Can LUC differentiate complicated appendicitis in the geriatric age group?

Authors

Abstract

Aim Appendicitis in the geriatric age group accounts for 5%-10% of all acute appendicitis. In this study, we aimed to find out the diagnostic value of LUC, which is investigated as a new inflammatory parameter in acute complicated appendicitis in patients over 65 years of age, and whether WBC, neutrophil, lymphocyte, monocyte, platelet count, NLR, lymphocyteto-monocyte ratio (LMR), CRP and DNI, procalcitonin, can differentiate complicated appendicitis in geriatric age group.
Materials and Methods Between January 2020 and December 2023, 274 patients aged ≥65 years who were operated for acute appendicitis at Ankara Bilkent City Hospital and histopathologically proven to have acute appendicitis were included in the study. Patients were divided into two groups according to the pathology report: simple-noncomplicated appendicitis or complicated appendicitis (intra-abdominal abscess, gangrene/necrosis, perforation). Demographic and clinical characteristics, laboratory findings, surgical procedure, and histopathologic results were obtained from the patients’ medical records. Non- complicated and complicated groups were compared in terms of LUC at diagnosis as well as WBC, neutrophil, lymphocyte, monocyte, platelet count, NLR, lymphocyte-to-monocyte ratio (LMR), CRP, and DNI values.
Results WBC, neutrophil, lymphocyte, monocyte, L/M ratio, N/L ratio, and procalcitonin values were significantly higher in the complicated appendicitis group.
Discussion We think that the LUC value cannot distinguish complicated appendicitis in a patient over 65 years of age diagnosed with acute appendicitis; other parameters that we found to be significant should be taken into consideration, and we can plan the treatment accordingly.

Keywords

Introduction

Acute appendicitis (AA) is the most common cause of acute abdominal pain requiring surgery [1] and has a lifetime incidence of approximately 7% [2]. Appendicitis in the geriatric age group accounts for 5%-10% of all acute appendicitis cases [3]. According to the World Health Organization, the geriatric age group is divided into three age groups: early senility, between the ages of 65 and 74; old age, between the ages of 75 and 84; and advanced old age.
(superelderly), at ages 85 and older. Therefore, the prevalence of appendicitis in the geriatric group is expected to increase in the future.
Since it is less common in elderly patients and presents age- specific differences, its diagnosis and treatment involve certain challenges. In this age group, complications and mortality associated with appendicitis are more frequent due to delayed diagnosis and higher prevalence of comorbidities [4]. In elderly patients, the lumen narrows due to fibrosis and vascular sclerosis of the appendix, and the muscle layers become thinner as a result of fat infiltration. These changes increase the risk of perforation [5]. It has been reported that complicated appendicitis resulting in perforation is 70% more frequent in this age groupand morbidity is higher [6]. Given the increased morbidity and mortality of complicated appendicitis in elderly patients, it becomes even more crucial to detect and plan the treatment of appendicitis before complications develop in this group. Surgical treatment for uncomplicated appendicitis is associated with low complication rates, while conservative treatment with antibiotics is successful in the majority of cases [7].
It is crucial to determine whether acute appendicitis is associated with complications, particularly in patients with comorbidities and for whom surgery is not the first-line treatment. In acute appendicitis, markers indicating acute inflammation may be observed as normal at very low rates [8], but they are elevated in the majority of cases, and studies in this field have focused on identifying which inflammatory parameter is specifically elevated. Many inflammatory markers have been investigated for diagnosing acute appendicitis, particularly to differentiate between complicated and uncomplicated cases.
White blood cell (WBC) and C-reactive protein (CRP) are the most commonly employed markers, and recent studies have increasingly investigated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratio [9] and delta neutrophil index [10] and hyponatremia [11]. On the other hand, studies on the diagnostic value of laboratory parameters in complicated acute appendicitis in geriatric patients remain limited.
The LUC value is a component of the complete blood count that reflects activated lymphocytes and peroxidase-negative cells, and is also a novel marker that provides information on the course of infection [12]. While there has been a recent increase in studies on the LUC value and its differential diagnostic value in acute complicated appendicitis [13], the research in the geriatric patient group remains limited.
In this study, we aimed to evaluate the diagnostic value of LUC, a novel inflammatory marker, in acute complicated appendicitis among patients aged over 65 years, and we also assessed whether WBC, neutrophil, lymphocyte, monocyte, platelet count, NLR, lymphocytetomonocyte ratio (LMR), CRP, DNI, and procalcitonin can differentiate complicated appendicitis in the geriatric age group.

