Introduction

In the past two decades, we have witnessed remarkable progress in the surgical treatment of lymphedema. Excluding the debulking methods, such as the Charles procedure and liposuction, the landscape of physiological reconstruction has broadened significantly. Today, we have at our disposal procedures, such as vascularized lymph node transplant (VLNT), vascularized lymph vessel transplant (VLVT), and lymphaticovenular anastomosis (LVA), each with unique strengths and challenges [1,2,3,4]. VLNT, while effective, results in significant lymphatic trauma at the donor site and can lead to deformities at the recipient site. VLVT, on the other hand, poses fewer risks to the donor lymphatics and tends to be more esthetically pleasing [5]. However, its technical intricacy, coupled with the inherent “robbing Peter to pay Paul” trade-off in tissue transfer, suggests that it still may not be the ideal solution.

LVA, devoid of the drawbacks associated with VLNT and VLVT, emerges as the most nuanced and technically demanding procedure. It is a humbling endeavor that requires utmost precision and expert skill [6, 7]. In our experience, it took the senior surgeon hundreds of cases to surmount the steep learning curve and begin to see consistently favorable results. It is within this context that the emergence of inguinal lymph node-to-vein anastomosis (LNVA) signals a significant advancement. Conceptually, a single LNVA can drain numerous collectors in a lymphosome, offering an efficient and less technically challenging alternative to LVA. This paper will detail our approach to this innovative technique.

Historical Background

The lymph node-to-vein anastomosis (LNVA) technique, first introduced in 1967, involved a partial excision of an inguinal lymph node, carefully preserving its afferent/efferent vessels and hilar blood vessels and suturing the node’s capsule to a venotomy near the saphenofemoral junction [8, 9•, 10]. Jamal modified the technique in 1981 by reducing the extent of nodal excision [11]. This modified method has been successfully employed in treating filarial lymphedema [12, 13]. Despite its pioneering nature, LNVA did not achieve widespread acceptance due to inconsistent outcomes, likely due to the excessive additional trauma inflicted on already pathologically compromised lymph nodes.

In recent years, LNVA has experienced a resurgence as an adjunct to lymphaticovenular anastomosis (LVA) for reducing lower limb volume. The contemporary approach utilizes supermicrosurgical techniques to anastomose a small opening in the inguinal node capsule directly to the end of a small vein, avoiding partial node excision. A pivotal study in 2021 by JP Hong and colleagues, involving 160 patients with early-stage lower extremity lymphedema, demonstrated that the combination of LVA and LNVA achieved more substantial reductions in limb circumference than LVA alone. Their technique focused on preoperative identification of functional groin lymph nodes using lymphoscintigraphy, MRI, and size criteria [14••].

Our initial adoption of LNVA followed Hong’s methodology, but over time, we have significantly refined and evolved our technique. We outline our current approach in the following sections.

Our Technique: The Cleveland Clinic Approach

Patient Selection

Lymph node-to-vein anastomosis (LNVA) is a physiologic procedure that addresses the fluid component of lymphedema. It is most suitable for patients diagnosed with International Society of Lymphology (ISL) stage I or Campisi stage IB disease, who do not have a solid disease component, or pathologic lipodystrophy or fibrosis. While both LVA and LNVA prove effective in treating lower extremity lymphedema, LNVA is particularly beneficial for patients experiencing fluid accumulation in the lower abdomen, genital region, groin, and proximal thigh. For enhanced or synergistic results, LNVA can be implemented either in conjunction with LVA or as a follow-up treatment.

Preoperative Preparation

In LNVA, as with LVA, the success of the procedure is closely tied to the quality of the lymphatic structures involved. For LNVA, this means the condition of the lymph nodes is crucial. We use duplex ultrasound to assess lymph node quality, favoring those that are larger and exhibit clear nodal architecture, including a distinct capsule, cortex, medulla, and hilar vascularity. During the ultrasound, we conduct a qualitative analysis to identify the most suitable lymph node. Concurrently, any adjacent veins are meticulously identified and marked (Fig. 1a, b).

Fig. 1
figure 1

a Duplex ultrasound (B mode, 14 MHz) showing a healthy oval lymph node, 2.1 cm length and 0.8 cm width, with clearly visualized capsule (white outer layer), cortex (purple triangle), and medulla (hypoechoic, seen with arterial signal). Clearly visualized nodal architecture in combination with hilar vascularity indicates healthy, functioning lymph node. b A vein is seen adjacent to the lymph node that is distinct from the hilar vessel. This vein is of appropriate caliber and may be recruited as recipient vein for LNVA

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Once the optimal lymph node is selected, we employ SAVI SCOUT® technology for accurate and efficient intraoperative localization [15]. This nonradioactive radar technology utilizes an 8-mm reflector seed, which is carefully placed by our interventional radiologist just superficial to the lymph node, carefully ensuring the lymph node remains undamaged. Post-reflector placement, the patient is prepared for the operating room.

