Lymphedema of the extremities following cancer treatment is not considered curable. However, newer surgical techniques may offer some patients an effective alternative to conservative therapies such as compression techniques and manual lymphatic drainage.
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Surgical procedures have been reserved for cases of lymphedema that are refractory to conservative or decongestive treatment. More recently there has been a shift toward earlier surgical intervention, which has the potential to reduce lymphatic load and slow lymphedema progression.
Vascularized lymph node transfer (VLNT) is a surgical technique that involves moving lymph nodes with an intact blood supply — an artery and a vein that can be anastomosed to the recipient site — to restore or augment lymphatic drainage. VLNT may be performed in patients with breast cancer–related lymphedema of the upper limb and can be done simultaneously with breast reconstruction. Although results are promising, VLNT is relatively new and thus still in the exploratory stage.
This Q&A with Cleveland Clinic plastic and reconstructive surgeon Graham Schwarz, MD, details the complexities of VLNT and its application.
Q: How long has VLNT been used for breast cancer-related lymphedema?
A: The vascularized lymph node transfer was first used clinically in a patient in the early 1980s. VLNT gained some popularity during the‘90s, but mostly in Europe. It was not until the last five years or so that the procedure gained interest in the U.S. And we’re starting to see some encouraging results — the data are beginning to accumulate. The technique is still in its early stages, but enthusiasm for VLNT and its potential is increasing.
Q: What are potential advantages of this method, compared to decongestive treatments and ablative or debulking surgeries?
A: We generally explain to patients that there are two basic categories of surgery for lymphedema: ablative/debulking surgery and functional /physiologic surgery.
Ablative or debulking procedures have been in use since the early to mid-20th century and include radical excisional procedures to reduce the volume of lymphedematous limbs. These procedures can be quite disfiguring but can be functionally beneficial in the most severe cases. They evolved into liposuction, which is a less invasive form of tissue removal and limb size reduction. While liposuction can reduce limb volume, it does not obviate the need for lifelong compressive therapy for maintenance. In contrast, following a successful VLNT, compression therapy is used initially but may not be needed long-term.
Functional techniques include VLNT and lymphacticovenular bypass, which in the most rudimentary terms, can be described as “trying to fix the plumbing.” We are effectively trying to redirect some of the fluid that’s retained in the limb back into the venous system and attempting to generate new pathways for lymphatic drainage. In lymphaticovenular bypass, we identify working lymphatic vessels and connect them to tiny sub-millimeter venules. This supermicrosurgical procedure has shown promise, but outcomes are varied at this point. In VLNT, we borrow lymph nodes from one area of the body and transplant them with a blood supply and some surrounding fat to the area affected by lymphedema.
There are several schools of thought about mechanisms that may underlie success with VLNT. One hypothesis focuses on the vascularized lymph node functioning as a catchment basin or lymphatic pump, collecting and transporting fluid into venous circulation. Lymphangiogenesis also occurs, and new lymphatic channels may be generated as a result of the chemicals and factors that the VLNT elaborates. Additionally, people with lymphedema may have recurrent infections, and with VLNT you are transferring a working immunological center into an area that has been damaged.
Q: Has a direct comparison been performed to evaluate the efficacy of VLNT compared with other procedures?
A: There have not yet been head-to-head comparisons in a matched, cohort trial. At this point there are a number of retrospective and prospective case series. A recent randomized controlled trial comparing VLNT to standard complex decongestive therapy has been reported, with promising results. The community of reconstructive microsurgeons who is performing VLNTs is paying more attention to standardizing perioperative management and measuring short- and long-term outcomes, which will eventually help us better understand how VLNT compares to other treatments.
Q: What is Cleveland Clinic’s experience with the procedure?
A: We started using VLNT in 2012, and have performed it on approximately 25 patients. Many, but not all of these procedures have been on patients with breast cancer-related or post-mastectomy lymphedema; however, the vast majority do have secondary lymphedema due to prior oncologic treatment. We’ve also performed VLNT in conjunction with microsurgical autologous breast reconstruction.
Q: When is the use of VLNT appropriate?
A: Our main focus at Cleveland Clinic has been on lymphedema that results from oncologic treatment. Usually, these patients have had a combination of lymph node removal and/or radiation that has damaged the lymphatic system. Lymphedema can also occur as a congenital disorder, from a traumatic event or from a parasitic infection. While VNLT may ultimately be applicable in these instances, there has been less investigation using the procedure to treat lymphedema resulting from these conditions.
Q: Who are the best surgical candidates for VLNT?
A: This certainly requires a lot more research, but we believe that patients with earlier stages of lymphedema are better candidates for VLNT. Lymphedema is progressive, and if the lymphatic fluid stasis isn’t managed appropriately in the early stages, chronic inflammation ensues, which induces scarring and fat deposition. Once this occurs, limb volume discrepancy and morbidity from lymphedema may have less to do with the fluid component in the limb. So we’re basically choosing patients who have some component of reversible lymphedema, typically from stage one to possibly stage three. We then use a physical exam and imaging tests to determine the components of fluid, scar and fat in their extremity while measuring lymphatic transit.
We also use two criteria to determine if a patient should be considered:
- The patient has had a consultation with a lymphedema therapist and has been compliant with their lymphedema treatment regimen of decongestive therapy, but has reached a point where they are not improving.
- With cancer patients, I’d like them to have no evidence of recurrence of their disease for at least one year after their treatment.
Q: How complex is the procedure?
A: It is a specialized procedure that requires microsurgical technique. We borrow a lymph node and the 1-2 mm blood vessels that supply it from a donor site, such as the groin, axilla or supraclavicular area. We disconnect the lymph node-containing tissue and transplant it to the recipient site after it has been prepared. Finally, we reconnect the blood vessels using very fine suture under the microscope. The length of the procedure can vary: If it’s a lymph node transfer alone, it can take from four to eight hours. If it’s in conjunction with a breast reconstruction, it can take closer to eight hours for a single side.
