Hot of the Press May 2022

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

Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema - click for abstract

Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema

Masaki Sano, Satoshi Hirakawa, Takeshi Sasaki, Kazunori Inuzuka, Kazuto Katahashi, Takafumi Kayama, Yuta Yamanaka, Hajime Tsuyuki, Yusuke Endo, Ena Naruse, Yurina Yokoyama, Kohji Sato, Katsuya Yamauchi, Hiroya Takeuchi, Naoki Unno. Lymphat Res Biol. 2022 Apr 7.

Secondary lymphedema (LE) occurs due to the disruption of lymphatic circulation. Lymphatic fluid accumulation in subcutaneous tissues induces adipocyte proliferation. Obesity is an important risk factor for the occurrence and deterioration of LE. Although the relationship between LE and subcutaneous adipose tissue increase has been reported clinically, their pathophysiological relationship remains unknown. Thus, we aimed to verify whether subcutaneous adipose tissue increase is involved in the pathophysiology of secondary LE. Methods and Results: The hindlimb model of secondary LE was created using male Sprague-Dawley rats (control and LE groups; n = 5 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines, tumor necrosis factor-alpha (Tnf-α), C-C chemokine ligand 2 (Ccl2), and interleukin-6 (Il-6) were performed. Limb volume and subcutaneous adipose tissues significantly increased in the LE group compared with those in the control. Macrophages aggregated in the augmented adipose tissues, around the adipocytes, and formed crown-like structures (CLSs). The number of CLSs significantly increased in the LE group. These macrophages expressed transforming growth factor-beta 1 (TGF-β1). Inflammatory adipokine secretion was not observed. Although Il-6 expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes. Conclusion: As TGF-β1 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-β1 derived from adipose tissues may also play a similar role. Drug treatment for subcutaneous adipose tissue reduction may improve the skin condition in secondary LE and may be a new therapeutic strategy.

Hypoxia and Hypoxia-Inducible Factors in Lymphedema

Xinguo Jiang, Wen Tian, Dongeon Kim, Alexander S McQuiston, Ryan Vinh, Stanley G. Rockson, Gregg L Semenza, Mark R Nicolls. Front Pharmacol. 2022 Mar 28;13:851057

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Frequent Onsets of Cellulitis in Lower Limbs with Lymphedema Following COVID-19 mRNA Vaccination

Tatsuma Okazaki, Momoko Matashiro, Gaku Kodama, Takeshi Tshubota, Yoshihito Furusawa, Shin-Ichi Izumi. Vaccines (Basel). 2022 Mar 26;10(4):517.

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Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema

Cynthia J Sung, Kshitij Gupta, Jin Wang, Alex K Wong. Bioengineering (Basel). 2022 Apr 6;9(4):162.

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Relationship between lymphedema after breast cancer treatment and biophysical characteristics of the affected tissue

Carla S Perez, Carolina Mestriner, Leticia T N Ribeiro, Felipe W Grillo, Tenysson W Lemos, Antônio A Carneiro, Rinaldo Roberto de Jesus Guirro, Elaine C O Guirro

PLoS One. 2022 Apr 20;17(4):e0264160

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Prevalence and Risk Factors

Five-Year Cumulative Incidence of Axillary Web Syndrome and Comparison in Upper Extremity Movement, Function, Pain, and Lymphedema in Breast Cancer Survivors With and Without Axillary Web Syndrome - click for abstract

Five-Year Cumulative Incidence of Axillary Web Syndrome and Comparison in Upper Extremity Movement, Function, Pain, and Lymphedema in Breast Cancer Survivors With and Without Axillary Web Syndrome

Linda Koehler, Amanda Day, David Hunter, Anne Blaes, Tufia Haddad, Ryan Shanley. Arch Phys Med Rehabil. 2022 Apr 6:S0003-9993(22)00291-X.

OBJECTIVE: To determine the cumulative incidence and natural history of axillary web syndrome (AWS) and its related postoperative risk for physical impairments in a cohort of women followed for 5 years post breast cancer surgery.

