Appendicolith in non-operative management of acute appendicitis: Implications for recurrence and future directions

Abstract

Appendicoliths are frequently encountered in acute appendicitis (AA) and historically considered a risk factor for treatment failure in nonoperative management (NOM). However, the impact of appendicoliths on recurrence rates in uncomplicated AA remains controversial. This editorial critically appraises the study by Kupietzky et al, which explored the relationship between appendicolith characteristics and NOM outcomes. Kupietzky et al conducted a retrospective analysis of 797 patients with uncomplicated AA, comparing recurrence rates between those with and without appendicoliths. The study focused on long-term follow-up (median 44.2 months) and subgroup analyses of stone characteristics. The study revealed no significant difference in overall recurrence rates between groups (26.5% vs 19.1%, P = 0.14). However, patients with appendicoliths experienced earlier recurrence (3.9 months vs 5.9 months, P = 0.04) and had larger appendix diameters (10.2 mm vs 8.5 mm, P = 0.001). Subgroup analyses showed no correlation between stone size, location, or number and recurrence risk. Appendicoliths do not independently increase the overall recurrence risk after NOM for uncomplicated AA but may accelerate recurrence timelines. Clinical decisions should prioritize individualized risk assessment, considering patient age, symptom severity, and radiological features. These findings challenge traditional paradigms and advocate for shared decision-making between clinicians and patients.

Key Words: Acute appendicitis; Conservative treatment; Appendectomy; Nonoperative management; Surgical intervention

Core Tip: Kupietzky et al’s study challenges traditional paradigms by demonstrating that appendicoliths alone do not independently elevate long-term recurrence risks in uncomplicated acute appendicitis, thereby reframing nonoperative management as a viable option for low-risk patients. Instead, clinical decisions should prioritize individualized risk assessments—incorporating symptom severity, imaging markers (e.g., appendix diameter > 1 cm), and shared decision-making with patients—while emphasizing close surveillance (especially within the initial 6-12 months) to enable timely intervention for recurrences.

TO THE EDITOR

Acute appendicitis is a common surgical emergency, traditionally managed by appendectomy. However, the advent of effective antibiotic therapies has prompted a shift towards non-operative management (NOM) for uncomplicated cases, offering patients a less invasive treatment option. One of the main concerns with NOM is the risk of recurrence, which can vary significantly based on patient characteristics and disease severity. Appendicolith, a calcified deposit within the appendix, has been implicated in the pathogenesis of acute appendicitis (AA) and is often perceived as a predictor of treatment failure and recurrence.

In their study, Kupietzky et al[1] set out to elucidate the role of appendicolith and its specific characteristics in influencing the recurrence rate after NOM of AA. By retrospectively analyzing a large cohort of patients, the authors aimed to provide evidence-based guidance for clinicians faced with the challenging decision of whether to offer NOM to patients with appendicolith.

The study by Kupietzky et al[1] represents an important contribution to the growing body of literature on NOM of AA. By focusing specifically on patients with appendicolith, the authors have addressed a significant gap in knowledge regarding the impact of this radiological finding on long-term outcomes.

SIGNIFICANCE OF THE STUDY

The most novel and clinically relevant finding of the study is that the presence of an appendicolith does not significantly increase the overall recurrence rate following NOM of AA. This contradicts the prevailing notion that appendicolith is a harbinger of treatment failure and recurrence. Instead, the authors demonstrate that while patients with appendicolith may experience a recurrence sooner than those without, the overall recurrence risk remains comparable. This finding has important implications for patient counseling and risk stratification. Clinicians can now inform patients with appendicolith that while they may have a higher chance of experiencing an earlier recurrence, the absolute risk of recurrence remains low, and NOM remains a viable option.

Another important insight from the study is the lack of influence of appendicolith characteristics (number, size, and location) on recurrence rates. This suggests that the presence of an appendicolith alone, regardless of its specific features, does not independently predict recurrence. This finding challenges the need for intricate radiological assessment of appendicoliths in the context of decision-making for NOM.

STRENGTHS OF THE STUDY

The study by Kupietzky et al[1] boasts several strengths that enhance its credibility and generalizability. First, the large sample size of 797 patients provides robust statistical power to detect meaningful differences in recurrence rates. Second, the retrospective nature of the study allowed for the inclusion of a heterogeneous patient population, reflecting real-world clinical practice. This enhances the external validity of the findings. Third, the authors meticulously documented patient characteristics, radiological findings, and outcomes, enabling a comprehensive analysis of the impact of appendicolith on recurrence.

LIMITATIONS AND CONSIDERATIONS

Despite its strengths, the study by Kupietzky et al[1] is not without limitations (Table 1). The retrospective design introduces the potential for selection bias and information bias. Patients with appendicolith who underwent surgery were excluded, potentially skewing the recurrence rates in the NOM group. Additionally, the follow-up period varied among patients, potentially underestimating the true long-term recurrence rate in the appendicolith group. Another consideration is the generalizability of the findings to different patient populations. The study was conducted in a single institution, and the results may not apply to all settings. Furthermore, the study included only patients with uncomplicated AA, and the findings may not extend to those with complicated disease.

