Abstract
Objective
We describe the feasibility and short-term outcome of our surgical technique to repair the lymph vessel disruption directly after axillary lymph node dissection during breast cancer surgery. This procedure is called immediate lymphatic reconstruction to prevent breast cancer treatment-related lymphedema (BCRL), which frequently occurs after axillary lymph node dissection. The surgical technique consisted of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis. We named the procedure lymphatic bypass supermicrosurgery (LBS).
Methods
This study used a retrospective cohort design of patients with breast cancer between May 2020 and February 2023. LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels lymphaticolymphatic anastomosis.
Results
A total of 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, and most had stage III breast cancer (n = 59 [72%]). LVA was the most common type of lymphatic bypass (94.6%). The median number of LVA was 1 (range, 1-4) and 1 (range, 1-3) for lymphaticolymphatic anastomosis. The median follow-up time was 12.5 months (range, 1-33 months). The 50 patients who had postoperative indocyanine green lymphography described arm dermal backflow stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. The proportion of BCRL was 11 (22%), and subclinical lymphedema was 19 (38%) in this period. Most cases were in stable subclinical lymphedema (10, 58.8%). The 1-year and 2-year BCRL rates were 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively.
Conclusions
Along with the emerging immediate lymphatic reconstruction, LBS is a feasible supermicrosurgery technique that may have a potential role in BCRL prevention. A randomized controlled study would confirm the effectiveness of the technique.
Keywords: Supermicrosurgery, Immediate lymphatic reconstruction, Breast cancer, Axillary lymph node dissection, Lymphedema
Article Highlights.
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Type of Research: Single-center retrospective cohort study.
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Key Findings: Immediate supermicrosurgery lymphatic reconstruction is technically feasible after axillary lymph node dissection, with the 1-year and 2-year breast cancer treatment-related lymphedema rate being 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively.
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Take Home Message: In patients with breast cancer who undergo axillary lymph node dissection, immediate lymphatic reconstruction with a supermicrosurgery technique is a feasible surgical technique for primary prevention of breast cancer treatment-related lymphedema, although comparison with the control group and long-term follow-up should be elaborated to confirm the effectiveness.
Immediate lymphatic reconstruction (ILR) is an emerging surgical approach for primary prevention of lymphedema after lymph node removal.1, 2, 3, 4 In breast cancer surgery, axillary lymph node dissection (ALND) is the main risk factor for breast cancer treatment-related lymphedema (BCRL), which causes significant morbidity in patients with breast cancer.5 Lymphedema is a progressive disease, and treatments have not achieved a real cure.6,7 It may be caused by the progressed lymph flow obstruction, which induces severe lymphosclerosis.8,9 Consequently, preventing obstruction is theoretically a better way than treating if the obstruction has occurred. This concept is known as ILR, which serves as primary prevention for secondary lymphedema.6,7
Microsurgical lymphaticovenous implantation, or the implantation technique, is commonly used for the primary prevention of BCRL1,2 Although the technique is reliable, it is considered a less physiological surgery because the lymph vessel wall and perilymphatic adipose tissue are introduced into a vein lumen, which is prone to obstruction10 and leads to anastomosis failure.11 Supermicrosurgery anastomosis, which consists of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis, is considered a more physiological surgery because of the feasibility of creating intima-to-intima coaptation.10 Hence, they should be considered an alternative technique to increase the effectiveness of ILR for the primary prevention of lymphedema.
The lymph-venous shunt microsurgical technique has been adopted widely for lymphedema treatment, with the implantation technique and LVA being the two common surgical techniques.12 Multiple studies have confirmed the effectiveness of LVA for curative treatment, especially in the early stage.13, 14, 15 Since then, the concept of lymphedema treatment has shifted from a curative to a preventive approach, with LVA as the preferred surgical technique. For instance, efferent lymphatic vessel-to-venous anastomosis is the implementation of LVA for lower extremity lymphedema prevention.16
We also think that primary prevention should be a better approach based on our previous study.17 In that study, we found that 56% of lymphedema cases were at an advanced stage, and LVA could not restore the affected arm's size fully.17 This result highlights the challenge of achieving a complete cure for lymphedema.6,18 So, we propose primary prevention is the better option and surgical innovation in this field should be developed.