DESIGN: Prospective, longitudinal study

SETTING: Academic health center

PARTICIPANTS: Women (n=36) with and without AWS following breast cancer surgery with sentinel node biopsy or axillary lymph node dissection

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participants were assessed for AWS, shoulder goniometric flexion and abduction range of motion (ROM), function (Disability of the Arm, Shoulder, and Hand), lymphedema (bioimpedance spectroscopy, girth measures, and tissue dielectric constant), and pain (visual analog scale) at 2-, 4-, 12-, and 78- weeks and 5-years after breast cancer surgery. Analysis of variance compared ROM, function, lymphedema, and pain in women identified with AWS to those without AWS across visits. Univariate logistic regression assessed if AWS was a risk factor for physical impairment at 5-years.RESULTS: The cumulative incidence of AWS was 57%. Fifty percent (14/28) of the women that completed all study visits had signs of AWS at 5-years. Abduction active ROM was significantly lower in women with AWS at 2- and 4- weeks post-surgery. AWS was identified as a risk factor for reduced shoulder motion at 5-years. Regardless of AWS, 75% of the women experienced one or more upper extremity physical impairments at 5-years, which is an increase from 66% at 78-weeks in the same cohort.

CONCLUSIONS: AWS is associated with reduced shoulder ROM in the early post-operative time period, can persist for 5-years after breast cancer surgery, and increases the risk of long-term reduced shoulder ROM. Long-term physical issues are apparent following breast cancer surgery regardless of AWS

Co-occurring Fatigue and Lymphatic Pain Incrementally Aggravate Their Negative Effects on Activities of Daily Living, Emotional Distress, and Overall Health of Breast Cancer Patients

Mei R. Fu, Melissa L McTernan, Jeanna M Qiu, Christine Miaskowski, Yvette P Conley, Eunjung Ko, Deborah Axelrod, Amber Guth, Tamara J Somers, Lisa J Wood, Yao Wang. Integr Cancer Ther. 2022 Jan-Dec;21:15347354221089605.

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Assessment

How we approach lymphedema in the pediatric population - click for abstract

How we approach lymphedema in the pediatric population

Irina Pateva, Arin K Greene, Kristen M Snyder. Pediatr Blood Cancer. 2022 Apr 1

Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities

Can Tissue Stiffness Measured Using Shear-Wave Elastography Represent Lymphedema in Breast Cancer? - click for abstract

Can Tissue Stiffness Measured Using Shear-Wave Elastography Represent Lymphedema in Breast Cancer?

Dong Gyu Lee, Jang Hyuk Cho. Lymphat Res Biol. 2022 Apr 7.

Lymphedema causes skin and subcutaneous fibrosis. However, quantitative methods for estimating the severity of fibrosis due to lymphedema have not been established. We evaluated skin stiffness using shear-wave elastography (SWE) and aimed to identify stiffness-associated factors in patients with breast cancer-related lymphedema (BCRL). Methods and Results: Thirty-six women (mean age, 57.5 ± 1.78 years; range, 39-77 years) were retrospectively recruited for this study. The mid-arm and mid-forearm circumferences were measured. The percentage differences in arm and forearm circumferences were used as an indicator of the severity of lymphedema at the time of SWE measurement and the measurement taken when the symptoms were most severe. Not subcutaneous tissues but cutaneous tissues of the affected arm and forearm showed a significant increase in shear-wave velocity (SWV) compared with those of the unaffected side. However, SWV was not correlated with the severity of lymphedema as a percentage difference when symptoms were most severe. Body mass index and lymphedema duration showed no significant correlation with the SWV of cutaneous tissues on the affected upper extremities. Conclusions: SWE can adequately estimate cutaneous fibrosis between the affected and unaffected limbs in patients with BCRL. However, evaluation of subcutaneous fibrosis is limited. Therefore, SWE can be an effective tool for evaluating cutaneous fibrosis in patients with BCRL.

