Hot off the Press June 2023
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 Function of T Cell Immunity in Lymphedema: A Comprehensive Review.- click for abstract
The Function of T Cell Immunity in Lymphedema: A Comprehensive Review.
Ao Fu, Chunjun Liu. Lymphat Res Biol. 2023 May 26.
Lymphedema is a debilitating disease characterized by extremity edema, fibroadipose deposition, impaired lymphangiogenesis, and dysfunctional lymphatics, often with lymphatic injury secondary to the treatment of malignancies. Emerging evidence has shown that immune dysfunction regulated by T cells plays a pivotal role in development of lymphedema. Specifically, Th1, Th2, Treg, and Th17 cells have been identified as critical regulators of pathological changes in lymphedema. In this review, our aim is to provide an overview of the current understanding of the roles of CD4+ T cells, including Th1, Th2, Treg, and Th17 subsets, in the progression of lymphedema and to discuss associated therapies targeting T cell inflammation for management of lymphedema
Clinical Characteristics and Implications of Indocyanine Green Lymphography-Identified Contralateral Inguinal Pathway of Lower-Limb Lymphedema.- click for abstract
Clinical Characteristics and Implications of Indocyanine Green Lymphography-Identified Contralateral Inguinal Pathway of Lower-Limb Lymphedema
Mackie, Helen MBBS, FAFRM1,2; Thompson, Belinda M. PhD, MClinExPhys3; Koelmeyer, Louise A. PhD, BAppSc (OT)4; Blackwell, Robbie BAppSc (OT)5; Gaitatzis, Katrina BA (Hons)6; Heydon-White, Asha MRes, BPhty7; Boyages, John PhD, MBBS (Hons), FRANZCR8,9; Suami, Hiroo MD, PhD10. Rehabilitation Oncology 41(1):p 47-54, January 2023.
Background and Objectives:
The contralateral inguinal pathway (CIP) to the inguinal nodal region of the contralateral limb has been described in lower-limb lymphedema (LLLE). This audit aimed to use indocyanine green (ICG) lymphography to determine characteristics of patients with CIP to inform conservative therapy.
Methods:
Patients with confirmed LLLE (n = 278) were categorized into secondary cancer-related (n = 82), secondary non–cancer-related (n = 86), or primary (n = 110). Patient characteristics, limb volume and bioimpedance spectroscopy (BIS) extracellular fluid ratio, and ICG lymphography of lymphatic pathways and dermal backflow areas were recorded.
Results:
Forty-seven patients (16.9%) had movement of ICG dye via CIP. Of these, 30 (63.8%) had secondary cancer-related, 8 (17.0%) had secondary non–cancer-related, and 9 (19.1%) had primary LLLE. Cancer-related LLE (P < .001) and unilateral LLLE (P = .017) were significant indicators of CIP, with 36.6% of patients with cancer-related LLLE demonstrating this pathway. CIP was significantly associated with dermal backflow in shin (P = .016), calf (P = .006), thigh (P < .001), inguinal (P < .001), pubic (P < .001), and abdominal regions (P = .001). Patients with CIP had significantly higher volume differences between limbs (P < .001), severity of lymphedema (P < .001), and BIS measurements (P < .001) than patients without CIP.
Conclusion:
A compensatory lymphatic drainage pathway from the affected limb to the contralateral inguinal lymph node region was evident in 16.9% of patients with LLLE. This pathway was most observed in unilateral cancer-related lymphedema, particularly where edema was present in proximal thigh, inguinal, pubic, and lower abdominal regions. Directing manual lymphatic drainage to the contralateral inguinal drainage region should be considered especially for patients with cancer-related LLLE.
Skin microbiome alterations in upper extremity secondary lymphedema
Adana-Christine Campbell, Teng Fei, Jung Eun Baik, Hyeung Ju Park, Jinyeon Shin, Kevin Kuonqui, Stav Brown, Ananta Sarker, Raghu P Kataru, Babak J Mehrara. PLoS One. 2023 May 17;18(5):
Peripheral T cell profiling reveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic venous anastomosis
Hirofumi Imai, Takakazu Kawase, Shuhei Yoshida, Toshiro Mese, Solji Roh, Asuka Fujita, Toshio Uchiki, Ayano Sasaki, Shogo Nagamatsu, Atsushi Takazawa, Tatsuo Ichinohe, Isao Koshima. iScience. 2023 May 6;26(6):106822.
