Clinical and Demographics Aspects of Foot Angioleiomyomas: Case Reports and Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The paper describes two patient cases and a litterature review concerning a seldom benign smooth muscle tumor in the feet. Similar studies are available.

Critique:

Re. The cases. L. 102 and L.116, "Neoplastic cellularity". How is this defined, when no mitoses are seen (l. 101 and l.115).

Re. The systematic review: a) L.168-169. Inclusion criteria are not clear.                    b) To which extent does the present study overlap with previous studies/includes the same patients (e.g. ref 19)? c)  Abstract: The reader is told that 921 cases are reported (l. 29). This number differs much from the 168 mentioned l. 238. Also, l. 31-33 the description of location is not consistent ("location was" vs "location could not be determined" vs "most frequent location").

L.244 and 307: "lesions on the heel generally smaller than on the forefoot" - please, test this statistically.

L.320 " accurate classification" - why is this relevant? For e.g. treatment, prognosis?

Table 3: Heading of second coloumn: "% of total analyzed" - meaning? In the same coloumn numbers are given either with full stops or commas. The heading of the sixth coloumn not understandable. Furthermore, many numbers are missing, which is not consistent with L.361: "The review provides complete information".

Linguistics: L.47 myoma(s), not mioma(s). L. 284 "case reports" or "reported cases". L.327 "wide range of histological variants of ALM"- please describe, we have only heard about three. L. 358: do you mean "assisting clinicians"? L. 364 "occur".

Author Response

Reviewer 1
Dear reviewer, we greatly appreciate all your comments to improve our manuscript.
Comment: The paper describes two patient cases and a literature review concerning a seldom benign smooth muscle tumor in the feet. Similar studies are available.
REPLY: As you rightly mention, a recent systematic review related to ALM was published after ours had already begun. However, our review is based solely on case series with two or more cases of ALM in the foot, excluding ankle
Critique:
Comment: The cases. L. 102 and L.116, "Neoplastic cellularity". How is this defined, when no mitoses are seen (l. 101 and l.115).
REPLY: The term "neoplastic cellularity" can be used interchangeably for malignant and benign tumors. It is, however, commonly used in oncology to describe malignant tumors. To avoid confusion, we have removed the term from the text.
Re. The systematic review:
Comment: a) L.168-169. Inclusion criteria are not clear.
REPLY: The following criteria were used for the initial selection: human clinical studies, retrospective studies, case series (two or more cases) with no restrictions on follow-up after surgical removal. Studies prior to July 1984 (first and largest published series of cases on ALM), case reports (one case), letters to the editor, and manuscripts published in a non-English language or without full access to the text were excluded.
Comment: b) To which extent does the present study overlap with previous studies/includes the same patients (e.g. ref 19)?
REPLY: Our systematic review only examines cases of ALM of the foot. Our review is based solely on case series with two or more cases of ALM in the foot, excluding ankle. Of the 62 cases of ALMs reports included in the systematic review by Matos et al., 59 studies were reports with no more than one or two cases of ALMs in the foot and ankle.
Comment: c) Abstract: The reader is told that 921 cases are reported (l. 29). This number differs much from the 168 mentioned l. 238. Also, l. 31-33 the description of location is not consistent ("location was" vs "location could not be determined" vs "most frequent location").
REPLY: Thank you very much for pointing out the error. The line has been corrected to "This systematic review included 14 case series with 172 reported cases of ALM"
Comment: L.244 and 307: "lesions on the heel generally smaller than on the forefoot" - please, test this statistically.
REPLY: This information has been reviewed and corrected to “The mean maximum diameter of the tumours in the hindfoot (zone 1) was very similar to that recorded in zones 4 and 5 (9.93±7.15mm VS 10.36±9.4 mm) without significant differences”
Comment: L.320 " accurate classification" - why is this relevant? For e.g. treatment, prognosis?
REPLY: The sentence has been completed
Comment: Table 3: Heading of second column: "% of total analyzed" - meaning? In the same coloumn numbers are given either with full stops or commas. The heading of the sixth coloumn not understandable. Furthermore, many numbers are missing, which is not consistent with L.361: "The review provides complete information".
REPLY: The table has been revised and L.361 has been modified to “the present review provides detailed information about epidemiological…”
Comments: Linguistics: L.47 myoma(s), not mioma(s). L. 284 "case reports" or "reported cases". L.327 "wide range of histological variants of ALM"- please describe, we have only heard about three. L. 358: do you mean "assisting clinicians"? L. 364 "occur".
REPLY: The spelling errors have been corrected. Thank you very much for pointing this out.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Major critiques

