Aggressive Surgical Management of Bilateral Metachronous Lung Metastases in Fibrolamellar Hepatocellular Carcinoma, a Case Report

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In the case report ‘Aggressive Surgical Management of Bilateral Metachronous Lung Metastases in Fibrolamellar Hepatocellular Carcinoma, A Case Report’, the author reported a rare case that a young man with Fibrolamellar hepatocellular carcinoma and nodules in the lung was treated by the surgical resection. After surgery, 1 and 3 months later there was no disease recurrence. It was so exciting and touching to hear patient to be cured. It was very valuable.  However, there are some shortcomings and questions. Even considering the case report format, this report is still too simple and brief. Some parts should be improved.

 

1)    In the background, the disease prevalence and pathogenesis mechanism   should be introduced.

2)     3. Therapeutic Intervention and Outcome This part is the most important results in this case report. It is too short like a draft. In the line 78-79: LHCC metastasis with wide negative margins was histologically confirmed (Figure 3). The results are needed to be explain and fully describe. And how to confirm the nodules in the lung come from liver ? The surgery details may be important to the potential readers.

3)    All the figure legends too simple and  should be re-write.

Comments for author File: Comments.docx

Author Response

Comment 1: In the case report ‘Aggressive Surgical Management of Bilateral Metachronous Lung Metastases in Fibrolamellar Hepatocellular Carcinoma, A Case Report’, the author reported a rare case that a young man with Fibrolamellar hepatocellular carcinoma and nodules in the lung was treated by the surgical resection. After surgery, 1 and 3 months later there was no disease recurrence. It was so exciting and touching to hear patient to be cured. It was very valuable.  However, there are some shortcomings and questions. Even considering the case report format, this report is still too simple and brief. Some parts should be improved. In the background, the disease prevalence and pathogenesis mechanism should be introduced. Therapeutic Intervention and Outcome This part is the most important results in this case report. It is too short like a draft. In the line 78-79: LHCC metastasis with wide negative margins was histologically confirmed (Figure 3). The results are needed to be explain and fully describe. And how to confirm the nodules in the lung come from liver ? The surgery details may be important to the potential readers. All the figure legends too simple and  should be re-write.

Response 1: Thanks for your time and for your revision. As the case report format makes it difficult to explain in depth a large amount of details, it is clear that several points needed to be further explained. Consequently, we implemented, reorganized and emphasized the paragraph containing the introduction concerning FL-HCC; moreover, we extended the treatment section and we also reorganized figure legends. Updates can be checked in the main manuscript.  

 

Reviewer 2 Report

Comments and Suggestions for Authors

This article reports a case of successful treatment of bilateral metachronous lung metastases from fibrolamellar hepatocellular carcinoma (FLHCC) through aggressive surgical management, emphasizing the importance of a multidisciplinary approach and surgical intervention in improving patient outcomes. I suggest a major revision.

1. The manuscript lacks novelty. The authors concluded that "Given the lack of conclusive knowledge surrounding FLHCC, a proactive stance towards surgical intervention remains crucial for optimizing patient outcomes. 

2. In the abstract, the article should use 'an' instead of 'a' before '18-year-old'.

3. Immunohistochemical analysis should be provided for the three right lung nodules.

4. It is inappropriate to judge the condition based on the second postoperative follow-up, which occurred only three months after the first follow-up. The first follow-up was nine months post-surgery and showed an increase in the lung nodule volume.

5. The article lacks ethical approval and participant consent.

Comments on the Quality of English Language

I suggest the quality of English is OK.

Author Response

Comment 1: The manuscript lacks novelty. The authors concluded that "Given the lack of conclusive knowledge surrounding FLHCC, a proactive stance towards surgical intervention remains crucial for optimizing patient outcomes”. 

Response 1: As the reviewer rightly said, it is extremely difficult to describe novelty in the literature nowadays because of the large number of cases reported in recent years. Novelty is usually nowadays represented by a new description of case management or the undescribed evolution of rare cases rather than the unique report of a case. Therefore, considering that a single case still does not represent statistical significance, our aggressive surgical management stands as a treatment option that should be considered as an example of a feasible treatment in selected cases in the future. Our conclusions cannot provide a mandatory advice on surgical management for future cases, although our experience may serve as an example for the direction to follow in future similar cases.

Comment 2: In the abstract, the article should use 'an' instead of 'a' before '18-year-old'.

Response 2: Thanks for this point. We checked the sentence.

Comment 3: Immunohistochemical analysis should be provided for the three right lung nodules.

Response 3: Thanks for this comment. We discussed with our pathologists the possibility to perform other panels of high focused coloured stains but the availability of the electronic microscope and the high resolution photography is not possible these weeks. This is one of the reasons due to our delay in submitting the manuscript a few months ago. In fact we had to wait for the picture processing made by the pathology specialists. 

Comment 4: It is inappropriate to judge the condition based on the second postoperative follow-up, which occurred only three months after the first follow-up. The first follow-up was nine months post-surgery and showed an increase in the lung nodule volume.

Response 4: Thanks for this comment. This is an important point that we modified in the revised version of the manuscript. This sentence was written incorrectly and has therefore been rephrased

Comment 5: The article lacks ethical approval and participant consent.

Response 5: Thanks for this comment. Our Institution does not routinely require an Ethical Committee evaluation for single cases due to a general written statement that patients routinely sign what they are admitted to the hospital in which is expressly asked the agreement to contribute at the scientifical activity. This paper was sent to the Editorial Office submitting this manuscript. 

