The Treatment and Outcome of Superior Mesenteric Artery Embolism: a Hospital-based Survey

Objectives: The treatment for superior mesenteric artery (SMA) embolism is controversial because of the low prevalence of this disease. This study aimed to examine the treatment options for SMA embolism. Methods: We retrospectively reviewed the clinical data of twenty patients with SMA embolisms at the Toyohashi Municipal Hospital from April 2010 to March 2020. Clinical characteristics, ndings, treatment and outcomes were evaluated. Results: The overall median age of the patients was 80 years old. In 16 cases, the obstructed regions of the SMA were proximal to the ileocecal artery (ICA) bifurcation. Nine cases had pneumatosis intestinalis (PI). Two patients underwent surgery, twelve patients received endovascular intervention (EI) and four patients received heparin treatment. Five patients died in the hospital. A comparative study of the outcomes after EI showed that the nonsurvivor group had a signicantly higher rate of PI than the survivor group (P = 0.046). The patients that had obstructions proximal to the ICA bifurcation and the presence of PI had a high mortality rate of 60% after EI. Conclusions: Determining if there is the presence of PI and nding the obstructed region of the SMA are useful for evaluating the appropriate treatment for SMA embolisms.


Introduction
Superior mesenteric artery (SMA) embolisms are a type of acute mesenteric ischemia (AMI) disease and a rare disease among emergency abdominal diseases. The incidence of AMI is 12.9 per 100000 person-years, and the percentage of SMA embolisms among AMIs is 67.2% [1].
SMA embolisms are diseases with a poor prognosis, and the in-hospital mortality rate is 60%-80% [2]. The causes of the increase in mortality are likely due to the di culty in obtaining an early diagnosis and the development of intestinal necrosis due to the time that passes between the diagnosis and the onset of the disease [2]. Even if surgical treatment can save lives, the development of short bowel syndrome may impair the patient's quality of life.
Recent studies have reported the e cacy of endovascular intervention (EI) for SMA embolisms [3,4]. EI can preserve the small intestine and has a good outcome. Several studies have reported that EI was performed for patients with hemodynamic stability and without clinical or radiologic signs of advanced intestinal ischemia [5][6][7]. However, the indications of EI are controversial. The purpose of this study was to examine the treatment outcomes in SMA embolisms.

Methods
This study was approved by the institutional review board of the Toyohashi Municipal Hospital (approval no. 609) and was conducted according to the principles of the Declaration of Helsinki. Informed consent was obtained in the form of opt-out on the web-site. We performed a retrospective, single-center study of patients with SMA embolisms at the Toyohashi Municipal Hospital from April 2010 to March 2020. We collected the following data: age, sex, history of present illness, comorbidities, physical ndings (vital signs and peritoneal irritation sign), CT ndings, blood tests, treatments, and outcome.
The following was the treatment policy for SMA embolisms in this hospital. A SMA embolism was diagnosed when the contrast-enhanced CT of patients with acute abdomen revealed SMA defects. Clinicians (surgeons, radiologists, gastroenterologists, etc.) decided on the treatment plan after considering the onset, physical ndings, and imaging ndings. If extensive intestinal ischemia was suspected, we selected surgical treatment. If not, we selected EI or drug therapy such as heparin. However, best supportive care (BSC) was selected after considering the age, comorbidities, and intentions of the patients or the families.

Statistical analysis
The patients who received EI were divided into two groups based on the outcomes (survivors vs nonsurvivors). Patient demographics, clinical symptoms, physical examinations, CT ndings (obstructed region in the SMA (Fig. 1); proximal or distal to the bifurcation of the ileocecal artery (ICA), pneumatosis intestinalis (PI), ascitic uid), and blood test results were analyzed.
The data are expressed as medians (25th-75th percentiles) for continuous variables or as numbers/percentages for categorical variables. We compared the two groups using Fisher's exact test for categorical variables and the Mann-Whitney U test for numerical variables. P-values of 0.05 or less were considered signi cant. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).

