Hot off the Press October 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
Edema and lymphatic clearance: molecular mechanisms and ongoing challenges - click for abstract
Edema and lymphatic clearance: molecular mechanisms and ongoing challenges
Breslin, Jerome W. Clinical science (1979), 2023, Vol.137 (18), p.1451-1476
Resolution of edema remains a significant clinical challenge. Conditions such as traumatic shock, sepsis, or diabetes often involve microvascular hyperpermeability, which leads to tissue and organ dysfunction. Lymphatic insufficiency due to genetic causes, surgical removal of lymph nodes, or infections, leads to varying degrees of tissue swelling that impair mobility and immune defenses. Treatment options are limited to management of edema as there are no specific therapeutics that have demonstrated significant success for ameliorating microvascular leakage or impaired lymphatic function. This review examines current knowledge about the physiological, cellular, and molecular mechanisms that control microvascular permeability and lymphatic clearance, the respective processes for interstitial fluid formation and removal. Clinical conditions featuring edema, along with potential future directions are discussed.
Prevalence and Risk Factors
Preoperative Lymphedema-Related Risk Factors in Early-Stage Breast Cancer- click for abstract
Preoperative Lymphedema-Related Risk Factors in Early-Stage Breast Cancer
Iyigun, Zeynep Erdogan ; Duymaz, Tomris ; Ilgun, Ahmet Serkan ; Alco, Gul ; Ordu, Cetin ; Sarsenov, Dauren ; Aydin, Ayse Esra ; Celebi, Filiz Elbuken ; Izci, Filiz ; Eralp, Yeşim ; Ozmen, Vahit. Lymphatic research and biology, 2018, Vol.16 (1), p.28-35
Background
Prophylactic lymphatic bypass or LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) is increasingly offered to prevent lymphedema following breast cancer treatment, which develops in up to 47% of patients. Previous studies focused on intraoperative and postoperative lymphedema risk factors, which are often unknown preoperatively when the decision to perform LYMPHA is made. This study aims to identify preoperative lymphedema risk factors in the high-risk inflammatory breast cancer (IBC) population.
Methods
Retrospective review of our institution’s IBC program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on pathology, and need for adjuvant chemotherapy.
Results
Of 356 patients with IBC, 134 (mean age 51 years, range 22-89 years) had complete data. All 134 patients underwent surgery and radiation. Forty-seven percent of all 356 patients (167/356) developed lymphedema. Obesity (BMI>30) (OR 2.7, CI 1.2-6.4, p=0.02) and non-White race (OR 4.5, CI 1.2-23, p=0.04) were preoperative lymphedema risk factors.
Conclusions
Patients with IBC are high risk for developing lymphedema due to the need for ALND, radiation, and neoadjuvant chemotherapy. This study also identified non-White race and obesity as risk factors. Larger prospective studies should evaluate potential racial disparities in lymphedema development. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with IBC.
Upper Limb Morbidity in Newly Diagnosed Individuals After Unilateral Surgery for Breast Cancer: Baseline Results from the AMBER Cohort Study.- click for abstract
Upper Limb Morbidity in Newly Diagnosed Individuals After Unilateral Surgery for Breast Cancer: Baseline Results from the AMBER Cohort Study.
McNeely, M.L., Courneya, K.S., Al Onazi, M.M. et al. Ann Surg Oncol (2023). https://doi.org/10.1245/s10434-023-14316-3
Purpose. We aimed to examine potential associations between post-surgical upper limb morbidity and demographic, medical, surgical, and health-related ftness variables in newly diagnosed individuals with breast cancer.
Methods. Participants were recruited between 2012 and 2019. Objective measures of health-related fitness, body composition, shoulder range of motion, axillary web syndrome, and lymphedema were performed within 3 months of breast cancer surgery, and prior to or at the start of adjuvant cancer treatment.
