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Here are some landmark papers on acute appendicitis

  1. A randomized clinical trial evaluating the efficacy of quality of life of antibiotic-only treatment of acute uncomplicated appendicitis: Results of the COMMA trial.

 O'Leary DP, Walsh SM, Bolger J, Baban C, Humphreys H, O'Grady S, Hegarty A, Lee AM, Sheehan M, Alderson J, Dunne R, Morrin MM, Lee MJ, Power C, McNamara D, McCawley N, Robb W, Burke J, Sorensen J, Hill AD.

 Ann Surg. 2021 Aug 1;274(2):240-247.

 Abstract

Objective: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis.

Summary background data: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However, the reported failure rates are highly variable and there is a paucity of data in relation to quality of life.

Methods: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy.

Results: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001).

Conclusions: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

  1. Multicenter study of the treatment of appendicitis in America: Acute, Perforated and Gangrenous (MUSTANG), an EAST multicenter stud

Yeh D, Eid AI, Young KA, Wild J, Kaafarani HM, Ray-Zach M, Kana'an T, Lawless R, Cralley AL, Crandall M. EAST Appendicitis Study Group.

 Ann Surg. 2021 Mar 1;273(3):548-556.

 Abstract

Objective: We sought to describe contemporary presentation, treatment, and outcomes of patients presenting with acute (A), perforated (P), and gangrenous (G) appendicitis in the United States.

Summary background data: Recent European trials have reported that medical (antibiotics only) treatment of acute appendicitis is an acceptable alternative to surgical appendectomy. However, the type of operation (open appendectomy) and average duration of stay are not consistent with current American practice and therefore their conclusions do not apply to modern American surgeons.

Methods: This multicenter prospective observational study enrolled adults with appendicitis from January 2017 to June 2018. Descriptive statistics were performed. P and G were combined into a "complicated" outcome variable and risk factors were assessed using multivariable logistic regression.

Results: A total 3597 subjects were enrolled across 28 sites: median age was 37 (27-52) years, 1918 (53%) were male, 90% underwent computed tomography (CT) imaging, 91% were initially treated by appendectomy (98% laparoscopic), and median hospital stay was 1 (1-2) day. The 30-day rates of Emergency Department (ED) visit and readmission were 10% and 6%. Of 219 initially treated with antibiotics, 35 (16%) required appendectomy during index hospitalization and 12 (5%) underwent appendectomy within 30 days, for a cumulative failure rate of 21%. Overall, 2403 (77%) patients had A, whereas 487 (16%) and 218 (7%) patients had P and G, respectively. On regression analysis, age, symptoms >48 hours, temperature, WBC, Alvarado score, and appendicolith were predictive of "complicated" appendicitis, whereas co-morbidities, smoking, and ED triage to appendectomy >6 hours or >12 hours were not.

Conclusion: In the United States, the majority of patients presenting with appendicitis receive CT imaging, undergo laparoscopic appendectomy, and stay in the hospital for 1 day. One in five patients selected for initial non-operative management required appendectomy within 30 days. In-hospital delay to appendectomy is not a risk factor for "complicated" appendicitis.

 

  1. Appendectomy versus conservative treatment with antibiotics for patients with uncomplicated acute appendicitis: a propensity score-matched analysis of patient-centered outcomes (the ACTUAA prospective trial).

 Podda M, Poillucci G, Pacella D, Mortola L, Canfora A, Aresu S, Pisano M, Erdas E, Pisanu A, Cillara N. ACTUAA Study Collaborative Working Group.

 Int J Colorectal Dis. 2021 Mar;36(3):589-598.

Abstract

Purpose: The aim of this prospective multicenter study was to compare antibiotic therapy and appendectomy as treatment for patients with uncomplicated appendicitis confirmed by ultrasound and/or computed tomography.

Methods: The study was conducted from January 2017 to January 2018. Data regarding all patients discharged from the participating centers with a diagnosis of uncomplicated appendicitis were collected prospectively.