Operative Technique

To enhance the intraoperative identification of functioning lymph nodes, we inject both indocyanine green (ICG) and isosulfan blue in the groin and medial proximal thigh regions (Fig. 2). We then perform a repeat duplex ultrasonography to again confirm the optimal lymph node previously marked with the SAVI SCOUT® reflector. The SAVI SCOUT® handheld probe is utilized to verify the reflector’s functionality and to precisely locate this optimal lymph node. Ideally, these mapping techniques converge on the same dominant lymph node. Additionally, duplex ultrasound is employed to delineate the veins near the lymph node, preparing for their recruitment into the LNVA.

Fig. 2
figure 2

Indocyanine Green (ICG) lymphography demonstrates functioning lymphatic pathways leading to a healthy lymph node in the groin, marked with a red dot. This lymph node has also been confirmed as relatively healthy on preoperative duplex ultrasound imaging. The concordance between the ICG lymphography and duplex ultrasound enhances the assurance that the chosen lymph node is optimally functioning and suitable for LNVA

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Employing a surgical microscope at low magnification, we begin with a 6-cm sinusoidal incision directly above the marked lymph node. The SAVI SCOUT® signals guide our monopolar dissection toward this node. Throughout this process, we meticulously preserve all encountered lymphatic and blood vessels, as they may serve as afferent/efferent vessels of the target lymph node or its feeding hilar vessels.

Upon retrieval of the SAVI SCOUT® reflector (Fig. 3) and identification of the lymph node, meticulous dissection is performed to expose the anterior surface of the nodal capsule, a critical step for determining the optimal landing site for LNVA. This phase requires utmost care to protect all lymphatic and blood vessels related to the lymph node (Fig. 4). The node, typically embedded in adipose tissue, is exposed only at its anterior surface to avoid unnecessary skeletonization, which can lead to excessive nodal damage and compromised LNVA outcome. In most cases, a suitable vein is identified during the dissection toward the marked lymph node. If not, further dissection is pursued to locate an appropriate vein, leveraging insights from preoperative duplex ultrasound.

Fig. 3
figure 3

a SAVI SCOUT reflector allows for rapid skin-to-node dissection. Here, the reflector (blue arrow) was found immediately superficial to the targeted lymph node. b The reflector was retrieved, revealing the underlying lymph node (red circle)

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Fig. 4
figure 4

a Multiple lymphatic channels (indicated by blue arrows) can be seen converging on a lymph node (outlined by a red dashed circle). This anatomic configuration allows for a retrograde dissection approach by following these vessels to the node. b Visualization of lymphatic vessels (green arrows) is facilitated by the injection of either isosulfan blue or indocyanine green dye, allowing precise identification of lymphatic structures

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Now that we have both the chosen lymph node and an appropriate vein prepared, we proceed to anastomosis (Fig. 5). A capsulotomy at the ideal site on the anterior capsular surface is precisely executed with a 30-gauge needle, with its penetration depth determined by our preoperative nodal dimension assessments. We aim to target the needle’s entry to the node’s center without exceeding the depth. The presence and intensity of lymphorrhea at this stage serve as vital indicators of the LNVA’s effectiveness, with robust lymphorrhea being prognostically favorable (Video 1). When needed, the capsulotomy can be gently expanded to ensure a better size match with the chosen vein (Fig. 6). A side-to-end anastomosis is then performed between the nodal capsule and the vein using 11-0 or 12-0 sutures. Given the capsule’s rigidity, we recommend needles with sharper curvatures and a minimum cross-sectional diameter of 70 micron to facilitate this critical step.

Fig. 5
figure 5

The targeted lymph node with minimal disruption and a fully dissected nearby vein were prepared for anastomosis

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Fig. 6
figure 6

a Surgical preparation for anastomosis. A capsulotomy (encircled) in the lymph node (LN) is strategically positioned adjacent to a vein (V) and away from all afferent lymph vessels. b Successful completion of the LNVA (blue arrow)

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Post-anastomosis, we apply a fibrin sealant to the groin wound bed to discourage lymphocele formation. The superficial fascial system is then meticulously reapproximated, followed by the closure of the dermis and epidermis, ensuring a water-tight seal. To promote optimal flow through the newly created LNVA, both the lower extremity and lower abdomen are subjected to 30–40 mmHg of simulated compression.

Postoperative Management

LNVA procedures are conducted on an outpatient basis. Within a month following surgery, all patients’ transition from bandage compression to flat-knit waist-high garment compression, maintaining 30–40 mmHg pressure. As part of our standard protocol, we conduct routine evaluations of clinical outcomes and lymphatic function using ICG lymphography at 3-, 6-, and 12-month post-procedure.

Discussion

In our experience, LNVA behaves similarly to LVA. Both are physiological procedures aimed at enhancing lymphatic drainage, as opposed to debulking techniques. Their effectiveness primarily lies in addressing the fluid component of lymphedema, with limited impact on lymphedema-induced lipodystrophy or fibrosis. Hence, it is crucial during treatment planning to ascertain that patients are still in the fluid-predominant phase of lymphedema and have not progressed to lipodystrophy or fibrosis. In cases where lipodystrophy or fibrosis has already developed, debulking liposuction, with or without skin excision, becomes the preferred treatment approach [16].

