The Non Operative Treatment for Acute Appendicitis (NOTA) Study: Is Less Surgery Better Surgery?

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To the Editor:
We would like to congratulate Di Saverio et al for presenting the intriguing results of their single-cohort, prospective, observational study investigating the efficacy and safety of antibiotic treatment for patients with right lower abdominal pain. 1
The data presented here implies that in well-selected patients, treatment with antibiotics can be an option with good long-term efficacy. This is in concordance with the results of a meta-analysis of 4 randomized controlled trials with regard to this topic. 2 Some points, though, leave room for debate.
The authors used the appendicitis inflammatory response (AIR) score 3 and the Alvarado score 4 for validation of clinically suspected nonperforated acute appendicitis. The mean AIR score was stated to be 4.9 (range: 3.0–10.0), although the mean Alvarado score was 5.2 (range 5.0–9.0). These low scores translating to “indeterminate” and “equivocal” probabilities for acute appendicitis were already mentioned in an earlier Letter to the Editor by Lubrano and Menahem. 5 They note that these low scores may have overestimated the actual incidence of acute appendicitis in the collective. We agree with this and would like to point out a discrepancy in the article.
In Table 3 (“Characteristics of Included Patients”), the Alvarado score for all included patients is differentiated (62 patients with a score of 5–6, 81 patients with a score of 7–8, 14 patients with a score of 9). First, this adds up to only 157 patients, so the score is not stated for 2 patients included in the study.
Second, if the mean Alvarado score for these 157 patients is calculated with the lowest possible scores ([62 × 5 + 81 × 7 + 14 × 9]/157), the result is 6.4. Therefore, we would be interested to know how the authors calculated the mean Alvarado score of 5.2.
Because a higher score indicates a higher probability of actual acute appendicitis, we believe this to be of importance for the relevance of the study.
The short-term (<7 d) nonoperative management (NOM) failure rate was 11.9% (19/159). This group of patients is particularly interesting because they were evaluated by the proposed protocol for antibiotic treatment but had to be transferred to the surgical-therapy arm of the study because of consisting or relapsing symptoms. Interestingly, none of these patients had an Alvarado score of 9 (highly likely appendicitis) but 17 of 19 patients presented at surgery with “a variable degree of acute appendiceal inflammation (phlegmonous/gangrenous/perforated appendicitis).” It therefore seems questionable if the proposed pathway of patient selection for NOM is adequate. In a recent publication, the group of Hansson et al 6 proposed a model to identify patients with phlegmonous appendicitis, as these patients (in their study) had an 80% probability to recover with antibiotic therapy. In summary, it seems unclear at which stage of disease progression antibiotic therapy is still feasible.
Despite these controversial facts, the study by Di Saverio et al provides further evidence that antibiotic treatment can be safe and effective in selected patients with suspected acute appendicitis. Future studies have to elucidate how patients can be selected precisely. Furthermore, it has to be evaluated if the reduction of postsurgical complications in patients selected for NOM compensates for patients suffering recurrences or complications from not being operated initially.
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