Hot off the Press May 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

Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum

Stanley G. Rockson. Lymphat Res Biol. 2023 Apr;21(2):99-100. 

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Lymphoscintigraphic alterations in lower limbs in women with lipedema in comparison to women with overweight/obesity

Angelika Chachaj, Ilona Dudka, Małgorzata Jeziorek, Monika Sowicz, Agnieszka Adaszyńska, Andrzej Szuba
Front Physiol. 2023 Apr 10;14:1099555. eCollection 2023.

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A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema

Julia von Atzigen, Anna Burger, Lisanne Grünherz, Carlotta Barbon, Gunther Felmerer, Pietro Giovanoli, Nicole Lindenblatt, Stefan Wolf, Epameinondas Gousopoulos. Int J Mol Sci. 2023 Apr 20;24(8):7591. doi: 10.3390/ijms24087591.

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Prevalence and Risk Factors

The Axillary Lateral Vessel Thoracic Junction is Not an Organ-at-Risk for Breast Cancer Related Lymphedema

Erin Healy, Sasha Beyer, Sachin Jhawar, Julia R White, Jose G Bazan. Int J Radiat Oncol Biol Phys. 2023 Apr 12:S0360-3016(23)00362-0. doi: 10.1016/j.ijrobp.2023.04.003.

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Risk factors of breast cancer-related lymphoedema: protocol of an umbrella review

Aomei Shen, Qian Lu, Liyuan Zhang, Jingru Bian, Fei Zhu, Zijuan Zhang, Wanmin Qiang
BMJ Open. 2023 Apr 12;13(4):e070907. doi: 10.1136/bmjopen-2022-07090

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Risk factors for the development of severe breast cancer-related lymphedema: a retrospective cohort study

Xiaozhen Liu, Kewang Sun, Hongjian Yang, Lingli Xia, Kefeng Lu, Xuli Meng, Yongfeng Li. BMC Cancer. 2023 Apr 20;23(1):361. doi: 10.1186/s12885-023-10814-5.

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Assessment

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.

The Appraisal of Clinical Practice Guidelines for Breast Cancer-Related Lymphedema

Naomi D. Dolgoy, Mona M Al Onazi, Joanna F Parkinson, Haukur Gudmundsson, Lori L Radke, Liz Dennett, Kristin L Campbell, Susan R Harris, David H. Keast, Margaret McNeely. Lymphat Res Biol. 2023 Apr 10.
Background: Approaches to screening, assessment, and treatment of breast cancer-related lymphedema (BCRL) vary widely. We evaluated overall quality of clinical practice guidelines (CPGs) for managing BCRL using the Appraisal of Guidelines for REsearch and Evaluation II (AGREE II) tool, and relevance of consensus recommendations for the Canadian health context.
Methods and Results: We searched electronic databases, gray literature, national lymphedema frameworks, and expert opinions, to identify lymphedema CPGs, printed/published from January 2013 to October 2021. Using AGREE II, six health care professionals reviewed CPGs for consensus. Domain-specific AGREE II quality consensus scores were required (≥70% for Rigor of Development; ≥ 60% for Stakeholder Involvement and Editorial Independence; and ≥50% for Clarity of Presentation, Applicability, Scope, and Purpose). Results and overall recommendations from the CPGs were summarized and synthesized. Nine CPGs met inclusion criteria for review. Wide variability of evidence-based recommendations, and limited clinical considerations were found. Scope and Purpose, and Clarity of Presentation were adequate in six of nine CPGs; Stakeholder Involvement in seven of nine CPGs; and Editorial Independence in three of nine CPGs. Across all CPGs, Applicability was minimally reported. Only the Queensland Health CPG met quality consensus scores for Rigor and Development; however, the focus was limited to compression therapy.
Conclusions: No CPG reviewed could be adopted for the Canadian health context. The proposed Canadian BCRL CPG will focus on stakeholder engagement, methodology, and implementation/evaluation. Using AGREE II allowed for assessment of quality of methods used to develop identified CPGs from other countries before consideration of adoption in a Canadian Context.

