Novel treatment approaches for recurrent lower extremity venous insufficiency: Exploring the role of lymph node sclerotherapy

Abstract

Background

Recurrent lower extremity venous insufficiency remains a therapeutic challenge despite advances in surgical and endovenous techniques. Emerging evidence suggests that reflux within the inguinal lymph node venous network (LNVN) may contribute significantly to recurrence. This study evaluates the safety and effectiveness of ultrasound-guided lymph node sclerotherapy as a novel treatment targeting LNVN reflux.

Methods

This prospective observational study included 75 patients with prior treatment for varicose veins who presented with symptomatic recurrence between 2022 and 2024. All patients underwent color Doppler ultrasonography and dynamic lymph node venography to detect LNVN reflux. Eligible patients received ultrasound-guided injections of 0.5% sclerosant into affected lymph nodes. Clinical outcomes were assessed using CEAP classification and duplex ultrasound at 1-year follow-up. Statistical analyses were performed using Wilcoxon signed-rank and chi-square tests.

Results

Of the 75 patients (mean age: 47.4 ± 9.4 years), 80% (n = 60) showed significant clinical improvement. Among patients classified as C3, 90% reported edema resolution. Improvement rates in C4–C6 patients ranged from 70% to 72.2%. Duplex ultrasound demonstrated complete reflux resolution in 64% and partial improvement in 20%. The reduction in reflux was statistically significant (p < .001). No major complications were reported; minor injection-site inflammation occurred in 8% of cases.

Conclusion

Lymph node sclerotherapy appears to be a safe and effective outpatient intervention for recurrent venous insufficiency associated with LNVN dysfunction. By directly addressing a previously under-recognized source of reflux, this technique offers a minimally invasive and targeted alternative to conventional reinterventions. Further multicenter trials are warranted to confirm long-term outcomes and validate its role in standard venous treatment algorithms.

Keywords

recurrent varicose veins lymph node venous network LNVN sclerotherapy venous insufficiency lymphatic-venous reflux ultrasound-guided intervention

Introduction

Varicose vein recurrence remains a prevalent and persistent challenge in clinical practice, with recurrence rates reported between 20% and 60% within 5 years, often necessitating reintervention.^1–3 The pathogenesis is multifactorial, involving incomplete initial treatment, progressive disease, altered venous hemodynamics, and neovascularization.⁴ Despite increasing insights into these mechanisms, the potential contribution of the inguinal lymph node venous network (LNVN) to recurrence has not been sufficiently addressed in routine practice or consensus guidelines, including the Recurrent Varicose Veins After Surgery (REVAS) document.

The LNVN represents a complex anatomical structure consisting of venous channels that traverse superficial inguinal lymph nodes and connect to major venous systems, including the femoral vein, the great saphenous vein (GSV), and its anterior accessory branch (AAGSV).^5,6 Although Uhl et al. emphasized the anatomical complexity and functional significance of this network, and Lemasle et al. proposed its possible role in superficial venous insufficiency relapse, the clinical implications of LNVN dysfunction in varicose vein recurrence remain largely undefined.^3,5

Recent sonographic investigations by Liu et al. have provided additional insight into the LNVN’s anatomy, vascularity, and variability. In patients with chronic venous disease (CVD), inguinal lymph nodes exhibiting reflux were significantly enlarged and showed elevated hilar arterial velocities. These studies confirmed that LNVN outflow predominantly follows venous pathways through the saphenofemoral junction (SFJ), GSV, AAGSV, and anterolateral thigh tributaries. Additionally, the identification of valve-like structures within these channels highlights a possible role in reflux propagation and recurrence.⁶ The “ganglionic eye” sign—visualized as a dilated hilar vein within the lymph node—has emerged as a potential sonographic marker of pathological LNVN reflux.

While the presence of LNVNs is not exclusive to individuals with venous disease, their pathological role in recurrent varicosities warrants closer investigation. In contrast to neovascularization, which has been extensively documented as a cause of recurrence, LNVN-related reflux has received comparatively limited attention.^3,7,8 Notably, the LNVN demonstrates several key anatomical features: direct venous channels traversing lymph nodes, perforating communications with the femoral vein, and venous connections to the GSV and AAGSV.

