Hot of the Press June 2020

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

Assessing breast lymphoedema following breast cancer treatment using indocyanine green lymphography - click for abstract

Assessing breast lymphoedema following breast cancer treatment using indocyanine green lymphography.

Heydon-White A, Suami H, John Boyages, Koelmeyer L, Peebles KC. Breast Cancer Research and Treatment (2020) 181:635–644

Purpose Breast lymphoedema is a largely unrecognised survivorship issue for women following breast cancer treatment. While a few objective methods have previously been applied to assess breast lymphoedema, none are capable of imaging breast lymphatics or identifying lymphatic morphological changes indicative of breast lymphoedema. The purpose of this study was to determine if indocyanine green (ICG) lymphography, a validated assessment technique in breast cancer-related lymphoedema), can visualise breast lymphatics and identify breast lymphoedema. Additionally, ICG lymphography was utilised to investigate lymphatic drainage pathways of the afected breast following breast-conserving therapy.

Methods Twenty female participants (10 breast lymphoedema and 10 healthy controls) were recruited for this pilot study. All underwent a medical history, physical breast assessment, tissue dielectric constant measures of breast water content, and ICG lymphography.

Results ICG lymphography identifed lymphatic morphological changes in all breast lymphoedema participants (dermal backfow patterns=10, collateral lymphatic drainage=9) and none in the control group. The dominant lymphatic drainage pathway to the ipsilateral axilla was observed in all control participants but in only four breast lymphoedema participants. Collateral drainage pathways in the breast lymphoedema group were to: parasternal (6/10); contralateral axilla (4/10); intercostal (3/10); and clavicular (2/10) regions.

Conclusion These fndings suggest ICG lymphography, through the identifcation of morphological lymphatic changes, is a potential qualitative objective assessment technique for breast lymphoedema. Furthermore, in this group of breast lymphoedema patients it identifed changes to the normal drainage pathway of the breast. Understanding these changes will have implications for clinical management.

Update and audit of the St George’s classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis

Gordon K, Varney R, Vaughan L. Keeley, Riches K, Jeffery S, Van Zanten M, Peter S. Mortimer, Ostergaard P, Mansour S, J Med Genet. 2020 May 14

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Repetitive cellulitis caused by Streptococcus agalactiae isolates with different genotypic and phenotypic features in a patient having upper extremity with lymphedema after mastectomy and axillary lymph node dissection.

Taniyama D, Maruki T, Maeda T, Yoshida H, Takahashi T. IDCases. 2020

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Analysis of Collateral Lymphatic Circulation in Patients with Lower Limb Lymphedema Using Magnetic Resonance Lymphangiography - click for abstract

Analysis of Collateral Lymphatic Circulation in Patients with Lower Limb Lymphedema Using Magnetic Resonance Lymphangiography.

Soga S, Onishi F, Masahiro J, Mikoshi A, Minabe T, Shinmoto H. J Vasc Surg Venous Lymphat Disord. 2020 May 26

Objective: Although the development of lymphatic collaterals is expected following lymphedema, little is known regarding the anatomical details of such compensatory pathways or their association with symptoms. Magnetic Resonance lymphangiography (MRL) has shown to be superior to lymphoscintigraphy and indocyanine green lymphography in visualizing lymphatics. This study aimed to analyze MRL images of lower limbs to elucidate the patterns of lymphatic collateral formation and their association with the clinical stages of lymphedema.

Methods: We enrolled 56 consecutive patients (112 lower limbs) with lymphedema who underwent MRL. Two radiologists performed a consensus reading of MRL images for the presence or absence of collateral lymphatic pathways, and the results were compared with the clinical stages. Furthermore, the frequency of abnormal MRL findings in 43 asymptomatic lower limbs of patients with unilateral lymphedema was analyzed and compared with that in the 69 symptomatic lower limbs of the patients. The imaging findings were also compared with the etiology of lymphedema.

