Meta‐analysis of antibiotics versus appendicectomy for non‐perforated acute appendicitis. BJS 2016; 103: 656-667.

Published: 17th March 2016

Authors: V. Sallinen, E. A. Akl, J. J. You, A. Agarwal, S. Shoucair, P. O. Vandvik et al.

Background

For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non‐perforated appendicitis.

Method

A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non‐perforated appendicitis. Key outcomes were analysed using random‐effects meta‐analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference −2·6 (95 per cent c.i. –6·3 to 1·1) per cent (low‐quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference −7·2 (−18·1 to 3·8) per cent (very low‐quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high‐quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high‐quality evidence). For every 100 patients with non‐perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year.

Conclusion

The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value‐ and preference‐dependent, suggesting a change in practice towards shared decision‐making is necessary.

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4 Comments

BJS Admin

3 years ago

We have concerns about this meta-analysis by Sallinen and colleagues [1], comparing antibiotics (AB) versus appendicectomy (AP) for non-perforated acute appendicitis. This study uses the same method as Varadhan el al paper [2], which we similarly had issues with.

Sallinen writes:
"Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group".
“Major complications in the appendicectomy group included 32 appendiceal perforations, five deep infections, two incisional hernias, one laparoscopic adhesiolysis and one death. Major complications in the antibiotic therapy group included 23 appendiceal perforations, one adhesive bowel obstruction and one death.”

The choice of appendiceal perforation as a key outcome is misleading.

An appendiceal perforation is not a complication of appendicectomy, but of appendicitis. Appendicectomy is no less necessary than for an uncomplicated appendicitis, and no less effective. The rate of complications should be 9/489 (1.8%).

On the contrary, 114 of the 510 patients in the antibiotics group had to undergo an appendicectomy within one year. This should be counted as a major complication. The rate of complications should be 139/510 (27%) – and as this rate does not diminish with time, the antibiotic treatment could become a total failure after several years.

Appendicectomy [3] remains the “gold standard”.

Edmond Estour
Jacques Soufron

Clinique Notre-Dame
23 rue des Acres
14500 Vire
France
soufron@hotmail.com

References:
1. Sallinen, V., Akl, E. A., You, J. J., Agarwal, A., Shoucair, S., Vandvik, P. O., Agoritsas, T., Heels-Ansdell, D., Guyatt, G. H. and Tikkinen, K. A. O. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg 2016; doi: 10.1002/bjs.10147.
2. Krishna K Varadhan, Keith R Neal, Dileep N Lobo. Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials. BMJ 2012; 344: e2156.
3. Wilms IM, de Hoog DE, de Visser DC, Janzing HM. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database Syst Rev 2011; 11: CD008359.

    BJS Admin

    3 years ago

    We thank Drs. Estour and Soufron for their interest in our systematic review and meta-analysis comparing antibiotics first versus immediate surgery for non-perforated acute appendicitis (1). Choosing what events should be classified as a complication is challenging when one management strategy is medical and the other is surgical. For example, patients undergoing only medical treatment cannot have surgical complications unless they undergo a subsequent surgical procedure. The issue is important: the choice of which adverse events are counted as complications may shift the balance favouring one treatment over another. Consequently, we defined complications in both arms similarly in order to remain as neutral as possible. Further, as demonstrated by our findings in Appendix Table 3, the included RCTs differed in their complication classifications. Where one group of authors (2) considers recurrence as a complication, the other five included studies did not.

    Being aware of those challenges, we defined the outcomes in the way we hoped would maximize their usefulness for decision makers, both patients and physicians. Our assumption was that decision makers would be interested in knowing about salvage appendectomy separately from surgical complications. These entities have different clinical implications, and it is likely that patients would value them differently.

    Antibiotic treatment arm is best viewed as a stepwise approach where antibiotics are tried first, followed by appendectomy if unsuccessful. In this way of looking at the intervention, appendectomy is necessary part of the treatment plan rather than a complication.

    Finally, what is most interesting is that antibiotic treatment did not lead to increased appendiceal perforation rates.

    Ville Sallinen
    Gordon H. Guyatt
    Elie A. Akl
    Kari A.O. Tikkinen

    Department of Urology
    University of Helsinki and Helsinki University Hospital
    Haartmaninkatu 4
    00029 Helsinki
    Finland
    kari.tikkinen@gmail.com

    References:
    1. Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO, et al. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg 2016; 103: 656–667.
    2. Svensson JF, Patkova B, Almström M, Naji H, Hall NJ, Eaton S, et al. Nonoperative Treatment With Antibiotics Versus Surgery for Acute Nonperforated Appendicitis in Children. Ann Surg 2015; 261: 67–71.