In our previous publication, we proposed a pathophysiological link between LNVN dysfunction and recurrence in treated varicose veins, supported by imaging modalities such as color Doppler ultrasound and dynamic lymph node venography.⁷ Building upon those findings, this study investigates the role of lymph node sclerotherapy, a novel and minimally invasive technique, in the treatment of recurrent lower extremity venous insufficiency associated with LNVN reflux.

Methods

Study design and population

This was a prospective observational study conducted between 2022 and 2024. The study cohort comprised 75 patients (45 females, 30 males; mean age: 47.4 ± 9.4 years) with a prior history of treatment for lower extremity venous insufficiency who subsequently presented with symptom recurrence. These patients had been previously evaluated and partially described in our earlier publication.⁷

Inclusion criteria

Patients were eligible for inclusion if they met the following criteria:

• Prior interventional or surgical treatment for lower extremity varicose veins.

• Recurrent symptoms and evidence of superficial venous insufficiency confirmed on imaging.

• CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification of:

o Predominant C3 (edema),

o With additional inclusion of C4 (skin changes), C5 (healed ulcers), and C6 (active ulcers) cases.

Symptom presentation and assessment

Patients primarily reported symptoms including lower extremity heaviness, fatigue, aching pain, and edema. Symptom intensity was assessed using a standardized 10-point Visual Analog Scale (VAS), where 0 indicated no symptoms and 10 represented maximum severity. C4–C6 cases were further assessed for skin changes and ulceration during clinical examination.

Evaluation of treatment response

Treatment response was evaluated at 1, 3, 6 and 12 months post-procedure. Outcome measures included:

• Change in VAS score,

• Reduction in limb circumference (for C3 cases),

• Ulcer healing status (for C5–C6),

• Patient-reported satisfaction (5-point Likert scale),

• Duplex ultrasound evaluation of residual or recurrent reflux.

Improvement was defined as a decrease of ≥2 points in VAS score and/or resolution of objective clinical findings compared to baseline.

Exclusion criteria

Patients were excluded if they had:

• Primary lymphatic disorders,

• Deep vein thrombosis (DVT) or isolated deep venous insufficiency without superficial reflux,

• Incomplete clinical documentation or insufficient imaging for diagnostic assessment.

Diagnostic assessment

All patients underwent color Doppler ultrasonography and dynamic lymph node venography to evaluate the presence of reflux within the inguinal lymph node venous network (LNVN). LNVN involvement was characterized by dilated hilar veins, the presence of the “ganglionic eye” sign, and retrograde flow on spectral Doppler.

Assessment of pelvic venous reflux (PVR)

Given the high prevalence of pelvic venous reflux (PVR) in females and its potential hemodynamic connection to the groin area and LNVN, all female patients underwent duplex ultrasound (including Valsalva) and, where indicated, cross-sectional imaging.

Patients with confirmed pelvic reflux—including ovarian or internal iliac vein involvement—were excluded to eliminate confounding effects. The final cohort included only patients with isolated LNVN reflux. No pelvic interventions were performed.

Treatment protocol

Patients demonstrating LNVN reflux underwent ultrasound-guided lymph node foam sclerotherapy. Under real-time sonographic guidance, a 0.5% solution of polidocanol (Aethoxysklerol®, Kreussler Pharma, Germany) was prepared into foam form using the Tessari technique, mixing 1 part sclerosant with 4 parts air in a two-syringe system connected via a three-way stopcock.

The sclerosant was injected directly into the hilar veins within affected lymph nodes under real-time sonographic guidance, using the “ganglionic eye” sign for localization. The goal was to induce localized fibrosis and obliteration of refluxing venous channels.

Each limb received injections into 1–3 lymph nodes based on venographic findings, with 2 mL administered per node (maximum 6 mL per limb). The intervention was performed on an outpatient basis under sterile conditions. Patients were monitored for 30 min post-procedure.

The great saphenous vein (GSV) had previously been treated in all patients via endovenous thermal ablation or surgical stripping. Duplex imaging at baseline confirmed the absence of residual reflux in the GSV, anterior saphenous vein (ASV), or other superficial trunks.

Patients with persistent superficial reflux were excluded to isolate the therapeutic effect of LNVN-directed treatment. Reflux pathways extending from LNVN to proximal thigh superficial veins were noted in some patients, supporting the rationale for targeting the LNVN.

Follow-up management

All patients underwent a single session of LNVN sclerotherapy. No repeat injections were administered.

