive impact by reducing AL rates in left-sided colorectal anastomosis [109].

During left colorectal surgery, immediately following anastomosis, surgeons evaluate anastomotic integrity through assessment of anastomotic doughnut completeness, air leak testing, methylene blue testing or povidone-iodine testing, and/or endoscopic visualization with to reduce rate CAL. The most frequent test used is the air leak test which is considered as an important test during an anterior rectal resection for the majority of surgeons that collaborate in international meeting consensus [99]. Intra-operative endoscopy can be performed allowing the surgeon to assess for vascular insufficiency and staple line bleeding.

Making a protective stoma (ileostomy or colostomy) after low anterior resection remains debatable. The most commonly used form of stoma is the defunctioning loop ileostomy, but some surgeons advocate the use of loop colostomies. The meta-analysis made by Chen et al. and Rondelli et al. shows that temporary loop ileostomy when compared with temporary loop colostomy had a lower risk of prolapse and sepsis [110, 111]. Nonetheless, loop ileostomy has a risk of dehydration and occlusion after stoma closure [111].

The effect of a diverting stoma in this procedure is generally considered a reducer of CAL (mitigates the clinical effects of fistula), but there are studies demonstrating diverting stoma as an element to reduce CAL probability. In surgery for distal rectal cancer, Matthiessen et al. demonstrated, in a cohort of 234 patients a symptomatic leak rate of 10·3% and a significantly lower reoperation rate in the defunctioned group (ileostomy or colostomy), compared with 28% in the non-stoma group [112]. Similar results were obtained in a prospective randomized study by Chude et al. which demonstrated significantly reduced CAL rates in the group with a defunctioning ileostomy (2·3 vs. 9·3%); no patient in the ileostomy group required surgical intervention or died [113].

7.2.6 Peri and postoperative therapy

Hypothermia increases the risk of surgical-site infections and induces vasoconstriction, but there is no conclusive evidence that it is a risk factor for AL.

The use of inotropes is associated with a three-fold increase in AL; this risk is accentuated by the use of multiple agents and the duration of inotropic support. This risk is independent of medical status as determined by Acute Physiology And Chronic Health Evaluation (APACHE) II and Physiological and Operative Severity Score for Mortality and morbidity (POSSUM) physiological scoring systems.

The need of blood transfusion is also an independent risk factor for CAL as already asserted. During the surgery, the need of inotropes or blood transfusion are factors that by themselves, advise the creation of a diverting stoma or avoid the anastomosis confection.

Perioperative analgesia with non-steroidal anti-inflammatory drugs (NSAIDs) has controversial aspects. During the inflammatory process necessary for healing anastomotic, the enterocytes express high levels of cyclooxygenase 2 (COX-2) with the formation of E2 prostaglandins, responsible for increasing vascularization place, promoting the expression of the factor of endothelial growth and angiogenesis. Thus, some authors defend a direct association link between anastomotic leak and the anti-inflammatory effect of NSAIDs [114]. Because the greater expression of COX at the intestinal mucosa level is COX-1, theoretically, selective NSAIDs for COX-2 (celecoxib, parecoxib) could be less harmful to intestinal anastomotic healing than non-selective NSAIDs (diclofenac, ketorolac). However, there are no studies yet demonstrating unequivocally different CAL risks within classes of AINS, and even the higher risk associated with using NSAID during perioperative time is still controversial. A study by Burton et al. evaluated perioperative non-steroidal anti-inflammatory drugs (NSAIDs) used in colorectal resections and found no statistically significant effect on the CAL rate [115]. The meta-analysis “PROSPERO” realized by Chen et al. indicates that using ketorolac increases the risk of CAL [116]. Also, the study by Klein et al. established an increased CAL risk in colorectal surgery with the postoperative use of diclofenac. Gorissen et al. noted a significant association of a higher CAL rate with NSAIDs, mainly non-selective NSAIDs [117]. Holte et al. describe the risk of CAL augmentation in colorectal surgery even using celecoxib [118]. In conclusion, NSAID treatment could increase the proportion of patients with anastomotic leakage after colorectal surgery. Therefore, even Cyclo-oxygenase-2 selective NSAID should be cautiously used after colorectal resections [119]. Large-scale, randomized controlled trials are needed to clarify this issue.

