Hot off the Press September 2024

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

The emerging importance of lymphangiogenesis in aging and aging-associated diseases

RC Ji – Mechanisms of Ageing and Development, 2024

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Prevalence and Risk Factors

Clinical, Pathologic, and Dosimetric Predictors of Head and Neck Lymphedema Following Definitive or Adjuvant Radiation Therapy for Head and Neck Cancer

Kevin R. Rogacki, P. Troy Teo, Mahesh Gopalakrishnan, Suvidya Lakshmi Pachigolla, Clayton E. Lyons, Mohamed E. Abazeed, Indra Das, Bharat B. Mittal, Michelle Gentile. Adv Radiat Oncol. 2024 Aug 15. Sep.

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Risk Profiling of Breast Cancer-Related Lymphedema (BCRL) in Patients With Breast Cancer Via Using Body Composition and Tissue Dielectric Constant (TDC) Method: A Cross-Sectional Study

Alper Tuğral, Murat Akyol, Öykü Çolakoğlu, Yeşim Bakar. Clin Breast Cancer. 2024 Au

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The Effects of Daily-Living Risks on Breast Cancer-Related Lymphedema

MR Fu, B Liu, JM Qiu, Y Sun, D Axelrod, A Guth… – Annals of Surgical Oncology, 2024

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Characteristics of lymphoedema, in particular midline lymphoedema, after treatment for prostate cancer: a retrospective study

Charlotte Van Calster, Wouter Everaerts, Inge Geraerts, An De Groef, An-Kathleen Heroes, Tessa De Vrieze, Ceyhun Alar, Nele Devoogdt. BMC Urol. 2024 Sep 4.

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Incidence of lymphedema related to various cancers

ME Letellier, M Ibrahim, A Towers, G Chaput – Med Oncol 41, 245 (2024)

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Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation- click for abstract

Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation

A Engin – Advances in experimental medicine and biology, 2024

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Additionally, obese and postmenopausal women are at higher risk of all-cause and breast cancer-specific mortality compared with non-obese women with breast cancer. In this context, increased levels of estrogens, excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, adipocyte-derived adipokines, hypercholesterolemia, and excessive oxidative stress contribute to the development of breast cancer in obese women. Genetic evaluation is an integral part of diagnosis and treatment for patients with breast cancer. Despite trimodality therapy, the four-year cumulative incidence of regional recurrence is significantly higher. Axillary lymph nodes as well as primary lesions have diagnostic, prognostic, and therapeutic significance for the management of breast cancer. In clinical setting, because of the obese population primary lesions and enlarged lymph nodes could be less palpable, the diagnosis may be challenging due to misinterpretation of physical findings. Thereby, a nomogram has been created as the “Breast Imaging Reporting and Data System” (BI-RADS) to increase agreement and decision-making consistency between mammography and ultrasonography (USG) experts. Additionally, the “breast density classification system,” “artificial intelligence risk scores,” ligand-targeted receptor probes,” “digital breast tomosynthesis,” “diffusion-weighted imaging,” “18F-fluoro-2-deoxy-D-glucose positron emission tomography,” and “dynamic contrast-enhanced magnetic resonance imaging (MRI)” are important techniques for the earlier detection of breast cancers and to reduce false-positive results. A high concordance between estrogen receptor (ER) and progesterone receptor (PR) status evaluated in preoperative percutaneous core needle biopsy and surgical specimens is demonstrated. Breast cancer surgery has become increasingly conservative; however, mastectomy may be combined with any axillary procedures, such as sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection whenever is required. As a rule, SLNB-guided axillary dissection in breast cancer patients who have clinically axillary lymph node-positive to node-negative conversion following neoadjuvant chemotherapy is recommended, because lymphedema is the most debilitating complication after any axillary surgery. There is no clear consensus on the optimal treatment of occult breast cancer, which is much discussed today. Similarly, the current trend in metastatic breast cancer is that the main palliative treatment option is systemic therapy.

