Surgical management of lymphedema: prophylactic and therapeutic operations.

Purpose of Review: Lymphedema is chronic limb swelling from lymphatic dysfunction and is currently incurable. Breast-cancer related lymphedema (BCRL) affects up to 5 million Americans and occurs in one-third of breast cancer survivors following axillary lymph node dissection. Compression remains the mainstay of therapy. Surgical management of BCRL includes excisional procedures to remove excess tissue and physiologic procedures to attempt improve fluid retention in the limb. The purpose of this review is to highlight surgical management strategies for preventing and treating breast cancer-related lymphedema. Recent findings: Immediate lymphatic reconstruction (ILR) is a microsurgical technique that anastomoses disrupted axillary lymphatic vessels to nearby veins at the time of axillary lymph node dissection (ALND) and has been reported to reduce lymphedema rates from 30% to 4-12%. Summary: Postsurgical lymphedema remains incurable. Surgical management of lymphedema includes excisional procedures and physiologic procedures using microsurgical technique. Immediate lymphatic reconstruction has emerged as a prophylactic strategy to prevent lymphedema in breast cancer patients.

Immediate lymphatic reconstruction: Lessons learned over eight years.

Immediate lymphatic reconstruction (ILR) is recognized as a surgical approach used to reduce the risk of developing secondary lymphedema, and evidence demonstrating the efficacy of ILR is favorable. Our Lymphatic Center has become a centralized location offering ILR for the risk-reduction in breast cancer-related lymphedema (BCRL) in New England. Over the course of our experience, we made several modifications and adapted our approach to enhance the operative success of this procedure. These include advancements in our use of indocyanine green (ICG) imaging to identify baseline lymphatic anatomical variation, utilization of fluorescein isothiocyanate for lymphatic vessel visualization, application of the lymphosome concept to guide arm injection sites, verification of anastomotic patency (using ICG), localization of reconstruction to guide radiation therapy, incorporation of intraoperative tools to facilitate better anatomic visualization of the axilla, and addition of a lower extremity vein graft to mitigate venous-related complications. Collecting information from each surgery in a standardized manner, including intraoperative lymphatic channel measurements, and deploying clips for possible future radiation exposure, enables future studies on ILR patient outcomes. In this contribution, we aimed to share our institutional modifications with the surgical community to facilitate further adoption, conversation, and advancement of ILR for the risk-reduction in BCRL.

Supermicrosurgery lymphaticovenous and lymphaticolymphatic anastomosis: Technical detail and short-term follow-up for immediate lymphatic reconstruction in breast cancer treatment-related lymphedema prevention.

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.

Review of treatment strategies after lymphadenectomy: From molecular therapeutics to immediate microsurgical lymphatic reconstruction.

OBJECTIVE: Lymphedema is a common complication of cancer treatment, such as lymphadenectomy and radiation therapy. It is a debilitating condition with pathologic tissue changes that hinder effective curative treatment and jeopardize patients' quality of life. Various attempts to prevent the development of lymphedema have been made, with improvements in the incidence of the pathology. However, it is still prevalent among survivors of cancer. In this paper, we review both molecular therapeutics and immediate surgical lymphatic reconstruction as treatment strategies after lymphadenectomy. Specifically, we discuss pro-lymphangiogenic molecules that have proved efficient in animal models of lymphedema and clinical trials, and review currently available microsurgical techniques of immediate lymphatic reconstruction. METHODS: A literature search was conducted in PubMed, Embase, Cochrane Library, and Google Scholar through May 2022. Searches were done separately for molecular therapeutics and microsurgical techniques for immediate lymphatic reconstruction. Search terms used for (1) non-surgical methods include 'lymphangiogenesis,' 'lymphedema,' 'growth factor,' and 'gene therapy.' Search terms used for (2) surgical methods include 'lymphedema,' 'lymph node excision,' 'lymphatic vessels,' 'primary prevention,' and 'microsurgery.' RESULTS: Various pro-lymphangiogenic factors with therapeutic potential include VEGF-C, VEGF-D, HGF, bFGF, PDGF, IGF, Retinoic acid, Ang-1, S1P, TLR4, and IL-8. Microsurgical lymphatic reconstruction for prevention of secondary lymphedema includes lymphovenous anastomosis, vascularized lymph node flap transfer, and lymph-interpositional flap transfer, with promising clinical outcomes. CONCLUSIONS: With growing knowledge of the lymphangiogenic pathway and lymphedema pathology and advances in microsurgical techniques to restore lymphatic channels, molecular and surgical approaches may represent a promising method for primary prevention of lymphedema.

"The Uncertainty Principle"- studying immediate lymphatic reconstruction impacts the natural history of breast cancer related lymphedema.

