Abstract
Purpose
Effective lymphoedema management relies on early detection and treatment during its reversible phase, underlining the importance of accurate measurement tools. This systematic review aims to identify measurement instruments for quantitatively diagnosing lymphoedema and their diagnostic accuracy.
Methods
Literature was systematically searched on the diagnostic accuracy of instruments for assessing soft tissue oedema across body parts in adults. Inclusion criteria encompassed studies establishing diagnostic accuracy (sensitivity and/or specificity) of instruments for quantifying oedema through volume changes, tissue characteristics, or lymphatic system function. Searches included Embase, Medline, Web of Science, and CINAHL databases from inception to March 18, 2024. Methodological quality was assessed using the COSMIN checklist for criterion validity and QUADAS-2. Diagnostic value was evaluated through the Youden index, and the level of evidence was established using a new best-evidence synthesis approach.
Results
A total of 44 studies were included, identifying 14 index measurement instruments. The most frequently studied instruments were tape measurements, ultrasound, and multi-frequency bio-impedance analysis (MF-BIA). Instruments with very high diagnostic value (Youden index ≥ 0.90) included MF-BIA, perometry, and MRI. However, the quality of evidence supporting these instruments was lacking. Nine different instruments served as references, with tape measurements, consensus criteria, and water volumetry being the most applied.
Conclusion
This review underscores the complexity of accurately diagnosing lymphoedema, with no single instrument emerging as a definitive gold standard. Clinicians must weigh the available evidence and consider the clinical context, such as early detection, when selecting measurement instruments for diagnosing lymphoedema.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00520-026-10373-y.
Keywords: Diagnosis, Oedema, Lymphoedema, Sensitivity, Specificity
Introduction
Lymphoedema is a significant global health issue, affecting approximately 200 million people worldwide [1]. This condition is characterized by lymphatic fluid accumulation and occurs as either primary, due to genetic mutations, or secondary, arising from systemic disease, trauma, or interventions, especially cancer-related surgeries and radiotherapy [2–5].
The International Society of Lymphoedema (ISL) stages lymphoedema from subclinical (stage 0) to hard, fibrotic oedema (stage 3) [2]. Early symptoms are often subjective, like tightness or heaviness, progressing to visible swelling and tissue fibrosis [2]. Chronic lymphoedema can cause significant physical discomfort, including pain, swelling, heaviness, and reduced mobility of the affected area, and is associated with complications such as recurrent skin infections, skin ulcers, or, in the worst case, angiosarcoma [5]. Lymphoedema has major psychological and social impacts on the quality of life of patients [6]. Moreover, the condition is a major burden on the health care system because it is a chronic and progressive condition that often requires lifelong treatment [5].
Lymphoedema treatment is commonly a multi-modal approach of manual lymphatic drainage, compression, exercises, and skincare [7, 8]. Several adjunct treatment options have also been trialled, such as pneumatic compression, pharmaceuticals, laser therapy, and microvascular surgery [7]. Evidence suggests that early treatment of lymphoedema is both effective and cost-saving [4]. To commence early treatment of lymphoedema, early detection is crucial, underscoring the need for measurement instruments with good diagnostic capacity.
Lymphoedema can be quantified in multiple methods, including volume, tissue characteristics, and lymphatic system function, depending on its stage [2, 5]. However, no universally accepted gold standard for assessment exists, and multiple instruments with unique advantages and drawbacks are applied in research and clinical settings [9].
To our knowledge, only one systematic review has evaluated the diagnostic accuracy of lymphoedema measurement instruments [9]. This review highlighted limited and sometimes conflicting results for measuring upper extremity lymphoedema and recommended water volumetry as the reference test due to its superior reliability. Although various instruments were assessed, only one study used water volumetry as the reference, evaluating tape measurement with sensitivities from 0.05 to 0.90 and specificities from 0.69 to 1.00. Notably, advanced imaging modalities like computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) were excluded, though these could provide valuable information and could be applied in specific cases during regular clinical follow-up.
Given advancements in lymphoedema research since this review from 2015, a reassessment of measurement instruments and their properties is relevant and timely. This systematic review aims to identify instruments for quantitatively diagnosing soft-tissue oedema, including lymphoedema, across any body part and their diagnostic accuracy. We expect the results to assist clinicians in selecting appropriate instruments for their patients and support researchers in improving early diagnostic methods.
Methods
Protocol and registration
This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [10] and has been registered in PROSPERO (registration number: CRD42023474209). Given the extensive initial search, this review addresses the diagnostic accuracy of measurement instruments for soft tissue oedema, with other clinimetric properties covered in separate reviews (in preparation).
Eligibility criteria
Studies were included when describing measurement instruments that quantified soft tissue oedema. Although the primary focus was lymphoedema, studies assessing other types of soft tissue swelling, such as postoperative swelling that could mimic early-stage lymphoedema, were also included. Studies were excluded when describing measurements of temporary oedema in healthy subjects (e.g. individuals with standing jobs or those taking long flights), although cohort studies with patients and healthy subjects were included. Studies reporting on soft tissue oedema in skin conditions (e.g. ulcers, burn wounds, or psoriasis) or vascular oedema were excluded. Only prospective studies involving adults (≥ 16 years of age) were included; studies on paediatric cohorts were excluded. Instruments had to measure body part or tissue volume, tissue characteristics, or lymphatic system function. Clinical assessment of one of these aspects by a specialist was also considered relevant. Patient-reported outcomes were excluded. Studies on measurement instruments not aiming to quantify soft tissue oedema or those quantifying the quality of the venous system were excluded. Studies that reported both objective measures and patient-reported measures of lymphoedema were included, with only objective data extracted.
Studies had to report on the diagnostic accuracy with sensitivity or specificity. For cohort studies, data had to be presented separately for patients, patients at risk, and healthy subjects. Data was excluded when patients (at risk) and healthy subjects had a difference in the mean age of more than 10 years to minimize bias as aging leads to alteration of elastic properties of the skin [11]. Meta-analyses, systematic reviews, conference papers, case reports, and studies without accessible full text were excluded.
Information sources and search
Electronic databases Embase.com, Medline via Ovid, Web of Science Core Collection, and CINAHL via EBSCO were systematically searched from inception until March 18, 2024 (date last searched). The search strategy included terms related to the construct (e.g. lymphoedema, swelling) combined with a methodological search filter for finding studies on measurement properties [12]. Full search strategies are provided in Supplementary information 1.
Study selection
Two reviewers (MBB and JTH) independently assessed titles and abstracts of the studies retrieved by the literature search. Full-text articles were then retrieved and divided into two sets for examination. Each set was independently reviewed by two reviewers (MBB and EMG for set A; JTH and JDR for set B) to compile the final list of eligible studies. Disagreements were resolved by a third reviewer (CMS).
Data collection process
Two reviewers (MBB and EMG) independently extracted data from the included articles into a custom-built template in Microsoft Word. Extracted data included the first author, year of publication, index measurement instrument, reference measurement instrument, study population (age, gender, previous diagnosis, swelling type, and swelling stage), and diagnostic accuracy (sensitivity and specificity). Consensus was achieved through discussion in cases of disagreement.
Quality assessment
The methodological quality of included studies was independently assessed by two reviewers (MBB and EMG) using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2), which evaluates patient selection, index test, reference standard, and flow and timing [13]. Each domain contributes to the assessment of risk of bias, with the first three domains also assessing applicability. In addition, criterion validity was specifically evaluated using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist Box 8 [14]. The assessment protocol is detailed in Supplementary information 2. Disagreement was resolved by a third reviewer (CMS).
Data synthesis
Pooling of the studies was not possible due to the diversity in instruments and parameters. Therefore, a best-evidence synthesis for diagnostic accuracy has been established and conducted. Index measurement instruments are categorized into five levels of evidence as presented in Table 1.
Table 1.
Best-evidence synthesis for diagnostic accuracy
| Level of evidence | Criteria |
|---|---|
| Strong evidence | Provided by at least three studies with very good quality, defined as ≥ 3 good quality-scores (+) for QUADAS-2 Risk of bias, and 3 good-quality scores (+) for QUADAS-2 applicability, and no concerns for COSMIN Box 8 |
| Moderate evidence | Provided by at least two studies with very good quality, defined as ≥ 3 good quality-scores (+) for QUADAS-2 Risk of bias, and 3 good-quality scores (+) for QUADAS-2 applicability, and no important concerns for COSMIN Box 8 |
| Limited evidence | Provided by one study with very good quality, defined as ≥ 3 good quality-scores (+) for QUADAS-2 Risk of bias, and 3 good-quality scores (+) for QUADAS-2 applicability, and no important concerns for COSMIN Box 8, or at least two studies with good quality, defined as ≥ 2 good quality-scores (+) for QUADAS-2 Risk of bias, and ≥ 2 good-quality scores (+) for QUADAS-2 applicability, and no important concerns for COSMIN Box 8 |
| Insufficient evidence | In the case that eligible studies do not meet the criteria for one of the above stated levels of evidence |
| No evidence | In the case of no eligible studies |
For all extracted diagnostic accuracy data, the diagnostic evidence was given by the Youden index, which was calculated by deducting 1 from the sum of the sensitivity and specificity [15, 16]. The Youden index was interpreted as weak (< 0.4), moderate (≥ 0.4 and < 0.7), high (≥ 0.7 and < 0.9), and very high (≥ 0.9) as an indicator of the diagnostic value of measurement instruments. Diagnostic evidence was classified as conflicting when the Youden index differed ≥ 0.4 within or between studies.
Diagnostic accuracy data were interpreted as indicators of the index measurement instrument, not the reference measurement instrument. Index instruments could be experimental, while reference measurement instruments were commonly used clinically in the absence of a clear gold standard. Applicability of reference instruments was evaluated during quality assessment.
