Hot off the Press November 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

New Insights into the Pathophysiology of Primary and Secondary Lymphedema: Histopathological Studies on Human Lymphatic Collecting Vessels

Barone V, Borghini A, Tedone Clemente E, Aglianò M, Gabriele G, Gennaro P, Weber E. Lymphat Res Biol. 2020 Jul 20

Lymphedema is characterized by an accumulation of interstitial fluids due to inefficient lymphatic drainage. Primary lymphedema is a rare condition, including congenital and idiopathic forms. Secondary lymphedema is a common complication of lymph node ablation in cancer treatment. Previous studies on secondary lymphedema lymphatic vessels have shown that after an initial phase of ectasia, worsening of the disease is associated with wall thickening accompanied by a progressive loss of the endothelial marker podoplanin. Methods and Results: We enrolled 17 patients with primary and 29 patients with secondary lymphedema who underwent lymphaticovenous anastomoses surgery. Histological sections were stained with Masson’s trichrome, and immunohistochemistry was performed with antibodies to podoplanin, smooth muscle α-actin (α-SMA), and myosin heavy chain 11 (MyH11). In secondary lymphedema, we found ectasis, contraction, and sclerosis vessel types. In primary lymphedema, the majority of vessels were of the sclerosis type, with no contraction vessels. In both primary and secondary lymphedema, not all α-SMA-positive cells were also positive for MyH11, suggesting transformation into myofibroblasts. The endothelial marker podoplanin had a variable expression unrelatedly with the morphological vessel type. Conclusions: Secondary lymphedema collecting vessels included all the three types described in literature, that is, ectasis, contraction, and sclerosis, whereas in primary lymphedema, we found the ectasis and the sclerosis but not the contraction type. Some cells in the media stained positively for α-SMA but not for MyH11. These cells, possibly myofibroblasts, may contribute to collagen deposition.

Prevalence and Risk Factors

Evidence-based recommendations regarding risk reduction practices for people at risk of or with breast cancer-related lymphedema: consensus from an expert panel

Cheryl L. Brunelle, Katherine Jackson, Shirin Shallwani, Julie H. Hunley, Anna Kennedy, Sarah Fench, Alexandra Hill, Electra D. Paskett, Katrina Rush, Saskia R. J. Thiadens, Joan White, Paula Stewart. Med Oncol. 2024 Oct 23.

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Construction of a nomogram for personalized prediction of lower limb lymphedema risk after cervical cancer surgery

XuQing Chen, Jing Li, Qian Zeng, WeiYu Huang, NanXiag Lei, QiaoHong Zeng. BMC Womens Health. 2024 Nov 6.

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Are post-operative preventative measures effective in breast cancer-related lymphedema? A systematic review

Vivekanandan, Preksha ; Hashmi-Greenwood, Molly ; Omileye, Adebayo ; Gebrye, Tadesse ; Fatoye, Francis ; Mbada, Chidozie Emmanuel. Palliative medicine in practice, 2024-10

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A cross-sectional survey to assess breast cancer survivors’ knowledge about lymphedema risk, prevention, and management

M. Klugman, K. Tringale, S. Patil, G. Montagna, J. Finik, T.-T. Kuo, et al. TY . October 2024.

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Body Mass Index and Breast Cancer-Related Lymphedema: A Retrospective Cohort Study

QiHua Jiang, Hai Hu, Jing Liao, Peng Duan, ZhiHua Li, JunTao Tan. J Surg Oncol. 2024 Oct 28.

OBJECTIVE: This study aims to evaluate the association between body mass index (BMI) and the incidence of breast cancer-related lymphedema (BCRL).
METHODS: This retrospective cohort study analyzed data from 1464 breast cancer patients treated at The Third Hospital of Nanchang between 2018 and 2021. Patients were categorized based on BMI (<25, 25 to < 30, ≥ 30 kg/m²). Variables such as axillary lymph node dissection, infections, radiotherapy, and comorbidities were taken into account.
RESULTS: The incidence of BCRL was 23.4%. Higher BMI was associated with increased risk of BCRL, with significant incidence rates observed at 1, 2, and 3 years in the higher BMI groups. Multivariate analysis confirmed BMI as an independent risk factor for BCRL.
CONCLUSION: Elevated BMI is associated with increased BCRL risk and decreased BCRL-free survival, underscoring the significance of weight management in breast cancer care.:10.1002

Patient-reported persistent lymphedema and peripheral neuropathy among long-term breast cancer survivors in the Carolina Breast Cancer Study

Rina A. Yarosh, Hazel B. Nichols, Qichen Wang, Rachel Hirschey, Erin E. Kent, Lisa A. Carey, Sandra C. Hayes, Adeyemi A. Ogunleye, Melissa A. Troester, Eboneé N. Butler. Cancer. 2024 Nov 17.