Implementing an Enhanced Recovery After Surgery (ERAS) program in elective colorectal surgery reduces hospital stay and surgical morbidity. ERAS programs for colorectal surgery have significant variations in care between institutions. As already discussed, some differences, including perioperative analgesia and intestinal preparation, can interfere with the CAL rate.

Nonsteroidal anti-inflammatory drugs are a crucial component of contemporary perioperative analgesia in the ERAS program. They can avoid the side effects associated with opioids (postoperative ileus, urinary retention, change in consciousness, and central respiratory depression), contributing to the early mobilization of patients [120]. Despite its advantages, the set of reactions and adverse effects associated with NSAIDs, namely in the gastrointestinal tract (such as bleeding, nausea, vomiting, and ulceration) and the eventual increase of CAL rate in colorectal surgery, are not despicable [121]. Cyclo-oxygenase-2 selective NSAID utilization for a short period may be the best analgesic option if the ERAS program includes the use of NSAIDs.

The utilization of mechanical intestinal preparation with oral antibiotics in the ERAS program for colorectal surgery does not happen in wall programs. Therefore, implementing this procedure can reduce the benefits of enhanced recovery after the surgery program but eventually may reduce CAL risk, as already stated.

8. CAL suspicion

The signs of CAL presence and the speed of installation are variable. The CAL manifestations range from exuberant to subtle. In situations not evident, the suspicion frequently is based on the presence of many factors already mentioned of CAL risk, associated with several clinical, analytical, and imaging CAL manifestations. Therefore, nomograms of CAL risk quantifications and scores of CAL presence probability can be utilized to make decisions on CAL diagnosis and treatment.

9. CAL detection

Detection of anastomotic leak and assessment of its severity is crucial. Anastomotic leakage has a wide range of clinical features ranging from radiological-only findings to peritonitis and sepsis with multi-organ failure. Timely diagnosis of CAL is paramount to limit related morbidity and mortality. Thus, it is essential to invest in the early identification of colorectal anastomotic dehiscence. Both clinical criteria parameters (clinical condition and abdominal pain) seem to be useful early markers for this condition, producing the best overall diagnostic accuracy of the parameters analyzed. C-reactive protein and procalcitonin have been identified as early analytical predictors of anastomotic leakage starting from postoperative days (Second to third postoperative day). Nevertheless, an abdominal-pelvic computed tomography scan is still the gold standard for diagnosis [122, 123]; however, a CT scan can be insufficiently accurate for CAL detection due to its high false negative rate (around 30%) [124]. Several treatments can be adopted for anastomotic leakage. However, there is not a universally accepted flowchart for the management, which should be individualized based on the patient’s general condition, anastomotic defect size, location, indication for primary resection, and presence of the proximal stoma.

9.1 Clinical parameters

The clinical presentation of CAL is varied from sudden and aggressive sepsis with multisystemic organ failure to an insidious progression, such as an extended postoperative ileus. Nonspecific signs and symptoms may anticipate a fast and often abrupt clinical deterioration or an unrecognized subclinical CAL. This last situation can respond to 50% of the total CAL. In those circumstances, additional imaging is necessary to establish the diagnosis.

9.1.1 Abdominal pain

Abdominal pain is a significant warning sign. Abdominal pain can be caused by other problems such as urinary tract infections, acute urinary retentions, pneumonia, insufficient analgesia policy, or peritonitis manifestation. The utilization of the numerical rating scale (NRS) seems to be an essential tool for measuring postoperative pain in postoperative colorectal surgery. According to a study by Bostrom et al., pain is an important marker of CAL. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage [125]. Abdominal pain is one of the symptoms included on the DULK score, a scoring system developed from clinical predictors of CAL. The presence of exuberant pain requires imaging and reassessment after 12 hours.

