Low-Grade Pseudomyxoma Peritonei Behaving as a High-Grade Disease: A Case Series and Literature Review

Round 1

Reviewer 1 Report

Principal Limitations:

1-      Absence of assessment of the Peritoneal Carcinomatosis Index (PCI): The Peritoneal Carcinomatosis Index (PCI) and Completeness of Cytoreduction (CC-score) hold substantial prognostic significance in low-grade pseudomyxoma. It is crucial that PCI is calculated and documented in the medical history of patients, as it often represents a key prognostic factor (*).  Although the PCI values for your patients have not been reported, it is plausible that the observed poor survival outcomes are associated with high PCI scores and the inability to achieve complete cytoreductions.

2-      Non-representative sample and non-extrapolable data

Lines 254-255: “All previous observational reports have shown that overall survival is significantly better in low-grade PMP tumors [8, 21, 22, 23]. “

It's noteworthy that previous observational studies have consistently shown significantly better overall survival in low-grade PMP tumors. However, it's important to recognize that these studies encompassed considerably larger sample sizes (e.g., Chua et al. with 2298 patients, Gonzalez-Moreno with 501 patients, Stewart et al. with 110 patients). Therefore, it might not be appropriate to directly compare their findings with those presented in your series, which involves only four patients.

(*) Blaj S, Dora D, Lohinai Z, Herold Z, Szasz AM, Herzberg J, Kodacsi R, Baransi S, Schlitt HJ, Hornung M, Werner JM, Slowik P, Acs M, Piso P. Prognostic Factors in Pseudomyxoma Peritonei with Emphasis on the Predictive Role of Peritoneal Cancer Index and Tumor Markers. Cancers (Basel). 2023 Feb 19;15(4):1326. doi: 10.3390/cancers15041326. PMID: 36831667; PMCID: PMC9954733.

Recommendations:

I strongly recommend including a table in the article summarizing the most critical clinicopathological characteristics, PCI, CC scores, overall survival, and disease-free survival data. This table will provide readers with a concise overview of the key findings in your study.

It would be beneficial to include a section discussing the limitations and strengths of your study. This will help readers and reviewers better understand the context and scope of your research, providing transparency regarding potential biases or constraints in the data and analysis.

By implementing these recommendations, the manuscript will likely become more informative and robust, facilitating a clearer understanding of the research outcomes

Author Response

I hope this email finds you well. It is with deep gratitude that I express my sincerest appreciation for your invaluable recommendation.

Your constructive critique and insightful comments have proven to be of tremendous value to me. I am grateful for your time and effort in thoroughly reviewing my work. Your attention to detail and meticulous analysis have undoubtedly helped me identify improvement areas and fueled my determination to enhance my skills further.

Our research has extensively investigated the median characteristics of patients with clinically aggressive diseases in comparison to those with Low-Grade Appendiceal Mucinous Neoplasms (LAMN). Through this analysis, we have discovered notable variations in patient characteristics.
In the Revised manuscript, we add two indexes. In the first index, we observed distinct features that directly correspond to clinically aggressive disease. These patients exhibited aggressive symptoms, such as rapid tumor progression, metastasis, and resistance to conventional treatments. It is imperative that these characteristics are given due consideration in order to develop appropriate treatment strategies and ensure the best possible outcomes for these patients.
Furthermore, when comparing the median characteristics of clinically aggressive disease patients to those with LAMN, stark differences emerged. Patients with clinically aggressive diseases display a greater presence of genetic mutations, higher levels of tumor invasiveness, and an overall poorer prognosis. These contrasting characteristics underscore the urgent need for tailored treatment approaches and closer monitoring for patients with clinically aggressive diseases.

Once again, I extend my deepest gratitude for your time and consideration. Rest assured that I will carefully implement your suggestions to enhance the quality of my work.  Thank you again for your valuable support and feedback. I am grateful for your mentorship, and I look forward to the opportunity to receive your guidance in the future.

Reviewer 2 Report

The current case report has addressed the the clinical characteristics, treatment, and outcomes of patients with low-grade appendiceal mucinous carcinomas (LAMN) who exhibit clinically aggressive behavior despite treatment with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).This manuscript is poorly written although it is a rare case. The quality of the manuscript is not sufficient for publication. Only 20 % of references are from the last 5 years. The manuscript's literature review is insufficient, and it fails to provide a comprehensive overview of existing research in the field.The inclusion of more recent results would be highly appreciated by the general reader interested in this topic. The introduction and discussion section are scarce and they do not sufficiently highlight the originality and the significant contributions of the study. Therefore, they need to be reformulated. Previous published case reports on this topic can be tabulated.

Moderate editing of English language required

Author Response

I hope this email finds you well. It is with deep gratitude that I express my sincerest appreciation for your invaluable recommendation.

Your constructive critique and insightful comments have proven to be of tremendous value to me. I am grateful for your time and effort in thoroughly reviewing my work. Your attention to detail and meticulous analysis have helped me identify improvement areas and fueled my determination to further enhance my skills.

