*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

*Colorectal Anastomosis: The Critical Aspect of Any Colorectal Surgery DOI: http://dx.doi.org/10.5772/intechopen.107952*

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 smokingrelated 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
