Abstract
Background
Endoscopic direct-vision appendicitis therapy (EDAT) is an emerging ultra-minimally invasive technique for acute uncomplicated appendicitis (AUA). Its comparative effectiveness against antibiotic therapy remains unclear.
Purpose
To compare short-term outcomes and recurrence rates of EDAT versus antibiotic therapy in AUA.
Methods
This retrospective cohort study included 92 AUA patients (41 EDAT, 51 antibiotics). Outcomes included symptom relief, hospital stay, inflammatory markers, treatment success, and recurrence. Subgroup analyses were performed based on fecalith presence and baseline inflammation severity.
Results
Baseline characteristics were comparable between groups (all P > 0.05), except for a significantly higher prevalence of fecaliths in the EDAT group (43.9% vs. 21.6%, P = 0.022). EDAT was associated with significantly faster abdominal pain relief [median 12.0 (IQR 12.0–24.0) h vs. 24.0 (12.0–36.0) h, P = 0.008], shorter hospital stay [3.0 (2.0–3.5) days vs. 4.0 (3.0–5.0) days, P < 0.001], and lower postoperative inflammatory markers (WBC =6.83 ± 1.39 vs. 8.53 ± 1.87 × 109/L, P < 0.001; CRP =7.89 ± 2.98 vs. 21.16 ± 12.21 mg/L, P < 0.001). Initial treatment success was 100% in both groups (EDAT = 41/41, antibiotics = 51/51; P = 1.000). At a mean follow-up of 7.88 ± 3.52 months (EDAT) and 14.92 ± 2.61 months (antibiotics), recurrence rates were 7.3% (3/41) vs. 27.5% (14/51), respectively (P = 0.014). Subgroup analyses confirmed that EDAT’s advantages were consistent across patients with and without fecaliths, as well as across different levels of baseline inflammation severity.
Conclusion
In selected patients with AUA, EDAT offers faster symptom resolution, better early inflammatory control, and significantly lower recurrence rates compared with antibiotic therapy. The presence of fecaliths and elevated baseline CRP predicts a higher risk of antibiotic failure, suggesting that EDAT may be particularly valuable in these subgroups. Further prospective studies are warranted to clarify the role of EDAT relative to surgical appendectomy.
Keywords: Appendicitis, Endoscopic direct-vision appendicitis therapy, Anti-bacterial agents, Recurrence, Fecalith
Introduction
Acute appendicitis remains one of the most common surgical emergencies worldwide, with a lifetime incidence of approximately 7–8% [1]. For more than a century, appendectomy has been the standard of care. However, accumulating evidence suggests that surgical resection may be unnecessary for acute uncomplicated appendicitis (AUA) [2], particularly given the appendix’s emerging role as a reservoir for gut microbiota and a lymphoid organ involved in immune regulation [3].
The management landscape for AUA has evolved substantially over the past two decades. Antibiotic therapy has emerged as a viable non-invasive alternative, with multiple randomized controlled trials demonstrating that a substantial proportion of patients can avoid surgery [4–6]. The landmark APPAC trial and its 5-year follow-up reported that while antibiotics were non-inferior to appendectomy in the short term, the recurrence rate exceeded 30% [5, 7]. More recently, the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial confirmed that antibiotics are an effective initial treatment, though 29% of patients required appendectomy within one year[8].
In parallel, endoscopic approaches have been developed to preserve the appendix while providing definitive source control. Endoscopic retrograde appendicitis therapy (ERAT), first described by Liu et al. in 2012 [9], represents a paradigm shift toward organ-preserving treatment. A recent network meta-analysis by Wang et al. highlighted the trade-offs among treatment options: appendectomy offers the lowest recurrence but carries surgical risks, while antibiotic therapy is non-invasive but associated with higher recurrence rates[10].
Endoscopic direct-vision appendicitis therapy (EDAT), a refinement of ERAT, utilizes a subscope for real-time visualization of the appendiceal lumen, thereby avoiding radiation exposure and enabling more precise intervention [11]. Our previous study demonstrated that EDAT is superior to laparoscopic appendectomy (LA) in terms of faster recovery and better inflammatory control, with a recurrence rate of 7.3% at a mean follow-up of 7.9 months [12]. However, the comparative effectiveness of EDAT versus antibiotic therapy remains unexplored. Building on this finding, the present study aims to address this gap by comparing short-term outcomes and recurrence rates between EDAT and antibiotic treatment in patients with AUA.
