EVALUATION OF URINE ANALYSIS IN ADULTS WITH SIMPLE AND COMPLICATED APPENDICITIS

Objectives: Acute appendicitis is one of the common abdominal emergencies. We aimed in this study to evaluate whether routine urinalysis may use in discriminating between simple appendicitis and complicated appendicitis in the emergency department. Materials and Methods: Patients over 18 years of age with a pathological diagnosis of acute appendicitis and those who underwent urine analysis in the emergency department were included in the study. Patients with missing data were excluded. According to pathology reports, patients were classified as simple and complicated appendicitis. Results: Compared to simple appendicitis, the complicated appendicitis group had significantly higher urine ketone body, protein, and nitrite counts on admission (p<0.05 for all parameters). Urine ketone bodies and positive urine nitrite were found to predict statistically significant complicated appendicitis in multivariate logistic regression analysis (for all values p<0.001). Conclusion: Urine analysis is one of the routine tests performed in patients with suspected acute abdomen. Therefore, we think that especially urine ketone bodies and positive urine nitrite in urine analysis may be a warning for complicated appendicitis.


Introduction
Acute appendicitis (AA) is one of the most common surgical emergencies. In about 7% of the population, AA may occur at any time of their lifetime. AA is an inflammation usually caused by obstruction of the vermiform appendix. 1,2 It is known that delayed treatment is associated with high mortality and morbidity, also early diagnosis and treatment is lifesaving. 3 In the literature, appendicitis is classified as simple and complicated. 4 According to this classification a suppurative appendix is considered as simple appendicitis, however gangrenous appendicitis, perforated appendicitis, and periappendicular abscess are considered as complex appendicitis. In simple appendicitis congestion, color changes, increased diameter, exudate, and pus can be seen macroscopically; transmural inflammation, ulceration, or thrombosis, with or without extramural pus can be seen microscopically. Friable appendix with purple, green, or black color changes and transmural inflammation with necrosis are pathological findings of gangrenous appendicitis. Untreated gangrenous appendicitis eventually becomes perforated. Similarly, periappendicular abscesses with transmural inflammation with pus also carry a high risk for postoperative complications. 4,5 Diagnostic methods purposes principally to confirm the diagnosis of AA, and after to classify simple or complex diseases. 6 Biomarkers are used to support patients' physical examination and clinical history when a diagnosis of AA is suspicious. No laboratory test, such as white blood cell count, C-reactive protein, or procalcitonin, can diagnose AA with high specificity and sensitivity. 7 Although urinalysis is a part of the routine evaluation in patients presenting with acute abdominal pain, its role in the diagnosis of AA is still unclear. 1 This study aimed to identify whether routine urine analysis may inform in discriminating between simple appendicitis and complicated appendicitis in the adult emergency department population.

Materials and Methods
Before our retrospective study, local ethics committee approval was obtained (09/10/2019, 2012-KAEK-15/1940). All patients older than 18 years old who were admitted to our emergency department between 01.04.2014-31.03.2019 and diagnosed with acute appendicitis and operated in the general surgery clinic were included in the study. Patients with no urine test and missing data were excluded from the study. Patients' demographic data, urine analysis results, surgical notes, and pathology reports were obtained by scanning the hospital data system and patient files. Urine analysis was performed on BT URICELL 1280-1600 devices (BT products, İzmir, Turkey).
The urine analysis tests detect and measure the specific gravity (SG), pH, leukocyte esterase, protein, nitrite, ketone, erythrocyte, and leukocyte value.
According to pathology reports, patients were classified as simple and complicated appendicitis. Perforated appendicitis, gangrenous/necrotic appendicitis, and periappendicular abscesses were accepted as complicated appendicitis.

Statistical analysis
Data were analyzed using IBM SPSS16.0 (Chicago, IL, USA) statistical program. Kolmogorov Smirnov test was used to determine whether the distribution of discrete and continuous numerical variables was suitable for normal distribution. As the data did not conform to the normal distribution, median values, and interquartile range (IQR, 25% -75) were shown, and categorical variables were shown as the number of cases and (%).