Results
Included studies
The search identified 8,510 unique articles, with 413 eligible for full-text assessment. Of these, 210 articles were excluded based on the eligibility criteria, and 179 articles assessed clinimetric outcome measures other than diagnostic accuracy, which will be addressed in subsequent reviews. Ultimately, 45 articles on diagnostic accuracy were included in this review, as detailed in the study selection flowchart (Fig. 1).
Fig. 1.
Study selection flowchart
Study characteristics
The characteristics of the included studies are presented in Table 2, sorted by index and reference measurement instruments. An overview of the identified measurement instruments is provided in Table 3.
Table 2.
Study characteristics of included articles
| Author, year | Index measurement instrument | Reference measurement instrument | Diagnose | Versus | Diagnostic classification system/threshold | Body part | Population | Measurement instrument specification and threshold | Diagnostic accuracy | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Previous diagnosis | N (%F) | Age; mean ± SD median (range) | Sensitivity | Specificity | Youden index | ||||||||||
| Wiser et al. [31], 2020 | LSG | Perometry | All stages LE | No LE | Interlimb volume difference > 10% | Upper extremities unilateral | Various | 118 (98) | 54 ± 11 | Presence of dermal backflow or lack of radiotracer uptake after 3 h | 0.88 | 0.41 | 0.29 | ||
| Sampathirao et al. [58], 2021 | LSG | ISL consensus criteria 2020 | LE | No LE | ISL consensus criteria 2020 | Lower extremities | Various |
LE: 86 (43) No LE: 9 (56) |
LE: (Range = 18–78) No LE: (Range = 20–45) |
Nodal uptake ≤ 22.18% | 1.00 | 0.80 | 0.80 | ||
| Keo et al. [60], 2013 | Fluorescence lymphography | Lymphedema Framework International consensus 2006 | LE | No LE | Lymphedema Framework International consensus 2006 | Lower extremities | Not specified |
LE: 89 (66) No LE: 82 (74) |
LE: 47 (IQR = 29–56) No LE: 48 (IQR = 37–58) |
Maximum spread of dye | ≥ 8 mm | 0.94 | 0.28 | 0.22 | |
| ≥ 10 mm | 0.91 | 0.40 | 0.31 | ||||||||||||
| ≥ 12 mm | 0.87 | 0.64 | 0.51 | ||||||||||||
| ≥ 14 mm | 0.79 | 0.83 | 0.62 | ||||||||||||
| ≥ 15 mm | 0.78 | 0.83 | 0.61 | ||||||||||||
| ≥ 16 mm | 0.72 | 0.84 | 0.56 | ||||||||||||
| Keo et al. [59], 2015a | Fluorescence lymphography | Lymphedema Framework International consensus 2006 | LE | No LE | Lymphedema Framework International consensus 2006 | Lower extremities | Not specified | 70 (66) | 45 (IQR = 27–56) | Maximum spread of dye | ≥ 10 mm | 0.94 | 0.51 | 0.45 | |
| ≥ 12 mm | 0.94 | 0.79 | 0.73 | ||||||||||||
| ≥ 14 mm | 0.92 | 0.86 | 0.78 | ||||||||||||
| ≥ 16 mm | 0.76 | 0.89 | 0.65 | ||||||||||||
| Aldrich et al. [61], 2022 | Fluorescence lymphography | Perometry | Mild to moderate LE | No LE | Relative volume change ≥ 5% to baseline | Upper extremities | BC | 42 (100) | 54 (28–68) | Dermal backflow present | 0.97 | 0.50 | 0.47 | ||
| Berlit et al. [35], 2012 | SF-BIA | Tape measurements | LE | No LE | NR | Upper extremities | BC unilateral | 33 (100) | 59.9 ± 9.3 | Resistance, threshold NR | 0.75 | 0.86 | 0.61 | ||
| Phase angle, threshold NR | 0.75 | 0.83 | 0.58 | ||||||||||||
| Berlit et al. [36], 2013b | SF-BIA | Tape measurements | LE | No LE | NR | Upper extremities | BC unilateral |
LE: 7 (100) No LE: 35 (100) |
LE: 60.3 ± 10.6 No LE: 60.4 ± 11.3 |
Resistance, threshold NR | 0.86 | 0.97 | 0.83 | ||
| Lim et al. [41], 2019 | SF-BIA | Tape measurements | LE | No LE | > 2 cm interlimb difference | Upper extremities | BC unilateral |
LE: 22 (100) No LE: 206 (100) |
LE: 56.3 ± 12.0 No LE: 52.8 ± 9.7 |
5 kHz, interlimb ratio > 1.047 | 0.63 | 0.95 | 0.58 | ||
| Dylke et al. [17], 2016 | MF-BIA | LSG | Dermal backflow score 1 and 2 | Dermal backflow score 0 |
0: no dermal backflow 1: small area or localized backflow 2: circumferential dermal backflow in < 50% of the forearm 3: circumferential dermal backflow in > 50% of the forearm |
Upper extremities | BC unilateral |
LE: 68 (100) At risk: 6 (100) No LE: 13 (100) |
LE: 60.7 ± 11.1 At risk: 50.5 ± 7.5 No LE: 55.9 ± 17.6 |
Impedance interlimb ratio | 3SD | 0.96 | 0.67–0.72 | 0.63–0.68 | |
| 2SD | 0.93 | 0.81–0.87 | 0.74–0.80 | ||||||||||||
| Pichonnaz et al. [29], 2015 | MF-BIA | MF-BIA (preoperative) | Postoperative (TKA) swelling | No swelling | Percentage difference between the healthy and involved limb (threshold NR) | Lower extremities (unilateral) | Osteoarthritis | 24 (50) | 69.5 ± 9.7 | Postoperative day 2, interlimb difference > 13.4% | 0.96 | 0.96 | 0.92 | ||
| Postoperative day 8, interlimb difference > 13.8% | 1.00 | 0.96 | 0.96 | ||||||||||||
| Bundred et al. [37], 2015 | MF-BIA | Perometry | LE | No LE | > 10% volume increase from baseline | Upper extremities | BC | 612 (100) | 55 (24–90) | ≥ 10 units difference from baseline | 0.73 | 0.84 | 0.57 | ||
| Wiser et al. [31], 2020 | MF-BIA | Perometry | All stages LE | No LE | Interlimb volume difference > 10% | Upper extremities unilateral | Various | 118 (98) | 54 ± 11 | L-Dex > 10 | 0.91 | 0.76 | 0.67 | ||
| Cornish et al. [38], 2001 | MF-BIA | Tape measurements | Early LE | No LE | > 0.139 volume ratio from baseline | Upper extremities | BC unilateral | 102 (NR) | 51 (25–82) | > 0.102 ratio from baseline | 1.00 | 0.98 | 0.98 | ||
| Fu et al. [39], 2013 | MF-BIA | Tape measurement + clinical assessment + self-report | LE | At risk | Tape measurement > 200 ml interlimb difference | Upper extremities | BC unilateral |
LE: 42 (100) At risk: 148 (100) |
LE: 58.0 ± 10.7 At risk: 55.8 ± 11.6 |
L-Dex interlimb ratio | > + 10 | 0.66 | 0.95 | 0.61 | |
| > + 7.1 | 0.80 | 0.90 | 0.70 | ||||||||||||
| Barrio et al. [34], 2015 | MF-BIA | WV | LE | No LE | > 10% interlimb difference | Upper extremities | BC unilateral | 186 (100) | 60 (27–83) | L-Dex interlimb ratio > 10 | 0.75 | 0.93 | 0.68 | ||
| Brandini Da Silva Tozzo et al. [21], 2023 | MF-BIA | WV | LE | No LE | Interlimb volume difference of ≥ 200 mL | Upper extremities | BC | 462 (100) | 57 ± 9 | L-Dex interlimb ratio | ≥ 10 | 0.44 | 0.95 | 0.39 | |
| ≥ 7.35 | 0.57 | 0.91 | 0.48 | ||||||||||||
| ≥ 6.5 | 0.57 | 0.89 | 0.46 | ||||||||||||
| ≥ 1.35 | 0.74 | 0.67 | 0.41 | ||||||||||||
| Lahtinen et al. [40], 2015 | MF-BIA | 2 of the following 3: WV, clinical assessment (palpation), self-report | LE | No LE | WV ≥ 5% interlimb difference | Upper extremities | BC unilateral | 100 (100) | 57.4 ± 11.5 | Interlimb ratio 1.066 nondominant arm and 1.139 dominant arm | 0.42 | 0.94 | 0.36 | ||
| Thomis et al. [33], 2020 | TDC measurements | Fluorescence lymphography | Dermal backflow stage I-V | No dermal backflow |
Dermal backflow stage: I: splash pattern II: stardust pattern proximally to the olecranon III: stardust pattern exceeds olecranon IV: stardust pattern whole arm V: diffuse pattern |
Upper extremities (unilateral) | Hand | BC | 45 (NR) | 61.3 ± 9.9 | Water content interlimb ratio ≥ 1.2 | 0.65 | 0.90 | 0.55 | |
| Ventral forearm | 0.81 | 0.67 | 0.48 | ||||||||||||
| Dorsal forearm | 0.78 | 0.75 | 0.53 | ||||||||||||
| Elbow | 0.85 | 0.11 | -0.04 | ||||||||||||
| Ventral upper arm | 0.67 | 0.85 | 0.52 | ||||||||||||
| Dorsal upper arm | 0.72 | 0.67 | 0.39 | ||||||||||||
| Shoulder | 0.33 | 0.98 | 0.31 | ||||||||||||
| Overall | 0.75 | 0.75 | 0.50 | ||||||||||||
| Thomis et al. [30], 2022c | TDC measurements | Fluorescence lymphography | Dermal backflow stage I-IV | No dermal backflow |
