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

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A Correction to this article was published on 28 January 2021

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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.

Trial registration

Clinicaltrials.gov identifier (NCT number): NCT03080103

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References

  1. Humes DJ, Simpson J (2006) Acute appendicitis. BMJ 333(7567):530–534. https://doi.org/10.1136/bmj.38940.664363.AE

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. DeFrances CJ, Podgornik MN (2006) 2004 National Hospital Discharge Survey. Adv Data 371:1–19

    Google Scholar 

  3. 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 (2015) Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA 313(23):2340–2348. https://doi.org/10.1001/jama.2015.6154

    Article  CAS  PubMed  Google Scholar 

  4. Podda M, Gerardi C, Cillara N, Fearnhead N, Gomes CA, Birindelli A, Mulliri A, Davies RJ, Di Saverio S (2019) Antibiotic treatment and appendectomy for uncomplicated acute appendicitis in adults and children: a systematic review and meta-analysis. Ann Surg 270(6):1028–1040. https://doi.org/10.1097/SLA.0000000000003225

    Article  PubMed  Google Scholar 

  5. Reinisch A, Schröder SR, Ulrich F, Padberg W, Liese J (2019) Antibiotic-treated acute appendicitis-reception in social media. Langenbeck’s Arch Surg 404(3):343–349. https://doi.org/10.1007/s00423-019-01777-y

    Article  Google Scholar 

  6. Sceats LA, Kin C, Staudenmayer KL (2019) Questioning the higher abscess rate and overall cost of care associated with nonoperative management of uncomplicated acute appendicitis-reply. JAMA Surg 154(8):784–785. https://doi.org/10.1001/jamasurg.2019.1162

    Article  PubMed  Google Scholar 

  7. Podda M, Pata F, Pellino G, Ielpo B, Di Saverio S (2020) Acute appendicitis during the COVID-19 lock-down: never waste a crisis! Br J Surg:znaa073 (Published ahead of print)

  8. Hanson AL, Crosby RD, Basson MD (2018) Patient preferences for surgery or antibiotics for the treatment of acute appendicitis. JAMA Surg 153(5):471–478. https://doi.org/10.1001/jamasurg.2017.5310

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yeh DD, Eid AI, Young KA, Wild J, Kaafarani HMA, Ray-Zack M, Kana’an T, Lawless R, Cralley AL, Crandall M, EAST Appendicitis Study Group (2019) Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous (MUSTANG), an EAST multicenter study. Ann Surg doi Publish Ahead of Print. https://doi.org/10.1097/SLA.0000000000003661

  10. Podda M, Cillara N, Balestra F, Agresta F, Birindelli A, Di Saverio S (2017) A short commentary on “Nonoperative management of uncomplicated appendicitis in adults: what do we need to get certainty?”. Int J Surg 40:109–111. https://doi.org/10.1016/j.ijsu.2017.02.059

    Article  PubMed  Google Scholar 

  11. Ehlers AP, Talan DA, Moran GJ, Flum DR, Davidson GH (2016) Evidence for an antibiotics-first strategy for uncomplicated appendicitis in adults: a systematic review and gap analysis. J Am Coll Surg 222(3):309–314. https://doi.org/10.1016/j.jamcollsurg.2015.11.009

    Article  PubMed  Google Scholar 

  12. 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 (2018) Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA 320(12):1259–1265. https://doi.org/10.1001/jama.2018.13201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, Karoui M, Alves A, Dousset B, Valleur P, Falissard B, Franco D (2011) Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet 77(9777):1573–1579. https://doi.org/10.1016/S0140-6736(11)60410-8

    Article  CAS  Google Scholar 

  14. Poillucci G, Mortola L, Podda M, Di Saverio S, Casula L, Gerardi C, Cillara N, Presenti L, ACTUAA-R Collaborative Working Group on Acute Appendicitis (2017) Laparoscopic appendectomy vs antibiotic therapy for acute appendicitis: a propensity score-matched analysis from a multicenter cohort study. Updat Surg 69(4):531–540. https://doi.org/10.1007/s13304-017-0499-8

    Article  Google Scholar 

  15. Sippola S, Haijanen J, Viinikainen L, Grönroos J, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Hurme S, Mecklin JP, Sand J, Jartti A, Salminen P (2020) 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. JAMA Surg 155(4):283–289. https://doi.org/10.1001/jamasurg.2019.6028

    Article  PubMed  Google Scholar 

  16. Kadera SP, Mower WR, Krishnadasan A, Talan DA (2016) Patient perspectives on antibiotics for appendicitis at one hospital. J Surg Res 201(2):253–257. https://doi.org/10.1016/j.jss.2015.11.016

