Neutrophil to lymphocyte ratio in diagnosis of complicated and non-complicated appendicitis *

Introduction: Acute appendicitis is one of the most common surgical problems of childhood. Late or misdiagnosis may increase the morbidity and mortality of this condition. Objective: To test the utility of some laboratory methods, especially Neutrophil/Lymphocyte (N/L) ratio in rapid diagnosis of simple and complicated acute appendicitis Method: The records of 498 cases hospitalized in paediatric surgery departments in Turkey between the years 2008 and 2014 with the suspicion or prediagnosis of acute appendicitis were retrospectively evaluated. Among these, 279 were diagnosed as non-complicated appendicitis while 73 were diagnosed as complicated appendicitis. The remaining 146 cases without the appendectomy requirement comprised the control group. Clinical, haematologic and radiologic data of all cases were investigated. Results: Among the patients who had appendectomy, 214 (60.8%) were male. The mean age of the patients was 9.8 ± 3.5 years. The mean C-reactive protein (CRP) (46.6±54.1 vs. 17.3±17.1, p=0.048), white blood cell count (WBC) (18.2±4.8 vs. 10.3±4.6, p<0.001), polymorphonuclear leucocyte (14.5±4 vs. 7.3±4.6, p<0.001) and N/L (8.4±6 vs. 4.4±3.8, p=0.024) values of the patients who had appendectomy were significantly higher. In diagnosis of acute appendicitis, the cut off value for N/L was determined as 5 (p=0.003) (Sensitivity 72.7%, specificity 67.8%). Among complicated acute appendicitis cases, N/L value was significantly higher (10.9±7.2 vs. 6.7±3.3, p=0.04), and the number of patients with WBC greater than 12x10 and CRP value greater than 15 mg/dl were _________________________________________ Department of Pediatrics, Abant Izzet Baysal University Faculty of Medicine, Bolu, Turkey *Correspondence: vanbek@gmail.com (Received on 16 May 2016: Accepted after revision on 17 June 2016) The authors declare that there are no conflicts of interest Personal funding was used in formulating the article. Open Access Article published under the Creative Commons Attribution CC-BY License. significantly higher than the non-complicated group (65.8% vs. 34.3%, p=0.035 and 67.1% vs. 32.9%, p=0.046, respectively). In diagnosis of complicated acute appendicitis, the cut off value for N/L was determined as 7.2 (p=0.017) (Sensitivity 83.6%, specificity 69.6%). Conclusions: In our study the most appropriate cut off value of N/L in differentiating complicated acute appendicitis from non-complicated appendicitis was 7.2. In our study, WBC>12x10 and CRP>15 mg/dl values were important parameters distinguishing complicated appendicitis from non-complicated one. DOI: http://dx.doi.org/10.4038/sljch.v46i1.8238 (


Introduction
Abdominal pain is a common symptom of childhood.The important point that doctors should judge promptly in children admitted with this symptom is differentiation of acute appendicitis.Acute appendicitis is a common surgical problems in childhood 1,2 .Appendectomy is one of the most commonly performed operations with an incidence of about 10% lifelong 3 .In childhood, it is mostly reported in 2 nd decade 4 .The reduction in fibres and increase in refined carbohydrates in diet is regarded as a risk factor for acute appendicitis 5 .
In appendicitis diagnosis, history and physical examination findings are important.Abdominal pain starting around umbilicus, nausea and anorexia are the classical admission symptoms.The most valuable finding in physical examination is tenderness of right lower quadrant.However, only 60% of acute appendicitis cases present with typical symptoms 6 .Especially symptoms in early periods may cause misdiagnosis of the clinical picture with other diseases 7 .Although with the history and physical examination the disease is commonly diagnosed, in some cases laboratory tests such as Creactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) 8,9 and IL-6 ve IL-10 10 and imaging techniques such as ultrasonography or computed tomography 11 may be required.With the increase in number of tests, the cost is also increasing.For this reason, more simple and trustworthy parameters like Neutrophil /Lymphocyte (N/L) ratio are necessary 12 .
The main reason for this high interest in the topic is the aim of decreasing morbidity and mortality of the disease.In early periods of the disease, with hurried diagnosis of the clinician, there are negative appendectomies and with late decision, perforations may take place 6 .These clinical pictures are generally reported in atypical cases that comprise 31.7% of acute appendicitis cases 13 .In this study, our aim is to test the utility of some laboratory methods and especially N/L ratio in rapid diagnosis of simple and complicated acute appendicitis and by this way in reducing the diagnostic delays and negative appendectomy rates in childhood period.