Associations between health-related fitness and quality of life in newly diagnosed breast cancer patients

Kerry S Courneya, Ki-Yong An, Fernanda Z Arthuso, Gordon J Bell, Andria R Morielli, Jessica McNeil, Qinggang Wang, Spencer J Allen, Stephanie M Ntoukas, Margaret McNeely, Jeff K Vallance, S. Nicole Culos-Reed, Karen Kopciuk, Lin Yang, Charles E Matthews, Myriam Filion, Leanne Dickau, John R. Mackey, Christine M Friedenreich. Breast Cancer Res Treat. 2023 Apr 14.
PURPOSE: Newly diagnosed breast cancer patients face substantial stress and uncertainty that may undermine their quality of life (QoL). The purpose of the present study was to examine the associations between health-related fitness (HRF) and QoL in newly diagnosed breast cancer patients from the Alberta Moving Beyond Breast Cancer Study.
METHODS: Newly diagnosed breast cancer patients with early-stage disease (n = 1458) were recruited between 2012 and 2019 in Edmonton and Calgary, Canada to complete baseline HRF and QoL assessments within 90 days of diagnosis. HRF assessments included cardiorespiratory fitness (VO2peak treadmill test), muscular fitness (upper and lower body strength and endurance tests), and body composition (dual x-ray absorptiometry). QoL was assessed by the Medical Outcomes Study Short Form 36 (SF-36) version 2. We used logistic regression analyses to examine the associations between quartiles of HRF and poor/fair QoL (bottom 20%) after adjusting for key covariates.
RESULTS: In multivariable analysis, the least fit groups compared to the most fit groups for relative upper body strength (OR = 3.19; 95% CI = 1.98-5.14), lean mass percentage (OR = 2.31; 95% CI = 1.37-3.89), and relative VO2peak (OR = 2.08; 95% CI = 1.21-3.57) were independently at a significantly higher risk of poor/fair physical QoL. No meaningful associations were found for mental QoL.
CONCLUSIONS: The three main components of HRF (muscular fitness, cardiorespiratory fitness, and body composition) were independently associated with physical QoL in newly diagnosed breast cancer patients. Exercise interventions designed to improve these components of HRF may optimize physical QoL and help newly diagnosed breast cancer patients better prepare for treatments and recovery.  PMID:37055681 | DOI:10.1007/s10549-023-06935-x

A Low-Cost, Portable, and Mobile-Based Bioimpedance Lymphedema Diagnosis and Monitoring System (Mobilymph): A Validation Study

Syarifah Aisyah Syed Ibrahim, Fatimah Ibrahim, Nur Aishah Mohd Taib, Jongman Cho. Lymphat Res Biol. 2023 Apr 24
 
Breast cancer-related lymphedema (BCRL) is a debilitating chronic illness. Early management and prevention of disease progression rely on lymphedema monitoring and assessment. At present, lymphedema monitoring systems are costly and do not promote remote monitoring. Thus, a low-cost, portable, mobile-based bioimpedance lymphedema monitoring system (Mobilymph) was developed to ensure continuous lymphedema surveillance. Method and Results: Forty-five healthy and 100 BCRL participants were recruited in this study. Mobilymph bioimpedance measurement was validated with a Quadscan 4000 on healthy participants’ arms. The interarm bioimpedance ratio was determined to evaluate the discriminatory capability of Mobilymph to detect BCRL. Mobilymph’s bioimpedance results show no significant difference compared to Quadscan 4000. The interarm bioimpedance ratios were significantly different (p < 0.001), between participants in healthy and Stage 1, Stage 0 and Stage 1, and Stage 1 and Stage 2. Healthy and Stage 0 participants had similar interarm impedance ratios (p = 0.63). Conclusion: The bioimpedance results show that Mobilymph bioimpedance measurement is comparable to Quadscan 4000 and can detect BCRL arms. Thus, Mobilymph lymphedema monitoring system offers a feasible solution for early lymphedema diagnosis and treatment monitoring. Clinical trial registration number