BJS Admin

3 years ago

I read with the great interest the study by Sallinen et al. (1). It is too early for such meta-analysis due to small number of patients and short follow-up. Currently, laparoscopic appendectomy is still a better option and the reasons are; antibiotic resistance, recurrence of 22% within year, with possibly a more challenging operation with further attacks and longer duration of antibiotics and higher complication rate. Then, due to the recurrence there is presumably higher probability of abdominal CT use. The study did not comment a subgroup with chronic right lower quadrant pain. Appendectomy in patients with chronic intra-abdominal diseases, such as inflammatory bowel disease, endometriosis, polycystic ovaries, nephro/urolithiasis, does eliminate one possible aetiology during repetative attacks of right lower quadrant pain. There is also the risk that in 0.7% of appendectomy specimens a tumour is found (2) and diagnosis delayed because of treatment with antibiotic. These patients can then be detected in more advance disease.

Goran Augustin
University Hospital Center Zagreb and School of Medicine University of Zagreb
Kišpatićeva 12
Zagreb 10000
Croatia
augustin.goran@gmail.com

References:
1. Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik Po et al. Meta-analysis of antibitics versus appendicectomy for non-perforated acute appendicitis. BJS 2016; 103: 656-667.
2. Lee WS, Choi ST, Lee JN, Kim KK, Park YH, Baek JH. A retrospective clinicopathological analysis of appendiceal tumors from 3,744 appendectomies: a single-institution study. Int J Colorect Dis 2011; 26: 617-621.

    BJS Admin

    3 years ago

    We thank Dr. Augustin for his interest in our meta-analysis (1). We agree that upfront appendectomy has advantages, most importantly no recurrence rate. However, there is no evidence that subsequent surgery for recurrence would be any more challenging than the initial surgery, nor any evidence that the complication rate is higher. Indeed, the RCT by Salminen et al. reported 7% complication rate for appendectomy for recurrent appendicitis versus their 21% complication rate for upfront appendectomy (2).

    Further, Salminen et al. diagnosed their recurrent appendicitis by clinical means without a CT scan and all patients with a recurrent, or suspected recurrent, appendicitis underwent appendectomy. This seems a rational choice, which does not increase the use of CT scan and limits the number of possible recurrences to one.

    Dr. Augustin is right that we did not discuss the issue of patients who suffer from chronic right lower quadrant pain. These patients are a completely separate population and their treatment is not relevant to how we will treat the first occasion of uncomplicated appendicitis. No one is suggesting treating this patient population by repetitive antibiotics only.

    We agree that appendix might harbour tumours. Uncomplicated appendicitis seems to be associated with low rates of this, with a incidence of approximately 1% as cited by Dr. Augustin. In the RCTs included in the meta-analysis (1), only four out of 725 appendectomy specimens harboured a tumour (0.6%, range 0 – 1.5% between the studies). These tumours included three up to 10 mm neuroendocrine tumours and one adenoma with low-grade dysplasia. In order to decide whether this frequency of tumours in the appendix warrants immediate appendectomy in patients with uncomplicated appendicitis, knowledge of the incidence of appendiceal tumours in similar population without uncomplicated appendicitis is essential. A publication reporting results of incidental appendectomy at the time of another operation suggested that the rate of neoplasms in asymptomatic patients is 1.8% (3). Given that no one would argue that everyone should undergo prophylactic appendectomy because of a small risk of harbouring a tumour, we do not think this frequency of neoplasms should preclude consideration of the antibiotic first approach either.

    Ville Sallinen
    Gordon H. Guyatt
    Elie A. Akl
    Kari A.O. Tikkinen

    Department of Urology
    University of Helsinki and Helsinki University Hospital
    Haartmaninkatu 4
    00029 Helsinki
    Finland
    kari.tikkinen@gmail.com

    References:
    1. Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO, et al. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg 2016; 103: 656–667.
    2. Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA 2015; 313: 2340–2348.
    3. Exner R, Sachsenmaier M, Horvath Z, Stift A. Incidental appendectomy–standard or unnecessary additional trauma in surgery for colorectal cancer? A retrospective analysis of histological findings in 380 specimens. Colorectal Dis 2012; 14: 1262–1266.