Breast cancer-related lymphedema: A comprehensive analysis of risk factors - click for abstract

Breast cancer-related lymphedema: A comprehensive analysis of risk factors

C Siotos, SH Arnold, M Seu, L Lunt, J Ferraro… – Journal of surgical oncology. 2024 Aug 27. doi: 10.1002/jso.27841.

Background: Breast cancer-related lymphedema is a devastating condition that negatively affects the quality of life of breast cancer survivors. We sought to identify risk factors that predicted the timing and development of lymphedema.

Methods: Women with breast cancer that underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) at our institution between 2007 and 2022 were identified and sociodemographic and clinical information was extracted. We used logistic regression analysis to identify risk factors for lymphedema and performed cox-regression analysis to predict the timing of lymphedema presentation after surgery.

Results: We identified 1,223 patients, of which 161 (13.2%) developed lymphedema within 1.8 (mean, SD = 2.5) years postoperatively. Patients with SLNB had significantly lower odds for lymphedema development (vs. ALND, OR = 0.29 [0.14-0.57]). Patients between 40 and 49 years of age, and 50-59 (vs. <40 years, OR = 2.14 [1.00-4.60]; OR = 2.42, [1.13-5.16] respectively), African American patients (vs. Caucasian, OR = 1.86 [1.12-3.09]), patients with stage II, III, and IV disease (vs. stage 0, OR = 3.75 [1.36-10.33]; OR = 6.62 [2.14-20.51]; OR = 9.36 [2.94-29.81]), and patients with Medicaid (vs. private insurance, OR = 3.56 [1.73-7.28]) had higher rates of lymphedema. Cox-regression analysis showed that African American (HR = 1.71 [1.08-2.70]), higher BMI (HR = 1.03 [1.00-1.06]), higher stage (stage II, HR = 2.22 [1.05-7.09]; stage III, HR = 5.26 [1.86-14.88]; stage IV, HR = 6.13 [2.12-17.75]), and Medicaid patients (HR = 2.15 [1.12-3.80]) had higher hazards for lymphedema. Patients with SLNB had lower hazards for lymphedema (HR = 0.43 [0.87-2.11]). Conclusion: Lymphedema has identifiable risk factors that can reliably be used to predict the chances of lymphedema development and enable clinicians to educate patients better and formulate treatment plans accordingly.

Assessment

Lower Extremity Lymphatic Flow/Drainage Assessment by Indocyanine Green Fluorescent Lymphography in Heart Failure Patients

Barbara Ponikowska, Jan Biegus, Marat Fudim, Gracjan Iwanek, Mateusz Guzik, Roman Przybylski, Andrzej Szuba, Angelika Chachaj, Robert Zymliński. JACC Basic Transl Sci. 2024 Jul 22. 

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Arm symptom pattern among breast cancer survivors with and without lymphedema: a contemporaneous network analysis

Aomei Shen, Zhongning Zhang, Jingming Ye, Yue Wang, Hongmeng Zhao, Xin Li, Peipei Wu, Wanmin Qiang, Qian Lu. Oncologist. 2024 Aug 2..1093/oncolo/oya

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Current diagnostic and quantitative techniques in the field of lymphedema management: a critical review

Mary Vargo, Melissa Aldrich, Paula Donahue, Emily Iker, Louise Koelmeyer, Rachelle Crescenzi, Andrea L. Cheville. Med Oncol. 2024 Sep 5

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Development and Validation of Upper Limb Lymphedema in Patients After Breast Cancer Surgery Using a Practicable Machine Learning Model: A Retrospective Cohort Study

Xixi Peng, Ziyue Lu. Int J Gen Med. 2024 Sep 2

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The Role of Body Composition Analyzer in the Preoperative Assessment of Breast Cancer Patients

L Zhang, Q Zhong, Y Ding, J Li, Q Luo, L Zhang, Y Guo… – Journal of Cancer Therapy, 2024

