Early Detection of Intestinal Ischemia: The Sooner the Better

The syndrome of the so-called “acute abdomen” is sustained by several different pathologic entities. Among them, mesenteric ischemia is characterized by the worst prognosis, mainly due to diagnostic delay [1,2]. In fact, emergency laparotomy has the highest diagnostic accuracy, albeit does not represent an early, helpful tool against a mostly irreversible infarcted intestinal segment requiring resection. Therefore, timing in diagnosis is of utmost importance to reversing intestinal ischemia and for an early salvage of the intestine. Unfortunately, the biological indicators available are either nonspecific or develop too late to be detected (e.g. leucocyte count, L-lactate, CPK) [3]. The paper by Cekic et al. [4] investigates novel serological biomarkers of intestinal ischemia such as Ischemia-Modified Albumin (IMA) and the Signal peptide-CUB-EGF domaincontaining protein-1 (SCUBE-1). These may represent a fundamental aspect of deep clinical relevance to the field of abdominal, emergency surgery. In a recent systematic review and meta-analysis, Treskes et al. [5] reported a large amount of data on different serological biomarkers of acute intestinal ischemia. In a pooled estimate, they found a significant role for Intestinal Fatty Acid Binding Protein (I-FABP), D-lactate, alpha-Gutathione-S-Transferase (alpha-GST), and Ischemia-Modified Albumin (IMA) as predictors of acute mesenteric ischemia and a promising role for Citrulline. However, all of the markers investigated in the mentioned reports showed a certain degree of bias mitigating their role (false negative rates of 9-14% in I-FABP and IMA for instance) and thus potentially delaying laparotomy. In cases of complete mechanical bowel obstruction, the timing of operation is crucial to a successful surgical strategy. We currently rely upon several clinical, imaging, and biological markers, but they are far from being reliable indicators for early timing of laparotomy. The investigation by Cekic is a valuable contribution to the discovery of indicators for emergency surgery. However, similar to previous work, an undisputed conclusion is not yet reached. The presence of ischemic intestinal segments resulting from obstruction-induced changes deeply impacts the patient’s surgery; the operation can progress from a relatively safe procedure (cutting adhesions) to extensive resection surgery, sometime necessitating a second look with related morbidity and mortality. In this respect, intestinal ischemia represents the final, late complication of an unresolved bowel occlusion, especially in cases of “dileptic” mechanism leading to perforation. Similarly, a strangulated bowel implies an early mechanism of intestinal ischemia, worsening the clinical picture and leading to a necrotic intestinal segment. In these severe conditions, it is obvious that identifying early markers of intestinal ischemia, like those investigated by the authors, can play a helpful role. This may be particularly true in doubtful or ambiguous clinical cases. In the experiments conducted by the authors, the two markers IMA and SCUBE-1 rise sharply in the animals treated by cecum ligation compared to those undergoing shamoperation. In addition, the highest peak is observed between the fourth and sixth hour from the onset of experimental ligature of the cecum, i.e., from the start of the strangulation mechanism. This represents a common delay of patient observation from the appearance of symptoms. Unfortunately, the histopathology of the intestine sampled at those times already shows severe alterations that are suggestive of a non-viable bowel necessitating resection. Undoubtedly, given such a situation in the clinical setting, several physical signs and symptoms (peritonism, severe continuous pain), radiologic features (abdominal fluid, ischemia at CT scan), and biological markers (marked leucocytosis, metabolic acidosis, dehydration) will be detected, supporting the indications for emergency laparotomy and resection. In conclusion, the ideal early marker of intestinal ischemia should appear just after the occurrence of mechanical bowel obstruction with strangulated mesentery. In this respect, the alterations observed in intestinal samples from the animals in group 2, although characterized by a degree of not completely reversible changes, seem to suggest that a conservative approach may be attempted, provided that the patient is observed very early after onset of mechanical occlusion with strangulated bowel. I fear that this will be a very rare condition seldom encountered in routine clinical practice. On the other hand, a sharp increase in IMA and SCUBE-1 is suggestive of ischemic intestine and thus emergency laparotomy is indicated. This result may be helpful in those doubtful cases and it may find a place as a unique marker of intestinal ischemia, avoiding other costly diagnostic tools. Last but not least, when serum levels are below a cutoff level, they may be adopted as indicators able to rule out intestinal infarction and ischemia.