Appendicitis Publications

Multi-institutional Trial of Non-operative Management and Surgery for Uncomplicated Appendicitis in Children: Design and Rationale

Minneci PC, Hade EM, Lawrence AE, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Fischer BA, Cooper JN, Deans KJ; MidwestPediatric Surgery Consortium. Multi-institutional trial of non-operative management and surgery for uncomplicated appendicitis in children: Design and rationale. Contemp Clin Trials. 2019 Aug;83:10-17. doi: 10.1016/j.cct.2019.06.013. Epub 2019 Jun 26. PMID: 31254670

  • Abstract

    Traditionally, children presenting with appendicitis are referred for urgent appendectomy. Recent improvements in the quality and availability of diagnostic imaging allow for better pre-operative characterization of appendicitis, including severity of inflammation; size of the appendix; and presence of extra-luminal inflammation, phlegmon, or abscess. These imaging advances, in conjunction with the availability of broad spectrum oral antibiotics, allow for the identification of a subset of patients with uncomplicated appendicitis that can be successfully treated with antibiotics alone. Recent studies demonstrated that antibiotics alone are a safe and efficacious treatment alternative for patents with uncomplicated appendicitis. The objective of this study is to perform a multi-institutional trial to examine the effectiveness of non-operative management of uncomplicated pediatric appendicitis across a group of large children's hospitals. A prospective patient choice design was chosen to compare non-operative management to surgery in order to assess effectiveness in a broad population representative of clinical practice in which non-operative management is offered as an alternative to surgery. The risks and benefits of each treatment are very different and a "successful" treatment depends on which risks and benefits are most important to each patient and his/her family. The patient-choice design allows for alignment of preferences with treatment. Patients meeting eligibility criteria are offered a choice of non-operative management or appendectomy. Primary outcomes include determining the success rate of non-operative management and comparing differences in disability days, and secondarily, complication rates, quality of life, and healthcare satisfaction, between patients choosing non-operative management and those choosing appendectomy.

    Cite

    Minneci PC, Hade EM, Lawrence AE, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Fischer BA, Cooper JN, Deans KJ; MidwestPediatric Surgery Consortium. Multi-institutional trial of non-operative management and surgery for uncomplicated appendicitis in children: Design and rationale. Contemp Clin Trials. 2019 Aug;83:10-17. doi: 10.1016/j.cct.2019.06.013. Epub 2019 Jun 26. PMID: 31254670

Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis Over 1 Year

Gil LA, Asti L, Chen HF, Saito JM, Pattisapu P, Deans KJ, Minneci PC; Midwest Pediatric Surgery Consortium. Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis for 1 Year. J Am Coll Surg. 2025 Mar 1;240(3):288-298. doi: 10.1097/XCS.0000000000001232. Epub 2025 Feb 14. PMID: 39560281

  • Abstract

    Background: Nonoperative management (NOM) with antibiotics alone for pediatric uncomplicated appendicitis is accepted to be safe and effective. However, the relative cost-effectiveness of this approach compared with appendectomy remains unknown. We aimed to evaluate the cost-effectiveness of nonoperative vs operative management for pediatric uncomplicated acute appendicitis.

    Study design: A trial-based real-world economic evaluation from the healthcare sector perspective was performed using data collected from a multi-institutional nonrandomized controlled trial investigating NOM vs surgery. The time horizon was 1 year, with costs in 2023 US dollars. Ratio of costs-to-charges-based data for the initial hospitalization, readmissions, and unplanned emergency department visits were extracted from the Pediatric Health Information System. Utility data were derived from patient-reported disability days and health-related quality-of-life scores. Multiple scenarios and 1-way deterministic and probabilistic sensitivity analyses accounted for parameter uncertainty. Willingness-to-pay threshold was set at $100,000 per quality-adjusted life year (QALY) or disability-adjusted life year. Primary outcome measures included total and incremental mean costs, QALY, disability-adjusted life year, and incremental cost-effectiveness ratios.

