We recently read the article “Correlation between the serum and tissue levels of
oxidative stress markers and the extent of inflammation in acute appendicitis” by
Dumlu et al. with great interest (11. Dumlu EG, Tokac M, Bozkurt B, Yildirim MB, Ergin M, Yalç in
A, et al. Correlation between the serum and tissue levels of oxidative stress
markers and the extent of inflammation in acute appendicitis. Clinics.
2014;69(10):677-82, 10.6061/clinics
10.6061/clinics...
). The
study’s primary objective was to determine serum and tissue levels of
oxidative/antioxidative markers in acute appendicitis. The authors concluded that
oxidative/antioxidative imbalance plays a pathological role in acute appendicitis. The
authors should be praised for their study design, objectives, methodology and results.
Nonetheless, we unearthed several interesting points during our reading of the
article.
Ischemia-modified albumin (IMA) detection has generated a great deal of interest
worldwide. Initially, IMA was examined as a promising but relatively nonspecific marker
of myocardial ischemia (22. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin
binding and its potential as a marker for myocardial ischemia - a preliminary
report. J Emerg Med. 2000;19(4):311-5,
10.1016/S0736-4679(00)00255-9
10.1016/S0736-4679(00)00255-9...
). Recently, IMA has
been widely accepted as a marker of oxidative stress in several pathological states,
including acute appendicitis (11. Dumlu EG, Tokac M, Bozkurt B, Yildirim MB, Ergin M, Yalç in
A, et al. Correlation between the serum and tissue levels of oxidative stress
markers and the extent of inflammation in acute appendicitis. Clinics.
2014;69(10):677-82, 10.6061/clinics
10.6061/clinics...
–33. Awadallah SM, Atoum MF, Nimer NA, Saleh SA. Ischemia modified
albumin: An oxidative stress marker in β-thalassemia major. Clinica
Chimica Acta. 2012;413(9-10):907-10, 10.1016/j.cca.2012.01.037
10.1016/j.cca.2012.01.037...
). Notably, Dumlu et al. measured IMA using an
albumin cobalt binding (ACB) assay and reported the results in absorbance units (ABSU).
In principle, the ACB assay involves the binding of cobalt to albumin protein. In cases
involving oxidative stress, the ability of albumin to bind cobalt decreases; as a
result, there are greater quantities of unbound free cobalt and therefore elevated IMA
values (22. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin
binding and its potential as a marker for myocardial ischemia - a preliminary
report. J Emerg Med. 2000;19(4):311-5,
10.1016/S0736-4679(00)00255-9
10.1016/S0736-4679(00)00255-9...
). Thus, the ACB assay and the IMA
results it produces are sensitive to changes in serum albumin concentrations.
Interestingly, even within the physiological range of albumin levels (35-45 g/L), there
is a strong negative association between albumin and IMA; in particular, a change of 1
g/L in albumin produces an opposite change of 2.6% in IMA (44. Zapico-Muniz E, Santalo-Bel M, Merce-Muntanola J, Montiel JA,
Martı´nez-Rubio A, Jordi Ordonez-Llanos J. Ischemia-Modified Albumin
during Skeletal Muscle Ischemia. Clinical Chemistry. 2004;50(6):1063-5,
10.1373/clinchem.2003.027789
10.1373/clinchem.2003.027789...
). Importantly, appendicitis is associated with changes in serum
albumin (55. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-Lymphocyte Ratio
Has a Close Association With Gangrenous Appendicitis in Patients Undergoing
Appendectomy. Int Surg. 2012;97(4):299-304, 10.9738/CC161.1
10.9738/CC161.1...
). Given prior evidence indicating that
serum albumin changes in acute appendicitis (55. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-Lymphocyte Ratio
Has a Close Association With Gangrenous Appendicitis in Patients Undergoing
Appendectomy. Int Surg. 2012;97(4):299-304, 10.9738/CC161.1
10.9738/CC161.1...
–66. Kaya M, Boleken ME, Kanmaz T, Erel O, Yucesan S. Total
antioxidant capacity in children with acute appendicitis. Eur J Pediatr Surg.
2006;16(1):34-8, 10.1055/s-2006-923905
10.1055/s-2006-923905...
) and that albumin levels
can affect the estimation of IMA (44. Zapico-Muniz E, Santalo-Bel M, Merce-Muntanola J, Montiel JA,
Martı´nez-Rubio A, Jordi Ordonez-Llanos J. Ischemia-Modified Albumin
during Skeletal Muscle Ischemia. Clinical Chemistry. 2004;50(6):1063-5,
10.1373/clinchem.2003.027789
10.1373/clinchem.2003.027789...
