Hot off the Press August 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.

Prevalence and Risk Factors

Risk Factors for the Development of Clinical and Subclinical Lymphedema Detected by Bioimpedance Spectroscopy
Mutlay Sayan,1 Sarah S. Kilic,2 Irina Vergalasova,3 Imraan Jan,3, Firas Eladoumikdachi,4 Bruce Haffty,3 Shicha Kumar,4 Nisha Ohri3. Clinical Breast Cancer, Vol. 22, No. 6, 553–559 © 2022
The treatment of breast cancer can cause lymphedema, which greatly impact patients’ quality of life. Earlier
treatment of lymphedema is more effective, but preclinical lymphedema is difficult to detect. We used a new tool,
bioimpedance spectroscopy, to detect preclinical lymphedema. This tool may allow physicians to intervene on
lymphedema early, before patients develop irreversible symptoms.
Background: Breast cancer-related lymphedema can significantly compromise quality of life. Bioimpedance
spectroscopy (BIS) measures extracellular fluid in lymphedema. The purpose of this study was to determine the
incidence of BIS-detected lymphedema using the L-Dex and identify risk factors associated with a positive score.
Materials and Methods: We performed a retrospective review of our institutional database to identify patients who underwent L-Dex U400 measurements. Patients with a score of > 10 L-Dex units or with an increase of > 10 units from baseline had a positive score. Clinical lymphedema was determined by documentation in the chart at the time of positive measurement. Otherwise, patients were considered to have subclinical lymphedema.
Results: Fifty-three patients met study criteria. Thirty patients (56.6%) underwent mastectomy, 22 (41.5%) axillary lymph node dissection (ALND), and 33 (62.3%) received radiation (RT). Twelve patients (22.6%) had a positive score. There were no differences in age, race, laterality, breast surgery, T stage, N stage, chemotherapy, or RT fields (none, breast only, breast with LNs) in patients with a positive score. ALND was more common (66.7% vs. 34.2%, P= .04). BMI > 30 approached significance (58.3% vs. 29.3%, P= .06). Seven patients had subclinical lymphedema. No differences were identified comparing patients with subclinical lymphedema to those with negative scores. All 5 patients with clinical lymphedema underwent ALND and received nodal RT.
Conclusion: The combination of ALND and regional nodal RT is strongly associated with development of clinical lymphedema. It is difficult to identify patients at risk for subclinical BIS-detected lymphedema

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment

Clara R Farley, Shelby Irwin, Taiwo Adesoye, Susie X Sun, Sarah M DeSnyder, Anthony Lucci, Simona F. Shaitelman, Edward I Chang, Naoto T Ueno, Wendy A Woodward, Mediget Teshome. Ann Surg Oncol. 2022 Jul 19.
BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy.
METHODS: IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured.
RESULTS: Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12).
CONCLUSIONS: IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.
Factors Influencing Lower Limb Lymphedema After Cervical Cancer Surgery: A Case–Control Study
Gaoming Liu, PhD, Jin Hu, MS, Yuanyuan Liu, MS, and Meifang Yuan, MS. Lymphatic Research and Biology July 2022.
Background: To analyze the factors influencing lower limb lymphedema (LLL) after cervical cancer surgery and provide a scientific reference for its effective prevention and control.
Methods and Results: Patients at a tertiary tumor hospital between January 2010 and January 2020 who received surgical treatment for cervical cancer were included in this study. Patients were divided into lymphedema case group (n = 253) and control group (n = 506) according to lymphedema occurrence, and univariate and multivariate analyses were used to analyze the factors influencing the occurrence of LLL after cervical cancer surgery. Multifactor conditional logistic regression analysis revealed that risk factors for lymphedema occurrence included body mass index, level of education, the presence of preoperative radiotherapy and chemotherapy, radiotherapy within 3 months after postoperative chemoradiotherapy, emergence of coronary heart disease within 3 months, vaginal disease, occurrence of postoperative complications, cervical cancer diagnosis before the manifestation of menstrual abnormalities, and a history of previous surgery.
Conclusion: Postoperative LLL after cervical cancer surgery is a chronic progressive disease, and no cure for LLL has been identified. Thus, determining the risk factors associated with LLL occurrence after uterine and cervical cancer surgery and the development of targeted prevention and early intervention strategies is urgently needed.

Prediction of lymphedema occurrence in patients with breast cancer using the optimized combination of ensemble learning algorithm and feature selection

Anaram Yaghoobi Notash, Aidin Yaghoobi Notash, Zahra Omidi, Shahpar Haghighat. BMC Med Inform Decis Mak. 2022 Jul 25;22(1):195

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Assessment

Water Distribution Changes in Complex Decongestive Treatment for Leg Lymphedema: Quantitative Evaluation by Direct Segmental Multi-Frequency Bioimpedance Analysis

Masahiro Toshima, Yoshihisa Morino. Ann Vasc Dis. 2022 Jun 25;15(2):94-100

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Tissue Dielectric Constant of the Lower Leg as an Index of Skin Water: Temporal Variations

Harvey N. Mayrovitz. Cureus. 2022 Jul 1;14(7):e26506.

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Bioimpedance Analysis for Predicting Outcomes of Complex Decongestive Therapy for Gynecological Cancer Related Lymphedema: A Feasibility Study

Bae SH, Kim WJ, Seo YJ, Kim J, Jeon JY. Ann Rehabil Med. 2020 Jun;44(3):238-245

OBJECTIVE: To determine whether the bioimpedance analysis (BIA) ratios of upper to lower extremities could predict treatment outcomes after complex decongestive therapy (CDT) for gynecological cancer related lymphedema (GCRL).

