Histopathological Investigation of Dura-like Membrane in Vestibular Schwannomas

Round 1

Reviewer 1 Report

The article “Histopathological investigation of dura-like membrane in vestibular schwannomas” is an interesting study which discuss a not well-known anatomical aspect of these tumors. However, several considerations must be made:

• The anatomical and microsurgical arrangement of the “dura-like membrane” and its relationship with the bone and dura should be better clarified.
• Why only several vestibular schwannomas show the dural-like membrane? It is not related to the tumor volume in this series. Is it correct to the high tumor vascularization? The authors should clarify this aspect.
• Three among the 10 patients (30%) developed postoperative facial palsy. This rate is higher than that reported in the surgical series. Does it depend upon the DML taken just behind the initial auditory canal, an area at risk of cranial nerve damage?
• The resection rate is associated to the tumor volume, mainly for the giant acoustic schwannomas. The post-operative remnants are mainly found a the brainstem surface or within the internal auditory canal. Does the presence of DML hinder the tumor resection at level of the DML. The location of the post-operative remnant on MRI after partial resection must be specified to define whether the incomplete resection depends upon the presence of DML.
• The number of the cases (5 with MDL versus 5 with no MDL) is too small to obtain a statistical significance.

In conclusion, this article is rather interesting, but it needs to include a larger number of cases. It may be evaluated after the above discussed points

Author Response

We are very grateful to the reviewers for their insightful comments and suggestions, which have undoubtedly helped us to improve our manuscript immensely. As indicated in the responses below, we have taken all their comments and suggestions into account when generating the revised version of the manuscript. Responses to the reviewers’ comments appear after the arrows, in blue text.

 

＃Reviewer 1:

1. The article “Histopathological investigation of dura-like membrane in vestibular schwannomas” is an interesting study which discuss a not well-known anatomical aspect of these tumors. However, several considerations must be made:

The anatomical and microsurgical arrangement of the “dura-like membrane” and its relationship with the bone and dura should be better clarified.

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Thank you very much for your comments. DLM and its relationship with the bone and dura was described in our previous paper. We have attached the image below.

The DLM continues from the dura mater of the petrous bone and enveloped the complex of tumor and nerves from the outside. The DLM appeared to be derived from the contiguous dura mater. There was a tight adhesion between the DLM and the tumor or nerves.

[Tomio R. Surg Neurol Int. 2016]

 

 

2. Why only several vestibular schwannomas show the dural-like membrane? It is not related to the tumor volume in this series. Is it correct to the high tumor vascularization? The authors should clarify this aspect.

→

Thank you very much for your comments.

As the reviewer indicated, the reason why only several VSs show the DLM is not fully elucidated. To understand the mechanism, we have cited the following manuscript in the revised manuscript. Walcocha et al. has also demonstrated the similar capsule around uterine leiomyoma. During development of leiomyoma, the pre-existing blood vessels undergo regression and new vessels invade the tumor from the periphery probably promoted by growth factors secreted by the tumor (e.g., basic fibroblast growth factor [bFGF] and adrenomedullin [ADM]). The formation of a 'vascular capsule' was responsible for supply of blood to the growing tumor under the hypoxic condition [Walocha JA. Hum Reprod. 2003].

Therefore, as the reviewer indicated, the formation of DLM may be associated with not only high vascularization but also other growth factors and microenvironment described above.

We have added these sentences in the revised manuscript.

 

Reference

Walocha JA, Litwin JA, Miodoński AJ. Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy. Hum Reprod. 2003;18(5):1088-93.

 

3. Three among the 10 patients (30%) developed postoperative facial palsy. This rate is higher than that reported in the surgical series. Does it depend upon the DML taken just behind the initial auditory canal, an area at risk of cranial nerve damage?

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Thank you very much for your comments.

Permanent facial palsy was observed in only one patient with DLM. The facial palsy of other two patients without DLM was completely improved several months after the operation.

During the operation, we usually try to confirm the location of the facial nerve by facial electromyography (EMG) monitoring at the IAM and identify a border between the tumor and the facial nerve. The presence of the DLM has a possibility to negatively affect the surgical outcome in some cases. The DLM was fibrous tissue. There was a tight adhesion between the DLM and the tumor or nerves, which made preservation of the nerves more challenging at the beginning of the subcapsular dissection. It becomes more difficult to identify correct layer for dissection when the DLM envelopes the tumor and nerves. However, as the reviewer indicated, the resection rate and functional preservation of the facial and cochlear nerves may be associated with several factors including tumor volume, preoperative hearing status, age, expertise of the surgeons. Furthermore, the main limitation of the present study was the small number of VSs with DLM. We have added the limitation in the revised manuscript.

 

4. The resection rate is associated to the tumor volume, mainly for the giant acoustic schwannomas. The post-operative remnants are mainly found a the brainstem surface or within the internal auditory canal. Does the presence of DML hinder the tumor resection at level of the DML. The location of the post-operative remnant on MRI after partial resection must be specified to define whether the incomplete resection depends upon the presence of DML.