BACKGROUND: Improved breast cancer treatment has lengthened survival but also has long-term impacts. Lymphedema and peripheral neuropathy are treatment-related sequelae that extend into survivorship. Co-occurrence of these conditions may further impair functional well-being. Few studies have estimated the burden of these conditions among diverse survivors.
METHODS: Carolina Breast Cancer Study Phase 3 enrolled survivors diagnosed between 2008 and 2013 in North Carolina. Black and younger women (aged <50 years at diagnosis) were oversampled. With the use of ≥10 years of follow-up data, the prevalence of persistent lymphedema, peripheral neuropathy, and their co-occurrence was assessed. Prevalence differences (PDs) and 95% confidence intervals (CIs) were assessed according to patient and disease characteristics.
RESULTS: A total of 1688 survivors were included, with an average of 11.1 years (SD, 0.6) postdiagnosis. The prevalence of persistent lymphedema, peripheral neuropathy, and their co-occurrence was 18.7%, 27.7%, and 8.8%, respectively. Lymphedema was higher among those receiving a mastectomy and with >5 lymph nodes removed, and peripheral neuropathy was higher among women treated with taxane-based chemotherapy. Co-occurrence was higher among women with >5 lymph nodes removed (vs. <5; PD, 5.4; 95% CI, 2.1 to 8.8) and those treated with taxane-based chemotherapy (vs. no chemotherapy; PD, 6.8; 95% CI, 3.9 to 9.7). The burden of lymphedema (PD, 2.7; 95% CI, 0.9 to 6.3) and peripheral neuropathy (PD, 5.8; 95% CI, 1.7 to 9.9) was higher among Black than White women. The prevalence of lymphedema (PD, 1.8; 95% CI, -1.5 to 5.1) and peripheral neuropathy (PD, 4.6; 95% CI, 0.8 to 8.4) was elevated among younger compared to older women.
CONCLUSIONS: Lymphedema and peripheral neuropathy affect a substantial proportion of survivors. Interventions are needed to reduce this burden.:10.1002

Assessment

Biomarkers in lymphedema assessment: integrating elastography and muti-frequency bioimpedance analysis

Hyeonwoo Jeon, Doo Young Kim, Si-Woon Park, Bum-Suk Lee, Daham Kim, Hyeong-Wook Han, Namo Jeon. Biomark Med. 2024 Oct 24.-11.

Aim: Multi-frequency bioimpedance analysis (MFBIA) is used to measure lymphedema, but it is a biomarker that is sensitive to stiffness. Lymphedema is a condition that can be accompanied by stiffness, but no studies have considered this, so we tried to use non-invasive elastography as a biomarker for stiffness.
Methods & results: This retrospective study included 102 patients with lymphedema, divided into two groups according to the elastography strain ratio: stiff group (elastography strain ratio <0.7, n = 48) and non-stiff group (elastography strain ratio >0.7, n = 54). We estimated the volume of the affected arm based the extracellular water (ECW) volume calculated using MFBIA through a simple linear regression method. The adjusted R2 was 0.044 in the stiff group and 0.729 in the non-stiff group. Stepwise multivariate linear regression was used to investigate the significant factors for estimating the affected arm volume for each group. In the non-stiff group, the significantly associated factors were impedance at 50 kHz, weight, and height (adjusted R2 = 0.724; p = 0.003). In the stiff group, significant associations were observed among impedance at 250 kHz, impedance at 1 kHz, weight, and height (adjusted R2 = 0.705, p = 0.041).
Conclusion: Considering the characteristics of lymphedema, using MFBIA concurrently with elastography can be useful biomarker for estimating lymphedema.:10.1080/17520363.2024.2415283

Skin tissue dielectric constant: Time of day and skin depth dependence

Harvey N. Mayrovitz. Clin Physiol Funct Imaging. 2024 Nov 17.