Table 1 Limitations of the Kupietzky et al’s study[1].

Limitation type	Specific issue	Potential impact
Design limitations	Retrospective design prone to selection/information bias; Excluded patients with complicated appendicitis	Recurrence rates in NOM group may be skewed; Findings may not generalize to mixed populations
Sample size/Power	Only 68 patients with appendicoliths (8.5% of cohort); Follow-up duration varied (median 44.2 months)	Underpowered to detect subgroup differences; Long-term recurrence risks underestimated
Clinical Heterogeneity	Multiple surgeons involved in NOM decisions; Non-standardized imaging follow-up protocols	Variability in intervention consistency; Reduced reliability of results
External validity	Single-center study (Hadassah Medical Center, Israel)	Findings may not apply to other healthcare settings or cultural contexts

NOM: Nonoperative management.

COMPARISON OF KUPIETZKY ET AL’S STUDY WITH EXISTING RESEARCH

Kupietzky et al’s research[1] aligns with existing systematic reviews in confirming that appendicoliths are associated with an increased risk of recurrence after NOM for uncomplicated AA. While their retrospective analysis of 797 patients did not identify a statistically significant difference in overall recurrence rates between groups with and without appendicoliths (26.5% vs 19.1%, P = 0.14), the study highlighted shorter recurrence times (3.9 months vs 5.9 months, P = 0.04) and larger appendix diameters (10.2 mm vs 8.5 mm, P = 0.001) in the appendicolith group. These findings are corroborated by systematic reviews, such as one reporting a 2.75-fold higher recurrence risk in patients with appendicoliths (odds ratio [OR] = 2.75; 95% confidence interval [CI]: 1.05-7.20)[2,3], and mechanistic studies attributing this risk to mechanical obstruction and bacterial overgrowth[3]. Clinical guidelines uniformly recommend prioritizing surgical interventions, such as laparoscopic appendectomy, to mitigate recurrence risk[4,5].

Key controversies

Recurrence rate discrepancy: Kupietzky et al’s study[1], limited to uncomplicated cases, observed no significant difference in overall recurrence rates between patients with and without appendicoliths (26.5% vs 19.1%, P = 0.14). However, their analysis revealed a critical nuance: Patients with appendicoliths experienced earlier recurrence (median 3.9 months vs 5.9 months, P = 0.04), even if the cumulative risk remained comparable over longer follow-up. This distinction challenges the assumption that appendicoliths uniformly worsen outcomes. In contrast, prior studies of mixed populations (including complicated appendicitis) reported a 2.75-fold higher risk of recurrence in appendicolith carriers (OR = 2.75; 95%CI: 1.05-7.20)[6]. The discrepancy likely arises from heterogeneous study populations (Table 2).

Table 2 Comparative analysis of the impact of appendicoliths on nonoperative management of uncomplicated acute appendicitis.

Dimension	Conclusion of Kupietzky et al’s study[1] conclusion (797 patients)	Conclusion of other studies (systematic reviews/meta-analyses)	Difference in perspective
Overall recurrence rate	No significant difference (26.5% vs 19.1%, P = 0.14)	Significantly increased (OR = 2.75; 95%CI: 1.05-7.20)	Study populations differ (current study restricted to uncomplicated cases; other studies include complicated cases)
Treatment failure rate	No statistical difference (26.5% vs 19.1%, P = 0.14; short-term follow-up within 30 days)	Significant failure (OR = 0.42; 95%CI: 0.21-0.84; long-term follow-up including 30 days to 2 years)	Definition of failure varies (short-term vs extended follow-up)
Impact of appendicolith characteristics	No correlation with recurrence (sample size n = 68; insufficient power for subgroup analysis)	Stone size, location (e.g., proximal), and number may increase risk (mechanistic studies suggest mechanical obstruction)	Limited by sample size and study design
Pediatric patients	Not specifically analyzed (mean age 254 years)	Stronger negative impact in children	Age stratification missing
Clinical recommendations	Prioritize surgery (e.g., laparoscopic appendectomy); if NOM is chosen, close surveillance is warranted	Recommend surgery for appendicoliths; inform patients of recurrence risks (approximately 23%-30%) and consider interval appendectomy	Variability in evidence strength

NOM: Nonoperative management.

Definition of treatment failure: The study focused on short-term failure (within 30 days, 26.5% recurrence), while others incorporated extended follow-up periods (30 days to 2 years)[7-9], leading to divergent conclusions.

Role of appendicolith characteristics: With only 68 appendicolith cases (8.5% of the cohort), Kupietzky et al’s study[1] lacked statistical power to evaluate the impact of stone size, location, or number. Mechanistic studies, however, suggest that proximal or larger stones may exacerbate inflammation.

For patients with appendicoliths, multiple studies advocate for surgical intervention (e.g., laparoscopic appendectomy) over conservative management[6,10]. If NOM is pursued, close imaging surveillance is essential, given the elevated recurrence risk (23%-30%)[6,11], and interval appendectomy is often recommended to reduce recurrence and address undiagnosed malignancies[12]. In summary, appendicoliths represent a critical risk factor for recurrent disease in NOM of uncomplicated AA. Clinical decision-making should balance surgical and conservative approaches, with individualized risk assessment based on patient-specific factors.