Using the Indocyanine Green (ICG) Lymphography to Screen Breast Cancer Patients at High Risk for Lymphedema - click for abstract

Using the Indocyanine Green (ICG) Lymphography to Screen Breast Cancer Patients at High Risk for Lymphedema

Miao Liu, Siyao Liu, Quanping Zhao, Ying Cui, Jin Chen, Shu Wang. Diagnostics (Basel). 2022 Apr 14;12(4):983.

BACKGROUND: Indocyanine green (ICG) lymphography is a newer technique for diagnosing lymphedema. Our study aimed to find whether the abnormality of ICG lymphography can predict the occurrence of early lymphedema and then select candidates at high risk of developing lymphedema.

METHODS: Postoperative breast cancer patients who visited the lymphedema clinic of Peking University People’s Hospital from December 2016 to September 2019 were consecutively enrolled and received ICG lymphography and circumference measurement. Data were collected on the patients’ characteristics and correlation between ICG lymphography and the occurrence of lymphedema.

RESULTS: The analysis included 179 patients. There were 91 patients in the lymphedema group and 88 patients in the non-lymphedema group. By multivariate analysis, age, axillary surgery, radiotherapy, and time since breast cancer surgery were regarded as risk factors for lymphedema (p < 0.05). According to the results of ICG lymphography, patients in the non-lymphedema group (n = 88) were divided into ICG-positive (n = 47) and ICG-negative (n = 41) groups. The incidence of lymphedema in the ICG-positive group was significantly higher than that in the ICG-negative group (19.1% vs. 2.4%, p = 0.027).

CONCLUSION: Lymphatic disorder can be detected before circumference change using ICG lymphography. Abnormal ICG lymphography is an independent risk factor for lymphedema. Patients with abnormal dermal backflow patterns are considered to be a high-risk group for lymphedema and should undergo early interventions to prevent lymphedema

The Comparative Frequency of Breast Cancer-Related Lymphedema Determined by Bioimpedance Spectroscopy and Circumferential Measurements

Pınar Borman, Ayşegül Yaman, Lütfi Doğan, Ayşe Arıkan Dönmez, Esra Gizem Koyuncu, Ayşegül Balcan, Sercan Aksoy, Cihangir Özaslan, Rabiye Akın, Kaniye Üneş. Eur J Breast Health. 2022 Apr 1;18(2):148-154

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Management Strategies

Decongestive progressive resistance exercise with an adjustable compression wrap for breast cancer-related lymphoedema (DREAM): protocol for a randomised controlled trial

Mona M Al Onazi, Kristin L Campbell, Richard B Thompson, Sunita Ghosh, John R. Mackey, Anne Muir, Margaret McNeely. BMJ Open. 2022 Apr 4;12

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Update to the Canadian clinical practice guideline for best-practice management of breast cancer-related lymphedema: study protocol

Margaret McNeely, Susan R Harris, Naomi D. Dolgoy, Mona M Al Onazi, Joanna F Parkinson, Lori Radke, Xanthoula Kostaras, Liz Dennett, Jean Ann Ryan, Mary-Ann Dalzell, Anna Kennedy, Lauren C. Capozzi, Anna M. Towers, Kristin L Campbell, Jill Binkley, Karen M. King, David H. Keast. CMAJ Open. 2022 Apr 12

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Manual lymphatic drainage with or without fluoroscopy guidance did not substantially improve the effect of decongestive lymphatic therapy in people with breast cancer-related lymphoedema (EFforT-BCRL trial): a multicentre randomised trial

Tessa De Vrieze, Nick Gebruers, Ines Nevelsteen, Steffen Fieuws, Sarah Thomis, An De Groef, Wiebren Aa Tjalma, Jean-Paul Belgrado, Liesbeth Vandermeeren, Chris Monten, Marianne Hanssens, Nele Devoogdt. J Physiother. 2022 Apr 12:S1836-9553(22)00018-2

