Diagnostic accuracy of systemic immune-inflammation index for acute appendicitis in the geriatric population

Abstract

Aims

This study aimed to evaluate the diagnostic accuracy of the systemic immune-inflammation index (SII) in distinguishing acute appendicitis from non-appendicitis cases in geriatric patients who underwent surgery with a preliminary diagnosis of appendicitis.

Methods

A retrospective study was conducted on geriatric patients with suspected acute appendicitis at a tertiary healthcare center. Demographic data, clinical features, and laboratory values were obtained from medical records. The SII was calculated based on neutrophil, platelet, and lymphocyte counts, and the patients were classified according to histopathological outcomes. The primary outcome was the diagnostic accuracy of SII in identifying appendicitis in the elderly population.

Results

The study included 64 geriatric patients with suspected appendicitis, comprising 45 patients with confirmed appendicitis (70.3%) and 19 patients without appendicitis (29.7%). The mean age of the patients was 71 years (interquartile range: 67–76), with no significant difference between the appendicitis and non-appendicitis groups (p = 0.590). Females constituted 50% of the total cohort. The SII was significantly higher in the appendicitis group (median: 3687, interquartile range: 2420–5930) compared to the non-appendicitis group (median: 1589, interquartile range: 1134–2248, p < 0.001). The area under the receiver operating characteristic curve for the index was 0.81 (95% confidence interval: 0.68–0.93, p < 0.001), indicating good diagnostic accuracy. A threshold of greater than 2289 yielded a sensitivity of 0.78 and specificity of 0.79. The positive predictive value was 0.90, while the negative predictive value was 0.60.

Conclusions

The SII demonstrated high diagnostic accuracy in differentiating between acute appendicitis and non-appendicitis cases in geriatric patients. SII may be a valuable diagnostic tool in elderly patients with suspected appendicitis, aiding timely and accurate clinical decision-making.

Introduction

Acute appendicitis remains one of the most common causes of acute abdominal pain requiring emergency surgery worldwide [1,2,3]. While diagnosis is generally straightforward in younger patients due to typical clinical symptoms, diagnosing acute appendicitis in the geriatric population presents significant challenges. In elderly patients, the presence of atypical symptoms and symptomatic overlap with other abdominal conditions, such as diverticulitis or malignancy, can lead to delays in diagnosis and increased complication rates. Furthermore, age-related physiological changes in immune response and inflammatory markers further reduce the reliability of clinical assessments in this population [4,5,6,7].

The systemic immune-inflammation index (SII) is a novel biomarker calculated using neutrophil, platelet, and lymphocyte values obtained from peripheral blood counts. This index, which reflects systemic inflammation, is gaining increasing attention in various fields, including oncology, cardiology, and infectious diseases. SII provides prognostic information in conditions characterized by systemic inflammation by evaluating immune and inflammatory responses together [8,9,10]. In this regard, it is considered a promising marker for diagnosing acute inflammatory conditions, such as acute appendicitis.

However, the role of SII in diagnosing acute appendicitis, particularly in the geriatric population, has not been clearly established. Although previous studies have examined various inflammatory markers, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in the context of appendicitis, the diagnostic value of SII in elderly patients has not been sufficiently investigated [11, 12]. Given that the geriatric population is at high risk for delayed diagnosis and complications in acute appendicitis, there is a need to explore reliable diagnostic tools that can aid in early and accurate diagnosis of this condition.

The aim of this study is to evaluate the diagnostic accuracy of SII in geriatric patients who underwent surgery with a preliminary diagnosis of acute appendicitis.

Methods

This study was conducted with the approval of the Istanbul Yeni Yüzyıl University’s Clinical Research Ethics Committee (Date: 04.11.2024, Decision No: 2024/11–1360). The study was carried out in accordance with the ethical principles of the Declaration of Helsinki. This retrospective study was conducted on patients aged 65 and over who underwent surgery with a preliminary diagnosis of acute appendicitis in the emergency department of a tertiary healthcare institution between January 1, 2019, and January 1, 2024. Due to the retrospective nature of the study, informed consent was not obtained from the patients, and exemption was granted by the ethics committee.