Results: All three collateral pathways (anterolateral, deep, and posteromedial lymphatics) were visualized at a higher (p<0.05) frequency in stage II than in stage 0 lower limbs. The frequency of visualization of the three collaterals was significantly higher in symptomatic (stages I-III) lower limbs than in asymptomatic (stage 0) lower limbs. Most (76.8%) of the symptomatic limbs exhibited at least one of these collaterals, and the frequency was significantly higher than that in the asymptomatic limbs (p<0.001). Most (81.4%) of the asymptomatic (stage 0) lower limbs had at least one abnormal finding in terms of lymphatic circulation, although this proportion was significantly lower when compared with that of the symptomatic limbs (98.6%). The collaterals tended to appear less frequently in primary lymphedema than in secondary lymphedema, reaching statistical significance in the posteromedial lymphatics. Conclusions: These results suggested that the two superficial lymphatic groups and the deep lymphatic system act as major collaterals of the lower limbs in patients with lymphedema. Furthermore, MRL of most patients with unilateral lymphedema demonstrated abnormal findings, including collateral formation, not only in the affected lower limb but also in the asymptomatic lower limb. In primary lymphedema, the collaterals may appear less frequently than in secondary lymphedema. Collaterals should be taken into consideration when planning the site of lymphaticovenous anastomosis and assessing disease progression. MRL can visualize preclinical alterations in lymphatic flow and compensatory pathways; therefore, we expect that it will be useful for the early diagnosis of lymphedema.

Anatomical Theories of the Pathophysiology of Cancer-Related Lymphoedema.

Suami H. Cancers (Basel). 2020 May 23;12(5)

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Prevalence and Risk Factors

The impact of radiation on lymphedema: a review of the literature.

Allam O, Park KE, Chandler L, Mozaffari MA, Ahmad M, Lu X, Alperovich M. Gland Surg. 2020 Apr;9(2):596-602.

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Impact of body mass index on long-term surgical outcomes of vascularized lymph node transfer in lymphedema patients.

Ciudad P, Forte AJ, Huayllani MT, Boczar D, Manrique OJ, Bustos SS, Bustamante A, Chen HC. Gland Surg. 2020 Apr;9(2):603-613

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Application of imaging in lymphedema surgical therapies.

Du X, Liu C. Gland Surg. 2020 Apr;9(2):582-588

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The basics of ultrasound elastography for diagnosis, assessment, and staging breast cancer-related lymphedema: a systematic review of the literature.

Forte AJ, Huayllani MT, Boczar D, Cinotto G, Ciudad P, Manrique OJ, Lu X, McLaughlin SA.  Gland Surg. 2020 Apr;9(2):589-595

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Precision and reliability of tape measurements in the assessment of head and neck lymphedema.

Chotipanich A, Kongpit N. PLoS One. 2020;15(5)

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A systematic review of magnetic resonance lymphography for the evaluation of peripheral lymphedema - click for abstract

A systematic review of magnetic resonance lymphography for the evaluation of peripheral lymphedema.

Miseré RML, Wolfs JAGN, Lobbes MBI, van der Hulst RRWJ, Qiu SS. J Vasc Surg Venous Lymphat Disord. 2020 May 13

Objective: Visualization of the lymphatic system is necessary for both early diagnosis and associated treatments. A promising imaging modality is magnetic resonance lymphography (MRL). The aim of this review was to summarize different MRL protocols, to assess the clinical value in patients with peripheral lymphedema, and to define minimal requirements necessary for visualization of lymphatics.

Methods: A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library in December 2018. Studies performing MRL in patients with peripheral lymphedema or healthy participants were included. Study design, population, etiology, duration of lymphedema, clinical staging, contrast agent, dose, injection site, and technical magnetic resonance imaging details were analyzed. No meta-analyses were performed because of different study aims and heterogeneity of the study populations.

Results: Twenty-five studies involving 1609 patients with both primary lymphedema (n = 669) and secondary lymphedema (n = 657) were included. Upper and lower limbs were examined in 296 and 602 patients, respectively. Twenty-two studies used a gadolinium-based contrast agent that was injected intracutaneously or subcutaneously in the interdigital web spaces. Contrast-enhanced T1-weighted combined with T2-weighted protocols were most frequently used. T1-weighted images showed lymphatics in 63.3% to 100%, even in vessels with a diameter of ≥0.5 mm. Dermal backflow and a honeycomb pattern were clearly recognized.

Conclusions: MRL identifies superficial lymphatic vessels with a diameter of ≥0.5 mm with high sensitivity and specificity and accurately shows abnormal lymphatics and lymphatic drainage patterns. Therefore, MRL could be of clinical value in both early and advanced stages of peripheral lymphedema. Minimum requirements of an MRL protocol should consist of a gadolinium-based contrast-enhanced T1-weighted gradient-recalled echo sequence combined with T2-weighted magnetic resonance imaging, with acquisition at least 30 minutes after injection of contrast material.

Implementing a Wearable Sensor for Lymphedema Garments: A Prospective Study of Training Effectiveness - click for abstract

Implementing a Wearable Sensor for Lymphedema Garments: A Prospective Study of Training Effectiveness.