1. Small number of cases reported.
2. Results section is very sparse. Can you describe more about the characteristics reported in these case series? In particular, it would be helpful to report the rate of recurrence in the literature. Are there any differences in clinical outcomes (especially recurrence but also patient characteristics such as age, sex, etc) based on the 3 different subtypes?
3. Based on your cases and the reviewed cases in the literature, are there certain recommendations you have for clinicians caring for patients with ALMs? For example, is a certain size of surgical margin recommended? How frequently to follow up and is any imaging required?
4. Do these ever transform to leiomyosarcomas? If so, at what rate?
5. It is odd to me to exclude case reports/series with 1 or 2 cases, as this would mean your analysis would exclude your own paper. How many more cases could potentially be added if you removed this exclusion criterion? It might be worth doing this to expand the review.

 

Minor critiques

1. Abstract
   1. This sentence on lines 20-23 is unclear (Regarding two reported cases...). I would recommend changing to something like this: we summarize 2 cases of ALM and perform a systematic review to provide foot surgeons…
   2. Missing a period at the end of line 28.
   3. The Results section should comment on the 2 cases you present from your institution.
   4. Please add rate of recurrence and median time to recurrence following resection.
   5. Line 41, should be “Solid histologic subtype is…”
   6. Line 42, remove “usually”
   7. Line 66, should be “acral ALM”
2. Introduction
   1. Line 47, angioleiomioma is misspelled (should be angioleiomyoma).
   2. Line 48, insert “smooth” between venous and muscle
3. Case Presentation
   1. Lines 82-84, I would reword to: A 57-year-old male with history of hypertension and hyperthyroidism presented with a lump in his left heel for over 2 years.”
4. Methods
   1. Appropriate use of PICO and PRISMA guidelines.
   2. Line 148, change “deadline” to “data cutoff”
5. Discussion
   1. Line 343, “pregression” is misspelled
6. Tables/Figures
   1. Combine figures 1-4 into 1 figure with 4 panels (A-D).
   2. Combine figures 5-7 into 1 figure with 2 panels (A-C).
   3. Add scale bars to micrographs.
   4. Figure 4 legend says smooth muscle actin and desmin. Which is it here? Can you show both?
   5. Table 3 – change to “Mean duration of symptoms”

