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Peer-Review Record

Microwave and Radiofrequency Ablation: A Comparative Study between Technologies in Ex Vivo Tissues

Drugs Drug Candidates 2024, 3(3), 550-565; https://doi.org/10.3390/ddc3030032
by Fabio Lobascio 1,*, Rocco Di Modugno 1, Marco Fiore 1, Nicola Di Modugno 1, Cristian Bruno 1, Thomas De Nicolo 1, Rossella Veronica Barberis 2, Karine Cabiale 2 and Marilena Radoiu 3
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Drugs Drug Candidates 2024, 3(3), 550-565; https://doi.org/10.3390/ddc3030032
Submission received: 25 June 2024 / Revised: 22 July 2024 / Accepted: 31 July 2024 / Published: 6 August 2024

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

The revised version improved significantly. I have no further comment for the author. I recommend accepting the paper for publication in its present form.

Author Response

Comment: [The revised version improved significantly. I have no further comment for the author. I recommend accepting the paper for publication in its present form.]

Response: [We thank the reviewer for his comments and suggestions, which helped the authors to improve the paper. We are happy to have clarified any doubts.]

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

The revised version with all the changes marked is impressive, but it would be very tedious to check in detail what actually has been modified. Thankfully there also is a cleaned version, after removal of the discarded text passages. I'll try to wind my way through that version.

On one hand I see clear improvements in the introduction, on the other I am shocked about serious deficiencies in the physics knowledge of the authors.

Lines 52 - 55: "A good example of application in diagnostic imaging is magnetic resonance imaging (MRI), where radiofrequency is used to induce a strong magnetic field in a superconductor, which is then used to magnetize various tissue molecules based on their biochemical composition [5]. " This is scientific nonsense.
Superconductors characteristically expel magnetic fields, and the MRI process depends on proton spins, whose response to a trigger pulse may be modified by the environment of the hydrogen atom.
The strong magnetic field (possibly produced by the high electrical current in coils made of superconducting material) orients the proton spins, the sudden relaxation of which is then monitored. May I suggest not to cite a paper the physics content of which has not been understood by the present manuscript authors, but to actually read a basic textbook on the topic, or the Nobel lectures of the respective laureates that address the educated (but not scientifically specialized) public?

Page 3 sounds like advertising material for medical equipment

Line 119/120 The reader is treated to the triviality that frequency in Hertz means frequency in cycles/second. Is that basic definition warranted in a scientific paper? Again, is this advertorial material or a contribution to a
science journal?

Line 134, the mysteriously precise factor 0.368 is the same as 1/e in an exponential curve: clearly science is conceptually simple, while the medical device development has "secret" factors of possibly important economic value ...
The manuscript is in jeopardy between a sales brochure and a sensible introduction to a field of interest.

Line 172, "Unlike RFA, MW energy is not an electric current but a propagating EM field "
According to the text, RFA is radiofrequency ablation (ablation by absorption of radiofrequency radiation), and energy is not the same -
of course not. This text section is garbled nonsense. The paragraph degrades to recommendations on procedures - where is the topic of the manuscript?

Line 214, Microwave generator
This reads like a customer-addressing product leaflet, not a scientific protocol.

In Section 4, conclusions, the advertising continues, "including the latest technologies and algorithms", and so on.
The manuscript only marginally touches on the scientific study of the ablation effects in two EM frequency bands. It mostly tells how grand the achievement of building an apparatus is about which details must not be told, in order to preserve commercial competitiveness.

By my estimate, half of the text may be useful as an introduction to the merit of the topic, but does not actually explain
the scientific process and achievement of a specific trial.

In the author contributions, first names have not been corrected as in the author list.

I am shocked at the lack of merit of the revised text. I see merit in the actual study, but the present text is grossly inadequate.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report (New Reviewer)

Comments and Suggestions for Authors

The document titled “Microwave and Radiofrequency ablation: a comparative study between technologies in ex-vivo tissues” presents a methodology that has so far been little studied by the scientific community. The document emphasizes the advantages and limitations provided by each method. In general, the document requires better organization of the information. Below we list some additional observations.

Line 178, correct Mcycles/s

Line 348, this paragraph appears to be missing

-please define RI from the equation (roundness index)

-Please improve the image labels, some are difficult to see.

