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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 2  |  Issue : 3  |  Page : 62-65

The role of ischemia-modified albumin levels in the diagnosis of acute appendicitis


1 Department of General Surgery, Beyhekim State Hospital, Konya, Turkey
2 Department of General Surgery, Usak University Medical School, Usak, Turkey
3 Department of Biochemistry, Konya Training and Research Hospital, Konya, Turkey
4 Department of General Surgery, Konya Training and Research Hospital, Konya, Turkey

Date of Submission29-May-2017
Date of Acceptance14-Aug-2017
Date of Web Publication15-Sep-2017

Correspondence Address:
Baris Sevinç
Department of General Surgery, Usak University Medical School, Usak
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ts.ts_13_17

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  Abstract 

Aim: Although there are several auxiliary laboratory tests, diagnosis of acute appendicitis (AA) mainly depends on clinical findings. The aim of this study was to evaluate the role of ischemia-modified albumin (IMA) in the diagnosis of AA. Methods: IMA levels of histopathologically confirmed AA cases and healthy volunteers were evaluated. Results: Mean IMA levels were 9.6 ± 12.5 absorbance units (ABSU) in the AA group and 3.04 ± 0.47 ABSU in the control group. Moreover, IMA levels positively correlated with the diagnosis of AA (r = 0.309, P = 0.013). The preoperative mean IMA level was 9.6 ± 12.5 ABSU, while the postoperative mean IMA level was 6.9 ± 11.7 ABSU (P = 0.001). There was a significant decrease in IMA levels after appendectomy. Conclusion: This study shows elevated IMA levels in patients with AA and a significant decrease of IMA levels after appendectomy. Oxidative stress plays a role in the pathogenesis of AA, and IMA levels can be used as an accessory parameter in diagnosis.

Keywords: Acute appendicitis, diagnosis, ischemia-modified albumin


How to cite this article:
Turan E, Sevinç B, Kurku H, Simsek G, Demirgül R, Karahan &. The role of ischemia-modified albumin levels in the diagnosis of acute appendicitis. Transl Surg 2017;2:62-5

How to cite this URL:
Turan E, Sevinç B, Kurku H, Simsek G, Demirgül R, Karahan &. The role of ischemia-modified albumin levels in the diagnosis of acute appendicitis. Transl Surg [serial online] 2017 [cited 2017 Nov 23];2:62-5. Available from: http://www.translsurg.com/text.asp?2017/2/3/62/214806


  Introduction Top


Acute appendicitis (AA) is one of the most common surgical emergencies all around the world. The diagnosis of AA mainly depends on clinical findings.[1],[2],[3],[4] There are several auxiliary laboratory tests for AA diagnosis. The most commonly used ones are leukocyte count and C-reactive protein levels. There are several studies evaluating the relation between serum inflammatory markers and AA.[5],[6] None of these inflammatory markers are specific to AA and can be increased or in normal range in any inflammatory disorder.

Despite the developments in laboratory and radiological studies, the diagnosis of AA still depends on clinical findings. Recently, there have been several studies about medical treatment of AA.[7],[8],[9],[10] Common sense is that uncomplicated AA can be treated medically. However, in large-scale studies, the negative appendectomy rate is still about 15%, and the main debate of those studies is that the rate of negative cases treated medically is not known. There is a need for a definitive diagnosis of AA.

Ischemia-modified albumin (IMA) is a molecule that is produced by decreased albumin metal-binding capacity in case of acute ischemic stroke. It is accepted as a sensitive biochemical marker for myocardial ischemia, muscle ischemia, pulmonary embolism, and mesenteric ischemia.[11] IMA has been extensively studied in ischemic heart diseases, and the Food and Drug Authority has approved the measurement for the extent of cardiac ischemia.[12] Recently, IMA has been widely accepted as a marker of oxidative stress in several pathological states, including AA.[13],[14] According to Reddy et al.,[15] IMA levels are affected by serum albumin and bilirubin levels. Therefore, while evaluating IMA levels, serum albumin and bilirubin levels should be considered too.

The aim of this study was to evaluate IMA levels in patients with AA compared to controls and their response to surgery.


  Methods Top


Ethical committee approval was obtained from Selçuk University Medical School Ethical Committee. The study was conducted between January 2014 and January 2015. The study was conducted in accordance with the latest version of Declaration of Helsinki. All participants were informed about the study and signed the informed consent form.

