Appendicolith as a Sign of Complicated Appendicitis: A Myth or Reality? A Retrospective Study

Appendicolith, which is a conglomeration of firm feces and some mineral deposits in the lumen of the appendix [1], can be incidentally found on abdominal computer tomography (CT) without any signs of appendicitis [2]. Most appendicoliths are asymptomatic, but they may also obstruct the lumen of the appendix and can be associated with appendicitis [2]. However, as a risk factor for appendicitis [3], it has also been reported to be a risk factor for failure of nonoperative management in acute appendicitis [4‒6].

Although appendectomy is the most common emergency operation in general surgery, in recent years, increasing evidence suggests broad-spectrum antibiotics as an alternative treatment option for acute appendicitis [4, 7, 8]. Randomized studies and meta-analyses have shown that nonoperative management of uncomplicated acute appendicitis is comparable with the results of surgical treatment [5, 9, 10]. In their study (the APPAC trial), Salminen et al. [10] concluded that even a 5-year follow-up supports the feasibility of antibacterial treatment for acute appendicitis despite a 39% probability of recurrence within 5 years. In addition, in the APPAC trial, the patients were included in the cost-effectiveness analysis, demonstrating lower costs of antibiotic therapy than surgical therapy [11].

Considering the clinical and economic efficacy, it is essential to apply selection criteria for successful nonoperative treatment of acute appendicitis to reduce postoperative complications and medical costs. These criteria should also include the presence of appendicolith, which some studies have associated with a higher risk of appendiceal perforation [12]. Some studies have found it in 28% of patients with negative appendectomies [13]. The present retrospective study aimed to evaluate whether appendicolith predicts complicated appendicitis in patients with any appendicitis.

A retrospective chart review was done for all adult patients (aged ≥18 years) who underwent appendectomy or laparoscopy and drainage for acute appendicitis at Tartu University Hospital in the period from January 2016 to December 2018.

The following data were collected: demographic data, body mass index, duration of symptoms (from the patient-reported onset until arrival to the emergency department), body temperature at admission (°C), results of blood tests (white blood cell count, C-reactive protein [CRP]) at admission, CT finding (presence of appendicolith), surgical method (laparoscopic appendectomy, open appendectomy, laparoscopy and drainage, drainage in addition to appendectomy), operative finding (catarrhal, phlegmonous, gangrenous, gangrenous perforative appendicitis, no acute inflammation, another finding), duration of operation (min), postoperative antibacterial treatment, and finding of histological specimen (catarrhal, phlegmonous, gangrenous, gangrenous perforative appendicitis, other).

Appendicolith was considered present when it was visualized in CT scans in patients with acute appendicitis. Patients without a CT scan were excluded from the study (Fig. 1). CT for suspected acute appendicitis was conducted more often than usual during the study period because of another ongoing clinical study of acute appendicitis at Tartu University Hospital (“Uncomplicated acute appendicitis: antibacterial treatment vs. surgical treatment”; unpublished). Appendicitis was considered a complicated disease in the case of gangrenous or gangrenous perforated appendicitis in the histology report. To avoid inconsistency in the interpretation of data, all data were recorded by the same author.

The software package Statistica version 13.3 (TIBCO Software Inc., USA) was used for statistical analysis. Continuous variables were expressed as means with standard deviation in the case of normally distributed variables or medians with 25% and 75% percentiles in the case of a nonnormal distribution. Categorical variables were presented in counts and percentages. Comparison between the study groups was made using Pearson’s chi-square or Fisher’s exact test for categorical data. t test was used for normally distributed variables, and the Mann-Whitney U test was used for non-normally distributed variables. A multivariate logistic regression model was employed to check for appendicolith as a sign of complicated appendicitis adjusted for confounding variables: sex, age group (age ≤50 vs. >50 years), and duration of symptoms (≤24 vs. >24 h). All statistical tests were two-sided; p < 0.05 was considered statistically significant.

During the 3-year study period (2016–2018), 709 patients with acute appendicitis were admitted to Tartu University Hospital. Nonsurgical management was used in 75 cases (due to participation in another unpublished study), and surgical treatment without a CT scan was administered in 367 cases. These patients were excluded from the analysis, leaving 267 patients for the study (Fig. 1).

Table 1 shows the clinical baseline characteristics of the 267 patients. Patients with appendicolith had a higher mean white blood cell count than patients without appendicolith (p = 0.008), but this was a clinically insignificant difference (Table 1). All other baseline characteristics were similar.