Method
After the approval of local ethics committee, the study was started.The records of patients who were hospitalised in the paediatric surgery departments of Abant İzzet Baysal University Medical Faculty and Bolu Izzet Baysal Obstetrics and Paediatrics Hospital in Turkey between years 2008 and 2014 with the symptom of acute abdominal pain were retrospectively evaluated.Among these patients, those who were diagnosed with urinary system infection, respiratory tract infection, Familial Mediterranean Fever and acute gastroenteritis which may also cause the same symptoms were excluded.The patients included in the study were divided into 2 groups as patients with non-specific abdominal pain (n=146) and patients operated for acute appendicitis (n=352).The patients operated with conventional method with the diagnosis of acute appendicitis were also divided into 2 groups as non-complicated (n=279) or complicated (n=73) regarding the presence of phlegmon, abscess or perforation cases.The patients with non-specific abdominal pain were diagnosed with mesenteric lymphadenitis, ovarian cyst, peptic ulcer or cholelithiasis after the follow-up of 12-24 hours and performed tests.Patients with histologically proven negative appendectomy were not included in this study.
The clinical (location and duration of the abdominal pain, nausea, vomiting, fever, anorexia, diarrhoea, constipation, and dysuria) and laboratory data (haemoglobin, thrombocyte count, mean platelet volume (MPV), white blood cell (WBC), polymorphonuclear (PNL), lymphocyte count, CRP and abdominal ultrasonography) of included patients were investigated.The ultrasonographic evaluations of patients were performed by the radiologists of the medical centres.Regarding the complete blood counts, neutrophil/lymphocyte ratios were calculated.The data were analyzed with the Statistical Package for Social Sciences (SPSS, Inc., Chicago, IL) for Windows 15.0 statistical programme.The data were expressed as mean ±standard deviation.In statistical evaluations, student-t, chi-square (χ 2 ) tests and ROC curve analyses were performed.The p value of <0.05 was considered as statistically significant.

Results
Totally 567 patients, who were admitted to the paediatric emergency, and paediatric outpatient departments of 2 hospitals in Turkey and hospitalized with the pre-diagnosis of acute appendicitis in paediatric surgery departments in the study period were investigated; and 498 of those patients with the comprehensive data in their records were included in the study.Among those patients, 320 (64.2%) were children while 178 (35.7%) were adolescents.Conventional appendectomy was performed in 352 (70.6%) of those patients with the diagnosis of acute appendicitis.Among the patients who had appendectomy, 214 (60.8%) were male while 138 (39.2%) were female.The mean age of the patients was 9.8±3.5 years (7 months-17 years).The features of patients with abdominal pain are summarized in Table -1.In patients who had appendectomy, male gender (p=0.038),nausea (p=0.001),vomiting (p=0.002),anorexia (p<0.001) and constipation (p<0.001)symptoms were significantly more common.In laboratory evaluation of patients who had appendectomy, CRP (p=0.048),WBC (p<0.001),PNL (p<0.001) and N/L (p=0.024)values were determined to be significantly higher.
The characteristics of patients with complicated and non-complicated acute appendicitis are shown in Table 2.For that cut off value sensitivity was 83.6%, and specificity was 69.6%.

