Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review

Hyun Gu Lee; In Ja Park

doi:10.3393/ac.2023.00192.0027

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Review Inflammatory/benign bowel disease Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review: Hyun Gu Lee¹, In Ja Park²; Annals of Coloproctology 2025;41(2):107-118.
DOI: https://doi.org/10.3393/ac.2023.00192.0027
Published online: April 16, 2025

¹Department of Surgery, Kyung Hee Universitiy Hospital at Gangdong, Kyung Hee Universtiy College of Medicine, Seoul, Korea

²Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: In Ja Park, MD, PhD Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Email: ipark@amc.seoul.kr

• Received: March 8, 2023 • Revised: April 2, 2023 • Accepted: April 6, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
Graphical abstract
INTRODUCTION
METHODS
CONCLUSION
ARTICLE INFORMATION
REFERENCES

Abstract

Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.
Keywords: Appendicitis; Nonoperative management; Antibiotics; Appendectomy; Indication

Graphical abstract

INTRODUCTION

Acute appendicitis is one of the most common causes of acute abdominal pain in both adults and children, as well as the most frequent indication for abdominal emergency surgery. The lifetime risk of acute appendicitis is about 8.6% for males and 6.7% for females in the United States [1]. Accordingly, acute appendicitis has significant societal influences and healthcare burdens.

Since the first description of appendectomy in 1735 [2], open appendectomy, a surgical procedure that can remove the entire appendix, has been the standard treatment for acute appendicitis. After the introduction of laparoscopy in the 1980s [3], laparoscopic appendectomy has gradually become a routine surgical approach. Laparoscopic approach has several advantages over open approach, including less postoperative pain, a lower risk of surgical wound infection, and faster recovery to normal bowel function [4–6]. Laparoscopy could also be used as a diagnostic modality to reduce the risk of a negative appendectomy, which means removal of a normal, uninflamed appendix [7].

Even though an open or laparoscopic appendectomy is generally considered a simple and common procedure for surgeons, it is not a harmless operation. In a study of 117,424 patients who underwent appendectomy, the standardized mortality increased sevenfold after appendectomy compared with the general population [8]. In addition, Flum and Koepsell [9] reported a 3-fold increase in mortality following negative appendectomy compared to appendectomy for acute appendicitis. As early as the 1950s, Coldrey [10] advocated that patients with acute appendicitis over 24 hours old should be treated conservatively. Substantial research on the nonoperative management of acute appendicitis has also been performed to find an effective treatment strategy with a lower risk of complications and the chance of avoiding unnecessary surgery. Antibiotic-first treatment can be an attractive option due to its benefits, which include the avoidance of surgical wounds and postoperative pain and a rapid return to normal health [11]. There may also be potential benefits for healthcare providers by reducing medical resources, such as operating rooms and instruments [12]. This review summarizes the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults.

METHODS

Identification

PubMed, Embase, and Cochrane Library databases were searched for English-language studies on the nonoperative management of acute appendicitis. PubMed was searched using the keywords and MeSH terms of appendicitis, nonoperative, conservative, antibiotic, and adult in combination with Boolean operators AND or OR. The same strategy was used to search other databases. Restriction was applied to include only human studies published up to December 31, 2022. Following the initial electronic search, articles were further manually searched. Each identified article was evaluated separately for inclusion. Then, titles and abstracts of research were screened to exclude those irrelevant to the study subject (Fig. 1).

Study selection

Full text was reviewed for study selection. Relevant reports that compared nonoperative management to appendectomy and identified risk factors for treatment failure with nonoperative management were retrieved. Studies were excluded if they met the following criteria: (1) the study design was editorials, comments, technical notes, or letters to the editor; (2) the type of publication was a conference proceeding or abstract; and (3) the full text was written in a language other than English. In the case of duplicate publication, the review was based on the most recent study with the most adequate design and the largest patient series.

Different clinical course between uncomplicated and complicated appendicitis

In determining the treatment strategy for acute appendicitis, stratification of severity is essential. On the basis of macroscopic and microscopic pathology, acute appendicitis can be classified as an uncomplicated disease presenting as suppurative and nonperforated or a complicated disease manifesting as gangrenous, perforated, or abscess-forming (Fig. 2) [13, 14].