Comments on the Quality of English Language

no comments

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

The abstract has improved over Revision 1. It is still on the long side of what an abstract is supposed to be.

The introduction shows that the authors have not yet grasped the insight that phrases and laboratory slang are not a demonstration of competency, but reveal a lack of thought.
"The use of microwaves (MW) and radio frequency (RF) " is meaningless and incomplete, unless some word like "radiation" is added at the end. "The use of ... radiofrequency" on its own makes no sense. Apparently the authors have to be reminded that volunteer reviewers are not wishing to spend their own time on having to tell authors repeatedly that publications meant to be of the authors' interest have to be prepared by the authors. If the authors are unable to match the intellectual requirement of writing cogently, coherently and correctly, they should not try to publish in a learned journal.

The tone of the introduction reminds me of public outreach; Great Scientists are mentioned that the audience has probably heard of, introducing a feeling of importance and meaning, although the actual topic of the manuscript has little to do with the topic as outlined in the title and abstract. Why mention Hertz and Marconi, if the report is on radiation absorption by chicken tissue? No wonder the text overall is twice as long as befits the task at hand - as has been pointed out in a previous reviewer comment. Evidently, the authors do not want to heed reviewer advice - why should the reviewer opinion yield? The first two paragraphs of the introduction are superfluous and do not serve the manuscript.

Line 127 translates a frequency (in MHz) into "oscillations/s". This tautology (criticized in a previous review) is useless. Why write such trivialities in a learned journal? Why maintain such a statement after being told abot it (still correctly)? Being told about a meaningless numerical pseudo-precision (1/e is mathematics, the many decimals have no merit here), the authors even expand that - a refusal to think, or an insult to the reader who is expected to be uneducated?

There are many small changes to the text which are tedious to work through. I presume that the changes are to the better of the text. However, I refuse to dig into this patch, seeing that the authors are unwilling to recognise that their general style of presentation needs re-orientation.

The conclusion repeats the aforementioned nonsense, "In the medical applications of microwaves and radiofrequency".
Radiofrequency is never applied, radiofrequency is a term that designates a frequency band in the electromagnetic spectrum.
This nonsense is followed by "in situ energy", apparently a new form of energy that is "converted into heat within tumours".
How much worse can this writing get? Since the authors have demonstrated rather little enthusiasm towards improving their poorly phrased text, I am not going to alleviate their disinterest by suggesting more correct sentences, which can easily be phrased after some thinking about what the present manuscript actually (and possibly unintentionally) says.

Comments on the Quality of English Language

The problem is not the foreign language, but the insufficient thought about what is being said. It is an intellectual problem, not one of language command.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.


Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review on Microwave and Radiofrequency ablation: a comparative study between technologies in ex-vivo tissues

I have completed my review on manuscript ddc-2701547, entitled, Microwave and Radiofrequency ablation: a comparative study between technologies in ex-vivo tissues.”

This paper discusses the use of a custom-designed solid-state hybrid microwave and radiofrequency generator for cancer ablation. The generator operates at 2.45 GHz and 480 kHz, offering increased accuracy in controlling emitted power and temperature profiles during treatment. Ex-vivo tests on chicken breast and bovine liver demonstrate the effectiveness of radiofrequency ablation (RFA) for small, controlled ablations and microwave ablation (MWA) for larger ablations in highly vascularized tissues like liver cancer. The study emphasizes the importance of precise solid-state generators and highlights the potential for improving radiofrequency and microwave ablation procedures through advanced technologies and control systems.

 

The subject and findings of this article are interesting and useful. Before making a positive decision, I have some concerns and comments about the present form of the manuscript that must be addressed first.

 

Comments for authors

Comment 1: The background information and introduction section is so weak. I encourage authors to add some background and the latest information for new readers to understand the significance of the study. Also, it is important to describe the mechanism of how electromagnetic fields interact with biological systems. The suggested article may assist authors in expanding and strengthening their background knowledge. So, I suggest to add the following article in your introduction section:

Article: Microwave Radiation and the Brain: Mechanisms, Current Status, and Future Prospects. International Journal of Molecular Sciences vol. 23 (2022). [https://doi.org/10.3390/ijms23169288].