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In these case series with DLM, remnants were mainly found around the IAC. Therefore, the presence of the DLM has a possibility to negatively affect the surgical outcome in some cases. However, as the reviewer indicated, no valid conclusions can be drawn from this sample size. Small number of patients frequently leads to low statistical power. We will continue to collect the data from the patients with DLM.

 

5. The number of the cases (5 with MDL versus 5 with no MDL) is too small to obtain a statistical significance. In conclusion, this article is rather interesting, but it needs to include a larger number of cases. It may be evaluated after the above discussed points.

→

Thank you for your comments.

As the reviewer indicated, the main limitation of the present study was the small number of VSs with DLM. DLM was rarely observed around the VS. Studies using a larger number of patients are warranted to confirm our findings. We have added the discussion and limitation, as the reviewer indicated.

 

 

 

 

 

 

 

 

 

 

Author Response File: Author Response.docx

Reviewer 2 Report

This is an interesting pathological study where I would completely leave out the clinical correlations: though mean dimensions did not differ between groups, the group  DLM+ have larger tumors and this explains in my opinion why the resection was more difficult, besides other known factors (preop hearing status, HB grade, age, expertise of the surgeons, etc.)

Author Response

We are very grateful to the reviewers for their insightful comments and suggestions, which have undoubtedly helped us to improve our manuscript immensely. As indicated in the responses below, we have taken all their comments and suggestions into account when generating the revised version of the manuscript. Responses to the reviewers’ comments appear after the arrows, in blue text.

 

＃Reviewer 2:

This is an interesting pathological study where I would completely leave out the clinical correlations: though mean dimensions did not differ between groups, the group DLM+ have larger tumors and this explains in my opinion why the resection was more difficult, besides other known factors (preop hearing status, HB grade, age, expertise of the surgeons, etc.)

→

Thank you very much for your review.

There was no significant different of the average tumor volumes between DLM group and non-DLM group (p= 0.39). However, a small sample size implies low statistical power.

The presence of the DLM has a possibility to negatively affect the surgical outcome in some cases. The DLM was fibrous tissue. There was a tight adhesion between the DLM and the tumor or nerves, which made preservation of the nerves more challenging at the beginning of the subcapsular dissection. It becomes more difficult to identify correct layer for dissection when the DLM envelopes the tumor and nerves. Thus, the DLM could be a risk factor in VS surgery.

The main limitation of the present study was the small number of VSs with DLM.

Furthermore, as the reviewer indicated, the resection rate and functional preservation of the facial and cochlear nerves were associated with several factors including tumor volume, preoperative hearing status, age, expertise of the surgeons. Therefore, we have added the limitation in the revised manuscript.

 

 

 

 

 

 

 

 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

I would like to thank for the opportunity of reading this very intersting manuscript.

I have small comments: in 2003 there was an article published in Human Reproduction 

Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy

 

By

Walocha, JA (Walocha, JA) Litwin, JA (Litwin, JA) Miodonski, AJ (Miodonski, AJ

Volume 18 Issue 5 Page 1088-1093 DOI 10.1093/humrep/deg213

MAY 2003

It was dealing with the uterine leiomyomata - during expansion they develop the "same" capsule supplied by numerous vessels and proliferating under the influence of many factors i.e. hypoxia. Please read it and see if there are any analogies.

 

Author Response

We are very grateful to the reviewers for their insightful comments and suggestions, which have undoubtedly helped us to improve our manuscript immensely. As indicated in the responses below, we have taken all their comments and suggestions into account when generating the revised version of the manuscript. Responses to the reviewers’ comments appear after the arrows, in blue text.

 

#Reviewer 3:

I would like to thank for the opportunity of reading this very intersting manuscript.

I have small comments: in 2003 there was an article published in Human Reproduction

Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy

By Walocha, JA (Walocha, JA) Litwin, JA (Litwin, JA) Miodonski, AJ (Miodonski, AJ Volume 18 Issue 5 Page 1088-1093 DOI 10.1093/humrep/deg213 MAY 2003

It was dealing with the uterine leiomyomata - during expansion they develop the "same" capsule supplied by numerous vessels and proliferating under the influence of many factors i.e. hypoxia. Please read it and see if there are any analogies.

 

→

Thank you very much for your comments.

We have cited the indicated paper in the revised manuscript.

Walcocha et al. has also demonstrated the similar capsule around uterine leiomyoma. During development of leiomyoma, the pre-existing blood vessels undergo regression and new vessels invade the tumor from the periphery probably promoted by growth factors secreted by the tumor (i.e.; basic fibroblast growth factor [bFGF] and adrenomedullin [ADM]). The formation of a 'vascular capsule' was responsible for supply of blood to the growing tumor under the hypoxic condition [Walocha JA. Hum Reprod. 2003].

 

Reference

Walocha JA, Litwin JA, Miodoński AJ. Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy. Hum Reprod. 2003;18(5):1088-93.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

You've made the suggested corrections.