The hypothesis that untreated, uncomplicated appendicitis gradually progresses to perforation has been commonly accepted for years; however, it has also been widely challenged. An increasing amount of evidence suggests that not all cases of untreated, nonperforated appendicitis will progress to perforation, and spontaneous resolution is common [15]. It is also suggested that acute appendicitis can be divided into 2 separate types of acute inflammatory processes with distinct outcomes: the simple inflamed type and the more severe inflammatory type that rapidly progresses to gangrene or perforation [13, 15, 16]. A population-based study reporting the disconnection of epidemiologic trends between the 2 forms of appendicitis supports the concept that nonperforated and perforated appendicitis may have separate pathophysiologies [17]. In a recent meta-analysis, the incidence of acute appendicitis decreased significantly, while the number of patients presenting with complicated appendicitis increased during the COVID-19 pandemic [18]. This may be another evidence that uncomplicated appendicitis and complicated appendicitis show different progressions and that the treatment strategies for each type should be tailored accordingly.

The discrimination of complicated appendicitis before treatment mainly depends on imaging studies. Imaging findings of complicated appendicitis include periappendiceal or intraperitoneal fluid, appendiceal wall defect, extraluminal appendicoliths, extraluminal gas, or severe periappendiceal inflammation [19]. However, it has been reported that imaging alone cannot safely differentiate between uncomplicated and complicated appendicitis [20–23]. Recent studies have proposed scoring systems that combine clinical and imaging characteristics to differentiate between complicated and uncomplicated appendicitis [24, 25]. Although the distinction between uncomplicated and complicated appendicitis is still challenging, it is essential in determining the treatment strategy, especially nonoperative management.

Outcomes of nonoperative management for uncomplicated appendicitis

Several randomized controlled trials (RCTs) and systematic reviews have suggested that antibiotic therapy can be an effective and safe treatment for acute uncomplicated appendicitis [26–36]. The characteristics of included trials are detailed in Table 1 [27–35]. With the accumulation of vast amounts of data, the guidelines from the World Society of Emergency Surgery (WSES) [37], the American Association for the Surgery of Trauma (AAST) [38], and the Eastern Association for the Surgery of Trauma (EAST) [39] also include antibiotic-first treatment for acute uncomplicated appendicitis. However, since each trial has different inclusion and exclusion criteria and different definitions of treatment outcomes, care should be taken when interpreting the results.

Treatment success

In most clinical trials comparing antibiotic therapy and appendectomy for acute uncomplicated appendicitis, recurrence within 1 year was set as the primary end point, and the 1-year treatment failure rate for antibiotic therapy ranged from 21.9% to 29.0% [27–32, 34, 35]. In some trials that separately defined cases of no clinical improvement within 24 to 72 hours as early treatment failure, surgical treatment was required in about 8% to 12% of patients who received antibiotic-first treatment [31, 34, 35]. In a meta-analysis of 3,618 patients with acute uncomplicated appendicitis, the failure rate of antibiotic therapy during primary hospitalization and the recurrence rate at 1-year follow-up were 8.5% and 19.2%, respectively [40]. The Appendicitis Acuta (APPAC) RCT was the only trial to compare long-term results of more than 1 year, with a 1-year recurrence rate of 27% and a 5-year recurrence rate of 39% [27, 28]. During the 5-year follow-up period, only 2.3% of patients who underwent surgery for recurrent appendicitis were identified as having complicated appendicitis, which supports the feasibility of nonoperative management for acute uncomplicated appendicitis in terms of long-term outcomes [28].

