Hot off the Press September 2026

Article to ponder

The study found that asymptomatic lower limb lymphatic abnormalities detected by ICG lymphography were strongly associated with subsequent development of clinical lymphedema following gynaecological cancer surgery. However, not all subclinical cases progressed, supporting the need for risk-based surveillance rather than assuming inevitable progression.

Natural History of Subclinical Lower Limb Lymphedema After Gynecologic Cancer Surgery Using Indocyanine Green Lymphography

Masato Tsuchiya, Izumi Yasutake, Yukako Ishihara, Kohei Matsuno, Hiroshi Futami, Satoshi Kubo, Ryuichi Azuma. Plast Reconstr Surg Glob Open. 2026 Aug 5. Aug.

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Key Takeaway: Abnormal ICG findings indicate an increased risk of progression to clinical lymphedema, supporting risk-based surveillance.

We have collated some great articles and material published over the last month. Click on the links below to read the  abstract or download the full paper.

Anatomy / Physiology /Pathophysiology

From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics

Annica R. Stull-Lane, Xizhao Chen, Abraham J. Book, Radomir Kratchmarov, Sarit Pal, Jinyeon Shin, Gopika Ashokan, Geoffrey E. Hespe, Babak J. Mehrara, Raghu P. Kataru. Front Immunol. 2026 Jul 20.

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Mechanistic Insights into Secondary Lymphedema: The Role of Inflammatory Cytokines and Fibrotic Pathways in Post-Surgical Patients

Liquan Gao, Zhiyao Chen, Yuhang Wang, Jie Gao, Ni Yan, KuanYe Huang. Ann Vasc Surg. 2026 Aug.

BACKGROUND: Secondary lymphedema is a debilitating complication following oncologic surgery, characterized by progressive tissue fibrosis and chronic inflammation. Although transforming growth factor-beta 1 (TGF-β1) has been established as a central mediator of fibrotic remodeling, the broader interplay between pro-inflammatory cytokines and downstream fibrotic signaling cascades in post-surgical lymphedematous tissue remains poorly understood.
METHODS: Skin and subcutaneous tissue biopsies were prospectively collected from 126 patients with unilateral breast cancer-related lymphedema and 58 matched controls across three tertiary centers between January 2024 and December 2025. Tissue specimens were analyzed using immunohistochemistry, quantitative real-time PCR, multiplex cytokine profiling, and Western blotting. Correlations between cytokine expression, fibrotic markers, and clinical severity were evaluated.
RESULTS: Lymphedematous tissues exhibited significantly elevated expression of TGF-β1, interleukin-6 (IL-6), interleukin-13 (IL-13), and tumor necrosis factor-alpha (TNF-α) compared with controls (all P < 0.01). Concurrent activation of Smad2/3 and STAT3 signaling pathways was observed, with both correlating positively with disease severity. Multivariate regression identified TGF-β1, IL-6, and IL-13 as independent predictors of fibrotic burden, whereas TNF-α lost significance after adjustment for confounders. Lymphatic vessel density was inversely associated with cytokine levels and fibrotic severity.
CONCLUSION: Secondary upper extremity lymphedema following breast cancer surgery is driven by a coordinated inflammatory and fibrotic axis involving TGF-β1, IL-6, and IL-13 through convergent Smad2/3 and STAT3 signaling. These findings support the development of multi-pathway therapeutic strategies beyond single-agent anti-fibrotic approaches for post-surgical lymphedema.:10.1016/j.avsg.2026.07.045

Prevalence and Risk Factors

Using Machine Learning to Predict Breast Cancer-Related Lymphedema Following Axillary Lymph Node Dissection

Benjamin D. Wagner, Jonlin Chen, Lillian A. Boe, Francis D. Graziano, Arielle N. Roberts, Andrea V. Barrio, Michelle R. Coriddi, Jonas A. Nelson, Babak J. Mehrara, Danielle H. Rochlin. Ann Surg Oncol. 2026 Jul 29

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Construction and Validation of a Risk Prediction Model for Lower Limb Lymphedema After Cervical Cancer Surgery: A Prospective Cohort Study

Guorui Zhao, Jiali Xu, Gaoming Liu, Sen Li, Xiang Liu, Jie Long. Cancer Med. 2026 Aug 15.

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The impact of hand grip strength on quality of life, fatigue, physical performance, and functional capacity in patients with post-mastectomy lymphedema

Emine Esra Ergül, Bilge Ekinci, Serhat Hayme. Turk J Phys Med Rehabil. 2026 Aug 6.