All patients with a clinical diagnosis of AA were considered for the study, and preoperative serum samples were collected and stored for IMA level measurement. All patients' serum albumin and bilirubin levels were also evaluated, and patients with hypoalbuminemia and hyperbilirubinemia were not included in the study. Since IMA levels can increase in cardiovascular disorders, patients with a history of any kind of cardiovascular disease or symptoms were not included in the study. Patients underwent standard appendectomy operation. Resected appendices were evaluated at the pathology laboratory and only cases with histologically confirmed diagnosis of AA were included in the study. Postoperative serum samples were collected 24 h after the surgery. The control group consisted of healthy volunteers without any cardiac and abdominal complaints. A serum separator tube was used, and all the samples were allowed to clot for 30 min before centrifugation for 20 min at 3,000 g. The samples were stored at −70°C and centrifuged again after thawing before the assay. The IMA levels were analyzed using human IMA ELISA kits (catalog number: CK-E11169, Hangzhou EastBiopharm Co., Ltd., Hangzhou, China). IMA levels were presented in absorbance units (ABSUs).

As there is no study for IMA levels in AA, we performed a pilot study including seven cases with AA and seven cases without AA. In AA groups, the mean preoperative IMA level was 11.7 ± 10.5 and the mean postoperative IMA level was 6.4 ± 8.3. In the control group, mean IMA level was found to be 2.9 ± 0.22. Therefore, power analysis was made according to pre- and post-operative IMA levels. With a power of 80% and beta error of 0.05, the AA group must contain forty cases.

For the study group, 54 cases were evaluated. However, two cases did not have AA at the pathological evaluation, one case had Crohn's disease, and one case had hypoalbuminemia. After exclusion of those cases, 40 patients were included in the study. No cases were excluded from the study because of any cardiac disease.

For statistical analysis, IBM SPSS 20 (IBM corp, New York, USA) software package was used. Data were presented as mean ± standard deviation. In comparison of the groups, Student's t-test was used. For categorical data, Chi-square test, and for determination of correlation, Pearson's correlation analysis was used; correlation coefficients are presented. IMA levels in predicting AA were analyzed using receiver operating characteristics (ROC) curve analysis. When a significant cutoff value was observed, the sensitivity and specificity were presented. Statistical significance level was accepted as 0.05.


  Results Top


There were 40 cases in the AA group and 24 healthy volunteers in the control group. There were 52 males and 12 females in the study population. The mean age of the participants was 27.9 ± 9.6 years. It was 29.1 ± 11.3 years in the study group and 26.04 ± 5.6 years in the control group. The groups were similar in terms of age and gender (P = 0.215 and 0.09, respectively). Demographic data, hemoglobin level, leukocyte count, and baseline IMA levels are summarized in [Table 1]. Pathological diagnoses of the operated cases are summarized in [Table 2]. All the cases had serum albumin and total bilirubin levels within normal range.
Table 1: Demographic data, leukocyte count, hemoglobin level, and baseline ischemia-modified albumin levels

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Table 2: Pathological diagnosis of the operated cases

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Mean IMA levels were 9.6 ± 12.5 ABSU in AA group and 3.04 ± 0.47 ABSU in control group. The difference was statistically significant (P = 0.01). Moreover, IMA levels positively correlated with the diagnosis of AA (r = 0.309, P = 0.013).

According to ROC curve, the optimal IMA value for AA is 3.4 ABSU with a sensitivity of 95% and a specificity of 80% (area under the ROC curve = 0.935, P < 0.001) [Figure 1]. At this level, positive predictive value of IMA was found to be 84%. Negative predictive value was found to be 10%, and the accuracy of the IMA value for detection of AA was found to be 78%.
Figure 1: Receiver operating characteristics curve for ischemia-modified albumin values in the diagnosis of acute appendicitis. According to receiver operating characteristics curve, the optimal ischemia-modified albumin value for acute appendicitis was found to be 3.4 absorbance unit with a sensitivity of 95% and specificity of 80% (area under the receiver operating characteristics curve = 0.935, P < 0.001) [Figure 1]. At this level, positive predictive value of ischemia-modified albumin was found to be 84%

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Preoperative mean IMA level was 9.6 ± 12.5 ABSU, whereas postoperative mean IMA level was 6.9 ± 11.7 ABSU (P = 0.001). There is a significant decrease in IMA levels after appendectomy [Table 3].
Table 3: Pre- and post-operative ischemia-modified albumin values

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  Discussion Top


Despite the improvements in laboratory and imaging studies, the diagnosis of AA still depends mainly on clinical evaluation. As one of the most common surgical emergency conditions, delays in diagnosis of AA may cause morbidity and mortality. On the other hand, false-positive diagnosis or negative appendectomy rate is still about 10% at best.[16] False-positive diagnosis may cause unnecessary hospital stays and unnecessary operations. Therefore, several methods for diagnosis of AA were evaluated worldwide. Sensitivity and specificity of ultrasonography and computed tomography were reported as 99.1% and 91.7% and 96.4% and 95.4%, respectively.[4] However, routine use of radiological studies also increases the cost. There are several studies about serum markers to diagnose AA. The most commonly studied markers are leukocyte count and C-reactive protein.

