Advances in the prevention and treatment of breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies. FINDINGS: Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful. CONCLUSION: Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.

The Prevalence of the Axillo-Inguinal Lymphatic Pathway in Lymphedema of the Extremities and Potential Therapeutic Implications.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.

Manual lymphatic drainage treatment for lymphedema: a systematic review of the literature.

PURPOSE: Manual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This systematic review aims to examine the methodologies used in recent research and evaluate the effectiveness of MLD for those at-risk of or living with lymphedema. METHODS: The electronic databases Embase, PubMed, CINAHL Complete and Cochrane Central Register of Controlled Trials were searched using relevant terms. Studies comparing MLD with another intervention or control in patients at-risk of or with lymphedema were included. Studies were critically appraised with the PEDro scale. RESULTS: Seventeen studies with a total of 867 female and two male participants were included. Only studies examining breast cancer-related lymphedema were identified. Some studies reported positive effects of MLD on volume reduction, quality of life and symptom-related outcomes compared with other treatments, while other studies reported no additional benefit of MLD as a component of complex decongestive therapy. In patients at-risk, MLD was reported to reduce incidence of lymphedema in some studies, while others reported no such benefits. CONCLUSIONS: The reviewed articles reported conflicting findings and were often limited by methodological issues. This review highlights the need for further experimental studies on the effectiveness of MLD in lymphedema. IMPLICATIONS FOR CANCER SURVIVORS: There is some evidence that MLD in early stages following breast cancer surgery may help prevent progression to clinical lymphedema. MLD may also provide additional benefits in volume reduction for mild lymphedema. However, in moderate to severe lymphedema, MLD may not provide additional benefit when combined with complex decongestive therapy.

Implementing a prospective surveillance and early intervention model of care for breast cancer-related lymphedema into clinical practice: application of the RE-AIM framework.

PURPOSE: Chronic lymphedema following breast cancer (BC) affects individuals physically, functionally, psychologically, and financially. Despite national guidelines and evidence-based research supporting a prospective surveillance and early intervention model of care (PSM), bridging the gap between research and clinical practice has been difficult. METHOD: As part of an international randomized controlled trial (RCT), Australian women with BC from four hospitals were recruited, monitored for lymphedema at regular intervals over a 3-year period, and were provided a compression garment if intervention was triggered. The reach, effectiveness, adoption, implementation and maintenance (RE-AIM) evaluation framework was used retrospectively to assess a PSM at the individual and organizational level for those who had completed at least 2-year follow-up (N = 219) in the RCT. RESULTS: The application of the RE-AIM framework retrospectively demonstrated an extensive reach to patients across public and private settings; the effectiveness of prospective surveillance and early intervention was achieved through low progression rates to clinical lymphedema (1.8%), and all hospital sites initially approached adopted the research study. Key implementation strategies necessary for effectiveness of this model of care included education to health professionals and patients, staff acceptability, and development of a referral and care pathway. Maintenance dimensions were evaluated both at the individual level with 92-100% adherence rates for all nonoptional study appointments over the 2-year period, and at the organizational-level, PSM was sustained after recruitment ceased for the research study. CONCLUSION: The PSM for lymphedema in BC can be successfully implemented using the RE-AIM framework applied retrospectively. The implementation of the PSM used in the RCT has assisted in changing clinical practices and improving the quality and effectiveness of the health care system.

Personalizing Conservative Lymphedema Management Using Indocyanine Green-Guided Manual Lymphatic Drainage.