METHODS: A retrospective study, from March 2015 to December 2018, was conducted. The study sample comprised patients receiving CDT, 30 minutes per day, for 10 days. Bioimpedance was measured pre- and post-CDT. Circumference measurements were obtained at 20 and 10 cm above the knee (AK) and 10 cm below the knee (BK). We calculated the expected impedance at 0 Hz (R0) of extremities and upper/lower extremity R0 ratios (R0U/L). We evaluated the relationship between R0U/L and changes in R0U/L and circumferences, pre- and post-CDT.

RESULTS: Overall, 59 patients were included in this study. Thirty-one lower extremities in 26 patients comprised the acute group, and 38 lower extremities in 33 patients comprised the chronic group. Pre-treatment R0U/L was significantly correlated with R0U/L change after adjusting for age and BMI (acute: R=0.513, p<0.01; chronic: R=0.423, p<0.01). In the acute group, pre-treatment R0U/L showed a tendency to be correlated with circumference change (AK 20 cm: R=0.427, p=0.02; AK 10 cm: R=0.399, p=0.03). CONCLUSION: Our study results suggested that pre-treatment BIA could predict volume reductions after CDT in the early stages of GCRL. These findings implied that BIA value could be one possible parameter to apply in treatment outcomes prediction, during the early stage of GCRL. Therefore, further large-scale prospective studies will be beneficial.

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer

Rebecca A Uhlmann, Sarah L Mott, Melissa Curry, Sneha Phadke, Sonia L Sugg, Lillian M Erdahl, Ronald J Weigel, Ingrid M Lizarraga. Ann Surg Oncol. 2022 Aug 1.
BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs.
PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information.
RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment.
DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.

Management Strategies

How we approach lymphedema in the pediatric population.

Pateva I; Greene AK; Snyder KM; Pediatric blood & cancer [Pediatr Blood Cancer] 2022 Aug; Vol. 69 (8), pp. e29611

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.

The impact of rehabilitation sport on breast cancer-related lymphoedema and quality of life

Bettina Boeer, Anna Seller, Birgitt Schoenfisch, Ute Krainick-Strobel, Andreas Dietrich, Sara Y Brucker, Diethelm Wallwiener, Andreas Niess, Markus Hahn. Arch Gynecol Obstet. 2022 Jul 26.
PURPOSE: Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS).
METHODS: Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL.
RESULTS: The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training-the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time.
CONCLUSION: PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.

Self-efficacy to overcome exercise barriers in individuals with cancer-related lymphedema

J Buchan, M Janda, R Box, L Q Rogers, S Hayes. Lymphology. 2022;55(1):10-20.

Although cancer survivors are recommended to exercise, they may lack confidence (self-efficacy) to be active. This research aimed to measure exercise barriers and related selfefficacy in individuals with cancer-related lymphedema as well as examine relationships between self-efficacy and participant characteristics. A cross-sectional survey was undertaken in individuals with cancer-related lymphedema using a validated 14-item Likert scale assessing self-efficacy to overcome general and lymphedema-specific exercise barriers (0%=not at all confident, 100%=extremely confident). Demographic, medical and lymphedema data were also collected. Of 109 participants (52% response), 79% (n=86) had breast cancer-related lymphedema. Participants were found to be moderately confident to exercise when facing general (48% [95% CI: 44, 52]) and lymphedema- specific exercise barriers (51% [95% CI: 47, 55]). Participants who were female, sedentary (p<0.05), had lymphedema for ≥2 years, and reported greater symptom burden (p<0.05) recorded lower general exercise barriers self efficacy. Lower lymphedema-specific exercise barriers self-efficacy was reported by individuals who were sedentary, had cancers other than breast, and higher symptom burden. These findings suggest general and lymphedema- specific barriers challenge exercise confidence in those with cancer-related lymphedema, and strategies tailored to improve confidence in overcoming exercise barriers are warranted. Supporting individuals to be sufficiently active during and following cancer treatment should consider behavior change strategies tailored to the unique needs faced by individuals with lymphedema.

Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review

Alessandro de Sire, Luigi Losco, Lorenzo Lippi, Davide Spadoni, Juste Kaciulyte, Gokhan Sert, Paola Ciamarra, Marco Marcasciano, Roberto Cuomo, Alberto Bolletta, Marco Invernizzi, Emanuele Cigna
Medicina (Kaunas). 2022 Jul 19;58(7):954. doi: 10.3390
Lymphedema is a chronic disabling condition affecting a growing number of patients worldwide. Although lymphedema is not life-threatening, several reports underlined detrimental consequences in terms of distress, pain, functional impairment, and infections with a relevant decrease in quality of life. Currently, there is no cure, and the therapeutic management of this condition aims at slowing down the disease progression and preventing secondary complications. Early diagnosis is paramount to enhance the effects of rehabilitation or surgical treatments. On the other hand, a multidisciplinary treatment should be truly integrated, the combination of microsurgical and reductive procedures should be considered a valid strategy to manage extremity lymphedema, and rehabilitation should be considered the cornerstone of the multidisciplinary treatment not only for patients not suitable for surgical interventions but also before and after surgical procedures. Therefore, a specialized management of Plastic Reconstructive Surgeons and Physical and Rehabilitative Medicine physicians should be mandatory to address patients’ needs and optimize the treatment of this disabling and detrimental condition. Therefore, the aim of this review was to characterize the comprehensive management of lymphedema, providing a broad overview of the potential therapy available in the current literature to optimize the comprehensive management of lymphedema and minimize complications.

Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema

Ryohei Ogino, Tomoharu Yokooji, Maiko Hayashida, Shota Suda, Sho Yamakawa, Kenji Hayashida. Int J Mol Sci. 2022 Jul 9;23(14):7614

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Wound Awareness Week 2022Journal of Lymphoedema August 2022