OBJECTIVES: Lymphedema, which may develop following mastectomy due to breast cancer, can negatively affect hand grip strength in women. This study aims to determine the effects of lymphedema on hand grip strength and quality of life (QoL) and to identify the factors influencing QoL.
PATIENTS AND METHODS: This study was designed as a cross-sectional observational study involving 100 patients with post-mastectomy lymphedema. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) was used to assess QoL, and the Checklist Individual Strength (CIS-20) was utilized to evaluate fatigue. Hand grip strength was measured using a hand dynamometer.
RESULTS: A significant difference was found between the hand grip strength measurements of the affected and non-affected upper extremities (p<0.001). Hand grip strength on the affected side was significantly correlated with both the functional subscales of the EORTC-QLQ-C30 and the CIS-20 (p<0.001).
CONCLUSION: This study objectively evaluated the impact of lymphedema on hand grip strength based on evidence. Assessing QoL, fatigue, and functional status also provided a comprehensive and objective understanding of the multifaceted effects of lymphedema. This study was not registered as a clinical trial.:10.4274.16766

Prediction Models for Lower Limb Lymphedema after Surgery in Patients with Gynecological Malignancies: A Systematic Review

Hongli Li, Yawen Zhang, Wen Li, Hong Yang. Lymphat Res Biol. 2026 Aug 5:1557 858 52.

The incidence of gynecological malignancies continues to increase worldwide. Lower limb lymphedema is perhaps the most dreaded long-term complication related to gynecological malignancy surgery. Identifying the early risk factors for lower limb lymphedema can facilitate targeted prevention and improve the prognosis of patients. To systematically review and evaluate existing studies on prediction models for lower limb lymphedema after surgery in patients with gynecological malignancies. PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, China Biomedical Literature Database, ProQuest Dissertations & Theses, medRxiv, and Google Scholar were systematically searched from inception to December 1, 2024. Studies were appraised critically, and data were extracted by two authors independently based on the Prediction Model Risk of Bias Assessment Tool and Data Extraction for Systematic Reviews of Prediction Modeling Studies. A total of 9 studies were included, involving 10 relevant prediction models. Five studies reported calibration; validation involved internal (n = 7) or both (n = 2). Discrimination varied across models (the area under the curve [AUC] range: 0.63-1.00), with 9 of 10 models reporting AUC values >0.70. However, calibration reporting was incomplete, and all studies were rated as high risk of bias. Although all studies demonstrated good applicability, all were rated as high risk of bias. Across all included studies, age, body mass index, hypertension, diabetes, tumor stage, postoperative drainage time, lymph node dissection, and radiotherapy were the most frequently reported predictors. Among them, lymph node dissection-related variables were included in eight of the ten models, while radiotherapy was included in 7 of 10 models. Although several models reported moderate to good discrimination, overall methodological quality was limited. The predominance of high risk of bias, scarce external validation, and restricted geographic diversity constrains the strength of the current evidence. More rigorously designed and externally validated models are needed before routine clinical implementation.:10.1177/15578585261470704

Assessment

Ultrasonographic Evaluations of Tendons/Fascia in Lower Limb Lymphedema and Lipedema

Abdullah Emre Uğur, Feray Soyupek, Levent Özçakar. Am J Phys Med Rehabil. 2026 Aug 11.

OBJECTIVE: To evaluate ultrasonographic changes in lower extremity tendons and plantar fascia of patients with chronic edema and their relationship with edema volume, pain, function, and quality of life.
DESIGN: This observational case-control study included 53 patients with chronic lower extremity edema and 55 age- and sex-matched controls. Ultrasonography assessed the Achilles, tibialis posterior, peroneal, and patellar tendons and plantar fascia. Edema volume was calculated from limb circumferences. Outcomes included the Lower Extremity Functional Scale (LEFS), Lymphedema Quality of Life Questionnaire-Leg (LYMQOL-Leg), and Visual Analogue Scale (VAS).
RESULTS: All tendons (except the patellar tendon) and plantar fascia were thicker in the edema group than controls (P<0.05). Differences in Achilles tendon and plantar fascia thickness remained significant after BMI adjustment (all P<0.01) and correlated positively with edema volume (P<0.05). Plantar fasciitis (50.9%) and Achilles tendinopathy (22.6%) were more frequent in the edema group (P<0.05). Patients had lower LEFS and higher LYMQOL-Leg and VAS scores (all P<0.01).
CONCLUSION: Chronic lower extremity edema was associated with alterations in tendon and fascial morphology, particularly the Achilles tendon and plantar fascia. Musculoskeletal ultrasonography may complement clinical evaluation by providing information regarding tendon and fascial involvement.:10.1097

Novel Ultrasound Technique for Assessing Fibrosis in Subcutaneous Fat in Lymphedematous Limbs

Hisako Hara, Makoto Mihara. Lymphat Res Biol. 2026 Aug 8:1557 858 52.