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Skin mechanical properties measured with skin elasticity measurement device in patients with lymphedema: Scoping review

Y Fujimoto, Y Yuri, H Tamiya – Skin Research and Technology, 2024

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Assessment Modalities for Lower Extremity Edema, Lymphedema, and Lipedema: A Scoping Review

M Biura, T Carel, K Moreira, P Sneha, M Neethu… – Cureus, 2024

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Factors Predicting the Effect of a Complex Decongestive Therapy in Patients with Mild Lymphedema Following Mastectomy for Early Stage Breast Cancer - click for abstract

Factors Predicting the Effect of a Complex Decongestive Therapy in Patients with Mild Lymphedema Following Mastectomy for Early Stage Breast Cancer

Ju Hyeon Kim, Han Eum Choi, Jae Hyun Lee, Young-Joo Sim, Ho Joong Jeong, Ghi Chan Kim. Lymphat Res Biol. 2024 Sep 4.

Background: Complex decongestive therapy (CDT) is being used in breast cancer-related lymphedema (BCRL). The degree of initial edema and bioimpedance analysis (BIA) are known to be related with the therapeutic effect of CDT. D-dimer can indirectly reflect lymphangiogenesis because IL-6 regulates D-dimer and vascular endothelial growth factor, which is the most important lymphangiogenic factor. We assessed whether D-dimer could be used for the prediction of therapeutic effect of CDT, as well as BIA and initial edema.
Methods: The participants were patients who took inpatient treatment for BCRL from July 2016 to May 2020. Percent excess volume (PEV) was calculated by dividing the difference in volume of both arms by the edema arm, and the difference in PEV before and after 2 weeks of CDT was defined as the CDT effect. BIA and D-dimer tests were performed before treatment.
Results: The single frequency bioimpedance analysis (SFBIA) ratio and D-dimer showed significant correlations with β coefficients of 0.581 and 0.402 (p < 0.01), respectively, and the explanatory power of these models was confirmed to be 0.704.The areas under the curve of initial PEV, SFBIA ratio, D-dimer for determining the CDT effect were identified as 0.849, 0.795, and 0.725, respectively.
Conclusions: Initial PEV, SFBIA ratio, and blood D-dimer levels could be used as predictors for CDT treatment effect. Their usefulness order was in the order of initial PEV, SFBIA ratio, and D-dimer. These factors could be used as predictors to establish therapeutic plan in patients with mild lymphedema.:10.1089.0021

Relation Between Characteristics of Indocyanine Green Lymphography and Development of Breast Cancer-Related Lymphedema - click for abstract

Relation Between Characteristics of Indocyanine Green Lymphography and Development of Breast Cancer-Related Lymphedema

Sarah Thomis, Sophie Ronsse, Beate Bechter-Hugl, Inge Fourneau, Nele Devoogdt. Lymphat Res Biol. 2024 Sep 10.

Background: Breast cancer-related lymphedema (BCRL) is a disabling and frequently occurring condition after treatment for breast cancer. Studying lymph anatomy by means of indocyanine green (ICG) lymphography is a promising tool to help better understand BCRL. The aim of this study is to investigate the relation between ICG lymphography characteristics and the risk of developing BCRL.
Methods and Results: Patients scheduled for breast surgery with either unilateral axillary lymph node dissection or sentinel lymph node biopsy between November 2017 and May 2019 were included. Patients were assessed at baseline and up to 36 months postsurgery. BCRL was defined as an increase of ≥5% relative arm volume difference compared with the presurgical difference. In total, 128 patients were included. During 36 months of follow-up, 45 patients (35.2%) developed BCRL. The number of lymph vessels before surgery was not a statistically significant risk factor for developing BCRL (p = 0.8485). However, an increase in the number of lymph vessels compared with baseline was a significant protective factor for developing BCRL (odds ratio = 0.8). An increase of one lymph vessel corresponds to a 19% relative risk reduction of developing BCRL. The presence of lymph nodes at baseline and the change in the presence of lymph nodes compared with baseline were no predictors for the development of BCRL (p = 0.0986 and p = 0.8910, respectively).
Conclusions: An increase in the number of lymph vessels visualized by ICG lymphography compared with baseline is a protective factor for developing BCRL. Therapies with the ability to increase the number of lymph vessels can thus possibly decrease the risk of developing BCRL.:10.1089.0009

