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Preoperative neutrophil-to-lymphocyte ratio may contribute to the prediction of postoperative infectious complications in patients with acute appendicitis: a retrospective study
BMC Surgery volume 22, Article number: 78 (2022)
Several studies have assessed various clinical variables to identify risk factors for postoperative complications in patients with acute appendicitis. However, few studies have focused on the relationships between systemic inflammatory variables and postoperative complications in patients with acute appendicitis. We investigated the relationships between postoperative complications and systemic inflammatory variables, and assessed the clinical utility of these variables as predictors of postoperative complications in patients with acute appendicitis.
We retrospectively reviewed 181 patients who underwent immediate appendectomy for acute appendicitis. All postoperative complications were classified as infectious or noninfectious, and we evaluated the relationships between postoperative complications and clinical factors including the preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.
In total, 28 patients (15.5%) had postoperative Clavien-Dindo grade II–IV complications; 17 patients (9.4%) and 11 patients (6.1%) were categorized as the infectious and noninfectious complication groups, respectively. The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for all complications was 11.3, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of any postoperative complication (odds ratio: 4.223, 95% confidence interval: 1.335–13.352; P = 0.014). The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for infectious complications was 11.4, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of infectious complications (odds ratio: 4.235, 95% confidence interval: 1.137–15.776; P = 0.031).
In patients with acute appendicitis, the preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of all postoperative complications, especially infectious complications.
Acute appendicitis is considered one of the most common diseases of the acute abdomen, with an estimated lifetime risk rate of 7–8% worldwide [1, 2]. Acute appendicitis can be clinically and epidemiologically classified as uncomplicated or complicated acute appendicitis, and 70–80% of all patients with appendicitis are diagnosed with uncomplicated acute appendicitis . Although some randomized clinical trials have demonstrated that antibiotic therapy for acute appendicitis may be feasible as an alternative to immediate appendectomy [4,5,6,7,8,9,10], immediate appendectomy is still the standard treatment for acute appendicitis. Appendectomy is a cardinal surgical procedure with low mortality but a postoperative complication rate of 5–28% [5, 10,11,12,13,14,15,16]. Several studies have suggested that clinical variables such as age, operation timing, type of surgery, and type of acute appendicitis are risk factors for postoperative complications [11,12,13,14,15,16].
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are well-known systemic inflammatory variables related to the prognosis of colorectal, gastric, and pancreatic cancer [17,18,19]. Some recent studies suggest that systemic inflammatory variables may be useful for the prediction of postoperative complications in patients with various cancers [20,21,22]. However, few studies have focused on the relationships between systemic inflammatory variables and postoperative complications in patients with acute appendicitis. Therefore, we investigated the relationships between postoperative complications and systemic inflammatory variables, and assessed the clinical utility of these variables as predictors of postoperative complications in patients with acute appendicitis.
The study protocol was approved by the Institutional Review Board of our institution. We retrospectively reviewed the electronic medical records of 181 patients with acute appendicitis who underwent appendectomy within 48 h after hospital admission between January 2010 and August 2021 at Secomedic Hospital, Japan. The patient inclusion criteria were age ≥ 15 years, emergency operation for acute appendicitis, and histologically confirmed diagnosis of acute appendicitis. We excluded patients who were pregnant, did not have histologically confirmed acute appendicitis, or underwent an interval appendectomy after initial antibiotic therapy. In this study, perforated appendicitis, gangrenous appendicitis, or appendicitis with a periappendiceal abscess was defined as complicated acute appendicitis; catarrhal or phlegmonous appendicitis was defined as uncomplicated acute appendicitis.
Assessment of preoperative systemic inflammatory variables
A routine blood examination was performed at the time of hospitalization. We assessed the preoperative white blood cell count (pWBC), platelet count (pPLT), serum C-reactive protein level (pCRP), NLR (pNLR), and PLR (pPLR) as representative systemic inflammatory variables. As previously reported, the NLR and PLR were calculated by dividing the neutrophil and platelet count, respectively, by the lymphocyte count [17,18,19].
Visual assessment of acute appendicitis on computed tomography images
In all patients, the maximum diameter of the appendix and the presence of fecalith, periappendiceal effusion, periappendiceal abscess, and ascites were evaluated on computed tomography (CT) images before surgery.
