Effectiveness of protocol-based medical treatment in selected uncomplicated acute appendicitis: a retrospective cohort study

Abstract

Objective

To describe the short-term treatment outcomes and intermediate-term appendectomy rates following protocol-based medical treatment in carefully selected patients with uncomplicated acute appendicitis without appendicolith.

Methods

This single-arm retrospective cohort study was conducted at a single tertiary center. Patients with uncomplicated acute appendicitis without appendicolith on computed tomography (CT) were treated following a standardized protocol consisting of intravenous antibiotics, a 48-hour in-hospital observation period, and systematic follow-up. The primary outcome was treatment success during initial hospitalization, defined as symptom resolution and discharge without the need for appendectomy. Secondary outcomes included appendectomy rates and complications during the follow-up period.

Results

Sixty-eight patients received protocol-based medical treatment. All 68 patients (100%) completed initial hospitalization successfully without requiring appendectomy. During a median follow-up of 2.8 years, six patients (8.8%) underwent appendectomy; however, only one of these (1.5%) represented true symptomatic recurrence, while the remaining five (7.4%) underwent surgery for non-clinical reasons including patient preference, anxiety, and pregnancy-related concerns. No major complications were observed among patients managed with antibiotics.

Conclusion

Protocol-based medical treatment achieved complete short-term treatment success in this selected cohort of patients with uncomplicated acute appendicitis without appendicolith. The overall appendectomy rate during follow-up remained low, with true symptomatic recurrence observed in only one patient. These findings, while limited by the single-arm observational design and small sample size, supported the feasibility of this approach when combined with reliable imaging assessment, systematic patient selection, and structured follow-up.

Introduction

Acute appendicitis remains the most prevalent surgical emergency encountered in adult populations worldwide [1, 2]. Since McBurney first described appendectomy in 1894, surgical removal of the appendix has remained the standard treatment for acute appendicitis [1, 3, 4]. However, the advancements in diagnostic imaging techniques, particularly computed tomography (CT), along with the improvements in effective antibiotic treatments, have led to reconsideration of treatment approaches [4, 5].

Over the past two decades, several randomized controlled trials investigated medical treatment as an alternative to appendectomy for uncomplicated acute appendicitis. The Appendicitis Acuta (APPAC) trial excluded patients with appendicoliths and demonstrated a 27% recurrence rate at one year, increasing to 39% at five years among patients treated with antibiotics [4]. More recently, the Comparison of Outcomes of Antibiotics Drugs and Appendectomy (CODA) trial adopted broader inclusion criteria, enrolling patients with appendicoliths, and reported treatment failure rates of 41% in patients with appendicoliths compared to 25% in those without appendicoliths at 90 days [5]. These findings suggested that appendicoliths may have a significant role in the prediction of antibiotic treatment failure.

Systematic reviews and meta-analyses confirmed that medical treatment for uncomplicated appendicitis resulted in lower morbidity, reduced costs, and improved quality of life compared to appendectomy [6, 7]. However, the optimal patient selection criteria for non-operative management remained unclear, particularly regarding the role of appendicoliths in treatment decision-making.

Despite accumulating evidence supporting medical treatment, implementation in clinical practice remained inconsistent, partly due to variability in patient selection criteria and treatment protocols [4–7]. Most existing studies either excluded patients with appendicoliths or included them without stratification, making interpretation of results challenging for clinical application. Additionally, long-term recurrence patterns beyond the first year remained insufficiently characterized in many studies [4–5].

Despite accumulating evidence supporting medical treatment, data on the real-world implementation of APPAC-type antibiotic protocols in routine clinical practice remained limited. Accordingly, the aim of this study was to describe the outcomes of a standardized, protocol-based approach to medical management in patients with uncomplicated acute appendicitis without appendicolith, and to report both short-term treatment success and intermediate-term appendectomy patterns in a real-world clinical setting.