Materials and methods
Study design and patient selection
This retrospective cohort study was conducted at Zhejiang Hospital, a tertiary referral center in Hangzhou, China. The EDAT group comprised 41 patients who underwent endoscopic direct-vision therapy between December 2023 and December 2024 according to the same institutional protocol [12]. The antibiotic group included 51 consecutive patients with AUA who received antibiotic therapy as the initial treatment between December 2023 and December 2024. Treatment allocation was not randomized. Patients and physicians jointly decided on the treatment after detailed discussion of the benefits and risks of each option, which may have introduced selection bias.
All patients were diagnosed with AUA based on (1) abdominal computed tomography (CT) or ultrasound findings showing appendiceal diameter ≥ 6 mm, wall thickening ≥ 3 mm, without evidence of perforation, abscess, or diffuse peritonitis [13]; and (2) an Alvarado score of 5–7 (moderate inflammation, excluding severe inflammation with Alvarado score ≥ 8) [13, 14].
Inclusion criteria were (1) age 18–75 years; (2) confirmed AUA meeting the aforementioned diagnostic criteria; and (3) no contraindications to either treatment modality. Exclusion criteria were (1) complicated appendicitis (perforation, abscess, peritonitis); (2) severe organ dysfunction; (3) pregnancy or lactation; (4) other causes of acute abdominal pain; and (5) appendiceal diameter > 10 mm or fecalith diameter ≥ 5 mm (predicted to be difficult for endoscopic removal, applied to both groups to maintain comparability).
This study was approved by the Ethics Committee of Zhejiang Hospital (Approval No. ZJHIRB-003K), with a waiver of informed consent due to the retrospective nature.
Treatment protocols
EDAT group: All patients in the EDAT group underwent the procedure within 12 h of admission, a uniform criterion applied to all included patients, and all procedures were performed by three senior endoscopists, each with over 10 years of experience in therapeutic endoscopy and having completed at least 20 EDAT cases prior to this study. A colonoscope with a transparent cap was advanced to the cecum to identify the appendiceal orifice. Intubation of the appendiceal lumen was achieved using a guidewire (0.035'', Changzhou Leao Medical Technology) and, when necessary, a high-frequency incision knife (Boston Scientific). A disposable electronic appendiceal subscope (Hangzhou Lesite Medical Technology) was advanced through the biopsy channel to directly visualize the appendiceal lumen. The lumen was examined for fecaliths, pus, and mucosal inflammation. Irrigation was performed using 100 mL of metronidazole sodium chloride injection followed by normal saline until the effluent was clear. Systemic antibiotics were not routinely administered after EDAT. Only patients with preoperative CRP > 80 mg/L (n = 6, 14.6%) received oral cefuroxime axetil (500 mg twice daily) for 3 days post-procedure [12]. Oral cefuroxime axetil was selected for its broad-spectrum activity against common enteric pathogens and favorable oral bioavailability. No other patients in the EDAT group received systemic antibiotics. For large or impacted fecaliths that could not be completely removed, a 5Fr × 5-cm plastic stent (Flex Ltd.) was placed to ensure drainage. Stent placement was performed in 6 patients (14.6%) in the EDAT group. All stents were observed to pass spontaneously with bowel movements within 2–4 weeks post-procedure, and no endoscopic retrieval was required. No stent-related complications were observed during follow-up. Detailed procedural steps have been previously described [12, 15].
Antibiotic group: Patients received intravenous antibiotics according to local guidelines. The most common regimen was intravenous ceftriaxone (2 g daily) plus metronidazole (500 mg three times daily) for 2–3 days, followed by oral antibiotics (amoxicillin-clavulanate or ciprofloxacin plus metronidazole) for a total duration of 5–7 days, consistent with published protocols [4, 8]. The choice of antibiotics was at the discretion of the treating physician. Treatment failure was defined as the need for appendectomy during the initial hospital stay due to symptom progression or lack of improvement.
Procedural images
Key steps of the EDAT procedure are illustrated in Fig. 1. After colonoscopic identification of the appendiceal orifice (Fig. 1A), a guidewire was advanced into the appendiceal lumen, often facilitated by a high-frequency incision knife (Fig. 1B). A disposable electronic subscope was then inserted over the guidewire to directly visualize the appendiceal lumen, allowing assessment of mucosal inflammation and detection of fecaliths (Fig. 1C). In cases where complete fecalith removal was not feasible, a plastic stent was placed to ensure drainage patency (Fig. 1D). All images are representative cases from the EDAT cohort.
Fig. 1.
