Over the last quarter century and more reconstructive plastic surgery has been transformed greatly by micro-surgical skills and these have become the basic skill set for any reconstructive surgeon. What has been added to this repertoire in the last couple of decades is microsurgery on very fine lymphatic vessels as well as the free microvascular transfer of live lymph glands to treat lymphedema. This blog already has chapters on that subject. In India filarial infections is a major cause of a large percentage of patients with lymphedema. Lymphedema due to congenital lymphatic dysplasia and as a result of cancer (mainly of the breast and pelvic pathology) as well as the treatment of those cancers involving removal of lymphatic tissue constitute a smaller subset of all cases of lymphedema. In very recent times surgeons have added protocols to prevent lymphedema following surgery for cancer of the breast.
In front of this backdrop it was extremely gratifying for the compiler of these short notes (Ravin Thatte) to listen and see the presentation of Dr. Mayur Mantri, a consultant at the Tata memorial hospital in Mumbai India at a clinical educational meeting at the Nair hospital in July 2024 on the subject of ‘preventive lymphatic surgery for post -surgery lymphedema in breast cancer. He was therefore requested to write this short chapter on the subject.
Prophylactic lymphatic surgery to prevent lymphedema after surgery for breast cancer
Surgery for breast cancer has changed dramatically since Halsted introduced radical mastectomy for the treatment of breast cancer. Although radical mastectomies greatly improved survival of patients with breast cancer, they resulted in considerable mutilation. Surgeons have since then transitioned from performing large resections to conserving as much breast tissue as possible. A good breast surgeon’s distinguishing feature is no longer how radical a resection he or she can perform, but rather how much conservation they achieve without reducing the survival rates. We have progressed from radical mastectomies to modified radical mastectomies to breast conservation operations. Axillary lymph node removal is also part of the treatment for breast cancer. Lymphedema of the limb is a feared consequence of this surgical procedure particularly when axillary lymph nodes are removed “en-masse”. The incidence of lymphedema following axillary clearing has been recorded in the literature as varying from 13% to 65%. Most doctors concur that at least 25% of patients who undergo axillary clearance of lymph nodes develop clinically severe lymphedema. As in mastectomy, axillary clearance surgery too has evolved in order to prevent lymphedema. Surgeons now attempt to avoid axillary clearance wherever possible ( for example early breast cancer, clinically node negative lesions). Even when indicated, an attempt is made to reduce the amount of axillary dissection. Reverse axillary mapping and sentinel node biopsy were introduced as tools to limit the amount of axillary dissection. Sentinel lymph node biopsy is performed when appropriate, and if the sentinel node is negative, axillary clearance is avoided. It has been demonstrated that metastatic cells spread through regional lymphatics in an orderly manner. The sentinel lymph node (SLN) is the initial nodes that drains the lymph from a particular organ before draining into subsequent nodes (non-SLNs). Thus, identification and assessment of SLN provides us an accurate clinical window into the regional basin. SLN for breast is most commonly located in Level 1 or Level 2 axillary lymph nodes. There are various methods to identify it – radionucleotide, Isosulphan blue dye, Indocyanin green dye etc. Once identified, the biopsy of that node is done and if it is negative, further axillary clearance is not done. Axillary reverse mapping is another technique used to reduce the amount of axillary dissection. A dye is injected in the medial arm (Isosulphan blue, Methylene blue, Radionucleotide, ICG). After waiting for some time for the dye to reach axilla, axillary clearance is done taking care to avoid removing the nodes that have the injected dye. The incidence of lymphedema following sentinel lymph node biopsy is approximately 4-5%, when negative and further clearance is not done, compared to 25-30% with axillary clearance. However, there is a large subset of patients, particularly in our country, who will require complete axillary clearance (for example positive sentinel lymph node, clinically node positive at diagnosis, inflammatory breast cancer, node positive after neoadjuvant chemotherapy), making them susceptible to lymphedema. Given the high occurrence of lymphedema in these patients, as well as the significant morbidity associated with lymphedema, numerous strategies have been attempted to avoid lymphedema in this population of patients.
LyMPHA is one such technique designed to minimize lymphedema after axillary clearance. The abbreviation LyMPHA stands for Lymphedema Microsurgical Preventive Healing Approach. Francesco Boccardo et al originally described LyMPHA in 2009. The authors reported that using this method reduced the incidence of lymphedema to roughly 4%, compared to 30% in the control group. Following its first description, several authors published their findings using the approach, which yielded encouraging results. Several changes to this treatment were introduced, and some publications began referring to it as Immediate Lymphatic Reconstruction (ILR).
Selection of Patients:
Not every patient having axillary clearance develops lymphedema. As a result, identifying high risk patients is critical for avoiding wasteful procedures in the low risk group and making the most use of available resources. The ‘Lymphedema Risk Score’ has been developed to identify high-risk patients.
Lymphedema Risk score:
- Age > 65 1 point
- BMI > 30 3 points
- Previous operations:
- Sentinel node biopsy (negative) 1 point
- Orthopedic or other operation on same limb 1 point
- Current surgery:
- Sentinel node biopsy (without clearance) 1 point
- Complete node dissection 3 points
- Previous lymphangitis 2 points
- Signs of peripheral lymphatic stasis (edema) 2 points
- Radiotherapy (Previous or planned) 3 points
- Chemotherapy (Previous or Planned) 2 points
Total of these gives the Lymphedema Risk Score. Score of >5 is High Risk, 3-4 is Medium Risk and 1-2 is Low Risk. Our current strategy is to offer LyMPHA to high-risk group and observe the medium and low risk groups.