Goldman RJ. Wound Manag Prev. 2020 Jan;66(1):39-48

Lymphedema garments apply therapeutic pressure to maintain minimum leg volume. Practitioners and patients apply these garments and seek to achieve appropriate compression pressure “by feel.”

PURPOSE: A study was conducted to assess the feasibility of applying a sensor-feedback device to train staff to accurately apply garments.

METHODS: A convenience sample of wound care and rehabilitation staff volunteered for a prospective, randomized, unblinded, single-center pilot study. Participants were randomized to instruction+feedback (ie, receiving training on compression application and using the device to determine whether they achieved desired pressure) or instruction only groups (n = 6 each). Each volunteer applied hook-and-loop closures on the author’s leg pre- and post-training with a target of 35 mm Hg, or |Ppre- 35|= |Ppost- 35|=0. (|P| is absolute value of P). The feedback group used a device to measure the applied compression; the device consists of a capacitive sensor of thin polyurethane foam between conductive fabric layers and a microcomputer/Bluetooth transmitter under a vacuum seal that fits into a fabric pocket of a lymphedema garment at the posterior ankle and pairs with a mobile device. A lymphology-certified therapist coordinated training. Data were collected with a pen/paper tool and analyzed with Student’s t test.

RESULTS: The instruction+feedback group was closer to target after training (|Ppre – 35|= 10 ± 12 mm Hg; |Ppost – 35|=5 ± 4 mm Hg; P <.05; paired t test) than the instruction only group (|Ppre- 35|=19 ± 11 mm Hg; |Ppost - 35|=12 ±12 mm Hg; not significant). CONCLUSION: This wearable mobile pressure sensor device assists practitioners in applying hook-and-loop lymphedema garments closer to target pressure. Larger studies with clinicians and research that involves patient application of compression are warranted.

Bioimpedance Spectroscopy for Assessment of Breast Cancer-Related Lymphedema: A Systematic Review - click for abstract

Bioimpedance Spectroscopy for Assessment of Breast Cancer-Related Lymphedema: A Systematic Review.

Forte AJ, Huayllani MT, Boczar D, Ciudad P, Lu X, Kassis S, Parker AS, Moore PA, McLaughlin SA. Plast Surg Nurs. 2020 Apr/Jun;40(2):86-90.

Bioimpedance spectroscopy is currently used to evaluate patients with breast cancer-related lymphedema (BCRL). We aimed to describe published studies on the use of bioimpedance spectroscopy for assessment for BCRL. We queried the PubMed, Ovid Medline, and Embase databases to identify studies that evaluated the use of bioimpedance spectroscopy as an assessment tool. We searched for the keywords “bioimpedance” AND (“lymphedema” OR “lymphoedema”). We included English-language studies that reported the use of bioimpedance spectroscopy for assessment of BCRL. Out of 152, 116, and 235 articles identified in each database, respectively, only a total of 11 articles were included. Bioimpedance spectroscopy was studied as a method to assess and predict response to BCRL treatment, assess volume changes, and calibrate L-Dex scores for conversion to units of volume. All studies reported that bioimpedance spectroscopy is a promising tool for predicting response to BCRL treatment and measuring volume changes. Bioimpedance spectroscopy can be used for assessment of BCRL. However, the accuracy of bioimpedance spectroscopy for BCRL assessment has not been determined, and consequently further studies are needed.

Alternate Electrode Positions for the Measurement of Hand Volumes Using Bioimpedance Spectroscopy - click for abstract

Alternate Electrode Positions for the Measurement of Hand Volumes Using Bioimpedance Spectroscopy.

Edwick DO, Hince DA, Rawlins JM, Wood FM, Edgar DW. Lymphat Res Biol. 2020 May 25

Background: Bioimpedance spectroscopy (BIS) is a tool that can be used to measure body composition in a variety of populations. Previous studies have investigated novel applications to utilize BIS to measure localized body composition, including in the hand. According to BIS guidelines, there should be no skin wounds at the site of electrodes, and that electrode positions may be modified in specific circumstances, as our group has validated previously in burn wound populations.

Methods and Results: To determine in noninjured participants, whether BIS measurements recorded using alternate electrode positions on the palm of the hand and forearm, or a combination of electrodes on the dorsum and volar surface of the hand and forearm, were comparable with electrode positions on the dorsum of the hand and forearm. The study demonstrated that drive and sense electrodes on the palm of the hand and volar forearm, and a combination of electrodes on the palm of the hand and dorsum of the forearm, resulted in comparable measures of impedance of extracellular water (difference from reference position: 1.26%-4.75%, p = 0.411-0.558) and total water (difference from reference: 2.15%-2.40%, p = 0.258-0.781). Electrodes on the dorsum of the hand and volar forearm resulted in significantly different measures for the same BIS variables (percentage difference range 4.66%-6.15%, p < 0.001-0.003). Conclusion: Electrode positions on the palm of the hand and volar forearm, or on the palm of the hand and dorsum of the forearm, are interchangeable as clinical measures of hand lymphedema and total water impedance.