Results
During the study period, 1198 patients were identified who supply the inclusion criteria of having undergone appendectomy for suspected acute appendicitis. 397 patients were excluded due to lack of data and urine analysis. 323 (40.32%) of the 801 patients included in the study were female and the median age of all patients was 30 (IQR 25-75: 24-39). Ketone positivity was detected in urine analysis of 141 (%17.60) patients.
According to pathology reports, 569 (71.04%) patients were simple and 232 (28.96%) were complicated appendicitis. Demographics and some laboratory results of all patients are shown in Table 1. Comparison of characteristics and urine parameters among patients with simple appendicitis and complicated appendicitis were shown in Table 2. We found that nitrite, ketone, protein positivity, and urine specific gravity were statistically higher in urine analysis compared to simple appendicitis in complicated appendicitis patients (p<0.001 for all values).
Multivariate logistic regression analysis was performed to examine the effects of variables in Table 2 with other variables. In the multivariate model, protein positivity, ketone positivity, specific gravity, nitrite positivity, urine erythrocyte count, as well as age and gender parameters, with p values of 0.20 and below, were included.
After the model associated with the Hosmer-Lemeshow test is seen to be fit statistical analysis revealed that positive urine ketone bodies and positive urine nitrite were important parameters for predicting complicated appendicitis (for all values p<0.001) ( Table 3).

Discussion
Early diagnosis of AA is not always easy, also diagnostic methods may not always be sufficient to distinguish between simple and complicated appendicitis. There may not be enough imaging methods to diagnose AA in rural areas, however, sometimes ultrasound and tomography may not help diagnose AA. 4-6 Therefore, simple and cheap auxiliary tests are still needed to make a diagnosis. In this study, we think that the two parameters analyzed in urine analysis can be useful in predicting complicated appendicitis.
In our study, 71.04% of the patients, who underwent appendectomy, were simple appendicitis and 28.96% were complicated appendicitis. These findings were consistent with the literature. 5 Complicated appendicitis was determined from the pathology reports and surgical notes of the patients according to the pathological classification in the review published by Bhangu et al. 4 According to pathology reports, 12% of our patients were perforated. The perforation rate in the literature is similarly 13-20%. 8 In this study, we found that urine ketone bodies, nitrite, and protein positivity were significant factors in complicated appendicitis. In our regression analysis, we found that the incidence of complicated appendicitis was 2.25 times more in ketone positive patients. Similarly, Chen et al. found that ketone, nitrite, and protein positivity were significantly higher in child patients with perforated appendicitis. 9 As we know, ketone bodies increase in urine in cases such as hunger, diabetes mellitus, dehydration, high fever, vomiting, diarrhea, severe liver disease. 10,11 Ketone positivity in patients with appendicitis may also be due to hunger, nausea, and vomiting, which are expected symptoms of acute appendicitis. Complicated appendicitis may result in more severe loss of appetite and vomiting than simple ones, and our findings may be explained by this condition.
Patients with complicated appendicitis may present with more severe clinical findings than simple patients, and positive ketone and nitrite parameters detected during urinalysis at the time of admission may stimulate the emergency physician for complicated appendicitis.
In the literature, it has been reported that in acute appendicitis, urinary tract infection may be caused by peritoneal irritation due to urinary tract compression. 12 This may be the reason for the significantly higher nitrite positivity in patients with complicated appendicitis. We think that; patients with positive ketone and nitrite in urine analysis who are at higher risk of perforation could be operated on earlier.
According to classical knowledge, the treatment of appendicitis is surgical appendectomy. However, recent studies have reported that simple appendicitis can be managed with medical treatment without surgery. 13,14 At this point, the distinction between simple and complicated appendicitis becomes more important in the diagnostic process.
Furthermore, a simple or a perforated patient may affect the surgeon's choice of surgical method. 15 Additionally, early diagnosis of appendicitis may prevent perforation, abscess, and postoperative complications, as well as may reduce hospital stay and costs.
In the literature, there are many studies investigating laboratory parameters predicting complicated appendicitis. Some studies have shown that CRP levels correlate with the severity of appendix inflammation and may be sensitive to predict appendix perforation. 16,17 Yang et al. reported that higher white blood cell count, CRP level, neutrophil percentage, and low serum sodium level could be used to predict perforated appendicitis. 18 There are also studies showing that the neutrophil-lymphocyte ratio is a promising marker that can predict both the diagnosis and severity of appendicitis. 19 In the literature, there is no test to detect complicated appendicitis with 100% sensitivity and specificity before surgery, so there is still a need for further studies on auxiliary tests.
In conclusion, urine analysis is one of the routine tests performed in patients with suspected acute abdomen.
Therefore, we think that especially urine ketone bodies and positive urine nitrite in urine analysis may be warning for complicated appendicitis without increasing the cost.

Limitations
There are a few limitations to be considered regarding this study. First, this is a single-center retrospective study. The relationship between urine parameters and the degree of perforation, gangrene, or necrosis could not be determined due to the limited pathology reports.