Patients aged 65 and over who were admitted to the emergency department with a preliminary diagnosis of acute appendicitis and had a histopathologically confirmed diagnosis of appendicitis following surgery were included in the study. Patients under the age of 65, those with non-appendicitis pathologies, those with a history of previous appendectomy, and those with insufficient or incomplete data were excluded from the study.

Demographic data (age, gender), clinical characteristics (symptom duration, length of hospital stay), and laboratory findings (white blood cells count, neutrophil count) were retrospectively obtained from the medical records of the patients. Preoperative evaluations were conducted using a combination of clinical examination, laboratory markers, and imaging studies. For patients without classic appendicitis signs, the decision to perform an appendectomy was primarily based on imaging findings (e.g., enlarged appendiceal diameter or inflammatory changes on computed tomography or ultrasound) and elevated laboratory markers, such as leukocytosis. In our institution, patients with suspected appendicitis who have equivocal findings are managed conservatively through close observation and repeated imaging. Surgical decisions are made when clinical suspicion remains high despite inconclusive imaging findings. In addition, pathology results were reviewed to confirm the diagnosis of acute appendicitis histopathologically. Based on the histopathological results, patients were classified into two groups: non-appendicitis and confirmed appendicitis.

The SII was calculated using the following formula based on neutrophil, platelet, and lymphocyte counts [13]:

$${\text{SII}} = \left( {{\text{Neutrophil}} \times {\text{Platelet}}} \right)/{\text{Lymphocyte}}.$$

SII values, calculated using the complete blood count results at the time of admission, were compared between the groups.

Analysis

All statistical analyses were performed using IBM SPSS Statistics for Windows, version 29.0 (IBM Corp., Armonk, NY, USA) and MedCalc version 20.104 (MedCalc Software Ltd., Ostend, Belgium). Descriptive statistics were calculated for all variables, with continuous data reported as medians with interquartile ranges (IQR) or means ± standard deviation (SD), depending on normality, and categorical data summarized as frequencies and percentages. Data normality was evaluated using histograms and the Shapiro–Wilk test. Comparisons between groups were conducted using the Student’s t test for normally distributed continuous variables and the Mann–Whitney U test for non-normally distributed data. Categorical variables were compared using the Chi-square test or Fisher’s exact test, as appropriate.

The diagnostic performance of the SII in detecting appendicitis was assessed through receiver operating characteristic (ROC) curve analysis, with the area under the ROC curve (AUROC) calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined at the optimal threshold based on Youden’s Index. Statistical significance was defined by a p value of < 0.05.

Results

The study included 64 geriatric patients with suspected appendicitis, comprising 19 patients without appendicitis (29.7%) and 45 patients with confirmed appendicitis (70.3%). The 19 patients without appendicitis included those diagnosed with diverticulitis (6 patients, 31.6%), ileitis (4 patients, 21.1%), other non-specific inflammatory conditions (7 patients, 36.8%), and appendiceal tumors (2 patients, 10.5%). Baseline characteristics and laboratory findings are detailed in Table 1. The mean age of patients was similar between the groups: 71 years (IQR: 67–76) in the overall population, with no statistically significant difference between non-appendicitis and appendicitis cases (p = 0.590). Females constituted 50% of the total cohort, with 42.1% (n = 8) in the non-appendicitis group and 53.3% (n = 24) in the appendicitis group, showing no association with appendicitis diagnosis (p = 0.412).

Table 1 Baseline characteristics and laboratory findings in geriatric patients with suspected appendicitis

Length of stay was statistically significantly shorter in the appendicitis group, with a median of 3 days (IQR: 1–6) compared to 7 days (IQR: 2.5–7) in the non-appendicitis group (p = 0.037). Symptom duration was also statistically significantly shorter in the appendicitis group, with a median of 20 h (IQR: 10–48) compared to 72 h (IQR: 41–88) in those without appendicitis (p < 0.001). Laboratory results showed statistically significantly higher WBC and neutrophil counts in the appendicitis group, with mean WBC levels of 13,146 ± 4823 cells/µL versus 9041 ± 3381 cells/µL (p = 0.001; mean difference: 4105, 95% CI 1670–6540) and mean neutrophil counts of 10,335 ± 4205 cells/µL compared to 6999 ± 3772 cells/µL (p = 0.004; mean difference: 3335, 95% CI 1102–5569). The comparison of SII levels between non-appendicitis and appendicitis groups is illustrated in Fig. 1. SII was also statistically significantly higher in the appendicitis group (median: 3687, IQR: 2420–5930) compared to the non-appendicitis group (median: 1589, IQR: 1134–2248, p < 0.001).