Key procedural steps of endoscopic direct-vision appendicitis therapy (EDAT). A Appendiceal orifice identified during colonoscopy. B Guidewire insertion into the appendiceal lumen using a high-frequency incision knife. C Subscope visualization showing mucosal inflammation and an appendicolith. D Plastic stent placed to ensure drainage patency
Data collection and outcomes
The following data were extracted from electronic medical records: demographics (age, sex), clinical characteristics (Alvarado score, presence of fecaliths on imaging), laboratory parameters (white blood cell [WBC] count, C-reactive protein [CRP] before treatment and on day 2 post-treatment), and treatment outcomes.
Primary outcomes were (1) treatment success (resolution of symptoms without need for surgery during initial hospitalization) and (2) recurrence rate during follow-up (defined as reappearance of symptoms with imaging confirmation of acute appendicitis).
Secondary outcomes included (1) time to abdominal pain relief (hours until Visual Analog Scale ≤ 2); (2) length of hospital stay (days); (3) postoperative inflammatory markers (WBC, CRP); and (4) complications.
Follow-up was conducted via telephone interviews and outpatient clinic records. For the antibiotic group, follow-up was extended to a minimum of 12 months where possible.
Definitions
Treatment success was defined as complete resolution of symptoms without the need for appendectomy during the index hospitalization. Recurrence was defined as reappearance of symptoms consistent with acute appendicitis, confirmed by imaging (CT or ultrasound), after initial discharge. Time to pain relief was defined as the interval from treatment initiation to the first time the patient reported a Visual Analog Scale score ≤ 2.
Statistical analysis
Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). Continuous variables were tested for normality using the Shapiro-Wilk test. Normally distributed data were expressed as mean ± standard deviation and compared using the independent samples t-test. Non-normally distributed data were expressed as median (interquartile range) and compared using the Mann-Whitney U test. Categorical variables were expressed as frequencies (percentages) and compared using the chi-square test or Fisher’s exact test as appropriate.
To address potential confounding due to the retrospective design and baseline differences, we performed subgroup analyses stratified by (1) fecalith presence and (2) baseline inflammation severity (CRP ≤ 60 mg/L vs. > 60 mg/L). Intragroup comparisons of preoperative and postoperative indicators were performed using paired t-test or Wilcoxon signed-rank test. A two-tailed P-value < 0.05 was considered statistically significant.
This was a retrospective exploratory study; therefore, no formal a priori sample size calculation was performed. A post hoc power analysis indicated that, based on the observed recurrence rates (7.3% vs. 27.5%), the study had > 80% power to detect a significant difference at a two-sided alpha level of 0.05. However, the sample size was limited for subgroup analyses, and those results should be interpreted with caution. This manuscript was prepared in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement for cohort studies. The completed STROBE checklist is provided as Supplementary Material.
Results
Baseline characteristics
A total of 92 patients were included (41 EDAT, 51 antibiotics). Baseline characteristics are summarized in Table 1. The EDAT group had a numerically higher proportion of male patients (46.3% vs. 62.7%, P = 0.116) and was slightly older (43.41 ± 15.00 vs. 39.37 ± 12.81 years, P = 0.167), although these differences did not reach statistical significance. The Alvarado score was comparable between groups [6.0 (5.0–6.0) vs. 6.0 (5.0–6.0), P = 0.689].
Table 1.
Baseline characteristics
| Characteristic | EDAT group (n = 41) | Antibiotic group (n = 51) | Test statistic | P-value |
|---|---|---|---|---|
| Age (years), mean ± SD | 43.41 ± 15.00 | 39.37 ± 12.81 | t = 1.393 | 0.167 |
| Sex, male, n (%) | 19 (46.3) | 32 (62.7) | χ2 = 2.476 | 0.116 |
| Alvarado score, median (IQR) | 6.0 (5.0–6.0) | 6.0 (5.0–6.0) | U = 957.50 | 0.456 |
| Fecalith present, n (%) | 18 (43.9) | 11 (21.6) | χ2 = 5.252 | 0.022 |
| Preoperative WBC (×109/L), mean ± SD | 14.82 ± 2.03 | 14.13 ± 3.12 | t = 1.279 | 0.204 |
| Preoperative CRP (mg/L), mean ± SD | 60.97 ± 24.32 | 70.96 ± 31.93 | t = −1.655 | 0.102 |
EDAT, endoscopic direct-vision appendicitis therapy, SD, standard deviation, IQR, interquartile range, WBC, white blood cell, CRP, C-reactive protein
Notably, the prevalence of fecaliths on preoperative imaging was significantly higher in the EDAT group (43.9% vs. 21.6%, P = 0.022). This reflects the different treatment selection pathways: patients with visible fecaliths were more likely to be offered EDAT due to concerns about antibiotic failure. Preoperative WBC was comparable between groups (14.82 ± 2.03 vs. 14.13 ± 3.12, P = 0.204), while preoperative CRP showed a trend toward higher levels in the antibiotic group (60.97 ± 24.32 vs. 70.96 ± 31.93, P = 0.102), though the difference did not reach statistical significance.