Materials and Methods

The study was designed as a single-center, retrospective study, between January 2020 and December 2023, and 274 patients over the age of 65 who underwent surgery for acute appendicitis in Ankara Bilkent City Hospital, and histopathologically confirmed to have acute appendicitis, were included in the study. Patients were divided into two groups according to the pathology report: simple noncomplicated appendicitis or complicated appendicitis (intra-abdominal abscess, gangrene/ necrosis, perforation). Demographic and clinical characteristics, laboratory findings, surgical procedures, and histopathological results were obtained from patients’ medical records.
WBC, neutrophil, lymphocyte, monocyte, platelet count, NLR, lymphocyte-to-monocyte ratio (LMR), LUC%, CRP, and DNI values at diagnosis were compared between the uncomplicated and complicated appendicitis groups. Pregnant women, patients receiving chemotherapy or immunosuppressive agents for any reason, patients being treated for acute bacterial or viral infections, and patients with known immunodeficiency disorders were excluded from the study.SPSS 27.0 package program was used for statistical analyses (IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp). A p-value less than 0.05 was considered statistically significant. Descriptive analyses of the variables were performed, with categorical variables presented as numbers and percentages, and continuous variables reported as median, Q1, and Q3 values. The Pearson chi-square test was used for independent categorical variables. The normality of continuous variables was assessed using the Shapiro-Wilk and Kolmogorov-Smirnov tests. Continuous variables were compared between categorical groups using the Mann-Whitney U test due to non-normal distribution. Variables associated with mortality were included in the logistic regression analysis using the Enter method, and the results were reported as odds ratios (OR), 95% confidence intervals, and p-values.
Ethical Approval
This study was approved by the Ethics Committee of Bilkent City Hospital (Date: 2025-05-30, No:TABED 2-25-1108).

Results

WBC, neutrophil, lymphocyte, monocyte, L/M ratio, N/L ratio, and procalcitonin values were statistically significantly higher in the complicated appendicitis group (Tables 1 and 2).
When evaluating the relationship between patients’ demographic and laboratory findings and pathological results, WBC, neutrophil %, and procalcitonin values were statistically significantly higher in the complicated appendicitis group (Table 1). Furthermore, when the correlation between age and laboratory values with pathological findings was examined, it was determined that WBC, neutrophil %, lymphocyte %, N/L ratio, L/M ratio, and procalcitonin values were significantly higher (Table 2). No relationship was found with gender, type of surgery, platelet count, monocyte count, CRP, LUC, LUC%, or DNI.

Discussion

In designing this study, before evaluating other inflammatory parameters, we aimed to find the answer to the question of whether we can reach results suggesting that appendicitis is complicated by looking at the LUC value and whether we can consider medical treatment in this age group with high surgical morbidity, in the geriatric patient group diagnosed with acute appendicitis. However, we found that the LUC parameter could not distinguish complicated appendicitis in geriatric patients, and the most significant parameters for diagnosing complicated acute appendicitis in patients aged over 65 years were WBC, neutrophils, lymphocytes, NLR, LMR, and procalcitonin.
Erdinç et al. [13] reported that the LUC value can indicate complications in acute appendicitis in the patient group with a normal WBC count. This finding is particularly valuable for resolving the uncertainties that create doubt in the diagnosis with a normal WBC count, especially when the LUC value is not examined. Although the LUC value indicating complicated appendicitis when WBC is normal creates a strong suspicion for the diagnosis of perforated appendicitis based on the LUC value alone, this study found that whether the WBC count was normal or high in the geriatric age group is not a significant marker. Immune ageing, also called immunosenescence, results in a decline in the immune system function as a process, affecting the composition, amount, and function of all organs and cells and cytokines involved in the immune response [14]. We suggest that the decreased or inadequate capacity of patients in the geriatric age group to develop immune responses due to immunosenescence, compared to healthy young people, younger adults, and adults, may contribute to this finding.
On the other hand, leukocytosis, a commonly used and well-known parameter, is an inflammatory laboratory marker expected to be seen in the diagnosis of acute appendicitis (AA), but unfortunately, its specificity and sensitivity are not high. Guidelines recommend that a high leucocyte count should be evaluated significantly in the diagnosis of AA in the geriatric age group (Strong recommendation, low quality evidence) [5]. Studies across all age groups have shown that the specificity and sensitivity of the diagnostic value of leukocytosis in acute appendicitis vary widely [15]. Therefore, it may not always be possible to distinguish complicated cases, especially in the elderly patient group. Although guidelines state that WBC elevation is significant primarily for the diagnosis of appendicitis, since WBC, neutrophil, lymphocyte values were significantly higher in the complicated AA group in this study, we think that when we observe high leukocyte values, we should also consider complicated appendicitis in elderly patients, in the same way as studies [16] stating that neutrophil and lymphocyte values are significantly higher in perforated appendicitis in close relation with leukocytosis.
Studies have shown that procalcitonin, a universally well-known inflammatory parameter and frequently used in the diagnosis of appendicitis, is significant in detecting complicated appendicitis [17]. Although these studies included patients of all ages, our findings indicate that procalcitonin is also significant in differentiating complications in the elderly patient group in our study, and when we observe high procalcitonin values, our results suggest that we are faced with complicated appendicitis in geriatric patients, and treatment should be planned accordingly. CRP is the most widely recognized marker of inflammation and is the parameter most commonly evaluated by clinicians, together with WBC and procalcitonin. As an acute phase reactant, CRP starts to rise after leukocyte counts increase, typically between the 8th and 12th hours of inflammation, and reaches its highest levels in the 24th-48th hours [18]. Although some studies found that CRP elevation alone may suggest acute appendicitis, it is significant in terms of perforation in the elderly patient group [19] or may indicate complications in all age groups [20], our study concluded that CRP value was not significant in the diagnosis of complicated appendicitis in the elderly patient group. Our findings indicate that CRP elevation was not seen in the elderly and complicated group. Considering the physiopathology of CRP, this study suggests that the fact that CRP levels, which are expected to rise especially after seeing high WBC levels, are not significantly elevated to help diagnose complicated appendicitis should be attributed to the decreased ability of elderly patients to develop an inflammatory response.
Delta neutrophil index (DNI) is a new inflammation marker that has been frequently studied recently. Although previous studies suggest that DNI is important in differentiating complicated appendicitis in elderly patients [10], our study found the opposite result and showed that DNI was not discriminative for the diagnosis of complicated appendicitis in elderly patients. Numerous studies have evaluated the diagnostic value of NLR and LMR, which are inflammation markers derived from proportional counts of peripheral blood cells, in acute appendicitis [21, 22]. Studies for both parameters report a wide range in terms of the ability to differentiate geriatric complicated appendicitis. However, our study suggests that both proportional parameters are discriminative for the development of complicated appendicitis in the elderly patient group.