Results. Upper limb morbidity was identifed in 54% of participants and was associated with poorer upper limb function and higher pain. Multivariable logistic regression analysis identifed mastectomy versus breast-conservingsurgery (odds ratio [OR] 3.51, 95% confdence interval [CI] 2.65–4.65), axillary lymph node dissection versus sentinel lymph node dissection (OR 2.67, 95% CI 1.73–4.10),
earlier versus later time from surgery (OR 1.58, 95% CI 1.15–2.18), and younger versus older age (OR 1.01, 95% CI
1.00–1.03) as signifcantly associated with a higher odds of upper limb morbidity, while mastectomy (OR 1.57, 95% CI
1.10–2.25), axillary lymph node dissection (OR 2.20, 95% CI 1.34–3.60), lower muscular endurance (OR 1.10, 95% CI
1.01–1.16) and higher percentage body fat (OR 1.04, 95% CI 1.00–1.07) were signifcantly associated with higher odds of
moderate or greater morbidity severity.
Conclusions. Upper limb morbidity is common in individuals after breast cancer surgery prior to adjuvant cancer treatment. Health-related ftness variables were associated with severity of upper limb morbidity. Findings may facilitate prospective surveillance of individuals at higher risk of developing upper limb morbidity
Risk Factors for Breast Cancer-Related Lymphedema: An Umbrella Review
Aomei Shen MS, Wanmin Qiang BS, Liyuan Zhang BS, Jingru Bian BS, Fei Zhu MS, Zijuan Zhang BS & Qian Lu PhD. Annals of Surgical Oncology (2023)
Assessment
Assessment of proprioception, muscle strength and endurance during dynamic isokinetic test in patients with breast cancer-related lymphedema - click for abstract
Assessment of proprioception, muscle strength and endurance during dynamic isokinetic test in patients with breast cancer-related lymphedema
Zabit, Ferdiye ; Iyigun, Gozde ; Malkoc, Mehtap. Clinical biomechanics (Bristol), 2023, p.106100, Article 106100
Background: Breast cancer-related lymphedema is a common complication after breast cancer treatment.This study examined isokinetic proprioception, muscular strength, and endurance by comparing extremity with lymphedema and the extremity without lymphedema in women with breast cancer-related lymphedema.
Methods: A total of 15 individuals aged between 35 and 70 years participated in this study. Cybex Humac NORM Isokinetic dynamometer (CSMi, Stoughton, MA) were used to assess upper extremity passive proprioception, active proprioception, kinesthesia, muscle strength, and muscle endurance. The upper extremity lymphedema was measured with the water displacement arm volumetry test using a volumeter.
Findings: All isokinetic measurements demonstrated a statistically significant difference between the extremity with lymphedema and the extremity without lymphedema, suggesting lower scores in the extremity with lymphedema (p <.05). There was a positive correlation between passive internal rotation in the extremity with lymphedema and the time after mastectomy (r=0.628, p =.012) and a moderate positive relationship was found between the time after lymphedema and passive internal rotation (r =0.577; p =.024), and active external rotation position sense (r =0.540; p =.038) in the extremity with lymphedema. Also, a unidirectional positive moderate (r =0.594; p =.020) relationship was found between the lymphedema stage and passive external rotation in the extremity with lymphedema. Interpretation: The difference in proprioception, muscle strength, and endurance between the extremity with lymphedema and the extremity without lymphedema in women with breast cancer-related lymphedema will provide valuable information in terms of prioritizing these parameters in treatment. [/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_one_full] [av_hr class='short' height='40' shadow='no-shadow' position='left' 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' admin_preview_bg=''] [av_one_full first min_height='' vertical_alignment='' space='' custom_margin='' margin='0px' padding='0px' border='' border_color='' radius='0px' background_color='' src='' background_position='top left' background_repeat='no-repeat' animation='' mobile_breaking='' mobile_display=''] [av_textblock size='' font_color='' color='' av-medium-font-size='' av-small-font-size='' av-mini-font-size='' admin_preview_bg='']
Management Strategies
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Quality of evidence supporting the role of acupuncture for breast cancer-related lymphoedema: an overview of systematic reviews and meta-analyses - click for abstract
Quality of evidence supporting the role of acupuncture for breast cancer-related lymphoedema: an overview of systematic reviews and meta-analyses
Wang, Lei ; Du, Xueyuan ; Hu, Peng ; Zhang, Yaling ; Yao, Mingchao ; Che, Xiaoling. Journal of cancer research and clinical oncology, 2023
BACKGROUND: Breast cancer-related lymphedema (BCRL) may benefit from acupuncture as a therapeutic. However, the findings of systematic reviews (SRs) and meta-analyses (MAs) are inconsistent and their quality needs to be evaluated critically. We aimed to provide an overview of the methodological quality, risk of bias, quality of reporting, and quality of evidence for SRs/MAs of acupuncture for BCRL.