,77. Koc F, Erdem S, Altunkaş F, Ozbek K, Gül EE, Kurban S,
et al. Ischemia-modified albumin and total antioxidant status in patients with
slow coronary flow: a pilot observational study. Anadolu Kardiyol Derg.
2011;11(7):582-7.), it is extremely important to provide serum
albumin levels and IMA values that are corrected for albumin interference, as previously
reported (77. Koc F, Erdem S, Altunkaş F, Ozbek K, Gül EE, Kurban S,
et al. Ischemia-modified albumin and total antioxidant status in patients with
slow coronary flow: a pilot observational study. Anadolu Kardiyol Derg.
2011;11(7):582-7.). This evidence could strongly
suggest the need to evaluate IMA as an oxidative stress marker in combination with
albumin in individuals with acute appendicitis.
Furthermore, albumin is known to bind with and transport bilirubin in circulation.
Recently, a significant association between IMA and bilirubin has been reported (88. Chen CY, Tsai WL, Lin PJ, Shiesh SC. The value of serum
ischemia-modified albumin for assessing liver function in patients with chronic
liver disease. Clin Chem Lab Med. 2011;49(11):1817-21,
10.1515/cclm.2011.675
10.1515/cclm.2011.675...
). Literature findings have demonstrated that in
cases of appendicitis and appendiceal perforation, serum bilirubin is significantly
increased; thus, hyperbilirubinemia has been suggested as an independent marker of these
conditions. Hyperbilirubinemia has exhibited better sensitivity for acute appendicitis
than white cell count or C-reactive protein level, and it has been suggested that
bilirubin evaluation should be included in the assessment of appendicitis patients
(99. Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD,
Bajwa FM, et al. The diagnostic value of white cell count, C-reactive protein
and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl.
2013;95(3):215-21, 10.1308/003588413X13511609957371
10.1308/003588413X13511609957371...
). Therefore, we speculate that it is
necessary to examine hyperbilirubinemia in appendicitis patients because elevated
bilirubin levels could partially explain IMA differences among study groups.
Thus, it would have been interesting if Dumlu et al. had evaluated serum levels of
albumin and bilirubin because it is highly plausible that changes in these levels could
have influenced their IMA results. The following important reasons also support the need
to study albumin and bilirubin. 1) Preoperative total bilirubin is positively associated
with morbidity; in contrast, preoperative albumin is negatively associated with
morbidity (1010. Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Oprian CA,
Henderson WG, et al. Risk factors for adverse outcomes after the surgical
treatment of appendicitis in adults. Ann Surg.
2003;238(1):59-66.). 2) Preoperative hypoalbuminemia
is an independent risk factor for the development of surgical site infection following
gastrointestinal surgery (1111. Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC,
Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the
development of surgical site infection following gastrointestinal surgery: a
multi-institutional study. Ann Surg. 2010;252(2):325-9,
10.1097/SLA.0b013e3181e9819a
10.1097/SLA.0b013e3181e9819a...
). 3) Hypoalbuminemic
patients have significantly longer hospital stays than other patients (1212. Nisar PJ, Appau KA, Remzi FH, Kiran RP. Preoperative
hypoalbuminemia is associated with adverse outcomes after ileoanal pouch
surgery. Inflamm Bowel Dis. 2012;18(6):1034-41,
10.1002/ibd.21842
10.1002/ibd.21842...
). 4) Serum albumin measurements are regarded as
objective markers of nutritional status but also reflect ongoing acute inflammatory
processes and immunological compromise (1212. Nisar PJ, Appau KA, Remzi FH, Kiran RP. Preoperative
hypoalbuminemia is associated with adverse outcomes after ileoanal pouch
surgery. Inflamm Bowel Dis. 2012;18(6):1034-41,
10.1002/ibd.21842
10.1002/ibd.21842...
). 5)
Serum albumin serves as an important antioxidant (1313. Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E. The
antioxidant properties of serum albumin. FEBS Lett. 2008;582(13):1783-7,
10.1016/j.febslet.2008.04.057
10.1016/j.febslet.2008.04.057...
). 6) Because albumin is an acute phase protein, albumin levels reflect
the activity of inflammatory cytokines (55. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-Lymphocyte Ratio
Has a Close Association With Gangrenous Appendicitis in Patients Undergoing
Appendectomy. Int Surg. 2012;97(4):299-304, 10.9738/CC161.1
10.9738/CC161.1...
).
