Introduction

Acute appendicitis (AA) is one of the most common surgical emergency in modern surgical era.1 Its incidence rate is 100 per 100.000 inhabitants and lifetime risk for appendicitis is 8.6% for males and 6.7% females.2 Natural history of disease remains unclear, it means progression to perforation is not predictable and spontaneous resolution is common,3 so noncomplicated and complicated appendicitis may be discussed as different diseases.4 Traditionally, management of the patient is based on several steps like medical history, physical findings, laboratory tests and imaging studies; negative appendectomy only within reasonable limits is acceptable for fear of morbidity and mortality due to perforation. Therefore many scoring systems and serum biomarkers were investigated in order to diagnose the disease properly to avoid negative laparotomies.5,6,7

In literature, many of the studies focused on diagnosis of AA. Although the increased use of computerized tomography (CT) lowered the rate of negative appendectomies,8 the rate of misdiagnosed cases are still an important problem (15%).9,10

But major mortality of appendicitis is arising from complicated cases which fewer diagnostic biomarkers were investigated and stated in literature. Following uncomplicated appendectomy complication rates are lower than complicated cases.11

Studies have shown inconsistent information regarding the use of white blood cells (WBC) count. Most studies show an association between elevated WBCs count in diagnostic process, however its significance varies greatly. Several reports suggest an elevated leukocyte count is usually the earliest serum biomarker to show appendiceal inflammation.12

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to- lymphocyte ratio (PLR) are associated with worse outcome in various diseases stated in literature. Also, NLR is a new biomarker.13,14 Nevertheless we did not find any other study investigating PLR in case of discrimination of complicated cases of AA.

In this study, we aimed to investigate the predictive value of PLR on discrimination of complicated and noncomplicated AA.

Materials and Methods

A retrospective analysis of collected data was carried out on all patients admitted to emergency care unit with abdominal pain and underwent urgent laparotomy who prediagnosed as acute appendicits over a 2 year period (from January 2012-December 2014). AA was diagnosed preoperatively by clinical history, laboratory tests and in some patients by imaging studies like ultrasonography (USG) or CT. Laboratory tests were performed on blood samples. PLR which obtained from complete blood count sample and WBCs count were measured. According to intraoperative surgical findings and pathology reports, patients were divided into two groups. Group 1 was noncomplicated appendicitis group and group 2 was complicated appendicitis groups (cases with perforation, plastrone appendicitis, periappendicular abscess). WBC and PLR results were compared between two groups.

Immunocompromised patients, patients who had transfused blood within seven days, patients with coronary artery disease, cerebrovascular event, malignity, hematologic disorders and patients with negative appendectomies were excluded from this study. The leukocyte count and platelet count percentages were measured by an automated hematology analyzer (Coulter Counter Model S-Plus Jr, Coulter Electronics, Hialeah, FL). The reference interval of WBC was 4500-10.300/mm3.

Statistical Analysis

The data was analyzed by using the Statistical Package for the Social Sciences for Windows, version 17.0 (SPSS Inc, Chicago, IL, USA). Shapiro-Wilk test was showed whether the distributions of continuous variables were normal or not. Data were shown as mean ± standard deviation or median (minimum-maximum), where applicable. Student’s t or Mann-Whitney U test were used to compare the differences between groups, where appropriate. Categorical data were analyzed by Pearson’s chi-square test, where appropriate. Receiver operating characteristic (ROC) analysis was used to determine discriminative results by cutoff values of parameters between groups. At each value, the sensitivity and specificity for each outcome under study were plotted, thus generating an ROC curve. A p value less than 0.05 was considered statistically significant.

Results

Median value for 239 patients age who were included to the study was 28 (12-85) and male/female ratio was 1.37. There were 196 patients in group 1 and 43 patients in group 2.

When gender disribution between groups was analyzed there was male dominancy in group 1 and female dominancy in group 2 (p=0.020), furthermore mean age of group 2 was higher than group 1 (p<0.001). Demographic characteristics were shown at Table 1.

When groups were compared considering PLR and WBC values, PLR and WBC values are significantly higher in group 2 (p<0.001 and p=0.029 respectively). Distribution of PLR and WBC values between groups is given in Figure 1 and Figure 2. Multivariate Cox regression analysis showed that PLR could predict complications independently of age and gender (p<0.001) (Table 2).

Cutoff value of PLR which was assessed by Roc curve analysis was 169.7, giving a sensitivity of 74.4% and specificity of 73.5% (Roc curve analysis is given in Figure 3).

