*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.
