Opportunistic Salpingectomy at the Time of General Surgery Procedures: A Systematic Review and Narrative Synthesis of Current Knowledge

Round 1

Reviewer 1 Report

This systematic review (SR) summarizes the literature on opportunistic salpingectomy (OS) at general non-gynecological surgery. It is conducted according to the principles described in the PRISMA statement and MOOSE guidelines, and a PRISMA checklist is provided. However, in the checklist it is stated that registration of a protocol was not applicable. That is difficult to understand, since the registration of a protocol (commonly in PROSPERO) is the first step in performing a SR, and act as a quality indicator of the review.

Another important criticism is the long interval between the search date (October 2021) and submission (February 2024). Normally, a SR with an interval > 1 year would not be published, unless the search was updated.

Other specific comments are:

The numbers in the text do not match with the flowchart (13 or 15 fulltext articles?). Several numbers need to be corrected.

The risk of bias assessment of articles could not be assessed since Supplemental Material 2, Table 1S was not included in the supplementary download. It is noted that there was no comparative study in the review. One-armed studies are often classified as having low or very low quality or validity, but the included papers seem to have a higher classification.

In Table 1, it is stated that Myriokefalitaki et al included ovarian surgery (not OS). If that is the case, the study should not have been included.

Both the Introduction and the Discussion reveals an undisputable approach to OS, focusing on the risk reduction of ovarian cancer. References to safety seem to be highly selected, without any reference to studies with complications associated with OS. The concern of impairment of ovarian function and premature menopause and its associated risks are hardly mentioned. References are mainly observational studies and ongoing RCTs on the topic which will provide high quality evidence are not mentioned.

Below are a few references that provide a more comprehensive picture to the topic of OS and its potential risks:

Collins E, Strandell A, Granåsen G, Idahl A. Menopausal symptoms and surgical complications after opportunistic bilateral salpingectomy, a register-based cohort study. Am J Obstet Gynecol. 2019 Jan;220(1):85.e1-85.e10. doi: 10.1016/j.ajog.2018.10.016. Epub 2018 Oct 12. PMID: 30321526.

van Lieshout LAM, Steenbeek MP, De Hullu JA, Vos MC, Houterman S, Wilkinson J, Piek JM. Hysterectomy with opportunistic salpingectomy versus hysterectomy alone. Cochrane Database Syst Rev. 2019 Aug 28;8(8):CD012858. doi: 10.1002/14651858.CD012858.pub2. PMID: 31456223; PMCID: PMC6712369.

Mandelbaum RS, Matsuzaki S, Sangara RN, Klar M, Matsushima K, Roman LD, Paulson RJ, Wright JD, Matsuo K. Paradigm shift from tubal ligation to opportunistic salpingectomy at cesarean delivery in the United States. Am J Obstet Gynecol. 2021 Oct;225(4):399.e1-399.e32. doi: 10.1016/j.ajog.2021.06.074. Epub 2021 Jun 26. PMID: 34181896.

Author Response

Reviewer #1:

This systematic review (SR) summarizes the literature on opportunistic salpingectomy (OS) at general non-gynecological surgery. It is conducted according to the principles described in the PRISMA statement and MOOSE guidelines, and a PRISMA checklist is provided. However, in the checklist it is stated that registration of a protocol was not applicable. That is difficult to understand, since the registration of a protocol (commonly in PROSPERO) is the first step in performing a SR, and act as a quality indicator of the review.

Response: Thank you for your review of our submitted manuscript and for the helpful feedback. We have provided a point-by-point response to each comment below. With regards to the protocol registration, this study was not registered but did have a study protocol and search plan developed prior to beginning the study. We have now included this study protocol as a supplementary document for review.

Another important criticism is the long interval between the search date (October 2021) and submission (February 2024). Normally, a SR with an interval > 1 year would not be published, unless the search was updated.