Fig. 1

Comparison of systemic immune-inflammation index levels between non-appendicitis and appendicitis groups

As shown in Table 2, symptoms and physical examination findings revealed statistically significant associations with appendicitis. Migratory pain was present in 84.4% (n = 38) of appendicitis patients compared to 36.8% (n = 7) of those without (p < 0.001). Right lower quadrant tenderness was more frequent in the appendicitis group (88.9%, n = 40) versus the non-appendicitis group (68.4%, n = 13; p = 0.047). Guarding was statistically significantly more common in the appendicitis group (80%, n = 36) than in the non-appendicitis group (26.3%, n = 5; p < 0.001), as were rebound tenderness (68.9% vs. 42.1%, p = 0.045) and Rovsing’s sign (80% vs. 21.4%, p < 0.001). Anorexia and nausea did not show statistically significant differences between groups (p = 0.559 and p = 0.690, respectively).

Table 2 Symptoms and physical examination findings in geriatric patients with suspected appendicitis

Diagnostic performance metrics for SII are presented in Table 3. The area under the Receiver Operating Characteristic (AUROC) curve for SII was 0.81 (95% CI 0.68–0.93, p < 0.001), indicating good diagnostic accuracy. The optimal SII threshold was > 2289, yielding a Youden’s Index of 0.57, with sensitivity of 0.78 (95% CI 0.64–0.87) and specificity of 0.79 (95% CI 0.57–0.91). The positive predictive value (PPV) was 0.90 (95% CI 0.76–0.96), while the negative predictive value (NPV) was 0.60 (95% CI 0.41–0.77), indicating substantial predictive ability.

Table 3 Diagnostic performance metrics for systemic immune-inflammation index (SII) in detecting appendicitis in geriatric patients

The receiver operating characteristic curve for SII is depicted in Fig. 2, illustrating the discriminative capacity of SII in identifying appendicitis among geriatric patients.

Fig. 2

Receiver operating characteristic curve for systemic immune-inflammation index in detecting appendicitis among geriatric patients

Discussion

One of the most important findings of this study is the high diagnostic accuracy of the SII in diagnosing acute appendicitis in geriatric patients. This result supports the usability of SII as a rapid and reliable diagnostic tool in emergency surgical conditions, such as acute appendicitis in the geriatric population.

Diagnosing acute appendicitis in geriatric patients can be challenging due to age-related physiological changes and the presence of atypical symptoms. Inflammatory responses are often weakened in elderly patients, making the clinical presentation less pronounced. Non-specific symptoms such as abdominal pain, anorexia, and nausea can replace typical clinical findings, leading to misdiagnosis or delayed diagnosis. In addition, the weakened immune response and atypical levels of inflammatory markers in the geriatric population further complicate the diagnostic process [14, 15]. In this context, the need for reliable biomarkers for early diagnosis and treatment becomes even more critical. SII, by reflecting systemic inflammation, may be a suitable candidate to overcome these diagnostic challenges.

The components of the SII—neutrophils, platelets, and lymphocytes—play important pathophysiological roles in acute appendicitis. Neutrophils are critical cells in the initial phase of the inflammatory response, and an increase in neutrophil count during appendicitis reflects pathological inflammation. Platelets, in addition to their role in coagulation processes, also play a part in regulating inflammation and immune responses. Platelet activation in acute appendicitis may contribute to the progression of the inflammatory cascade. Although lymphocytes are involved in regulating the immune response, their numbers may decrease during acute inflammatory processes [16, 17]. By integrating the immune and inflammatory responses through the combination of these three components, SII provides a comprehensive assessment of the severity and extent of inflammation. Therefore, SII is expected to emerge as a strong predictive biomarker in the diagnosis of acute appendicitis.

