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Page 8 of 10 Onishi et al. Plast Aesthet Res 2024;11:5 https://dx.doi.org/10.20517/2347-9264.2023.102

The efficacy of LVA is influenced by residual lymphatic function. To obtain a sufficient LVA outcome,
[11]
functional lymphatic vessels that suit the anastomosis must remain in the affected extremity . Lee et al.
argued that it would be ideal to perform reconstructive surgery while the function of lymphatic transport is
[4]
salvageable before damage to the lymphatic vessels becomes irreversible . In terms of residual lymphatic
function, in future studies, it would be informative to directly compare ICG findings between earlier versus
delayed LVA groups. This analysis could determine if preoperative lymphatic imaging characteristics
correlate with surgical outcomes. Additionally, as the mechanisms of LVA are based on a pressure gradient
[12]
through the bypass , the benefit of LVA would be greater in the presence of lymphatic hypertension.
Considering that lymphatic pressure rises at the beginning of lymphatic obstruction , whereas it declines
[13]
[14]
due to lymphatic pump failure from chronic excessive afterload to lymphatic smooth muscle cells , LVA
should be performed in the early phase of the disease.
For how long should preoperative CDT be performed? CDT has been effective in reducing edema and
improving the patients’ quality of life; however, it does not address the cause of the disease and remains
incomplete . Studies have demonstrated the long-term efficacy of CDT, with an edema reduction rate of
[5]
[15]
approximately 60% . The remaining chronic edema continued to damage the lymphatic system, causing
further tissue fibrosis and fat accumulation . Given the dilemma of LVA, the earliest evaluation of the
[16]
efficacy of CDT and indications for reconstructive microsurgery is paramount. According to Hwang et al.,
the greatest decrease in percent excess volume was observed at 6 months after CDT, suggesting that
[17]
evaluation for the indication of LVA can be performed at 6 months after the initiation of CDT . Moreover,
another study stated that surgical intervention is considered after 3-6 months of the CDT protocol . Based
[18]
on our results, it may be reasonable to consider LVA as early as 6 months or less to maximize treatment
outcomes.

Our study has some limitations. First, our cohort had a limited sample size (n = 50), accrued over 7 years
with an average of 7 cases annually, which may limit the generalizability of our findings. Additionally, upper
extremity cases are less common than lower extremity cases in many Japanese institutions, further
impacting external validity. However, we argue that our cohort of breast cancer-related lymphedema
represents an appropriate population for evaluating this intervention’s efficacy. Still, caution is warranted
when extrapolating these findings to other populations and settings. Further research is necessary to
validate and expand on our observations. Second, even a propensity score analysis with overlap weighting
or inverse probability weighting cannot be fully adjusted for potential biases. Randomized controlled trials
are needed to determine the true effects of the early indications for LVA in the management of
lymphedema. Third, the observed results include not only the LVA but also the CDT, which we should be
aware of. The treatment effect should always be combined because these modalities are complementary.

CONCLUSION
LVA would be more beneficial if performed less than 6 months compared to if performed more than 6
months after CDT initiation for stage II upper extremity lymphedema. The present study suggests a
potential improvement in the treatment prognosis of lymphedema by considering the early indication of
LVA while impaired lymphatic function remains reversible and fibroadipose tissue accumulation is
reduced.

DECLARATIONS
Authors’ contributions
Conception and design of the study: Onishi F, Nagashima H, Minabe T, Okuda N