Complication

Each trial had heterogeneity in the definition and classification of complications and adverse events. In most trials, the incidence of antibiotics-related adverse events, such as allergic reactions or Clostridium difficile infection, was relatively low (<1%) and the antibiotics group reported a lower rate of major complications than the surgery group [27, 28, 30, 32, 34, 35]. In an RCT of 530 patients with a 5-year follow-up, Salminen et al. [28] reported complication rates of 6.5% for the antibiotics group versus 24.4% for the surgery group (P<0.001). In another recent RCT involving 318 patients with acute uncomplicated appendicitis, Podda et al. [30] reported a 4.3% complication rate in the antibiotics group compared to a 13% complication rate in the surgery group. A meta-analysis that included 20 studies comparing antibiotic treatment to appendectomy demonstrated that nonoperative management with antibiotics does not significantly increase the perforation rate, indicating that the decision to delay appendectomy does not increase the risk of postoperative complications [40]. In another recent meta-analysis of 3,528 patients in 8 studies, there were no differences in the percentage of major adverse effects between operative and nonoperative management cohorts (relative risk, 0.62; 95% confidence interval [CI], 0.29–1.79), indicating that both approaches for acute uncomplicated appendicitis are relatively safe [41]. On the other hand, in the RCT of 1,552 patients including 419 with clinical evidence of an appendicolith, the antibiotics group had a higher complication rate than the surgery group (8.1% vs. 3.5%) [33]. Notably, the presence of an appendicolith increased the complication rate in the antibiotics group to 20.2% [33], suggesting that nonoperative management may not be suitable for patients with appendicoliths.

Total cost, length of stay, and quality of life

Several RCTs that compared the costs of antibiotics treatment versus appendectomy reported that total costs were less in the antibiotics group. O’Leary et al. [32] reported that the mean total cost in the antibiotics group was significantly lower than surgery group (€3,077 vs. €4,816, P<0.001). Sippola et al. [42] compared not only total hospital charges but also productivity losses, demonstrating that the overall societal costs for the surgery group were 1.6 times higher than those for the antibiotics group. However, these results may vary depending on the healthcare system or clinical environment, so it is difficult to generalize based on current evidence.

Most RCTs reported no significant differences in length of hospital stay between the antibiotics and surgery groups. Interestingly, in a meta-analysis of 46 studies comparing a time period before and during the COVID-19 pandemic, the rate of antibiotic treatment for acute uncomplicated appendicitis increased significantly, whereas length of hospital stay did not increase [18]. These results support the noninferiority of nonoperative management compared with appendectomy in terms of the length of hospital stay.

In terms of quality of life (QOL), conflicting data have been reported in different studies [30–35]. O’Leary et al. [32] reported the antibiotics group had a lower QOL score at 1 year after treatment (0.888 vs 0.976, P<0.001), whereas Podda et al. [30] reported a higher score in the antibiotics group. In a secondary analysis of APPAC RCT with a 7-year follow-up, long-term QOL and patient satisfaction were not significantly different between the antibiotics group and the surgery group [29]. However, antibiotics group patients who later underwent appendectomy were less satisfied than patients with appendectomy or successful antibiotic therapy, highlighting the importance of proper patient selection [29].

Outcomes of nonoperative management for complicated appendicitis

It is generally accepted that emergency surgery is necessary in patients with evidence of generalized peritonitis, unstable vital signs, and/or organ failure. In contrast, the optimal approach to acute complicated appendicitis with phlegmon or abscess is still controversial. Therefore, there have been significant differences in treatment strategies between surgeons [43–46]. The initial dilemma is whether to operate immediately or treat conservatively with antibiotics and—if available—percutaneous drainage. It also remains debatable whether an elective interval appendectomy will be needed after successful conservative treatment. Treatment options for complicated appendicitis and their characteristics are summarized in Fig. 3.

Treatment success

The lack of consensus in defining what constitutes successful nonoperative management for complicated appendicitis is a limitation in analyzing the current literature; therefore, it would be appropriate to divide it into early treatment failure and recurrence based on the index admission: Early treatment failure of nonoperative management can be defined as the need for prompt surgery due to aggravation or no improvement of symptoms during the index admission, whereas recurrence can be defined as the need for surgery or additional intervention due to recurrent appendicitis or a posttreatment intraabdominal abscess.