Dermal backflow stage: 0: No I: splash pattern II: stardust pattern III: diffuse pattern IV: no transport |
Upper extremities | All regions | BC unilateral | 128 (99) | 56.7 ± 12.2 | Water content interlimb ratio ≥ 1.2 | 0.36 | 0.92 | 0.28 | |
| Ventral upper arm | 0.38 | 0.91 | 0.29 | ||||||||||||
| Bakar et al. [42], 2018 | TDC measurements | Tape measurements | Grade 1–3 LE | Grade 0 LE |
Circumference interlimb difference Grade 1: 5–10% Grade 2: 10–30% Grade 3: > 30% |
Upper extremities | BC unilateral |
LE: 31 (100) No LE: 32 (100) |
LE: 54.5 ± 13.0 No LE: 53.3 ± 12.9 |
Local tissue water interlimb ratio ≥ 1.20 | 0.65 | 0.94 | 0.59 | ||
| Lahtinen et al. [40], 2015 | TDC measurements | 2 of the following 3: WV, clinical assessment (palpation), self-report | LE | No LE | WV ≥ 5% interlimb difference | Upper extremities | BC unilateral | 100 (100) | 57.4 ± 11.5 | Interlimb ratio 1.45 upper arm and 1.30 forearm | 0.66 | 0.84 | 0.50 | ||
| Riches et al. [43], 2023 | TDC measurements | Clinical assessment | LE | No LE | Pitting oedema present ≥ 1 breast quadrant | Breast | BC | 89 (NR) | 61.1 ± 9.6 | Interbreast ratio > 1.34 | 0.88 | 0.80 | 0.68 | ||
| Liu et al. [27], 2022 | TDC measurements | ISL consensus criteria 2016 | Stage 0 LE | No LE | ISL consensus criteria 2016 | Upper extremities | BC unilateral | 69 (100) | 54.4 ± 9.3 | Interlimb ratio ≥ 1.2 | 0.44 | NR | NA | ||
| Stage 1 LE | No LE | 0.52 | NR | NA | |||||||||||
| Stage 2 LE | No LE | 0.96 | NR | NA | |||||||||||
| Dylke et al. [17], 2016 | Perometry | LSG | Dermal backflow score 1 and 2 | Dermal backflow score 0 |
0: no dermal backflow 1: small area or localized backflow 2: circumferential dermal backflow in < 50% of the forearm 3: circumferential dermal backflow in > 50% of the forearm |
Upper extremities | BC unilateral |
LE: 68 (100) At risk: 6 (100) No LE: 13 (100) |
LE: 60.7 ± 11.1 At risk: 50.5 ± 7.5 No LE: 55.9 ± 17.6 |
Whole arm volume | 3SD, truncated cone | 1.00 | 0.57 | 0.57 | |
| 2SD, truncated cone | 1.00 | 0.81 | 0.81 | ||||||||||||
| 3SD, perometry cut-off | 1.00 | 0.62 | 0.62 | ||||||||||||
| 2SD, perometry cut-off | 1.00 | 0.78 | 0.78 | ||||||||||||
| 200 ml difference | 0.96 | 0.78 | 0.74 | ||||||||||||
| 10% increase | 0.96 | 0.78 | 0.74 | ||||||||||||
| Circumferences | 3SD, single elevation | 1.00 | 0.81 | 0.81 | |||||||||||
| 3SD, 2 + elevation | 1.00 | 0.58 | 0.58 | ||||||||||||
| 2SD, single elevation | 0.96 | 0.94 | 0.90 | ||||||||||||
| 2SD, 2 + elevation | 1.00 | 0.77 | 0.77 | ||||||||||||
| 3SD, SOAC | 1.00 | 0.64 | 0.64 | ||||||||||||
| 2SD, SOAC | 1.00 | 0.77 | 0.77 | ||||||||||||
| Single 2 cm difference | 1.00 | 0.85 | 0.85 | ||||||||||||
| 2 + 2 cm difference | 1.00 | 0.65 | 0.65 | ||||||||||||
| SOAC: 5 cm difference | 1.00 | 0.77 | 0.77 | ||||||||||||
| Jeffs and Purushotham [18], 2016 | Perometry | Clinical assessment | LE | No LE | Presence of one or more symptoms: decreased visibility of veins, increased thickness of skin and subcutis, fullness of tissues or smoothing of natural limb contours, pitting oedema | Upper extremities | BC | 40 (100) | 62 (IQR 55–66) | ≥ 10% interlimb difference | 0.17 | 1.00 | 0.17 | ||
| Hayes et al. [24], 2005 | Tape measurements | MF-BIA | LE | No LE | Interlimb ratio > 3SD | Upper extremities | BC unilateral | 176 (100) | 54 ± 10 | Sum of arm circumference interlimb difference | > 5 cm | 0.35 | 0.89 | 0.24 | |
| > 10% | 0.05 | 1.00 | 0.05 | ||||||||||||
| Hayes et al. [25], 2008d | Tape measurements | MF-BIA | LE | No LE | Interlimb ratio > 3SD | Upper extremities | BC unilateral | 211 (100) | 54 ± 10 | Sum of arm circumference interlimb difference > 5 cm | 0.42 | 0.88 | 0.30 | ||
| Wiser et al. [31], 2020 | Tape measurements | Perometry | All stages LE | No LE | Interlimb volume difference > 10% | Upper extremities unilateral | Various | 118 (98) | 54 ± 11 | Circumference difference > 2 cm | 0.83 | 0.85 | 0.68 | ||
| Asim et al. [19], 2012 | Tape measurements | Tape measurements | Moderate LE | No or mild LE | Lymphedema Framework International consensus 2006; volume ≥ 20% interlimb difference | Upper extremities | BC unilateral | 73 (100) | 61 ± 11e | Circumference interlimb difference | ≥ 7.5% | 0.83 | 0.81 | 0.64 | |
| ≥ 10% | 0.66 | 0.89 | 0.55 | ||||||||||||
| ≥ 2 cm | 0.66 | 0.80 | 0.46 | ||||||||||||
| Hidding et al. [26], 2018 | Tape measurements | Tape measurements | LE | No LE | Volume ≥ 10% interlimb difference | Upper extremities | BC unilateral | 51 (98) | 51.3 ± 8.5 | Circumference > 4% interlimb difference | 0.85 | 0.85 | 0.70 | ||
| Bland et al. [20], 2003 | Tape measurements | Tape measurements with clinical assessment specialist | LE | No LE | > 10% increase in volume from baseline or > 1 cm increase in circumference from baseline, both with confirmation from a lymphoedema specialist (method not specified) | Upper extremities | Elbow | BC |
LE: 38 (100) No LE: 52 (100) |
LE: 54.8 ± 13.4 No LE: 54.4 ± 10.3 |
Circumference increase from baseline | > 5% | 0.80 | 0.71 | 0.51 |
| > 10% | 0.37 | 0.92 | 0.29 | ||||||||||||
| > 2 cm | 0.59 | 0.85 | 0.44 | ||||||||||||
| Any site | > 5% | 0.91 | 0.46 | 0.37 | |||||||||||
| > 10% | 0.49 | 0.81 | 0.30 | ||||||||||||
| > 2 cm | 0.70 | 0.76 | 0.46 | ||||||||||||
| Pichonnaz et al. [29], 2015 | Tape measurements | Tape measurements (preoperative) | Postoperative (TKA) swelling | No swelling | % difference between the healthy and involved limb (threshold NR) | Lower extremities (unilateral) | Osteoarthritis | 24 (50) | 69.5 ± 9.7 | Postoperative day 2 | Volume, interlimb difference > 6.1% | 0.83 | 0.79 | 0.62 | |
| Circumference, interlimb difference > 5.6% | 0.92 | 0.83 | 0.75 | ||||||||||||
| Postoperative day 8 | Volume, interlimb difference > 7.7% | 0.92 | 0.92 | 0.84 | |||||||||||
| Circumference, interlimb difference > 5.8% | 0.96 | 0.88 | 0.84 | ||||||||||||
| Brandini Da Silva Tozzo et al. [21], 2023 | Tape measurements | WV | LE | No LE | Interlimb volume difference of ≥ 200 mL | Upper extremities | Breast cancer | 462 (100) | 57 ± 9 | Interlimb difference ≥ 2 cm | 0.85 | 0.83 | 0.68 | ||
| Godoy et al. [23], 2007 | Tape measurements | WV | LE | No LE | ≥ 200 mL interlimb difference | Upper extremities | BC unilateralf | 90 (100) | 54.8 ± 11.7 | Interlimb difference | ≥ 2 cm | 0.90 | 0.72 | 0.62 | |
| ≥ 100 mL interlimb difference | ≥ 2 cm | 0.87 | 0.69 | 0.56 | |||||||||||
| ≥ 10% interlimb difference | ≥ 10% | 0.73 | 0.78 | 0.51 | |||||||||||
| Furlan et al. [22], 2021 | Tape measurements | WV | LE | No LE | Interlimb volume difference of ≥ 200 mL | Upper extremities | BC unilateral | 85 (NR) |
21% < 55y 79% > 55y |
Interlimb difference ≥ 2 cm | for two contiguous points | 0.53 | 0.99 | 0.52 | |
| any point | 0.63 | 0.92 | 0.55 | ||||||||||||
| Lopez Penha et al. [28], 2011 | Tape measurements | WV | LE | No LE | > 299 mL interlimb difference | Upper extremities | BC | 145 (100) | 55 (33 -86)g | Circumference interlimb difference > 2 cm | 0.82 | 0.73 | 0.55 | ||
| Sum of circumferences interlimb difference > 5 cm | 0.82 | 0.90 | 0.72 | ||||||||||||
| Liu et al. [27], 2022 | Tape measurements | ISL consensus criteria 2016 | Stage 0 | No LE | ISL consensus criteria 2016 | Upper extremities | BC unilateral | 69 (100) | 54.4 ± 9.3 | Interlimb difference circumference ≥ 2 cm at any point, or volume ≥ 200 mL and/or ≥ 10% | 0.00 | NR | NA | ||