METHODS: Publications were retrieved from four Chinese databases and four English databases. The methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs were assessed by two independent researchers using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Grading of Recommendations, Assessment, Development and Evaluation (GRADE), respectively.
RESULTS: There were a total of 8 SRs/MAs included. By AMSTAR-2, all SRs/MAs were graded as having low or very low methodological quality. By ROBIS, all SRs/MAs in phase 1, domain 1, and domain 4 of phase 2 were at low risk, while in domain 2 were at high risk. By PRISMA, reporting weaknesses in protocol and registration, as well as search method, were identified. By GRADE, the level of evidence quality was “low” to “very low”, and the most commonly downgraded factor was the risk of bias.
CONCLUSIONS: Acupuncture may be beneficial in improving BCRL. However, due to the identified limitations and conflicting findings, further more prescriptive and rigorous SRs/MAs are required to give strong evidence for final judgments.
Managing the Morbidity: Individualizing Risk Assessment, Diagnosis, and Treatment Options for Upper Extremity Lymphedema - click for abstract
Managing the Morbidity: Individualizing Risk Assessment, Diagnosis, and Treatment Options for Upper Extremity Lymphedema
Giacomo Montagna 1, Andrea V Barrio 2. Surg Oncol Clin N Am. 2023 Oct;32(4):705-724.
In the setting where breast cancer-related lymphedema (BCRL) remains a feared and common complication of breast cancer, here we review important factors for the development, diagnosis, prevention, and treatment of BCRL. We find that race/ethnicity affect BCRL development risk, that future studies should focus on understanding the biological reasons behind the increased susceptibility of certain racial minorities to BCRL, that surveillance, early detection, exercise programs, and arm compression can reduce the risk of BCRL, and that surgical techniques to preserve and restore lymphatic drainage being evaluated in randomized trials may become transformative in reducing BCRL risk for high-risk patients.
Effectiveness of a Nonpneumatic Active Compression Device in Older Adults with Breast Cancer-Related Lymphedema: A Subanalysis of a Randomized Crossover Trial - click for abstract
Effectiveness of a Nonpneumatic Active Compression Device in Older Adults with Breast Cancer-Related Lymphedema: A Subanalysis of a Randomized Crossover Trial
Stanley G. Rockson, Roman Skoracki, Lymphat Res Biol. 2023 Sep 20.
Background: A recently completed clinical trial compared a novel nonpneumatic compression device (NPCD) with a traditional advanced pneumatic compression device (APCD) for the treatment of breast cancer-related lymphedema (BCRL); the study revealed that the NPCD produced superior clinical and quality-of-life (QOL) outcomes. In this subanalysis, we sought to examine these results within the subset of trial subjects aged ≥65 years.
Methods: A randomized crossover head-to-head trial was conducted to compare the NPCD with a commercially available APCD. Patients were randomly assigned to one or the other device for 28 days of use, followed by a 4-week washout period before a comparable 28-day utilization of the alternate device. Limb edema, adherence to daily device use, and QOL measures were collected at day 0 and 28 of each period.
Results: A total of 14 subjects were aged ≥65. During NPCD use, subjects experienced a mean decrease in limb edema of 100.3% (p = 0.0082) as well as improvements in mean overall and subscale scores of the Lymphedema Quality of Life Questionnaire (LYMQOL). By comparison, during APCD use limb edema decreased by a mean of 2.9% (p = 0.8899) with no significant changes in any LYMQOL scores. Mean adherence was significantly higher during NPCD use (96.6%) than during APCD use (58.3%, p < 0.0001).
Conclusions: The novel NPCD produced superior clinical and QOL outcomes in older subjects with BCRL