Materials and method

Study design and ethical considerations

This observational retrospective cohort study was conducted at the Department of General Surgery, Duzce University Faculty of Medicine, between January 2020 and December 2024. While the treatment protocol was applied prospectively in clinical practice, data collection and analysis were performed retrospectively, making this a retrospective cohort study. It involved a retrospective review of medical records from patients presenting to the emergency department with acute appendicitis, who were treated by a single surgeon following a consistently applied, standardized treatment algorithm. The study was approved by the Non-Interventional Clinical Research Ethics Committee of Duzce University Faculty of Medicine (Decision No: 2021/113). All patients admitted to the hospital provided general informed consent at the time of admission, which included authorization for the use of anonymized clinical data in research studies. Given the retrospective observational design and the use of fully anonymized data, the Non-Interventional Clinical Research Ethics Committee of Duzce University Faculty of Medicine waived the requirement for additional individual study-specific informed consent. All procedures adhered to the principles outlined in the Declaration of Helsinki.

Patient selection

Patients were identified through systematic review of electronic medical records and surgical databases. Patients were eligible if they were at least 18 years old, had radiologically confirmed acute appendicitis, complete medical records, and were managed by the same surgeon under our institutional protocol during the study. We excluded patients who underwent appendectomy as part of another concurrent surgical procedure, those with suspected appendiceal neoplasms, cases requiring interval appendectomy, and patients with plastron formation requiring initial conservative management followed by delayed surgery. These exclusions were necessary because our primary objective was to evaluate the effectiveness of the applied treatment algorithm in straightforward acute appendicitis cases rather than in complex or unusual presentations.

Diagnostic approach

The diagnosis of acute appendicitis was established through a comprehensive evaluation integrating clinical assessment, laboratory data, and imaging, following the imaging-confirmed standards utilized in the APPAC and CODA trials [4, 5]. While contrast-enhanced abdominal CT scanning served as the primary diagnostic modality to determine disease if the disease is complicated or uncomplicated, we utilized additional ultrasound (US) imaging when necessary to ensure the inclusion of a diverse patient population for whom contrast CT was contraindicated, such as pregnant women or patients with chronic kidney disease. Consistent with established trial criteria, uncomplicated appendicitis was identified by an appendiceal diameter exceeding 6 mm, wall thickening, abnormal contrast enhancement, inflammatory edema in the periappendiceal fat, and periappendiceal fluid accumulation. Critically, we assessed whether the appendiceal lumen remained patent, as this finding was considered particularly important for selecting candidates for nonoperative management. In contrast, complicated appendicitis was defined by the presence of perforation, abscess formation, widespread extraluminal air or fluid, significant phlegmon, or imaging features raising suspicion of an appendiceal neoplasm. We paid special attention to the presence of appendicoliths, which we categorized as a major finding indicating luminal obstruction and a direct indication for surgical intervention, reflecting the increased risk for complications and treatment failure noted in the larger literature and trial subgroups.

Treatment algorithm and patient allocation

The cornerstone of our approach was a systematic, protocol-based algorithm that determined treatment allocation based on specific imaging findings (Fig. 1). This algorithm was applied prospectively to all patients presenting with acute appendicitis during the study period, ensuring consistent decision-making and minimizing variation in treatment selection.

Fig. 1.

Treatment algorithm and patient allocation

To avoid ionizing radiation exposure, pregnant patients did not undergo computed tomography (CT) scans and were instead monitored via serial ultrasonography. No radiological deterioration was observed during the follow-up period. All ultrasound examinations were evaluated through a multidisciplinary approach involving both the Departments of Radiology and Obstetrics and Gynecology. Patients diagnosed with acute appendicitis who demonstrated an appendicolith on CT imaging were scheduled for appendectomy regardless of whether complications had developed. We considered the presence of an appendicolith to be a direct indication for surgical intervention based on published evidence linking appendicoliths to higher rates of treatment failure with medical treatment and increased risk of complicated appendicitis. Similarly, patients who presented with complicated appendicitis, which was defined as perforation, abscess formation, or peritonitis, were offered immediate surgical management.

In contrast, patients whose CT scans showed patent appendiceal lumen without appendicoliths or complicating features were considered candidates for conservative medical management. Before initiating antibiotic therapy, we obtained informed consent from these patients, explaining both the rationale for medical treatment and the alternative option of appendectomy. We emphasized that if clinical or laboratory improvement did not occur within 24 to 48 h, we would proceed with surgical intervention. Patients who declined medical management or expressed strong preference for immediate surgery were referred for appendectomy, either at our institution or at another center of their choosing. Two patients refused definitive treatment at our institution after being informed. They were later reported to have had non-complicated appendectomies at another center outside the province.