BACKGROUND: Skin water measurements are used to investigate skin physiology, clinically study dermatological issues, and for conditions like diabetes, oedema, and lymphedema with measurements done at various times of day (TOD). One method used is skin’s tissue dielectric constant (TDC), often clinically measured to a single depth of 2.5 mm. This report characterizes intraday variations measured to multiple depths to guide expected TOD and depth dependence.

MATERIALS AND METHODS: Twelve medical students self-measured TDC on their forearm to depths of 0.5, 1.5, 2.5, and 5.0 mm every 2 h from 08:00 to 24:00 h on 2 consecutive days. All were trained in the procedure.

RESULTS: TDC declined slightly from morning through evening, mostly at 0.5 mm for which TDC was reduced by 4%. TDC values were not related to participants’ whole-body fat or water percentages. The TDC decrease was less at 1.5 mm where the reduction was 2.7%. At depths of 2.5 or 5.0 mm, there was no significant decrease in TOD.

CONCLUSION: Skin TDC shows a minor decreasing trend with an effect greater for shallower depths. In part, the clinical relevance of the findings relates to the confidence level associated with skin water estimates, based on TDC measurements, when measured at different TOD and depths during normal clinic hours. Based on the present data the TOD change is at most 4% and insignificant for measurement depths of 2.5 mm.:10.1111

Reliability, concurrent validity and clinical feasibility of measurement methods determining local tissue water in patients with lower limb lymphedema and healthy controls

An-Kathleen Heroes, Nele Devoogdt, Robert J. Damstra, Inge Fourneau, Kristiana Gordon, Vaughan L. Keeley, Sarah Thomis, Charlotte Van Calster, Malou Van Zanten, Tessa De Vrieze. Disabil Rehabil. 2024 Oct 29.

PURPOSE: To investigate reliability, concurrent validity and clinical feasibility of local tissue water measurements in patients with lower limb lymphedema and healthy controls.

METHODS: In this cross-sectional study the Moisture Meter D Compact device® (MMDC) measurement and “pitting test” were performed three times by two assessors to test intra- and inter-rater reliability in 47 patients and 30 healthy controls. To investigate the between-session reliability, 29 patients and 21 healthy controls were reassessed two weeks later. Time efficiency and practical limitations were evaluated. The concurrent validity was investigated between the two tests. Clinical trial registration number: NCT:05269264.

RESULTS: Of the MMDC values, 58% showed strong to very strong intra-rater reliability, 32% showed strong to very strong inter-rater reliability and 36% had strong to very strong between-session reliability. Absolute values had generally a higher reliability than inter-limb or leg-to-arm ratio values. The pitting test had nil to perfect agreement between assessments (Cohen’s kappa = -0.03-1.00) with fewer practical limitations and shorter performance time than the MMDC. Between both tests nil to a moderate relationship was found (Kendall’s tau c = 0.00-0.60).

CONCLUSION: The MMDC and pitting test are reliable and feasible measurements to assess local tissue water depending on the location, but should not be used interchangeably.:10.1080/09638288.2024.2419958

The Relationship Between Disease Variables, Pain Coping, and Functional Status of Patients with Lower Extremity Lymphedema

L Huseyinli, A.B. Aydin, D Altug, M.A. Cakmak, O.B. Tuncer, Y Tuglu, O Kenis-Coskun, C Sanal-Toprak. Lymphology. 2024.