Prevalence and Risk Factors
Self-reported lower extremity lymphedema and quality of life after surgical staging of endometrial carcinoma: A population based cross-sectional study
Assessment
Tissue Dielectric Constant and Skin Stiffness Relationships in Lower Extremity Lymphedema - click for abstract
Tissue Dielectric Constant and Skin Stiffness Relationships in Lower Extremity Lymphedema
Lower extremity lymphedema or edema (LELE) may progressively transition from a state of excess tissue fluid to increased fat accumulation and collagen deposition, with tissue fibrosis and hardening. Such changes may lead to altered tissue water holding and thereby impact tissue dielectric constant (TDC). This study seeks to evaluate the relationship between TDC and tissue indentation force (TIF) in patients with LELE and assess the utility of the leg/arm TDC ratio (LAR) as an indicator of LELE.
Methods and Results: Thirty females (49-91 years) with previously diagnosed LELE were evaluated during a scheduled session. TDC and TIF were measured 8 cm proximal to the medial malleolus on the medial and lateral aspects of both legs and on one forearm 8 cm distal to the antecubital fossa. The TDC-TIC relationship and the LAR were subsequently determined. Main results showed an absence of a significant correlation between TDC and TIF on medial or lateral leg sites but a positive correlation on the normal forearm site. Further, LAR values exceeded the published proposed threshold of 1.35 for 29/30 patients when using medial-side TDC values and 28/30 patients when using lateral-side TDC values.
Conclusions: Findings suggest that for patients with LELE, TDC values are significantly elevated on medial and lateral standardized sites. The LAR determined using either medial or lateral sites that are similar to each other and have values consistent with a lymphedema threshold of 1.35. In edematous legs of the type evaluated herein, there is no apparent relationship between TDC values and indentation force.
Static and Dynamic Imbalance in Patients with Breast Cancer-Related Lymphedema - click for abstract
Static and Dynamic Imbalance in Patients with Breast Cancer-Related Lymphedema
Ozlem Karasimav, Pinar Borman, Meltem Dalyan, Elif Yalcin, Zahide Betul Eliuz, Saadet Selin Koc, Seren Turhan. Lymphat Res Biol. 2023 May 17
Background: Breast cancer–related lymphedema (BCRL) was associated with postural imbalance, but the immature knowledge introduced debate about which component of the balance was affected by BCRL in the literature. The aim of this study was to determine the static and dynamic balance of patients with BCRL in comparison with healthy subjects.
Methods and Results: This case-control designed study recruited 30 BCRL patients and 30 healthy individuals. The demographic and clinical variables of the subjects were recorded. The static balance stability parameters on four conditions (eyes opened-stable ground, eyes closed-stable ground, eyes opened-unstable ground, eyes closed-unstable ground) and dynamic stability of all participants were evaluated. The values of both stable ground conditions were similar between the groups ( p < 0.05). However, values of both eyes opened-unstable ground ( p = 0.032) and eyes closed-unstable ground ( p = 0.034) conditions were significantly impaired in BCRL in comparison with controls. Besides, comparison of sway area of the opened versus closed eyes conditions on unstable ground ( p = 0.036), and movement speed while correcting the center of pressure on unstable ground (with opened and closed eyes, p = 0.014 and p = 0.004 respectively) revealed increased values in the BCRL group. Likewise, the dynamic stability was significantly disrupted in the BCRL group ( p = 0.043).
Conclusion: Closing eyes did not affect the postural balance in patients with BCRL, whereas the deterioration of ground altered the balance significantly in the BCRL group compared with healthy subjects. We suggest the inclusion of balance exercises and guidance for selection of correct shoes and insoles in routine lymphedema rehabilitation program.
