Previous Article in Journal
Personalized Frontline Therapy in Diffuse Large B-Cell Lymphoma: Integrating Circulating Tumor DNA for Real-Time Adaptive Treatment Stratification
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Lymphatics
Volume 3
Issue 4
10.3390/lymphatics3040035
lymphatics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Physiologic Lymphedema Surgery: Current Treatments and Future Trends

by
Ethan L. MacKenzie
†,
Anne Huang
†,
Min-Jeong Cho
,
Roman J. Skoracki
and
Rohini L. Kadle
*
Department of Plastic and Reconstructive Surgery, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work and should be considered co-first authors.
Lymphatics 2025, 3(4), 35; https://doi.org/10.3390/lymphatics3040035
Submission received: 18 March 2025 / Revised: 28 July 2025 / Accepted: 22 September 2025 / Published: 20 October 2025
Review Reports Versions Notes

Abstract

Lymphedema is a chronic, progressive, and debilitating disease of the lymphatic system with no current cure. Physiologic procedures, which address the underlying pathophysiology of lymphatic dysfunction, have gained traction in both treatment and prevention of lymphedema. This narrative review examines current physiologic lymphedema surgical techniques and emerging developments in this rapidly evolving field. While the two most common physiologic surgeries remain lymphovenous bypass (LVB) and vascularized lymph node transfer (VLNT), newer physiologic surgery techniques such as vascularized lymph vessel transfer (VLVT) and lymph node to vein anastomosis (LNVA) have been described in an effort to reduce donor site morbidity, with early promising clinical outcomes. The use of bioengineering with stem cells, pro-lymphangiogenic growth factors, and biomaterials such as Biobridge can be applied in conjunction with surgery to help promote lymphangiogenesis. Technological advances in robotic surgical systems and 3D exoscopes are helping to make supermicrosurgery more technically feasible and ergonomic, and increasing accessibility to lymphedema surgery. As our surgical armamentarium expands, treatment algorithms must be updated to determine how various surgical techniques can be combined and sequenced, how the indications for physiologic surgery can be expanded, and how surgical treatment can be tailored to the patient and disease process.

1. Introduction

Lymphedema is a chronic and progressive disease affecting up to 250 million people worldwide and 10 million people within the United States [1]. While primary lymphedema is relatively rare, secondary lymphedema is more common, associated with infectious diseases, trauma, and direct tumor invasion and the surgical dissection of lymph node basins for cancer treatment. Prior research has suggested that the rate of lymphedema following breast cancer treatment ranges from 5–65% with risk factors including radiation, extent of axillary surgery, chemotherapy (especially taxane-based) and BMI [2,3]. Secondary lymphedema results from the functional disruption of lymphatic transport following these surgeries. The International Society of Lymphology (ISL) defines four stages of lymphedema ranging from subclinical disease (stage 0), to fluid predominant disease (stage 1 and early stage 2), to fibrofatty deposition and elephantiasis (stage 3 and 4) [4].
Existing treatments fall into two categories. Debulking procedures remove accumulated tissue through either liposuction or direct excision and are generally reserved for patients with later stage diseases when fat hypertrophy and/or fibrosis are more prevalent. Physiologic procedures utilize understanding of the lymphatic system to reconstruct function and treat lymphedema in its earlier stages, thus ameliorating the need for debulking procedures. Currently, the two most commonly performed physiologic procedures include lymphovenous bypass (LVB) and vascularized lymph node transfer (VLNT) (Table 1). Newer techniques such as vascularized lymph vessel transfer (VLVT) and lymph node to vein anastomosis (LNVA) are being developed in an effort to minimize the risk of donor site morbidity and expand the indications for physiologic surgery. Advancements in bioengineering, tissue engineering, and supermicrosurgical technologies are also expanding the scope and efficacy of lymphedema treatment. This review aims to appraise current physiologic procedures, emerging developments, and unresolved challenges in the treatment of lymphedema.

2. Lymphovenous Bypass

Lymphovenous bypass (LVB), also known as lymphaticovenular anastomosis or bypass, is one of the most prominent techniques in lymphedema surgery. The earliest literature dates back to the 1960s, and although there have been modifications to the technique over time, the basic concepts have not changed [5,6]. All lymphovenous bypass methods depend on re-routing the lymphatic system to drain lymph fluid via the venous system through microsurgical anastomoses connecting the two systems, akin to creating heterotopic thoracic duct—like connections. A variety of vessel arrangements have been described. Some practitioners are working to expand the scope of diseases treated by this technique including primary lymphedema and neurodegenerative diseases. Most commonly, LVB is used in secondary lymphedema which can develop following any intervention involving disruption or resection of lymph node basins. This section will focus on secondary lymphedema.

2.1. Proposed Mechanism of Action of LVB

Normally, the lymphatic system is responsible for transporting up to 12 L of fluid per day. This is accomplished through the pumping actions of both muscles intrinsic to lymph vessels as well as contractions of skeletal muscle [7]. Secondary lymphedema is an obstructive disease in which lymphatic drainage is anatomically blocked, frequently due to lymphadenectomy. Following lymphadenectomy, the afterload pressure on the lymphatic system rises, causing lymphatic valve failure and backflow [7]. Likely owing to prolonged inflammation, lymphatics then become sclerotic and smooth muscle is lost, leading to a reduction in contractility. LVB microsurgically reroutes lymphatics to drain via patent veins, with the hydrostatic pressure of lymph overcoming the relatively low pressure in draining veins [8,9,10]. Additionally, there is some evidence that correcting the adverse accumulation of lymph can reverse findings of inflammation and skin changes [11]. Like traditional vessel anastomoses, LVB success is highly dependent on anastomotic technique and patency as well as muscular and valvular competence of the lymphatic channel chosen for anastomosis, necessitating specialized instrumentation and high-magnification microscopes [12].

2.2. Indications and Contraindications of LVB

Traditionally, LVBs have been performed in patients with existing, fluid predominant disease, typically patients in stage 1 or 2 of the ISL staging system [13]. Prior to consideration of surgery, patients should have undergone courses of complete decongestive therapy in conjunction with lymphedema therapists [14]. Additionally, conditions which may mimic lymphedema should be ruled out or treated prior to LVB. Typically this includes diseases affecting the venous system including venous reflux, stenosis, and thrombosis, and lymphovenous bypass should be avoided in the patient with active deep vein thrombosis [15,16].
Preoperative and intraoperative imaging allows surgeons to confirm the presence of functioning lymphatics and select targets for bypass. Lymphoscintigraphy and magnetic resonance lymphography (MRL) can each be used to reliably diagnose lymphedema with high sensitivity and specificity [17,18]. MRL has the additional advantages of being able to demonstrate areas of edema as well as identify and map both deep and superficial lymphatics for use in anastomosis [19,20]. We generally find clinical exam is sufficient to make a diagnosis of lymphedema, but additional imaging can be useful in less straightforward cases. Indocyanine green (ICG) lymphography is versatile and can be performed both in the office and at the time of surgery, allowing for real-time lymphatic mapping and incision planning [21,22]. Successful bypass requires the identification of functional lymphatics as well as available venous targets.

2.3. Surgical Technique of LVB

Prior to incision, intraoperative imaging allows for confirmation of lymphatics and surgical planning. ICG lymphography and, more recently, ultra-high frequency ultrasound (UHFUS) are utilized to this end as the ICG lymphography has limited penetration of 2 cm. Intraoperatively, ICG is injected intradermally at a concentration of 2.5 mg/mL into the distal upper extremity. Near infrared fluorescence imaging is used and the linear path of lymphatics are marked as well as areas of dermal backflow [8,23].
UHFUS systems are becoming more prominent as they not only allow for identification of lymphatics and adjacent veins, but also allow for submillimeter resolution imaging of lymphatic vessels to that are smaller than 0.3 mm. Both 48 and 70 MHz probes provide adequate resolution for lymphatic identification, with the higher resolution of the 70 MHz somewhat offset by limited tissue penetrance [24]. Exact frequencies of probes vary between systems. Using this technology, the depth, diameter, and relationship of lymphatics to veins can be determined and incisions planned accordingly [25]. Furthermore, studies have demonstrated that UHFUS has changed the paradigm of lymphatic surgery by expanding the indications for LVB. In the absence of UHFUS, vein finder systems or traditional ultrasound can be used to identify areas of crossing veins potentially amenable for use in bypass. In addition to mapping lymphatics in conjunction with ICG, UHFUS identifies lymph vessel sclerosis, correlating with histologic findings. Some data suggests this can be used to identify bypass targets more likely to be successful [26,27].
The actual bypass technique varies across providers and institutions with a vast array of different lymphatic and vein anastomotic geometries having been described. The classic configuration is an end-to-end technique. This is generally preferred at it provides direct flow from the lymphatic into the venous system [28]. If there is a size mismatch between the recipient vein and the chosen lymphatic, an end-to-side anastomosis (anastomosing the end of a lymphatic channel into the side of a vein) may be preferred. Side-to-end anastomosis (anastomosing an antegrade vein to the side of a lymphatic channel) has also been described, with the proposed benefit of including both antegrade venous and preserved antegrade lymphatic drainage, the venous connection acting as a type of pop-off pressure valve. Some studies have suggested that side-to-end anastomosis may be more efficacious at reducing lymphedema [29,30]. Alternative geometries have also been proposed, including the lambda shaped anastomoses, sequential anastomoses, Pi anastomoses, and intussusception anastomoses [10,31,32,33,34]. Each of these more esoteric techniques are developed to find solutions either to account for vessel mismatch or account for a difference in number of available veins and lymphatics, although none have shown superiority over standard end-to-end or side-to-end techniques. Intussusception allows for the intubation of multiple lymphatics into a single vein, typically secured first with a 10-0 U stitch followed by multiple smaller reinforcing sutures using 11-0 or 12-0 nylon [34,35]. The number of anastomoses does not appear to be a determining factor in the improvement in lymphedema; rather the quality of anastomosis appears to be more critical [36]. Ultimately, it has been proposed that the size discrepancy between available lymphatics and veins should determine the appropriate configuration [37].
The anastomosis is typically performed with 11-0 or 12-0 nylon suture with vessel sizes ranging anywhere from 0.3-0.9 mm. All steps of surgery are performed under the operating microscope as loupes offer insufficient magnification. Patency can be confirmed with the near-infrared camera function in the operating microscope, which should show flow of ICG from the lymphatic into the antegrade flowing vein.