    Article  PubMed  Google Scholar 

  17. Podda M, Serventi F, Mortola L, Marini S, Sirigu D, Piga M, Pisano M, Coppola M, Agresta F, Virdis F, Di Saverio S, Cillara N, ACTUAA Study Collaborative Working Group (2017) A prospective non-randomized controlled, multicenter trial comparing appendectomy and conservative treatment for patients with uncomplicated acute appendicitis (the ACTUAA study). Int J Color Dis 32(11):1649–1660. https://doi.org/10.1007/s00384-017-2878-5

    Article  Google Scholar 

  18. Mällinen J, Vaarala S, Mäkinen M, Lietzén E, Grönroos J, Ohtonen P, Rautio T, Salminen P (2020) Appendicolith appendicitis is clinically complicated acute appendicitis-is it histopathologically different from uncomplicated acute appendicitis. Int J Color Dis 34(8):1393–1400. https://doi.org/10.1007/s00384-019-03332-z

    Article  Google Scholar 

  19. 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, Wiebusch A, Winchell RJ, Clark S, Krishnadasan A, Fannon E, Lavallee DC, Comstock BA, Bizzell B, Heagerty PJ, Kessler LG, Talan DA (2020) A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med 383:1907–1919. https://doi.org/10.1056/NEJMoa2014320

    Article  Google Scholar 

  20. Prechal D, Damirov F, Grilli M, Ronellenfitsch U (2019) Antibiotic therapy for acute uncomplicated appendicitis: a systematic review and meta-analysis. Int J Color Dis 34(6):963–971. https://doi.org/10.1007/s00384-019-03296-0

    Article  Google Scholar 

  21. Prechal D, Post S, Pechlivanidou I, Ronellenfitsch U (2019) Feasibility, acceptance, safety, and effectiveness of antibiotic therapy as alternative treatment approach to appendectomy in uncomplicated acute appendicitis. Int J Color Dis 34(11):1839–1847. https://doi.org/10.1007/s00384-019-03392-1

    Article  Google Scholar 

  22. Talan DA, Saltzman DJ, Mower WR, Krishnadasan A, Jude CM, Amii R, DeUgarte DA, Wu JX, Pathmarajah K, Morim A, Moran GJ, Olive View–UCLA Appendicitis Study Group (2017) Antibiotics-first versus surgery for appendicitis: a US pilot randomized controlled trial allowing outpatient antibiotic management. Ann Emerg Med 70(1):1–11.e9. https://doi.org/10.1016/j.annemergmed.2016.08.446

    Article  PubMed  Google Scholar 

  23. Grigorian A, Kuza CM, Schubl SD, Nguyen NT, de Virgilio C, Kim D, Lekawa M, Nahmias J (2019) Same-day discharge after non-perforated laparoscopic appendectomy is safe. J Investig Surg 20:1–6. https://doi.org/10.1080/08941939.2019.1630065

    Article  Google Scholar 

  24. Agresta F, Campanile FC, Podda M, Cillara N, Pernazza G, Giaccaglia V, Ciccoritti L, Ioia G, Mandalà S, La Barbera C, Birindelli A, Sartelli M, Di Saverio S, Joined Italian Surgical Societies Working Group (2017) Current status of laparoscopy for acute abdomen in Italy: a critical appraisal of 2012 clinical guidelines from two consecutive nationwide surveys with analysis of 271,323 cases over 5 years. Surg Endosc 31(4):1785–1795. https://doi.org/10.1007/s00464-016-5175-4

    Article  PubMed  Google Scholar 

  25. Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, Boermeester M, Sartelli M, Coccolini F, Tarasconi A, De’ Angelis N, Weber DG, Tolonen M, Birindelli A, Biffl W, Moore EE, Kelly M, Soreide K, Kashuk J, Ten Broek R, Gomes CA, Sugrue M, Davies RJ, Damaskos D, Leppäniemi A, Kirkpatrick A, Peitzman AB, Fraga GP, Maier RV, Coimbra R, Chiarugi M, Sganga G, Pisanu A, De’ Angelis GL, Tan E, Van Goor H, Pata F, Di Carlo I, Chiara O, Litvin A, Campanile FC, Sakakushev B, Tomadze G, Demetrashvili Z, Latifi R, Abu-Zidan F, Romeo O, Segovia-Lohse H, Baiocchi G, Costa D, Rizoli S, Balogh ZJ, Bendinelli C, Scalea T, Ivatury R, Velmahos G, Andersson R, Kluger Y, Ansaloni L, Catena F (2020) Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg 15(1):27. https://doi.org/10.1186/s13017-020-00306-3