In the CT scan, appendicolith was found in 120 cases (44.9%, 95% CI: 38.9–51.1) and was absent in 147 cases (Fig. 1). Although clinically insignificant, a comparison of the diameter of the appendix between the study groups with appendicolith and without appendicolith revealed that in the case of appendicolith, the mean diameter of the appendix was significantly larger (12.5 and 11.5 mm, respectively, p = 0.011). There was no significant difference between the appendicolith and the no appendicolith groups regarding the presence of free fluid in the right lower abdominal quadrant in CT scans (31.7 and 29.9%, respectively, p = 0.760). In the appendicolith group, there were significantly more patients with free fluid in the other abdominal regions (including the pelvic area) (39.2 and 23.8%, respectively, p = 0.007). The presence of periappendicular infiltration was observed in both study groups in 80% of the cases. Free gas in the right lower quadrant, as well as in the other abdominal regions, was infrequently present in the patients of both study groups (in the right lower quadrant, 9.2% in the appendicolith group and 6.1% in the no appendicolith group, p = 0.347; in the other abdominal regions, 1.7 and 2%, respectively, p = 0.999).

Table 2 presents the operative data. The rate of complicated appendicitis was higher in the appendicolith group (45% vs 32.6%, p = 0.039).

According to the pathology reports, the histological findings of specimens in the appendicolith and no appendicolith groups were the following: catarrhal appendicitis, 2.5 and 4.8%; phlegmonous appendicitis, 50.8 and 66%; gangrenous appendicitis, 34.2 and 19.1%; gangrenous perforated appendicitis, 12.5 and 10.2%, respectively (p = 0.022).

In 66.4% of the cases in the appendicolith group and 63.5% in the no appendicolith group, the result of the intraoperational evaluation of the appendix was consistent with the final histological finding. Although, in several cases, the surgeon under or overestimated the intraoperational finding versus the histological finding in both groups, there was no difference between the groups (p = 0.931).

In the case of complicated appendicitis (gangrenous and gangrenous perforated appendicitis in the histology report), an appendicolith was visible in the CT scan in 57.7% (95% CI: 47.3–67.6) of the patients. Of the patients with uncomplicated appendicitis, 38.3% had an appendicolith in the CT scan (p = 0.002).

Univariate analysis revealed that the presence of appendicolith, male sex, age >50 years, duration of symptoms >24 h, and CRP were all associated with complicated appendicitis (Table 3). When the combined effect of these variables was analyzed using logistic regression, only the presence of appendicoliths, male sex, age >50 years, and duration of symptoms >24 h remained significant (Table 3).

The appendicolith group was analyzed based on the duration of symptoms (≤24 h vs >24 h). The results are presented in Table 4. Based on pathology reports, there were significantly more cases of phlegmonous appendicitis in patients with appendicolith in a group with a duration of symptoms ≤24 h (69.7% vs. 27.8%) and more cases of complicated (gangrenous and gangrenous perforated) appendicitis in a group with a duration of symptoms >24 h (28.8% vs. 68.5%) (p < 0.001).

In 59.2% of cases in the appendicolith group and 50.3% in the no appendicolith group, antibacterial treatment was administered postoperatively (p = 0.175). In both groups, amoxicillin/clavulanic acid or cefuroxime plus metronidazole was usually used (p = 0.359). The median duration of hospitalization was 2 days in the appendicolith and no appendicolith study group. The rehospitalization rate to the same hospital within 30 days was 5.8% for the appendicolith group and 2.7% for the no appendicolith group (p = 0.230).

In our study, appendicolith was an independent risk factor for complicated (gangrenous or gangrenous perforated) appendicitis, which is in accordance with previous studies [6]. However, appendicoliths are often asymptomatic and are detected incidentally with CT in an otherwise normal appendix [2].

Like in our study, Vons et al. [5] reported that appendicolith was seen in CT scans in 53% of patients with complicated appendicitis. However, compared to our research, these authors found a much lower rate of appendicolith in uncomplicated cases (15%) [5]. Although less than in our study, Lee et al. [2] had a higher rate of appendicolith in uncomplicated appendicitis cases (23%). We also showed an overall significantly higher rate of appendicolith (44.9%) compared with that reported, e.g., by Flum et al. [6] (27%). Like in our study, Kubota et al. [14] demonstrated a similar rate of appendicolith in acute appendicitis cases (44.6%). In the pediatric cohort, Yoon et al. [12] found the prevalence of appendicolith to be 54.6%. Singh et al. [13] speculate that in different regions of the world, the etiologies of appendicitis might differ. In some areas, appendicolith may play a more critical role in the development of acute inflammation of the appendix [13].