The reported early treatment success rate of nonoperative management ranged from 82.9% to 96.8% [47–50]. If there is a drainable abscess, percutaneous drainage could increase the success rate of nonoperative management. A cohort study of 1,225 patients treated nonoperatively for an appendiceal abscess demonstrated that percutaneous drainage with antibiotics decreased recurrence and complication rates compared to antibiotics alone [51].

The recurrence rate after nonoperative management ranges from 5% to 30% [39, 43, 52–56]. To prevent recurrent appendicitis, some surgeons prefer a routine elective interval appendectomy after initial conservative treatment. However, the reported morbidity (9%–19%) of interval appendectomy is not negligible [43, 57–59]. In a systematic review of 21 studies and 1,943 patients, interval appendectomy and repeated nonoperative management for recurrent appendiceal abscess were found to have comparable morbidity [52]. While the recurrence rate is relatively low, elective interval appendectomy also incurs additional operative costs. Therefore, in current guidelines, routine interval appendectomy after nonoperative management is not recommended for all patients [37, 39].

Complication

It has been generally accepted that an immediate appendectomy for appendicitis with abscess or phlegmon was technically challenging due to the distorted anatomy and the difficulty in closing the appendiceal stump because of inflammation [43]. In metaanalyses of patients with appendiceal abscess or phlegmon, immediate appendectomy was associated with a higher morbidity, including abdominal abscess, bowel obstruction, wound infection, and reoperation, than nonoperative management [43, 44].

However, as laparoscopy has become the standard approach for appendectomy, the morbidity of surgery, including surgical site infection, has decreased. Recent evidence shows that immediate appendectomy for appendicitis with abscess or phlegmon may be preferable to nonoperative management when advanced laparoscopic expertise is available [47, 50, 55]. In an RCT involving 60 patients treated with laparoscopic appendectomy or nonoperative management, laparoscopic surgery was linked to fewer additional interventions and readmissions than nonoperative management with a comparable length of hospital stay [55]. Young et al. [50] reported that nonoperative management was associated with a higher incidence of bowel resection than immediate appendectomy (17.1% vs. 3.3%, P=0.048). On the other hand, a Japanese nationwide study showed that the rates of morbidity, severe morbidity, and mortality were significantly higher in emergency appendectomy than elective appendectomy [60]. As it is still unclear whether immediate appendectomy offers any benefit in terms of complications compared to nonoperative management [46], both immediate appendectomy and nonoperative management are feasible treatment options for appendicitis with abscess or phlegmon [37].

Optimal indications for nonoperative management

Uncomplicated appendicitis

Careful patient selection is essential for the success of the nonoperative management of acute appendicitis. The presence of appendicoliths has been regarded as an essential determinant in selecting treatment strategy, although it is still debatable whether acute appendicitis with appendicoliths should be classified as complicated or uncomplicated appendicitis [61]. In an RCT involving 239 patients with acute uncomplicated appendicitis, Vons et al. [31] reported that the presence of an appendicolith on the preoperative computed tomography (CT) scan was the only factor associated with failure of antibiotic treatment (P=0.0072) as well as a risk of complicated appendicitis (P<0.0001). Among the recent trials that compared nonoperative management with appendectomy over the past decade [27, 28, 30, 32], the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial [33], an RCT of 1,552 patients with acute uncomplicated appendicitis, was the only one to include patients with an appendicolith. In that trial, the 90-day recurrence rate for patients with appendicolith was 41%, compared to 25% for patients without appendicolith, indicating that appendicolith is a factor that increases the risk of recurrence after antibiotic therapy [33]. According to a recent study, an appendicolith of ≤5 mm in diameter and a serum C-reactive protein (CRP) concentration ≤5 mg/dL were predictive of successful nonoperative management [62]. On the other hand, an appendicolith>10 mm in diameter and a serum CRP concentration>10 mg/dL were significantly associated with appendiceal perforation; these may be indications for appendectomy [62].