Recent findings suggest the need to assess the effectiveness of the implantation technique for primary prevention of BCRL. Refinement of surgical techniques with supermicrosurgery anastomosis should be explored. To the bet of our knowledge, few studies have reported the intima-to-intima coaptation technique without the technical description and outcomes.19, 20, 21 Recently we reported a patient with breast cancer with preoperative lymphedema who underwent ILR with LVA. This immediate LVA was intended to cure or prevent lymphedema progression.22 In the current study, we describe further the feasibility of immediate supermicrosurgery LVA or lymphaticolymphatic anastomosis and the short-term result for primary prevention of BCRL. We named the technique lymphatic bypass supermicrosurgery (LBS).
Methods
Patients
Patients with breast cancer who presented to Dharmais Hospital National Cancer Center and Bogor City General Hospital between May 2020 and February 2023 were included in the study. The inclusion criteria were patients with breast cancer of any stage who underwent ALND. We excluded patients with preoperative subclinical or clinical upper extremity lymphedema based on abnormal indocyanine green (ICG) lymphography. Patients with a history of axillary surgeries or radiotherapy at the chest wall and axilla were also excluded. The study was approved by Dharmais Cancer Hospital - National Cancer Center ethical committee board (112/KEPK/V/2022), and informed consent was given by the patients.
Preoperative ICG lymphography
ICG lymphography screening was performed preoperatively to rule out lymphatic abnormalities. We used ICG dye made in our hospital (Premix Indocyanine Green USP 0.5%). A 2% lidocaine solution was applied to the injection sites, and 0.1 mL ICG dye was injected subcutaneously into the second and fourth web spaces of the hand and the ulnar border of the palmaris longus tendon at the level of the wrist joint. In a supine position, circumferential fluorescent images were taken with a near-infrared camera (Fluoro 4000 XL). Evaluation of the lymphatic system was done at 5 minutes (transient phase) and 2 hours (plateau phase) after injection to determine the arm dermal backflow (ADB) stage. The classification of ADB was as follows: stage 0, linear pattern only; stage 1, linear pattern and splash pattern; stage 2, linear pattern and stardust/diffuse pattern in one region; stage 3, linear pattern and stardust/diffuse pattern in two regions; stage 4, linear pattern and stardust/diffuse pattern in three regions; and stage 5, stardust and/or diffuse pattern.23 Only patients with normal ICG lymphography (stage 0) proceeded to surgery.
Surgical technique
The patient was placed supine with the arm in an abduction position. After anesthesia, ICG dye was given to the injection sites at hand before the incision (Fig 1). The mastectomy incision was created with an oblique design, allowing better access to axillary space for ALND and lymphatic bypass (Fig 1). A lower axillary hairline incision extended to the lateral inframammary fold was the approach to the axillary space in breast-conserving surgery (Fig 1).
Fig 1.
Indocyanine green (ICG) and axillary lymph node dissection (ALND) procedure. (I) The injection site for ICG: (A) Second and (B) fourth web spaces of the hand and (C) the ulnar border of the palmaris longus tendon at the level of the wrist joint. (II) Incision design for axillary approach, (A) in mastectomy and (B) breast-conserving surgery. (III) Direction and the lower limit of the recipient vein dissection. (A) The distal to proximal dissection of the lateral thoracic vein (red vessel), (B) proximal to distal dissection of the thoracoepigastric vein (green vessel) at the distal part of the axillary space, (C) inframammary line as the lower limit of dissection. (IV) The preserved veins at the end of ALND. CX, circumflex scapular vein; ICG, indocyanine green; LTV, Lateral thoracic vein; TE, thoracoepigastric vein; SV, superficial vein of axillary base; TD, thoracodorsal.
Recipient vein preservation and axillary lymph nodes dissection
The approach to the axillary space was performed after breast cancer removal (mastectomy or breast-conserving surgery). The first step to identifying the recipient's veins was looking at the distal lateral chest wall to find the lateral thoracic vein. Once located, the dissection starts from distal to proximal until reaching the axillary vein. The dissection proceeded to find the thoracoepigastric vein at the distal part of the axillary space. If the lateral thoracic or thoracoepigastric vein could not be found distally, we went proximally to find the veins that originally came from the axillary vein and dissected them distally. The lower border of the distal dissection was the inferior inframammary line or until the length was sufficient to reach the lateral axillary region where the afferent lymph vessel is usually found. Fig 1 shows the direction and lower limit of the dissection.