Definitions of postoperative complications
All complications occurring within 30 days after surgery were defined as postoperative complications and were graded using the Clavien-Dindo classification (C-D) system . A diagnosis of postoperative intra-abdominal abscess, cholangitis, or paralytic ileus was based on the patient’s symptoms, laboratory data, abdominal radiography, and CT findings. All postoperative complications were categorized as infectious or noninfectious.
The relationships between postoperative complications and systemic inflammatory variables were evaluated by the area under the curves (AUCs) of the receiver operating characteristic (ROC) curves. The cutoff values of continuous variables (including systemic inflammatory variables) were set at the point on the ROC curve closest to the (0,1) point; these points corresponded to the optimal sensitivity and specificity yielding the minimal value for (1-sensitivity)2 + (1-specificity)2 . The relationships between postoperative complications and type of appendectomy (open or laparoscopic) in patients with acute appendicitis were evaluated by Fisher’s exact test. Univariate analyses of postoperative complications were performed using logistic regression to determine whether there were significant associations between the clinical factors and postoperative complications. Multivariate analysis was performed using logistic regression to determine the statistical significance of the clinical factors identified by univariate analysis. P values < 0.05 indicated statistical significance. P values in multiple comparisons using Fisher’s exact test were corrected using a false discovery rate. All statistical analyses were performed using SPSS for Windows (version 26.0; IBM Corp., Armonk, NY, USA).
The clinical characteristics of 181 patients (70 women, 111 men) with acute appendicitis who underwent immediate appendectomy are summarized in Table 1. Among 181 patients with acute appendicitis, 28 patients developed a postoperative complication classified as C-D grade II–IV.
Relationships between postoperative complications and appendectomy type in patients with acute appendicitis
Among 28 patients with C-D grade ≥ II postoperative complications (15.5%), 17 patients (9.4%) were defined as the infectious complication group, including 11 patients with intra-abdominal abscess (6.1%), four with wound infection (2.2%), one with cholangitis (0.6%), and one with enteritis (0.6%). All 11 patients (6.1%) in the noninfectious complication group had paralytic ileus. In the ‘all complications’ group and the infectious complications group, the incidence of complications significantly differed between patients who underwent open versus laparoscopic appendectomy (P < 0.001). In the infectious complication group, patients who underwent open appendectomy had a higher incidence of intra-abdominal abscess (P < 0.023) and wound infection (P < 0.001) than those who underwent laparoscopic appendectomy. In the noninfectious complication group, the incidence of paralytic ileus significantly differed between patients who underwent open versus laparoscopic appendectomy (P = 0.023) (Table 2).
Identification of useful predictors of all postoperative complications in patients with acute appendicitis
Based on the ROC curves, the cutoff values of the pWBC, pPLT, pCRP, pNLR, and pPLR for all complications were set at 12.8 × 109/L, 254 × 109/L, 89.4 mg/L, 11.3, and 212.2, respectively (Fig. 1). Of the 20 clinical factors assessed using univariate analysis, the variables significantly associated with all postoperative complications were age (odds ratio (OR), 4.856; 95% confidence interval (CI) 2.003–11.772; P < 0.001), body mass index (BMI) (OR, 2.590; 95% CI 1.141–5.879; P = 0.023), American Society of Anesthesiologists physical status classification (OR, 2.486; 95% CI 1.137–5.437; P = 0.023), preoperative body temperature (OR, 3.043; 95% CI 1.263–7.334; P = 0.013), pNLR (OR, 3.363; 95% CI 1.427–7.927; P = 0.006), pCRP (OR, 5.409; 95% CI 2.315–12.640; P < 0.001), presence of periappendiceal effusion (OR, 4.545; 95% CI, 1.312–15.748; P = 0.017), presence of periappendiceal abscess (OR, 3.940; 95% CI 1.186–13.093; P = 0.025), presence of ascites (OR, 2.844; 95% CI 1.175–6.884; P = 0.020), type of appendectomy (OR, 0.125; 95% CI 0.051–0.306; P < 0.001), operative time (OR, 8.195; 95% CI 3.242–20.713; P < 0.001), estimated blood loss (OR, 6.202; 95% CI 2.622–14.672; P < 0.001), and complicated acute appendicitis (OR, 8.344; 95% CI 2.760–25.221; P < 0.001). Multivariate analysis of the significant factors identified using univariate analysis revealed that the independent risk factors for all postoperative complications were BMI (OR, 3.623; 95% CI 1.116–11.757; P = 0.032), pNLR (OR, 4.223; 95% CI 1.335–13.352; P = 0.014), operative time (OR, 4.850; 95% CI 1.410–16.682; P = 0.012), and complicated acute appendicitis (OR, 4.590; 95% CI 1.004–20.972; P = 0.049) (Table 3).