A few studies have investigated the factors associated with successful nonoperative management of uncomplicated appendicitis. Hansson et al. [63] proposed a model to select patients suitable for nonoperative management and found that patients who met all criteria, including serum CRP <6 mg/dL, white blood cell count<12× 10⁹/L, and age<60 years, had an 89% probability of recovery with antibiotics alone. In another retrospective cohort analysis of 81 patients treated with nonoperative management, an appendiceal diameter of less than 13 mm (odds ratio, 17.6; 95% CI, 1.3–237.3) was an independent predictor of successful nonoperative management, along with a longer duration of symptoms prior to admission (>25 hours), a lower maximum temperature (<37.3 °C), and a lower modified Alvarado score (<4) [64]. Although there is no definite indicator other than the appendicolith, Moris et al. [19] suggested CT findings of an appendicolith, a dilated appendix greater than 13 mm, and mass effect as relative contraindications for nonoperative management.

Complicated appendicitis

Nonoperative management for complicated appendicitis with localized abscess or phlegmon could avoid the risk of complications incurred by an immediate appendectomy. However, treatment failure in nonoperative management was associated with a longer length of stay and intensive care unit admission [65, 66]. Maxfield et al. [65] found that patients who smoke or have generalized abdominal tenderness, tachycardia, and abscesses smaller than 50 mm were linked to failure of nonoperative management. In another retrospective analysis, a longer duration of symptoms was independently associated with treatment success in complicated appendicitis [66]. It indicates that the duration of symptoms is an independent predictor for both uncomplicated [64] and complicated appendicitis [66].

When determining nonoperative management, it must be taken into account that acute appendicitis may be an early presentation of a malignant tumor. The reported incidence of appendiceal neoplasms ranged from 3% to 17%, and the risk gradually increases after age 40 years [67–71]. Thus, age over 40 years is one of the important factors in determining a treatment strategy, and an immediate or interval appendectomy after successful nonoperative management is recommended [39]. Additional screening and surveillance with colonoscopy, CT, and magnetic resonance are also recommended for detecting hidden malignancies in patients treated nonoperatively who are older than 40 years [70, 71].

In addition to these patient factors, the availability of laparoscopic expertise is a crucial element in determining the optimal treatment approach for appendicitis with abscess or phlegmon [37]. The current trend is toward an immediate laparoscopic appendectomy as a better option for appendicitis with abscess or phlegmon. However, there is insufficient evidence to use laparoscopic appendectomy as a standard treatment in all clinical settings.

CONCLUSION

Nonoperative management with antibiotics is a safe and feasible option for both uncomplicated and complicated appendicitis. The 1-year failure rate of nonoperative management for uncomplicated appendicitis was less than 30%, and the 5-year failure rate was about 40%. Nonoperative management was not inferior to appendectomy in terms of complications and length of stay, and the risk of perforation and postoperative complications did not increase even if nonoperative management failed. The presence of an appendicolith was associated with a higher risk of treatment failure and complications, so it could be an indication for appendectomy.

Nonoperative management for complicated appendicitis with localized abscess or phlegmon could prevent the risk of complications incurred by immediate appendectomy, with a greater than 80% treatment success rate. The recurrence rate is relatively low (5%–30%), and repeated nonoperative management for recurrent appendicitis has a comparable morbidity rate; therefore, interval appendectomy after successful nonoperative management is not recommended for all patients. As the incidence of appendiceal neoplasms increases after age 40 years, interval appendectomy and additional screening and surveillance are recommended.

Nonoperative management is an alternative to surgery for patients who want to avoid or delay it or are ineligible for surgery or general anesthesia due to comorbidities, without increasing the risk of complications. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure. There are no indicators with sufficient evidence available for patient selection except for the appendicolith, which should be investigated through further research.

ARTICLE INFORMATION

Conflict of interest

In Ja Park is the current editor-in-chief of this journal, but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: IJP; Data curation: HGL; Formal analysis: HGL; Investigation: all authors; Methodology: all authors; Project administration: IJP; Visualization: all authors; Writing–original draft: HGL; Writing–review & editing: IJP. All authors read and approved the final manuscript.

Fig. 1.

Flowchart of the study identification and selection process.

Fig. 2.

Classification of acute appendicitis based on macroscopic and microscopic pathology.

Fig. 3.

Treatment options for complicated appendicitis.

Table 1.