| Stage 1 LE | No LE | 1.00 | NR | NA | |||||||||||
| Stage 2 LE | No LE | 1.00 | NR | NA | |||||||||||
| Thomis et al. [30], 2022c | Tape measurements (arm) and water volumetry (hand) | Fluorescence lymphography | Dermal backflow stage I-IV | No dermal backflow |
Dermal backflow stage: 0: No I: splash pattern II: stardust pattern III: diffuse pattern IV: no transport |
Upper extremities | All regions | BC unilateral | 128 (99) | 56.7 ± 12.2 | Interlimb volume difference | ≥ 3% | 0.60 | 0.86 | 0.46 |
| ≥ 5% | 0.46 | 0.92 | 0.38 | ||||||||||||
| Ventral upper arm | ≥ 3% | 0.67 | 0.65 | 0.32 | |||||||||||
| ≥ 5% | 0.51 | 0.18 | -0.31 | ||||||||||||
| Thomis et al. [33], 2020 | WV | Fluorescence lymphography | Dermal backflow stage I-V | No dermal backflow |
Dermal backflow stage: I: splash pattern II: stardust pattern proximally to the olecranon III: stardust pattern exceeds olecranon IV: stardust pattern whole arm V: diffuse pattern |
Upper extremities (unilateral) | Hand | BC | 45 (NR) | 61.3 ± 9.9 | Interlimb difference ≥ 5% | 0.85 | 0.79 | 0.64 | |
| Ventral forearm | 0.94 | 0.56 | 0.50 | ||||||||||||
| Dorsal forearm | 0.97 | 0.75 | 0.72 | ||||||||||||
| Elbow | 0.85 | 0.16 | 0.01 | ||||||||||||
| Ventral upper arm | 0.94 | 0.22 | 0.16 | ||||||||||||
| Dorsal upper arm | 1.00 | 0.26 | 0.26 | ||||||||||||
| Overall | 0.93 | 0.39 | 0.32 | ||||||||||||
| Brandini Da Silva Tozzo et al. [21], 2023 | WV (indirect) | WV (direct) | LE | No LE | Interlimb volume difference of ≥ 200 mL | Upper extremities | BC | 462 (100) | 57 ± 9 | Interlimb difference | ≥ 200 ml | 0.66 | 0.96 | 0.62 | |
| Lu et al. [32], 2014 | WV | ISL consensus criteria 2009 | Stage 1 LE | Stage 0 LE | ISL consensus criteria 2009 | Lower extremities (unilateral) | Calf | GC: cervical or endometrial |
LE stage 0: 25 (100) 1: 22 (100) 2: 28 (100) 3: 20 (100) |
Median = 57 | ≥ 10% | 0.58 | 0.97 | 0.55 | |
| Interlimb volume difference (56 ml) | 0.86 | 0.76 | 0.62 | ||||||||||||
| Stage 2 LE | Stage 1 LE | Volume (2620 ml) | 0.68 | 0.71 | 0.39 | ||||||||||
| Interlimb volume difference (364 ml) | 0.84 | 0.86 | 0.70 | ||||||||||||
| Stage 3 LE | Stage 2 LE | Volume (3450 ml) | 0.95 | 0.87 | 0.82 | ||||||||||
| Interlimb volume difference (1033 ml) | 0.90 | 0.87 | 0.77 | ||||||||||||
| Koo et al. [44], 2019 | CT | LSG | LSG Stage IV | LSG Stages I, II and III |
Stage 1: normal Stage 2: visible, but dysfunctional epifascial lymph nodes Stage 3: dermal backflow and no visible epifascial lymph nodes Stage 4: visible dermal backflow and no epifascial or subfascial lymph nodes |
Upper and lower extremities | Various | 24 (100) | 57.5 ± 13.4 | Interlimb ratio number of pixels of tissue layer between skin and muscle 17.57 | 0.78 | 0.60 | 0.38 | ||
| LSG Stages III and IV | LSG Stages I and II | 0.75 | 0.56 | 0.31 | |||||||||||
| Li et al. [45], 2015 h | MRI | ISL consensus criteria 2009 | Stage 1 LE | Stage 0 LE | ISL consensus criteria 2009 | Lower extremities (unilateral) | Calf | GC: uterine |
LE stage 0: 22 (100) 1: 15 (100) 2: 38 (100) 3: 19 (100) |
Median = 57 | Total soft tissue thickness (105.4 mm) | 0.60 | 0.82 | 0.42 | |
| Interlimb difference total soft tissue thickness (5.65 mm) | 0.60 | 0.77 | 0.37 | ||||||||||||
| Subcutaneous tissue thickness (23.7 mm) | 0.67 | 0.96 | 0.63 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (3.45 mm) | 0.93 | 0.82 | 0.75 | ||||||||||||
| Interlimb difference muscle tissue thickness (0.10 mm) | 0.73 | 0.64 | 0.37 | ||||||||||||
| Stage 2 LE | Stage 1 LE | Total soft tissue thickness (111.05 mm) | 0.71 | 0.80 | 0.51 | ||||||||||
| Interlimb difference total soft tissue thickness (13.85 mm) | 0.84 | 0.80 | 0.64 | ||||||||||||
| Subcutaneous tissue thickness (30.6 mm) | 0.76 | 0.73 | 0.49 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (11.1 mm) | 0.84 | 0.87 | 0.71 | ||||||||||||
| Interlimb difference muscle tissue thickness (0.90 mm) | 0.61 | 0.60 | 0.21 | ||||||||||||
| Stage 3 LE | Stage 2 LE | Total soft tissue thickness (124.45 mm) | 0.90 | 0.82 | 0.72 | ||||||||||
| Interlimb difference total soft tissue thickness (31.63 mm) | 0.84 | 0.90 | 0.74 | ||||||||||||
| Subcutaneous tissue thickness (46.95 mm) | 0.95 | 0.90 | 0.85 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (29.3 mm) | 0.95 | 0.92 | 0.87 | ||||||||||||
| Interlimb difference muscle tissue thickness (0.65 mm) | 0.47 | 0.40 | -0.13 | ||||||||||||
| Stage 1 LE | Stage 0 LE | Thigh | Total soft tissue thickness (133.25 mm) | 0.60 | 0.59 | 0.19 | |||||||||
| Interlimb difference total soft tissue thickness (7.8 mm) | 0.73 | 0.82 | 0.55 | ||||||||||||
| Subcutaneous tissue thickness (37.05 mm) | 0.73 | 0.73 | 0.46 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (3.65 mm) | 0.73 | 0.73 | 0.46 | ||||||||||||
| Interlimb difference muscle tissue thickness (0.05 mm) | 0.60 | 0.59 | 0.19 | ||||||||||||
| Stage 2 LE | Stage 1 LE | Total soft tissue thickness (144.60 mm) | 0.73 | 0.60 | 0.33 | ||||||||||
| Interlimb difference total soft tissue thickness (19.85 mm) | 0.76 | 0.72 | 0.48 | ||||||||||||
| Subcutaneous tissue thickness (46.9 mm) | 0.66 | 0.60 | 0.26 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (15.2 mm) | 0.76 | 0.60 | 0.36 | ||||||||||||
| Interlimb difference muscle tissue thickness (4.55 mm) | 0.64 | 0.60 | 0.24 | ||||||||||||
| Stage 3 LE | Stage 2 LE | Total soft tissue thickness (158.35 mm) | 0.79 | 0.68 | 0.47 | ||||||||||
| Interlimb difference total soft tissue thickness (44.45 mm) | 0.74 | 0.87 | 0.61 | ||||||||||||
| Subcutaneous tissue thickness (62.3 mm) | 0.74 | 0.68 | 0.42 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (38.85 mm) | 0.68 | 0.87 | 0.55 | ||||||||||||
| Interlimb difference muscle tissue thickness (7.65 mm) | 0.63 | 0.66 | 0.29 | ||||||||||||
| Lu et al. [32], 2014 | MRI | ISL consensus criteria 2009 | Stage 1 LE | Stage 0 LE | ISL consensus criteria 2009 | Lower extremities (unilateral) | Calf | GC: cervical or endometrial |
LE stage 0: 25 (100) 1: 22 (100) 2: 28 (100) 3: 20 (100) |
Median = 57 | Total soft tissue thickness (970 mm) | 0.74 | 0.72 | 0.46 | |
| Interlimb difference total soft tissue thickness (4.6 mm) | 0.71 | 0.92 | 0.63 | ||||||||||||
| Subcutaneous tissue thickness (18.1 mm) | 0.93 | 0.84 | 0.77 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (3.5 mm) | 0.96 | 1.00 | 0.96 | ||||||||||||
| Stage 2 LE | Stage 1 LE | Total soft tissue thickness (1111 mm) | 0.70 | 0.79 | 0.49 | ||||||||||
| Interlimb difference total soft tissue thickness (13.9 mm) | 0.84 | 0.93 | 0.77 | ||||||||||||
| Subcutaneous tissue thickness (29.2 mm) | 0.78 | 0.71 | 0.49 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (11.5 mm) | 0.88 | 0.94 | 0.82 | ||||||||||||
| Stage 3 LE | Stage 2 LE | Total soft tissue thickness (129.6 mm) | 0.84 | 0.89 | 0.73 | ||||||||||
| Interlimb difference total soft tissue thickness (31.7 mm) | 0.84 | 0.89 | 0.73 | ||||||||||||
| Subcutaneous tissue thickness (48.2 mm) | 0.90 | 0.92 | 0.82 | ||||||||||||
| Interlimb difference subcutaneous tissue thickness (29.3 mm) | 0.90 | 0.97 | 0.87 | ||||||||||||
| Wang et al. [46], 2018 | MRI | ISL consensus criteria 2013 | Stage 1 LE | Stage 0 LE | ISL consensus criteria 2013 | Lower extremities | Various | 138 (NR) | NR | Total area soft-tissue (6180 mm2) | 0.76 | 0.43 | 0.19 | ||
| Difference total area soft-tissue (306 mm2) | 0.76 | 0.64 | 0.40 | ||||||||||||
| Water area soft-tissue (17 mm2) | 1.00 | 1.00 | 1.00 | ||||||||||||