The gold standard treatment method of AA is surgery. However, recently, some authors support the view of medical treatment.[7],[8],[9],[10] There are reports favoring antibiotic treatment in uncomplicated cases. However, the main defect of the reports favoring medical treatment is just that false-positive diagnosis rate is not known. Therefore, especially in the era of medical treatment, there is a need for further diagnostic tools for AA.

There are several reports on the oxidative stress in AA.[5],[6] Total antioxidant status, total oxidant status, superoxide dismutase, malondialdehyde, and paraoxonase activity are recently evaluated as oxidative markers. According to Ozdogan et al.,[6] plasma total antioxidant status cannot be used for the diagnosis of AA; however, they concluded that a decrease in its value could be a predictor of progression from inflammation to perforation. On the other hand, Köksal et al.[17] found that increase in total antioxidant status can be due to progression of inflammation to perforation. Those controversial results show that better and more controlled trials are needed to highlight the issue.

IMA is widely accepted as a marker of oxidative stress in several conditions. It is accepted as a promising marker of myocardial ischemia. In a recent prospective study, Kılıç et al.[18] showed a positive correlation between the severity of AA and IMA levels. Moreover, Dumlu et al.[13] evaluated the use of IMA in the diagnosis of AA. They showed a positive correlation between IMA and AA; however, they could not show the decrease in IMA level after appendectomy. They concluded that there is a need for a time span for IMA level to decrease. However, in the current study, we found elevated IMA levels in patients with AA and significant decrease after appendectomy. According to our findings, after resolution of the inflammation, IMA levels turn to normal levels within 24 h.

The main limitation of the study is that IMA levels can increase in several conditions. Although the main reasons for the IMA increase were excluded from the study group, this issue remains a challenging item. A significant decrease, however, after appendectomy may show that increased IMA levels are associated with appendiceal inflammation.

In conclusion, oxidative stress plays a role in the pathogenesis of AA. IMA levels can be used as an accessory parameter in the diagnosis of AA. As there are several markers having a role in the diagnosis of AA, further studies with a combination of those markers can form a diagnostic criterion with significant accuracy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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McGowan DR, Sims HM, Zia K, Uheba M, Shaikh IA. The value of biochemical markers in predicting a perforation in acute appendicitis. ANZ J Surg 2013;83 (1-2):79-83.  Back to cited text no. 5
    
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Okuş A, Ay S, Karahan Ö, Eryılmaz MA, Sevinç B, Aksoy N. Monitoring C-reactive protein levels during medical management of acute appendicitis to predict the need for surgery. Surg Today 2015;45 (4):451-6.  Back to cited text no. 10
    
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Can S, Akdur O, Yildirim A, Adam G, Cakir DU, Karaman HI. Myelin basic protein and ischemia modified albumin levels in acute. Pak J Med Sci 2015;31 (5):1110-4.  Back to cited text no. 11
    
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Gothe PR, Jose M, Pai VR, Harish S, D'Souza J, Prabhu V. Investigation of the possibility of using serum Ischemia Modified Albumin (IMA) as a novel and early marker of the extent of oxidative stress induced by various tobacco products. J Clin Diagn Res 2015;9 (11):ZC33-5.  Back to cited text no. 12
    
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Dumlu EG, Tokac M, Bozkurt B, Yildirim MB, Ergin M, Yalçin A, Kiliç M. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis. Clinics (Sao Paulo) 2014;69 (10):677-82.  Back to cited text no. 13
    
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Awadallah SM, Atoum MF, Nimer NA, Saleh SA. Ischemia modified albumin: An oxidative stress marker in β-thalassemia major. Clin Chim Acta 2012;413 (9-10):907-10.  Back to cited text no. 14
    
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Reddy VS, Perugu B, Garg MK. Ischemia-modified albumin must be evaluated as an oxidative stress marker together with albumin and bilirubin in individuals with acute appendicitis. Clinics (Sao Paulo) 2015;70 (7):531-2.  Back to cited text no. 15
    
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Wagner PL, Eachempati SR, Soe K, Pieracci FM, Shou J, Barie PS. Defining the current negative appendectomy rate: For whom is preoperative computed tomography making an impact? Surgery 2008;144 (2):276-82.  Back to cited text no. 16
    
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Köksal H, Kurban S, Doğru O. Total oxidant status, total antioxidant status, and paraoxonase activity in acute appendicitis. Ulus Travma Acil Cerrahi Derg 2015;21 (2):139-42.  Back to cited text no. 17
    
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Kılıç MÖ, Güldoğan CE, Balamir İ, Tez M. Ischemia-modified albumin as a predictor of severity of acute appendicitis. Am J Emerg Med 2017;35 (1):92-5.  Back to cited text no. 18
    


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