Current Diagnostic Measures for Lymphedema: A Comprehensive Review - click for abstract

Current Diagnostic Measures for Lymphedema: A Comprehensive Review

Ricardo A. Torres-Guzman, Virginia Bailey, Andrew J. James, Brian C. Drolet, Huseyin Karagoz. Ann Plast Surg. 2024 Sep 1.S Suppl 2):.

Lymphedema presents diagnostic challenges due to complex symptomatology and multifaceted onset. This literature review synthesizes diagnostic measures ranging from clinical assessments to advanced imaging techniques and emerging technologies. It explores the challenges in early detection and delves into the disparities in access to advanced diagnostic tools, which exacerbate health outcome differences across populations. This review not only provides insights into the effectiveness of current diagnostic modalities but also underscores the necessity for ongoing research and innovation. The goal is to enhance the accuracy, affordability, and accessibility of lymphedema diagnostics. This is crucial for guiding future research directions and for the development of standardized diagnostic protocols that could help mitigate the progression of lymphedema and enhance the quality of life for affected individuals.:10.1097

Analysis of Different Lymphedema Assessment Tools in Women with Breast Cancer After Mastectomy - click for abstract

Analysis of Different Lymphedema Assessment Tools in Women with Breast Cancer After Mastectomy

Rocío Abalo-NúñezIria Da Cuña-CarreraAlejandra Alonso-Calvetealejalonso@uvigo.esEva M. Lantarón-Caeiro, and Mercedes Soto-González. Lymphatic Research and BiologyVol. 22, No. 4, 2024
Background: Lymphedema is a common complication after mastectomy in women with breast cancer. Several methods have been described to assess and diagnose lymphedema, one of the most studied being the perimeter and ultrasonography. However, the reliability of these methods and the correlation between them are still controversial. The aim of this study was to analyze the reliability of cytometry and ultrasound imaging in the assessment of lymphedema after mastectomy in women with breast cancer and to study the correlation between them.
Methods and Results: A cross-sectional study was conducted in 29 women with mastectomy after breast cancer. Lymphedema in the arm was measured both with cytometry and ultrasonography. Reliability was calculated with intraclass correlation coefficient. The correlation between the two methods was carried out with the Pearson correlation coefficient. Both cytometry (M1: α = 0.999, ICC = 0.996; M2: = α = 0.998, ICC = 0.994) and ultrasonography (M1: α = 0.992, ICC = 0.976; M2: = α = 0.991, ICC = 0.973) are reliable methods to assess lymphedema in the arm. No significant correlation was found between them (p > 0.05).
Conclusions: Cytometry and ultrasonography appear to be adequate for the measurement of edema in women with breast cancer after mastectomy. However, for an accurate measurement of lymphedema, these measurements should not be used interchangeably.

Management Strategies

Resources on lymphedema surgery: How effective are they for patients? - click for abstract

Resources on lymphedema surgery: How effective are they for patients?

Artur Manasyan, Sasha Lasky, Eloise W. Stanton, Brigette Cannata, Tayla Moshal, Idean Roohani, Emma Koesters, David A. Daar.  Surg Oncol. 2024 Aug 19.

