We thank Javanmard-Emamghissi and colleagues for their interest in our analysis article, and for their response.
While the cited meta-analysis did not report an increase in the rate of complications, the authors did report that antibiotic treatment had a reduced efficacy compared to appendicectomy (RR 0.75, 95% CI 0.63 to 0.89) and a six-fold increase in the readmission rate with antibiotics. Looking at complications alone is inadequate as longer-term sequalae can impact overall patient well-being and associated healthcare costs.
The comparison of appendicitis recurrence to cancer recurrence is wholly inappropriate and demonstrates a lack of understanding in the pathophysiology of both diseases. Cancer is a systemic disease, with the propensity to affect multiple organs, while appendicitis is a localised infection. Recurrence-free survival is an important metric for assessing treatment efficacy in surgical oncology, and we believe that recurrence is an important risk associated with antibiotic treatment. A proportion of patients may be accepting of the recurrence risk with antibiotics, however surgeons must ensure that this risk is appropriately explained. Adequate shared decision-making involves explaining this risk, and explaining that the recurrence risk with appendicectomy is substantially lower, with the patient free to make their own decision.
Javanmard-Emamghissi and colleagues state that the CODA trial reported no mention of organ failure. The CODA collaborative reported “NSQIP-defined complications” which include intubation, cardiac complications and renal dysfunction which are all examples of ‘organ-failure’. Secondly, we draw Javanmard-Emamghissi and colleagues attention to the supplementary data provided by the authors, which is important to review – comparing the antibiotic group with appendicectomy, 4 vs 0 patients had an unplanned admission to the intensive-care unit (most likely for ‘organ failure’ requiring invasive monitoring and/or support), 1 vs 0 patients developed renal failure requiring dialysis, and 11 vs 1 patients developed sepsis (which is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection”), of whom 2 vs. 0 developed septic shock. Therefore the CODA trial reports organ failure, with antibiotics having a higher rate than appendicectomy.
We agree that appendicitis with faecolith is a different pathology, and associated with a different clinical course, compared to appendicitis without a faecolith, and continue to advocate surgery first-line in this group.
We agree that appendiceal malignancy is a rare entity, and more likely in older populations. We highlight both points in our analysis article. However given the significant implications of malignancy to an individual patient and their healthcare outcome this risk should not be minimised, especially when appendicectomy can eliminate this risk altogether. Appendiceal cancer is most likely to present as appendicitis. Therefore in older patients presenting with appendicitis, histopathological examination of the appendix specimen provides the highest diagnostic certainty regarding malignancy.
Javanmard-Emamghissi and colleagues write that the cost-analysis we cited was ‘robust’, however as highlighted in our analysis article, this analysis was based on Italian data using UK costings (from an NHS perspective) which significantly confounds their analysis as resource costs, supply chains, and practices are likely to vary between Italy and the UK. Therefore we argue that this analysis was not ‘robust’, and should not be used to justify antibiotics for appendicitis based on cost. While the CODA trial provided information on missed work and carer days, this was not for subsequent admissions up to 3 years, and as reported recurrence risk is up to 40% at 3 years post-index presentation, the analysis may not capture the true long-term burden. The APPAC economic analysis also did not factor in costs associated with recurrent disease beyond 1-year, limiting the validity of claiming cost-effectiveness with antibiotics.
We wholeheartedly disagree with the statement that we omitted patient choice. We specifically stated that patients should be empowered to make their own decisions regarding their treatment, but that feasibility of antibiotics should not be equated with equivalence in efficacy and risks when presenting antibiotics and appendicectomy as treatment options. Surgeons should offer antibiotics as an option, but must present the associated risks and how this compares with appendicectomy. Global access to anaesthesia and safe surgery is a pertinent issue, however that does not change the evidence base – patients managed with antibiotics in a low- or middle-income country will still experience associated complications, and appendicectomy is still recommended first-line but access to healthcare will heavily influence which treatment pathway is undertaken. Finally, we focussed our analysis article on treatment in adults. A thorough discussion of antibiotic management would warrant an article of its own, as the evidence-base, risk profiles, and patient-specific considerations differ to adults.
1. Herrod PJJ, Kwok AT, Lobo DN. Randomized clinical trials comparing antibiotic therapy with appendicectomy for uncomplicated acute appendicitis: meta-analysis. BJS Open. 2022;6(4).
2. Collaborative C, Flum DR, Davidson GH, Monsell SE, Shapiro NI, Odom SR, et al. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. N Engl J Med. 2020;383(20):1907-19.
3. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.
4. Sippola S, Gronroos J, Tuominen R, Paajanen H, Rautio T, Nordstrom P, et al. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial. Br J Surg. 2017;104(10):1355-61.
Re: Appendicectomy remains treatment of choice for patients with acute appendicitis