In the literature, there is no specific study examining the effectiveness of the SII in diagnosing acute appendicitis in the geriatric population. Therefore, there are limited data with which we can directly compare the results of this study. However, there are several studies that evaluate the diagnostic accuracy of SII in different age groups and populations. For example, Şener et al. reported that SII is an effective marker in the diagnosis of acute appendicitis with a sensitivity of 82% and a specificity of 66.7% [18]. Similarly, Tekeli et al. emphasized that SII is a strong biomarker for predicting complicated appendicitis in pediatric patients [19]. Altuğ et al. also noted that SII is a reliable marker for diagnosing acute and complicated appendicitis in pregnant women [20]. These studies support the role of SII as a powerful biomarker reflecting inflammation in various populations and present results consistent with our findings.

Contrary to the general perception of atypical presentations in geriatric patients, this study revealed that a significant portion of confirmed appendicitis cases exhibited classic symptoms, such as migratory pain, right lower quadrant tenderness, and rebound tenderness. These findings are consistent with studies showing that, despite age-related changes, some elderly individuals retain robust inflammatory responses [6, 21]. This highlights the heterogeneity within the geriatric population and suggests that clinicians should not dismiss classic signs in elderly patients when evaluating acute appendicitis [22]. In addition, for patients lacking these signs, appendectomy decisions were based on imaging findings, such as appendiceal diameter on ultrasound or CT, and clinical suspicion based on laboratory markers.

The 29.7% negative appendectomy rate observed in this study reflects the inherent diagnostic difficulties in geriatric patients. These challenges arise from atypical presentations and overlapping symptoms with other abdominal conditions. Similar studies have reported negative appendectomy rates of up to 35% in elderly patients, emphasizing the limitations of current diagnostic modalities [21, 22]. This finding underlines the necessity for further advancements in imaging techniques and diagnostic algorithms to enhance preoperative accuracy in this population.

The negative appendectomy rate of 29.7% in this study, compared to the 9% reported in studies, such as Segev et al. [23], reflects the unique challenges of diagnosing appendicitis in geriatric populations. Several factors contribute to this difference. First, our institution employs a conservative approach for patients with equivocal clinical findings, involving close observation and repeated imaging. When clinical suspicion remains high, surgery is performed to avoid the potentially severe consequences of missed appendicitis, particularly in elderly patients with higher morbidity and mortality risks. Moreover, the alternative diagnoses found in 19 patients without appendicitis, such as diverticulitis (31.6%), ileitis (21.1%), and appendiceal tumors (10.5%), demonstrate the overlap in clinical and radiological presentations with appendicitis. These conditions are well-documented to mimic appendicitis and can complicate diagnostic accuracy in this population. In addition, these alternative conditions frequently require prolonged observation, additional diagnostic evaluations, and tailored therapeutic interventions, such as intravenous antibiotics for diverticulitis or oncological consultations for appendiceal tumors. This explains the longer length of stay (LOS) observed in the non-appendicitis group in this study compared to patients with confirmed appendicitis. The complexity of managing these conditions highlights the challenges of differential diagnosis in geriatric patients presenting with acute abdominal symptoms.

Limitations

This study has several limitations that should be acknowledged. First, the retrospective design may introduce bias due to incomplete or missing data, despite efforts to ensure accuracy in data collection. Second, the study was conducted in a single tertiary healthcare center, which may limit the generalizability of the findings to other settings or populations. In addition, the relatively small sample size, particularly in the non-appendicitis group, may affect the robustness of the statistical analyses. Future studies with larger, multi-center cohorts would be beneficial to confirm the diagnostic accuracy of the SII in geriatric patients with suspected appendicitis.

Conclusion

The SII demonstrated high diagnostic accuracy in distinguishing acute appendicitis from non-appendicitis cases in geriatric patients. Given the diagnostic challenges associated with atypical presentations in the elderly, SII represents a valuable biomarker that can aid in the timely and accurate diagnosis of acute appendicitis. Its integration into clinical practice may improve diagnostic decision-making and outcomes in this vulnerable population. Further prospective studies are needed to validate these findings and explore the potential of SII in broader clinical settings.