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Rajaram et al. Plast Aesthet Res. 2025;12:6 https://dx.doi.org/10.20517/2347-9264.2024.147 Page 9 of 13

Efficacy in human studies
Lymph node grafting in the animal model appears viable, efficacious, repeatable, and augmentable.
However, the translation of this research to the human setting is often complicated and unpredictable. This
is evidenced by the fact that despite proof of concept of NVLNT by Pabst and Rothkötter in animals over
three decades ago, there have only been three human studies of NVLNT in lymphoedema populations
[Table 2].

The most encouraging of these is a 10-year follow-up controlled trial on lower limb lymphoedema patients
[20]
by Belcaro et al. . The study recruited 9 intervention patients who received NVLNT and also selected 8
patients who underwent mainstream lymphoedema management with CDT. NVLNT was performed as
follows: 1-3 lymph nodes were harvested in the neck, groin, and axilla, fragmented similarly to salami
slicing, and placed without suturing along the course of the great saphenous vein within the subdermal
plane. Patients were followed up over 10 years and had their limb volumes, limb circumference, and
ultrasound-measured tissue thickness tracked. Limb volume was significantly different between the two
groups, with the NVLNT group demonstrating an 11% reduction in volume increase. Circumference was
similarly encouraging within the intervention groups. Finally, tissue thickness was 59% less in the
intervention group. While this demonstrates early optimism for NVLNT in humans, it must be noted that
in addition to a small sample size and modest findings, this study was done exclusively in non-cancer
patients who did not undergo radiotherapy.

A more recent study undertaken by Travis et al. in 2015 examined the effect of NVLNT on upper limb
[21]
lymphoedema in an uncontrolled cancer population . The cohort of 10 underwent a procedure similar to
that of Belcaro et al.’s study, with the key difference being that whole lymph nodes were grafted into the
patients’ wrists and the follow-up period was shorter, lasting only 12 weeks . While many patients in this
[20]
study reported a subjective feeling of relief and modest return of function, objective volumetric
measurements demonstrated a non-significant volume reduction of 89.6 mL with a 95% confidence interval
of -320.4 mL to +141.1 mL.

Supplementary to this, a case report by Brian et al. described a 3-year follow-up on a patient with upper
limb lymphoedema secondary to breast cancer-related lymph node clearance who received whole node
[22]
grafting . The patient experienced a 36% reduction in limb volume with a significant recovery of function.
However, it must be noted that no control measures were undertaken, and this patient also continued their
regular CDT postoperatively.

Limitations and future directions
An examination of animal studies on NVLNT reveals that, in experimental settings, its efficacy has been
proven and reproducibility is strong. Furthermore, mechanistic explanations for lymphangiogenesis and
lymphatic remodelling are beginning to be formed. However, in human populations, the evidence base is
much more tenuous, with a small number of low-power studies demonstrating modest outcomes. This is a
common theme when translating animal-based research into human models due to the increased biological,
ethical, and social complexity that is associated with human research. In the case of NVLNT in
lymphoedema, among many others, the incongruence between animal and human studies may be explained
by three methods of reasoning.

Advanced lymphoedema
In humans, the burden of lymphoedema is disproportionately concentrated among patients who have
advanced-stage lymphoedema (ISL 2 and higher). In these stages, fibro-fatty transformation is predominant,