Background: The Australian Lymphoedema Education, Research and Treatment Program (ALERT) at Macquarie University in Sydney, Australia is one of the flagship programs of Australia's first fully integrated academic health sciences centre, MQ Health. The aim of this study was to describe our findings of compensatory drainage demonstrated by indocyanine green (ICG) lymphography in cancer-related upper and lower limb lymphedema and how this may be translated into clinical practice. Methods and Results: Retrospective data from 339 patients aged between 18 and 90 years with secondary cancer-related unilateral or bilateral lymphedema of the upper or lower limb who underwent ICG lymphography assessment at the ALERT clinic between February 2017 and March 2020 were analyzed. In patients with upper limb lymphedema, the ipsilateral axilla was the most frequent drainage region (74.9%), followed by clavicular (41.8%) and parasternal (11.3%). For patients with mild upper limb lymphedema, 94.4% drained to the ipsilateral axilla. No patients drained to the ipsilateral inguinal region. For lower limb lymphedema, drainage to the ipsilateral inguinal was most common (52.3%), followed by contralateral inguinal (30.7%), popliteal (26.1%), and gluteal (21.6%) regions. Three main patterns of superficial lymphatic compensation were identified based on which anatomical structure carried lymph fluid. Manual lymphatic drainage (MLD) was used to facilitate movement of the dye. A light/effleurage technique was sufficient to move the dye through patent lymphatic vessels; a slow and firmer technique was required to move the dye through areas of bridging dermal backflow. Conclusion: The introduction of ICG lymphography to our program and its use in guiding personalized conservative management plans, including facilitative MLD techniques, has translated into clinical practice and changed research and educational priorities within the ALERT program.

Assessing breast lymphoedema following breast cancer treatment using indocyanine green lymphography.

PURPOSE: Breast lymphoedema is a largely unrecognised survivorship issue for women following breast cancer treatment. While a few objective methods have previously been applied to assess breast lymphoedema, none are capable of imaging breast lymphatics or identifying lymphatic morphological changes indicative of breast lymphoedema. The purpose of this study was to determine if indocyanine green (ICG) lymphography, a validated assessment technique in breast cancer-related lymphoedema), can visualise breast lymphatics and identify breast lymphoedema. Additionally, ICG lymphography was utilised to investigate lymphatic drainage pathways of the affected breast following breast-conserving therapy. METHODS: Twenty female participants (10 breast lymphoedema and 10 healthy controls) were recruited for this pilot study. All underwent a medical history, physical breast assessment, tissue dielectric constant measures of breast water content, and ICG lymphography. RESULTS: ICG lymphography identified lymphatic morphological changes in all breast lymphoedema participants (dermal backflow patterns = 10, collateral lymphatic drainage = 9) and none in the control group. The dominant lymphatic drainage pathway to the ipsilateral axilla was observed in all control participants but in only four breast lymphoedema participants. Collateral drainage pathways in the breast lymphoedema group were to: parasternal (6/10); contralateral axilla (4/10); intercostal (3/10); and clavicular (2/10) regions. CONCLUSION: These findings suggest ICG lymphography, through the identification of morphological lymphatic changes, is a potential qualitative objective assessment technique for breast lymphoedema. Furthermore, in this group of breast lymphoedema patients it identified changes to the normal drainage pathway of the breast. Understanding these changes will have implications for clinical management.

A new indocyanine green fluorescence lymphography protocol for identification of the lymphatic drainage pathway for patients with breast cancer-related lymphoedema.

BACKGROUND: Breast cancer related lymphoedema (BCRL) is a common side effect of cancer treatment. Recently indocyanine green (ICG) fluorescent lymphography has become a popular method for imaging the lymphatics, however there are no standard protocols nor imaging criteria. We have developed a prospective protocol to aid in the diagnosis and therapeutic management of BCRL. METHODS: Lymphatic imaging procedures were conducted in three phases. Following initial observation of spontaneous movement of ICG in phase one, manual lymphatic drainage (MLD) massage was applied to facilitate ICG transit via the lymphatics in phase two. All imaging data was collected in phase three. Continuous lymphatic imaging of the upper limb was conducted for approximately an hour and lymphatic drainage pathways were determined. Correlations between the drainage pathway and MD Anderson Cancer Centre (MDACC) ICG lymphoedema stage were investigated. RESULTS: One hundred and three upper limbs with BCRL were assessed with this new protocol. Despite most of the patients having undergone axillary node dissection, the ipsilateral axilla drainage pathway was the most common (67% of upper limbs). We found drainage to the ipsilateral axilla decreased as MDACC stage increased. Our results suggest that the axillary pathway remained patent for over two-thirds of patients, rather than completely obstructed as conventionally thought to be the case for BCRL. CONCLUSIONS: We developed a new ICG lymphography protocol for diagnosing BCRL focusing on identification of an individual patient's lymphatic drainage pathway after lymph node surgery. The new ICG lymphography protocol will allow a personalised approach to manual lymphatic drainage massage and potentially surgery.