2.4. Outcomes of LVB

Strong evidence exists supporting positive outcomes for both objective and subjective measures of lymphedema and quality of life. Although there is center-to-center variability in techniques utilized, subjective response is high among patients, including improvement in limb heaviness, use of compression garments, and reduction in episodes of cellulitis [38]. While variable between studies, objective volumetric improvement has been consistently demonstrated [8,35,39]. This variability is likely related to anastomotic patency long-term and technique differences among providers [40]. Improvement appears to be greater in earlier stages of lymphedema as compared to later [8].

2.5. Preventive Lymphatic Surgery

As lymphedema is incurable, there has been significant increase in efforts to prevent the development of lymphedema. In 2009, Boccadro et. al. introduced lymphedema microsurgical preventative healing approach (LYMPHA), through which lymphatic channels are anastomosed to veins in the axilla at the time of high risk surgeries such as an axillary lymph node dissection (ALND) to decrease the incidence of lymphedema [41]. Several studies have demonstrated that these procedures, often now referred to as immediate lymphatic reconstruction (ILR) or prophylactic LVB (pLVB), can be beneficial in reducing the risk of lymphedema [42]. A recent randomized controlled trial demonstrated the preliminary results of a 9.5% lymphedema rate in the immediate lymphatic reconstruction group compared with 32% in the control group at a 2-year follow-up [43]. Long-term cumulative results from several studies demonstrate that these techniques can decrease the incidence of breast cancer-related lymphedema [41,42,43].

3. Vascularized Lymph Node Transfer (VLNT)

Vascularized lymph node transfer uses microsurgical techniques to harvest function-ing lymph nodes from an unaffected area of the body with their blood supply and transfer them to the lymphedematous extremity. They may be transferred as a pedicled or free flap. VLNT was first described in 1982 as a pedicled groin flap containing vascularized inguinal lymph nodes to treat lower extremity lymphedema [44]. Today, a variety of VLNT donor and recipient sites have been described to treat lymphedema. Though these techniques are diverse and surgeon dependent, VLNT has been shown to be effective in treating extremity lymphedema.

3.1. Proposed Mechanism of Action of VLNT

The exact mechanism of action of VLNT is still not fully understood. There are currently two proposed theories. The first theory is that the transplanted lymph nodes induce lymphangiogenesis at the recipient site by secreting lymphatic growth factors, such as vascular endothelial growth factor C (VEGF-C), which induces the formation of new lymphatic channels which have been shown grow along a concentration gradient toward the highest concentration of VEGF-C which is at the level of the node. This theory has been supported by the observation that transferred lymph nodes in mouse models had a massive infiltration of functional lymphatic channels, which correlated with increased expression of VEGF-C in the perinodal fat and infiltrating lymphatics [45]. The second theory posits that the transferred lymph nodes act as a “pump” which wicks lymphatic fluid from the surrounding interstitial space into the venous system. This theory has been supported by studies in animal models and human patients showing that when vascularized lymph node flaps were immersed in a solution containing ICG, the ICG was absorbed into the flap and could be seen draining into the flap vein [46,47].

3.2. Indications and Contraindications of VLNT

The indications for VLNT are broader than LVB, as they can be performed in cases of severe lymphedema with little to no functional lymphatics. However, it is contraindicated in cases with active malignancy and should be carefully considered in patients with venous hypertension, stenosis, or thrombosis in the affected limb. VLNT is also a more invasive surgery than LVB, with similar risks related to free flap surgery such as microvascular thrombosis, partial or total flap failure, hematoma, wound healing complications, and donor site morbidity. A 2022 systematic review and meta-analysis of VLNT for BCRL reported a pooled complication risk of 12.1% for donor site related complications and 7.3% for recipient site related complications [48].

3.3. VLNT Donor Sites

A variety of VLNT donor sites have been described including the supraclavicular, submental, lateral thoracic, and inguinal lymph node basins, as well as intra-abdominal donor sites such as omentum, mesenteric or jejunal lymph nodes and lymphoid tissue surrounding the appendix. The surgical techniques for harvesting lymph nodes from each of these donor sites have been previously described [49,50,51,52]. The donor site is typically chosen based on surgeon and patient preference, scar location, amount of lymphatic tissue required, and risk of donor site lymphedema.
The main benefit of using intra-abdominal VLNT donor sites is eliminating the risk of donor site lymphedema, which has been estimated to be 1.6% in a 2018 systematic re-view of VLNT performed for BCRL [53]. If an inguinal or lateral thoracic donor site is chosen, the risk of donor site lymphedema risk can be minimized with reverse lymphatic mapping, where the lymph nodes draining the donor extremity are localized with radioactive tracer such as technetium-99 or dye such as ICG and spared during VLN harvest [54].
The amount of lymphatic tissue required depends on how much space is available to inset the flap at the recipient site. Larger lymph node flaps may be preferable if the recipient site preparation involves significant scar release, such as a previously dissected axilla. Whether the quantity of lymph nodes transferred directly correlates with improvement in lymphedema remains to be seen. In a rat hind limb lymphedema model, the number of vascularized lymph nodes transferred positively correlated with the degree of limb volume reduction [55]. In addition, a 2018 study of 35 patients undergoing submental VLNT for lower extremity lymphedema secondary to gynecologic cancer found that there was greater limb circumference reduction when 3 or more lymph nodes were transferred [56].

3.4. VLNT Recipient Sites

Vascularized lymph nodes can be transferred to recipient sites located anywhere along the affected extremity, going as proximal as the axilla or groin and as distal as the wrist or ankle. However, bulkier flaps can be difficult to inset in distal recipient sites, which can lead to poor contour and aesthetic outcome. A 2022 systematic review and meta-analysis compared axilla and wrist recipient sites in VLNT for BCRL and found no significant differences between circumference reduction rate or excess volume reduction. They also found no differences in postoperative decrease in infections per year, postoperative discontinuation of compression garments, and overall pooled complication rate [57].
Some authors are proponents of dual level VLNT, where lymph nodes are trans-planted simultaneously into 2 recipient sites on the affected extremity simultaneously. The orthotopic or proximal placement of vascularized lymph nodes, such as the axilla, is thought to act as a “bridge” where the new lymph nodes induce lymphangiogenesis and bridge the defect from prior lymph node [58]. In addition, the accompanying scar release and decompression of nearby vasculature that occurs during VLNT recipient site preparation are thought to help lymphatic drainage as well. Vascularized lymph nodes placed in a heterotopic or distal recipient site are thought to act as a “pump,” where interconnections within the lymph nodes shunt interstitial lymphatic fluid into the venous circulation [59]. Heterotopic VLNT placement is also believed to be more beneficial for distal extremity lymphedema and in cases of severe lymphedema with delayed or no ICG uptake in the proximal limb, where lymphatic fluid does not make it into the lymphatic system to be drained by orthotopically placed VLNT.

3.5. Outcomes of VLNT

VLNT has been shown to improve both quantitative and qualitative outcomes in lymphedema treatment, with a 2021 meta-analysis reporting grade 1B evidence [60]. A 2022 systematic review and meta-analysis specifically studying VLNT for BCRL showed an average limb volume reduction of 40% and significantly reduced rates of infection and cellulitis [48]. Qualitative outcomes have also shown improved patient reported quality of life measures, with the previous meta-analysis reporting that 45% of patients were able to discontinue compression garments post operatively [48]. In addition, a cost effectiveness analysis from 2021 found that VLNT was less costly ($22,492 vs. $31,927) and more effective (31.82 vs. 29.24 quality adjusted life years) than LVB [61].

4. Vascularized Lymph Vessel Transfer

Vascularized lymph vessel transfer (VLVT) is a relatively newer technique in which lymph vessels rather than nodes are transferred, relying on the intrinsic pumping mechanism of the transplanted lymphatics to transport lymph fluid from the affected area. Without transferring lymph nodes, VLVT theoretically reduces the risk of donor site lymphedema [62]. Described donor sites include the back, groin, and foot. Although outcome studies are limited, the data that does exist suggests VLVT is similarly efficacious to VLNT.