Treatment outcomes
All 41 patients (100%) in the EDAT group underwent successful procedures without intraoperative complications. In the antibiotic group, all 51 patients (100%) achieved initial treatment success without requiring appendectomy during the index hospitalization. The initial treatment success rate was 100% in both groups (P = 1.000).
As shown in Table 2, EDAT was associated with significantly faster symptom resolution compared to antibiotics. The median time to abdominal pain relief was 12.0 (IQR 12.0–24.0) hours in the EDAT group versus 24.0 (IQR 12.0–36.0) hours in the antibiotic group (P = 0.008). Hospital stay was also shorter in the EDAT group [3.0 (2.0–3.5) days vs. 4.0 (3.0–5.0) days, P < 0.001].
Table 2.
Clinical outcomes
| Outcome | EDAT group (n = 41) | Antibiotic group (n = 51) | Test statistic | P-value |
|---|---|---|---|---|
| Time to pain relief (h), median (IQR) | 12.0 (12.0–24.0) | 24.0 (12.0–36.0) | U = 715.50 | 0.008 |
| Hospital stay (days), median (IQR) | 3.0 (2.0–3.5) | 4.0 (4.0–5.0) | U = 345.00 | < 0.001 |
| Day 2 WBC (× 109/L), mean ± SD | 6.83 ± 1.39 | 8.53 ± 1.87 | t = −4.841 | < 0.001 |
| Day 2 CRP (mg/L), mean ± SD | 7.89 ± 2.98 | 21.16 ± 12.21 | t = −6.788 | < 0.001 |
IQR, interquartile range, SD, standard deviation, WBC, white blood cell, CRP, C-reactive protein
Postoperative inflammatory markers were markedly lower in the EDAT group. Day 2 WBC count was 6.83 ± 1.39 × 109/L in the EDAT group versus 8.53 ± 1.87 × 109/L in the antibiotic group (P < 0.001). Day 2 CRP was 7.89 ± 2.98 mg/L versus 21.16 ± 12.21 mg/L, respectively (P < 0.001).
No intraoperative or postoperative complications, including perforation, bleeding, or intra-abdominal abscess, occurred in the EDAT group. During follow-up, three patients (7.3%) developed recurrent appendicitis and subsequently underwent laparoscopic appendectomy without complications. No adverse events related to the EDAT procedure itself were observed.
Serum inflammatory markers
Table 3 presents the changes in serum inflammatory markers before and after treatment. Both groups showed significant reductions in WBC and CRP after treatment (all P < 0.001). The magnitude of WBC reduction was significantly greater in the EDAT group (7.99 ± 1.63 vs. 5.60 ± 2.03 × 109/L, P < 0.001). Although the absolute reduction in CRP was similar between groups (53.07 ± 21.87 vs. 49.80 ± 22.59 mg/L, P = 0.485), the significantly lower postoperative levels in the EDAT group (7.89 ± 2.98 vs. 21.16 ± 12.21 mg/L, P < 0.001) indicate more complete resolution of inflammation.
Table 3.
Serum inflammatory markers before and after treatment
| Parameter | EDAT group (n = 41) | Antibiotic group (n = 51) | Between-group P-value |
|---|---|---|---|
| WBC (× 109/L), mean ± SD | |||
| Preoperative | 14.82 ± 2.03 | 14.13 ± 3.12 | 0.204 |
| Postoperative day 2 | 6.83 ± 1.39 | 8.54 ± 1.87 | < 0.001 |
| Change (pre–post) | 7.99 ± 1.63 | 5.60 ± 2.03 | < 0.001 |
| Within-group P-value | < 0.001 | < 0.001 | - |
| CRP (mg/L), mean ± SD | |||
| Preoperative | 60.97 ± 24.32 | 70.96 ± 31.93 | 0.102 |
| Postoperative day 2 | 7.89 ± 2.98 | 21.16 ± 12.21 | < 0.001 |
| Change (pre–post) | 53.07 ± 21.87 | 49.80 ± 22.59 | 0.485 |
| Within-group P-value | < 0.001 | < 0.001 | - |
Data are presented as mean ± standard deviation. Change = preoperative value–postoperative value. Within-group comparisons were performed using paired t-test or Wilcoxon signed-rank test
Recurrence and long-term outcomes
The mean follow-up duration was significantly longer in the antibiotic group than in the EDAT group (14.92 ± 2.61 vs. 7.88 ± 3.52 months, P < 0.001). During follow-up, 3 patients (7.3%) in the EDAT group experienced recurrent appendicitis, compared to 14 patients (27.5%) in the antibiotic group (P = 0.014). The median time to recurrence was 3 months (range 1–6 months) in the EDAT group and 5 months (range 2–14 months) in the antibiotic group.
