Supplementary data:
Background information about the revised manuscript and about the study concept:
Following the comments of the reviewers about the manuscript, we would like to point out that the experiments were performed as previously described in the manuscript. Thin tissue sections and doxorubicin florescence microscopy has been performed at the Department of Neuroanatomy at the Ruhr University Bochum.
The concept for this study is based on the fact that homogenous distribution of drug aerosols using PIPAC has been previously reported. Yet until today, this fact has never been explored in detail.
Having performed more than 400 PIPAC procedures I became quite aware of the fact that PIPAC does not deliver homogenous application of aerosolised drugs. We observed during PIPAC procedures, which have been video monitored, that most of the delivered drug is absorbed by the peritoneum which is in the extension line of the PIPAC nozzle (spray jet - impactation). The majority of the droplets do not show homogenous distribution - in fact, we observe impaction of the peritoneum and formation of a local liquid chemotherapy film on the peritoneal structures.
A first experiment was performed: undiluted methylene blue was aerosolized in the ex-vivo PIPAC model. After five seconds of a PIPAC burst, the PIPAC box was opened and optically analysed (Figure 1). It became obvious for us that the drug distribution pattern cannot be as homogenous as previously reported. Based on these initial findings, the experiments were performed with doxorubicin and the thus derived results are now presented in our manuscript.
Figure 1: Ex-vivo PIPAC model: the front of the plastic box is removed for better demonstration. In the centre tissue sample A which is in the spray jet of the PIPAC nozzle. After five seconds of a PIPAC burst with methylene blue undiluted, maximal staining of the tissue sample A whereas the tissue sample under the plastic tunnel (B) and at the side wall (C) still show no visual staining.