4.1. Proposed Mechanism of Action of VLVT

Vascularized lymph vessel transfer is an evolution of vascularized lymph node transfer techniques (VLNT). Unlike VLNT, VLVT does not involve the transfer of lymph nodes and was developed on the hypothesis that normal lymphatic flow can be restored via the transfer of healthy lymph vessels without accompanying nodes. Two mechanistic explanations have been offered for this. First, studies have demonstrated lymphovenous communication following free flaps, suggesting a “bridge” phenomenon due to lymphangiogenesis [63,64]. Additionally, as lymphedema progresses, smooth muscle is lost from lymphatic vessels and these vessels lose their contractility [7]. It is suggested that once this process is advanced, the utility of bypass techniques decreases due to a lack of functional lymphatics. The loss of the lymphatic pump mechanism leads to worsening of lymphedema. VLVT aims to provide healthy lymphatics to a lymphedematous extremity, restoring the lymphatic pump system [65]. It has been suggested that the most important aspect of restoring these mechanisms is maintaining the axiality of lymphatic flow between donor and recipient sites [66]. Yamamoto et al. termed this concept lymph-interpositional flap transfer (LIFT) by which ICG lymphography was used to map lymphatic pathways of soft tissue free flaps, which were transferred to maintain lymphatic axiality [67]. Yoshimatsu advocates for a related flap design but includes both vascularized lymph nodes as well as afferent draining lymphatics, terming this lymphatic system transfer (LYST) [68].

4.2. Indications and Contraindications of VLVT

Like other physiologic procedures, VLVT is well-suited to patients who have fluid predominant disease, but who have ICG findings that have progressed beyond a linear flow pattern [62,69]. Similarly, patients should have pursued courses of complete decongestive therapy and have had completed workups ruling out mimickers of lymphedema [14,15,16]. Potential donor sites should be free from trauma or scars from prior surgery and patients should be optimized to undergo free tissue transfer and be able to adhere to postoperative restrictions.

4.3. Surgical Technique of VLVT

Koshima et al. first published VLVT techniques with first metatarsal artery flaps in 2016 and since then, donor sites have expanded to include superficial circumflex iliac perforator (SCIP) and thoracodorsal artery perforator flaps [65,69]. The lower extremity donor sites are excluded in cases of bilateral lower extremity lymphedema. In the LIFT technique, ICG is injected and donor lymphatics marked. A variety of donor sites including anterolateral thigh, SCIP, or deep inferior epigastric artery perforator flaps have been described. It is important to mark flap orientation to preserve the direction of flow of the lymphatics from donor to recipient sites. Appropriate perforators are identified using either CT angiogram or duplex ultrasonography. The level of harvest and perforator size often necessitates a perforator-to-perforator or end-to-side anastomosis using 11-0 or 12-0 suture [69,70]. Lymphatic vessels are approximated by inset of the flap, and further supermicrosurgical anastomoses are not performed between donor lymphatics and recipient lymphatics or veins [66,67]. The LYST technique describes harvest from the groin donor site, with ICG lymphography used to map both lymphatic vessels of a SCIP flap as well as their draining lymph nodes. The entire flap is harvested and transferred in a similar manner [68].

4.4. Outcomes of VLVT

There is limited long-term data assessing the outcomes of lymph vessel transfer. Those studies that do exist suggest that improvements in lymphedema are roughly similar to those seen in VLNT [65,69,70]. Yamamoto et al. have shown a decrease in lymphedema rates in patients with free tissue transfer using LIFT technique versus free flaps without. [67]. The LYST technique has demonstrated a significant improvement in the degree of lymphedema after transfer [71]. However, appropriately designed head-to-head studies are lacking at this time. Complications appear to be largely related to flap-based and wound-healing complications and do not seem to include donor-site lymphedema [68]. As further studies are published, the role for VLVT in lymphatic surgery and its position relative to VLNT will become clearer.

5. Emerging Developments in Physiologic Lymphedema Surgery

Physiologic surgery for lymphedema treatment is continuously advancing. As more research is done to better understand the underlying pathophysiology of lymphedema, new treatment algorithms, alternative targets, and novel developments in biomaterials and tissue engineering are being applied to physiologic lymphedema surgery. In addition, improvements in surgical and imaging technology are also being utilized to advance this nascent field. This section highlights some of the exciting developments in physiologic lymphedema surgery (Table 2).

5.1. Updated Treatment Algorithms: Combining and Sequencing Lymphedema Surgery

The selection of surgical treatment for lymphedema has historically depended on clinical presentation and lymphedema stage. Physiologic surgery has conventionally been considered first line for stage 1 and 2 disease with mostly fluid causing volume excess, while debulking surgery is preferred for more advanced disease with fibrofatty tissue deposition. However, there is debate over whether these surgeries can be combined or sequenced to maximize limb reduction, and whether different treatment approaches should be applied depending on the anatomic location and etiology of lymphedema [72].
Currently, there is no consensus on combining or sequencing lymphedema surgery. Some authors advocate for simultaneous VLNT and LVB. Garza et al. reported that the majority of their cohort of 220 patients who underwent simultaneous VLNT and LVB experienced volume reduction of up to 36.2% at 2 years post operatively [73]. Patient reported outcomes also improved, with median lymphedema life impact scale (LLIS) scores improving progressively over time to 27.5 points lower at 3 year follow up. Interestingly, they noted a temporal trend in these patients, with initial improvement that was attributed to the effects of lymphovenous bypass, a rebound period at 6 months to 1 year postoperatively, and then a period of gradual improvement. The progressive improvement phase that occurred after 1 year was attributed to the VLNT as it becomes more effective in reducing excess volume through shunting and lymphangiogenesis.
Other groups have combined debulking and physiologic surgeries. Liposuction and LVB have been performed both simultaneously and as staged procedures with early promising results [74,75]. When performed simultaneously, the reported surgical technique generally begins with ICG lymphangiography to map patent lymphatic channels and potential LVB targets. The LVBs are performed, and then selective liposuction is performed to the other areas of the lymphedematous limb. Proponents of combining debulking and physiologic surgeries hypothesize that while debulking surgeries are more effective at reducing limb volume, adding physiologic surgeries can help maintain this volume reduction with less compression [74]. However, long term follow up is needed to determine if different treatment algorithms lead to improved outcomes.
Our current institutional approach to lymphatic reconstruction relies on a multi-disciplinary lymphedema program consisting of certified lymphedema therapists, vascular medicine, and surgical oncology. Patients who are referred for evaluation of lymphedema first undergo a screening visit to determine whether further workup or diagnostic imaging is needed to confirm the diagnosis of lymphedema. They are then referred to certified lymphedema therapy to optimize non-surgical treatment. Once optimized, patients undergo ICG lymphangiography in clinic for MDACC staging and treatment planning.
Like many centers, our first line surgical option for patients with MDACC stage 1 and 2 lymphedema is LVB. With the recent addition of UHFUS in clinic, we are able to augment our surgical planning by identifying patent lymphatic channels that may not be visualized with ICG lymphangiography, as well as identifying potential LVB locations with favorable lymphatic channels and venules to bypass. This has helped our team to perform LVB on patients who were traditionally not thought to be candidates, expanding our indications for surgery. In patients with severe lymphedema and no suitable lymphatic channels for LVB, we favor dual level VLNT using intra-abdominal donor sites, typically omentum for the orthotopic (proximal) location and mesenteric lymph nodes for the heterotopic (distal) location. While other donor sites can be used, there is a small risk of donor site lymphedema even with reverse mapping.
We routinely offer pLVB to patients undergoing ALND for breast cancer treatment and have a lymphedema surveillance program for high-risk patients. The surveillance program involves close monitoring every 3 months for 2 years after surgery, and ICG lymphangiography if any clinical symptoms of lymphedema and/or significant changes in extremity measurements occur [42]. In our recently reported institutional experience with pLVB, we have found that pLVB patients have a significantly lower rate of BCRL compared to ALND alone patients (8.7% vs. 20.1%) [76]. Observational data suggest that pLVB patients who do develop BCRL have less severe symptoms and different patterns of arm swelling, resulting in less surgical treatment [76]. We have recently expanded our indications of pLVB to include groin dissection for urologic, gynecologic, or other oncologic treatments.

5.2. Biomaterials and Tissue Engineering

An area of active research in lymphedema treatment is the use of biomaterials and the application of bioengineering. BioBridge (Fibralign Corporation, Union City, CA, USA) is a nanofibrillar type 1 porcine collagen scaffold which has been used in preclinical and early clinical studies to augment surgical treatment of lymphedema. It has been theorized to help lymphangiogenesis by serving as a scaffold for cellular migration, attachment, and alignment of endothelial cells [77]. A 2016 report on BioBridge in a pig lymphedema model found that 3 months after implantation, immunofluorescence staining of lymphatic vessels demonstrated a significant increase in lymphatic collectors within close proximity to the scaffolds, and limb bioimpedance also improved in the animals who received BioBridge [78]. Early clinical studies on BioBridge have used it in combination with physiologic and/or debulking surgeries, with the hope that adding BioBridge can improve lymphatic function by helping to induce lymphangiogenesis between areas of patent lymphatic channels and functional lymph node basins [77].
As the molecular mechanisms and pathophysiology of lymphedema are becoming better understood, lymphatic tissue bioengineering and regeneration have emerged as potential therapeutic options. Stem cells such as adipose derived stem cells (ADSCs) are being studied as a potential source for lymphangiogenesis [79,80]. ADSCs are abundant and autologous sources of stem cells, but further studies are needed to determine if they can be used in lymphatic tissue engineering and regeneration. Pro-lymphangiogenic growth factors such as VEGF-C have been experimentally delivered in an effort to induce lymphangiogenesis [81]. While most of these ideas are still being developed in in vitro and animal models and have not made it to clinical studies yet, they still represent one of the exciting new developments in lymphedema research.