The Utility of CT Venography in the Routine Evaluation of Patients that Present to a Lymphedema Center with Lower Extremity Edema - click for abstract
The Utility of CT Venography in the Routine Evaluation of Patients that Present to a Lymphedema Center with Lower Extremity Edema
Emily R Finkelstein, Taylor E Crist, Tony Shao, Juan Mella-Catinchi, Kyle Y Xu. J Vasc Surg Venous Lymphat Disord. 2023 May 15
Objective: Computed tomography venography (CTV) is not routinely used to screen patients presenting with a presumed lower extremity lymphedema diagnosis for left iliac vein obstruction (IVO) or May-Thurner syndrome (MTS). The objective of this study is to determine the utility of routine CTV screening for these patients by evaluating the proportion presenting with clinically significant CTV-identified left IVO.
Methods: We retrospectively reviewed 121 patients who had presented to our lymphedema center with lower extremity edema between November 2020 and May 2022. Information regarding demographics, comorbidities, lymphedema characteristics, and imaging reports was collected. Cases of IVO present on CTV were reviewed by a multidisciplinary team to determine the clinical significance of the CTV findings.
Results: Of the patients with complete imaging studies, 49% (n = 25) had abnormal lymphoscintigraphy findings, 45% (n = 46) had reflux on ultrasound, and 11.4% (n = 9) had IVO on CTV. Seven patients (6%) had CTV findings of IVO and edema of either the isolated left (n = 4) or bilateral (n = 3) lower extremities. Cases of IVO on CTV were determined by the multidisciplinary team to be the predominant cause of lower extremity edema for three of these seven cases (43%; or 2.5% of all 121 patients).
Conclusions: Six percent of patients presenting to a lymphedema center with lower extremity edema had left-sided IVO on CTV suggestive of MTS. However, the cases of IVO were determined to be clinically significant <50% of the time or for 2.5% of all patients. CTV should be reserved for patients with isolated left-sided or bilateral lower extremity edema with a greater left-sided component and a history of findings that raise clinical suspicion for MTS. [/av_toggle] [/av_toggle_container] [av_toggle_container initial='0' mode='accordion' sort='' styling='' colors='' font_color='' background_color='' border_color=''] [av_toggle title='Non-Invasive Portable Technologies for Monitoring Breast Cancer Related Lymphedema to Facilitate Telehealth: A Scoping Review - click for abstract' tags=''] Non-Invasive Portable Technologies for Monitoring Breast Cancer Related Lymphedema to Facilitate Telehealth: A Scoping Review
Arifur R Anik, Kamrul Hasan, Md Manirul Islam, Md Mehedi Hasan, Md Firoj Ali, Sajal K Das. IEEE J Biomed Health Inform. 2023 May 29;PP.
Breast cancer related lymphedema (BCRL) is a common, debilitating condition that can affect up to one in five breast cancer surviving patients (BCSP). BCRL can significantly reduce the quality of life (QOL) of patients and poses a significant challenge to healthcare providers. Early detection and continuous monitoring of lymphedema is crucial for the development of client-centered treatment plans for post-cancer surgery patients. Therefore, this comprehensive scoping review aimed to investigate the current technology methods used for the remote monitoring of BCRL and their potential to facilitate telehealth in the treatment of lymphedema. Initially, five electronic databases were systematically searched and analyzed following the PRISMA flow diagram. Studies were included, specifically if they provided data on the effectiveness of the intervention and were designed for the remote monitoring of BCRL. A total of 25 included studies reported 18 technological solutions to remotely monitor BCRL with significant methodological variation. Additionally, the technologies were categorized by method of detection and wearability. The findings of this comprehensive scoping review indicate that state-of-the-art commercial technologies were found to be more appropriate for clinical use than home monitoring, with portable 3D imaging tools being popular (SD 53.40) and accurate (correlation 0.9, p 0.05) for evaluating lymphedema in both clinic and home settings with expert practitioners and therapists. However, wearable technologies showed the most future potential for accessible and clinical long-term lymphedema management with positive telehealth outcomes. In conclusion, the absence of a viable telehealth device highlights the need for urgent research to develop a wearable device that can effectively track BCRL and facilitate remote monitoring, ultimately improving the quality of life for patients following post-cancer treatment
Association Between Bioimpedance Spectroscopy and Magnetic Resonance Lymphangiography in the Diagnosis and Assessment of Lymphedema - click for abstract
Kaamya Varagur, Anup S Shetty, Karim Saoud, Esther Ochoa, Rachel Skladman, Gary B Skolnick, Justin Michael Sacks, Joani M Christensen. J Reconstr Microsurg. 2023 May 26.