In their results section, Dumlu et al. reported that they had found no significant differences between the preoperative and postoperative levels of any serum parameters (p>0.05 for all parameters). However, Table 3 indicates that there was a significant difference between the preoperative and postoperative levels of advanced oxidized protein products (AOPP) (p=0.039). This apparent contradiction should have been clearly addressed. The authors used the Alvarado score as a diagnostic tool for acute appendicitis because this score can predict the presence and extent of appendicitis. Similarly, it has been suggested that oxidative/antioxidative imbalances influence the degree of inflammation in acute appendicitis and that the Alvarado score can be used to predict the severity of inflammation. Although the authors did address correlations between serum and tissue parameters, we feel that an examination of the correlations between oxidative stress parameters and the Alvarado score would produce important findings.
Finally, a question that must be asked is if the authors considered determining whether the age difference between the control group (19-64 yrs) and the appendicitis group (17-73 yrs; mean±SD: 31.4±12.06 yrs) was significant. The mean age for the control group was not mentioned. This issue is important because age per se plays a significant role in the generation of oxidative stress. We believe that the aforementioned issues must be addressed in future studies of IMA in acute appendicitis.
REFERENCES
-
1Dumlu EG, Tokac M, Bozkurt B, Yildirim MB, Ergin M, Yalç in A, et al. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis. Clinics. 2014;69(10):677-82, 10.6061/clinics
» 10.6061/clinics -
2Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia - a preliminary report. J Emerg Med. 2000;19(4):311-5, 10.1016/S0736-4679(00)00255-9
» 10.1016/S0736-4679(00)00255-9 -
3Awadallah SM, Atoum MF, Nimer NA, Saleh SA. Ischemia modified albumin: An oxidative stress marker in β-thalassemia major. Clinica Chimica Acta. 2012;413(9-10):907-10, 10.1016/j.cca.2012.01.037
» 10.1016/j.cca.2012.01.037 -
4Zapico-Muniz E, Santalo-Bel M, Merce-Muntanola J, Montiel JA, Martı´nez-Rubio A, Jordi Ordonez-Llanos J. Ischemia-Modified Albumin during Skeletal Muscle Ischemia. Clinical Chemistry. 2004;50(6):1063-5, 10.1373/clinchem.2003.027789
» 10.1373/clinchem.2003.027789 -
5Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-Lymphocyte Ratio Has a Close Association With Gangrenous Appendicitis in Patients Undergoing Appendectomy. Int Surg. 2012;97(4):299-304, 10.9738/CC161.1
» 10.9738/CC161.1 -
6Kaya M, Boleken ME, Kanmaz T, Erel O, Yucesan S. Total antioxidant capacity in children with acute appendicitis. Eur J Pediatr Surg. 2006;16(1):34-8, 10.1055/s-2006-923905
» 10.1055/s-2006-923905 -
7Koc F, Erdem S, Altunkaş F, Ozbek K, Gül EE, Kurban S, et al. Ischemia-modified albumin and total antioxidant status in patients with slow coronary flow: a pilot observational study. Anadolu Kardiyol Derg. 2011;11(7):582-7.
-
8Chen CY, Tsai WL, Lin PJ, Shiesh SC. The value of serum ischemia-modified albumin for assessing liver function in patients with chronic liver disease. Clin Chem Lab Med. 2011;49(11):1817-21, 10.1515/cclm.2011.675
» 10.1515/cclm.2011.675 -
9Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bajwa FM, et al. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl. 2013;95(3):215-21, 10.1308/003588413X13511609957371
» 10.1308/003588413X13511609957371 -
10Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Oprian CA, Henderson WG, et al. Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults. Ann Surg. 2003;238(1):59-66.
-
11Hennessey DB, Burke JP, Ni-Dhonochu T, Shields C, Winter DC, Mealy K. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery: a multi-institutional study. Ann Surg. 2010;252(2):325-9, 10.1097/SLA.0b013e3181e9819a
» 10.1097/SLA.0b013e3181e9819a -
12Nisar PJ, Appau KA, Remzi FH, Kiran RP. Preoperative hypoalbuminemia is associated with adverse outcomes after ileoanal pouch surgery. Inflamm Bowel Dis. 2012;18(6):1034-41, 10.1002/ibd.21842
» 10.1002/ibd.21842 -
13Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E. The antioxidant properties of serum albumin. FEBS Lett. 2008;582(13):1783-7, 10.1016/j.febslet.2008.04.057
» 10.1016/j.febslet.2008.04.057
Publication Dates
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Publication in this collection
July 2015