5.3. Innovations in Supermicrosurgical Technology

Currently, physiologic lymphedema surgery is predominantly performed using conventional operating microscopes such as the Mitaka MM51 supermicroscope (Mitaka USA, Wheat Ridge, CO, USA) and microsurgical or supermicrosurgical instruments. Innovations in robotic microsurgical systems and 3D exoscopes are being applied to physiologic lymphedema surgery, especially LVB, with the hopes that they may enhance the magnification and resolution of the surgical field, reduce tremor, improve surgeon ergonomics, and supplement surgical [82,83,84].
LVB requires a high level of magnification over 25–30×, an optimal surgical view, and comfortable positioning for both the surgeon and assistant, which can be difficult depending on the surgical site location on a patient’s extremity. In addition, LVB is technically challenging to execute as it involves thin walled, submillimeter lymphatic channels and venules, requiring specialized surgical training. Robotic microsurgical systems such as the MUSA (MicroSure, Eindhoven, The Netherlands) and the Symani Surgical System (Medical Microinstruments, Inc., Wilmington, NC, USA) can help overcome these difficulties due to advances such as motion scaling, tremor elimination, and combined instruments with more degrees of articulation, which can help make LVB less technically challenging to perform, particularly in deeper surgical sites, and reduces the need for a surgical assistant [82].
Early studies of the first human trials of robotic-assisted lymphatic surgery have demonstrated successful and safe implementation of robotic microsurgical systems with equivalent early clinical outcomes to lymphatic surgery performed with conventional techniques, when reported [85,86,87,88,89,90]. All studies also showed significantly longer anastomosis times with robotic microsurgical systems, but with a steep decline leading to comparable times to conventional LVB with more experience. In addition, advocates for robotic supermicrosurgical systems believe that robotic platforms will expedite microsurgical training and help make supermicrosurgery more widely available [91]. A study of the learning curve of robotic-assisted microsurgery using 2 mm vessel models in surgeons of different skill levels found rapid improvement in performance across all skill levels, with no significant difference in mean anastomotic time between groups after just three sessions [92]. Current limitations to widespread adoption of robotic-assisted lymphedema surgery are the high costs of purchasing and maintaining the robotic microsurgical systems, high cost of disposables needed for each surgery, additional set-up and docking times, time needed to train surgeons and surgical staff, and lack of haptic feedback.
Similar to robotic microsurgical systems, there is growing interest in using 3D exo-scopes in physiologic lymphedema surgery. 3D exoscopes are high-definition video tele-scope operating monitor systems with wider fields of view and deeper focus than conven-tional operating microscopes, minimizing the need for repositioning and refocusing dur-ing procedures and improving surgeon ergonomics [84]. However, the current limitations of 3D exoscope systems include, limited magnification, high costs leading to limited accessibility, additional training, steep learning curve, and some reports of bothersome symptoms such as nausea with the use of 3D polarized glasses [93].

5.4. Lymph Node to Vein Anastomosis

Current treatments for lymphedema such as LVB or VLNT each have their drawbacks including technical difficulty, risk of donor site complications, and limited area of effect. Lymph node to vein anastomosis (LNVA) aims to overcome these limitations through decompressing entire lymphosomes with a single anastomosis to a target lymph node. The technique was originally described in the 1960s but remained largely unused until more recently [94,95]. Chen and colleagues advocate for using the technique in patients with more proximal extremity lymphedema, as well as that involving the groin and lower abdomen. In their technique, a lymph node is identified with duplex ultrasonography, selecting one with preserved nodal architecture. A non-radioactive reflector seed is then placed and intraoperative lymphangiography is performed to localize the desired node. This is then bypased with a microsurgical anastomosis of a vein to a nodal capsulotomy [96].
J.P. Hong and colleagues advocate for using this technique in combination with LVB to address both proximal and distal lymphedema. In a retrospective study of 160 patients, they noted improved outcomes in patients who underwent both LVB and LNVA compared to those who underwent LVB alone [97]. Additionally, they have also seen success in limited reports using this technique for the treatment both of primary lymphedema and for chylothorax [98,99]. Although it shows early promise, larger studies with head-to-head comparisons of various techniques and combinations thereof are necessary to better delineate the role of LNVA within the treatment of lymphedema.

5.5. Unresolved Challenges

The treatment of lymphedema has progressed enormously since the advent of microsurgical approaches to managing this disease. However, it remains a disease without a cure and one which is incompletely understood. Although the menu of techniques that a surgeon can choose from to address lymphedema continues to grow, there is limited data comparing techniques and when to use them. Traditionally LVB has been limited to fluid predominant disease, however its role has expanded with time and pairing with other techniques such as liposuction. There is center-to-center variation of what techniques are used when, but much of this is based on surgeon preference. The field as a whole would benefit from comparisons between treatment algorithms to delineate what works when. The role of prophylactic LVB is also under study and while this appears to be an effective preventative measure, we do not fully understand why some patients progress to disease regardless and when to intervene further. Similarly, we do not understand why some patients respond well to LVB and VLNT while others do not. Additionally, further research would be beneficial to understand the role of repeat surgery and when physiologic treatment results in diminishing returns.

6. Conclusions

Surgical treatment of lymphedema can be sub-divided into debulking and physiologic procedures. Physiologic procedures address the underlying pathophysiology of lymphedema and have been shown to be effective in reducing limb volume. These procedures include LVB, VLNT, and VLVT. Newer techniques and technologies are being applied to physiologic procedures, helping to expand their scope and efficacy.

Author Contributions

Conceptualization, E.L.M., A.H. and R.L.K.; investigation, E.L.M. and A.H.; data curation, E.L.M. and A.H.; writing—original draft preparation, E.L.M. and A.H.; writing—review and editing, E.L.M., A.H., R.L.K., M.-J.C. and R.J.S.; supervision, R.L.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ISLInternational Society of Lymphology
LVBLymphovenous bypass
VLNTVascularized lymph node transfer
VLVTVascularized lymph vessel transfer
BCRLBreast cancer related lymphedema
ICGIndocyanine green
UHFUSUltra-high frequency ultrasound
LYMPHALymphedema microsurgical preventative healing approach
ALNDAxillary lymph node dissection
LLISLymphedema life impact scale
VEGF-CVascular endothelial growth factor C
ADSCAdipose derived stem cell