Among the 51 patients in the antibiotic group, all achieved initial treatment success without requiring appendectomy during the index hospitalization. During follow-up, 14 patients (27.5%) experienced recurrent appendicitis. Among these 14 patients with recurrence, 12 underwent laparoscopic appendectomy (all uneventful), and 2 were successfully treated with a second course of antibiotics. All 3 patients with recurrence in the EDAT group underwent laparoscopic appendectomy without complications.
Given the significant difference in follow-up duration between the two groups (EDAT =7.88 ± 3.52 months; antibiotics =14.92 ± 2.61 months; P < 0.001), a Kaplan-Meier survival analysis was performed. The cumulative recurrence rate was lower in the EDAT group, with a borderline significant difference (log-rank test, P = 0.054). This finding is consistent with the crude recurrence rates (7.3% vs. 27.5%, P = 0.014) and supports the direction of treatment benefit favoring EDAT.
Subgroup analysis: impact of fecaliths
Given the significant baseline difference in fecalith prevalence, we performed a stratified analysis based on fecalith presence (Table 4). Among patients without fecaliths, both treatments achieved excellent initial success rates (EDAT =100% [23/23]; antibiotics =100% [40/40]; P = 1.000). However, EDAT was associated with significantly faster pain relief, shorter hospital stay, and lower postoperative inflammatory markers (all P < 0.05, Table 4). The recurrence rate was numerically lower in the EDAT group, though the difference did not reach statistical significance (EDAT = 4.3% [1/23] vs. antibiotics = 17.5% [7/40]; P = 0.218).
Table 4.
Subgroup analysis by fecalith presence
| Stratification standard | Group | Postoperative WBC (10 ^ 9/L) | Postoperative CRP (mg/L) | Postoperative abdominal pain relief time (hour) | Hospital stay (day) |
|---|---|---|---|---|---|
| Without fecaliths | EDAT (n = 23) | 7.22 ± 1.35 | 8.32 ± 1.74 | 12.00 (12.00, 24.00) | 3.00 (2.00, 4.00) |
| Antibiotics (n = 40) | 8.49 ± 1.91 | 20.71 ± 11.42 | 24.00 (12.00, 36.00) | 4.00 (4.00, 5.00) | |
| P | 0.006 | < 0.001 | 0.022 | < 0.001 | |
| With fecaliths | EDAT (n = 18) | 6.35 ± 1.31 | 7.35 ± 4.06 | 12.00 (10.50,24.00) | 3.00 (2.00, 3.25) |
|
Antibiotics (n = 11) |
8.69 ± 1.81 | 22.80 ± 15.29 | 24.00 (12.00, 36.00) | 4.00 (4.00, 5.00) | |
| P | < 0.001 | 0.007 | 0.165 | 0.001 |
In contrast, among patients with fecaliths, the differences were striking. Both treatments achieved 100% initial success (EDAT = 18/18; antibiotics = 11/11). However, EDAT was associated with significantly faster pain relief, shorter hospital stay, and markedly lower postoperative inflammatory markers (Table 4). The recurrence rate was 11.1% (2/18) in the EDAT group versus 54.5% (6/11) in the antibiotic group (P = 0.021), representing a nearly five-fold reduction.
Subgroup analysis: impact of baseline inflammation severity
To further explore the consistency of treatment effects, we stratified patients by baseline CRP level (≤ 60 mg/L vs. > 60 mg/L), as shown in Table 5. EDAT demonstrated superior outcomes across both strata, with faster symptom relief, shorter hospital stay, and lower postoperative inflammatory markers in all comparisons.
Table 5.