| Stage 2 LE | Stage 1 LE | Total area soft-tissue (7006.5 mm2) | 0.75 | 0.59 | 0.34 | ||||||||||
| Difference total area soft-tissue (1281 mm2) | 0.89 | 0.91 | 0.80 | ||||||||||||
| Water area soft-tissue (913 mm2) | 0.81 | 0.94 | 0.75 | ||||||||||||
| Stage 3 LE | Stage 2 LE | Total area soft-tissue (120,200 mm2) | 0.54 | 0.85 | 0.39 | ||||||||||
| Difference total area soft-tissue (4809 mm2) | 0.86 | 0.89 | 0.75 | ||||||||||||
| Water area soft-tissue (10479.5 mm2) | 0.72 | 0.75 | 0.47 | ||||||||||||
| Wiser et al. [31], 2020 | MRA | Perometry | All stages LE | No LE | Interlimb volume difference > 10% | Upper extremities unilateral | Various | 118 (98) | 54 ± 11 | Fluid accumulation | 0.94 | 0.44 | 0.38 | ||
| Fat hypertrophy | 0.96 | 0.64 | 0.60 | ||||||||||||
| Lee et al. [53], 2020 | US | LSG | Stage 1 or 2 LE | Stage 0 LE |
Stage 0: normal Stage 1: partial lymphatic obstruction Stage 2: total lymphatic obstruction |
Lower extremities (unilateral) | Not specified | 60 (90) | 59.0 ± 11.7 | Evenlope amplitude, threshold NR | 0.70 | 0.48 | 0.18 | ||
| Nakagami parameter, threshold NR | 0.70 | 0.75 | 0.45 | ||||||||||||
| Shannon entropy, threshold NR | 0.95 | 0.88 | 0.83 | ||||||||||||
| Chan et al. [47], 2018 | US | LSG | Lymphatic obstruction (partial and total) | No lymphatic obstruction |
No: lymph nodes and lymphatic collectors are well visualized and without dermal backflow Partial: either decreased visualization of proximal lymph nodes or dermal backflow Total: absence of lymphatic collector and proximal lymph nodes and dermal backflow |
Upper (N = 19) and lower extremities (N = 45) | Cancer (N = 56) or none (primary LE, N = 8) | 64 (89) | 58.4 ± 11.9 | Cutaneous shear wave velocity > 2.10 m/s | 0.83 | 0.86 | 0.69 | ||
| Subcutaneous shear wave velocity > 1.43 m/s | 0.80 | 0.70 | 0.50 | ||||||||||||
| Hara and Mihara [52], 2021 | US | Fluorescence lymphography | All stages LE | No LE | Presence dermal backflow | Lower extremities | GC | 14 (100) |
Mean 59.7 (range 48–84) |
Presence dilated or sclerotic lymphedema vessels | 0.43 | 0.94 | 0.37 | ||
| Devoogdt et al. [48], 2014 | US | Tape measurements | Mild LE | No LE | > 5% volume interlimb difference | Upper extremities | Wrist | BC unilateral | 42 (NR) | 54.9 ± 11.4 | Thickness subcutis (> 20% interlimb difference) | 0.40 | 0.93 | 0.33 | |
| Echogenicity cutis (disturbed) | 1.00 | 0.75 | 0.75 | ||||||||||||
| Echogenicity subcutis (disturbed) | 0.33 | 0.93 | 0.26 | ||||||||||||
| Ventral | Thickness cutis (> 0.3 mm interlimb difference) | 0.33 | 0.93 | 0.26 | |||||||||||
| Thickness subcutis (> 20% interlimb difference) | 0.67 | 0.59 | 0.26 | ||||||||||||
| Echogenicity cutis (disturbed) | 0.20 | 0.96 | 0.14 | ||||||||||||
| Echogenicity subcutis (disturbed) | 0.13 | 0.96 | 0.09 | ||||||||||||
| Dorsal | Thickness cutis (> 0.3 mm interlimb difference) | 0.33 | 0.93 | 0.23 | |||||||||||
| Thickness subcutis (> 20% interlimb difference) | 0.20 | 0.63 | -0.17 | ||||||||||||
| Echogenicity cutis (disturbed) | 0.27 | 1.00 | 0.27 | ||||||||||||
| Echogenicity subcutis (disturbed) | 0.27 | 0.93 | 0.20 | ||||||||||||
| Biceps | Thickness cutis (> 0.3 mm interlimb difference) | 0.14 | 0.86 | 0.00 | |||||||||||
| Thickness subcutis (> 20% interlimb difference) | 0.24 | 0.81 | 0.05 | ||||||||||||
| Echogenicity cutis (disturbed) | 0.10 | 1.00 | 0.10 | ||||||||||||
| Echogenicity subcutis (disturbed) | 0.14 | 0.90 | 0.04 | ||||||||||||
| Triceps | Thickness cutis (> 0.3 mm interlimb difference) | 0.25 | 0.65 | -0.10 | |||||||||||
| Thickness subcutis (> 20% interlimb difference) | 0.67 | 0.67 | 0.34 | ||||||||||||
| Echogenicity cutis (disturbed) | 0.24 | 1.00 | 0.24 | ||||||||||||
| Echogenicity subcutis (disturbed) | 0.43 | 0.76 | 0.19 | ||||||||||||
| Erdinç Gündüz et al. [49], 2021 | US | Tape measurements | Grade 3 LE | Grade 2 LE | ISL consensus criteria 2009; > 5 cm interlimb difference | Upper extremities | BC unilateral | 34 (100) | 59.8 ± 10.7 | > 0.22 cm interlimb difference | 0.80 | 0.75 | 0.55 | ||
| Giray and Yağcı [51], 2019 | US | Tape measurements | All stages LE | No LE | > 200 ml interlimb difference | Upper extremities | BC unilateral | 45 (NR) | 50.8 ± 8.7 | Subcutaneous tissue thickness > 0.17 cm interlimb difference | 0.79 | 0.69 | 0.48 | ||
| Riches et al. [43], 2023 | US | Clinical assessment | LE | No LE | Pitting oedema present ≥ 1 breast quandrant | Breast | Lower outer quadrant | BC | 89 (NR) | 61.1 ± 9.6 | Skin thickness | ≥ 2.3 mm | 0.84 | 0.87 | 0.71 |
| Lower inner quadrant | ≥ 2.6 mm | 0.79 | 0.84 | 0.63 | |||||||||||
| Upper outer quadrant | ≥ 2.5 mm | 0.92 | 0.92 | 0.84 | |||||||||||
| Upper inner quadrant | ≥ 3.0 mm | 0.91 | 0.93 | 0.84 | |||||||||||
| Erdogan Iyigun et al. [50], 2019 | US | ISL 2013 consensus criteria | Stage 2 LE | Stage 1 LE | ISL consensus criteria 2013 | Upper extremities | BC unilateral | 36 (100) | 50.8 (30–69) | Shear wave velocity > 1.78 m/s | 0.63 | 0.65 | 0.28 | ||
| Omura et al. [54], 2022 | US | ISL consensus criteria 2016 | Stage ≥ 1 LE | Stage 0 LE | ISL consensus criteria 2016 | Lower extremities | NR |
ISL stage 0: 54 (89) 1: 18 (89) IIa: 22 (95) IIb: 26 (89) |
ISL stage 0: 60 ± 14 1: 57 ± 19 IIa: 63 ± 12 IIb: 68 ± 15 |
Thickness (threshold NR) | Dermis | 0.73 | 0.91 | 0.64 | |
| Dermis SD | 0.59 | 0.64 | 0.23 | ||||||||||||
| % echogenic region (threshold NR) | Hypodermis | 0.69 | 0.73 | 0.42 | |||||||||||
| a part of Gaussian form factor (threshold NR) | Dermis | 0.45 | 0.80 | 0.25 | |||||||||||
| Dermis, SD | 0.64 | 0.67 | 0.31 | ||||||||||||
| Dermis, Combination | 0.55 | 0.73 | 0.28 | ||||||||||||
| Hypodermis | 0.54 | 0.83 | 0.37 | ||||||||||||
| Hypodermis, SD | 0.71 | 0.61 | 0.32 | ||||||||||||
| Hypodermis, Combination | 0.84 | 0.49 | 0.33 | ||||||||||||
| Effective scatter diameter (threshold NR) | Dermis | 0.56 | 0.87 | 0.43 | |||||||||||
| Dermis, SD | 0.83 | 0.57 | 0.40 | ||||||||||||
| Hypodermis | 0.61 | 0.60 | 0.21 | ||||||||||||
| Hypodermis, SD | 0.46 | 0.74 | 0.20 | ||||||||||||
| Effective acoustic concentration (threshold NR) | Dermis | 0.54 | 0.93 | 0.47 | |||||||||||
| Dermis, SD | 0.78 | 0.76 | 0.54 | ||||||||||||
| Hypodermis | 0.53 | 0.76 | 0.29 | ||||||||||||
| Hypodermis, SD | 0.59 | 0.79 | 0.38 | ||||||||||||
| Homodyned K distribution scatter clustering (threshold NR) | Dermis | 0.61 | 0.57 | 0.18 | |||||||||||
| Dermis, SD | 0.68 | 0.59 | 0.27 | ||||||||||||
| Hypodermis | 0.71 | 0.81 | 0.52 | ||||||||||||
| Hypodermis, SD | 0.84 | 0.56 | 0.40 | ||||||||||||
| Homodyned K distribution ratio of coherent to diffuse signal (threshold NR) | Dermis | 0.73 | 0.73 | 0.46 | |||||||||||
| Dermis, SD | 0.90 | 0.36 | 0.26 | ||||||||||||
| Hypodermis | 0.61 | 0.83 | 0.44 | ||||||||||||
| Hypodermis, SD | 0.74 | 0.57 | 0.31 | ||||||||||||
| Combination effective scatter diameter and effective acoustic concentration parameters | Dermis | 0.71 | 0.86 | 0.57 | |||||||||||
| Hypodermis | 0.44 | 0.93 | 0.37 | ||||||||||||
| Combination homodyned K parameters | Dermis | 0.65 | 0.91 | 0.56 | |||||||||||
| Hypodermis | 0.75 | 0.81 | 0.56 | ||||||||||||
| Combination effective scatter diameter, effective acoustic concentration and homodyned K parameters | Dermis | 0.73 | 0.89 | 0.62 | |||||||||||
| Hypodermis | 0.90 | 0.66 | 0.56 | ||||||||||||
| Combination thickness effective scatter diameter and effective acoustic concentration parameters | Dermis | 0.71 | 0.96 | 0.67 | |||||||||||