A Methodological Assessment of Lymphoedema Clinical Practice Guidelines - click for abstract

A Methodological Assessment of Lymphoedema Clinical Practice Guidelines

Tan M, Salim S, Beshr M, Guni A, Onida S, Lane T, Davies AH. J Vasc Surg Venous Lymphat Disord. 2020 May 23

Objectives: To determine the methodological quality of current lymphoedema clinical practice guidelines (CPGs) to assist healthcare professionals in selecting accessible, high-quality guidance and to identify areas for improvement in future CPGs.

Methods: Medline, EMBASE, online CPG databases and reference lists of included guidelines were searched up to 31st January 2020. Full-text CPGs reporting on evidence-based recommendations in lymphoedema diagnosis and/or management in English were included. CPGs based on expert consensus, CPG summaries or CPGs that were not freely available were excluded. Two reviewers identified eligible CPGs, extracted data and assessed their quality independently using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Significant scoring discrepancies were discussed with a third reviewer. An overall scaled quality score of ≥80% was the threshold to recommend guideline use.

Results: Six relevant CPGs were identified. One was subsequently excluded as its full-text could not be obtained. Overall, there was very good inter-reviewer reliability of scores with ICC of 0.952 (95% CI, 0.921-0.974). No single CPG scored highest in all domains, with methodological heterogeneity observed. Poor performance was noted in domains 5 (mean scaled score 23.8±17.1%) and 6 (22.9±26.7%). No CPG achieved an overall scaled quality score of ≥80%, with the top CPG scoring 79.2%.

Conclusions: According to the defined threshold, no lymphoedema CPG was considered adequate for use in clinical practice. All current lymphoedema CPGs have areas for improvement with elements of methodological quality lacking, particularly with respect to rigour of development. A structured approach, guided by the use of CPG creation tools and checklists such as the AGREE II instrument, should help CPG development groups in improving the quality of future CPGs; this is of particular importance in a complex, multidisciplinary condition such as lymphoedema.

Management Strategies

Lymphaticovenous Anastomosis for Lower Extremity Lymphedema: A Systematic Review.

Forte AJ, Khan N, Huayllani MT, Boczar D, Saleem HY, Lu X, Manrique OJ, Ciudad P, McLaughlin SA. Indian J Plast Surg. 2020 Mar;53(1):17-24

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Surgical management of lymphedema: a review of current literature.

Park KE, Allam O, Chandler L, Mozzafari MA, Ly C, Lu X, Persing JA. Gland Surg. 2020 Apr;9(2):503-511

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Combined microvascular breast and lymphatic reconstruction with deep inferior epigastric perforator flap and gastroepiploic vascularized lymph node transfer for postmastectomy lymphedema patients.

Ciudad P, Manrique OJ, Bustos SS, Vargas MI, Reynaga C, Agko M, Huang TCT, Benites EF, Mayer HF, Forte AJ. Gland Surg. 2020 Apr;9(2):512-520

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Gastroepiploic vascularized lymph node transfer for the treatment of extremity lymphedema: comparison between middle and distal inset.

Manrique OJ, Bustos SS, Kapoor T, Lin J, Ciudad P, Forte AJ, Del Corral G, Mani M, Maruccia M, Terzic A. Gland Surg. 2020 Apr;9(2):528-538

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Lymphaticovenular anastomosis for breast cancer-related upper extremity lymphedema: a literature review.

Forte AJ, Sisti A, Huayllani MT, Boczar D, Cinotto G, Ciudad P, Manrique OJ, Lu X, McLaughlin S. Gland Surg. 2020 Apr;9(2):539-544

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Single-stage VASER-assisted liposuction and lymphatico-venous anastomoses for the treatment of extremity lymphedema: a case series and systematic review of the literature.

Ciudad P, Manrique OJ, Bustos SS, Agko M, Huang TC, Vizcarra L, Nuñez ML, Lo Torto F, Forte AJ. Gland Surg. 2020 Apr;9(2):545-557.

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Surgical reconstruction of primary genital lymphedema-long term therapeutic efficacy.

Yu Z, Sheng L, Cao W, Li S, Lu W, Gao W, Jiang Z. Gland Surg. 2020 Apr;9(2):575-581

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Resistance exercise and breast cancer-related lymphedema-a systematic review update and meta-analysis - click for abstract

Resistance exercise and breast cancer-related lymphedema-a systematic review update and meta-analysis.