9.1.2 Heart rate (HR)

Heart rate (HR) was studied and correlated with the development of CAL in some studies [126, 127, 128]. On POD 2 and 3, with an HR threshold higher than 89/min, the sensitivity and specificity were 62.5% and 89.2%, respectively [127]. As above-mentioned, HR higher than 100/min is a clinical criterion included in the DULK score [129].

9.1.3 Respiratory rate (RR)

In some studies, respiratory rate (RR) was also correlated with CAL development [126, 127, 128, 129]. The RR of patients with CAL was significantly higher from POD1 to 7. RR above 30/min or 20/min are included in the DULK score and its modified version, respectively [126, 129].

9.1.4 Body temperature

Body temperature increase was associated with the development of CAL in several studies [126, 127, 128, 129]. Hyperthermia, defined as a body temperature above 38.0°C is enclosed in the original version of the DULK score [129].

9.1.5 Other clinical findings

A significant rate of CAL is asymptomatic (subclinical), and diagnosis is often delayed. Neurological alterations, ileus, presence of significant edema, and enteric drainage through the abdominal tube or wound are signs that alert to CAL possibility. Rectal examination, for example, can not only confirm suspicious rectal drainage (bloody or purulent, for example) but also enables the confirmation of anastomotic defects in the rectal walls or the rectovaginal septum. Therefore, digital rectal examination to identify lower rectal dehiscence may have sufficient accuracy for diagnosis.

9.1.6 Systemic inflammatory response syndrome (SIRS)

SIRS/SEPSIS was defined as the set of systemic manifestations that represent the systemic response of the body to inflammation or infection, expressing the concept of serial reactions to injury, depending on the individual characteristics, regardless of the original cause. It was defined as the presence of two or more of the following signs: body temperature above 38°C or below 36°C, heart rate above 90/min, hyperventilation [respiratory rate (RR) above 20/min or PaCO2 below 32 mmHg), with a serum WBC higher than 12,000 cells/μL or lower than 4000/μL. Alterations in consciousness, presence of significant edema (or a positive fluid balance above 20 ml/kg), and hyperglycemia (higher than 120 mg/dl, without previous diabetes) were included posteriorly to the initial concept. Quick SOFA (Sequential [Sepsis-related] Organ Failure Assessment) was introduced. This score would allow prompt identification of suspected cases of infection that had the risk of adversely evolving to sepsis. Patients are at risk if they presented at least two out of the following criteria: RR ≥ 22/min, alterations in consciousness (Glasgow Coma Scale ≤13), and systolic arterial pressure ≤ 100 mmHg. The usefulness of the concept of SIRS/SEPSIS lies in its sensitivity to identify early responses, timely warning clinicians for the possibility of sepsis.

9.2 Analytical parameters

Plasma biomarkers, such as white blood count (WBC), the eosinophil cells count (ECC), plasma C-reactive protein (CRP), procalcitonin (PCT) and calprotectin (CLP) for identifying CAL-patients, and the usefulness of cut-off values of CRP, PCT, and CLP for early discharge of patients, considering the routine adoption of enhanced recovery programs. These parameters increased their sensitivity and specificity for CAL detection when used together.

9.2.1 White blood cells count

The role of white blood cells (WBC) in the early diagnosis of CAL is still controversial due to its nonspecific nature and wide variability. WBC may increase after the surgical injury or signaling a postoperative complication, regardless of whether they are medical (pneumonia or urinary infection) or surgical (surgical site infection or organ/ space infection), among others. Warschkow et al. found that the WBC level had a fair contribution to the early detection of septic complications, offering a lower diagnostic accuracy than the plasma CRP [130].