Response: This is a great point. Unfortunately this study has been under review for nearly 2-years at the Canadian Journal of Surgery, which has significantly delayed its submission and is the primary reason for the long interval. We have updated the search for this manuscript and this has resulted in the inclusion of 2 more manuscripts after review of 3977 studies.

Other specific comments are:

The numbers in the text do not match with the flowchart (13 or 15 fulltext articles?). Several numbers need to be corrected.

Response: Thank you for pointing this out. Figure 1 has been updated to accurately represent the number of studies, which has been updated with an up-to-date search.

The risk of bias assessment of articles could not be assessed since Supplemental Material 2, Table 1S was not included in the supplementary download. It is noted that there was no comparative study in the review. One-armed studies are often classified as having low or very low quality or validity, but the included papers seem to have a higher classification.

Response: Thank you for pointing this out, the MINORS assessment has been included in supplementary material 3, Table 1S. We agree that non-comparative studies typically yield lower quality scores, however, the MINORS assessment allows for different scoring assessment for comparative and non-comparative studies. We have clarified in the results section that studies were being assessed based on non-comparative MINORS assessment and that scores should be evaluated under than context.

In Table 1, it is stated that Myriokefalitaki et al included ovarian surgery (not OS). If that is the case, the study should not have been included.

Response: Thank you for capturing this mistake, table 1 should more accurately state that patients underwent salpingectomy, not ovarian surgery.

Both the Introduction and the Discussion reveals an undisputable approach to OS, focusing on the risk reduction of ovarian cancer. References to safety seem to be highly selected, without any reference to studies with complications associated with OS. The concern of impairment of ovarian function and premature menopause and its associated risks are hardly mentioned. References are mainly observational studies and ongoing RCTs on the topic which will provide high quality evidence are not mentioned.

Below are a few references that provide a more comprehensive picture to the topic of OS and its potential risks:

Collins E, Strandell A, Granåsen G, Idahl A. Menopausal symptoms and surgical complications after opportunistic bilateral salpingectomy, a register-based cohort study. Am J Obstet Gynecol. 2019 Jan;220(1):85.e1-85.e10. doi: 10.1016/j.ajog.2018.10.016. Epub 2018 Oct 12. PMID: 30321526.

van Lieshout LAM, Steenbeek MP, De Hullu JA, Vos MC, Houterman S, Wilkinson J, Piek JM. Hysterectomy with opportunistic salpingectomy versus hysterectomy alone. Cochrane Database Syst Rev. 2019 Aug 28;8(8):CD012858. doi: 10.1002/14651858.CD012858.pub2. PMID: 31456223; PMCID: PMC6712369.

Mandelbaum RS, Matsuzaki S, Sangara RN, Klar M, Matsushima K, Roman LD, Paulson RJ, Wright JD, Matsuo K. Paradigm shift from tubal ligation to opportunistic salpingectomy at cesarean delivery in the United States. Am J Obstet Gynecol. 2021 Oct;225(4):399.e1-399.e32. doi: 10.1016/j.ajog.2021.06.074. Epub 2021 Jun 26. PMID: 34181896.

 Response: Thank you for this suggestion, we have incorporated all of these citations and tried to provide a more balanced discussion highlighting potential risks associated with OS and the need for ongoing large RCT data before making definitive conclusions regarding its safety. These comments have been included in both the introduction and discussion to highlight your points.

Reviewer 2 Report

Systematic review of studies evaluating opportunistic salpingectomy at the time of general surgery procedures with narrative synthesis of current knowledge. Appropriately described search strategies with inclusion and exclusion criteria with a total of seven studies included in the analysis.

Of the studies included one was a single case report and another was a comment on to another published paper. These two seemed to add little to the paper in particular the comment neither reports an outcome of interest nor evaluates OS during general surgical procedures.  The concept of the paper itself is sound and potentially addresses a gap in knowledge. The references are up to date.

The figures table and images are appropriate.

The analysis and conclusions are supported.