Subgroup analysis by baseline inflammation severity
| Stratification standard | Group | Postoperative WBC (10 ^ 9/L) | Postoperative CRP (mg/L) | Postoperative abdominal pain relief time (hour) | Hospital stay (day) |
|---|---|---|---|---|---|
| Preoperative CRP ≤ 60 mg/L (EDAT n = 22; antibiotics n = 21) | EDAT | 6.30 ± 1.23 | 6.81 ± 1.41 | 12.00 (10.50, 24.00) | 3.00 (2.00, 3.00) |
| Antibiotics | 7.26 ± 1.28 | 11.90 ± 4.51 | 24.00 (12.00, 42.00) | 4.00 (3.50, 5.00) | |
| P | 0.017 | < 0.001 | 0.015 | 0.001 | |
| Preoperative CRP > 60 mg/L (EDAT n = 19; antibiotics n = 30) | EDAT | 7.45 ± 1.32 | 9.15 ± 3.79 | 24.00 (12.00, 24.00) | 3.00 (3.00, 4.00) |
| Antibiotics | 9.43 ± 1.71 | 27.64 ± 11.73 | 24.00 (12.00, 36.00) | 4.00 (4.00, 5.00) | |
| P | < 0.001 | < 0.001 | 0.378 | 0.002 |
In patients with mild inflammation (CRP ≤ 60 mg/L), the recurrence rate was 1/22 (4.5%) in the EDAT group versus 4/21 (19.0%) in the antibiotic group (P = 0.354). In patients with moderate-to-severe inflammation (CRP > 60 mg/L), the difference was more pronounced and statistically significant: 2/19 (10.5%) versus 10/30 (33.3%) (P = 0.042). This suggests that the benefits of EDAT over antibiotics are particularly evident in patients with more severe baseline inflammation.
Discussion
To the best of our knowledge, this study provides the first direct comparison between EDAT and antibiotic therapy for AUA. Our findings demonstrate that EDAT offers significant advantages over antibiotics in terms of faster symptom resolution, shorter hospital stay, better control of systemic inflammation, and, most importantly, substantially lower recurrence rates. These benefits were consistent across subgroup analyses stratified by fecalith presence and baseline inflammation severity, suggesting that EDAT’s advantages are robust across a spectrum of disease presentations.
The management of AUA has evolved from a purely surgical paradigm to a more nuanced approach that incorporates both conservative and interventional options [16]. Antibiotic therapy has gained traction following multiple RCTs demonstrating its feasibility [4–6]. The APPAC trial reported 1-year treatment success of 72.7% with antibiotics [5], while the CODA trial found that 29% of patients randomized to antibiotics underwent appendectomy within 1 year [8]. A recent meta-analysis by Salminen et al. confirmed that while antibiotics are effective in the short term, long-term recurrence remains a significant concern, exceeding 30% at 5 years [7, 17].
Together with our previous finding that EDAT outperforms LA [12], the present results position EDAT as a versatile treatment option that offers faster recovery than surgery and lower recurrence than antibiotics, while preserving the appendix. EDAT occupies a unique middle ground between these two extremes. Unlike antibiotics, which rely on the host immune response and spontaneous resolution of obstruction, EDAT provides mechanical relief of luminal obstruction through direct visualization, irrigation, and fecalith removal when present [9]. This mechanistic difference likely explains the superior outcomes observed in our study, particularly the dramatic reduction in recurrence compared to antibiotics (7.3% vs. 27.5%). Our recurrence rate for EDAT aligns closely with the 7–10% reported for ERAT-like techniques in a recent network meta-analysis [10], while the antibiotic recurrence rate is consistent with the 30% figure reported in long-term follow-up studies [7, 17]. The Kaplan-Meier survival analysis showed a borderline significant difference (P = 0.054), which is likely attributable to the shorter follow-up duration and the small number of recurrence events in the EDAT group (n = 3). Despite this, the consistent direction of effect across both crude and adjusted analyses, as well as across subgroup analyses, supports the conclusion that EDAT is associated with a lower recurrence risk compared with antibiotic therapy. Notably, when recurrence occurred, the majority of patients in both groups ultimately underwent appendectomy. However, surgery after failed conservative or endoscopic treatment is often performed as a planned procedure rather than an emergency, which may be associated with lower morbidity.
Our subgroup analysis identified fecalith presence as the most important factor influencing outcomes, particularly in the antibiotic group. Among patients with fecaliths treated with antibiotics, the recurrence rate was 54.5% (6/11), compared to only 17.5% (7/40) in those without fecaliths. This finding is consistent with a growing body of evidence suggesting that fecaliths are a marker of more severe disease and a predictor of antibiotic failure [18–20].
A post hoc analysis of the APPAC trial by Haijanen et al. demonstrated that the presence of an appendicolith was associated with a significantly higher risk of treatment failure (hazard ratio [HR] 3.47) [18]. Similarly, the CODA trial reported that patients with appendicoliths had a higher rate of appendectomy within 90 days (25% vs. 13%) [8]. Our findings extend these observations by showing that EDAT effectively mitigates this risk: patients with fecaliths treated with EDAT had an 11.1% (2/18) recurrence rate, which was not significantly different from the 4.3% (1/23) rate in patients without fecaliths treated with EDAT (P = 0.218).