The purpose of this study is to investigate the relationship between reported symptoms, functional outcomes, and pain coping mechanisms in participants with lower limb lymph-edema. This research has been designed as cross-sectional. Participants’ age, sex, height, weight, pain, tightness, and stiffness levels reported by the participants were documented with a 10 cm visual analogue scale. The Pain Coping Inventory scale has been used to evaluate coping strategies. Functional status was measured with timed-up-and-go test (TUGT), six-minute walk test (6MWT), and quadriceps muscle strength measurement with a hand-held dynamometer. The functional outcomes were also measured in a healthy control group. The difference in muscle strength in both lower extremities was evaluated using the t-test, and the correlations were assessed using the Spearman correlation test. Twenty-eight participants with lymphedema (PWL) and 23 controls were included in the study. Twenty-three of the PWL were female (82%). The mean age of the PWL was 54.43 ± 14.12, and the mean body mass index was 33.84 ± 6.17. There were no significant differences between the PWL and healthy controls regarding age and sex. The mean muscle strength of the affected lower extremity was 4.21 ± 1.10 kgs and was significantly lower compared to the contralateral lower extremity (6.10 ± 2.98 kgs) and control group (10.92 ± 1.25 kgs) (p<0.05 and p=0.007 respectively). In functional outcomes, TUGT was significantly worse in PWL when compared to the control group (11.17 ± 3.28 seconds vs 9.04 ± 1.33 seconds, p=0.004). A significant correlation was observed between the TUGT result and the level of tightness felt by the PWL (r= 0.43, p=0.02). There were significant correlations between pain coping strategies and patient reported symptoms. No correlations were found between coping strategies and functional measurements. Lymphedema disrupts the functional status of the participants, and these functional disruptions may be related to symptoms reported by the participants. The correlation between pain coping strategies and patient reported tightness may indicate that tightness may be more influential on coping with pain, but further research is needed to determine a cause-and-effect relationship.

Lymphatic Mapping with Multi-Lymphosome Indocyanine Green Lymphography in Legs with Lymphedema

Hisako Hara, Makoto Mihara. Arch Plast Surg. 2024 Sep 17.-596.

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Management Strategies

The Effects of a Web Application for Reducing the Risk of Breast Cancer-Related Lymphedema on Health Literacy and Self-Efficacy in Managing Symptoms Among Patients With Breast Cancer

Ausanee Wanchai, Somsri Panploy. Int J Nurs Pract. 2024 Oct 20.

AIMS: This study aimed to examine the effectiveness of a web application on health literacy and self-efficacy in managing arm oedema symptoms among patients with breast cancer.

METHODS: The research was carried out in four phases as follows: Phase 1, using a qualitative approach to explore problems and information needs in educating breast cancer patients through in-depth interviews with 10 professional nurses who had experiences in caring for breast cancer patients and 20 breast cancer patients. Data were analysed by content analysis; Phase 2, designing and developing a web application and confirming its quality by five experts with experience caring for breast cancer patients; Phase 3, testing the web application with five breast cancer patients; and Phase 4, examining the effectiveness of a web application in breast cancer patients using a quasiexperimental research method. Patients were divided into 15 persons in control and 15 in intervention groups, a total of 30 persons. The tools used in the study consisted of (1) a web application on practices for reducing risk for arm oedema after breast cancer treatment, (2) a health literacy assessment tool, (3) a self-efficacy for managing symptoms questionnaire and (4) a web application satisfaction questionnaire. Data were analysed using descriptive statistics, chi-square and t test.

RESULTS: Qualitative findings: The web application should cover patients’ and nurses’ views on arm oedema causes, assessment, prevention and self-care for managing swelling after breast cancer treatment. Characteristics of a web application required: large text, bright colours, clear visibility, accompanying pictures or videos, using simple language without official terminology, easy to access, convenient to use, concise, interesting content and shareable to others. Quantitative findings: The intervention group had significantly higher health literacy and self-efficacy in managing symptom scores than before the trial (p < 0.001). Sample groups were satisfied with the developed web application at a high level. When considering each item, it was found that all items were rated at high levels. Two items with the same highest score were ease of use and the attractiveness of the presentation style. CONCLUSION: This web application, aimed at reducing the risk of arm oedema after breast cancer treatment, is an effective tool for educating all hospitalized patients. In addition, further research should be conducted to monitor the sustainability of long-term and clinical outcomes.:10.1111

Quantitative analysis of pressure levels in manual lymphatic drainage across stages of breast cancer-related lymphedema: implications for optimized treatment protocols

Naifang Xing, Daiqing Liu, Lufeng Chen, Guorong Wang, Yuan Tian, Chen Yang, Yingjie Leng, Xin Jiang, Chengxiang Li, Ruonan Xie, Zhuomiao Nie, Tian Zhang. Breast Cancer Res Treat. 2024 Nov 4.