Author Response

Reviewer #2:

Systematic review of studies evaluating opportunistic salpingectomy at the time of general surgery procedures with narrative synthesis of current knowledge. Appropriately described search strategies with inclusion and exclusion criteria with a total of seven studies included in the analysis.

Of the studies included one was a single case report and another was a comment on to another published paper. These two seemed to add little to the paper in particular the comment neither reports an outcome of interest nor evaluates OS during general surgical procedures.  The concept of the paper itself is sound and potentially addresses a gap in knowledge. The references are up to date.

The figures table and images are appropriate.

The analysis and conclusions are supported.

Response: Thank you for the time spent reviewing our study and for your overall positive outlook on the value that this systematic review provides. We look forward to seeing this paper as a contribution in Surgeries.

Reviewer 3 Report

This was a great paper. the issue is important and well presented. I liked how the authors were careful to include surgical guidelines for salpingectomy. My one suggestion is to add a sentence about why removing the fallopian reduces risk of "Ovarian cancer" in the introduction (they do in discussion) to frame why we are talking about this.

Also explain why not the ovary and fallopian tube - because of epidemiologic data showing an increase in all-cause mortality in women who undergo premenopausal removal of ovaries.

thank you

Author Response

Reviewer #3:

This was a great paper. the issue is important and well presented. I liked how the authors were careful to include surgical guidelines for salpingectomy. My one suggestion is to add a sentence about why removing the fallopian reduces risk of "Ovarian cancer" in the introduction (they do in discussion) to frame why we are talking about this.

Also explain why not the ovary and fallopian tube - because of epidemiologic data showing an increase in all-cause mortality in women who undergo premenopausal removal of ovaries.

thank you

Response: Thank you for your review and for the overall positive response to this study. We have included both of your suggestions in the updated manuscript and agree that they have further improved the study. We hope with these additions the manuscript is suitable for publication in Surgeries.

Round 2

Reviewer 1 Report

I have had a second look after revision of the manuscript I find it improved and some of the important questions explained. There are, however, a few points that need to be addressed. Several of them still concern the wording indicating a validity of results that are not yet present.

Abstract:

L13. Suggest to omit “frequently” ….. in frequently performed

L16. Suggest to omit “major” …..  in major part

Background

LL 44-46. The risk reduction on ovarian cancer of OS is not known. The references 8-10 do not compare OS with no OS during surgery. E.g. nr 9 is a comparison of non-OS vs no surgery at all (wrong comparator). These sentences have to be rewritten to clarify that the magnitude of a risk reduction is unknown.

LL 46-48. Furthermore, the issue of salpingectomy causing impairment in vascular and nervous supply and thus an earlier menopause is not settled. The literature is contradictory and no RCT on menopausal symptoms is available yet. There are only small RCTs on hormone measurements (like AMH) in the short term. This sentence also needs to be rewritten in a more balanced way.

LL53-54. It is true that there is a growing body of evidence suggesting a risk reduction in ovarian cancer after OS, but the cost-effectiveness can hardly be calculated, since there are no valid estimates of risk reduction to base such a calculation on. It could certainly be mentioned that there is an uncertainty about the cost-effectiveness results.

Results

Fig 1. The numbers still do not add up correctly in the flowchart.  If 9 articles are included, there is something wrong with the numbers in the preceding boxes.

Table of included articles. In the study by Myriokefalitaki et al., I would suggest using the term adnexectomy if both ovary and tube were removed, and the term salpingectomy if only the tube was removed.

Discussion

L 193. Suggest replacing “is” with “can be” preferred…

The discussion is extremely long, although interesting. I believe it could be shortened, but it is up to the journal to set the limits of the length.

Conclusion

L 399. In the sentence “Few studies have evaluated…” it should be noted that none of these studies include a control group, which is essential for evaluation of OS and strengthens the need for further research even further.

There are some minor spelling errors. Some sentences are extremely long  and could be split for the benefit of easier reading.