Discussion
To decrease the morbidity and mortality rates caused by acute appendicitis; its prompt and definite diagnosis is warranted.Performance of some different hematological and radiological tests is not enough every time for the exact diagnosis in children.For those cases, simple parameters are required for prompt and correct diagnosis 13 .As in our study, acute appendicitis is more common in males 4,14 .The exact cause of this is still not defined.However, there are some studies more commonly reporting acute appendicitis in females 15 .
The diagnosis of acute appendicitis in childhood is mainly suspected by doctors with the admission symptoms.Together with the abdominal pain; nausea-vomiting and anorexia are the most commonly determined admission symptoms 16 .In our study, along with those symptoms, constipation was also determined as significantly higher.In complete blood count, a simple test, WBC, absolute neutrophil count and N/L ratio can be obtained and these parameters were investigated in many other studies as inflammatory determinants 8,9 .Low cost is the main advantage of these parameters.With the augmented inflammation, increase in those parameters is another advantage.On the other hand, there are also studies reporting low sensitivity and specificity rates of especially WBC and absolute neutrophil count in inflammatory conditions 17 .In our study, we have determined significantly increased CRP, WBC and N/L ratio in acute appendicitis cases compared with the cases admitted with non-specific abdominal pain.Dueholm et al 18 defined that normal WBC, N/L and CRP values excludes the diagnosis of acute appendicitis while Gronroos 19 suggested just the opposite.
In 10-20% of people, appendix may be located atypically 20,21 .Despite the evolutions in diagnostic methods in recent years, the perforation rate of 19% and mis-diagnosis rate of 10% in acute appendicitis in children still could not be improved 22 .Especially keeping atypical cases may increase the perforation possibility while operating them may cause the negative appendectomies.On the other hand, Saraç et al 23 defined the most common cause of perforated appendicitis as not distinguishing the clinical picture by the doctors.Especially in children younger than 5 years of age, the causes of perforation were determined as barely expression of children themselves, and difficulty in performance of physical examination 24 .In that aspect, N/L ratio seems to solve these problems.In diagnosis of acute appendicitis, N/L by itself is a better parameter than CRP, WBC and absolute neutrophil count 25 but different cut-off values were determined in previous studies.In our study, the best cut-off value of N/L that can differentiate the inflamed appendix from the normal one was determined as 5 (75.2% sensitivity and 67.8% specificity).This obtained value was between the values of 3.5 reported by Yazıcı et al 12 and Białas et al 26 and 6 reported by Markar et al 25 .
Complicated acute appendicitis pictures due to phlegmon, abscess or perforation are still important.Generally these situations take place due to the delay in interventions with a rate ranging between 21.5% 27 and 28% 28 .In our study, we have determined that localized abdominal pain in right lower quadrant was significantly more common in this condition.In those conditions with more severe inflammation, higher CRP and neutrophil counts were determined 29 .Nevertheless, N/L ratio is more valuable in diagnosis of complicated acute appendicitis compared with WBC, 26 and moreover it may reach higher values compared with the noncomplicated appendicitis 25,29,30 .
In our study, the most appropriate cut off value of N/L in differentiating complicated acute appendicitis from non-complicated one was determined as 7.2 (83.6% sensitivity, 69.6% specificity).This obtained value was between the values of 5.7 reported by Kahramanca et al 13 and 8 reported by Ishizuka et al 29 .In early periods of acute appendicitis, due to the consumption of PNL in marginal pool, PNL increases more than WBC which is the reason of increase in N/L ratio in early periods.In complicated appendicitis, PNL production intensifies while lymphocyte count decreases in bone marrow and this alteration is an important cause of increase in N/L ratio in complicated appendicitis [31][32][33] .
In clinical pictures other than acute appendicitis, admitting with similar symptoms; WBC rarely exceeds 12x10 3 /mm 3,26 .Erturk et al 16 reported that, in childhood acute appendicitis cases, total leucocyte count higher than 11.8x10 3 /μL and CRP values higher than 13.5 mg/dl have high sensitivities.In our study, we have determined that WBC>12x10 3 and CRP>15 mg/dl values were important parameters distinguishing complicated appendicitis from non-complicated one.

Conclusions
• In our study the most appropriate cut off value of N/L in differentiating complicated acute appendicitis from non-complicated appendicitis was 7.2.
• In our study, WBC>12x10 3 and CRP>15 mg/dl values were important parameters distinguishing complicated appendicitis from non-complicated one.