Like LVA, LNVA not only provides regional relief but also imparts systemic therapeutic benefits. This means that when performed on a specific part of the body, it can alleviate symptoms in areas beyond the actual site of the procedure. The systemic effects of LNVA are partially elucidated by recent findings on LVA’s immunomodulatory properties, including its ability to reduce exhaustion markers and increase antioxidative capacity [17, 18]. This unique attribute allows for strategic use of both LVA and LNVA. They can be employed either to directly address a readily accessible anatomic region or to remotely treat an area that is too invasive for direct surgical intervention. This approach underpins the success of treating post-traumatic chylothorax [19] and protein-losing enteropathy [20] with groin LNVA, demonstrating the procedure’s versatility and far-reaching impact.

In our practice, LNVA is recommended for patients experiencing fluid edema in the lower abdomen, genitalia, buttocks, and proximal thigh. While LVA directly targeting the affected areas remains a viable option, we have observed more brisk improvements in patients treated with LNVA compared to those undergoing LVA. Our standard approach often involves combining LVA and LNVA, with LVA addressing the leg and LNVA targeting the groin. This combination offers comprehensive coverage of the affected lower extremity and leverages their synergistic effects.

Additionally, LNVA can be effectively paired with debulking liposuction in cases where lymphedema-induced lipodystrophy is primarily localized in the distal segment of the lower extremity. This combined approach is viable when debulking liposuction does not interfere with the groin lymphatics essential for LNVA.

Early in our experience, we adopted Hong et al.’s methodology, employing preoperative MRI for lymph node assessment and lymphoscintigraphy for localization. Although effective, we found this protocol to be burdensome, costly, and time intensive for patients. Intraoperatively, using the gamma probe often led to a ‘field of signal’ from multiple lymph nodes, complicating the identification of a singular, optimal node. This often resulted in inefficient, overly extensive dissection, risking damage to the surrounding delicate lymphatics. Moreover, the radiation safety of this technique remains unverified. Current assumptions about its safety are merely extrapolations from studies on oncologic lymph node extirpations, which typically involve shorter procedures and lymph nodes embedded in adipose tissue. This context differs significantly from our applications, raising concerns about the direct applicability of these safety assumptions.

In response to safety concerns, our first technical modification was to eliminate lymphoscintigraphy. Instead, we started using isosulfan blue and ICG, injected just before surgery, as lymph node markers. However, as expected, these markers proved inconsistent in pinpointing lymph nodes. Their efficacy hinges on the lymphatic system’s ability to transport lymph effectively, a function often compromised in lymphedema patients. As a result, these markers may fail to reach the lymph nodes due to weakened lymphatic transport. Additionally, they tend to highlight all functioning lymph nodes, not just the optimal one for treatment.

This challenge was resolved by adopting SAVI SCOUT® technology, already prevalent in breast surgery for the extirpation of breast tumors and lymph nodes [15, 21]. Utilizing a small, nonradioactive radar reflector, SAVI SCOUT® allows us to mark a specific lymph node for quick and precise intraoperative identification and dissection, streamlining the process considerably.

Our next challenge was refining the method for identifying the most suitable lymph node for LNVA. Leveraging our proficiency in ultra-high-frequency duplex ultrasound (UHF-DU) for perforator flap and LVA planning, we, in conjunction with our radiologists, explored the effectiveness of UHF-DU at 22 MHz in assessing lymph node morphology and architecture. These characteristics are key indicators of a lymph node’s functional status. For example, the shape of a lymph node—whether oval, round, lobulated, or speculated—can denote a healthy node, one affected by metastasis, a reactive node, or one infiltrated by cancer, respectively [22•]. The visibility of a node’s structural features, such as its capsule, cortex, medulla, and hilar vascularity on UHF-DU, indicates its health and suitability for LNVA. Moreover, this sonographic examination also maps the venous anatomy, enabling preoperative selection of an appropriate vein for LNVA.

Our refined technical approach, which integrates comprehensive preoperative ultra-high-frequency duplex ultrasound (UHF-DU) assessment of both lymph nodes and veins, coupled with precise SAVI SCOUT® marking of the optimal lymph node, has enabled us to consistently perform LNVA with heightened success and efficiency. We anticipate that our techniques will continue to evolve, leading to the development of even more efficient and less invasive methods that may surpass the effectiveness of our current practices. Furthermore, we foresee the application of the LNVA procedure expanding to include lymph nodes in various other regions of the body. This progression marks a promising future in the field of lymphedema treatment, bringing hope for more comprehensive and less burdensome therapeutic options for patients.

Conclusion

The renaissance of LNVA, initially conceptualized in 1966, exemplifies how revisiting the visionary ideas of our predecessors can lead to groundbreaking advancements in modern medicine. Our technical refinement process underscores the importance of creative thinking in surgery, reminding us not to be confined by dogma but to remember that innovation often lies in reimagining and revitalizing the insights of those who came before us.