Clinicopathological evaluation of anoxic mucosal injury in strangulation ileus

Strangulation ileus is a critical condition leading to emergency surgeries, in which patients require early diagnosis and surgical decision making. Even when an immediate laparotomy is performed, many patients must undergo a bowel resection due to severe anoxic injury. To avoid undesirable outcomes for the patients, the clinicians must detect bowel strangulation as soon as possible using diagnostic equipment. Although previous studies have investigated several diagnostic parameters for strangulation ileus [1‐6], the severity of bowel ischemia remains to be unpredictable before surgery. To consider a grading scale of anoxic injury, we evaluated the pathological findings in resected bowel specimens and investigated predictive factors for bowel gangrene.

Can we evaluate the severity of anoxic injury in patients with strangulation ileus? We propose a grading scale for ischemic mucosal injury, which Chiu et al initially discovered in the dogs [7]. They categorized ischemic changes of the mucosal lesion into 6 grades (graded from 0 to 5); grade 0 − normal mucosal villi; grade 1 − development of subepithelial Gruenhagen’s space; Grade 2 − extension of the subepithelial space with moderate lifting of epithelial layer from the lamina propria; Grade 3 − massive epithelial lifting down the sides of villi; Grade 4 − denuded villi with lamina propria and dilated capillaries exposed; Grade 5 − digestion and disintegration of lamina propria. They confirmed that the speed of mucosal injury depended on arterial blood flow of the small bowel. Our grading scale of mucosal injury corresponded to each grade of their criteria, such as our grade 1 to their grade 0 – 2, our grade 2 to their grade 3 – 4, and our grade 3 to their grade 5, respectively.

To predict bowel strangulation and its severity, which radiographic finding is helpful? Our evaluation of contrast CT scans found that mesenteric congestion, closed bowel loop, and decreased bowel enhancement are helpful in discovering bowel strangulation. A meta-analysis of 15 separate studies found CT scans to be 83% sensitive and 92% specific in detecting an ischemic bowel in patients with obstructive ileus [8]. Sheedy et al found that decreased segmental enhancement was the most specific sign for small bowel ischemia [9]. Hayakawa et al mentioned that the direct CT findings (without contrast) suggestive bowel strangulation include high-density bowel wall, mesenteric congestion, and localized pneumatosis, while the indirect CT findings include C- or U-shaped loops with mesenteric vessels converging toward the obstruction site, ascites, target sign, two adjacent collapsed round loops, and whirl sign [10]. Our results suggested that a decrease in bowel enhancement is associated with the degree of mucosal injury. The other diagnostic approaches include ascites analysis by abdominocentesis and laparoscopic surgery/adhesiolysis for selected patients with small bowel strangulation [11, 12].

After making a decision to do a laparotomy, the surgeon must release the strangulated bowel and decide whether to resect or not. The decision regarding bowel resection or conservation is made based on the surgeon’s impression of the ischemic damage and viability. Therefore, it is very important to understand the progression of anoxic injuries after the strangulation. Sullins et al compared pathological changes for the arteriovenous and venous occlusions in horses with small bowel strangulation [13]. After 1 to 3 hour intervals, segments of arteriovenous occlusion became dark without edema and hemorrhage, while segments of venous occlusion were characterized by progressive congestion, edema, and hemorrhage especially in the mucosal layer. Park et al confirmed that ischemic periods of more than 20 minutes caused villous injuries and extensive tissue injury in rats, but there was no exacerbation of tissue injury after the reperfusion [14]. Otherwise, an isolated arterial occlusion of 40 to 60 minutes induced significant exacerbation of tissue injuries at reperfusion [14]. Although these animal experiments indicate that the mesenteric arterial occlusion rapidly induces exacerbation of tissue injury and necrosis, only few studies have evaluated pathological findings of strangulated bowel and non-occlusive mesenteric ischemia (NOMI) in humans [15‐19]. Pathologically, intimal thickening in the vasa recta and arteritis without organic vascular occlusion are associated with the development of NOMI [19]. In our study, 4 of the 36 cases (11%) showed fibromuscular intimal thickening of the vasa recta. Generally, NOMI accounts for 20 − 30% of all cases of acute mesenteric ischemia with a mortality rate of nearly 50% [20]. One German article analyzed 62 patients with NOMI and concluded that leukocytosis, elevated serum lactate, and increased CK/CK-MB levels are specific parameters to diagnose NOMI [21]. Since we did not investigate serum lactate and CK-MB levels in our patients, further investigations should be performed to evaluate these biomarkers in strangulation ileus.

Ischemic or hemorrhagic bowel wall infarction results in anoxia and necrosis, providing ideal conditions for bacteria growth and multiplication [22]. Tissue damages progress with progressive mucosal epithelial cell slough, collagen disruption, edema, neutrophil infiltration of submucosa and muscular layers and serosa [23]. Bowel gangrene, caused by these types of tissue damage, promotes anaerobic acidosis and lactate production [6, 24]. Furthermore, smooth muscle cells degenerate and eventually disrupt leading to the release of CK and its isoenzymes. Graeber et al reported that levels of serum CK and each of its isoenzymes became significantly elevated in dogs with strangulated infarction [25]. Despite the fact that we have to perform surgery as soon as possible, there was no correlation between time to surgery from onset time of symptom and bowel gangrene. Since the progression of anoxic damage showed many variations, time to surgery from onset time could not be a reliable predictor for bowel gangrene. Although our study evaluated a limited number of patients and blood samples at different times from onset, elevated CK and a low base excess which indicates the degree of acidosis could predict severe mucosal injury. These biomarkers and decreased bowel enhancement on the contrast CT could indicate the severity of anoxic mucosal injury in patients with strangulation ileus.

In strangulation ileus, anoxic mucosal injury progresses gradually after rapid spreading of bowel congestion. Before surgical intervention, elevated CK, a low base excess, and decreased bowel enhancement on the contrast CT could indicate the severity of anoxic damage. These biomarkers could be the predictor for bowel resection before surgery.