A major clinical challenge in the care of children with cancer is how to take care of those patients with chemotherapy-induced neutropenia who develop acute appendicitis. How do we weigh the risk of perforation and sepsis against the risk of surgery in these high-risk patients? In this issue of Pediatrics, Many et al1 report a 7-year retrospective review across 15 North American pediatric tertiary-level institutions comparing management strategies and outcomes for 66 children with neutropenia and image-confirmed acute appendicitis. The authors found that those who undergo appendectomy within 24 hours of diagnosis have fewer postoperative complications, shorter length of stay, and fewer delays in chemotherapy compared with those who are initially treated nonoperatively, with the worst outcomes occurring among children with a delayed appendectomy during the admission.1 Although the sample size of this study is relatively small, the authors have amassed the largest study to date to evaluate the management of acute appendicitis in children with neutropenia. A notable strength is that the subjects are similar across treatment groups by factors such as age and important clinical characteristics including malignancy type, symptom duration, maximum temperature, and absolute neutrophil count.
In this report, the authors also describe significant practice variability in the rate of upfront appendectomy across institutions (0%–100%). There was also likely heterogeneity across different institutions in the antibiotic choice, duration, and resistance patterns in those managed nonoperatively; we are thus unclear as to how this may have influenced outcomes. The hemodynamic status and degree of systemic sepsis of the patients at the time of diagnosis is not reported and we cannot know (a limitation of a retrospective study of this kind) whether this influenced the choice of management strategy. Also unknown is the impact, if any, of the administration of granulocyte colony-stimulating factor in the 29 patients to whom it was given. Assuming count recovery occurred more frequently in this subpopulation, did that influence outcomes in any way? In this review, those with count recovery who subsequently underwent appendectomy were not analyzed separately from those who had failure of nonoperative management, so we are unable to determine if this subgroup fared better nor if there is any benefit to waiting on count recovery if the outcomes are ultimately equivalent or better. It is also interesting that the majority of patients in this study who successfully completed initial nonoperative management went on to require no further treatment (75%). Prospectively acquired long-term outcomes data comparing this subgroup to those who underwent upfront appendectomy may add strength to the argument for initial surgery.
Concerns about operative interventions in patients with neutropenia have been largely focused on wound and infectious complications. Consistent with smaller studies, the authors provide additional evidence that timely appendectomy should be the priority in these patients.2,3
Although the authors demonstrate delays in chemotherapy administration among those patients treated nonoperatively, the immediate and long-term effects on oncologic outcomes of these delays are unknown. Given that these children were all receiving chemotherapy and became neutropenic as a result, these likely represent interruptions in treatment as opposed to delays in initiation. Studies in which authors have examined the effects of delays in chemotherapy on oncologic outcomes have been largely focused on delays in initiation, and even among these studies, the data are mixed with some researchers suggesting no effect.4,5 The clinical relevance of the interruptions in treatment shown by the authors is therefore unknown.
Nevertheless, we congratulate the authors on tackling an important question on surgery in neutropenic appendicitis. They have nicely laid the groundwork for a potential algorithm for the management of acute appendicitis in children with neutropenia, in which upfront appendectomy can be safely offered and may likely be preferred in those patients most likely to benefit. Decreases in hospital length of stay, postoperative complications, and, as a result, cost of care in this particularly vulnerable population can only serve to improve the overall quality of care that they receive.
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
FUNDING: No external funding.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2020-027797.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.