Author Response

Reviewer #1:

I have had a second look after revision of the manuscript I find it improved and some of the important questions explained. There are, however, a few points that need to be addressed. Several of them still concern the wording indicating a validity of results that are not yet present.

Response: Thank you again for reviewing our study and providing additional helpful suggestions to further improve the manuscript. We have made all the recommended changes and hope that with these the paper is ready for readers of Surgeries.  

Abstract:

L13. Suggest to omit “frequently” ….. in frequently performed

Response: Thank you for this suggestion, in the updated manuscript we have removed frequently from the abstract.

L16. Suggest to omit “major” …..  in major part

Response: This is a good point and in the updated abstract we have clarified that OS may play a role in ovarian cancer prevention, rather than a major role.

Background

LL 44-46. The risk reduction on ovarian cancer of OS is not known. The references 8-10 do not compare OS with no OS during surgery. E.g. nr 9 is a comparison of non-OS vs no surgery at all (wrong comparator). These sentences have to be rewritten to clarify that the magnitude of a risk reduction is unknown.

Response: This is a good point and in the updated manuscript we have clarified that the results discussed in the introduction relate to outcomes during salpingectomy in the general population with outcomes from such studies being extended to opportunistic salpingectomy.

LL 46-48. Furthermore, the issue of salpingectomy causing impairment in vascular and nervous supply and thus an earlier menopause is not settled. The literature is contradictory and no RCT on menopausal symptoms is available yet. There are only small RCTs on hormone measurements (like AMH) in the short term. This sentence also needs to be rewritten in a more balanced way.

Response: Thank you for these suggestions and in the updated introduction we have clarified that outcomes on menopause induction remain limited and under evaluation.

LL53-54. It is true that there is a growing body of evidence suggesting a risk reduction in ovarian cancer after OS, but the cost-effectiveness can hardly be calculated, since there are no valid estimates of risk reduction to base such a calculation on. It could certainly be mentioned that there is an uncertainty about the cost-effectiveness results.

Response: We have edited this section of the introduction to clarify that cost evaluation modelling has suggested cost savings associated with OS using early data from OS. We have specifically cited the study by Kwon et al. (DOI: 10.1097/AOG.0000000000000630) in this section.

Results

Fig 1. The numbers still do not add up correctly in the flowchart.  If 9 articles are included, there is something wrong with the numbers in the preceding boxes.

Response: Thank you for catching this typo – the figure has been updated to be accurate with our search results.

Table of included articles. In the study by Myriokefalitaki et al., I would suggest using the term adnexectomy if both ovary and tube were removed, and the term salpingectomy if only the tube was removed.

Response: This is a good suggestion and we have updated this table to clarify adnexectomy.

Discussion

L 193. Suggest replacing “is” with “can be” preferred…

Response: We have updated the discussion to change to “can be”, thank you.

The discussion is extremely long, although interesting. I believe it could be shortened, but it is up to the journal to set the limits of the length.

Response: We have left the current discussion as we believe each aspect is interesting to readers (specifically to potential General Surgeons who may know very little about this topic) and important to guide future research in this area. For example, while the first two sections of the discussion are primarily a review of the topic for readers who may not be familiar with this topic. However, this is a fair point and if Surgeries would like us to shorten the discussion we are happy to do so – if this is the case, we would request suggestions on sections to shorten specifically that the editors or reviewers find unnecessary.  

Conclusion

L 399. In the sentence “Few studies have evaluated…” it should be noted that none of these studies include a control group, which is essential for evaluation of OS and strengthens the need for further research even further.

Response: This is a good point and certainly helpful to guide future research – we have updated the conclusion to highlight this point.

Comments on the Quality of English Language

There are some minor spelling errors. Some sentences are extremely long  and could be split for the benefit of easier reading.

Response: We have edited the entire manuscript to shorten sentences and improve readability where possible.