Role of Laboratory Markers in Predicting Severity of Acute Appendicitis

Abstract

Background:

Accurately differentiating simple and complicated acute appendicitis (CAA) in children preoperatively can be challenging. The aim of this study is to evaluate the ability of the neutrophil-to-lymphocyte ratio (NLR), total leukocyte count (TLC), percentage lymphocyte, and percentage neutrophil counts to predict the type of appendicitis a patient has preoperatively and to determine the better indicator among these.

Materials and Methods:

Record of 233 patients under 18 years of age who underwent appendectomy from 2005 to 2014 was evaluated. Based on perioperative findings of the surgeon, the patients were grouped under categories simple acute appendicitis (SAA) and CAA. Information such as age, gender, and laboratory investigations of the patients were recorded and analyzed.

Results:

SAA included 185 patients and CAA included 48 patients. An NLR >4.8, TLC >13,500 cells/mm³, percentage lymphocyte count <14.8%, and percentage neutrophil count >75% were found to be associated with complicated appendicitis. The highest sensitivity and specificity among these findings were found with the percentage lymphocyte count, which were 70.8% and 63.8%, respectively.

Conclusion:

The preoperative percentage lymphocyte count serves as a better indicator than TLC, NLR, and percentage lymphocyte count and is a useful parameter in differentiating simple and complicated appendicitis and can be used as a valuable adjunct to the surgeon's clinical evaluation.

INTRODUCTION

Acute appendicitis is one of the most common causes of abdominal pain and is the most frequent cause of emergency abdominal surgery in children. It is common between the ages of 7–15 years but can occur at any age. The diagnosis of acute appendicitis is mainly based on clinical assessment, and this involves the use of well-known symptoms and signs such as right lower quadrant abdominal pain, fever, vomiting, and McBurney's point tenderness.[1] The laboratory predictors are not constant and their accuracy is questionable, especially the leukocyte count and C-reactive protein (CRP), which are sensitive tests but are not specific for acute appendicitis. However, a combination of both tests in the presence of symptoms and signs seems to increase their specificity significantly,[2] but the diagnosis of acute appendicitis is unlikely when both investigations are normal.[3] It has, however, been reported that the neutrophil-to-lymphocyte ratio (NLR) is a good predictor in the preoperative diagnosis of acute appendicitis.[4,5,6]

In this context, other inflammatory markers such as interleukins,[7] leukocyte elastase activity,[8] phospholipase A2,[9] serum amyloid A,[10] and D-lactate[11] have been studied, but most of these investigations are available only in tertiary centers and laboratories in third world countries. We aimed to study the usefulness of universally available investigations total leukocyte count (TLC), percentage neutrophil count, percentage lymphocyte counts, and NLR as obtained from doing differential leukocyte count (DLC) in the diagnosis of acute appendicitis in children. We also tried to determine the role of NLR in positively diagnosing types of appendicitis (simple and complicated).

MATERIALS AND METHODS

We retrospectively reviewed the medical records of 233 patients below the age of 18 years who underwent appendectomy for appendicitis between the years 2005 and 2014 at the department of paediatric surgery which was proved peroperatively and histopathologically. The clinical diagnosis of appendicitis was established preoperatively by means of clinical history (abdominal pain, vomiting, and fever), physical examination (tenderness at McBurney's point), traditional laboratory tests (hemoglobin, TLC, and DLC), and in some patients, by imaging studies such as ultrasonography. Laboratory tests were performed on blood samples obtained on the day of admission to the hospital. Data collected from the medical records of these patients included the age, gender, the time taken from the onset of the first symptom to the day of presentation (duration of symptoms), clinical symptoms and signs, the TLC, DLC, operative findings, and the histopathology reports.

The data of a total of 233 patients were analyzed. Pathology reports were used to confirm the presence of an inflamed appendix. According to the intraoperative findings, the patients were grouped into two categories, simple acute appendicitis (SAA), and complicated acute appendicitis (CAA). Complicated appendicitis was defined as the presence of intra-abdominal abscess, perforated appendix, phlegmon, gangrenous appendix, and appendicular mass.

Statistical analysis

The data analysis was performed using the Statistical Package for the Social Sciences for Windows, version 15.0, published by SPSS Inc., Chicago, USA. The cutoff values of parameters for discrimination of the groups were determined using the receiver operator characteristic (ROC) analysis. At each value, the sensitivity and specificity for each outcome under study were plotted, thus generating an ROC curve. Area under the ROC curve was used to determine the predictive (diagnostic) ability of TLC, NLR, and percentage neutrophil and lymphocyte counts for predicting simple and complicated cases of acute appendicitis. An optimum cutoff value was selected which gave high sensitivity as well as specificity for CAA.

RESULTS

Of the 233 patients studied, there were 185 patients in group SAA and 48 patients in group CAA. There was no significant difference in the mean age of the two groups (11.83 years of age for SAA and 10.42 years of age for CAA). The percentage of males in group SAA was 78.9% while the percentage of males in group CAA was 79.7%.

The TLC, NLR, and percentage lymphocyte counts were compared in Table 1. The TLC cutoff value was 13,500 cells/mm³. Values greater than this cutoff value were considered to be complicated and values lower than the cutoff value were considered to be simple appendicitis. The sensitivity was 68.8%, specificity was 60.5%, positive predictive value (PPV) was 31.1%, and negative predictive value (NPV) was 88.1% [Figure 1].

