Modern approaches to lymphatic surgery: a narrative review.

BACKGROUND AND OBJECTIVE: Lymphedema is a chronic, progressive disease secondary to damage to the lymphatic system that results in interstitial fluid accumulation, fat deposition and inflammation. Lymphatic surgery includes a spectrum of procedures aimed to treat these sequelae of lymphedema as well as decrease the risk of lymphedema if performed as prophylactic surgery. We reviewed the literature regarding current surgical treatment options for lymphedema, imaging approaches, and directions the field may head towards both in treatment access and techniques. METHODS: We systematically reviewed PubMed, Embase, and Cochrane Library databases to identify approaches to surgical management of lymphedema, including physiologic and reductive methods, as well as challenges that lymphedema patients face for adequate access and insurance coverage to surgical treatment options. KEY CONTENT AND FINDINGS: Lymphatic surgery can be broadly categorized as physiologic or reductive. Physiologic lymphatic surgery functions to decrease the fluid burden associated with lymphedema and includes lymphovenous bypass as well as vascularized lymph node transplant procedures. Reductive lymphatic surgery reduces the fibroadipose component of lymphedema and include suction lipectomy and excisional procedures. Advances in imaging technology as well as supermicrosurgical techniques have allowed for reproducible, positive clinical outcomes after lymphatic procedures. Access to care and coverage of procedures are persistent challenges in the field, though increasing adoption and research have led to important strides forward to providing patients with this care. CONCLUSIONS: Lymphatic surgery can improve symptoms and quality of life for lymphedema patients. A clear understanding of the predominant pathology in a patient (i.e., fluid dominant vs. fat dominant) can help guide counseling and surgical management options for patients. Despite the established benefits for patients, equitable access and insurance coverage for lymphedema surgery are still required

Indocyanine Green (ICG) Lymphography Is Superior to Lymphoscintigraphy for Diagnostic Imaging of Early Lymphedema of the Upper Limbs

BACKGROUND: Secondary lymphedema causes swelling in limbs due to lymph retention following lymph node dissection in cancer therapy. Initiation of treatment soon after appearance of edema is very important, but there is no method for early diagnosis of lymphedema. In this study, we compared the utility of four diagnostic imaging methods: magnetic resonance imaging (MRI), computed tomography (CT), lymphoscintigraphy, and Indocyanine Green (ICG) lymphography. PATIENTS AND METHODS: Between April 2010 and November 2011, we examined 21 female patients (42 arms) with unilateral mild upper limb lymphedema using the four methods. The mean age of the patients was 60.4 years old (35-81 years old). Biopsies of skin and collecting lymphatic vessels were performed in 7 patients who underwent lymphaticovenous anastomosis. RESULTS: The specificity was 1 for all four methods. The sensitivity was 1 in ICG lymphography and MRI, 0.62 in lymphoscintigraphy, and 0.33 in CT. These results show that MRI and ICG lymphography are superior to lymphoscintigraphy or CT for diagnosis of lymphedema. In some cases, biopsy findings suggested abnormalities in skin and lymphatic vessels for which lymphoscintigraphy showed no abnormal findings. ICG lymphography showed a dermal backflow pattern in these cases. CONCLUSIONS: Our findings suggest the importance of dual diagnosis by examination of the lymphatic system using ICG lymphography and evaluation of edema in subcutaneous fat tissue using MRI

The LYMPH trial: Comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - Study protocol of a pragmatic randomised international multicentre superiority trial

INTRODUCTION: Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment. METHODS AND ANALYSIS: The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will be evaluated in routine practice across the globe. Patients with BCRL will be randomly allocated to either surgical or conservative therapy. The primary end point of this trial is the patient-reported quality of life (QoL) outcome \u27lymphoedema-specific QoL\u27, which will be assessed 15 months after randomisation. Secondary end points are further patient-reported outcomes (PROs), arm volume measurements, economic evaluations and imaging at different time points. A long-term follow-up will be conducted up to 10 years after randomisation. A total of 280 patients will be recruited in over 20 sites worldwide. ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki and the International Council for Harmonisation-Good Clinical Practice (ICH-GCP) E6 guideline. Ethical approval has been obtained by the lead ethics committee \u27Ethikkommission Nordwest- und Zentralschweiz\u27 (2023-00733, 22 May 2023). Ethical approval from local authorities will be sought for all participating sites. Regardless of outcomes, the findings will be published in a peer-reviewed medical journal. Metadata detailing the dataset\u27s type, size and content will be made available, along with the full study protocol and case report forms, in public repositories in compliance with the Findability, Accessibility, Interoperability and Reuse principles. TRIAL REGISTRATION NUMBER: NCT05890677