Results: Of the 318 patients enrolled in the study, 27.4% underwent antibiotic-first therapy, and 72.6% underwent appendectomy. The matched group was composed of 87 patients in both study arms. Of the 87 patients available of 1-year follow-up in the antibiotic-first group, 64 (73.6%) did not require appendectomy. The complication-free treatment success in the antibiotic-first group was 64.4%. A statistically significant higher complication-free treatment success was found in the appendectomy group: 81.8% in the pre-matching sample and 83.9% in the post-matching sample. Patients in the antibiotic-first group reported lower VAS scores compared to those treated with an appendectomy, both at discharge (2.0 ± 1.7 vs 3.6 ± 2.3) and at 30-day follow-up (0.3 ± 0.6 vs 2.1 ± 1.7). The mean of the days of absence from work was higher in the appendectomy group (β 0.63; 95% CI 0.08-1.18).

Conclusion: Although laparoscopic appendectomy remains the gold standard of treatment for uncomplicated appendicitis, conservative treatment with antibiotics is a safe option in most cases. Approximately 65% of patients treated with antibiotics are symptom-free at 1 year, without increased risk of adverse events should symptoms recur, and better outcomes in terms of less pain and shorter period of absence from work compared to patients undergoing an appendectomy.

 

  1. A randomized trial comparing antibiotics with appendectomy for appendicitis.

 CODA Collaborative; Flum DR, Davidson GH, Monsell SE, Shapiro NI, Odom SR, Sanchez SE, Drake FT, Fischkoff K, Johnson J, Patton JH, Evans H, Cuschieri J, Sabbatini AK, Faine BA, Skeete DA, Liang MK, Sohn V, McGrane K, Kutcher ME, Chung B, Carter DW, Ayoung-Chee P, Chiang W, Rushing A, Steinberg S, Foster CS, Schaetzel SM, Price TP, Mandell KA, Ferrigno L, Salzberg M, DeUgarte DA, Kaji AH, Moran GJ, Saltzman D, Alam HB, Park PK, Kao LS, Thompson CM, Self WH, Yu JT, Wiebush A, Winchell RJ, Clark S, Krishnadasan A, Fannon E, Lavallee DC, Comstock BA, Bizzel B, Heagerty PJ, Kessler LG, Talan DA.

 N Engl J Med. 2020 Nov 12;383(20):1907-1919.

 Abstract

Background: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis.

Methods: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith.

Results: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50).

Conclusions: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

 

 

  1. Quality of life and patient satisfaction at 7-year follow-up of antibiotic therapy vs appendectomy for uncomplicated acute appendicitis: A secondary analysis of a randomized clinical trial.

 Sippola S, Haijanen J, Viinikainen L, Grönroos J, Paajanen H, Rautio T, Norström P, Aarnio M, Rantanen T, Hurme S, Mecklin J, Sand J, Jartti A, Salminen P.

 JAMA Surg. 2020 Apr 1;155(4):283-289.

 Abstract

Importance: Long-term results support antibiotics for uncomplicated acute appendicitis as an alternative to appendectomy. To our knowledge, treatment-related long-term patient satisfaction and quality of life (QOL) are not known.

Objective: To determine patient satisfaction and QOL after antibiotic therapy and appendectomy for treating uncomplicated acute appendicitis.

Interventions: Open appendectomy vs antibiotics with intravenous ertapenem, 1 g once daily, for 3 days followed by 7 days of oral levofloxacin, 500 mg once daily, and metronidazole, 500 mg 3 times per day.

Design, setting, and participants: This observational follow-up of the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics included 530 patients age 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis who were randomized to undergo appendectomy (273 [52%]) or receive antibiotics (257 [49%]). The trial was conducted from November 2009 to June 2012; the last follow-up was May 9, 2018. The data were analyzed in February 2019.

Main outcomes and measures: In this analysis, post hoc secondary end points of postintervention QOL (EQ-5D-5L) and patient satisfaction and treatment preference were evaluated.