Author Response

Reviewer 2
Dear reviewer, we greatly appreciate all your comments to improve our manuscript.
Major critiques
1.
Small number of cases reported.
REPLY: We have highlighted this as a limitation of the study. More than half of the studies were small case series, given the rarity of ALM of the foot.
2.
Comment: Results section is very sparse. Can you describe more about the characteristics reported in these case series? In particular, it would be helpful to report the rate of recurrence in the literature. Are there any differences in clinical outcomes (especially recurrence but also patient characteristics such as age, sex, etc) based on the 3 different subtypes?
REPLY: Results section has been expanded.
3.
Based on your cases and the reviewed cases in the literature, are there certain recommendations you have for clinicians caring for patients with ALMs? For example, is a certain size of surgical margin recommended? How frequently to follow up and is any imaging required?
REPLY: A final paragraph in the conclusions section has been added regarding the recommendations.
4.
Do these ever transform to leiomyosarcomas? If so, at what rate?
REPLY: Un paragraph in the discussion section related with malign transform has been incorporated.
5.
It is odd to me to exclude case reports/series with 1 or 2 cases, as this would mean your analysis would exclude your own paper. How many more cases could potentially be added if you removed this exclusion criterion? It might be worth doing this to expand the review.
REPLY: Thank you very much for your recommendation. Based on your suggestion, we consider it appropriate to modify the selection criteria by incorporating case series with two or more reported ALMs. Following the established criteria for manuscript selection, two small case series have been included in the review.
Minor critiques:
1.
Abstract
1.
This sentence on lines 20-23 is unclear (Regarding two reported cases...). I would recommend changing to something like this: we summarize 2 cases of ALM and perform a systematic review to provide foot surgeons…
2.
Missing a period at the end of line 28.
3.
The Results section should comment on the 2 cases you present from your institution.
4.
Please add rate of recurrence and median time to recurrence following resection.
5.
Line 41, should be “Solid histologic subtype is…”
6.
Line 42, remove “usually”
7.
Line 66, should be “acral ALM”
2.
Introduction
1.
Line 47, angioleiomioma is misspelled (should be angioleiomyoma).
2.
Line 48, insert “smooth” between venous and muscle
3.
Case Presentation
1.
Lines 82-84, I would reword to: A 57-year-old male with history of hypertension and hyperthyroidism presented with a lump in his left heel for over 2 years.”
4.
Methods
1.
Appropriate use of PICO and PRISMA guidelines.
2.
Line 148, change “deadline” to “data cutoff”
5.
Discussion
1.
Line 343, “pregression” is misspelled
6.
Tables/Figures
1.
Combine figures 1-4 into 1 figure with 4 panels (A-D).
2.
Combine figures 5-7 into 1 figure with 2 panels (A-C).
3.
Add scale bars to micrographs.
4.
Figure 4 legend says smooth muscle actin and desmin. Which is it here? Can you show both?
5.
Table 3 – change to “Mean duration of symptoms”
REPLY: The spelling errors have been corrected. Thank you very much for pointing this out. All suggestions have been incorporated into the text and table 3.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Critique: I still think that readers will like to know how much overlap there may be between data (included patients) in the present review and that presented recently in ref. 19, a similar review. This is the more so, because the authors have changed (surprisingly) the criteria for inclusion in their own study. Now they state that they included patients with two or more cases of ALM in the foot, whereas the numbers were three or more cases according to the Discussion l.283 of the former version of the paper. In ref 19 patients had one or two cases of ALM. 

Minor queries:

L. 248: "with a"-what?. And "lager" - what is that?

L. 263: "three studies" - give references.

Author Response

Reviewer 1

Critique: I still think that readers will like to know how much overlap there may be between data (included patients) in the present review and that presented recently in ref. 19, a similar review. This is the more so, because the authors have changed (surprisingly) the criteria for inclusion in their own study. Now they state that they included patients with two or more cases of ALM in the foot, whereas the numbers were three or more cases according to the Discussion l.283 of the former version of the paper. In ref 19 patients had one or two cases of ALM.

REPLY

Thank you very much for your comments. The present review is based solely on case series with two or more cases of ALM in the foot, excluding the ankle. Of the 62 cases of ALM reported in the systematic review by Matos et al., 59 studies were reports with no more than one or two cases of ALM in the foot and ankle, and only six studies included in this review are coincident. A paragraph has been included in the discussion to clarify this aspect for readers.

Based on the other reviewer's suggestion, we considered it appropriate to modify the selection criteria by incorporating case series with two or more reported ALMs. Following the other criteria established for manuscript selection, two small case series were included in the review.

Minor queries:

1. 248: "with a"-what?. And "lager" - what is that?

REPLY

The paragraph has been corrected to “Most tumors presented as a single, painful lump with a mean diameter of 21.7 ± 9.0 mm and a mean duration until confirmed diagnosis and surgical excision of 6.1 ± 5.4 year”.

1. 263: "three studies" - give references.

REPLY

References have been incorporated

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

I applaud the authors for revising the manuscript as I have recommended.

My only remaining critique is regarding the last sentence in the Conclusion section. Are there any data to suggest that certain amount of follow up or use of ultrasound are helpful to detect recurrence and make a difference in patient outcomes? This might warrant a paragraph in the Discussion section to speculate on the optimal follow up plan before dropping this sentence in the Conclusion section.

Author Response

I applaud the authors for revising the manuscript as I have recommended.
My only remaining critique is regarding the last sentence in the Conclusion section. Are there any data to suggest that certain amount of follow up or use of ultrasound are helpful to detect recurrence and make a difference in patient outcomes? This might warrant a paragraph in the Discussion section to speculate on the optimal follow up plan before dropping this sentence in the Conclusion section.
REPLY
Dear reviewer, we greatly appreciate all your suggestions for improving the manuscript. Based on your suggestion, we have incorporated a paragraph in the discussion section to speculate on the optimal follow-up plan before placing this sentence in the Conclusion section.

Kind regards

Author Response File: Author Response.pdf