Background: This study assesses associations between bioimpedance spectroscopy (BIS) and magnetic resonance lymphangiography (MRL) in staging and assessment of lymphedema. Methods: Adults who received MRL and BIS between 2020-2022 were included. We collected fluid, fat, and lymphedema severity ratings, and measured fluid stripe thickness, subcutaneous fat width, and lymphatic diameter on MRL. BIS Lymphedema Index (L-Dex®) scores were collected from patient charts. We assessed sensitivity and specificity of L-Dex scores to detect MRL-identified lymphedema, and examined associations between L-Dex scores and MRL imaging measures. Results: 48 limbs across 40 patients were included. L-Dex scores had 72.5% sensitivity and 87.5% specificity for detecting MRL-defined lymphedema, with a 96.7% estimated positive predictive value and 38.9% negative predictive value. L-Dex scores were associated with MRL fluid and fat content scores (p≤0.05), and lymphedema severity (p=0.01), with better discrimination between fluid than fat content levels on pairwise analysis, and poor discrimination between adjacent severity levels. L-Dex scores were correlated with distal and proximal limb fluid stripe thickness (distal: rho=0.57, p<0.01; proximal: rho=0.58, p<0.01), partially correlated with distal subcutaneous fat thickness when accounting for BMI (rho=0.34, p=0.02), and were not correlated with lymphatic diameter (p=0.25). Conclusion: L-Dex scores have high sensitivity, specificity, and positive predictive value for the identification of MRL-detected lymphedema. L-Dex has difficulty distinguishing between adjacent severity levels of lymphedema and a high false negative rate, explained in part by reduced discrimination between levels of fat accumulation. [/av_toggle] [/av_toggle_container] [av_toggle_container initial='0' mode='accordion' sort='' styling='' colors='' font_color='' background_color='' border_color=''] [av_toggle title='Investigation of physical activity, fear of falling, and functionality in individuals with lower extremity lymphedema - click for abstract' tags=''] Investigation of physical activity, fear of falling, and functionality in individuals with lower extremity lymphedema
Cansu Sahbaz Pirincci1 · Emine Cihan2 · Bayram Sönmez Ünüvar3 · Hasan Gerçek3 · Aydan Aytar1 ·Pınar Borman4. Supportive Care in Cancer (2023) 31:360
Purpose To investigate the fear of falling, physical activity, and functionality in patients with lymphedema in the lower extremities.
Methods Sixty-two patients who developed stage 2–3 lymphedema in the lower extremities due to primary or secondary causes (age: 56.03 ± 7.83 years) and 59 healthy controls (age: 54.61 ± 5.43 years) were included in the study. The sociodemographic and clinical characteristics of all individuals included in the study were recorded. In both groups, fear of falling was evaluated with the Tinetti Falls Efficacy Scale (TFES), lower extremity functionality with the Lower Extremity Functional Scale (LEFS), and physical activity with the International Physical Activity Questionnaire-Short Form (IPAQ-SF).