Results: Of the 530 patients enrolled in the trial (appendectomy group: 273 [174 men (64%)] with a median age of 35 years; (antibiotic group: 257 [155 men (60%)] with a median age of 33 years), 423 patients (80%) were available for phone interview at a median follow-up of 7 years; 206 patients (80%) took antibiotics and 217 (79%) underwent appendectomy. Of the 206 patients taking antibiotics, 81 (39%) had undergone appendectomy. The QOL between appendectomy and antibiotic group patients was similar (median health index value, 1.0 in both groups; 95% CI, 0.86-1.0; P = .96). Patients who underwent appendectomy were more satisfied in the treatment than patients taking antibiotics (68% very satisfied, 21% satisfied, 6% indifferent, 4% unsatisfied, and 1% very unsatisfied in the appendectomy group and 53% very satisfied, 21% satisfied, 13% indifferent, 7% unsatisfied, and 6% very unsatisfied in the antibiotic group; P < .001) and in a subgroup analysis this difference was based on the antibiotic group patients undergoing appendectomy. There was no difference in patient satisfaction after successful antibiotic treatment compared with appendectomy (cumulative odds ratio [COR], 7.8; 95% CI, 0.5-1.3; P < .36). Patients with appendectomy or with successful antibiotic therapy were more satisfied than antibiotic group patients who later underwent appendectomy (COR, 7.7; 95% CI, 4.6-12.9; P < .001; COR, 9.7; 95% CI, 5.4-15.3; P < .001, respectively). Of the 81 patients taking antibiotics who underwent appendectomy, 27 (33%) would again choose antibiotics as their primary treatment.

Conclusions and relevance: In this analysis, long-term QOL was similar after appendectomy and antibiotic therapy for the treatment of uncomplicated acute appendicitis. Patients taking antibiotics who later underwent appendectomy were less satisfied than patients with successful antibiotics or appendectomy.

 

  1. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial

 Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Hurme S, Mecklin JP, Sand J, Virtanen J, Jartti A, Grönroos JM.

 JAMA. 2018;320(12):1259-1265.

 Abstract

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.

Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.

Design, setting, and participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.

Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.

Main outcomes and measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.

Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).

Conclusions and relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.

 

  1. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial.

 Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Tuominen R, Hurme S, Virtanen J, Mecklin JP, Sand J, Jartti A, Rinta-Kiikka I, Grönroos JM.

 JAMA. 2015 Jun 16;313(23):2340-8.

Abstract

Importance: An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.

Objective: To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT).

Design, setting, and participants: The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period.

Interventions: Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy.

Main outcomes and measures: The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period.

Results: There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment.

Conclusions and relevance: Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications.

 

  1. Antibiotics versus Appendectomy for Acute Appendicitis - Longer-Term Outcomes.

 CODA Collaborative, Davidson GH, Flum DR, Monsell SE, Kao LS, Voldal EC, Heagerty PJ, Fannon E, Lavallee DC, Bizzell B, Lawrence SO, Comstock BA, Krishnadasan A, Winchell RJ, Self WH, Thompson CM, Farjah F, Park PK, Alam HB, Saltzman D, Moran GJ, Kaji AH, DeUgarte DA, Salzberg M, Ferrigno L, Mandell KA, Price TP, Siparsky N, Glaser J, Ayoung-Chee P, Chiang W, Victory J, Chung B, Carter DW, Kutcher ME, Jones A, Holihan J, Liang MK, Faine BA, Cuschieri J, Evans HL, Johnson J, Patton JH, Coleman N, Fischkoff K, Drake FT, Sanchez SE, Parsons C, Odom SR, Kessler LG, Talan DA.

 N Engl J Med. 2021 Dec 16;385(25):2395-2397. doi: 10.1056/NEJMc2116018. Epub 2021 Oct 25.

 

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This page was last updated on 21 November 2022.