9.2.2 Eosinophil cells count

Eosinopenia (ECC) is a common inflammatory response in acute infections. It has been proposed as a useful biomarker to identify severe sepsis and to distinguish it from other causes of SIRS. Shaaban et al. consider an ECC cutoff point of 50 cells/mm³ a good marker of sepsis presence [131]. Recently, ECC monitoring was proposed as a marker for positive evolution in septic patients under antibiotic therapy [132]. Due to its availability, fastness, simplicity, and low cost, ECC can be used in the daily clinical diagnosis of sepsis [133]. However, its specific usefulness in the early diagnosis of CAL is yet to be established.

9.2.3 C-reactive protein

Plasma C-reactive protein (CRP) is an acute phase reactant with liver synthesis. In healthy individuals, plasma levels are under 0.8 mg/L. It has shown a strong correlation with postoperative complications, namely after abdominal surgery. In addition, due to its short half-life (19 hours), plasma CRP is a reliable marker of SIRS secondary to surgery since it increases in response to surgical injury for up to 72 hours, decreasing afterward. Serum CRP is the most widely studied biomarker for CAL diagnosis. In patients with postoperative complications, CRP levels remain high. Plasma CRP higher than 140 mg/L on POD3 is a strong predictor of major abdominal septic complications [134].

9.2.4 Procalcitonin

Procalcitonin (PCT) is a prohormone of calcitonin produced by thyroid C-cells, neuroendocrine cells from the gastrointestinal tract, and lung K-cells, and with baseline levels under 0.1 ng/ml. PCT release is induced directly by the lipopolysaccharide of circulating bacteria, or indirectly by several inflammatory cytokines, such as IL-6 and TNF-α [135]. Levels of PCT increase significantly, from 2 to 4 hours, in patients with severe sepsis, persisting until recovery. Some authors have highlighted the usefulness of PCT as an early, more sensitive, and reliable subclinical marker of CAL [136]. Some authors considered the combination of PCT and CRP on postoperative day 5 an important index that improved the diagnosis of CAL [137].

9.2.5 Other biomarkers

Shimura et al. showed that CAL patients had a markedly low level of albumin when compared with the non-CAL population [138]. Thereby, recent studies suggested the relationship between CRP/albumin as a clinically helpful inflammatory composite biomarker to predict postoperative complications in different surgical fields [139]. High levels of calprotectin and the presence of hyponatremia are biomarkers with low specificity when used alone. Quantitative PCR for E. faecalis performed on drain fluid may be an objective, affordable, and fast screening tool for symptomatic colorectal anastomotic leakage [140].

9.3 Main score systems

The “Score approach” is a decision system developed to help with early CAL diagnosis. There are three main score systems: the Dutch leakage (DULK) score (modified version), the Diagnostic Score Leakage (DIACOLE), and the Adam system [126, 141, 142]. Adam’s system is a score developed using artificial intelligence methods. These tools use clinical parameters to create a simple score format that can be used daily to help early CAL detection and clinical decision-making. These scores systems have limitations of implementation in clinical practice. Simplified score systems based on fewer parameters/variables must be easily applied regularly without wasting time.

9.4 Image parameters

Diagnosis of CAL is challenging, and imaging plays a significant role, especially in insidious subclinical cases, preventing the consequences of diagnostic delay and unnecessary re-operations with potential morbidity and mortality (Figure 1). Moreover, imaging may guide abdominal or pelvic collections drainage, avoiding further interventions.

Figure 1.