Breast cancer-related lymphedema (BCRL) following axillary lymph node dissection (ALND) is a life-altering sequela for patients and a challenging problem for their surgeons. In order to prevent BCRL, immediate lymphatic reconstruction (ILR) is a surgical technique that has been devised to restore lymphatic drainage to the operative limb. Although ILR is becoming popular in the literature, we have identified several challenges within our own ILR research, including a lack of a clear definition of lymphedema, a lack of common outcome measures and possible alteration of the natural history of lymphedema through early compression therapy. Given these challenges, we must move forward with caution, while striving to develop clear and universally agreed upon definitions and outcomes, so that we can advance the body of evidence in support of ILR.

United States insurance coverage of immediate lymphatic reconstruction.

INTRODUCTION: Immediate Lymphatic Reconstruction (ILR) is a prophylactic microsurgical lymphovenous bypass technique developed to prevent breast cancer related lymphedema (BCRL). We investigated current coverage policies for ILR among the top insurance providers in the United States and compared it to our institutional experience with obtaining coverage for ILR. METHODS: The study analyzed the publicly available ILR coverage statements for American insurers with the largest market share and enrollment per state to assess coverage status. Institutional ILR coverage was retrospectively analyzed using deidentified claims data and categorizing denials based on payer reason codes. RESULTS: Of the 63 insurance companies queried, 42.9% did not have any publicly available policies regarding ILR coverage. Of the companies with a public policy, 75.0% deny coverage for ILR. In our institutional experience, $170,071.80 was charged for ILR and $166 118.99 (97.7%) was denied by insurance. CONCLUSIONS: Over half of America's major insurance providers currently deny coverage for ILR, which is consistent with our institutional experience. Randomized trials to evaluate the efficacy of ILR are underway and focus should be shifted towards sharing high level evidence to increase insurance coverage for BCRL prevention.

Non-Linear Lymphatic Anatomy in Breast Cancer Patients Prior to Axillary Lymph Node Dissection: A Risk Factor For Lymphedema Development.

Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has become increasingly utilized for the prevention of breast cancer related lymphedema. Preoperative indocyanine green (ICG) lymphography is routinely performed prior to an ILR procedure to characterize baseline lymphatic anatomy of the upper extremity. While most patients have linear lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017-June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study's findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND.

Quantifying radiation in the axillary bed at the site of lymphedema surgical prevention.

PURPOSE: Immediate lymphatic reconstruction (ILR) is a procedure known to reduce the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). However, patients who receive adjuvant radiotherapy are at increased risk of lymphedema. The aim of this study was to quantify the extent of radiation at the site of surgical prevention. METHODS: We recently began deploying clips at the site of ILR to identify the site during radiation planning. A retrospective review was performed to identify breast cancer patients who underwent ILR with clip deployment and adjuvant radiation therapy from October 2020 to April 2022. Patients were excluded if they had not completed radiotherapy. The exposure and dose of radiation received by the site was determined and recorded. RESULTS: In a cohort of 11 patients, the site fell within the radiation field in 7 patients (64%) and received a median dose of 4280 cGy. Among these 7 patients, 3 had sites located within tissue considered at risk of oncologic recurrence and the remaining 4 sites received radiation from a tangential field treating the breast or chest wall. The median dose to the ILR site for the 4 patients whose sites were outside the radiation fields was 233 cGy. CONCLUSION: Our findings suggest that even when the site of surgical prevention was not within the targeted radiation field during treatment planning, it remains susceptible to radiation. Strategies for limiting radiation at this site are needed.

Mitigating Breast-Cancer-Related Lymphedema-A Calgary Program for Immediate Lymphatic Reconstruction (ILR).

With increasing breast cancer survival rates, one of our contemporary challenges is to improve the quality of life of survivors. Lymphedema affects quality of life on physical, psychological, social and economic levels; however, prevention of lymphedema lags behind the progress seen in other areas of survivorship such as breast reconstruction and fertility preservation. Immediate lymphatic reconstruction (ILR) is a proactive approach to try to prevent lymphedema. We describe in this article essential aspects of the elaboration of an ILR program. The Calgary experience is reviewed with specific focus on team building, technique, operating room logistics and patient follow-up, all viewed through research and education lenses.

Oncologic safety of axillary lymph node dissection with immediate lymphatic reconstruction.