Imaging of the Lymphatic Vessels for Surgical Planning:A Systematic Review

Background Secondary lymphedema is a common complication after surgical or radiotherapeutic cancer treatment. (Micro) surgical intervention such as lymphovenous bypass and vascularized lymph node transfer is a possible solution in patients who are refractory to conventional treatment. Adequate imaging is needed to identify functional lymphatic vessels and nearby veins for surgical planning. Methods A systematic literature search of the Embase, MEDLINE ALL via Ovid, Web of Science Core Collection and Cochrane CENTRAL Register of Trials databases was conducted in February 2022. Studies reporting on lymphatic vessel detection in healthy subjects or secondary lymphedema of the limbs or head and neck were analyzed. Results Overall, 129 lymphatic vessel imaging studies were included, and six imaging modalities were identified. The aim of the studies was diagnosis, severity staging, and/or surgical planning. Conclusion Due to its utility in surgical planning, near-infrared fluorescence lymphangiography (NIRF-L) has gained prominence in recent years relative to lymphoscintigraphy, the current gold standard for diagnosis and severity staging. Magnetic resonance lymphography (MRL) gives three-dimensional detailed information on the location of both lymphatic vessels and veins and the extent of fat hypertrophy; however, MRL is less practical for routine presurgical implementation due to its limited availability and high cost. High frequency ultrasound imaging can provide high resolution imaging of lymphatic vessels but is highly operator-dependent and accurate identification of lymphatic vessels is difficult. Finally, photoacoustic imaging (PAI) is a novel technique for visualization of functional lymphatic vessels and veins. More evidence is needed to evaluate the utility of PAI in surgical planning.</p

The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial

INTRODUCTION Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment. METHODS AND ANALYSIS The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will be evaluated in routine practice across the globe. Patients with BCRL will be randomly allocated to either surgical or conservative therapy. The primary end point of this trial is the patient-reported quality of life (QoL) outcome 'lymphoedema-specific QoL', which will be assessed 15 months after randomisation. Secondary end points are further patient-reported outcomes (PROs), arm volume measurements, economic evaluations and imaging at different time points. A long-term follow-up will be conducted up to 10 years after randomisation. A total of 280 patients will be recruited in over 20 sites worldwide. ETHICS AND DISSEMINATION This study will be conducted in compliance with the Declaration of Helsinki and the International Council for Harmonisation-Good Clinical Practice (ICH-GCP) E6 guideline. Ethical approval has been obtained by the lead ethics committee 'Ethikkommission Nordwest- und Zentralschweiz' (2023-00733, 22 May 2023). Ethical approval from local authorities will be sought for all participating sites. Regardless of outcomes, the findings will be published in a peer-reviewed medical journal. Metadata detailing the dataset's type, size and content will be made available, along with the full study protocol and case report forms, in public repositories in compliance with the Findability, Accessibility, Interoperability and Reuse principles. TRIAL REGISTRATION NUMBER NCT05890677

HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema

Introduction Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. Methods and analysis This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. Ethics and dissemination The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020

