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Guiotto et al. Plast Aesthet Res 2023;10:26 https://dx.doi.org/10.20517/2347-9264.2023.15 Page 7 of 14

recurrency
resolution
Mean 54.3 29.1 11.5 2.5 1.2 40.5

Regarding the clinical reported outcomes, we noticed a significant improvement in objective and subjective symptoms complained by the patients. Particularly,
infections recurrency resolution, and scrotal oedema reduction (or resolution) were observed in 93.8% and 46.7% of the patients, respectively.

Interestingly, penile oedema seemed more complex than scrotal oedema to resolve, (53.3% free of symptom), while surgical treatments were particularly

effective on persistent lymphorrhea, which was reported postoperatively in two patients only (28.6%) [Figure 2].

One patient (number 1) benefited from staged microsurgical procedures. The physiologic operation consisted of MLVA for active scrotal lymphorrhea and
penoscrotal oedema. This resulted in a total cessation of lymphorrhea and a decrease in scrotal oedema. However, he presented after 3 years with a recurrence

of scrotal-penile lymphoedema, requiring lymph node transfer by gastroepiploic vascularized lymph node transfer (GE-VLNT). Clinically, after this second
intervention, the patient manifested a global amelioration with cessation of active lymphorrhea and residual penile oedema, responding to CDT [Figure 3]. A
lymphoscintigraphic exam at a one-year follow-up after the second intervention showed a normalised bilateral lower limbs lymphatic drainage, and a stable

scrotal dermal backflow with improved left lymphatic drainage.

DISCUSSION

Genital lymphoedema (GL) is a chronic invalidating disease that causes a significant physical and psychological impact on patient quality of life .
[7]

In patients with secondary GL, a specific external determinant (surgery, radiation, malignancy, infection, or trauma) explains the physiological lymphatic flow
disruption (e.g., obstruction in the lymphatic system, lymph nodes, and/or lymphatic vessel removal or damage). By contrast, most primary GLs are caused by
[18]
lymphatic malformations which arise during lymphangiogenesis .

In spite of the aetiology, the classification of severity lymphoedema (ISL) is essential to choose the right treatment for GL and predicting its outcomes.

Regarding the therapeutic options for GL, recent literature defines different strategies from conservative intensive physiotherapy to super microsurgery
[7]
techniques, but no standardised protocols exist . Finally, front-line research has recently proposed the application of stem cell therapy approaches to treat
lymphoedema. Stem cells (mesenchymal stromal cells (MSC), bone marrow-derived MSC, and adipose-derived MSC) have a wide range of therapeutic effects
in terms of anti-inflammation, antifibrosis, anti-oxidative stress, as well as promoting the regeneration of different tissues. These properties have been
suggested as promoting factors for lymphatic vessel regeneration with interesting results in in vitro studies. However, at the moment, stem cell therapy has no

approved clinical indication in lymphoedema treatment and multiple pre-clinical in vitro and in vivo studies are ongoing .
[19]