Hasenoehrl T, Palma S, Ramazanova D, Kölbl H, Dorner TE, Keilani M, Crevenna R. Support Care Cancer. 2020 May 15

Background: The purpose of this systematic review update and meta-analysis was to analyze resistance exercise (RE) intervention trials in breast cancer survivors (BCS) regarding their effect on breast cancer-related lymphedema (BCRL) status and upper and lower extremity strength.

Methods: Systematic literature search was conducted utilizing PubMed, MEDLINE, and Embase databases. Any exercise intervention studies-both randomized controlled and uncontrolled-which assessed the effects of RE on BCRL in BCS in at least one intervention group published between 1966 and 31st January 2020 were included. Included articles were analyzed regarding their level of evidence and their methodological quality using respective tools for randomized and nonrandomized trials of the Cochrane collaboration. Meta-analysis for bioimpedance spectroscopy (BIS) values as well as upper and lower extremity strength was conducted.

Results: Altogether, 29 studies were included in the systematic review. Results of six studies with altogether twelve RE intervention groups could be pooled for meta-analysis of the BCRL. A significant reduction of BCRL after RE was seen in BIS values (95% CI – 1.10 [- 2.19, – 0.01] L-Dex score). Furthermore, strength results of six studies could be pooled and meta-analysis showed significant improvements of muscular strength in the upper and lower extremities (95% CI 8.96 [3.42, 14.51] kg and 95% CI 23.42 [11.95, 34.88] kg, respectively).

Conclusion: RE does not have a systematic negative effect on BCRL and, on the contrary, potentially decreases it.

Early prevention of complex decongestive therapy and rehabilitation exercise for prevention of lower extremity lymphedema after operation of gynecologic cancer.

Wu X, Liu Y, Zhu D, Wang F, Ji J, Yan H. Asian J Surg. 2020 May 10

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A systematic review of guidelines for lymphedema and the need for contemporary intersocietal guidelines for the management of lymphedema - click for abstract

A systematic review of guidelines for lymphedema and the need for contemporary intersocietal guidelines for the management of lymphedema.

O’Donnell TF, Allison GM, Iafrati MD. J Vasc Surg Venous Lymphat Disord. 2020 May 20

Objective: Lymphedema (LED) affects an estimated 35 million patients in the United States and a staggering 140,200 million people worldwide, yet LED is the forgotten vascular disease. Whereas the diagnosis and treatment of arterial and venous diseases have been strengthened by the development of clinical practice guidelines (CPGs), few CPGs are available for LED. Moreover, for CPGs to have their greatest impact, they should be both of high quality and developed using the most rigorous evidence-based methods. We performed a systematic review of the available CPGs for LED, which were assessed for breadth of content and methodologic strength.

Methods: A literature search was conducted from National Guideline Clearinghouse (www.Guidelines: gov), BMJ Clinical Evidence (, and National Institute for Health and Care Excellence ( as well as from MEDLINE and Google, which selected 271 documents. After a horizon scan that identified 13 potential CPGs, 4 satisfied the criteria for LED. These were analyzed for inclusion of key elements of diagnosis and treatment.

Results: A horizon scan (abstract review) of the 271 documents identified 10 potential CPGs. Of the 10 documents, 6 claimed to be CPGs, but 2 were limited in scope (rehabilitation or compression only), 2 were consensus statements, 1 was a position statement, and 1 was a systematic review. This process yielded four CPGs: Lymphedema Framework Best Practice for the Management of Lymphedema; Japanese Lymphedema Study Group-A Practice Guideline for the Management of Lymphedema; Clinical Resource Efficiency Support Team Guidelines for the Diagnosis, Assessment and Management of Lymphedema; and Guidelines of the American Venous Forum. Only one of four CPGs was based on a contemporary systematic review (2016 end date of references), whereas the remainder had older systematic reviews (end dates of 2005, 2007, and 2007). Several areas of contemporary diagnosis, treatment, and monitoring of LED were absent.

Conclusions: This systematic review of available LED CPGs demonstrates a limited number of guidelines. The four CPGs identified lack contemporary references while demonstrating low overall study quality. Therefore, it is imperative for our vascular societies to develop contemporary high-quality evidence-based CPGs for LED, as they have for other vascular diseases.

Effectiveness and Safety of Acupuncture Moxibustion Therapy Used in Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis.

Jin H, Xiang Y, Feng Y, Zhang Y, Liu S, Ruan S, Zhou H

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