ALND was started after either one or both vessels could be preserved. If the vessels were not identified, ALND was still performed, preserving any identified vein branches from the thoracodorsal, circumflex scapular, and superficial vein of the axillary base. By the end of ALND, the following veins should be preserved (Fig 1): (1) lateral thoracic and thoracoepigastric veins (commonly used) and (2) branches from the thoracodorsal vein, circumflex scapular vein, and superficial vein of the axillary base (less common).24 The vein should be dissected as distal as possible for several reasons: (1) to reach the lateral part of the axillary space for a tension-free anastomosis; (2) including several vein valves to prevent or reduce venous reflux; and (3) incorporating vein side branches to achieve an equal vein-to-lymph diameter for anastomosis.
Standard ALND levels I, II, and III (if necessary) were used. When there was no extensive metastatic lymph node involvement near the axillary vein, the upper boundary dissection was limited to the axillary vein's inferior surface to prevent disruption of the superiorly located lymph vessels.25
Lymphatic vessels and veins preparation
Identification of the afferent and efferent lymphatic vessels was assisted by a microscope with ICG lymphography navigation (Zeiss Kinevo 900; Zeiss, Jena, Germany) or by a hand-held near-infrared camera when using a standard microscope (Fig 2). The next step was the evaluation of venous reflux. If there was any reflux, external valvuloplasty was created to prevent or decrease venous reflux.26,27 The lymph vessels and veins were prepared by cutting the distal stump to get a healthy margin. For our study purpose, the distal stump was sent for a histopathology examination to rule out cancer deposits.
Fig 2.
Identification of types of lymphatic vessels, anastomosis, and dermal backflow pattern. (I) Identification of afferent lymphatic vessels with (A) microscope-integrated ICG lymphography and (B) external near-infrared camera. (∗) Afferent lymphatic vessels. (II) Types of anastomosis. (A) End-to-end LVA with small-caliber side branches vein. (B) End-to-side LVA. (C) Funnelization. (D) Buffalo skull shape. (E) Y-Shaped venoplasty. (F) Lymphaticolymphatic anastomosis. (G) Vein graft for lymphaticolymphatic anastomosis (upper) or LVA (lower). (III) Clinical outcomes of the patients. (A) A patient without BCRL showed a linear pattern. (B) Subclinical lymphedema with splash pattern. (C) BCRL patient, which showed a stardust diffuse pattern. BCRL, breast cancer treatment-related lymphedema; ICG, indocyanine green; LVA, lymphaticovenous anastomosis.
LBS
LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels (lymphaticolymphatic anastomosis.). We chose the small caliber side branches vein as our first option for LVA in an end-to-end fashion. When only a large caliber vein was available, end-to-side or modified end-to-end anastomoses such as funnelization,28 buffalo skull-shape,29 and Y-shape venoplasty30 (Fig 2) can be selected. Lymphaticolymphatic anastomosis was also performed when the efferent lymph vessels were close to the afferent vessels. If the distance between vessels was too far, a vein graft from the remaining veins at the axillary space was used for LVA or lymphaticolymphatic anastomosis.
The anastomosis patency was evaluated by observing minimal one of the following signs: (1) ICG flow from the afferent lymph vessels to the veins or from the afferent to efferent lymphatic vessels; (2) direct visualization of spontaneous lymph flow in the veins or efferent lymphatic vessels; or (3) veins or efferent lymph vessel dilatation. We classified the type of anastomosis flow into normal, backflow, and mixed. The normal type is defined as when the lymph fluid drains to the vein without blood reflux, and the backflow type is when blood reflux to the lymph vessel or lymph fluid is blocked at the anastomosis site. If multiple anastomoses were performed and had normal and backflow types, it is classified as the mixed type. The complete surgical procedure is described in the Supplementary Video.