 

Comment 2: In the context of microwave heating, can you provide more details on the mechanisms by which electromagnetic energy is converted into heat within tumors and how this is utilized for cancer ablation? Add this information in the background information.

 

Comment 3: How do authors control the emitted electromagnetic power versus temperature profile during cancer ablation?

 

Comment 4: Specify the type of microwave and RF sources. Microwave source is pulsed or continuous? What is the exposure duration? Explain in the manuscript.

Comment 5: In Figures 1 and 2, the authors have presented schematics of the microwave and radiofrequency generators separately, while Figure 3 displays a photograph of the hybrid dual-frequency generator. However, the manuscript lacks clarity regarding the treatment protocol. It is unclear whether the authors administered microwave and radiofrequency treatments individually before combining them (MW+RF) or followed a different treatment sequence. Further clarification is needed regarding the treatment methodology.

Comment 6: figure 3 does not carry any scientific information it is just a photograph without any labeling. I recommend authors to present it in a scientific manner by labeling each part of the device shown in the photograph. and why it is important to show.

Comment 7: What caused the significant increase in impedance after 210 seconds, even though the temperature remained constant? Also, what is time along the x-axis? is it treatment time?

Comment 8: What is the source of equation 1?

Comment 9: The figure captions require revision as they do not adequately reflect the results presented in the figures. Moreover, the unlabeled photographs make it challenging to discern the intended meaning and key findings. It is advisable for the authors to enhance the figures with proper labeling and adjust the captions to provide more informative descriptions.

Comment 10: The literature review in the introduction and discussion is insufficient, considering that microwave ablation is an active research field. It's recommended that the authors expand the review by including recent advancements in the field and comparing their findings with the latest research. Additionally, the number of cited references, currently only 22, should be increased to encompass a broader range of relevant literature.

Comment 11: Authors are strongly encouraged to explicitly articulate the mechanisms and reasons behind the effectiveness of the combined MW+RF treatment.

 

Comment 12: The paper contains errors and typos that make it difficult to understand and distort its intended meaning. I encourage authors to reread carefully and fix any grammatical errors.

Comments on the Quality of English Language

The paper contains errors and typos that make it difficult to understand and distort its intended meaning. I encourage authors to reread carefully and fix any grammatical errors.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript guides the thought right into the practical processes of how to take tissue samples reproducibly and meaningfully, without destroying the "crime scene" and evidence before evaluation.

Among previous applications of microwaves (only a few of which are mentioned in the manuscript), RADAR (since WW II) arguably predates food cooking (medical issues concerning the health of human
radar technicians have been contemplated since the 1950s); the auxiliary heating of fusion plasmas by radio or microwave radiation (at the megawatt level) clearly exceeds the present power levels
by many orders of magnitude, while studies of the cosmic microwave background may not count as a technical application, but their mentioning would widen the scope of a lively field.

Line 113; " ... the introduction of solid-state generators" is baffling, until one realizes that "RF" or "MW" ought to have been inserted before "generators".

Lines 152-157: why is the text set in boldface?

Section 2.1.4 gives me the impression of being under-organised. Maybe it would help to outline the problems before telling of the countermeasures: Measurement problem; foreseeable problem with leak currents etc.;
measures to avoid this and achieve that, etc.

Lines 236 - 243 talks (with low specificity) about case numbers and typical cost of treatment, leading to optimistic expectations about a market for medical devices. What has this marketing statement to do with "Results and discussion" in the section title?

Line 254, "The heating in RFA is due to the joule associated with the current flow, ..." means what? This section needs to be re-organised until a storyline becomes apparent to the reader.

The roundness index is used in Fig. 5 and explained only near Fig. 7. Why is a roundness index required; won't a simple axis ratio of an ellipsoid not do? The introduction and discussion needs to be more systematic.

The caption of Fig. 9 does not explain what is displayed; one has to find the explanation in the text, which is not good.

Section 4, Conclusion, is better structured than the preceding section.

Overall,  I have the impression of a sensible experiment done with appropriate technical equipment. However, the  structure and clarity of the report fall short of what is needed in a scientific presentation. This is not a matter of a correction here and/or there, but one of stringency and logic. The text does not need to be longer, but  the work deserves to be presented with more thought.

Comments on the Quality of English Language

The quality of English is appropriate, but the thought before formulating the text has been insufficient.

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