OBJECTIVE: To quantify the pressure levels necessary for effective Manual Lymphatic Drainage (MLD) in managing Breast Cancer-Related Lymphedema (BCRL) across various stages, and to contribute to the development of standardized protocols for MLD therapy.
METHODS: The study included 42 patients with BCRL (Stages I-III) and 14 certified lymphedema therapists. Forearms and upper arm circumferences were measured pre and post a 21-day MLD intervention. A tactile sensor system recorded the applied pressure during treatment. The data were preprocessed and statistically analyzed to assess pressure patterns and their stage-specific impacts on lymphedema.
RESULTS: The mean age of the patients was 52.4 years, and that of the therapists was 39.1 years. A statistically significant reduction in arm circumference was observed post-MLD treatment (P < 0.05). The pressure applied varied across stages: I forearm 16.5-20.1 mmHg, I upper arm 16.1-20.7 mmHg; II forearm 16.6-19.8 mmHg, II upper arm 19.7-23.8 mmHg; III forearm 29.3-34.3 mmHg, III upper arm 29.7-34.3 mmHg. No statistically significant difference was found between forearm and upper arm treatment pressures within Stages I (P = 0.283) and III (P = 0.08), while Stage II exhibited a significant difference (P < 0.001). Across the same treatment area, pressures for Stages I and II in the forearm were significantly lower than those in Stage III (P < 0.001). The treatment pressure differences between forearm stages I and II were not statistically significant (P > 0.05). Differences in upper arm treatment pressures across Stages I, II, and III were also statistically significant (P < 0.001).
DISCUSSION: The study provides quantitative evidence on the pressure ranges needed for MLD across different stages of BCRL. It highlights the importance for stage-specific pressure adjustments to optimize treatment outcomes. These findings contribute to the existing body of knowledge on MLD and offer valuable data that could inform the development of rehabilitation technologies, including intelligent robots and visualization systems, as well as enhance therapist training programs.:10.1007

Toe-Brachial Index Rise in Lymphedema Patients with Multilayer Bandage

J.E. Trihan, S Mestre, I Quere, D Laneelle, A Perez-Martin. Lymphology. 2024.

Multilayer compression bandaging (MLB) remains the primary treatment in lymphedema in association with manual lymphatic drainage. However, MLB can be contraindicated in patients with advanced lower extremity artery disease (LEAD). Presently, the prevalence of LEAD in lymphedema patients remains unknown. The goals of this study included i) to estimate the prevalence of LEAD, defined by toe-brachial index (TBI) less than 0.7, and ii) to measure the evolution of TBI after 30 min of MLB. A cross-sectional study was performed during a 3-month period on patients presenting with lower extremity lymphedema. Demographic data, basal TBI (T=0min) and TBI after 30 min of MLB at rest (T=30min) were recorded. Twenty-four patients with a total of 29 lymphedema limbs were included with a mean age of 62 years-old [Inter-quartile range (IQR) = 48 – 68] and 65.5% presenting with primary lymph-edema. Non-symptomatic LEAD, defined as TBI < 0.7, was found in 8 lymphedema limbs (27.6%). Advanced age, severe stages, and longer duration of lymphedema were associated with LEAD in univariate analysis. Median TBI increased significantly between T=0min and T=30min of MLB: 0.81 [IQR: 0.68 - 0.93] and 0.96 [IQR: 0.82 - 1.12] respectively (p= 0.004). Distal localization of lymphedema was associated with a decrease in TBI at T=30min in univariate analysis. Subclinical LEAD was found in over a quarter of lymphedema limbs and was more frequent in patients with advanced age, severe stages, and longer duration of lymphedema. Based on these findings, sub-clinical peripheral artery disease may be widely underestimated in lymphatic pathologies.

Complete decongestive therapy phase 1: an expert consensus document

Shelley DiCecco, Claire C. Davies, Laura Gilchrist, Kim Levenhagen, Marie-Eve Letellier, Amy Rivera, Janet Weiss, Guenter Klose, Linda Hodgkins, Elizabeth Anderson, Andrea L. Cheville, Keith Moore, Linda Koehler. Med Oncol. 2024 Nov 2

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‘Care and Compress’: A different way to look at garment choice

Kat Stevens; Susan Knight. Wounds Uk Journal Vol 20, Issue 4, 2024.

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Lymphedema in head and neck cancer survivors: From diagnosis to daily life

C.R. Arends. Thesis. Nov 2024.

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