Randomized controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis

Study	No. of patients	Inclusion criteria	Treatment failure (antibiotics group)	Complication/adverse event	Other outcome
O'Leary et al. [32] (2021)	186 (93 laparoscopic appendectomy vs. 93 antibiotics)	Age >16 yr	25.3% (within 1 yr)	Surgery (overall, 5.4%)	Better QOL score in the surgery group at 1 yr after treatment (0.976 vs. 0.888, P<0.001)
		Uncomplicated appendicitis (no evidence of abscess, collection, fecolith, and/or perforation)		Postoperative collection, 4.3%	The accumulated 12-mo sickness days was 3.6 days shorter for the antibiotics only group (5.3 days vs. 8.9 days, P<0.01)
				Wound infection, 1.1%	The mean length of stay in both groups was not significantly different (2.3 days vs. 2.8 days, P=0.13)
				Antibiotics (overall, 1%)	The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs. €3,077, P<0.001)
				Cellulitis at the cannula site, 1%
Podda et al. [30] (2021)	318 (231 laparoscopic or open appendectomy vs. 87 antibiotics)	Age 18–65 yr	26.4% (within 1 yr)	Surgery (overall, 13%)	QOL score at 30-day follow-up was higher in the surgery group, while QOL score at 1-yr follow-up was lower in the surgery group
		Uncomplicated appendicitis (no evidence of appendicolith, perforation, and abscess)		Surgical site infection, 6.1%
				Postoperative abdominal abscess, 2.6%
				Bowel obstruction, 2.6%	Pain score was lower in the antibioticsgroup (P<0.001)
				Incisional hernia, 1.3%	The days of absence from work was higher in the surgery group
				Antibiotics (overall, 4.3%)
				Incisional hernia, 0.4%
CODA Collaborative et al. [33] (2020)	1,552 (776 laparoscopic or open appendectomy vs. 776 antibiotics)	Age >18 yr	29% (within 90 days; 41% of patients with appendicolith and 25% of patients without appendicolith)	Surgery (overall, 3.5%)	Based on 30-day QOL score, antibiotics were noninferior to surgery (mean difference, 0.01 points; 95% CI, –0.001 to 0.03)
		Uncomplicated appendicitis (no evidence of diffuse peritonitis, recurrent appendicitis, severe phlegmon, walled-off abscess, and free air)		Serious adverse events, 3.0%
				Antibiotics (overall, 8.1%)	Antibiotics group missed less time from work than surgery group
				Serious adverse events, 4.0% (presence of appendicolith increased complication rate to 20.2%)	Emergency department visits and hospitalizations were more common in the antibiotics group after the index treatment
Salminen et al. [27] (2015), Salminen et al. [28] (2018), and Sippola et al. [29] (2020)	273 (16 open appendectomy vs. 257 antibiotics)	Age 18–60 yr	27.3% (within 1 yr)	Surgery (overall, 24.4%)	The QOL between surgery group and antibiotics group was similar at 7-yr follow-up (95% CI, 0.86 to 1.0, P=0.96)
		Uncomplicated appendicitis (no evidence of appendicolith, abscess, or perforation)	34.0% (within 2 yr)	Surgical site infection, 9.8%
			35.2% (within 3 yr)	Incisional hernia, 0.8%	Patients taking antibiotics who later underwent appendectomy were less satisfied than those with successful antibiotics or appendectomy
			37.1% (within 4 yr)	Abdominal pain or obstructive symptoms, 15.4%
			39.1% (within 5 yr)	Antibiotics (overall, 6.5%)
				Surgical site infection, 0.4%	There was no difference in length of hospital stay between 2 groups
				Incisional hernia, 1.2%	The median time used for sick leave was longer in surgery group than antibiotics group (22 days vs. 11 days, P<0.001)
				Abdominal pain or obstructive symptoms, 5.3%
Vons et al. [31] (2011)	239 (119 laparoscopic or open appendectomy vs. 120 antibiotics)	Age >18 yr	12% (within 1 mo)	Surgery (overall, 2.5%)	No significant difference in duration of pain, duration of hospital stay, and duration of disability
		Uncomplicated appendicitis (no evidence of peritonitis: extraluminal gas, periappendiceal fluid, or disseminated intraperitoneal fluid)	26% (within 1 yr)	Posttherapeutic peritonitis, 2%
				Surgical site infection, 0.8%
				Antibiotics (overall, 11.7%)	In the antibiotics group, the presence of a stercolith was the only factor associated with increased risk of complicated appendicitis (P<0.0001) and failure of antibiotic treatment for appendicitis (P=0.0072)
				Posttherapeutic peritonitis, 8%
				Surgical site infection, 1.7%
				Bowel obstruction, 0.8%
Hansson et al. [34] (2009)	369 (167 laparoscopic or open appendectomy vs. 202 antibiotics)	Age >18 yr	9.2% (within 1 mo)	Surgery	Total costs for treatment were 50% less in the antibiotics group
		Unselected appendicitis	21.9% (within 1 yr)	Major complications, 10.8%
		Patients diagnosed according to established practice		Minor complications, 22.2%	Duration of posttreatment pain were shorter in the antibiotics group
				Antibiotics
				Major complications, 5.4%	Long-term abdominal discomfort was more frequent in the antibiotics group
				Minor complications, 19.8%’
Styrud et al. [35] (2006)	252 (124 laparoscopic or open appendectomy vs. 128 antibiotics)	Age 18–50 yr	11.7% (within 24 hr)	Surgery (overall, 14%)	No significant difference in length of hospital stay and duration of sick leave
Styrud et al. [35] (2006)		Male sex (no evidence of perforated appendicitis)	25.8% (within 1 yr)	Antibiotics (overall, 3.1%)