Medical management protocol

For patients who consented to medical treatment, we implemented a standardized antibiotic regimen. Initial therapy consisted of intravenous ceftriaxone (1 g twice daily) and metronidazole (500 mg three times daily), administered for 48 h while patients remained hospitalized for observation. During this period, we closely monitored clinical parameters including abdominal pain, tenderness on examination, fever, and appetite, as well as laboratory markers of inflammation. Patients who demonstrated clinical and biochemical improvement after 48 h were transitioned to oral ciprofloxacin (500 mg twice daily) and discharged to complete a 7-day course of medical treatment.

We maintained a low threshold for surgical intervention during the observation period. Any patient who failed to show improvement within 24 to 48 h, or who demonstrated clinical deterioration at any point, was promptly taken to the operating room for appendectomy. This safety mechanism was built into our protocol to ensure that medical management did not delay necessary surgical treatment in patients who were not responding appropriately to antibiotics.

Surgical technique

Appendectomy was performed using a standardized laparoscopic approach in the vast majority of cases. We employed a three-port technique that has become routine in our practice. In a small number of cases where laparoscopic access was not feasible due to extensive adhesions, severe inflammation, or patient-specific factors, we converted to an open approach. All surgical specimens were sent for histopathological examination to confirm the diagnosis and assess the severity of appendicitis.

Follow-up and outcome assessment

Patients who received medical treatment were followed systematically through telephone contact and, when necessary, clinic visits. The date of each follow-up contact was recorded, and patients were specifically asked about any recurrent symptoms, emergency department visits, or subsequent surgical procedures. The primary outcome was treatment success during initial hospitalization, defined as resolution of acute symptoms and discharge without the need for appendectomy. Secondary outcomes included the overall appendectomy rate during follow-up, complications, and time to appendectomy for those who ultimately underwent surgery. For patients in the medical treatment group who underwent appendectomy during the follow-up period, the timing, indication, and operative and pathological findings were carefully documented. Each appendectomy was classified as either clinically indicated (performed for symptomatic recurrence) or non-clinically indicated (performed for patient preference, anxiety, or other non-acute reasons). This distinction was considered important for accurate interpretation of the appendectomy rate, as not all appendectomies after initial medical treatment necessarily represented treatment failure due to disease recurrence.

Data collection and variables

We extracted study data from electronic medical records, including demographic information (age, sex), clinical presentation details, laboratory values at admission, CT imaging reports and findings, treatment allocation (medical versus surgical), details of medical management for those receiving antibiotics, operative findings and techniques for those undergoing surgery, histopathological reports, complications, and long-term follow-up outcomes.

For patients in the surgical group, we specifically recorded the indication for surgery (appendicolith, complicated appendicitis, or perforated appendicitis and compared preoperative) imaging findings with intraoperative observations and final pathology reports to assess the accuracy of our imaging-based treatment algorithm.

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA). Continuous variables are presented as mean ± standard deviation (SD) for normally distributed data or as median with interquartile range for non-normally distributed data, if present. The normality was assessed using the Shapiro-Wilk test and visual inspection of histograms. Categorical variables are reported as frequencies and percentages.

Within the medical treatment group, baseline characteristics between patients who completed treatment successfully and those who ultimately underwent appendectomy were examined descriptively.

To describe the temporal pattern of appendectomies in the medical treatment group, Kaplan-Meier analysis was performed with appendectomy (for any reason) as the event of interest. Patients who completed follow-up without undergoing appendectomy were censored at their last contact date. Given that appendectomies in this cohort included both clinically indicated procedures and those performed for non-clinical reasons, this analysis was intended as a descriptive representation of appendectomy-free status over time rather than a conventional failure analysis assuming a uniform endpoint. As a sensitivity measure, the recurrence-free rate was also calculated after excluding non-clinically indicated appendectomies.