However cutoff value of WBC which was assessed by Roc curve analysis was 13.45, giving a sensitivity of 55.8% and specifity 55.6.

Discussion

Diagnostic process of AA is not always easy. Preventing complications by means of observing the patient until the diagnosis becomes obvious or operating early seems to be a serious dilemma for surgeons. Rapid intervention may result in the removal of uncomplicated appendicitis with a small risk of morbidity.15 Delay in the diagnosis may lead to appendix rupture and secondary complications.16 Considering surgeons who work in rural areas, they may not have radiological imaging facilities. Furthermore, USG or CT imaging may not always help to achieve an accurate diagnosis.15 Increased use of CT lowered the rate of negative appendectomies8 however the rate of misdiagnosed cases are still an important problem (15%).9,10 There is also an increasing concern over radiation exposure and long-term cancer risk related with CT.17 Consequently surgeons are still seeking of an consistent and easy laboratory test to diagnose appendicitis appropriately.

Our results revealed that PLR with a cutoff value off 169.7, giving a sensitivity of 74.4% and specificity of 73.5%. These results showed that PLR could be an important marker to predict complicated cases.

Our study has some limitations like the retrospective nature of the study. Only a two year of period for collected data and 239 patients may not show the real potential of WBCs count and PLR in discrimination of noncomplicated and complicated appendicitis.

The degree of WBC elevation in appendicitis has been analyzed widely in many studies. It is usually elevated in patients who had AA. Nevertheless it is not an accepted specific marker and is usually raised higher laboratory degrees in patients with other inflammatory conditions.17 In our study when groups were compared considering WBC values, there was significant difference in terms of WBC values.

Although Sack et al.18 showed that WBCs count was elevated in children with complicated appendicitis, Mughal and Soomro19 found leucocytes elevated in all their patients. Also, Yokoyama et al.20 reported that WBCs count are not a useful for surgical indication.

PLR is a marker of serious inflammation and it was used in various clinical conditions to determine the degree of inflammatory process which leads to the release of proinflammatory cytokines and it promotes megakaryocytes’ proliferation. The activation of platelets is a hallmark in the course of cancer, by promoting neoangiogenesis, degradation of extracellular matrix, release of adhesion molecules, and growth factors.21,22 Lee et al.23 demonstrated that PLR was an independent prognostic factor for overall survival with advanced gastric cancer. Another studies showed that PLR may be a valuable marker for determination of prognosis in colorectal cancer.24,25 There are also some studies about the role of PLR in terms of prognosis of the patients with breast and gynaecological malignancies.26,27 However we did not find any study about PLR and AA in literature. There are also few data about serum biomarkers for discrimination of complicated and non-complicated AA.

In our study PLR value was significantly higher in complicated appendicitis group and, PLR could predict complicated cases indepentenly of age and gender. Moon et al.28 reported that complicated appendicitis was significantly high in patients who were older than 40 years. Our study showed similar result that mean age of group 2 was higher than group 1 which was significant statistically.

In our study the number of complicated cases in group 2 may be also a limitation. It seems surgeons participated in this study did not wait until cases were complicated and difference in number between groups may lead this result. However, Drake el al.29 showed that perforation was not associated with elapsed time from hospital presentation to operating room start among adult patients. This result is compatible with the view that disease progression in appendicitis has a more complex pathophysiology and complicated appendicitis may be a separate biological or host-response entity.29

Laboratory markers may contribute to the diagnostic process of AA however they can not to change the diagnosis of suspected cases on their own. When they used in a combination with physical examination, medical history and radiological findings they show greater promise.17

In conclusion, our results showed that PLR could predict complicated cases more accurately with a high sensitivity and specifity than WBCs count.

Ethics

Ethics Committee Approval: The study was approved by the Kafkas University Local Ethics Committee (Approval no: 80576354-050-99/76), Informed Consent: Due to its retrospective nature of study informed consent was not needed however preoperative detailed surgical informed consent was filled out by all patients.

Peer-review: Internally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Ali Cihat Yıldırım, Turgut Anuk, Burak İrem, Concept: Ali Cihat Yıldırım, Design: Ali Cihat Yıldırım, Data Collection or Processing: Ali Cihat Yıldırım, Turgut Anuk, Elnare Günal, Analysis or Interpretation: Ali Cihat Yıldırım, Saygı Gülkan, Literature Search: Ali Cihat Yıldırım, Elnare Günal, Saygı Gülkan, Writing: Ali Cihat Yıldırım, Turgut Anuk.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.