References

  1. Greene, A.K. Epidemiology and Morbidity of Lymphedema. In Lymphedema: Presentation, Diagnosis, and Treatment; Springer: Berlin/Heidelberg, Germany, 2015; pp. 33–44. [Google Scholar] [CrossRef]
  2. Shah, C.; Arthur, D.; Riutta, J.; Whitworth, P.; Vicini, F.A. Breast-Cancer Related Lymphedema: A Review of Procedure-Specific Incidence Rates, Clinical Assessment Aids, Treatment Paradigms, and Risk Reduction. Breast J. 2012, 18, 357–361. [Google Scholar] [CrossRef] [PubMed]
  3. McLaughlin, S.A.; Brunelle, C.L.; Taghian, A. Breast Cancer–Related Lymphedema: Risk Factors, Screening, Management, and the Impact of Locoregional Treatment. J. Clin. Oncol. 2020, 38, 2341. [Google Scholar] [CrossRef] [PubMed]
  4. Greene, A.K.; Goss, J.A. Diagnosis and Staging of Lymphedema. Semin. Plast. Surg. 2018, 32, 12. [Google Scholar] [CrossRef] [PubMed]
  5. Laine, J.B.; Howard, J.M. Experimental Lymphatico-Venous Anastomosis. Surg. Forum 1963, 14, 111–112. [Google Scholar]
  6. Yamada, Y. The Study of Lymphatic Venous Anastomoses in Lymphe-Dema. Nagoya J. Med. Sci. 1969, 32, 1–21. [Google Scholar]
  7. Scallan, J.P.; Zawieja, S.D.; Castorena-Gonzalez, J.A.; Davis, M.J. Lymphatic Pumping: Mechanics, Mechanisms and Malfunction. J. Physiol. 2016, 594, 5749. [Google Scholar] [CrossRef]
  8. Chang, D.W.; Suami, H.; Skoracki, R. A Prospective Analysis of 100 Consecutive Lymphovenous Bypass Cases for Treatment of Extremity Lymphedema. Plast. Reconstr. Surg. 2013, 132, 1305–1314. [Google Scholar] [CrossRef]
  9. Matsubara, S.; Sakuda, H.; Nakaema, M.; Kuniyoshi, Y. Long-Term Results of Microscopic Lymphatic Vessel-Isolated Vein Anastomosis for Secondary Lymphedema of the Lower Extremities. In Surgery Today; Springer: Berlin/Heidelberg, Germany, 2006; Volume 36. [Google Scholar] [CrossRef]
  10. Koshima, I.; Inagawa, K.; Urushibara, K.; Moriguchi, T. Supermicrosurgical Lymphaticovenular Anastomosis for the Treatment of Lymphedema in the Upper Extremities. J. Reconstr. Microsurg. 2000, 16, 437–442. [Google Scholar] [CrossRef]
  11. Torrisi, J.S.; Joseph, W.J.; Ghanta, S.; Cuzzone, D.A.; Albano, N.J.; Savetsky, I.L.; Gardenier, J.C.; Skoracki, R.; Chang, D.; Mehrara, B.J. Lymphaticovenous Bypass Decreases Pathologic Skin Changes in Upper Extremity Breast Cancer-Related Lymphedema. Lymphat. Res. Biol. 2015, 13, 46–53. [Google Scholar] [CrossRef]
  12. Baxter, T.J.; Gilbert, A.; O’Brien, B.M.C.; Sykes, P.J.; Vorrath, J.W.; Bennett, R.C. The Histopathology of Microlymphaticovenous Anastomosis. Aust. N. Z. J. Surg. 1980, 50, 320–328. [Google Scholar] [CrossRef]
  13. 2023 Consensus. The Diagnosis and Treatment of Peripheral Lymphedema: 2023 Consensus Document of the International Society of Lymphology. Lymphology 2023, 56, 133–151. [Google Scholar] [CrossRef]
  14. Hamner, J.B.; Fleming, M.D. Lymphedema Therapy Reduces the Volume of Edema and Pain in Patients with Breast Cancer. Ann. Surg. Oncol. 2007, 14, 1904–1908. [Google Scholar] [CrossRef]
  15. Raju, S.; Furrh, J.B.; Neglén, P. Diagnosis and Treatment of Venous Lymphedema. J. Vasc. Surg. 2012, 55, 141–149. [Google Scholar] [CrossRef] [PubMed]
  16. Tiwari, A.; Cheng, K.S.; Button, M.; Myint, F.; Hamilton, G. Differential Diagnosis, Investigation, and Current Treatment of Lower Limb Lymphedema. Arch. Surg. 2003, 138, 152–161. [Google Scholar] [CrossRef] [PubMed]
  17. Pappalardo, M.; Cheng, M.-H. Lymphoscintigraphy for the Diagnosis of Extremity Lymphedema: Current Controversies Regarding Protocol, Interpretation, and Clinical Application. J. Surg. Oncol. 2020, 121, 37–47. [Google Scholar] [CrossRef] [PubMed]
  18. Quartuccio, N.; Agugliaro, F.; Alongi, P.; Sturiale, L.; Arnone, G.; Corrao, S. A Systematic Review Comparing Lymphoscintigraphy and Magnetic Resonance Imaging Techniques in the Assessment of Peripheral Lymphedema. Curr. Med. Imaging 2022, 19, 469–475. [Google Scholar] [CrossRef]
  19. Yasunaga, Y.; Nakajima, Y.; Mimura, S.; Yuzuriha, S.; Kondoh, S. Magnetic Resonance Lymphography as Three-Dimensional Navigation for Lymphaticovenular Anastomosis in Patients with Leg Lymphedema. J. Plast. Reconstr. Aesthet. Surg. 2021, 74, 1253–1260. [Google Scholar] [CrossRef]
  20. Miseré, R.M.L.; Wolfs, J.A.G.N.; Lobbes, M.B.I.; van der Hulst, R.R.W.J.; Qiu, S.S. A Systematic Review of Magnetic Resonance Lymphography for the Evaluation of Peripheral Lymphedema. J. Vasc. Surg. Venous Lymphat. Disord. 2020, 8, 882–892.e2. [Google Scholar] [CrossRef]
  21. Yamamoto, T.; Yamamoto, N.; Doi, K.; Oshima, A.; Yoshimatsu, H.; Todokoro, T.; Ogata, F.; Mihara, M.; Narushima, M.; Iida, T.; et al. Indocyanine Green-Enhanced Lymphography for Upper Extremity Lymphedema: A Novel Severity Staging System Using Dermal Backflow Patterns. Plast. Reconstr. Surg. 2011, 128, 941–947. [Google Scholar] [CrossRef]
  22. Narushima, M.; Yamamoto, T.; Ogata, F.; Yoshimatsu, H.; Mihara, M.; Koshima, I. Indocyanine Green Lymphography Findings in Limb Lymphedema. J. Reconstr. Microsurg. 2016, 32, 72–79. [Google Scholar] [CrossRef]
  23. Hara, H.; Mihara, M.; Seki, Y.; Todokoro, T.; Iida, T.; Koshima, I. Comparison of Indocyanine Green Lymphographic Findings with the Conditions of Collecting Lymphatic Vessels of Limbs in Patients with Lymphedema. Plast. Reconstr. Surg. 2013, 132, 1612–1618. [Google Scholar] [CrossRef] [PubMed]
  24. Mlosek, R.K.; Migda, B.; Migda, M. High-Frequency Ultrasound in the 21st Century. J. Ultrason. 2020, 20, e233. [Google Scholar] [CrossRef] [PubMed]
  25. Czedik-Eysenberg, M.; Steinbacher, J.; Obermayer, B.; Yoshimatsu, H.; Hara, H.; Mihara, M.; Tzou, C.-H.J.; Chieh-Han, J.; Meng, S. Exclusive Use of Ultrasound for Locating Optimal LVA Sites-A Descriptive Data Analysis. J. Surg. Oncol. 2020, 121, 51–56. [Google Scholar] [CrossRef] [PubMed]
  26. Mihara, M.; Hara, H.; Kawakami, Y. Ultrasonography for Classifying Lymphatic Sclerosis Types and Deciding Optimal Sites for Lymphatic-Venous Anastomosis in Patients with Lymphoedema. J. Plast. Reconstr. Aesthetic Surg. 2018, 71, 1274–1281. [Google Scholar] [CrossRef]
  27. Bianchi, A.; Visconti, G.; Hayashi, A.; Santoro, A.; Longo, V.; Salgarello, M. Ultra-High Frequency Ultrasound Imaging of Lymphatic Channels Correlates with Their Histological Features: A Step Forward in Lymphatic Surgery. J. Plast. Reconstr. Aesthetic Surg. 2020, 73, 1622–1629. [Google Scholar] [CrossRef]
  28. Rodriguez, J.R.; Yamamoto, T. A Systematic Stepwise Method to Perform a Supermicrosurgical Lymphovenous Anastomosis. Ann. Plast. Surg. 2022, 88, 524–532. [Google Scholar] [CrossRef]
  29. AlJindan, F.K.; Lin, C.Y.; Cheng, M.H. Comparison of Outcomes between Side-to-End and End-to-End Lymphovenous Anastomoses for Early-Grade Extremity Lymphedema. Plast. Reconstr. Surg. 2019, 144, 486–496. [Google Scholar] [CrossRef]
  30. Kwon, J.G.; Jeong, S.; Pak, C.J.; Suh, H.P.; Hong, J.P. Comparative Analysis between Side-to-End and End-to-End Lymphaticovenous Anastomosis for Secondary Lower Limb Lymphedema. Plast. Reconstr. Surg. 2022, 150, 1138–1148. [Google Scholar] [CrossRef]
  31. Ayestaray, B.; Bekara, F. π-Shaped Lymphaticovenular Anastomosis: The Venous Flow Sparing Technique for the Treatment of Peripheral Lymphedema. J. Reconstr. Microsurg. 2014, 30, 551–560. [Google Scholar] [CrossRef]
  32. Yamamoto, T.; Yoshimatsu, H.; Narushima, M.; Yamamoto, N.; Shim, T.W.H.; Seki, Y.; Kikuchi, K.; Karibe, J.; Azuma, S.; Koshima, I. Sequential Anastomosis for Lymphatic Supermicrosurgery: Multiple Lymphaticovenular Anastomoses on 1 Venule. Ann. Plast. Surg. 2014, 73, 46–49. [Google Scholar] [CrossRef]