    Results: Of 1,068 participants, 370 (35%) selected NOM and 698 (65%) selected urgent laparoscopic appendectomy. Operative management cost an average of $9,791 per patient and yielded an average of 0.884 QALYs, whereas NOM cost an average of $8,044 per patient and yielded an average of 0.895 QALYs. NOM was both less costly and more effective in base case and scenario analyses using disability days and alternate methods of calculating uses.

    Conclusions: NOM is cost-effective compared with laparoscopic appendectomy for pediatric uncomplicated appendicitis for 1 year.

    Cite

    Gil LA, Asti L, Chen HF, Saito JM, Pattisapu P, Deans KJ, Minneci PC; Midwest Pediatric Surgery Consortium. Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis for 1 Year. J Am Coll Surg. 2025 Mar 1;240(3):288-298. doi: 10.1097/XCS.0000000000001232. Epub 2025 Feb 14. PMID: 39560281.

Demographic and Clinical Characteristics Associated With the Failure of Nonoperative Management of Uncomplicated Appendicitis in Children: Secondary Analysis of a Nonrandomized Clinical Trial

Minneci PC, Hade EM, Gil LA, Metzger GA, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ; Midwest Pediatric Surgery Consortium. Demographic and Clinical Characteristics Associated With the Failure of Nonoperative Management of Uncomplicated Appendicitis in Children: Secondary Analysis of a Nonrandomized Clinical Trial. JAMA Netw Open. 2022 May 2;5(5):e229712. doi: 10.1001/jamanetworkopen.2022.9712. PMID: 35499827.

  • Abstract

    Importance: The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown.

    Objectives: To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed.

    Design, setting, and participants: This study was a planned subgroup secondary analysis conducted in 10 children's hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022.

    Interventions: Nonoperative management with antibiotics vs surgery.

    Main outcomes and measures: Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management.

    Results: Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]).

    Conclusions and relevance: This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year.

    Cite

    Minneci PC, Hade EM, Gil LA, Metzger GA, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ; Midwest Pediatric Surgery Consortium. Demographic and Clinical Characteristics Associated With the Failure of Nonoperative Management of Uncomplicated Appendicitis in Children: Secondary Analysis of a Nonrandomized Clinical Trial. JAMA Netw Open. 2022 May 2;5(5):e229712. doi: 10.1001/jamanetworkopen.2022.9712. PMID: 35499827.

Association of Initial Treatment With Antibiotics vs Surgery With Treatment Success and Disability in Subgroups of Children With Uncomplicated Appendicitis

Minneci PC, Hade EM, Metzger GA, Saito JM, Mak GZ, Deans KJ; Midwest Pediatric Surgery Consortium. Association of Initial Treatment With Antibiotics vs Surgery With Treatment Success and Disability in Subgroups of Children With Uncomplicated Appendicitis. JAMA. 2021 Jun 22;325(24):2502-2504. doi: 10.1001/jama.2021.6710. PMID: 34156416; PMCID: PMC8220457.

  • Abstract

    This study investigates differences in 1-year outcomes by clinical and socioeconomic factors among US children with uncomplicated appendicitis who were treated with antibiotics vs surgery.

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    Conflict of interest statement

    Conflict of Interest Disclosures: Dr Saito reported receipt of grants from the Agency for Healthcare Research and Quality and the National Institutes of Health. Dr Mak reported receipt of grants from Thrasher. No other disclosures were reported.

    Cite

    Minneci PC, Hade EM, Metzger GA, Saito JM, Mak GZ, Deans KJ; Midwest Pediatric Surgery Consortium. Association of Initial Treatment With Antibiotics vs Surgery With Treatment Success and Disability in Subgroups of Children With Uncomplicated Appendicitis. JAMA. 2021 Jun 22;325(24):2502-2504. doi: 10.1001/jama.2021.6710. PMID: 34156416; PMCID: PMC8220457.

Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis.

Minneci PC, Hade EM, Lawrence AE, Sebastião YV, Saito JM, Mak GZ, Fox C, Hirschl RB, Gadepalli S, Helmrath MA, Kohler JE, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ; Midwest Pediatric Surgery Consortium. Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis. JAMA. 2020 Jul 27. doi: 10.1001/jama.2020.10888. Online ahead of print.PMID: 32730561

  • Abstract

    Importance: Nonoperative management with antibiotics alone has the potential to treat uncomplicated pediatric appendicitis with fewer disability days than surgery.

    Objective: To determine the success rate of nonoperative management and compare differences in treatment-related disability, satisfaction, health-related quality of life, and complications between nonoperative management and surgery in children with uncomplicated appendicitis.

    Design, setting, and participants: Multi-institutional nonrandomized controlled intervention study of 1068 children aged 7 through 17 years with uncomplicated appendicitis treated at 10 tertiary children's hospitals across 7 US states between May 2015 and October 2018 with 1-year follow-up through October 2019. Of the 1209 eligible patients approached, 1068 enrolled in the study.

    Interventions: Patient and family selection of nonoperative management with antibiotics alone (nonoperative group, n = 370) or urgent (≤12 hours of admission) laparoscopic appendectomy (surgery group, n = 698).

    Main outcomes and measures: The 2 primary outcomes assessed at 1 year were disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care (expected difference, 5 days), and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year (lowest acceptable success rate, ≥70%). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome assessments.

    Results: Among 1068 patients who were enrolled (median age, 12.4 years; 38% girls), 370 (35%) chose nonoperative management and 698 (65%) chose surgery. A total of 806 (75%) had complete follow-up: 284 (77%) in the nonoperative group; 522 (75%) in the surgery group. Patients in the nonoperative group were more often younger (median age, 12.3 years vs 12.5 years), Black (9.6% vs 4.9%) or other race (14.6% vs 8.7%), had caregivers with a bachelor's degree (29.8% vs 23.5%), and underwent diagnostic ultrasound (79.7% vs 74.5%). After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.31%; P = .86). Nonoperative management was associated with significantly fewer patient disability days at 1 year than did surgery (adjusted mean, 6.6 vs 10.9 days; mean difference, -4.3 days (99% CI, -6.17 to -2.43; P < .001). Of 16 other prespecified secondary end points, 10 showed no significant difference.

    Conclusion and relevance: Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not statistically significant, and the hypothesized difference in disability days was not met.

    Cite

    Minneci PC, Hade EM, Lawrence AE, Sebastião YV, Saito JM, Mak GZ, Fox C, Hirschl RB, Gadepalli S, Helmrath MA, Kohler JE, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ; Midwest Pediatric Surgery Consortium. Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis. JAMA. 2020 Jul 27. doi: 10.1001/jama.2020.10888. Online ahead of print.PMID: 32730561

Comparing Antibiotics and Surgery to Treat Appendicitis in Children

Minneci P; on behalf of the following co-investigators and the Midwest Pediatric Surgery Consortium; Hade EM, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ. Comparing Antibiotics and Surgery to Treat Appendicitis in Children [Internet]. Washington (DC): Patient-Centered Outcomes Research Institute (PCORI); 2021 May. PMID: 38556973.

  • Excerpt

    Background: Although curative, appendectomy is a major intra-abdominal operation with associated perioperative risks, pain, and disability. A nonoperative management strategy with antibiotics alone has the potential to treat the disease effectively with less negative impact on the child and the family.

    Objectives: To determine the effectiveness of nonoperative management by characterizing its success rate and comparing treatment-related disability, health-related quality of life (HRQOL), health care satisfaction, and treatment-associated complications of nonoperative management vs surgery in children with uncomplicated appendicitis.