Table 1.

Comparison of total leukocyte count, neutrophil-to-lymphocyte ratio, and percentage lymphocyte count

Parameter	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
NLR (>4.8)	66.7	60.5	30.4	87.5
TLC (>13,500 cells/mm3)	68.8	60.5	31.1	88.1
Lymphocyte (<14.8)	70.8	63.8	33.6	89.3

PPV: Positive predictive value, NPV: Negative predictive value, NLR: Neutrophil-to-lymphocyte ratio, TLC: Total leukocyte count

Figure 1.

Receiver operator characteristic curve for total leukocyte count

The NLR cutoff value was 4.8; values greater than this were considered to be complicated and values lesser than this were considered to be simple. This resulted in sensitivity of 66.7%, specificity of 60.5%, PPV of 30.4%, and NPV of 87.5% [Figure 2].

Figure 2.

Receiver operator characteristic curve for neutrophil-to-lymphocyte ratio

The cutoff value for neutrophil count was 75%. Values greater than this cutoff value were considered to be complicated and values lesser than this were considered to be simple. The sensitivity was 58% and specificity was 60% [Figure 3].

Figure 3.

Receiver operator characteristic curve for percentage neutrophil count

The cutoff value for lymphocyte count was 14.8%. Values greater than this cutoff value were considered to be simple and values lesser than this were considered to be complicated. The sensitivity was 70.8%, specificity was 63.8%, PPV was 33.6%, and NPV was 89.3% [Figure 4].

Figure 4.

Receiver operator characteristic curve for percentage lymphocyte count

The duration of symptoms which was the period between the appearance of the first symptom and presentation at the hospital was noted.

For all cases with duration of symptoms within the first 24 h before presentation, 96.5% were in group SAA. For all cases with duration of symptoms between 24 h and 48 h before presentation, 79.6% of the cases were in group SAA. For all cases with symptoms having started more than 48 h before presentation, 71.7% were in group SAA [Table 2].

Table 2.

Comparison of duration of symptoms with severity of appendicitis

Duration of symptoms (h)	SAA (%)	CAA (%)	Total (%)
<24	55 (96.5)	2 (3.5)	57 (100)
24-48	39 (79.6)	10 (20.4)	49 (100)
>48	91 (71.7)	36 (28.3)	127 (100)
Total	185 (79.4)	48 (20.6)	233 (100)

SAA: Simple acute appendicitis, CAA: Complicated acute appendicitis

DISCUSSION

Most studies done in the past have successfully proved that the NLR ratio has better accuracy than white blood cell counts and CRPs. This study shows that NLR with a cutoff value of 4.8 can significantly help in differentiating a simple case of acute appendicitis from a complicated one. This ratio is similar to the ratio derived in previous reports such as in the reports by Kahramanca et al.,[12] Goodman et al.,[4] and Yazici et al.,[6] but quite low compared to the value reported by Ishizuka et al.[13] Kahramanca et al.[12] reported a sensitivity and specificity of 70.8% and 48.5%, respectively, at NLR of 5.74, while Ishizuka et al.[13] found a sensitivity and specificity of 73% and 39%, respectively, at NLR of 8. The sensitivity of NLR in our study is slightly lower, whereas the specificity is much higher as compared to these studies.

Studies have shown that WBC counts are always elevated in complicated appendicitis such as phlegmon and perforation.[14,15] Our study, however, shows that at a TLC cutoff value of 14,000 cells/mm³, the specificity remains the same, whereas the sensitivity is slightly higher, when compared to the NLR ratio. Thus, TLC and NLR seem to be equally dependable indicators of simple or complicated appendicitis. Al-Gaithy et al. reported a cutoff limit of TLC 11,100 cells/mm³¹⁶ and Hotic et al. reported a neutrophil cutoff count of 15,760 cells/mm³¹⁷ to differentiate complicated appendicitis from simple appendicitis.

This study also shows the relationship between the duration of symptoms and the likelihood of a case being simple or complicated. It was observed that cases with short duration of symptoms were much more likely to be SAA, whereas complicated appendicitis was more likely to have longer duration of symptoms. Bickel et al. reported a duration longer than 36 h between onset of pain and surgery to carry higher risk of perforation,[18] whereas Moon et al. found no correlation between the two.[19]

We have found that the percentage lymphocyte count serves as a much better indicator in the diagnosis of complicated appendicitis than TLC and NLR ratio, due to its high level of sensitivity and specificity. Although Kahramanca et al. suggested that the lymphocyte count decreases in complicated appendicitis and has relevance in diagnosis, they have not found high values of sensitivity and specificity.[12]

CONCLUSION

Although NLR and TLC are both reliable parameters that can be considered in distinguishing complicated appendicitis from SAA, the percentage lymphocyte count has proven to be a much better indicator than NLR and TLC. However, the values are not high enough to supersede the surgeon's clinical evaluation and imaging studies but may help as an added indicator for the surgeon to expect complications and determine better outcome for the child.

Financial support and sponsorship

This study was financially supported by the Department of Statistics, Medical Records Department, KMC, Manipal.

Conflicts of interest

There are no conflicts of interest.