Results There was no statistically significant difference between the demographic characteristics of the groups (p > 0.05). The primary and secondary lymphedema groups had similar LEFS (p = 0.207, d = 0.16), IPAQ (p = 0.782, d = 0.04), and TFES (p = 0.318, d = 0.92) scores. However, the TFES score of the lymphedema group was significantly higher than that of the control group (p < 0.01, d = 0.52), while the LEFS (p < 0.01, d = 0.77) and IPAQ scores (p = 0.001, d = 0.30) were signifcantly higher in the latter. There was a negative correlation between LEFS and TFES (r = −0.714, p < 0.001) and between TFES and IPAQ (r = −0.492, p < 0.001). LEFS and IPAQ were positively correlated (r = 0.619, p < 0.001). Conclusion It was determined that individuals with lymphedema developed a fear of falling, and their functionality was negatively afected. This negative efect on functionality can be attributed to reduced physical activity and an increased fear of falling [/av_toggle] [/av_toggle_container] [av_hr class='invisible' height='50' shadow='no-shadow' position='center' custom_border='av-border-thin' custom_width='50px' custom_border_color='' custom_margin_top='30px' custom_margin_bottom='30px' icon_select='yes' custom_icon_color='' icon='ue808' font='entypo-fontello'] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']
Evaluating telehealth for the education and monitoring of lymphoedema and shoulder dysfunction after breast cancer surgery
Leonie Naumann1 · Hildegard Reul‑Hirche1,2,3 · Tracy Comans4,5 · Clare L. Burns6 · Jenny Paratz1,3 · Michelle Cottrell1. Supportive Care in Cancer (2023) 31:239
Download full paper
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Management Strategies
Effectiveness of Mobiderm Autofit in the Intensive Phase of Breast Cancer-Related Lymphedema Treatment: A Case Series - click for abstract
Effectiveness of Mobiderm Autofit in the Intensive Phase of Breast Cancer-Related Lymphedema Treatment: A Case Series
Sławomir Mazur, Dorota Szczęśniak, Hanna Tchórzewska-Korba. Lymphat Res Biol. 2023 May 22
Background: The objective of this case series was to evaluate the effectiveness of wearing Mobiderm® Autofit compressive garment as part of the complete decongestive therapy (CDT) of upper limb lymphedema.
Materials and Methods: Ten women and men with stage II breast cancer-related lymphedema underwent a CDT intensive phase for 12 days, combining Mobiderm Autofit compression garment with manual lymphatic drainage. Arm volume was calculated with the truncated cone formula using circumferential measurements taken at each appointment. The pressure under the garment and the overall satisfaction of patients and physicians were also assessed.
Results: The mean (standard deviation [SD]) age of the patients was 60.50 (11.70) years. The mean (SD) lymphedema excess volume decrease was 343.11 (266.14) mL, which represents a 36.68% decrease between day 1 and day 12, whereas the mean (SD) absolute volume difference was 420.03 (251.27) mL corresponding to a 10.12% decrease during this same period. The mean (SD) device pressure by using the PicoPress® was 30.01 (0.45) mmHg. The majority of patients were satisfied with the ease of use and the comfort of wearing Mobiderm Autofit. Such positive assessment was confirmed by the physicians. During this case series, no adverse event was reported.
Conclusion: A lymphedema volume decrease of the upper limb was reported after 12 days of treatment with Mobiderm Autofit during the CDT intensive phase. Moreover, the device was well tolerated, and its use was appreciated by the patients and the physicians.
Night-time compression: a valuable addition to the lymphoedema management toolkit- click for abstract
Night-time compression: a valuable addition to the lymphoedema management toolkit
As an incurable condition, lymphoedema, whether primary or secondary, is a significant burden for patients, impacting every aspect of their lives, ranging from the personal to the professional. While daytime compression is a pillar of lymphoedema management, night-time compression delivery is also gaining credence. Health writer Francesca Ramadan summarises the exploration of this growing phenomenon in the literature, overviewing the benefits and dispelling the myths.