During follow-up, no additional sclerotherapy or ablation was required, as patients had already undergone definitive GSV treatment and had no residual reflux on baseline imaging. Thus, all reported outcomes reflect the isolated effect of LNVN-directed therapy.

Statistical analysis

Statistical analysis was performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). Continuous variables, such as patient age, were expressed as mean ± standard deviation (SD), while categorical variables (e.g., CEAP stage, outcome category) were presented as frequencies and percentages.

Changes in clinical symptoms and imaging findings before and after sclerotherapy were analyzed using the Wilcoxon signed-rank test, suitable for paired, non-normally distributed data. Chi-square tests were applied to assess associations between CEAP classification and treatment response, while Fisher’s exact test was used when expected frequencies were less than 5. A p-value <.05 was considered statistically significant.

Results

At the 1-year follow-up, 60 out of 75 patients (80%) demonstrated significant clinical improvement following ultrasound-guided lymph node sclerotherapy. Improvement was assessed based on symptom resolution (pain, heaviness, edema), CEAP classification changes, and duplex ultrasound findings.

Clinical outcomes by CEAP classification

Among patients classified as C3 (n = 40), 90% (n = 36) exhibited a substantial reduction or resolution of limb edema. In higher CEAP stages, the response was similarly favorable: 72.2% of C4, 70% of C5, and 71.4% of C6 patients showed marked clinical improvement, including stabilization of skin changes and ulcer healing or non-recurrence.

Imaging outcomes

Duplex ultrasound follow-up revealed:

- Complete resolution of LNVN reflux in 64% (n = 48) of patients.

- Partial improvement (reduction in reflux intensity or number of affected nodes) in 20% (n = 15).

- Persistent reflux in 16% (n = 12).

The difference in reflux severity between pre- and post-treatment evaluations was statistically significant (p < .001, Wilcoxon signed-rank test).

Safety and complications

The procedure was generally well tolerated. Mild post-procedural inflammation of the injected lymph nodes occurred in 8% of patients (n = 6), presenting as localized tenderness and swelling, and resolved spontaneously within 1 week without the need for intervention.

No cases of lymphadenitis, nodal abscess, nodal necrosis, or secondary lymphedema were observed. Additionally, no allergic reactions, deep vein thrombosis (DVT), or systemic complications were reported during or after the treatment period.

These findings affirm both the efficacy and safety of lymph node sclerotherapy in patients with recurrent lower extremity venous insufficiency attributed to LNVN dysfunction (Tables 1 and 2).

Table 1.

Clinical outcomes by CEAP classification.

CEAP classification	Patients (n)	Improved after treatment (n)	Improvement rate (%)
C3	40	36	90.0
C4	18	13	72.2
C5	10	7	70.0
C6	7	5	71.4

Table 2.

Post-treatment duplex ultrasound findings and complications.

Outcome	Patients (n)	Percentage (%)
Complete resolution of LNVN reflux	48	64.0
Partial improvement (reduced reflux)	15	20.0
No change in reflux	12	16.0
Mild post-procedural inflammation	6	8.0
Allergic reaction	0	0.0
Deep vein thrombosis (DVT)	0	0.0

Discussion

Study outcomes and clinical improvement

In this prospective series of 75 patients with recurrent lower extremity venous insufficiency, ultrasound-guided lymph node sclerotherapy was associated with substantial clinical benefit at 1-year follow-up. Eighty percent of patients demonstrated clinical improvement by 12 months, indicating that targeting reflux in the inguinal lymph node venous network (LNVN) can effectively alleviate symptoms in a majority of cases. This rate of improvement is notable given the challenging nature of recurrent varicose veins, which historically show high relapse rates despite treatment. Comparable short-term success has been reported with other aggressive minimally invasive approaches for recurrent varices – for example, one study using comprehensive imaging-guided interventions observed no symptomatic varicose recurrence at 1 year in treated patients.⁹ The favorable outcomes in our cohort reinforce the potential of lymph node sclerotherapy as an effective strategy to address a critical source of venous reflux that is often missed by conventional treatments (Figures 1–3).

Figure 1.

Pre-treatment color Doppler ultrasound image demonstrating the ‘ganglionic eye’ sign, indicating pathological reflux within the lymph node venous network (LNVN).

Figure 2.

