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Hot off the Press December 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

A Prospective, Longitudinal and Exploratory Study of Head and Neck Lymphoedema and Dysphagia Following Chemoradiotherapy for Head and Neck Cancer- click for abstract

A Prospective, Longitudinal and Exploratory Study of Head and Neck Lymphoedema and Dysphagia Following Chemoradiotherapy for Head and Neck Cancer

Claire Jeans, Bena Brown, Elizabeth C Ward, Anne E Vertigan, Amanda E Pigott, Jodie L Nixon, Chris Wratten, May Boggess. Dysphagia. 2022 Oct 29.
The aim of the study was to examine the following: (a) the trajectory of external and internal head and neck lymphoedema (HNL) in patients with head and neck cancer (HNC) up to 12 months post-chemoradiotherapy (CRT) and (b) the relationship between HNL and swallowing function. Using a prospective longitudinal cohort study, external/internal HNL and swallowing were examined in 33 participants at 3, 6 and 12 months post-CRT. External HNL was assessed using the Assessment of Lymphoedema of the Head and Neck and the MD Anderson Cancer Centre Lymphoedema Rating Scale. Internal HNL was rated using Patterson’s Radiotherapy Oedema Rating Scale. Swallowing was assessed via clinical, instrumental and patient-reported measures. Associations between HNL and swallowing were examined using multivariable regression models. External HNL was prevalent at 3 months (71%), improved by 6 months (58%) and largely resolved by 12 months (10%). In contrast, moderate/severe internal HNL was prevalent at 3 months (96%), 6 months (84%) and at 12 months (65%). More severe penetration/aspiration and increased diet modification were associated with higher severities of external HNL (p=0.006 and p=0.031, respectively) and internal HNL (p<0.001 and p=0.007, respectively), and more diffuse internal HNL (p=0.043 and p=0.001, respectively). Worse patient-reported swallowing outcomes were associated with a higher severity of external HNL (p=0.001) and more diffuse internal HNL (p=0.002). External HNL largely resolves by 12 months post-CRT, but internal HNL persists. Patients with a higher severity of external and/or internal HNL and those with more diffuse internal HNL can be expected to have more severe dysphagia

Estimation of Neural Tissue Mobility in Breast Cancer Survivors with Lymphedema

Sandeep Shinde, Devanshi Joshi, Sanjaykumar Patil, Piyusha Pawar
Asian Pac J Cancer Prev. 2022 Oct 1;23(10):3355-3360.

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Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients

Stefan Wolf, Julia von Atzigen, Bettina Kaiser, Lisanne Grünherz, Bong-Sung Kim, Pietro Giovanoli, Nicole Lindenblatt, Epameinondas Gousopoulos. Biomolecules. 2022 Nov 11;12(11):1667

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Prevalence and Risk Factors

Quantification of breast lymphoedema following conservative breast cancer treatment: a systematic review - click for abstract

Quantification of breast lymphoedema following conservative breast cancer treatment: a systematic review

Nicola Fearn, Catalina Llanos, Elizabeth Dylke, Kirsty Stuart, Sharon Kilbreath. J Cancer Surviv. 2022 Oct 27.
PURPOSE: Breast lymphoedema is a possible side effect of breast conserving surgery, but it is poorly understood. This is due, in part, to difficulty assessing the breast. This systematic review described outcome measures that quantify breast lymphoedema signs and symptoms and evaluated the measurement properties for these outcome measures.
METHOD: Seven databases were searched using terms in four categories: breast cancer, lymphoedema and oedema, clinician reported (ClinROM) and patient reported outcome measures (PROM) and psychometric and measurement properties. Two reviewers independently reviewed studies and completed quality assessments. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology was used for studies including measurement property evidence.
RESULTS: Fifty-six papers were included with thirteen questionnaires, eight patient-reported rating scales, seven physical measures, seven clinician-rating scales and four imaging techniques used to quantify breast lymphoedema. Based on COSMIN methodology, one ClinROM had sufficient reliability, ultrasound measuring dermal thickness. Tissue dielectric constant (TDC) measuring local tissue water had promising reliability. Four questionnaires had sufficient content validity (BLYSS, BLSQ, BrEQ and LYMQOL-Breast).
CONCLUSIONS: Ultrasound is recommended to reliably assess breast lymphoedema signs. No PROM can be recommended with confidence, but BLYSS, BLSQ, BrEQ and LYMQOL-Breast are promising. Further research is recommended to improve evidence of measurement properties for outcome measures.
IMPLICATIONS FOR CANCER SURVIVORS: There are many approaches to assess breast lymphoedema, but currently, only ultrasound can be recommended for use, with others, such as TDC and questionnaires, showing promise. Further research is required for all approaches to improve evidence of measurement properties.

Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema

F Buntinx, A Lebeau, L Gillot, L Baudin, R Ndong Penda, F Morfoisse, F Lallemand, G Vottero, C Nizet, J L Nizet, S Blacher, A Noel. Front Pharmacol. 2022 Oct 18;13:1016138

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The Prevalence of Lower Limb and Genital Lymphedema after Prostate Cancer Treatment: A Systematic Review

Andries Clinckaert, Klaas Callens, Anne Cooreman, Annabel Bijnens, Lisa Moris, Charlotte Van Calster, Inge Geraerts, Steven Joniau, Wouter Everaerts
Cancers (Basel). 2022 Nov 18;14(22):5667.

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Management Strategies

Doxycycline for the treatment of breast cancer-related lymphedema

Stav Brown, Joseph H Dayan, Michelle Coriddi, Leslie McGrath, Raghu P Kataru, Babak J Mehrara. Front Pharmacol. 2022 Oct 20;13:1028926.

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Strategies in activating lymphatic system to promote lymph flow on lymphedema symptoms in breast cancer survivors: A randomized controlled trial

Xinwen Du, Yuan Li, Lan Fu, Lan Fu, Huaying Chen, Xiaoxia Zhang, Yuping Shui, Aihua Zhang, Xianqiong Feng, Mei R. Fu. Front Oncol. 2022 Oct 24;12:1015387

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Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study - click for abstract

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study

Chao Lu, Guang-Liang Li, De-Hou Deng, Wen-Long Bao, Yan Wang, Ai-Qin Zhang. Chin J Integr Med. 2022 Nov 14. doi: 10.1007/s11655-022-3684-7.
OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).
METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.
RESULTS: The patients’ AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.
CONCLUSIONS: TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone.

The breast cancer-related lymphedema multidisciplinary approach: Algorithm for conservative and multimodal surgical treatment- click for abstract

The breast cancer-related lymphedema multidisciplinary approach: Algorithm for conservative and multimodal surgical treatment

Pedro Ciudad, Alberto Bolletta, Juste Kaciulyte, Luigi Losco, Oscar J Manrique, Emanuele Cigna, Horacio F Mayer, Joseph M Escandón. Microsurgery. 2022 Nov 26. doi: 10.1002/micr.30990
BACKGROUND: Multiple surgical alternatives are available to treat breast cancer-related lymphedema (BCRL) providing a variable spectrum of outcomes. This study aimed to present the breast cancer-related lymphedema multidisciplinary approach (B-LYMA) to systematically treat BCRL.
METHODS: Seventy-eight patients presenting with BCRL between 2017 and 2021 were included. The average age and BMI were 49.4 ± 7.8 years and 28.1 ± 3.5 kg/m2 , respectively. Forty patients had lymphedema ISL stage II (51.3%) and 38 had stage III (48.7%). The mean follow-up was 26.4 months. Treatment was selected according to the B-LYMA algorithm, which aims to combine physiologic and excisional procedures according to the preoperative evaluation of patients. All patients had pre- and postoperative complex decongestive therapy (CDT).
RESULTS: Stage II patients were treated with lymphaticovenous anastomosis (LVA) (n = 18), vascularized lymph node transfer (VLNT) (n = 12), and combined DIEP flap and VLNT (n = 10). Stage III patients underwent combined suction-assisted lipectomy (SAL) and LVA (n = 36) or combined SAL and VLNT (n = 2). Circumferential reduction rates (CRR) were comparable between patients treated with LVA (56.5 ± 8.4%), VLNT (54.4 ± 10.2%), and combined VLNT-DIEP flap (56.5 ± 3.9%) (p > .05). In comparison to LVA, VLNT, and combined VLNT-DIEP flap, combined SAL-LVA exhibited higher CRRs (85 ± 10.5%, p < .001). The CRR for combined SAL-VLNT was 75 ± 8.5%. One VLNT failed and minor complications occurred in the combined DIEP-VLNT group.
CONCLUSION: The B-LYMA protocol directs the treatment of BCRL according to the lymphatic system’s condition. In advanced stages where a single physiologic procedure is not sufficient, additional excisional surgery is implemented. Preoperative and postoperative CDT is mandatory to improve the outcomes.

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