  33. Yamamoto, T.; Narushima, M.; Kikuchi, K.; Yoshimatsu, H.; Todokoro, T.; Mihara, M.; Koshima, I. Lambda-Shaped Anastomosis with Intravascular Stenting Method for Safe and Effective Lymphaticovenular Anastomosis. Plast. Reconstr. Surg. 2011, 127, 1987–1992. [Google Scholar] [CrossRef] [PubMed]
  34. Chen, W.F.; Yamamoto, T.; Fisher, M.; Liao, J.; Carr, J. The “Octopus” Lymphaticovenular Anastomosis: Evolving beyond the Standard Supermicrosurgical Technique. J. Reconstr. Microsurg. 2015, 31, 450–457. [Google Scholar] [CrossRef] [PubMed]
  35. Campisi, C.C.; Ryan, M.; Boccardo, F.; Campisi, C. A Single-Site Technique of Multiple Lymphatic-Venous Anastomoses for the Treatment of Peripheral Lymphedema: Long-Term Clinical Outcome. J. Reconstr. Microsurg. 2016, 32, 42–49. [Google Scholar] [CrossRef] [PubMed]
  36. Onoda, S.; Satake, T.; Kinoshita, M. Relationship Between Lymphaticovenular Anastomosis Outcomes and the Number and Types of Anastomoses. J. Surg. Res. 2022, 269, 103–109. [Google Scholar] [CrossRef]
  37. Tsai, P.L.; Wu, S.C.; Lin, W.C.; Mito, D.; Chiang, M.H.; Hsieh, C.H.; Yang, J.C.S. Determining Factors in Relation to Lymphovascular Characteristics and Anastomotic Configuration in Supermicrosurgical Lymphaticovenous Anastomosis-A Retrospective Cohort Study. Int. J. Surg. 2020, 81, 39–46. [Google Scholar] [CrossRef]
  38. Coriddi, M.; Dayan, J.; Sobti, N.; Nash, D.; Goldberg, J.; Klassen, A.; Pusic, A.; Mehrara, B. Systematic Review of Patient-Reported Outcomes Following Surgical Treatment of Lymphedema. Cancers 2020, 12, 565. [Google Scholar] [CrossRef]
  39. Scaglioni, M.F.; Fontein, D.B.Y.; Arvanitakis, M.; Giovanoli, P. Systematic Review of Lymphovenous Anastomosis (LVA) for the Treatment of Lymphedema. Microsurgery 2017, 37, 947–953. [Google Scholar] [CrossRef]
  40. Boccardo, F.; Santori, G.; Villa, G.; Accogli, S.; Dessalvi, S. Long-Term Patency of Multiple Lymphatic-Venous Anastomoses in Cancer-Related Lymphedema: A Single Center Observational Study. Microsurgery 2022, 42, 668–676. [Google Scholar] [CrossRef]
  41. Boccardo, F.; Casabona, F.; De Cian, F.; Friedman, D.; Villa, G.; Bogliolo, S.; Ferrero, S.; Murelli, F.; Campisi, C. Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema after Mastectomy. Ann. Surg. Oncol. 2009, 16, 703–708. [Google Scholar] [CrossRef]
  42. Cho, M.J.; Flores Garcia, J.; Myung, Y.; Cha, H.G.; Hayashi, A.; Hong, J.P.; Skoracki, R. Evolving Role of Lymphedema Surgery on Breast Reconstruction: A Systematic Review and Multi-Institutional Algorithmic Approach. J. Clin. Med. 2024, 13, 6518. [Google Scholar] [CrossRef]
  43. Coriddi, M.; Dayan, J.; Bloomfield, E.; McGrath, L.; Diwan, R.; Monge, J.; Gutierrez, J.; Brown, S.; Boe, L.; Mehrara, B. Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-Related Lymphedema: Preliminary Results of Randomized Controlled Trial. Ann. Surg. 2023, 278, 630–637. [Google Scholar] [CrossRef] [PubMed]
  44. Clodius, L.; Smith, P.J.; Bruna, J.; Serafin, D. The Lymphatics of the Groin Flap. Ann. Plast. Surg. 1982, 9, 447–458. [Google Scholar] [CrossRef] [PubMed]
  45. Aschen, S.Z.; Farias-Eisner, G.; Cuzzone, D.A.; Albano, N.J.; Ghanta, S.; Weitman, E.S.; Ortega, S.; Mehrara, B.J. Lymph Node Transplantation Results in Spontaneous Lymphatic Reconnection and Restoration of Lymphatic Flow. Plast. Reconstr. Surg. 2014, 133, 301–310. [Google Scholar] [CrossRef] [PubMed]
  46. Ito, R.; Zelken, J.; Yang, C.Y.; Lin, C.Y.; Cheng, M.H. Proposed Pathway and Mechanism of Vascularized Lymph Node Flaps. Gynecol. Oncol. 2016, 141, 182–188. [Google Scholar] [CrossRef]
  47. Cheng, M.H.; Huang, J.J.; Wu, C.W.; Yang, C.Y.; Lin, C.Y.; Henry, S.L.; Kolios, L. The Mechanism of Vascularized Lymph Node Transfer for Lymphedema: Natural Lymphaticovenous Drainage. Plast. Reconstr. Surg. 2014, 133, 192e–198e. [Google Scholar] [CrossRef]
  48. Winters, H.; Tielemans, H.J.P.; Paulus, V.; Hummelink, S.; Slater, N.J.; Ulrich, D.J.O. A Systematic Review and Meta-Analysis of Vascularized Lymph Node Transfer for Breast Cancer-Related Lymphedema. J. Vasc. Surg. Venous Lymphat. Disord. 2022, 10, 786–795.e1. [Google Scholar] [CrossRef]
  49. Chang, E.I.; Chu, C.K.; Hanson, S.E.; Selber, J.C.; Hanasono, M.M.; Schaverien, M.V. Comprehensive Overview of Available Donor Sites for Vascularized Lymph Node Transfer. Plast. Reconstr. Surg. Glob. Open 2020, 8, e2675. [Google Scholar] [CrossRef]
  50. Coriddi, M.; Wee, C.; Meyerson, J.; Eiferman, D.; Skoracki, R. Vascularized Jejunal Mesenteric Lymph Node Transfer: A Novel Surgical Treatment for Extremity Lymphedema. J. Am. Coll. Surg. 2017, 225, 650–657. [Google Scholar] [CrossRef]
  51. Inbal, A.; Teven, C.M.; Chang, D.W. Latissimus Dorsi Flap with Vascularized Lymph Node Transfer for Lymphedema Treatment: Technique, Outcomes, Indications and Review of Literature. J. Surg. Oncol. 2017, 115, 72–77. [Google Scholar] [CrossRef]
  52. Mardonado, A.A.; Chen, R.; Chang, D.W. The Use of Supraclavicular Free Flap with Vascularized Lymph Node Transfer for Treatment of Lymphedema: A Prospective Study of 100 Consecutive Cases. J. Surg. Oncol. 2017, 115, 68–71. [Google Scholar] [CrossRef]
  53. Demiri, E.; Dionyssiou, D.; Tsimponis, A.; Goula, O.C.; Mlothridis, P.; Pavlidis, L.; Spyropoulou, G.A.; Foroglou, P. Donor-Site Lymphedema Following Lymph Node Transfer for Breast Cancer-Related Lymphedema: A Systematic Review of the Literature. Lymphat. Res. Biol. 2018, 16, 2–8. [Google Scholar] [CrossRef]
  54. Dayan, J.H.; Dayan, E.; Smith, M.L. Reverse Lymphatic Mapping: A New Technique for Maximizing Safety in Vascularized Lymph Node Transfer. Plast. Reconstr. Surg. 2015, 135, 277–285. [Google Scholar] [CrossRef]
  55. Nguyen, D.H.; Chou, P.Y.; Hsieh, Y.H.; Momeni, A.; Fang, Y.H.D.; Patel, K.M.; Yang, C.Y.; Cheng, M.H. Quantity of Lymph Nodes Correlates with Improvement in Lymphatic Drainage in Treatment of Hind Limb Lymphedema with Lymph Node Flap Transfer in Rats. Microsurgery 2016, 36, 239–245. [Google Scholar] [CrossRef]
  56. Gustafsson, J.; Chu, S.Y.; Chan, W.H.; Cheng, M.H. Correlation between Quantity of Transferred Lymph Nodes and Outcome in Vascularized Submental Lymph Node Flap Transfer for Lower Limb Lymphedema. Plast. Reconstr. Surg. 2018, 142, 1056–1063. [Google Scholar] [CrossRef] [PubMed]
  57. Chocron, Y.; Azzi, A.J.; Bouhadana, G.; Kokosis, G.; Vorstenbosch, J. Axilla versus Wrist as the Recipient Site in Vascularized Lymph Node Transfer for Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis. J. Reconstr. Microsurg. 2022, 38, 539–548. [Google Scholar] [CrossRef] [PubMed]
  58. Liu, H.L.; Pang, S.Y.; Lee, C.C.; Wong, M.M.K.; Chung, H.P.; Chan, Y.W. Orthotopic Transfer of Vascularized Groin Lymph Node Flap in the Treatment of Breast Cancer-Related Lymphedema: Clinical Results, Lymphoscintigraphy Findings, and Proposed Mechanism. J. Plast. Reconstr. Aesthet. Surg. 2018, 71, 1033–1040. [Google Scholar] [CrossRef] [PubMed]
  59. Kenworthy, E.O.; Nelson, J.A.; Verma, R.; Mbabuike, J.J.; Mehrara, B.J.; Dayan, J.H. Double Vascularized Omentum Lymphatic Transplant (VOLT) for the Treatment of Lymphedema. J. Surg. Oncol. 2018, 117, 1413–1419. [Google Scholar] [CrossRef]
  60. Chang, D.W.; Dayan, J.; Greene, A.K.; MacDonald, J.K.; Masia, J.; Mehrara, B.; Neligan, P.C.; Nguyen, D. Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference. Plast. Reconstr. Surg. 2021, 147, 975–993. [Google Scholar] [CrossRef]
  61. Sekigami, Y.; Char, S.; Mullen, C.; Huber, K.; Cao, Y.; Buchsbaum, R.; Graham, R.; Nardello, S.; Singhal, D.; Chatterjee, A. Cost-Effectiveness Analysis: Lymph Node Transfer vs Lymphovenous Bypass for Breast Cancer-Related Lymphedema. J. Am. Coll. Surg. 2021, 232, 837–845. [Google Scholar] [CrossRef]
  62. Pappalardo, M.; Patel, K.; Cheng, M.H. Vascularized Lymph Node Transfer for Treatment of Extremity Lymphedema: An Overview of Current Controversies Regarding Donor Sites, Recipient Sites and Outcomes. J. Surg. Oncol. 2018, 117, 1420–1431. [Google Scholar] [CrossRef]