BACKGROUND: There is no standardized method for identifying fibrosis in the subcutaneous tissue of lymphedematous limbs. This study evaluated the relationship between ultrasonographic findings and fibrosis severity in patients with lower limb lymphedema.
METHODS: A retrospective analysis included 92 sites in 40 limbs of 26 female patients undergoing lymphaticovenous anastomosis. Skin thickness and subcutaneous echogenicity were assessed preoperatively using an 18-MHz linear ultrasound probe and classified into four grades (). Fibrosis severity was evaluated intraoperatively and classified into five grades (). Receiver operating characteristic (ROC) curve analysis determined the diagnostic accuracy of skin thickness for predicting severe fibrosis (F3/F4), and a regression model was developed to predict fibrosis severity.
RESULTS: Skin thickness was significantly greater in the calves (2.7 mm) than in the thighs (2.1 mm, p < 0.01) and increased with lymphedema stage. Fibrosis severity was higher above the superficial fascia and more prevalent in calves (p < 0.01). ROC analysis showed an area under the curve of 0.80 for calf (above the superficial fascia), with a cutoff of 2.65 mm. The regression model (R2 = 0.51, p < 0.001) demonstrated that skin thickness and fat echogenicity significantly predicted fibrosis severity: Fibrosis severity = 0.21 + 0.32 × skin thickness (mm) + 0.45 × fat echogenicity grade.
CONCLUSIONS: Ultrasound-based measurements of skin thickness and fat echogenicity are reliable and noninvasive predictors of fibrosis severity in patients with lymphedema. These findings support the use of ultrasound imaging to guide treatment planning and improve surgical outcomes. However, further validation is needed in diverse populations.:10.1177/15578585261477183

Exploring Lower Limb Volume Estimation: Application and Evaluation of Limb Volume Equations with Ideal Circumferential Measurement Intervals

Wen-Han Huang, Min-Lan Lin, Tong-Yu Liu. Lymphat Res Biol. 2026 Aug 23.

BACKGROUND: Accurate limb volume measurement is essential for the early detection and continuous monitoring of lower limb lymphedema. We aim to validate the applicability of existing upper limb volume formulas for lower limb volume measurement and to determine the optimal interval for such measurements.
METHODS AND RESULTS: Eighty-seven patients who underwent whole lower limb computed tomography (CT) scans due to lower limb edema were enrolled. The volume of the lower limbs was examined using the CT method and the formula method. The measurement range extended from a horizontal line 8 cm below the inferior border of the pubic symphysis to a line 5 cm above the medial malleolus. Differences and consistency between the two methods were compared to identify the optimal measurement interval. There were statistical differences between the formula and CT-calculated volumes at different measurement intervals, with the smallest difference at an interval of 5 cm (Z = -4.664, p < 0.001). Also, good consistency and correlation were shown at 5 cm (intraclass correlation coefficient = 0.971, r = 0.993, p < 0.001).
CONCLUSIONS: This study confirms the feasibility and effectiveness of applying upper limb volume formulas to lower limb volume measurement. From a clinical perspective, we recommend a measurement interval of 5 cm as the optimal choice.:10.1177/15578585261473404

A Systematic Review on Imaging and Diagnostic Modalities for the Detection, Evaluation, and Surgical Planning of Upper and Lower Extremity Lymphedema

Star-Kayla Lewis, Courtney Pina, Adam Iddriss, Brooke Rothberg, Jacyln Morales, Samantha Cotes, Noah J. Sirkin, Thomas O’Donnell, Neil Tanna, Alisha Oropallo. J Vasc Surg Venous Lymphat Disord. 2026 Aug 3:102592

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AI-Empowered Mechanomedicine for Cancer-Related Lymphedema

Zhe Liu, Oscar Gonzalez, Minli You, Feng Xu, Ting Wen. Research (Wash D C). 2026 Aug 4

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Management Strategies

Safety Evaluation of a Device for Treatment of Lymphedema of the Upper Extremity

Evgeniya Molotkova, Seth Jarvis, Leah Thomas, Selah Wangler, Tara Newberry Cota/L, Christopher Arena, Andre Muelenaer. Lymphat Res Biol. 2024 Dec 5.

Lymphedema is a chronic condition characterized by dysfunction of the lymphatic system. There is currently no available cure. The standard of care is complete decongestive physiotherapy performed by a lymphedema therapist. However, lymphedema may flare between appointments, making home care important. There are several medical devices available to treat lymphedema at home, but they can be expensive, noisy, and bulky, restricting patient mobility. Thus, there is a demand for other devices that can be utilized at home, between appointments. The overall goal of this research study is to assess the safety of a newly developed vibratory device that may be utilized to supplement lymphedema treatment. Fourteen healthy subjects were recruited and treated with the device, all while measuring pre-treatment and post-treatment upper extremity circumference/induration, vital signs, pain, side effects, and intra-treatment acceleration produced by the device. There were no significant changes in reported pain or vital signs, and side effects were largely mild and transient. We believe that this device is safe for use in healthy subjects, and further studies should assess the efficacy of this device in treating patients with lymphedema.:10.1089.0070

Lymphedema: current treatment strategies and future directions in tissue engineering

Alina Stoian, Mariana Jian, Angela Babuci, Vitalie Cobzac, Ana-Maria Nacu, Mihaela Sîromeatnicov, Dumitru Hîncota, Nicolae Caproş, Grigore Verega, Viorel Nacu. Front Med (Lausanne). 2026 Aug 5.

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