Post-treatment color Doppler ultrasound image showing absence of Doppler coding within the lymph node venous network (LNVN), suggesting effective occlusion following lymph node sclerotherapy.

Figure 3.

Post-treatment spectral Doppler ultrasound image demonstrating absence of flow in the previously refluxing lymph node venous network (LNVN), confirming successful treatment.

Comparison with conventional treatments

Our findings must be interpreted alongside existing therapies. Traditional high ligation and stripping (HL/S) procedures historically achieved early success but suffered from high recurrence, largely attributed to neovascularization.^1,10 Van Rij et al. demonstrated microscopic evidence of new neovascular channels at previous ligation sites in 94% of reoperative groin specimens.¹⁰ Endovenous thermal ablation (EVTA) techniques offered a minimally invasive alternative but recurrence via recanalization or residual tributaries still occurs, with 15%–23% reopened segments over 5 years.¹¹

Compared to these modalities, lymph node sclerotherapy uniquely targets occult reflux pathways overlooked by conventional therapies. Foam sclerotherapy is already accepted for recurrent varices, especially when neovascular networks are identified.¹² Our 1-year 80% success rate compares favorably to outcomes reported for repeat surgeries or standard foam treatments. Thus, lymph node sclerotherapy offers a promising complementary approach, particularly in cases of occult lymphatic-venous reflux.

Recurrence mechanisms: Neovascularization and lymphatic-venous networks

Two key processes drive varicose vein recurrence: neovascularization and incompetent collateral pathways, including the LNVN. Neovascularization remains a well-established cause of recurrence after surgery.^1,10 However, recent studies highlight that LNVN reflux also significantly contributes to recurrence.^5,7

Our prior study demonstrated LNVN reflux in 41.3% of recurrent cases, associated with significantly shorter recurrence-free intervals.⁷ Similar findings by Uhl et al. and Creton et al. emphasize that reflux via lymph node venous connections can be frequent but historically overlooked.^5,13 Conventional imaging often misses these pathways unless specifically sought. Addressing these previously ignored mechanisms is crucial for achieving durable outcomes.

By directly targeting LNVN reflux, lymph node sclerotherapy interrupts venous hypertension feedback loops fueling recurrent varices. Our clinical improvement rates suggest that many recurrences are driven by these treatable hidden channels, supporting emerging views that lymphatic-venous incompetence is a major cause of recurrence.^5,7,13

Clinical implications and novelty of lymph node sclerotherapy

The clinical success of lymph node sclerotherapy validates the LNVN as a new therapeutic target in chronic venous insufficiency. This novel, mechanism-based approach moves beyond treating visible varices, addressing a fundamental driver of recurrence.

The technique is also highly minimally invasive, requiring only ultrasound-guided percutaneous injections. No surgical incisions were needed, and the procedure had excellent safety, with only mild transient inflammation seen in a minority of cases. No deep vein thrombosis (DVT) or systemic complications occurred, aligning with previous studies demonstrating the safety of foam sclerotherapy for recurrent varices.¹²

Our outcomes are comparable to reports where ultrasound-guided foam sclerotherapy achieved 87%–93% success rates in recurrent varices without major complications.^12,13 Thus, lymph node sclerotherapy may represent an evolution of targeted sclerotherapy techniques, offering a less invasive but highly effective option for recurrence management.

While it is commonly believed that reflux confined solely to the LNVN is often asymptomatic, our study provides evidence that in a subset of patients, such localized reflux may still produce clinical symptoms. These patients had no detectable reflux in the GSV, its tributaries, or pelvic veins, yet presented with symptoms such as localized heaviness, discomfort, or visible superficial varicosities at the site of prior interventions. The symptomatic relief following targeted LNVN sclerotherapy in these cases suggests that under certain anatomic or hemodynamic conditions—such as lymphatic congestion, localized venous hypertension, or post-ablation redistribution of flow—the LNVN may act as a pathologic reservoir contributing to symptom recurrence. This may represent an underrecognized clinical scenario, emphasizing the need for heightened awareness and targeted imaging protocols to assess LNVN involvement.

Conclusion

This study demonstrates that ultrasound-guided lymph node sclerotherapy is a promising and minimally invasive treatment option for recurrent lower extremity venous insufficiency associated with lymph node venous network (LNVN) dysfunction.