At the end of the procedure, we use the gravity effect to decrease venous reflux by positioning the veins lower than the lymph vessels. Then, secure the anastomoses by suturing the fat tissue surrounding the recipient vessels to the nearby tissue. Lastly, we checked the anastomosis position in shoulder adduction to prevent kinking. LBS was facilitated with supermicrosurgery instruments (EMI Factory, Nagano, Japan) and 11.0 and 12.0 needles (Crownjun, Tokyo, Japan).
Postoperative treatment
No postoperative compression garments were applied, and regular physiotherapy was performed to facilitate the upper limb and shoulder range of motion without any attempt to perform manual massage. When the general and local conditions were good, we discharged the patients with the drain.
Follow-up
Postoperative follow-up was performed every 3 months during the first year and every 6 months during the second year with ICG lymphography. BCRL was defined when at least ADB stage 2 was presented at ICG lymphography.31 On the contrary, ADB stage 1 was defined as subclinical lymphedema (SCL). Physiotherapy management was started once BCRL developed. ICG lymphography follow-up was scheduled as mentioned above for the patients without BCRL.
Statistical analyses
This study used a retrospective cohort design from medical records. Numeric data distribution was analyzed using the Kolmogorov-Smirnov test. Normally distributed data are presented as mean ± standard deviation, and non-normally distributed data are shown as median (range). The Kaplan-Meier method was used to produce a cumulative incidence curve from initial breast cancer surgery to the occurrence of BCRL in the cohort by predicting survival function estimates. Data analysis presented with a 95% confidence interval. Statistical Package for the Social Sciences (SPSS) version 29.0 was used to analyze all data (SPSS, Inc., College Station, TX).
Results
During the study period, there were 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, with a mean body mass index of 25.8 ± 4.6 kg/m2. Stage III breast cancer was found commonly (n =59 [72.0%]). Fifty-eight patients (70.7%) had adjuvant locoregional radiotherapy, and 75 patients (91.5%) received chemotherapy. The median number of axillary lymph nodes was 13 (range, 6-31), with the median positive nodes of 3 (range, 1-22). Table I describes the patient characteristics.
Table I.
Patient characteristic (n = 82)
| Variables | No. (%), mean ± standard deviation, or median (range) |
|---|---|
| Age, years | 50 ± 12 |
| BMI, kg/m2 | 25.8 ± 4.6 |
| Breast cancer stage | |
| II | 11 (13.4) |
| III | 59 (72) |
| IV | 12 (14.6) |
| Radiotherapy | |
| Yes | 58 (70.7) |
| No | 24 (29.3) |
| Chemotherapy | |
| Yes | 75 (91.5) |
| No | 7 (8.5) |
| Number of nodes, (n = 76) | 13 (6-31) |
| Number of positive nodes, (n = 76) | 3 (1-22) |
| Recipient vein (n = 87) | |
| Lateral thoracic | 66 (75.9) |
| Superficial vein of the axillary base | 12 (13.8) |
| Thoracodorsal branch | 6 (6.9) |
| Thoracoepigastric | 3 (3.4) |
| Lymph vessel diameter, mm (n = 130) | 0.5 (0.3-1.8) |
| Vein diameter, mm (n = 123) | 0.8 (0.3-2.2) |
BMI, body mass index.
All afferent lymph vessels and recipient veins could be identified. The lateral thoracic vein was constantly found during ALND, but was only used for the recipient's veins in 66 cases (75.9%); the rest were infiltrated by the tumor. The median number of suitable lymph vessels and veins diameter for anastomosis was 0.5 mm (range, 0.3-1.8 mm) and 0.8 mm (range, 0.3-2.2 mm), respectively. Table I provides a description of the lymph vessels and recipient's vein characteristics. The type, length of anastomosis, and hospitalization are shown in Table II. Of the 130 anastomoses, LVA was the most common type of lymphatic bypass (94.6%), and lymphaticolymphatic anastomosis was feasible in 7 cases (5.3%). Analysis of LVA showed a median of 1 (range, 1-4) and a mean of 1.68 ± 0.9, while lymphaticolymphatic anastomosis resulted in a median of 1 (range, 1-3) and a mean of 1.66 ± 0.8. End-to-end anastomosis accounted for 127 cases (97.7%), and some of them used a modification of buffalo skull-shape anastomosis in 6 cases (27.3%), funnelization in 8 cases (36.4%), Y-shape venoplasty in 2 cases (9%), and vein graft in 6 cases (27.3%). Valvuloplasty was indicated in 8 cases (6.2%) owing to venous reflux. The type of anastomosis flow was demonstrated to have normal flow in 55 (67.1%), backflow type in 16 (19.5%), and mixed type in 11 (13.4%) cases. The median time to perform per LVA was 60 minutes (range, 17-290 minutes), and the mean time for lymphaticolymphatic anastomosis was 66 ± 32 minutes. The median length of surgery was 270 minutes (range, 145-705 minutes), and all patients were discharged from the hospital within a median postoperative time of 2 days (range, 1-3 days). No surgical complications were identified during the follow-up period. Based on histopathology examination, we found no metastasis in the afferent lymph vessels.