QOL, quality of life; CI, confidence interval.

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Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review

Ann Coloproctol. 2025;41(2):107-118. Published online April 16, 2025

DOI: https://doi.org/10.3393/ac.2023.00192.0027

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Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review

Fig. 1. Flowchart of the study identification and selection process.

Fig. 2. Classification of acute appendicitis based on macroscopic and microscopic pathology.

Fig. 3. Treatment options for complicated appendicitis.

Graphical abstract

Fig. 1.

Fig. 2.

Fig. 3.

Graphical abstract

Clinical outcomes and optimal indications for nonoperative management of acute appendicitis in adult patients: a comprehensive literature review

Study	No. of patients	Inclusion criteria	Treatment failure (antibiotics group)	Complication/adverse event	Other outcome
O'Leary et al. [32] (2021)	186 (93 laparoscopic appendectomy vs. 93 antibiotics)	Age >16 yr	25.3% (within 1 yr)	Surgery (overall, 5.4%)	Better QOL score in the surgery group at 1 yr after treatment (0.976 vs. 0.888, P<0.001)
		Uncomplicated appendicitis (no evidence of abscess, collection, fecolith, and/or perforation)		Postoperative collection, 4.3%	The accumulated 12-mo sickness days was 3.6 days shorter for the antibiotics only group (5.3 days vs. 8.9 days, P<0.01)
				Wound infection, 1.1%	The mean length of stay in both groups was not significantly different (2.3 days vs. 2.8 days, P=0.13)
				Antibiotics (overall, 1%)	The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs. €3,077, P<0.001)
				Cellulitis at the cannula site, 1%
Podda et al. [30] (2021)	318 (231 laparoscopic or open appendectomy vs. 87 antibiotics)	Age 18–65 yr	26.4% (within 1 yr)	Surgery (overall, 13%)	QOL score at 30-day follow-up was higher in the surgery group, while QOL score at 1-yr follow-up was lower in the surgery group
		Uncomplicated appendicitis (no evidence of appendicolith, perforation, and abscess)		Surgical site infection, 6.1%
				Postoperative abdominal abscess, 2.6%
				Bowel obstruction, 2.6%	Pain score was lower in the antibioticsgroup (P<0.001)
				Incisional hernia, 1.3%	The days of absence from work was higher in the surgery group
				Antibiotics (overall, 4.3%)
				Incisional hernia, 0.4%
CODA Collaborative et al. [33] (2020)	1,552 (776 laparoscopic or open appendectomy vs. 776 antibiotics)	Age >18 yr	29% (within 90 days; 41% of patients with appendicolith and 25% of patients without appendicolith)	Surgery (overall, 3.5%)	Based on 30-day QOL score, antibiotics were noninferior to surgery (mean difference, 0.01 points; 95% CI, –0.001 to 0.03)
		Uncomplicated appendicitis (no evidence of diffuse peritonitis, recurrent appendicitis, severe phlegmon, walled-off abscess, and free air)		Serious adverse events, 3.0%
				Antibiotics (overall, 8.1%)	Antibiotics group missed less time from work than surgery group