Management Strategies

Acupuncture Treatment for Breast Cancer-Related Lymphedema: A Randomized Pilot Study

Rosie Friedman, Anna Rose Johnson, Kathy Shillue, Aaron Fleishman, Chris Mistretta, Leo Magrini, Bao Ngoc N Tran, Stanley G. Rockson, Weidong Lu, Gloria Y Yeh, Dhruv Singhal. Lymphat Res Biol. 2023 Apr 20. 
Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures.
Methods and Results: Patients with BCRL were randomized 2:1 to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of three of three measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patient-centered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. Fourteen patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. Ninety-three percent of all participants completed all three measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred.
Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.

Patient Experience of Photobiomodulation Therapy in Head and Neck Chronic Lymphedema

Jie Deng, John N Lukens, Jonathan Zhu, Joy C. Cohn, Lucy P Andersen, Bryan A Spinelli, Ryan J Quinn, Jesse Chittams, Erin McMenamin, Alexander Lin. J Palliat Med. 2023 Apr 28. 
Purpose: Lymphedema is a common late effect of head and neck cancer treatment that causes various symptoms, functional impairment, and poor quality of life. We completed a pilot, prospective, single-arm clinical trial to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema. In this study, we report patients’ perceived treatment experience of PBM therapy and provide suggestions to better understand head and neck cancer survivors’ experience of PBM therapy.
Methods: Head and neck cancer patients who underwent PBM therapy completed face-to-face semi-structured interviews. Interviews were audio-recorded and then transcribed verbatim. Qualitative content analysis was used to analyze the transcriptions from the interviews.
Results: Among 12 participants who consented for the study, 11 (91.7%) completed the PBM therapy. Participants described positive experiences and unique benefits about the PBM therapy, for example, decreased swelling, reduced tightness, increased range of motion, increased saliva production, and improved ability to swallow. Some participants (n = 5, 45.5%) delineated challenges related to traffic, travel time, and distance from study location. Many participants proposed suggestions for future research on PBM therapy, for example, research on internal edema and its relationship with swallowing, and indicated patients with severe lymphedema and fibrosis may be more likely to benefit.
Conclusions: Findings from this study suggested the potential benefits of PBM therapy in treatment of chronic head and neck lymphedema. Rigorously designed clinical trials are needed to evaluate the effect of PBM therapy for head and neck cancer-related lymphedema.

Effects of an early intervention with Hyperbaric Oxygen Treatment on arm lymphedema and quality of life after breast cancer-an explorative clinical trial