GUIDANCE ON SURGICAL INTERVENTION AND MEDICO-LEGAL CONSIDERATIONS

NOM is primarily indicated for uncomplicated AA, with evidence of safety and efficacy demonstrated in both children and adults. For instance, the initial success rate of NOM in pediatric patients can reach up to 73.1%[13]. However, some cases may subsequently require surgical intervention. Special high-risk groups, such as elderly patients and those with compromised immune function, necessitate careful evaluation[14,15], as they are more prone to gangrene or perforation when complicated by appendicolith. The overall recurrence rate of NOM is approximately 18%. Large appendicoliths (> 1.5 cm) or a proximal location may increase the risk of mechanical obstruction. Persistent leukocytosis or worsening abdominal pain (unresponsive to antibiotics for more than 48-72 hours) are signs of NOM failure[5,16]. Compared with surgery, NOM can shorten the length of hospital stay but is associated with higher rates of readmission and subsequent surgical needs. In pediatric patients, the complication rate of NOM is comparable to that of surgery, so the risk of recurrence needs to be carefully weighed. The absolute indications for surgical intervention include complicated appendicitis (perforation, abscess, and peritonitis), high-risk features associated with appendicolith (large appendicolith and radiological evidence of free fluid or local peritonitis), and failure of NOM. For special populations, such as elderly patients and those with compromised immune function, surgery is generally preferred due to delayed diagnosis, a higher risk of perforation, and an increased likelihood of infection progression.

In terms of forensic medicine and informed consent, it is imperative to clearly inform patients about the recurrence risk of NOM, the possibility of subsequent surgery, and potential complications. A comparison of the pros and cons of NOM and surgery should also be provided. Standardized informed consent documents can help reduce legal disputes. Moreover, patient preferences should be incorporated into the treatment decision-making process, and the discussion should be documented, including an assessment of the patient's adherence to follow-up.

For high-risk cases, it is advisable to prioritize surgery to avoid adverse outcomes caused by delays in NOM. Adhering to institutional guidelines and meticulously documenting the basis for clinical decisions can mitigate the risk of medical disputes.

In summary, NOM can serve as an alternative for selected cases of uncomplicated appendicitis, but stringent patient selection and close monitoring are essential. Surgery remains the first-line treatment for complicated cases or high-risk populations, particularly the elderly, those with compromised immune function, or those with appendicolith-related complications. Compliance with forensic medicine standards hinges on adequate informed consent, shared decision-making, and standardized documentation, emphasizing the importance of individualized treatment and risk communication.

FUTURE DIRECTIONS

Building on Kupietzky et al’s findings[12], future investigations should prioritize actionable, evidence-based pathways to optimize NOM outcomes in appendicolith-positive patients. Below is an expanded roadmap for research and implementation.

Prospective multicenter validation studies are urgently needed to confirm these findings across diverse populations, incorporating international registries that account for age, comorbidities, and stone characteristics while extending follow-up periods to elucidate long-term recurrence patterns and antibiotic stewardship efficacy.

Precision medicine approaches hold promise through the development of machine-learning algorithms integrating clinical, imaging, and stone-specific biomarkers to refine risk stratification and personalize surveillance protocols, enabling tailored interventions based on individual recurrence risk profiles.

To enhance the success rates of NOM for appendicolith-positive appendicitis, it is crucial to advance minimally invasive solutions through a multifaceted approach. Novel diagnostic and therapeutic modalities should consider fecal calprotectin, gut microbiome signatures, and image-guided endoscopic stone removal as minimally invasive alternatives. Additionally, pharmacological adjuncts aimed at biofilm disruption and inflammation reduction can be incorporated. Among these potential solutions, endoscopic retrograde appendicitis therapy (ERAT) shows great promise as a minimally invasive substitute for surgery, particularly for patients with obstructive stones larger than 1 cm. These trials can assess the procedural efficacy of ERAT and determine the long-term recurrence rates, thereby providing valuable insights for optimizing the management of appendicolith-positive appendicitis.

Global implementation strategies must address disparities in resource-limited settings through simplified clinical prediction rules and community health worker training, coupled with digital decision aids to enhance shared decision-making and patient engagement.

Finally, cost-effectiveness analyses are critical to quantify the long-term economic impact of NOM vs early appendectomy, balancing healthcare expenditures, recurrence-related morbidity, and societal productivity losses. These integrated efforts will advance precision care for appendicolith-positive appendicitis, ensuring equitable, evidence-driven management globally.

CONCLUSION

In conclusion, the study by Kupietzky et al[1] provides valuable insights into the impact of appendicolith on recurrence after NOM of AA. By demonstrating that the presence of an appendicolith does not significantly increase the overall recurrence rate, the authors have challenged long-standing perceptions about the role of appendicolith in predicting treatment outcomes. Their findings have important implications for patient counseling, risk stratification, and the broader adoption of NOM for uncomplicated AA.