				Serious adverse events, 4.0% (presence of appendicolith increased complication rate to 20.2%)	Emergency department visits and hospitalizations were more common in the antibiotics group after the index treatment
Salminen et al. [27] (2015), Salminen et al. [28] (2018), and Sippola et al. [29] (2020)	273 (16 open appendectomy vs. 257 antibiotics)	Age 18–60 yr	27.3% (within 1 yr)	Surgery (overall, 24.4%)	The QOL between surgery group and antibiotics group was similar at 7-yr follow-up (95% CI, 0.86 to 1.0, P=0.96)
		Uncomplicated appendicitis (no evidence of appendicolith, abscess, or perforation)	34.0% (within 2 yr)	Surgical site infection, 9.8%
			35.2% (within 3 yr)	Incisional hernia, 0.8%	Patients taking antibiotics who later underwent appendectomy were less satisfied than those with successful antibiotics or appendectomy
			37.1% (within 4 yr)	Abdominal pain or obstructive symptoms, 15.4%
			39.1% (within 5 yr)	Antibiotics (overall, 6.5%)
				Surgical site infection, 0.4%	There was no difference in length of hospital stay between 2 groups
				Incisional hernia, 1.2%	The median time used for sick leave was longer in surgery group than antibiotics group (22 days vs. 11 days, P<0.001)
				Abdominal pain or obstructive symptoms, 5.3%
Vons et al. [31] (2011)	239 (119 laparoscopic or open appendectomy vs. 120 antibiotics)	Age >18 yr	12% (within 1 mo)	Surgery (overall, 2.5%)	No significant difference in duration of pain, duration of hospital stay, and duration of disability
		Uncomplicated appendicitis (no evidence of peritonitis: extraluminal gas, periappendiceal fluid, or disseminated intraperitoneal fluid)	26% (within 1 yr)	Posttherapeutic peritonitis, 2%
				Surgical site infection, 0.8%
				Antibiotics (overall, 11.7%)	In the antibiotics group, the presence of a stercolith was the only factor associated with increased risk of complicated appendicitis (P<0.0001) and failure of antibiotic treatment for appendicitis (P=0.0072)
				Posttherapeutic peritonitis, 8%
				Surgical site infection, 1.7%
				Bowel obstruction, 0.8%
Hansson et al. [34] (2009)	369 (167 laparoscopic or open appendectomy vs. 202 antibiotics)	Age >18 yr	9.2% (within 1 mo)	Surgery	Total costs for treatment were 50% less in the antibiotics group
		Unselected appendicitis	21.9% (within 1 yr)	Major complications, 10.8%
		Patients diagnosed according to established practice		Minor complications, 22.2%	Duration of posttreatment pain were shorter in the antibiotics group
				Antibiotics
				Major complications, 5.4%	Long-term abdominal discomfort was more frequent in the antibiotics group
				Minor complications, 19.8%’
Styrud et al. [35] (2006)	252 (124 laparoscopic or open appendectomy vs. 128 antibiotics)	Age 18–50 yr	11.7% (within 24 hr)	Surgery (overall, 14%)	No significant difference in length of hospital stay and duration of sick leave
Styrud et al. [35] (2006)		Male sex (no evidence of perforated appendicitis)	25.8% (within 1 yr)	Antibiotics (overall, 3.1%)

Table 1. Randomized controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis

QOL, quality of life; CI, confidence interval.