Abstract
Acute appendicitis is the most common surgical emergency; however, its etiology and diagnosis are still discussed with a considerable proportion of wrong diagnosis resulting in appendectomies for non inflamed appendix. Moreover, the biologic function of the appendix is still unclear. For uncomplicated acute appendicitis the conservative treatment with antibiotics has been proposed with interesting results. The aim of this study was to compare surgical treatment vs. antibiotics in uncomplicated acute appendicitis. This is a monocentric randomized controlled trial comparing surgery with antibiotic therapy in adults with uncomplicated acute appendicitis. The primary outcome was the success rate (resolution of symptoms within 2 weeks and no need for further treatments); secondary outcomes were complication rate; negative appendectomy rate (only in surgical arm); and long-term outcomes within a year as recurrence. The study was designed as a non-inferiority trial. From September 2011 to December 2014, 224 patients fulfilled the eligibility criteria and 45 patients were randomized. Twenty four patients (53.3%) were randomly assigned to surgery and 21 (46.6%) to antibiotic therapy. In surgical group primary outcome was reached for all the patients; secondary negative outcomes were recorded in five patients (22.7%): two cases of negative appendectomies, three wound infections. In antibiotics group treatment fails in 16.8% of cases; secondary negative outcomes were recorded in one patient who experienced relapse of AA at 30 days No further events or complications were observed at 1-year follow-up. Due to the poor patients’ accrual the study had no enough statistical power to demonstrate the non-inferiority of conservative treatment and results were inconclusive. Due to the poor patient’s accrual rate the study failed to demonstrate the non-inferiority of conservative treatment in uncomplicated acute appendicitis. On the other hand the study demonstrates the difficulty in performing randomized trials in emergency surgery and focus on the ethical aspects.
Similar content being viewed by others
References
Ceresoli M, Zucchi A, Allievi N, Harbi A, Pisano M, Montori G, Heyer A, Nita GE, Ansaloni L, Coccolini F (2016) Acute appendicitis: epidemiology, treatment and outcomes—analysis of 16544 consecutive cases. World J Gastrointest Surg 8:693. https://doi.org/10.4240/wjgs.v8.i10.693
Fitz RH (1886) Perforating inflammation of the vermiform appendix with special reference to its early diagnosis and treatment. Am J Med Sci 92:321–346
Treves F (2016) The Cavendish lecture on some phases of inflammation of the appendix: delivered before the West London Medico-Chirurgical Society on June 20th, 1902. Br Med J 1(1902) 1589–1594. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2512729&tool=pmcentrez&rendertype=abstract. Accessed 15 May 2016
Seetahal SA, Bolorunduro OB, Sookdeo TC, Oyetunji TA, Greene WR, Frederick W, Cornwell EE, Chang DC, Siram SM (2011) Negative appendectomy: a 10-year review of a nationally representative sample. Am J Surg 201:433–437. https://doi.org/10.1016/j.amjsurg.2010.10.009
Bhangu A, Søreide K, Di Saverio S, Hansson Assarsson J, Drake FT (2015) Emergency surgery 1 acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. Lancet 386:1278–1287. https://doi.org/10.1016/s0140-6736(15)00275-5
Andersson M, Andersson RE (2008) The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado score. World J Surg 32:1843–1849. https://doi.org/10.1007/s00268-008-9649-y
Alvarado A (1986) A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 15:557–564. https://doi.org/10.1016/S0196-0644(86)80993-3
Andersson REB (2004) Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 91:28–37. https://doi.org/10.1002/bjs.4464
Andersson M, Kolodziej B, Andersson RE (2017) Randomized clinical trial of appendicitis inflammatory response score-based management of patients with suspected appendicitis. Br J Surg 2017:1451–1461. https://doi.org/10.1002/bjs.10637