The 95% CIs for success rates were also calculated using the Wilson score method, which provides more accurate intervals for proportions, particularly when the proportion is close to 0 or 1. Statistical significance was defined as a two-tailed p-value less than 0.05 for all analyses.

Results

During the five-year study period, we identified 120 patients who were diagnosed with acute appendicitis and managed by a single surgeon according to our standardized protocol. After applying our exclusion criteria, 112 patients remained in the final analysis cohort (Fig. 2). The mean ± SD age of the entire cohort was 39.2 ± 15.8, with a range from 19 to 80 years. The sex distribution showed a slight male predominance, with 65 patients (58%) being male and 47 (42%) female.

Fig. 2.

Work flow chart

Based on imaging study findings and application of the treatment protocol algorithm, 68 patients (60.7%) were allocated to medical management, while 44 patients (39.3%) underwent appendectomy. This distribution reflects the systematic application of the protocol, which directed patients with patent appendiceal lumens and no appendicoliths or complications toward medical treatment, while those with appendicoliths or complicated disease were referred for surgery.

Patient demographics and imaging-based disease classification

Table 1 presents the patient demographics and imaging-based disease classification stratified by treatment allocation. Patients in the medical treatment group had a mean age of 38 ± 14.8 years, while those in the surgical group were 41 ± 17.3 years. The medical treatment group included 36 males (52.9%) and 32 females (47.1%), whereas the surgical group comprised 29 males (65.9%) and 15 females (34.1%).

Table 1.

Patient demographics and imaging-based disease classification by treatment allocation

Variable	Total	Medical Tx	Surgical Tx	p-value
Age, year, mean ± SD	39.2 ± 15.8	38 ± 14.8	41 ± 17.3	0.336
Sex, Female, n (%)	47 (42)	32 (47.1)	15 (34.1)	0.174
Appendix status
Patent lumen, n (%)	68 (60.7)	68 (100)	0 (0)
Obliterated, n (%)	26 (23.2)	0 (0)	26 (59.1)
Complicated, n (%)	8 (7.1)	0 (0)	8 (18.2)
Perforated, n (%)	10 (8.9)	0 (0)	10 (22.7)	< 0.001

Tx Treatment, SD Standard deviation

All 68 patients in the medical treatment group had patent appendicular lumens on imaging (62 CT, 6 ultrasound). Six pregnant patients were evaluated using ultrasound. In the surgical group, 31 patients (70.5%) had obliterated lumens with or without appendicoliths and 13 patients (29.5%) had complicated appendicitis with features such as perforation or abscess.

Among the 68 patients who received protocol-based medical treatment, all completed initial hospitalization without requiring appendectomy (100% primary outcome success). No patient experienced clinical deterioration or required emergency surgery during the 48-hour observation period. During the follow-up period (median 2.8 years; range 0.01–5.1 years), six patients (8.8%; 95% CI: 4.1%–17.9%) underwent appendectomy. Detailed review of medical records and follow-up data revealed that only one of these six patients (1.5%) had surgery for symptomatic recurrence of appendicitis. The remaining five patients (7.4%) underwent appendectomy for non-clinical indications: two for pregnancy-related concerns, one on the advice of a physician family member, one for patient anxiety about the disease, and one at the patient’s preference at another hospital (Table 2). Pathological examination of all six specimens confirmed uncomplicated appendicitis without appendicoliths, perforation, or abscess formation.

Table 2.

Characteristics of medical treatment failures

No	Age	Sex	Time-to-surgery	Reason for surgery
1	20–29	Female	79 days	Concerns regarding pregnancy loss (14 week)
2	25–34	Female	98 days	Recurrence
3	20–29	Male	101 days	Patient preference for another hospital
4	25–34	Male	30 days	Patient concerns about disease
5	35–44	Female	3 days	Patient anxiety about potential obstetric complications for concurrent pregnancy (13 week)
6	35–44	Female	145 days	The advice of a physician family member

Table 2 provides data for these six patients. The single patient with symptomatic recurrence underwent surgery 98 days after initial treatment. The five patients who underwent surgery for non-clinical reasons did so at varying time points between 3 and 145 days after initial medical treatment.