In the case of suspected acute appendicitis, the most common radiological modalities are ultrasound and CT scan [4]. At our hospital, a CT scan is not used as a mandatory modality for diagnosing acute appendicitis, as clinical examination and ultrasound have commonly proved to be sufficient. Ultrasound as the first modality is also recommended by the European Association for Endoscopic Surgery [15]. However, when nonsurgical treatment is considered, a CT scan is the preferred modality in several studies to exclude complicated appendicitis [5, 6]. The CODA Collaborative included patients with appendicolith in their research, comparing antibiotics and surgical treatment for appendicitis, and found that participants with appendicolith were at higher risk for cross-over to the surgery group and for the development of complications [6]. Considering that appendicolith may be a sign of complicated appendicitis, the presence of appendicolith has been an exclusion criterion for nonsurgical treatment in many studies [10, 16]. Also, the World Society of Emergency Surgery’s Jerusalem guideline recommends nonsurgical therapy in selected patients with uncomplicated appendicitis and absence of appendicolith [17]. Interestingly, Mällinen et al. [18] demonstrated that complicated appendicitis with an appendicolith and uncomplicated appendicitis differ in histopathology. In the first case, there is significantly more mucosal damage and microabscesses. They concluded that those differences might be the reason for different outcomes of complicated acute appendicitis with appendicolith and uncomplicated cases [18]. Kubota et al. [14] found that the size of the appendicolith is essential. They concluded that an appendicolith measuring >10 mm in diameter is associated with appendiceal perforation and, therefore, is an indication for surgery [14]. However, Kohga et al. [19] found that the presence of appendicolith was not a risk factor for failure of nonsurgical treatment. Still, incarceration of an appendicolith on CT images was significantly associated with the failure of conservative management of acute appendicitis [19].

According to the literature data, we do not have an ideal method to exclude the presence of appendicolith preoperatively. Kaewlai et al. [20] reported sensitivities in detecting appendicolith on the venous phase CT scan, 88% per appendicolith and 82% per patient. Considering the high sensitivity of CT scans in diagnosing appendicolith and the correlation between appendicolith and complicated appendicitis makes CT scans crucial for excluding complicated appendicitis when planning conservative treatment. However, Mariadason et al. [21] reported CT sensitivity for appendicolith in a cohort of patients with acute appendicitis between 2011 and 2019 to be only 66%. These studies were retrospective, and further high-quality studies are needed. However, Dölling et al. [22] also found in their prospective study that if a CT scan visualized appendicolith in 21% of cases, then intraoperative examination detected the presence of appendicolith in 64% of cases. So, this raises the question of whether a CT scan is always necessary when conservative treatment of acute appendicitis is considered. Of course, a CT scan also enables the visualization of other signs that refer to complicated appendicitis (abscess, extraluminal air, etc.) [23]. Therefore, a low-dose CT scan has become the diagnostic technique of choice in the evaluation of patients suspected of having acute appendicitis in many countries [24].

As expected, duration of symptoms >24 h and older age were also independent risk factors for complicated appendicitis, but the male sex was also a risk factor for gangrenous/gangrenous perforated appendicitis. Previous studies have also reported male sex as a risk factor for complicated appendicitis [25]. However, for understandable reasons, male sex has not been an exclusion criterion in studies comparing nonoperative management and surgical treatment for acute appendicitis [4]. Prospective studies are probably needed to clarify this issue.

Sammalkorpi et al. [26] demonstrated in their study that a longer duration of symptoms of acute appendicitis (median 22 h vs 36 h) was a significant risk factor for the development of complicated appendicitis. We analyzed patients with appendicolith based on the duration of symptoms ≤24 h and >24 h. In our study, patients in the appendicolith group with a longer duration of symptoms were statistically significantly older and had higher mean body temperature at admission. However, clinically, those differences are irrelevant. Sammalkorpi et al. [26] also demonstrated a trend of increased risk for complicated appendicitis along with higher CRP values. In our study, a longer history was associated with higher CRP levels and the development of complicated appendicitis in the appendicolith group.

Our study has some limitations which could not be avoided. First, as this is a retrospective study, a prospective study is needed to confirm the results. Also, mainly because of retrospectivity, some data are missing, which can cause some biases. Second, the study population is relatively small, so fundamental conclusions cannot be drawn. The fact that we included only patients in whom the CT scan had been done might have also caused somewhat biased results. Although a CT scan was not performed because of diagnostic challenges, it might still be that the study population is older, more obese, or with more comorbidities, etc., compared to the average appendicitis cohort. In addition, not all appendicoliths are identifiable on the CT scan, and we do not have data on whether appendicoliths were present in the pathology report so that some biases might have occurred.

Our study found that appendicolith can be considered an independent risk factor for complicated appendicitis. Therefore, in the presence of appendicolith, surgical treatment should probably be preferred over nonsurgical treatment in acute appendicitis.

The study was conducted under the Declaration of Helsinki and was approved by the Research Ethics Committee of the University of Tartu (protocol # 315/T-9; 356/M-11). The need for written informed consent was waived by the Research Ethics Committee of the University of Tartu. The manuscript was edited using Grammarly for grammar and spelling mistakes (www.grammarly.com).

The authors have no conflicts of interest to declare.

No sponsor or funder supported this study.

Conception and design: C.N. and U.L. Data collection: M.M. Statistical analysis: Ü.K. Writing the article: C.N. Critical revision of the article: U.L.

The data supporting this study’s findings are not publicly available due to requirements from the Local Ethics Committee (Research Ethics Committee of the University of Tartu). However, the data can be requested from the corresponding author.