| Combination echogenic region and homodyned K parameters | Hypodermis | 0.75 | 0.81 | 0.56 | |||||||||||
| Combination thickness, effective scatter diameter, effective acoustic concentration parameters for the dermis and echogenic region and homodyned K parameters for the hypodermis | 0.75 | 0.91 | 0.66 | ||||||||||||
| Stage ≥ IIa LE | Stage ≤ 1 LE | Thickness (threshold NR) | Dermis | 0.88 | 0.84 | 0.72 | |||||||||
| Dermis SD | 0.59 | 0.59 | 0.18 | ||||||||||||
| % echogenic region (threshold NR) | Hypodermis | 0.80 | 0.69 | 0.49 | |||||||||||
| a part of Gaussian form factor (threshold NR) | Dermis | 0.46 | 0.75 | 0.21 | |||||||||||
| Dermis, SD | 0.71 | 0.64 | 0.35 | ||||||||||||
| Dermis, Combination | 0.57 | 0.67 | 0.24 | ||||||||||||
| Hypodermis | 0.63 | 0.79 | 0.42 | ||||||||||||
| Hypodermis, SD | 0.79 | 0.57 | 0.36 | ||||||||||||
| Hypodermis, Combination | 0.91 | 0.45 | 0.36 | ||||||||||||
| Effective scatter diameter (threshold NR) | Dermis | 0.61 | 0.79 | 0.40 | |||||||||||
| Dermis, SD | 0.86 | 0.49 | 0.35 | ||||||||||||
| Hypodermis | 0.61 | 0.54 | 0.15 | ||||||||||||
| Hypodermis, SD | 0.54 | 0.73 | 0.27 | ||||||||||||
| Effective acoustic concentration (threshold NR) | Dermis | 0.70 | 0.90 | 0.60 | |||||||||||
| Dermis, SD | 0.86 | 0.67 | 0.53 | ||||||||||||
| Hypodermis | 0.54 | 0.69 | 0.23 | ||||||||||||
| Hypodermis, SD | 0.71 | 0.77 | 0.48 | ||||||||||||
| Homodyned K distribution scatter clustering (threshold NR) | Dermis | 0.50 | 0.46 | -0.04 | |||||||||||
| Dermis, SD | 0.70 | 0.53 | 0.23 | ||||||||||||
| Hypodermis | 0.86 | 0.77 | 0.63 | ||||||||||||
| Hypodermis, SD | 0.91 | 0.50 | 0.41 | ||||||||||||
| Homodyned K distribution ratio of coherent to diffuse signal (threshold NR) | Dermis | 0.79 | 0.65 | 0.44 | |||||||||||
| Dermis, SD | 0.91 | 0.30 | 0.21 | ||||||||||||
| Hypodermis | 0.71 | 0.78 | 0.49 | ||||||||||||
| Hypodermis, SD | 0.79 | 0.52 | 0.31 | ||||||||||||
| Combination effective scatter diameter and effective acoustic concentration parameters | Dermis | 0.82 | 0.78 | 0.60 | |||||||||||
| Hypodermis | 0.50 | 0.87 | 0.37 | ||||||||||||
| Combination homodyned K parameters | Dermis | 0.77 | 0.84 | 0.61 | |||||||||||
| Hypodermis | 0.89 | 0.76 | 0.65 | ||||||||||||
| Combination effective scatter diameter, effective acoustic concentration and homodyned K parameters | Dermis | 0.86 | 0.81 | 0.67 | |||||||||||
| Hypodermis | 0.98 | 0.56 | 0.54 | ||||||||||||
| Combination thickness effective scatter diameter and effective acoustic concentration parameters | Dermis | 0.86 | 0.87 | 0.73 | |||||||||||
| Combination echogenic region and homodyned K parameters | Hypodermis | 0.86 | 0.73 | 0.59 | |||||||||||
| Combination thickness, effective scatter diameter, effective acoustic concentration parameters for the dermis and echogenic region and homodyned K parameters for the hypodermis | 0.89 | 0.83 | 0.72 | ||||||||||||
| Dylke et al. [55], 2018 | US | NR | LE | No LE | NR | Breast | Superior | BC | 38 (100) | Range = 36–70 | Dermal thickness | 1.6 mm | 0.84 | 0.91 | 0.75 |
| 1.9 mm | 0.68 | 0.74 | 0.42 | ||||||||||||
| 2.1 mm | 0.60 | 0.87 | 0.47 | ||||||||||||
| Medial | 2.0 mm | 0.90 | 0.92 | 0.82 | |||||||||||
| 2.2 mm | 0.83 | 0.97 | 0.80 | ||||||||||||
| 2.5 mm | 0.80 | 0.87 | 0.67 | ||||||||||||
| Inferior | 2.0 mm | 0.90 | 0.92 | 0.82 | |||||||||||
| 2.1 mm | 0.83 | 0.95 | 0.78 | ||||||||||||
| 2.4 mm | 0.80 | 0.87 | 0.67 | ||||||||||||
| Lateral | 1.6 mm | 0.84 | 0.91 | 0.75 | |||||||||||
| 1.5 mm | 0.88 | 0.83 | 0.71 | ||||||||||||
| 1.8 mm | 0.72 | 0.74 | 0.46 | ||||||||||||
| Thomis et al. [33], 2020 | Clinical assessment | Fluorescence lymphography | Dermal backflow stage I-V | No dermal backflow |
Dermal backflow stage: I: splash pattern II: stardust pattern proximally to the olecranon III: stardust pattern exceeds olecranon IV: stardust pattern whole arm V: diffuse pattern |
Upper extremities (unilateral) | Hand | BC | 45 (NR) | 61.3 ± 9.9 | Pitting doubtful or clearly present | 0.54 | 0.95 | 0.49 | |
| Ventral forearm | 0.83 | 0.67 | 0.50 | ||||||||||||
| Dorsal forearm | 0.89 | 0.75 | 0.64 | ||||||||||||
| Elbow | 0.58 | 0.58 | 0.16 | ||||||||||||
| Ventral upper arm | 0.33 | 0.85 | 0.18 | ||||||||||||
| Dorsal upper arm | 0.67 | 0.89 | 0.56 | ||||||||||||
| Shoulder | 0.33 | 0.91 | 0.24 | ||||||||||||
| Overall | 0.68 | 0.83 | 0.51 | ||||||||||||
| Hand | Interlimb difference (increase) in skinfold thickness | 0.92 | 0.58 | 0.50 | |||||||||||
| Ventral forearm | 0.92 | 0.33 | 0.25 | ||||||||||||
| Dorsal forearm | 0.92 | 0.75 | 0.67 | ||||||||||||
| Elbow | 0.96 | 0.32 | 0.28 | ||||||||||||
| Ventral upper arm | 0.56 | 0.82 | 0.38 | ||||||||||||
| Dorsal upper arm | 0.89 | 0.44 | 0.33 | ||||||||||||
| Shoulder | 0.33 | 0.81 | 0.14 | ||||||||||||
| Overall | 0.87 | 0.62 | 0.49 | ||||||||||||
| Hand | Interlimb difference (hard oedema) in elasticity | 0.23 | 1.00 | 0.23 | |||||||||||
| Ventral forearm | 0.33 | 0.89 | 0.22 | ||||||||||||
| Dorsal forearm | 0.32 | 0.88 | 0.20 | ||||||||||||
| Elbow | 0.07 | 0.95 | 0.02 | ||||||||||||
| Ventral upper arm | 0.06 | 0.96 | 0.02 | ||||||||||||
| Dorsal upper arm | 0.11 | 0.85 | -0.04 | ||||||||||||
| Shoulder | 0.33 | 1.00 | 0.33 | ||||||||||||
| Overall | 0.22 | 0.95 | 0.17 | ||||||||||||
| Thomis et al. [30], 2022c | Clinical assessment | Fluorescence lymphography | Dermal backflow stage I-IV | No dermal backflow |
Dermal backflow stage: 0: No I: splash pattern II: stardust pattern III: diffuse pattern IV: no transport |
Upper extremities | All regions | BC unilateral | 128 (99) | 56.7 ± 12.2 | Pitting present | 0.19 | 0.98 | 0.17 | |
| Increased skinfold thickness | 0.29 | 0.97 | 0.26 | ||||||||||||
| Ventral upper arm | Pitting present | 0.14 | 0.99 | 0.13 | |||||||||||
| Increased skinfold thickness | 0.29 | 0.97 | 0.26 | ||||||||||||
| Svensson et al. [56], 2020 | Clinical assessment | MF-BIA | LE | No LE | Interlimb ratio > 2SD or 3SD | Upper extremities (unilateral) | BC | 100 (100) | 61.8 ± 10.6 | Pitting test, interlimb difference in depth and resolution time | 0.92 | 0.77 | 0.69 | ||
| Forearm pinch test, interlimb difference in tissue texture | 0.94 | 0.75 | 0.69 | ||||||||||||
| Upper arm pinch test, interlimb difference in tissue texture | 0.73 | 0.77 | 0.50 | ||||||||||||
| Chung et al. [57], 2006 | Cuff-leak test | Endoscopy | Severe oedema | No severe oedema | Swollen bilateral vocal cords and attachment to opposite side of the larynx | Laryngeal | Not specified | 32 (34) | 71.3 ± 13.6 | Volume < 140 mL | 0.89 | 0.90 | 0.79 | ||
Abbreviations: BC breast cancer, CT computed tomography, GC gynecological cancer, LE lymphedema, LSG lymphoscintigraphy, MF-BIA multi-frequency bioimpedance analysis, MRA magnetic resonance angiography, MRI magnetic resonance imaging, NR not reported, SF-BIA single-frequency bioimpedance analysis, TDC tissue dielectric constant, TKA total knee arthroplasty, US ultrasound, WV water volumetry
aPartly same study population as Keo et al. [60]
bPartly same study population as Berlit et al. [35]
cPartly same study population as Thomis et al. [33]
dPartly same study population as Hayes et al. [24]
eData for full group (N = 193)
fUnilaterality assumed since measurement instrument compares affected to unaffected side
gAge at surgery
hPartly same study population as Lu et al. [32]
Table 3.