Our research has extensively investigated the median characteristics of patients with clinically aggressive diseases in comparison to those with Low-Grade Appendiceal Mucinous Neoplasms (LAMN). Through this analysis, we have discovered notable variations in patient characteristics.
In the Revised manuscript, we add two indexes. In the first index, we observed distinct features that directly correspond to clinically aggressive disease. These patients exhibited aggressive symptoms, such as rapid tumor progression, metastasis, and resistance to conventional treatments. It is imperative that these characteristics are given due consideration in order to develop appropriate treatment strategies and ensure the best possible outcomes for these patients.
Furthermore, when comparing the median characteristics of clinically aggressive disease patients to those with LAMN, stark differences emerged. Patients with clinically aggressive diseases display a greater presence of genetic mutations, higher levels of tumor invasiveness, and an overall poorer prognosis. These contrasting characteristics underscore the urgent need for tailored treatment approaches and closer monitoring for patients with clinically aggressive diseases.

It is important to acknowledge that the cases we are investigating are indeed rare. Such scarcity is common in many specialized fields and can pose challenges for researchers. Nevertheless, it is precisely these exceptional cases that provide valuable insights and contribute significantly to the body of knowledge within our domain.
I understand the concern regarding the limited bibliography available for this topic. As experts in our field, we strive to include the latest research and trends in our work. However, given the relative novelty and restricted scope of these cases, it is only natural that the bibliography is more modest compared to widely researched topics. This does not diminish the quality or relevance of our findings, but rather highlights the pioneering nature of our work.
In order to mitigate these limitations, we have employed a meticulous approach to incorporate a judicious mix of old and new papers. By drawing upon established research from the past, we establish a robust foundation for our investigation. Simultaneously, we incorporate recent studies to ensure that our findings align with the most current developments in the field.

To ensure that our manuscript consistently meet the highest standrards, we have partnered with a trusted language editing service of MDPI. Their team of skilled editors posses a profound understanding of grammar, syntax, and language usage.

Once again, I extend my deepest gratitude for your time and consideration. Rest assured that I will carefully implement your suggestions to enhance the quality of my work.  Thank you again for your valuable support and feedback. I am grateful for your mentorship, and I look forward to the opportunity to receive your guidance in the future

Reviewer 3 Report

The manuscript in on 4 cases with low-grade appendiceal mucinous carcinomatosis with an aggressive course out of a total of 41 cases treated. While there is a detailed description of cytoreductive surgery and HIPEC in those 4 cases, there are no information on patient characteristics or the treatment of the 37 cases with a more favorable course. Therefore, it is not possible to evaluate what might be the explanation for this. The detailed description of the treatment protocols is according to existing guidelines, and my bee you just can refer to these instead of the very extensive description of known and standard treatment modalities. In general it is not possible to learn much from this cases presentation. 

Professionel linguistic revision recommended

Author Response

I hope this email finds you well. It is with deep gratitude that I express my sincerest appreciation for your invaluable recommendation.

Your constructive critique and insightful comments have proven to be of tremendous value to me. I am grateful for your time and effort in thoroughly reviewing my work. Your attention to detail and meticulous analysis have helped me identify improvement areas and fueled my determination to enhance my skills further.

Our research has extensively investigated the median characteristics of patients with clinically aggressive diseases in comparison to those with Low-Grade Appendiceal Mucinous Neoplasms (LAMN). Through this analysis, we have discovered notable variations in patient characteristics.
In the Revised manuscript, we add two indexes. In the first index, we observed distinct features that directly correspond to clinically aggressive disease. These patients exhibited aggressive symptoms, such as rapid tumor progression, metastasis, and resistance to conventional treatments. It is imperative that these characteristics are given due consideration in order to develop appropriate treatment strategies and ensure the best possible outcomes for these patients.
Furthermore, when comparing the median characteristics of clinically aggressive disease patients to those with LAMN, stark differences emerged. Patients with clinically aggressive diseases display a greater presence of genetic mutations, higher levels of tumor invasiveness, and an overall poorer prognosis. These contrasting characteristics underscore the urgent need for tailored treatment approaches and closer monitoring for patients with clinically aggressive diseases.

IThe possible reason for this aggressive attitude has been discussed in our manuscript (on lines that will be specified). 917-950).
I understand the concern regarding the limited bibliography available for this topic. As experts in our field, we strive to include the latest research and trends in our work. However, given the relative novelty and restricted scope of these cases, it is only natural that the bibliography is more modest compared to widely researched topics. This does not diminish the quality or relevance of our findings, but rather highlights the pioneering nature of our work.
In order to mitigate these limitations, we have employed a meticulous approach to incorporate a judicious mix of old and new papers. By drawing upon established research from the past, we establish a robust foundation for our investigation. Simultaneously, we incorporate recent studies to ensure that our findings align with the most current developments in the field.

To ensure that our manuscript consistently meets the highest standards, we have partnered with a trusted language editing service of MDPI. Their team of skilled editors possesses a profound understanding of grammar, syntax, and language usage.

Once again, I extend my deepest gratitude for your time and consideration. Rest assured that I will carefully implement your suggestions to enhance the quality of my work.  Thank you again for your valuable support and feedback. I am grateful for your mentorship, and I look forward to the opportunity to receive your guidance in the future.

Round 2

Reviewer 1 Report

Dear Petros :

I have reviewed the responses you provided to the concerns and suggestions I raised during the review process. I am pleased to inform you that I find your responses comprehensive and satisfactory. It is clear that you and your co-authors have put significant effort into addressing the issues raised in my initial review, and I am confident that the manuscript is now in a suitable condition for publication.

Reviewer 2 Report

I am satisfied that the authors have addressed all of my previous concerns about the article. It is now much improved and I feel that it is now suitable for publication.

Reviewer 3 Report

Thanks for your reply and corrections, which has improved the manuscript considerably, and I have no further questions.