  63. Slavin, S.A.; Upton, J.; Kaplan, W.D.; Van Den Abbeele, A.D. An Investigation of Lymphatic Function Following Free-Tissue Transfer. Plast. Reconstr. Surg. 1997, 99, 730–743. [Google Scholar] [CrossRef]
  64. Miranda Garcés, M.; Pons, G.; Mirapeix, R.; Masià, J. Intratissue Lymphovenous Communications in the Mechanism of Action of Vascularized Lymph Node Transfer. J. Surg. Oncol. 2017, 115, 27–31. [Google Scholar] [CrossRef]
  65. Koshima, I.; Narushima, M.; Mihara, M.; Yamamoto, T.; Hara, H.; Ohshima, A.; Kikuchi, K.; Todokoro, K.; Seki, Y.; Iida, T.; et al. Lymphadiposal Flaps and Lymphaticovenular Anastomoses for Severe Leg Edema: Functional Reconstruction for Lymph Drainage System. J. Reconstr. Microsurg. 2016, 32, 50–55. [Google Scholar] [CrossRef]
  66. Yamamoto, T.; Iida, T.; Yoshimatsu, H.; Fuse, Y.; Hayashi, A.; Yamamoto, N. Lymph Flow Restoration after Tissue Replantation and Transfer: Importance of Lymph Axiality and Possibility of Lymph Flow Reconstruction without Lymph Node Transfer or Lymphatic Anastomosis. Plast. Reconstr. Surg. 2018, 142, 796–804. [Google Scholar] [CrossRef]
  67. Yamamoto, T.; Yamamoto, N.; Kageyama, T.; Sakai, H.; Fuse, Y.; Tsukuura, R. Lymph-Interpositional-Flap Transfer (LIFT) Based on Lymph-Axiality Concept: Simultaneous Soft Tissue and Lymphatic Reconstruction without Lymph Node Transfer or Lymphatic Anastomosis. J. Plast. Reconstr. Aesthetic Surg. 2021, 74, 2604–2612. [Google Scholar] [CrossRef] [PubMed]
  68. Yoshimatsu, H.; Visconti, G.; Karakawa, R.; Hayashi, A. Lymphatic System Transfer for Lymphedema Treatment: Transferring the Lymph Nodes with Their Lymphatic Vessels. Plast. Reconstr. Surg. Glob. Open 2020, 8, e2721. [Google Scholar] [CrossRef] [PubMed]
  69. Orfahli, L.M.; Fahradyan, V.; Chen, W.F. Vascularized Lymph Vessel Transplant (VLVT): Our Experience and Lymphedema Treatment Algorithm. Ann. Breast Surg. 2022, 6, 8. [Google Scholar] [CrossRef]
  70. Chen, W.F.; McNurlen, M.; Ding, J.; Bowen, M. Vascularized Lymph Vessel Transfer for Extremity Lymphedema-Is Transfer of Lymph Node Still Necessary? Int. Microsurg. J. 2019, 3, 1. [Google Scholar] [CrossRef]
  71. Yoshimatsu, H.; Cho, M.J.; Karakawa, R.; Okada, A.; Hayashi, A.; Fuse, Y.; Yano, T. The Role of Lymphatic System Transfer (LYST) for Treatment of Lymphedema: A Long-Term Outcome Study of SCIP Flap Incorporating the Lymph Nodes and the Afferent Lymphatic Vessels. J. Plast. Reconstr. Aesthet. Surg. 2025, 101, 15–22. [Google Scholar] [CrossRef]
  72. Salibian, A.A.; Yu, N.; Patel, K.M. Staging Approaches to Lymphatic Surgery: Techniques and Considerations. J. Surg. Oncol. 2024, 131, 12–21. [Google Scholar] [CrossRef]
  73. Garza, R.M.; Beederman, M.; Chang, D.W. Physical and Functional Outcomes of Simultaneous Vascularized Lymph Node Transplant and Lymphovenous Bypass in the Treatment of Lymphedema. Plast. Reconstr. Surg. 2022, 150, 169–180. [Google Scholar] [CrossRef] [PubMed]
  74. Brazio, P.S.; Nguyen, D.H. Combined Liposuction and Physiologic Treatment Achieves Durable Limb Volume Normalization in Class II-III Lymphedema: A Treatment Algorithm to Optimize Outcomes. Ann. Plast. Surg. 2021, 86, S384–S389. [Google Scholar] [CrossRef]
  75. Gabriele, G.; Nigri, A.; Chisci, G.; Massarelli, O.; Cascino, F.; Komorowska-Timek, E.; Kazuki, K.; Hara, H.; Mihara, M.; Gennaro, P. Combination of Supramicrosurgical Lymphatico-Venular Anastomosis (SLVA) and Lymph-Sparing Liposuction in Treating Cancer-Related Lymphedema: Rationale for a Regional One-Stage Approach. J. Clin. Med. 2024, 13, 2872. [Google Scholar] [CrossRef]
  76. Cho, M.J.; Senger, J.L.; Park, K.U.; Hansotia, K.; Chratian, S.; Kadle, R.; Skoracki, R.J. Preventing Breast Cancer-Related Lymphedema: A Comprehensive Analysis of a 9-Year Single-Center Experience of Prophylactic Lymphovenous Bypass. Ann. Surg. Oncol. 2025, 32, 2007–2015. [Google Scholar] [CrossRef] [PubMed]
  77. Deptula, P.; Zhou, A.; Posternak, V.; He, H.; Nguyen, D. Multimodality Approach to Lymphedema Surgery Achieves and Maintains Normal Limb Volumes: A Treatment Algorithm to Optimize Outcomes. J. Clin. Med. 2022, 11, 598. [Google Scholar] [CrossRef]
  78. Hadamitzky, C.; Zaitseva, T.S.; Bazalova-Carter, M.; Paukshto, M.V.; Hou, L.; Strassberg, Z.; Ferguson, J.; Matsuura, Y.; Dash, R.; Yang, P.C.; et al. Aligned Nanofibrillar Collagen Scaffolds-Guiding Lymphangiogenesis for Treatment of Acquired Lymphedema. Biomaterials 2016, 102, 259–267. [Google Scholar] [CrossRef]
  79. Hayashida, K.; Yoshida, S.; Yoshimoto, H.; Fujioka, M.; Saijo, H.; Migita, K.; Kumaya, M.; Akita, S. Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis. Plast. Reconstr. Surg. 2017, 139, 639–651. [Google Scholar] [CrossRef]
  80. Forte, A.J.; Boczar, D.; Sarabia-Estrada, R.; Huayllani, M.T.; Avila, F.R.; Torres, R.A.; Guliyeva, G.; Aung, T.; Quiñones-Hinojosa, A. Use of Adipose-Derived Stem Cells in Lymphatic Tissue Engineering and Regeneration. Arch. Plast. Surg. 2021, 48, 559–567. [Google Scholar] [CrossRef]
  81. Lähteenvuo, M.; Honkonen, K.; Tervala, T.; Tammela, T.; Suominen, E.; Lähteenvuo, J.; Kholová, I.; Alitalo, K.; Ylä-Herttuala, S.; Saaristo, A. Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema. Circulation 2011, 123, 613–620. [Google Scholar] [CrossRef]
  82. Engström, O.; Mani, M. Surgical Treatments of Lymphedema—A Literature Review on Robot-Assisted Lymphovenous Anastomosis (LVA). Gland. Surg. 2024, 13, 1066–1075. [Google Scholar] [CrossRef]
  83. Stögner, V.A.; Pucciarelli, D.M.; Pomahac, B.; Ayyala, H.S. Robotic-Assisted Microsurgery in Lymphatic Reconstruction. J. Craniofac Surg. 2025, 36, 359–362. [Google Scholar] [CrossRef]
  84. Frosolini, A.; Benedetti, S.; Catarzi, L.; Massarelli, O.; Gennaro, P.; Gabriele, G. Exoscope and Supermicrosurgery: Pros and Cons of 3D Innovation in Lymphatic Surgery. J. Clin. Med. 2024, 13, 4974. [Google Scholar] [CrossRef] [PubMed]
  85. von Reibnitz, D.; Weinzierl, A.; Barbon, C.; Gutschow, C.A.; Giovanoli, P.; Grünherz, L.; Lindenblatt, N. 100 Anastomoses: A Two-Year Single-Center Experience with Robotic-Assisted Micro- and Supermicrosurgery for Lymphatic Reconstruction. J. Robot. Surg. 2024, 18, 164. [Google Scholar] [CrossRef] [PubMed]
  86. Weinzierl, A.; Barbon, C.; Gousopoulos, E.; von Reibnitz, D.; Giovanoli, P.; Grünherz, L.; Lindenblatt, N. Benefits of Robotic-Assisted Lymphatic Microsurgery in Deep Anatomical Planes. JPRAS Open 2023, 37, 145–154. [Google Scholar] [CrossRef] [PubMed]
  87. van Mulken, T.J.M.; Wolfs, J.A.G.N.; Qiu, S.S.; Scharmga, A.M.J.; Schols, R.M.; Spiekerman van Weezelenburg, M.A.; Cau, R.; van der Hulst, R.R.W.J.; Winkens, B.; Verheijden, D.A.; et al. One-Year Outcomes of the First Human Trial on Robot-Assisted Lymphaticovenous Anastomosis for Breast Cancer-Related Lymphedema. Plast. Reconstr. Surg. 2022, 149, 151–161. [Google Scholar] [CrossRef]
  88. Barbon, C.; Grünherz, L.; Uyulmaz, S.; Giovanoli, P.; Lindenblatt, N. Exploring the Learning Curve of a New Robotic Microsurgical System for Microsurgery. JPRAS Open 2022, 34, 126–133. [Google Scholar] [CrossRef]
  89. Lindenblatt, N.; Grünherz, L.; Wang, A.; Gousopoulos, E.; Barbon, C.; Uyulmaz, S.; Giovanoli, P. Early Experience Using a New Robotic Microsurgical System for Lymphatic Surgery. Plast. Reconstr. Surg. Glob. Open 2022, 10, E4013. [Google Scholar] [CrossRef]
  90. van Mulken, T.J.M.; Schols, R.M.; Scharmga, A.M.J.; Winkens, B.; Cau, R.; Schoenmakers, F.B.F.; Qiu, S.S.; van der Hulst, R.R.W.J.; Keuter, X.H.A.; Lauwers, T.M.A.S.; et al. First-in-Human Robotic Supermicrosurgery Using a Dedicated Microsurgical Robot for Treating Breast Cancer-Related Lymphedema: A Randomized Pilot Trial. Nat. Commun. 2020, 11, 757. [Google Scholar] [CrossRef]