Results
A total of 20 patients with SMA embolisms were included in this study. Patient characteristics, clinical features and outcomes are listed in Table 1. The median age of the patients was 80 years (range 69-100 years), and the female-to-male ratio was 9:11. All patients had comorbidities (11 patients had arrhythmias such as atrial brillation). The obstructed regions of the SMA were proximal to the bifurcation of the ICA in 16 cases. Nine cases had PI based on the CT ndings. There were 2 cases that underwent surgery, 12 cases who had EI, 4 cases who had heparin treatment and 2 cases who had BSC for the initial treatment. Two surgical cases required small bowel resection and the length of the remnant small bowel was 70 and 100 cm. One patient who underwent EI (case 15) required small bowel resection due to recurrence of SMA embolism on the 17th day after EI, and the remnant small bowel was 200 cm. EI was approached from the femoral artery. One case (Case 7) underwent stent placement and 11 cases underwent mechanical thrombectomy. All 12 patients had concomitant intra-arterial injection of urokinase. Fifteen patients survived, and ve patients died in the hospital. In the survivors, two patients needed parenteral nutrition because of the development of short bowel syndrome (case9, 15). * column indicates whether the obstructed region of the superior mesenteric artery is proximal or distal to the ileocecal artery.
** indicates that operation was performed because of the relapsed SMA embolism on the 17th day after EI.
All three deaths, excluding the patient who received BSC, received EI. They had intestinal necrosis after EI, but did not seek further treatment. To assess the risk factors for mortality in the patients who received EI, we compared the clinical features (age, sex, time to diagnosis, vital signs, peritoneal irritation sign), CT ndings (obstructed region in the SMA, PI, ascitic uid), and blood test results (WBC, Plt, D-dimer, CK, LDH, CRP, lactate) between the survivor group and the nonsurvivor group ( Table 2). The rate of PI in the nonsurvivor group was signi cantly higher than that in the survivor group (100% vs 22.2%, P=0.046). * indicates that the superior mesenteric artery occlusion occurred proximal to the ileocecal artery bifurcation.
All 20 patients were classi ed into 3 groups according to the obstructed region in the SMA and the existence of PI based on the CT ndings; the ndings of group A were that the obstructed region was proximal to the ICA bifurcation and that PI was present, the ndings of group B were that the obstructed region was proximal to the ICA bifurcation and PI was not present and the ndings of group C were that the obstructed region was distal to the ICA bifurcation and PI was not present. Table 3 shows the treatment and outcomes of each group. There were 9 cases in group A (Case1-9 in Table 1). The mortality rate in the cases that received BSC was 100% in group A. No deaths were found among the operated cases, but all the cases had short bowel syndrome. The mortality rate after EI was 60% (3 out of 5 cases), and 3 patients had died within 3 days after starting treatment. These patients needed surgical treatment because of their deteriorated general condition after EI. However, these patients and their families did not wish to receive treatment. There were 7 cases in group B (Case10-16 in Table 1). Six patients received EI, and one patient received heparin therapy. There were no deaths, and one patient had a recurrence of the SMA embolism 17 days after EI. He received a small bowel resection, which resulted in short bowel syndrome. There were 4 cases in group C (Cases 17-20 in Table 1). One patient received EI, and the others received heparin treatment. There were no deaths or recurrence of the SMA embolism. Heparin, 3 0 (0) Note: Group A included the patients with a superior mesenteric artery occlusion that was proximal to the ileocecal artery bifurcation and pneumatosis intestinalis, group B included the patients with a superior mesenteric artery occlusion that was proximal to the ileocecal artery bifurcation and no pneumatosis intestinalis and group C included the patients with a superior mesenteric artery occlusion that was distal to the ileocecal artery bifurcation and no pneumatosis intestinalis.

Discussion
SMA embolism is a rare life-threatening condition, and the in-hospital mortality rate is as high as 60%-80% [2]. Surgical treatment or EI is mainly selected as the treatment for SMA embolisms. Recent studies have shown the e cacy of EI [3,4]. EI has the advantage of being minimally invasive compared to surgical treatment. Short bowel syndrome and activities of daily living decline after emergency surgery are major problems for elderly patients. In our hospital, 60% (12 cases) received EI, and the success rate was 75% (9 cases). This rate was almost the same as the previously reported success rate of 70-73% in recent reports [7,8]. A comparative study of the survivor group and the nonsurvivor group after EI showed no difference in the clinical factors or the blood test ndings, but the nonsurvivor group had a signi cantly higher rate of PI based on the CT ndings (P = 0.046). It is necessary to consider the absence of PI when considering EI for treatment. The presence of PI on CT scans is an important nding that suggests intestinal necrosis, and if intestinal necrosis has already occurred, the reperfusion of blood ow with EI treatment would have no therapeutic effect.
We classi ed all cases into 3 groups and examined them regarding the obstructed region in the SMA and for the existence of PI. Group A (obstruction proximal to the bifurcation of the ICA and PI) had a poor prognosis with a mortality rate of 55.6%. There were no surgical deaths, although there was a high possibility of short bowel syndrome. On the other hand, the survival rate after EI was as low as 40%. All of the dead patients died within 3 days after starting EI. It was possible that these patients already had intestinal necrosis. If surgical treatment was chosen as the initial treatment, it might have been lifesaving for these patients. Group B (obstruction proximal to the bifurcation of the ICA and no PI) had a relatively good prognosis. Only one patient required surgery, but it was possible to treat these patients with EI or heparin. We could not evaluate whether EI or heparin medication should be selected for Group B patients because of the small number of cases. However, if the therapeutic response to heparin medication was poor, it could lead to intestinal necrosis. EI treatment may be more useful for Group B patients. Group C (obstruction distal to the bifurcation of the ICA and no PI) had a good prognosis. Only one patient underwent EI, but 3 patients could be treated with heparin therapy. Patients with an obstruction distal to the bifurcation of the ICA have a narrow range of intestinal ischemia, and the blood ow from the marginal artery would remain. Therefore, it takes time to develop intestinal necrosis. We believe that intestinal necrosis can be prevented by anticoagulant therapy with heparin. However, careful follow-up is important because the SMA embolism might worsen or recur.
Based on the above results, we propose a treatment owchart for SMA embolism, which is shown in Fig. 2. If the CT showed PI, surgical treatment was selected. If not, we would select the treatment based on the region that was obstructed in the SMA. We selected EI for obstructions that were proximal to the bifurcation of the ICA and heparin treatment for obstructions that were distal to the bifurcation of the ICA. This study was a retrospective observational study, and the number of cases was limited. This owchart is a hypothesis and requires prospective multicenter research. Further studies to evaluate a larger number of patients are needed to examine the treatment strategy and the prognostic factors for SMA embolisms.
This study was approved by the institutional review board of the Toyohashi Municipal Hospital (approval no. 609). Informed consent was obtained in the form of opt-out on the web-site.

Consent for publication
Informed consent was obtained in the form of opt-out on the web-site.

Availability of data and materials
All data generated or analysed during this study are included in this published article and its supplementary information le (Supplementary table 1) Funding This study was not funded.
Authors' contributions RI analyzed and interpreted the patient data regarding the SMA embolism and wrote the manuscript. All authors read and approved the nal manuscript.