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Impact of Activity-Oriented Propioceptive Antiedema Therapy on the Health-Related Quality of Life of Women with Upper-Limb Lymphedema Secondary to Breast Cancer-A Randomized Clinical Trial - click for abstract

Impact of Activity-Oriented Propioceptive Antiedema Therapy on the Health-Related Quality of Life of Women with Upper-Limb Lymphedema Secondary to Breast Cancer-A Randomized Clinical Trial

María Nieves Muñoz-Alcaraz, Luis A Pérula-de Torres, Antonio José Jiménez-Vílchez, Paula Rodríguez-Fernández, María Victoria Olmo-Carmona, María Teresa Muñoz-García, Presentación Jorge-Gutiérrez, Jesús Serrano-Merino, Esperanza Romero-Rodríguez, Lorena Rodríguez-Elena, Raquel Refusta-Ainaga, María Pilar Lahoz-Sánchez, Belén Miró-Palacios, Mayra Medrano-Cid, Rosa Magallón-Botaya, Mirian Santamaría-Peláez, Luis A Mínguez-Mínguez, Jerónimo J González-Bernal. J Clin Med. 2022 Mar 28;11(7):1884.

BACKGROUND: Alterations derived from lymphedema in the upper-limb secondary to breast cancer-related lymphedema (BCRL) decrease the health-related quality of life (HRQoL), but there is limited evidence of the impact of the different interventions on it. The aim of this research was to compare the effect of conventional treatment with another treatment based on Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) on HRQoL in women diagnosed with BCRL.

METHODS: A prospective clinical study was designed with two parallel arms. The study population consisted of women diagnosed with BCRL in stage I and II, belonging to different institutions in Córdoba and Aragon, Spain. Sociodemographic and HRQoL-related variables, pain, tightness, heaviness and functionality were obtained before and after treatments.

RESULTS: 51 women participated in the study, 25 received the conventional treatment and 26 the TAPA, with a mean age of 59.24 ± 9.55 years. HRQoL was significantly related to upper-limb function and pain on the participants’ affected side. In addition, covariance analysis (ANCOVA) showed that the TAPA treatment interfered less in the performance of activities of daily life and produced significant improvements in the social dimension of HRQoL.

CONCLUSIONS: the non-use of compressive elements in the rehabilitative treatment of the BCRL that is proposed with TAPA improves aspects such as self-image and participation in social and recreational activities

How to Care and Minimize the Sequelae of Lower Extremity Lymphedema - click for abstract

How to Care and Minimize the Sequelae of Lower Extremity Lymphedema

Katherine Bobrek, Reza Nabavizadeh, Behnam Nabavizadeh, Viraj Master. Semin Oncol Nurs. 2022 Apr 15:151270.

OBJECTIVE: The objective of this review is to provide information regarding the care of patients with lower extremity lymphedema in the setting of urologic cancer.

DATA SOURCES: Literature regarding lower extremity lymphedema was examined. Relevant information was integrated to create a review of the pathophysiology, management, and potential complications of lower extremity lymphedema.

CONCLUSION: Lower lymphedema is a chronic, debilitating condition with no definitive cure. It may affect patients undergoing treatment for malignancies, especially those undergoing lymph node removal. Management of this condition is multimodal, and complex decongestive therapy is currently the gold standard. For patients who do not respond to this management, surgical options exist. More research should be done in understanding the prevalence and management of lower extremity lymphedema in patients suffering from urologic cancers because this is underdeveloped research.