Summary of the index and reference measurement instruments identified for measuring oedema in the included studies
CT computed tomography, MF-BIA multi-frequency bioimpedance analysis, MRA magnetic resonance angiography, MRI magnetic resonance imaging, SF-BIA single-frequency bioimpedance analysis, TDC tissue dielectric constant
The studies evaluated various instruments for diagnosing soft-tissue oedema. Seventeen studies assessed volume measurement instruments, including perometry [17, 18], tape measurements [19–31], and water volumetry [21, 32, 33]. Sixteen studies focused on measurement instruments for tissue characteristics, involving bio-electrical impedance analysis (BIA) [17, 21, 29, 31, 34–41] and tissue-dielectric constant (TDC) [27, 30, 40, 42, 43]. Nineteen studies examined instruments measuring both volume and tissue characteristics, including CT [44], MRI [32, 45, 46], magnetic resonance angiography (MRA) [31], US [43, 47–55], clinical assessment [30, 33, 56], and cuff leak test [57]. Additionally, five studies evaluated the function of the lymphatic system using lymphoscintigraphy [31, 58] and fluorescence microlymphography [59–61].
Reference measurement instruments included volume measurements in 20 studies using perometry [31, 37, 61], tape measurements [19, 20, 26, 29, 35, 36, 38, 41, 42, 48, 49, 51] or water volumetry [21–23, 28, 34]. Tissue characteristics measurements served as reference in three studies using multi-frequency (MF)-BIA [24, 25, 29]. A combination of volume and tissue characteristics measurements was used as reference in 14 studies, involving clinical assessment [18, 39, 40, 43], consensus criteria [27, 32, 45, 46, 50, 54, 58–60] and endoscopy [57]. The lymphatic system function was used as reference in seven studies, using lymphoscintigraphy [17, 44, 47, 53], or fluorescence lymphography [30, 33, 52]. One study did not report the reference instrument [55].
The types of swelling considered were lymphoedema in 44 studies [17–28, 30–61] and postoperative swelling in one study [29]. Secondary lymphoedema arose from (treatment for) various conditions, including breast cancer [17–28, 30, 33–43, 48–51, 55, 56, 61], gynaecological cancer [32, 45, 52], or various causes [31, 44, 46, 47, 58]. In some cases, the cause of lymphoedema was unspecified [53, 54, 57, 59, 60]. The postoperative swelling study focused on total knee arthroplasty for osteoarthritis [29]. Of the 45 included studies, 30 focused on oedema in the upper extremities [17–28, 30, 31, 33–36, 38–42, 48–51, 56, 61], 10 in the lower extremities [29, 32, 45, 46, 52–54, 58–60], 2 in both upper and lower extremities [44, 47], 2 in the breast [43, 55] and 1 in the larynx [57], as illustrated in Table 4. The total number of participants across the studies was 4644, with 94% of the patients being female when gender was reported. Seven studies did not report gender distribution [22, 33, 38, 43, 46, 48, 51]. The mean or median age of participants ranged from 45.0 to 71.3 years.
Table 4.
Summary of the oedema location and stage per identified index measurement instruments in the included studies
CT computed tomography, MF-BIA multi-frequency bioimpedance analysis, MRA magnetic resonance angiography, MRI magnetic resonance imaging, N.R. not reported, SF-BIA single-frequency bioimpedance analysis
Risk of bias within studies
The quality assessment of the included studies is summarized in Table 5, with detailed assessment available in Supplementary information 3. According to QUADAS-2 assessment, no study was free from bias in all domains. Thirty-seven studies (82%) exhibited a high risk of bias in at least one domain [17–22, 24–26, 29–33, 35–39, 41, 43–51, 53–55, 57–61], while eight studies (18%) showed an unclear risk of bias in at least one domain [23, 27, 28, 34, 40, 42, 52, 56]. Common bias sources included unspecified patient enrolment, unspecified blinding, and non-prespecified thresholds. Nevertheless, all studies, except one [55], were considered applicable to the research question. All studies, except one [27], employed very good statistical methods as per COSMIN Box 8.
Table 5.
Methodological quality assessment with QUADAS-2 and COSMIN Box 8
Best-evidence synthesis
Only two studies received three or more good quality scores on the QUADAS-2 risk of bias assessment, limiting the overall level of evidence for index measurements [33, 57]. Limited evidence was found for TDC, water volumetry, MRI, ultrasound, clinical assessment, and cuff leak test. Insufficient evidence was found for lymphoscintigraphy, fluorescence lymphography, SF-BIA, MF-BIA, perometry, tape measurements, CT, and MRA.
Oedema measurement instruments
Instruments assessing lymphatic system function
Lymphoscintigraphy (LSG), using a radioactive tracer, was reported in two studies as an index measurement instrument, demonstrating insufficient evidence with a conflicting diagnostic value (Youden index = 0.29–0.80) [31, 58]. LSG was applied to both upper and lower extremities to quantify lymphoedema by assessing the presence of dermal backflow and the uptake of the radiotracer.
Fluorescence lymphography, e.g. indocyanine green (ICG) lymphography or near-infrared fluorescence imaging (NIRF), was assessed in three studies, although two of these included overlapping populations. Lymphoscintigraphy displayed insufficient evidence with a conflicting diagnostic value (Youden index = 0.22–0.78) for lower extremities, where the diagnosis of lymphoedema was based on the maximum spread of the fluorescent dye [59, 60]. A moderate diagnostic value (Youden index = 0.47) was reported for mild and moderate lymphoedema in upper extremities by measuring dermal backflow [61].
Instruments assessing tissue characteristics
Single-frequency (SF) bio-impedance analysis (BIA) was reported in three studies as an index measurement instrument for upper extremities, showing insufficient evidence with a moderate to high diagnostic value (Youden index = 0.58–0.83) [35, 36, 41]. Multi-frequency (MF) BIA, also known as bio-impedance spectroscopy, was evaluated in nine studies. MF-BIA showed insufficient evidence with a conflicting diagnostic value (Youden index = 0.36–0.98) across both upper and lower extremities [17, 21, 29, 31, 34, 37–40]. Notably, for mild lymphoedema in upper extremities, MF-BIA displayed a very high diagnostic value with a Youden index of 0.98, although the risk of bias was unclear to high [38]. Mild and moderate lymphoedema in upper extremities had moderate to high Youden indexes (0.63–0.80) with also an unclear to high risk of bias [17]. In the context of post-operative swelling, MF-BIA exhibited very high diagnostic accuracy (Youden index = 0.92–0.96) by measuring the interlimb difference; however, there was a high risk of bias on two domains of QUADAS-2 [29]. MF-BIA often assessed lymphoedema by evaluating the L-DEX ratio, which compares the impedance of extracellular fluid between the unaffected and affected body parts, with MF-BIA’s ability to distinguish between intracellular and extracellular fluids, in contrast to SF-BIA.
Tissue dielectric constant (TDC) was reported in six studies, presenting limited evidence with a conflicting diagnostic value (Youden index = −0.04 to 0.68) [27, 30, 33, 40, 42, 43]. The Youden index could not be calculated in one study that assessed mild and moderate lymphoedema in the upper extremities [27]. A high-quality study comparing TDC with fluorescence lymphography for all stages of lymphoedema in the upper extremities demonstrated conflicting Youden indexes (−0.04 to 0.52) [33]. Another high-quality study compared TDC with clinical assessment in the breast, showing a moderate Youden index of 0.68 [43]. In all studies, lymphoedema was diagnosed by measuring the water content ratio between affected and unaffected body parts using TDC.
Instruments assessing volume
Perometry was evaluated in two studies as an index measurement instrument, demonstrating insufficient evidence with a conflicting diagnostic value (Youden index = 0.17–0.90) in the upper extremities [17, 18]. For the diagnosis of mild and moderate lymphoedema, perometry yielded moderate to very high Youden indexes (0.57–0.90) with an unclear to high risk of bias [17]. The highest Youden index (0.90) was observed when diagnosing oedema using a single elevated circumference, with LSG serving as the reference instrument [17]. In addition to obtaining circumference measurements, volume was also calculated based on the circumference or perometry directly measured volume.
Tape measurements, reported in 13 studies, showed insufficient evidence with a conflicting diagnostic value (Youden index = −0.31 to 0.84) [19–31]. The Youden index could not be calculated in one study that assessed mild and moderate lymphoedema in the upper extremities [27]. For the diagnosis of moderate lymphoedema in the upper extremities, tape measurements yielded moderate Youden indexes (0.46–0.64) when comparing circumferences to calculated volumes, though the studies exhibited a high risk of bias in three domains of the QUADAS-2 [19]. Tape measurements were also applied in the lower extremities. Across the studies, tape measurements were used to evaluate differences between affected and unaffected limbs in 12 studies [19, 21–29, 31], while one study measured differences from the baseline [20]. The method involved measuring various circumferences, and sometimes volume was calculated based on these circumferences.