Identification of useful predictors of infectious complications in patients with acute appendicitis
The cutoff values of the pWBC, pPLT, pCRP, pNLR, and pPLR for the infectious complication group were set at 13.8 × 109/L, 259 × 109/L, 146.6 mg/L, 11.4, and 235.7, respectively (Fig. 2). Univariate analysis showed that the variables significantly associated with infectious complications were age (OR, 4.160; 95% CI 1.398–12.380; P = 0.010), BMI (OR, 4.629; 95% CI 1.553–13.795; P = 0.006), pNLR (OR, 3.655; 95% CI 1.230–10.863; P = 0.020), pCRP (OR, 6.255; 95% CI 2.204–17.754; P = 0.001), type of appendectomy (OR, 0.138; 95% CI 0.048–0.395; P < 0.001), operative time (OR, 7.628; 95% CI 2.369–24.563; P = 0.001), estimated blood loss (OR, 6.650; 95% CI 2.337–18.926; P < 0.001), and complicated acute appendicitis (OR, 5.676; 95% CI 1.571–20.502; P = 0.008). Multivariate analysis of the significant factors identified using univariate analysis revealed that the independent risk factors for infectious complications were BMI (OR, 4.471; 95% CI 1.275–15.676; P = 0.019) and pNLR (OR, 4.235; 95% CI 1.137–15.776; P = 0.031) (Table 4).
Identification of useful predictors of noninfectious complications in patients with acute appendicitis
The cutoff values of the pWBC, pPLT, pCRP, pNLR, and pPLR for the noninfectious complication group were set at 9.6 × 109/L, 188 × 109/L, 89.4 mg/L, 11.3, and 212.2, respectively (Fig. 3). Univariate analysis showed that the variables significantly associated with noninfectious complications were age (OR, 5.149; 95% CI 1.316–20.149; P = 0.019), preoperative body temperature (OR, 5.062; 95% CI 1.062–24.128; P = 0.042), pWBC (OR, 0.151; 95% CI 0.042–0.543; P = 0.004), pCRP (OR, 7.876; 95% CI 1.999–31.033; P = 0.003), presence of fecalith (OR, 10.000; 95% CI 1.252–79.845; P = 0.030), presence of periappendiceal abscess (OR, 6.000; 95% CI 1.376–26.166; P = 0.017), presence of ascites (OR, 3.889; 95% CI 1.114–13.582; P = 0.033), type of appendectomy (OR, 0.217; 95% CI 0.062–0.762; P = 0.017), operative time (OR, 7.265; 95% CI 2.008–26.285; P = 0.003), and complicated acute appendicitis (OR, 11.795; 95% CI 1.477–94.190; P = 0.020). Multivariate analysis of the significant factors identified using univariate analysis revealed that the only independent risk factor for noninfectious complications was the pWBC (OR, 0.125; 95% CI 0.021–0.729; P = 0.021) (Table 5).
We assessed the relationships between systemic inflammatory variables and postoperative complications after immediate appendectomy. An increased pNLR was identified as an independent risk factor for all postoperative complications, especially infectious complications, in patients with acute appendicitis.
Although recent accumulating evidence suggests that early surgical intervention may not always be required for acute appendicitis because of the relatively high success rate of antibiotic therapy [4,5,6,7,8,9,10], some studies have suggested that nonoperative management with antibiotics is not always effective in patients with acute appendicitis with a high serum CRP level, presence of an appendicolith, large appendiceal diameter, or complicated acute appendicitis [25,26,27]. Therefore, immediate appendectomy is considered the main treatment for acute appendicitis.