One pregnant patient underwent appendectomy three days after discharge at another center, without acute symptoms, due to concerns about potential obstetric complications. All other patients showed clinical improvement or stable status, allowing safe discharge after completion of intravenous antibiotics and transition to oral therapy. No complications directly attributable to medical management were observed during the initial hospitalization or follow-up period.

The mean follow-up duration of the medical treatment group was 1029 days (2.8 years), with a range from 2 to 1871 days (0.01 to 5.1 years). Kaplan-Meier analysis of appendectomy-free status demonstrated that all six appendectomies occurred within the first 145 days, after which the curve plateaued with no additional events during subsequent follow-up extending to 5.1 years (Fig. 3). The estimated mean appendectomy-free time was 1707 days (4.7 years; 95% CI: 1582–1832 days). It should be noted that this analysis treated appendectomy for any reason as the event; given the heterogeneous indications described above, the curve reflects appendectomy-free status rather than recurrence-free survival in the conventional sense. When only the single clinically indicated appendectomy was considered as an event, the recurrence-free rate was 98.5% (67/68).

Fig. 3.

Kaplan-Meier analysis of appendectomy-free status in the medical treatment group (n = 68). Appendectomy for any reason was treated as the event. All six appendectomies occurred within the first 145 days. Of note, only one event represented symptomatic recurrence; the remaining five were performed for non-clinical indications

Descriptive subgroup data were examined in an exploratory fashion, though the small number of events (n = 6) precluded any meaningful statistical inference. Appendectomy-free rates were 85.2% (23/27) in patients younger than 30 years, 93.3% (28/30) in those aged 30–50, and 100% (11/11) in patients older than 50. By sex, 34 of 36 males (94.4%) and 28 of 32 females (87.5%) remained appendectomy-free. These figures are reported for completeness only and should not be interpreted as evidence of differential treatment effect.

Forty-four patients were directed to appendectomy based on the treatment algorithm. The indications were appendicolith or obliterated lumen in 31 patients (70.5%) and complicated appendicitis in 13 (29.5%). All underwent successful appendectomy; 42 (95.5%) laparoscopically and 2 (4.5%) by open conversion. Pathological examination confirmed acute appendicitis in all specimens. In two cases (4.5%), the severity anticipated on preoperative CT was not confirmed at surgery, representing a minor discordance between imaging and operative findings.

No patient in the medical treatment group experienced serious complications attributable to conservative management. No patient developed abscess formation, perforation, or peritonitis during or after medical treatment. Among the six patients who ultimately underwent appendectomy, pathological examination showed uncomplicated appendicitis in all cases. In the surgical group, all appendectomies were completed successfully without major intraoperative or postoperative complications. The conversion rate from laparoscopic to open surgery was 4.5% (2/44).

Discussion

In this single-arm retrospective cohort study, protocol-based medical management was applied to 68 carefully selected patients with uncomplicated acute appendicitis without appendicolith. All patients completed initial hospitalization without requiring appendectomy. During a median follow-up of 2.8 years, six patients (8.8%) underwent appendectomy, but only one of these represented true symptomatic recurrence; the remaining five were performed for non-clinical reasons. These outcomes were achieved through a standardized treatment algorithm that utilized appendicolith presence on CT as the primary criterion directing patients toward surgical management.

The treatment strategy employed in this study aligned more closely with the APPAC trial approach than with the CODA trial. The APPAC trial excluded patients with appendicoliths and reported a 27% recurrence rate at one year, increasing to 39% at five years [4]. In contrast, the 8.8% first-year recurrence rate observed in this study appeared lower than APPAC results. This difference might be attributed to several factors. First, the 48-hour observation period implemented in this protocol allowed early identification and conversion to surgery for patients not responding to initial medical treatment. Second, all patients underwent imaging study, ensuring accurate diagnosis and exclusion of complicated appendicitis, whereas APPAC included patients diagnosed by clinical criteria alone in approximately 70% of cases.

The CODA trial adopted a broader approach by including patients with appendicoliths and reported substantially different outcomes. Among patients without appendicoliths, 25% required appendectomy within 90 days, while this rate increased to 41% in patients with appendicoliths [5]. Furthermore, among patients randomized to antibiotics who subsequently underwent appendectomy, 16% were found to have perforated appendicitis in the CODA trial, compared to less than 2% in APPAC [4]. By excluding appendicolith-positive patients from antibiotic therapy, the current protocol avoided exposing this higher-risk group to increased failure rates and potential complications associated with delayed surgery.