Water volumetry, evaluated in three studies, displayed limited evidence with a conflicting diagnostic value (Youden index = 0.01–0.82) [21, 32, 33]. In one high-quality study comparing water volumetry with fluorescence lymphography, conflicting Youden indexes (0.01 to 0.72) were reported for the upper extremities [33]. In the lower extremities, water volumetry was used to assess mild, moderate, and severe lymphoedema, yielding weak to high Youden indexes (mild, 0.55–0.62; moderate, 0.39–0.70; severe, 0.77–0.82), with an unclear or high risk of bias in two domains of the QUADAS-2 [32]. All three studies focused on evaluating the volume difference between the affected and unaffected sides. Additionally, one of these studies assessed the diagnostic accuracy of water volumetry using the absolute limb volume, resulting in Youden indexes ranging from 0.39 to 0.82 [32].
Imaging techniques assessing both tissue characteristics and volume
Computed tomography (CT) was reported in one study as an index measurement instrument, showing insufficient evidence with a weak diagnostic value (Youden index = 0.31–0.38) for diagnosing moderate and severe lymphoedema in upper and lower extremities [44]. The diagnosis of oedema using CT was based on the ratio of the number of pixels of the tissue layer between skin and muscle between the affected and unaffected sides.
Magnetic resonance imaging (MRI), assessed in three studies, displayed limited evidence with a conflicting diagnostic value (Youden index = −0.13 to 1.00). MRI was used to evaluate mild, moderate, and severe lymphoedema, with each stage showing conflicting Youden indexes (mild, 0.19–1.00; moderate, 0.21–0.82; severe, −0.13 to 0.87) [32, 45, 46]. Notably, very high Youden indexes were observed for diagnosing mild lymphoedema by measuring the difference in subcutaneous tissue thickness between affected and unaffected limbs (Youden index = 0.96) [32] and assessing the absolute water area (Youden index = 1.00) [46]. MRI measurements involved the thickness or area of specific tissue, allowing for the differentiation between water, muscle, subcutaneous tissue, and total soft tissue.
Magnetic resonance angiography (MRA) was evaluated in a single study, providing insufficient evidence with weak to moderate diagnostic value (Youden index = 0.38–0.60) for all stages of lymphoedema in the upper extremities [31]. The diagnosis of lymphoedema using MRI was based on measurements of fluid accumulation and fat hypertrophy.
Ultrasound (US) was evaluated in ten studies, showing limited evidence with a conflicting diagnostic value (Youden index = −0.17 to 0.84) [43, 47–55]. Among these studies, three were of high quality. One high-quality study compared US to clinical assessment and found moderate to high diagnostic value (Youden index = 0.63–0.84) in the breast [43]. Another high-quality study compared US to LSG across all stages of lymphoedema, showing moderate diagnostic value (Youden index = 0.50–0.69) for US in both upper and lower extremities [47]. A third high-quality study compared US to tape measurements for severe lymphoedema in the upper extremities, also demonstrating moderate diagnostic value (Youden index = 0.55) for US [49]. For other stages and locations, the Youden indexes were weak for moderate and severe lymphoedema in the lower extremities (0.18–0.64) [54], conflicting for lymphoedema in the breast (0.42–0.82) [55] and conflicting for mild (−0.17 to 0.75) [48] or moderate lymphoedema (0.28) [50] in the upper extremities. Besides, each of these studies had a risk of bias.
Various outcome parameters were measured using US, with some showing high diagnostic value. For instance, the thickness of the skin yielded Youden indexes as high as 0.84 [43] and the thickness of the dermis reached up to 0.82 [54, 55]. Disturbed echogenicity of the cutis was another parameter with high diagnostic value, achieving a Youden index up to 0.75 [48]. Additionally, some calculated parameters based on algorithmic schemes and mathematical formulas, such as Shannon entropy (Youden index = 0.83) [53] or a combination of various calculated parameters (Youden index up to 0.73) [54], showed strong diagnostic performance. Other outcomes, such as share wave velocity [47, 50], which depends on the tissue density, and the presence of dilated or sclerotic lymphedema vessels [52], demonstrated lower diagnostic value.
Other methods assessing both tissue characteristics and volume
Clinical assessment was evaluated in three studies as an index measurement instrument, showing limited evidence with a conflicting diagnostic value (Youden index = −0.04 to 0.69) in the upper extremities [30, 33, 56]. Clinical assessment involved evaluating the presence of pitting, increased skinfold thickness, and deviations in tissue texture. In one high-quality study that compared clinical assessment with fluorescence lymphography, the Youden indexes for the presence of pitting and increased skinfold thickness were weak, ranging from 0.13 to 0.26 [33].
Cuff-leak test was reported once, showing limited evidence with a high diagnostic value (Youden index = 0.79) for laryngeal oedema. Endoscopy was used as the reference instrument [57].
Discussion
This systematic review aimed to identify measurement instruments for quantitatively diagnosing soft-tissue oedema, including lymphoedema, across any body part and their diagnostic accuracy. The findings highlight both advancements and ongoing challenges in accurately diagnosing lymphoedema.
Our review identified a variety of instruments focused on measuring volume, tissue characteristics, and lymphatic system function. Tape measurements, US, and MF-BIA were the most frequently studied. Index instruments with very high diagnostic value (Youden index ≥ 0.90) included MF-BIA, perometry, and MRI. However, when considering the quality of these studies, evidence is lacking. Limited evidence was found for TDC, water volumetry, MRI, US, clinical assessment, and cuff leak test, while insufficient evidence was found for lymphoscintigraphy, fluorescence lymphography, SF-BIA, MF-BIA, perometry, tape measurements, CT, and MRA. These methodological limitations require cautious interpretation of the current evidence.
Interpretation of evidence is also hampered by the absence of a universal gold standard, resulting in the use of various measurement instruments as reference, making comparisons between studies challenging. The most used reference instruments were tape measurements, consensus criteria, and water volumetry, applied in 12, nine, and five studies, respectively. The frequent use of water volumetry aligns with recommendations from an earlier review suggesting it as the preferred reference standard [23]. The suitability of instruments as a reference depends on the body part being assessed and the stage of lymphoedema. In ISL stage 0, only impaired lymph transport and subtle changes in tissue fluid or composition can be measured, while volumetric measurement becomes more relevant in later stages [2, 9]. Furthermore, a single body part may present with multiple stages simultaneously [2].
Effective lymphoedema management relies on early detection, ideally before irreversible changes such as fibrotic tissue formation occur. The diagnostic accuracy of index measurement instruments for early lymphedema was evaluated for MF-BIA, TDC, tape measurements, water volumetry, MRI, and US in extremities. Diagnostic value was very high for MF-BIA, weak to high for water volumetry, conflicting for MRI and ultrasound, and could not be determined for TDC and tape measurements. However, all evidence was restricted by the limited number of studies.
Strength and limitations
A key strength of this review is the inclusion of a wide variety of instruments and parameters for diagnosing lymphoedema. However, the inclusion of various instruments and parameters and lack of a uniform and reliable gold (reference) standard precluded meta-analysis and poses a challenge in assessing potential publication bias. This precluded standard methods like funnel plots or Egger’s test for a comprehensive evaluation. Although a best-evidence synthesis was conducted to summarize the overall level of evidence per instrument, it did not account for potential bias in subgroup outcomes for oedema stages or locations.
Implications for clinical practice
Given the chronic and progressive nature of lymphoedema, early detection is critical for effective management. Despite the extensive range of instruments studied, no single instrument emerged as a definitive gold standard for diagnosing lymphoedema. This finding reflects the multifaceted nature of lymphoedema, which manifests through various physical changes including fluid accumulation and tissue fibrosis. Consequently, the choice of measurement instrument should depend on the specific clinical context and the stage of lymphoedema. However, this review found insufficient evidence on the diagnostic accuracy of specific instruments to recommend their use in particular stages, especially the early stage. Practical tools like tape measurements, consensus criteria, and water volumetry are commonly used because they are inexpensive and easy to use, while advanced imaging techniques may be more appropriate for complex cases (e.g. presence of significant comorbidity) [2] or research settings.
Recommendations
To enhance the early detection and treatment of lymphoedema, it is essential to focus on several key areas. First, developing standardized protocols for lymphoedema measurement is crucial to reduce variability and improve comparability across studies. This standardization would help in establishing more consistent and reliable diagnostic criteria. In addition, there is a need for comprehensive evaluations through high-quality studies that assess the diagnostic accuracy of measurement instruments. Such studies should aim to fill the gaps in current knowledge and provide robust evidence to support clinical decision-making. Exploring the integration of different measurement techniques could also be beneficial. By combining various tools, healthcare providers may achieve a more accurate and comprehensive assessment of lymphoedema, which could improve diagnosis and management strategies.
In conclusion, this systematic review underscores the complexity of accurately diagnosing lymphoedema. While several measurement instruments are available, there remains a need for more high-quality research to improve standardization. Clinicians must carefully consider the available evidence and the specific clinical context, for example, early detection, when selecting measurement instruments for diagnosing lymphoedema.
Supplementary Information
Below is the link to the electronic supplementary material.
Author Contribution
MB: conceptualization, design, electronic data search, data extraction, data synthesis, writing – original draft, review and editing. EG: conceptualization, design, electronic data search, data extraction, data synthesis, writing – review and editing. JH: conceptualization, design, electronic data search, data extraction, writing – review and editing. JR: conceptualization, design, electronic data search, data extraction, writing – review and editing. WB: conceptualization, design, electronic data search, writing – review and editing. RB: conceptualization, design, writing – review and editing. CS: conceptualization, design, electronic data search, data extraction, data synthesis, writing – review and editing.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval
This was a systematic review. No ethics approval was required.
Competing interests
The authors declare no competing interests.
Footnotes
PROSPERO registration number: CRD42023474209.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
No datasets were generated or analysed during the current study.