Several studies have identified various clinical variables, including older age, delayed or night operation, longer operative time, open surgery, and complicated acute appendicitis, as risk factors of postoperative complications such as wound infection, intra-abdominal abscess, and prolonged ileus [11,12,13,14,15,16]. Segev et al.  demonstrated that the rate of postoperative complications was higher in older adult patients with a longer delay from symptom onset to admission or from admission to surgery, complicated acute appendicitis, and a longer operative time. Regarding the optimal operation timing, some studies have suggested that delayed appendectomy may be unsafe or ineffective for adult patients with complicated acute appendicitis [11, 13,14,15]. In contrast, other studies have reported that delayed appendectomy is not associated with an increase in the occurrence of postoperative complications [16, 28, 29]. Laparoscopic appendectomy has become the main surgical treatment for acute appendicitis, and several studies have reported that laparoscopic appendectomy is the most effective surgical treatment for acute appendicitis and is associated with a lower incidence of postoperative complications, shorter hospital stay, and better quality-of-life scores compared with open appendectomy [30,31,32]. The incidence of postoperative complications after immediate appendectomy for uncomplicated acute appendicitis is generally 10–19%. However, the incidence of postoperative complications after immediate appendectomy for complicated acute appendicitis increases to 30%, and some studies have proposed that antibiotic therapy, percutaneous drainage, or interval appendectomy may have some advantages over immediate appendectomy for complicated acute appendicitis [33, 34]. In our study, the incidence of any postoperative complication was 15.5%; this is slightly higher than the incidence reported in previous studies because 48.6% of our patients were diagnosed with complicated acute appendicitis, which may affect the incidence of postoperative complications. As seen in previous studies, our results showed a significant association between postoperative complications and operative time or complicated acute appendicitis; however, we found no significant association between postoperative complications and age, operation timing, or open appendectomy.
Increased leukocyte and platelet counts are usually observed in the systemic inflammatory response. Neutrophils are the predominant leukocyte subset that is recruited to inflamed tissue by the initial innate immune system response , and platelets serve as a major contributor of several pro-inflammatory chemokines and possess a whole inventory of surface receptors and adhesion molecules that enable platelets to bind to leukocytes, circulating pathogens, and bacteria . To our knowledge, ours is the first study to demonstrate that the pNLR is a useful predictor of postoperative infectious complications in patients with acute appendicitis. An increased pNLR indicates both a heightened neutrophil-dependent inflammatory response and a decreased lymphocyte-mediated antibacterial immune reaction, which may affect the development of postoperative infectious complications. Therefore, postoperative infectious complications in acute appendicitis patients with an increased NLR may be reduced by a combination of perioperative antimicrobial treatment (using broad-spectrum antibiotics) and anti-inflammatory therapy with immediate appendectomy, or nonsurgical treatment with antibiotics substituted for immediate appendectomy.
Our study has limitations. Because this was a retrospective study conducted in a single institution with a small sample size and patient selection bias, there were differences in patients’ characteristics, which may have led to biased estimates of postoperative complications. Moreover, it is difficult to precisely diagnose other complications with different severities. Although our findings should be interpreted with caution, we believe that their potential clinical significance justifies further investigation.
Our study demonstrated that the pNLR was the most useful predictor of postoperative complications, especially infectious complications, after immediate appendectomy for acute appendicitis. Although further investigation is required to verify the utility of the pNLR as a predictor of infectious complications after immediate appendectomy for acute appendicitis, a high NLR in patients with acute appendicitis before appendectomy may contribute to the prediction or prevention of postoperative infectious complications.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Preoperative white blood cell count
Preoperative platelet count
Preoperative serum C-reactive protein level
Receiver operating characteristics
Area under the ROC curve
Body mass index
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We thank Kelly Zammit, BVSc, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript.
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The study was conducted in accordance with the principals of the Declaration of Helsinki. Secomedic Hospital Ethics Review Board approved the retrospective data collection and analysis (Reference Number: 2021-001). All patients gave written informed consent for the collection of their medical data for scientific purposes.
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Mori, M., Narushima, K., Hirano, A. et al. Preoperative neutrophil-to-lymphocyte ratio may contribute to the prediction of postoperative infectious complications in patients with acute appendicitis: a retrospective study. BMC Surg 22, 78 (2022). https://doi.org/10.1186/s12893-022-01529-8
- Acute appendicitis
- Postoperative complications