CT scan images of anastomotic leaks in colorectal surgery: (a) male, 68 years old, with a complete intestinal obstruction due to Crohn’s disease. He was submitted to ileocecal resection by laparotomy. An anastomotic leak was detected on postoperative day 3. Treated with percutaneous drainage, antibiotic therapy, and total parenteral nutrition followed by exclusive enteral nutrition for 2 months. (b) Male, 67 years old, right colon cancer, submitted to right colectomy. Anastomotic leak detected on postoperative day 5. He was treated with percutaneous drainage, antibiotic therapy, and total parenteral nutrition. (c) Male, 85 years old, colon obstruction due to sigmoid carcinoma, submitted to laparoscopic sigmoidectomy. Anastomotic leak detected on postoperative day 5. He was treated with percutaneous, antibiotic therapy, and total parenteral nutrition during the ileus. (d) Female, 43 years old, locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by low anterior rectal resection. Anastomotic leak detected on postoperative day 2. Re-laparoscopy on day 2 with manual suture reinforcement of the left side of the anastomosis, derivative ileostomy, antibiotic therapy, and total parenteral nutrition during the ileus. Ileostomy closure after adjuvant chemotherapy months later after low anterior resection.

9.4.1 Simple abdominal X-ray

Generally, CAL occurred from the POD5 to 7; in this period, less than 30% of patients had subphrenic air signs on the x-ray. Nevertheless, the high volume of subphrenic air suggests the need for further accurate imaging modalities, such as the CT scan.

9.4.2 Water-soluble contrast enema

Current evidence is not consensual about the best imaging method for CAL diagnosis, but water-soluble contrast enema (WSCE) and contrasted CT scan (CCT) are the most used techniques. Some authors consider WSCE was less precise, with a significantly higher rate of false positives than digital rectal examination [143]. Others defended the systematic use of WSCE, emphasizing its advantages and providing relevant information on lower rectal anastomoses [144].

9.4.3 Contrast CT scan

A contrast CT scan (CCT) is frequently used to detect postoperative complications in colorectal procedures. In many centers, the preferred modality was the abdominal and pelvic CCT, providing a more detailed image of anastomosis and neighboring structures or findings, such as abscesses or hematoma (Figure 1). A combination of CCT with WSCE can identify a set of highly suggestive findings of CAL, such as the endoluminal contrast extravasation, presence of pneumoperitoneum, or perianastomotic collection. CCT with WSCE may reduce this false-negatives rate, mainly in lower colorectal anastomosis [145].

9.5 Surgery

The consensual definition of CAL detected by laparoscopy or laparotomy includes typical intra-operative findings, such as necrosis of the anastomosis, necrosis of the blind loop, dehiscence of the anastomosis, and signs of peritonitis. Laparoscopy is a valid and effective approach for treating complications following primary laparoscopic colorectal surgery [146]. Similarly, Rotholtz et al. concluded that early redo-laparoscopy (within 48 hours after the suspicion of a complication) provides higher chances for the use of a laparoscopic approach for management, providing a higher probability of good postoperative outcomes (Figure 1d), despite a greater risk of negative findings in the re-operation [147].

10. Procedures to be carried out in the anastomotic leak depending on its severity

The International Study Group of Rectal Cancer proposed a definition of anastomotic leakage based on severity grading for surgical intervention. Grade A anastomotic leakage results in no change in patients’ management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy [1]. However, other studies prefer to characterize CAL in two subsets: free and contained leakages. Free leakage presents significant anastomotic disruption with generalized peritonitis, while contained leakage presents as a minor anastomotic defect with localized peritonitis, including intra-abdominal abscess and fistula [148, 149]. In the same way, this classification tries to establish a correspondence to aggressive treatment or a procedure more conservative, respectively.

10.1 Conservative procedures

Conservative procedures are the option when patients are clinical and analytically stable and imaging findings can be managed with antibiotics therapy and/or percutaneous drainage (Figure 1a–c). Usually, non-operative management is usually preferred in patients who underwent proximal fecal diversion at the initial operation. In patients without a stoma who do not require abdominal reoperation for a contained pelvic leak, there are several treatment options, including laparoscopic diverting ileostomy combined with trans-anal anastomotic tube drainage, percutaneous drainage, or recently developed endoscopic procedures, such as a stent or clip placement or endoluminal vacuum-assisted therapy [122].