This has important clinical implications. For patients presenting with AUA and visible fecaliths on imaging, antibiotic therapy alone may be suboptimal, and early intervention with EDAT should be strongly considered. Conversely, in patients without fecaliths and mild-to-moderate inflammation, antibiotic therapy remains a reasonable first-line option, though patients should be counseled about the approximately 15–20% recurrence risk.
The superior inflammatory control observed with EDAT warrants discussion. Post-treatment CRP was nearly three times lower in the EDAT group compared to the antibiotic group (7.89 vs. 21.16 mg/L), and the magnitude of WBC reduction was significantly greater. This difference likely reflects the fundamental distinction between source control (EDAT) and systemic therapy (antibiotics). By directly removing the obstructing nidus and purulent material, EDAT rapidly reduces the bacterial load and intraluminal pressure, leading to faster resolution of the inflammatory cascade [21]. Antibiotics, while effective against systemic bacterial dissemination, do not address the mechanical obstruction and may take longer to achieve clinical response.
The faster symptom relief (12 vs. 24 h) and shorter hospital stay (3 vs. 4 days) associated with EDAT have practical implications for healthcare resource utilization and patient satisfaction. It is worth noting that with enhanced recovery after surgery (ERAS) protocols, the hospital stay for laparoscopic appendectomy has been substantially reduced in many centers, which should be considered when interpreting the observed differences. A cost-effectiveness analysis would be valuable to quantify these benefits, though it was beyond the scope of this retrospective study.
We have previously observed that EDAT is associated with faster recovery and improved inflammatory control compared to laparoscopic appendectomy in a retrospective cohort [12]. The current study extends this evidence by demonstrating that EDAT also offers advantages over antibiotic therapy, particularly in patients with fecaliths or more severe baseline inflammation. These findings suggest that EDAT occupies a unique therapeutic niche, providing faster recovery than surgery and lower recurrence than antibiotics, while preserving the appendix. However, given the retrospective nature of the available data, further prospective studies are required to definitively establish its role relative to the established gold standard of appendectomy. While recurrence occurred in a small proportion of patients, these cases were successfully managed with subsequent surgery without additional morbidity, suggesting that EDAT does not compromise the safety of eventual surgical intervention when needed.
It is important to acknowledge the limitations of the current evidence base comparing EDAT to surgical appendectomy. While our prior study [12] suggested favorable short-term outcomes for EDAT, that analysis—like the present study—was a retrospective, single-center investigation with inherent selection biases. Appendectomy remains the definitive treatment for acute appendicitis, offering a recurrence rate approaching zero and well-established long-term safety profiles. In contrast, EDAT requires specific endoscopic expertise, may involve stent placement, and carries a small but non-zero recurrence risk. Therefore, EDAT should currently be viewed not as a replacement for surgery, but as an organ-preserving alternative for patients who prioritize avoiding an operation and are willing to accept a modest recurrence risk. Large-scale, prospective randomized trials comparing EDAT, antibiotics, and surgery are warranted to better define the optimal treatment algorithm.
The 14.6% stent placement rate in our EDAT cohort is comparable to other published series [15, 22] and reflects the technical reality that complete fecalith removal is not always achievable. Stent placement ensures drainage patency and may reduce the risk of early recurrence, though this requires prospective validation.
Our findings support a stratified approach to treatment selection for AUA. For patients without fecaliths and with mild inflammation (CRP ≤ 60 mg/L), antibiotic therapy remains a reasonable first-line option, with an expected recurrence rate of approximately 15–20%. However, patients should be counseled about this risk and offered EDAT if they prioritize faster recovery and lower recurrence. For patients with fecaliths or more severe inflammation (CRP > 60 mg/L), antibiotic therapy is associated with a high failure rate (up to 54.5%), and EDAT should be strongly recommended when available.
It is worth noting that systemic antibiotics were used sparingly in the EDAT group (only 14.6% of patients), whereas all antibiotic group patients received full-course systemic therapy. Despite this, EDAT achieved significantly lower recurrence rates, underscoring the primacy of mechanical source control over systemic antimicrobial therapy alone.