Q: What are the potential risks of VLNT? Are there risks associated with the donor site?
A: Though rare, vascular compromise may cause the tissue to lose its viability. Another risk is fluid collection at the surgical sites. Donor site-associated lymphedema has been reported after VLNT, but it’s also quite rare. To further reduce the risk, we use a technique called reverse lymphatic mapping using a combination of vital and fluorescent dyes to identify the lymph nodes that are primarily responsible for drainage of the donor extremity. This allows us to harvest lymph nodes for transfer that don’t contribute to these important drainage pathways.
Q: How long is the recovery period after VLNT, and how soon are outcomes of the procedure apparent?
A: Patients are usually hospitalized for one to three days after the procedure, and recovery time varies from about four to six weeks. Mobility limitations of patients will also vary. It’s important to work with each patient’s occupational or physical therapist both pre- and post-operatively, because typically we try to get patients back into their lymphedema therapy fairly quickly to keep the swelling down. We’ve had a range of results after VLNT, with some patients experiencing improvement very quickly, within a matter of weeks, and others who have taken much longer to recover. On average, we tend not to see results for the first three to four months, and sometimes not for a year or more. We are careful to counsel our patients extensively, explaining that the procedure is not a cure and that they may not have complete resolution of signs and symptoms of lymphedema, but we believe the procedure can improve quality of life in properly selected patients.
Q: What outcomes should patients expect? What is the likelihood of restoring normal limb proportion?
A: It really depends on the patient. Any one of multiple factors can characterize VLNT success:
- Reduction or elimination of the need for compression therapy
- Reduction in limb volume
- Increase in limb suppleness
- Elimination of discomfort or low-grade pain from lymphedema
- Reduction or elimination of cellulitis episodes
- Subjective improvement of quality of life
So, with these in mind, the ability to eliminate the need for lymphedema therapy and compression therapy completely, as well as reducing the patient’s limb size to almost normal, would essentially be considered a home run. If we can reduce or eliminate the amount of compression without any lymphedema progression, that would also be a big win for the patient. If you look across the literature available on the topic, it seems that about a 30 to 40 percent reduction of limb size compared to the previous size is the average result after the procedure.
Q: What about the timing of VLNT? Is it done at the time of breast or other cancer surgery as a preventive step; in combination with breast reconstruction; or later, to treat lymphedema?
A: At this point, we’re not typically using VLNT in a prophylactic way. It may be performed on its own or in combination with breast reconstruction. The situations in which we use it include:
- In those women with lymphedema who have had no reconstruction. This would be in conjunction with breast reconstruction in the delayed setting. We encounter this situation mostly in women with higher-stage cancer that requires post-mastectomy radiation in addition to chemotherapy. These patients often will have undergone complete lymph node dissection.
- In patients who have had mastectomy and possibly reconstruction with implants, but who don’t like their implants or have implants that have become extremely scarred or contracted, a common result of radiation after mastectomy. These types of patients want to change their reconstruction from the implants to their own abdominal tissue, and while we’re dissecting the deep inferior epigastric perforators (DIEP) flap or free transverse rectus abdominis (TRAM) flap, we can do the lymph node transfer as well. (See Figure 2.)
- In patients who have had lumpectomies with radiation and axillary surgery and who have lymphedema alone or in conjunction with a contour deformity. We’ve seen women in whom we have been able to perform VLNT alone or with partial breast reconstruction.
Q: What tissue harvest site(s) do you prefer and why?
A: We have done transfers using three different sites:
- From the inguinal nodes of the groin (The scar there is beneath the underwear line.)
- From the lateral chest wall with some of the lower lymph nodes that continue lower than the armpit
- From the neck (Even though it leaves a more prominent scar, there’s a great redundancy of lymph nodes and lymphatic channels in the neck, so the possibility of problems with lymphedema are less.)
I discuss the pros and cons with the patient, and if all sites are available, we go with their preference.
Q: What implantation site(s) do you prefer, and is the choice affected by the proposed mechanism of action of the transferred lymph node (i.e., functioning as a pump vs. promoting lymphangiogenesis)?
A: We still don’t know which is the “right” site for implantation. Regarding the proposed mechanism of action, based on the available clinical studies and also from our basic science experience, it seems like both mechanisms exist. In patients who have post-mastectomy lymphedema, I typically choose the armpit area because I use that opportunity to release the scar that’s formed in and around the axilla, allowing a space to put healthy non-irradiated and vascularized tissue in the area that had been damaged. In one way this serves to bridge the lymphatic gap once lymphangiogenesis comes into play. VLNT can also serve as a lymphatic fluid wick, drawing fluid into the lymph node flap and pumping it into the venous system.
Q: How do you prepare the recipient site? Is removal of scar tissue or fibrosis necessary? Do you use endothelial growth factor?
A: Absolutely, removal of scar tissue and fibrosis is critically important, and I think that some patients experience a degree of relief from even just doing that initially. I don’t use endothelial growth factor. No group in the U.S. has used that with VLNT yet.
Q: What additional research do you believe is needed on the topic?
A: There is certainly much to study in this exciting field. We still don’t really know which of the two mechanisms – pump or lymphangiogenesis – predominates in VLNT, so I’d like to see a continuation of this type of research. This might better inform our decision on where to place the transferred nodes in the extremity (distal or proximal) and optimize our surgical approach. Importantly, we do not know exactly which subset of patients with lymphedema will benefit most from the procedure. In order to tease out these answers we need ongoing, coordinated outcomes reporting, basic science research on mechanisms of action in VLNT and an increased understanding of the pathobiology of lymphedema.