Table II.
Anastomosis, hospitalization, arm dermal backflow (ADB) stage and lymphedema status
| Variables | No. (%), median (range), or mean ± standard deviation | 95% CI |
|---|---|---|
| Types of lymphatic reconstruction (n = 130) | ||
| LVA | 123 (94.6) | |
| Lymphaticolymphatic anastomosis | 7 (5.3) | |
| No. of LVA | 1 (1-4) | |
| No. of LVA | 1.68 ± 0.9 | |
| No. of lymphaticolymphatic anastomosis | 1 (1-3) | |
| No. of lymphaticolymphatic anastomosis | 1.66 ± 0.8 | |
| Type of anastomosis | ||
| ETE | 127 (97.7) | |
| ETS | 3 (2.3) | |
| Subtype anastomosis (n = 22) | ||
| Buffalo skull-shape | 6 (27.3) | |
| Funnelization | 8 (36.4) | |
| Y-shape venoplasty | 2 (9) | |
| Vein graft | 6 (27.3) | |
| Valvulopasty (n = 130) | ||
| Yes | 8 (6.2) | |
| No | 122 (93.8) | |
| Types of anastomosis flow (n = 82) | ||
| Normal | 55 (67.1) | |
| Mix | 11 (13.4) | |
| Backflow | 16 (19.5) | |
| Time per LVA, minutes | 60 (17-290) | |
| Time per lymphaticolymphatic anastomosis, minutes | 66 ± 32 | |
| Time of surgery, minutes | 270 (145-705) | |
| Length of stay, days (n = 39) | 2 (1-3) | |
| Afferent lymph vessel metastasis (n = 112) | 0 (0) | |
| Follow-up ICG, months | 12.5 (1-33) | 11.1-15.5 |
| ADB stage postoperative | ||
| 0 | 20 (40) | 28-54 |
| 1 | 19 (38) | 22-50 |
| 2 | 2 (4) | 0-12 |
| 3 | 9 (18) | 8-28 |
| BCRL status (n = 50) | ||
| No | 20 (40) | 26-54 |
| SCL | 19 (38) | 22-50 |
| BCRL | 11 (22) | 12-34 |
| SCL progression status (n = 50) | ||
| Improvement | 4 (23.5) | 5.9-47.1 |
| Stable | 10 (58.8) | 35.3-82.4 |
| Progressed | 3 (17.7) | 0-35.3 |
BCRL, breast cancer-related lymphedema; CI, confidence interval; ETE, end to end; ETS, end to side; ICG, indocyanine green; SCL, subclinical lymphedema; LVA, lymphaticovenular anastomosis.
As presented in Table II, the median follow-up time was 12.5 months (range, 1-33 months). The 50 patients that had postoperative ICG lymphography described ADB stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. Types of dermal backflow after the surgery were presented in Fig 2. The proportion of BCRL was 11 (22%), and SCL was 19 (38%) in this period. We also looked at the SCL progression status; interestingly, most cases were in stable SCL (10, 58.8%). Improvement of SCL into normal condition was observed in 4 (23.5%) cases, stable in 10 (58.8%), and progressing in 3 (17.7%) cases. With these findings, the 1- and 2-year BCRL rates were 14% (95% CI, 4%-23.9%) and 22% (95% CI, 10.1%-33.9%), respectively. Fig 3 shows the Kaplan-Meier curve of the BCRL rate.