The decision to use appendicolith presence as an absolute indication for surgery was supported by multiple lines of evidence. Meta-analyses demonstrated that appendicoliths were associated with both higher rates of complicated appendicitis and increased antibiotic treatment failure [7]. In the current study, among 44 patients who underwent surgery, 31 (70.5%) had appendicoliths and 13 (29.5%) had complicated appendicitis, confirming the association between appendicoliths and disease severity. Interestingly, pathological examination revealed discordance with imaging in 2 cases, where appendicoliths or complications suspected on computed tomography were not confirmed surgically. This finding highlighted the imperfect specificity of imaging but did not negate its overall utility for risk stratification.

A distinction that deserves emphasis is the nature of the six appendectomies observed during follow-up. Only one patient underwent surgery for documented symptomatic recurrence, yielding a true clinical recurrence rate of 1.5% (1/68). The other five appendectomies were driven by non-clinical factors: patient anxiety, pregnancy-related concerns, family advice, and preference for definitive surgery. Labeling all six as “recurrences” would have misrepresented the data; therefore, the overall appendectomy rate of 8.8% was reported as such, with the important caveat that the majority of these procedures did not result from disease recurrence. This heterogeneity also limited the interpretability of the Kaplan-Meier analysis, which treated appendectomy for any reason as the event. Unlike the APPAC trial, where appendectomy reliably represented clinical failure, the appendectomies in this cohort reflected a mixture of clinical and non-clinical decisions. Accordingly, the Kaplan-Meier curve was presented as a descriptive tool illustrating the temporal pattern of appendectomies rather than as a conventional failure analysis. When only the single true recurrence was counted, the recurrence-free rate was 98.5%. In the APPAC trial, recurrences continued to accumulate over time, with rates increasing from 27% at one year to 39% at five years [4]. In the current study, all appendectomies occurred within the first 145 days, and no events were documented during subsequent follow-up, though longer observation would be needed to confirm this plateau definitively.

Acute appendicitis during pregnancy represented a particularly challenging scenario where avoiding surgery carried additional appeal. In this study, four of five pregnant patients (80%) were successfully managed with antibiotics, though the small sample size limited definitive conclusions. A prospective study focusing on pregnant patients reported successful antibiotic treatment in 17 of 20 cases (85%), demonstrating that non-operative management was feasible during pregnancy without causing serious maternal or fetal complications [4]. However, given the potential consequences of misdiagnosis or treatment failure during pregnancy, careful patient selection and close monitoring remained essential.

The success of the protocol-based approach employed in this study depended fundamentally on accurate imaging assessment. Systematic reviews demonstrated that CT had high specificity for identifying complicated appendicitis and appendicoliths, though sensitivity varied [8]. The requirement for imaging confirmation in this study ensured that treatment decisions were based on objective imaging criteria rather than clinical judgment alone. However, the 4.5% discordance rate between imaging and surgical findings highlighted that radiological interpretation was not infallible. This emphasized the importance of experienced radiological evaluation and suggested that equivocal cases might be better managed surgically rather than risking treatment failure.

Interpreting these results requires consideration of several aspects of our case definition. Our diagnostic criteria for uncomplicated appendicitis, defined as an appendiceal diameter greater than 6 mm without signs of perforation, abscess, or appendicolith, may be more permissive than some studies, potentially encompassing milder cases. Furthermore, our definition of ‘complicated’ appendicitis was notably strict, specifically excluding patients exhibiting any signs of perforation, abscess, or appendicolith. This selective methodology likely contributed to our high treatment success rate by precluding patients at an elevated risk of medical treatment failure. Moreover, in contrast to the APPAC and CODA trials, which employed more inclusive criteria, our protocol deliberately excluded patients with appendicoliths, a recognized predictor of treatment failure. Consequently, our observed success rate of 91.2% appears to reflect both the efficacy of the treatment protocol and the meticulous selection of appropriate candidates. Therefore, direct comparisons with randomized trials necessitate careful consideration of these distinctions in case definition and patient selection. Ultimately, our findings are best understood as demonstrating the effectiveness of protocol-based medical treatment in carefully selected patients with uncomplicated acute appendicitis, rather than implying superiority over the outcomes reported in the APPAC or CODA trials.