    Methods: We conducted a multi-institutional trial with patient choice between antibiotics alone (nonoperative group) and appendectomy (surgery group) in children aged 7 to 17 years with uncomplicated appendicitis. Uncomplicated appendicitis was defined by focal abdominal pain ≤48 hours before receiving antibiotics, a white blood cell count of ≤18 000 cells/μL, and an ultrasound or computed tomography (CT) scan diagnosis of acute appendicitis (appendiceal diameter ≤1.1 cm, with no phlegmon, abscess, or appendicolith). All patients and their caregivers were counseled on each treatment option, and then chose either nonoperative management or surgery. Nonoperative management consisted of hospital admission with at least 24 hours of intravenous (IV) antibiotics, followed by oral antibiotics at home to complete a total antibiotic course of 7 days. Surgical management consisted of hospital admission with IV antibiotics and urgent laparoscopic appendectomy. The 2 primary outcomes assessed at 1 year were disability days (expected difference, 5 days) and success rate of nonoperative management, defined as the proportion of patients who were initially managed nonoperatively and who did not undergo appendectomy by 1 year (lowest acceptable success rate ≥70% based on surgeon input). Secondary outcomes included differences in caregiver disability days, HRQOL, health care satisfaction, rates of complicated appendicitis, and posttreatment-related complications. Outcomes were assessed at 30 days and 1 year. Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome comparative assessments. In addition, IPTW was used to account for differences between treatment groups to create an “unbiased” cohort for the single-group outcome of the success of nonoperative management.

    Results: We enrolled 1068 patients from May 2015 through November 2018 across 10 tertiary care children's hospitals, with 370 patients choosing nonoperative management and 698 choosing surgery. Patients choosing nonoperative management were younger, more often non-White (Black or other race), had caregivers with higher education (college or higher), and were more likely to have undergone an ultrasound rather than a CT scan. The success rate of nonoperative management was analyzed in all 370 patients so treated, and disability days were analyzed in 806 of the 1098 participating patients (follow-up rates: nonoperative, 284/370 [77%]; surgery, 522/698 [75%]).

    Primary outcomes: After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.3%; P = .86 using lowest acceptable success rate ≥70%). Nonoperative management was associated with significantly fewer patient disability days at 1 year than with surgery (mean, 6.6 vs 10.9 days, respectively; difference = −4.3 days (99% CI, −6.17 to −2.43).

    Secondary outcomes: Health care satisfaction scores at 30 days were not different between groups. Although differences were observed in decision satisfaction scores at 30 days and 1 year, these are not likely clinically meaningful differences, as both groups had scores indicative of very high satisfaction with their decision. HRQOL scores reported by the child and caregiver at 30 days were higher in the nonoperative management group than in the surgery group (child-reported difference = 2.73 [95% CI, 1.00-4.46]; parent proxy difference = 3.20 [95% CI, 1.60-4.81]).

    Conclusions: Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1%, and, compared with urgent surgery, was associated with fewer cumulative disability days at 1 year. However, the prespecified threshold for an acceptable success rate of nonoperative management of ≥70% was not met. Health care satisfaction scores were not different between families choosing surgery and those choosing nonoperative management.

    Limitations: The generalizability of these results may be limited because this study was performed specifically at tertiary children's hospitals and because of substantial rates of incomplete follow-up. In addition, there may be residual treatment selection bias despite using robust inferential methods to aid in accounting for treatment confounding bias.

    Cite

    Minneci P; on behalf of the following co-investigators and the Midwest Pediatric Surgery Consortium; Hade EM, Saito JM, Mak GZ, Hirschl RB, Gadepalli S, Helmrath MA, Leys CM, Sato TT, Lal DR, Landman MP, Kabre R, Fallat ME, Cooper JN, Deans KJ. Comparing Antibiotics and Surgery to Treat Appendicitis in Children [Internet]. Washington (DC): Patient-Centered Outcomes Research Institute (PCORI); 2021 May. PMID: 38556973.