The NOTA study: non-operative treatment for acute appendicitis: prospective study on the efficacy and safety of antibiotic treatment (amoxicillin and clavulanic acid) in patients with right sided lower abdominal pain

Gregorio Tugnoli, Eleonora Giorgini, Andrea Biscardi, Silvia Villani, Nicola Clemente, Gianluca Senatore, Filippo Filicori, Nicola Antonacci, Franco Baldoni, Carlo De Werra, Salomone Di Saverio, Gregorio Tugnoli, Eleonora Giorgini, Andrea Biscardi, Silvia Villani, Nicola Clemente, Gianluca Senatore, Filippo Filicori, Nicola Antonacci, Franco Baldoni, Carlo De Werra, Salomone Di Saverio

Abstract

Background: Case control studies that randomly assign patients with diagnosis of acute appendicitis to either surgical or non-surgical treatment yield a relapse rate of approximately 14% at one year. It would be useful to know the relapse rate of patients who have, instead, been selected for a given treatment based on a thorough clinical evaluation, including physical examination and laboratory results (Alvarado Score) as well as radiological exams if needed or deemed helpful. If this clinical evaluation is useful, the investigators would expect patient selection to be better than chance, and relapse rate to be lower than 14%. Once the investigators have established the utility of this evaluation, the investigators can begin to identify those components that have predictive value (such as blood analysis, or US/CT findings). This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid risks and costs of needless surgery.

Methods/design: This will be a single-cohort prospective observational study. It will not interfere with the usual pathway, consisting of clinical examination in the Emergency Department (ED) and execution of the following exams at the physician's discretion: full blood count with differential, C reactive protein, abdominal ultrasound, abdominal CT. Patients admitted to an ED with lower abdominal pain and suspicion of acute appendicitis and not needing immediate surgery, are requested by informed consent to undergo observation and non operative treatment with antibiotic therapy (Amoxicillin and Clavulanic Acid). The patients by protocol should not have received any previous antibiotic treatment during the same clinical episode. Patients not undergoing surgery will be physically examined 5 days later. Further follow-up will be conducted at 7, 15 days, 6 months and 12 months. The study will conform to clinical practice guidelines and will follow the recommendations of the Declaration of Helsinki. The protocol was approved on November 2009 by Maggiore Hospital Ethical Review Board (ID CE09079). Trial Registration ClinicalTrials.gov identifier: NCT01096927.

Conflict of interest statement

Competing interests: <?release-delay 0|0 >None.

Figures

Figure 1
Figure 1
Non-operative treatment for acute appendicitis: patient outcomes and follow-up in a single-cohort prospective observational study. Flow diagram of the study according to CONSORT 2010.
Figure 2
Figure 2
CONSORT 2010 flow diagram.

References

    1. Malik AA, Bari SU. Conservative management of acute appendicitis. J Gastrointest Surg 2009;13:966–70
    1. Deutsch AA, Shani N, Reiss R. Are some appendicectomies unnecessary? An analysis of 319 white appendices. J R Coll Surg Edinb 1983;28:35–40
    1. Pieper R, Kager L, Nasman P. Acute appendicitis: a clinical study of 1018 cases of emergency appendectomy. Acta Chir Scand 1982;148:51–62
    1. Eriksson S, Granstrom L. Randomized controlled trial of appendectomy versus antibiotic therapy for acute appendicitus. Br J Surg 1995;82:166–9
    1. Styrud J, Eriksson S, Nilsson I, et al. Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial. World J Surg 2006;30:1033–7
    1. Stengel A. Appendicitis. In: Osler W, McCrae T, eds. Modern Medicine, Vol V. Diseases of the Alimentary Tract. Philadelphia: Lea & Febiger; 1908
    1. Andersson RE. 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 2007;31:86–92
    1. Barber MD, McLaren J, Rainey JB. Recurrent appendicitis. Br J Surg 1997;84:110–12
    1. Blomqvist PG, Andersson RE, Granath F, et al. Mortality after appendectomy in Sweden, 1987–1996. Ann Surg 2001;233:455–60
    1. Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch Surg 2002;137:799–804; discussion 804.
    1. Shindoh J, Niwa H, Kawai K, et al. Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J Gastrointest Surg 2010;14:309–14
    1. Mason RJ. Surgery for appendicitis: is it necessary? Surg Infect (Larchmt) 2008;9:481–8
    1. Sakorafas GH, Mastoraki A, Lappas C, et al. Conservative treatment of acute appendicitis: heresy or an effective and acceptable alternative to surgery? Eur J Gastroenterol Hepatol 2011;23:121–7
    1. Tekin A, Kurtoğlu HC, Can I, et al. Routine interval appendectomy is unnecessary after conservative treatment of appendiceal mass. Colorectal Dis 2008;10:465–8
    1. Simillis C, Symeonides P, Shorthouse AJ, et al. A meta-analysis comparing conservative treatment versus acute appendectomy for complicated appendicitis (abscess or phlegmon). Surgery 2010;147:818–29
    1. Hansson J, Korner U, Khorram-Manesh A, et al. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg 2009;96:473–81
    1. Andersson RE. Small bowel obstruction after appendicectomy. Br J Surg 2001;88:1387–91
    1. Leung TT, Dixon E, Gill M, et al. Bowel obstruction following appendectomy: what is the true incidence? Ann Surg 2009;250:51–3
    1. Brügger L, Rosella L, Candinas D, et al. Improving outcomes after laparoscopic appendectomy: a population-based, 12-year trend analysis of 7446 patients. Ann Surg. Published Online First: 17 December 2010. doi:
    1. Page AJ, Pollock JD, Perez S, et al. Laparoscopic versus open appendectomy: an analysis of outcomes in 17,199 patients using ACS/NSQIP. J Gastrointest Surg 2010;14:1955–62
    1. Ingraham AM, Cohen ME, Bilimoria KY, et al. Comparison of outcomes after laparoscopic versus open appendectomy for acute appendicitis at 222 ACS NSQIP hospitals. Surgery 2010;148:625–35; discussion 635–7.
    1. Kouhia ST, Heiskanen JT, Huttunen R, et al. Long-term follow-up of a randomized clinical trial of open versus laparoscopic appendicectomy. Br J Surg 2010;97:1395–400
    1. Andersson R, Lambe M, Bergström R. Fertility patterns after appendicectomy: historical cohort study. BMJ 1999;318:963–7
    1. Andersson R, Hugander A, Thulin A, et al. Indications for operation in suspected appendicitis and incidence of perforation. BMJ 1994;308:107–10
    1. Styrud J, Eriksson S, Segelman J, et al. Diagnostic accuracy in 2,351 patients undergoing appendicectomy for suspected acute appendicitis: a retrospective study 1986–1993. Dig Surg 1999;16:39–44
    1. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64
    1. Andersson M, Andersson RE. The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado score. World J Surg 2008;32:1843–9
    1. Vandenbroucke JP, von Elm E, Altman DG, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med 2007;4:e297.
    1. Körner H, Söndenaa K, Söreide JA, et al. Incidence of acute nonperforated and perforated appendicitis: age-specific and sex-specific analysis. World J Surg 1997;21:313–17
    1. Ohmann C, Franke C, Kraemer M, et al. [Status report on epidemiology of acute appendicitis] (In German). Chirurg 2002;73:769–76
    1. World Medical Association Declaration Of Helsinki Ethical Principles for Medical Research Involving Human Subjects. 59th WMA General Assembly, Seoul, October 2008. World Medical Association DoH, 2008
    1. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007;335:806–8

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