Regarding: Inflammatory Response Is No Different in Children Randomized to Laparoscopic or Open Appendectomy

In a randomized trial, Simon et al. ¹ compared laparoscopic and open appendectomy by analyzing the data of 40 children. This study is very welcome, as it points to the important question of whether the tissue trauma or the change of the peritoneal environment by laparoscopy is similar to open surgery or not. However, there are some important limitations. The authors chose pediatric patients with acute appendicitis requiring appendectomy for such a comparison. Appendicitis is an infectious disease associated with a highly inflammatory host response. ² Tissue trauma caused by laparoscopy should be a much less inflammatory stimulus than appendicitis itself, and also, a small laparotomy should be a much more subtle stimulus. It seems, therefore, conceivable that in the context of a major inflammation caused by appendicitis, a minor additional inflammatory surgical stimulus cannot be easily discriminated. If a really small difference exists, it can only be assessed with high numbers of studied patients to achieve a corresponding statistical power. Such a hypothesis is supported by the systematic trend toward lower inflammation parameters in virtually all readouts. Simon et al. have not taken into account, in their statistical analysis, the much more powerful repeated measurement design, which, further, eliminates multiple measurements and their correction and is much less prone to statistical type II or beta error. Their statistical analysis clearly underestimates any potential real difference in their dataset.

Further points could influence outcome. The use of antibiotics is not mentioned, although its effect and its influence on the immune defense system, especially in appendicitis, is well known. ⁷ Similarly, the use of nonsteroidal anti-inflammatory drugs has not been reported. ⁸ Surgical experience may further influence outcome, especially in single-center studies, a factor that is not easily corrected for in surgical research.

The authors' conclusion is virtually exclusively based on the evolution of blood or serum surrogates of systemic inflammation. In the experimental surgical literature, more sophisticated general or local immune balance readouts can be used. They include skin tests to assess the temporary suppression of delayed-type hypersensitivity as a parameter of recall immunity, ³ biologic behavior of peritoneal macrophages, including their cytokine production, or number and survival of polymorphonuclear granulocytes as a marker for local immune response.^4–6 In the context of a randomized, clinical study, similar assessments are clearly difficult to obtain.

Despite the evident nonblinded study design, it is very difficult to neglect the highly significant difference in hospital-stay length of nearly 2 days. At a first glance, it is an imprecise parameter of disease, including recovery. In the context of a “standard disease,” it primarily reflects recovery and, thus, quality of treatment. Although the study was nonblinded, this integral patients' evolution parameter strongly underlines that such a huge difference is of both high clinical and biologic relevance. It, therefore, suggests a less favorable recovery after open operated appendicitis, if compared to laparoscopically operated patients.

Actually, both expert opinion as well as literature tend to a minimally invasive approach for appendicitis.^9,10 The interpretation of the article of Simon et al. ¹ as a study that suggests equal biologic consequences of laparotomy versus laparoscopy seems very doubtful to us. Only excellent study designs can, in the longer course, bridge the gap between experimental and clinical surgery and, in the longer course, translate into improved clinical care.