Fig 3.
Kaplan-Meier curve of the BCRL rate. BCRL, breast cancer treatment-related lymphedema.
Discussion
The combination of sentinel lymph node biopsy (SLNB), modern systemic therapy, and adjuvant radiotherapy has replaced ALND, especially for early-stage breast cancer.32 Research on the axillary reverse mapping (ARM) technique to reduce arm lymphedema risk is ongoing.33,34 However, ALND remains relevant, particularly in cases of locally advanced breast cancer with a substantial nodal tumor burden.35
SLNB and ARM can help to prevent arm lymphatic vessel injury in early breast cancer. However, nearly 90% of our cases were at advanced stages with significant axillary nodal metastasis (median of three positive nodes). In these patients, avoiding arm lymphatic vessel injury with SLNB or ARM might not be safe oncologically. For this stage, ALND, followed by radiotherapy, remains the most effective treatment, despite the increased risk of BCRL.36, 37, 38
ALND generates lymph vessel disruption and lymph fluid obstruction, which leads to upper arm lymphedema if the rerouting mechanism and lymphangiogenesis do not work.39 Once the obstruction progresses, the lymph vessels will undergo pathological changes from mild to severe lymphosclerosis, which increases the severity of lymphedema and treatment difficulty.8,9 Therefore, preventing obstruction by direct repair of the disrupted lymph vessels after ALND may prevent BCRL. Based on this notion, the surgical concept for lymphedema has shifted from curative to preventive intention.6,7 Currently, ILR has become a promising surgery for primary prevention of BCRL. It is facilitated by the advancement of supermicrosurgery techniques and instruments.23
In the past, surgeons might not have been able to visualize lymphatic collecting vessels during surgery owing to their small diameter, ranging from 0.15 to 0.50 mm.40 However, with the emerging supermicrosurgery techniques and instruments,23 surgeons can now visualize and repair damaged lymph vessels during axillary surgery.
LBS is an alternative to the implantation technique for preventive surgery. LBS facilitates bypassing afferent lymph vessels to the vein or efferent lymph vessels. In our study, LVA is more common than lymphaticolymphatic anastomosis. LVA could be performed comfortably when lymph vessels had suitable diameters relative to the recipient's veins (0.5 and 0.8 mm, respectively). When the afferent and efferent lymphatic vessels were in close proximity in the lateral section of the pectoralis minor muscle, it was also possible to perform lymphaticolymphatic anastomosis.
We must address several critical technical aspects. First, we look for small caliber side branch veins of similar vessel sizes. In cases without tumor infiltration, we dissect the lateral thoracic or thoracoepigastric vein distally to include these small caliber side branches. If they cannot be identified or require resection, alternative veins can be used.41 Second, lymph vessels should be anastomosed to veins without venous reflux. If the veins' valves are not competent, valvuloplasty is essential to prevent or minimize venous reflux.26,27
Venous reflux increases the risk of anastomosis failure,27,30 because it causes excessive blood contact with the lymph fluid that leads to thrombosis.42 Creating a competent valve would prevent reflux. Various open and closed valvuloplasties have been described to treat chronic venous insufficiency.43 The closed technique, that is, transcommisural external valvuloplasty, has been studied to be effective in preventing venous reflux during LVA. Moreover, venoplasty generates a better lymphedema index reduction compared with the control group after LVA.27,30 Therefore when the reflux was positive before the anastomosis, we performed transcommisural external valvuloplasty to prevent anastomosis failure.
Third, the choice of anastomosis type and number should be based on the accessibility and positioning of lymphatic vessels and veins. Our preference is for end-to-end anastomosis and multiple LVAs to enhance the lymphatic pressure gradient. In cases where suitable vessel sizes are unavailable, we consider end-to-side or modified end-to-end anastomosis methods, such as funnelization, buffalo skull head, and venous branch plasty.28,29,44 When performing multiple anastomoses is challenging, we prioritize the largest lymph vessel with a diameter of >0.3 mm for LVA to ensure higher lymphatic pressure and effective lymph flow.45 Fourth, lymphaticolymphatic anastomosis can be conducted when the afferent and efferent lymph vessels are within level I axillary space; it becomes complex if the efferent lymph vessel is located below (level II) or medially (level III) to the pectoralis minor. Fifth, if there is a considerable distance between the vessels, a vein graft is used to facilitate the anastomosis.