Effects of inpatient rehabilitation in leg lymphedema: a naturalistic prospective cohort study with intra-individual control of effects - click for abstract
Effects of inpatient rehabilitation in leg lymphedema: a naturalistic prospective cohort study with intra-individual control of effects
OBJECTIVE: To quantify therapy-attributable effects of a comprehensive inpatient rehabilitation program for lower-leg lymphedema (LLL) and to compare the levels of health-related quality of life (HRQL) to population-based norms. DESIGN: Naturalistic prospective cohort study with intra-individual control of effects.SETTING: Rehabilitation hospital.PARTICIPANTS: Patients with LLL (n=67; 46 women).INTERVENTIONS: Comprehensive, multidisciplinary inpatient rehabilitation with 45-60 hours of therapy.MAIN OUTCOME MEASURES: Short Form 36 (SF-36) for HRQL, lymphedema-specific Freiburg Quality of Life Assessment for lymphatic disorders, Short Version (FLQA-lk), knee-specific Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), and Symptom Checklist-90Standard (SCL-90S). Observed pre/post rehabilitation effects were individually corrected by subtracting the home waiting-time effects and expressed as standardized effect sizes (ESs) and standardized response means (SRMs). Score differences to norms were quantified by standardized mean differences (SMDs). RESULTS: Participants were on average aged 60.5 years, not yet obese, and had 3 comorbidities (n=67). The greatest improvement was in HRQL on the FLQA-lk with ES=0.767/SRM=0.718, followed by improvements in pain and function with ES/SRM=0.430 to 0.495 on the SF-36, FLQA-lk, and KOS-ADL (all p<..001). Vitality, mental health, emotional well-being, and interpersonal sensitivity improved most by ES/SRM=0.341 to 0.456 on all four measures (all p≤0.003). Post rehabilitation scores were significantly higher than population norms on SF-36 bodily pain (SMD=1.140), vitality (SMD=0.886), mental health (SMD=0.815), and general health (SMD=0.444) (all p<..001), and comparable on the other scales. CONCLUSIONS: Those affected by LLL stages II and III benefited substantially from the intervention, attaining equal or higher levels of HRQL than expected compared to the general population norms. Multidisciplinary, inpatient rehabilitation should be recommended for LLL management [/av_toggle] [/av_toggle_container] [av_hr class='invisible' height='50' shadow='no-shadow' position='center' custom_border='av-border-thin' custom_width='50px' custom_border_color='' custom_margin_top='30px' custom_margin_bottom='30px' icon_select='yes' custom_icon_color='' icon='ue808' font='entypo-fontello'] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']
Effect of progressive resistance exercise using Thera-band on edema volume, upper limb function, and quality of life in patients with breast cancer-related lymphedema
Yun-Jin Park, Song-Ju Na, Myung-Ki Kim. J Exerc Rehabil. 2023 Apr 27;19(2):105-113.
Download full paper Impact on Health-Related quality of life after wearing compression garment or not for six months in women with mild breast cancer-related arm lymphedema. A cross-sectional study Katarina Y. Blom, Karin Johansson, Lena B. Nilsson-Wikmar, Pia E. Klernäs, Christina B. Brogårdh. Acta Oncol. 2023 May 2 Low-intensity pulsed ultrasound reduces lymphedema by regulating macrophage polarization and enhancing microcirculation Investigation of the effect of Low-Level Laser Therapy on arm lymphedema in breast cancer patients: A noninvasive treatment for an intractable morbidity Lymphoscintigraphy as a Therapeutic Guidance Tool Can Improve Manual Lymphatic Drainage for the Physical Treatment of Patients with Upper Limb Lymphedema: Randomized Clinical Trial Romain Barbieux, Sabrina Doyenard, Agathe Pluska, Keoma Enciso, Mirela Mariana Roman, Olivier Leduc, Albert Leduc, Pierre Bourgeois, Steven Provyn. Lymphat Res Biol. 2023 May 17. doi Current Concepts in the Management of Primary Lymphedema Jenna-Lynn B Senger, Rohini L Kadle, Roman J Skoracki. Medicina (Kaunas). 2023 May 6;59(5):894 Postoperative Effectiveness of Comprehensive Nursing Intervention for Lymphedema in Gynecological Cancer: A Controlled Study Effects of a lymphedema prevention program based on the theory of knowledge-attitude-practice on postoperative breast cancer patients: A randomized clinical trial
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Zihao Liu, Jia Li, Yu Bian, Xiaojie Zhang, Xiaojun Cai, Yuanyi Zheng. Front Bioeng Biotechnol. 2023 May 5;11:1173169.
Farshid Farhan, Mahmood Samei, Alireza Abdshah, Ali Kazemian, Shahriar Shahriarian, Farnaz Amouzegar-Hashemi, Mostafa Farzin, Reza Ghalehtaki, Fatemeh Jafari, Francesco Cuccia. Health Sci Rep. 2023 May 17;6(5):e1261.
Xiuting Liao, Guo Cao, Ling Yang, Chunli Wang, Changying Tian