Gunn Ammitzbøll, Ole Hyldegaard, Martin Forchhammer, Henrik Rottensten, Charlotte Lanng, Niels Kroman, Bo Zerahn, Lars Thorbjørn Jensen, Christoffer Johansen, Susanne Oksbjerg Dalton. Support Care Cancer. 2023 May 1;31(5):313. doi: 10.1007/s00520-023-07774-8
PURPOSE: Lymphedema (LE) is a common complication after breast cancer treatment, which negatively affects the quality of life (QOL). Hyperbaric Oxygen Treatment (HBOT) is an established treatment for radiation-induced tissue injury, but evidence of effect on breast cancer-related LE is inconclusive. We aimed to explore effects of HBOT on early breast cancer-related LE and the implications for QOL.
METHODS: We invited women with breast cancer treated with surgery, axillary dissection and radiotherapy, who had participated in a randomized controlled trial and who presented with LE 1 year after surgery. In a prospective observational study design, change in LE was assessed with perometry, dual-energy X-ray absorptiometry (DXA) and lymphoscintigraphy, and QOL by validated self-report scales. Participants were offered 40 sessions of HBOT on every weekday for 8 weeks and were followed for 6 months.
RESULTS: Out of 50 eligible participants, 20 women accepted participation. Nineteen women initiated and completed treatment and follow-up. None of the objective measures of LE severity showed consistent changes during the study period, but participants reported significant improvements in QOL (physical functioning, fatigue, insomnia and breast and arm symptoms), with improvements peaking at 6-month follow-up.
CONCLUSION: Participants receiving HBOT experienced improved QOL without consistently significant changes in arm mass, volume or lymphatic drainage. These results call for studies into differential effect in patient sub-groups, and a large-scale, randomized placebo-controlled trial with long-term follow-up to assess the effect of HBOT in patients with soft tissue radiation injuries after breast cancer seems warranted.
Compression therapy in peripheral artery disease: a literature review
Melissa A Nickles, William J Ennis, Thomas F O’Donnell, Igor A Altman.  J Wound Care. 2023 May 1;32(Sup5):S25-S30.
OBJECTIVE: Our objective is to examine the pathophysiology of oedema in the ischaemic and post-revascularised limb, compare compression stockings to pneumatic compression devices, and summarise compression regimens in patients with severe peripheral artery disease (PAD) without revascularisation, after revascularisation, and in mixed arterial and venous disease.
METHOD: A scoping literature review of the aforementioned topics was carried out using PubMed.
RESULTS: Compression therapy has been shown to increase blood flow and aid in wound healing through a variety of mechanisms. Several studies suggest that intermittent pneumatic compression (IPC) devices can be used to treat critical limb ischaemia in patients without surgical options. Additionally, compression stockings may have a role in preventing oedema after peripheral artery bypass surgery, thereby diminishing pain and reducing the risk of surgical wound dehiscence.
CONCLUSION: Oedema may occur in the ischaemic limb after revascularisation surgery, as well as in combination with venous disease. Clinicians should not fear using compression therapy in PAD

The Effect of Manual Lymph Drainage and Compression Bandaging for Stage 2 Breast Cancer-Related Lymphedema: A Randomized Controlled Trial

Ying Liu, Xiaoyi Zhao, Jian Song, Wowa Zhao, Ying Ge, Jinghong Guan. Lymphat Res Biol. 2023 May 4. doi: 10.1089/lrb.2022.0074. 
Aim: To explore the effect of manual lymph drainage (MLD), compression bandaging (CB), or combined decongestive therapy (CDT), including MLD and CB, on stage 2 breast cancer-related lymphedema (BCRL).
Methods: Sixty women with stage 2 BCRL were enrolled. They were randomly divided into the MLD group, the CB group or the CDT group. Each group, respectively, received MLD alone, CB alone, or CDT composed of MLD and CB, for 2 weeks. The volume and the local tissue water (LTW) of affected arms were measured before and after treatment. Arm circumferences were measured at 4 cm interval starting from the wrist to the shoulder with a tape measure. LTW was detected using the (tissue dielectric constant, TDC) method and was expressed as TDC value in two sites on the ventral midpoint of upper arm and forearm.
Results: The volume of affected arms in each group after 2-weeks’ treatment was lower than their baseline and the difference was statistically significant (p < 0.05). But there was no significant difference in volume change among three groups. The TDC value of the upper arm and forearm in the group CB and the group CDT decreased distinctly compared with baseline (p < 0.05). But the TDC value of the upper arm and forearm after MLD did not change (p > 0.05). Compared with the group MLD and the group CDT, the reduction of the TDC value in the group CB was more significant (p < 0.05).
Conclusions: MLD or CB alone could effectively reduce the volume of affected arms for patients with stage 2 BCRL, and CB also could reduce the LTW more significantly. CDT did not seem to show an extra advantage. Therefore, CB may be the first choice for stage 2 BCRL. But for patients who are unwilling or intolerant to CB, MLD can be selected

Treatment approaches and outcomes of a head and neck lymphedema service at an Australian comprehensive cancer center

Rebecca Louise Venchiarutti, Sandra Templeton, Lara Mathers, Emma Charters, Jonathan Robert Clark. Head Neck. 2023 Apr 17. doi: 10.1002/hed.27369.