This study has several limitations that should be acknowledged. First, the retrospective design introduces potential selection bias. The higher prevalence of fecaliths in the EDAT group suggests that clinicians preferentially offered EDAT to patients with more complex disease, which would be expected to bias results against EDAT. Despite this, EDAT demonstrated superior outcomes, strengthening our conclusions. Furthermore, treatment allocation was not randomized. Patients and physicians jointly decided on the treatment after detailed discussion of the benefits and risks of each option, which may have introduced additional selection bias. The higher prevalence of fecaliths in the EDAT group (43.9% vs. 21.6%) reflects a clinical tendency to offer mechanical intervention to patients with visible obstruction, as clinicians anticipated higher failure rates with antibiotics in this subgroup. However, unmeasured confounders cannot be excluded.
Second, the sample size is modest, limiting our ability to detect small differences in some subgroup analyses. The imbalance in fecalith prevalence between groups, while informative, complicates direct comparisons and necessitates stratified analysis.
Third, the follow-up duration differed between groups, with the antibiotic group having longer follow-up (14.9 vs. 7.9 months). This difference would tend to favor antibiotics in terms of recurrence detection, yet EDAT still demonstrated significantly lower recurrence rates, reinforcing the robustness of this finding.
Fourth, the antibiotic regimens were not standardized, reflecting real-world practice but introducing heterogeneity. However, the consistency of our findings with published RCTs suggests that this heterogeneity did not materially affect conclusions.
Fifth, the assessment of appendicoliths was subject to detection bias. In the EDAT group, fecaliths were confirmed by direct endoscopic visualization, whereas the antibiotic group relied solely on preoperative imaging, which may have missed small fecaliths. This may have led to underestimation of the true impact of fecaliths on antibiotic failure.
Sixth, long-term outcomes such as quality of life, functional status, and patient-reported outcomes were not assessed. Future prospective studies should incorporate these measures to provide a more comprehensive evaluation.
Finally, as a single-center study from a tertiary referral center with expertise in EDAT, our findings may not be generalizable to centers without such expertise. The learning curve for EDAT is not trivial, and outcomes may vary with operator experience [23].
Despite these limitations, our findings have several important clinical implications. For patients with AUA, particularly those with visible fecaliths or elevated baseline CRP, EDAT offers a compelling alternative to both surgery and antibiotics. It provides the benefits of organ preservation with faster recovery than surgery and lower recurrence than antibiotics. Formal cost-effectiveness analysis was beyond the scope of this study and represents an important direction for future research.
For clinical practice, our results support a stratified approach to treatment selection. Patients without fecaliths and mild inflammation may reasonably choose between antibiotics and EDAT, with antibiotics offering a non-invasive option and EDAT providing faster recovery and lower recurrence. Patients with fecaliths or more severe inflammation should be counseled about the higher risk of antibiotic failure and recurrence, and EDAT should be strongly recommended when available.
Future research should focus on (1) large-scale, multicenter randomized controlled trials comparing EDAT with both antibiotics and surgery, with long-term follow-up to 3–5 years; (2) development of validated prediction models to identify patients most likely to benefit from each treatment approach; (3) cost-effectiveness analyses to inform healthcare policy; and (4) standardization of EDAT procedure and the establishment of structured training programs are essential to ensure reproducible outcomes across different centers [24].
Conclusion
This study provides the first evidence comparing EDAT with antibiotic therapy for acute uncomplicated appendicitis. EDAT offers faster symptom resolution, shorter hospital stay, better inflammatory control, and significantly lower recurrence rates compared to antibiotics alone. The presence of fecaliths and elevated baseline CRP identify subgroups of patients at particularly high risk of antibiotic failure who may derive the greatest benefit from EDAT. These findings support the integration of EDAT into the therapeutic armamentarium for AUA as an organ-preserving alternative that occupies a unique and valuable niche between conservative management and surgical resection. However, given the retrospective, single-center design and modest sample size, these findings should be considered preliminary, and confirmation in large-scale prospective randomized trials is warranted.
Author contribution
Chen LP: study concept and design, data collection, manuscript drafting, statistical analysis; Zhou F: data collection, manuscript revision; Cheng QR: data collection, follow-up; Feng YL: endoscopic procedures, critical revision. All authors approved the final version.
Funding
The authors declared that this study has received no financial support.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy and ethical restrictions, as they contain information that could compromise the privacy of research participants.
Declarations
Ethics approval and consent to participate
Ethical committee approval was received from the Ethics Committee of Zhejiang Hospital (Approval no: ZJHIRB-003K). Waiver of informed consent was obtained due to the retrospective nature of the study, as approved by the Ethics Committee of Zhejiang Hospital.
Conflict of interest
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy and ethical restrictions, as they contain information that could compromise the privacy of research participants.