Reviewer 3 Report

Comments and Suggestions for Authors

Nicotra and colleagues present an interesting case report of a patient suffering from metastatic fibrolamellar hepatocellular carcinoma (FL-HCC). This 18-year-old male patient was successfully treated with aggressive intra-thoracic bilateral lung metastasectomy following primary tumor resection and adjuvant chemotherapy. The case report is well-documented and contains meaningful images including total body computed tomography scans and histopathological images of the metastasectomy specimen.

The report is written in a clear and concise style and is interesting for the readership of Livers. In particular, the study is intriguing because there is currently no available therapy for the treatment of FL-HCC. However, in my view, there are some minor issues that need to be addressed prior to publication.

1.       There is a short information available about FL-HCC that serves as a summary for this disease. It can be found at: https://www.ncbi.nlm.nih.gov/books/NBK553113/. I would ask the authors to cite this reference because it provides additional information on the disease, including treatment and management strategies currently in use. Consequently, it would be helpful to change the abbreviation FLHCC to FL-HCC, which is more common in the field.

2.       The authors state that the patient was treated with a first-line systemic therapy with Oxaliplatin and Fluoropyrimides. Please provide the concentrations of the respective drugs.

3.       Figure 1 and 2 can be combined.

4.       Line 80: The authors state “……that the patient was discharged from our department in excellent general condition”. How is this condition defined? Please add a short commentary on that issue.

5.       In Figure 3, some arrows would be helpful to indicate the mentioned features (e.g. large, polygonal, and exhibited well-defined cell borders). Moreover, I would suggest showing the scale bars in black.

6.       The case report describes a successful treatment of an 18-year-old patient. Do the authors think that this therapy will also be successful in older patients. Please comment on this.

7.       A short paragraph on the limitations of this study should be added.

8.       Informed consent statement: Besides the informed consent of the patient to publish this paper, have you received approval from an ethics committee? If yes, please provide permit number.

9.       The format of the references is inconsistent. Moreover, several sentences from the template were not removed (e.g. after Refs 3 and 5). Please remove them and bring the references into a uniform format.

Comments on the Quality of English Language

is o.k.

Author Response

Comment 1: There is a short information available about FL-HCC that serves as a summary for this disease. It can be found at: https://www.ncbi.nlm.nih.gov/books/NBK553113/. I would ask the authors to cite this reference because it provides additional information on the disease, including treatment and management strategies currently in use. Consequently, it would be helpful to change the abbreviation FLHCC to FL-HCC, which is more common in the field.

Response 1: Thanks to the reviewer for this precious comment. We implemented the references with the manuscript suggested and we changed the abbreviation as requested for a more understandable manuscript. 

Comment 2: The authors state that the patient was treated with a first-line systemic therapy with Oxaliplatin and Fluoropyrimides. Please provide the concentrations of the respective drugs.

Response 2: Thanks to the reviewer for this comment. We added the scheme protocol in the manuscript. 

Comment 3: Figure 1 and 2 can be combined.

Response 3: Thanks for the comment. Due to the presence of a multipanel Figure 1, it would be difficult to combine a single Figure 2 with the longer Figure 1, rendering the visualization more difficult. We at the moment preferred to maintain a separate frame, but if the unification of figures is found more suitable, we will provide the suggested version.

Comment 4: Line 80: The authors state “……that the patient was discharged from our department in excellent general condition”. How is this condition defined? Please add a short commentary on that issue.

Response 4: Thanks to the reviewer for this comment. We specified the sentence tempering the phrase. 

Comment 5: In Figure 3, some arrows would be helpful to indicate the mentioned features (e.g. large, polygonal, and exhibited well-defined cell borders). Moreover, I would suggest showing the scale bars in black.

Response 5: Thanks to the reviewer for this suggestion. We  implemented the figures with the indications mentioned.  

Comment 6: The case report describes a successful treatment of an 18-year-old patient. Do the authors think that this therapy will also be successful in older patients. Please comment on this.

Response  6: Thanks to the reviewer for this comment. This is an important question that deserves our attention. FL-HCC is generally discovered in young adults and this is strictly related with the necessity of an aggressive management to take cancer under control. We assume that for patients under 40 years (the general higher age cut-off for FL-HCC) our case could fit as a feasible treatment, supposing that Fl-HCC is dominated by a general common biological behavior in terms of aggressiveness. It is possible that in older patients this type of neoplasm should present a different biological behavior but their reports are anecdotal and we are far from being able to discuss this question in patients older than 40-years-old (https://doi.org/10.1016/j.dld.2014.05.010). The greater impact that case reports could have is represented by the growing case series they produce, providing stronger evidence about FL-HCC and a more clear understanding of their behavior

Comment 7: A short paragraph on the limitations of this study should be added. 

Response 7: Thanks to the reviewer for this comment. The most relevant limitations have been outlined in the main text. 

Comment 8: Informed consent statement: Besides the informed consent of the patient to publish this paper, have you received approval from an ethics committee? If yes, please provide permit number.

Response 8: Thanks to the reviewer for this comment. Thanks for this comment. Our Institution does not routinely require an Ethical Committee evaluation for single cases due to a general written statement that patients routinely sign what they are admitted to the hospital in which is expressly asked the agreement to contribute at the scientifical activity. This paper was sent to the Editorial Office submitting this manuscript. We apologize but we do not have the ethical number approval. 

Comment 9: The format of the references is inconsistent. Moreover, several sentences from the template were not removed (e.g. after Refs 3 and 5). Please remove them and bring the references into a uniform format.

Response 9: Thanks to the reviewer for this comment. We apologize for typos and for unclear references. We checked the references and the sentences to be sure that they fit in the text remaining coherent. 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I have no other suggestion. 

Author Response

Comment 1: I have no other suggestion.

Response 1: We thank the Reviewer for their comments and we look forward to collaborate again.