At 1-year follow-up, a significant proportion of patients experienced clinical improvement and reduction of reflux, suggesting that targeting lymphatic-venous reflux pathways can effectively address an important, yet often overlooked, mechanism of varicose vein recurrence.

Compared to traditional surgical revision or endovenous ablation techniques, lymph node sclerotherapy offers a novel, patient-tailored approach that focuses on the hidden sources of reflux rather than re-treating major truncal veins alone. Its excellent safety profile, technical simplicity, and outpatient feasibility make it an attractive therapeutic alternative, especially for patients with complex recurrent disease.

Nonetheless, the current findings must be interpreted in light of the study’s limitations, including small sample size, single-center experience, and short-term follow-up. Future randomized controlled trials with larger, multicenter cohorts and longer-term evaluations are needed to confirm these preliminary results and to determine the durability and broader applicability of lymph node sclerotherapy in venous practice.

By addressing both traditional and lymphatic-venous mechanisms of recurrence, this technique may contribute significantly to improving the long-term outcomes of patients suffering from chronic venous disease.

Footnotes

ORCID iD

Fatemeh Azizi

Ethical considerations

This study was approved by IMU Faculty of Medicine Ethics Committee (IRB: 2025.05.08-562). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study received approval from the Institutional Review Board (IRB), and informed consent was obtained from all patients in accordance with the Declaration of Helsinki and relevant regulations concerning human and animal rights.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Contributorship

Fatemeh Azizi conceptualized the study and wrote the manuscript. Emrah Karatay, Abdulkadir Eren, Zafer Unsal Coskun contributed to data analysis and manuscript revision. All authors read and approved the final manuscript.

Guarantor

FA.

References

De Maeseneer

MGR

Tielliu

IFJ

Van Schil

PEY

, et al. Clinical relevance of neovascularisation on duplex ultrasound in the long-term follow-up after varicose vein operation. Phlebology 1999; 14(3): 118–122.

Jones

Braithwaite

Selwyn

, et al. Neovascularisation is the principal cause of varicose vein recurrence: results of a randomised trial of stripping the long saphenous vein. Eur J Vasc Endovasc Surg 1996; 12(4): 442–445.

Lemasle

Uhl

Lefebvre-Vilardebo

, et al. Veines lympho-ganglionnaires inguinales: aspects anatomiques et échographiques. Phlebologie 1999; 52(5): 263–269.

Eklof

Perrin

Delis

, et al. Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg 2009; 49(2): 498–501.

Uhl

Lo Vuolo

Labropoulos

. Anatomy of the lymph node venous networks of the groin and their investigation by ultrasonography. Phlebology 2016; 31(5): 334–343.

Liu

Clarke

Liu

, et al. The sonographic features of lymph node venous networks and flow patterns in patients with primary chronic venous disease. Phlebology 2024; 39(6): 414–427.

Azizi

Zü

. Overlooked and neglected aspects in the management of recurrent lower extremity venous insufficiency: unveiling the significance of the lymphatic venous network. Phlebology 2025; 40(4): e112–e120.

Kohler

Dirsch

Brunner

. Veno-lymphatic angiodysplasia as the cause of recurrent inguinal varicose veins. Vasa 1997; 26(1): 52–54.

Huang

Niu

, et al. CT venography combined with ultrasound-guided minimally invasive treatment for recurrent varicose veins: a pilot paired-design clinical trial. Clin Radiol 2024; 79(5): 363–370.

10.

Van Rij

Jones

Hill

, et al. Neovascularization and recurrent varicose veins: more histologic and ultrasound evidence. J Vasc Surg 2004; 40(2): 296–302.

11.

Van der Velden

Biemans

AAM

De Maeseneer

MGR

, et al. Five-year results: surgery, endovenous ablation, and foam sclerotherapy for GSV incompetence. Br J Surg 2015; 102(10): 1184–1194.

12.

Kakkos

Bountouroglou

Azzam

Kalodiki

Daskalopoulos

Geroulakos

, et al. Effectiveness and safety of ultrasound-guided foam sclerotherapy for recurrent varicose veins: immediate results. J Endovasc Ther 2006; 13(3): 357–364.

13.

Creton

Uhl

. Foam sclerotherapy combined with surgical treatment for recurrent varicose veins: short term results. Eur J Vasc Endovasc Surg 2007; 33(5): 619–624.