The surgical technique:
Axillary Lymph nodes drain the lymphatics from the breast as well the arm. When axillary dissection is done, the lymphatics draining the arm are also severed and the severed ends are present in the axilla. These are the proximal ends of arm lymphatics that were draining in the axillary lymph nodes.
Image of axilla after axillary clearance showing axillary vein and thoracodorsal pedicle
For LyMPHA procedure, we need to identify the cut ends of the lymphatics in the axilla. It can be done by blue dye (Isosulfan blue or Methylene blue) or Indocyanine green dye. Some authors also prefer Fluorescein dye. We use both Methylene blue as well as ICG dye for Lymphatic mapping.
Methylene blue dye is injected in the medial arm, around 5-10 cm from axillary crease before starting axillary clearance so that there is sufficient time for the dye to reach axilla by the time axillary dissection is completed. If any lymphatic is identified during dissection due to oozing of methylene blue, they are marked during dissection. Breast surgeon is also advised to preserve at least one of the tributary of axillary vein with good length during dissection.
After completion of axillary clearance, LyMPHA procedure is started. For LyMPHA we must identify a tributary of axillary vein having competent valve and no backflow of blood. Most common options available are thoraco-epigastric vein which is lateral to the thoracodorsal pedicle, the serratus branch of thoracodorsal and the lateral thoracic which lies medial to thoracodorsal pedicle.
(Coriddi M, Mehrara B, Skoracki R, Singhal D, Dayan JH. Immediate Lymphatic Reconstruction: Technical Points and Literature Review)
Once a suitable vein is identified, ICG dye is injected in the medial arm, about 10 cm from axillary crease.
Lymphatics are then tracked using the near infra-red camera. Gith gentle massage, the dye can be seen ascending towards the axilla and the proximal cut ends of the lymphatics in axilla are identified under microscope using ICG dye as well as staining by methylene blue.
We use both the methylene blue and ICG for identification of lymphatics. Methylene blue dye takes longer time to ascend, so it is injected before starting axillary clearance (approximately 20 mins before starting the LyMPHA). ICG dye is injected after the axillary clearance just as we start the LyMPHA procedure. It can be done with any one dye alone as well.
(Identified cut ends of the lymphatics in the Axilla)
Once the vein and the lymphatics are identified, Lymphaticovenous anastomosis is performed. Depending on the size of the vein, size of the lymphatic channel and number of lymphatic channels identified, it can be an end-to-end microvascular anastomosis or an anastomosis by intussusception. Most commonly multiple (3-4) small lymphatics are identified, and they are then anastomosed to the axillary vein tributary by the intussusception technique which is our favored technique. Performing an end-to-end anastomosis in axilla is difficult because of the depth of the field and the mismatch between the vein and the lymphatic. Also, performing end to end anastomosis in axilla is time consuming. With intussusception technique, multiple lymphatics are evaginated in a single anastomosis and it is easier and faster. For intussusception a ‘U’ stitch is first taken, for which needle is passed in the vein from outside in. The needle is then passed through the adventitia of the identified lymphatics and then it is passed back into the vein from inside out. The suture is then tied evaginating the lymphatics inside the lumen of the vein.
After this multiple (3-4) sutures are taken between the vein wall and the adventitia of the lymphatic to avoid any leak. The ‘U’ stitch may then be removed.
(Completed Lymphaticovenous anastomosis)
After completion of the anastomosis, the patency of the anastomosis is confirmed on ICG where the dye should be seen going in the vein.
Drains are placed in the axilla away from the anastomotic site and the wound is closed like a routine mastectomy. There is no restriction of movement in the post-operative period and the physiotherapy exercises are started as the standard practice.
Technical Difficulties:
- No blue lymphatics identified – Injecting the dye immediately after induction so that sufficient time is given for the dye to reach, Using ICG
- Short vein – Careful dissection during resection is very important to preserve veins for LyMPHA. If no other tributary is available, serratus branch of thoracodorsal is used which is almost always preserved. Rarely a branch of cephalic vein has been used by us. Some authors have suggested putting vein graft with a valve to reduce backpressure and attain tension free anastomosis, but we never needed a vein graft in our practice.
Alternative techniques:
Immediate Lymphatic reconstruction – In this proper end to end anastomosis is performed between the lymphatic and vein. The advantage is better quality of anastomosis and less backpressure because of smaller vein. The disadvantage is that microvascular anastomosis in the depth is very difficult, and it is time consuming.
Distal Lymphaticovenous anastomosis (Distal LVA) – Distal LVA is a technique in which Lymphaticovenous anastomosis are performed distally in the arm and not in axilla.
Advantages:
- Away from radiation zone
- Better lymphatic and vein match
- Backpressure in veins is less
- Easier superficial anastomosis
Disadvantages:
- Longer time
- Additional cost and expertise
- Additional scars
Future perspectives:
The results of LyMPHA have been promising. Several writers have reported their results using the method, and the majority of the published data demonstrate a reduction in the incidence of lymphedema. However, there are still questions about the long-term results, particularly following a newly published study that found no advantage with LyMPHA after four years of follow-up. There is an ongoing Randomised Control Trial examining the efficacy of LyMPHA, with interim data indicating a reduction in incidence. More results from large randomised trials are required before LyPMHA can be recommended as the standard of therapy for all patients receiving axillary clearing. There is also a need for research that compare the various modifications of LyMPHA and LyMPHA with alternative methods such as Distal LVA.
Short Notes in Plastic Surgery 