Solvent Matters!

We gladly read the article by Xing et al.¹  suggesting that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. We would like to congratulate the authors for this in vitro and in vivo trial bringing new information to the subspecialty of onco-anesthesia.

However, we would like to point out a bias in the methodology. According to the Materials and Methods section, the authors purchased Lidocaine from Sigma-Aldrich (USA). The authors did not specify how it was diluted. It can be assumed that they followed the product specification sheet indicating that the powder is soluble in ethanol, absolute. This solvent could have an effect on cancer cells, per se. Indeed, percutaneous ethanol injection therapy is commonly used to treat hepatocellular carcinoma,^2,3  and ethanol is also combined with transarterial chemoembolization.⁴  Ethanol causes tumor destruction by dehydrating tumor cells, thereby denaturing the structure of cellular proteins. As lidocaine must be solubilized at a maximal concentration of 0.21 M, ethanol is present in a range varying from 0.00446 to 4.46% in the in vitro experiments of Xing et al. Moreover, according to preclinical and clinical studies, quantifying ethanol regimens depending on the tumor size improves its curative effect.³  Therefore, the effects shown by the authors could be a consequence of the addition of ethanol to the lidocaine. To be strictly rigorous in terms of methodology, the authors should have added another control group using only the solvent.

Furthermore, as onco-anesthesia is an emergent research field, we believe it is important to promote exhaustive and clean methodology to enhance reproducibility of experiments for further research in this area.

The authors received funds from the French Society of Anesthesia and Intensive Care Medicine (SFAR; Paris, France). Thiên-Nga Chamaraux-Tran is an Institute of Genetics and Molecular and Cellular Biology (IGBMC; Illkirch, France) International PhD Program fellow supported by LabEx INRT (Integrative Biology: Nuclear Dynamics, Regenerative and Translational Medicine) funds ANR-10-LABX-0030-INRT, a French state fund managed by the National Research Agency (Paris, France) under the frame program “Investissements d’Avenir” labeled ANR-10-IDEX-0002-02.

The authors declare no competing interests.