Limitations

Since the retrospective nature of this study does not allow us to see the post-treatment results of the data we obtained, we think that it would be appropriate to plan this study prospectively together with a morbidity and mortality study, which could yield more significant results with the prospective arm. In addition, the determination of cut-off values for the inflammation parameters across different age groups, which were not included in this study, is expected to improve the diagnostic accuracy of these markers, and we believe that a study planned in this way would likely make a significant contribution to our research topic.

Conclusion

In conclusion, it is important to identify highly accurate blood parameters that can differentiate complicated appendicitis in elderly patients with clinical and imaging findings suggestive of acute appendicitis, but it is also known that inflammatory parameters are less significant in the differential diagnosis in geriatric patients [16]. The primary aim of this study was to understand the ability of the LUC value to differentiate complicated appendicitis in the geriatric age group and to find out whether it has a diagnostic value, relative to other inflammation parameters. However, we found that the LUC parameter could not differentiate complicated geriatric appendicitis. This finding may be attributed to the influence of immunosenescence on large unstained cells (LUC).
The results of studies evaluating inflammatory biomarkers to aid in diagnosing acute appendicitis are quite heterogeneous when different age groups are considered. Research in this area focuses on identifying a parameter with an accuracy and specificity that can override others among highly variable symptoms, imaging, and laboratory findings. However, especially in the geriatric age group, considering that the immune response development capacity of patients is more variable than in young people and the course of diseases has a different physiopathology, completely different results are observed compared to other age groups. According to the results of our study, we suggest that appendicitis should not be considered complicated based solely on the LUC value among the inflammation indices in a patient diagnosed with acute appendicitis over 65 years of age; other parameters that we found to be significant should also be taken into consideration, and treatment can be planned accordingly. The inflammation process is an extremely complex condition, influenced by many factors such as age, gender, disease, medication, and even psychological state. At the same time, it is a heterogeneous process with variable diagnostic outcomes. Therefore, it does not seem possible to finalize the diagnosis using inflammatory markers alone, especially in patients over 65 years of age, due to altered disease physiopathology, as observed in our study. Inflammation parameters, which have been found to be accurate between 18-65 years of age in many studies, do not yield the same results in the geriatric population, as found in this study. We believe that the LUC value, which has been investigated in recent studies, is not discriminative for complicated appendicitis in the geriatric age group, that the immune response develops differently after 65 years of age, and that it is not possible to finalize the diagnosis by evaluating only LUC without considering other markers. In addition, a study including a medical follow-up arm would provide greater value. On the other hand, the question of why some parameters are affected by immunosenescence, i.e., immune ageing, while others are not, should be the subject of a separate study.

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