Allievi N, Harbi A, Ceresoli M, Montori G, Poiasina E, Coccolini F, Pisano M, Ansaloni L (2017) Acute appendicitis: still a surgical disease? Results from a propensity score-based outcome analysis of conservative versus surgical management from a prospective database. World J Surg. https://doi.org/10.1007/s00268-017-4094-4
Andersson RE (2007) The natural history and traditional management of appendicitis revisited: spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than an early diagnosis. World J Surg 31:86–92. https://doi.org/10.1007/s00268-006-0056-y
Hansson J, Körner U, Khorram-Manesh A, Solberg A, Lundholm K (2009) Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg 96:473–481. https://doi.org/10.1002/bjs.6482
Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, Rex L, Badume I, Granström L (2006) Appendectomy versus antibiotic treatment in acute appendicitis: A prospective multicenter randomized controlled trial. World J Surg 30:1033–1037. https://doi.org/10.1007/s00268-005-0304-6
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 377:1573–1579. https://doi.org/10.1016/S0140-6736(11)60410-8
Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T (2015) Antibiotic therapy vs. appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA 313:2340–2348
Ansaloni L, Catena F, Coccolini F, Ercolani G, Gazzotti F, Pasqualini E, Pinna AD (2011) Surgery versus conservative antibiotic treatment in acute appendicitis: a systematic review and meta-analysis of randomized controlled trials. Dig Surg. https://doi.org/10.1159/000324595
Liu ZH, Li C, Zhang XW, Kang L, Wang JP (2014) Meta-analysis of the therapeutic effects of antibiotic versus appendicectomy for the treatment of acute appendicitis. Exp Ther Med 7:1181–1186. https://doi.org/10.3892/etm.2014.1584
Varadhan KK, Neal KR, Lobo DN (2012) Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials. BMJ 344:e2156–e2157. https://doi.org/10.1136/bmj.e2156
Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO, Agoritsas T, Heels-Ansdell D, Guyatt GH, Tikkinen KAOO (2016) Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg 103:656–667. https://doi.org/10.1002/bjs.10147
Park HC, Kim MJ, Lee BH (2017) Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis. Br J Surg 1:1. https://doi.org/10.1002/bjs.10660
Kooij IA, Sahami S, Meijer SL, Buskens CJ, te Velde AA (2016) The immunology of the vermiform appendix: a review of the literature. Clin Exp Immunol 186:1–9. https://doi.org/10.1111/cei.12821
Horton R (1996) Surgical research or comic opera: questions, but few answers. Lancet 347:984–985. https://doi.org/10.1016/S0140-6736(96)90137-3
Solomon MJ, McLeod RS (1995) Should we be performing more randomized controlled trials evaluating surgical operations? Surgery 118:459–467. https://doi.org/10.1016/S0039-6060(05)80359-9
Daya S (2004) Clinical equipoise, evidence-based. Obstet Gynecol 6:1–2. https://doi.org/10.1016/j.ebobgyn.2004.01.001
Fung EK, Loré JM (2002) Randomized controlled trials for evaluating surgical questions. Arch Otolaryngol Head Neck Surg 128:631–634
Djulbegovic B (2009) The paradox of equipoise: the principle that drives and limits therapeutic discoveries in clinical research. Cancer Control 16:342–347. https://doi.org/10.1016/j.biotechadv.2011.08.021.Secreted
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflict of interest.
Research involving human participants and/or animals
The study was conducted according to the Helsinki declaration about ethical standards; the study protocol was approved by the etical committee of the Papa Giovanni XXIII hospital.
Informed consent
Informed consent to partecipate was obtained from each patient.
Rights and permissions
About this article
Cite this article
Ceresoli, M., Pisano, M., Allievi, N. et al. Never put equipoise in appendix! Final results of ASAA (antibiotics vs. surgery for uncomplicated acute appendicitis in adults) randomized controlled trial. Updates Surg 71, 381–387 (2019). https://doi.org/10.1007/s13304-018-00614-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13304-018-00614-z