Online patient education materials (PEMs) on lymphedema surgery were assessed for quality, readability, and content. A total of 37 PEMs were identified, primarily authored by academic/medical organizations. Readability scores indicated materials were difficult to read, with an average Flesch-Kincaid Grade Level of 10.4. PEM Assessment Tools showed acceptable understandability (72.3%) but poor actionability (28.5%). PEMs often lacked information on surgical risks, postoperative care, and long-term follow-up. Simplifying language and adding visual aids could improve PEM effectiveness.:10.1002

The effects of the-optimal-lymph-flow health IT system application on treatment-related high risk lymphedema in breast cancer patients: a randomized controlled trial - click for abstract

The effects of the-optimal-lymph-flow health IT system application on treatment-related high risk lymphedema in breast cancer patients: a randomized controlled trial

Xinwen Du, Xuan Huang, Xianqiong Feng, Yuping Shui, Aihua Zhang, Jialing Li, Chujin Qiu, Guan Wan. Breast Cancer Res Treat. 2024 Aug 23.

PURPOSE: To evaluate the application effects of The-Optimal-Lymph-Flow IT System in Chinese patients at high risk of developing breast cancer-related lymphedema.
METHODS: A total of 104 breast cancer patients were randomly assigned to either the control group or the intervention group. The intervention group was provided with the The-Optimal-Lymph-Flow program, while the control group received the usual care. Trial outcomes including symptom experience, quality of life, and limb volume were evaluated at baseline, and at end of the 1- and 3-month trials.
RESULTS: After controlling for covariates, the incidence of eight symptoms was significantly higher in the control group than in the intervention group. There were significant differences in the changes in the severity of symptoms and arm volume between the two groups from baseline to 3 months after the intervention.
CONCLUSIONS: The application of TOLF in patients at high risk of developing lymphedema following breast cancer treatment significantly improved the lymphedema-related symptoms experienced in the early stage after surgery. Trial registration ChiCTR1800016713.:10.1007

Breast cancer-related arm lymphoedema: a critical unmet need

Sandra C. Hayes, Michael J. Bernas, Melanie L. Plinsinga, Christopher Pyke, Christobel Saunders, Neil B. Piller, Christine Moffatt, Vaughan L. Keeley, Natalie Kruger, Hildegard Reul-Hirche, Alexandra L. McCarthy. EClinicalMedicine. 2024 Jul 26

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Closing the Gaps: An Integrative Review of Yoga’s Benefits for Lymphedema in Breast Cancer Survivors

Sara Freguia, Daniela Platano, Danilo Donati, Federica Giorgi, Roberto Tedeschi. Life (Basel). 2024 Aug 11..3390/lif

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Results from A Comparative Study to Evaluate the Treatment Effectiveness of a Non-Pneumatic Compression Device versus an Advanced Pneumatic Compression Device for Lower Extremity Lymphedema Swelling (TEAYS study)

Michael Barfield, Ron Winokur, Todd Berland, Sandi Davis, Vicky Ralph, Nancy Chatham, Stanley G. Rockson, Thomas S. Maldonado. J Vasc Surg Venous Lymphat Disord. 2024 Aug 31.

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Efficacy of intermittent pneumatic compression on breast cancer-related upper limb lymphedema: a systematic review and meta-analysis in clinical studies

Shengqun Hou, Yun Li, Weiwu Lu, Xiaoju Zhang, Huiyu Luo, Jiajia Qiu, Zhenqi Lu. Gland Surg. 2024 Aug 28.

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Adjustable Velcro® compression devices as compared to 4-layer compression bandages for the treatment of venous leg ulcers and optimisation of patient satisfaction

Sharon L Boxall, Keryln Carville, Joanna Smith, Shirley Jansen. Wound Practice and Research. 2024;32(3):120-128. DOI 10.33235/wpr.32.3.8-120-128

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Primary LYmphedema Multidisciplinary Approach in Patients Affected by Primary Lower Extremity Lymphedema

Pedro Ciudad, Alberto Bolletta, Juste Kaciulyte, Oscar J. Manrique, Joseph M. Escandón. J Clin Med. 2024 Aug 30.

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Evidence for the clinical effectiveness of decongestive lymphoedema treatment for breast cancer–related arm lymphoedema, a systematic review

E Jeffs, E Ream, C Taylor, A Purushotham, D Bick – Supportive Care in Cancer, 2024

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