The median bypass time in our study was 60 minutes, which was longer compared with other studies using the implantation technique (typically 15-45 minutes).4,6 However, we achieved a median hospital discharge within 2 days after surgery without notable complications. Improving the surgical learning curve is essential to decreasing the operation duration. Despite the added time needed for LBS, it seems a worthwhile addition if its effectiveness in preventing BCRL is validated.
Bypassing the afferent lymph vessel to the vein might raise oncological concerns. Nevertheless, our research did not reveal cancer deposits at the afferent lymph vessels, and no studies to date have reported adverse oncological events after ILR.3,4,7,46 We consider ILR to be oncologically safe and would not increase the risk of cancer progression.
Data from a cohort study indicated that approximately 30% of patients with lymphatic abnormalities (like stardust or no flow pattern) postaxillary surgery could see an improvement to a normal or lower ADB stage through conservative treatment.31 Patient compliance with compression therapy is crucial for successful conservative management,47,48 which can be challenging, especially in Indonesia owing to limited lymphedema physiotherapy units and a lack of insurance coverage for compression garments. With LBS, more than one-half of patients with SCL did not experience progression, and even 23% showed improvement to normal lymph flow.
The 2-year BCRL rate in our study is 22%. Compared with other studies without ILR, the rate of developing lymphedema in our study was lower than that found by Monleon et al49 (34.6%) and Hahamof et al50 (40%). Moreover, the advantage of ILR was shown by a lower probability of BCRL with the implantation technique (12%) than the group with only ALND (40%) in Hahamof et al50 studies. Although our results do not have a control arm and cannot be compared equally with other studies owing to different methods of BCRL diagnosis and surgical intervention, LBS might be considered as a part of preventive treatment.
Our study has several limitations. First, the limited number of patients affects the external validity of the results. Second, the relatively short follow-up period (12.5 months). It is ideal to observe BCRL within 12 to 24 months after ALND.38 Third, there was no blinding during the evaluation of ICG lymphography, which could introduce measurement bias in BCRL diagnosis. Fourth, the efficacy of LBS in preventing BCRL cannot be confirmed because there was no control group in this study. However, despite these limitations, we believe LBS has the potential to be a part of immediate BCRL prevention. Currently, we are conducting a randomized clinical trial to assess the effectiveness of LBS, registered under the title 'The Effectiveness of Lymphatic Bypass Supermicrosurgery (ELYBS)' with identifier number NCT05682885 on Clinicaltrial.gov.
Conclusions
LBS represents a feasible supermicrosurgery technique for primary prevention of BCRL. The 2-year BCRL rate is lower compared with other studies. However, it requires verification through long-term follow-up with a sufficient number of cases. A well-designed randomized controlled trial is essential to confirm the efficacy of LBS and other associated outcomes for primary prevention of BCRL.
Author Contributions
Conception and design: BB, TY, SP, SH, PY, PP, KH, AT
Analysis and interpretation: BB, TY, SP, KH
Data collection: BB
Writing the article: BB, TY
Critical revision of the article: BB, TY, SP, SH, PY, PP, KH, AT
Final approval of the article: BB, TY, SP, SH, PY, PP, KH, AT
Statistical analysis: BB, TY, KH
Obtained funding: BB
Overall responsibility: TY
Disclosures
None.
Acknowledgments
The authors thank Faza Soelaeman, MD, and Adhitya Bayu Perdana for their encouragement and support on this project, especially for manuscript preparation.
Footnotes
Funded by Dharmais Cancer Hospital – National Cancer Center Indonesia. Dharmais Cancer Hospital – National Cancer Center Indonesia had no involvement in the study design or collection, analysis, and interpretation of data. Dharmais Cancer Hospital – National Cancer Center Indonesia was not involved in the decision to submit the manuscript for publication.
The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.
Supplementary Data
Lymphatic bypass supermicrosurgery.
References
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Supplementary Materials
Lymphatic bypass supermicrosurgery.