PURPOSE: Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) can reduce the incidence of lymphedema in patients with breast cancer. The oncologic safety of ILR is unknown and has not been reported. The purpose of this study was to evaluate if ILR is associated with increased breast cancer recurrence rates. METHODS: Patients with breast cancer who underwent ALND with ILR from September 2016 to December 2020 were identified from a prospective institutional database. Patient demographics, tumor characteristics, and operative details were recorded. Follow-up included the development of local recurrence as well as distant metastasis. Oncologic outcomes were analyzed. RESULTS: A total of 137 patients underwent ALND with ILR. At cancer presentation, 122 patients (89%) had clinically node positive primary breast cancer, 10 patients (7.3%) had recurrent breast cancer involving the axillary lymph nodes, 3 patients (2.2%) had recurrent breast cancer involving both the breast and axillary nodes, and 2 patients (1.5%) presented with axillary disease/occult breast cancer. For surgical management, 103 patients (75.2%) underwent a mastectomy, 22 patients (16%) underwent lumpectomy and 12 patients (8.8%) had axillary surgery only. The ALND procedure, yielded a median of 15 lymph nodes pathologically identified (range 3-41). At a median follow-up of 32.9 months (range 6-63 months), 17 patients (12.4%) developed a local (n = 1) or distant recurrence (n = 16), however, no axillary recurrences were identified. CONCLUSION: Immediate lymphatic reconstruction in patients with breast cancer undergoing ALND is not associated with short term axillary recurrence and appears oncologically safe.

ICG lymphographic findings following immediate lymphatic reconstruction in breast cancer patients.

BACKGROUND: Immediate lymphatic reconstruction (ILR), performed at the time of axillary lymph node dissection (ALND), has demonstrated promising reductions in breast cancer-associated lymphedema. However, questions remain over the effects of adjuvant therapies on the continued patency of the lymphaticovenous anastomosis. Our study aimed to assess lymphographic outcomes, including ICG pattern and LVB patency, in patients at high risk for breast cancer-associated lymphedema following axillary ILR. METHODS: Baseline ICG lymphography studies performed during ILR of 15 patients were compared to repeat ICG studies obtained during second-stage breast reconstructive procedures to assess for changes in lymphatic flow patterns through the at-risk arm and transit into the axilla. RESULTS: All 15 patients in this study demonstrated linear lymphatic flow in baseline lymphography. Repeat lymphographic studies showed linear lymphatic transit in 12/15 patients. Of these 12 patients, 10 received chemotherapy, and all 12 received post-mastectomy radiation (PMRT). Dermal backflow patterns were recorded in 3/15 patients. All 3 patients received chemotherapy and 2/3 underwent PMRT. Additionally, repeat ICG studies of 7/12 lymphedema-free patients demonstrated clear visualization of linear ICG flow from the lymphatics of the arm into the axilla. CONCLUSION: We have demonstrated that ICG lymphography can be implemented as a postoperative tool to assess lymphatic function in patients who have undergone ILR in the axilla. Repeat ICG studies in the majority of patients demonstrated linear ICG flow similar to baseline studies. Additionally, ICG flow patterns through the axilla in repeat lymphography provided visual evidence supporting sustained LVB patency, despite axillary irradiation.

Immediate Lymphatic Reconstruction for Prevention of Secondary Lymphedema: A Meta-Analysis.

BACKGROUND: Secondary lymphedema remains one of the most notorious complications of axillary and pelvic lymph node surgery following mastectomy. There is a lack of high-level evidence found on the effectiveness of immediate lymphatic reconstruction (ILR) in preventing secondary lymphedema. This meta-analysis evaluates the outcomes of ILR for prevention of secondary lymphedema in patients undergoing different surgeries, and provides suggestions for lymphatic microsurgical preventive healing approach (LYMPHA). METHODS: A review of PubMed, Embase, and Web of Science was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. All English-language studies published from January 1, 2009 to June 1, 2020 were included. We excluded non-ILR interventions, literature reviews/letters/commentaries, and nonhuman or cadaver studies. A total of 789 patients that were enrolled in 13 studies were included in our one-arm meta-analysis. RESULTS: A total of 13 studies (n=789) met inclusion criteria: upper extremity ILR (n=665) and lower extremity ILR (n=124). The overall incidence of lymphedema for upper extremity ILR was 2.7% (95%CI: 1.1%-4.4%) and lower extremity ILR was 3.6% (95%CI: 0.3%-10.1%). For upper extremity ILR, the average follow-up time was 11.6 ± 7.8 months and the LE incidence appeared to be the highest approximately 1 to 2 years postoperation. CONCLUSIONS: Lymphedema is a common complication in cancer treatment. ILR, especially LYMPHA, may be an effective technique to facilitate lymphatic drainage at the time of the index procedure but future studies will be required to show its short-term efficacy and long-term outcomes.

Advances and current concepts in reconstructive surgery for breast cancer.

In this article, we report on recent advancements in reconstructive care of the breast cancer patient. New developments in sensate breast reconstruction to help address the problem of numbness after mastectomy have emerged and show promise. Methods to restore lymphatic physiologic flow after axillary lymphadenectomy using supermicrosurgical techniques have begun to show benefit by reducing the short-term incidence of breast cancer related lymphedema (BRCL). Breast implant safety has received significant recent attention and we explore the emergence of BIA-ALCL (Breast Implant Associated Anaplastic Large Cell Lymphoma) and its implications for the breast cancer patient and their multidisciplinary care team.