The single-surgeon design of this study provided consistency in decision-making and treatment application but also introduced limitations. The standardized approach to preoperative evaluation and postoperative follow-up, combined with comprehensive patient counseling, represented strengths that might be difficult to replicate in multi-provider settings. However, implementation of such an approach required reliable access to CT imaging, experienced radiological interpretation, and infrastructure for systematic patient follow-up. The 48-hour observation period, while allowing early detection of treatment failures, also required hospital resources and patient acceptance of initial hospitalization rather than immediate definitive surgery. Also, the single-center, non-randomized design limited generalizability. The relatively small sample size of 112 patients, while reflecting the reality of single-surgeon practice, precluded multivariate analysis of factors predicting treatment success or failure. Additionally, patient preference played a role in treatment selection, as some patients elected surgery at other institutions after being informed of treatment options, potentially introducing selection bias.

The requirement for radiologist confirmation of appendicitis without appendicoliths added a layer of quality control but also increased complexity in case selection. Furthermore, the absence of standardized pathology reporting for acute appendicitis necessitated verification through both radiology and surgical reports, highlighting a broader issue in appendicitis research regarding outcome standardization. The median follow-up of 2.8 years provided meaningful data on recurrence patterns, though extended follow-up beyond five years would strengthen conclusions about long-term outcomes.

Several questions warranted further investigation. First, whether refinements in imaging could further improve patient selection remained unclear. Advanced imaging techniques or specific radiological signs might better predict which patients would benefit most from medical treatment. Second, optimal antibiotic regimens required clarification, as different studies employed varying protocols with different durations and drug combinations. Third, the role of the appendix in immune function and gut microbiota regulation suggested that appendix preservation might have benefits beyond simply avoiding surgery, though these potential advantages required formal study [9].

From a broader perspective, comparative effectiveness research incorporating patient-reported outcomes, quality of life measures, and cost-effectiveness analyses would help inform treatment decisions. The CODA trial pioneered such an approach by engaging patient stakeholders in study design and prioritizing outcomes that patients considered most important [5]. Future studies should continue this patient-centered orientation while also addressing questions about optimal patient selection, antibiotic protocols, and long-term outcomes.

In conclusion, protocol-based medical treatment achieved complete short-term treatment success in this carefully selected cohort of patients with uncomplicated acute appendicitis without appendicolith. The overall appendectomy rate during follow-up was 8.8%, though true symptomatic recurrence was observed in only one patient (1.5%). These findings, while limited by the single-arm observational design and small sample size, supported the feasibility of this approach when combined with reliable imaging assessment, systematic patient selection, and structured follow-up. The results contributed to the growing body of real-world evidence on APPAC-type antibiotic protocols implemented outside of trial settings.

Abbreviations

CT

Computed Tomography

US

Ultrasound

APPAC

Appendicitis Acuta

CODA

Comparison of Outcomes of Antibiotics Drugs and Appendectomy

SD

Standard Deviation

CI

Confidence Interval

Authors' contributions

SD designed the study, collected and analyzed the data, performed the surgical operations, interpreted the results, and wrote the manuscript. The author read and approved the final manuscript.

Funding

The author received no financial support for the research and/or authorship of this article.

Data availability

All data and materials can be requested from Dr. Sami Doğan when needed.

Declarations

Ethics approval and consent to participate

This study was approved by the Non-Interventional Clinical Research Ethics Committee of Duzce University Faculty of Medicine (Decision No: 2021/113). All patients admitted to the hospital provided general informed consent at the time of admission, which included authorization for the use of anonymized clinical data in research studies. Given the retrospective observational design and the use of fully anonymized data, the Non-Interventional Clinical Research Ethics Committee of Duzce University Faculty of Medicine waived the requirement for additional individual study-specific informed consent. All procedures were conducted in accordance with the principles of the Declaration of Helsinki.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.