Hemodynamic Challenges of Lower Extremity Lymphovenous Anastomosis: A Critical Reappraisal
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDr Kang conducted a narrative review of the topic of lymphovenous anastomosis for lower limb lymphedema. He stressed the consideration of unfavored pressure gradient between the lymphatic vessel and the veins in the upright position. Hemodynamic changes in the lower extremities in postures may facilitate deterioration of the lymphovenous anastomosis and cause thrombosis around the anastomotic sites. This theory is speculated by Virchow’s triad.
He also pointed out the critical controversy about the inconsistent correlation between anastomotic patency and clinical improvement studies by Maegawa’s group. He considered three potential scenarios to explain the controversy: effects of intensive compression therapy, selection bias of surgical candidates, and behavioral modifications.
The manuscript is well-written and is easy to read. The structures are logical and composed of proper references. As the author mentioned in the manuscript, many LVA articles have been published, and they described their favorable outcomes. However, the majority of them were non-randomized control studies and focused more on technical aspects. LVA is traditionally explained to release the blocked lymph flow and reroute it to the nearby vein. However, this rationale is supported only by weak scientific evidence to justify performing the surgery.
I agree with the author that a broader view, including hemodynamic effects and other adjunctive treatments, should be noted.
I would like to provide minor suggestions.
On page 3, lines from 91 to 95, incompetent valves have been believed to occur in secondary lower extremity lymphedema. However, a recent article by Mackie H et al. (Mackie H et al. J Vasc Surg Venous Lymphat Disord. 2022 Sep;10(5):1101-1106.) was against this idea. It may need to discard “where valvular incompetence and lymphangion dysfunction disrupt segmental compartmentalization.”
The paragraphs of conclusions may be too long, and there are many rephrased sentences. Conclusions should be written more concisely.
I believe this manuscript is important for all plastic surgeons to reconsider the practical benefits of LVA for lymphedema patients. If the proposed surgical outcomes have been provided or masked by other potential factors mentioned in this article, a huge controversy exists between what plastic surgeons aim for and what actually happens.
Author Response
Reviewer 1
Comment 1:
“On page 3, lines from 91 to 95, incompetent valves have been believed to occur in secondary lower extremity lymphedema. However, a recent article by Mackie H et al. (J Vasc Surg Venous Lymphat Disord. 2022;10(5):1101-1106) was against this idea. It may need to discard ‘where valvular incompetence and lymphangion dysfunction disrupt segmental compartmentalization.’”
Response:
Thank you for this excellent suggestion and for bringing the Mackie et al. study to the author’s attention. This observation proved highly consequential for the manuscript’s central argument.
The original text assumed valvular incompetence as a given in lymphedematous limbs. However, Mackie et al. demonstrated that retrograde lymph flow due to valve incompetence was identified in only 3.7% of 566 lymphedema patients and was virtually absent in cancer-related lower limb lymphedema—directly contradicting this conventional assumption.
Rather than simply deleting the passage, the author took the opportunity to substantially strengthen the hemodynamic argument by presenting both scenarios. If lymphatic valves are incompetent, intralymphatic pressure may rise to 50–60 mmHg, still well below the venous pressure of 80–100 mmHg, leaving a 30–40 mmHg gradient favoring venous reflux. If lymphatic valves remain competent—as the Mackie et al. data suggest—segmental compartmentalization is preserved, intralymphatic pressure during standing would be considerably lower, and the adverse pressure gradient would widen further. The revised text now explicitly states: “incompetent valves make LVA unlikely to work; competent valves make it even less likely to work.”
The Mackie et al. reference has been added as Reference [14], and the relevant passage in Section 2.1 has been revised accordingly (see highlighted text in the revised manuscript).
Comment 2:
“The paragraphs of conclusions may be too long, and there are many rephrased sentences. Conclusions should be written more concisely.”
Response:
The author agrees that the original Conclusions section contained substantial redundancy. The section has been entirely rewritten to eliminate repetitive rephrasing while sharpening the manuscript’s core messages. The revised Conclusions now (1) directly addresses the fundamental question of whether lower extremity LVA provides sustained therapeutic benefit, incorporating the valve-status analysis added in response to Comment 1; (2) raises the ethical dimension of continuing to perform procedures whose mechanism of action cannot be justified by elementary hemodynamic principles; and (3) includes the author’s self-reflection as a surgeon who performs these procedures, acknowledging the uncertainty that accompanies each case. The revised version is more concise, more focused, and—the author hopes—more impactful.
The author is grateful for Reviewer 1’s recognition that this manuscript is “important for all plastic surgeons to reconsider the practical benefits of LVA.” This is precisely the discussion the author hopes to stimulate.
Reviewer 2 Report
Comments and Suggestions for AuthorsAuthors should be congratulated for their interesting idea to write an updating narrative review article examining the patency of LVA in relation to postural hemodynamics of the lower extremity in the every day real conditions. It was a real pleasure to read the different sections of this manuscript.
Their Introduction was adequate.
The ensuing sections of Hemodynamic and Pathophysiological considerations were well presented, associated with explicative drawings and fifures that ideally complete the main text.
Clinical evidence
Excellent presentation and explanation of anastomotic patency over time, along with methodological limitations and patency-outcome which ensues in the raising of the “fundamental question” of the real clinical impovement offered by LVA in various uncotrolled studies compared to conservative therapy.
Knowledge gaps and research priorities
Authors present and thoroughly analyze the so called fundamental gaps observed in the evidence base LVA of the lower extremity. Special mention was made to the necessity of a meta-analysis and the future research orientation which will give priority to several objectives (e.g. new monitoring protocols at recipient venules sites, development of standardized upright ICG lymphography, realization of randomized trials comparing LVA with conservative measures and finally consensus on stadardized functional measures in the upright posture instead of supine)
Conclusions
They are considered as adequate stressing that the mecanistic LVA rational remains an assumption needing a thorough investigation after the clinical practice of three decades.
General Considerations
It is a well-written manuscript that deserves to be published.
Author Response
Reviewer 2
The author is deeply grateful for Reviewer 2’s generous and encouraging evaluation. No specific revisions were requested. The modifications made in response to Reviewer 1’s comments have further strengthened the hemodynamic analysis, particularly the demonstration that the unfavorable pressure gradient persists regardless of lymphatic valve status. The author hopes these revisions enhance the manuscript’s contribution as recognized by Reviewer 2.