IMPLICATIONS FOR NURSING PRACTICE: To care for patients with lower extremity lymphedema postoperatively, a multimodal approach is warranted. Different techniques include complex decongestive therapy, intermittent pneumatic compression, physical therapy, skin care, patient education, social support, and, in some cases, surgery

Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial - click for abstract

Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial

María Nieves Muñoz-Alcaraz, Antonio José Jiménez-Vílchez, Mirian Santamaría-Peláez, Luis A Pérula-de Torres, María Victoria Olmo-Carmona, María Teresa Muñoz-García, Presentación Jorge-Gutiérrez, Jesús Serrano-Merino, Esperanza Romero-Rodríguez, Lorena Rodríguez-Elena, Raquel Refusta-Ainaga, María Pilar Lahoz-Sánchez, Belén Miró-Palacios, Mayra Medrano-Cid, Rosa Magallón-Botaya, Luis A Mínguez-Mínguez, Josefa González-Santos, Jerónimo J González-Bernal. J Clin Med. 2022 Apr 16;11(8):2234.

BACKGROUND: Lymphedema, secondary to breast cancer (BCRL), is the abnormal accumulation of protein-rich fluid in the interstitium caused by a malfunction of the lymphatic system. It causes swelling, deficiencies in upper limb functions and structures, sensory pain and emotional alterations, which have a chronic course and affect the upper limb’s functionality. This study aims to verify the efficacy and efficiency in the upper limb´s functionality of a protocolized experimental approach based on occupational therapy, TAPA (activity-oriented proprioceptive antiedema therapy), in the rehabilitation of BCRL in stages I and II, comparing it with the conservative treatment considered as the standard, complex decongestive therapy (CDT), through a multicenter randomized clinical trial.

METHODS: a randomized and prospective clinical trial was conducted with experimental and control groups. Women diagnosed with BCRL belonging to institutions in Córdoba and Aragon (Spain) participated. Sociodemographic variables and those related to the functionality of the affected upper limb were evaluated before and after the intervention.

RESULTS: The results showed statistically significant differences in the analysis of covariance performed for the variable joint balance of the shoulder´s external rotation (p = 0.045) that could be attributed to the intervention performed; however, the effect size was minimal (η2 ≤ 0.080). In the rest of the variables, no significant differences were found.

CONCLUSIONS: TAPA may be an alternative to the conservative treatment of women with BCRL. It was shown to be just as effective for volume reduction and activity performance as CDT but more effective in improving external rotation in shoulder joint balance.

Home-Based Intermittent Pneumatic Compression Therapy: The Impact in Chronic Leg Lymphedema in Patients Treated for Gynecologic Cancer - click for abstract

Home-Based Intermittent Pneumatic Compression Therapy: The Impact in Chronic Leg Lymphedema in Patients Treated for Gynecologic Cancer

Yoon Kim, Seonghee Kim, Ji Young Lim, Chea Min Hwang, Myoung-Hwan Ko, Ji Hye Hwang. Healthcare (Basel). 2022 Mar 28;10(4):638.

We conducted a prospective study of cancer patients to investigate the efficacy, quality of life, satisfaction, and safety of a home-based intermittent pneumatic compression (IPC) device during the maintenance phase of lower extremity lymphedema. This device has a unique mode designed to mimic the manual lymphatic drainage (MLD) technique and thereby gently facilitate lymphatic draining of proximal extremities. Thirty patients with stage 3 chronic secondary unilateral leg lymphedema in the maintenance phase underwent IPC and conventional compression therapy for 4 weeks at home. The participants were guided to use 1 h course (30 min of MLD-mimicking mode and 30 min of conventional mode) of IPC device twice a day for 4 weeks. We assessed the patients’ limb-volume measurement, quality of life (QOL), and satisfaction four times. There were no significant time-dependent interactions in the inter-limb volume difference ratio (Vratio). In a subgroup analysis, participants who used the home-based IPC device and maintained their routine self-maintenance program of short-stretch bandages (group B, n = 21) showed a more significant decline in Vratio than those who did not maintained their routine care (group A, n = 9). All scores of QOL decreased significantly after the intervention without subgroup difference. All participants were satisfied with the 4-week intervention. This study demonstrated that a home-based IPC device with an MLD-mimicking program is a useful option for maintaining the volume of limbs and improving the QOL of patients with stage 3 chronic leg lymphedema during the maintenance phase.