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Assessing the preventive effect of immediate lymphatic reconstruction on the upper extremity lymphedema

Jae-Ho Chung, Sang-Ho Kwon, Seung-Pil Jung, Seung-Ha Park, Eul-Sik Yoon. Gland Surg. 2023 Mar 31;12(3):334-343. doi: 10.21037/gs-22-554

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Exercise during chemotherapy: Friend or foe?

Melanie Potiaumpai, Erica A Schleicher, Ming Wang, Kristin L Campbell, Kathleen Sturgeon, Kathryn H. Schmitz. Cancer Med. 2023 Apr 19.

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Liposuction for Advanced Lymphedema in a Multidisciplinary Team Setting in Australia – Five-Year Follow-Up

Tobias Karlsson, Helen Mackie, Louise Koelmeyer, Asha Heydon-White, Robyn Ricketts, Kim Toyer, John Boyages, Håkan Brorson, Thomas Lam. Plast Reconstr Surg. 2023 Apr 28.

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Exercises in activating lymphatic system on fluid overload symptoms, abnormal weight gains, and physical functions among patients with heart failure: A randomized controlled trial

Yuan Li, Qingtong Meng, Biru Luo, Minlu Li, Jinbo Fang, Sarah R Allred, Mei R. Fu. Front Cardiovasc Med. 2023 Apr 11;10:1094805

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Combination of conservative and surgical methods in the treatment of giant lymphedema of the scrotum: A case report

Andrey L Istranov, Ivan G Makarov, Natalya V Makarova, Inna Tulina, Ilya V Ulasov, Yuliya I Isakova. Front Surg. 2023 Apr 12;10:1048159. doi: 10.3389/fsurg.2023.1048159

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Inpatient Decongestive Therapy for Lymphedema in Acute Postsurgical Head and Neck Cancer Patients

John Christian Lemoine, Vilija Vaitaitis, Trisha Jarreau, Joel St Germain, Leslie Son, Anna M Pou, Ashley Mays
Int Arch Otorhinolaryngol. 2023 Apr 28;27(2):e329-e335.

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Adjustable Compression Wraps (ACW) vs. Compression Bandaging (CB) in the Acute Phase of Breast Cancer-Related Arm Lymphedema Management-A Prospective Randomized Study

Katarzyna Ochalek, Joanna Kurpiewska, Tomasz Gradalski. Biology (Basel). 2023 Mar 31;12(4):534. doi: 10.3390/biology12040534
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Advances in the prevention and treatment of breast cancer-related lymphedema

Paula M C Donahue, Adrien MacKenzie, Aleksandra Filipovic, Louise Koelmeyer. Breast Cancer Res Treat. 2023 Apr 27. doi: 10.1007/s10549-023-06947-7
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A Prospective Preliminary Study Examining the Physiological Impact of Pneumatic Compression Dosing in the Treatment of Lower Extremity Lymphedema

Vaughan L. Keeley, Katie Riches, Leigh Ward, Peter J Franks. Lymphat Res Biol. 2023 May 4.

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Retrospective study on the trajectories of lower limb volume after outpatient-based complex decongestive therapy in post-operative gynecological cancer patients with lymphedema

Ayano Masui, Tsuyoshi Harada, Yoshihiro Noda, Ryo Soeda, Hisashi Kida, Tetsuya Tsuji. Support Care Cancer. 2023 May 6;31(6):318. doi: 10.1007/s00520-023-07783-7

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How lifting weights could improve your body and your mindBest Practice Statement: The use of compression therapy for peripheral oedema:...