    Article  PubMed  PubMed Central  Google Scholar 

  26. Podda M, Cillara N, Di Saverio S, Lai A, Feroci F, Luridiana G, Agresta F, Vettoretto N, ACOI (Italian Society of Hospital Surgeons) Study Group on Acute Appendicitis (2017) Antibiotics-first strategy for uncomplicated acute appendicitis in adults is associated with increased rates of peritonitis at surgery. A systematic review with meta-analysis of randomized controlled trials comparing appendectomy and non-operative management with antibiotics. Surgeon 15(5):303–314. https://doi.org/10.1016/j.surge.2017.02.001

    Article  PubMed  Google Scholar 

  27. Koumarelas K, Theodoropoulos GE, Spyropoulos BG, Bramis K, Manouras A, Zografos G (2014) A prospective longitudinal evaluation and affecting factors of health related quality of life after appendectomy. Int J Surg 12(8):848–857. https://doi.org/10.1016/j.ijsu.2014.06.015

    Article  PubMed  Google Scholar 

  28. Sippola S, Grönroos J, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Hurme S, Salminen P (2017) Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial. Br J Surg 104(10):1355–1361. https://doi.org/10.1002/bjs.10575

    Article  CAS  PubMed  Google Scholar 

  29. Andersson RE, Petzold MG (2007) Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg 246(5):741–748. https://doi.org/10.1097/SLA.0b013e31811f3f9f

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank and express gratitude to Professor Silvio Garattini and Doctor Vittorio Bertele’ (Istituto di Ricerche Farmacologiche Mario Negri – IRCSS) for the intellectual review of the ACTUAA study protocol.

The ACTUAA Study Collaborative Working Group: Fernando Serventi, Stefano Marini, Danilo Sirigu, Michela Piga, Massimiliano Coppola, Francesco Balestra, Carlo De Nisco, Marco Pazzona, Marco Anania, Fabio Pulighe, Antonio Lai, Roberto Ottonello, Renato De Angelis, Silverio Piro, Pietro Giorgio Calò, Francesco Podda, Luca Saba, Vincenzo Bottino, Patrizia Dalla Caneva, Luisa Canu, Emanuele Piras, Antonello Deserra, Francesco Virdis, Chiara Gerardi, Luca Gordini, Silvia Sanna.

Writing group: Mauro Podda, Gaetano Poillucci, Nicola Cillara.

IT support: Lorenzo Mortola.

Statistical analysis: Daniela Pacella, Gaetano Poillucci.

Author information

Authors and Affiliations

Authors

Consortia

Contributions

Mauro Podda and Nicola Cillara: study principal investigators; Mauro Podda, Lorenzo Mortola, Nicola Cillara: ideated and designed the study; Mauro Podda, Gaetano Poillucci, Daniela Pacella, Lorenzo Mortola, Alfonso Canfora, Simona Aresu, Marcello Pisano, Enrico Erdas, Adolfo Pisanu, Nicola Cillara: acquisition, analysis, and interpretation of data; drafting and critically revising the manuscript for important intellectual contents; and final approval of the version to be published; the ACTUAA Study Collaborative Working Group: acquisition of data, critically revising the manuscript for important intellectual contents, and final approval of the version to be published.

Corresponding author

Correspondence to Mauro Podda.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Independent Ethics Committee of the University of Cagliari (Azienda Ospedaliero-Universitaria di Cagliari): acceptance code PG/2017/8426 29/05/2017.

Informed consent

A written informed consent was obtained from all enrolled patients for being included in the study. Additional written informed consent for the treatment of personal and sensible data was obtained from all patients prior to the data collection and evaluation.

Research involving human participants

All the investigators conducted the study in accordance with the principles of the Declaration of Helsinki of 1975 (as revised in 2008) and in accordance with the ethical standards of the responsible committee on human experimentation (Independent Ethics Committee of the University of Cagliari, Italy). All the investigators conducted the study according to the rules of the ethics committee regarding prospective collection of data.

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The original online version of this article was revised: All authors and affiliations of the The ACTUAA Study Collaborative Working Group are listed in the Acknowledgments section of the original published version of this article however, Luca Gordini and Silvia Sanna should have been added in the list. Thus, the names are now presented and cited correctly.

Mauro Podda and Gaetano Poillucci share the first authorship.

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Podda, M., Poillucci, G., Pacella, D. et al. Appendectomy versus conservative treatment with antibiotics for patients with uncomplicated acute appendicitis: a propensity score–matched analysis of patient-centered outcomes (the ACTUAA prospective multicenter trial). Int J Colorectal Dis 36, 589–598 (2021). https://doi.org/10.1007/s00384-021-03843-8

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