  91. Levin, L.S.; Payne, M.M.; Van Vleet, J.D.; Azoury, S.C. Robotic-Assisted Lymphedema Surgery: Bridging the Gap in Training and Expanding Complex Surgical Options. J. Craniofac. Surg. 2025, 36, 357–359. [Google Scholar] [CrossRef]
  92. von Reibnitz, D.; Weinzierl, A.; Grünherz, L.; Giovanoli, P.; Lindenblatt, N. Learning Curve of Robotic Assisted Microsurgery in Surgeons with Different Skill Levels: A Prospective Preclinical Study. J. Robot. Surg. 2024, 18, 353. [Google Scholar] [CrossRef]
  93. Garcia, J.P.; Avila, F.R.; Torres, R.A.; Maita, K.C.; Borna, S.; Rinker, B.D.; Forte, A.J.; Ho, O.A. Evaluating the Exoscope as an Alternative to the Operating Microscope in Plastic Surgery. J. Plast. Reconstr. Aesthet. Surg. 2023, 85, 376–386. [Google Scholar] [CrossRef] [PubMed]
  94. Calnan, J.S.; Reis, N.D.; Rivero, O.R.; Copenhagen, H.J.; Mercurius-Taylor, L. The Natural History of Lymph Node-to-Vein Anastomoses. Br. J. Plast. Surg. 1967, 20, 134–145. [Google Scholar] [CrossRef] [PubMed]
  95. Rivero, O.R.; Calnan, J.S.; Reis, N.D.; Mercurius-Taylor, L. Experimental Peripheral Lympho-Venous Communications. Br. J. Plast. Surg. 1967, 20, 124–133. [Google Scholar] [CrossRef] [PubMed]
  96. Bailey, E.A.; Pandey, S.K.; Chen, W.F. Advances in Surgical Lymphedema Management: The Emergence and Refinement of Lymph Node-to-Vein Anastomosis (LNVA). Curr. Surg. Rep. 2024, 12, 83–88. [Google Scholar] [CrossRef]
  97. Pak, C.S.; Suh, H.P.; Kwon, J.G.; Cho, M.J.; Hong, J.P. Lymph Node to Vein Anastomosis (LNVA) for Lower Extremity Lymphedema. J. Plast. Reconstr. Aesthet. Surg. 2021, 74, 2059–2067. [Google Scholar] [CrossRef]
  98. Alshomer, F.; Cho, J.; Noh, H.; Pak, C.J.; Suh, H.P.; Hong, J.P. Lymphaticovenous and Lymph Node-to-Vein Anastomosis to Improve Milroy Disease-Related Chylothorax and Lymphedema. Plast. Reconstr. Surg. 2025, 155, 10–1097. [Google Scholar] [CrossRef]
  99. Kim, Y.; Kim, H.B.; Pak, C.J.; Suh, H.P.; Hong, J.P. Using Lymphovenous Anastomosis and Lymph Node to Vein Anastomosis for Treatment of Posttraumatic Chylothorax with Increased Thoracic Duct Pressure in 3-Year-Old Child. Arch. Plast. Surg. 2022, 49, 549–553. [Google Scholar] [CrossRef]
Table 1. Summary of current techniques in physiologic lymphedema surgery.
Table 1. Summary of current techniques in physiologic lymphedema surgery.
SurgerySummary of TechniqueIndicationsContraindications
LVB
  • Intra-operative identification of functional lymphatic channels distal to an area of dermal backflow using ICG lymphography
  • Supermicrosurgical anastomosis of lymphatic channels to adjacent venules
  • A variety of supermicrosurgical anastomotic techniques have been described: end-to-end, end-to-side, side-to-end, and intussusception
  • Traditionally limited to early, fluid predominant stage lymphedema
  • Indications may expand with advanced imaging such as UHFUS, which can identify more lymphatic channels for bypass compared to ICG lymphography alone
  • Advanced stage lymphedema with no functional lymphatic channels available for bypass
pLVB
  • LVB performed at the time of lymph node dissection (LND) to reduce the risk of secondary lymphedema
  • Supermicrosurgical anastomosis of lymphatic channels cut during LND to adjacent veins, using similar anastomotic techniques as described for LVB
  • Historically performed in the setting of ALND for breast cancer treatment
  • Indications are expanding to LND performed for other types of malignancy (ex: melanoma, urogynecologic cancer)
  • Pre-existing lymphedema
  • Metastatic disease
VLNT
  • A functional lymph node basin is harvested on its own blood supply and transferred to a lymphedematous extremity either as a pedicled or free flap
  • Donor sites include supraclavicular, lateral thoracic, inguinal, and intra-abdominal (ex: omentum, mesenteric, jejunal)
  • Recipient sites may be proximal or distal on the affected extremity, or dual level
  • Typically performed for more advanced stage lymphedema
  • Active malignancy
  • Pre-existing lymphedema at donor site
  • Any contraindication to free flap surgery
VLVT
  • A perforator-based skin flap with functional lymphatic channels is harvested on its own blood supply and transferred to a lymphedematous extremity as a free flap
  • It is essential to make note of flap orientation to preserve the direction of lymphatic flow
  • Donor sites include SCIP, ALT, DIEP, TDAP, first dorsal metatarsal artery flaps
  • Typically performed for early, fluid predominant stage lymphedema
  • Some authors have expanded indications for VLVT to more advanced stage lymphedema cases that would be historically treated with VLNT
  • Any contraindication to free flap surgery
Table 2. Summary of emerging developments and unresolved challenges in physiologic lymphedema surgery.
Table 2. Summary of emerging developments and unresolved challenges in physiologic lymphedema surgery.
Areas of Emerging
Developments
Treatment algorithms for lymphedema surgery
  • Many surgical treatments, both debulking and physiologic, have been described for lymphedema treatment.
  • However, there is debate over which surgeries are indicated, and whether these surgeries can be combined or sequenced, depending on clinical presentation, lymphedema stage, anatomic location, or etiology of lymphedema.
  • Unresolved challenges: No consensus on combining and/or sequencing debulking and/or physiologic lymphedema surgical techniques into a unified treatment algorithm.
Biomaterials and tissue engineering
  • Biomaterials, tissue engineering, stem cells, and growth factors are being studied as potential sources of lymphangiogenesis, which may be used to augment surgical treatment.
  • Unresolved challenges: Most of this research has been done in in vitro or animal models and has made it to clinical studies yet.
Innovations in microsurgical equipment, imaging, and technology
  • Robotic-assisted supermicrosurgical platforms and 3D exoscopes have been developed to enhance magnification and surgical view, improve surgeon ergonomics, reduce tremor, and supplement surgical education.
  • Unresolved challenges: Current limitations in adopting these innovations include high costs, additional training, steep learning curve, and limited accessibility.
Developing new surgical techniques
  • New surgical techniques are being developed, such as LNVA, which can expand surgical treatment of lymphedema to primary and central lymphedema.
  • Unresolved challenges: Longer follow up is need to determine the efficacy of these newer techniques compared to conventional surgical techniques.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

MacKenzie, E.L.; Huang, A.; Cho, M.-J.; Skoracki, R.J.; Kadle, R.L. Physiologic Lymphedema Surgery: Current Treatments and Future Trends. Lymphatics 2025, 3, 35. https://doi.org/10.3390/lymphatics3040035

AMA Style

MacKenzie EL, Huang A, Cho M-J, Skoracki RJ, Kadle RL. Physiologic Lymphedema Surgery: Current Treatments and Future Trends. Lymphatics. 2025; 3(4):35. https://doi.org/10.3390/lymphatics3040035

Chicago/Turabian Style

MacKenzie, Ethan L., Anne Huang, Min-Jeong Cho, Roman J. Skoracki, and Rohini L. Kadle. 2025. "Physiologic Lymphedema Surgery: Current Treatments and Future Trends" Lymphatics 3, no. 4: 35. https://doi.org/10.3390/lymphatics3040035

APA Style

MacKenzie, E. L., Huang, A., Cho, M.-J., Skoracki, R. J., & Kadle, R. L. (2025). Physiologic Lymphedema Surgery: Current Treatments and Future Trends. Lymphatics, 3(4), 35. https://doi.org/10.3390/lymphatics3040035

Article Metrics

Back to TopTop