Surgical treatment algorithm for breast cancer lymphedema—a systematic review

Background: Various surgical treatments are increasingly adopted and gaining popularity for lymphedema treatment. However, challenges persist in selecting appropriate treatment modalities targeted for individual patients and achieving consensus on choice of treatment as well as outcomes. The systematic review aimed to create a treatment algorithm incorporating the latest scientific knowledge, to provide healthcare professionals and patients with a tool for informed decision-making, when selecting between treatments or combining them in a relevant manner. This systematic review evaluated and synthesized the evidence on the effectiveness of three surgical treatments for breast cancer-related lymphedema (BCRL): lymphovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and liposuction. Methods: We conducted a systematic search of electronic databases on 18 June 2023, including Medline, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.org. Eligible studies were randomized controlled trials, non-randomized comparative studies, and observational studies that assessed the outcomes of LVA, VLNT, or liposuction in managing BCRL. The primary results of interest were changes in arm volume, lymphatic flow, and quality of life. Two independent reviewers performed the study selection and data extraction. Following this, we systematically reviewed and conducted a risk of bias assessment. Results were qualitatively presented, and a treatment algorithm was developed based on the available data. Results: We identified 16,593 papers, after removal of duplicates. Following assessment of studies, 73 articles met the inclusion criteria, including 2,373 patients. We were not able to conduct a meta-analysis due to considerable heterogeneity in the methodologies and outcome measures across the studies. Liposuction appears effective for patients presenting with non-pitting lymphedema. LVA indicates variable success rate, with some evidence indicating a reduction in limb volume and symptomatic relief amongst early stages of lymphedema. VLNT showed promising results for limb volume reduction and symptom improvement in patients presenting with mild and moderate lymphedema. Conclusions: Liposuction, LVA, and VLNT seem to be effective treatments for BCRL, when targeted for the appropriate patient. Well-conducted high evidence clinical studies in the field are still lacking to uncover the efficacy of surgical treatment for BCRL.</p

The Impact of Economic Evaluation on Lymphoedema Services Research in Wales

Lymphoedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. There are two types of lymphoedema, primary and secondary lymphoedema, which have different causes. This thesis comprises of eight papers, a research body that examines the impact of economic evaluations on lymphoedema research and practice in Wales via the Lymphoedema Wales clinical service. These research papers present a body of evidence of the demonstrably positive impact that economic evaluation research is having on people living with lymphoedema in Wales. This evidence has enabled WG to permanently allocate the funds needed for both the LVA and OGEP programme. This has enabled LW to continue to implement their interventions and innovative practice. This has also given LW the time and resources to bring their experiences and evidence of best practice to other health practitioners

Prevalence of lower extremity edema following inguinal lymphadenectomy: A systematic review and meta-analysis

Background: Lower extremity lymphedema (LEL) can develop because of inguinal lymph node dissection in the treatment of gynecologic, genitourinary, and dermatological malignancies. To optimize patient counseling and patient selection for microsurgical interventions aimed at preventing or treating LEL, its prevalence and associated patient characteristics must be accurately documented. This systematic review and meta-analysis provides a comprehensive overview of literature on the reported prevalence of LEL in patients undergoing inguinal lymphadenectomy. Methods: From Embase, PubMed, and Web of Science databases, 23 studies were identified that met the inclusion criteria. This review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. Risk of bias was assessed using the Risk of Bias in Non-randomized Studies-of Exposure tool. Results: Random-effects meta-analyses of proportions estimated a 24% (95% confidence interval [CI]: 17-31) pooled prevalence of LEL with a high degree of heterogeneity between the studies (I2=96%, p < 0.01). Subgroup analysis revealed significant differences in LEL prevalence based on the indications for inguinal lymphadenectomy. The pooled LEL prevalence was 25.75% (95% CI: 0.00-96.16) for patients who underwent lymphadenectomy for melanoma, 12.22% (95% CI: 1.03-23.40) for penile cancer, 30.96% (95% CI: 21.08-40.84) for vulvar cancer, and 13.62% (95% CI: 0.00-51.02) for miscellaneous indications. Conclusion: The findings from this study emphasize the importance of considering malignancy etiology when assessing the risk of LEL following inguinal lymphadenectomy. This knowledge could aid physicians in informing patients about the risk of LEL, while also facilitating proper patient selection for microsurgical interventions

Microsurgical versus complex physical decongestive therapy for chronic breast cancer-related lymphoedema

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of microsurgery versus complex physical decongestive therapy in people with chronic breast cancer-related lymphoedema