10.2 Surgical procedures

Whenever there is a formal indication for surgical reintervention (open or laparoscopic approach) due to the detection of CAL in the postoperative period, the general principles that govern the procedure are: eradication vs. control of CAL; reduction of fecal contamination in the abdominal cavity, and prevention vs. treatment of abdominal compartment syndrome.

Laparoscopy can be attempted after minimal invasive surgery and can reduce surgical stress in patients allowing a definitive treatment [150]. Reoperation for sepsis control is rarely necessary for those patients who already have a diverting stoma at the time of the leak, especially in extraperitoneal anastomoses. In the other cases, the eradication vs. control of CAL generally can be achieved by anastomosis dismantling and terminal colostomy confection or diversion ileostomy, and drainage of the CAL site [151].

The reduction of fecal contamination, when it exists, is made by peritoneal cavity lavage.

Patients with anastomotic leakage that develop peritonitis and an accentuated third space have a risk of intra-abdominal hypertension. The increase in intra-abdominal pressure can provoke aggravation of organ dysfunction with the development of abdominal compartment syndrome (ACS). The prevention/ treatment of ACS must be thought out and planned hallways if intravesical pressure is greater than 20 mmHg or if there is a worsening of cardiorespiratory or renal function whenever an attempt is made to proceed with the closure of the abdominal wall during the surgery [152]. In those cases, wound dressing systems with subatmospheric pressure can be a good option [153].

10.3 Advanced life support

The presence of SIRS/SEPSIS and the septic shock allows the identification of the patients needing advanced life support after the CAL identification, as already addressed. In addition, the Quick SOFA (Sequential [Sepsis-related] Organ Failure Assessment) helps identify suspected cases of infection that had the risk of adverse outcomes. There is a significant incidence of septic shock following an anastomotic leak in patients with lower mean arterial pressure, higher heart rate, and high APACHE II score. In those cases, the ICU admission time must be short, independently of all other therapeutic measures. These patients need support for all failing organs, the broad spectrum antibiotic therapy, control of the patient immune response beyond glucose control, administration of steroids, recombinant human activated protein C, and total parenteral nutrition [154].

11. Learning points

• Anastomotic Leaks happen, and they are potentially catastrophic.

• The incidence of CAL range between 2% and 19%. It is a significant incidence, and an effort must be made to avoid them.

• There are modifiable and non-modifiable promotor factors of anastomotic leaks.

• Modifiable CAL risk factors must be identified, and measures must be applied to reduce their presence.

• Nonmodifiable CAL risk must be quantified, and scores or nomograms may be applied to assess the real risk of a leak.

• In those cases, high-risk surgical plans can be modified to avoid or minimize the presence and consequence of the leak.

• In those cases of high risk of CAL, the vigilance must be tight and the suspicion level high.

• In the case of CAL, diagnostic exams must be performed early, the grade of the leak established, and the therapeutic measures taken according to the leak grade and patient clinical state.

• The infectious focus must be identified, controlled, treated, and, if possible, eradicated.

• When CAL appears must be primarily thought of and treated as a wound infection. Enterococcus fecalis and Pseudomonas aeruginosa can be a main factor in lack of CAL cicatrization.

• The way to do that depends on the rapid identification of the leak and its size and asses of the infection and inflammatory host response, the physiological host reserve, the host’s comorbidities, and the immune host response.

• The start of treatment should be quick and range from simple antibiotic coverage through percutaneous drainage, surgical reintervention, or even advanced life support.

• Several factors interfere with the final result of CAL treatment.

• The microbiota is crucial in CAL appearance, maintenance, gravity, and perpetuation. However, little is known about how to modify microbiota composition to increase beneficial agents and reduce the virulence of pathogens. It may be the area where research will invest more in the coming years to prevent and help in CAL treatment.